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Biomedical subjects

A Shibuya

Publications and source records attributed to A Shibuya.

At least 55 records · Page 3Linked to original sources

Prevalence of hepatitis G virus RNA and anti-E2 in a Japanese haemodialysis population.

BACKGROUND: Patients on maintenance haemodialysis (HD) are at greater risk of parenterally transmitted infection with not only A-E hepatitis virus but also with hepatitis G virus (HGV) that has been recovered from patients with non A-E hepatitis. The prevalence of HGV infection in HD patients, which is based on the detection of HGV RNA using reverse transcription-polymerase chain reaction techniques, differs widely between countries. Recently, a new assay has been developed that detects an antibody to the envelope protein (E2) of HGV (anti-E2) that appears to be associated with the loss of HGV RNA from the serum and which may be a useful marker for previous HGV infection. METHODS: To determine the actual prevalence of HGV infection in maintenance HD patients, we examined both HGV RNA and anti-E2 antibody in sera from 200 patients undergoing maintenance HD. RESULTS: Thirty patients (15%) tested positive for HGV RNA, and 14 (7%) tested positive for E2 antibody. Of these, two individuals tested positive for both markers. Overall, 21% of these HD patients had been exposed to HGV. A logistic regression analysis failed to show any clinical feature associated with the detection of HGV RNA. The duration of HD and the presence of HCV RNA were associated with anti-E2. Male gender and HCV RNA were risk factors for the elevation of serum ALT activities. HGV RNA sequences of the patients were not identical to each other. CONCLUSIONS: Our data indicate that HGV infection is prevalent in patients undergoing HD but that liver abnormalities are rare. The nosocomial transmission of HGV in the HD unit was not confirmed.

Aged↗

An autopsy case of troglitazone-induced fulminant hepatitis.

OBJECTIVE: To study an autopsy case of troglitazone-induced fulminant hepatitis. CASE REPORT: A 58-year-old man contracted severe hepatitis 2 months after administration of troglitazone for the treatment of type 2 diabetes. Liver damage progressed gradually, even after withdrawal of the agent. Despite intensive therapy, the hepatitis became fulminant and the patient died 8 weeks after the onset of liver damage. Autopsy revealed massive hepatic necrosis and cholestasis with inflammatory cell infiltration. The pathological findings and the positive result of the drug-induced lymphocyte stimulation test for troglitazone indicated that the liver damage was mediated by hypersensitivity to troglitazone. CONCLUSIONS: One report has attributed troglitazone-induced liver damage in less severe cases to idiosyncratic reactions. However, the present case indicates that troglitazone can induce hypersensitivity resulting in fulminant hepatitis. Careful monitoring of serum liver enzymes during troglitazone therapy is therefore essential.

Alanine Transaminase↗

Variable expression on lung cancer cell lines of HLA-A2-binding MAGE-3 peptide recognized by cytotoxic T lymphocytes.

Cytotoxic T lymphocytes (CTL) specific for HLA-A2-binding MAGE-3 peptide (FLWGPRALV) were generated by repetitive stimulation of PBMC with the peptide in the presence of EBV-transformed B blasts and IL-2. Using these CTL, we investigated the expression of the HLA-A2-binding MAGE-3 peptide on lung cancer cell lines. Of 14 cell lines investigated, 1-87, PC-9, OU-LC-KI, 11-18 and LK87 were derived from HLA-A2 positive patients. But cytofluorometry analysis showed that 1-87, PC-9 and OU-LC-KI, but not 11-18 or LK87 expressed the HLA-A2 antigen. All five cell lines expressed MAGE-3 gene mRNA. Twelve of thirteen CTL lines from two HLA-A2 positive donors showed no cytotoxicity against any of the 14 lung cancer cell lines. CTL line TI-1 showed cytotoxicity against 1-87 but not against any of the other cell lines. Treatment of 1-87 with IFN-gamma greatly augmented the cytotoxicity of TI-1 and induced it in the other 12 CTL lines, confirming the expression of the peptide on 1-87. No cytotoxicity was induced by IFN-gamma treatment of PC-9 or OU-LC-KI. However, PC-9 and OU-LC-KI pulsed with the peptide were killed efficiently by all of the CTL lines, suggesting no expression of the peptide on those cells. A low level of cytotoxicity was induced on 11-18 but not LK87 by IFN-gamma treatment, although expression of the HLA-A2 antigen was not observed by cytofluorometry. These findings showed that expression of the HLA-A2-binding MAGE-3 peptide recognized by CTL was variable on lung cancer cell lines.

Amino Acid Sequence↗

Restoration of sexual behavior and dopaminergic neurotransmission by long term exogenous testosterone replacement in aged male rats.

PURPOSE: We investigated the effects of long-term testosterone replacement on copulatory behavior and dopaminergic neurotransmission in the medial preoptic area of aged male rats. MATERIALS AND METHODS: The rats were divided into 3 groups depending on testosterone replacement. Those in the long-term replacement group were castrated at the age of 12 months and received testosterone replacement thereafter for 12 months. In the short-term replacement group, rats were castrated at the age of 22 months and high or low dose testosterone replacement was done for 2 months. The control group consisted of aged rats 24 months old and young rats 12 weeks old, neither of which had been castrated or received testosterone replacement. We observed sexual behavior in rats of these groups. After a behavioral test, we measured the tissue concentration of dopamine in the MPOA and the change rate of the extracellular dopamine level induced by infusion of N-methyl-D-aspartic acid (NMDA) in the MPOA and compared the long-term replacement and no-replacement groups. RESULTS: The rats in the long-term replacement group showed a mount rate at the same level as that of young rats at 6 weeks after starting replacement and it was maintained to 24 months of age. Their mount rate was significantly higher than that of the rats with the short-term replacement. A significantly higher change rate of dopamine release was recognized in the long-term group; however, no significant difference in the concentration of dopamine was recognized between aged rats with long-term replacement and those without replacement. CONCLUSIONS: Aged rats (24 months old) with long-term testosterone replacement maintained almost the same level of mount behavior as young rats (12 weeks old). The results imply that long-term testosterone replacement may favorably alter the decline in the process of sexual activity with aging. The restoration by testosterone replacement of dopaminergic activity in the MPOA may be involved in the maintenance of sexual function in aged rats.

Aging↗

[The problems of nursing and medical expenses in end-stage home therapy].

Recently, many end-stage patients and their families desire home care in their last days, because Japanese tend to think "quality of life" is the most important thing in their life. Home therapy for end-stage patients has become popular with the support of the government. The cooperation between medical staff and patients has overcome many problems derived from this new therapy system. Problems related to the person who looks after the patient, however, remain to be solved. Ninety-four home therapy cases of end-stage cancer have been treated as a private clinic experience since 1994. Although the medical expenses for home therapy are greater than for hospital treatment under the Japanese medical insurance system, the nursing fees for the person who looks after the patient are not considered enough. A heavy burden, not only by the nursing but also by their own occupation, has been imposed upon the nursing person. Differences in the expenses between home therapy and hospital treatment, and also the situation of the nursing person in the home therapy are reported in this paper.

Adult↗

[The background factors influencing loss of sexual intercourse after transurethral resection of the prostate (TUR-P)--A study using the Sapporo Medical University-Questionnaire].

BACKGROUND: Sexual dysfunction after transurethral resection of the prostate (TUR-P) depends on multiple factors including preoperative erectile function itself. Using the Sapporo Medical University-questionnaire, we analyzed background factors contributing to loss of sexual intercourse after the operation. PATIENTS AND METHODS: We sent the self-administered questionnaires to 1,000 patients who had received TUR-P. Answers to questions were ranked as scores. Multiple regression analysis was used to identify factors significant for loss intercourse after TUR-P. RESULTS: The response rate was 63.5%. Patient with incomplete answers and those having diseases affecting voiding or sexual function and antiandrogen medication were excluded from the study. Leaving 536 patients for the final analysis. Scores for sexual desire and erectile function in the patients who received TUR-P were lower than those of age-matched healthy males. When we divided the patients according to frequency of sexual intercourse before and after TUR-P, there was distinct differences in age, scores for sensory disturbance, depression, the cooperative value of the sexual partner, sexual desire, erectile function, nocturia, residual sensation and urgency between those maintaining sexual intercourse and those having lost it. Multiple regression analysis using these factors indicated that the scores of erectile function was the most significant determinant for maintaining sexual intercourse after TUR-P in patients aged from 50 to 69 years, followed by the cooperative value of the sexual partner, residual sensation and sensory disturbance. In those 70 old and older, the score for erectile function was the most significant determinant, followed by the cooperative value of sexual partner. CONCLUSION: Our results suggest that, irrespective of age, the cooperation of the patient's sexual partner as well as erectile function significantly influence the maintenance of sexual intercourse after TUR-P. In addition, voiding condition and psychological status after TUR-P may affect the maintenance of sexual intercourse in patients in their fifties and sixties.

Aged↗

[Western blot analysis of anti-M2 antibodies in anti-mitochondrial antibody-negative primary biliary cirrhosis].

One variety of anti-mitochondrial antibody(AMA) is characteristically found in sera from patients with primary biliary cirrhosis(PBC). The major target antigens of this type of AMA are M2s. It is well known, however, that AMA-negative PBC also exists. An alternative disease concept, called autoimmune cholangiopathy, recently has been advocated. This new concept is defined by the following criteria: 1)the failure to detect AMA and anti-M2, 2)the detection of a diffuse type of anti-nuclear antibody and anti-smooth muscle antibody, 3)pathological findings compatible with PBC, and 4)the effectiveness of prednisolone. However, the difference between AMA-negative PBC and autoimmune cholangiopathy is controversial. Therefore, we analyzed antibodies to four major M2 proteins with Western blotting in 34 cases of immunofluorescent AMA-negative PBC. In 31(91.2%) of these 34 AMA-negative sera, antibodies to at least one of these four major M2 proteins was detected. In serum samples from 34 control patients with AMA-positive PBC, antibodies to at least one of these four proteins were detected in all cases. In addition, we studied the frequency of cases which satisfied the serological criteria of autoimmune cholangiopathy. In only one(0.7%) of 141 cases was the serological criteria met. We conclude that to clarify the serological differences between autoimmune cholangiopathy and AMA-negative PBC, the analysis of M2 proteins by Western blotting is essential.

Adult↗

Identification of the subunit loci in the extracellular multisubunit hemoglobin from annelid Perinereis aibuhitensis.

Giant hemoglobin (Hb) from Perinereis aibuhitensis is made of several types of protein components including single-chain globin (a), disulfide-bridged globin trimer (A-b-B), disulfide-bridged dimers of nonglobin chain (or linkers; L1-L1, L2-L2, and L1-L2), and oligomers of L1-L2 [(L1-L2)n]. The intact form of this giant Hb is a two-tiered hexagonal structure composed of 12 identical units, or so-called submultiples (six submultiples to a tier). To obtain a view of the three-dimensional architectural arrangement of these components in the intact form, we identified the subunit loci by using two mutually complementary chemical modifications and a colloidal gold labeling technique. Using the chemical modifications, we discovered that (i) linkers L1-L2 and L2-L2 were located at the exterior of the Hb, (ii) linker L1-L1 and globin a were buried in the interior, and (iii) linker (L1-L2)n and globin trimer A-b-B were located at both exterior and interior loci. The labeling with an L2-specific colloidal gold revealed the predominant loci of L2 at the outer and inner boundaries between neighboring submultiples in a hexagonal form. By combining these results with those from our previous reports [S. Ebina, K. Matsubara, K. Nagayama, M. Yamaki, and T. Gotoh (1995) Proc. Natl. Acad. Sci. USA 92, 7367-7371; K. Matsubara, M. Yamaki, Nagayama, H. Ishii, K. Imai, T. Gotoh, and S. Ebina (1996), in press], we deduced the following conclusions concerning the Hb architecture. The L1-L1 chains perhaps together with (L1-L2)n chains form a scaffold on which submultiples assemble into a two-tiered hexagonal arrangement, probably by connecting the carbohydrates in globin a. The L1-L2 and L2-L2 chains reinforce the connections of the submultiples by binding carbohydrates, perhaps those carbohydrates in globin A. We proposed to call this type of non-protein-dependent structural level as seen in such a carbohydrate-glued protein aggregate "protein-plus structure."

Animals↗

DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes.

Intercellular adhesion molecules play an important role in the generation of T lymphocyte-mediated immune responses. Here, we describe a novel accessory molecule, DNAX accessory molecule-1 (DNAM-1), that is constitutively expressed on the majority of peripheral blood T lymphocytes. DNAM-1 is a 65 kDa transmembrane glycoprotein consisting of 318 aa including two immunoglobulin-like domains. Anti-DNAM-1 monoclonal antibody (MAb) inhibits T and NK cell-mediated cytotoxicity against a variety of tumor cell targets and blocks cytokine production by alloantigen-specific T cells. In addition, DNAM-1 is a tyrosine-phosphorylated signal-transducing molecule that participates in primary adhesion during cytotoxic T lymphocyte (CTL)-mediated cytotoxicity.

Amino Acid Sequence↗

Applications of retrovirus-mediated expression cloning.

We have recently established a novel expression cloning system using retroviral vectors. The system is based on a high-efficiency packaging cell line, BOSC23, and a simplified retroviral vector, pBabeX, carrying no selection marker. cDNA libraries, constructed in the pBabeX vector, are transiently transfected into BOSC23 cells. The supernatant contains more than 3X10(6)/mL, which would cover large complexities of cDNA libraries. The retrovirus stock gave 100% infection efficiency in NIH3T3 cells and 5-40% infection efficiency in various hematopoietic cell lines. In contrast to the conventional expression cloning system, in which it is necessary to transfect cDNA libraries transiently into particular cell types such as COS cells, retrovirus-mediated expression cloning allows us to transduce cDNAs into a wide variety of cell types. This method therefore makes it possible to select cells expressing a cDNA of interest by various functional assays. When combined with polymerase chain reaction (PCR)-driven random mutagenesis, this system is also useful in searching for mutations of various molecules that will result in alterations of their functions.

3T3 Cells↗

Efficient screening of retroviral cDNA expression libraries.

Expression cloning of cDNAs was first described a decade ago and was based on transient expression of cDNA libraries in COS cells. In contrast to transient transfection of plasmids, retroviral gene transfer delivers genes stably into a wide range of target cells. We utilize a simple packaging system for production of high-titer retrovirus stock from cDNA libraries to establish a cDNA expression cloning system. In two model experiments, murine interleukin (IL)-3-dependent Ba/F3 cells were infected with libraries of retrovirally expressed cDNA derived from human T-cell mRNA or human IL-3-dependent TF-1 cell line mRNA. These infected Ba/F3 cells were selected for the expression of CD2 by flow cytometry or for the alpha subunit of the human IL-3 receptor (hIL-3R alpha) by factor-dependent growth. CD2 (frequency, 1 in 10(4)) and hIL-3R alpha (frequency, 1 in 1.5 x 10(5)) cDNAs were readily detected in small-scale experiments, indicating this retroviral expression cloning system is efficient enough to clone low-abundance cDNAs by their expression or function.

3T3 Cells↗

Dopamine release in the medial preoptic area during male copulatory behavior in rats.

In vivo microdialysis was employed to measure the extracellular concentrations of dopamine (DA) in the medial preoptic area (MPOA) of rats during male sexual activity to look for a correlation with sexual activity. During copulation, the concentration of DA in the MPOA was significantly increased. A significant difference was detected in changes of DA between copulators and non-copulators. These findings were consistent with the assertion that DA neuron activity in the MPOA facilities male copulatory behavior.

3,4-Dihydroxyphenylacetic Acid↗

Lymphokine requirement for the generation of natural killer cells from CD34+ hematopoietic progenitor cells.

We have established a cell culture system without stromal cells that allows the CD34+ hematopoietic progenitor cells (HPC) to differentiate into natural killer (NK) cells. CD34+Lin (CD3, CD16, CD56)- cells were purified using fluorescence-activated cell sorting from normal adult bone marrow (BM) and cultured for 28 days in medium supplemented with interleukin-2 (IL-2) and stem cell factor (SCF). NK (CD3-CD16-CD56+) cells were generated in a dose-dependent manner in response to SCF. NK cells originated from CD34+CD33+Lin- cells, but they were barely detectable in cultures of CD34+CD33-Lin- cells. However, on addition of IL-3, an induced differentiation of NK cells from CD34+CD33-Lin- cells was observed, although at a lower frequency. Supplementing of the cell cultures with SCF alone or both SCF and IL-3 for the first 7 days followed by IL-2 for the next 21 days is essential for production of NK cells from CD34+CD33+Lin- cells and from CD34+CD33-Lin- cells, respectively. These data provide direct evidence that NK cells arise from CD34+HPC and show the minimum lymphokine requirement for their differentiation.

Antigens, CD↗

[Clinical efficacy of lomefloxacin (100 mg or 300 mg) single-dose therapy in female acute uncomplicated cystitis].

Female acute uncomplicated cystitis responds relatively well to antimicrobial chemotherapy. In particular, new quinolones are suited for use as antimicrobial agents in single-dose therapy of female acute uncomplicated cystitis since they have a long serum half-life and express potent antimicrobial activity against the causative microbes of this infection. Lomefloxacin (LFLX) is one such new quinolone which shows a long serum half-life, expresses potent antimicrobial activity against Escherichia coli (E. coli) and maintains an effective urinary drug concentration for approximately three days after a single administration. The authors carried out a comparative investigation of the clinical efficacy of single doses of 100 mg and 300 mg of LFLX in the treatment of female acute uncomplicated cystitis. The clinical efficacy rates with these doses, evaluated on the 3rd day after administration, were 98.2% (56/57 cases) for the 100mg-LFLX dose and 100% (62/62 cases) for the 300-mg LFLX dose. When the evaluation was performed on the 7th day after administration, the clinical efficacy rates were 91.3% (42/46 cases) for the 100-mg LFLX dose and 95.8% (46/48 cases) for the 300-mg LFLX dose. In addition, the microbial eradication rates were 73.7% (42/57 cases) for the 100-mg LFLX group and 75.8% (47/62 cases) for the 300-mg LFLX group on the 3rd day after administration, and 71.7% (33/46 cases) for the 100-mg LFLX group and 83.3% (40/48 cases) for the 300-mg LFLX group on the 7th day after administration. Although there were no statistically significant differences between the two LFLX dosage groups for these parameters at either of the evaluation times, the rates for the 300-mg LFLX dose were slightly superior. The investigators judged the efficacy of the LFLX treatment as having been insufficient in 12 patients, and urological examinations performed on six of those cases determined that there were mild underlying diseases in four cases, such as stenosis of the urethral meatus. On the basis of the findings described above, it is clear that a single 100-mg dose of LFLX provided sufficient clinical efficacy in the treatment of female acute uncomplicated cystitis, but the efficacy of the 300-mg dose of LFLX was even better. In addition, it was surmised that performance of detailed urological examinations provides an opportunity to detect mild underlying diseases that may be the cause of the intractability in female acute uncomplicated cystitis cases showing an insufficient response to treatment with antimicrobial agents such as LFLX.

Acute Disease↗

[Long-term monitoring of female acute uncomplicated cystitis cases after lomefloxacin single-dose therapy].

Female acute uncomplicated cystitis responds relatively well to antimicrobial chemotherapy, but this is also a disease which shows a high frequency of recurrence. However, there have been no published reports regarding long-term monitoring of the course of this disease after therapy has been administered. Accordingly, using primarily a questionnaire, the authors carried out long-term monitoring (for a mean of 242 days) of the natural course of cases of female acute uncomplicated cystitis after single-dose therapy with lomefloxacin (LFLX), a new quinolone antimicrobial agent. The subjects of this study were female patients diagnosed as having acute uncomplicated cystitis with pain upon urination, pyuria (> or = 10 WBCs/hpf) and bacteriuria (> or = 10(4) cfu/ml). LFLX was orally administered as a single dose of 100 mg or 300 mg, and the therapeutic efficacy was evaluated on the 3rd and 7th days thereafter. In principle, the evaluation of cure was performed on the 7th day after LFLX administration, and monitoring was conducted to detect early recurrence during the next 7 days (i.e., through the 14th day after treatment). Then the subjects were monitored for late recurrence during a mean follow-up period of 242 days by means of a questionnaire. Confirmation of recurrence was carried out to the greatest extent possible. It was possible to carry out long-term monitoring of the natural course of 101 cases of female acute uncomplicated cystitis in which the clinical efficacy on the 3rd day after LFLX treatment had been evaluated as good or excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

CRST syndrome (calcinosis cutis, Raynaud's phenomenon, sclerodactyly, and telangiectasia) associated with autoimmune hepatitis.

A case of Raynaud's phenomenon, was complicated with autoimmune hepatitis (AIH) during the clinical course, and subsequently with gangrene of the fingertips caused by CRST syndrome (calcinosis cutis, Raynaud's phenomenon, sclerodactyly and telangiectasia). The presence of anticentromere antibodies is rare in AIH; to date, there has been only one report of a combination of AIH and CRST syndrome. This combination of the two diseases has been identified only in Japan.

Antibodies, Antinuclear↗

[The preventive effect of indeloxazine hydrochloride to the sexual dysfunction caused by anti-androgenergic agent (allylestrenol)].

Anti-androgenergic agents are usually used for patients with benign prostatic hypertrophy (BPH). However steroidal anti-androgenergic agents tend to suppress the sexual function. This side effect is very significant in middle-aged men. Therefore we studied the preventive effect of indeloxazine hydrochloride (INDX), which induces an increase of the dopamine level in the brain, on the sexual dysfunction induced by an anti-androgenergic agent (allylestrenol: ALE). Thirty-six patients with BPH were classified into two groups, one used ALE only, and the other ALE with INDX. For the subjective evaluation of the sexual function, a self assessment questionnaire method was employed before and after administration. We especially studied 3 questions, "morning erection", "erectile capacity" and "frequency of sex". For the objective evaluation of the sexual function, nocturnal penile tumescence (NPT) was measured using an erectometer. NPT occurs in healthy males as a physiological phenomenon and it shows the erectile capacity objectively. The levels of LH, total testosterone and free testosterone were also determined. In the ALE only group, sexual dysfunction was found subjectively and objectively, but in the ALE with INDX group, it was not found. Levels of LH, total testosterone and free testosterone were decreased in the both groups. There was no significant difference between the two groups. We hypothesized that the sexual dysfunction due to ALE is related with not only to the decrease of androgen, but also to suppression of the central nervous system; for example, the suppression of the area of the brain mediating sexual behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗