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Biomedical subjects

H Kitamura

Publications and source records attributed to H Kitamura.

At least 55 records · Page 3Linked to original sources

Membranoproliferative glomerulonephritis in the aged and its possible causal relationship with CD8+CD57+ lymphocytes.

Membranoproliferative glomerulonephritis (MPGN) is a chronic progressive glomerulonephritis that occurs primarily in patients under the age of 30, and is rare in the elderly. We report eight aged patients with MPGN associated with CD8+CD57+ lymphocytosis. All eight patients showed a significant increase in CD8+CD57+ lymphocytes with a significant decrease in the ratio of CD4+ cells to CD8+ cells. Infiltration of CD8+CD57+ lymphocytes was observed within capillary lumens to various degrees according to the severity of endocapillary proliferation in each case. Expression of endothelial-leukocyte adhesion molecule-1 was observed in a focal and segmental manner on glomerular endothelial cells and on the endothelium of arterioles and arteries in kidney tissue in four cases in which a pronounced endocapillary proliferation was simultaneously seen. These findings suggest that cell-mediated cytotoxic mechanisms against glomerular endothelial cells may be involved in the pathogenesis of MPGN in the aged.

Age Factors

Expression of facilitative glucose transporter isoforms in lung carcinomas: its relation to histologic type, differentiation grade, and tumor stage.

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.

Adenocarcinoma

Expression of MUC1 and MUC2 mucins in gastric carcinomas: its relationship with the prognosis of the patients.

Our previous immunohistochemical studies for the expression of MUC1 mucin antigen (which was detected by monoclonal antibody DF3) and MUC2 mucin antigen (which was detected by polyclonal antibody anti-MRP) in pancreatic and intrahepatic bile duct tumors demonstrated that invasive carcinoma with poor outcome showed a pattern of MUC1+ and MUC2- expression, whereas many of the noninvasive tumors with favorable outcome showed a pattern of MUC1- and MUC2+ expression. To clarify the relationship between the expression of these mucin antigens and the biological properties of gastric cancers, the expression of MUC1 and MUC2 mucin antigens was examined immunohistochemically in 136 patients with gastric cancer invading the submucosa or the deeper layer, and the survival of the antigen-positive and antigen-negative patient groups was compared using the Kaplan-Meier method. For MUC1 mucin expression, different glycoforms of MUC1 were examined using four monoclonal antibodies (NCL-MUC-1-CORE, DF3, MY.1E12, and HMFG-1). The patients with MUC1+ mucin antigen staining in the carcinoma showed significantly worse survival than those with MUC1- mucin antigen staining. In contrast, the patients with MUC2+ mucin antigen staining in the carcinoma showed significantly better survival than those with MUC2- mucin antigen staining. In conclusion, MUC1 antigen expression was associated with a poor outcome in patients with gastric cancer, irrespective of its glycosylation status, and MUC1 is thus considered to be a useful prognostic factor for poor outcome in patients. In contrast, MUC2 antigen expression is a prognostic factor associated with a favorable outcome in patients. In addition, combined evaluation of the MUC1 and MUC2 mucin staining is clinically useful to predict outcome in patients with gastric cancer.

Adult

Noninvasive measurement of renal function with 99mTc-MAG3 gamma-camera renography based on the one-compartment model.

OBJECTIVE: The aim of this study was to develop a method for measuring renal function with 99mTc-MAG3 gamma-camera renography without blood or urine sampling and evaluate its feasibility. PATIENTS, MATERIAL AND METHODS: Twelve patients with nephrological disorders underwent 99mTc-MAG3 renography and para-aminohippurate clearance measurement. Plasma clearance of 99mTc-MAG3 (ClMAG) was calculated through early renal uptake of 99mTc-MAG3 after appropriate correction of parameters (background, measured attenuation coefficient of 99mTc, and the actual depth of kidneys measured with computed tomography), and on one-compartment assumption of the kinetics of 99mTc-MAG3. We compared the resultant ClMAG with standard effective renal plasma flow (ERPF), using the para-aminohippurate clearance method and with simulated ClMAG derived from the two-compartment model. RESULTS: ClMAG calculated by the one-compartment model (283+/-131 ml/min, mean +/- SD) correlated with ERPF (r = 0.94, p <0.001), and was similar to the simulated ClMAG estimated from the two-compartment model in all patients (283+/-139 ml/min). CONCLUSION: This alternative method, which employs theoretical modeling of the pharmacokinetics of 99mTc-MAG3, may provide easy, noninvasive measurement of individual renal function without blood sampling or in vitro equipment. Further studies should be warranted.

Computer Simulation

Safety and kinetic properties of a humanized antibody to human interleukin-6 receptor in healthy non-human primates.

A monoclonal antibody, hPM-1, was constructed by grafting the complementarity determining regions to human interleukin-6 (IL-6) receptor, raised in mouse, onto a human antibody backbone (humanized antibody). It is expected to be useful as a therapeutic agent for IL-6-related diseases such as multiple myeloma. To investigate the toxicological and kinetic properties of hPM-1 preliminarily, normal cynomolgus monkeys, which showed cross-reactivity with hPM-1, were intravenously administered with hPM-1 at doses of 0 (vehicle), 4 or 40 mg/kg once a week for 13 weeks. Upon toxicological examination, there were no changes in clinical signs, food consumption, body weights, urinalyses, body temperatures, electrocardiograms, hematological and biochemical parameters including blood platelet counts, serum levels of immunoglobulin G and C-reactive protein, and pathological findings. In a kinetic study, serum concentrations of hPM-1 showed a linearity between doses of 4 and 40 mg/kg. The serum concentrations, even at a dose of 4 mg/kg, were maintained at a high enough level to inhibit the IL-6 functions throughout the period of the study. Concentrations of hPM-1 in bone marrow were almost equal to those in serum. The antibodies against hPM-1 were detected only in one of four monkeys receiving hPM-1. This study suggests that blockage of the IL-6 receptor by hPM-1 does not induce any influence on a healthy living body, and hPM-1 is not toxic under the conditions of this investigation.

Animals

Immobilization stress increases hepatic IL-6 expression in mice.

When mice were subjected to restriction of movement in a small cylinder (immobilization stress), the serum interleukin (IL)-6 level rose in 1 h, following increased expression of IL-6 mRNA in both the liver and the spleen. The IL-6 mRNA induction was much greater in the liver than in the spleen when compared on a whole-organ basis. Intraperitoneal injection of bacterial lipopolysaccharide (LPS) also increased IL-6 mRNA expression in these organs, but more preferentially in the spleen. Immunohistochemical examinations of liver tissue using an antibody against murine IL-6 revealed that immobilization stress induced IL-6 mainly in hepatic parenchymal cells, whereas LPS injection did so only in sinusoidal mononuclear cells. These results indicate that immobilization stress induces IL-6 production in the liver, especially in hepatic parenchymal cells, probably by a different mechanism from that for IL-6 induction by LPS.

Animals

Expression of matrilysin in vascular endothelial cells adjacent to matrilysin-producing tumors.

Matrilysin is believed to play important roles in tumor progression and metastasis. In the present study, we analyzed matrilysin-producing cells in various human cancer tissues by immunohistochemistry and in situ hybridization. Tumor cells in colorectal carcinomas, pancreatic carcinomas, transitional-cell carcinomas of the kidney and small-cell lung carcinomas were frequently positive for matrilysin. In addition, we found that endothelial cells of arterioles and venules adjacent to matrilysin-positive tumors expressed matrilysin mRNA and protein. The endothelial cells adjacent to matrilysin-negative tumors and those in normal tissues were negative for matrilysin. Furthermore, analyses by casein zymography, Western blotting and RT-PCR showed that matrilysin was weakly expressed by cultured human umbilical vein endothelial cells. Our results suggest that the expression of matrilysin in vascular endothelial cells and in tumor cells may be regulated by common soluble factors, and that endothelial cell-derived matrilysin may contribute to tumor angiogenesis and tumor metastasis.

Animals

Cytodifferentiation of atypical adenomatous hyperplasia and bronchioloalveolar lung carcinoma: immunohistochemical and ultrastructural studies.

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.

Adenocarcinoma, Bronchiolo-Alveolar

Preoperative diagnosis of strangulated obturator hernia using ultrasonography.

BACKGROUND: Obturator hernia is rarely recognized before surgical intervention, since it is relatively infrequent and its definitive diagnosis is difficult. To change this situation, we introduced ultrasound examination in 1993 for differential diagnosis of strangulated obturator hernia among patients with bowel obstruction of unknown cause. PATIENTS AND METHODS: Between 1993 and 1995, we encountered 15 patients with suspected obturator hernia based on the presence of bowel obstruction of unknown cause and so-called predisposing factors. These patients underwent ultrasound examinations. RESULTS: The 4 patients with bowel obstruction caused by strangulated obturator hernia were all correctly diagnosed preoperatively by ultrasonography and were successfully cured by surgery. The time required for diagnosis was shorter than reported previously (average 16.5 h). CONCLUSIONS: Ultrasonography is useful and reliable for the diagnosis of strangulated obturator hernia and can decrease the morbidity and mortality associated with delayed diagnosis.

Aged

Expression of gelatinase A, tissue inhibitor of metalloproteinases-2, matrilysin, and trypsin(ogen) in lung neoplasms: an immunohistochemical study.

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.

Adult

MUC2 gene expression is found in noninvasive tumors but not in invasive tumors of the pancreas and liver: its close relationship with prognosis of the patients.

We have previously reported that MUC2 apomucin was highly expressed in noninvasive tumors of the pancreas (intraductal papillary tumor [IdPT]) and liver (bile duct cystadenocarcinoma [BdCC]), which show more favorable outcomes than invasive carcinomas. In contrast, MUC2 was rarely expressed in invasive carcinomas of the pancreas (invasive ductal carcinoma [IDC]) and the liver (invasive cholangiocarcinoma [ICC]). In the present study, we examined localization of MUC2 messenger RNA (MUC2 mRNA) by using a complementary DNA (cDNA) probe for the MUC2 tandem repeat for in situ hybridization (pHAM1). Localization of MUC2 apomucin was determined by using an antibody directed against MUC2 apomucin (anti-MRP) for immunohistochemistry study. Eleven IdPTs and 10 IDCs of the pancreas, and 8 BdCC and 8 ICCs of the liver were examined. Nine (82%) of 11 IdPTs showed positive expression of MUC2 mRNA in the neoplastic cells, whereas none (0%) of the IDCs showed expression of MUC2 mRNA. Six (75%) of the 8 BdCCs showed positive expression of MUC2 mRNA in the neoplastic cells, whereas none (0%) of the 8 ICCs showed expression of MUC2 mRNA. The localization of MUC2 mRNA and that of MUC2 apomucin usually coincided, although a few cases (1 IDC, 1 BdCC, and 1 ICC) showed focal expression of MUC2 apomucin despite the absence of detectable MUC2 mRNA. These results indicate that the expression of MUC2 apomucin in IdPTs and BdCCs correlates with expression of MUC2 mRNA. In both patient groups with pancreatic tumors and hepatic tumors, patients with positive MUC2 mRNA expression in the tumors showed significantly better survival than those with negative MUC2 mRNA expression in the tumors. The production of MUC2, an abundant extracellular mucin, by most IdPTs and BdCCs may be correlated with tumors that display lower levels of invasion and metastasis.

Aged

Involvement of neutrophil elastase in crescentic glomerulonephritis.

To elucidate the role of neutrophils in the tissue damage of crescentic glomerulonephritis (GN), we examined neutrophils infiltrated in renal tissues and the localization of neutrophil elastase (NE), as a neutrophil-derived tissue destructive mediator, using an immunohistochemical technique with antibodies specific for neutrophils and neutrophil elastase; the enzyme histochemical technique (chloroesterase staining) also was used to detect neutrophils. In normal controls, neutrophil infiltration was scarce, and NE was localized in neutrophil cytoplasm. Neutrophils were abundant in crescentic GN and infiltrated in the glomerulus and interstitium; the infiltrating neutrophils were often aggregated. NE was localized in the cytoplasm of neutrophils and also appeared extracellularly (in granular or diffuse patterns) in glomerular necrotizing lesions, crescents, ruptured portions of Bowman's capsules, and in periglomerular and perivascular sites of the interstitium. Moreover, urinary concentration of NE measured by enzyme-linked immunosorbent assay (ELISA) in crescentic GN patients was significantly higher than in normals (93.6 +/- 13.3 v 1.4 +/- 0.5 microg/g x Cr, respectively; P < .001). These data suggest that NE plays a significant role in renal tissue damage, especially in the formation of glomerular necrotizing and crescentic lesions and in periglomerular interstitial lesions of crescentic GN.

Antigens, CD

Marked effect of DNA on collagen fibrillogenesis in vitro.

Growth of collagen fibrils in the presence of DNA was more rapid than that in the absence of DNA. Some of collagen fibrils formed in the presence of DNA were significantly wider than those in the absence of DNA. Moreover, the cross-bandings were also very distinct in spite of using pepsin-digested collagen. These results suggest that DNA not only adsorbs to collagen but induces the extraordinary fibrillogenesis of collagen.

Collagen

Suppression for the proliferation of fibroblasts by external DNA.

Phase-contrast and fluorescence microscopic observation showed that DNA added in the cell-culture medium for fibroblasts localized just on the surface of fibroblasts. The DNA bound to fibroblasts was found to be eluted by treating with collagenase. The suppression for the proliferation of fibroblasts by external DNA was confirmed with microscopic observation for the cells cultured in the presence and absence of DNA. Proliferation of the cells decreased from 412 to 155% by the addition of DNA. These results indicate that DNA has an affinity for collagen, the most major extracellular-matrix produced by fibroblasts, and suppresses the growth of fibroblasts.

Cell Division

DNA-alginate complex recognized by autoantibodies against DNA.

Double-stranded DNA was effectively complexed with alginic acid and immobilized on a surface of polystyrene microtiter plate. Dose-dependent binding of anti-DNA autoantibodies was finely observed to the solid phase DNA-alginate complex in enzyme-linked immunosorbent assay (ELISA). In contrast, non-specific binding of antibodies to alginate was scarcely detected rather than to poly-L-lysine. These results shown an availability of the solid phase DNA-alginate complex as an antigen in ELISA for detection of anti-DNA antibodies.

Alginates

Pure ovarian ependymoma: report of a case treated with surgery, chemotherapy, irradiation and hyperthermotherapy.

Ependymomas usually develop from neuroectodermal organs. Pure ovarian ependymoma is an extremely rare tumor. We report a patient with ovarian ependymoma who died at the age of 28, 9 years after initial surgery and subsequent intensive combination therapy (chemotherapy, irradiation and hyperthermotherapy) for repeated relapses and metastatic tumors. The diagnosis was confirmed by histopathological and immunohistochemical studies. For recurrent and persistent ependymoma, a combination of the treatment modalities described above is suggested to be beneficial in attenuating the rapid progress and spread of this disease.

Adolescent

Detection and clinical significance of red cell aggregation in the human subcutaneous vein using a high-frequency transducer (10 MHZ): a preliminary report.

To assess ultrasonic measurements for quantitative analysis of red cell aggregation in humans, 50 patients admitted to our hospital were examined without selection. The extent of the aggregates was a assessed by videodensitometry in the subcutaneous vein in the forearm after 2 min of occlusion by manual compression over the skin. Determinants of aggregability were also evaluated by laboratory blood testing to identify potential correlations with ultrasound data. Multiple regression analysis showed that echogenicity was significantly associated with plasma fibrinogen (p < 0.0001), serum total cholesterol (p = 0.0006) and serum protein fraction excluding albumin (p = 0.0049) and was inversely associated with serum total triglyceride (p = 0.0425), but not with age or hematocrit. Ultrasound measurements of red cell aggregation seemed to be useful for the assessment not only for a part of the rheological condition of the blood, but also concomitant changes in plasma macromolecules.

Cholesterol