Biomedical subjects

Y Yamaguchi

Publications and source records attributed to Y Yamaguchi.

At least 163 records · Page 9Linked to original sources

PubMed2001

[A study on the clinical features of pulmonary tuberculosis in elderly patients].

The clinical findings of pulmonary tuberculosis in elderly patients aged 75 years of age or older (elderly group) were compared with the middle-aged patients aged between 45 and 54 years of age (middle-aged group) and the young patients aged 34 years of age or younger (young group). The elderly patients who died in hospital were also compared with the elderly patients who survived. Study subjects were culture-positive pulmonary tuberculosis patients who were discharged from our hospital from December 1996 to November 1998. There were 79 patients in the elderly group, 95 in the middle-aged group, and 88 in the young group. The results were as follows. 1) The male/female ratio was significantly lower in the elderly group (1.9:1) than the middle-aged group (6.9:1). 2) Complication was noted more frequently in the elderly group. However, diabetes mellitus was noted less frequently in the elderly group (12.7%) than the middle-aged group (28.4%). 3) The frequency of cavitation was lower in the elderly group (59.5%) than the middle-aged group (87.4%). 4) The fever over 38 degrees C was noted less frequently in the elderly group (17.7%) than the other groups, while the frequency of the fever over 37 degrees C showed no significant difference between the elderly group and the other groups. 5) The frequencies of hypoalbuminemia and appetite loss were higher in the elderly group than the other groups. 6) The elderly group showed high mortality rate of 31.6%. The complication with cerebrovascular disease was noted significantly higher in the patients who died in hospital than those who survived. The frequency of widespread infiltrates, fever over 38 degrees C, neutrophilia, hypoalbuminemia and appetite loss were all significantly higher in the patients who died in hospital while their sputa were still positive on culture than those who survived. Our study clearly showed the features of elderly pulmonary tuberculosis patients in comparison with middle-aged patients and young patients. These features are very important to suspect the diagnosis of pulmonary tuberculosis in elderly patients with some atypical manifestation. Our study also suggests that the delay in diagnosing tuberculosis causes more frequently the patients' deterioration and death in elderly patients than in middle-aged patients and young patients.

Adult↗

PubMed2001

[Type I IFN receptor].

Interferon(IFN) alpha and IFN beta apparently share the same receptor structure, the type I IFN receptor, which consist of at least two subunits. The subunits are referred to as IFN AR1(IFN alpha receptor) and IFNAR2(IFN alpha/beta receptor). As IFN elicits antiviral activity by binding to receptors on the cell surface, the expression of the type I IFN receptor in liver may be directly involved in the pathogenesis of viral hepatitis and response to IFN therapy. Here we discuss if the IFN receptor expression in liver and peripheral blood mononuclear cells can be a predictive factor for the response to IFN therapy in patients with chronic hepatitis C.

Forecasting↗

PubMed2001

[Evaluation of a combination chemotherapy with nedaplatin and 5-FU for oral cancers].

Nedaplatin (cis-diammine-glycolato platinum: CDGP) is a platinum compound with a molecular weight of 303.18 that was recently developed in Japan. There have been reports of the antineoplastic effects of Nedaplatin on cancers in the cranio-cervical region, lung, esophagus, urinary bladder, testis, ovary, and uterus. In this study, we performed combined therapy of CDGP and fluorouracil (5-FU) for 8 patients with oral cancers, and evaluated the results to elucidate the clinical effect and adverse side effects. The subjects were 8 patients with squamous cell carcinoma (5 males and 3 females aged 33-65 years). The primary carcinoma regions were the tongue in 5 patients, oral floor in 2 patients, and mandibular gingiva in 1 patient. The T-classification was T2 in 6 patients and T4 in 2 patients, and the clinical staging was Stage II in 5 patients, Stage III in 1 patient and Stage IV in 2 patients. We first administered 700 mg/m2 5-FU per day from day 1 to day 5 (total dose 3,500 mg/m2), then 90 mg/m2 CDGP on day 5. The clinical effect was evaluated as a partial response in all cases, showing a 100% success rate. The histopathological findings of resected tumors were evaluated by Ohboshi and Shimozato's classification. One patient was Grade IIA, 5 patients Grade IIB, and 2 patients Grade III. The adverse side effects were slight myelotoxicity, gagging, nausea, alopecia, and stomatitis less than Grade II. Although the oral cancers in this study were extroverted superficial ulcerative cancers, and the number of patients was low at 8, this combined therapy is considered useful and worth evaluating in further accumulated cases.

Adult↗

PubMed2001

A graph-based clustering method for a large set of sequences using a graph partitioning algorithm.

A graph-based clustering method is proposed to cluster protein sequences into families, which automatically improves clusters of the conventional single linkage clustering method. Our approach formulates sequence clustering problem as a kind of graph partitioning problem in a weighted linkage graph, which vertices correspond to sequences, edges correspond to higher similarities than given threshold and are weighted by their similarities. The effectiveness of our method is shown in comparison with InterPro families in all mouse proteins in SWISS-PROT. The result clusters match to InterPro families much better than the single linkage clustering method. 77% of proteins in InterPro families are classified into appropriate clusters.

Algorithms↗

PubMed2001

Presence of Vicia graminea or Vicia unijuga lectin-binding (Vgu) glycoproteins with and without Thomsen-Friedenreich (T) antigen in normal human seminal plasma.

Vgu glycoprotein (Vicia graminea lectin- or Vicia unijuga lectin-binding glycoprotein) has been reported as oncofetal antigen, which is found in many kind of tumor tissues, amniotic fluid and fetal membranes. In autoradiography with an 125I-labeled Vicia unijuga lectin (VUA) probe and an 125I-labeled Arachis hypogaea lectin (PNA, anti-T lectin) probe, seminal plasma samples of eight healthy men gave 2-7 Vgu glycoproteins without T antigen, 1-2 Vgu glycoproteins with Thomsen-Friedenreich antigen (T antigen) and 1-8 T-antigen glycoproteins, respectively. These results show that in addition to T-antigen glycoproteins, normal human seminal plasma contains Vgu glycoproteins and Vgu glycoproteins with T antigen as seminal plasma components as well as other tumor markers such as CA19-9, CA-125 and CEA.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed2000

The kinetics of growth of semiconductor nanocrystals in a hot amphiphile matrix.

The first comprehensive study on the kinetics of nanocrystal growth in a hot amphiphile medium is presented. An example is given with CdSe semiconductor nanocrystals grown after the injection of precursor (a mixture of Cd- and Se-reagents) in concentrated tri-octylphosphine oxide matrix (heated to more than 300 degrees C). The particle size distribution is reconstructed as a function of time from the absorption and photoluminescence spectra collected during the synthesis process. For this purpose a new expression is used relating the exciton energy due to quantum confinement with the nanocrystal radius. The growth kinetics is considered as a two-stage process in order to describe the time variation of nanoparticle size. During the first stage, called reaction-limited growth, the size of initial nucleus rapidly increases due to a sort of surface reaction exhausting the precursor in the nanoparticle vicinity. The growth in such conditions favors also a remarkable narrowing of the size distribution. The nanocrystal develops further on account of a slow precursor transfer from a distant space driven by the concentration gradient--classical diffusion-limited growth. The width of size distribution also increases proportional to the average particle size. Any growth will stop after the precursor concentration reaches a minimum value defining the limit for the final nanocrystal size in a batch. Solving the kinetic equations for the growth rate in each case of kinetics derives analytical expressions for the mean radius and variance of size distribution. Then the respective expressions are matched in a uniform solution valid during the entire synthesis. The theoretical model is in a good quantitative agreement with the experimental data for independent syntheses. Important characteristic scales of the processes (time-constant and length) and microscopic parameters of the reacting system (interfacial energy and reaction rate constant) are estimated from the data. It turns out that the fast reaction-limited growth is important to obtain well-defined nanocrystals of high optical quality by using less energy, time and consumable. However, to make them reproducibly uniform one should control also the ultra-fast nucleation process preceding the nanocrystal growth, which is still unknown. Nevertheless, our current findings allow the conceptual design of a new continuos-flow reactor for the manufacturing of a large amount of uniform nanocrystals.

Journal Article↗

PubMed2000

Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites.

Brevican is a member of the lectican family of chondroitin sulfate proteoglycans that is predominantly expressed in the central nervous system. The susceptibility of brevican to digestion by matrix metalloproteinases (MMP-1, -2, -3, -7, -8, -9, -10, and -13 and membrane type 1 and 3 MMPs) and aggrecanase-1 (ADAMTS4) was examined. MMP-1, -2, -3, -7, -8, -10, and -13 degraded brevican into a few fragments with similar molecular masses, whereas the degradation products of aggrecanase-1 had apparently different sizes. NH(2)-terminal sequence analyses of the digestion fragments revealed that cleavages of the brevican core protein by these metalloproteinases occurred commonly within the central non-homologous domain. MMP-1, -2, -3, -7, -8, -10, and -13 preferentially attacked the Ala(360)-Phe(361) bond, whereas aggrecanase-1 cleaved the Glu(395)-Ser(396) bond, which are similar to the cleavage sites observed with cartilage proteoglycan (aggrecan) for the MMPs and aggrecanase-1, respectively. These data demonstrate that MMP-1, -2, -3, -7, -8, -10, and -13 and aggrecanase-1 digest brevican in a similar pattern to aggrecan and suggest that they may be responsible for the physiological turnover and pathological degradation of brevican.

ADAM Proteins↗

PubMed2000

The mechanism of action of inhibitors of bacterial two-component signal transduction systems.

Two-component signal transduction systems allow bacteria to sense and respond rapidly to changes in their environment leading to specific gene activation or repression. These two-component systems are integral in the ability of pathogenic bacteria to mount and establish a successful infection within the host and, consequently, have been recognized as targets for new anti-microbial agents. In this paper, we define the site and mechanism of action of several previously identified inhibitors of bacterial two-component systems. We show that the most potent inhibitors target the carboxyl-terminal catalytic domain of the sensor kinase and exert their affect by causing structural alterations of the kinase leading to aggregation. Recognition of this phenomenon has important implications for the development of novel inhibitors of two-component systems and should facilitate the rapid identification and elimination of compounds with nonspecific affects from medicinal chemistry drug discovery programs.

Anti-Bacterial Agents↗

PubMed2000

A regulator of transcriptional elongation controls vertebrate neuronal development.

The development of distinct vertebrate neurons is defined by the unique profiles of genes that neurons express. It is accepted that neural genes are regulated at the point of transcription initiation, but the role of messenger RNA elongation in neural gene regulation has not been examined. Here we describe the mutant foggy, identified in a genetic screen for mutations that affect neuronal development in zebrafish, that displayed a reduction of dopamine-containing neurons and a corresponding surplus of serotonin-containing neurons in the hypothalamus. Positional cloning disclosed that Foggy is a brain-enriched nuclear protein that is structurally related to the transcription elongation factor Spt5 (refs 5-12). Foggy is not part of the basic transcription apparatus but a phosphorylation-dependent, dual regulator of transcription elongation. The mutation disrupts its repressive but not its stimulatory activity. Our results provide molecular, genetic and biochemical evidence that negative regulators of transcription elongation control key aspects of neuronal development.

Amino Acid Sequence↗

PubMed2000

Posttransplant infusion of donor-specific blood induces immunological unresponsiveness in rat hepatic allografts.

BACKGROUND: We previously reported that pretransplant donor-specific blood transfusion (DST) induces CD45RC-CD4+ T cells, Th2-like effector cells, and prolongs rat hepatic allograft survival. Our study investigated the effects of posttransplant DST on rat hepatic allograft survival. METHODS: Three days after transplantation, LEW (RT1(1)) recipient rats with ACI (RT1a) livers were injected i.v. with freshly heparinized donor-specific blood. The time kinetics of CD45RC-CD4+ and CD45RC+CD4+ T cell subsets in hepatic infiltrates were examined. RESULTS: Posttransplant DST significantly prolonged rat hepatic allograft survival. Interferon (IFN)-gamma, interleukin (IL)-12, and IL-18 mRNA levels in hepatic allografts of untreated recipients were significantly greater than in recipients treated with posttransplant DST. However, hepatic allografts of recipients treated with posttransplant DST showed significantly higher IL-4, IL-10, and transforming growth factor (TGF)-beta mRNA levels than untreated recipients. The ratio of CD45RC-CD4+ T cells to CD45RC+CD4+ T cells was significantly higher in hepatic allografts treated with posttransplant DST than in untreated animals. Immunostaining with anti-rat dendritic cell (OX-62) monoclonal antibody revealed that OX-62+ cells were distributed to the splenic red pulp of animals treated with posttransplant DST and to the splenic white pulp in untreated animals. Most OX62+ cells isolated from the spleen of recipients treated with posttransplant DST expressed donor RT1Ba class II major histocompatibility complex antigens, suggesting that OX-62+ cells were of donor origin. CONCLUSION: Posttransplant DST was associated with persistent infiltration of CD45RC-CD4+ T cells, Th2-like effector cells, in rat hepatic allografts, causing immunologic unresponsiveness and establishment of microchimerism in the spleen.

Animals↗

PubMed2000

Attenuation of expression of gamma-glutamylcysteine synthetase by ribozyme transfection enhance insulin secretion by pancreatic beta cell line, MIN6.

Low levels of intracellular antioxidant enzyme activities as well as glutathione (GSH) concentrations have been described in pancreatic beta cells. We examined the effects of intracellular GSH depletion on insulin secretion and the role of intracellular GSH in signal transduction in beta cell line, MIN6 cells. Anti-gamma-glutamylcysteine synthetase (gamma-GCS) heavy subunit ribozyme was stably transfected to MIN6 cells to reduce intracellular GSH concentration. In the presence of 10 mM glucose, ribozyme-transfected cells (RTC) increased insulin secretion from 0.58 microg/10(6) cells/h in control cells (CC) to 1.48 microg/10(6) cells/h. This was associated with increased intracellular Ca(2+) concentration in RTC, detected by fluo-3 staining. Our results demonstrated that intracellular GSH concentration might influence insulin secretion by MIN6 cells, and suggest that enhanced insulin secretion by beta cells conditioned by chronic depletion of GSH is mediated by increased intracellular Ca(2+) concentration.

Adenosine Triphosphate↗

PubMed2000

Synbindin, A novel syndecan-2-binding protein in neuronal dendritic spines.

Dendritic spines are small protrusions on the surface of dendrites that receive the vast majority of excitatory synapses. We previously showed that the cell-surface heparan sulfate proteoglycan syndecan-2 induces spine formation upon transfection into hippocampal neurons. This effect requires the COOH-terminal EFYA sequence of syndecan-2, suggesting that cytoplasmic molecules interacting with this sequence play a critical role in spine morphogenesis. Here, we report a novel protein that binds to the EFYA motif of syndecan-2. This protein, named synbindin, is expressed by neurons in a pattern similar to that of syndecan-2, and colocalizes with syndecan-2 in the spines of cultured hippocampal neurons. In transfected hippocampal neurons, synbindin undergoes syndecan-2-dependent clustering. Synbindin is structurally related to yeast proteins known to be involved in vesicle transport. Immunoelectron microscopy localized synbindin on postsynaptic membranes and intracellular vesicles within dendrites, suggesting a role in postsynaptic membrane trafficking. Synbindin coimmunoprecipitates with syndecan-2 from synaptic membrane fractions. Our results show that synbindin is a physiological syndecan-2 ligand on dendritic spines. We suggest that syndecan-2 induces spine formation by recruiting intracellular vesicles toward postsynaptic sites through the interaction with synbindin.

Amino Acid Motifs↗

PubMed2000

Anti-AB titer changes in patients with ABO incompatibility after living related kidney transplantations: survey of 101 cases to determine whether splenectomies are necessary for successful transplantation.

BACKGROUND: A shortage of organ donors for transplantation has become a serious problem throughout the world. To overcome this problem, transplantations across ABO blood barriers have been performed with some success. In general, however, the graft survival rate for transplantation with ABO incompatibility is lower than that of transplantation with ABO compatibility. Unfortunately, the mechanism by which isohemagglutinins might injure an ABO-incompatible graft remains uncertain. Here, the pre- and posttransplantation anti-AB titers in patients who received transplants from ABO-incompatible living donors are reviewed and the pathological findings are compared. METHODS: One hundred and one patients underwent ABO-incompatible living related kidney transplantation (i-LKT) between January 1989 and October 1999 at our hospital. Plasmapheresis and immunoadsorption were performed in all of the i-LKT patients before the transplantation to remove anti-AB antibodies. A splenectomy was also performed during the operation, followed by the local irradiation of the graft with a dose of 150 rad. The anti-AB titers and pathological findings for 93 i-LKT patients, excluding 8 patients who died, were then examined. RESULTS: Immediately after the i-LKT, the anti-AB titer dropped rapidly to below 1:4 in all 93 cases. Seventy of patients (70/93, 75%) showed no elevation in their anti-AB titer during their follow-up. However, the remaining 23 patients (23/93, 25%) showed a significant elevation of their anti-AB titer to over 1:16. Sixteen of these patients (16/93, 17%) exhibited an anti-AB titer of over 1:32. Out of these 16 patients, 11 patients (11/16, 69%) lost their grafts. The anti-AB titer in the remaining five patients (5/16, 31%) spontaneously decreased without any special treatment. Seven patients (7/93, 8%) exhibited an elevated titer of 1:16. Out of these patients, only one patient (1/7, 14%) lost his graft. The elevated titers in the remaining six patients (6/7, 86%) eventually decreased. The graft function improved in patients whose elevated anti-AB titers eventually decreased. Control patients (ABO-compatible kidney transplant patients) showed a normal elevation of their titer values compared with preoperative titers. Pathological findings showed severe humoral rejections in all cases with high anti-AB titers that lost grafts. Humoral rejection was also detected in most of the patients whose anti-AB titer was elevated to over 1:16 after the transplantation, but excellent renal function was resumed once the titers decreased to below 1:4. CONCLUSIONS: In 23 out of 93 i-LKT patients (25%), the anti-AB titers were significantly elevated after the splenectomy. In view of other reports of i-LKT without splenectomy, we feel that a splenectomy in i-LKT patients might be unnecessary. Pathological evidence suggests that the decrease in the anti-AB titer after transplantation might be the net result of plasmapheresis before the operation and the adsorption of antibodies to the endothelium of the transplanted organ after the operation, neither of which is influenced by a splenectomy.

ABO Blood-Group System↗

PubMed2000

Manganese deposition in the globus pallidus in patients with biliary atresia.

BACKGROUND: Chronic liver diseases may alter trace element contents in the brain. Among these trace elements, manganese is a ubiquitous transition metal excreted by the liver into the bile. Blood concentrations of manganese are elevated in patients with biliary atresia who have undergone hepatic portoenterostomy. The present study investigated the effects of liver transplantation on manganese deposition in the brain in such patients. METHODS: The signal intensity of the globus pallidus was calculated as an index defined as the percentile ratio of signal intensity in the globus pallidus to the subcortical frontal white-matter in sagittal T1-weighted magnetic resonance imaging planes. RESULTS: Brain magnetic resonance imaging revealed hyperintense signals in the globus pallidus due to manganese deposition in biliary atresia patients. Few neurologic symptoms related to manganese intoxication were observed. However, one 23-year-old female with biliary atresia had depressive symptoms and dyskinesia; she improved after oral administration of the dopamine precursor, L-DOPA. Manganese deposition disappeared in two patients after living-related reduced-size hepatic transplantation. CONCLUSIONS: Manganese accumulates in the brain during cholestasis associated with biliary atresia and disappears after hepatic transplantation. Manganese deposition is likely to be subclinical and reversible but may be associated with some age-related neurologic symptoms.

Adult↗

PubMed2000

Design, synthesis and SAR of a series of 2-substituted 4-amino-quinazoline neuropeptide Y Y5 receptor antagonists.

The design of a novel series of NPY-Y5 receptor antagonists is described. Key elements for the design were the identification of weak Y5 hits from a Y1 program, results from a combinatorial approach and database mining. This led to the discovery of the quinazoline 4 and the aryl-sulphonamide moiety as major components of the pharmacophore for Y5 affinity. The synthesis and SAR towards CGP71683A is described.

Drug Design↗

PubMed2000

Evidence of modified LDL in the plasma of hypercholesterolemic WHHL rabbits injected with aqueous extracts of cigarette smoke.

Cigarette smoking is a major risk factor for atherosclerosis, and oxidative modification of low density lipoprotein (LDL) is a key event in the development of atherosclerosis. The aim of the present study was to determine whether modified LDL would be formed in the plasma of Watanabe heritable hyperlipidemic (WHHL) rabbits injected with nicotine-free cigarette smoke extracts (CSE). In order to assess this, cigarette smoke-modified LDL (CS-LDL) was prepared by incubation of rabbit native LDL (N-LDL) with CSE for 24 h. The oxidative modification in CS-LDL was well established by the reduced ratio between two LDL subfractions (LDL2/LDL3) separated by anion-exchange HPLC, together with the fast migration in the anodic direction in agarose gel electrophoresis and the increased lipid peroxide levels. Very similar modification was noted with mildly oxidatively modified LDL prepared by incubation of N-LDL with 5 µM CuCl(2) for 1 h. When WHHL rabbits (n=4) intravenously received a single injection of CSE, the ratio of LDL2/LDL3 was markedly reduced compared with the control rabbits (n=4) while total cholesterol levels in the plasma gradually decreased until 24 h after the injection. These results suggest that oxidatively modified LDL, probably like CS-LDL, is produced in the plasma of WHHL rabbits injected with CSE.

Journal Article↗

PubMed2000

Sialyl Lewis(x) (CD15s) monitoring as a means to select antirejection therapy in patients with rejection after renal transplantation: CD15s monitoring for treatment and diagnosis in patients with acute rejection after renal transplantation.

BACKGROUND: Sialyl Lewis(x) (CD15s), which is known to serve as a ligand for the cell adhesion molecules E-selectin and P-selectin, is expressed on peripheral lymphocytes in renal transplant patients with rejection. In this study, we examined whether CD15s monitoring could differentiate the patients with rejection in whom steroids were effective from those in whom steroids were not effective. METHODS: To investigate CD15s expression on peripheral lymphocytes, flow cytometry was performed before and after steroid pulse therapy in 20 recipients with rejection after renal transplantation, including 5 recipients resistant to steroid therapy. We also compared CD15s expression with pathological findings before and after steroid pulse therapy. RESULTS: CD15s expression was stronger before steroid pulse therapy in the 5 patients resistant to steroids than in the 15 patients responsive to steroid treatment. In addition, CD15s expression remained high without any pathological improvement in the 5 patients resistant to steroids after steroid treatment, although CD15s recovered to normal levels with remarkable improvement of pathological findings in the other 15 patients. Five patients in whom steroids were not effective, had full recovery of serum creatinine levels as well as CD15s expression after muromonab (OKT3) therapy. CONCLUSIONS: CD15s monitoring might help clinicians to select antirejection therapy.

Adult↗

PubMed2000

Pairing of oligosaccharides in the Fc region of immunoglobulin G.

The Fc portion of immunoglobulin G (IgG) expresses paired oligosaccharides with microheterogeneities, which are associated with efficiencies of effector functions and with pathological states. A comparison of electrospray ionization mass spectrometry data obtained using a variety of Fc fragments derived from human and mouse IgG that do and do not retain the inter-chain disulfide bridge(s) revealed that (1) the Fc portion can be asymmetric as well as symmetric with respect to glycosylation and (2) the ratios of the individual glycoforms are different from what is expected from the random pairing.

Animals↗