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K Wake

Publications and source records attributed to K Wake.

At least 37 records · Page 2Linked to original sources

Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride.

In acute liver injury induced by the injection of CCl4, cell death has been attributed to the necrosis of hepatocytes in the centrilobular area. In the present study, we re-examined the hepatic injury evoked by CCl4 in rats and explored the possibility that apoptosis may also contribute to its pathogenesis. Apoptotic hepatocytes were identified and quantified by light and electron microscopy, the in situ immunohistochemical labeling of nuclear DNA fragmentation, flow cytometry, and DNA gel electrophoresis. We found that a substantial number of hepatocytes underwent apoptosis. Apoptotic changes were also observed in ballooned hepatocytes. Apoptotic hepatocytes increased in number at 3 hours and peaked at 6 hours after the CCl4 injection. Apoptotic bodies were sequestrated in the adjacent hepatocytes and sinusoidal cells. Double staining of the cells with immunostaining for phagocytes and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining for labeling of DNA fragmentation showed that the majority of apoptotic hepatocytes were phagocytosed by Kupffer cells and macrophages. The results indicated that apoptosis occurs in the ballooned and injured hepatocytes of the centrilobular area. What occurs after CCl4 administration may be important in reducing inflammation, shortening the course of acute hepatic injury, and preventing the development of fibrosis.

Animals↗

Lack of promoting effects of the electromagnetic near-field used for cellular phones (929.2 MHz) on rat liver carcinogenesis in a medium-term liver bioassay.

The possible cancer promotion potential of local exposure to a pulse modulated 929.2 MHz electromagnetic near-field on chemically-initiated rat liver carcinogenesis was investigated employing a medium-term bioassay. A 929.2-MHz electromagnetic near-field of time division multiple access (TDMA) signal for PDC (Personal Digital Cellular, Japanese cellular telephone standard) system was directed to rats through a quarter-wavelength monopole antenna. Maximum local specific absorption rates (SARs) on temporal average were 7.2-6.6 W/kg within the whole body and 2.0-1.7 W/kg within the liver, which was the target organ. The whole-body average SARs on temporal average were 0.80-0.58 W/kg. Temporal peak SARs had three times these values due to the duty ratio of the PDC signal. Exposure was for 90 min a day, 5 days a week, over 6 weeks. The exposure apparatus was specially designed for this experiment, to allow exposure of the lateral mid-section of the rat body to the electromagnetic near-field. Male F344 rats, 6 week-old, were initially (at week 0) given a single dose of diethylnitrosamine (DEN, 200 mg/kg body wt, i.p.). At 2 weeks later, exposure (48 rats) or sham-exposure (48 rats) was started. The exposure of electromagnetic near-fields was performed using the exposure apparatus mentioned above. At week 3, all rats were subjected to a 2/3 partial hepatectomy. At week 8 (i.e. after 6 weeks exposure or sham-exposure), the experiment was terminated and all rats were killed. Carcinogenic potential was scored by comparing the numbers and areas of the induced glutathione S-transferase placental form (GST-P) positive foci in the livers of the exposed and sham-exposed rats. A further group of 24 animals, given only DEN and partial hepatectomy, served as the controls. The numbers (no./cm2) of GST-P positive foci were 4.61 +/- 1.77, 5.21 +/- 1.92 (P < 0.05, versus control) and 4.09 +/- 1.47 and the areas (mm2/cm2) were 0.30 +/- 0.16, 0.36 +/- 0.21 and 0.28 +/- 0.15, for the exposed, sham-exposed and control groups, respectively. There were no significant differences between the exposed and sham-exposed groups. These findings clearly indicated that local body exposure to a 929.2-MHz field, modulated in a PDC waveform, has no significant effect on rat liver carcinogenesis under the experimental conditions employed.

Adrenocorticotropic Hormone↗

[Anesthetic management of a patient with hypertrophic cardiomyopathy using propofol, fentanyl and ketamine].

A 59-year-old male with hypertrophic cardiomyopathy was scheduled for resection of a maxillary cyst. Metoprolol was discontinued the day before surgery. Thirty min before anesthesia, meperidine 35 mg was administered intramuscularly. After intravenous administration of midazolam 3 mg, a pulmonary catheter was inserted for monitoring hemodynamic parameters. Anesthesia was induced with propofol 75 mg, fentanyl 0.15 mg and ketamine 75 mg. Anesthesia was maintained with continuous infusion of propofol 5 mg.kg-1.h-1 and ketamine 1 mg.kg-1.h-1. Moreover, fentanyl was added as necessary during surgery. Blood pressure (BP), pulmonary arterial pressure (PA), systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI) were measured using a pulmonary catheter during anesthesia. Since BP decreased after intubation, dopamine 3 micrograms.kg-1.min-1 was administered for 20 min. The hemodynamic state was stable during surgery. However, BP, PA, SVRI and PVRI increased temporally at extubation. His postoperative course was uneventful. In conclusion, total intravenous anesthesia with propofol, fentanyl and ketamine may be useful for anesthetic management of a patient with hypertrophic cardiomyopathy.

Anesthesia, Intravenous↗

Remodeling of pineal epithelium in the fetal rat as delineated by immunohistochemistry of laminin and cadherin.

Epithelial remodeling in the rat pineal during fetal development was immunohistochemically analyzed by using antibodies for laminin and cadherin as molecular markers of basal lamina and intercellular junctions, respectively. The proliferation and differentiation of pinealocytes were also investigated in relation to the advance of epithelial remodeling. The pineal anlage of embryonic day 16 is completely covered by basal lamina immunolabeled for laminin. After embryonic day 17, local dissolution of the basal lamina occurs on the epithelial folds, which develop predominantly in the rostral pineal wall. Some pineal cells migrate through these interruptions and form cellular aggregations outside the basal lamina. Cadherin immunostaining reveals focal dissolution of intercellular junctions in epithelial regions protruding into the pineal lumen. Dissolution of the basal lamina and intercellular junctions accompanied by cellular migration into the stromal tissue or into the pineal lumen continues until birth. The distribution of mitotic cells immunolabeled for BrdU is homogeneous throughout the organ during the fetal period, whereas that of differentiating pinealocytes immunoreactive for synaptophysin shows striking regional heterogeneity in close correlation with the remodeling of the pineal epithelium. The migrating cell populations located either outside the basal lamina or inside the pineal lumen are more liable to become synaptophysin-positive than the rest of the epithelium. These results suggest that epithelial remodeling in the fetal pineal is induced, at least in part, by epithelial infolding and that this remodeling promotes the differentiation of pinealocytes.

Animals↗

[One hundred years of sinusoidal cells in the liver].

Kupffer (1898) reported that the stellate cells were phagocytic endothelial cells, retracting his earlier view that these cells were perivascular cells. His new concept stimulated studies on the vital staining and the RES theory, while it ensued several controversies in liver histology. The original stellate cells were rediscovered in 1971, and were proved to be identical with several perisinusoidal cells reported previously. For this cell the term hepatic stellate cell has recently been adopted as the standardized name. The space of Disse is newly defined as the space between the endothelial cell-stellate cell complex and the parenchymal cells. The stellate cells display vitamin A-storage, collagen synthesis and may contract to regulate the sinusoidal blood flow and the fluid-exchange between the sinusoidal lumen and the space of Disse. The sinusoidal endothelial cells uptake injected lithium carmine and macromolecules by coated vesicles. Kupffer cells clear endotoxin, bacteria and apoptotic neutrophils and release various cytokines. The pit cells are the liver-associated NK cells and are activated by the administration of biological response modifiers, preventing tumor metastasis. Extrathymic pathways of T cell differentiation exist in the hepatic sinusoid. The dendritic cells differentiate in the sinusoid and translocate to the Glisson's sheath. Intralobular heterogeneity of sinusoidal cells have been observed. The sinusoidal cells communicate each other with autocrine and paracrine mechanisms to regulate various functions of the liver.

Anatomy↗

Contribution of immune response to the hepatic fibrosis induced by porcine serum.

To investigate whether hepatic fibrosis induced by porcine serum in rats is caused by an immune reaction to porcine serum, rats that were immunologically tolerant exclusively to porcine serum were subjected to the repeated injection of porcine serum over a long period. This porcine serum-tolerant group consisted of 15 Wistar rats that had been injected intraperitoneally with porcine serum twice a week from the first postnatal day for 18 weeks. The control group consisted of 16 Wistar rats, aged 8 weeks, that were injected intraperitoneally with porcine serum twice a week for 10 weeks. Livers were fixed and examined by light microscopy. The serum of each rat was subjected to indirect enzyme-linked immunosorbent assay (ELISA) to measure the level of antibody to porcine albumin. In addition, immunohistochemical staining for ED1 was performed on untreated normal and porcine serum-induced fibrotic rat livers to examine the distribution of macrophages and their precursors, the monocytes. All rats in the tolerant group showed an extremely low antibody level (x = 68.27 +/- 4.53), and none (0/15) developed hepatic fibrosis. The majority of rats in the control group showed a very high antibody level (x = 1242.19 +/- 201.15); 75 percent (12/16) developed hepatic fibrosis. Data indicate that, despite the prolonged, repeated injections of porcine serum, if an immune response to porcine serum does not occur, the rats do not develop hepatic fibrosis. The porcine serum-tolerant rats developed hepatic fibrosis after 4 weeks of CCl4 treatment, indicating that injection of porcine serum into neonatal rats did not cause anergy of fibrogenesis, thereby preventing the animal from developing hepatic fibrosis. In normal rat liver, ED1-positive cells, which include nearly all Kupffer cells, were located pre-dominantly in the periportal area. In fibrotic rat liver, ED1-positive cells aggregated prominently in the newly formed and advanced connective tissue septa developed mainly between the neighboring central veins, and in fibrotic parts of the liver capsule. Aggregation of ED1-positive cells was rarely observed in nonfibrotic parts of the liver capsule. The difference between normal and fibrotic rat liver in distribution of EDl-positive cells suggests an involvement of macrophages in fibrogenesis and septum formation. In conclusion, our study showed a significant contribution by the immune response to porcine serum antigens leading to porcine serum-induced rat hepatic fibrosis--processes in which macrophages may be important. This study may lead to an understanding of the mechanism responsible for this form of experimental hepatic fibrosis.

Animals↗

Apoptosis of neutrophils and their elimination by Kupffer cells in rat liver.

The fate of neutrophils in the peripheral circulation is poorly understood. In this study, the role of Kupffer cells in eliminating aged and apoptotic neutrophils was investigated. Liver, spleen, lung, and blood samples from Wistar rats were examined by light and electron microscopy, the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method, and immunohistochemistry after the intravenous injection of OK-432, a streptococcal preparation. Neutrophils were trapped predominantly in the periportal and midzonal regions of hepatic lobules and were in contact with endothelial cells and Kupffer cells, or were surrounded by Kupffer cells. The trapping of neutrophils peaked after 6 hours. Apoptotic neutrophils, with or without buds, were found in the lumen of hepatic sinusoids as early as 6 hours, reached maximal levels after 12 hours, and represented greater than 60% of the total number of neutrophils in the liver. The presence of apoptotic neutrophils was correlated with the degree of neutrophil phagocytosis. Double-staining showed that TUNEL-positive neutrophils were phagocytosed or encircled by ED1- or ED2-positive Kupffer cells. In contrast, apoptosis and phagocytosis of neutrophils were rare in the spleen, lung, and peripheral blood. These results suggested that the appearance of apoptotic neutrophils in the hepatic sinusoids and their rapid clearance by Kupffer cells occurs after the invasion of bacteria (i.e., bacteremia or bacteriotoxemia) or the release of inflammatory mediators into the blood stream. These findings have important implications for the regulation of neutrophil homeostasis, the limitation of inflammation and tissue injury, and provide insight into the physiological removal of circulating, senescent neutrophils.

Animals↗

Mesangial cells of the lamprey, Lampetra japonica, store vitamin A.

Structure and vitamin A-storage of the mesangial cells in the lamprey kidney are documented using the gold chloride method, fluorescence histochemistry and electron microscopy. Abundant lipid droplets in the cytoplasm of the mesangial cells release intense, but quickly fading vitamin A-fluorescence under a fluorescence microscope and react with gold chloride. Characteristic tubular invaginations of the plasma membrane which usually occur in the lamprey smooth muscle cells are observed in these cells. We discuss similarities of the lamprey mesangial cells with hepatic stellate cells in the lamprey and mammals, such as vitamin A-storage, blood flow-regulation and proliferative potential. To the best of our knowledge, this is the first report on and proof of vitamin A-storage in mesangial cells, providing evidence for a vitamin A-storing cell lineage in vertebrates.

Animals↗

Expression of neuron-specific enolase in the pineal organ of the domestic fowl during post-hatching development.

Immunohistochemistry for neuron-specific enolase (NSE) revealed that NSE is localized in both a limited number of pinealocytes and intrinsic afferent neurons in the pineal organ of the domestic fowl. Furthermore, a computer-assisted three-dimensional imaging technique allowed to clarify the reverse distributional pattern of both elements: NSE-positive pinealocytes displayed a dense distribution especially in the vesicular portion of the gland, whereas NSE-immunoreactive nerve cells were mainly found in the pineal stalk. The number of NSE-positive intrinsic neurons in the pineal organ of chickens decreased rapidly after hatching, with a concentration of these elements in the basal portion (stalk) of the pineal organ. On the other hand, immunoreactive pinealocytes increased remarkably in the end-vesicle of the organ with age, followed by a gradual expansion toward the proximal portion. Thus, the spectacular increase in NSE-positive pinealocytes and the progressive reduction of reactive neurons occurred in parallel during the course of post-hatching development. NSE-immunoreactive pinealocytes displayed morphological characteristics of bipolar elements, endowed with an apical protrusion into the pineal lumen and a short basal process at younger stages, whereas multipolar types of NSE-positive pinealocytes were predominantly found in the adult domestic fowl. These results indicate that in the pineal organ of the domestic fowl (1) the ontogenetic expansion of NSE-immunoreactive pinealocytes is paralleled by a regressive afferent innervation, (2) the NSE-positive pinealocytes transform from a bipolar (columnar) type to a multipolar type during post-hatching development, and (3) these ontogenetic changes in the NSE-immunoreactivity and morphology of pinealocytes may reflect the development of a neurosecretory-like capacity of the organ.

Animals↗

Expression of neuron-specific enolase in the developing rat retina as revealed by immunocytochemistry.

Expression of neuron-specific enolase (NSE) in retinal neurons was immunocytochemically investigated during the development of the rat retina. At embryonic day 14 (E14), the first immunoreaction of NSE was identified in the pigment epithelium. NSE-positive ganglion cells occurred at the inner surface of the retina by E15. Horizontal cells and photoreceptor cells became stainable for NSE in the outer portion of the neuroblastic layer as early as E17. At E20, when the majority of ganglion cells were intensely positive for NSE, immunoreactive amacrine cells first appeared at the outer surface of the developing inner plexiform layer. It was not until postnatal day 7 (P7) that NSE-positive bipolar cells occurred in the middle of the inner nuclear layer. At this stage, most of the photoreceptor cells located in the outer nuclear layer were immunolabeled, whereas the ectopic photoreceptor cells in the inner nuclear layer were devoid of immunoreaction. Most identifiable retinal neurons became strongly immunostained for NSE by P14. Our results indicate that the NSE expression of retinal neurons occurs just after their migration to the final location and prior to establishing the synaptic structures. In this paper, the characteristic sequence in which different types of retinal neurons exhibit NSE immunoreaction is discussed in the light of certain autoradiographic data on the sequence of retinal cell genesis.

Aging↗

Morphometric analysis of infiltrating cells that adhere to the sinusoidal wall and migrate into the space of disse in the orthotopically transplanted rat liver.

To reveal the kinetics of infiltrating cells in the hepatic parenchyma after the liver transplantation, we identified the cell type (macrophages, monocytes, agranular lymphocytes, large granular lymphocytes, and neutrophils) and localization on toluidine blue-stained sections of perfusion-fixed liver grafts in rejecting and tolerant combinations and performed quantitative analysis of the density of each cell species infiltrating inside and outside the sinusoid at days 4 and 7. The number of total infiltrating cells per unit square became 9 times as high as that of an untreated liver at day 4 and 30 times as high at day 7. Macrophages accounted for a large part of the infiltrating cells both in and around the sinusoid: 72% of intrasinusoidal infiltrating cells and 88% of extrasinusoidal ones at day 4; 73% of intrasinusoidal ones and 93% of extrasinusoidal ones at day 7. The ratio of extrasinusoidal cell to intrasinusoidal cell of macrophages was 9:91 at day 4 and 34:66 at day 7, much higher than ratios of other infiltrating cells. This fact means that macrophages show a marked tendency to migrate out of the sinusoid in the liver graft. The proportion of macrophages to total infiltrating cells dropped at day 4 and went up again at day 7, while that of monocytes showed a reverse pattern. Histologically, immature macrophages, possibly derived from recipient monocytes, coexisted with vacuolated donor macrophages in the sinusoid at day 4, but the latter cells were diminished at day 7. These data indicate that transformation of recipient monocytes into macrophages in the sinusoid and subsequent extrasinusoidal migration of newly formed macrophages occur soon after the cell influx into the liver graft begins at day 4. The present study has revealed that macrophages, especially those migrating into the space of Disse, will be closely related to the pathogenesis of the liver transplantation.

Animals↗

Analysis of the heterogeneity within bovine pineal gland by immunohistochemistry and in situ hybridization.

In the present study, we demonstrate a cortical and medullary arrangement of parenchymal cells in the bovine pineal gland by using antibodies for neuron-specific enolase, synaptophysin, and hydroxyindole O-methyltransferase (HIOMT) as markers of pinealocytes, and glial fibrillary acidic protein (GFAP) as a marker of interstitial (glial) cells. Furthermore, by means of probes specific for HIOMT mRNA, we have examined possible differences in melatonin synthesis between the cortex and the medulla. Immunoreactive pinealocytes for each antigen investigated are more densely distributed in the cortex than in the medulla. In the cortex, GFAP-positive interstitial cells have large intenselystained somata endowed with several long, thin cytoplasmic processes, whereas in the medulla, they display smaller, less intensely labeled perikarya from which numerous fine short processes emerge. Golgi staining has confirmed these morphological differences between the interstitial cells in the cortex and those in the medulla. An analysis using confocal laser microscopy together with in situ hybridization for HIOMT mRNA has shown that the expression of mRNA transcripts in the cortex is more intense than that in the medulla. The expression of the HIOMT gene in a cluster of cells in the medial habenular nucleus is lower than that in pinealocytes of the pineal organ proper.

Acetylserotonin O-Methyltransferase↗

Light and electron microscopic analysis of liver sinusoids during hepatocarcinogenesis with 2-acetylaminofluorene in rats.

To clarify the sequential changes and morphological differences of the sinusoidal structures between hepatocellular carcinoma (HCC) and hepatocellular adenoma (HA), we examined morphological changes of sinusoidal cells and related structures such as basement membrane during hepatocarcinogenesis in the rat. During continuous feeding of carcinogenic diets containing 2-acetylaminofluorene to rats, HA appeared at the 8th week in the peripheral area and then extended toward the centrolobular area. The appearance of HCC was recognized at the 27th week. In the HA lesion, the morphology of sinusoidal cells and related structures was basically the same as that of normal liver except for a slight thickening of the basement membrane and a decreased amount of vitamin A-lipid droplets of stellate cells. In HCC, the fenestrations of endothelial cells disappeared and the basement membrane became continuous, thick and often multilayered. Stellate cells contained almost no vitamin A-lipid droplets and were associated with abundant collagen fibers. Kupffer cells and pit cells were not seen inside the sinusoid. All these features of the sinusoids in HCC resembled the morphological characteristics of the capillary. The present study has revealed that HCC possesses sinusoid structures distinct from those of HA. This suggests that HCC may not derive directly from HA but may develop newly within the HA.

2-Acetylaminofluorene↗

Intralobular heterogeneity of perisinusoidal stellate cells in porcine liver.

The aim of the present investigation was to elucidate the intralobular heterogeneity of the perisinusoidal stellate cells (fat-storing cells, lipocytes) in the porcine liver. Their three-dimensional structure, desmin immunoreactivity and vitamin-A storage were studied by use of the Golgi silver, immunocytochemical and gold chloride methods. In order to locate the stellate cells, the hepatic lobules were divided into 10 zones. The stellate cells were readily identified in Golgi preparations by their striking dendritic appearance with branching processes encompassing the sinusoids. The stellate cells in the centrolobular zones were conspicuously dendritic with longer processes in comparison to those emitted by periportal elements. Such arborizations were studded with numerous thorn-like microprojections. Desmin immunoreaction in the periportal zones was stronger than that in the centrolobular zones. Vitamin-A storage in the stellate cells was well developed in zones 2-4, but reduced gradually toward the central region. The perisinusoidal stellate cells display marked heterogeneity in morphology and function based on their zonal location in the hepatic lobule.

Animals↗

Granuloma formation in the liver of Balb/c mice intoxicated with carbon tetrachloride.

Hepatic granulomas induced by a single or several subcutaneous injections of carbon tetrachloride (CCl4) in Balb/c mice were examined electronmicroscopically and immunocytochemically. Stellate cells (fat-storing cells; lipocytes; Ito cells) were identified by the detection of cytoplasmic desmin, while T-lymphocytes and monocytes/macrophages were identified with monoclonal antibodies Thy 1.2 and MOMA-2, respectively. Following pericentral necrosis induced with CCl4, clear foci containing lymphocytes, monocytes, macrophages and perisinusoidal stellate cells occurred in the surrounding hepatic parenchyma on day 5. These clear foci developed to granulomas with increasing numbers of macrophages and stellate cells. Mitotic and apoptotic figures in randomly distributed macrophages, and direct contacts between macrophages and stellate cells were frequently seen within the granulomas. The stellate cells were characterized by a well-developed granular endoplasmic reticulum and Golgi complex. Collagen fibrils were closely applied to the stellate cells and connective tissue septa extended between neighboring granulomas and/or the pericentral necrotic areas after several injections of CCl4. CCl4-induced hepatic granulomas provide a model for investigating paracrine and/or autocrine modulation within a well-organized microenvironment during progressive hepatic inflammation and fibrosis.

Animals↗

Tissue kallikrein in the rat pineal gland: an immunocytochemical study.

Tissue kallikrein in the rat pineal gland was immunocytochemically investigated with the aid of specific antiserum against rat urinary kallikrein. We also compared the tissue kallikrein immunoreactivity of the pineal gland with that of the submandibular gland and kidney, which have been well established as tissue kallikrein-synthesizing organs. The cytoplasm of pinealocytes from both the superficial and the deep portion of the gland exhibited specific immunolabeling for tissue kallikrein, but the immunoreaction was weaker than that observed in exocrine organs. Two types of tissue kallikrein-immunoreactive pinealocytes were distinguished; the first predominant type displayed moderate immunostaining, whereas a small number of cells, the second type, were so intensely labeled that their cytoplasmic processes were clearly outlined. The results of the present study suggest the existence of different types of pinealocytes and a potential physiological role of tissue kallikrein in the rat pineal gland.

Animals↗

Role of mesenchymal cell populations in porcine serum-induced rat liver fibrosis.

The role of liver mesenchymal cell populations in porcine serum-induced rat liver fibrosis were studied morphologically and immunohistochemically. Five-week-old rats were intraperitoneally injected with porcine serum twice a week and examined at various intervals between 3 and 24 wk after the initial injection. At an early phase, numbers of fibroblasts and extracellular matrix increased in the walls of central veins and in portal and capsular connective tissues. In the walls of central veins, the number of "second-layer cells" (i.e., the fibroblasts located at the second layer of the wall) increased. Connective tissue septa, accompanying some fibroblasts, extended from these interstitial tissues into the hepatic parenchyma, and their foremost edges came into direct contact with the perisinusoidal stellate cells. The sinusoids adjacent to the newly formed septa collapsed and later disappeared; this process resulted in the formation of hepatic limiting plates along the septa. At a more advanced stage, the interstitial fibroblasts and septal cells-which were derived from interstitial fibroblasts and the stellate cells-increased and became multilayered, constructing three-dimensional cell networks. These networks, together with increased collagen fibrils and elastic fibers, constitute the fibrotic dense connective tissue. In the control rat, smooth muscle cells were positive on vimentin, desmin and smooth muscle-alpha-actin staining. The stellate cells, second-layer cells, capsular and portal fibroblasts were shown to be vimentin and desmin positive and smooth muscle-alpha-actin negative. In the fibrotic liver, septal(fibroblastic) cells were vimentin and desmin positive and smooth muscle-alpha-actin negative. We conclude that not only the perisinusoidal stellate cells but also the interstitial fibroblasts, including the second-layer cells, play substantial role in the development of porcine serum-induced septal fibrosis in rat liver.

Actin Cytoskeleton↗