Biomedical subjects
Publications and source records attributed to S Hashimoto.
FR109615, a new antibiotic active against Candida, was isolated from Streptomyces setonii No. 7562. Based on the spectroscopic data, the structure of FR109615 was elucidated as cis-2-aminocyclopentane-1-carboxylic acid (1). The compound showed the excellent in vivo efficacy in a generalized infection test of mice.
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WS1358A1, a novel inhibitor of renal dehydropeptidase (DHP), augmented the urinary recovery of a carbapenem antibiotic imipenem and improved its protective effect in experimental infections when simultaneously administered to mice with the antibiotic. WS1358A1 was a competitive DHP inhibitor with a Ki value of 1.6 x 10(-7) M.
WS1358A1 (FR104007) and B1 (FR104008), new potent inhibitors of renal dehydropeptidase, were isolated from the culture broth of strain No. 1358 which was identified as Streptomyces parvulus subsp. In vitro inhibitory activities (IC50 value) of WS1358A1 and B1 against porcine renal DHP were 3 and 600 nM, respectively.
The structures of compounds 3 (and 4) and 5 (and 6) derived from the natural products WS1358A1 (1) (and B1 (2)) have been determined by their spectroscopic evidence. By taking advantage of these transformations, an improved synthesis of A1 (1, racemate) has been achieved.
The structures of WS1358A1 and B1, new dehydropeptidase inhibitors isolated from Streptomyces parvulus subsp. tochigiensis No. 1358, have been established to be 2-hydroxy-2-hydroxyaminocarbonyl-3-methylglutaric acid (1) and 2-hydroxy-2-hydroxyaminocarbonylglutaric acid (2), respectively, on the basis of spectroscopic evidence and synthesis of the racemates.
FR112123 is a new oligopeptide antibiotic produced by Streptomyces viridochromogenes No. 7587. The structure of FR112123 is elucidated as N-(N6-(N2-glycyl-L-glutaminyl)-D-lysyl)-D-alanine (1) by spectroscopic and chemical evidence. It resembles a partial structure of peptidoglycan in bacteria. The compound has a superior activity against an Escherichia coli mutant sensitive to inhibitors of cell wall synthesis, although it has a weak activity against the parent strain. These suggest that FR112123 might act on the biosynthesis of bacterial cell wall.
The structure of FR109615, a new antifungal antibiotic, was determined to be (1R,2S)-2-aminocyclopentane-1-carboxylic acid ((-)-cis-2-ACPC: 8a) by X-ray analysis. (-)-cis-2-ACPC (8a) was also synthesized via optical resolution of 3a and 3b derived from (+/-)-cis-2-ACPC hydrochloride (1). 8a showed potent antifungal activity, while its antipode (+)-cis-2-ACPC (8b) had no activity.
When supernatants of thymic epithelial cell cultures (STEC) or thymosin fraction 5 were incubated with washed platelets (37 degrees C for 30 min), the levels of platelet guanosine 3',5'-cyclic monophosphate (cyclic GMP) were increased in a dose-dependent manner. In contrast the supernatants from Chang, HeLa, or HCC-M cell cultures did not significantly affect the levels of intracellular cyclic GMP. The increment of intracellular cyclic GMP levels following treatment with STEC increased with longer incubation times until a plateau was reached at 30 min. This activity of STEC was found in fractions with a molecular weight below 10,000 daltons. Contents of guanine and guanosine in STEC were lower than those observed in other culture supernatants. STEC did not affect guanylate cyclase activity in platelets, but significantly inhibited cyclic GMP phosphodiesterase activities in platelet soluble and membrane fractions. Thymosin fraction 5 inhibited the phosphodiesterase activity of the soluble but not the membrane fraction.
To assess the usefulness of transesophageal Doppler echocardiography (TEE) in diagnosing atrial septal defect (ASD), we studied eight cases with secundum type ASD, in which the diagnosis was confirmed by cardiac catheterization and surgery. In all cases, TEE provided clear images of the interatrial septum with its defect. Shunt flow through the defect was observed by color Doppler technique, and its velocity was measured using the FFT mode. In two cases, right-to-left shunt blood flow was detected. Two types of probes were used in this study, a lateral scanning probe and a longitudinal scanning probe. The scanning plane of the former was perpendicular to the axis of the probe, and that of the latter was parallel to it. The two probes facilitated the measurement of the two right-angled dimensions, with which we could calculate the defect area, assuming the defect to be an ellipse. The volume of a left-to-right shunt was obtained by multiplying the defect area by the integration of flow velocity against time. Shunt volume per cardiac cycle obtained by this method correlated well with that obtained by the Fick's method during cardiac catheterization. In six cases without a right-to-left shunt, the coefficient of correlation was 0.98, and in all eight cases it was reduced to 0.72. Thus, we concluded that TEE is useful for diagnosing and evaluating ASD.
The usefulness of transesophageal Doppler echocardiography (TEE) was assessed in patients with various cardiovascular diseases including 15 patients with dissecting aortic aneurysm (DAA), two with thoracic aneurysm, 16 with ischemic heart disease and 14 with acquired valvular diseases. In dissecting aortic aneurysms, TEE provided clear images of the intimal flaps even in the aortic arch and descending aorta in which clear images could not be obtained by conventional external Doppler echocardiography. The entry site was detected in 11 of the 15 (73%) cases using TEE, but in only three of the 15 cases using conventional Doppler technique. In two cases of true aortic aneurysms, TEE provided clear images of the aneurysm in the descending thoracic aorta, which was discriminated precisely from DAA. In valvular disease, all four valves (aortic, pulmonary and atrio-ventricular valves) were easily observed without disturbance by any other tissues using a transesophageal approach. In addition, valve aneurysms in the posterior mitral leaflets were detected using TEE in two cases. In two cases of mitral stenosis, a thrombus was observed in the left atrial appendage. These findings were confirmed during surgery, but could not be obtained by the conventional external studies. In 16 cases, TEE was performed during aorto-coronary bypass surgery under general anesthesia. In two of these cases, left ventricular assist devices were applied after surgery. In these cases, where conventional Doppler echocardiography was not applicable, cardiac function could be monitored by TEE. Thus, TEE is useful not only in evaluating morphological function in the cardiovascular system but also in monitoring cardiac hemodynamics during and after heart surgery.
To predict the time required for low-birth-weight (LBW) infants to catch-up with standard weight, the growth curves for weight in 156 LBW infants with no medical abnormalities were examined. The proportion of infants who caught-up with standard weight by 1.5 years of age was significantly higher in appropriate-for-dates (AFD) infants than in small-for-dates (SFD) infants (93% vs. 70%). The age of catch-up with standard weight had a significant inverse correlation with birth weight in AFD infants, and not in SFD infants. The age of catch-up standard weight of AFD infants, as predicted by the regression analysis was 4-8 months for 2,000 g of birth weight, 8-12 months for 1,500 g, and 12-15 months for 1,000 g, with about 80% accuracy. This prediction may be valuable in providing health advice to mothers with LBW infants.
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To find the most adequate method for estimating the number of patients in nationwide epidemiological surveys of intractable diseases, we examined six existing methods using reported data on 13 selected diseases. Estimated numbers of patients by the methods, except for methods with theoretical inadequacy or other problems, were almost equal to each other. The simple method, by which the number of patients is estimated as the reported one divided by the response rate, is recommended.
Basal cell adenoma of the parotid gland was studied with immunohistochemical methods. We observed cells in the tumor with positive reaction to polyclonal keratin, prekeratin, monoclonal PKK-1, polyclonal S-100 protein, monoclonal S-100 protein (alpha), secretory component, actin and laminin. However, no cells which stained positively with monoclonal KL-1, amylase, carcinoembryonic antigen, or epithelial membrane antigen were recognized. From these immunohistochemical results and our ultrastructural observations reported previously, we conclude that the cells constituting the basal cell adenoma are ductal, myoepithelial, and squamous cells but not secretory ones. It is also suggested that the origins of basal cell ademona as well as those of pleomorphic and clear cell adenoma are undifferentiated cells of intercalated duct.
A case of ossifying fibroma of the maxillary left suspected as fibrous dysplasia was reported. The patient was a 21 year-old man complaining of a swelling of the gingiva at the left upper molar region. X-ray examination showed a border distinct imradiolucent, a ground glass appearance in partially at the left maxillary region. In the histological findings, the specimen showed a large number of comparatively ripe bone that suspected as Osteoma. At about 3 years postoperatively, no evidence of recurrent has appeared.
Serum amyloid P component (SAP) has been designated as a female protein in hamsters. To investigate the effects of sex steroids on SAP concentration in rats, SAP was purified from Wistar rats by affinity chromatography. Anti-SAP was raised. Sample sera were obtained from 150 young and old rats, after which, they were injected with either estradiol (E2), testosterone (T), or dehydroepiandrosterone (DHA). Sera were serially obtained from the tail vessels until the 8th day after injection. Serum levels of SAP were measured by micro single radial immuno-diffusion with a standard pooled serum as 100%. As the rats aged, the SAP levels in untreated female rats increase with age from 93% at 11 weeks to 346% at 58 weeks. In 28-week-old rats, the SAP levels in females (135 +/- 40%) were significantly (p less than 0.01) higher than those in males (80 +/- 32%). When old female rats (56 wk) were injected with DHA (3.5 mg), the SAP decreased significantly (p less than 0.01) to 70.8% of the preinjection level on the 8th day after injection. When young male rats (11 wk) were jnjected with E2 (0.5 mg), the SAP levels increased rapidly to 188% of the prelevel on the 5th day. Serum E2 levels reached a peak on the 2nd day. After the injection of T, the SAP levels did not change.
In order to clarify the mechanism of N-isopropyl-p-iodoamphetamine (IMP) liver accumulations, liver dynamic study by the portal injection of 123I-IMP and liver microautoradiography by 125I-IMP were performed using 5, 2 male rats, respectively. The initial uptake of 123I-IMP in the liver was very high and thereafter 123I-IMP showed relatively rapid wash-out (count ratio of lung to liver at 10 min after the injection was 0.12, 0.15). On the other hand, the addition of 5 mg, 8 mg ketamine hydrochloride decreased the initial 123I-IMP liver uptake and its lung accumulation was noted immediately after the injection (count ratio of lung to liver at 10 min was 0.20). Microautoradiography of the liver using 125I-IMP showed grain density in the central vein and sinusoids, but not in the liver parenchymal cell. These results suggest that non-specific amine receptor (binding site) may exist in the endothelial cell in the central vein, although the number of experimental rats in this series was small for conclusion.