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Biomedical subjects

N Takata

Publications and source records attributed to N Takata.

At least 19 recordsLinked to original sources

Autoimmune neutropenia in pregnant women causing neonatal neutropenia.

Autoimmune neutropenia (AIN) can occur during pregnancy. However, neonatal neutropenia occurring in an infant born to a mother with AIN has only rarely been documented. Recently, we have experienced two cases of AIN during pregnancy, both of which caused severe yet transient neonatal neutropenia (< 0.3 x 10(9)/l), probably as a result of transplacental maternal anti-neutrophil autoantibodies. The anti-neutrophil antibodies seemed to be against antigens other than NA1/NA2 because the autoantibodies did not bind to neutrophils of specific NA types selectively in the granulocyte indirect immunofluorescence test. Although AIN is a relatively uncommon disease, neonatal neutropenia caused by maternal AIN may not be quite as rare.

Adult↗

Change in plasma viral load, and viral DNA and mRNA burdens, in peripheral blood mononuclear cells from patients infected with HIV-1.

OBJECTIVES: To clarify the virological state of human immunodeficiency virus (HIV)-1-infected patients, we compared the plasma HIV-1 RNA copy number (plasma viral load (VL)), viral DNA and mRNA burdens in peripheral blood mononuclear cells (PBMCs), and the other clinical predictors. METHODS: One hundred and thirty-one samples of PBMCs and plasma from 26 patients infected with HIV-1 were obtained during 20 consecutive months for the measurement of VL, viral DNA and mRNA burdens, and CD4 positive (CD4+) cells count. The quantitative polymerase chain reaction (PCR) method with detection by solid phase DNA was utilized for the assay of VL, viral DNA and mRNA burdens. RESULTS: Eighty-six VL, 101 viral mRNA and 129 viral DNA out of 131 samples were detected. There was a significant positive correlation between VL and the viral mRNA burden (r = 0.600, P < or = 0.001), and between VL and the viral DNA burden (r = 0.368, P < or = 0.001). Focused on individuals, the viral mRNA burdens varied in a manner relatively dependent on VL when both values were detectable. However, viral DNA burdens varied relatively independently of VL and the viral mRNA burdens. In six patients the viral mRNA burden was detectable and changed even if the VL was undetectable throughout the observation period. CONCLUSIONS: Both viral DNA and viral mRNA burdens still showed detectable changes even when the VLs became undetectable in most patients. The measurement of viral mRNA or DNA burdens may be clinically available to identify viral replication when VL is undetectable.

Adolescent↗

Neurosteroid synthesis by cytochrome p450-containing systems localized in the rat brain hippocampal neurons: N-methyl-D-aspartate and calcium-dependent synthesis.

Neurosteroidogenesis has not been well elucidated due to the very low level of steroidogenic proteins in the brain. Here we report the first demonstration of the neuronal localization of neurosteroidogenic systems as well as the regulation of neurosteroidogenic activity in the adult rat hippocampus. Significant localization of cytochrome P450scc was observed in pyramidal neurons and granule neurons by means of immunohistochemical staining of slices. We also observed the colocalization, in hippocampal neurons, of P450scc with redox partners, hydroxysteroid sulfotransferase and steroidogenic acute regulatory protein. The distributions of astroglial cells and oligodendroglial cells showed very different patterns from that of the P450scc-containing cells. The expression of P450scc, redox partners, the sulfotransferase, and steroidogenic acute regulatory protein was also confirmed by Western blot analysis. The process of active neurosteroidogenesis was stimulated by exposing neurons to N-methyl-D-aspartate. Upon stimulation with N-methyl-D-aspartate, Ca(2+) influx through the N-methyl-D-aspartate subtype of glutamate receptors occurred, and significant net production of pregnenolone and pregnenolone sulfate was observed in the hippocampus. This neurosteroid production was considerably suppressed by the addition of antagonists of N-methyl-D-aspartate receptors, by Ca(2+) depletion, or by the addition of an inhibitor of P450scc. Upon stimulation with N-methyl-D-aspartate, the processing of full-length steroidogenic acute regulatory protein (37-kDa) to the truncated 30-kDa steroidogenic acute regulatory protein was observed. Taken together, these observations imply that hippocampal neurons synthesize neurosteroids. This synthesis may be stimulated and regulated by glutamate-mediated synaptic communication.

Animals↗

Sulindac and a cyclooxygenase-2 inhibitor, etodolac, increase APC mRNA in the colon of rats treated with azoxymethane.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to protect against the development of colon cancer. However, the mechanism(s) by which NSAIDs exert their effects is not clear. AIMS: The aim of this study was to examine the effects of NSAIDs on mRNA expression of tumour suppressor adenomatous polyposis coli (APC) gene in rat colon mucosa. METHODS: Starting at six weeks of age, three groups of rats (groups 1, 2, and 3) were treated with azoxymethane (AOM), a colon specific carcinogen, and another three groups (groups 4, 5, and 6) were not given AOM. Groups 2 and 3 were given 10 mg/kg of sulindac or etodolac, respectively, three times weekly during the experiment. Groups 4 and 5 were also given sulindac or etodolac, respectively, in the same manner as in groups 2 and 3. Group 6 (untreated control) was not given any agent (AOM or NSAIDs). At 10 weeks of age, preneoplastic lesions (aberrant crypt foci (ACF)) induced by AOM in the colon were counted, and the level of expression of APC mRNA in the colonic mucosa was estimated by the reverse transcription-competitive polymerase chain reaction method and northern blot analysis. RESULTS: Mean occurrence of ACF in rats in groups 2 and 3 was reduced to approximately 50% of that in group 1. The level of APC mRNA expression in group 1 (AOM alone) was lower than that in group 6 (untreated control) (p<0.05); however, levels of APC mRNA expression in groups 2, 3, 4, and 5, to which NSAIDs had been administered, were significantly increased compared with levels in groups 1 and 6 (p<0.01). CONCLUSIONS: Both sulindac and etodolac reduced the occurrence of ACF and induced an increase in APC mRNA in rat colon mucosa.

Animals↗

Potential interaction between ritonavir and carbamazepine.

Ritonavir (RTV), a protease inhibitor, and carbamazepine (CBZ), an anticonvulsant, were administered concurrently to a patient who had human immunodeficiency virus infection and epilepsy. The combination resulted in elevated serum concentrations of CBZ, with accompanying vomiting, vertigo, and transient liver dysfunction. After discontinuing RTV and reducing the dosage of CBZ, the serum concentration of CBZ returned to the optimal range, symptoms subsided, and liver function returned to baseline. Carbamazepine is metabolized in the liver to a large extent by the cytochrome P450 (CYP) system, especially CYP3A4, 2C8, and 1A2, whereas RTV is metabolized primarily by CYP3A and is a potent inhibitor of this enzyme. Careful clinical monitoring may help prevent adverse drug interactions when these drugs are administered concurrently.

Adult↗

[Multimodality therapy for synchronous liver metastases of gastric cancer--significance of aggressive hepatic resection of liver lesions].

We analyzed 15 gastric cancer patients with synchronous liver metastases, and studied the significance of hepatic resection with multimodality therapy. 1. Both gastric and hepatic resections followed by intra-arterial or systemic chemotherapy were performed for six patients, two of whom had intra-operative MCT or EIT. The survival time of four patients without recurrence was 5 Y 4 M, 4 Y 5 M, 2 Y 4 M and 11 M. Two patients died of recurrence in the retroperitoneum or residual liver 3 Y 10 M and 8 M after therapy, respectively. The three-year survival rate was 83%. 2. The longest survival among the five patients treated with gastric resection without hepatic resection followed by intra-arterial or systemic chemotherapy was 1 Y 1 M. 3. Four patients with non-curative factors (P, N, M) were treated with systemic chemotherapy only, and the longest survival was 1 Y 1 M. In conclusion, when local control is obtained during surgery in patients with gastric cancer with synchronous liver metastasis, aggressive hepatic resection supported with MCT or EIT should be performed on liver lesions to improve the prognosis.

Aged↗

[A long-survival case of gastric cancer with multiple liver metastasis: usefulness of intraoperative multimodality therapy and post-operative intra-arterial chemotherapy for liver lesions].

A 62-year-old man was found to have advanced cancer of the gastric cardia with multiple liver metastasis. Total gastrectomy was performed, and 11 hepatic lesions were simultaneously treated by intraoperative multimodality therapy. The therapy included hepatic resections for seven easily-resectable lesions, microwave coagulation therapy for two lesions, and ethanol injection therapy for two. Post-operative intra-arterial infusion of 1,000 mg of 5-FU was performed weekly or every two weeks through the hepatic artery using a reservoir. No recurrence was found during the follow-up period of 35 months. When local control is obtained during surgery in patients with gastric cancer with multiple liver metastasis, intraoperative multimodality therapy and post-operative intra-arterial chemotherapy should be performed for liver lesions.

Adenocarcinoma↗

Interleukin-9 receptor alpha chain mRNA formation in CD8+ T cells producing anti-human immunodeficiency virus type 1 substance(s).

A search for gene(s) associated with anti-human immunodeficiency virus type 1 (HIV-1) activity of CD8+ T cells was attempted using molecular cloning and the relation between the anti-HIV activity of CD8+ T cells and the interleukin-9 receptor alpha chain (IL-9R-alpha) mRNA expression from the cDNA clones obtained was examined. The anti-HIV-1 activity of CD8+ T cell culture supernatants was assessed by measuring the level of HIV-1 replication of a CD4+ T cell line transfected with an infectious HIV-1 DNA clone. IL-9R-alpha mRNA was assayed by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 5 cases showing high level of anti-HIV-1 activity (more than 80% suppression of HIV-1 replication), the mRNA was detected in 4 cases. Of 10 cases showing low level of anti-HIV-1 activity (less than 80% suppression of HIV-1 replication), the mRNA was detected in one case. Soluble recombinant human IL-9 receptor (rhIL-9sR) did not suppress HIV-1 replication at a concentration of 1 microgram/ml. These data suggest that the IL-9R-alpha mRNA formation in CD8+ T cells may correlate with and play some role in the anti-HIV-1 activity of CD8+ T cells from HIV-1-infected individuals.

CD4-Positive T-Lymphocytes↗

Suppression of hepatic allograft rejection in the rat by mitomycin C-treated donor splenocytes: in situ splenic distribution of donor class I major histocompatibility complex antigen-positive cells in the recipient.

A single intravenous injection of 3 x 10(6) donor splenocytes treated with mitomycin C (MMC) 7 days before hepatic transplantation prolongs survival of hepatic allografts in the ACI(RT1a) to LEW(RT1(1)) rat combination. This effect is donor specific. The in situ distribution in the recipient of the donor cells administered preoperatively was investigated using intracellularly fluorescence-labeled donor splenocytes. The donor cells were accumulated mainly in the splenic white pulp and lymph nodes at 12 and 24 hr after injection. Contrarily, very few cells were seen in the thymus, liver, kidney, and lung. The number of cells with dull and weak fluorescence began to increase in the splenic white pulp and lymph nodes at 24 hr after injection. This may indicate the breakdown of donor cells by recipient cells. In contrast, a number of donor cells could be detected even after 48 hr and a few cells at 7 days after splenocyte injection in the LEW-to-LEW isogeneic combination. As we previously revealed the role of class I major histocompatibility complex (MHC) antigens in prolonging hepatic allograft survival in the rat, the splenic distribution of donor class I MHC-positive cells in the recipient after intravenous administration of MMC-treated donor splenocytes was studied using immunostaining with a MN4-91-6 mouse anti-rat RT1.Aa class I MHC monoclonal antibody. The donor class I-positive cells accumulated mainly in the splenic white pulp at 12 and 24 hr after injection. This is similar to that observed in the fluorescence study. Within 48 hr after injection, most cells had disappeared from the recipient tissue. These findings suggest that the splenic white pulp, a T-dependent area, may play an important role in inducing immunological unresponsiveness.

Animals↗

Identification and characterization of a mitochondrial endonuclease from yeast, Schizosaccharomyces pombe.

Schizosaccharomyces pombe mitochondria were isolated from the cells treated with Novozyme 234, and purified in a Percoll gradient. A zymographic assay in a SDS-polyacrylamide gel containing single-stranded DNA revealed that an endonuclease of 32 kDa is associated with the mitochondria. The endonuclease was extracted from the mitochondria with 0.5 M KCl and was partially purified. The 32-kDa enzyme degraded both DNA and RNA at a weak alkaline pH, but preferred single-stranded DNA. The enzyme required Mg2+ or Mn2+, but not Ca2+ or Zn2+ for activity, and was inhibited by 50% with a 150 mM salt solution. Nicks generated by the enzyme could be resealed with T4 DNA ligase, indicating that the enzyme produces 5'-P and 3'-OH ends.

DNA, Single-Stranded↗

Characterization of hepatic allograft infiltrates in rats pretreated with donor-specific blood transfusion (DST).

A single intravenous injection of 1 ml freshly heparinized donor blood given 7 days prior to transplantation prolonged significantly the survival of subsequent hepatic allografts in fully allogeneic ACI(RT1a)-to-LEW(RT1(1)) rats. The cellular identity of allograft infiltrates was investigated at various times after transplantation using OX8 (CD8) and W3/25 (CD4) monoclonal antibodies. The number of CD8+ cells increased rapidly and reached a peak on Day 3 after transplantation of the untreated allografts. Similarly, the number of CD8+ cells in the allografts from DST-treated rats was maximum on Day 3 and decreased gradually thereafter. The maximum number of CD4+ cells was found on Day 3 in untreated allografts. In contrast, no significant infiltration of CD4+ cells occurred during the first 7 days after transplantation in DST-treated allografts. Thereafter, the number of CD4+ cells increased rapidly and reached a peak on Day 14. CD4+ cells remained persistently elevated in hepatic allografts of rats pretreated with DST, but did not become functionally competent or initiate rejection. These findings suggest that persistent infiltration by CD4+ cells is a characteristic feature of long-surviving hepatic allografts in rats pretreated with DST.

Animals↗