Susumu Kishimoto

Age-related decrease in frequencies of B-cell precursors and specific helper T cells involved in the IgG anti-tetanus toxoid antibody production in humans

Abstract B cells from each of 12 aged subjects (72 to 83 years old) and 12 young adults (24 to 32 years old) were cocultured with pokeweed mitogen (PWM) and an equal number of T cells isolated from a single tetanus toxoid-boosted donor for 7 days. The quantities of IgG antibody produced were significantly different in the two groups, with geometric means of 142 and 181 ng/ml in young adults, and 14 and 33 ng/ml in aged donors at 2 and 4 weeks after booster immunization, respectively ( P P = 0.02 at 4 weeks). There was no evidence indicating increased specific suppressor activity in the aged. Precursor frequency of B cells active in IgG antibody production was approximately 5.2-fold less in the aged than in young adults ( P = 0.01). Tetanus toxoid-specific helper T-cell frequency also decreased by 3.5-fold in the aged as compared with young adults ( P = 0.05).

Thrombopoiesis‐ and Megakaryocyte Colony‐stimulating Factors in the Urine of Patients with Idiopathic Thrombocytopenic Purpura

The urinary extract from patients with severe, chronic idiopathic thrombocytopenic purpura (ITP) was capable of inducing significant thrombocytosis in rats in vivo and enhancing megakaryocyte colony formation in culture of mouse bone marrow cells. The apparent specific activity of megakaryocyte colony stimulating factor (MEG‐CSF) in the ITP extract was approximately one‐half of that of the urinary extract from patients with aplastic anaemia (AA). Daily injections of ITP extract did not cause an increase in Hb concentration, while rats receiving AA urinary extract revealed profound erythropoiesis 3 weeks later. In vitro assay of erythropoietin (EPO) failed to show significant EPO activity in the extract from patients with ITP. These findings excluded the possibility that the observed activities of thrombopoiesis‐stimulating factor (TSF) and MEG‐CSF in the ITP urinary extract are due to contaminating EPO. Urine of patients with severe ITP appears to be a good source of TSF and MEG‐CSF.

Thrombopoiesis and Megakaryocyte Colony Stimulating Factor in the Urine of Patients with Aplastic Anaemia

Summary The urinary extracts from patients with aplastic anaemia and from healthy donors were investigated in vivo and in vitro for their ability to stimulate megakaryopoiesis and platelet production. There was a significantly higher concentration of thrombopoiesis stimulating factor (TSF) and megakaryocyte colony stimulating factor (MEG‐CSF) in the urine from patients with aplastic anaemia than in that from healthy donors. Neuraminidase treatment did not affect the thrombopoietic activity of TSF, whereas coexisting erythropoictin (EPO) in the extract lost its activity in vivo. These findings suggest that TSF and/or MEG‐CSF seems to be different from EPO and that the urine from aplastic anaemia patients would be a good source of TSF and MEG‐CSF for purification and characterization.

A new hemoglobin variant: HB yatsushiro α2Aβ260Val→Leu

Abstract This study was performed to establish the structural abnormality of a new hemoglobin variant discovered in a Japanese patient with angina pectoris. The hybridization of the separated hemoglobin with canine hemoglobin revealed a β-chain anomaly. Peptide βTp-6 was found to be abnormally located on the peptide map of tryptic digests of the S-carboxymethylated β-chain from the variant hemoglobin. A structural study on the abnormal βTp-6 revealed that the variant hemoglobin differs from hemoglobin A by substitution of leucine for valine at residue 60 of the β-chain. This new variant hemoglobin is designated as hemoglobin Yatsushiro after the name of the city where the propositus lived. The patient is hematologically healthy and his clinical history has nothing to do with this abnormal hemoglobin.

31P-NMR study on nucleotides and intracellular pH of hereditary spherocytes.

As determined by31p-NMR spectroscopy, intracellarar pH of hereditary spherocytes was lower (pH 6.7–6.9) than that of normal red cells. The level of adenosine diphosphate in hereditary spherocytes was found to be persistently high. The metabolism of nucleotides and other phosphoryl compounds in human red blood cells have been studied in detail by31p-NMR spectroscopy1–3. However, to our knowledge, there seems to be no report describing the result of31p-NMR spectroscopy on red blood cells from hereditary spherocytosis.

T-cell suppression of immunoglobulin synthesis in ataxia telangiectasia: Restriction of suppressor activity to B cells from unrelated donors

Abstract Ataxia telangiectasia is a genetically transmitted disorder, characterized by progressive neurologic dysfunction, superficial telangiectasia, and abnormalities of cellular and humoral immunity. We examined a 13-year-old female with this disorder, whose peripheral T cells were found deficient in their ability to collaborate with B cells from unrelated normal individuals, but not from each of her parents and her sisters upon coculturing in the presence of pokeweed mitogen (PWM). In addition, the patients T cells (Tp) suppressed the Ig production by PWM-stimulated peripheral blood lymphocytes (PBL) from allogeneic normal individuals but not from her parents. In contrast, irradiated T cells from this patient could collaborate to produce Ig with allogeneic B cells. HLA studies revealed that PWM-induced Ig production by PBL from the relatives was not suppressed by Tp irrespective of HLA phenotype of the donor. These data strongly suggest that Tp subpopulation has both a genetically unrestricted helper and a genetically restricted suppressor, a hitherto unreported phenomenon.