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Macroalgal canopies, which provide nutrients and habitats for many invertebrates and fishes in coastal waters, are disappearing worldwide. The simultaneous assessment of changes in macroalgae and fish distribution before and after coastal desertification, including deeper coastal waters where beyond macroalgae growth need attention. Therefore, we investigated their spatial distribution in the coastal waters off southwestern Japan in late autumn and winter using the acoustic method combined with visual observation. The number of fish schools was higher in late autumn than in winter, while they had similar acoustic backscattering strength (Sv) and school size, tended to be distributed in shallower waters. The number was lower after the macroalgae disappeared in both seasons, while the average Sv was higher, and the size was larger. They were distributed in similar water depths during the winter season. Fewer fish schools and higher Sv were observed in deeper waters after the macroalgae disappeared. We concluded that more fishes moved to shallower waters in the autumn than in the winter because of higher water temperatures. Macroalgae benefited small juvenile fishes in both shallow and deep coastal waters. Further studies on the distribution of specific species are expected for the assessment and restoration of the macroalgal ecosystem. [ABSTRACT FROM AUTHOR]

The response spectra of multidimensional analyses are compared with one-dimensional (1D) local models to couple the irregular soil stratification effect at a site. In recent studies, the surface motion 2D/1D or 3D/1D spectra ratios are defined as the spectral aggravation factors for each region of a site. Particularly in alluvial basins, where the soil media is typically formed by fault ruptures or topographic depressions filled with sediments, the inclination of the rock outcrop at the edge of the basin has a considerable effect on the site response, and such an effect has not yet been taken into consideration in recent seismic building codes and general engineering applications. In this study, the natural alluvial basin near the North Anatolian Fault in Gemlik, Marmara region, Turkey, was investigated by 40 seismic site tests and 4 validation borings. The 2D and 1D nonlinear response history analyses in the north–south and east–west directions in the Gemlik basin were performed by numerical models on a finite difference scheme considering nonlinear elastoplastic material behaviors and geometric discontinuities. Twenty-two strong ground motions recorded at the rock site were excited vertically as SH waves. The numerical results showed that narrow basin effects were derived not only by reflection, refraction, and shifting behavior but also by the focusing and superposition of the seismic waves propagating from opposite basin edges. As a result, the site-specific spectral aggravation factors SAF2D/1D defined by the ratio between the 2D and 1D acceleration response spectra for each period and any location on the site were proposed for the Gemlik basin. The variations in the aggravation factors were observed as values increasing to 1.2–2.2 near the edge and at the basin center. [ABSTRACT FROM AUTHOR]

Simultaneous estimation of effects of source, propagation path, and local site amplification was carried out using observed strong motion records in a frequency range from 0.8 to 20 Hz for the purpose of empirical evaluation of the local site effects in different geological conditions in the northwestern part of Turkey. The analyzed data are S-wave portions of 162 accelerograms from 39 shallow events observed at 14 sites of BYTNet array. A spectral separation method was applied to the observed S-wave spectra. The solutions for source spectra, inelasticity factor of propagation path for S-waves ( Q -value), and factor of site amplification at each site were obtained in a least squares sense. In the analysis, we assumed that the factor of the site amplification at a reference site is the same as that of theoretical amplification of S-waves to the soil model whose bottom layer has an S-wave velocity around 2.15 km/s. The estimated Q -value of the propagation path is modeled as Q ( f) = 87.4f. The estimated site amplifications are characterized into three groups. The sites in the first group belong to rock site with no dominant peaks at a frequency range of 2 to 10 Hz. The second group of hard soil sites is characterized with moderately dominant peaks at a frequency of 5 Hz. The last group for soft soil sites has common peaks at a frequency of 4 Hz with larger amplitudes than those in the hard soil group. We, then, compare the amplifications with average S-wave velocity in top 30 m of the shallow S-wave profiles and proposed linear empirical formula between them at each frequency. We, furthermore, inverted the observed amplification factors into S-wave velocity and Q -value profiles of the deep soil over the basement. [ABSTRACT FROM AUTHOR]

Summary: Despite improvements in rheumatoid arthritis disease activity of in the past 10 years, the incidence of self-reported non-vertebral fractures did not decrease in our cohort of 9,987 patients. This study may indicate that osteoporosis treatment and non-vertebral fracture prevention remain important regardless of the rheumatoid arthritis disease activity. Introduction: Although rheumatoid arthritis (RA) is a risk factor for osteoporosis and fractures, few studies have described the association between disease activity and the fracture incidence in patients with RA. This study aimed to investigate changes in the non-vertebral fracture incidence between 2001 and 2010 in our Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort. Methods: The IORRA is a prospective observational cohort study of Japanese RA patients. A total of 9,987 patients with RA were enrolled in this cohort from 2000 to 2010. The clinical parameter and non-vertebral fracture occurrence data were collected biannually through self-reported questionnaires. Incidences of self-reported non-vertebral fractures were also analyzed via standardization according to gender, age, and disease activity during each 2-year period. Results: From 2001 to 2010, the percentage of patients with 28-joint disease activity score remission increased from 7.8 to 39.7 %, prednisolone intake decreased from 51.4 to 41.3 %, and bisphosphonate intake increased from 5.0 to 23.4 %. The non-vertebral fracture incidence rates were 24.6/1,000 person-years in 2001 and 35.5/1,000 person-years in 2010, with no apparent change even after standardization. The overall non-vertebral fracture incidence was significantly higher in the autumn/winter than in the spring/summer ( p = 0.02). Conclusion: Despite improvements in disease activity and functional disability, the non-vertebral fracture incidence exhibited no apparent change between 2001 and 2010 in our patients with RA. Osteoporosis treatment and non-vertebral fracture prevention remain important regardless of the disease control in patients with RA. [ABSTRACT FROM AUTHOR]

The mitotic spindle is assembled by the coordinated action of centrosomes and kinetochore microtubules. An evolutionally conserved protein family, transforming acidic coiled-coil (TACC), has been shown to be involved in this process. In humans, TACC3 is aberrantly expressed in a variety of human cancers, but its biological significance remains to be elucidated. Here, using a novel compound targeting TACC3, spindlactone (SPL), we show that the perturbation of TACC3 selectively inhibited the nucleation of centrosome microtubules in ovarian cancer cells. In contrast to centrosome microtubules, the kinetochore microtubules were robustly assembled, forming ectopic spindle poles that resulted in multipolar spindles. Interestingly, the extensive inhibition of TACC3 partially suppressed the nucleation of kinetochore microtubules. These dose-dependent effects of SPL were consistent with the results observed by the depletion of TACC3 and its binding partner, colonic and hepatic tumor overexpressed gene protein (TOGp). Although these proteins both have roles in the assembly of centrosome and kinetochore microtubules, their contributions were spatiotemporally different. Notably, SPL did not affect spindle assembly in normal cells. Furthermore, the oral administration of SPL significantly suppressed tumor growth in vivo. The unique mechanism of action of SPL not only enables it to be used as a tool to dissect the molecular basis of spindle assembly but also to provide a rationale for the use of TACC3 as a molecular target for cancer treatment. This rationale offers an opportunity to develop new strategies for cancer chemotherapy that overcome the limitations of microtubule toxins and expand their scope and clinical efficacy. [ABSTRACT FROM AUTHOR]

The cynomolgus macaque ( Macaca fascicularis) is currently used as an animal model in various fields of immunology especially in the development of innovative vaccines for the prevention and treatment of infectious diseases. The polymorphism of the major histocompatibility complex (MHC) influences the development of adaptive immune responses and it is crucial to characterize the polymorphism of cynomolgus MHC genes. We present here a systematic study of the MHC class II haplotypes in the Filipino macaque population. By the study of a large sample of Filipino animals ( N = 353), we have characterized 18 MHC class II haplotypes by means of genotyping seven microsatellites. The animals were DRB genotyped by means of PCR-SSO or DGGE-sequencing on genomic amplified fragments. We cloned and sequenced the complementary DNA (cDNA) of DQA, DQB, DPA, and DPB genes of 117 animals. Combining the microsatellite genotyping and cDNA characterized in the 117 animals, we defined genetic association between the cDNA and the microsatellites and characterized 18 MHC class II haplotypes. For 104 animals out of the 353 studied, the presence of a recombinant haplotype was highly probable. Thirty-four percent of recombination was located in 256 kb segment between D6S2876 and D6S2747 microsatellites, a region encompassing several hot spots of recombination in the human MHC. [ABSTRACT FROM AUTHOR]

Summary: Risk factors associated with the occurrence of hip fracture in Japanese patients with rheumatoid arthritis (RA) were evaluated in a prospective, observational cohort study. Physical disability, advanced age, history of total knee replacement (TKR), and low body mass index (BMI) appear to be associated with the occurrence of hip fracture. Introduction: This study seeks to evaluate the association between potential risk factors and the occurrence of hip fractures in Japanese RA patients. Methods: A total of 9,720 patients (82.1 % female; mean age, 55.7 years) with RA were enrolled in a prospective observational study from 2000 to 2010. Self-reported hip fractures were verified using patient medical records. Cox proportional hazards models were used to analyze independent contributions of various risk factors to hip fracture occurrence. Results: During a mean follow-up of 5.2 years, 152 patients reported 152 hip fractures. Among these patients, 97 hip fractures in 97 patients (15 males, 82 females) were verified with medical records. Japanese version of the Health Assessment Questionnaire (J-HAQ) disability score [per 1 score, hazard ratio (HR), 2.64; 95 % confidence interval (CI), 1.94-3.58], age (per 10 years; HR, 1.53; 95 % CI, 1.25-1.87), history of TKR (HR, 3.75; 95 % CI, 1.57-8.96), and BMI (per 1 kg/m, HR, 0.92; 95 % CI, 0.86-0.99) were significantly associated with hip fractures. Among the scores on the eight domains of the J-HAQ, J-HAQ (arising) (HR, 1.74; 95 % CI, 1.28-2.36) and J-HAQ (hygiene) (HR, 1.58; 95 % CI, 1.11-2.24) were significantly correlated with the occurrence of hip fracture. Conclusions: High J-HAQ disability score, advanced age, history of TKR, and low BMI appear to be associated with the occurrence of hip fractures in Japanese RA patients. Among the eight domains of the J-HAQ, arising and hygiene disabilities appear to be correlated with the occurrence of hip fractures in this patient population. [ABSTRACT FROM AUTHOR]

Background:In the era when various treatment agents for advanced-stage prostate cancer are available, it is important to investigate overall survival for metastatic prostate cancer treated with step-up hormonal treatment as a reference against new treatment regimens, including antitumor agents and/or new hormonal derivatives, and it is desirable to explore pretreatment, biopsy-related and post-treatment prognostic factors to establish tailor-made treatment strategies.Methods:Between 1992 and 2002, 94 patients were diagnosed with prostate cancer with distant metastases in our facility. Various pretreatment clinical findings including serum PSA, testosterone, alkaline phosphatase (ALP), digital rectal examination (DRE) and extension of disease score were investigated for predicting outcomes in step-up hormonal treatment. We also investigated the impact of pathological findings including Gleason grading, tumor volume indices, various Gleason grade 5 volume indices in biopsy specimens, and post-treatment PSA nadir following step-up hormonal treatment on overall survival.Results:The 3- and 5-year overall survival was 72.4% and 62.5%, respectively. According to univariate analyses, patients with PSA 100 ng ml-1, ALP <440 IU l-1, T1c to T3 on DRE, extension of disease (EOD) score 0-3, no Gleason grade 5 cancer in biopsy specimens or less such cancer and good response at any stage of hormonal therapy had significantly better overall survival than did patients with alternative status. A multivariate Cox proportional hazard model revealed that PSA nadir after first-line hormonal treatment, PSA nadir after second-line treatment and Gleason grade 5 volume index were independent prognostic factors.Conclusions:Even in very advanced prostate cancer, local pathological indices, a Gleason grade 5 volume index in particular, could differentiate patients with better prognosis from worse prognosis. Step-up hormonal therapy including luteinizing hormone-releasing hormone agonist, estrogen derivatives and steroid hormones may be valuable in patients with metastatic prostate cancer, especially in good responders at any stage of hormonal therapy. [ABSTRACT FROM AUTHOR]

The dominant clinical feature of polymyositis/dermatomyositis is weakness in proximal, rather than distal, musculature. Although rare, cases of focal/localized myositis in which polymyositis-like muscle inflammation is present in only one muscle or extremity have also been reported. The underlying mechanisms dictating involvement of specific muscle groups in polymyositis/dermatomyositis and focal/localized myositis have not been identified. Here, we describe a rare case of dropped-head syndrome due to localized idiopathic inflammatory myopathy (IIM) in the splenius capitis (neck extensor) muscle where major histocompatibility complex (MHC) class I expression was up-regulated in involved muscle fibers. Interestingly, the adjacent trapezius muscle was not affected, corresponding to muscle biopsy findings that did not show any sign of inflammation or MHC class I expression. Our case report therefore suggests that selection of affected muscle in IIM might be influenced by the MHC class I expression of the muscle. [ABSTRACT FROM AUTHOR]

Objective: Various studies worldwide have found that sound levels in hospitals significantly exceed the World Health Organization (WHO) guidelines, and that this noise is associated with audible signals from various medical devices. The pulse oximeter is now widely used in health care; however the health effects associated with the noise from this equipment remain largely unclarified. Here, we analyzed the sounds of variable-pitch pulse oximeters, and discussed the possible associated risk of sleep disturbance, annoyance, and hearing loss.Methods: The Nellcor N 595 and Masimo SET Radical pulse oximeters were measured for equivalent continuous A-weighted sound pressure levels (L(Aeq)), loudness levels, and loudness. Pulse beep pitches were also identified using Fast Fourier Transform (FFT) analysis and compared with musical pitches as controls.Results: Almost all alarm sounds and pulse beeps from the instruments tested exceeded 30 dBA, a level that may induce sleep disturbance and annoyance. Several alarm sounds emitted by the pulse oximeters exceeded 70 dBA, which is known to induce hearing loss. The loudness of the alarm sound of each pulse oximeter did not change in proportion to the sound volume level. The pitch of each pulse beep did not correspond to musical pitch levels.Conclusions: The results indicate that sounds from pulse oximeters pose a potential risk of not only sleep disturbance and annoyance but also hearing loss, and that these sounds are unnatural for human auditory perception. [ABSTRACT FROM AUTHOR]

A novel extracellular serine protease derived from Thermoanaerobacter tengcongensis, designated tengconlysin, was successfully overexpressed in Escherichia coli as a soluble protein by recombination of an N-terminal Pel B leader sequence instead of the original presequence and C-terminal 6× histidine tags. The purified protein was activated by 0.1% sodium dodecyl sulfate (SDS) treatment but not by thermal treatment. The molecular weight of tengconlysin estimated by SDS-polyacrylamide gel electrophoresis analysis and gel filtration chromatography was 37.9 and 36.2 kDa, respectively, suggesting that the enzyme is monomeric. The N-terminal sequence of mature tengconlysin was LDTAT, suggesting that it is a preproprotein containing a 29 amino acid presequence (predicted from the SigP program) and a 117 amino acid prosequence in the N-terminus. The C-terminal putative propeptide (position 469–540 in the preproprotein) did not inhibit the protease activity. The optimum temperature for tengconlysin activity was 90°C in the presence of 1 mM calcium ions and the optimum pH ranged from 6.5 to 7.0. Activity inhibition studies suggest that the protease is a serine protease. The protease was stable in 0.1% SDS and 1–4 M urea at 70°C in the presence of calcium ions and was activated by the denaturing agents. [ABSTRACT FROM AUTHOR]

Formate oxidase was found in cell-free extracts of Debaryomyces vanrijiae MH201, a soil isolate. After purification by column chromatography, the preparation showed a protein band corresponding to a molecular mass (MM) of 64 kDa on sodium dodecyl sulfate–polyacrylamide gel electrophoresis. The MM, estimated by a gel filtration, was 99 kDa. The preparation showed two and three bands on isoelectric focusing under denaturing and native conditions, respectively. These results suggest that the preparation contained three isoforms, each of which might be composed of αα, αβ, and ββ subunits with apparently similar MM. The preparation acted on formate with K m and V max values of 11.7 mM and 262 μmol min−1 mg−1, respectively, at pH 4.5 and 25°C, but showed no evidence of activity on the other compounds tested. The optimum pH and temperature were pH 4.0 and 35°C, respectively. The preparation showed activities of 85% of the initial activity after storage at pH 6.0 and 4°C for 8 weeks. When 10 mM formaldehyde was reacted with 2.0 U ml−1 of the enzyme preparation at pH 5.5 and room temperature in the presence of 2.0 U ml−1 of a microbial aldehyde oxidase and 100 U ml−1 of catalase for 180 min, neither of formate nor formaldehyde was detected, suggesting that the reaction involved the quantitative conversion of formaldehyde to carbon dioxide. [ABSTRACT FROM AUTHOR]

Diethylstilbestrol (DES) is a synthetic oestrogen, and its anticancer effects are exerted in androgen-dependent prostate cancer. The administration of DES decreases serum testosterone to castration levels. However, in androgen-independent prostate cancer patients, who are already orchiectomised, the administration of DES improves symptoms and decreases prostate-specific antigen (PSA). The mechanisms responsible for these direct inhibitory effects have been explained as biological actions not mediated by oestrogen receptors. We assessed the gene expression profiles of prostate cancer cells treated with DES, and investigated direct inhibitory effects of DES. DES inhibited the proliferation of LNCaP and PC-3 cells. cDNA microarray analysis showed that expression of many genes was downregulated by DES. However, insulin-like growth factor binding protein 6 (IGFBP-6) gene expression levels were upregulated in PC-3 cells. IGFBP-6 gene expression and protein levels significantly increased after DES treatment. Recombinant IGFBP-6 inhibited cell proliferation, and the inhibitory effect of DES was neutralised by anti-IGFBP-6 antibody. From the immunohistochemical analysis of IGFBP-6 using biopsy samples from androgen-independent prostate cancer, we found IGFBP-6 expression in androgen independent prostate cancer, and that DES treatment increased the IGFBP-6 staining intensity of the cancer cells in one sample. These findings suggested that DES induces IGFBP-6, which inhibits cell proliferation in an androgen-independent prostate cancer cell line, PC-3. IGFBP-6 therefore might be involved in the direct effects of DES in androgen-independent prostate cancer.British Journal of Cancer (2005) 92, 1538-1544. doi:10.1038/sj.bjc.6602520 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Purpose. The effects of cigarette smoking on the association between inflammation and cancer were studied, since some bacteria induce the production of tumor necrosis factor-α (TNF-α), a proinflammatory cytokine and endogenous tumor promoter, in cells. Methods. Bacteria from a gargled solution from the buccal cavity of 20 individuals were cultured in the presence of 4 mg/ml cigarette-smoke condensates. Although cigarette-smoke condensates inhibited growth of Staphylococcus aureus strongly and that of Staphylococcus warneri weakly, tobacco tar-resistant S. aureus and S. warneri were obtained. Results. One tobacco tar-resistant S. aureus strain (Sa-TA10) induced expression of the TNF-α gene in both Bhas 42 cells (v-Ha-ras transfected BALB/3T3 cells) and human lung cancer cell line H226B, while one tobacco tar-resistant S. warneri (Sw-TA75) did not induce it significantly. Moreover, Sa-TA10 induced formation of transformed foci and soft-agar colony in Bhas 42 cells in cooperation with the v-Ha-ras gene. The results suggested that Sa-TA10 has carcinogenic potential, whereas Sw-TA75 does not. Conclusion. These data suggest that tobacco tar-resistant S. aureus, with carcinogenic potential, is present in the buccal cavity of some individuals, and that cigarette smoking simultaneously inhibits growth of most of the bacteria and selects carcinogenic bacteria. [ABSTRACT FROM AUTHOR]

The RNASEL gene on chromosome 1q25 has been identified as a prostate cancer susceptibility gene. We screened for RNASEL germline mutations in familial prostate cancer patients, and performed a case-control study to examine the association of specific variants with prostate cancer risk in the Japanese. Three variants within the RNASEL gene, G282A, G1385A and T1623G were identified. G1385 and T1623G variants result in previously reported Arg462Gln and Asp541Glu variants, respectively. The novel G282A variant does not cause amino-acid substitution. A case-control study consisting of 101 familial prostate cancer cases and 105 noncancer controls showed that the Gln/Gln genotype of codon462 was observed in 7.6% of controls. However, the Gln/Gln genotype was not observed in cases, and reduced prostate cancer risk (odds ratio (OR)=0.061, P=0.014). The Asp/Asp genotype of codon541 increased the familial prostate cancer risk (OR=7.37, P=0.0004). In subset analysis, a significant association was observed in patients with more than two affected members (OR=3.15, P=0.028), and weak associations were found in patients with metastatic disease (OR=2.40, P=0.11) and high-grade disease (Gleason score >or=7) (OR=3.07, P=0.14). These findings suggested that the polymorphic changes within the RNASEL gene may be associated with familial prostate cancer risk in a Japanese population. [ABSTRACT FROM AUTHOR]

We encountered two pedigrees of hereditary prostate cancer. In one family, the father and his two sons had prostate cancer, and in the other family, three brothers developed prostate cancer. The mean age of these six individuals at the first examination was 65.3 years. Two individuals had stage B disease; three individuals, stage D disease; and one individual, disease of unknown stage. Histopathologically, two, one, and three individuals had well-, moderately, and poorly differentiated adenocarcinoma, respectively. As of September 28, 2000, five of the six individuals were still alive. In a search of the literature, these were found to be the seventh and eighth pedigrees in Japan that met the criteria of hereditary prostate cancer proposed by Carter and colleagues in 1993. [ABSTRACT FROM AUTHOR]

Inflammatory cytokines, such as interleukin (IL)-6, have been shown to reflect clinical signs in certain conditions in diseased animals. In this study, we quantified the IL-6 concentrations in the serum and milk whey from 94 dairy cows with acute clinical mastitis and 55 healthy lactating cows. The IL-6 concentrations in serum from mastitic cows were significantly higher on the first day of illness compared to those of normal cows. Higher concentrations of IL-6 were also detected in the whey from mastitic cows, whereas low concentrations of IL-6 were detected in both serum and whey samples from normal cows. IL-6 concentrations in the serum taken at the onset of illness from cows that later required euthanasia were significantly higher than those in samples from cows that later recovered. These results suggest that serum IL-6 concentrations may be of prognostic value in identifying cows with severe mastitis. [ABSTRACT FROM AUTHOR]

Although brain lesions have been described in some cases with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), little is known about the nature of brain lesion and its relation to the spinal cord lesion. In the present study, we performed histopathological analysis of the brain and the spinal cord of four autopsied cases with HAM/TSP to clarify the relationship between the brain and the spinal cord lesions. In two cases with active-chronic inflammation in the spinal cord, perivascular inflammatory infiltration was also seen in the brain, and the composition of cell subsets was similar both in the spinal cord and in the brain. No active inflammatory change was seen in the brain in two cases with inactive-chronic spinal cord lesions. Inflamed vessels were distributed mainly in the deep white matter and in the area between cerebral cortex and white matter of the brain. In the spinal cord inflamed vessels were mainly seen in the bilateral lateral and the ventral posterior columns. Parenchymal infiltration was diffused in the spinal cord but very sparse in the brain, suggesting the importance of parenchymal infiltration in the destruction of tissues. These results suggest that inflammatory changes occurred simultaneously in the spinal cord and in the brain, and that distribution of inflamed vessels closely correlated with the characteristics of vascular architecture of the brain and the spinal cord, which lead to a slow blood flow. This study may help promote a better understanding of the pathogenesis of HAM/TSP. [ABSTRACT FROM AUTHOR]

SUMMARY:In order to clarify the effects of habitat temperatures on crustacean myofibrillar ATPase activities, the activities were measured in the muscle of American lobster Homarus americanus and Japanese spiny lobster Panulirus japonicus. Magnesium (Mg2+)-ATPase activities of the Japanese spiny lobster in the presence and absence of calcium (Ca2+) were lower than the corresponding activities of the American lobster. The American lobster lost Ca2+ sensitivities in myofibrillar Mg2+-ATPase activities over 35°C, while the Japanese spiny lobster lost sensitivities over 40°C. Inactivation profiles in Mg2+- and Ca2+-ATPase activities showed that myofibrillar thermal stability of the American lobster was lower than that of the Japanese spiny lobster. No seasonal change in Mg2+-ATPase activity was observed in either species. These results suggest that the myofibrils of both lobster species would adapt to their habitat temperatures. [ABSTRACT FROM AUTHOR]

The inhibition of thermolysin by an optically active silicon-containing amino acid, 3-trimethylsilylalanine (TMS-Ala), and its derivatives was examined by considering the similarity of structure between TMS-Ala and leucine. Although free l- and d-TMS-Ala did not show the inhibition, several derivatives of l-TMS-Ala, especially Z-l-TMS-Ala and l-Leu-(l-TMS-Ala), exhibited a higher inhibitory activity toward thermolysin than did Z-l-Leu and l-Leu-l-Leu respectively. Effects of TMS-Ala on the activity of its derivatives and the mode of interaction between the derivatives of TMS-Ala and thermolysin are also discussed. [ABSTRACT FROM AUTHOR]

In this study, the enzymatic synthesis of silicon-containing dipeptides with a silicon-containing amino acid, 3-trimethylsilylalanine (TMS-Ala), was attempted in ethyl acetate, and the effects of TMS-Ala on thermolysin-catalyzed dipeptide synthesis are also discussed. Benzyloxycarbonyl(Z)-TMS-Ala was recognized by thermolysin as a better substrate than Z-Leu, and various silicon-containing dipeptides, Z-(TMS-Ala)-Xaa-OMe (Xaa = Leu, Ile, Phe, etc.), could be obtained. The acceleration of the reaction rate in the synthesis of Z-(TMS-Ala)-Leu-OMe compared with Z-Leu-Leu-OMe synthesis was explained by the higher hydrophobicity of the side-chain of TMS-Ala containing a trimethylsilyl group. On the other hand, TMS-Ala-OMe was not accepted as the amino component because of the bulkiness of the trimethylsilyl group. The enantioselectivity of thermolysin was very high. Z- d-TMS-Ala was not a substrate, while Z- l-TMS-Ala served as a good substrate. [ABSTRACT FROM AUTHOR]

The monoclonal antibody against estramustine-binding protein (EMBP) was produced by immunizing a mouse with EMBP antigen purified from rat ventral prostate. On western blotting analysis this antibody recognized the EMBP C component, and in an absorption test it recognized the EMBP antigen. Immunohistochemically, this antibody revealed positive staining for the ventral and dorsolateral prostate. In the epithelium of the ventral prostate, intense immunostaining was observed in the intraluminal secretory product; however, in the epithelium of the dorsolateral prostate, the staining was intense in the cytoplasm of the epithelial cells. These findings suggested differences of EMBP localization in the ventral and the dorsolateral prostate. Since the intensity of immunostaining for EMBP was decreased in the prostate of castrated rats, we considered that this antibody reflected the androgen dependency of EMBP. [ABSTRACT FROM AUTHOR]

To assess the prognostic value of beta-HCG positive stage I seminoma, clinical records of 122 patients with testicular germ cell tumour were reviewed. Fifty-five patients (mean age 38.7 years) of 122 (45.1%) had stage I seminoma. Preorchiectomy beta-HCG level was determined in 54 patients. Twenty-nine patients of 54 (53.7%) had elevated preorchiectomy beta-HCG level. No significant relationship was found in the rate of locally progressive cancer between beta-HCG positive and negative cases. Treatment consisted of radiotherapy after inguinal orchiectomy for beta-HCG negative cases, and chemotherapy or radiotherapyfor beta-HCG positive cases. Tumour recurrence was found in one patient with normal beta-HCG level. Our limited series demonstrated that preorchiectomy elevated beta-HCG had no significant relationship to local tumour invasion or prognostic value. Therefore, infradiaphragmatic radiation therapy may be useful for beta-HCG positive stage I seminoma. [ABSTRACT FROM AUTHOR]

Sequential changes in creatinine clearance (Ccr) were determined in 14 patients undergoing operation for phaeochromocytoma. All patients had been given alpha-adrenergic antagonists 2 weeks before surgery. In the younger group (mean age 40±2 years), Ccr improved following adrenal surgery. Urinary concentrations of epinephrine, norepinephrine and total catecholamines correlated inversely with Ccr. A similar inverse relationship was noted between tissue norepinephrine concentration expressed as μg/g and Ccr to a lesser extent. In older patients (mean age 69±2 years) Ccr remained unchanged by this surgical procedure. No significant correlations were found between both parameters in the older group. It appears resonable to presume that excessive amount of catecholamine plays an important role in the impairment of Ccr in relatively young patients with phaeochromocytoma, but other possibilities as regards the sequence of this phenomenon must be pursued in older patients. [ABSTRACT FROM AUTHOR]

To assist in the evaluation of inflammatory changes of the affected bowel, we classified the transabdominal ultrasonographic findings into types A-C. We compared the in vivo and in vitro sonographic images to the histopathologic findings of resected specimens. A total of 22 bowel specimens (five normal, 12 with Crohn's disease, five with ulcerative colitis) were examined sonographically with a 3.75-MHz curved and a 7.5-MHz linear array scanner; histologic examination of the same area of tissue was performed afterwards. These three examinations corresponded well to each other. Our classification scheme is useful in quantifying the severity of inflammatory changes in the affected bowel. [ABSTRACT FROM AUTHOR]

Background: Prediction of the recovery of left ventricular (LV) ischemic dysfunction after revascularization is important in patients with coronary artery disease (CAD). We investigated whether the improvement in LV ischemic dysfunction after revascularization could be predicted preoperatively by exercise-induced ST-segment changes.Methods and Results: Regional myocardial blood flow (RMBF) and cardiac output were measured with nitrogen 13-ammonia positron emission tomography at rest and during low-level exercise in 28 patients with angiographically proven CAD before and after successful revascularization and in 9 normal subjects. Before revascularization, exercise-induced upsloping ST-segment depression <1 mm 80 msec after the J-point was observed in 11 patients (group 1), horizontal depression of 1 to 1.5 mm was observed in 9 patients (group 2), and downsloping depression > or =1.5 mm was observed in 8 patients (group 3). The number of regions of critical CAD was greater in group 3 than in groups 1 and 2 (3.6 +/- 1.4 vs 1.6 +/- 0.7 and 2.2 +/- 1.1, p < 0.001, p < 0.02). Increase of RMBF in regions of critical CAD with exercise was lower in group 3 than in groups 1 and 2 (0.15 +/- 0.01 vs 0.22 +/- 0.01 and 0.18 +/- 0.02 ml/min per gram, p < 0.0001, p < 0.01). After revascularization, RMBF in regions of critical CAD both at rest and during exercise improved in groups 1 (0.49 +/- 0.15 to 0.60 +/- 0.18, 0.70 +/- 0.26 to 0.86 +/- 0.33 ml/min per gram, both p < 0.05) and 2 (0.50 +/- 0.15 to 0.62 +/- 0.19, 0.67 +/- 0.26 to 0.89 +/- 0.31 ml/min per gram, both p < 0.02), but was unchanged in group 3 (0.47 +/- 0.09 to 0.47 +/- 0.15, 0.62 +/- 0.17 to 0.64 +/- 0.23 ml/min per gram, both p = NS). Cardiac output at rest improved in groups 1 (4.98 +/- 0.43 to 5.35 +/- 0.50 L/min, p < 0.02) and 2 (5.08 +/- 0.52 to 5.53 +/- 0.28 L/min, p < 0.02), but was unchanged in group 3 (4.76 +/- 0.48 to 4.88 +/- 0.82 L/min, p = NS).Conclusions: Our results suggest that marked downsloping ST-segment depression induced by preoperative low-level exercise may predict a lack of improvement in LV ischemic dysfunction after revascularization. [ABSTRACT FROM AUTHOR]

It is generally accepted that early human prostate cancers reveal higher androgen dependency than do advanced ones. In the present study, we examined whether the animal model of prostate cancer has already lost androgen dependency at the early stages of carcinogenesis. At experimental week 46, androgen deprivation was induced in rats and the incidences of atypical hyperplasia and cancer were examined in the ventral, dorsolateral prostate, coagulating glands, and seminal vesicles. Androgen deprivation significantly lowered the incidence of atypical hyperplasia in all four organs. As for the incidence of cancer, no significant differences were observed in the coagulating glands and seminal vesicles. Regarding atypical hyperplasia, androgen deprivation significantly decreased the proliferative cell nuclear antigen labeling index in the coagulating gland and seminal vesicles. The presence of cancer was also decreased in the coagulating gland but not in the seminal vesicles. With control group specimens, more intense staining of androgen receptor was observed in atypical hyperplasias than in cancers. Compared with the atypical hyperplasias, the cancers revealed low androgen dependency at the early stages of carcinogenesis. The cancers in the seminal vesicles also revealed higher androgen independency than did those in the coagulating gland. [ABSTRACT FROM AUTHOR]

In this paper we report on the enzymatic preparation of d- p-trimethylsilylphenylalanine ( d-TMS-Phe). First, dl-5-( p-trimethylsilylphenylmethyl)hydantoin␣( dl-TMS-Phe-Hyd) was synthesized chemically and subjected to bacterial hydrolysis to obtain N-carbamoyl- d- p-trimethylsilylphenylalanine (C- d-TMS-Phe), but no strains examined showed sufficient hydantoinase activity on this compound. However, Blastobacter sp. A17p-4, which is known to produce N-carbamoyl- d-amino acid amidohydrolase (DCase), was found to be able to hydrolyze C- dl-TMS-Phe prepared chemically from the hydantoin. When C- dl-TMS-Phe was hydrolyzed with cells of Blastobacter sp. A17p-4, its optical purity was low because N-carbamoyl- l-amino acid amidohydrolase (LCase) coexisted in the cells. DCase and LCase in the cell-free extract of Blastobacter sp. A17p-4 could be separated by DEAE-Sephacel column chromatography. The optimum pH for the hydrolysis of C- dl-TMS-Phe by the partially purified DCase was 8.0 and addition of 2.5 % N, N-dimethylformamide was effective in raising the substrate concentration without inactivation of DCase. Under the optimized conditions, highly optically pure (98 % enantiomeric excess) d-TMS-Phe could be obtained from C- dl-TMS-Phe with partially purified DCase. [ABSTRACT FROM AUTHOR]

We constructed an efficient system for preparing optically active 3-trimethylsilylalanine (TMS-Ala) by kinetic resolution with acylase I (aminoacylase; N-acylamino-acid amidohydrolase, EC 3.5.1.14). Racemic TMS-Ala was chemically synthesized and acetylated. Enantioselective deacetylation of N-acetyl- dl-TMS-Ala with acylase I from porcine kidney or from Aspergillus melleus was then attempted. Both enzymes could catalyze the deacetylation of N-acetyl- dl-TMS-Ala, and the porcine enzyme was found to have much higher activity than the enzyme from A. melleus. The optimum pH of the porcine-acylase-catalyzed reaction was 7.5, and the addition of 0.5 mM Co accelerated the reaction. Optically pure l-TMS-Ala (> 99% enantiomeric excess, ee) was obtained in 72% yield under the optimized conditions. Furthermore, highly optically pure d-TMS-Ala (96% ee) could also be obtained in 76% yield by chemically hydrolyzing the residual substrate. [ABSTRACT FROM AUTHOR]

A specimen of the stonefish Synanceja verrucosa was captured in Okinawa in March 1988. Live specimens of the scorpionfish Inimicus japonicus were purchased from the Tokyo Central Wholesale Market in November 1988 and those of four species of zebrafish Pterois lumulata, P. volitans, P. antennata and Dendrochirus zebra from an aquarium in December 1988. Crude venoms were extracted from dorsal spines of the six species. All venoms exhibited lethal activity against mice and hemolytic activity specific for rabbit erythrocytes. The lethal activity (or hemolytic activity) of each venom was very unstable to freezing, lyophilization and heating. Both lethal and hemolytic activities of S. verrucosa venom were remarkably neutralized by the commerical stonefish ( Synanceja trachynis) antivenom. This antivenom was also effective, to some extent, in counteracting the other venom activities. The neutralizing capacities of the antivenom were calculated to be 7310 LD ml for S. verrucosa venom and 1 220 to 2 990 LD ml for the other venoms. Results of neutralization tests suggest that venoms from the six species were comparable in terms of antigenecity. [ABSTRACT FROM AUTHOR]

A sequential polydepsipeptide containing a tripeptide sequence L-alanyl-Lalanylγ-ethyl L-glutamyl and an α-hydroxy acid L-lactic acid, poly(Ala-Ala-Glu(OEt)-Lac), was synthesized to prepare the microspherical particles by the solvent evaporation process. In this case, the solvents play the most important role for the preparation of polydepsipeptide microspheres and, as an example, when 200 mg of the polydepsipeptide dissolved in 10 ml of 98/2% chloroform/dichloroacetic acid mixture was stirred at 400 rpm and 30 ‡C, the microspherical particles with mean diameter of 58 Μm were formed after pouring into 200 ml of 1% (w/v) poly(vinyl alcohol) solution. 17 Β-Estradiol was incorporated into the particles, and the resulting particles were found to contain 5 mg of drug per 25 mg of the particle. The in vivo release of drug from the microspherical formulation was evaluated by measuring the pharmacological influence on rat prostate. It was found that the sufficient amount of drug, keeping the effective pharmacological influence, is supplied during the first 12-week period, followed by an incomplete supplying of drug intil the implant is perfectly degraded in vivo in the 25th week from the start of implantation. [ABSTRACT FROM AUTHOR]

Neither Flavobacterium sp. nor Pseudomonas sp. grew on a polyethylene glycol (PEG) 6000 medium containing the culture filtrate of their mixed culture on PEG 6000. The two bacteria did not grow with a dialysis culture on a PEG 6000 medium. Flavobacterium sp. grew well on a dialysis culture containing a tetraethylene glycol medium supplemented with a small amount of PEG 6000 as an inducer, while poor growth of Pseudomonas sp. was observed. Three enzymes involved in the metabolism of PEG, PEG dehydrogenase, PEG-aldehyde dehydrogenase and PEG-carboxylate dehydrogenase (ether-cleaving) were present in the cells of Flavobacterium sp. The first two enzymes were not found in the cells of Pseudomonas sp. PEG 6000 was degraded neither by intact cells of Flavobacterium sp. nor by those of Pseudomonas sp., but it was degraded by their mixture. Glyoxylate, a metabolite liberated by the ether-cleaving enzyme, inhibited the growth of the mixed culture. The ether-cleaving enzyme was remarkably inhibited by glyoxylate. Glyoxylate was metabolized faster by Pseudomonas sp. than by Flavobacterium sp., and seemed to be a key material for the symbiosis. [ABSTRACT FROM AUTHOR]

2,8-Dihydroxyadenine urolithiasis associated with partial deficiencies of adenine phosphoribosyltransferase (APRT) has been found only among Japanese families. All Caucasian patients with the same lithiasis are completely deficient in this enzyme. Partially purified APRT from one of the Japanese families with the lithiasis associated with a partial deficiency of APRT had a reduced affinity for 5-phosphoribosyl-1-pyrophosphate (PRPP). In the present investigations, we have shown that this characteristic is common in mutant enzymes from all the four separate Japanese urolithiasis families associated with partial APRT deficiencies so far tested. The mutant enzymes also had several other characteristics in common including increased resistance to heat in the absence of PRPP and reduced sensitivity to the stabilizing effect of PRPP. These data suggest that these families have a common mutant allele ( APRT J) at the APRT gene locus. [ABSTRACT FROM AUTHOR]

The major arsenic compound in the shrimp Sergestes lucens was isolated and identified as arsenobetaine (CH)ACHCOO. Arsenobetaine accounted for 80% of the total arsenic in the shrimp. [ABSTRACT FROM AUTHOR]