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Biomedical subjects

J Kumagai

Publications and source records attributed to J Kumagai.

At least 37 records · Page 2Linked to original sources

Role of radical oxygen species in rat testicular germ cell apoptosis induced by heat stress.

The present study was designed to clarify the role of radical oxygen species in testicular germ cell apoptosis induced by heat stress. Testicular cells isolated from immature rats were cultured with or without elevated temperature, and occurrence of apoptosis in these cells was defined by the appearance of DNA fragmentation following agarose gel electrophoresis and by flow cytometric quantification of apoptotic cells. At 32.5 degrees C, < 1% of cells showed signs of apoptosis throughout the culture period, whereas under heat stress, the proportion of apoptotic cells increased to 5% at 37 degrees C after 24 h of culture, or to 14% after 1-h exposure at 43 degrees C followed by 23-h culture at 32.5 degrees C. Similar to the effect of heat stress, exogenously supplied oxygen free radicals also induced apoptosis. In contrast, treatment with catalase significantly attenuated heat stress-induced apoptosis. Furthermore, heat stress of testicular cells was associated with an increased intracellular peroxide level as measured by a fluorescent probe, 2', 7'-dichlorofluorescin diacetate. In conclusion, our data indicate the involvement of radical oxygen species during testicular germ cell apoptosis induced by heat stress. This study provides a useful in vitro model for the study of testicular germ cell apoptosis.

Animals↗

Interleukin-6 localization and the prognosis of IgA nephropathy.

Various cytokines and growth factors may be involved in IgA nephropathy. To clarify whether interleukin-6 was a prognostic factor for this disease, we investigated interleukin-6 positivity of renal biopsy specimens and its relationship with the prognosis. The subjects were 90 patients with IgA nephropathy (42 males and 48 females with a median age of 32.7 +/- 13.8 years). Renal biopsy specimens were stained for interleukin-6 using an enzyme-antibody method. Fifty-two of 90 patients showed glomerular positivity for interleukin-6. Among the patients positive for interleukin-6, 24-hour urinary protein excretion and serum creatinine levels were significantly higher at the time of biopsy than in the patients without interleukin-6 positivity, while creatinine clearance was significantly lower. In the interleukin-6-positive patients without steroid therapy, serum creatinine increased significantly after 1 year (Deltas-Cr; 1.04 +/- 0.45 mg/dl) and creatinine clearance decreased significantly (DeltaCcr; -11.7 +/- 3.2 ml/min) compared to the interleukin-6-negative patients without steroid therapy. Steroid therapy improved 24-hour urinary protein excretion, serum creatinine, and creatinine clearance in the interleukin-6-positive patients, while these parameters worsened without steroid therapy. On the other hand, the IL-6-negative patients showed no differences of clinical parameters irrespective of the presence or absence of steroid therapy. In conclusion, glomerular interleukin-6 positivity may be a prognostic factor and an indicator of the need for steroid therapy in IgA nephropathy.

Adolescent↗

Differences in the sensitivity to UVB radiation of two cultivars of rice (Oryza sativa L.) based on observation of long-lived radicals.

Free radicals with a long lifetime were observed in the leaves of two rice cultivars (Oryza sativa L.), Sasanishiki (UVB resistant) and Norin-1 (UVB sensitive), by electron spin resonance spectroscopy. The leaves of both cultivars grown with visible light show very similar ESR spectra composed of radical 1 (R1) and radical 2 (R2), which may be attributable to P700 cation radicals in the reaction center of photosystem I, and tyrosine cation radicals in the reaction center of photosystem II, respectively. The ESR spectrum composed of R1 and R2 radicals in the leaves of Sasanishiki grown under visible light with supplemental UVB was similar to that in the plant grown without supplemental UVB. On the other hand, the amount of R2 radicals in the leaves of Norin-1 grown under visible light with supplemental UVB was significantly smaller than that in the plant grown without supplemental UVB. It is suggested that the loss of R2 radicals in Norin-1 upon UVB irradiation is related to the instability of the plant.

Electron Spin Resonance Spectroscopy↗

Relationship between erythropoietin and chronic heart failure in patients on chronic hemodialysis.

In the present study, the relationship between the blood erythropoietin level and cardiac function was investigated in 15 patients on chronic hemodialysis who developed chronic heart failure. Another 45 patients without cardiac dysfunction were selected as a control group that was matched for gender, age, and the duration of dialysis. The erythropoietin level was 256.3 +/- 481.8 mU/ml in the heart failure group, which was significantly higher than that in the control group (17.0 +/- 10.0 mU/ml, P < 0.01). Eight of the 15 patients in the heart failure group maintained a hematocrit of more than 30% without receiving recombinant human erythropoietin therapy, whereas 29 of the 45 patients in the control group required erythropoietin. In the heart failure group, the erythropoietin level was significantly correlated with the levels of atrial natriuretic peptide and brain natriuretic peptide (P < 0.01). These results suggest that heart failure can increase the erythropoietin level in proportion to the severity of cardiac dysfunction, even in patients on long-term dialysis.

Adult↗

[Changes in endoscopic features and histological findings of H. pylori-related gastritis with a follow-up over a year after eradication of H. pylori].

This study reviews the cases of patients examined repeatedly by endoscopy with biopsies for over one year after eradication of H. pylori, measured according to the Sydney system. For 81 patients in whom H. pylori was successfully eradicated, the endoscopic features of edema, erythema, friability, exudate, erosion and rugal hypertrophy disappeared or diminished at 1-3 months after the therapy and endoscopic features of nodularity disappeared or diminished 12-15 months after the therapy. In these H. pylori-eradicated patients, the histological findings of inflammation and activity regressed 1-3 months after therapy, and atrophy and intestinal metaplasia regressed in 22(27%) and 28(35%) of the 81 patients examined 12-15 months after therapy. Regression of the atrophic pattern was observed in 38(47%) of these H. pylori-eradicated patients. In some H. pylori-eradicated patients, the regressions of atrophy and intestinal metaplasia were observed over one year after H. pylori eradication therapy. Inflammation and activity in the histological findings were related to the endoscopic findings of edema, erythema, friability, exudate, erosion and rugal hypertrophy.

Atrophy↗

Myeloperoxidase antineutrophil cytoplasmic antibody-positive necrotizing crescentic glomerulonephritis and membranous glomerulonephropathy.

In September 1997, a 68-year-old woman was found to have proteinuria and renal dysfunction. In December 1997, renal biopsy revealed necrotizing crescentic glomerulonephritis and membranous glomerulonephropathy. We diagnosed myeloperoxidase antineutrophil cytoplasmic antibody-positive necrotizing crescentic glomerulonephritis and membranous glomerulonephropathy because of the presence of necrotizing cellular crescents and spike lesions in the subepithelial region of the glomerular basement membrane. After steroid therapy, the antibody level and the incidence of cellular crescents showed a decrease. This is a rare case of myeloperoxidase antineutrophil cytoplasmic antibody-positive necrotizing crescentic glomerulonephritis associated with membranous glomerulonephropathy.

Aged↗

Disappearance of hyperplastic polyps in the stomach after eradication of Helicobacter pylori. A randomized, clinical trial.

BACKGROUND: Helicobacter pylori infection is common in patients with hyperplastic gastric polyps. OBJECTIVE: To study the effect of eradication of H. pylori on the clinical course of patients with hyperplastic gastric polyps. DESIGN: Single-blind, randomized, controlled trial. SETTING: University-based gastroenterology outpatient clinic. PATIENTS: 35 patients with H. pylori infection and hyperplastic gastric polyps at least 3 mm in diameter. INTERVENTION: Patients were randomly assigned to a treatment group (n = 17), which received a proton-pump inhibitor (omeprazole or lansoprazole), amoxicillin, and either clarithromycin or ecabet sodium, or to a control group (n = 18), which received no treatment. MEASUREMENTS: Patients underwent endoscopy before enrollment and 12 to 15 months after the end of treatment. Serum gastrin levels and titers of IgG to H. pylori were measured. RESULTS: In the treatment group, the polyps had disappeared by 3 to 15 months (average, 7.1 +/- 1.2 months) after the end of treatment in 12 of all 17 patients (71%) and in 12 of the 15 patients (80%) in whom H. pylori was eradicated. However, 12 to 15 months after the start of the study, no change in polyps or H. pylori status was seen in any controls (P < 0.001). Histologic findings of inflammation and activity, serum gastrin levels, and titers of IgG to H. pylori showed significant regression in the treatment group compared with the control group (P < 0.01). CONCLUSIONS: Most hyperplastic polyps disappeared after eradication of H. pylori. Thus, eradication should be attempted before endoscopic removal is done in patients with hyperplastic gastric polyps and H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Plasmapheresis for removal of myeloperoxidase antineutrophil cytoplasmic antibodies: a case report.

We report on a patient with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated glomerulonephritis who had an elevated MPO-ANCA level and necrotizing crescentic glomerulonephritis on renal biopsy. She was treated by double filtration plasmapheresis and immunoadsorption plasmapheresis combined with steroid therapy and immunosuppressive agents. After plasmapheresis, the MPO-ANCA level decreased, and the cellular crescents were reduced. We conclude that plasmapheresis combined with steroid and immunosuppressive therapy may be useful to decrease the activity of MPO-ANCA associated crescentic glomerulonephritis.

Adult↗

Precise ultrastructural localization of endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in patients with IgA nephropathy.

Using light and electron microscopy, we performed an immunohistochemical study of endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in 15 patients with IgA nephropathy to clarify the localization of these adhesion molecules. The normal portions of 2 kidneys removed due to localized carcinoma and 3 biopsies from patients without glomerular disease were used as a control. By light microscopy, ELAM-1, VCAM-1, and ICAM-1 all showed positive staining in IgA nephropathy, with the intensity of staining following the sequence ICAM-1 > VCAM-1 > ELAM-1. ELAM-1 and VCAM-1 showed a patchy distribution of moderate staining in the tissues, including the mesangium, crescents, adhesions, and tubules. In contrast, there was marked linear ICAM-1 staining throughout the vascular walls. ELAM-1 and VCAM-1 were positive on the basolateral surfaces of a few proximal tubular epithelial cells in association with inflammatory cell infiltration, while ICAM-1 was found on the brush border. ICAM-1 was positive in the glomerular capillary walls and interstitial vessels of the control kidney tissue, while ELAM-1 and VCAM-1 were virtually absent. By electron microscopy, ELAM-1 positivity on the urinary surface of the parietal/visceral epithelial cells was often associated with adherent mononuclear cells in the urinary space. VCAM-1 positivity was increased in the perinuclear space and/or cytoplasm of mesangial cells as well as at the mesangial cell-endothelial cell interface. These findings suggest that ELAM-1 and VCAM-1 may be more closely related than ICAM-1 to the major histopathological changes occurring in IgA nephropathy, including mesangial expansion, formation of crescents and adhesions, and tubulointerstitial injury.

Adolescent↗

A case of nephrotic syndrome with rapid spontaneous remission in an elderly patient.

In July 1994, a 70-year-old woman was diagnosed as having nephrotic syndrome with proteinuria of 8 to 10 g/day and a serum albumin level of 1.8 g/dl. She was hospitalized in August 1994 for investigation. The urinary findings then normalized, with urinary protein and occult blood both negative and total urinary protein excretion at 0 g/day. A renal biopsy was performed, and spontaneous remission of minimal change nephrotic syndrome was diagnosed. This is an interesting case involving rapid remission of minimal change nephrotic syndrome in an elderly patient.

Aged↗

Ultrastructural localization of vascular cell adhesion molecule-1 in proliferative and crescentic glomerulonephritis.

Recent studies have demonstrated an important role of vascular cell adhesion molecule-1 (VCAM-1) in the pathogenesis of nephritis. In the present study, renal biopsy specimens from patients with proliferative and crescentic glomerulonephritis were subjected to immunoelectron microscopy using an anti-VCAM-1 monoclonal antibody. In control normal kidney tissue, VCAM-1 expression was restricted to the free surface of parietal epithelial cells. In diseased glomeruli, VCAM-1 was expressed on the free surface of parietal and visceral epithelial cells, on the luminal surface of capillary endothelial cells, on infiltrating monocyte/macrophage-like cells, on mesangial cells, and in the matrix of the expanded mesangium. There was also VCAM-1 expression on almost all cell types in the crescents, including macrophage-like cells, fibroblast-like cells, and epithelial cells. Some cells also showed VCAM-1 positivity in the rough endoplasmic reticulum and the perinuclear space. Both the glomerular capillary lumen and urinary spaces of Bowman's capsule contained positive reaction products, which were often associated with exocytosis by the surrounding cells. VCAM-1 was predominantly expressed on the basal and lateral surfaces of a few proximal tubules, but it could not be localized ultrastructurally. These findings suggest that production and secretion of VCAM-1 by both infiltrating monocyte/macrophages and resident glomerular cells may be related to the pathogenesis of proliferative and crescentic glomerulonephritis.

Antibodies, Monoclonal↗

Leuchtenberger bodies in flat adenomas of the colorectal mucosa: a comparison between Japanese and Swedish patients.

The dysplastic epithelium of flat colorectal adenomas was found to contain DNA inclusion granules, known as Leuchtenberger bodies (LB). Hematoxylin and eosin-stained sections of 263 colorectal flat neoplastic lesions (i.e., flat adenomas, and flat adenocarcinomas) collected in Japan and Sweden were scrutinized for the presence of such intraepithelial inclusions. LB were recorded in 87.1% of the 263 flat colorectal neoplastic lesions. The frequency of flat colorectal lesions having LB was similar in Japan (160 of 178 or 89.8%) to that in Sweden (69 of 85 flat lesions or 81.2%), suggesting that the occurrence of LB may not be influenced by race or environment. Direct immunoperoxidase detection of nuclear DNA fragmentation and transmission electron microscopy studies indicated that the inclusions contained apoptotic material. The semiquantitative assessment of histochemically labeled apoptotic granules indicated that the number of lesions having moderate to large numbers of apoptotic granules (++/ ) was higher in flat adenomas with high-grade dysplasia, suggesting that the occurrence of these granules may be related to the degree of severity of the dysplastic process. A better knowledge of LB may improve our understanding of the possible relationship between apoptosis, host immune response and carcinogenesis in flat colorectal adenomas.

Adenoma↗

Flat adenomas and flat adenocarcinomas of the colorectal mucosa in Japanese and Swedish patients. Comparative histologic study.

PURPOSE: In recent years, flat adenomas of the colorectal mucosa have been intensively investigated by Japanese pathologists. Results of that work indicate that flat adenomas may antedate the development of colorectal carcinomas. Because of differences in the histologic definition of flat adenomas with severe dysplasia and with intramucosal carcinoma within the group, one single observer having both Western and Asian training in pathology reviewed the material. METHODS: A total of 287 flat colorectal lesions were reviewed: 109 from the Karolinska Hospital, Stockholm, 137 from the Tokyo Medical and Dental University (TMDU) (which included 5 cases from the Nagoya City University), and 41 from the Cancer Institute (CI), Tokyo. Lesions were histologically classified following strict histologic criteria. Thus, flat adenomas were divided into those having low-grade dysplasia (LGD; having dysplastic cells in the deeper half of the epithelium), high-grade dysplasia (HGD; dysplastic cells were found even in the superficial half of the epithelium), intramucosal carcinoma (dysplastic glands displayed molding with buddings and often a cribriform pattern), and adenocarcinoma (braking through the muscularis mucosa, with neoplastic cells in the submucosal layer or deeper). RESULTS: Whereas in Stockholm only 14.7 percent of lesions had HGD, as much as 56.9 percent and 56.1 percent, respectively, had HGD at the two Tokyo Hospitals. Intramucosal carcinomas were not found in the Stockholm material but occurred in 2.2 percent of lesions seen at TMDU and in 4.9 percent of those seen at the CI. Notably, only 2.7 percent of the specimens at Karolinska Hospital had invasive adenocarcinoma, but it was seen in as many as 4.4 percent at TMDU and 21.9 percent at the CI. CONCLUSIONS: This study indicates that there were histologic differences between flat neoplasias of the colorectal mucosa harvested in Stockholm and Tokyo. In Japan lesions were obviously more advanced (in terms of HGD) and more aggressive (in terms of intramucosal and submucosal invasion). The cause for the differences found in those two disparate geographic regions remains poorly understood. The results, however, may help us understand some of the unclear points and discussions appearing in the literature on this subject.

Adenocarcinoma↗

Serotonin uptake and its modulation in rat jejunal enterocyte preparation.

In order to determine the properties of the intestinal serotonin (5-HT) transport system, we studied 5-HT uptake by villous cell preparations isolated from the rat jejunum. These enterocytes, probably heterogenous in cell population, accumulated 5-HT against concentration gradient up to a concentration 28 times that in the medium; this accumulation occurred in a temperature-dependent fashion. Most of the uptake was the result of a saturable process at low substrate concentrations. The saturable uptake was inhibited by 1 mM potassium cyanide or 1 mM ouabain or by substitution of other cations and sugars for Na+ in the medium. On the other hand, neither several amino acids nor putrescine had any effect on 5-HT uptake. Kinetic analysis yielded a Km value of 3.63 x 10(-7) M and a Vmax value of 5.76 pmol.10(6) cells-1.min-1 for this uptake process. Imipramine inhibited 5-HT uptake in a concentration-dependent fashion, with a Ki value of 3.66 x 10(-7) M. 5-HT uptake was also inhibited by ethyleneglycol-0,0'-bis(2-aminoethyl)-N,N,N',N'-tetraacetic acid, by verapamil, by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and by phorbol 12-myristate 13-acetate. These findings suggest that the present enterocyte preparation had a relatively specific secondary active transport system for 5-HT.

Animals↗

The collagen types in the attachment zone of rotator cuff tendons in the elderly: an immunohistochemical study.

OBJECTIVE: The attachment zone of the rotator cuff tendons in the elderly was studied immunohistochemically in order to determine how degenerative changes affected the pattern of collagen fiber distribution. METHODS: Twenty-seven cuffs with their bony insertion were obtained from 22 postmortem cases of both sexes ranging in age from 52 to 90 years and without a history of shoulder ailments. In addition, 3 cuff specimens from cadavers in the 3rd and 4th decades were examined for comparison. Sections of formalin fixed tissues were stained by peroxidase antiperoxidase (PAP) technique using monoclonal antibodies against types I, II and III collagen. RESULTS: Degenerative changes affecting the fibrocartilage primarily were characterized by calcification, fibrovascular proliferation and microtears. In addition, they were found in all the cuff tendons of elderly individuals but not in those from younger subjects. Immunohistochemically, the attachment zone in areas without degenerative lesions showed collagen type I labelling strongly in bone but only moderately in the fibrocartilage. The predominant labelling in the fibrocartilage was for collagen type II, and collagen type III labelled principally in perichondrocytic areas. The tide-mark showed inconsistent labelling for any of the collagen types. In the presence of degenerative lesions, the disposition of fiber types was interrupted by calcification and microtears. Collagen type II composition of the fibrocartilage was markedly altered by the presence of fibrovascular tissue which labelled only for collagen type III. CONCLUSION: We conclude that severe degenerative changes in the cuff tendons of elderly individuals, alter the collagen characteristic of the rotator cuff and that the changes could be associated with impairment of biomechanical properties of the attachment zone, and may give rise to the clinical syndrome of enthesopathy.

Aged↗

Immunohistochemical distribution of type I, II and III collagens in the rabbit supraspinatus tendon insertion.

The collagen fibres in the area of attachment of the supraspinatus tendon to bone were studied immunohistochemically in 12 mature female New Zealand white rabbits. The labelling of type I collagen was uniformly prominent in the bone as well as in the fascicles of the tendon proper but inconspicuously scattered in the unmineralised and mineralised zones of the fibrocartilage. Type II collagen, not detected in the tendon proper, was widespread in both zones of the fibrocartilage. Type III collagen, on the other hand, appeared to be confined mainly to the zone of unmineralised fibrocartilage, in addition to its presence in the endotenon of the tendon proper. The region of the tidemark failed to show immunostaining for any of the collagen fibre types. In conclusion, this study demonstrates that, although all the principal fibrous collagen types are constituents of the supraspinatus tendon at its attachment site, the distribution pattern of immunolabelling varies from zone to zone.

Animals↗