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Biomedical subjects

M Usami

Publications and source records attributed to M Usami.

At least 37 records · Page 2Linked to original sources
PubMed2000

Clinical significance of nonpalpable prostate cancer with favorable biopsy features in Japanese men.

OBJECTIVE: To assess the clinical significance of nonpalpable localized prostate cancers with relatively favorable six sextant biopsy features in Japanese men. PATIENTS AND METHODS: 136 nonpalpable prostate cancers of which biopsy features confined to (1) a Gleason score of 6 or less, (2) one or two positive cores per six sextant cores, and (3) 50% or less involvement of any positive core were collected. The Gleason score, tumor extension, and cancer volume were compared with preoperative serum PSA and PSA density for the patients who underwent radical prostatectomy. PSA doubling time was measured for the patients who were treated expectantly. RESULTS: Treatments chosen for 136 patients with favorable biopsy features were radical prostatectomy alone for 48 and with preoperative androgen deprivation for 30, radiation to the prostate for 12, androgen deprivation therapy for 21, and watchful waiting for 25. Of 48 patients who underwent radical prostatectomy without androgen deprivation therapy, 25% had nonorgan-confined cancers. Seven cancers (14.6%) were Gleason score of 7, but no cancers were 8 or greater. Among 42 prostatectomy specimens for which cancer volume was measured, 22 (52.4%) had cancer volume >0.5 cm(3). Pretreatment serum PSA levels were correlated neither with the Gleason score, tumor extension nor cancer volume. There was only one nonorgan-confined cancer in the 23 cancers for which PSA density was <0.2 ng/ml/g. The ability of PSA density to predict cancer volume <0. 5 cm(3) was 0.61 using a cut-off of 0.2 ng/ml/g. Of the 25 patients treated expectantly, the PSA doubling time was less than 2 years for 3 patients, while it was stable or fluctuated for 13. CONCLUSIONS: Tumor extension can be predicted based on PSA density in nonpalpable prostate cancer with favorable biopsy features, but predictability of cancer volume based on PSA or PSA density is not satisfactorily high. New parameters or biomarkers that complement needle biopsy findings are needed to predict clinical significance of T1c prostate cancer with favorable biopsy features.

Aged↗
PubMed2000

Molecular interactions between presenilin and calpain: inhibition of m-calpain protease activity by presenilin-1, 2 and cleavage of presenilin-1 by m-, mu-calpain.

Several mutations of presenilin (PS)-1, 2 result in early onset Alzheimer disease. Using the yeast two-hybrid system, the interaction between PS2 loop domain and the C-terminal region of mu-calpain was previously identified. Calpain is a calcium dependent-protease and there are two isoforms, m-calpain and mu-calpain, which differ in the calcium concentration required for activation. m-Calpain needs about 10(-3) M calcium ions, whereas mu-calpain about 10(-5) M. When PS and calpain were separately expressed in COS cells by cDNA transfection and then combined in vitro, or both were co-transfected to be co-expressed in vivo in COS cells, PS1 and PS2 reduced the casein proteolysis activity of m-calpain but not that of mu-calpain. Some of the PS mutations related to Alzheimer disease decreased this inhibitory activity. On the other hand, PS1 was cleaved by m-calpain and mu-calpain at a different site from those already reported (constitutive cleavage or alternative cleavage). These results suggest a regulatory function of presenilin on the calpain system.

Animals↗
PubMed2000

Comparative developmental toxicity study of indium in rats and mice.

The developmental toxicity of indium was examined in both rats and mice using comparable experimental protocols. Pregnant rats received a single intravenous administration of indium trichloride (InCl(3)) at 0.4 mg In/kg, on day 9, 10, or 11 of pregnancy and their fetuses were examined on day 20. Pregnant mice were treated in the same manner at 0.8 or 1.6 mg In/kg on day 7, 8, or 9 of pregnancy and their fetuses were examined on day 18. In rats, indium caused fetal weight decrease and fetal gross malformations, such as brachyury, kinked tail, cleft palate, and oligodactyly, most severely by the administration on day 10. In mice, however, indium did not cause fetal gross malformations, although it caused fetal weight decrease at 0.8 mg In/kg or more and fetal death at 1.6 mg In/kg, most severely by the administration on day 8. It was concluded from these results that rats and mice were susceptible to the embryotoxicity of indium at similar developmental stages in the early organogenetic period, but mice were less susceptible to the teratogenicity of indium than rats in terms of gross malformation. Toxicokinetic factors may be involved in this different susceptibility. Teratogenesis Carcinog. Mutagen. 20:219-227, 2000.

Abnormalities, Drug-Induced↗
PubMed2000

[Teratogenicity study of 2,2,3,3,3-pentafluoro-1-propanol (5FP) in rats by oral administration].

Teratogenicity of 2,2,3,3,3-pentafluoro-1-propanol (5FP), an alternative cleaning agent for chlorofluorocarbon, was examined in rats. 5FP was diluted with sesame oil and given to pregnant rats (Crj: Wistar) by gavage once a day from day 7 to 17 of pregnancy at doses of 0, 250, 500 and 1000 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their fetuses were examined for malformation. In the pregnant rats, 5FP caused wheezing, salivation, ptosis, reduced body weight gain and reduced food consumption at 500 and 1000 mg/kg/day. In the fetuses, 5FP reduced body weight, increased the incidences of skeletal variations and retarded the ossification at 1000 mg/kg/day, but did not increase the incidences of malformations. It was concluded from these results that 5FP has no teratogenicity in rats when given by gavage. The no-observed-adverse-effect level was 500 mg/kg/day for rat fetuses, and 250 mg/kg/day for pregnant rats.

Abnormalities, Drug-Induced↗
PubMed2000

[Teratogenicity study of morpholine salts of fatty acids (oleic acid, 50% water solution) in rats by oral administration].

Teratogenicity of morpholine salts of fatty acids was examined in Wistar rats (Crj: Wistar). Morpholine salts of fatty acids (oleic acid, 50% water solution) was given to pregnant rats by gavage once a day from day 6 through day 15 of pregnancy at doses of 0, 234, 468 and 936 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their fetuses were examined for malformation. Morpholine salts of fatty acids caused nasal discharge, dirty nose and salivation in pregnant rats at doses from 234 mg/kg/day. However, fetal effects, such as malformation and growth retardation, were not observed even at 936 mg/kg. It was concluded that morpholine salts of fatty acids has no teratogenicity in rats when given by oral administration. The no-observed-adverse-effect level was 936 mg/kg/day for rat fetuses and less than 234 mg/kg/day for pregnant rats.

Abnormalities, Drug-Induced↗
PubMed1999

Incidence rate of satellite tumors in renal cell carcinoma.

BACKGROUND: Nephron-sparing surgery for incidentally detected small renal tumors has been performed. The main objection to such surgery concerns the incidence rate of satellite renal tumors. In this study, the authors analyzed the rate of incidence and proliferative potential of satellite renal tumors. METHODS: The tumors of 124 renal cell carcinoma patients with a clinically identified unilateral and single tumor measuring </=90 mm who were examined between November 1991 and May 1997 were analyzed prospectively. The authors determined whether these specimens obtained by radical nephrectomy had satellite tumors, and whether the satellite tumors were reactive with a monoclonal antibody (MoAb), MIB-1, to assess their proliferative potential. RESULTS: Satellite renal cell carcinomas were detected in 8 of the 124 patients (6.5%). None of the pathologic variables examined (tumor grade, tumor stage, main tumor size, cell pattern, and vascular invasion) were found to be predictive of the presence of satellite tumors. Of these eight tumors, two main tumor specimens and three satellite tumor specimens reacted with the MIB-1 MoAb. The reactivity of MIB-1 correlated with the tumor grade. The satellite tumors were observed to have a proliferative potential compared with the main tumors. Among 86 kidney specimens from patients with urothelial tumors after total nephroureterectomy, 2 (2.3%) contained small renal cell carcinoma but did not show positive staining with the MoAb MIB-1. CONCLUSIONS: The incidence rate of satellite tumors among 124 renal cell carcinoma patients was 6.5% and the presence of satellite tumors was not predictable. Some of these satellite tumors showed positive staining with the MIB-1 MoAb, but small renal tumors detected in kidney specimens with urothelial tumors did not.

Adult↗
PubMed1999

Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis.

Analysis of the gene cluster from Streptomyces avermitilis that governs the biosynthesis of the polyketide anthelmintic avermectin revealed that it contains four large ORFs encoding giant multifunctional polypeptides of the avermectin polyketide synthase (AVES 1, AVES 2, AVES 3, and AVES 4). These clustered polyketide synthase genes responsible for avermectin biosynthesis together encode 12 homologous sets of enzyme activities (modules), each catalyzing a specific round of polyketide chain elongation. The clustered genes encoding polyketide synthase are organized as two sets of six modular repeats, aveA1-aveA2 and aveA3-aveA4, which are convergently transcribed. The total of 55 constituent active sites makes this the most complex multifunctional enzyme system identified to date. The sequenced DNA region contains 14 additional ORFs, some of which encode polypeptides governing other key steps in avermectin biosynthesis. Between the two sets of polyketide synthase genes lie two genes involved in postpolyketide modification, one of which encodes cynthochrome P450 hydroxylase that probably catalyzes furan ring formation at C6 to C8a. Immediately right of the large polyketide synthase genes is a set of genes involved in oleandrose biosynthesis and its transglycosylation to polyketide-derived aglycons. This cluster includes nine genes, but one is not functional in the biosynthesis of avermectin. On the left side of polyketide synthase genes, two ORFs encoding methyltransferase and nonpolyketide synthase ketoreductase involved in postpolyketide modification are located to the left of the polyketide synthase genes, and an adjacent gene encodes a regulatory function that may be involved in activation of the transcription of avermectin biosynthetic genes.

Anthelmintics↗
PubMed1999

Presenilin-1 exists in the axoplasm fraction in the brains of aged Down's syndrome subjects and non-demented individuals.

Missense mutations in the presenilin-1 (PS-1) gene are known to be responsible for early-onset familial Alzheimer's disease (AD). The normal physiological functions of PS-1 are still incompletely understood, although data on the intracellular localization of PS-1 are accumulating, indicating that it exists mainly in endoplasmic reticulum and Golgi compartments. To investigate the localization and functions of PS-1 in the human brain, we separated axoplasm fractions from the cerebral white matter of Down's syndrome (DS) subjects with AD pathology and non-demented individuals using the axonal flotation method, and analyzed them immunocytochemically. All axoplasm fractions contained the 28-34 kDa amino-terminal fragment and the 18 kDa carboxy-terminal fragment of PS-1, although there was no specific abnormality of this protein in the DS brains with AD pathology. This finding indicates that there is intracellular trafficking of PS-1 through the axons in the human brain, and thus provides new information about the physiology of PS-1.

Adult↗
PubMed1999

The tau mutation (val337met) disrupts cytoskeletal networks of microtubules.

The missense point mutation found in the tau gene, which was segregated in a family with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), has proved to be the causal molecule for widely spread dementia diseases. Here we examined the effects of the tau mutation using confocal analysis. When wild-type tau cDNA was introduced into cells, extensive cell processes and well-developed thick bundles of microtubules were induced. On the other hand, when altered tau cDNA with the mutation (valine337-methionine) was introduced, cell lost processes and microtubule networks resulted in more round cell shape but showed intact mitochondria or endoplasmic reticulum. We conclude that the tau mutation primarily affects the microtubules and resultantly causes the loss of cellular organization and function due to microtubule disruption.

Amino Acid Sequence↗
PubMed1999

Effects of ascorbic acid on selenium teratogenicity in cultured rat embryos.

The effects of ascorbic acid, as an exogenous antioxidant, on selenium (Se) teratogenicity were examined using rat embryo culture. Rat embryos at day 9.5 of gestation were cultured for 48 h in the presence of sodium selenite at 10 and 20 microM or sodium selenate at 30 and 100 microM with or without the addition of 1 mM of L-ascorbic acid (AsA). Selenite or selenate alone increased the incidence of embryonic malformation. With AsA, the incidence of selenite-induced embryonic malformation was increased. On the contrary, the incidence of selenate-induced embryonic malformation was decreased with AsA. It was considered from these results that the redox states in the embryonic environment and of Se are critical in Se teratogenicity.

Animals↗
PubMed1999

Impact of tumor size on the clinical outcomes of patients with Robson State I renal cell carcinoma.

BACKGROUND: In the TNM classification of renal cell carcinoma released in 1997, T1 tumors were defined as organ-confined tumors 7.0 cm or less in size, and T2 as those larger than 7.0 cm. The consideration of tumor size should be predicated on its prognostic value in predicting survival, because the goal of clinical staging is to separate patients into similar classes of survival based on the extent of disease at presentation. The authors examined the impact of tumor size on the clinical outcomes of patients with Robson Stage I disease to determine a size cutoff that would maximize the predictive value of the TNM staging system. METHODS: Between 1962 and 1995, 382 patients with renal cell carcinoma were treated at the Department of Urology at the Osaka Medical Center for Cancer and Cardiovascular Diseases in Osaka, Japan, and the TNM staging of 350 of those patients was recorded. Of 350 patients, 157 (45%) were at TNM Stage I, 47 (13%) at Stage II, 65 (19%) at Stage III, and 81 (23%) at Stage IV, according to the TNM stages defined in 1997. Robson Stage I includes TNM Stages I and II, and 204 patients in these stages were analyzed in this study. This study group included 146 men and 58 women with a mean age of 57.8 years (range, 26-84 years). The mean follow-up period was 5.4 years. RESULTS: The patient survival periods were not significantly different for those with TNM Stages I and II. This finding indicated that the tumor size cutoff of 7.0 cm was not useful in predicting the prognosis. The patients at TNM Stages I and II were then divided into two groups at each size cutoff, from 2.5 cm to 9.0 cm, at 0.5-cm intervals. The tumor size cutoff of 5.5 cm was most predictive of patient survival (P = 0.0121). None of other patient characteristics varied significantly between the two groups at this dichotomous point. Tumor size and microscopic intrarenal venous invasion, but not grade or infiltration pattern, were found in univariate and multivariate analyses to be significantly predictive of the survival of Robson Stage I patients after radical nephrectomy. CONCLUSIONS: The current data indicate that the tumor size cutoff of 5.5 cm was most significantly predictive of the survival of Robson Stage I patients after radical nephrectomy. The tumor size cutoff of 5.5 cm was also shown to be significant in univariate and multivariate analyses.

Adult↗
PubMed1999

Enteral nutrition prevents bacterial translocation but does not improve survival during acute pancreatitis.

OBJECTIVE: To evaluate the effect of enteral nutrition (EN) in attenuating bacterial and/or endotoxin translocation, maintaining immune responsiveness, and improving outcome in early acute pancreatitis (AP) in Wistar male rats. DESIGN: Acute pancreatitis was induced in rats receiving total parenteral nutrition (TPN) (AP/TPN group) (n=34) and EN (AP/EN group) (n=35) by pressure injection of 1% deoxycholate into the biliopancreatic duct (0.6 mg/kg of body weight). Rats in the sham/TPN and sham/EN groups (n=10 each) underwent laparotomy without induction of AP. Catheters for TPN and EN were placed into the external jugular vein and jejunum, respectively. Rats were infused with Ringer lactate solution for 48 hours followed by TPN in the AP/TPN and sham/TPN groups, and EN in the AP/EN and sham/EN groups until day 7. The fluid volume and energy (calories) intake were similar in all groups. SETTING: Medical school research laboratory. MAIN OUTCOME MEASURES: Survival, blood endotoxin level, villus height, 5-bromo-2'-deoxyuridine (BrdU) uptake in the jejunum and ileum, bacterial culture of mesenteric lymph nodes, and CD4/CD8 ratio of T cells in mesenteric lymph nodes, spleen, and peripheral blood. RESULTS: There was no difference in survival and pancreatic healing between the AP/TPN and AP/EN groups. Colony-forming units of the mesenteric lymph nodes and the endotoxin level were significantly lower in the AP/EN group than in the AP/TPN group (P<.05). Villus height and BrdU intake was significantly higher in the AP/EN group than in the AP/TPN group (P<.05). The CD4/CD8 ratio of T cells in spleen and peripheral blood was higher in the AP/EN group than in the AP/TPN group (P<.05), whereas there was no difference in mesenteric lymph nodes. CONCLUSIONS: Jejunal administration of EN is well tolerated in early AP, maintains immune responsiveness and gut integrity, and reduces bacterial and/or endotoxin translocation. However, compared with TPN, EN does not improve outcome. These results suggest that factors other than bacterial and/or endotoxin translocation may be responsible for mortality in this rat model of early AP. However, additional studies of both early bacterial and/or endotoxin translocation and late assessment of outcome are indicated.

Acute Disease↗
PubMed1999

Developmental toxicity of indium in cultured rat embryos.

Developmental toxicity of indium was examined using rat embryo culture with reference to toxicokinetics. Rat embryos at day 9.5 of pregnancy were cultured for 48 h under various exposure conditions to indium trichloride. Indium was embryotoxic to cultured rat embryos at concentrations ranging from 25 to 50 microM for 24 h exposure according to the embryonic age, and the exposure concentration was more critical than the exposure time. The embryotoxic concentrations were comparable to the serum concentration at a developmentally toxic dose by intravenous administration in an in vivo experiment. It was considered from these results that the developmental toxicity of indium is a direct effect on the embryo or yolk sac and that weak developmental toxicity of indium by oral administration was due to low exposure concentrations in the embryo.

Animals↗
PubMed1999

Effects of glutathione depletion on selenite- and selenate-induced embryotoxicity in cultured rat embryos.

Effects of depletion of reduced glutathione (GSH) on selenium (Se) embryotoxicity in cultured rat embryos were examined. Rat embryos at day 9.5 of gestation were cultured for 48 h in the presence of Se as either sodium selenite at 10 and 20 microM or sodium selenate at 30 and 100 microM. Embryonic GSH was depleted by the addition of 0.1 mM of L-buthionine-[S,R]-sulfoximine (BSO) without embryotoxicity, i.e., significant growth retardation and malformation of the embryos. Selenite at 10 microM or selenate at 100 microM significantly increased the incidence of malformation of the embryos. The incidence of selenite-induced malformation of the embryos at 20 microM was significantly decreased with BSO. On the contrary, the incidence of selenate-induced malformation at 30 microM was significantly increased with BSO. It was noted that the major malformed regions of the embryos by the embryotoxic concentration of BSO alone were the same to those affected by selenite or selenate. It was considered from these results that embryonic GSH was involved in the embryotoxicity of selenite and selenate. The embryotoxicity of selenate may not be mediated through the reduction to selenite. It was suggested that the formation of selenodiglutathione and the oxidative stress were involved in the embryotoxicity of selenite and selenate, respectively.

Animals↗
PubMed1999

A high incidence of apolipoprotein E epsilon4 allele in middle-aged non-demented subjects with cerebral amyloid beta protein deposits.

We examined the apolipoprotein E (ApoE) genotypes of 19 middle-aged non-demented subjects with cerebral amyloid beta protein (Abeta) deposits, and compared the results with those of 16 patients with sporadic Alzheimer's disease (AD) and those of 34 age-matched controls. The frequency of the ApoE epsilon4 allele was higher (P = 0.0256) in these 19 subjects (0.211) than in controls (0.059), and was close to that in AD patients (0.281). This result suggests that middle-aged non-demented subjects with cerebral Abeta deposits are at high risk of developing AD, and that the diffuse Abeta deposits in these cases represent an early stage of AD pathology. We speculate that in the majority of late-onset sporadic AD patients, cerebral Abeta deposition commences when these patients are in their forties or fifties, and that the pathological process progresses gradually, taking 20 to 30 years for clinical manifestation of dementia.

Adult↗
PubMed1999

Long-term results of a randomized trial for the treatment of Stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities.

OBJECTIVES: To improve the treatment of locally advanced prostate cancer (Stages B2 and C), a prospective randomized trial was conducted to compare radical prostatectomy versus external beam radiotherapy with the combination of endocrine therapy in both modalities. METHODS: One hundred patients were enrolled and 95 were evaluated. Forty-six patients underwent radical prostatectomy with pelvic lymph node dissection, and 49 were treated with radiation by linear accelerator with 40 to 50 Gy to the whole pelvis and a 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiation, and continued thereafter. The living patients were asked to respond to a quality-of-life questionnaire. RESULTS: The follow-up period ranged from 6.0 to 94.4 months (median 58.5). The progression-free and cause-specific survival rates at 5 years were 90.5% and 96.6% in the surgery group and 81.2% and 84.6% in the radiation group, respectively. The surgery group had better progression-free and cause-specific survival rates (P = 0.044 and 0.024, respectively). More patients in the surgery group complained of urinary incontinence. The questionnaire revealed that quality of life was less disturbed in the radiation group. CONCLUSIONS: Radical prostatectomy combined with endocrine therapy may contribute to the survival benefit of patients with locally advanced prostate cancer. External beam radiotherapy in combination with endocrine therapy can be used in selected patients because of its low morbidity.

Adenocarcinoma↗
PubMed1999

Early results of radical prostatectomy and adjuvant endocrine therapy for prostate cancer with or without preoperative androgen deprivation. The Prostate Cancer Study Group.

BACKGROUND: The effects of preoperative androgen deprivation were explored in the patients who received radical prostatectomy and subsequent adjuvant endocrine therapy for prostate cancer. METHODS: Stage A2, B or C prostate cancers were randomized to one of two groups: (i) group I (n=90), who received androgen deprivation (leuploride and chlormadinone acetate) for 3 months preoperatively followed by radical prostatectomy and adjuvant endocrine therapy (leuploride only); and (ii) group II (n=86), who underwent the surgery followed by 3 month androgen deprivation and subsequent adjuvant endocrine therapy. The effects of preoperative androgen deprivation on clinical relapse (serum prostate specific antigen (PSA) > 1.98 ng/mL, local recurrence or distant metastasis) and PSA relapse (PSA >0.2ng/mL) were evaluated at 2 years after randomization. RESULTS: There was no significant difference in clinical or PSA relapse-free survival and quality of life measures between the two groups, although relapses occurred significantly more frequently in patients who had more advanced stages, higher pretreatment PSA values or lower histologic differentiation in either group. Subgroup analysis indicated that clinical relapse-free survival in stage C cancer tended to be better in patients with preoperative androgen deprivation than in those patients without it (P< 0.1). CONCLUSIONS: Preoperative androgen deprivation may be beneficial for stage C prostate cancer patients receiving radical prostatectomy and adjuvant endocrine therapy over the 2 year observation period. A longer follow up is needed to clarify the exact extent of benefit in terms of survival and quality of life.

Aged↗