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Biomedical subjects

M Usami

Publications and source records attributed to M Usami.

At least 19 recordsLinked to original sources

Culture of postimplantation rat embryos in rabbit serum for the identification of the growth factor in fractionated rat serum.

The growth factor for postimplantation rat embryos was investigated on the basis of the serum species-specificity in supporting embryonic development in culture. We used rabbit serum as a basal medium for the culture of head-fold stage rat embryos, and examined the effects of various fractions of rat serum on their development. In rabbit serum alone, rat embryos developed poorly. With the rat serum ultrafiltrate of molecular weight (MW) < 300,000, embryonic development improved, but not with the ultrafiltrate of MW < 100,000. With dialyzed rat serum or the globulin fraction of rat serum, embryonic development improved, but the albumin fraction had no effect. It was concluded from these results that some macromolecular growth factor for cultured postimplantation rat embryos was present in the globulin fraction of rat serum. The molecular weight of this growth factor was estimated to be between 65,000 and 300,000. Rabbit serum was considered to be suitable as a medium for the identification of this growth factor.

Animals

Characteristics of substrates and inhibitors in binding to rat liver L-tryptophan 2,3-dioxygenase: a Fourier transform infrared and kinetic study.

Infrared spectroscopy and steady-state kinetics were applied to rat liver L-tryptophan 2,3-dioxygenase, in order to find relations between the structure and binding characteristics of its substrates and inhibitors. The binding characteristics were reflected by changes in the infrared CO stretch band(s) of an Fe(II)-CO complex of the enzyme upon addition of L-tryptophan and 12 analogs. The CO stretch band around 1961 cm-1 of the complex was not much affected by 1-methyl-D,L-tryptophan, a noncompetitive inhibitor, implying a binding at a site distant from the Fe(II)-CO vicinity. The spectral pattern was significantly changed by any of the other compounds which conserved an indole NH, indicative of its binding to the catalytic site. All substrates, which contained a complete CH(NH2)COOH group in addition to the NH, gave spectra similar to that of an L-tryptophan-bound complex. Spectral changes caused by six inhibitors, which lacked the complete CH(NH2)COOH, were different from one another and from those by the substrates. Hence, for an analog, the indole NH is indispensable to bind to the catalytic site, and the CH(NH2)COOH is important to take a correct configuration appropriate to the catalytic reaction. The reason why L- and D-isomers of 5-hydroxytryptohan are not substrates, in spite of their conservation of the required functional groups and correct binding to the catalytic site, has been ascribed to a possible distortion of the protein structure in the heme pocket due to a strong hydrogen bond from the hydroxyl group to an amino acid side chain.

Animals

Glucagon, insulin and somatostatin secretion in response to sympathetic neural activation in streptozotocin-induced diabetic rats. A study with the isolated perfused rat pancreas in vitro.

Changes in glucagon, insulin and somatostatin secretion induced by electrical splanchnic nerve stimulation were examined in rats treated with streptozotocin as neonates and as adults. In order to study the direct neural effects we used the isolated perfused rat pancreas with intact left splanchnic nerve in vitro. In normal rats splanchnic nerve stimulation causes significant decreases in insulin (30-40%) and somatostatin (30-50%) secretion at both 16.7 mmol/l and 1 mmol/l glucose concentrations. In the neonatal streptozotocin-diabetic rat splanchnic nerve stimulation at 16.7 mmol/l glucose decreased insulin secretion (14%) further than in the control rats (30%), however, somatostatin secretion did not decrease to the same extent. Similar results were also observed at the low (1 mmol/l) glucose concentration. On the other hand, percent decreases of insulin and somatostatin secretion induced by splanchnic nerve stimulation in the streptozocin-diabetic rats were similar to the values observed in the normal control rats. The glucagon secretion in response to splanchnic nerve stimulation at 16.7 mmol/l glucose from pancreatic Alpha cells in both types of induced diabetes is exaggerated, and the degree of exaggeration seems to parallel the severity of the hyperglycaemia. However, the splanchnic nerve stimulation-induced glucagon secretion at 1 mmol/l glucose was impaired in the streptozotocin-diabetic rats, but not in the neonatal streptozotocin-diabetic rats. These data suggest that the sensitivity of diabetic Alpha and Delta cells to sympathetic neural activation are blunted, whereas the sensitivity of Beta cells is enhanced in the diabetic animal model.

Animals

Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (OECD): familiarization using cyclophosphamide.

A familiarization study was conducted on the "Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox)" proposed by the OECD. Cyclophosphamide (CP) at doses of 6.7, 4.5, 3, 2, and 0 mg/kg body wt was given daily by gavage to groups of 12 male and 12 female Sprague-Dawley rats. As a result, anemia and leukopenia were evident in treated males. The absolute and relative thymus and spleen weights were decreased in treated rats. Histopathologically, atrophy of the thymus, spleen, and bone marrow was observed. With respect to the reproductive/developmental toxicity, dose-dependent increases in postimplantation loss of fetuses and postnatal death were found in dams given CP. The body weight of pups treated with CP was significantly lowered in a dose-related manner. Thus the results demonstrated most of the known toxicological properties of CP, except the adverse effects on spermatogenesis and fertility. Therefore ReproTox can be considered as a useful screening test for assessing repeat dose and reproductive/developmental toxicity of existing chemicals of high production volume.

Animals

[Surveillance after orchiectomy for stage I testicular seminoma].

The results of treatment by orchiectomy and radiotherapy for stage I testicular seminoma are excellent with cure rates exceeding 95% and relapse rates less than 5%. However, after the development of successful surveillance programs for stage I nonseminomatous testicular cancers, the role of radiotherapy has been questioned by some authors and they proposed a "surveillance policy" for these patients. The purpose of this study was to determine the percentage of patients cured by orchiectomy alone, percentage who ultimately required therapy for occult metastases, site of recurrence, and over-all cure rate and treatment morbidity. And these data were compared with those of adjuvant radiotherapy group retrospectively. Twenty seven patients were treated with adjuvant radiotherapy (RT group). Since 1986, 23 patients with stage I testicular seminoma entered the "surveillance only" protocol at our institution (S group) with a follow-up between 14 and 70 months (median 43 months). Informed consent for the policy of surveillance was obtained. Follow up consisted of physical examination, determination of serum tumor markers and chest X-ray bimonthly for 2 years, every 3 months for 1 year, every 6 months for 2 years and annually thereafter to 10 years. CT scans were performed every 4 months for 3 years, every 6 months for 2 years. Two patients in S group (8.7%) relapsed at 4 and 7 months after orchiectomy with nonbulky retroperitoneal disease (less than 5 cm in diameter), whereas only 1 (3.7%) irradiated patients did so after 4 months.

Adult

Comparison of various assay systems for prostate-specific antigen standardization.

To avoid confusion between serum prostate-specific antigen (PSA) values among various assay systems, clinical studies on the possibility of conversion among detection values were performed. The assay kits used for the PSA comparisons were MARKIT-F PA, MARKIT-M PA, EIKEN PA, PA test WAKO, Ball ELSA PSA, E-Test Tosoh II PA, PROS-CHECK PSA, DELFIA PSA and TANDEM-R PSA. Using each kit, the standards attached to each assay system were detected, and 142 sera samples from benign hypertrophies or prostate cancers were assayed for serum PSA values. By detecting the standards for each kit, slopes were obtained which were almost identical to those obtained from original assay system. The coefficients of correlation among the PSA detection systems, using patients' sera, were very high, and linear regression lines were also obtained. The results suggest that almost identical serum PSA values may be detected either by multiplying by a coefficient to bring it to the standard or using the conversion formula.

Adenocarcinoma

[Studies on the teratogenic potential of p-tert-butylphenolformaldehyde resin in rats].

p-tert-Butylphenolformaldehyde resin, an adhesive, was given orally to pregnant Wistar rats by stomach intubation at the dose levels of 250, 500 and 1000 mg/kg body weight during days 7 to 17 of gestation, and the effects of the compound on dams and fetal developments were examined. No changes in general conditions, maternal body weight, food consumption, numbers of corpora lutea and implantation ratio were observed. There was no evidence of an increase in fetal death or of malformation attributable to the treatment with p-tert-butylphenolformaldehyde resin in any of dose levels examined. It was concluded that p-tert-butylphenolformaldehyde resin has no teratogenic effect in rats.

Administration, Oral

[Therapeutic inventions of perioperative metabolic care in diabetic patients].

Perioperative metabolism was evaluated in diabetic patients and animal models. Experimental model of diabetes mellitus (DM) model was obtained by streptozotocine injection. Each 14C-labeled substrates and combination of carbohydrates mixture was administered intravenously in a dose of 1 g/kg before and after laparotomy and cumulative curves of expired 14CO2 was calculated. Biochemical analysis in the liver, blood and urine were performed following infusion of two different solutions, GFX (glucose, fructose, xylitol) solution, 4:2:1 ratio by weight vs. glucose solution, with 12% amino acids solution. In a clinical study, incidence of DM in digestive surgery was examined in 3481 cases. Retrospective evaluation of GFX solution was performed in cases after total gastrectomy. Incidence of DM was 14% and it has been increased recently, Glucose metabolism in DM rats was disturbed after surgery. Amino acids (alanine and valine) and lipid metabolism was slightly suppressed after surgery in DM rats. The best combination of carbohydrate mixture was determined as GFX solution in animal and clinical experiments. GFX solution improved not only glucose metabolism but also lipid and amino acid metabolism in DM rats. Decreased insulin requirement and increased total caloric intake were observed in DM and borderline DM cases treated by GFX solution.

Amino Acids

Long-term clinical study on luteinising hormone-releasing hormone agonist depot formulation in the treatment of stage D prostatic cancer. The TAP-144-SR Study Group.

The results of long-term administration of leuprorelin acetate depot (TAP-144-SR), a sustained-release preparation of luteinising hormone-releasing hormone (LH-RH) agonist, to 40 stage D prostate cancer patients who had had no previous hormonal therapy, have been analyzed. The drug was administered by subcutaneous injection once every four weeks at a dose of 3.75 or 7.5 mg. The mean duration of treatment was 480 (141-1,266) days, and treatment continued for more than one year for 60% of the 40 patients. Objective response was evaluated in accordance with Japanese Response Criteria. The best objective response in the overall evaluation was a partial response in 68.6% of the total patient group (3.75 mg, 64.3%; 7.5 mg, 71.4%). During the administration period, 21 patients were diagnosed as having progressive disease (PD), and the mean time to onset of PD was 308 days. The earliest diagnoses of PD were made on bone metastases (17 cases) and prostatic acid phosphatase levels (12 cases). The survival rate, as determined by Kaplan-Meier's method, was 81.2% (3.75 mg, 80.5%; 7.5 mg, 81.3%) two years after starting the regimen and 66.0% (3.75 mg, 65.1%; 7.5 mg, 66.0%) after three years. There was no dose dependency between either of the two drug doses, which we adopted as functions of the objective response rate, and patients' survival. Serum levels of testosterone, LH and follicle-stimulating hormone (FSH) were monitored from the first-dose until the 148th week of administration. In all patients receiving the drug as scheduled, the testosterone level was maintained at less than 1 ng/ml, and the LH and FSH levels were maintained at levels lower than their respective upper normal limits. There were no particular adverse reactions specific to the long-term administration subsequent to the foregoing 12-week administration study. In conclusion, LH-RH analogue treatment is thought to be a long-lasting, effective, palliative measure for patients with previously-untreated, advanced, prostatic cancer.

Aged

[Surgical treatment under extracorporeal circulation for renal cell carcinoma with tumor thrombus in inferior vena cava].

Three cases of renal cell carcinoma with tumor thrombus extending into the inferior vena cava are reported. Radical nephrectomy and thrombectomy were performed under extracorporeal circulation in all the cases. The level of tumor thrombus was preoperatively determined by computed tomography, magnetic resonance imaging or venacavography. The tumor thrombus extended into the right atrium in one, and above the hepatic vein in two cases. One patient whose thrombus reached the right atrium died of multiple metastasis of renal cell carcinoma 5 months after operation. Another patient with lung metastasis was given interferon-alpha and is alive 5 months after operation. The other patient is clinically free of disease and in good health 7 years after operation. We believe that extracorporeal circulation allows an opportunity to resect the tumor thrombus in a controlled situation, and makes the operation safer.

Aged

[Spontaneous peripelvic extravasation associated with primary ureteral tumor: a case report].

A case of spontaneous peripelvic extravasation associated with primary ureteral tumor is reported. A 56-year-old woman presented with left flank pain. Excretory urogram and abdominal computed tomographic (CT) scan demonstrated left hydronephrosis with extravasation of contrast materials around the renal pelvis. Retrograde pyelogram showed the filling defect in the left upper ureter. Under diagnosis of ureteral tumor, total nephroureterectomy was performed. Histological findings revealed transitional cell carcinoma. 80 cases of spontaneous peripelvic extravasation in Japan were reviewed and discussed briefly.

Carcinoma, Transitional Cell

[Assessment of myocardial viability by exercise stress myocardial tomography with 201Tl--the usefulness of 201Tl washout rate].

Exercise stress (Ex) and redistribution (RD) myocardial tomography with thallium-201 (Tl-201) has been widely used for evaluating myocardial viability. But recent studies have demonstrated that reinjection (ReI) study following RD study is necessary for detecting reversible ischemic myocardium. On the other hand, decreased myocardial washout of Tl-201 after Ex is an indicator of myocardial ischemia. So we have studied the usefulness of myocardial Tl-201 washout rate (WOR) for the evaluation of myocardial viability by comparing it with ReI images. Ex and RD myocardial tomographies were obtained immediately after Ex and 3 hours later. After RD study a small amount of Tl-201 was injected and ReI imaging was repeated. We studied 64 myocardial segments (in 58 patients with coronary artery disease) in which Ex-induced perfusion defects persisted in RD images. According to the changes of perfusion defects between Ex, RD and ReI images, they were classified into 3 types: Type I; perfusion defect on the RD image was identical to ReI image (75%) Type I was divided into 2 subgroups whether perfusion defect at Ex was unchanged (Ia, 42%) or improved (Ib, 33%) on the RD image. Type II; perfusion defect at Ex was reduced on the RD image and it improved furthermore at ReI image (17%). Type III; perfusion defect was the same at Ex and RD but it was reduced on the ReI image (8%). WOR less than 30% was defined as abnormal when Ex heart rate exceeded 120 bpm and lung-myocardial Tl-201 uptake ratio was less than 0.45.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[A case of complete remission of lymph nodes metastasis from esophageal cancer with combination treatment of UFT and radiation].

A 65 year old female patient, who had developed left atelectasis because of mediastinal lymph nodes metastasis after esophageal resection for esophageal cancer, underwent the combination treatment with UFT (300 mg/day) and radiation (1.5 Gy/day, total dosage: 70.2 Gy). The symptoms soon subsided, and mediastinal CT and bronchoscopy revealed a complete disappearance of metastatic lymph nodes after one month. During one year of CR she enjoyed her daily life, however the relapse occurred. It is suggested that the combination treatment is an effective and safe way even in a patient who went through a lot of invasive surgeries.

Aged

[Myocardial perfusion in patients with left bundle branch block and without coronary artery disease].

For the evaluation of myocardial perfusion in patients with left bundle branch block (LBBB), we performed exercise stress (Ex)-redistribution (RD) myocardial tomography with thallium-201 (201Tl) in 23 patients with LBBB and without coronary artery disease (CAD). Myocardial images in patients with LBBB were compared with those of 9 patients with CAD who showed Ex induced transient septal defect. Bull'-eye maps (201Tl distribution maps at Ex and RD and 201Tl washout rate [WOR] map) were made from myocardial tomograms. In 23 patients with LBBB, 15 patients (65%) developed myocardial perfusion abnormality. In 10 (67%) of these 15 patients, transient perfusion defect appeared in the entire septum (diffuse type). On the other hand in 5 patients (33%), localized fixed perfusion defect developed at the boundary between septum and anterior wall (focal type). In focal type, every patient had other disease such as hypertension, aortic stenosis or sick sinus syndrome. While in patients with diffuse type, other diseases were observed in 30% (p less than 0.05) and they were limited to hypertension or diabetes mellitus. These facts suggested that mechanisms of perfusion abnormalities might be different between these two groups. We compared the perfusion abnormality between LBBB diffuse type and CAD. The extent of the defects was not different between two groups. Although apex was included within the defect in 89% of CAD population, apical defect was observed in only 20% of diffuse type (p less than 0.05). Minimal 201Tl WOR and 201Tl uptake ratio of septum to lateral wall indicated that exercise induced septal defect was slighter in diffuse type than CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Metabolic effects of GFX+BCAA solution in the old aged rats after operation].

Effects of total parenteral nutrition (TPN) on the perioperative metabolism in old aged rats were evaluated. Extremely old rats (over 100 weeks old) and young rats undergoing laparotomy were treated with TPN (200 ml/kg/days, 182 cal/kg/day, 148 nonprotein cal/N ratio) consisting of carbohydrate mixtures (combination of glucose, fructose, and xylitol, 4:2:1 GFX solution) and 10% amino acids solution with 30% of branched chain amino acids (BCAA). Blood, liver, and urine samples were analyzed on 1, 3 postoperative days. Increased body weight, positive balance in daily nitrogen excretion, and decreased water content of the liver were observed in old rats. Protein, glycogen, and triglyceride contents of the liver tissue increased in old rats. However the young rats showed negative nitrogen balance and stronger catabolic effect than the old rats. It suggested negative nutritional balance in young rats with this decreased dosage of GFX+BCAA solution suitable for the old rats. In conclusion, decreased amounts of GFX+BCAA solution improved perioperative metabolism in the extremely old.

Age Factors

Mutation of Glu693 to Gln or Val717 to Ile has no effect on the processing of Alzheimer amyloid precursor protein expressed in COS-1 cells by cDNA transfection.

One of the features of Alzheimer's disease (AD) is the formation of senile plaques, of which the main component is a 42 amino acid beta-protein (beta P). Molecular cloning of beta P revealed the presence of a 90-130 kDa precursor, amyloid precursor protein (APP). Since APP is expressed in normal brain without producing beta P, some abnormal processing is the cause of the formation of beta P in AD. Two kinds of mutations of APP, Glu693 to Gln and Val717 to Ile, were reported in AD-related diseases. Site-directed mutagenesis was applied, and the mutated APPs were expressed in COS-1 cells by cDNA transfection. They showed apparently the same processing as wild APP. This means that these mutations might not be a direct cause for the abnormal processing of APP or the formation of beta P in AD.

Amino Acid Sequence