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Biomedical subjects

K Ohe

Publications and source records attributed to K Ohe.

At least 55 records · Page 3Linked to original sources

Type 1 angiotensin II receptors of adrenal tumors.

The present study was designed to clarify the transcriptional regulation of the human type 1 angiotensin II receptor (AT1) gene and its pathophysiological roles in steroidogenesis by adrenal tumors. A cDNA encoding type 1 angiotensin II receptor (AT1) was isolated from a human liver cDNA library encoding a protein of 359 amino acids with seven transmembrane segments. It is very likely that human has only one type of AT1 receptor, in contrast with rodents. A genomic clone containing 217 bp of exon 1 and 2558 bp of the 5'-flanking region of human AT1 receptor gene was isolated. Its proximal promoter region contained putative TATA and GC boxes, CRE and AP1 sites. Aldosterone-producing adenoma (APA) contained significantly higher levels of mRNA for AT1 and ACTH receptors than normal tissues adjacent to APA. There were no mutations within the cytoplasmic third loops of AT1 and ACTH receptors in APAs examined. APA showed increased expression of the mRNA for P450c11 and decreased expression of the mRNA for P450c17. These results suggest that renin-independent overproduction and clinically observed ACTH-dependent production of aldosterone in APAs may results from the enhanced transcription of P450c11 and ACTH receptor genes. The mechanism of the discordantly increased expression of AT1 receptor in APA remains to be clarified.

Adenoma↗

Effect of an aldose reductase inhibitor on glomerular basement membrane anionic sites in streptozotocin-induced diabetic rats.

The present study was conducted in order to determine whether an aldose reductase inhibitor (ARI), epalrestat, prevents the progression of diabetic nephropathy in rats. Rats were made diabetic by intravenous injection of streptozotocin (STZ 50 mg/kg) and epalrestat (100 mg/kg) was administered orally through a gastric tube once daily for 4 weeks. Examination by electron microscope revealed that the number of anionic sites (AS) in the lamina rara externa per 1000 nm of glomerular basement membrane (GBM) was significantly decreased in diabetic rats compared to control values (17.6 + or - 0.4 vs. 21.9 + or -0.4, P < 0.01), whereas, significant recovery (20.3 + or - 0.7, P < 0.05) was observed after 4 weeks of epalrestat treatment. Urinary albumin excretion (UAE) rate was markedly increased in diabetic rats and the treatment resulted in its significant suppression from diabetic rats. In conclusion, administration of epalrestat to diabetic rats is capable of preventing a reduction in the number of AS in GBM which would ameliorate an increased permeability of the basement membrane leading to albuminuria.

Administration, Oral↗

Protective effect of heparin on renal glomerular anionic sites of streptozotocin-injected rats.

Albuminuria at the rate of 500 micrograms/24 h was observed in rats treated with 50 mg/kg body wt. i.v. streptozotocin (STZ). When STZ was combined with heparin, administered twice daily (250 IU/kg subcutaneous injection) after 24 h following STZ injection, the daily urinary albumin excretion (U-AE) was less than half the amount found in non-heparinized rats (280.3 micrograms/24 h). The observation period in both instances was 8 weeks. When animals were permitted to develop albuminuria over the first 4 weeks, subsequent heparin administration for another 4 weeks lowered U-AE from 500 micrograms/24 h to less than half the amount (227.8 micrograms/24 h). A significantly negative correlation (P < 0.001) existed between U-AE and the number of anionic sites (AS) in the lamina rara externa of glomerular basement membranes, as visualized by electron microscopy. The number of AS per 1000 nm in STZ-injected rats (15.5 +/- 0.2) was lower than that in control rats (23.1 +/- 0.6); however, in heparinized animals, regardless of STZ, the values were not significantly different from normal. Heparin by itself had no effect on the number of AS in normal rats. All STZ-injected animals became hyperglycemic (400-550 mg/dl), but received no insulin. Heparin had no effect on plasma glucose levels. From these results, it is concluded that heparin suppressed both of an increase in U-AE and a decrease in AS count of glomerular basement membranes in STZ-injected rats.

Albuminuria↗

[CD7 positive acute myelogenous leukemia exhibiting pleural involvement as an initial manifestation].

A 51-year-old man had suffered from massive pleural effusion due to invasion of malignant cells. The analysis of bone marrow aspiration showed the proliferation of myeloperoxidase-positive blasts. The surface marker analysis of the blasts revealed the positivities for CD7 and CD19 as well as CD13, CD33 and CD34, while the karyotypes of 20 cells were normal. Therefore, CD7 positive AML was diagnosed. The patient was treated with araC and daunorubicin as a remission induction therapy. Peripheral blood stem cells were harvested by leukapheresis after first and second consolidation therapies. Then, 3 x 10(4) cells/kg of CFU-GM were infused. Complete remission has been maintained for 8 months after autologous blood stem cell transplantation. Pleural involvement as an initial manifestation is rare in AML. Extramedullary growth of AML cells may be related to their immaturity, indicated by the expression of the cell surface antigens.

Antigens, CD↗

[Modified CHOP and radiation therapy in an aged patient with angioendothelial lymphoma].

A 77-year-old man was admitted because of high fever and general malaise. Whole-body CT showed large bilateral adrenal masses and para-aortic lymphadenopathy. Needle biopsy of the adrenal mass revealed mononuclear tumor cells within the lumens of small vessels, indicating the features of angioendothelial lymphoma. Immunohistochemically, these tumor cells were B cell lineage (positive for LCA, Mx-pan B, MB-1, and negative for factor VIII-related antigen, UEA-1, QB/ENDO 10). We used a modified CHOP therapy (500 mg of cyclophosphamide, 40mg of 4'-o-tetrahydropyranyl doxorubicin, 2mg of vindesine, and 50 mg of prednisolone) due to the patient's advanced age and general condition. Following the first course of this modified CHOP, the adrenal masses and para-aortic lymph nodes decreased dramatically in size, and his subjective symptoms also improved remarkably. Following three courses of modified CHOP, the patient developed dementia and disturbance of consciousness. Brain MRI revealed enhanced multiple nodular lesions. A diagnosis of multiple brain metastasis was made and modified CHOP and radiation therapy were begun, which relieved his symptoms for some time. However, he later died of pneumonia with severe leukopenia. A postmortem examination was performed. Microscopic examination showed no residual tumor cells in the adrenal gland. brain lymph nodes, or other organs. These results suggest that modified CHOP and radiation therapy may have beneficial anti-tumor effects against angioendothelial lymphoma.

Adrenal Gland Neoplasms↗

[Development of coding system for respiratory diseases and its application to classifying cases reported in the Japanese Journal of Thoracic Diseases].

We developed a coding system for respiratory diseases and related conditions for computer-aided analyses of these diseases. It is a one-axis alphanumeric system with a list of three-character categories and additional digits separated by a decimal point for subcategories. Respiratory and related diseases are categorized into eight groups; diseases of (1) the lung and airway, (2) the pleura, (3) the mediastinum, (4) the diaphragm, (5) the chest wall, (6) the heart and cardiovascular system, (7) the esophagus, and (8) clinical conditions predisposing to pulmonary disease. The first character, a letter from the A to G, represents a major disease category of (1) to (7) and X that of (8); and subdivisions are shown in the second position using the numbers from 0 to 9. Further subdivisions are provided in the third position also using numbers. Actual coding was done on case reports which appeared in the Japanese Journal of Thoracic Diseases from 1973 to 1993, and all cases were coded properly. The system is expected to prove useful in computer aided analyses of respiratory diseases.

Computers↗

[A case report of mitral valve replacement for infective endocarditis in pregnancy].

Infective endocarditis in pregnancy is uncommon. A 37-week pregnant woman presented with infective endocarditis. Echocardiography revealed prominent mitral valve vegetations. The patient underwent cesarean section and a 2,800 g male infant was delivered. In order to prevent embolization, mitral valve replacement was performed 3 days after cesarean section with SJM valve. Both mother and child are doing well now.

Adult↗

[Comparison of the casual serum triglyceride levels at health check-up with the values during fasting].

Since higher levels of serum triglycerides were frequently found during the UOEH physical check-up for employees and students in 1989, we analysed subjects with higher triglyceride levels and discussed ways of handling them. Blood sampling to determine serum lipids was done between 13:00-15:00. Of the total (males 1257, females 1267), 272 had higher serum triglyceride levels (over 200 mg/dl) (males 246, females 26) (1st TG). One hundred and twenty-one of the group with higher TG levels in the 1st examination were reevaluated by blood sampling the morning after overnight fasting (2nd TG). There was a significant positive correlationship between the TG levels from the 1st examination and those from the 2nd examination (r = 0.62, n = 121, P < 0.0001). The predictive value calculated from the equation between the TG in the first and second measurements was 341.7 mg/dl. There was a 14.9% rate of false negatives in subjects under 341.7 mg/dl on the first TG measurement. However, there were only 6.3% false negatives in the subjects under 250 mg/dl on the first TG measurement. Age, body mass index and serum cholesterol level were significantly higher in the group with the higher TG level on reevaluation (more than 160 mg/dl) than those in the group with the lower TG level on reevaluation (less than 160 mg/dl). We concluded from these results that the casual serum TG levels above 250 mg/dl might be a suitable cut off level in physical check-ups.

Adolescent↗

[Changes in anionic sites on glomerular basement membrane following mesangiolysis--observation in incipient anti-rat Thy1 nephritis].

To clarify whether heparan sulfate proteoglycans (HSPG) on glomerular basement membrane (GBM) are produced by mesangial cell in vivo, the number of anionic sites (AS) on lamina rara externa of GBM and the changes in urinary albumin excretion rate (UAE) were observed on mesangiolysis in rats induced by monoclonal anti-rat Thy1 antibody. Mesangiolysis was remarkable at day 3 after the administration of anti-rat Thy1 antibody, whereas GBM as well as epithelial cell remained well preserved, and detached endothelial cell was observed. The number of AS on GBM was significantly (p < 0.001) decreased in anti-rat Thy1 antibody treated rats (18.6 +/- 0.4/1000nm), when compared with that of normal control rats (22.8 +/- 0.4/1000nm). Furthermore, UAE was markedly (p < 0.05) increased at day 3 (1692.6 +/- 627.5 micrograms/24h) compared with the value before (188.2 +/- 30.6 micrograms/24h) administration of anti-rat Thy1 antibody. From these results, it can be concluded that some part of AS on GBM may be produced by the mesangial cell.

Animals↗

[The significance of obesity in UOEH medical students--multiple regression analysis of the annual physical checkup data in 1991].

For the purpose of evaluating the significance of obesity in a young population as a risk factor toward various chronic diseases, a multiple regression analysis was performed on the data from the annual physical checkup of medical students of UOEH in 1991. The following results were obtained. (1) The average obesity index of the students showed a progressive and significant increase in the past 13 years from 1979 to 1991. (2) A close correlation between the obesity index and serum GPT was recognized by elevation of the standard partial regression coefficient of serum GPT to obesity index and that of obesity index to serum GPT when the data from all 617 students was analysed in one group. This finding was intensified in 142 obese students with an obesity index of over 10%, but it was not seen in the remaining non-obese students. (3) The correlation between the obesity index and serum GPT was found solely in the group of students with constant obesity; i.e., whose obesity index was always more than 10% during a maximum of 9 years in the past. (4) Systolic blood pressure was related to the red blood cell count rather than to the obesity index in this young population. (5) No particularly close correlation to serum cholesterol was found with any of 10 representative items examined in this physical checkup, including the obesity index, indicating that the other factors should be related to serum cholesterol levels. From the above findings, it can be concluded that constant obesity in students is related to liver dysfunction, probably due to fatty liver frequently seen in the precise examination of these individuals.

Adolescent↗

[Characteristic features of proton pump inhibitors in the inhibition of gastric acid secretion: long-acting and complete inhibition].

Proton pump inhibitor is a compound recently applied for the treatment of peptic ulcers for its strong action to inhibit the gastric acid secretion. It works through inhibition of H+, K(+)-ATPase, so called proton pump, on the luminal surface of secretory canaliculi in the parietal cells, showing remarkable characteristics in the inhibition of gastric acid secretion; e.g., the long-acting and complete inhibition. At neutral pH, the unionized form of this compound as a weak base is lipophilic, and passes through the cell membrane to accumulate as the ionized form in an acidic environment in the secretory canaliculi of parietal cells, where it is transformed to an active molecule which binds covalently to the active site of H+, K(+)-ATPase, forming a highly stable complex. The long-acting and complete inhibition of gastric acid secretion by this compound is derived from this physico-chemical nature. The above characteristics of the proton pump inhibitor have been confirmed with the basal, stimulated and nocturnal gastric acid secretion and the 24-hour intragastric pH of healthy volunteers by several investigators prior to its nation-wide clinical trial in Japan. On the other hand, the increased endocrine and exocrine secretion, such as pepsin secretion and gastrin release, and the increased turnover of gastrointestinal endocrine cells by this compound have been reported in animal models, probably due to its accumulation in the acidic environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

Synthesis and pharmacological effects of optically active 2-[4-(4-benzhydryl-1-piperazinyl)phenyl]-ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate hydrochloride.

Optically active 2-[4-(4-benzhydryl-1-piperazinyl)phenyl]ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate [(S)-(+)-1 and (R)-(-)-1] hydrochlorides were synthesized with high optical purities from (R)-(-)- and (S)-(+)-1,4-dihydro-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)- 3-pyridinecarboxylic acids [(R)-(-)-6 and (S)-(+)-6], which are available from (+/-)-6 by optical resolution using quinidine and cinchonidine, respectively. From pharmacological investigations of (S)-(+)-1 and (R)-(-)-1 such as the antihypertensive effect on spontaneously hypertensive rats and inhibition of [3H]nimodipine binding to rat cardiac membrane homogenate, the active form of 1 was defined to be the (4S)-(+)-enantiomer of 1.

Animals↗

[Characteristics of the effect of 16,16-dimethyl prostaglandin E2 on the alkaline secretion of the proximal duodenal mucosa in rats--a comparison with the effect of secretin].

Effect of intravenous infusion of 16,16-dimethyl prostaglandin E2 (16,16-dmPGE2) on the alkaline secretion of the proximal duodenal mucosa was investigated using a lumen perfusion system of the duodenal loop in rats. The following results were obtained: 1) 0.001 to 1 microgram/kg/hr of 16,16-dmPGE2 increased the alkaline secretion significantly and dose-dependently. 2) Indomethacin (5 mg/kg) inhibited the alkaline secretion and 16,16-dmPGE2 (0.1 microgram/kg/hr) completely repaired this inhibition. 3) In cysteamine-treated rats, 16,16-dmPGE2 (1 microgram/kg/hr) completely repaired the inhibition of the alkaline secretion induced by cysteamine. 4) Prostaglandin was a potent stimulator of alkaline secretion of the proximal duodenal mucosa not only in cysteamine-treated rats but also in normal rats. This is in contrast to our previous report which showed that secretin repaired the alkaline secretion in cysteamine-treated rats without affecting it in normal rats. We have concluded that prostaglandin and secretin may be involved differently in the mechanism of alkaline secretion of the proximal duodenal mucosa. Further investigation is required to elucidate the mechanism.

16,16-Dimethylprostaglandin E2↗

Tumorigenicity study of sodium erythorbate administered orally to mice.

Sodium erythorbate (SE) was administered at concentrations of 0, 1.25, or 2.5% (maximum tolerated dose, MTD) in the drinking-water to groups of 50 male B6C3F1 mice respectively. Female groups, each consisting of 50 mice, received SE in the drinking-water at concentrations of 0, 2.5 or 5% (MTD). Treatment continued for 96 wks and the experiment was terminated during wk 110. Tumors were observed at various sites including the liver, hematopoietic system, lung and soft tissue. However, at any of the sites, the tumor incidence, the time to death with tumors or the histological distribution of tumors did not differ significantly from those in the untreated control group. Thus, the present study did not demonstrate a tumorigenic effect of SE on B6C3F1 mice by means of oral administration.

Administration, Oral↗

Cysteamine-induced inhibition of mucosal and pancreatic alkaline secretion in rat duodenum.

To determine the effect of cysteamine on the alkaline secretion by the duodenal epithelium, pancreas, and Brunner's glands in relation to the pathogenesis of duodenal ulceration, the alkaline secretion by various types of duodenal loops was comparatively studied. The results obtained were as follows: (1) Cysteamine significantly reduced both mucosal and pancreatobiliary alkaline secretion in the proximal duodenum of rats. (2) The ratio of contribution of pancreatobiliary alkaline secretion to total neutralization of acid in the proximal duodenum was 55.9% under continuous perfusion. (3) There was no significant difference between the amounts of alkali per unit volume of the proximal and distal duodenal loops. (4) The alkaline substance secreted by the proximal duodenal mucosa was confirmed to be the bicarbonate. From these findings, it has been concluded that the impairment of bicarbonate secretion by the mucosal epithelium of proximal duodenum, not by Brunner's glands, plays a causative role in cysteamine-induced duodenal ulceration.

Animals↗

Malignant and benign ovarian neoplasms among atomic bomb survivors, Hiroshima and Nagasaki, 1950-80.

For 1950-80, 194 ovarian cancer cases were ascertained among the 70,030 females of the Radiation Effects Research Foundation's Life-Span Study E-85 sample, and 106 autopsied cases with benign ovarian neoplasms were ascertained among all 3,046 autopsies performed in the same sample. On the basis of microscopic review, 66% of the cancer and 84% of the benign tumor cases were classified by histologic type. The age-adjusted ovarian cancer incidence rates showed a statistically significant increase with increased exposure dose, both in the entire exposed group (P less than .01) and in the microscopically reviewed subset (P less than .01). This dose response was only significant (P less than .01) in the latter half of the study period, 1965-80. The radiation effect was higher in the younger age group at the time of the bomb (ATB) for the specific attained age or was adjusted for attained age. In general, relative risk (greater than or equal to 100 rad vs. 0 rad) did not differ by attained age, except for the youngest age group, less than 20 years old ATB, where the relative risk tended to decrease with increased attained age, although cases were few in number and follow-up study was necessary. Estimated minimum latent period for radiation-induced ovarian cancer seemed to be 15-20 years. The proportion of autopsied cases with benign ovarian tumor increased with increasing exposure dose, both in the entire series of cases (P less than .05) and in the microscopically reviewed subset. Statistical significance, however, was not achieved in the latter group (P greater than .10). The distribution of histologic types of both cancer and benign tumor of the ovary did not vary significantly with radiation dose. The data are consistent with the hypothesis that radiation injury of the ovaries and secondary excess of gonadotropic hormones are important causative factors in the development of ovarian neoplasms.

Adult↗

Early cancer and related lesions in the bronchial epithelium in former workers of mustard gas factory.

The bronchial epithelium in stepwise transverse sections was examined histologically in 66 male autopsy cases, composed of the groups of 19 mustard gas (MG) ex-workers with lung cancer, 17 MG ex-workers with non-lung cancer, 10 non-MG lung cancer cases, and 20 non-MG non-lung cancer cases. Foci of moderate or severe atypical cellular lesion or dysplasia, or of carcinoma in situ (CIS) in total slides of each group, were counted as 146 in 3,485, 72 in 2,226, 70 in 3,797, and 18 in 4,611, respectively. The relative frequency of moderate or severe dysplasia and CIS in MG exposed non-lung cancer cases resembled that found in lung cancer cases of both MG and non-MG exposed. Seven CIS lesions were detected from among all MG-exposed cases and one CIS was found in a non-MG lung cancer case. Six out of eight CIS examples were adjoined by dysplasia. A multi-variate analysis revealed a significant correlation between the incidence of atypical lesions and MG exposure, though the incidence of atypical lesions was also influenced significantly by age, smoking, and chronic bronchitis. The incidence of atypical lesions was significantly higher in cases of squamous cell lung cancer than those of other histological types, particularly small cell cancer.

Adenocarcinoma↗