[Autopsy case of Werner's syndrome].
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Autopsy↗
Biomedical subjects
G Asano
Publications and source records attributed to G Asano.
Clinico-neuropathological study of incontinentia pigmenti achromians--an autopsy case.
A clinico-neuropathological study of a Japanese girl with hypomelanosis of Ito, one of the neurocutaneous syndromes, is reported. At birth, typical skin hypopigmentation on the trunk and a hypopigmented streak on the left lower extremity were noted. From 2 months of age, intractable convulsions occurred and EEG showed various abnormalities. Psychomotor development was severely retarded and she died of pneumonia at the age of 13 months. Neuropathological examination revealed brachycephaly, micropolygyria and asymmetry of lateral ventricles. A histological examination showed a disarray of cortical lamination, and the existence of nerve cells in the white matter. These pathological findings showed a migration anomaly during brain maturation.
Autopsy↗
Differential expression of hepatocyte growth factor and its receptor (c-Met) in a rat artificial anus model.
Hepatocyte growth factor is a multifunctional polypeptide that has been implicated in cancer growth, tissue development and wound repair. It is mainly synthesized in mesenchymal cells and acts on epithelial cells, where its actions are dependent on binding to a specific cell-surface hepatocyte growth factor receptor (c-Met). In an artificial anus, two different types of epithelial cells (ductal cells of the colon and squamous cells of the skin) intermingle with each other. In the present study, we examined the localization of hepatocyte growth factor and c-Met during the process of repair in a rat artificial anus model, and attempted to clarify the cell types that express hepatocyte growth factor or c-Met messenger RNA by in situ hybridization. Western blot analysis revealed abundant localization of the mature form of hepatocyte growth factor in artificial anal tissues. Moderate hepatocyte growth factor immunoreactivity was noted in regenerated squamous cells in the skin and colonic ductal cells, and strong expression in macrophages and fibroblasts. Moderate c-Met immunoreactivity was present in regenerated epithelial cells in the skin and colon. Throughout the repair process, hepatocyte growth factor and c-Met immunoreactivities were more prominently localized in the squamous cells of the skin than in colonic ductal cells. Competitive reverse transcription-polymerase chain reaction analysis revealed that hepatocyte growth factor mRNA was maximal on day 14 after the operation; however, c-Met mRNA expression had two peaks, on day 1 and day 7. Hepatocyte growth factor mRNA was expressed more in the stromal fibroblasts, macrophages and endothelial cells, and c-Met mRNA was predominant in regenerated squamous cells of the skin. These findings suggest the possibility that hepatocyte growth factor may act in a paracrine manner to mainly enhance the growth of squamous cells of the skin and to a lesser extent the ductal cells of the colon in the artificial anus.
Animals↗
Canine mesenteric artery Na+,K+-ATPase: vasopressor receptor for digitalis?
Localization and characterization studies of Na+,K+-ATPase in canine superior mesenteric artery were undertaken to examine the role of the Na+-K+ pump in the vasopressor response of cardiac glycosides. The enzymatic component of the membrane-bound Na+-K+ pump, Na+,K+-ATPase, was found by histochemical and cell fractionation techniques to be localized primarily in the sarcolemma of the smooth muscle cell in superior mesenteric artery. The enzyme could be enriched in microsomal and partially purified sarcolemma preparations of superior mesenteric artery and first-order arterial side branches. Binding of [3H]ouabain to arterial microsomes followed pseudo-first-order reaction kinetics. In the presence of magnesium plus ATP, sodium stimulates and potassium inhibits the rate of binding. Scatchard analysis indicated a single class of [3H]ouabain binding sites with a KD of 2-9 nM and a Bmax of 2.3-3.5 pmol/mg protein. Although the characteristics of [3H]ouabain binding to mesenteric artery microsomes resemble the characteristics of [3H]ouabain binding to purified Na+,K+-ATPase, the density or total number of Na+-K+ pump sites in mesenteric artery is small compared with either heart muscle or kidney parenchyma. In isolated mesenteric arterial strips, more than 80% of a 2.5 microM ouabain-induced contraction could be inhibited or reversed by alpha-adrenoceptor blockade with 1 microM phentolamine. These data indicate that although cardiac glycosides interact with specific receptor sites in smooth muscle of canine superior mesenteric artery, the direct vasoconstrictor effect, which may be related to this digitalis-smooth muscle Na+,K+-ATPase interaction, is meager and may be a reflection of the low density of Na+-K+ pump sites.
Animals↗
Establishment and characterization of a human rectal neuroendocrine carcinoma xenograft into nude mice.
BACKGROUND: Carcinoid tumor has been recognized as having a much wider spectrum than was previously thought. Now the term 'neuroendocrine carcinoma' (NEC) has been suggested to describe malignant epithelial tumors of neuroendocrine differentiation. Its biological behavior has not been well characterized because of the lack of in vivo models. MATERIALS AND METHODS: A metastatic inguinal lymph node from rectal NEC was used for heterotransplantation into nude mice. Histochemical and immunohistochemical stainings were performed in addition to ultrastructural investigations. Hormonal peptides were measured in both xenograft tumor tissue and serum. RESULTS: We succeeded in heterotransplantation of human rectal NEC into nude mice. To date tumorigenicity has been retained for approximately 38 months. The xenograft tumor was a histopathologically identical tumor. The immunohistochemical expression of the various hormonal peptides in the xenograft was essentially the same as that of the primary rectal tumor. Tissue and serum hormonal peptides in the xenografted tumor were measured. Serum glucagon and serotonin were significantly higher than in control mice. CONCLUSIONS: The expression of various hormonal peptides in NEC may vary depending on the surrounding environment. The establishment of NEC in xenografts provides a model for further study of the biological behavior of NEC, as well as the in vivo effects of chemotherapeutic agents on tumor growth and the release of hormonal peptides.
Animals↗
Ultrastructural observations of small blood vessels in leprosy patients.
In lepromatous leprosy, blood vessels revealed the luminal protrusions of endothelial cells containing M. leprae and thickening of the basement membrane of endothelial and smooth cells. Endothelial projections with increased pinocytotic vesicles were more often encountered in lepromatous leprosy than in the other types of leprosy. On the other hand, in tuberculoid leprosy, the extensive rough endoplasmic reticulum suggesting protein synthesis was observed in the endothelial cells compared with the other types of leprosy and non-specific lesions. It seems that the blood vessels associated with hyperfunction and proliferation in the endothelium could aggravate the degenerative changes in peripheral nerve fibers including the Schwann cells.
Endothelium, Vascular↗
Immunohistochemical expression of T, Tn and sialyl-Tn antigens and clinical outcome in human breast carcinoma.
BACKGROUND: The extent of expression of reactive T (Thomsen-Friedenreich), Tn and sialyl-Tn antigens has been assumed to predict carcinoma aggressiveness. We studied the expression of T, Tn and sialyl-Tn antigens in a relatively large cohort of breast carcinoma patients with known long-term outcome to assess the clinical and biological significance of these antigens. MATERIALS AND METHODS: T, Tn and sjalyl-Tn antigens were examined in 72 consecutive primary breast carcinomas by immunohistochemistry using well defined monoclonal antibodies and their semiquantitative values were correlated with established clinicopathologic prognostic parameters of the disease to determine their relationship with long-term clinical outcome. RESULTS: Of the 72 carcinomas, 63 (87.5%) each expressed T or Tn antigens, while 16 (22%) expressed sialyl-Tn antigens. Most carcinomas (81%) expressed more than one of the antigens simultaneously, being the most frequent combination T/Tn antigen expression. No significant correlation was noted between the expression of T, Tn and sialyl-Tn antigens (whether individually or in combination) and the prognostic parameters including patient age, disease stage, tumor size, lymph node status, nuclear and histologic grades, histologic types, hormone receptor status and menopausal status. Univariate survival analyses showed that disease stage, tumour size and lymph node metastasis were significant predictors of overall survival. Interestingly, a significant inverse correlation was found between the Tn antigen expression (p = 0.04), as well as the combined T/Tn (p = 0.03) and Tn/sialyl-Tn (p = 0.02) antigen expressions and long-term overall survival. In a multivariate Cox proportional hazard model, disease stage and a negative or low Tn antigen expression emerged as significant predictors of overall survival. CONCLUSION: Our data suggested that the expression of T, Tn and sialyl-Tn antigens does not appear to predict the outcome of patients with breast carcinoma in a long-term run. Moreover, the findings signified a potential value for a negative or low Tn antigen expression in prognostic stratification of breast carcinomas.
Adult↗
Effects of simvastatin on serum lipids and atherosclerosis in WHHL rabbits.
Watanabe heritable hyperlipidemic rabbits aged three months (young group) or 10 months (adult group) received 10 mg/kg of simvastatin daily for 24 weeks. Serum levels of total cholesterol, triglycerides, and beta-lipoproteins were reduced significantly in the treated animals but not in untreated controls. The decreases were greater in the young than in the adult animals. Levels of high-density lipoprotein cholesterol were not affected by treatment. At 24 weeks, the extent of atheromatous lesions on the thoracic-abdominal aorta was lower in the treated animals than in the controls, but the difference was significant only in the young animals. The results indicate that simvastatin would be effective in the treatment of atherosclerosis.
Age Factors↗
Production of granulocyte-macrophage colony-stimulating factor by adult murine parenchymal liver cells (hepatocytes).
In order to investigate the hematolymphoid system in the adult murine liver, we examined colony-stimulating factor (CSF) released from primary cultured liver cell fractions, parenchymal and nonparenchymal liver cells (more than 99% pure. Using a fibrin clot culture system, we found colony-stimulating activity not only in the culture supernatant from nonparenchymal fraction of normal liver cells (NP-NLC sup), but also in the culture supernatant from parenchymal fraction of normal liver cells (P-NLC sup). Clusters and colonies, which were generated in 4-day cultures of bone marrow cells or spleen cells with P-NLC sup or NP-NLC sup, were mainly composed of granulocytes (G), macrophages (M), and granulocytes and macrophages (GM). Both P-NLC sup and NP-NLC sup proliferated IC2, which is a GM-CSF and IL-3 dependent cell line, and this proliferation was completely inhibited by rabbit anti-murine GM-CSF antibody. Furthermore, both Northern blot analysis and in situ hybridization with specific cDNA probe for murine GM-CSF showed that parenchymal liver cells expressed GM-CSF mRNA transcripts. The present findings indicate that cultured murine parenchymal liver cells produce GM-CSF. The possibility, therefore, is suggested that parenchymal liver cells also play an important role in the regional hematolymphoid system of the liver.
Animals↗
[Pathologic analysis of nerve injury in leprosy].
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Arteries↗
Pulmonary edema induced by intravenous administration of contrast media: experimental study in rats.
An experimental study of changes in the lung induced by the intravenous administration of iodinated contrast media was carried out using rats. The increase in the relative lung weight and histological findings, especially pulmonary edema, were evaluated in control, physiological saline, diatrizoate sodium meglumine, iohexol, and ioxaglate groups. The relative lung weight increased significantly in all contrast media groups. Proximal and distal perivascular edema were confirmed microscopically. No statistically significant differences among the contrast media were noted in the increase in relative lung weight or in the degree of perivascular edema. There was a close correlation between the increase in relative lung weight and the degree of perivascular edema. These physiological and histological changes in the lung occurred irrespective of the osmolality of the contrast materials. We considered these phenomena to be induced by non-osmolality related toxicity of the contrast medium.
Animals↗