Microvenular haemangioma in a patient with Wiskott-Aldrich syndrome.
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Biomedical subjects
Publications and source records attributed to O Yamamoto.
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An immunohistochemical analysis of 8 cases of the apocrine type of cutaneous mixed tumor is reported. Histologically, 7 cases of the tumor were suggested to have follicular and/or sebaceous differentiation. Carcinoembryonic antigen (CEA), epithelial membrane antigen and gross cystic disease fluid protein-15 were present in the inner surface and/or in the luminal cell bodies of the tubular structures. CEA and non-specific cross-reacting antigen were also detected in the keratinous cysts. Positive reactions for S-100 protein and vimentin were observed in the solid nests, the outer layer of the tubular structures and some stromal cells. However, smooth muscle actin was only focally expressed in the outer cells of the tubular nests in one case. Involucrin was positive in the inner layers of the keratinous cysts. Various staining patterns were observed in the keratin immunohistochemistry. The solid nests showed heterogeneous expressions of CK1/5/10/14, CK7, CK10/11, CK14, CK8/18 and CK19. The inner cells of the tubular structures were constantly positive for CK7, CK8/18 and CK19, and heterogeneously for CK1/5/10/14, CK10/11 and CK14. The outer cells were heterogeneously positive for CK1/5/10/14 and CK14. The keratinous cysts showed positive reactions for CK1/5/10/14 throughout the whole cell layers, and for CK14 in the basal layer. The inner layers in some keratinous cysts expressed CK6, CK10/11 and CK17, but only CK10 in others. CK13 was positively stained in the transitional portion between the matricial structure and the column of shadow cells in the cyst wall in only one case. When compared with the immunohistochemistry of the normal skin, the apocrine type of cutaneous mixed tumor can show various immunophenotypical patterns similar to those of entire structures of hair follicles, sebaceous glands and all components of apocrine glands, that is to say, the folliculosebaceous-apocrine unit.
A 62-year-old Japanese woman came to our clinic because of melanotic macules on the lip, palatoglossal arch, lingual margin and palm. Endoscopic examination revealed a melanotic macule on the midesophageal mucosa but no polyposis in the gastrointestinal tract. Histologically, the specimens taken from the labial, esophageal and palmar lesions showed an acanthosis and basal hyperpigmentation in the epithelium. The patient had not taken any medication which could lead to pigmentation. As far as we know, this is the first case report of an esophageal melanocytic macule which occurred in a patient with Laugier-Hunziker syndrome. When confronted with an isolated pigment spot, we emphasize the necessity of systematic examinations for others. Because the pathologic relationship between Laugier-Hunziker syndrome and the esophageal melanocytic lesion is not proven, further studies should clarify this issue.
We have examined novel benzylhydroxylamine derivatives for their inhibitory effects on the replication of human immunodeficiency virus (HIV) in cell cultures. Among the series, O-(2-chloro-6-fluorobenzyl)hydroxylamine (RD6-Y664) was found to be the most potent inhibitor of HIV-1. The EC50 for HIV-1 strain IIIB was 1.6 micrograms/ml with a selectivity index greater than 38 in MT-4 cells. It also inhibited the replication of other HIV strains including a non-nucleoside reverse transcriptase (RT) inhibitor-resistant mutant, a nucleoside RT inhibitor-resistant mutant and HIV-2, in acutely infected cells. However, the compound did not affect HIV-1 production in chronically infected cells. A time-of-addition experiment and detection of proviral DNA synthesis suggested that RD6-Y664 targeted an early step of the viral replication cycle, presumably a process prior to reverse transcription. In fact, an assay for HIV-1 RT revealed that the compound did not suppress enzyme activity. Furthermore, RD6-Y664 did not show any inhibition of gp120-CD4 interaction, or binding of anti-CXCR4 antibody to CXCR4.
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We examined the clinicopathologic features of 11 surgically resected hepatocellular carcinomas (HCCs) less than 3 cm in diameter with marked inflammatory cell infiltration (LHCCs). In comparison with the other 152 HCCs without such an infiltration (controls), there were no significant differences in male/female ratio, age, serum alpha-fetoprotein levels, and laboratory and imaging findings. All the 11 LHCC cases were hepatitis B surface antigen (HBsAg) negative and hepatitis C virus antibody positive. Among the 152 controls, 116 cases were also HBsAg negative and HCVAb positive and were referred to as HCV-only controls. The clinical features were not significantly different between the LHCC and the HCV-only controls. The LHCC group tended to have higher numbers of lymphocytes and monocytes in pre- and post-operative peripheral blood, but there were no significant group differences. Recurrence rate was 9.1% in the LHCC group, 47.7% in the controls and 47.5% in the HCV-only controls (P < .01). Five-year survival rate was 100% in the LHCC group, 65.1% in the controls and 68.1% in the HCV-only controls (P < .01). Histologically, remarkable inflammatory cell infiltration, mostly lymphocytic, was observed in the cancerous tissue of the LHCC group. Varying degrees of piecemeal necrosis of cancer nests produced by infiltrating lymphocytes were observed in all the 11 cases. Lymph follicle formation was also found in 10 of 11 cases (90.9%). Liver cirrhosis was associated in 6 LHCC cases (54.5%), in 117 control cases (77.0%), and in 91 HCV-only controls (78.4%). Tumor invasion into the portal vein in the vicinity of the tumor was found in 1 LHCC case (9.1%), in 54 controls (35.5%), and in 34 HCV-only controls (29.3%). Immunohistochemically, most of the infiltrating lymphocytes, other than those in the lymph follicle, were identified as T lymphocyte, and CD8+ T lymphocyte was more predominant than CD4+ T lymphocyte. Better prognosis of the LHCC group could attribute to the anti-tumor effect induced by cellular immunity of CD8+ and CD4+ T lymphocytes, and partly by humoral immunity of B cells which formed lymph follicles.
A small non-functioning islet-cell tumor of the pancreas in a 79-year-old man is reported. Ultrasonography showed a solid small mass in the body of the pancreas. All laboratory data, including serum hormones and tumor markers, were within normal limits. A distal pancreatectomy was performed. Cut sections of the specimen revealed a small, hard, solid mass measuring 2.8 x 2.2 x 2.0 cm. Histologically, the tumor consisted of large acidophilic cells with round nuclei, and these cells were similar to those normally found in solid and cystic tumors (SCT) of the pancreas. However, the tumor cells were slightly positive for somatostatin and neuron-specific enolase. Ultrastructural studies revealed clear nuclei with no zymogen but immature neurosecretory granules in the cytoplasm of the tumor cells. These findings were consistent with those of non-functioning islet-cell tumors. We describe the clinical and histological differences between non-functioning islet-cell tumors and SCT based on an analysis of the literature.
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Nodular localized cutaneous amyloidosis (NLCA) is a disorder characterized by deposition of amyloid derived from immunoglobulin light chains. We used semi-nested polymerase chain reaction (PCR) to analyse archival paraffin-embedded sections from a previous patient and from four additional, previously reported patients with NLCA to determine whether involvement of monoclonal plasma cells is a universal feature of this condition. The semi-nested PCR analysis revealed one or two amplified bands, around 100-120 bp, for all five cases of NLCA, although the yields varied from case to case. These results suggest that clonal expansion of plasma cells in NLCA may occur locally.
Alpha2-adrenoceptor antagonists have been reported to stimulate colonic motor activity, but the effect on colonic motor dysfunction is unclear. We have investigated the effect of alpha 2-adrenoceptor antagonists on wrap-restraint stress-stimulated and normal colonic propulsion in rats. Colonic propulsion was evaluated by the transit of a charcoal marker along the colon. Faecal pellets output was also measured. A 30-min exposure to wrap-restraint stress starting 120 min after infusion of the charcoal marker significantly stimulated colonic transit with a concomitant increase in faecal pellets. Yohimbine and idazoxan, alpha 2-adrenoceptor antagonists, clonidine, an alpha 2-adrenoceptor agonist, and atropine suppressed wrap-restraint stress-stimulated colonic transit and faecal excretion in a dose-dependent manner. Ondansetron and YM060, 5-hydroxytryptamine3 (5-HT3) receptor antagonists, potently inhibited wrap-restraint stress-stimulated colonic transit, but only weakly inhibited faecal excretion. Neither alpha 2-adrenoceptor antagonists nor atropine had any significant effect on normal colonic transit, whereas clonidine and the 5-HT3 receptor antagonists inhibited it. alpha 2-Adrenoceptor antagonists as well as clonidine, atropine and 5-HT3 receptor antagonists inhibit the stress-induced colonic motor dysfunction in rats.
PURPOSE: To investigate the biological effect of tritium on mouse at low dose-rates. MATERIALS AND METHODS: Mice ([C57BL/6N x C3H/He]F1) were exposed to beta-rays by continuous administration of tritiated drinking water throughout their lives at low dose-rates of 3.6, 0.9, and 0.2 mG/day. RESULTS: Including the previous study, the tumour frequency was 70 to approximately 80% for exposure in the range 240 mGy/day to 9.6 mGy/day. Frequency of tumours decreased with decrease of dose-rate to 50% comparable to the controls. Restricting to thymic lymphomas, a linear relationship in a semi-log plot was found between the frequency and the dose-rate above a threshold dose-rate of 12 mGy/day. There was a 'tail' to this relationship down to 0.9 mGy/day. A similar pattern resulted for the relationship between the life-shortening and the dose-rate. The threshold dose-rate of 3H beta-rays, 2 mGy/day (with a tail down to 0.2 mGy/day), was much lower than that of gamma-rays, 20 mGy/day (tail down to 2 mGy/day) derived from other studies. CONCLUSIONS: These studies suggest that there exists the threshold dose-rate in the biological effects of radiation, and that the threshold dose-rate for 60Co gamma-irradiation is higher than that for 3H beta-irradiation.
To discover a novel NK1-NK2 dual antagonist, we have synthesized a series of spiro-substituted piperidines utilizing YM-35375 as a lead compound, and evaluated affinities for NK1 and NK2 receptors. In the N-methylbenzamide moiety, introduction of methoxy groups increased affinity for the NK1 receptor without a significant loss of affinity for the NK2 receptor. We also found that a conformation in which the phenyl groups of the N-methylbenzamide and 3,4-dichlorophenyl moieties are close to each other through a cis-amide bond, may be favorable for showing high affinity for the NK1 receptor and that a hydrogen bond-accepting group in the spiro-substituted piperidine moiety may be crucial for exhibiting high affinity for the NK2 receptor. Among the compounds prepared, YM-44778 (31) showed high and well-balanced affinity for NK1 and NK2 receptors (IC50 values of 18 and 16 nM, respectively). This compound also exhibited potent antagonistic activities against both NK1 and NK2 receptors (IC50 values of 82 and 62 nM, respectively) in isolated tissues.
In the course of our research on spiro-compounds as neurokinin receptor antagonists, N-[2-aryl-4-(spiro-substituted piperidin-1'-yl)butyl]carboxamides were designed, based on YM-35375 (3) as a lead compound, and evaluated for NK2 receptor-antagonistic activities. Some derivatives inhibited the binding of radio-labeled neurokinin A to the NK2 receptor with IC50 values at the level of 10(-9) M. Among these compounds, (+/-)-1'-[4-(N-benzoyl-N-methylamino)-3- (3,4-dichlorophenyl)butyl]spiro[benzo[c]thiophene-1(3H), 4'-piperidine] 2-oxide (58, YM-38336) showed 10 times more potent NK2 receptor binding affinity than compound 3 (IC50 values of 8.9 and 84 nM, respectively). It showed more potent inhibitory activity (ID50 20 micrograms/kg (i.v.)) against [beta-Ala8]-NKA(4-10)-induced bronchoconstriction in guinea pigs than compound 3 (ID50 41 micrograms/kg (i.v.)). This compound was also effective intraduodenally in the same model, exhibiting an ID50 value of 0.41 microgram/kg.
Halobacterium salinarium, a member of the extremely halophilic archaebacteria, contains a C50-carotenoid namely bacterioruberin. We have previously reported the high resistance of this organism against the lethal actions of DNA-damaging agents including ionizing radiation and ultraviolet light (UV). In this study, we have examined whether bacterioruberin and the highly concentrated salts in this bacterium play protective roles against the lethal actions of ionizing radiation, UV, hydrogen peroxide, and mitomycin-C (MMC). The colourless mutant of H. salinarium deficient in bacterioruberin was more sensitive than the red-pigmented wild-type to all tested DNA-damaging agents except MMC. Circular dichroism (CD) spectra of H. salinarium chromosomal DNA at various concentrations of KCl (0-3.5 M) were similar to that of B-DNA, indicating that no conformational changes occurred as a result of high salt concentrations. However, DNA strand-breaks induced by ionizing radiation were significantly reduced by the presence of either bacterioruberin or concentrated KCl, presumably due to scavenging of free radicals. These results suggest that bacterioruberin and intracellular KCl of H. salinarium protect this organism against the lethal effects of oxidative DNA-damaging agents.
A 35-year-old female had been clinically diagnosed as having epidermolysis bullosa hereditaria since her skin formed blisters from the time of her birth. Her left and right corneas become clouded at the age of 17 and 31 years, respectively. She was diagnosed as having bilateral secondary glaucoma at the age of 31 years and was medicated with antiglaucoma drugs. When examined by us, both corneas were invaded by conjunctival tissues and intraocular pressure in both eyes was 38 mmHg. Visual acuity was 0.09 (n.c.) in the right eye and she had no light perception in the left eye. A trabeculectomy OD was performed at our hospital. For confirmatory diagnosis, a pathological examination of the conjunctival and dermal tissues was done. Electron microscopic study demonstrated blister formation beneath the basal lamina and lost anchoring fibrils of both tissues. This finding confirmed that she had a receive form of dystrophic epidermolisis bullosa. This is a rare case of dystrophic epidermolisis bullosa with severe corneal changes and glaucoma diagnosed from electron microscopic observations.
We studied effects of a novel alpha-2 adrenoceptor antagonist, YNS-15P (N-[(2R,11bS)-9-methoxy-1,3,4,6,7, 11b-hexahydro-2H-benzoquinolizin-2-yl]-N-methylmethanesulfonami de hydrochloride), on colonic propulsion stimulated by wrap-restraint stress (WRS) or bethanechol, on normal colonic propulsion and on diarrhea induced by castor oil in rats. Alpha-2 adrenoceptor antagonists, rauwolscine and RX821002, decreased the increase in the number and weight of fecal pellets induced by WRS. YNS-15P also inhibited WRS-stimulated fecal excretion in a dose-dependent manner. A 5-hydroxytryptamine3 receptor antagonist, granisetron, trimebutine and diazepam, but not a 5-hydroxytryptamine4 receptor antagonist, GR113808, significantly inhibited WRS-stimulated fecal excretion. YNS-15P inhibited WRS-stimulated colonic transit in a dose-dependent manner. However, YNS-15P had no significant effect on normal fecal excretion and colonic transit or on bethanechol-stimulated fecal excretion. YNS-15P also failed to inhibit castor-oil-induced diarrhea. These results indicate that YNS-15P selectively inhibits WRS-stimulated colonic propulsion, and that alpha-2 adrenoceptors may be involved in stress-induced colonic motor dysfunction in fed rats.
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Nucleolar organizer region proteins, which can be stained and visualized by an argyrophil technique (AgNORs), are markers of cell activities, such as DNA transcription and proliferation, and they are useful for differential diagnosis between benign and malignant tumors. We counted both AgNOR numbers in 25 parathyroid lesions (three carcinomas, 11 adenomas, 10 hyperplasias, and one hyperplasia with carcinoma) to determine if the AgNOR number could be useful as a diagnostic aid in parathyroid neoplasms and hyperplasias, because it is often difficult to histopathologically distinguish among these lesions. The AgNOR numbers were significantly higher in carcinomas (3.18 +/- 0.05) than in adenomas (1.67 +/- 0.30, P < .001) or hyperplasias (1.85 +/- 0.16, P < .001), but there was no significant difference between adenomas and hyperplasias. These results suggest that AgNORs may be useful as an adjunct to discriminating carcinomas from adenomas or hyperplasias in the parathyroid gland.