Expression of ecalectin, a novel eosinophil chemoattractant, in nasal polyps.

CONCLUSION: Ecalectin, which is produced in the mucosa of nasal polyps, seems to play an important role in the accumulation and activation of eosinophils in nasal polyps, regardless of the presence or absence of atopic predisposition. OBJECTIVE: Ecalectin is a recently discovered eosinophil chemoattractant which elongs to the galectin family. We investigated the expression of ecalectin in nasal polyp tissues associated with various nasal and paranasal diseases in order to clarify the pathogenesis of eosinophilia in nasal polyposis. MATERIAL AND METHODS: Nasal polyps were taken from 56 patients diagnosed as having chronic sinusitis with nasal polyposis. The surgically resected polyps and nasal turbinates were immunohistochemically stained using antibodies against EG2, human mast cell tryptase, CD3 and ecalectin. RESULTS: The number of EG2- and ecalectin-positive cells was significantly higher in nasal polyps than control turbinates. Ecalectin-positive cells were observed in the subepithelial layer, where many EG2-positive cells were present. The number of ecalectin-positive cells correlated significantly with the number of EG2-positive cells in nasal polyps. Many ecalectin mRNA-positive cells were also observed in nasal polyps with an accumulation of EG2-positive cells.

Herpes simplex virus types 1 and 2 infect the mouse pituitary gland and induce apoptotic cell death.

Herpes simplex virus (HSV) infected the anterior lobe of the pituitary gland resulting in cytopathic changes following intravenous (i.v.) inoculation of male mice. Both HSV type 1 (HSV-1) and type 2 (HSV-2) were isolated from pituitary gland following i.v. infection, but not after intraperitoneal inoculation. HSV-infected pituitary cells were microscopically visible beginning at 24 h or 48 h following i.v. inoculation and were localized in the anterior pituitary. In both HSV-1 and -2 infections the pituitary lesions were apoptotic, as determined by light and electron microscopy, TUNEL, and DNA gel electrophoresis. However, the pituitary infection does not appear to be life-threatening since pituitary lesions were also observed following i.v. infection with HSV-1 strain -GC which possesses low virulence. These results suggest that the pituitary gland is one of the target organs of HSV infection.

Equine endotoxemia: pathomorphological aspects of endotoxin-induced damage in equine mesenteric arteries.

To evaluate the effects of endotoxin on the morphology of the equine mesenteric vasculature, each of two thoroughbred horses were given two intravenous injections (24 h apart) of a sublethal dose of endotoxin (10 microg/kg). Each injection produced results similar to those of clinical cases of equine colic with obstructive nature of the loop of bowel: diarrhoea within 2 h after administration, followed by cessation of both faecal excretion and sounds of intestinal peristalsis. The most prominent morphological change was the development of moniliform appearance of small mesenteric arteries, in which there were contracted and dilated segments of the small mesenteric arteries. This was accompanied by parietal hyalinization and intramural and extramural haemorrhage. These mesenteric vascular changes appear to reflect dynamic vasoconstriction in the living animal, resulting in reduction of mesenteric and intestinal blood flow and possibly inducing alterations of gastrointestinal function such as cessation of intestinal peristalsis.

Acute adrenal infection by HSV-1: role of apoptosis in viral replication.

Replication of herpes simplex virus type 1 (HSV-1) in the adrenal gland of mice was observed 12 h after intravenous inoculation, peaked at 48 h (7 x 10(7) PFU/tissue), and was maintained until death. Virus spread to the bilateral intermediolateral column of the thoracic spinal cord. Infected cells appeared in the fascicular zone of the adrenal cortex 12 h after infection, and cell death was evident in lesions found in the adrenal cortex. Lesions involved the medulla 48 h after inoculation. In cortical lesions, cell nuclei were fragmented or shrunken with little damage to the cytoplasm. DNA fragmentation appeared 12 h after inoculation and increased mainly in cortical lesions, which were characterized by apoptosis induced by HSV-1 infection. In the adrenal medulla, cells were fused and formed multinucleated giant cells but rarely displayed cell death. Macrophages, which serve as a frontal barrier to viral infection in the adrenal gland, especially the cortex, were fewer in number than those found in the liver or spleen. It is likely that HSV-1 easily infects the adrenal gland, resulting in suppression of local immunity, and that adrenal cell apoptosis serves as a primitive type of immunity to limit viral replication.

Are there histopathologic characteristics particular to fulminant hepatic failure caused by human herpesvirus-6 infection? A case report and discussion.

An 8-month-old boy was admitted to a neighboring hospital for severe liver dysfunction and drowsiness 4 days after a diagnosis of exanthem subitum. A diagnosis of fulminant hepatic failure was made, and liver biopsy was performed during the acute stage. The presence of human herpesvirus-6 variant B (HHV-6B) DNA was shown in liver tissue by polymerase chain reaction (PCR) and in the endothelium of the portal vein by in situ hybridization (ISH). Histologic examination showed microvesicular steatosis resembling that of Reye's syndrome, even though aspirin had not been prescribed. We considered HHV-6 to be the causative agent in this case and report what is perhaps the first precise histologic description of fulminant hepatic failure caused by HHV-6.

Immunohistochemistry of atrial natriuretic peptide in brain infarction.

Atrial natriuretic peptide (ANP) was originally isolated from cardiac atria, and has potent natriuretic, diuretic, and vasorelaxant properties. It has been localized in neurons and astrocytes in the cerebral cortex and the white matter. We hypothesize that glial ANP may contribute to the regulation of cerebral blood flow in brain infarction. In order to elucidate this possible role, the immunohistochemistry of ANP was studied in cases of brain infarction and in other cases of brain trauma for comparison. A statistically significant increase in the number of ANP-immunoreactive glial cells (mainly astrocytes) was observed in the white matter surrounding the brain infarction compared with the intact area. No statistically significant increase in ANP-immunoreactive glial cell number was observed in the cerebral white matter from brain haemorrhage, contusion and control cases. Our results indicate that glial ANP may increase in number in brain infarction, and that it may be involved in the regulation of the cerebral blood flow in the infarcted area.

Epstein-Barr virus infection resembling autoimmune hepatitis with lactate dehydrogenase and alkaline phosphatase anomaly.

A 73-year-old man had fever, lymphadenopathy, granulocytopenia, thrombocytopenia, ascites, pleural effusion, liver injury, and an allergic-like skin rash. Autoantibodies, such as anti-nuclear antibody, were shown, and there were lactate dehydrogenase and alkaline phosphatase anomalies and platelet-associated IgG. His liver injury resembled that in autoimmune hepatitis. He was diagnosed with Epstein-Barr virus (EBV) infection associated with autoimmunization because of his clinical course, fluctuation of anti EBV antibodies and positive EBV genome in circulating lymphocytes and serum. This case suggests a close relationship between EBV infection and autoimmunization or autoimmune-like hepatitis.

Herpes simplex virus hepatitis in macrophage-depleted mice: the role of massive, apoptotic cell death in pathogenesis.

Infection with herpes simplex virus or hepatitis viruses can lead to fulminant hepatitis, but there is controversy about the underlying conditions needed for such disease. To investigate how the impairment of host defences might be involved, macrophages were depleted by administration of silica to mice before intravenous injection with herpes simplex virus type 1 (HSV-1). Such mice died rapidly and their livers were yellowish and shrunken (acute yellow atrophy), and occasionally grossly haemorrhagic. Small foci of apoptotic cells developed in the liver lobules; these rapidly became confluent and zonal over time. The overall lesion pattern was similar to massive hepatic necrosis, and there was extensive HSV replication in the liver lesions. In the liver, DNA fragmentation characteristic of apoptosis followed the time course of HSV-1 propagation. These findings suggest that one of the underlying conditions for fulminant viral hepatitis may be inadequate macrophage response, and that the massive hepatic damage, often defined as cell necrosis, may actually be apoptosis of liver cells subsequent to virus infection.

Differential expression of S-adenosylmethionine synthetase isozymes in different cell types of rat liver.

Mammalian S-adenosylmethionine (AdoMet) synthetase exists as two isozymes, liver-type and nonhepatic-type enzymes, which are the products of two different genes. It is known that the liver-type isozyme is only expressed in adult liver. Whereas, the nonhepatic-type isozyme is widely distributed in various tissues. In addition to the liver-type isozyme, a minor amount of the nonhepatic-type isozyme is also detected in adult liver. To investigate the distribution of these two isozymes in the liver in detail, the localization of these two isozymes was examined in each cell type of liver using a combination of cell fractionation technique and Western blot analysis. In the parenchymal cells, the liver-type isozyme protein was predominantly expressed, and a small amount of the nonhepatic-type isozyme protein was also detected. On the other hand, in the stellate cells the nonhepatic-type isozyme protein was exclusively or only expressed. Interestingly, a large amount of both isozymes were present in endothelial and Kupffer cell fraction. Using both antibodies to anti-rat nonhepatic-type and liver-type isozymes, respectively, immunohistochemical analysis clearly confirmed these results. In addition, in cultured hepatocellular carcinoma cells (FAA-HTC1), the nonhepatic-type isozyme protein only was detected, and the liver-type isozyme protein completely disappeared. This result indicates that the changes in the isozyme expression is regulated within the parenchymal cells. Administration of hepatotoxic drug carbon tetrachloride (CCl4) to rats resulted in about 40% to 50% reduction of enzyme activity in parenchymal cells and stellate cells compared with those of control rats. However, enzyme activity in endothelial and Kupffer cell fraction was not changed.

Systemic lupus erythematosus with multiple perivascular spongy changes in the cerebral deep structures, midbrain and cerebellar white matter: a case report.

A 42-year-old woman with systemic lupus erythematosus developed an episode of tonic seizures and progressive disturbance of consciousness at the terminal stage. Neuropathological examination of the brain revealed a nearly symmetrical distribution of multiple spongy foci in the internal capsules, thalami, globus pallidus, mesencephalic tegmentum, cerebral peduncles and hilus of the dentate nuclei. The spongy lesions were obviously distributed along apparently intact medium-sized veins, and contained large numbers of macrophages, and axonal spheroids and a few reactive astrocytes, without inflammatory cell infiltration. In addition, the perivenous spongy lesions exhibited IgG immunoreactivity, so it is surmised that some neurotoxic factor(s) that exuded from the veins in the center of the perivenous lesions may have brought about such a unique pathology.

T lymphocytes and silica-induced pulmonary inflammation and fibrosis in mice.

BACKGROUND: Silica-induced pulmonary inflammation and fibrosis in animals provides a good model for chronic pulmonary inflammation and fibrosis. Although lymphocytes are implicated in the pathogenesis of pulmonary fibrosis, experimental models using silica-treated athymic nude mice have not been successful in showing the fibrogenic mechanism regulated by T cells. The aim of this study was to re-evaluate the role of T lymphocytes in the development of silicosis by comparing the response to silica administration of nude athymic mutants with that of euthymic animals. METHODS: Suspensions of silica particles were transnasally administered to nude athymic mice (Balb/c nu/nu) as well as to their euthymic littermates (Balb/c nu/+). The degree of pulmonary inflammation and fibrosis was assessed on days 14, 28, and 56 based upon histological observation, analysis of collagen deposition in the lungs, and analysis of the cellular constituent, protein, and phospholipid content in the bronchoalveolar lavage fluid. RESULTS: Histologically, athymic mice developed less severe interstitial pneumonitis than euthymic mice. In euthymic mice the lung hydroxyproline content increased with time after silica administration from 6.48 (0.38) micrograms hydroxyproline/mg dry lung weight on day 0 to 8.87 (0.41) micrograms/mg on day 56. A gradual increase in lung hydroxyproline content was also observed in athymic mice but the increase was significantly smaller than in euthymic mice (6.63 (0.43) micrograms/mg on day 0, 7.90 (0.19) micrograms/mg on day 56). Administration of silica resulted in an increase in the number of macrophages and neutrophils and in the total protein and phospholipid content of the bronchoalveolar lavage (BAL) fluid in both mouse strains. No significant difference was detected between athymic and euthymic mice in the numbers of macrophages, but the increase in neutrophils in the BAL fluid of athymic mice was significantly smaller than in euthymic mice on days 14 and 56. The total protein and phospholipid content of the BAL fluid from athymic mice was lower than that from euthymic mice. CONCLUSIONS: T lymphocytes appear to be involved in the pathogenesis of silica-induced pneumonitis. Since pulmonary fibrosis develops even in nude athymic mice, T cells do not seem to play a primary part in fibrogenic response but they regulate, at least to some extent, the response of inflammatory cells and fibrogenesis of the lung.

[Dystrophin abnormality in a patient with polymyositis associated with primary biliary cirrhosis and myocardial injury].

We have reported a 58-year-old Japanese female with polymyositis, primary biliary cirrhosis (PBC) and arrhythmia. In contrast to the previously reported 13 cases of polymyositis associated with PBC, symptoms and laboratory data abnormalities responded to oral administration of predonisolone. Interestingly, immunohistochemical and immunoblot analyses of biopsied skeletal muscle revealed diminished expression of dystrophin carboxyl-terminal domain in the sarcolemma, suggesting that, in analogy to Duchenne muscular dystrophy, secondary abnormality of the link between the basal lamina and cytoskeleton via the dystrophinglycoprotein complex may have played a role in the molecular pathogenesis of muscle fiber degeneration in this patient.