Biomedical subjects

M Usami

Publications and source records attributed to M Usami.

At least 145 records · Page 8Linked to original sources

PubMed1993

The triplet of lysine residues (Lys724-Lys725-Lys726) of Alzheimer's amyloid precursor protein plays an important role in membrane anchorage and processing.

One of the pathological changes of Alzheimer's disease is the deposit of beta/A4 protein, which is derived from Alzheimer amyloid precursor protein (APP). In the secretory pathway, APP is cleaved at an internal region of beta/A4 protein by a hypothetical enzyme "secretase." Our previous study showed that the site of cleavage of APP by secretase is determined by the length from the membrane-spanning region. To investigate the role of the transmembrane region in APP secretion, we constructed the mutations of triplet lysine residues (Lys724-Lys725-Lys726), which are located just in the carboxyl region after the proposed membrane domain. The mutations were as follows: VVK, Val724-Val725-Lys726; LLI, Leu724-Leu725-Ile726; and EEE, Glu724-Glu725-Glu726. Wild-type APP and mutant APPs were expressed transiently in COS-1 cells by cDNA transfection. The hydrophobic mutant VVK and LLI were processed and secreted in a way similar to that of the wild-type APP, although the rate of secretion was decreased. The acidic mutant EEE was not secreted into medium. Proteinase K treatment and cell surface biotinylation of the COS-1 cells expressing APP revealed that APP was located in the plasma membrane with a short intracellular carboxyl region. However, EEE was completely digested by proteinase K treatment, which suggested that the whole residues of this mutant are located at the outer surface of the cell, including its proposed membrane domain and carboxyl region. This mutant was not cleaved at all by secretase. These findings suggested that the triplet lysine residues of AP after the predicted membrane spanning domain play an important role in the membrane anchorage.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗

PubMed1993

[Assessment of the quality of life of prostate cancer patients].

Assessing the QOL in cancer clinical trials is becoming increasingly important. However, a suitable device of assessment of QOL has not been developed yet for prostate cancer patients in Japan. We tried to assess the QOL of prostate cancer patients using the EORTC questionnaire translated in Japanese, and examined its validity and reliability. Thirty-six patients filled in a questionnaire. The reliability of this device was confirmed by the results of test-retest reproducibility. Good correlation was shown between the results and patients performance status, and between the results and clinical stages, which support the validity of the device. As for the results of assessment of QOL, these patients were severely damaged in sexuality. Those factors of functional status, physical symptoms and fatigue/malaise were closely related to disease activity and clinical stage.

Aged↗

PubMed1993

[Neoadjuvant therapy for prostatic cancer].

Neoadjuvant therapy for prostatic cancer might be important to increase cure rates of the disease and preservability of the organs. There were 43 cases in a period of 1975-1990 in which total prostatectomy were performed after neoadjuvant therapy. According to the clinical stage, there were 14 cases in B, 23 in C, 4 in D1 and 2 in D2. The median duration of neoadjuvant therapy was 4 months. Clinical response of the prostate in 37 evaluable cases was as follows; 6 cases were PR (16%), 12 cases were MR (32%) and 19 cases were NC (52%). Histopathological effect was as follows; 5 cases were grade 0a (12%), 12 cases were grade 0b (28%), 16 cases were grade 1 (37%), 8 cases were grade 2 (19%) and 2 cases were grade 3 (5%). In 2 cases with histopathological effect of grade 3, lymph node metastases were thought to have obviously disappeared. Histopathological effect seemed related to clinical response. In cases given neoadjuvant therapy for less than 2 months, no adequate clinicopathological effect was obtained. Cases that could achieve downstaging were 8; 1 in grade 0a, 2 in grade 1, 3 in grade 2 and 2 in grade 3. These results suggest that neoadjuvant therapy plays an important role in advanced prostatic cancer.

Aged↗

PubMed1993

[Successful interferon therapy of renal cell carcinoma with tumor thrombus extending into the inferior vena cava--a case report].

It is a fact that there are few effective drugs available except for interferon for that treatment of renal cell carcinoma, and the efficacy rate of interferon is less than 10% even if multiple drug regimens are included. We have experienced a case of renal cell carcinoma in whom interferon therapy was successful in reducing the primary lesion and tumor thrombus extending into the inferior vena cava. A 57-year-old man was admitted to our department with a complaint of macroscopic hematuria. Computed tomography and magnetic resonance imaging revealed a right renal tumor and the tumor thrombus. Because of the past history of his myocardial infarction, a radical operation was considered risky. So we started interferon therapy. Four months after the start of interferon therapy, the primary lesion and the tumor thrombus markedly reduced in their size, and the clinical response was evaluated as partial response by response criteria for urological cancer treatment. Therefore, radical nephrectomy and tumor thrombectomy were performed with extracorporeal circulation. Histopathologically, necrosis and lymphocyte infiltration into the cancer cell focus were seen, and these immunologic reactions were considered at the affection of interferon. In some case, interferon therapy is a useful and safe in the treatment of the primary lesion of renal cell carcinoma, and further investigation must be studied.

Carcinoma, Renal Cell↗

PubMed1993

A randomized phase II trial of flutamide vs chlormadinone acetate in previously untreated advanced prostatic cancer. The Japan Flutamide Study Group.

We have conducted a double-blind comparative study of flutamide and chlormadinone acetate (CMA) on patients with stage C or D prostatic cancer and with no prior experience of hormone therapy. This is believed to be the first such trial entered in the medical literature, fifty-four patients were randomly selected to undergo flutamide (p.o.) monotherapy at a daily dose of 375 mg, which was determined as the optimal dose in Japan in our previous phase II study. Forty-nine others were randomly selected to undergo CMA (p.o.) monotherapy at a daily dose of 100 mg, which is the most commonly used dosage in Japan for patients with prostatic cancer. Ultimately, 47 patients from the flutamide group and 40 patients from the CMA group were judged eligible, with efficacy being evaluated after 12 weeks of treatment. Similar objective responses were seen in both groups: 48.9% (95% confidence limits 34.1-63.9%) in the flutamide group, 45% (95% confidence limits 29.3-61.5%) in the CMA group. The response at each organ site was also similar between the groups. Serum prostatic specific antigen decreased by more than 50% of the abnormal pretreatment level in 87.5% of the flutamide group and in 85.7% of the CMA group. Serum luteinizing hormone, follicle-stimulating hormone, testosterone and 5 alpha-dihydrotestosterone decreased significantly in the CMA group, but increased significantly in the flutamide group. The serum testosterone level after 12 weeks of treatment was 0.955 +/- 0.13 ng/ml in the CMA group and 6.64 +/- 0.38 ng/ml in the flutamide group. The serum estradiol level also increased significantly in patients in the flutamide group. The serum prolactin level decreased significantly in the flutamide group, but increased significantly in the CMA group. Eight patients on flutamide manifested gynecomastia. Diarrhea and hepatic toxicity were observed in both groups, but only rarely, and were well tolerated. We have thus concluded that flutamide is as effective as CMA in maintaining libido and potency without decreasing testosterone levels.

Aged↗

PubMed1993

[Assessment of myocardial viability by exercise stress-redistribution myocardial scintigraphy with thallium-201: the usefulness of C-map].

Standard exercise (Ex)-redistribution (RD) myocardial imaging with thallium-201 (201Tl) may not differentiate viable myocardium from necrosis. This study was intended to clarify whether 201Tl washout rate (WOR) abnormality after Ex can detect myocardial viability in the myocardium with perfusion defect using routine RD image. We performed Ex-RD (three hours after) myocardial tomography with 201Tl in 29 patients with coronary artery disease. From myocardial tomography, 201Tl distribution Bull's-eye maps (Ex and RD) and WOR Bull's-eye map were made. At RD image before PTCA, by referring to the original image, the activity of the myocardial region below 40% to 55% of the maximal 201Tl activity was considered as perfusion defect (RD-Map). Then we constructed a new image (C-Map) by adding the location of WOR abnormality (< or = 30%) to the RD-Map and each map was divided into 17 segments. If the defect-segment in the RD-Map corresponded to WOR abnormality, the segment in the C-Map was judged as viable (no defect). The C-Map and myocardial imaging after PTCA (Post-Map) were compared. In the RD-Map before PTCA, defect was found in 152 segments but in the C-Map they decreased to 59 segments, while defect was found in 62 segments in the Post-Map. In 23 patients the number of defect-segments in the C-Map decreased as compared with those in the RD-Map. And in 22 of them, the Post-Map showed the reduction of defect-segments in comparison with the RD-Map, but in one of them defect did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

[Tuberculosis of the female urethra: a case report].

A 52-year-old female with the chief complaint of miction pain was referred for the examination of a urethral nodule. Physical inspection revealed the meatus to be reddish and swollen. The painless nodule (1 x 1 x 2 cm) was situated between the urethra and vagina on transvaginal examination. Chest X-ray, drip infusion pyelography (DIP) and urethrocystography (UCG) showed no evidence of tuberculosis. Bladder mucosa was normal on cystoscopy. Mycobacterium tuberculosis was not detected from urine or sputum. The nodule was resected along with a portion of the urethra. Histopathological examination revealed tuberculous granuloma of the urethra.

Drug Therapy, Combination↗

PubMed1993

[Inhibitory effect of portal pooling, bacterial translocation, and Kupffer cell activation on hepatic regeneration after partial hepatectomy by repeated portal triad cross clamping in rats].

Effect of hepatic ischemia and reperfusion on hepatic regeneration after 70% partial hepatectomy was evaluated in rats. Total hepatic ischemia by portal triad cross clamping (15 minutes) and reperfusion (15 minutes) was repeated two times during partial hepatectomy in the PS, non-PS, and G groups. In the C group, partial hepatectomy was made as a control without ischemia and reperfusion. In order to evaluate the effect of portal pooling, portal systemic shunt (PS shunt) was made by splenic transposition to subcutaneous space in the PS group, and compared with the non-PS group. Gadolinium chloride (GdCl3), the selective blocker of Kupffer (K) cell, was intravenously administered to the rat in the G group. Hepatic regeneration rates, labelling index of liver cells, rates of bacterial infection of mesenteric lymph nodes (MLN), blood levels of endotoxin (Ex) and tumor necrosis factor-alpha (TNF) were compared. Hepatic regeneration at 28 days was suppressed by total hepatic ischemia in the non-PS group. Increased positive rates of MLN culture and blood levels of Ex showed bacterial translocation induced by the portal pooling during portal triad clamping. PS shunt reduced both bacterial translocation and the suppression of hepatic regeneration occurred in the PS group. Hepatic regeneration was not suppressed and blood TNF level did not increased in the G group by the inhibition of K cell function. In conclusion, repeated total hepatic ischemia and reperfusion induced portal pooling, bacterial translocation, and activated K cell, then inhibited hepatic regeneration after partial hepatectomy.

Animals↗

PubMed1993

[Effect of ischemia and reperfusion on hepatic regeneration following partial hepatectomy in cirrhotic rat liver].

Hepatic regeneration of cirrhotic liver following partial hepatectomy was evaluated in the rats following portal triad cross clamp (Pringle's maneuver). Cirrhotic rats were induced by repeated intraperitoneal injection of thioacetamide. Sixty eight percent of partial hepatectomy was performed under general anesthesia with or without total hepatic normothermic ischemia. Pringle's maneuver consisted of 4 times repetition of the combination of 15-minute ischemia and 15-minute reperfusion. Rats were sacrificed on 1, 7, and 28 postoperative days. The increasing rate of regenerated liver, the labeling index (LI) by histochemical measurement of BrdU positive hepatocyte, biochemical tests of the blood were evaluated in non cirrhotic and cirrhotic rats. Cirrhotic rats tolerated Pringle's maneuver well, without portal congestion as observed in non cirrhotic rats, suggesting the formation of porto-systemic shunt in cirrhotic rats. The inhibition in DNA synthesis and hepatic regeneration rate was observed in liver cirrhosis. However, no statistical significant difference in hepatic regeneration was observed in cirrhotic rats with or without Pringle's maneuver. In conclusion, the rat with cirrhotic liver tolerated Pringle's maneuver well and the maneuver itself was not harmful for hepatic regeneration following the partial resection.

Animals↗

PubMed1993

[Experimental study of liver regeneration and tumor growth following partial hepatectomy].

An experimental study was performed aiming to clarify the mechanism of early recurrence of hepatocellular carcinoma following hepatectomy. AH109A ascites hepatoma cells were implanted in a liver or subcutaneous tissue of male Donryu rats 5 days prior to 70% partial hepatectomy (H group) or simple laparotomy (L group) or non operation control (C group). Rats were sacrificed at 1, 3, 7 postoperative days. Tumor size, labelling index (LI), tissue blood flow (TBF) and regeneration rate of the remnant liver were measured. Tumor size of the remnant liver in hepatectomy group was 492 +/- 117 mm3 against 129 +/- 63 mm3 in laparotomy group showing enhancement of tumor growth following partial hepatectomy with statistical significance (p < 0.01). On the contrary, there was no difference in the growth of subcutaneous tumor among H, L, C group. A significant increase of LI in both liver and subcutaneous tumor cells comparable to regenerating liver cells at 24 hours after hepatectomy was observed in H group. It suggests that some humoral hepatotrophic factors increased DNA synthesis of not only tumor cells but liver cells. TBF in the tumor and remnant area of the liver were increased. This result supports that increased hepatotrophic factors and TBF led to the enhancement of tumor growth in the remnant liver following partial hepatectomy.

Animals↗

PubMed1993

Epidural compression of the spinal cord caused by vertebral osteoblastic metastasis of prostate carcinoma. A case report.

A 71-year-old man with prostate cancer developed epidural compression of the spinal cord caused by bony protuberances expanding from a vertebral osteoblastic metastasis. Pathologic examination of the metastatic lesion showed that both tumor and thickened vertebral trabeculae broke through the cortex and formed bony protuberances. The periosteal new bone appeared not to arise from a reactive periosteum but from the tumor breaking through the cortex. A biologic interaction between the tumor and the host may be responsible for the rare periosteal new bone formation.

Adenocarcinoma↗

PubMed1993

[Chronic daily oral low-dose etoposide therapy for an aged patient with aggressive lymphoma: a successful case report].

A 72-year-old female from Fukuoka Prefecture was admitted to our hospital complaining of puffy face and general malaise in April, 1992. Physical examinations revealed generalized lymphadenopathy and hepatosplenomegaly complicated with superior vena cava syndrome. A histological diagnosis of diffuse large cell-type malignant lymphoma was made by cervical lymph node biopsy according to the Working Formulation. Immunohistochemical staining showed the lymphoma cells were of T cell lineage (CD43+). Though anti-human T lymphotropic virus type I (HTLV-I) antibody was positive, southern blot analysis of the cells did not reveal monoclonal integration of HTLV-I proviral DNA. Her liver and renal function were almost normal but there was slight elevation of LDH. Considering her age, oral administration of low-dose etoposide (25 mg/day) was started. In 4 days, her lymph nodes decreased in size with subjective improvements. Ten weeks later, examinations of the hand, ultrasonogram and CT scan showed lymphadenopathy and hepatosplenomegaly had disappeared completely. The neutrophil count was consistently above 1,500/microliters, with no remarkable adverse effects and only a moderate degree of alopecia. Thus, low-dose etoposide therapy was considered to be very useful in such a case of malignant lymphoma in the elderly.

Administration, Oral↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

[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↗

PubMed1992

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↗