Nephrotic syndrome due to membranous glomerulonephritis in a patient with idiopathic thrombocytopenic purpura.
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Biomedical subjects
Publications and source records attributed to Y Inayama.
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Desmoplastic small round-cell tumor typically occurs in the abdomen of young men, but it can also develop at other anatomic sites and in older people, presenting greater diagnostic difficulties. We report a case of this tumor arising from the paratesticular region in a 43-year-old man. The tumor showed histologic, immunohistochemical, and ultrastructural evidence of multilineage differentiation, including epithelial, mesenchymal, and neuronal features. In addition, the presence of an EWS and WT1 chimeric messenger RNA was demonstrated by the reverse transcriptase-polymerase chain reaction using an EWS exon 7 primer and WT1 exon 8 and exon 9 primers, which revealed single polymerase chain reaction products with a junction of EWS exon 7 to WT1 exon 8. Our study demonstrates that desmoplastic small round-cell tumors of the paratesticular region share not only morphologic but also molecular genetic features with those of the abdomen and that reverse transcriptase-polymerase chain reaction analysis using paraffin sections is useful for a conclusive diagnosis.
We have examined the distribution of calcium-binding proteins (CaBPs) in adult and fetal lungs of Syrian golden hamsters (Mesocricetus auratus) using immunostaining with confocal laser microscopy and electron microscopy. Single and grouped (neuroepithelial body; NEB) endocrine cells were distributed from bronchi to alveolar ducts in the adult lung. Serial frozen sections immunostained for CaBPs in combination with immunostaining for endocrine markers such as calcitonin gene-related peptide, serotonin, PGP9.5, and synaptophysin revealed that positive immunostaining for calbindin-D28K (CB-D28K) was seen in single endocrine cells and NEBs. However, other so-called EF-hand family CaBPs, parvalbumin and calretinin, were not detected. Electron microscopically, positive immunoreaction for CB-D28K was mainly in the organelle-free cytoplasmic matrix of endocrine cells, and partly in nuclei and associated with secretory granules and endoplasmic reticulum. In fetal developing lungs, endocrine cells appeared first on gestational day 13, and they were positive for all the endocrine markers used. However, pulmonary endocrine cells were positively immunostained for CB-D28K from gestational days 15 and 16 onward. In summary, our observations suggest that CB-D28K is a useful marker for endocrine cells of the lung, and CB-D28K could function as a mediator of endocrine stimulation or calcium homeostasis in pulmonary endocrine cells.
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Segmental mediolytic arteritis is a very rare vascular disease which causes sudden intraabdominal hemorrhage. The disease is characterized by degeneration of the arterial media, followed by aneurysmal dilatation and rupture of the involved artery. Up to now, only 13 cases have been reported, and this unique disease is not fully recognized among general pathologists and physicians. Here, we present a case of segmental mediolytic arteritis involving the propria hepatic artery, which resulted in intraabdominal hemorrhage, and consequently hypovolemic circulatory disturbance. Histologically, the rupture focus showed degeneration and desquamation of the intima and media with fibrin-like material covering the exposed adventitia. Inflammatory infiltrates were only noted in the rupture focus as a secondary reactive change. Other than the rupture focus, there were two foci showing similar findings. This disease has rarely been reported and is seldom recognized as a cause of arterial rupture. In cases of sudden intraabdominal hemorrhage, segmental mediolytic arteritis should be considered as a possible cause in addition to atherosclerotic and mycotic aneurysm, traumatic injury and vasculitis syndromes.
Seven cases of high-grade adenocarcinoma of fetal lung type (H-FLAC) are compared with nine cases of pulmonary endodermal tumor resembling fetal lung or low-grade adenocarcinoma of fetal lung type (L-FLAC). Of the seven patients with of H-FLAC, four were men and three were women. All of the patients but one were in their 60s or 70s. Five patients were smokers. After resection of the tumor, three patients died of metastases, two patients are alive with no evidence of disease, and two patients died of a postoperative complication. Histologically, H-FLAC and L-FLAC have both complex glandular structures resembling fetal lung and neuroendocrine differentiation. Two cases of H-FLAC had stromal proliferation typical of biphasic pulmonary blastoma. The H-FLAC was distinguished from L-FLAC by the presence of disorganized glands, large vesicular nuclei, prominent nucleoli, pronounced anisonucleosis, absence of morules, transition to conventional adenocarcinoma, broad areas of necrosis, desmoplastic stroma, overexpression of p53 protein, and production of alpha-fetoprotein. High and low grades of FLAC explain discrepancies in previously reported clinicopathologic features of FLAC. The H-FLAC needs to be distinguished from L-FLAC. Both forms may have stromal components, so both have been referred to as blastomas. The H-FLAC represents the prototype of so-called pulmonary blastoma predominantly seen in the elderly, whereas L-FLAC and its biphasic form predominate in the middle-aged population.
Expression of facilitative glucose transporter (Glut) isoforms was studied immunohistochemically in lung carcinomas. Glut-1 was expressed in 45 (74%) of 61 lung carcinomas, including 19 (100%) of 19 squamous cell carcinomas. No Glut-1 staining was seen in normal lung epithelium surrounding the tumors. In squamous cell carcinomas and small cell carcinomas, Glut-1 immunostaining was stronger in the central area of tumor cell nests corresponding to the hypoperfused region. Focal staining was seen in 14 (58%) of 24 adenocarcinomas, and positive staining was correlated to lesser differentiation, larger tumor size, and positive lymph node metastasis. Glut-2 was detected in normal airway epithelium, but no positive staining was seen in lung carcinomas. Glut-3 and Glut-4 were not positively stained in normal lung epithelia, but a few lung carcinoma samples showed positive reaction (9 of 61 in Glut-3; 4 of 61 in Glut-4). Glut-4 immunoexpression was seen in regenerating alveolar and bronchiolar epithelia around and in cancer tissues. Glut-5 expression was not detected in normal and tumor tissues. Reverse transcriptase-polymerase chain reaction for Glut-1, Glut-3, and Glut-4 confirmed the expression revealed by immunohistochemical analysis. Overexpression of Glut could enhance uptake of glucose into lung carcinoma cells, and the increased glucose influx could be involved in cell biologic activities.
We examined the allelic association between the dopamine D2 receptor (DRD2) gene and alcoholism in 100 biologically unrelated Japanese alcoholics and 93 unrelated controls. Genomic DNA was prepared from peripheral white blood cells using the phenol-chloroform method. A 310-bp region surrounding the TaqA site at the DRD2 locus was amplified by polymerase chain reaction (PCR), and the PCR product was incubated with TaqI. The A1 allele remained intact while the A2 allele was cut. The frequency of the A1/A1 genotype and the frequency of the A1 allele were higher in early-onset alcoholics than in controls, P < 0.05 and P < 0.01, respectively. Moreover, the frequency of the A1/A1 genotype and the frequency of the A1 allele were higher in early-onset alcoholics with family histories of alcohol dependence than in controls, P < 0.01 and P < 0.01, respectively. The results indicate that the DRD2 gene is associated with susceptibility to early-onset alcoholism, and that each additional A1 allele shifts onset of alcoholism to an earlier age.
We used immunohistochemistry and electron microscopy to evaluate the differentiation of cells comprising atypical adenomatous hyperplasia (AAH; n = 26), early bronchioloalveolar lung carcinoma (BAC; n = 11), and overt BAC (n = 16), which are assumed to constitute a continuous spectrum of developmental steps of BAC. Surfactant apoprotein (SAP), a marker for type 2 alveolar cells, was expressed in cells from all the lesions of AAH, early BAC, and overt BAC. However, the proportion of SAP-positive cells decreased and their distribution became more heterogeneous with advancing lesion grade. Urine protein 1, which is identical to the Clara cell-specific 10 kDa protein, was expressed in 70% of overt BAC, whereas only 20% of early BAC showed weak reactivity and none of AAH lesions showed any reactivity at all. Ultrastructurally, type 2 alveolar cell differentiation was predominant among cells from AAH and early BAC. Our results suggest that precursor cells of BAC differentiate predominantly towards type 2 alveolar cells. Cells comprising overt BAC retain this differentiation phenotype, but to a reduced extent. In contrast, concomitantly with progression, cells with Clara cell differentiation emerge and their proportion increases. Such phenotypic changes may reflect metaplasia occurring in tumour cells during the development of BAC.
Lung cancer is a heterogeneous tumor in terms of clinical and biological behavior, and its aggressiveness depends on its invasive and metastatic properties. Matrix metalloproteinases and serine proteinases are believed to play a crucial role in invasion and metastasis of malignant tumor cells. In the present study, the authors evaluated immunohistochemically the expression of gelatinase A; tissue inhibitor of metalloproteinases-2 (TIMP-2), an inhibitor of gelatinase A; matrilysin; and trypsin(ogen) in 67 lung tumors from a variety of histological types including 17 squamous cell carcinomas, 16 adenocarcinomas, 15 small cell carcinomas, and 12 carcinoids. Interestingly, normal bronchial, bronchiolar, and alveolar epithelial cells expressed gelatinase A, TIMP-2, matrilysin, and trypsin(ogen) at varying frequencies and intensities. Bronchial smooth muscle cells and cartilage cells expressed gelatinase A alone, whereas endothelial cells, fibroblasts, and macrophages expressed gelatinase A and TIMP-2. Gelatinase A was expressed at high levels in most lung tumors examined (47% to 80%). TIMP-2 was also expressed at high levels except in the small cell carcinomas, which showed TIMP-2 expression at a lower frequency (60%) compared with other types of lung tumors (80% to 100%). Although matrilysin was expressed by tumor cells of all the histological types at various frequencies (13% to 63%), its expression was most common in adenocarcinomas. Expression of trypsin(ogen) was observed almost exclusively in adenocarcinomas (56%); other types of lung tumors expressed trypsin(ogen) far less frequently (0% to 12%). The present results, taken together with those of previous studies, suggest that gelatinase A is associated with malignant behavior of all the types of lung tumors, whereas its activity may be controlled by the endogenous inhibitor TIMP-2. The aggressive clinical behavior of small cell carcinoma may be attributable, at least in part, to a loss of the inhibitory effect of TIMP-2, as a significant proportion of these tumors showed negative or low levels of TIMP-2 expression. Matrilysin and trypsin(ogen) expressions are unlikely to be correlated with the aggressiveness of lung tumors. The expression of trypsin (ogen) may rather reflect the differentiation of adenocarcinoma cells toward normal airway epithelial cells.
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It has been hypothesized that glutamatergic neurons play an important role in clinical manifestations of schizophrenia and that the therapeutic effect of antipsychotic drugs is related to glutamatergic neurotransmission. To elucidate the effect of antipsychotic drugs on glutamatergic transmission, we examined gene expressions of NMDA receptor subunits R1, R2A, R2B and R2C in the whole brains of rats after acute and chronic administrations of haloperidol and sulpiride, using the Northern blot technique. The levels of NMDAR2B mRNAs decreased after the acute administration of haloperidol, but showed no change after the chronic administration. The levels of NMDAR2A and R2B mRNAs decreased after the acute administration of sulpiride, whereas the levels of R2A and R2B increased following the chronic administration. Neither haloperidol nor sulpiride influenced NMDAR1 mRNA levels. These data support differential expression of NMDA receptor subunits in rats upon treatment with haloperidol and sulpiride. The results imply that NMDAR2 subunits may be crucial in the regulation and modification of antipsychotic drugs.
A 36-year-old man with schizoaffective disorder was found to have a de novo 46 XY inv (9) (q31.2q34.3). Phenotypical abnormalities are short stature, depressed nasal bridge, hypertelorism and slender shoulders. Paracentric inversion of chromosome 9 is a rare chromosome aberration. This case suggests a new candidate region related to schizoaffective disorder.
A 42-year-old woman with diabetes mellitus lost consciousness and was transferred to the Yokohama City University Hospital. Blood chemistry findings indicated low blood sugar levels and chest X-ray examination revealed cardiomegaly and bilateral pleural effusions. These clinical abnormalities were corrected by treatment with glucose, diuretics, angiotensin converting enzyme inhibitor and digitalis. Cardiological laboratory examinations were performed after admission. Electrocardiography revealed first degree atrioventricular block and incomplete right bundle branch block. Ultrasonography showed lower grade of ejection fraction and diffuse hypokinesis of the cardiac wall. After admission, sinus arrest suddenly occurred. The diagnosis was sick sinus syndrome. Scintigraphy using iodine-123 betamethyl-p-iodophenyl-pentadecanoic acid showed abnormal mottled defects. Coronary angiography found no significant stenosis of the coronary artery. Electron microscopy showed abnormally shaped mitochondrial accumulations in an endomyocardial biopsy specimen. Mitochondrial DNA amplification by polymerase chain reaction followed by restriction enzyme Apa I digestion revealed adenine-to-guanine transition at 3243 of the mitochondrial tRNA(LEU)(UUR) gene.
Sixty-two patients with schizophrenia and 96 normal controls were investigated for genetic association with restriction fragment length polymorphisms (RFLPs) in the serotonin receptor genes. A positive association between the serotonin 2A receptor gene (HTR2A) and schizophrenia was found, but not between schizophrenia and the serotonin 1A receptor gene. The positive association we report here would suggest that the DNA region with susceptibility to schizophrenia lies in the HTR2A on the long arm of chromosomes 13.
The growth and differentiation potential of rabbit tracheal basal cells were investigated in vitamin A deficient mice. Denuded rat tracheal grafts were xenotransplanted into nude mice made vitamin A deficient by feeding them retinol-free pellets from mid-gestation. Rabbit tracheal epithelial cells harvested enzymatically or cells derived from a basal-cell-rich fraction obtained by elutriation (purity 93.3%) had previously been inoculated into the grafts (n = 8, each). The grafts were implanted into the vitamin A deficient or control mice aged about 10 weeks. Four weeks later, the grafts were retrieved for histological examination. The graft epithelium established by either basal cells or un-fractionated cells in vitamin A deficient hosts (groups 1 and 2, respectively) was atrophic, whereas grafts repopulated with both cell types in the controls had pseudostratified columnar epithelium. Group 1 and 2 grafts both showed squamous metaplasia; 10 metaplastic foci in 32 tracheal rings in group 1 (P < 0.02 or 0.002, compared with values for group 2 or controls, respectively), and 2 foci in 35 rings in group 2 (no statistical difference compared with controls). In conclusion, during vitamin A deficiency, rabbit tracheal epithelial cells, including the progeny of highly-purified basal cells, lost their potential for establishing a mucociliary epithelium and rather appeared to undergo squamous metaplasia.
Atypical adenomatous hyperplasia (AAH) of the lung is a putative precursor of bronchoalveolar carcinoma (BAC). To define the steps in its development and to clarify at which stage critical cellular events occur, we studied 65 lesions of AAH, early BAC, and overt BAC by morphometric analysis and immunohistochemical evaluation of expression of p53 protein and carcinoembryonic antigen (CEA). Both the nuclear area and lesion size increased from AAH to early BAC and to overt BAC; the standardized variation of nuclear area was smallest in overt BAC. Discriminant analysis using these morphometric parameters revealed high accuracy rates for the respective categories. Analysis of distribution of lung lesions in terms of nuclear area and lesion size yielded effective, potentially diagnostic cutoff values for distinction between AAH and early BAC. Both p53 and CEA expression tended to increase with the advance of atypia grade. In particular, high-level p53 expression was strongly correlated with overt BAC. These findings indicate that our classification of lung lesions is reproducible and thus useful for analyzing the development of BAC. Furthermore, some kinds of p53 gene abnormalities that are correlated with high-level p53 expression likely play an important role in the progression of early to overt BAC.
Although the serum level of carbohydrate antigen (CA) 19-9 is reportedly increased in patients with hydronephrosis, virtually no immunohistochemical studies of this condition have been performed. Therefore, we examined immunohistochemically 11 hydronephrotic kidneys and 3 normal control kidneys using antibodies against CA 19-9 and SPan-1, another sialylated carbohydrate antigen. Immunoreactivity for CA 19-9 was seen in the transitional and tubular epithelia in most of the hydronephrotic kidneys (9 of the 11 cases), and also detected in 2 of the 3 control specimens, although there the distribution appeared to be limited. SPan-1 immunoreactivity showed the same trend. CA 19-9 and SPan-1 immunoreactivity in hydronephrosis appeared to be more widely distributed than in controls, although its mechanism remains unclear.