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Biomedical subjects

M Shimizu

Publications and source records attributed to M Shimizu.

At least 1,027 records · Page 57Linked to original sources

Current clinical trials of cognitive enhancers in Japan.

The primary purpose of this paper is to review the clinicopharmacological properties of brain metabolism enhancers available in Japan. The major target symptoms of brain metabolism enhancers are peripheral psychiatric symptoms (symptoms of the noncognitive type) of demented patients. A review of double-blind studies of major brain metabolism enhancers in Japan revealed that 60-70% of patients were better than slightly improved and 20-30% better than moderately improved in treatment of cerebrovascular disorders. In treatment of Alzheimer-type dementia, on the other hand, the better than slightly improved patients comprised 30-70% in mild to moderately demented cases. Severe cases of dementia showed a lower improvement rate. The incidence of side effects ranged from 4-9%. In our geriatric outpatient clinic, 72.5% of elderly demented patients (85% were mild-moderate dementia) exhibited better than a moderate improvement with combined psychopharmacotherapy, so far as peripheral psychiatric symptoms were concerned. Psychophysiological analysis of cases in terms of improvement of scores on Hasegawa's dementia scale strongly suggested that sporadic cases with cognitive improvement were brought about, at least secondary to improved vigilance, or with improved concentration and attention.

Alzheimer Disease↗

Posttransfusion fulminant hepatitis B associated with precore-defective HBV mutants.

Fulminant hepatitis B developed in 8 recipients of blood units without detectable hepatitis B surface antigen on routine screening. All 124 hepatitis B virus (HBV) DNA clones propagated from their sera possessed defects in the precore region. A point mutation from guanine to adenine at nucleotide 83, converting codon 28 for tryptophan (TGG) to a stop codon (TAG), was the commonest, and it was found in all 113 clones from 7 cases. The remaining case displayed 1 clone with this point mutation and 10 clones with an insertion of 2 base pairs after nucleotide 26. Antibody to hepatitis B core antigen (anti-HBc) was detected in a high titer in 1 of 10 pilot plasma samples of blood units transfused to this case. HBV DNA clones propagated from it exhibited the same precore-region defects as those from the recipient. On the basis of these results HBV mutants, defective in the precore region, would appear to be responsible for posttransfusion fulminant hepatitis B, and the exclusion of blood units with high-titered anti-HBc would be efficacious in preventing it.

Amino Acid Sequence↗

Human gnathostomiasis.

Two patients became infested with Gnathostoma nipponicum after eating raw loach-fish they had caught in a rice field in central Japan. A fragment of Gnathostoma was found in a biopsy from one of them. The sera of both patients reacted with Gnathostoma antigen using indirect immunofluorescence. Scanning electron microscopy was performed on blocks of the paraffin-embedded parasite sample and the viscera of a fish from the same rice field. The risk of eating raw freshwater fish is discussed.

Animals↗

Isolation, characterization, and serial propagation of a bovine group C rotavirus in a monkey kidney cell line (MA104).

A virus (designated the Shintoku strain) which was morphologically indistinguishable from group A rotaviruses was detected in the feces of adult cows with diarrhea in Japan. The virus contained 11 segments of double-stranded RNA and had an electrophoretic migration pattern in polyacrylamide gels similar to that of other group C rotaviruses (4-3-2-2). Feces containing the bovine virus reacted with antiserum to porcine group C rotavirus (Cowden strain) but not group A or B rotaviruses in immunoelectron microscopy. The virus was adapted to serial propagation in roller tube cultures of a rhesus monkey kidney cell line (MA104) by using high concentrations of trypsin. Evidence for viral replication in MA104 cell cultures was demonstrated by immunoelectron microscopy and indirect immunofluorescence by using antiserum to porcine group C rotavirus and by electrophoretic analysis of extracted viral double-stranded RNA. A significant antibody response against the isolate was detected in convalescent-phase sera of cows which excreted the virus: no increased antibody response to bovine group A rotavirus was observed. To our knowledge, this is the first isolation of a group C rotavirus from cattle.

Animals↗

Urinary levels of interleukin-6 and disease activity in patients with IgA nephropathy.

We studied, using ELISA, 27 patients with IgA nephropathy to determine if levels of urinary interleukin-6 (IL-6) might reflect the disease activity. The levels of urinary IL-6 in patients with the advanced stage were significantly higher than those in patients with the mild stage of the disease or in healthy adults. The results showed a significant correlation between the levels of urinary IL-6 and the disease activity, i.e., levels of urinary cast and urinary protein. It was thus suggested that the measurement of urinary IL-6 is useful in evaluating the degree of glomerular injuries and/or prognosis in patients with IgA nephropathy.

Adult↗

Immunohistochemical localization of paraquat in lung and brain.

In order to observe the localization and dynamics of paraquat in lung and brain, immunohistochemical approaches were conducted by using animals. Experimental paraquat-poisoned rats were sacrificed 3 hours, 12 hours, 24 hours, 3 days, 7 days and 10 days after intravenous administration of paraquat (5 mg/kg). In lung tissues, paraquat was localized in histiocytes, walls of blood vessels and bronchiolar epithelial cells from 3 hours to 10 days after the paraquat exposure, and interstitial pulmonary fibrosis was being developed with time. On the other hand, in brain tissues, paraquat was localized only in capillary walls and glial cells but not observed in nerve cells 10 days after the administration of paraquat.

Animals↗

Evaluation of angelicae radix (Touki) by the inhibitory effect on platelet aggregation.

Quality evaluation of Angelicae Radix (Touki) was discussed referring to its inhibitory effect on platelet aggregation. No better correlation was observed in quality determined morphologically from the above-ground part of Touki and that determined by anti-platelet aggregation (APA) effects. Phthalides and adenosine, known to be the major components of Touki, were found not sufficient to evaluate the Touki quality as regards APA active components have been studied and it was concluded that the APA effect of Touki results from the combined action of plural components. The importance of determining quality based on the action of total extract to meet the purpose for which the substance is to be used was suggested.

Drugs, Chinese Herbal↗

Studies on aldose reductase inhibitors from natural products. IV. Constituents and aldose reductase inhibitory effect of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas.

The hot water extracts of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas, were found to have potent inhibitory activity towards lens aldose reductase (AR). Ellagic acid (4) was isolated from C. morifolium and I. batatas, isoscutellarein (7) from B. orellana and 3,5-dicaffeoylquinic acid (10) from I. batatas, respectively, as potent inhibitors.

Aldehyde Reductase↗

Time course of released atrial natriuretic peptide after acute myocardial infarction.

The plasma concentration of atrial natriuretic peptide (pANP) was investigated at fixed times during 48 h following the onset of an initial attack of mild acute myocardial infarction (AMI) in 11 patients. Six hours after onset, the mean pANP was elevated, but 6 h later pANP had returned to the baseline level. Forty-eight hours after onset the mean pANP increased again. Thus, the curve of the time course of pANP consisted of 2 peaks separated by a dip. Six hours after onset, systemic hemodynamics and humoral factors were measured in 27 patients. At 48 h they were measured in 14 patients. The late elevation of pANP correlated with mean pulmonary arterial wedge pressure (r = 0.63, n = 14, p less than 0.05), while the early elevation of pANP did not (r = 0.31, n = 27, n.s.). The early elevation of pANP correlated with plasma concentrations of both noradrenaline (r = 0.55, n = 27, p less than 0.01) and creatine phosphokinase (r = 0.54, n = 27, p less than 0.01). In addition, noradrenaline levels positively correlated with mean pulmonary arterial wedge pressure (r = 0.38, n = 27, p less than 0.05). The cause of the early elevation of pANP in AMI is unclear, but it is suggested that injury to myocardium and activated sympathetic nerve activity may be responsible in part.

Atrial Natriuretic Factor↗

Clinical significance of abnormal Q wave disappearance in acute transmural myocardial infarction.

The clinical features of acute myocardial infarction patients in whom abnormal Q wave disappeared were analyzed. Of 201 patients, 40 (20%) (Group A) showed disappearance of Q wave in serial electrocardiograms. Regional ejection fraction of the infarcted portion improved significantly (from 24 +/- 2 to 34 +/- 4%, p less than 0.001) during chronic phase in Group A, but no such improvement was present in Group B patients who showed no change in the Q wave. Global ejection fraction was greater and percent akinetic segment was smaller in Group A than in Group B at chronic phase. Coronary occlusion occurred more often at segment 7 in Group A; in Group B, occlusion occurred more frequently upstream at segment 6, suggesting Group A had a smaller area of risk. Spontaneous recanalization was more often (57%) and complete occlusion was less frequent in Group A. These indicate that Group A is characterized by a smaller area of risk, smaller infarct size, earlier reperfusion, and greater improvement in wall motion. Twenty-eight patients (70%) of Group A lost Q wave within one month and 12 patients (30%), after 3 months or more. Electrical stunning of the myocardium may be a possible mechanism for the early disappearance of Q waves, and anatomical healing for the late disappearance of Q waves.

Electrocardiography↗

Effects of residual coronary stenosis on myocardial salvage after reperfusion in dogs.

In order to study the effects of residual stenosis on myocardial salvage, we created 99% coronary stenosis with or without contrast washout delay at reperfusion in six groups of dogs. In Group A (n = 8), the artery was occluded for 1h before being fully reperfused. In Group B (n = 9), the artery was occluded for 1h, then subjected to 6h of 99% stenosis without contrast washout delay. In Group C (n = 8), the artery was occluded for 1h, followed by 1 week of 99% stenosis without contrast washout delay. In Group D (n = 10), again the artery was occluded for 1h, then subjected to 6h of 99% stenosis with contrast washout delay. In Group E (n = 8), the artery was occluded for 7h, then fully reperfused for 1 week. Finally, in Group F (n = 8), the occlusion lasted for a full week. All dogs were sacrificed 1 week after occlusion. In Group A, myocardial creatine phosphokinase activity (CK) in the inner layer was 43.8 +/- 12.5% that of non-infarcted myocardium. Myocardial CK in Group B (46.5 +/- 7.4%) was little different but in Group C it dropped to 26.6 +/- 8.4%, suggesting that 99% residual stenosis is not deleterious if it is continued for 6h or less but that it will result in considerable depletion of myocardial CK, it is is sustained for 1 week. In Group D, myocardial CK dropped markedly to 11.3 +/- 3.7%, little different from that for either Group E (13.3 +/- 2.6%) or Group F (9.3 +/- 3.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Increase in left ventricular chamber stiffness in patients with non-insulin dependent diabetes mellitus.

Indices of left ventricular ejection and diastolic filling were measured by cineventriculography in 11 patients with non-insulin dependent diabetes mellitus without significant coronary stenosis and 11 control subjects without diabetes mellitus. Indices of left ventricular ejection, such as ejection fraction and peak ejection rate, were the same in the two groups. The left ventricular end-diastolic volume index and the rapid filling volume index were significantly smaller, the peak filling rate was lower, the left ventricular end-diastolic pressure was higher and the modulus of left ventricular chamber stiffness was larger in the diabetic patients than in the control subjects. These results indicate that left ventricular chamber stiffness is increased in patients with non-insulin dependent diabetes mellitus.

Adult↗

The importance of good endocardial reflow immediately after reperfusion for myocardial salvage in dogs.

We studied the importance of reflow after reperfusion for myocardial salvage. In 19 open-chest dogs, the left anterior descending coronary artery was occluded for 3h and then reperfused. Non-radioactive colored microspheres were injected into the left atrium to measure regional myocardial blood flow (RMBF). Immediately after occlusion, RMBF was reduced to 23 +/- 2% (of control) in the inner layer and 32 +/- 2% in the outer layer. Five minutes after reperfusion, RMBF was increased to 170 +/- 20% and 156 +/- 11% of control in the inner and outer layers, respectively. One week later, RMBF in the inner layer was reduced to 63 +/- 4% but it was not reduced (100 +/- 6%) in the outer layer. There was a roughly positive correlation between the inner/outer flow ratio measured 5 min after reperfusion and myocardial creatine kinase activity. Myocardial necrosis determined by triphenyl tetrazolium chloride stain varied inversely with the inner/outer flow ratio. These results indicate that good reflow in the inner layer 5 min after reperfusion is a favorable indicator for myocardial salvage.

Animals↗

Isolation of bovine coronavirus from feces and nasal swabs of calves with diarrhea.

Fecal and nasal samples were collected from 180 calves with diarrhea and 36 clinically normal co-habitants, and tested for virus using HRT-18 cell cultures derived from human rectal adenocarcinoma. A cytopathic virus was isolated from 5 fecal and 56 nasal samples obtained from diarrheic calves. All calves in which the virus was isolated from diarrheic feces were positive for virus isolation from nasal swabs. The virus was also isolated from the nasal swabs of 10 clinically normal calves that were co-habitants with diarrheic calves. Because they were morphologically similar to coronavirus, agglutinated mouse erythrocytes and serologically identical with the Nebraska calf diarrhea coronavirus, new isolates were identified as bovine coronavirus. The demonstration of viral antigens in nasal epithelial cells by a direct immunofluorescence was in close agreement with the virus isolation in HRT-18 cell cultures. This is the first report on the isolation of bovine coronavirus from newborn calves with diarrhea in Japan. The evidence that the virus was frequently isolated from nasal swabs is of great interest for understanding the pathogenesis of bovine coronavirus infection.

Adenocarcinoma↗

Growth hormone (GH) profiles with successive provocation by GH-releasing hormone and arginine in children: a clinical appraisal.

To establish a single and reliable test for evaluating growth hormone (GH) secretion, we examined successive GH provocation by two agents with different modes of action, GH releasing-hormone (GHRH) and arginine (Arg) in 60 children of short stature, 6 patients with pituitary dwarfism and 9 normal young adults. Their GH profiles were qualitatively classified into 4 types: 25 children and 7 adults responded to both stimuli with 2 GH peaks (48.7 +/- 4.3 [SEM] micrograms/L for GHRH and 32.2 +/- 2.6 micrograms/L for Arg in children; 25.8 +/- 7.6 micrograms/L and 30.1 +/- 9.2 micrograms/L respectively in adults) (type A). A single peak for GHRH (57.7 +/- 4.6 micrograms/L) without an Arg-induced peak was obtained in 29 younger children (type B), which is considered to be a GHRH-dominant pattern. Two of them were diagnosed as hypothalamic GHRH deficiency based on a low nocturnal plasma GH and good response to GH treatment. Six adolescents and 2 adults showed a blunted response to GHRH (9.0 +/- 1.1 micrograms/L) but a normal response to Arg (40.6 +/- 9.5 micrograms/L) (type C), which appears to be caused by somatostatin (SRIH) hypertonicity. None with pituitary dwarfism responded to both stimuli (4.5 +/- 1.3 and 2.3 +/- 0.5 micrograms/L). Thus, the GHRH-Arg test makes it possible to evaluate the counterbalance between GHRH and SRIH as well as to differentiate pituitary GH deficiency from hypothalamic GHRH dysfunction.

Adolescent↗

Effect of the energy density of non-purified diets on growth, gestation and lactation in mice.

The effects of dietary energy density on the performance of growing, gestating and lactating C57BL/6J mice were determined in order to develop pelleted non-purified practical diets for use in all stages of the mouse life cycle. Experimental diets with 4 levels of energy at 24% crude protein (CP) were pelleted and the nutritional values were determined using adult rats. The nitrogen-corrected metabolizable energy (MEn) values ranged from 2.86 to 3.73 kcal/g and the digestive CP (DCP) contents ranged from 20.5 to 22.6% on a dry matter (DM) basis. Mice responded to decreased dietary energy by increasing their feed intake to maintain MEn intake levels, except for 1 week after weaning and during lactation periods. During these periods, mice fed lower energy diets could not consume as much MEn as those fed higher energy diets. The lowest energy diet, in comparison with the highest energy diet, resulted in approximately a 33% lower weaning weight of pups at 3 weeks of age, a 13.2 to 34.4% slower growth at 3 to 4 weeks of age, and a 9.3 day delay in the onset of vaginal opening in young females. Lower energy diets, however, did not affect the litter size or the birth weight of pups. The DCP intake usually increased with decreases in dietary energy but apparently this did not affect the performance of the mice. It was concluded that an optimal diet should have an MEn value of 3.73 kcal/g DM or more for both the one week post weaning growth period and during lactation, but a diet with an MEn value of 2.86 kcal/g DM was sufficient for growth after 4 weeks of age and during gestation.

Animal Feed↗