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Biomedical subjects

M Fujishima

Publications and source records attributed to M Fujishima.

At least 757 records · Page 42Linked to original sources

Sex differences in diabetes induced by neonatal streptozotocin treatment in spontaneously hypertensive rats.

We examined the sex differences in the development of diabetes due to neonatal streptozotocin (STZ) treatment in spontaneously hypertensive rats (SHR) which are more prone to diabetes than normotensive rats. Male and female SHR were intraperitoneally injected with various doses of STZ at 2 days after birth. In those treated with vehicle or 25 mg/kg of STZ, there were no sex differences in plasma glucose levels, which changed little during the 12 weeks of observation. When treated with 50 mg/kg of STZ, however, male SHR developed overt hyperglycemia greater than 300 mg/dl plasma glucose after 8 weeks of age, while females showed a minimal change in plasma glucose levels. When given 75 mg/kg of STZ, female rats developed overt hyperglycemia at 4-6 weeks of age, during which time male SHR showed no apparent hyperglycemia. At 8 weeks or later, however, both males and females had similarly high levels of plasma glucose. Glycosylated hemoglobin at 12 weeks was compatible with plasma glucose levels in each group. The present results indicate that there are sex differences in susceptibility to neonatal STZ treatment and in development of hyperglycemia.

Aging↗

Influence of age on deterioration of the remnant kidney in uninephrectomized rats.

To investigate the influence of age on the remnant kidney, unilateral nephrectomy was performed in rats at 1 day (group N-0), 2 weeks (group N-2), 4 weeks (group N-4) or 8 weeks (group N-8) of age. Serial changes in urinary protein during 48 weeks after the uninephrectomy and blood chemistries and renal histology at week 48 were compared between the groups. The increase in proteinuria was significantly greater in groups N-0, N-2 and N-4 than in group N-8 from week 32 to week 48 after the uninephrectomy. There was no significant difference in urinary protein between groups N-0, N-2 and N-4. Hypoproteinaemia and hypoalbuminaemia were also more severe in groups N-0, N-2 and N-4 than in group N-8 at week 48. A compensatory renal growth in groups N-0 and N-4 was significantly greater than that in group N-8 at week 48 after the uninephrectomy. Focal and segmental glomerular sclerosis, a characteristic finding in the uninephrectomy groups, was significantly more marked in groups N-0, N-2 and N-4 than in group N-8 at week 48. We conclude that uninephrectomy at young ages leads to increased incidence of glomerular sclerosis in rats compared with uninephrectomy in the adult.

Aging↗

Effect of different levels of protein intake on renal deterioration and nutritional state in experimental renal disease.

We examined the effects of various levels of dietary protein on the course of adriamycin-induced nephropathy in rats fed with high (30%), intermediately low (10%) or strictly low (5%) protein diets for 24 weeks. In the rats fed on the 30% protein diets, there were massive proteinuria, progressive increases in serum creatinine and focal glomerular sclerosis associated with severe tubulo-interstitial changes. With the 5% dietary protein, proteinuria was decreased, the levels of serum creatinine were preserved within normal ranges and renal histological changes diminished. Weight loss and hypoproteinaemia were more marked. With intermediate protein restriction (10% protein), renal function and plasma protein were preserved but body weight did not increase normally. Aggregated human immunoglobulin G, which had been intravenously injected at weeks 12 and 24, accumulated in the glomeruli more densely in rats fed on the 30% protein diet than in those fed on the 10% or 5% protein diets. We tentatively conclude that functional and histological deterioration of focal glomerular sclerosis can be prevented by appropriate restriction of dietary protein; however, severe protein restriction does aggravate nutritional states.

Animals↗

Influence of the sympathetic nervous system and vasopressin on the blood pressure lowering effect of nifedipine in deoxycorticosterone acetate-salt hypertensive rats.

1. The role of the sympathetic nervous system and the effect of vasopressin (AVP) on the hypotensive action of nifedipine (Nf) were evaluated in conscious, unrestrained normotensive and DOCA-salt hypertensive rats. 2. The hypotensive response to Nf was much greater in DOCA rats than in the controls. 3. Solitary blockade of the sympathetic nervous system or AVP, did not alter the Nf effect in either DOCA or control rats. However, a combination clearly diminished the effect of Nf in the DOCA group, but enhanced it in the controls. The inhibition of angiotensin II (ANG II) augmented the hypotensive effect of Nf in control animals, but not in the DOCA rats. The percentage fall in blood pressure with Nf was much the same in both groups after the combined inhibition of the sympathetic nervous system and AVP. 4. The enhanced hypotensive action of Nf in DOCA rats may be dependent on the hyperactivity of the sympathetic nervous system and AVP, which facilitates calcium influx, and in the normotensive animals the depressor response to Nf may relate to blockade of the calcium influx, independent of the sympathetic nervous system, AVP and ANG II.

Analysis of Variance↗

A profile of plasma branched chain amino acids in a totally pancreatectomized patient: effects of glucagon replacement under a steady feeding state.

Physiological amounts of glucagon replacement brought about the reduction of plasma branched chain amino acid levels as well as glucogenic amino acid levels in a totally pancreatectomized patient who was under a steady feeding state, i.e., constant administration of an elemental diet combined with continuous subcutaneous insulin infusion. This finding suggests that glucagon may play a physiological role not only on glucogenic amino acids but also branched chain amino acids in plasma in feeding state.

Amino Acids, Branched-Chain↗

Thyroid disorders in the general population of Hisayama Japan, with special reference to prevalence and sex differences.

Serum triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) and thyroid autoantibodies (TAA) to either microsome or thyroglobulin were measured in 1251 samples from the general population, 546 males and 705 females, aged 40 or over in Hisayama, a Japanese rural town. TAA was positive in 7.7% of men and 15.0% of women, and the male/female ratio was 1:2. This ratio was markedly different from those in hospital patients with thyroid disorders where ratios such as 1:8 for chronic thyroiditis and 1:4 for Graves' disease were found. Among the study subjects, definite hyperthyroidism was found in 0.2%, borderline hyperthyroidism in 0.7%, overt hypothyroidism in 0.3%, latent hypothyroidism in 4.2%, and non-thyroid illness in 2.4%. Overt thyroid dysfunction was more evident in women, while latent thyroid dysfunction or non-thyroidal illness was equally prevalent in men and women. These results indicate that the incidence of immunologically or functionally latent thyroid disorders is rather higher than expected, in both women and men. Some unknown factor(s) might act as a trigger to manifest thyroid dysfunction, mainly in females.

Autoantibodies↗

Acid thyroglobulin protease activities in human diseased thyroid glands.

The lysosomal acid protease is thought to be a main enzyme in hydrolysis of thyroglobulin. The protease activity of lysosome-rich fractions of various diseased thyroid glands were assayed by the sensitive and reproducible method developed in our laboratory. They included 78 diseased thyroid glands; 37 thyrotoxic goitres, five irradiated thyroids, five Hashimoto's thyroiditis, one granulomatous thyroiditis, six multinodular goitres, 14 'cold' adenomas, four 'hot' adenomas with three paranodular tissues, and six carcinomas. Fifteen paranodular tissues of cold and solitary thyroid nodules were served as controls. The protease activities were significantly increased in thyroid tissues of thyrotoxic goitres, Hashimoto's thyroiditis, adenomas and adenocarcinomas. In thyrotoxic goitres, the protease activity correlated well with the mean area size of colloid follicles. The 'hot' adenomas had higher protease activity than 'cold' ones. The protease activity of multinodular goitres was nearly normal. Only the irradiated thyroid glands had low protease activities. Therefore the high protease activities in hyperfunctioning goitres seem to reflect hormone secretory activities. On the other hand, cold neoplastic goitres seem to have lysosomal protease activities which are not associated with thyroidal secretory process. The assay of acid protease activity will be useful to understand the pathophysiology of lysosomal system in diseased thyroid glands.

Aspartic Acid Endopeptidases↗

Severe disability related to cerebral stroke: incidence and risk factors observed in a Japanese community, Hisayama.

To elucidate the incidence of severe disability due to cerebral stroke and its related factors, prospective data of 1,621 Hisayama residents aged 40 and over were examined. Severe disability resulting from stroke was defined as patients who were unable to dress, take care of their toilet needs, and feed themselves without assistance, or who required a wheel chair for ambulation three months after the most recent episode. During 20 years of follow-up 255 stroke patients were observed among the sample population. The annual incidence of stroke per thousand was 9.8, and rate of severe disability was 2.8 for men and 6.4 and 2.0 for women, respectively. Of the 74 cases with severe disability, approximately 92% were attributed to cerebral infarction. Related factors to severe disability due to cerebral infarction were recurrent attacks, hypertension, changes in ocular fundi and diabetes mellitus among predispositions and quadriplegia or muscular contraction, and intelligent or mental disorders among inhibiting factors for functional recovery. Furthermore, in 59 autopsy cases with multiple cerebral infarctions, the frequency of disability increased as the number of infarcts increased. Hypertension and diabetes mellitus, as risk factors for cerebral infarction and factors inhibiting post-ictal functional recovery were discussed.

Adult↗

Increased arachidonic acid composition of phospholipids in colonic mucosa from patients with active ulcerative colitis.

The long chain fatty acid composition of phospholipids in colonic mucosa was determined by high performance liquid chromatography in nine patients with active ulcerative colitis and eight healthy controls. The arachidonic acid composition was 12.5 +/- 1.4 mol % (mean +/- 2 SEM) in the inflamed colonic mucosa from the patients with active ulcerative colitis and 6.8 +/- 1.2 mol % in the intact mucosa from healthy controls (p less than 0.001). In the inflamed colonic mucosa, oleic acid and palmitoleic acid were concomitantly decreased (p less than 0.001 and p less than 0.02, respectively), while docosahexaenoic acid was increased (p less than 0.05). Histopathological examination showed that there was a three fold increase in the cell density of inflammatory infiltrate in the lamina propria of the inflamed colonic mucosa (p less than 0.001). The cell density of inflammatory infiltrate correlated with the arachidonic acid composition of phospholipids in colonic mucosa (r = 0.89, p less than 0.005). These findings indicate that inflammation alters the long chain fatty acid composition of phospholipids in colonic mucosa. The observed increase in the arachidonic acid composition of phospholipids in inflamed colonic mucosa may contribute to the enhanced arachidonic acid metabolism in patients with active ulcerative colitis.

Adolescent↗

Cerebrospinal fluid lactate in patients with hepatic encephalopathy.

Cerebrospinal fluid (CSF) lactate and pyruvate concentrations were determined in 16 patients with hepatic encephalopathy before and/or after treatment. CSF lactate was significantly increased to 1.92 +/- 0.11 mmol/l in hepatic encephalopathy before the treatment in comparison to 1.40 +/- 0.05 mmol/l in control subjects. In 9 of 11 patients with moderate or stage 2 encephalopathy, CSF lactate levels were below 2 mmol/l. In contrast, in 4 of 5 patients with stage 3-4 encephalopathy, CSF lactate levels were higher than 2 mmol/l. CSF lactate was decreased with the recovery of neurological symptoms by the treatment. These findings indicate that CSF lactate levels reflect the severity of metabolic impairment of the brain. Hypocapnia was frequently observed in these encephalopathic patients, and arterial PCO2 correlated inversely with CSF lactate and linearly with CSF HCO3-, suggesting that CSF lactic acidosis contributes to hyperventilation in hepatic encephalopathy. It is concluded from present results that metabolic disorder of neuronal cells might be one of the important factors for the development of hepatic encephalopathy.

Acid-Base Equilibrium↗

Cerebral hemorrhage in patients on maintenance hemodialysis. CT analysis of 25 cases.

Site of hematoma and clinical outcome in cerebral hemorrhage were analyzed in 25 maintenance hemodialysis (HD) patients and compared with those in 27 non-HD patients. Ganglionic-thalamic hemorrhage was found in 56% of HD and 74% of non-HD patients, lobar hemorrhage in 36% and 11%, respectively. Size of hematoma, expressed as a ratio (%) of hematoma area to entire brain on CT slice, was 6.5 +/- 4.2% (mean +/- SD) in HD, being significantly larger than that of 4.7 +/- 3.5% in non-HD patients (p less than 0.05). Mortality rate was 60% in HD patients, nearly twice as much as the 33% in non-HD patients. The hematomas were significantly larger in the death cases (8.4 +/- 3.7%) than the survivors on HD (3.6 +/- 3.1%, p less than 0.005). Likewise, the fatal cases in the non-HD group had bigger hematomas (6.9 +/- 4.3%) than the non-fatal ones (3.6 +/- 2.4%, p less than 0.05). Intraventricular hemorrhage (IVH) was found in 40% of HD and 44% of non-HD patients. Hematomas were significantly larger in HD patients with IVH (9.3 +/- 3.3%) than in those without IVH (4.6 +/- 3.7, p less than 0.005). Ninety percent of the HD patients with IVH but only 42% of non-HD patients died of hemorrhage. Hypertension was equally seen in HD (76%) and non-HD patients (74%). It is concluded that in HD patients cerebral hemorrhage is more severe in terms of hematoma size, association of IVH and clinical outcome. Chronic systemic heparinization might be responsible to the severity in HD patients.

Adult↗

Effects of acute reduction in blood pressure on the renal function of rats with diseased kidneys.

We studied the effect of an acute reduction in blood pressure, induced by diltiazem, on the renal hemodynamics of spontaneously hypertensive rats (SHR) with focal glomerular sclerosis, as induced by adriamycin (ADR). Renal plasma flow (RPF) and glomerular filtration rate (GRF) were determined before (first period) and during (second period) intravenous infusion of diltiazem in SHR 4-6 weeks after ADR treatment (group 1), 14-20 weeks after treatment (group 2), and in controls without treatment (group 3). Rats in group 1 had a normal renal function (RPF and GFR) in the first period, which was not significantly different from control rats (group 3). Rats in group 2 showed a reduced renal function, reflected by the lower levels of RPF and GFR, compared with groups 1 and 3. Mean blood pressure decreased equally in the 3 groups by about 50 mm Hg after the infusion of diltiazem. During the second period, 13.4 or 12.4% increase in RPF and a 29.0 or 23.2% elevation of GFR were evident in groups 1 or 3, respectively. In contrast, a 32.0% reduction of RPF was observed in group 2, accompanied by a 25.7% decline of GFR. A reduction in renal function (percent change of RPF or GFR) significantly correlated with the severity of renal dysfunction (RPF or GFR in the first period) in group 2. Thus, the renal function of rats with diseased kidneys is sensitive to an acute reduction in blood pressure by diltiazem, and the sensitivity depends on the degree of renal deterioration.

Animals↗

Reevaluation of the effects of methylmercaptoimidazole and propylthiouracil in patients with Graves' hyperthyroidism.

The effects of methylmercaptoimidazole (MMI) and propylthiouracil (PTU) were compared in patients with Graves' hyperthyroidism. Firstly, the duration of action of the drugs was studied by the perchlorate discharge test, which was performed 2, 12, or 24 h after administering a single dose of 15 mg MMI or 300 mg PTU. After 2 h, the 9 MMI-treated patients who were tested had marked discharge (mean +/- SD, 65.0 +/- 15.8%), as did the 6 patients treated with PTU (57.6 +/- 26.6%). The mean values for the percent discharge 12 and 24 h after drug administration were 34.9 +/- 31.9% (4 patients) and 36.5 +/- 26.9% (69 patients), respectively, in the MMI group and 19.1 +/- 11.7% (11 patients) and 8.6 +/- 10.5% (7 patients) in the PTU group, indicating that the effect of MMI lasted longer. Secondly, the clinical effects of long term administration of the drugs were compared in a different group of patients with Graves' hyperthyroidism. Within 5 weeks after the onset of treatment, 34 (52%) of 66 patients treated with MMI (10 mg, 3 times daily) were euthyroid, while only 1 of 17 patients treated with PTU (100 mg, 3 times daily) was euthyroid. The average time required to achieve euthyroidism, namely normal serum T3 and T4 levels, was significantly shorter in the MMI group [6.7 +/- 4.6 (+/-SD) weeks] than in the PTU group (16.8 +/- 13.7). In spite of the well known effect of PTU on the extrathyroidal conversion of iodothyronines, the serum T3 level normalized much faster with MMI than with PTU. These results indicate that in our patient population 15 mg MMI had a longer inhibitory effect on the organification of iodide than did 300 mg PTU, and that MMI was more rapidly effective in the treatment of Graves' hyperthyroidism.

Adult↗

Blood pressure changes in spontaneously hypertensive and normotensive rats with neonatal streptozotocin induced type 2 diabetes.

We examined the blood pressure changes in hypertensive and normotensive rats with Type 2 diabetes induced by neonatal streptozotocin (STZ) treatment. STZ was intraperitoneally injected at 2 days of age with the dose of 25, 50 and 75 mg/kg for male spontaneously hypertensive rats (SHR) and with 75, 100, 125 and 150 mg/kg for male normotensive Wistar Kyoto rats (WKY). Blood pressure was measured by indirect tail-cuff method until 12 weeks of age. STZ-treated SHR, of which plasma glucose and glycosylated hemoglobin increased and body weight decreased with the dose of STZ, developed and maintained hypertension, same as did the vehicle-treated control SHR. On the other hand, STZ-treated WKY which developed only mild hyperglycemia lost body weight with the dose of STZ but the blood pressures rose slightly, these changes being correlated with the glycemic levels. The explanation for these differences between SHR and WKY remained to be elucidated.

Animals↗