Recruitment of mononuclear leucocytes to osteoarthritic human synovial xenografts in the ears of SCID mice. (73/904)

A system has been established to assess the recruitment of 99mTc-hexamethylpropylene amine oxamine (99mTc-HMPAO)-labelled PBMC and [125I]iododeoxyuridine-labelled Con A stimulated lymphoblasts to allogeneic human synovial xenografts in the ears of SCID mice. Successful engraftment of osteoarthritic synovium was achieved in approximately 90% of cases and a connection between the human microvasculature of the xenograft and the circulation of the mouse was shown. Cells were delivered to the xenograft by a system of regional vascular perfusion, thus avoiding the major murine vascular beds. The accumulation of 99mTc-HMPAO-labelled PBMC in mouse ears was monitored in real time. Direct injection of xenograft-bearing ears with recombinant human TNF-alpha, 7 h prior to perfusion, increased the accumulation of both PBMC and lymphoblasts in cytokine-injected ears compared to contralateral control-injected ears. Autoradiography revealed the presence of [125I]iododeoxyuridine-labelled lymphoblasts associated with human microvasculature within the xenograft. However, the increased accumulation of lymphoblasts in cytokine-injected ears occurred in the tissues surrounding the xenograft, where lymphoblasts were associated more often with murine than human vessels. Although the system described offers advantages over similar models, the propensity for mouse endothelium to interact with human leucocytes is likely to be a generic disadvantage for models of human leucocyte recruitment to xenografts in immunodeficient mice.  (+info)

Effect of sympathetic denervation on smooth muscle cell proliferation in the growing rabbit ear artery. (74/904)

The effect of sympathetic denervation on the uptake of 3H-thymidine (3H-Tdr) into the ear artery of a growing rabbit was studied in vitro and in vivo. Uptake into the right artery was compared with that into the left 2 and 3 weeks after left superior cervical ganglionectomy in 4-week-old rabbits. Denervation was confirmed by the absence of catecholamine fluorescence. The total uptake of 3H--Tdr was determined by scintillation spectrometry, and its distribution in the artery wall was studied by light microscope autoradiography. The denervated ear artery took up significantly less DNA precursor and exhibited fewer labeled vascular smooth muscle cell nuclie in the tunica media than did the control artery. These findings suggest that sympathetic innervation influences the proliferation of vascular smooth muscle in growing rabbits.  (+info)

Civilian Health and Medical Program of the Uniformed Service (CHAMPUS); prosthetic devices. Office of the Secretary, DoD. Final rule. (75/904)

This final rule implements Section 702 of the National Defense Authorization Act for Fiscal Year 1998, which authorizes purchase of prosthetic devices, as determined by the Secretary of Defense, to be necessary because of significant conditions resulting from trauma, congenital anomalies, or disease. The Act changes the existing limited provisions for prosthetic devices, expanding coverage to include the cost sharing of other prostheses, e.g., noses, ears and fingers.  (+info)

Production and pharmacologic modulation of the granulocyte-associated allergic responses to ovalbumin in murine skin models induced by injecting ovalbumin-specific Th1 or Th2 cells. (76/904)

Because interferon-gamma, interleukin-4, and interleukin-5 have been identified at the mRNA and protein levels in the lesional skin of patients with atopic dermatitis, we investigated the roles played by granulocytes as effector cells in allergic inflammation by using two unique murine skin models. In vitro generated Th1 and Th2 cells from naive splenocytes of antiovalbumin T cell receptor transgenic BALB/C mice were adoptively transferred with ovalbumin into the ear pinnae or air-pouches produced in the back skin of naive, nontransgenic BALB/C mice. The injection of Th1 cells with ovalbumin induced delayed type ear swelling that peaked at 48 h, whereas that of Th2 resulted in ear swelling that peaked at a much earlier time, 24 h. Histologic study of the swollen ear skin and granulocytes recruited into the air-pouch demonstrated that, although the Th1-induced inflammation caused a neutrophil-predominant infiltrate with few eosinophils, larger numbers of eosinophils accumulated in the Th2-induced inflammation. Using these murine models, we further evaluated the effects of drugs used for the treatment of atopic diseases. The results showed that FK506 administration could effectively reduce skin inflammation induced by either Th cells. Interestingly, the neutrophil elastase inhibitor ONO-6818 efficiently inhibited Th1-induced inflammation. In contrast, a leukotriene receptor antagonist, ONO-1078, specifically suppressed Th2-induced inflammation. We also found that each ONO drug exerted direct influence on specified granulocytes, as neither affected in vitro production of relevant Th cytokines. Thus, we succeeded in developing animal skin inflammation models in which we can evaluate the contribution of protein antigen-specific Th1 or Th2 cells through the action of granulocytic effector cells.  (+info)

Vaccinia virus semaphorin A39R is a 50-55 kDa secreted glycoprotein that affects the outcome of infection in a murine intradermal model. (77/904)

Vaccinia virus (VV) protein A39R has amino acid similarity to the extracellular domain of a glycosylphosphatidylinositol-linked cell surface semaphorin (SEMA7A/CDw108) that has an immunological expression profile and binding properties, thereby implicating A39R as an immunomodulator. Previously, a closely related A39R protein expressed by ectromelia virus was shown to induce cytokine production and up-regulate ICAM-1 expression in mouse monocytes in vitro. In this study, we show that the A39R gene of VV strain Copenhagen (COP) encodes a 50-55 kDa secreted glycoprotein and is expressed late during infection. The A39R protein was secreted by eight of 15 strains of VV, but not by strain Western Reserve (WR). To analyse the VV A39R function, several recombinant viruses were made, including an A39R deletion mutant of VV COP and a WR mutant containing the A39R sequence from COP. Loss of the gene from COP did not affect virus growth in vitro, or VV virulence in a mouse intranasal model, and had only a slight effect on lesion size in an intradermal model. In contrast, expression of COP A39R by VV WR was associated with an increase in the severity and persistence of skin lesions after intradermal infection of mice. Finally, a histological examination of mouse skin infected with recombinant viruses suggested that A39R has direct or indirect pro-inflammatory properties.  (+info)

Muscle load and constriction of the rabbit ear artery. (78/904)

This isolated, perfused ear artery of the rabbit has been used to examine the effect of alterations in muscle load on the construction of arteries. The equilibrium muscle load, taken as the difference in wall stress between the relaxed and constricted artery at the same external radius, was varied by changing the transmural pressure and by constricting the artery. 2. The equilibrium muscle load increased initially and then declined with decreasing external radius when the transmural pressure was kept constant. The maximum muscle load was reached when the relaxed external radius had been reduced by 11% at 80 mmHg and by 4-5% (relative to the radius at 80 mmHg) at 160 mmHg. 3. Arteries from young rabbits (3-6 months in age) which were partially constricted by adrenaline or spontaneous activity responded better to 60 sec of 4 Hz field stimulation at transmural pressures above 100 mmHg than did relaxed arteries. Neither field stimulation nor high concentrations of noradrenaline ( is greater than 800 ng/ml.) were able to constrict most arteries effectively at pressures above 160-170 mmHg unless partial constriction was present. The partial constriction reduced the load placed on the muscle by the same transmural pressure. Constrictio n during field stimulation was due largely to the release of neurotransmitter. 4. Ear arteries from young and older rabbits differed little in their ability to constrict against different transmural pressures. The one major difference was a lesser maximum constriction of arteries from older rabbits (18-24 months in age). However, arteries from older rabbits constricted well at the higher transmural pressures only because wall thickening largely compensated for a decreased ability of the muscle to develop active tension. 5. It is concluded that a decrease in internal radius to wall thickness ratio by either sufficient partial vasoconstriction or by wall thickening favours constriction of arteries because the load placed on the muscle by the same transmural pressure is reduced. Wall thickening may be an important compensatory reaction for deteriorating muscle contraction.  (+info)

Neurogenin 1 null mutant ears develop fewer, morphologically normal hair cells in smaller sensory epithelia devoid of innervation. (79/904)

The proneuronal gene neurogenin 1 (ngn1) is essential for development of the inner-ear sensory neurons that are completely absent in ngn1 null mutants. Neither afferent, efferent, nor autonomic nerve fibers were detected in the ears of ngn1 null mutants. We suggest that efferent and autonomic fibers are lost secondarily to the absence of afferents. In this article we show that ngn1 null mutants develop smaller sensory epithelia with morphologically normal hair cells. In particular, the saccule is reduced dramatically and forms only a small recess with few hair cells along a duct connecting the utricle with the cochlea. Hair cells of newborn ngn1 null mutants show no structural abnormalities, suggesting that embryonic development of hair cells is independent of innervation. However, the less regular pattern of dispersal within sensory epithelia may be caused by some effects of afferents or to the stunted growth of the sensory epithelia. Tracing of facial and stato-acoustic nerves in control and ngn1 null mutants showed that only the distal, epibranchial, placode-derived sensory neurons of the geniculate ganglion exist in mutants. Tracing further showed that these geniculate ganglion neurons project exclusively to the solitary tract. In addition to the normal complement of facial branchial and visceral motoneurons, ngnl null mutants have some trigeminal motoneurons and contralateral inner-ear efferents projecting, at least temporarily, through the facial nerve. These data suggest that some neurons in the brainstem (e.g., inner-ear efferents, trigeminal motoneurons) require afferents to grow along and redirect to ectopic cranial nerve roots in the absence of their corresponding sensory roots.  (+info)

Rate representation of tones in noise in the inferior colliculus of decerebrate cats. (80/904)

Neurons in the central nucleus of the inferior colliculus (ICC) of decerebrate cats show three major response patterns when tones of different frequencies and sound-pressure levels (SPLs) are presented to the contralateral ear. The frequency response maps of type I units are uniquely defined by a narrow excitatory area at best frequency (BF: a unit's most sensitive frequency) and surrounding inhibition at higher and lower frequencies. As a result of this receptive field organization, type I units exhibit strong excitatory responses to BF tones but respond only weakly to broadband noise (BBN). These response characteristics predict that type I units are well suited to encode narrowband signals in the presence of background noise. To test this hypothesis, the dynamic range properties of ICC unit types were measured under quiet conditions and in multiple levels of continuous noise. As observed in previous studies of the auditory nerve and cochlear nucleus, type I units showed upward threshold shifts and discharge rate compression in background noise that partially degraded the dynamic range properties of neural representations at high noise levels. Although the other two unit types in the ICC showed similar trends in threshold shift and noise compression, their ability to encode auditory signals was compromised more severely in increasing noise levels. When binaural masking effects were simulated, only type I units showed an enhanced representation of spatially separated signals and maskers that was consistent with human perceptual performance in independent psychoacoustic observations. These results support the interpretation that type I units play an important role in the auditory processing of narrowband signals in background noise and suggest a physiological basis for spatial factors that govern signal detection under free-field listening conditions.  (+info)