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Biomedical subjects

H Shimada

Publications and source records attributed to H Shimada.

At least 757 records · Page 42Linked to original sources

Effects of combination treatment with FK506 and cyclosporine on survival time and vascular changes in renal-allograft-recipient dogs.

In our previous experiments studying the effects of FK506 on renal allografting in the dog, we encountered two major problems. One problem was anorexia and the other problem was vascular changes mainly in the recipient heart. Anorexia was generally dose dependent, but the vascular changes were seen to be more prominent at lower doses rather than at higher immunosuppressive doses. The present study was undertaken to study these two problems. A nonanorexic, vascular change-related, nonimmunosuppressive dose of FK506 was combined with a low dose of cyclosporine or prednisolone in beagle dogs after renal allografting. Treatment with either FK506 alone at a dose of 0.32 mg/kg or cyclosporine alone at 2.5 mg/kg was not effective in prolonging renal recipient survival. The recipient dogs died of rejection, and a variety of vascular changes were observed in the hearts of both groups. Combined treatment with FK506 and cyclosporine at these same doses resulted in statistically significant prolongation of the survival time of the renal recipient (P less than 0.01), and histologic studies showed that the frequency and severity of the vascular changes were suppressed in the recipient receiving the combined treatment. The combination of FK506 and prednisolone at 0.5 mg/kg was not effective in prolonging survival. Furthermore, the extent of vascular changes was similar to those found in recipients receiving FK506 alone. The data suggest that combined treatment with low doses of both FK506 and cyclosporine acted synergistically in prolonging canine renal allografts and that the vascular changes frequently seen at low doses of FK506 were reduced by additional immunosuppression with a low dose of cyclosporine.

Animals↗

Recurrence of embolic stroke in non-valvular atrial fibrillation (NVAF). An autopsy study.

From 3434 consecutive autopsied cases over 60 years of age, we performed retrospective, clinicopathological examinations on 81 patients with symptomatic embolic stroke and non-valvular atrial fibrillation (NVAF) who had not received anticoagulant therapy during their lives. Twenty-one had recurrent embolic strokes (recurrence rate: 25.9%). In the thrombotic infarction without NVAF, the recurrence rate was 21.4%. Recurrent strokes occurred earlier in the embolic infarction of NVAF than in the thrombotic infarction. Most of the lesions of initial embolic strokes were present in the territory of one middle cerebral artery (MCA), while many lesions of recurrent strokes were found in the territory of the contralateral MCA. Between the NVAF cases with and without recurrent embolic stroke, there was no significant difference in the background condition such as history of hypertension, duration of NVAF, severity of cerebral arterial atherosclerosis, heart weight, intracardiac thrombi, myocardial infarctions and infarctions in other systemic organs.

Aged↗

Nonvalvular atrial fibrillation as a cause of fatal massive cerebral infarction in the elderly.

By studying 3,408 consecutive autopsied elderly patients, we found that two thirds of the 132 massive cerebral infarctions (86) were embolic, of cardiac origin. Embolic infarction associated with nonvalvular atrial fibrillation was seen in 48 cases (36%), half due to the first stroke. Embolic infarction associated with heart disease other than nonvalvular atrial fibrillation was seen in 23 cases (17%), and that from nonbacterial thrombotic endocarditis was seen in 15 cases (11%). Thrombotic infarction or infarction of nonembolic cardiac origin was found in only 39 cases (30%). Of 56 patients with fatal massive cerebral infarction who died less than or equal to 2 weeks after their stroke, 25 (45%) had embolic strokes associated with nonvalvular atrial fibrillation. Our study shows that nonvalvular atrial fibrillation is a very important cause of fatal massive cerebral infarction in the elderly.

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Silent myocardial ischemia in the aged: a retrospective study from the evaluation of necropsy hearts.

The diagnosis of silent myocardial ischemia in the aged remains controversial. In this study to evaluate the basic state of silent ischemia in the aged, a total of 972 consecutive autopsy cases (mean 79.0 yrs of age) were analyzed in terms of coronary atherosclerotic diseases. The following results were obtained: (1) Severe coronary occlusive lesions simultaneously detected in the three major coronary arterial branches were found in 85 cases (8.7%), of which 10 (12%) had neither history of angina nor myocardial infarction (MI), which may correspond to one representation of silent ischemia. (2) There were 218 cases of MI (22.4%), of which 106 (49%) were never documented to have MI during life. The latter may correspond to unrecognized MI. It was considered to be caused by 1) small or middle-sized MI in 66 cases and 2) lateral or nontransmural MI in 29 out of 40 large MI cases (more than 4.9 cm in diameter). (3) 30 cases (54%) out of 56 fresh and large MI with a correct diagnosis revealed no chest pain. This is an incidence of painless MI in the aged. This painless group showed a significant difference in the incidence of a correct diagnosis of MI (51% vs 89%), combined arrhythmia (47% vs 79%) and the association of CVD (47% vs 11%) compared with chest pain group.

Aged↗

Interspecies homology of cytochrome P-450: inhibition by anti-P-450-male antibodies of testosterone hydroxylases in liver microsomes from various animal species including man.

P-450-male is one of the male-specific forms of cytochrome P-450 in liver microsomes of adult rats and functions as testosterone 2 alpha- and 16 alpha-hydroxylases. The purpose of this study was to examine whether forms of cytochrome P-450 cross-reactive with anti-P-450-male antibodies are present in liver microsomes of other animal species, such as male and female mice, rabbits, guinea pigs, hamsters, dogs and humans. The antibodies cross-reacted with a protein(s) in the liver microsomes of all animal species to show one or more bands on nitrocellulose paper by Western blot peroxidase-anti-peroxidase staining analysis. Qualitative as well as quantitative species differences were noted in the testosterone hydroxylases. The antibodies inhibited 2 alpha-hydroxylase in male rats, 16 alpha-hydroxylase in male rats and male and female dogs, 7 alpha-hydroxylase in female rats and male and female mice and hamsters, and 15 alpha-hydroxylase in female mice and hamsters. No clear inhibition of 6 beta-hydroxylase, which was present in all animal species, was observed. These results indicate that forms of cytochrome P-450 that are immunochemically related with P-450-male catalyze the hydroxylation of testosterone at varying positions depending on the animal species, with the exception of 6 beta-hydroxylation, which may be catalyzed by a distinct form of cytochrome P-450.

Animals↗

Effects of diltiazem on plasma uric acid level and renal uric acid excretion in rats.

The effects of diltiazem on plasma uric acid level (PUA) and renal uric acid excretion were investigated in oxonate-loaded rats. Diltiazem (0.5 mg/kg, i.v.) decreased PUA without producing uricosuria, and it decreased fractional excretion of uric acid and renal blood flow. The present results suggest that diltiazem produces hypouricemia not accompanied by uricosuria, probably by affecting uric acid metabolism, and it may also cause an alteration in the renal handling of uric acid partly due to changes in renal hemodynamics.

Animals↗

Stenotic lesions and length of the left main coronary artery in the aged.

To evaluate lesions of the left main coronary artery (LM) in the aged, a pathologic study was performed on a total of 972 consecutive autopsy cases over 60 years of age. The study population consisted of 503 men and 469 women with an average age at death of 79.0 years. In this study the degree of narrowing and length of the LM were evaluated in all cases (T), and the 141 cases with normal hearts (N) were compared with the 202 cases with myocardial infarction (MI). The following results were obtained: (1) the average coronary stenotic index (CSI) was 9.1/15 in T, 5.8/15 in N and 11.2/15 in MI (N less than MI, p less than 0.001), (2) the grade of narrowing in the LM (LMG), when 100% obstruction of the LM is counted as 5, was 1.8 +/- 0.9 in T, 1.3 +/- 0.6 in N and 2.3 +/- 1.1 in MI (N less than MI, p less than 0.001). Cases showing more than 75% narrowing of the LM were found in 58 (6%), of which 35 cases belonged to MI, but development of MI directly due to lesions in the LM was found in only 9 patients (4.5% among MI), (3) the average length of the LM (LML) was 9.4 +/- 4.4 mm in T, 9.0 +/- 4.2 mm in N and 9.3 +/- 3.8 mm in MI (N vs MI; n.s.). Cases presenting left coronary artery dominance (n = 82) or a balanced type (n = 159) showed shorter LML than those with right coronary artery dominance (n = 729) (8.5 +/- 4.0 mm, 8.8 +/- 4.6 mm and 9.7 +/- 4.4 mm, respectively, p less than 0.05), (4) in T there was a correlation between the LMG and CSI, but not between the LML and CSI. In conclusion, lesions of the LM in the aged were generally mild and the LMG showed a positive correlation with CSI and the narrowing of each coronary branch, while no relationship was noted between the LML and CSI.

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The measurement of gastric mucus using a computer image processing system.

The measurement of gastric mucus, and the effects of aspirin and some antiulcer drugs on the content or components of gastric mucus were investigated in normal rats by using a newly devised computer image processing system. The present method enabled us to separate mucus components into PAS positive mucus (PAS+), and AB positive mucus (AB+), and to measure the amount of each mucus. Aspirin induced significant decreases in both PAS+ and AB+, teprenone increased the total amount of gastric mucus (PAS+ plus AB+), secretin tended to increase AB+, and cimetidine and omeprazole caused no remarkable changes on mucus secretion. These changes in gastric mucus could be observed on both microscopic observation and with the computer image processing system. The results indicate that the computer image processing system is very useful for the measurement of gastric mucus.

Animals↗

Biosynthesis of monacolins: conversion of monacolin L to monacolin J by a monooxygenase of Monascus ruber.

The microbial metabolites monacolins J and L are specific inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme in cholesterol synthesis. The producing strain Monascus ruber M 4681 was found to convert exogenously added monacolin L to J. In this hydroxylation reaction 18O2 was incorporated into monacolin L, giving [18O]-monacolin J. The cell-free extracts of M. ruber quantitatively hydroxylated monacolin L to J, and molecular oxygen was required for the hydroxylation. The enzyme was located in the microsomal fraction and specific for NADPH. The enzyme activity was inhibited by metyrapone, carbon monoxide, sulfhydryl reagents and cytochrome c. The results indicate that monacolin L is the precursor of monacolin J, and that a monooxygenase is involved in this reaction.

Ascomycota↗

[A semiquantitative study on Alzheimer neurofibrillary tangles demonstrated immunohistochemically with anti-tau antibodies, in the brains of non-demented and demented old people].

Submitted for the study were 116 autopsy brains, from 65 non-demented people, 24 patients with dementia of Alzheimer type (DAT) and 27 patients with vascular dementia, aged between 50 s and 100 s. Formalin-fixed, paraffin-embedded coronal sections of the brains at the level of the lateral geniculate body were immunohistochemically stained with the avidin-biotin-peroxidase complex procedure, using the anti-bodies to tau protein purified from human brains (anti-tau) as the primary antibodies. Alzheimer neurofibrillary tangles (NFTs) which were specifically and selectively stained by anti-tau were semiquantitatively counted in the areas of the hippocampus, parahippocampal gyrus and lateral occipitotemporal gyrus. The results were as follows: 1) In non-demented subjects, NFTs in the hippocampus and parahippocampal gyrus were scanty in the 50 s: they increased markedly after 60 years until 90 as the patients' age increased; they tended to decrease over 90 years. In contrast, NFTs in the lateral occipitotemporal gyrus remained none or scanty, always less than 10/mm2 field, throughout the ages between 50 s and 100 s. 2) In DAT cases, NFTs in the hippocampus and parahippocampal gyrus were numerous in all cases at any ages. NFTs in the lateral occipitotemporal gyrus were also many, and always more than 10/mm2 in all cases except a few ones over 80 years of age. The numbers of NFTs of the three areas were significantly higher in DAT cases than in non-demented subjects. 3) In most cases of vascular dementia, the density and distribution pattern of NFTs were essentially similar to those of non-demented subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

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[Study on the plasma plasminogen activators in patients with malignant gynecologic tumors].

Increased plasminogen activator (PA) secretion has been observed in malignant cells and tissue and PA is thought to be involved in the processes of tumorigenesis, cancer invasion and metastasis. Recently two types of plasminogen activator--tissue type PA(tPA) and urokinase type PA(uPA)--have been detected in human plasma. In this study, to investigate the relationship between circulating PA and the malignant state, we measured the plasma PA concentrations (PA activity, tPA and uPA antigen) in 69 women with gynecologic malignancies (cervical cancer 50, ovarian cancer 19). These concentrations were compared to those in control groups of 33 women with benign gynecologic tumors (uterine tumor 8, ovarian tumor 25). An enzyme-linked immunoassay for tPA and uPA antigens was performed by the modified method described by Takada et al. (1986). PA activity was measured by the sensitive spectrophotometric assay of Verheijen et al. (1982). The blood samples were taken from an arm vein with a minimum of venous occlusion before treatment. There was no correlation between PA activity or uPA antigen levels and the malignant state. However, in the case of uterine tumors, a significantly higher concentration of tPA antigen (10.5 +/- 5.1 ng/ml) was found in patients with cervical cancer, in stage IV, than in those in the benign group (5.2 +/- 2.0 ng/ml). Moreover the tPA antigen concentration in cervical cancer, stage IV, was higher than in stages 0-III.(ABSTRACT TRUNCATED AT 250 WORDS)

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[Evaluation of a modified latex agglutination inhibitory reaction method for the quantitation of urinary estriol in pregnant women].

This study evaluated a modified latex agglutination inhibitory reaction method for the quantitation of urinary estriol in women during normal and abnormal pregnancy. The urinary levels of estriol in pregnant women measured by this method correlated with urinary and serum levels measured by radioimmunoassay. The urinary level of estriol rose during pregnancy and reached a peak at the time of delivery, after which it returned to the control level in a few days. In contrast, the urinary level of estriol in women with abnormal pregnancy did not rise during pregnancy. This method is useful to detect impaired function of the placenta in pregnant women.

Estriol↗

[Effects of an anti-prostaglandin agent added to the irrigation solution on damage to the anterior segment in monkey eyes induced by pars plana vitrectomy].

Flurbiprofen is a water-soluble, non-steroid anti-inflammatory agent and is capable of marked inhibition of prostaglandin synthesis. In a previous study by the authors, it was determined that the optimum concentration of flurbiprofen for intraocular irrigation solution in monkey retinas is 4 to 40 micrograms/ml. The present study was conducted to determine the optimum concentration of flurbiprofen for the irrigation solution, as well as to evaluate its toxic effects on the anterior segment tissues. In a pilot experiment, flurbiprofen was injected directly into the anterior chamber of pigmented Japanese rabbits to investigate its overall toxicity and to quantify the concentration at which it could become toxic to the cornea. This experiment showed that aqueous concentrations of flurbiprofen greater than 1,000 micrograms/ml were toxic. In a subsequent study, the twelve eyes of six Japanese monkeys (Macaca fuscata) underwent vitrectomy using balanced salt solution (BSS) containing concentrations of flurbiprofen from 4 to 800 micrograms/ml and BSS alone. This experiment showed that BSS containing 4 to 100 micrograms/ml of flurbiprofen prevented post-operative occurrence of edema in non-pigmented epithelial cells in the ciliary body. Furthermore, it was observed that infiltration of inflammatory cells into the trabecular meshwork and swollen mitochondria in the corneal endothelial cells were likewise prevented. This is thought to be due to the pharmacological action of flurbiprofen; which has an inhibitory effect on leucocyte migration and prostaglandin synthesis as well as stabilization of the cell membrane. However, these effects were not observed in the eyes vitrectomized with flurbiprofen concentrations between 400 and 800 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[G staining].

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Azure Stains↗