The effects of human erythropoietin on murine megakaryopoiesis.
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Biomedical subjects
Publications and source records attributed to M Sakaguchi.
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A new type of hypoxic cell sensitizer, 2-nitroimidazole substituted with an acyclic sugar analogue at the N-1 position of the imidazole ring (RK compounds) has been developed and tested on HeLa S3 and Chinese hamster V79 cells. As might be expected from their electron affinities, which are stronger than that of misonidazole, the abilities of RK compounds to sensitize hypoxic cells were correspondingly increased. One millimole of RK28 [1-(4'-hydroxy-2'-butenoxy)methyl-2-nitroimidazole] gave an enhancement ratio of 1.56 or 1.84 in comparison with 1.40 or 1.71 for the same concentration of misonidazole to HeLa S3 or V79 cells, respectively. RK28 showed slight cytotoxicity to aerobic HeLa S3 cells at a concentration of 5 mM after a three-hour exposure, whereas under hypoxic conditions, the agent was markedly cytotoxic. In vivo radiosensitization studies in ICR mice with Ehrlich ascites tumor indicated that RK28 produced an increase in DMF to hypoxic tumor cells with increased dose of the compound. Their DMF values were 1.63, 1.97 and 2.34 at 0.075, 0.15 and 0.3 mg/gbw of RK28, respectively. A dose of 0.3 mg/gbw of RK28 produced a DMF around 1.5 to two times greater than that resulting from the same dose of misonidazole. Pharmacokinetic studies of RK28 in ICR mice with Sarcoma-180 revealed a faster clearance from the serum and a slower decrease in the tumor than with misonidazole.
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The localization of measles virus proteins was analyzed by immunoperoxidase method using both monospecific and monoclonal antibodies. In Vero cells infected with the Edmonston or EB-L strain, the former being a laboratory strain and the latter a fresh isolate from a measles patient, nucleocapsid protein was located in the nuclei, and matrix protein, phosphoprotein, haemagglutinin and fusion protein were located in the cytoplasm. In the lung tissues of eight cases with measles giant cell pneumonia, the similar findings were obtained. The presence of haemagglutinin on the surface of giant cells at the luminal side was also noticed. Histopathologically, measles giant cells had nuclear and cytoplasmic eosinophilic inclusion bodies with some differences in appearance. The significance of localization of viral proteins is discussed in comparison with histopathological findings in measles giant cells.
A detailed investigation was carried out on the schizophrenics who committed suicide at the Tokyo Metropolitan Hospital Matsuzawa during the last 30 years. Of these 58 schizophrenics, 52 cases (male 25, female 27) were studied in this report. The mean age of suicide patients was 38.6 years (male: 34.3 years, female: 42.6 years); in males the suicide occurred between 20 and 39 years (80%), while females showed a wider distribution with two peaks in the 25 to 34 years group (26%) and the 40 to 54 years group (41%). 88% (22/25) of males were unmarried, whereas only 33% (9/27) of the women were unmarried. Suicide methods were comprised of hanging (51.9%-27 cases), being run over by a streetcar (28.8%-15 cases), drowning (6 cases), jumping off a high building (3 cases) and intoxication by creosol liquid soap (1 case). In case of male patients hanging was most frequent (72%), followed by jumping into a streetcar to get run over (24%). Likewise, hanging and jumping into a streetcar were most frequent in females (33.3%, respectively), followed by drowning (22.2%), a method selected by females only. From 1951 to 1960 (right before and after the introduction of psychopharmacotherapy) hanging ranked first, but the suicide methods were shifted to the jumping into a streetcar and drowning after installation of the Open-Door-System (around the years 1961-1970). During the last 10 years (from 1971 to 1980) suicide by jumping from a high building increased. Suicide committed in the open ward occurred 9 times only (17.3%); it was, therefore, a much rarer occurrence than had been expected. This fact may show that such an open ward system would be associated with a relatively low risk of suicide. After introduction of psychiatric pharmacotherapy and as social rehabilitation continued, the incidence was relatively stable and no increase was found in our data. Only 4 patients (7.7%) left suicide notes, which made it difficult to draw a clear conclusion on the motivations. Twenty-six cases (50%) died by the first attempted suicide, but in 13 cases (25%) suicide was finally accomplished after the second trial or more. Women performed several repeated suicide attempts (37%), whereas the male patients died at the first or second attempt (88%). Hospitalization lasted on an average for 5 years and 8 months (male: 3 years and 8 months, female: 7 years and 6 months); the shortest stay was 2 days and the longest was 25 years and 11 months.(ABSTRACT TRUNCATED AT 400 WORDS)
IgE antibody responses against Japanese cedar pollen in the mouse were investigated to develop a mouse model of human allergy for combinations of factors including pollen administration routes, elicitation antigens and inbred mouse strains. Daily short term inhalation of native pollen or intratracheal administration of pollen suspended in saline induced IgE antibody responses in DBA/2, BDF1 and Balb/c mice, but failed to induce any detectable responses in C57BL/6 and C57BL/10 mice. Intraperitoneal injection of pollen suspension also induced IgE antibody responses in DBA/2, BDF1 and Balb/c mice but not in C57BL/6 mice. IgE antibody responses against pollen described above were detected by passive cutaneous anaphylaxis (PCA) reactions using crude extract of pollen as an elicitation antigen. On the other hand, IgE antibodies specific for antigen Sugi basic protein (AgSBP), which is a major allergen of pollen in humans (Yasueda, H., Yui, Shimizu, T., and Shida, T., 1983. Isolation and partial characterization of the major allergen from Japanese cedar (Cryptomeria japonica) pollen. J. Allergy Clin. Immunol. 71: 77-86), were also detected by PCA reactions using AgSBP in the sera from mice which received secondary or the tertiary stimulation by pollen. These results suggest that IgE antibody responses against Japanese cedar pollen in the mouse can be induced by airway sensitization and that the responses are genetically controlled by H-2-linked immune response genes. The results also suggest that not only IgE antibody responses specific for components other than AgSBP but also responses specific for AgSBP can be induced in the mouse by repeating appropriate sensitization by pollen.
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The level of urinary Meg-CSF activity in patients with various thrombopoietic disorders was studied. Five out of eight patients with idiopathic thrombocytopenic purpura had megakaryocytic hyperplasia in the marrow and increased Meg-CSF activity in the urine. Urinary Meg-CSF activity in patients with polycythaemia vera and essential thrombocythaemia was normal. There was a significant inverse correlation between urinary Meg-CSF activity and peripheral blood platelet count but not bone marrow megakaryocyte mass. There was a significant increase of urinary Meg-CSF activity during the period of thrombocytopenia after chemotherapy in patients with acute leukaemia who were in complete remission. The timing of maximal Meg-CSF levels corresponded to the nadirs of platelet counts. These results support the concept that Meg-CSF may play a significant role in the regulation of megakaryopoiesis and/or thrombopoiesis in vivo.
The serum of a 50-year-old male with neutropenia and a bout of bacterial infection was studied. Anti-neutrophil IgG antibody was detected by indirect immunofluorescence using a laser flow cytometry system. Purified IgG from our patient's serum did not inhibit chemotaxis of neutrophils, but inhibited rosette formation of neutrophils with ox red blood cells (ORBC) coated with anti-ORBC rabbit IgG dose-dependently. Surface iodination of neutrophils followed by their immunoprecipitation by purified IgG and sodium dodecylsulfate polyacrylamide gel electrophoresis showed a single band that corresponded to 45 kilodaltons. Possibly the IgG antibody in our patient's serum recognizes molecules related to Fc receptors.
SA 96 (N-(2-mercapto-2-methylpropanoyl)-L-cysteine) is a new sulfhydryl compound having a relatively similar chemical structure to Tiopronin and D-penicillamine. An open trial of SA 96 treatment (300 mg/day after meals for 16 weeks) was carried out in 11 patients with definite or classical rheumatoid arthritis and with therapeutic failure of previous gold salts and/or D-penicillamine therapy. Two cases were withdrawn from the trial, because of a side effect (hepatitis) in one patient and an unrelated illness in another. The results in the 9 patients completing the trial demonstrated statistically significant improvement in the clinical and laboratory measurements. A marked abatement of disease activity was noted in 5 of 9 patients who did not benefit from, or suffered a relapse during previous chrysotherapy and in 1 of 5 patients without benefit, or with relapse following previous D-penicillamine treatment. Among 4 patients who had discontinued D-penicillamine because of its intolerable cutaneous side effects, 3 patients completed the trial, with favourable results. The results of this trial seem to indicate that SA 96 is possibly of value as a slow-acting antirheumatic drug in some patients with therapeutic failure of gold salts or D-penicillamine.
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Characteristics of fresh isolates of wild measles virus were studied by immunofluorescence using monoclonal antibodies, SDS-polyacrylamide gel electrophoresis, and electron microscopy. By the immunofluorescence test, hemagglutinin, nucleocapsid-associated phosphorylated, and fusion proteins were found only in the cytoplasm of cells infected with the virus at a low passage level. Nucleocapsid (NP) and membrane (M) proteins were found in both the cytoplasm and nuclei. Since the M protein is present only in the cytoplasm of cells infected with the laboratory strain of measles virus, this intranuclear M protein may be specific to the wild virus. At an increased passage level, the intranuclear M protein became undetectable, but the NP protein was still present in the nuclei. SDS-polyacrylamide and electron microscopy showed that wild measles viruses were shown to have characteristics similar to those of laboratory strains.
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To determine whether the kind of dietary fat affects colon carcinogenesis, male Donryu rats were fed a 5% fat diet containing linoleate, an unsaturated fat, or stearate, a saturated fat, in semipurified fat-free chow. The rats were given azoxymethane (7.4 mg/kg body weight) s.c. once a week for 11 weeks and killed 15 weeks after the last injection of the carcinogen. The rats on the unsaturated fat diet had a significantly higher incidence of colon tumors. Fatty acid analysis of cholesterol esters in the liver and examination of the amount of fecal bile acids showed that the unsaturated fat diet increased the level of cholesterol linoleate and arachidonate in the liver and also increased the fecal excretion of bile acids, especially that of lithocholic acid. The colon tumors in rats on the unsaturated fat diet, compared with those in rats on the saturated fat diet, contained a higher level of lysophosphatidylcholine. These results suggest that increased fecal excretion of bile acids due to increased polyunsaturated cholesterol esters in the liver stimulates phospholipase A2 activity of colon initiated cells and enhances colon carcinogenesis in rats on the unsaturated fat diet.
A defective subacute sclerosing panencephalitis (SSPE) virus which had been passaged in human embryonic lung cells was transferred to cultures of three neural cell types: neuroblastoma, oligodendroglioma and glioblastoma. The growth characteristics of the virus in these cells were essentially similar to those in non-neural cells. On the other hand, a marked difference in neurovirulence was noticed for the virus grown in neural cells when examined by intracerebral inoculation into mice. The virus passaged in neuroblastoma and oligodendroglioma cells showed high neurovirulence, inducing an acute encephalitis, whereas the virus passaged in human embryonic lung cells and that in glioblastoma cells did not show neurovirulence. These results suggest that the virus recovered its neurovirulence after passage in certain human neural cells.
The response of growth hormone (GH) to synthetic human growth hormone releasing factor (hGRF) administered intravenously was examined in 32 neonates aged 3-28 days. GH peaked at 30 min after hGRF administration and the mean +/- SEM level of GH at maximal response was 66.4 +/- 6.2 ng/ml. In the comparison between the neonates less than 7 days old and those more than 8 days old, between the neonates less than 37 weeks and those more than 38 weeks in gestational age, between the neonates under 2,500 g and those over 2,501 g in birth body weight, and between males and females, no significant statistical differences were observed.
We attempted to analyze the physiological meaning of abnormally low thyroid hormones in low birth weight (LBW) infants on the basis of cross-sectional data on free triiodothyronine (free T3) and T3 in addition to the other thyroid hormones. In LBW infants, the levels of free T3 and T3 were lower than those of normal infants, similar to the relation between free thyroxine (free T4) and T4. The ratio of free T3/T3 or free T4/T4, however, was not different between the groups. The levels of thyroid-stimulating hormone, thyroid hormone-binding globulin and reversed T3 in LBW infants were not significantly different from those of normal infants.