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A 2-year-old, male Japanese native fowl (Gallus gallus domesticus) was presented with an inability to feed and torticollis. At a necropsy, there were cylindrical enlargements and yellow discoloration of multiple peripheral nerves, including nerves of the lumbosacral plexus, brachial plexus, and spinal ganglia. On histologic examination, these lesions consisted of diffuse proliferations of spindle cells with characteristic onion bulb-like structures around residual axons. The spindle cells were immunohistochemically positive for glucose transporter 1 (GLUT1) and negative for S-100 α/β proteins. On the basis of microscopic, histologic, and immunohistochemical findings, the tumors were diagnosed as multiple perineuriomas.

The effects of PC-oligomer addition on the internal morphology and mechanical properties of injection mouldings of polycarbonate (PC)/Acrylonitrilebutadiene-styrene (ABS) blends were investigated. Incorporating PC-oligomer into PC/ABS blends caused a significant improvement in strain at break under tensile loading without sacrificing tensile modulus and strength. Highly elongated ABS phases along the flow direction were observed in the blend with PC-oligomer.

Fowl glioma-inducing virus (FGV), which belongs to subgroup A of avian leukosis virus (ALV), shows tumorigenicity and pathogenicity, mainly in the nervous system, and causes astrocytoma and perineurioma. Apart from these neoplasms, cerebellar anomaly was found in chickens infected with FGV in ovo. The study reported here describes the morphologic characteristics of the affected cerebellum. Specific-pathogen-free chickens (C/O) were inoculated with FGV through the yolk sac on the 7th day of incubation. The cerebellar anomaly included diffuse depletion of granular cells of the internal granular layer (IGL), remnants of the external granular layer (EGL), and disorganization of the Purkinje cell layer. These cerebellar changes were observed in all birds except one. in the infected embryos, the EGL was thicker and had an irregular arrangement with a thin molecular layer (ML) and IGL, compared with the control. The granular cells were immunohistochemically positive for ALV common antigen. immunohistochemical analysis for vimentin revealed disarrangement and decreased number of Bergmann's fibers. Use of the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method and electron microscopy indicated that apoptotic granular cells were frequently observed in the EGL and ML. These results suggested that the cerebellar anomaly was hypoplasia, principally resulting from the apoptosis of granular cells in the EGL and ML caused by FGV infection and that the cell loss induced obstruction of granular cell migration and disarrangement of Bergmann's fibers in the ML.

Intraneural perineurioma is an extremely rare condition characterized by perineurial cell proliferation within peripheral nerve (PN) sheaths. In the veterinary field, this entity has been reported only in a dog. We examined multiple enlargements of PNs in 11 chickens (Gallus gallus domesticus) (9 Japanese bantams and 2 specific pathogen-free White Leghorn), which were inoculated with an avian leukosis virus (ALV) causing so-called fowl glioma. All chickens clinically exhibited progressive leg paralysis. Lumbosacral plexus, brachial plexus, and/or spinal ganglion were commonly affected, and these nerves contained a diffuse proliferation of spindle cells arranged concentrically in characteristic onion bulb-like structures surrounded by residual axons and myelin sheaths. The spindle cells were immunohistochemically negative for S-100α/β protein. Electron microscopy revealed that these cells were characterized by short bipolar cytoplasmic processes, occasional cytoplasmic pinocytotic vesicles, and discontinuous basal laminae. These features are consistent with those of intraneural perineurioma. Furthermore, the specific sequence of the ALV was detected in the PN lesions of 8/11 (73%) birds by polymerase chain reaction. These results indicate that the multiple intraneural perineuriomas of chicken may be associated with the ALV-A causing fowl glioma.

During the past 20 years, primary liver cancer, 95% of which is hepatocellular carcinoma (HCC), has ranked third in men and fifth in women as a cause of death from malignant neoplasm in Japan. The numbers of deaths and death rate from HCC showed a sharp increase beginning in 1975. Although both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important causes, HCV-related HCC has accounted for most of the recent increase and now represents 75% of all HCC in Japan. Geographically, HCC is more frequent in western than eastern Japan, and the death rate of HCC in each prefecture correlates with prevalence of anti-HCV. Among patients with HCV-related HCC, a history of blood transfusion was a relatively important source of infection in the 1990s, whereas community-acquired infections increased after 2000. There was a negative correlation between the duration from onset of infection to development of HCC and the age at onset. Interferon therapy for chronic hepatitis C has reduced the risk for HCC, indicating that early detection of HCV carriers and better treatment will contribute to improved outcomes. Nationwide screening for HCV and HBV began in 2002 in Japan, and reduction of HCC is anticipated. Further research should focus on mechanisms of carcinogenesis by HCV and HBV, development of more effective treatments, and establishment of early detection and treatment approaches. Better understanding of HCC unrelated to HCV and HBV and possibly because of steatohepatitis and diabetes should also be a major concern in future studies.

Intranasally inoculated neurotropic influenza viruses in mice infect not only the respiratory tract but also the central nervous system (CNS), mainly the brain stem.26,34Previous studies suggested that the route of invasion of virus into the CNS was via the peripheral nervous system, especially the vagus nerve. To evaluate the transvagal transmission of the virus, we intranasally inoculated unilaterally vagectomized mice with a virulent influenza virus (strain 24a5b) and examined the distribution of the viral protein and genome by immunohistochemistry and in situ hybridization over time. An asymmetric distribution of viral antigens was observed between vagal (nodose) ganglia: viral antigen was detected in the vagal ganglion of the vagectomized side 2 days later than in the vagal ganglion of the intact side. The virus was apparently transported from the respiratory mucosa to the CNS directly and decussately via the vagus nerve and centrifugally to the vagal ganglion of the vagectomized side. The results of this study, thus, demonstrate that neurotropic influenza virus travels to the CNS mainly via the vagus nerve.

Adult rabbits were inoculated with liver homogenate from a rabbit that died in a Japanese outbreak of rabbit haemorrhagic disease (RHD). All experimentally infected rabbits died with typical clinical, gross and histological findings of RHD. Distribution of RHD virus in tissues of the infected rabbits was studied by non-isotopic in-situ hybridization. Both viral plus- and minus-strand RNAs were detected within the cytoplasm of hepatocytes, Kupffer cells and splenic and alveolar macrophages, mainly in morphologically intact cells. Strand-specific reverse transcriptase–polymerase chain reaction also demonstrated viral minus-strand RNA as well as plus-strand RNA in the liver, lung and spleen of infected rabbits. These results suggest that viral replication occurs not only in hepatocytes but also in macrophages. The infected macrophages may contribute to viral dissemination in RHD.

Equine herpesvirus-1 (EHV-1) infection was demonstrated in the lung tissue of seven aborted fetuses by immunohistochemical labelling and polymerase chain reaction. The placentas of the fetuses were also examined by non-isotopic in-situ hybridization for the EHV-1 glycoprotein B (gB) gene. Positive hybridization signals were observed in the cytoplasm of trophoblasts, especially in microcotyledons, of all seven placentas, and in villous epithelium of the allantochorion of six placentas. Despite the presence of EHV-1 RNA, EHV-1 antigens were not detected in placentas by immunohistochemical examination. The present study represents the first in-vivo demonstration of the EHV-1 gene in equine trophoblasts. The findings suggest direct cell-to-cell spread of EHV-1 from endometrial cells to trophoblasts.

Polyomavirus JC (JCV) causes the human demyelinating disease, progressive multifocal leukoencephalopathy (PML). The recent demonstration of cases of PML in association with human T-lymphotropic virus type I (HTLV-I) infection prompted us to examine whether the HTLV-I-encoded regulatory protein Tax activates JCV transcription. By employing a dual luciferase assay, we initially found that the expression of Tax activated the transcriptional potential of both early and late promoters of JCV in human neuronal but not in non-neuronal cells. We subsequently analyzed the mechanism of Tax-induced activation of the JCV promoter in neuronal cells with the following results: 1) the JCV promoter that lacks the NF-kappaB-binding motif could not be activated by Tax; 2) the overexpression of IkappaBalpha abolished Tax-induced transcriptional activation of the JCV promoter; 3) a Tax mutant (M22) lacking the potential for activation via the NF-kappaB pathway did not activate the JCV promoter. Furthermore, Tax enhances the gene expression of JCV T antigen and VP1. We examined mechanisms of the cell-specific activation of the JCV promoter by Tax. Electrophoretic mobility shift assay demonstrated the presence of Tax-bound protein(s) that were specifically present in non-neuronal cells. This study is the first demonstration of the activation of JCV promoter by HTLV-I Tax in an NF-kappaB-dependent manner.

To elucidate the mechanism of hepatocarcinogenesis of pentachlorophenol (PCP) in mice, critical effects related to carcinogenicity were studied in the livers of B6C3F₁ male mice administered PCP at concentrations of 600 and 1200 p.p.m. in the diet for 8 weeks. Oxidative stress was assessed by measurements of 8-oxodeoxyguanosine (8-oxodG) in the liver nuclear DNA and hepatocyte cell proliferation was quantified by bromodeoxyuridine incorporation. Also, initiation and promotion were assessed in a two-stage hepatocarcinogenesis model in which one group of mice was given PCP at concentrations of 600 and 1200 p.p.m. as initiator for the first 13 weeks with subsequent administration of phenobarbital (PB) as promoter at a concentration of 500 p.p.m. in the drinking water for 29 weeks. A second group was initiated with diethylnitrosamine (DEN) at 20 p.p.m. in the drinking water for the first 13 weeks followed after a 4 week recovery interval by PCP at concentrations of 300 and 600 p.p.m. in the diet for 25 weeks. Significant elevations in 8-oxodG levels and cell proliferation were observed in a dose-dependent manner. Incidences and multiplicities of hepatocellular tumors in mice treated with PCP after DEN initiation were increased compared with those in mice given initiation only. In contrast, in mice given PCP as initiator followed by PB no enhancement of neoplastic lesions occurred. These findings are interpreted to demonstrate that PCP exerts a promoting action, but not an initiating effect on liver carcinogenesis and that the promoting action is related to oxidative stress and compensatory hepatocellular proliferation.

The purpose of this study was to investigate the relationship between complications arising from silent cerebral infarction (SCI) and changes in the levels of serum-soluble adhesion molecules in 82 elderly diabetic patients aged 60 years and older. SCI was found in 43 % of the 82 patients, with incidence increasing in relation to age. The prevalence of SCI was higher in subjects with hypertension, poor metabolic control and increased fibrinolysis. The levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) were higher in diabetic patients than in non-diabetic subjects (p< 0.05, p< 0.001, and p< 0.05, respectively). Also, sICAM-1 and sVCAM-1 were found at increased levels in diabetic patients with SCI compared to those without SCI (p< 0.01 and p< 0.05, respectively). In particular, the level of sICAM-1 was increased in patients with SCI due to perforating arterial occlusion, while the level of sVCAM-1 was increased in patients with SCI due to cortical arterial occlusion. However, no significant difference was found in sE-selectin levels. Overall average of the intima and media thickness (IMT) of the common carotid arteries increased with age. IMT proved to be greater in patients with SCI than in patients without SCI (p< 0.05), and showed a weak but significant positive correlation with sVCAM-1, while no correlation was found with either sICAM-1 or sE-selectin levels. In conclusion, measurement of serum adhesion molecules may be useful for diagnosing the early stages of brain damage and for prophylactic treatment which may prevent the onset or progression of SCI. [Diabetologia (1998) 41: 911–917]The purpose of this study was to investigate the relationship between complications arising from silent cerebral infarction (SCI) and changes in the levels of serum-soluble adhesion molecules in 82 elderly diabetic patients aged 60 years and older. SCI was found in 43 % of the 82 patients, with incidence increasing in relation to age. The prevalence of SCI was higher in subjects with hypertension, poor metabolic control and increased fibrinolysis. The levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) were higher in diabetic patients than in non-diabetic subjects (p< 0.05, p< 0.001, and p< 0.05, respectively). Also, sICAM-1 and sVCAM-1 were found at increased levels in diabetic patients with SCI compared to those without SCI (p< 0.01 and p< 0.05, respectively). In particular, the level of sICAM-1 was increased in patients with SCI due to perforating arterial occlusion, while the level of sVCAM-1 was increased in patients with SCI due to cortical arterial occlusion. However, no significant difference was found in sE-selectin levels. Overall average of the intima and media thickness (IMT) of the common carotid arteries increased with age. IMT proved to be greater in patients with SCI than in patients without SCI (p< 0.05), and showed a weak but significant positive correlation with sVCAM-1, while no correlation was found with either sICAM-1 or sE-selectin levels. In conclusion, measurement of serum adhesion molecules may be useful for diagnosing the early stages of brain damage and for prophylactic treatment which may prevent the onset or progression of SCI. [Diabetologia (1998) 41: 911–917]

To study the tissue specificity of metallothionein (MT) expression, tissues of dogs ranging in age from 1 day to 18 years were examined immunohistochemically. Of the organs examined, liver and kidney showed the strongest immunoreactivity; a comparable intensity of MT immunolabelling was noted in the two organs in adult animals. In the central nervous system, astrocytes and ependymal cells showed MT immunoreactivity. MT labelling was shown in the sustentacular cells of the olfactory epithelium, but immunoreactivity was slight in the epithelium of the respiratory tract. Slight MT immunoreactivity was demonstrated in the epithelium of a variety of glands (sweat, uterine, mammary, olfactory, perianal and thyroid) and in parietal cells of the fundic glands of the stomach. Sporadic MT immunolabelling was demonstrated in the columnar and goblet cells of the small and large intestines, surface mucosal cells of the stomach and epithelial cells of the hair follicles. These findings may help in understanding important features of MT, such as its dynamic induction mechanism, its systemic degradation pathway and the possible biological functions.

A 5-month-old male calf showed neurological signs, including circling, inco-ordination, depression, blindness and eventual recumbency. On necropsy, a mass measuring 3.5x4x5x5 cm was found at the base of the brain, at the level of the pituitary gland. The hypothalamus and optic nerves were compressed by the dorsally expanding mass. Non-functional pituitary chromophobe adenoma was diagnosed from histochemical, immunohistochemical phobe adenoma was diagnosed from histochemical, immunohistochemical and electron microscopical findings.

To test the in vivo cooperativity between interleukin-3 (IL-3) and erythropoietin (Epo) in stimulating erythropoiesis and hemoglobin F (HbF) production in primates, we administered recombinant human IL-3 and recombinant human Epo to baboons and macaques. The effect of these treatments was assessed by serial bone marrow cultures and by measuring HbF production in the progeny of bone marrow progenitors and in peripheral-blood reticulocytes. Administration of IL-3 alone to hematologically normal or anemic baboons produced an early increase in erythroid colony-forming units (CFUe) and erythroid clusters (e- clusters) with an increase in reticulocyte counts and a late increment in the relative frequency of erythroid burst-forming units (BFUe). In parallel to the increase in peripheral-blood reticulocytes, IL-3 increased the frequency of F reticulocytes in the normal and anemic animals. When administration of IL-3 was followed by administration of Epo, expansion in all classes of erythroid progenitors and increase in reticulocytes occurred, beyond the levels observed when the animals were treated with Epo alone. The combination of IL-3 and Epo, however, did not increase consistently the rate of F reticulocytes beyond the level induced by Epo alone. These results suggest that IL-3 enhances the effect of Epo on erythropoiesis, but the combination of the two growth factors does not lead to a preferential and significant enhancement of HbF production.