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Biomedical subjects

Y Iwatani

Publications and source records attributed to Y Iwatani.

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

Interleukin 18 and interleukin 1beta production is decreased in HIV type 1-seropositive hemophiliacs but not in HIV type 1-seropositive nonhemophiliacs.

In Japan, the proportion of hemophiliacs infected with human immunodeficiency virus type 1 (HIV-1) is 40%, whereas more than 90% are infected with hepatitis C virus (HCV). To evaluate the immunological status of hemophiliacs infected with HIV-1, we investigated the pattern of cytokine production in peripheral blood mononuclear cells (PBMCs) of HIV-1-seropositive and -seronegative hemophiliacs, HIV-1-seropositive non-hemophiliacs, and healthy individuals. The production of IL-18 and IL-1beta from PBMCs stimulated with Staphylococcus aureus Cowan strain 1 (SAC) in the HIV-1-seropositive hemophiliacs was significantly decreased in comparison with the other groups. On the other hand, IL-12 production in both HIV-1-seropositive groups was significantly lower than in HIV-1-seronegative groups. TNF-alpha and IL-6 production was similar among the four groups. In contrast, plasma levels of TGF-beta1 were increased in HIV-1-seropositive hemophiliacs, HIV-1-seropositive nonhemophiliacs, and HIV-1-seronegative hemophiliacs, with the highest levels being in HIV-1-seropositive hemophiliacs, suggesting that coinfection with HIV-1 and HCV increases the level of plasma TGF-beta in HIV-1-seropositive hemophiliacs. Treatment of PBMCs from healthy individuals with TGF-beta1 inhibited IL-18 and IL-1beta production without affecting IL-6, IL-10, or TNF-alpha production. Suppression of the expression of caspase 1 mRNA, which is known to be an IL-1beta-converting enzyme and which also cleaves the precursor of IL-18, was observed in the SAC-stimulated PBMCs from healthy individuals after treatment with TGF-beta1 and in the SAC-stimulated PBMCs from HIV-1-seropositive hemophiliacs, suggesting that the decreased production of IL-18 and IL-1beta in HIV-1-seropositive hemophiliacs may be related to the downregulation of caspase 1 mRNA induced by high levels of TGF-beta1 in plasma.

Adolescent↗
PubMed2000

Functional association between the nef gene product and gag-pol region of HIV-1.

Nef gene function is diverse among virus isolates of primate immunodeficiency viruses. We found differential effects of nef mutation on the virus replication between two HIV-1 clones, NL432 and LAI. The nef mutation in NL432 affected the infectivity more severely compared with that in LAI, although the Nef functions of both clones were comparable. Analysis with a series of chimeric viruses between NL432 and LAI revealed that the gag-pol region was responsible for the differential effect of nef mutation. The functional association between Nef and gag-pol suggested that one of the potential targets of Nef was located within the gag-pol region.

Cell Line↗
PubMed2000

Resistance to Friend murine leukemia virus infection conferred by the Fv-4 gene is recessive but appears dominant from the effect of the immune system.

Fv-4 is a mouse gene that dominantly confers resistance to infection with Friend murine leukemia virus (F-MuLV) (S. Suzuki, Jpn. J. Exp. Med. 45:473-478, 1975). However, the resistance caused by Fv-4 is recessive in nude mice, which suggests that immunological effects play important roles in this resistance in vivo (K. Higo, Y. Kubo, Y. Iwatani, T. Ono, M. Maeda, H. Hiai, T. Masuda, K. Kuribayashi, F. Zhang, T. Lamin, A. Adachi, and A. Ishimoto, J. Virol. 71:750-754, 1997). To determine the immunological effect on the resistance in vivo, we infected immunologically immature newborn mice homozygous (Fv-4(r/r)) and heterozygous (Fv-4(r/-)) for Fv-4. Although the Fv-4(r/r) mice showed complete resistance to F-MuLV whether infected neonatally or as adolescents, the Fv-4(r/-) mice showed high sensitivity to viral proliferation and disease induction when infected as newborns but complete resistance when infected as adolescent mice. To confirm the immunological effect on the resistance in adolescent mice with the Fv-4(r/r) and Fv-4(r/-) genotypes, we examined the effect of an immunosuppressant drug, FK506, on the resistance. The mice with the Fv-4(r/r) genotype treated with FK506 still showed resistance, but the mice with the Fv-4(r/-) genotype became highly sensitive to F-MuLV infection. Flow cytometric analysis to detect the Fv-4 gene product showed that the Fv-4 gene product was expressed on the cells from newborn and adolescent mice. The Fv-4 gene product was also detected on the cells from the FK506-treated mice as well as on those from untreated mice. However, a quantitative difference in the gene product between the cells with the Fv-4(r/r) and Fv-4(r/-) genotypes was detected by indirect staining for flow cytometry. These results show that the resistance to F-MuLV infection conferred by the Fv-4 gene is originally recessive, but it looks dominant in adolescent mice mainly because of the effect of the immune system.

Animals↗
PubMed2000

[A case of gastric cancer with liver metastasis responding to low-dose CDDP/5-FU combination chemotherapy].

We reported a case of a 62-year-old female with gastric cancer accompanied by liver, Virchow and paraaortic lymph nodes, and bone metastasis (taken low-dose cisplatin (CDDP)/5-fluorouracil (5-FU) combination chemotherapy). CDDP (10 mg/body/day) was injected on 1-5 days i.v. and 5-FU (500 mg/body/day) was injected i.v. continuously on 1-7 days. This treatment cycle was repeated for 4 weeks. After 4 cycles, liver metastasis disappeared without severe side effects. Primary lesion and Virchow's lymph nodes metastasis were reduced. However, bone and paraaortic lymph node metastasis showed no response. It was considered that low-dose CDDP/5-FU combination chemotherapy was effective for liver and lymph nodes metastasis of gastric cancer in this case.

Adenocarcinoma↗
PubMed2000

[Clinical laboratory physicians and postgraduate training for laboratory technologists].

The number of clinical laboratory physicians is currently about 400, and is estimated to reach, at most, 1,500 after 20 years, even if we train 50 young clinical laboratory physicians every year. This is too few to display their abilities and to prove themselves as necessary specialists in the Japanese medical world. However, the number of laboratory technologists in Japanese hospitals and clinics is currently about 50,000. If we train excellent technologists to take part in the work of clinical laboratory physicians, we will be able to prove ourselves as necessary specialists in about 20 years. Postgraduate training for laboratory technologists is necessary to increasing their abilities and increasing the number of specialists in laboratory medicine. We consider this is the most effective method of developing Japanese laboratory medicine in the 21st century.

Education, Graduate↗
PubMed2000

[Percutaneous endoscopic gastrostomy (PEG) for the management of dysphagia: experiences in the neurosurgical care unit].

This report concerns percutaneous endoscopic gastrostomy (PEG) administered in the neurosurgical care unit to a patient with dysphasia. This reliable nutrition route has the major advantage of minimal surgical invasion and can be expected to become a standard nutritional method. Since patients with neurological disorders account for the majority of those who need PEG, neurosurgeons need to be aware of the importance of PEG.

Aged↗
PubMed1999

Induction of B-cell lymphoma in BALB/c nude mice with an ecotropic, B-tropic helper virus present in the murine AIDS virus stock.

The pathogenicities of the murine AIDS (MAIDS) virus complex (LP-BM5) and ecotropic helper virus (BM5eco) isolated from the complex to BALB/c nude mice were studied to elucidate the possible role of replication-competent helper virus in inducing the monoclonal outgrowth of lymphoid cells. Neither LP-BM5 nor BM5eco was pathogenic in adult BALB/c nude mice. However, B-cell lymphoma developed with a very high frequency when either virus was inoculated into newborn BALB/c nude (nu/nu) mice. The cells from the B-cell lymphoma were easily transplanted into nude mice. These results suggested that ecotropic helper virus in the MAIDS virus complex plays an important role in inducing the monoclonal outgrowth of lymphoid cells under immunodeficient conditions caused by defective virus.

Animals↗
PubMed1999

Proliferating cell nuclear antigen as a predictor of therapeutic effect of continuous 5-fluorouracil administration in gastric cancer.

The change of proliferating cell nuclear antigen (PCNA) expression was examined in three gastric cancer cell lines, MKN28, MKN45 and MKN74, during continuous or bolus exposure to 5-fluorouracil (5-FU). The cytotoxic effect of 5-FU was almost the same in all the cells. PCNA expression was higher at 24 and 72 h after continuous 5-FU treatment than before treatment. Continuous 5-FU treatment of cells revealed higher expression of PCNA protein and mRNA than did bolus treatment. Flow cytometry revealed that 5-FU increased cell population at the late G1 or S phase 24 and 72 h after treatment. PCNA values at the late G1 and S phase were significantly higher than those at other phases 24 h after treatment. These results suggest that PCNA expression increased due to cell cycle accumulation at late G1 and S phases. Thus PCNA values just after chemotherapy of gastric cancer may be useful in predicting the therapeutic effects of continuous 5-FU administration.

Antimetabolites, Antineoplastic↗
PubMed1998

Phosphorothioate hammerhead ribozymes targeting a conserved sequence in the V3 loop region inhibit HIV-1 entry.

Seven different phosphorothioate DNA-RNA chimeric hammerhead ribozymes (RzV3-nT, n = 1-7) targeted against the V3 loop region of HIV-1 were synthesized. Two of these, RzV3-1T and RzV3-3T, efficiently cleaved transcribed envelope RNA of HXB2 in vitro. The target sequence of RzV3-1T belongs to a conserved region and is completely identical in the HIV-1 HXB2, NL432, and ADA strains. Furthermore, RzV3-1T cleaved the envelope RNA of HIV-1 SF162 with a single base substitution in the distal site. U87 cells expressing CD4 and coreceptors were used as target cells for infections with the SF162 and NL432 strains. Replication of both the NL432 and SF162 strains in RzV3-1T-treated cells was significantly lower than that in control cultures. Envelope gene product formation was measured quantitatively with a single-cycle infection assay using pseudovirus generated from cotransfection with one vector containing a luciferase reporter gene and one vector containing the envelope gene of HXB2, SF162, or ADA. Production of pseudovirus in RzV3-1T-treated cells led to a marked (93% or 87%) inhibition of envelope-mediated entry of resultant HXB2-derived or ADA-derived pseudotype virions, respectively, and a moderate (44%) inhibition was seen for SF162-derived pseudotype virions. Thus, an efficient, stable ribozyme against a functionally important region of HIV-1 was identified by evaluating its activities in vitro and in vivo. This ribozyme may be useful for control of HIV-1 infection.

Animals↗
PubMed1998

The maternal immune system in health and disease.

Recent studies have clarified some characteristics of trophoblast and immune cells in the decidua and peripheral blood during pregnancy and the roles they play in the maternal immune system, and have added further evidence to the theory that maternal T helper cell type 1/2 cytokine balance shifts towards T helper cell type 2 dominance during pregnancy.

Autoimmune Diseases↗
PubMed1997

Opposite changes in serum soluble CD8 in patients at the active stages of Graves' and Hashimoto's diseases.

Serum concentrations of soluble CD8 (sCD8) were examined by enzyme immunoassay in 154 patients with autoimmune thyroid diseases and 46 healthy controls. The numbers of peripheral CD8+ cells were also examined in the same subjects by flow cytometry. The serum concentrations of sCD8 were increased in patients with stimulative thyrotoxicosis caused by active Graves' disease, and decreased in patients with transient destructive thyrotoxicosis caused by the aggravation of Hashimoto's disease, and normal in euthyroid and hypothyroid patients with Graves' or Hashimoto's disease. The ratios of serum sCD8 levels to the numbers of CD8+ cells were increased in thyrotoxic patients with active Graves' disease, but not with active Hashimoto's disease, suggesting an increase in sCD8 production by CD8+ cells in active Graves' disease. The serum concentrations of sCD8 were correlated with the serum levels of thyrotropin receptor antibody (TRAb) and thyroid hormones in Graves' disease. These data indicate that serum sCD8 proteins change in opposite directions in the active stages of Graves' and Hashimoto's diseases, and may represent the disease activities.

Acute Disease↗
PubMed1997

CD16 antigen density on neutrophils in chronic myeloproliferative disorders.

Using flow cytometry, we quantitatively examined the density of the CD16 (IgG Fc receptor III) antigen on neutrophils in healthy control subjects, in patients with neutrophilia due to bacterial infection, and in patients with chronic myeloproliferative disorders (chronic myeloid leukemia [CML], polycythemia vera, or essential thrombocythemia). The density was expressed as the mean fluorescence intensity of neutrophils stained with fluorescein isothiocyanate-labeled anti-CD16 monoclonal antibody. We also determined leukocyte alkaline phosphatase activity semiquantitatively in the same population. The mean (+/- SD) density of the CD16 antigen on neutrophils in patients with CML (n = 13; 240.4 +/- 134.8) was lower (P<.001 ) than in healthy control subjects (n = 25; 656.6 +/- 238.0), and the density was also lower than in patients with bacterial infection (n = 15; 671.5 +/- 288.1), polycythemia vera (n = 7; 552.6 +/- 99.9), or essential thrombocythemia (n = 11; 671.5 +/- 411.5). The density of the CD16 antigen was 300 or more in all healthy control subjects and in all patients examined, except for those with CML. The CD16 antigen density was less than 300 in 10 of the 13 patients with CML. Leukocyte alkaline phosphatase activity was also low in 10 of the 13 patients with CML. These findings indicate that flow cytometric analysis of the density of neutrophil CD16 antigen is useful for the differential diagnosis of CML from other chronic myeloproliferative disorders.

Adult↗
PubMed1997

Human immunodeficiency virus type 1 Vpu modifies viral cytopathic effect through augmented virus release.

We characterized two human immunodeficiency virus type 1 (HIV-1) strains, HIVMCK and HIV213, which have different cytopathic effects in infected cells. HIV213 was highly cytopathic, whereas HIVMCK was not. Biological analyses of chimeric viruses from the cloned infectious DNAs of HIVMCK and HIV213 showed that the Vpu region was responsible for the differing cytopathicity of these viruses. Although HIVMCK expressed Vpu protein, HIV213 did not because of a mutation at the start codon for Vpu. The amounts of envelope glycoprotein and virus particles associated with the cell surface were significantly increased on cells infected with Vpu-deficient viruses compared with Vpu-positive viruses. These data suggest that the highly cytopathic effects of HIV213 (Vpu-deficient) are due to an accumulation of envelope glycoprotein at the infected-cell surface, which would be caused by the retention of progeny virions in the absence of Vpu-facilitated virion release.

Base Sequence↗
PubMed1997

Changes in T, B, and NK lymphocyte subsets during and after normal pregnancy.

PROBLEM: Pregnancy affects the maternal immune system and the clinical course of maternal diseases. Here we report the changes in the detailed lymphocyte subsets of helper T cells, suppressor T cells, CD5+ B cells, T cell receptor (TCR) alpha beta-positive T cells (T alpha beta cells), TCR alpha beta-negative T cell (T gamma delta cells), and other during and after pregnancy through to one year postpartum, and discuss the significance of the changes. METHOD: The absolute numbers of helper T cells, suppressor T cells, cytotoxic T cells, TCR alpha beta-negative T cells (T gamma delta cells), CD5- B cells, CD5+ B cells, and NK cell subsets were examined by two-color flow cytometry in peripheral blood from 51 healthy non-pregnant women, 106 healthy pregnant women, and 148 healthy postpartum women. RESULTS: In early pregnancy, the numbers of suppressor T cells and NK cells with strong cytotoxicity (NK+3 cells) increased, and the number of cytotoxic T cells decreased. In late pregnancy, the helper T cell and NK+3 cell numbers decreased. T alpha beta, CD5- B and CD5+ B cells decreased during pregnancy. After delivery, helper T cells and cytotoxic T cells increased from 1 to 4 months postpartum, and suppressor T cells increased at 7 months postpartum. TCR alpha beta-negative T cells increased at 4 to 10 months postpartum. Both CD5- and CD5+ B cells decreased further at 1 month postpartum, but CD5+ B cells increased markedly at 7 to 10 months postpartum. CONCLUSIONS: These data indicate that 1) early increases of suppressor T cells and NK+3 cells during pregnancy may be related to the mechanism to accept or reject the fetus in early pregnancy, respectively; 2) late decreases of helper T cells and NK+3 cells may be related to the maintenance of pregnancy: 3) postpartum increases of helper T cells, cytotoxic T cells, TCR alpha beta-negative T cells (T gamma delta cells), and CD5+ B cells may be related to the postpartum aggravation of autoimmune diseases; and 4) the immunological effects of pregnancy remains until about 1 year after delivery.

Adult↗
PubMed1997

Susceptibility of nude mice carrying the Fv-4 gene to Friend murine leukemia virus infection.

Fv-4 is a mouse gene that dominantly confers resistance to infection with Friend murine leukemia virus (F-MuLV) (S. Suzuki, Jpn. J. Exp. Med. 45:473-478, 1975). Despite complete resistance to ecotropic MuLV infection in mice carrying the Fv-4 gene, it is known that cells carrying the resistance gene in tissue culture do not always show resistance as extensive as that in vivo (H. Yoshikura and T. Odaka, JNCI 61:461-463, 1978). To investigate the immunological effect on resistance in vivo, we introduced the Fv-4 gene into BALB/c nude mice (Fv-4-/- nude[nu/nu]) by mating them with Fv-4 congenic BALB/c mice (Fv-4r/r nude+/+) and examined the susceptibility of the F2 progeny to F-MuLV. All BALB/c nude mice without the Fv-4 gene (Fv-4-/- nude[nu/nu]) were permissive to F-MuLV and developed erythroleukemia within 2 weeks after virus inoculation. The BALB/c nude mice with the Fv-4 gene (Fv-4r/r nude[nu/nu]) did not develop leukemia, and no or little virus was detected in the spleen 7 weeks after virus inoculation. The resistance to F-MuLV was dominant in (Fv-4 congenic BALB/c x BALB/c nude) F1 mice with the Fv-4r/- nude(nu/+) genotype as strictly as in (Fv-4 congenic BALB/c x BALB/c) F1 mice with the Fv-4r/- nude+/+ genotype. However, almost all BALB/c nude mice with the Fv-4r/- nude(nu/nu) genotype developed the disease within 7 weeks, and the virus was detected in all of their spleens even in the mice without leukemia. These results show that the resistance caused by the Fv-4 gene is recessive in nude mice and dominant in BALB/c mice. Some immunological effects, perhaps cell-mediated immunity, may play important roles in the resistance to F-MuLV infection in vivo in addition to the dosage effect of the Fv-4 product.

Animals↗
PubMed1997

Unusual eosinophilia not detected by an automated haematological analyser in a patient with liver cirrhosis.

The use of automated haematological analysers to differentiate leucocytes has become more widespread. Unusual eosinophilia in a 57 year old man with liver cirrhosis, caused by hepatitis C infection, and abnormal blood counts detected using a manual method (eosinophils, 50%) was not detected by an automated analyser using the electrical impedance method (0.3%) or the optical method (14.1%). It is important to check blood films when cell counts are apparently abnormal, even for automated haematological examination.

Blood Cell Count↗