[Blood donation and HTLV-1 and HIV].
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Biomedical subjects
Publications and source records attributed to S Sekiguchi.
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Platelets collected from random and multiple donors were as effective on transfusion as those obtained from single donor by platelet pheresis if patients were not alloimmunized. In alloimmunized patients, effects of platelet transfusion were correlated with the HLA-matching grade; 100% effective in A-match, 92% in B-match and 65% in C-match. This correlation was not observed if the patient had infection. The transfusion of A- or B-matched platelets resulted in a lowering or disappearance of HLA antibody activities in most patients. However, the transfusion of C-matched platelets caused increasing or appearance of HLA antibody activities in some patients. The ABO-incompatibility did not show a significant effect on platelet transfusion when anti-A or anti-B antibody activities in donors and antiglobulin tests on patients' red cells were negligible. Non HLA, platelet specific antibodies were produced in some patients and presumed to be participated in the destruction of transfused HLA-matched platelets.
The frequencies of 80 HLA antigen phenotypes in 82 centenarians and 20 nonagenarians in Okinawa, Japan, were compared with those in other healthy adults in various age-brackets. Subjects aged over 90 had an extremely low frequency of HLA-DRw9 and an increased frequency of DR1. In this age-group the relative risk of corrected (for number of antigens) p value for HLA-DRw9 were 5.2 and 0.0001, respectively; those for HLA-DR1 were 13.3 and 0.0367, respectively. Since a high frequency of DRw9 and a low frequency of DR1 are associated with autoimmune or immune deficiency diseases, the genetic protection against these disorders may contribute to longevity.
Adult female mice of the ICR/JCL strain were injected intraperitoneally with an emulsion of Toxoplasma lysate antigen (TLA; 100 micrograms per head) in light mineral oil (LMO) twice at 2 weeks' interval. Each mouse was inoculated intraperitoneally with 10(2) erythrocytes infected with Babesia rodhaini 2 weeks after the second injection of the emulsion. The rates of decrease in the erythrocyte count, hemoglobin concentration, and hematocrit value 10 days after inoculation, as compared with the counterparts determined 1 day before inoculation, were distinctly lower in these treated mice than in untreated control mice. In the course of Babesia inoculations, substantial reduction in size and weight of the thymus became higher in untreated control than in TLA-treated mice as the infection progressed. In untreated controls, the number of Thy-1 positive (Thy-1 (+) ) cells was about 91.9% of the normal value being 3.7 X 10(7) cells in the whole thymus 1 day before inoculation while those in TLA-treated mice were 6.5 X 10(7) and 0.9 X 10(7) cells 1 day before inoculation and 10 days after inoculation, respectively. The size and weight of the spleen increased in both groups by day 10 after inoculation. The total number of Thy-1 (+) cells in the spleen was 3.9 X 10(7) and 11.7 X 10(7) 1 day before and 10 days after inoculations, respectively in untreated and 12.9 X 10(7) and 15.6 X 10(7), respectively in TLA-treated mice. The number of Thy-1 (+) cells in the liver was 0.5 X 10(7) and 1.2 X 10(7) 1 day before and 10 days after inoculations, respectively in untreated and 0.3 X 10(7) and 3.4 X 10(7), respectively, showing a rate increase of 1033.3% in TLA-treated mice. The rate of increase in count of Thy-1 (+) cells contained in the peripheral blood was 61.4% in the former and 64.1% in the latter. In untreated mice, degeneration and destruction of lymphocytes in the thymus and spleen follicles and aggregation of lymphocytes, which were not found in Thy-1 (+) staining, around pericapillary ducts in the liver were seen histopathologically 10 days after inoculation. In TLA-treated mice, however, perivascular infiltration by Thy-1 (+) lymphocytes and activation of Kupffer cells in the liver and activation of spleen follicles were observed locally 10 days after inoculation.
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A relatively simple and reproducible procedure involving copper-chelate affinity chromatography for the isolation of copper-zinc-superoxide dismutase (E.C. 1.15.1.1) and catalase (E.C. 1.11.1.6) from human erythrocytes has been developed. Using this method, the two enzymes were easily and highly purified and appeared to be homogeneous as judged by polyacrylamide gel electrophoresis.
4-Methylumbelliferyl (4-MU) lipase activity in human and mouse brain, measured with 4-MU palmitate, was characterized with respect to effects of pH and detergents, and subcellular and myelin localization. Purified myelin isolated by Norton's procedure [J. Neurochem. 21, 749-757 (1983)] contained higher specific activity of 4-MU lipase, particularly in alkaline pH. Myelin lipase activity was markedly affected by the addition of different types of detergents, the amount of detergents added, and substrate. The optimal pH in myelin was bimodal--pH 4.5 and up to 8.0, respectively. These data indicate that myelin possesses 4-MU lipase activity at alkaline pH, with lower levels at acidic pH.
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Sera and peripheral blood lymphocytes in 40 clinical cases of adult T-cell leukemia (ATL) and 66 cases of mature T-cell malignancies in Hokkaido district, the most northern part of Japan, were examined for the infection with ATL virus (ATLV). All of the 40 ATL patients (100%) had antibodies to ATLV-associated antigen (ATLA) and 13 (19.7%) of the 66 patients with mature T-cell malignancies other than ATL were also positive for anti-ATLA. When the peripheral ATL lymphocytes were assessed after short time cultivation, both ATLA antigen and C type virus particles were detectable. In contrast to the high prevalence of ATLV antibodies in these patients, the positivity in 30,000 control individuals in this district was 0.73%. It was calculated that 8 patients of a 40,000 seropositive population are diagnosed annually as ATL in this particular northern part of Japan.
In order to investigate the spread of adult T-cell leukemia (ATL) virus in the inhabitants of ATL-non-endemic Hokkaido, we surveyed the antibodies to ATL-associated antigen (ATLA) in 29516 healthy individuals by indirect immunofluorescence test using MT-1 for target cell. Of the healthy inhabitants, only 219 individuals (0.74%) were anti-ATLA positive as carriers. Prevalence of anti-ATLA was 0.63% (111 of 17590) in males and 0.91% (108 of 11926) in females. This difference by sex is significant. In several regions, the inhabitants were found to show relatively high incidence (greater than 2%) of the antibodies, and these regions have a tendency to cluster around the western side of Hidaka mountains or Akan area. The highest rate (5.2%) of anti-ATLA positive carriers was shown in a certain town of Hidaka area.
Five monoclonal antibodies to human rIFN-alpha A have been obtained and used them in a sandwich enzymeimmunoassay for IFN-alpha. In the assay, rIFN-alpha A was measured from approximately 100 U/ml to 1,000 U/ml, but the sensitivity and the extent to measurement were different among using monoclonal antibodies. Protease or heat denatured IFN-alpha could not be detected in the enzymeimmunoassay and thus only a biologically active form of IFN-alpha was measurable. The reproducibility of the enzymeimmunoassay was considerably high (variation coefficient was lower than 10%) and the correlation of IFN-alpha titers with CPE method was observed slightly. Although the same CPE titers, natural IFN-alpha was detected only 20% compared with rIFN-alpha A in the enzymeimmunoassay, so the assay system seemed to be very specific for rIFN-alpha A. From this observation, it was suggested that the monoclonal antibodies used in the enzymeimmunoassay should recognize a epitope specifically existed on the rIFN-alpha A molecule.
In order to examine the suitability of leukocyte migration inhibition test (LMIT) in the capacity of in vitro assay system for dialyzable leukocyte extracts (DLE), the effect of DLE on hepatitis B and its antigen-specificity, the migration inhibitory activities to purified hepatitis B surface antigen (HBsAg) was measured using the leukocyte MIF test with DLEs obtained from HBsAb-positive or HBsAb-negative blood. The direct LMIT using agarose plate was modified according to the technique of Clausen et al. In spite of our assay system was dose-dependent for PPD, a significant response for purified HBsAg was not observed. However, some meaningful migration inhibition appeared when HBsAg and DLE were added simultaneously to the migration cells. From these results, it is concluded that DLE has antigen-specific and/or antigen non specific influences to the cell-mediated immunity for HBsAg Though some problems remain, we think our results are interesting, since the assay system for DLE has not been established and our study is closely related to the effect of DLE concerning hepatitis B.
Since 1979, we have studied to establish large scale production of HU IFN by buffy coat collecting from blood donor. Up to the present, we produced HU IFN of 71.5 X 10(8) units and used clinically for 40 patients. Recently, we reported the process of HU IFN production and the result of clinical use by members of Hokkaido Interferon Research.
To estimate the functional change occurring in human serum albumin by nonenzymatic glucosylation, glucosylated human serum albumin was prepared by in vitro incubation with glucose. The rate of glucosylation proceeded as a first-order reaction. The binding of sulfonylureas to serum albumin was determined by equilibrium gel filtration. Through this method, it was possible to estimate the binding capacity of a low water solubility drug with a high affinity to protein. The amounts of the sulfonylureas bound to glucosylated HSA decreased by 44% with tolazamide and acetohexamide, 50% with glibenclamide, and 52% with tolbutamide, compared to human serum albumin (HSA). This suggests that a high concentration of glucosylated HSA in diabetic patients may possibly cause an increase in free drug concentration exceeding normal levels. This study shows that the decrease in the binding capacity of sulfonylureas with protein is due to the modification of albumin molecules by the covalent binding of glucose.
The qualitative and quantitative changes in behavioral development in the prenatal and perinatal periods have been insufficiently studied. We observed the occurrence of spontaneous body movements in three strains of mice (ICR, C3H, and BALB) and the pulse counts measured by EMG activity gestation period normal for mice. During the prenatal period, fetal movements changed from simple movements to complex and coordinated movements. Differences in the timing of the development of these movements were not found in the three strains of mice. During the perinatal period, the three kinds of simple movement decreased. This decrease was affected by the onset of pulmonary respiration after delivery. The time span of spontaneous movement did not change during the perinatal period, while the pulse counts measured by EMG activity increased with age.
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