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Biomedical subjects

H Fushimi

Publications and source records attributed to H Fushimi.

At least 55 records · Page 3Linked to original sources

Renal changes of streptozotocin-induced diabetic rats fed a low-zinc diet.

The changes in kidneys of streptozotocin (STZ)-induced diabetic rats fed a low-zinc (LZ) diet were observed. Calcium deposits were detected in the LZ-diabetic groups from the 2nd to the 8th week. The deposits were mainly detected in the corticomedullary junction, and found in the tubular lumina and epithelial cytoplasm and interstitium. Tubular morphological changes, including luminary distension, epithelial flattening, and paleness of cytoplasm and nuclei, were observed near the calcium deposits in the LZ-diabetic group over the 2nd week. Moreover, at the 8th week, wedge-shaped vasogenic lesions were found on the surface of the renal cortex in the LZ-diabetic group. No changes were detected in the control for the LZ or in the diabetic group fed a standard (SC) diet. When STZ was administered, plasma glucose level in groups fed LZ or SC diet increased in the 1st week, and over the 2nd week, glucose level was maintained at more than 400 mg/dL. Glucose level of the LZ-diabetic group did not differ from that of the SC-diabetic group. However, urinary N-acetyl-beta-D-glucosaminidase activity of the LZ-diabetic group at the 8th week was significantly higher than that of the SC-diabetic group. These findings suggested that low-zinc diet hastens renal damages in diabetic rats.

Animals↗

Diabetes mellitus and cerebral vascular disease.

Non-fatal or small infarction, especially with multiple occurrence, is a feature of cerebrovascular disease complicating diabetes mellitus. The atherosclerosis of the cervical and cerebral arteries, especially in the posterior circulation, in diabetes is more severe than that in non-diabetics. We reviewed the incidence of vascular lesions, and clinical history in 25 male and 26 female diabetic autopsy subjects. In addition, the long-term effects of blood pressure and glucose values were evaluated in 267 stroke patients without cerebral embolism, 99 of whom had diabetes mellitus. Asymptomatic cerebral infarction is not rare in diabetic subjects, and can now be accurately pathologically and clinically evaluated using MRI. The results of our study indicate that high blood pressure and poor blood glucose control are associated with the higher incidence of cerebral infarction in the diabetic patients.

Arteriosclerosis↗

Asymptomatic lacunes and their relationship to intellectual disturbances.

We studied risk factors and the relationship of lacunes to diabetes mellitus, age, hypertension, hyperlipidemia, atherosclerosis and also to intellectual impairment, comparing brain MRI (magnetic resonance imaging) findings to the multiple risk factors and the results of a cube-handdrawing test. Brain MRI was performed using a Shimazu SMT-150, 1.5 Tesla, in 118 asymptomatic NIDDM and 39 asymptomatic nondiabetic patients. In diabetics, 65 had lacunes and the incidence of lacunes was significantly higher in diabetics with coronary insufficiency by ECG and hypertension, but not significantly different in those with or without the other risk factors. Cube hand-drawing is a good indication of space cognition ability supported by the wide association areas of the brain. Drawing was tested in 41 diabetics and 39 nondiabetics. Correlation of lacunes to deformity in drawing and age was high in both diabetics and nondiabetics. Multiple lacunes were closely related to intellectual impairment.

Aged↗

Zinc deficiency exaggerates diabetic osteoporosis.

Streptozotocin diabetic rats showed an increase of bone fragility (11.9 +/- 2.1 kg/cm2 vs. 16.8 +/- 2.0, P < 0.005) which was normalized by insulin treatment (18.3 +/- 4.2), indicating that osteoporosis was induced in diabetic rats. The rats were fed a zinc-deficient diet (0.16 mg/100 g) or a control diet (5.2 mg/100 g). This mild zinc-deficient diet did not lower the serum zinc level. The cortical bone of diabetic rats was shown to be markedly thinner by microscopic examination of ground cross-sections of the tibia. Zinc deficiency induced a reduction in the calcium content of diabetic bone when compared with the rats on a control diet. Urinary excretion of calcium and phosphorus was significantly increased in diabetic rats, and increased further when the rats were fed a zinc-deficient diet. Moreover. the bone calcium and phosphorus concentrations were significantly lower in these animals. These changes in the zinc-deficiency rats were not reversed by insulin treatment. Our findings suggest that osteoporosis in the diabetic rats was due to thinning of the bone cortex secondary to mineral loss and can be reversed by insulin treatment, and that these skeletal changes are greatly enhanced by mild zinc deficiency. In addition the effects of zinc deficiency cannot be completely reversed by insulin treatment.

Alkaline Phosphatase↗

Effects of insulin and 1 alpha-hydroxy vitamin D3 on streptozotocin-induced diabetic rats fed a low zinc diet.

Streptozotocin-induced diabetic rats (LZ-DM rats) developed nephrocalcinosis after being fed a low zinc diet for 4 weeks. However, administration of 1 alpha-hydroxy vitamin D3 (1-OHD3) or insulin inhibited the formation of nephrocalcinosis. The urinary calcium level increased when 1-OHD3 was administered to these rats, but decreased in the group receiving insulin. It was also observed that the femur recovered its hardness when insulin was administered, although the hardness in the LZ-DM rats remained lower than that of the control rats. Rat femur hardness, however, did not completely recover with 1-OHD3 treatment. These results indicate that the effects of insulin and 1-OHD3 differ, even though nephrocalcinosis was reduced by administration of either insulin or 1-OHD3. It appears that insulin assists bone formation, and the 1-OHD3 hastens calcium excretion.

Animals↗

[Chronic daily oral low-dose etoposide therapy for an aged patient with aggressive lymphoma: a successful case report].

A 72-year-old female from Fukuoka Prefecture was admitted to our hospital complaining of puffy face and general malaise in April, 1992. Physical examinations revealed generalized lymphadenopathy and hepatosplenomegaly complicated with superior vena cava syndrome. A histological diagnosis of diffuse large cell-type malignant lymphoma was made by cervical lymph node biopsy according to the Working Formulation. Immunohistochemical staining showed the lymphoma cells were of T cell lineage (CD43+). Though anti-human T lymphotropic virus type I (HTLV-I) antibody was positive, southern blot analysis of the cells did not reveal monoclonal integration of HTLV-I proviral DNA. Her liver and renal function were almost normal but there was slight elevation of LDH. Considering her age, oral administration of low-dose etoposide (25 mg/day) was started. In 4 days, her lymph nodes decreased in size with subjective improvements. Ten weeks later, examinations of the hand, ultrasonogram and CT scan showed lymphadenopathy and hepatosplenomegaly had disappeared completely. The neutrophil count was consistently above 1,500/microliters, with no remarkable adverse effects and only a moderate degree of alopecia. Thus, low-dose etoposide therapy was considered to be very useful in such a case of malignant lymphoma in the elderly.

Administration, Oral↗

Detection of large cell component in small cell lung carcinoma by combined cytologic and histologic examinations and its clinical implication.

BACKGROUND: In the classification recently proposed by the Pathology Committee of International Association for the Study of Lung Cancer, small cell lung carcinoma (SCLC) was divided into three subtypes: pure SCLC, mixed small cell/large cell carcinoma (mixed SC/LC), and combined SCLC. METHODS: To examine the clinical utility of this classification, histologic specimens, cytologic specimens obtained by brushing or fine-needle aspiration, and sputum cytologic specimens from 430 patients with SCLC were reviewed. RESULTS: When the subtype of SCLC was determined from the biopsy specimen, cytologic specimen obtained by brushing or fine-needle aspiration, and sputum cytologic specimen, the frequency of mixed SC/LC was 25 of 299 (8.4%), 75 of 400 (18.8%), and 8 of 232 (3.4%), respectively. Whatever the diagnostic method, patients with mixed SC/LC showed a poorer response to treatment and worse prognosis than those with pure SCLC: a median survival of 144 days versus 285 days when classified with the use of biopsy specimens; 160 days versus 275 days with cytologic specimens obtained by brushing or fine-needle aspiration; and 47 days versus 259 days with sputum cytologic specimens, respectively. CONCLUSIONS: These findings showed that mixed SC/LC should be separated from pure SCLC as a distinctive group and that cytologic studies of specimens obtained by brushing or fine-needle aspiration were sensitive and useful procedures for this purpose.

Adult↗

Tumor necrosis factor and endotoxin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in the rat.

This study examines whether tumor necrosis factor and endotoxin are involved in the pathogenesis of primary nonfunction of graft and pulmonary complication after orthotopic liver transplantation. Livers from Lewis rats were stored for either 1 or 4 hr in ice-cold Euro-Collins solution (1-hr storage and 4-hr storage group, respectively). Subsequently, donor livers were implanted orthotopically. In some experiments, anti-tumor necrosis factor antibody was administered intravenously before and immediately after the surgery into animals that received livers stored for 4 hr. Blood samples for the measurement of tumor necrosis factor and endotoxin were collected by way of an indwelling catheter placed in the suprahepatic vena cava. Serum tumor necrosis factor was elevated at all time points studied postoperatively in rats of the 4-hr storage group; however, tumor necrosis factor was not detected in the serum in the 1-hr storage group. Endotoxin was also elevated significantly in the serum of the former group compared with levels in the serum of the latter group. The peak value of endotoxin occurred 1 hr earlier than that of tumor necrosis factor, suggesting that the rise in endotoxin stimulated release of tumor necrosis factor. The histological study of livers stored for 4 hr showed substantial hepatocellular degeneration 24 hr after surgery, whereas hepatocellular damage was minimal in the 1-hr storage group. Serum ALT levels 24 hr after the operation in the 1-hr and 4-hr storage groups were 169 +/- 46 IU/L and 374 +/- 41 IU/L (mean +/- S.E.M., p less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

Profound vasoconstrictive effect of cigarette smoking in diabetics with autonomic neuropathy.

Changes in leg skin temperature during and after cigarette smoking were examined in 25 diabetics with autonomic neuropathy (au-neuropathy) (mean age 52 +/- 2 years) and 23 without (mean age 49 +/- 2 years), and 15 normal controls (mean age 49 +/- 2 years) using a Thermoviewer JTG 3300. All subjects were habitual smokers. Japanese Seven Star cigarettes (each containing 1.2 mg nicotine) were used for the test. Tender brand cigarettes (0.3 mg) were used additionally to compare the effect of nicotine content on the results. The smoking-stimulated thermographic pattern in the control group was rather flat, with a slight decrease in temperature followed by a slight increase before returning to the baseline level 15-20 min after smoking. The frequency of the typical temperature decreasing pattern, characterized by a profound decrease and gradual return to the baseline level in about 1 h, was significantly higher in the diabetic group than in the control group (33/48 vs 1/15; P less than 0.005). A comparison of the two diabetic subgroups revealed that the frequency was considerably higher in the subgroup with au-neuropathy (23/25 vs 10/23). These results suggest that au-neuropathy affects smoking-induced vasoconstriction in diabetic subjects. The maximum temperature decreases recorded were 1.5 +/- 2.0 and 2.69 +/- 0.24 degrees C in the controls and diabetics with au-neuropathy, respectively. The effect of Tender cigarettes with a low nicotine content was much weaker than that of Seven Star, which further suggests that smoking-induced vasoconstriction was also nicotine-dependent.

Diabetic Angiopathies↗

[Adult T cell leukemia/lymphoma with hyperprolactinemia: successful treatment by OK432 and PSK].

A 48-year-old woman was admitted in September 1987, because of lumbago and galactorrhea. Peripheral blood analysis showed neutrophilia and eosinophilia without abnormal lymphocytes. The antibody to adult T-cell leukemia (ATL) virus-associated antigen was detected and a hyperprolactinemia was observed. The blastogenic responses to PHA, ConA and PWM were lowered. Brain CT and MRI scannings showed no abnormalities in the hypophysis and hypothalamus, but abdomen CT revealed markedly enlarged abdominal lymph nodes. Two months after the administration of OK432 and PSK, the lymph node swellings disappeared and the responses to PHA, ConA and PWM were normalized, but hyperprolactinemia and galactorrhea persisted. After four months of the remission period, the patient developed lymph node swellings again, and was diagnosed from the biopsy specimen of the retroperitoneal lymph node as having malignant lymphoma of diffuse mixed cell type. Southern blot analysis showed a monoclonal integration of HTLV-I proviral DNA. Despite repeated combination chemotherapies, she died of pneumonia in February 1989. Autopsy revealed marked infiltrations of lymphoma cells in the liver, spleen and lungs, but no abnormality accounting for hyperprolactinemia was detected in the suprasellar regions. This case was of interest in that immunotherapy was effective in achieving a remission and in normalizing immuno-parameters in ATLL.

Adjuvants, Immunologic↗

[Anti-allergic effects of tazanolast [butyl 3'-(1H-tetrazol-5-yl) oxanilate, WP-833] metabolites].

WP-833 is an orally active new antiallergic drug. The effects of WP-833 metabolites on experimental allergic reactions were investigated in various animal models. MTCC [3'-(1H-tetrazol-5-yl) oxanilic acid], the main metabolite of WP-833, dose-dependently inhibited 48-hr homologous passive cutaneous anaphylaxis (PCA) in rats and 8-day PCA in guinea pigs after intravenous administration. The inhibitory effect of MTCC on PCA was nearly equal to that of WP-833. MTCC also inhibited 48hr PCA in rats after the peroral administration, although its inhibitory effect was about 6 times weaker than that of WP-833. MTCC also showed a dose-dependent inhibition on the release of histamine or slow reacting substance of anaphylaxis (SRS-A) from passively sensitized rat peritoneal mast cells and guinea pig lung fragments in vitro with a similar potency to WP-833. MTA [3-(1H-tetrazol-5-yl) aniline] and MTAA [3'-(1H-tetrazol-5-yl) acetanilide], other metabolites of WP-833, inhibited PCA and anaphylactic histamine release from rat peritoneal mast cells at considerably higher doses than WP-833, and they showed no effects on the release of histamine and SRS-A from guinea pig lung fragments. Moreover, only small amounts of MTA and MTAA were detected in the blood after the oral administration of WP-833. From these results, it was suggested that MTCC may be the main active metabolite of WP-833.

Administration, Oral↗

Low testosterone levels in diabetic men and animals: a possible role in testicular impotence.

Poorly controlled NOD spontaneously diabetic mice were proven to have significantly less plasma and testicular testosterone than well-controlled diabetic mice (489 +/- 15 ng/dl and 3.89 +/- 0.79 micrograms/100 g tissue, vs. 176 +/- 24 and 9.00 +/- 1.24, respectively), and these in turn had significantly less than NOD non-diabetic control mice. These data were consistent with our previous observation of a decrease in total plasma and testicular testosterone levels in streptozotocin diabetic rats. A greater difference between total plasma testosterone levels and free testosterone levels was found in streptozotocin diabetic rats (17 +/- 4 ng/dl vs. 91 +/- 7 ng/dl) than in control rats (660 +/- 141 vs. 352 +/- 77). Fat droplets, depicting blocked testosterone synthesis, were found in the testicular Leydig cells of streptozotocin diabetic rats and disappeared with insulin treatment. No difference was found among plasma total testosterone concentrations in people in different stages of diabetes, as had been previously reported. However, human diabetic males, free of complications but poorly controlled, had less free testosterone than those without complications but well controlled (18.0 +/- 2.0 pg/ml vs. 22.8 +/- 1.3), who in turn had significantly less than age-matched controls (25.3 +/- 1.1 pg/ml). These data suggest gonadal dysfunction in diabetes mellitus.

Animals↗

Deficiency of the core proteins of dermatan sulphate proteoglycans in a variant form of Ehlers-Danlos syndrome.

A variant form of Ehlers-Danlos syndrome with single adrenocorticotrophic hormone (ACTH) deficiency and mild diabetes mellitus was studied by immunohistochemical and biochemical analyses of the connective tissue. The patient exhibited features characteristic of the Ehlers-Danlos syndrome, such as fragility, hyperextensibility, and bruisability of the skin and large veins were readily seen, but no hypermobility of any joint was detectable. Biochemical studies of the connective tissue confirmed that the apparent synthesis of collagens was within normal limits, but the deposition of the major proteoglycan in the skin of this patient was markedly reduced, mainly because the synthesis of core protein of dermatan sulphate proteoglycan was defective.

Adrenocorticotropic Hormone↗