Relation among portal segmentation, proper hepatic vein, and external notch of the caudate lobe in the human liver.
(65/2024)
OBJECTIVE: To identify portal segmentation and a portal fissure in the caudate lobe of the human liver in relation to the hepatic venous system and the external notch at the caudal edge of the caudate lobe. SUMMARY BACKGROUND DATA: Although the anatomy of the caudate lobe has been studied, the detailed anatomy has not yet been clarified; this is necessary to develop safe procedures for caudate lobe resection. METHODS: A total of 88 formalin-fixed human livers were dissected to visualize the portal vein and hepatic vein systems of the caudate lobe in relation to the external notch. RESULTS: The patterns of portal branching were classified into two types. In 58 livers (67.4%), the territories of the first-order portal branches were clearly divided into two areas (the Spiegel lobe and the paracaval portion). In the remaining 28 livers (32.6%), the territories of the second-order portal branches were clearly divided into two areas. These two areas were distinctly separated by an internal plane, which was coincident with the external notch. The caudate lobe had a systematized hepatic venous system that consisted of one (87.5%) or two (11.4%) proper hepatic veins and plural accessory hepatic veins. The proper hepatic veins laid along the internal plane between these two portal areas. CONCLUSION: The caudate lobe exhibited distinct portal segmentation with a portal fissure that was indicated internally by the proper hepatic vein and externally by the notch at the caudal edge of the caudate lobe. (+info)
Phenotypical and morphological alterations to rat sinusoidal endothelial cells in arterialized livers after portal branch ligation.
(66/2024)
The hepatic sinusoids are preferentially supplied with portal venous blood and equipped with fenestrated endothelial cells that are distinct from capillary endothelial cells. We previously observed in rats that sinusoidal capillarization proceeded concurrently with arterial blood supply during hepatocarcinogenesis. This study aimed to clarify the inducing role of arterialization in sinusoidal capillarization by investigating phenotypical, morphological and functional alterations to sinusoidal endothelial cells (SECs) in arterialized rat livers induced by portal branch ligation. At one week, after massive hepatic necrosis following ligation, the livers were restored to their normal architecture without causing post-necrotic fibrosis. At 12-21 weeks, they exhibited a normal histology except for mild pericellular fibrosis which developed along sinusoids or between adjacent hepatocytes. SECs expressed factor VIII-related antigen and showed a decrease in the number of fenestrae and porosity, still lacking any basement membrane but further retaining the functional capacity for carmine dye uptake. Stellate cells, while occasionally associated with large amounts of collagen bundles, contained many lipid droplets and expressed no alpha-smooth muscle actin, indicating a quiescent property. Kupffer cells were commonly found within the sinusoids. The present results indicate that arterialization of the liver induces a partial (but not complete) transition of SECs into capillary-type endothelial cells, suggesting that arterialization might be one of the factors which induce sinusoidal capillarization in the development of hepatocellular carcinoma. (+info)
Sustained expression of human factor VIII in mice using a parvovirus-based vector.
(67/2024)
Persistent therapeutic levels of human factor VIII (hFVIII) would signify a major advance in the treatment of hemophilia A. Here we report sustained expression of hFVIII in immunocompetent mice using recombinant adeno-associated virus (rAAV) vectors. AAV can stably transduce liver cells, the target tissue for efficient hFVIII production. Because of rAAV packaging constraints, we tested 2 constructs using small regulatory elements designed for liver-specific transgene expression linked to B-domain-deleted hFVIII (BDD-hFVIII) cDNA. More than 10(12)/mL rAAV/BDD-hFVIII virion particles were generated using a transfection scheme that eliminates adenovirus. Coatest and APTT assays confirmed the production of functional BDD-hFVIII protein after transduction of 293 and HepG2 cells. In vivo experiments were performed in C57BL/6 and NOD/scid mice receiving 10(10-11) rAAV/hFVIII particles via portal vein injection. All C57BL/6 mice tested developed anti-hFVIII antibody. In contrast, NOD/scid mice expressed hFVIII reaching 27% of normal human plasma levels. As expected, we could not detect hFVIII antigen from plasma samples isolated from control animals receiving equivalent doses of rAAV expressing enhanced green fluorescent protein (EGFP). Transgene mRNA expression was detected primarily in the liver and histologic analysis of the liver revealed no pathologic abnormalities. These results demonstrate a promising approach for treatment of hemophilia A. (Blood. 2000;95:1594-1599) (+info)
Treatment of intractable autoimmune diseases in MRL/lpr mice using a new strategy for allogeneic bone marrow transplantation.
(68/2024)
A new bone marrow transplantation (BMT) method for treating severe autoimmune diseases in chimeric resistant MRL/lpr mice is presented. The method consists of fractionated irradiation (5.5 Gy x 2), followed by portal venous (PV) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice and intravenous (IV) injection of whole B6 BMCs 5 days after the PV injection (abbreviated as 5.5 Gy x 2 + PV + IV). All recipients survived more than 1 year after this treatment (more than 64 weeks after birth). Abnormal T cells (Thy1.2(+)/B220(+)/CD3(+)/CD4(-)/CD8(-)) present in MRL/lpr mice before the treatment disappear, and hematolymphoid cells are reconstituted with donor-derived cells. The treated mice are free from autoimmune diseases. Levels of autoantibodies (IgG/IgM anti-ssDNA antibodies and IgG/IgM rheumatoid factors) decrease to normal levels. Successful cooperation is achieved among T cells, B cells, and antigen-presenting cells (APCs) of the treated MRL/lpr mice when evaluated by in vitro anti-SRBC responses. Newly developed T cells are tolerant to both donor (B6)-type and host (MRL/lpr)-type major histocompatibility complex (MHC) determinants. These findings clearly indicate that severe autoimmune diseases in MRL/lpr mice are completely ameliorated by the treatment without recourse to immunosuppressants, and that the treated MRL/lpr mice show normal immune functions, strongly suggesting that this strategy would be applicable to humans. (Blood. 2000;95:1862-1868) (+info)
Biphasic effects of NMDA on the motility of the rat portal vein.
(69/2024)
The effect of NMDA on the motility of the rat portal vein was studied in an isolated preparation. NMDA induced a concentration-dependent (10(-7) - 10(-4) M) increase of the contraction frequency (maximum increase, 148+/-6% of control at NMDA 10(-4) M). The NMDA-induced excitatory response was prevented by the competitive NMDA receptor antagonists (+/-)-2-Amino-5-phosphonopentanoic acid (AP-5, 5x10(-4) M) or (RS)-3-(2-carboxypiperazine-4-yl) propyl-1-phosphonic acid (CPP, 10(-4) M). Tetrodotoxin (TTX, 10(-6) M) or atropine (10(-4) M) abolished the NMDA-induced increase of the portal vein motility and reversed the excitatory effect to a concentration-dependent inhibition (maximum inhibition, 52+/-8 and 29+/-7% of controls, respectively, at NMDA 10(-3) M). Removal of the endothelium abolished the NMDA-induced inhibitory response. Sodium nitroprusside concentration-dependently (10(-7) - 10(-5) M) inhibited the portal vein motility, while L-N(G)-nitro-arginine methyl ester (L-NAME, 10(-4) M) reversed the inhibitory effect of NMDA (in the presence of TTX), restoring the portal vein spontaneous activity to control values. These results show that NMDA modulates the portal vein motility in a biphasic manner: via indirect activation, through prejunctional NMDA receptors presumably located on intrinsic excitatory neuronal afferences, or via direct inhibition, through endothelial NMDA receptors activating the nitric oxide pathway. Overall these findings support the hypothesis of the existence of a peripheral glutamatergic innervation modulating the contractile activity of the rat portal vein. British Journal of Pharmacology (2000) 129, 156 - 162 (+info)
Integrative physiology of splanchnic glutamine and ammonium metabolism.
(70/2024)
The substrates for hepatic ureagenesis are equimolar amounts of ammonium and aspartate. The study design mimics conditions in which the liver receives more NH(+)(4) than aspartate precursors (very low-protein diet). Fasted dogs, fitted acutely with transhepatic catheters, were infused with a tracer amount of (15)NH(4)Cl. From arteriovenous differences, the major NH(+)(4) precursor for hepatic ureagenesis was via deamidation of glutamine in the portal drainage system (rather than in the liver), because there was a 1:1 stoichiometry between glutamine disappearance and NH(+)(4) appearance, and the amide (but not the amine) nitrogen of glutamine supplied the (15)N added to the portal venous NH(+)(4) pool. The liver extracted all this NH(+)(4) from glutamine deamidation plus an additional amount in a single pass, suggesting that there was an activator of hepatic ureagenesis. The other major source of nitrogen extracted by the liver was [(14)N]alanine. Because alanine was not produced in the portal venous system, we speculate that it was derived ultimately from proteins in peripheral tissues. (+info)
Combined intraportal infusion of acetylcholine and adrenergic blockers augments net hepatic glucose uptake.
(71/2024)
Portal glucose delivery in the conscious dog augments net hepatic glucose uptake (NHGU). To investigate the possible role of altered autonomic nervous activity in the effect of portal glucose delivery, the effects of adrenergic blockade and acetylcholine (ACh) on hepatic glucose metabolism were examined in 42-h-fasted conscious dogs. Each study consisted of an equilibration (-120 to -20 min), a control (-20 to 0 min), and a hyperglycemic-hyperinsulinemic period (0 to 300 min). During the last period, somatostatin (0.8 microg. kg(-1). min(-1)) was infused along with intraportal insulin (1.2 mU. kg(-1). min(-1)) and glucagon (0.5 ng. kg(-1). min(-1)). Hepatic sinusoidal insulin was four times basal (73 +/- 7 microU/ml) and glucagon was basal (55 +/- 7 pg/ml). Glucose was infused peripherally (0-300 min) to create hyperglycemia (220 mg/dl). In test protocol, phentolamine and propranolol were infused intraportally at 0.2 microg and 0.1 microg. kg(-1). min(-1) from 120 min on. ACh was infused intraportally at 3 microg. kg(-1). min(-1) from 210 min on. In control protocol, saline was given in place of the blockers and ACh. Hyperglycemia-hyperinsulinemia switched the net hepatic glucose balance (mg. kg(-1). min(-1)) from output (2.1 +/- 0.3 and 1.1 +/- 0.2) to uptake (2.8 +/- 0.9 and 2.6 +/- 0.6) and lactate balance (micromol. kg(-1). min(-1)) from uptake (7.5 +/- 2.2 and 6.7 +/- 1.6) to output (3.7 +/- 2.6 and 3.9 +/- 1.6) by 120 min in the control and test protocols, respectively. Thereafter, in the control protocol, NHGU tended to increase slightly (3.0 +/- 0.6 mg. kg(-1). min(-1) by 300 min). In the test protocol, adrenergic blockade did not alter NHGU, but ACh infusion increased it to 4.4 +/- 0.6 and 4.6 +/- 0.6 mg. kg(-1). min(-1) by 220 and 300 min, respectively. These data are consistent with the hypothesis that alterations in nerve activity contribute to the increase in NHGU seen after portal glucose delivery. (+info)
Response to percutaneous transhepatic portal embolization: new proposed parameters by 99mTc-GSA SPECT and their usefulness in prognostic estimation after hepatectomy.
(72/2024)
Accumulation of 99mTc-galactosyl human serum albumin (GSA) in the liver correlates well with the parameters of hepatic function tests. We performed 99mTC-GSA SPECT before and after percutaneous transhepatic portal embolization (PTPE) to induce compensatory hypertrophy of the remnant lobe before extensive hepatic resection and analyzed the responses of new proposed parameters in the future remnant lobe that showed hypertrophy. The aim of this study was to evaluate the usefulness of these parameters in prognostic estimation after hepatectomy. METHODS: We studied 10 patients with cholangiocarcinoma and 1 patient with metastatic liver tumor from sigmoid colon cancer. 99mTc-GSA SPECT was performed immediately before and 2 wk after PTPE. We analyzed the responses of the liver uptake ratio (LUR), functional volume (FV), and liver uptake density (LUD) in the future remnant lobe and evaluated their relationship with the prognosis after subsequent hepatic resection. RESULTS: LUR and FV increased slightly but were not associated with the prognosis after hepatic resection. LUD increased significantly after PTPE in the group showing a good outcome after hepatic resection but decreased after PTPE in the group showing a poor outcome (post-PTPE LUD, 0.064+/-0.017%/cm3 versus 0.035+/-0.006%/ cm3, P<0.05; response rate, 22.2%+/-11.9% versus -8.9%+/-17.6%, P<0.01). CONCLUSION: Responses of LUD to PTPE before hepatic resection in the future remnant lobe represent changes in asialoglycoprotein receptor activity per hepatocyte and predict responses to subsequent hepatic resection. LUD may be an important parameter for determining the outcome after hepatic resection. (+info)