Biomedical subjects

K Shinohara

Publications and source records attributed to K Shinohara.

At least 109 records · Page 6Linked to original sources

PubMed1999

Functional and phenotypical characteristics of hepatic NK-like T cells in NK1.1-positive and -negative mouse strains.

We previously reported and partially characterized a unique monoclonal antibody (mAb), U5A2-13, which recognizes a T cell subset similar to NK1.1+ T cells, not only in NK1.1-positive mouse strains but also in NK1.1-negative strains. In NK1.1-positive C57BL/6 mice, U5A2-13+ TCRalphabeta+ cells produced abundant IL-4 as well as extremely high levels of IFN-gamma upon CD3 cross-linking, but this did not occur with U5A2-13- TCRalphabeta+ cells. In NK1.1-negative C3H/He mice, U5A2-13+ TCRalphabeta+ cells produced high levels of IL-4 and IFN-gamma upon CD3 cross-linking, but this was not observed with U5A2-13- TCRalphabeta+ cells. To the best of our knowledge, this is the first direct evidence of the presence of NK-like T cells defined phenotypically by U5A2-13 mAb and functionally by IL-4/IFN-gamma production in NK1.1-negative mouse strains. We also demonstrated that U5A2-13- NK1.1+ T cells and U5A2-13+ NK1.1- T cells in C57BL/6 mice could produce both IL-4 and IFN-gamma. In addition, Vbeta8 or Vbeta7 usage by U5A2-13+ NK1.1- T cells was lower than that by U5A2-13+ NK1.1+ T cells, but remained higher than that by U5A2-13- NK1.1- T cells. Based on the present results, U5A2-13 mAb appears to be a valuable tool in the study of NK-like T cells.

Animals↗

PubMed1999

A highly sensitive enzyme-linked immunoassay for serum free prostate specific antigen (f-PSA).

Monoclonal antibodies (MAbs) were generated against human prostate specific antigen (PSA) to allow development of a sensitive free-PSA (f-PSA) assay. Of a total of 211, 12 could detect only f-PSA, the other 199 MAbs binding to both f-PSA and complex-PSA. In the present study, one MAb (no. 5C6) specific for f-PSA and another (no. 79) reacting with both forms were used to develop an enzyme-linked immunoassay (ELISA) for serum f-PSA. The detection limit was established as 0.008 microg/l (n = 20, mean of zero standard + 3 S.D.) and the average recovery of f-PSA was 93-102%. The within-run and between-day coefficient of variation (CV) varied from 5.4-7.4% and 4.8-6.5%, respectively. The cross-reactivity of the assay to PSA-alpha1-antichymotrypsin complex was determined to be < 0.4%.

Animals↗

PubMed1999

Neonatal lupus erythematosus: results of maternal corticosteroid therapy.

OBJECTIVE: To assess the possibility of preventing cardiac or cutaneous manifestations of neonatal lupus erythematosus or treating the fetus with congenital heart block by administering corticosteroid therapy to the mother. METHODS: Eighty-seven offspring of 40 anti-Ro/SSA-positive mothers, followed up from 1979 to 1996, were evaluated. Autoantibodies against Ro/SSA and La/SSB antigens were detected by immunodiffusion and enzyme-linked immunosorbent assay. RESULTS: None of 26 neonates whose mothers received corticosteroid maintenance therapy initiated before 16 weeks' gestation demonstrated congenital heart block, whereas 15 of 61 neonates whose mothers received no corticosteroids during pregnancy or began receiving steroid therapy after 16 weeks' gestation had congenital heart block. Complete congenital heart block, once developed, did not respond to corticosteroid treatment in utero. Four infants whose mothers received steroid treatment before 16 weeks' gestation had skin lesions of neonatal lupus erythematosus. CONCLUSION: Once established, complete congenital heart block was irreversible and maternal corticosteroid therapy did not effectively prevent cutaneous lupus erythematosus. However, prenatal maintenance therapy with prednisolone or betamethasone given to the mother starting early in pregnancy (before 16 weeks' gestation) might reduce the risk of developing antibody-mediated congenital heart block in the offspring.

Adrenal Cortex Hormones↗

PubMed1999

Number of positive systematic sextant biopsies predicts surgical margin status at radical prostatectomy.

OBJECTIVES: To determine whether the number of positive sextant biopsies contributes to the prediction of positive surgical margins, as the value of systematic prostate biopsies in predicting margin status at radical prostatectomy is unclear. METHODS: Consecutive patients (n = 108) who underwent radical retropubic prostatectomy and systematic sextant biopsies were retrospectively evaluated. Serum prostate-specific antigen, digital rectal examination, primary Gleason grade, Gleason score, and the number and location of positive sextant biopsies were recorded for each patient. Radical prostatectomy specimens were evaluated by step-section techniques at 3 to 5-mm intervals. Univariate comparisons for each of these variables was performed between the positive and negative margin groups using the Mann-Whitney U test or chi-square analysis. Logistic regression analysis was performed for these variables. RESULTS: Twenty-two (20.4%) of 108 patients had a positive surgical margin because of extension of the tumor through the capsule. Patients with three or more positive biopsies were at higher risk of having a positive surgical margin (P = 0.009). Patients with bilaterally positive biopsies at either the base or midprostate were more likely to have a positive surgical margin. The risk of a positive surgical margin was not significantly determined by the primary Gleason grade, Gleason score, or prostate-specific antigen. Multivariate logistic regression models were created that consistently demonstrate that the number of positive biopsies was the best predictor of margin status. CONCLUSIONS: This study demonstrated that the number of positive sextant biopsies contributes to the prediction of margin status at radical prostatectomy.

Aged↗

PubMed1999

Phase dependent response of vasoactive intestinal polypeptide to light and darkness in the suprachiasmatic nucleus.

Responsiveness of the vasoactive intestinal polypeptide (VIP) content to light and darkness in the rat suprachiasmatic nucleus (SCN) was examined by enzyme immunoassay of micropunched tissues. VIP content in the SCN has been shown to decrease monotonically in animals maintained in illumination. Decreases in VIP content in the SCN in response to both 6-h light and dark pulses depended on the phase of the circadian cycle when the pulses were applied. Light imposed at circadian time (CT) 18 or CT 22 was more effective in suppressing VIP levels than light exposure of the same intensity imposed at CT 0 or CT 6. Darkness interrupting continuous light was more effective at around CT 0 and less effective at around CT 12. These results suggest that VIP responsiveness to light and darkness in the SCN is regulated by the circadian clock in different ways and are correlated with phase-dependent phase shifts in the activity rhythm after light and dark pulses.

Analysis of Variance↗

PubMed1999

Intravenous injections of nicotine decrease the pulsatile secretion of LH by inhibiting the gonadotropin-releasing hormone (GnRH) pulse generator activity in female rats.

Whether nicotine inhibits the electrical activity of the gonadotropin-releasing hormone (GnRH) pulse generator to suppress pulsatile LH secretion, and whether this suppression of LH secretion by nicotine is mediated by opioid neurons, were studied in ovariectomized rats by examining changes in LH secretion and the multiunit activity (MUA) of the medial basal hypothalamus. Intravenous (i.v.) injection of nicotine (nicotine bitartrate, 100 micrograms) significantly increased the interval between characteristic increases (volleys) in MUA and LH pulses. This inhibitory effect of nicotine on the GnRH pulse generator activity was not blocked by the prior injection of an opiate receptor antagonist naloxone (naloxone hydrochlolide, 2 mg/kg bw), which was effective in significantly decreasing the interval between MUA volleys. The results suggest that nicotine alters the activity of the GnRH pulse generator, and that cholinergic neurons appear to be directly involved in suppressing pulsatile secretion of LH.

Animals↗

PubMed1999

Methyl alpha-D-mannopyranoside-responsive release of microencapsulated glucoamylase.

Microcapsules are made of porous membranes through which enzymes or proteins can readily permeate. Glucoamylase was encapsulated into microcapsules in the presence of concanavalin A. Microencapsulated glucoamylase was released from the microcapsules into the bulk phase in the presence of methyl alpha-D-mannopyranoside, while it was not released in the absence of methyl alpha-D-mannopyranoside. The initiation and cessation of glucoamylase release from the microcapsules accurately corresponded to the addition and removal of methyl alpha-D-mannopyranoside, respectively. Methyl alpha-D-mannopyranoside served as a controller for the release of glucoamylase.

Journal Article↗

PubMed1999

Gene-mutated HIV-1/SIV chimeric viruses as AIDS live attenuated vaccines for potential human use.

To develop an AIDS vaccine for human use as well as a suitable animal model for AIDS research, we constructed a series of HIV-1/SIVmac chimeric viruses (SHIVs). We successfully generated a SHIV (designated as NM-3rN) having the HIV-1 env gene, which enabled the evaluation of the efficacy of HIV-1 Env-targeted vaccines in macaque monkeys instead of chimpanzees. Two NM-3rN derivatives (NM-3 and NM-3n) induced long-term anti-virus immunities without manifesting the disease. The monkeys vaccinated with NM-3 or NM-3n became resistant to a challenge inoculation with NM-3rN. Serum from a monkey vaccinated with NM-3 neutralized not only the parental HIV-1 (NL432), but also an antigenically different HIV-1 (MN). In vivo experiments confirmed the heterologous protection against an SHIV having the HIV-1 (MN) env. In addition to specific immunity including neutralizing antibodies and cytotoxic T lymphocyte activity, nonspecific immunity such as natural killer activity is associated with this protection. These data suggest that the live vaccine has the ability to protect individuals against various types of HIVs. These SHIVs should contribute to the development of future anti-HIV-1 live vaccines in humans.

AIDS Vaccines↗

PubMed1999

Second lung adenocarcinoma after combination chemotherapy in two patients with primary non-Hodgkin's lymphoma.

We report a rare complication of a secondary malignant solid tumor in two patients with non-Hodgkin's malignant lymphoma who developed lung adenocarcinoma after treatments with combination chemotherapies. The first was a case of primary malignant lymphoma of the cervical spinal cord which had been previously treated with radiation to the spinal lesion and combination chemotherapies and entered complete remission. The patient was further treated for relapse with autologous bone marrow transplantation preconditioned with high-dose chemotherapy. Lung adenocarcinoma developed 5.5 years after the initial diagnosis. The second case of malignant lymphoma of lymph nodes did not respond to conventional combination chemotherapies and did not enter remission. Lung adenocarcinoma developed 1 year after the initial diagnosis. The two patients died of lung carcinoma. The clinical profiles of these cases are presented and the causal relationship of primary malignant neoplasms to the second malignant neoplasms is discussed.

Adenocarcinoma↗

PubMed1999

Expression of DnaJ homologs and Hsp70 in the Japanese willow (Salix gilgiana Seemen).

We isolated three cDNA clones (pSGJ1, pSGJ2 and pSGJ3) for DnaJ-like proteins of the Japanese willow (Salix gilgiana Seemen). The insert in pSGJ2 included the entire nucleotide sequence of the insert in pSGJ1 that was separated into four parts by three intron-like sequences, and it might correspond to the cDNA for a precursor to the SGJ1 mRNA. The predicted amino acid sequences of SGJ1 (47.5 kDa) and SGJ3 (46.6 kDa) exhibited about 70 to 91% homology to plant cytoplasmic DnaJ-like proteins. SGJ1 was encoded by one or a few genes within the willow genome while SGJ3 was encoded by several genes. Expression of the SGJ1 and SGJ3 genes was compared with that of Hsp70 (SGK1) gene. Constitutive expression of SGJ1, SGJ3 and SGK1 was detected in all organs examined. The SGJ1 mRNA was most abundant in male catkins (inflorescences). High-level expression of SGJ3 and SGK1 was detected in catkins and roots of both male and female plants. The level of the SGJ3 mRNA in the leaves increased about 10-fold after 1 h of heat stress while the expression of SGJ1 mRNA reached a maximum level after 6 h. However, the extent of induction of SGJ1 mRNA was quite low. The levels of SGJ1 and SGJ3 mRNAs in the leaves increased about 6-fold and 2-fold, respectively, after 24 h of treatment with 100 mM NaCl. Thus, the SGJ1 and SGJ3 genes showed differential expression patterns in a variety of organs and in response to different environmental conditions.

Amino Acid Sequence↗

PubMed1999

A highly pathogenic simian/human immunodeficiency virus with genetic changes in cynomolgus monkey.

A highly pathogenic simian/human immunodeficiency virus (SHIV), designated C2/1, was obtained by serum passages in cynomolgus monkeys of p-SHIV, an SHIV strain that contains the env gene of pathogenic human immunodeficiency virus type 1 89.6. CD4+ lymphocyte depletion was induced within 1 week of the SHIV-C2/1 infection in peripheral blood as well as in various lymphoid organs in all the animals tested, with symptoms of diarrhoea and no increase in body weight, followed by intense viraemia. Serum antibody against Env protein was detected from 4 weeks after the virus infection, while the anti-Gag antibody response was absent in the SHIV-C2/1-infected animals. In contrast, both anti-Gag and anti-Env antibody responses were present in animals infected with p-SHIV or the non-pathogenic SHIV-MN. Sequencing of the env gene of isolates of SHIV-C strains showed conserved amino acid changes in the Env C2 and V3 regions that included changes to negatively charged amino acids, in the cytoplasmic region of gp41 that included a 42 amino acid deletion, and in the Nef protein. The pathogenic SHIV-C2/1-monkey model suggests that virus-specific pathogenicity in SHIV infection may be associated with the absence of anti-Gag antibody responses in animals and may be caused by genetic changes during serum passage in vivo.

Amino Acid Sequence↗

PubMed1999

Physiological changes in Pachinko players; beta-endorphin, catecholamines, immune system substances and heart rate.

Pachinko is a popular form of recreation in Japan. However, in recent years, along with Pachinko's popularity, "Pachinko dependence" has become topical news. The purpose of this study was to investigate beta-endorphin, catecholamines, immune system responses and heart rate during the playing of Pachinko. The following significant results were observed. (1) Plasma concentration of beta-endorphin increased before playing Pachinko and while in the Pachinko-center (p < 0.05). (2) Beta-endorphin and norepinephrine increased when the player began to win (i.e. at "Fever-start") compared to baseline (p < 0.05). (3) Beta-endorphin, norepinephrine and dopamine increased when the winning streak finished (i.e. at "Fever-end") compared to baseline (p < 0.05-0.01). (4) Norepinephrine increased past 30 minutes after "Fever-end" compared to baseline (p < 0.05). (5) Heart rate increased before "Fever-start" compared to baseline, peaked at "Fever-start" and rapidly decreased to match rates measured at rest. But the increase was observed from 200 seconds after "Fever-start" (p < 0.05-0.001). (6) There was a positive correlation between the number of hours subjects played Pachinko in a week and the differences between beta-endorphin levels at "Fever-start" and those at rest (p < 0.05). (7) The number of T-cells decreased while the number of NK cells increased at "Fever-start" compared to baseline (p < .05). These results suggest that intracerebral substances such as beta-endorphin and dopamine are involved in the habit-forming behavior associated with Pachinko.

Adult↗

PubMed1999

Resource for temporal information processing in interval production.

The resource required to process temporal information in interval production was investigated. 12 undergraduates performed 4-sec. interval production and nontemporal tasks, the probe digit task and the missing digit task. Although both tasks required memory search and employed the same modality for input and for responding, the probe digit task required a phonological resource and the missing digit task required a spatial resource. Analysis showed that both concurrent nontemporal tasks caused interval productions to be longer, suggesting that the temporal processing required a resource which both tasks used commonly. This resource may be a general purpose, capacity-limited resource associated with a central executive function in working memory.

Adult↗

PubMed1999

Correlation between unirradiated cell TP53 protein levels and radiosensitivity in MOLT-4 cells.

MOLT-4 cells undergo apoptosis after X irradiation. A radiosensitive variant, MOLT-4N1, and a radioresistant variant, MOLT-4N2, have been studied with respect to their radiosensitivity and its relationship to the levels of TP53 protein (formerly known as p53). X irradiation induces apoptosis in both cell lines with the following difference: The induction of apoptosis in MOLT-4N2 cells occurred later than in MOLT-4N1 cells as determined by the morphological changes and DNA fragmentation. The levels of cell death measured by the dye exclusion test coincided with the levels of apoptosis in both cell lines, suggesting that radiation-induced cell killing is determined by the induction of apoptosis. Unirradiated MOLT-4N1 cells contained a significantly higher intracellular level of TP53 protein and a much higher level of TP53 mRNA compared to MOLT-4N2 cells. X irradiation led to an accumulation of TP53 protein in both cell lines that was greater in MOLT-4N1 cells. This accumulation of TP53 protein preceded changes in DNA degradation and ladder formation and in nuclear morphology. These results strongly suggest that the radiosensitivity of MOLT-4 cells correlates well with the unirradiated control levels of TP53 mRNA and TP53 protein, and that the quantitative levels of TP53 protein must reach a threshold for the cells to undergo apoptosis.

Adult↗

PubMed1999

The efficacy of cryosurgical ablation of prostate cancer: the University of California, San Francisco experience.

PURPOSE: We analyze biopsy and prostate specific antigen (PSA) results following cryosurgery for patients with clinically localized prostate cancer. MATERIALS AND METHODS: A total of 176 patients underwent 207 cryosurgical procedures for clinically localized (stages T1 to T4) prostate cancer using a multiprobe cryosurgical device. Cancer stage was T1 in 8.7%, T2 in 30%, T3 in 59% and T4 in 2.3% of the 176 patients. Neoadjuvant androgen deprivation was delivered to 101 patients (57%). End points used to determine efficacy of the procedure included analysis of posttreatment serum PSA characteristics (nadir and nonrising status) and biopsy results (absence of cancer). Cryosurgery was considered successful if PSA reached a nadir of less than 0.5 ng./ml. and did not increase by more than 0.2 ng./ml. on 2 consecutive occasions. Mean followup for the entire group was 30.8 months, with 122 patients (60%) followed for 24 or more months and 75 (36%) followed for 36 or more months. RESULTS: Serial PSA data was available after 181 initial and repeat procedures. Nadir PSA was undetectable in 88 patients (49%), between 0.1 and 0.4 ng./ml. in 39 (21%) and 0.5 ng./ml. or greater in 54 (30%) following cryosurgery. After 78 of these procedures (43%) serum PSA reached a nadir of less than 0.5 ng./ml. and failed to increase greater than 0.2 ng./ml. on at least 2 occasions. Prostate biopsy was performed following 167 procedures and was positive after 64 (38%). CONCLUSIONS: Cryosurgery was associated with favorable serum PSA characteristics in 49% of patients 3 years after treatment. Undetectable PSA nadir and pretreatment PSA 10 ng./ml. or less were associated with a favorable outcome, with a biochemical disease-free survival of 77% and 61% 3 years after treatment, respectively.

Actuarial Analysis↗

PubMed1999

[Refractory anemia with trisomy-8 complicated by Behçet's disease with elevated levels of inflammatory cytokines].

A man with refractory anemia and trisomy 8 complained of repeated febrile episodes. He exhibited oral aphtha, exanthema, genital ulcer, and epididymitis. Laboratory data obtained during febrile episodes revealed leukocytosis with elevated CRP and ESR. Repeated examinations for infectious bacterial agents were negative. HLA analysis detected HLA-B51. Behçet's disease of incomplete type was diagnosed and successfully treated with prednisolone. It was speculated that the repeated febrile episodes may have been a manifestation of neutrophil hyper-function induced by increased blood levels of inflammatory cytokines, including IL-6, IL-8 and G-CSF, in association with rare complications of Behçet's disease.

Anemia, Refractory↗

PubMed1998

Luminance-dependent decrease in vasoactive intestinal polypeptide in the rat suprachiasmatic nucleus.

Light responsiveness of the vasoactive intestinal polypeptide (VIP) content in the suprachiasmatic nucleus (SCN) of the rat with pupils dilated by atropine was examined by enzyme immunoassay. After exposure to 6 h light at 3-1000 lux VIP levels in the SCN decreased as a monotonic function with a working range from 3 to 300 lux. At 12 h, 30 lux light decreased the VIP content to the minimum level that was attained by 300 lux light exposure in 6 h, suggesting that brighter illumination decreases VIP levels more rapidly, but light at a luminance of 0.05 lux for 3 days did not suppress VIP levels. These results suggest that VIP in the SCN codes visual information on luminance with a small working range and a relative high threshold.

Animals↗

PubMed1998

The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of the MTG8(ETO) family.

The t(16;21)(q24;q22) translocation is a rare but recurrent chromosomal abnormality associated with therapy-related myeloid malignancies and a variant of the t(8;21) translocation in which the AML1 gene on chromosome 21 is rearranged. Here we report the molecular definition of this chromosomal aberration in four patients. We cloned cDNAs from the leukemic cells of a patient carrying t(16;21) by the reverse transcription polymerase chain reaction using an AML1-specific primer. The structural analysis of the cDNAs showed that AML1 was fused to a novel gene named MTG16 (Myeloid Translocation Gene on chromosome 16) which shows high homology to MTG8 (ETO/CDR) and MTGR1. Northern blot analysis using MTG16 probes mainly detected 4.5 kb and 4.2 kb RNAs, along with several other minor RNAs in various human tissues. As in t(8;21), the t(16;21) breakpoints occurred between the exons 5 and 6 of AML1, and between the exons 1 and 2 or the exons 3 and 4 of MTG16. The two genes are fused in-frame, resulting in the characteristic chimeric transcripts of this translocation. Although the reciprocal chimeric product, MTG16-AML1, was also detected in one of the t(16;21) patients, its protein product was predicted to be truncated. Thus, the AML1-MTG16 gene fusion in t(16;21) leukemia results in the production of a protein that is very similar to the AML1-MTG8 chimeric protein.

Amino Acid Sequence↗