Biomedical subjects
Publications and source records attributed to T Nishimura.
Resorthiomycin was revealed to be a new antibiotic with a molecular weight of 284 and a chemical formula of C14H20O4S as determined by MS and elemental analysis. The structure of resorthiomycin was determined to be 6-acetyl-4-(3-hydroxybutyl)-2-methyl-5-methylthioresorcinol by IR spectrum and 1H and 13C NMR.
Resorthiomycin suppressed the clonogenic activity of a multidrug-resistant mutant cell line of Chinese hamster V79 cells more potently than its parental cells. Moreover, resorthiomycin at 40 micrograms/ml potentiated the cytotoxic activity of vincristine and actinomycin D on V79 cells over 3-fold. Uptake of [3H]actinomycin D into V79 cells was stimulated 2-fold by 40 micrograms/ml of resorthiomycin during 2 hours incubation. On the other hand, incorporation of [3H]thymidine and [3H]uridine into mouse leukemia L5178Y cells was inhibited in a dose-dependent manner at resorthiomycin concentrations ranging from 5 to 40 micrograms/ml. In ATP-depleted L5178Y cells, membrane transport of [3H]thymidine and 2-[3H]deoxyglucose was strongly suppressed by resorthiomycin. These results suggest that resorthiomycin acts on the plasma membrane and perturbes some membrane function.
An antifungal amino acid antibiotic, (S)2-amino-4-oxo-5-hydroxypentanoic acid (RI-331) isolated from Streptomyces sp., inhibited the biosynthesis of protein to a greater extent than that of RNA or DNA in growing Saccharomyces cerevisiae cells. Polypeptide biosynthesis in a cell-free system from the yeast was refractory to the antibiotic, suggesting the possibility that the biosynthesis of one or more amino acids might be inhibited. Intracellular amino acid pools, particularly those of methionine, isoleucine and threonine were significantly reduced when yeast cells were incubated in the presence of RI-331. Consistent with this, the growth-inhibitory activity of RI-331 was markedly reversed by the addition of these amino acids into the growth medium, and an even greater effect was exerted by homoserine which works as a common metabolic precursor for these amino acids in yeasts. It looks likely therefore that the inhibition of biosyntheses of some or all of these amino acids by RI-331 is primarily responsible for overall inhibition of protein biosynthesis in yeasts, ultimately leading to cytostasis. This possible mechanism of RI-331 action appears to explain favorably the selective toxicity of the antibiotic against yeasts, since mammalians lack enzymatic systems for synthesizing methionine, isoleucine and threonine which are required as essential amino acids for growth.
A survey of the total aminopeptidase activity of bovine, porcine, and chicken skeletal muscles at neutral pH was done, using the beta-naphthylamide derivatives of nine amino acids, DEAE-cellulose column chromatography of the muscle extract found at least four types of aminopeptidases in porcine and chicken muscles. Aminopeptidase B and aminopeptidase C were commonly recognized in bovine, porcine, and chickens muscles. Hydrolase H was recognized in porcine and chicken muscles. Aminopeptidase nC and hydrolase H had high activity against almost all substrates. The substrate specificities of both enzymes were fairly compatible with the pattern of free amino acids which increased during the storage of bovine, porcine, and chicken meats [Agric. Biol. Chem. 52, 2323 (1988)], indicating that aminopeptidase C and hydrolase H are responsible for the increment of free amino acids during aging of these muscles.
We measured immunoreactive endothelin-1 in plasma of a patient with malignant hemangioendothelioma. A 74-year-old female first visited our clinic in July, 1989. Physical examination revealed reddish nodule measured 4 x 5 x 1 cm and erythematous plaque with erosion on her scalp. A biopsy specimen showed extensive proliferation of atypical tumor cells intermingled with a large number of capillary vessels in dermis. Some of tumor cells were positively stained for factor VIII related antigen by PAP method. From these findings we diagnosed malignant hemangioendothelioma and resected the tumor on August 3. The measurement of immunoreactive endothelin-1 in plasma was performed by radio-immunoassay on August 2 (before operation), October 20 and December 27 (after operation). The results were 16.2, 4.3 and 5.6 pg/ml, respectively (normal range: 0.5 +/- 0.2 pg/ml). Plasma endothelin-1 level may be run parallel to quantity of tumor cells in malignant hemangioendothelioma.
The purpose of this study was to clarify the clinical significance of rest-redistribution in myocardial scintigraphy (SPECT) in acute myocardial infarction (AMI). Thirty patients with AMI within one week after the onset of attack were studied. SPECT images were obtained 10 min and three hours after injection of 201Tl. Bull's eye images and unfolded map images were prepared. A 201Tl uptake was studied at the infarct and non-infarct sites. Exercise SPECT and radionuclide angiography (RNA) were performed in all patients one month after the onset of AMI, and the findings were compared with clinical and coronary angiographic (CAG) findings. 1. Redistribution of thallium at rest was observed at the infarct sites in nine of the 30 patients. 2. Redistribution at rest was observed at the non-infarct sites in eight patients. 3. Redistribution at rest was observed during exercise SPECT one month after the onset of AMI in patients with redistribution at rest in the acute phase. 4. In patients with redistribution at rest at the infarct site, left ventricular ejection fraction (EF) improved one month after the onset of AMI (delta EF greater than 5%), but it decreased slightly during exercise. 5. Wall motion at the infarct site was not much impaired in patients who showed redistribution at rest at the infarct site. 6. Angina pectoris and recurrence of myocardial infarction were observed more frequently in those with redistribution at rest on SPECT. 7. No characteristic findings were obtained on CAG in those with redistribution at rest.(ABSTRACT TRUNCATED AT 250 WORDS)
Anti-influenza antibody (Ab) titers were measured in order to elucidate whether there are any disturbances in Ab production in chronic renal failure (CRF) patients. A total of 55 CRF patients plus 15 normal individuals were vaccinated with influenza vaccine twice, 4 weeks apart of the 55 CRF patients, 15 were not on dialysis, 10 were undergoing hemodialysis (HD), and 30 were on continuous ambulatory peritoneal dialysis (CAPD). Of the 30 CAPD patients, 14 had peritonitis. Serum Ab titers were measured by complement fixation (CF) and hemagglutination inhibition (HI) tests, and IgG and IgM class specific antibodies by ELISA. All groups responded to immunization, but CAPD patients with peritonitis and CRF patients not yet on dialysis did not show a significant elevation in IgM class Ab titers. The number of CAPD patients with peritonitis who achieved positive titers was significantly lower in HI (p less than 0.01) and IgG class antibodies (p less than 0.05) compared with normal controls. Two patients with frequent peritonitis did not show any response to vaccination. It was concluded that patients with renal dysfunction have some abnormalities in Ab production against influenza vaccine, the effects of which were more pronounced in the CAPD patients with frequent peritonitis.
Twenty-three children with hypertrophic cardiomyopathy (HCM) (aged 2 months to 15 years) were followed up for more than four years using thallium myocardial imaging (TMI) and echocardiography. With echocardiography, the left ventricular end-diastolic dimension (LVDd) and fractional shortening (FS) were measured. Perfusion defect (PD) was assessed using TMI. Cardiac catheterization and right ventricular endomyocardial biopsy were performed in 18 patients within one week before or after their TMI. During the follow-up period, two patients showed a marked increase in LVDd and a marked decrease in FS at ages 13 and 16 years, respectively. These two patients were judged to have progressed to the dilated phase. In these two patients, extensive PD was detected in the left ventricular wall on TMI, 15 and 31 months prior to the appearance of the echocardiographic changes, respectively. Right ventricular endomyocardial biopsy at the time of extensive PD revealed marked interstitial fibrosis along with hypertrophy and disarray of myocardial cells. In conclusion, progression to the dilated phase is not a rare event in children with HCM and TMI appears to be a useful tool for early detection of the progression.
5 alpha-Androstane-3 alpha, 17 beta-diol (3 alpha-diol) was measured in the submandibular gland (SMG) of male and female rats by radioimmunoassay (RIA) at 4 and 7 weeks of age. The raised and constant concentration of 3 alpha-diol was revealed in female SMG. The mean values of 3 alpha-diol in female SMG were found to be significantly higher than testosterone (T) and dihydrotestosterone (DHT). 3 alpha-diol in male SMG was similar to that of DHT and these two steroids decreased by the 7th week.
The antiinflammatory activity of 4-acetylaminophenylacetic acid (MS-932) was investigated. MS-932 did not suppress the acute inflammation of carrageenin-induced paw edema in rats or of primary swelling in adjuvant arthritic rats. However, prophylactic treatment with MS-932 inhibited secondary inflammation in adjuvant arthritic rats. MS-932 also restored to normal the weight of the spleen and the serum albumin/globulin ratio of adjuvant arthritic rats. In addition to its prophylactic effect, MS-932 had a therapeutic effect on adjuvant arthritis. In in vitro tests, MS-932 did not inhibit prostaglandin E2 biosynthesis from arachidonic acid by sheep seminal vesicle microsomal enzyme or superoxide generation by guinea pig neutrophils stimulated with opsonized zymosan. MS-932 had no analgesic effect in mice and no antipyretic effect in rats. These results indicate that MS-932 suppresses adjuvant arthritis through modulation of the immune system.
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Coronary artery territories were evaluated precisely by Bull's-eye and unfolded map generated from myocardial SPECT. In addition, unfolded maps including apical information were also developed. The coronary artery territories were determined by 54 cases of typical single vessel disease (more than 75% stenosis) with myocardial infarction and angina pectoris. There were 12 of right coronary artery disease, 24 of left anterior descending coronary artery disease, 5 of diagonal coronary artery disease, and 13 of left circumflex artery disease. Each diseased region was summed and normalized using the standard pattern (21 cases of normal male and 13 cases of normal female). Apical information was simply obtained using the anterior and posterior count from short and long axial image. Then, their data were added to the unfolded map. In conclusion, unfolded map was proven to be useful for the determination of coronary artery territory, since this map expressed the extent and site of myocardial damage precisely compared to Bull's-eye. The unfolded map to contain the apical information was also useful for the evaluation of left anterior descending coronary artery involvement.
Coronary territory map was developed on unfolded map of exercise Tl-201 myocardial SPECT. Each coronary territory was determined by summing the each unfolded map of 54 cases of single vessel disease respectively, and standardizing with normal pattern obtained from normal patients. The diagnostic accuracy of coronary territory map to identify the diseased coronary artery was analyzed in 104 clinical cases and was compared with that of planar and SPECT visual diagnosis, simple unfolded map (raw map) and extent & severity map. The results were as follows; 1) Territory map showed excellent diagnostic accuracy in single or double vessel disease, especially in diagnosis of left circumflex coronary artery lesion. 2) In triple vessel disease, the diagnostic accuracy of territory map or other unfolded maps was 30% at best, and was inferior to planar or SPECT visual analysis. The cause of this inferiority seemed that the quantitatively analyzed map had no information about the degree of Tl-uptake into lung or myocardium, which give useful information in visual diagnosis. 3) The diagnostic agreement ratio in two observers was the highest in territory map diagnosis, so that the territory map diagnosis seemed to be the most objective one. 4) The unfolded map diagnosis with apical display obtained from long-axis tomogram was useful to diagnose left anterior descending coronary (LAD) lesion, which improve not only the sensitivity of LAD but also specificity of right coronary artery single vessel disease.
111In-antimyosin Fab (AM) myocardial scintigraphy was carried out in (A) 10 patients with idiopathic dilated cardiomyopathy, (B) 7 with dilated phase of hypertrophic cardiomyopathy and (C) 8 with normal (control) individuals. Imaging was taken 48 hours after intravenous injection of 74 MBq of AM. Myocardial uptake of AM was evaluated qualitatively and quantitatively. Positive uptake was observed in 9/10 (90%), 7/7 (100%) and 0/8 (0%) in group A, B and C, respectively. AM index (heart/lung ratio) in group A and B were 2.04 +/- 0.24 and 2.46 +/- 0.49, values significantly higher than that obtained in the control patient without cardiomyopathy (1.51 +/- 0.13) (p less than 0.01). Positive monoclonal antimyosin antibody studies were highly prevalent in dilated cardiomyopathic and dilated phase of hypertrophic cardiomyopathic patients, even in the presence of negative right ventricular biopsy. It is suggested that this method was useful for the noninvasive assessment of active myocardial damage in these patients.
A case of juvenile Alzheimer's disease with various neurological features such as myoclonus, also showing grumose degeneration in the dentate nucleus was reported. In a 35 year old woman, at first myoclonus, and 5 years later, progressive dementia were found. She, then, fell into apallic syndrome 9 years later, and died of pneumonia at the age of 53. She had no particular family history. Neurological examination disclosed cerebellar ataxia, left hemiparesis, convulsion in addition to myoclonus. Neuropathologically, there were a lot of senile plaques and neurofibrillary tangles in the cerebral cortex. A marked myelin loss in the white matter and a neuronal loss in the basal ganglia were also found. And grumose degeneration in the cerebellar dentate nucleus distinctively characterize the present case. The myoclonus and cerebellar ataxia could be attributed to the grumose degeneration. Two similar cases had been previously reported. Juvenile Alzheimer's disease with grumose degeneration like the present case was considered to be one of the subgroups of Alzheimer's disease.
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We studied the efficacy of stress thallium scan in detecting restenosis after primary successful PTCA. There were 21 patients with angina pectoris and 16 patients with previous myocardial infarction. The sensitivity and the specificity of stress thallium scan in detecting restenosis were superior to those of stress electrocardiography or chest pain complained in follow-up period. In multi-vessel disease, we could assess the vessel developing restenosis more easily than stress electrocardiography. Initial thallium %UPTAKE RATIO was significantly improved after PTCA but redecreased in patients developing restenosis. In patients showing residual redistribution despite of not developing restenosis, we could judge vessel patency by gradually improving initial %UPTAKE RATIO after PTCA. Thus, stress thallium scan proved to be useful in detecting restenosis after PTCA.
123I-MIBG is taken up by sympathetic nerve ending and provides a scintigraphic image of myocardial sympathetic innervation. We investigated the scintigraphic detection of denervated but viable myocardium following acute myocardial infarction by serial 123I-MIBG and 201TlCl myocardial SPECT. Fourteen patients were studied at acute (10 +/- 2 days) and chronic stage (86 +/- 10 days). Simultaneous dual SPECT was carried out after IV administration of 111 MBq (3 mCi) of 201TlCl and 123I-MIBG. The defect size of 123I-MIBG and 201TlCl were compared visually by using Bull's eye display generated from each myocardial SPECT. In all patients, 123I-MIBG defect showed larger compared to 201T1Cl defect at acute stage, which suggest the existence of denervated but viable myocardium. Of these patients, seven showed significant improvement of both defects, though 123I-MIBG defect showed slightly larger compared to 201TlCl defect, even at chronic stage. These patients had exercise induced thallium transient defect at infarcted area. The remaining 7 patients had no improvement of both defects at chronic stage, which suggest the complete scar at infarcted area. In addition to above study, 4 patients of old myocardial infarction demonstrated larger 123I-MIBG defect compared to 201TlCl defect even at old stage, which thought to be pathogenesis of ventricular tachycardia. In conclusion, 123I-MIBG could evaluate sympathetic denervation and reinnervation noninvasively in the patients with acute myocardial infarction.