A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.
A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.
A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS. EC 5.2.1.-
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).
Proteins that bind to the 3' polyadenylated region of MRNA. When complexed with RNA the proteins serve an array of functions such as stabilizing the 3' end of RNA, promoting poly(A) synthesis and stimulating mRNA translation.
An antibiotic substance derived from Penicillium stoloniferum, and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1301)
The transference of a kidney from one human or animal to another.
Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons.
An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.
Transport proteins that carry specific substances in the blood or across cell membranes.
The transference of a part of or an entire liver from one human or animal to another.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A CALCIUM and CALMODULIN-dependent serine/threonine protein phosphatase that is composed of the calcineurin A catalytic subunit and the calcineurin B regulatory subunit. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including HISTONES; MYOSIN LIGHT CHAIN; and the regulatory subunits of CAMP-DEPENDENT PROTEIN KINASES. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes.
The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.
A poly(A) binding protein that has a variety of functions such as mRNA stabilization and protection of RNA from nuclease activity. Although poly(A) binding protein I is considered a major cytoplasmic RNA-binding protein it is also found in the CELL NUCLEUS and may be involved in transport of mRNP particles.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.
A family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (Int J Gynaecol Obstet 1992;39(1):3-9)
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Intracellular proteins that reversibly bind hydrophobic ligands including: saturated and unsaturated FATTY ACIDS; EICOSANOIDS; and RETINOIDS. They are considered a highly conserved and ubiquitously expressed family of proteins that may play a role in the metabolism of LIPIDS.
A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.
Therapy with two or more separate preparations given for a combined effect.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically.
The application of drug preparations to the surfaces of the body, especially the skin (ADMINISTRATION, CUTANEOUS) or mucous membranes. This method of treatment is used to avoid systemic side effects when high doses are required at a localized area or as an alternative systemic administration route, to avoid hepatic processing for example.
A poly(A) binding protein that is involved in promoting the extension of the poly A tails of MRNA. The protein requires a minimum of ten ADENOSINE nucleotides in order for binding to mRNA. Once bound it works in conjunction with CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR to stimulate the rate of poly A synthesis by POLY A POLYMERASE. Once poly-A tails reach around 250 nucleotides in length poly(A) binding protein II no longer stimulates POLYADENYLATION. Mutations within a GCG repeat region in the gene for poly(A) binding protein II have been shown to cause the disease MUSCULAR DYSTROPHY, OCULOPHARYNGEAL.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
Drugs used to treat or prevent skin disorders or for the routine care of skin.
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
Periplasmic proteins that scavenge or sense diverse nutrients. In the bacterial environment they usually couple to transporters or chemotaxis receptors on the inner bacterial membrane.
The transference of a pancreas from one human or animal to another.
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.
Adrenal cortex hormones are steroid hormones produced by the outer portion of the adrenal gland, consisting of glucocorticoids, mineralocorticoids, and androgens, which play crucial roles in various physiological processes such as metabolism regulation, stress response, electrolyte balance, and sexual development and function.
Elements of limited time intervals, contributing to particular results or situations.

Mammalian target of rapamycin-dependent phosphorylation of PHAS-I in four (S/T)P sites detected by phospho-specific antibodies. (1/181)

The role and control of the four rapamycin-sensitive phosphorylation sites that govern the association of PHAS-I with the mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), were investigated by using newly developed phospho-specific antibodies. Thr(P)-36/45 antibodies reacted with all three forms of PHAS-I that were resolved when cell extracts were subjected to SDS-polyacrylamide gel electrophoresis. Thr(P)-69 antibodies bound the forms of intermediate and lowest mobility, and Ser(P)-64 antibodies reacted only with the lowest mobility form. A portion of PHAS-I that copurified with eIF4E reacted with Thr(P)-36/45 and Thr(P)-69 antibodies but not with Ser(P)-64 antibodies. Insulin and/or amino acids increased, and rapamycin decreased, the reactivity of all three antibodies with PHAS-I in both HEK293 cells and 3T3-L1 adipocytes. Immunoprecipitated epitope-tagged mammalian target of rapamycin (mTOR) phosphorylated Thr-36/45. mTOR also phosphorylated Thr-69 and Ser-64 but only when purified immune complexes were incubated with the activating antibody, mTAb1. Interestingly, the phosphorylation of Thr-69 and Ser-64 was much more sensitive to inhibition by rapamycin-FKBP12 than the phosphorylation of Thr-36/45, and the phosphorylation of Ser-64 by mTOR was facilitated by phosphorylation of Thr-36, Thr-45, and Thr-69. In these respects the phosphorylation of PHAS-I by mTOR in vitro resembles the ordered phosphorylation of PHAS-I in cells.  (+info)

Solution structure of a neurotrophic ligand bound to FKBP12 and its effects on protein dynamics. (2/181)

The structure of a recently reported neurotrophic ligand, 3-(3-pyridyl)-1-propyl(2S)-1-(3,3-dimethyl-1, 2-dioxopentyl)-2-pyrrolidinecarboxylate, in complex with FKBP12 was determined using heteronuclear NMR spectroscopy. The inhibitor exhibits a binding mode analogous to that observed for the macrocycle FK506, used widely as an immunosuppressant, with the prolyl ring replacing the pipecolyl moiety and the amide bond in a trans conformation. However, fewer favourable protein-ligand interactions are detected in the structure of the complex, suggesting weaker binding compared with the immunosuppressant drug. Indeed, a micromolar dissociation constant was estimated from the NMR ligand titration profile, in contrast to the previously published nanomolar inhibition activity. Although the inhibitor possesses a remarkable structural simplicity with respect to FK506, 15N relaxation studies show that it induces similar effects on the protein dynamics, stabilizing the conformation of solvent-exposed residues which are important for mediating the interaction of immunophilin/ligand complexes with molecular targets and potentially for the transmission of the neurotrophic action of FKBP12 inhibitors.  (+info)

H(2)O(2) and ethanol act synergistically to gate ryanodine receptor/calcium-release channel. (3/181)

We examined the effect of low concentrations of H(2)O(2) on the Ca(2+)-release channel/ryanodine receptor (RyR) to determine if H(2)O(2) plays a physiological role in skeletal muscle function. Sarcoplasmic reticulum vesicles from frog skeletal muscle and type 1 RyRs (RyR1) purified from rabbit skeletal muscle were incorporated into lipid bilayers. Channel activity of the frog RyR was not affected by application of 4.4 mM (0.02%) ethanol. Open probability (P(o)) of such ethanol-treated RyR channels was markedly increased on subsequent addition of 10 microM H(2)O(2). Increase of H(2)O(2) to 100 microM caused a further increase in channel activity. Application of 4.4 mM ethanol to 10 microM H(2)O(2)-treated RyRs activated channel activity. Exposure to 10 or 100 microM H(2)O(2) alone, however, failed to increase P(o). Synergistic action of ethanol and H(2)O(2) was also observed on the purified RyR1 channel, which was free from FK506 binding protein (FKBP12). H(2)O(2) at 100-500 microM had no effect on purified channel activity. Application of FKBP12 to the purified RyR1 drastically decreased channel activity but did not alter the effects of ethanol and H(2)O(2). These results suggest that H(2)O(2) may play a pathophysiological, but probably not a physiological, role by directly acting on skeletal muscle RyRs in the presence of ethanol.  (+info)

Divergent functional properties of ryanodine receptor types 1 and 3 expressed in a myogenic cell line. (4/181)

Of the three known ryanodine receptor (RyR) isoforms expressed in muscle, RyR1 and RyR2 have well-defined roles in contraction. However, studies on mammalian RyR3 have been difficult because of low expression levels relative to RyR1 or RyR2. Using the herpes simplex virus 1 (HSV-1) helper-free amplicon system, we expressed either RyR1 or RyR3 in 1B5 RyR-deficient myotubes. Western blot analysis revealed that RyR1- or RyR3-transduced cells expressed the appropriate RyR isoform of the correct molecular mass. Although RyR1 channels exhibited the expected unitary conductance for Cs(+) in bilayer lipid membranes, 74 of 88 RyR3 channels exhibited pronounced subconductance behavior. Western blot analysis with an FKBP12/12.6-selective antibody reveals that differences in gating behavior exhibited by RyR1 and RyR3 may be, in part, the result of lower affinity of RyR3 for FKBP12. In calcium imaging studies, RyR1 restored skeletal-type excitation-contraction coupling, whereas RyR3 did not. Although RyR3-expressing myotubes were more sensitive to caffeine than those expressing RyR1, they were much less sensitive to 4-chloro-m-cresol (CMC). In RyR1-expressing cells, regenerative calcium oscillations were observed in response to caffeine and CMC but were never seen in RyR3-expressing 1B5 cells. In [(3)H]ryanodine binding studies, only RyR1 exhibited sensitivity to CMC, but both RyR isoforms responded to caffeine. These functional differences between RyR1 and RyR3 expressed in a mammalian muscle context may reflect differences in association with accessory proteins, especially FKBP12, as well as structural differences in modulator binding sites.  (+info)

Selectively suppressed Ca2+-induced Ca2+ release activity of alpha-ryanodine receptor (alpha-RyR) in frog skeletal muscle sarcoplasmic reticulum: potential distinct modes in Ca2+ release between alpha- and beta-RyR. (5/181)

We reported earlier that the two ryanodine receptor (RyR) isoforms (alpha- and beta-RyR) purified from frog skeletal muscle were equipotent in the Ca(2+)-induced Ca(2+) release (CICR) activity (Murayama, T., Kurebayashi, N., and Ogawa, Y. (2000) Biophys. J. 78, 1810-1824). Whether this is also the case with the native Ca(2+) release channel in the sarcoplasmic reticulum (SR), however, remains to be determined. Taking advantage of the facts that [(3)H]ryanodine binds only to the open form of the channels and that it is practically irreversible at 4 degrees C, we devised a method to separate the total binding to contributions of alpha- and beta-RyR, using immunoprecipitation with an alpha-RyR-specific monoclonal antibody. Surprisingly, the binding of alpha-RyR was strongly suppressed to as low as approximately 4% that of beta-RyR in the SR vesicles. The two isoforms, however, showed no difference in sensitivity to Ca(2+), adenine nucleotides, or caffeine. This reduced binding of alpha-RyR was ascribed to the low affinity for [(3)H]ryanodine, with no change in the maximal binding sites. Solubilization of SR with 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonic acid partly remedied this nonequivalence, whereas 1 m NaCl was ineffective. 12-kDa FK506-binding protein (FKBP12), however, could not be responsible for it, because FK506 treatment did not eliminate the suppression, in contrast to marked removal of 12-kDa FK506-binding protein from alpha-RyR. These results suggest that alpha-RyR in the SR may serve Ca(2+) release in a mode other than CICR, being selectively suppressed in CICR.  (+info)

The fission yeast TOR homolog, tor1+, is required for the response to starvation and other stresses via a conserved serine. (6/181)

Targets of rapamycin (TORs) are conserved phosphatidylinositol kinase-related kinases that are involved in the coordination between nutritional or mitogenic signals and cell growth. Here we report the initial characterization of two Schizosaccharomyces pombe TOR homologs, tor1(+) and tor2(+). tor2(+) is an essential gene, whereas tor1(+) is required only under starvation and other stress conditions. Specifically, Deltator1 cells fail to enter stationary phase or undergo sexual development and are sensitive to cold, osmotic stress, and oxidative stress. In complex with the prolyl isomerase FKBP12, the drug rapamycin binds a conserved domain in TORs, FRB, thus inhibiting some of the functions of TORs. Mutations at a conserved serine within the FRB domain of Saccharomyces cerevisiae TOR proteins led to rapamycin resistance but did not otherwise affect the functions of the proteins. The S. pombe tor1(+) exhibits different features; substitution of the conserved serine residue, Ser(1834), with arginine compromises its functions and has no effect on the inhibition that rapamycin exerts on sexual development in S. pombe.  (+info)

Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor. (7/181)

Transforming growth factor-beta (TGF-beta) signaling proceeds from the cell membrane to the nucleus through the cooperation of the type I and II serine/threonine kinase receptors and their downstream SMAD effectors. Although various regulatory proteins affecting TGF-beta-mediated events have been described, relatively little is known about receptor interactions at the level of the plasma membrane. Caveolae are cholesterol-rich membrane microdomains that, along with their marker protein caveolin-1 (Cav-1), have been implicated in the compartmentalization and regulation of certain signaling events. Here, we demonstrate that specific components of the TGF-beta cascade are associated with caveolin-1 in caveolae and that Cav-1 interacts with the Type I TGF-beta receptor. Additionally, Cav-1 is able to suppress TGF-beta-mediated phosphorylation of Smad-2 and subsequent downstream events. We localize the Type I TGF-beta receptor interaction to the scaffolding domain of Cav-1 and show that it occurs in a physiologically relevant time frame, acting to rapidly dampen signaling initiated by the TGF-beta receptor complex.  (+info)

Cytoplasmic-nuclear shuttling of FKBP12-rapamycin-associated protein is involved in rapamycin-sensitive signaling and translation initiation. (8/181)

Translation initiation is one of the key events regulated in response to mitogenic stimulation and nutrient availability, tightly coupled to mammalian cell cycle progression and growth. FKBP12-rapamycin-associated protein (FRAP; also named mTOR or RAFT1), a member of the ataxia telangiectasia mutated (ATM)-related kinase family, governs a rapamycin-sensitive membrane-to-cytoplasm signaling cascade that modulates translation initiation via p70 S6 kinase (p70(s6k)) and eIF-4E binding protein 1 (4E-BP1). Our studies reported here reveal a surprising regulatory mechanism of this signaling, which involves cytoplasmic-nuclear shuttling of FRAP. By using leptomycin B (LMB), a specific inhibitor of nuclear export receptor Crm1, we show that FRAP is a cytoplasmic-nuclear shuttling protein. Inhibition of FRAP nuclear export by LMB coincides with diminished p70(s6k) activation and 4E-BP1 phosphorylation. Further investigation by altering FRAP's nuclear shuttling activity with exogenous nuclear import and export signals has yielded results that are consistent with a direct link between nuclear shuttling of FRAP and mitogenic stimulation of p70(s6k) activation and 4E-BP1 phosphorylation. Furthermore, by using a reporter system, we provide evidence suggesting that nuclear shuttling of FRAP regulates mitogen-stimulated rapamycin-sensitive translation initiation. These findings uncover a function for the nucleus in the direct regulation of the protein synthesis machinery via extracellular signals.  (+info)

Tacrolimus Binding Protein 1A, also known as FKBP12 or FK506 binding protein 12, is a intracellular protein that binds to the immunosuppressive drug tacrolimus (FK506) and forms a complex. This complex inhibits the calcium-dependent serine/threonine phosphatase calcineurin, which plays a crucial role in T-cell activation. By inhibiting calcineurin, tacrolimus suppresses the immune response, particularly the activation of T-lymphocytes, and is used to prevent rejection in organ transplantation. FKBP12 is a member of the immunophilin family and has peptidyl-prolyl cis-trans isomerase activity.

Tacrolimus is an immunosuppressant drug that is primarily used to prevent the rejection of transplanted organs. It works by inhibiting the activity of T-cells, which are a type of white blood cell that plays a central role in the body's immune response. By suppressing the activity of these cells, tacrolimus helps to reduce the risk of an immune response being mounted against the transplanted organ.

Tacrolimus is often used in combination with other immunosuppressive drugs, such as corticosteroids and mycophenolate mofetil, to provide a comprehensive approach to preventing organ rejection. It is available in various forms, including capsules, oral solution, and intravenous injection.

The drug was first approved for use in the United States in 1994 and has since become a widely used immunosuppressant in transplant medicine. Tacrolimus is also being studied as a potential treatment for a variety of other conditions, including autoimmune diseases and cancer.

Tacrolimus binding proteins, also known as FK506 binding proteins (FKBPs), are a group of intracellular proteins that bind to the immunosuppressive drug tacrolimus (also known as FK506) and play a crucial role in its mechanism of action. Tacrolimus is primarily used in organ transplantation to prevent rejection of the transplanted organ.

FKBPs are a family of peptidyl-prolyl cis-trans isomerases (PPIases) that catalyze the conversion of proline residues from their cis to trans conformations in proteins, thereby regulating protein folding and function. FKBP12, a member of this family, has a high affinity for tacrolimus and forms a complex with it upon entry into the cell.

The formation of the tacrolimus-FKBP12 complex inhibits calcineurin, a serine/threonine phosphatase that plays a critical role in T-cell activation. Calcineurin inhibition prevents the dephosphorylation and nuclear translocation of the transcription factor NFAT (nuclear factor of activated T-cells), thereby blocking the expression of genes involved in T-cell activation, proliferation, and cytokine production.

In summary, tacrolimus binding proteins are intracellular proteins that bind to tacrolimus and inhibit calcineurin, leading to the suppression of T-cell activation and immune response, which is essential in organ transplantation and other immunological disorders.

Immunosuppressive agents are medications that decrease the activity of the immune system. They are often used to prevent the rejection of transplanted organs and to treat autoimmune diseases, where the immune system mistakenly attacks the body's own tissues. These drugs work by interfering with the immune system's normal responses, which helps to reduce inflammation and damage to tissues. However, because they suppress the immune system, people who take immunosuppressive agents are at increased risk for infections and other complications. Examples of immunosuppressive agents include corticosteroids, azathioprine, cyclophosphamide, mycophenolate mofetil, tacrolimus, and sirolimus.

Cyclosporine is a medication that belongs to a class of drugs called immunosuppressants. It is primarily used to prevent the rejection of transplanted organs, such as kidneys, livers, and hearts. Cyclosporine works by suppressing the activity of the immune system, which helps to reduce the risk of the body attacking the transplanted organ.

In addition to its use in organ transplantation, cyclosporine may also be used to treat certain autoimmune diseases, such as rheumatoid arthritis and psoriasis. It does this by suppressing the overactive immune response that contributes to these conditions.

Cyclosporine is available in capsule, oral solution, and injectable forms. Common side effects of the medication include kidney problems, high blood pressure, tremors, headache, and nausea. Long-term use of cyclosporine can also increase the risk of certain types of cancer and infections.

It is important to note that cyclosporine should only be used under the close supervision of a healthcare provider, as it requires regular monitoring of blood levels and kidney function.

Mycophenolic Acid (MPA) is an immunosuppressive drug that is primarily used to prevent rejection in organ transplantation. It works by inhibiting the enzyme inosine monophosphate dehydrogenase, which is a key enzyme for the de novo synthesis of guanosine nucleotides, an essential component for the proliferation of T and B lymphocytes. By doing this, MPA reduces the activity of the immune system, thereby preventing it from attacking the transplanted organ.

Mycophenolic Acid is available in two forms: as the sodium salt (Mycophenolate Sodium) and as the morpholinoethyl ester (Mycophenolate Mofetil), which is rapidly hydrolyzed to Mycophenolic Acid after oral administration. Common side effects of MPA include gastrointestinal symptoms such as diarrhea, nausea, and vomiting, as well as an increased risk of infections due to its immunosuppressive effects.

Kidney transplantation is a surgical procedure where a healthy kidney from a deceased or living donor is implanted into a patient with end-stage renal disease (ESRD) or permanent kidney failure. The new kidney takes over the functions of filtering waste and excess fluids from the blood, producing urine, and maintaining the body's electrolyte balance.

The transplanted kidney is typically placed in the lower abdomen, with its blood vessels connected to the recipient's iliac artery and vein. The ureter of the new kidney is then attached to the recipient's bladder to ensure proper urine flow. Following the surgery, the patient will require lifelong immunosuppressive therapy to prevent rejection of the transplanted organ by their immune system.

An ointment is a semi-solid preparation, typically composed of a mixture of medicinal substance with a base, which is usually greasy or oily. The purpose of the base is to act as a vehicle for the active ingredient and allow it to be applied smoothly and evenly to the skin or mucous membranes.

Ointments are commonly used in dermatology to treat various skin conditions such as eczema, psoriasis, rashes, burns, and wounds. They can also be used to deliver medication for localized pain relief, muscle relaxation, and anti-inflammatory or antibiotic effects.

The base of an ointment may consist of various ingredients, including petrolatum, lanolin, mineral oil, beeswax, or a combination of these. The choice of the base depends on the desired properties such as consistency, spreadability, and stability, as well as the intended route of administration and the specific therapeutic goals.

Graft rejection is an immune response that occurs when transplanted tissue or organ (the graft) is recognized as foreign by the recipient's immune system, leading to the activation of immune cells to attack and destroy the graft. This results in the failure of the transplant and the need for additional medical intervention or another transplant. There are three types of graft rejection: hyperacute, acute, and chronic. Hyperacute rejection occurs immediately or soon after transplantation due to pre-existing antibodies against the graft. Acute rejection typically occurs within weeks to months post-transplant and is characterized by the infiltration of T-cells into the graft. Chronic rejection, which can occur months to years after transplantation, is a slow and progressive process characterized by fibrosis and tissue damage due to ongoing immune responses against the graft.

Carrier proteins, also known as transport proteins, are a type of protein that facilitates the movement of molecules across cell membranes. They are responsible for the selective and active transport of ions, sugars, amino acids, and other molecules from one side of the membrane to the other, against their concentration gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate).

Carrier proteins have a specific binding site for the molecule they transport, and undergo conformational changes upon binding, which allows them to move the molecule across the membrane. Once the molecule has been transported, the carrier protein returns to its original conformation, ready to bind and transport another molecule.

Carrier proteins play a crucial role in maintaining the balance of ions and other molecules inside and outside of cells, and are essential for many physiological processes, including nerve impulse transmission, muscle contraction, and nutrient uptake.

Liver transplantation is a surgical procedure in which a diseased or failing liver is replaced with a healthy one from a deceased donor or, less commonly, a portion of a liver from a living donor. The goal of the procedure is to restore normal liver function and improve the patient's overall health and quality of life.

Liver transplantation may be recommended for individuals with end-stage liver disease, acute liver failure, certain genetic liver disorders, or liver cancers that cannot be treated effectively with other therapies. The procedure involves complex surgery to remove the diseased liver and implant the new one, followed by a period of recovery and close medical monitoring to ensure proper function and minimize the risk of complications.

The success of liver transplantation has improved significantly in recent years due to advances in surgical techniques, immunosuppressive medications, and post-transplant care. However, it remains a major operation with significant risks and challenges, including the need for lifelong immunosuppression to prevent rejection of the new liver, as well as potential complications such as infection, bleeding, and organ failure.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Calcineurin is a calcium-calmodulin-activated serine/threonine protein phosphatase that plays a crucial role in signal transduction pathways involved in immune response and neuronal development. It consists of two subunits: the catalytic A subunit (calcineurin A) and the regulatory B subunit (calcineurin B). Calcineurin is responsible for dephosphorylating various substrates, including transcription factors, which leads to changes in their activity and ultimately affects gene expression. In the immune system, calcineurin plays a critical role in T-cell activation by dephosphorylating the nuclear factor of activated T-cells (NFAT), allowing it to translocate into the nucleus and induce the expression of cytokines and other genes involved in the immune response. Inhibitors of calcineurin, such as cyclosporine A and tacrolimus, are commonly used as immunosuppressive drugs to prevent organ rejection after transplantation.

Graft survival, in medical terms, refers to the success of a transplanted tissue or organ in continuing to function and integrate with the recipient's body over time. It is the opposite of graft rejection, which occurs when the recipient's immune system recognizes the transplanted tissue as foreign and attacks it, leading to its failure.

Graft survival depends on various factors, including the compatibility between the donor and recipient, the type and location of the graft, the use of immunosuppressive drugs to prevent rejection, and the overall health of the recipient. A successful graft survival implies that the transplanted tissue or organ has been accepted by the recipient's body and is functioning properly, providing the necessary physiological support for the recipient's survival and improved quality of life.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

Sirolimus is a medication that belongs to a class of drugs called immunosuppressants. It is also known as rapamycin. Sirolimus works by inhibiting the mammalian target of rapamycin (mTOR), which is a protein that plays a key role in cell growth and division.

Sirolimus is primarily used to prevent rejection of transplanted organs, such as kidneys, livers, and hearts. It works by suppressing the activity of the immune system, which can help to reduce the risk of the body rejecting the transplanted organ. Sirolimus is often used in combination with other immunosuppressive drugs, such as corticosteroids and calcineurin inhibitors.

Sirolimus is also being studied for its potential therapeutic benefits in a variety of other conditions, including cancer, tuberous sclerosis complex, and lymphangioleiomyomatosis. However, more research is needed to fully understand the safety and efficacy of sirolimus in these contexts.

It's important to note that sirolimus can have significant side effects, including increased risk of infections, mouth sores, high blood pressure, and kidney damage. Therefore, it should only be used under the close supervision of a healthcare provider.

Insulin-like growth factor binding proteins (IGFBPs) are a family of proteins that bind to and regulate the biological activity of insulin-like growth factors (IGFs), specifically IGF-1 and IGF-2. There are six distinct IGFBPs (IGFBP-1 to IGFBP-6) in humans, each with unique structural features, expression patterns, and functions.

The primary function of IGFBPs is to modulate the interaction between IGFs and their cell surface receptors, thereby controlling IGF-mediated intracellular signaling pathways involved in cell growth, differentiation, and survival. IGFBPs can either enhance or inhibit IGF actions depending on the specific context, such as cell type, subcellular localization, and presence of other binding partners.

In addition to their role in IGF regulation, some IGFBPs have IGF-independent functions, including direct interaction with cell surface receptors, modulation of extracellular matrix composition, and participation in cell migration and apoptosis. Dysregulation of IGFBP expression and function has been implicated in various pathological conditions, such as cancer, diabetes, and cardiovascular diseases.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

RNA-binding proteins (RBPs) are a class of proteins that selectively interact with RNA molecules to form ribonucleoprotein complexes. These proteins play crucial roles in the post-transcriptional regulation of gene expression, including pre-mRNA processing, mRNA stability, transport, localization, and translation. RBPs recognize specific RNA sequences or structures through their modular RNA-binding domains, which can be highly degenerate and allow for the recognition of a wide range of RNA targets. The interaction between RBPs and RNA is often dynamic and can be regulated by various post-translational modifications of the proteins or by environmental stimuli, allowing for fine-tuning of gene expression in response to changing cellular needs. Dysregulation of RBP function has been implicated in various human diseases, including neurological disorders and cancer.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Fatty acid-binding proteins (FABPs) are a group of small intracellular proteins that play a crucial role in the transport and metabolism of fatty acids within cells. They are responsible for binding long-chain fatty acids, which are hydrophobic molecules, and facilitating their movement across the cell while protecting the cells from lipotoxicity.

FABPs are expressed in various tissues, including the heart, liver, muscle, and brain, with different isoforms found in specific organs. These proteins have a high affinity for long-chain fatty acids and can regulate their intracellular concentration by controlling the uptake, storage, and metabolism of these molecules.

FABPs also play a role in modulating cell signaling pathways that are involved in various physiological processes such as inflammation, differentiation, and apoptosis. Dysregulation of FABP expression and function has been implicated in several diseases, including diabetes, obesity, cancer, and neurodegenerative disorders.

In summary, fatty acid-binding proteins are essential intracellular proteins that facilitate the transport and metabolism of long-chain fatty acids while regulating cell signaling pathways.

Cytochrome P-450 CYP3A is a subfamily of the cytochrome P-450 enzyme superfamily, which are primarily involved in drug metabolism in the human body. These enzymes are found predominantly in the liver, but also in other tissues such as the small intestine, kidneys, and brain.

CYP3A enzymes are responsible for metabolizing a wide variety of drugs, including many statins, benzodiazepines, antidepressants, and opioids. They can also metabolize endogenous compounds such as steroids and bile acids. The activity of CYP3A enzymes can be influenced by various factors, including genetic polymorphisms, age, sex, pregnancy, and the presence of other drugs or diseases.

The name "cytochrome P-450" refers to the fact that these enzymes contain a heme group that absorbs light at a wavelength of 450 nanometers when it is complexed with carbon monoxide. The term "CYP3A" denotes the specific subfamily of cytochrome P-450 enzymes that share a high degree of sequence similarity and function.

Combination drug therapy is a treatment approach that involves the use of multiple medications with different mechanisms of action to achieve better therapeutic outcomes. This approach is often used in the management of complex medical conditions such as cancer, HIV/AIDS, and cardiovascular diseases. The goal of combination drug therapy is to improve efficacy, reduce the risk of drug resistance, decrease the likelihood of adverse effects, and enhance the overall quality of life for patients.

In combining drugs, healthcare providers aim to target various pathways involved in the disease process, which may help to:

1. Increase the effectiveness of treatment by attacking the disease from multiple angles.
2. Decrease the dosage of individual medications, reducing the risk and severity of side effects.
3. Slow down or prevent the development of drug resistance, a common problem in chronic diseases like HIV/AIDS and cancer.
4. Improve patient compliance by simplifying dosing schedules and reducing pill burden.

Examples of combination drug therapy include:

1. Antiretroviral therapy (ART) for HIV treatment, which typically involves three or more drugs from different classes to suppress viral replication and prevent the development of drug resistance.
2. Chemotherapy regimens for cancer treatment, where multiple cytotoxic agents are used to target various stages of the cell cycle and reduce the likelihood of tumor cells developing resistance.
3. Cardiovascular disease management, which may involve combining medications such as angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, diuretics, and statins to control blood pressure, heart rate, fluid balance, and cholesterol levels.
4. Treatment of tuberculosis, which often involves a combination of several antibiotics to target different aspects of the bacterial life cycle and prevent the development of drug-resistant strains.

When prescribing combination drug therapy, healthcare providers must carefully consider factors such as potential drug interactions, dosing schedules, adverse effects, and contraindications to ensure safe and effective treatment. Regular monitoring of patients is essential to assess treatment response, manage side effects, and adjust the treatment plan as needed.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

Drug monitoring, also known as therapeutic drug monitoring (TDM), is a medical practice that involves testing blood or other bodily fluids to determine the concentration of a particular medication. This information is used to ensure that the patient is receiving an appropriate dosage and to help guide adjustments in medication therapy. It can be especially important for medications with a narrow therapeutic index, meaning that there is a small range between the effective dose and a toxic dose.

The goal of drug monitoring is to optimize medication effectiveness while minimizing potential side effects. This may involve measuring the concentration of a drug at various times after dosing to determine how quickly it is being metabolized or eliminated from the body, as well as to assess compliance with the prescribed treatment regimen.

Drug monitoring can be performed using a variety of methods, including immunoassays, chromatography, and mass spectrometry. The specific method used will depend on the drug being monitored and the level of sensitivity required. Results from drug monitoring tests are typically interpreted in conjunction with other clinical information, such as the patient's age, weight, renal function, liver function, and overall health status.

Topical administration refers to a route of administering a medication or treatment directly to a specific area of the body, such as the skin, mucous membranes, or eyes. This method allows the drug to be applied directly to the site where it is needed, which can increase its effectiveness and reduce potential side effects compared to systemic administration (taking the medication by mouth or injecting it into a vein or muscle).

Topical medications come in various forms, including creams, ointments, gels, lotions, solutions, sprays, and patches. They may be used to treat localized conditions such as skin infections, rashes, inflammation, or pain, or to deliver medication to the eyes or mucous membranes for local or systemic effects.

When applying topical medications, it is important to follow the instructions carefully to ensure proper absorption and avoid irritation or other adverse reactions. This may include cleaning the area before application, covering the treated area with a dressing, or avoiding exposure to sunlight or water after application, depending on the specific medication and its intended use.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Treatment outcome is a term used to describe the result or effect of medical treatment on a patient's health status. It can be measured in various ways, such as through symptoms improvement, disease remission, reduced disability, improved quality of life, or survival rates. The treatment outcome helps healthcare providers evaluate the effectiveness of a particular treatment plan and make informed decisions about future care. It is also used in clinical research to compare the efficacy of different treatments and improve patient care.

Dermatologic agents are medications, chemicals, or other substances that are applied to the skin (dermis) for therapeutic or cosmetic purposes. They can be used to treat various skin conditions such as acne, eczema, psoriasis, fungal infections, and wounds. Dermatologic agents include topical corticosteroids, antibiotics, antifungals, retinoids, benzoyl peroxide, salicylic acid, and many others. They can come in various forms such as creams, ointments, gels, lotions, solutions, and patches. It is important to follow the instructions for use carefully to ensure safety and effectiveness.

Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) is a protein that binds to and regulates the bioavailability and activity of Insulin-like Growth Factors (IGFs), specifically IGF-1 and IGF-2. It plays a crucial role in the growth, development, and homeostasis of various tissues and organs by modulating IGF signaling. IGFBP-3 is the most abundant IGF binding protein in circulation and has a longer half-life than IGFs, allowing it to act as a reservoir and transport protein for IGFs. Additionally, IGFBP-3 has been found to have IGF-independent functions, including roles in cell growth, differentiation, apoptosis, and tumor suppression.

Periplasmic binding proteins (PBPs) are a type of water-soluble protein found in the periplasmic space of gram-negative bacteria. They play a crucial role in the bacterial uptake of specific nutrients, such as amino acids, sugars, and ions, through a process known as active transport.

PBPs function by specifically binding to their target substrates in the extracellular environment and then shuttling them across the inner membrane into the cytoplasm. This is achieved through a complex series of interactions with other proteins, including transmembrane permeases and ATP-binding cassette (ABC) transporters.

The binding of PBPs to their substrates typically results in a conformational change that allows for the transport of the substrate across the inner membrane. Once inside the cytoplasm, the substrate can be used for various metabolic processes, such as energy production or biosynthesis.

PBPs are often used as targets for the development of new antibiotics, as they play a critical role in bacterial survival and virulence. Inhibiting their function can disrupt essential physiological processes and lead to bacterial death.

Pancreas transplantation is a surgical procedure that involves implanting a healthy pancreas from a deceased donor into a recipient with diabetes. The primary goal of this procedure is to restore the recipient's insulin production and eliminate the need for insulin injections, thereby improving their quality of life and reducing the risk of long-term complications associated with diabetes.

There are three main types of pancreas transplantation:

1. Simultaneous pancreas-kidney (SPK) transplantation: This is the most common type of pancreas transplant, performed simultaneously with a kidney transplant in patients with diabetes and end-stage renal disease (ESRD). The new pancreas not only restores insulin production but also helps prevent further kidney damage.
2. Pancreas after kidney (PAK) transplantation: In this procedure, a patient receives a kidney transplant first, followed by a pancreas transplant at a later time. This is typically performed in patients who have already undergone a successful kidney transplant and wish to improve their diabetes management.
3. Pancreas transplantation alone (PTA): In rare cases, a pancreas transplant may be performed without a concurrent kidney transplant. This is usually considered for patients with brittle diabetes who experience severe hypoglycemic episodes despite optimal medical management and lifestyle modifications.

The success of pancreas transplantation has significantly improved over the years, thanks to advancements in surgical techniques, immunosuppressive medications, and post-transplant care. However, it is essential to weigh the benefits against the risks, such as potential complications related to surgery, infection, rejection, and long-term use of immunosuppressive drugs. Ultimately, the decision to undergo pancreas transplantation should be made in consultation with a multidisciplinary team of healthcare professionals, considering each patient's unique medical history and personal circumstances.

Calcium-binding proteins (CaBPs) are a diverse group of proteins that have the ability to bind calcium ions (Ca^2+^) with high affinity and specificity. They play crucial roles in various cellular processes, including signal transduction, muscle contraction, neurotransmitter release, and protection against oxidative stress.

The binding of calcium ions to these proteins induces conformational changes that can either activate or inhibit their functions. Some well-known CaBPs include calmodulin, troponin C, S100 proteins, and parvalbumins. These proteins are essential for maintaining calcium homeostasis within cells and for mediating the effects of calcium as a second messenger in various cellular signaling pathways.

The adrenal cortex hormones are a group of steroid hormones produced and released by the outer portion (cortex) of the adrenal glands, which are located on top of each kidney. These hormones play crucial roles in regulating various physiological processes, including:

1. Glucose metabolism: Cortisol helps control blood sugar levels by increasing glucose production in the liver and reducing its uptake in peripheral tissues.
2. Protein and fat metabolism: Cortisol promotes protein breakdown and fatty acid mobilization, providing essential building blocks for energy production during stressful situations.
3. Immune response regulation: Cortisol suppresses immune function to prevent overactivation and potential damage to the body during stress.
4. Cardiovascular function: Aldosterone regulates electrolyte balance and blood pressure by promoting sodium reabsorption and potassium excretion in the kidneys.
5. Sex hormone production: The adrenal cortex produces small amounts of sex hormones, such as androgens and estrogens, which contribute to sexual development and function.
6. Growth and development: Cortisol plays a role in normal growth and development by influencing the activity of growth-promoting hormones like insulin-like growth factor 1 (IGF-1).

The main adrenal cortex hormones include:

1. Glucocorticoids: Cortisol is the primary glucocorticoid, responsible for regulating metabolism and stress response.
2. Mineralocorticoids: Aldosterone is the primary mineralocorticoid, involved in electrolyte balance and blood pressure regulation.
3. Androgens: Dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEAS) are the most abundant adrenal androgens, contributing to sexual development and function.
4. Estrogens: Small amounts of estrogens are produced by the adrenal cortex, mainly in women.

Disorders related to impaired adrenal cortex hormone production or regulation can lead to various clinical manifestations, such as Addison's disease (adrenal insufficiency), Cushing's syndrome (hypercortisolism), and congenital adrenal hyperplasia (CAH).

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

No FAQ available that match "tacrolimus binding protein 1a"

No images available that match "tacrolimus binding protein 1a"