PubMed Health⌕ Search

Biomedical subjects

Satoshi Higasa

Publications and source records attributed to Satoshi Higasa.

7 recordsLinked to original sources

Difference of progression to AIDS according to CD4 cell count, plasma HIV RNA level and the use of antiretroviral therapy among HIV patients infected through blood products in japan.

BACKGROUND: It is important to examine progression to acquired immunodeficiency syndrome (AIDS) or death and its predictors among human immunodeficiency virus (HIV) infected persons before and after the introduction of the highly active antiretroviral therapy (HAART) available in Japan since 1997. METHODS: The data used were from a survey of persons with HIV infected through blood coagulation factor products in Japan. Progression to AIDS or death during two periods, between January 1994 and March 1997, and between April 1997 and March 2002, were observed. RESULTS: The AIDS-free proportion after 3 years was 74% among 417 participants for the earlier period and 94% among 605 participants in the later one. The hazard ratio of low CD4 cell count (less than 200 cells/microL) was 50.8 for the earlier period and 4.7 for the later one compared with that of 500 cells/microL or more. After adjustment by plasma HIV RNA levels and use of antiretroviral therapy, the hazard ratios of the low CD4 cell count for the later period were still significant. CONCLUSION: The AIDS-free proportion among people with HIV infected through blood products in Japan largely increased after the introduction of HAART. The CD4 cell count remains an important predictor of future progression, but its importance might be less because of HAART.

Acquired Immunodeficiency Syndrome↗

Relationship of CD4+CD25+ regulatory T cells to immune status in HIV-infected patients.

OBJECTIVE: To determine whether the frequencies of CD4+CD25+ regulatory T cells (T Reg) were related to immune status in HIV-infected patients. METHODS: Peripheral blood CD4 T-cell populations were examined for T-helper 1 cells (Th1), T-helper 2 cells (Th2), and T Reg by intracellular staining for interferon (IFN)-gamma and interleukin (IL)-4, and surface staining for CD25, respectively. The immunoregulatory properties of T Reg were assessed by measurement of the inhibitory effects of isolated CD4+CD25+ T Reg on CD4+CD25- T-cell proliferation. RESULTS: Isolated CD4+CD25+ T Reg from both HIV-infected patients and healthy controls strongly expressed CD45RO, HLA-DR, and FoxP3. HIV-infected patients with detectable plasma HIV-1 RNA showed a statistically significant increase in CD4+CD25high T Reg frequencies (P < 0.05) compared to healthy controls, with T Reg frequency inversely proportional to CD4 T-cell count (P < 0.01). However, in HIV-infected patients with undetectable plasma HIV-1 RNA, CD4+CD25high T Reg frequencies were not increased and were not related to CD4 T-cell counts. In both HIV-infected patient groups, T Reg frequency was inversely related to Th1 frequency (detectable HIV-1 RNA: P < 0.05; undetectable: P < 0.001), but positively related to Th2 frequency (detectable HIV-1 RNA: P < 0.01; undetectable: P < 0.001). T Reg activity was lower in patients with detectable plasma HIV-1 RNA than in patients with undetectable plasma HIV-1 RNA. CONCLUSIONS: Increased T Reg frequencies in peripheral blood were related to low peripheral blood CD4 T-cell counts and polarization toward Th2 immune responses in HIV-infected patients.

Adult↗

Venous thromboembolism in colorectal cancer patients with central venous catheters for 5-FU infusion-based pharmacokinetic modulating chemotherapy.

Colorectal cancer patients with central venous catheters (CVC) for pharmacokinetic modulating chemotherapy (PMC) have a substantial risk of venous thromboembolism (VTE). PMC, designed as a hybrid of lower metronomic and higher shorter plasma 5-FU concentrations, has been clinically successful. To determine the effectiveness and safety of D-dimer tests and multidetector-row CT (MDCT) for diagnosis in cancer patients with suspected VTE, we carried out a clinical outcome study on PMC outpatients. Patients received a D-dimer test before and after commencing the PMC regimen. MDCT was performed additionally if the D-dimer test appeared positive or showed signs of VTE. When CT results were positive for thromboembolism, anticoagulation was started. The overall prevalence of VTE in PMC patients was 2.0% (7 of 350 patients). In this study, 34 out of 102 colorectal cancer patients gave a positive D-dimer test (33.3%). CT identified venous thrombi in 2 of the 102 patients (2.0%), mural thrombosis on catheterized veins in another 3 patients (2.9%), and endothelial hyperplasia on catheterized veins in 8 patients (7.8%). The catheters of these patients did not show any significant abnormalities. Patients with negative D-dimer tests showed no signs or symptoms of VTE. In colorectal cancer patients receiving continuous 5-FU infusion via CVC, a D-dimer test can be safely used as the primary diagnostic test for ruling out VTE. We suggest 7.0 microg/ml as the D-dimer cut-off value. Thromboprophylaxis should be considered in the patients showing values >7.0 microg/ml.

Adult↗

Enhancing effect of advanced glycation end products on serotonin-induced platelet aggregation in patients with diabetes mellitus.

Advanced glycation end products (AGEs) are thought to be responsible for some complications of diabetes mellitus (DM), including microangiopathy. Plasma serotonin is increased in diabetes mellitus patients, and this increase is related, at least in part, to platelet hyperfunction. In order to clarify the relationship between advanced glycation end products, serotonin, and thrombotic complications in diabetes mellitus patients, we examined the effect of advanced glycation end products on serotonin-induced platelet aggregation. In diabetic patients, although serotonin-induced platelet aggregation was enhanced with an increase in serum-advanced glycation end products, there was no correlation between platelet aggregation and either hemoglobin A1c or fasting blood sugar. To examine the direct effect of advanced glycation end products on platelet aggregation, we prepared advanced glycation end products by in vitro incubation of human albumin with glucose (250 mM) at 37 degrees C for 8 weeks. Serotonin-induced platelet aggregation was dose-dependently increased by advanced glycation end products. Adenosine diphosphate-induced platelet aggregation also was increased by advanced glycation end products, but this increment was diminished by addition of sarpogrelate, a selective serotonin receptor antagonist. These results suggest that advanced glycation end products enhance platelet aggregation through the serotonin receptor, and perhaps influencing the development of thrombotic complications in diabetic patients.

Diabetes Mellitus, Type 2↗

Suitability of four polymorphic DNA markers for indirect genetic diagnosis of haemophilia A in Japanese subject.

Indirect genetic diagnosis using polymorphic DNA markers can detect carriers of haemophilia A (HA). These markers include CA repeat polymorphisms at intron 13 (CA-13) and CT-AG at intron 22 of the coagulation factor VIII (FVIII) gene, and also certain restriction fragment length polymorphisms (RFLPs) such as HindIII at intron 19 and BclI at intron 18. Recently, CA repeat polymorphism at intron 6 (CA-6) was also reported. We compared usefulness of the BclI RFLP, the HindIII RFLP, and CA-13 to that of CA-6. Heterozygosity of markers was examined in 282 X chromosomes obtained from 205 subjects including HA patients. Expected heterozygosity of the HindIII and BclI RFLPs was 30.0% and 27.9%, while observed heterozygosity was 28.0% and 26.5%. Expected heterozygosity of CA-13 was 45.6%, and observed heterozygosity was 40.0%. CA-6 showed two alleles with repeat numbers of 13 and 14, expected and observed heterozygosity were low (1.4% and 2.6%, respectively). When we used these markers in a HA lineage where the mother was a carrier according to coagulation factor assays, carrier diagnosis was possible using CA-13, the HindIII RFLP, and the BclI RFLP. This was not true for CA-6, for which the mother was homozygous. Although CA-13, and the HindIII and BclI RFLPs were useful for indirect genetic diagnosis of HA, CA-6 proved less useful because of low heterozygosity.

DNA↗