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Biomedical subjects

H Kitamura

Publications and source records attributed to H Kitamura.

At least 19 recordsLinked to original sources
PubMed1998

Laparoscopic repair of a paraduodenal hernia.

Paraduodenal hernias have traditionally been treated by conventional laparotomy. We report the first case of a left paraduodenal hernia treated laparoscopically. A 44-year-old man was admitted with abdominal pain and nausea. Computed tomography and an upper gastrointestinal series with small-bowel followthrough showed accumulation of the small bowel on the left side of the abdomen. A laparoscopic repair was performed. The small bowel was observed beneath a thin hernia capsule. Approximately 1.5 m of jejunum was easily reduced into the abdominal cavity. The hernia orifice (5-cm diameter) was closed intracorporeally with five interrupted sutures. Good exposure of the operative field is critical to this procedure; poor exposure may limit the applicability of the laparoscopic approach. This minimally invasive operation is currently indicated in nonobstructive paraduodenal hernias, especially on the left.

Adult↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

Pulmonary endocrine cell hyperplasia and papilloma in rats induced by intratracheal injections of extract from particulate air pollutants.

We investigated the effect of intratracheal injections of an extract of suspended particulate matter (SPM) obtained from the urban ambient air of Tokyo, upon the development of proliferative lesions of pulmonary endocrine cells (PECs) in the rat. We also examined the modification effects of nitrogen dioxide, sulfur dioxide, or both of them on the PEC lesions. Male F344 rats were divided into six experimental groups of 5 animals each. Twenty animals were treated with intratracheal instillations of SPM admixed with carbon once a week for 4 weeks with or without additional gaseous exposure (6 ppm nitrogen dioxide or 4 ppm sulfur dioxide) 16 hrs a day for 11 months. Five animals were given intratracheal injections of carbon suspended in saline and the other five were untreated. The subcardiac lobes of the right lung were fixed with 4% paraformaldehyde, and embedded in paraffin. PEC hyperplasias and papillomas were counted in 200 serial sections, 4 microns thick. The average incidences of PEC hyperplasia in the untreated animals and in those treated with carbon were 194 and 200/cm3, respectively. The average incidences of PEC hyperplasia in the animals exposed to SPM tar only, SPM tar plus nitrogen dioxide and sulfur dioxide, SPM tar with nitrogen dioxide and SPM tar with sulfur dioxide were 376, 378, 372 and 349/cm3, respectively. These were significantly higher than the levels of the control animals, and additional gaseous stimuli had no effect on the incidence of PEC hyperplasia. Besides PEC hyperplasia, a few PEC papillomas were found in the animals treated with SPM tar, regardless of gaseous exposure, but in the control animals no papilloma was evident. Thus, compounds in airborne particulates are considered to be responsible for the development of PEC hyperplasias and papillomas.

APUD Cells↗
PubMed1997

Plasma concentration of endothelin-1 does not reflect renal vasoconstriction as estimated by duplex ultrasonography in cirrhosis.

Endothelin, a potent vasoconstrictor, is thought to play a role in liver cirrhosis-related functional kidney failure. Our aim was to investigate the correlation between renal vasoconstriction, as detected by a Doppler ultrasound technique, and plasma concentrations of endothelin in cirrhotic patients. Fifty cirrhotic patients underwent Doppler examinations to detect renal vasoconstriction. The plasma concentration of endothelin was measured in 10 patients who exhibited vasoconstriction of the renal microvessels diagnosed by Doppler waveform analysis and was compared to that of patients in whom there was no sign of such vasoconstriction. No difference was observed in the plasma concentration of endothelin between patients in whom renal vasoconstriction was diagnosed and those in whom it was not. Our results suggested that the circulating endothelin does not reflect renal vasoconstriction, at least in the early phase of the functional renal failure associated with cirrhosis of the liver.

Endothelin-1↗
PubMed1997

Complexity of expression of the intermediate filaments of six new human ovarian carcinoma cell lines: new expression of cytokeratin 20.

Six permanent human ovarian carcinoma cell lines (OVISE, OVTOKO, OVMANA and OVSAYO from clear cell adenocarcinoma, and OVSAHO and OVKATE from serous papillary adenocarcinoma) were established from solid tumours. The cell lines have been in culture for 5-8 years, the passage number varying from 62 to 246. Immunohistochemical analysis has shown that five of the six cell lines express at least six cytokeratin (CK) polypeptides. OVISE and OVSAYO expressed CKs 6, 7, 8, 18, 19 and 15 and/or 16. OVTOKO was positive for CKs 7, 8, 18, 19 and 15 and/or 16. OVSAHO expressed CKs 6, 7, 8, 14, 18, 19 and 15 and/or 16. OVMANA expressed CKs 6, 7, 8, 18, 19, 20 and 15 and/or 16. OVKATE expressed CKs 6, 7, 8, 13, 17, 18, 19, 20 and 15 and/or 16. The expression of CK7, additional expression of vimentin, and clinical and histopathological findings enabled us to confirm that six cell lines had been established from primary ovarian cancers. Two of the six cell lines were positive for CK20, although CK20 was not expressed in the original tumours. The heterotransplanted tumours produced by CK20-positive cells also expressed CK20. This is the first report of ovarian carcinoma cell lines that express CK20 irrespective of their histological type. CK20 has been found in all colon carcinoma cell lines, but only in the mucinous type of ovarian tumours. These new ovarian carcinoma cell lines will therefore provide a relevant experimental system for elucidating the regulatory control mechanisms of intermediate filament expression.

Adenocarcinoma, Clear Cell↗
PubMed1997

Effects of partial nephrectomy on the expression of osmolyte transporters.

Na+/myo-inositol cotransporter (SMIT) and Na+/Cl-/betaine-gamma-amino-n-butyric acid transporter (BGT-1) are the major osmolyte transporters that are regulated by extracellular osmolarity. We have recently shown localization and rapid regulation of the mRNAs for these transporters in rat kidney. In the present study, we examined the expression of SMIT and BGT-1 in partial nephrectomized rats in order to assess the change in local osmolarity following reduction of renal mass. Four weeks after 5/6 nephrectomy (NX), the rats were compared to sham-operated control animals (CONT). Northern analysis using RNA of whole kidney indicated that there were little differences in the levels of SMIT and BGT-1 mRNAs between the two groups. In situ hybridization revealed that signals for both transporter mRNAs were markedly reduced in the inner medulla of the remnant kidney. In contrast, these signals in the outer medulla increased following nephrectomy. SMIT signals in the cortex increased as well. Grain density, determined by counting grain number per cell, revealed that the signals in the inner medullary collecting ducts were markedly reduced whereas those in the thick ascending limbs of Henle (TAL) as well as macula densa cells were significantly increased. The signals in the TAL and macula densa were reduced by furosemide administration. The increased expression in NX rats may reflect the increased NaCl transport and high local osmolarity in this segment.

Animals↗
PubMed1997

Ultrastructural study of capillary and myocytic changes in the masseter and heart of KK-Ay mice.

We studied the capillaries and myocytes of masseter and cardiac muscles of diabetic KK-Ay mice, using light microscopy, transmission electron microscopy and scanning electron microscopy. The following changes were observed for diabetic masseters: capillary tortuosity, diversity of capillary caliber, endothelial cell swelling accompanied by luminal narrowing, widening of the pericapillary space and pericapillary fibrosis, and subsarcolemmal accumulation of myocytic mitochondria in areas adjacent to capillaries. In addition, attenuated capillary segments were largely covered by pericytes with profuse processes. In contrast, cardiac muscles of KK-Ay mice exhibited subsarcolemmal accumulation of myocytic mitochondria in areas contiguous to capillaries, and degenerative changes of myocytes such as disarrangement of myofilaments, disappearance of Z-bands and clustering of lipid-like vacuoles, although conspicuous changes of capillaries were not noted. Microvascular and myocytic changes described above may suggest the presence of microangiopathy and myopathy in the masseter and heart of KK-Ay mice.

Animals↗