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Biomedical subjects

T Tsunematsu

Publications and source records attributed to T Tsunematsu.

At least 19 recordsLinked to original sources

Molecular cloning and characterization of a cDNA encoding monoclonal nonspecific suppressor factor.

The monoclonal nonspecific suppressor factor (MNSF) is a lymphokine product of a murine T-cell hybridoma that inhibits the generation of lipopolysaccharide-induced immunoglobulin-secreting cells in an antigen-nonspecific manner. A cDNA clone encoding MNSF beta (an isoform of MNSF) was isolated and expressed in bacteria. The sequence obtained is virtually identical to the Fau protein, a product of the ubiquitously expressed fau gene with unknown function. Northern blot analysis demonstrated a single, 0.6-kb transcript. Specific polyclonal antibodies against synthetic peptides corresponding to the deduced amino acid sequences were elicited in rabbits. Immunoprecipitation experiments with these antibodies showed that MNSF beta is released extracellularly in an aggregate form, albeit it lacks a signal peptide sequence. The anti-MNSF beta affinity eluate from the MNSF-producing murine hybridoma (E17) and concanavalin A-activated splenocyte culture supernatants inhibited the immunoglobulin production by lipopolysaccharide-activated splenocytes. Recombinant MNSF beta also showed a similar biologic activity. Thus, ubiquitin-like protein(s) may be involved in the regulation of the immune responses.

Amino Acid Sequence

Antinuclear antibodies in healthy aging people: a prospective study.

In order to evaluate the expression of antinuclear antibodies (ANA) in normal elderly individuals over time and clinical significance, a cross-sectional ANA testing in healthy Japanese was performed, followed by annual evaluations of ANA positive aged (> or = 65 years) and a control group. ANA was more prevalent in the aged (11.4% vs. 3.8%) and most were persistent after 4 years. Anti-ssDNA and anti-histone antibodies were increased in aged ANA positive as compared to ANA negative controls. Except for a history of spontaneous abortion, there was no differences in clinical findings. HLA DRB1*0901 and the DQB1*0602 + 0302 + 0303 set of alleles were increased in ANA positive. Therefore, ANA in the aged were persistent, apparently directed toward chromatin elements, and shared MHC associations with autoimmune diseases. Longer follow-up may be necessary to improve the evaluation of clinical significance of ANA in the aged.

Adult

Isolation and characterization of a human nonspecific suppressor factor from ascitic fluid of systemic lupus erythematosus. Evidence for a human counterpart of the monoclonal nonspecific suppressor factor and relationship to the T cell receptor alpha-chain.

The monoclonal nonspecific suppressor factor (MNSF) is a lymphokine produced by a murine T cell hybridoma capable of suppressing Ab production by LPS-stimulated B cells. The existence of a human counterpart of MNSF, designated as the human nonspecific suppressor factor (hNSF), was likely because the anti-MNSF mAb (MO6) recognizes a similar suppressive activity in supernatants of Con A-stimulated human PBMC. By using the MO6 mAb, we investigated the presence of hNSF in the ascitic fluid of a patient with SLE. A small amount of cross-reactive hNSF was isolated from concentrated ascitic fluid fractionated with the MO6-affinity column, and a specific anti-hNSF mAb (P2) was produced. The hNSF eluted from the P2-affinity column could suppress up to 80% of the PWM-induced IgG production of human PBMC in a dose-dependent manner, even when added in late culture periods. Moreover, hNSF could inhibit proliferation of PBMC triggered by either PWM or Con A, which also implies an effect on T cells. On SDS-PAGE, the isolated hNSF resolved as a single peak of about 66 kDa and probably represents an aggregate of hydrophobic subunits. On reverse-phase HPLC, the bioactivity could be recovered from a single peak at 18.3 min. The suppression of IgG production induced by hNSF could be partly neutralized by preincubation with an anti-TCR-alpha mAb, whereas an anti-TCR-beta did not have any effect. Anti-TCR-alpha could also directly bind to the isolated nNSF, demonstrating some serologic relationship, as has been reported for several Ag-specific suppressor systems.

Adult

Improvement of cerebral blood flow and cognitive function following pacemaker implantation in patients with bradycardia.

We investigated the effects of pacemaker implantation on cerebral blood flow and cognitive function in 14 severely bradycardic patients (mean age 75.2 years). Cerebral blood flow and verbal intelligence improved after the pacemaker implantation. Systolic and mean arterial blood pressure was significantly reduced after the implantation. Changes in cerebral blood flow significantly correlated with changes in heart rate in polynomial regression analysis, but not with changes in cardiac output. Before the implantation, verbal cognitive function was lower in bradycardic patients than in age-matched control subjects, and brain CT showed significant advanced atrophy in these patients. However, verbal cognitive function was also improved after the implantation. Pacemaker implantation in the severe bradycardic elderly should be beneficial not only for cardiac function but also for brain function. We concluded that these results suggest that heart rate is one of the important factors in the regulation of cerebral circulation in patients with severe bradycardia. Pacemaker implantation in the elderly improved quality of life and may prevent mental deterioration.

Aged

c-myc protein expression during cell cycle phases in differentiating HL-60 cells.

We examined c-myc protein expression in cell cycle phases during differentiation induction of HL-60 cells by flow cytometry using an indirect immunofluorescence method. In exponentially proliferating HL-60 cells, c-myc protein was expressed in a cell cycle dependent manner. During the differentiation induction of HL-60 cells with dimethylsulfoxide (DMSO), c-myc protein was rapidly down-regulated in the G1/0 specific phase prior to the appearance of differentiation associated markers. Our results indicate that c-myc protein functions in the G1/0 specific phase in cellular differentiation, and the rapid down-regulation of c-myc protein in G1/0 phase is closely associated with initial differentiation programs.

Cell Cycle

A favourable effect of long-term alpha-interferon therapy in refractory idiopathic thrombocytopenic purpura.

We successfully treated two patients with refractory idiopathic thrombocytopenic purpura (ITP) with a weekly or monthly administration of alpha-interferon followed by short-course treatment with alpha-interferon. In both cases an increase in platelet count was brought about within 1 week after administration of alpha-interferon and the favourable response in platelet count was sustained over a few years with the weekly or monthly administration of alpha-interferon in the absence of any noticeable side-effects except for fever. So, alpha-interferon therapy seems to be beneficial in some cases of refractory ITP in terms of both remission induction and maintenance therapy.

Aged

[Immunoglobulin levels and blood parameters in inhabitants of a remote island].

To clarify the alteration of serum immunoglobulin levels with age, serum immunoglobulin and other parameters (age, symptoms, blood biochemical parameters, etc.) of inhabitants (213 persons; 63 men, 150 women) of a remote island in Shimane Prefecture were studied. Their subjective symptoms were collected by means of a questionnaire and various blood parameters were measured. These data were analyzed by t-test and multivariate analysis. The IgM level was decreased with age and each immunoglobulin level correlated with the total-protein level in serum. The IgG level of the subjects feeling fatigue was higher than that of the subjects not feeling fatigue.

Adult

IFN-gamma enhances the expression of cell surface receptors for monoclonal nonspecific suppressor factor.

Monoclonal nonspecific suppressor factor (MNSF) is a lymphokine derived from a murine T cell hybridoma. The action of MNSF is mediated by specific cell-surface receptors. Since IFN-gamma alters the cellular response to MNSF (M. Nakamura, H. Ogawa, and T. Tsunematsu, J. Immunol. 138, 1799, 1987), we investigated whether IFN-gamma has an effect on the expression of MNSF receptor on target cells. IFN-gamma enhanced the expression of MNSF receptor on both MOPC-31C cells (a murine plasmacytoma line) and EL4 (a murine T lymphoma line). Incubation with IFN-gamma increased the number of specific MNSF-binding sites by about 50 to 90%, with no significant change in binding affinity. IFN-alpha and IFN-beta also increased MNSF binding, although the effect of the saturating amounts was lower than that seen with IFN-gamma. Maximal enhancement of receptor expression was observed after about 15 hr of incubation with IFN-gamma. No demonstrable change occurred in the kinetics of internalization of 125I-MNSF bound to MOPC-31C cells preincubated without or with IFN-gamma.

Animals

Characterization of N-terminal amino acid sequence of monoclonal nonspecific suppressor factor.

Monoclonal nonspecific suppressor factor (MNSF), a product of a murine T cell hybridoma, suppresses the antibody response to lipopolysaccharide. In an attempt to clarify the N-terminal sequence, MNSF was prepared and purified by affinity chromatography with the use of an anti-MNSF monoclonal antibody (MO6), and reverse-phase high-pressure liquid chromatography. On the SDS-PAGE, the purified MNSF showed a single band with a molecular weight of 12,000. The N-terminal amino acid sequence of the protein was determined and showed no strong homology to any of the sequences of known biologically active proteins. However, the sequence revealed significant (60%) amino acid identity to transforming growth factor beta 2 (TGF beta 2).

Amino Acid Sequence

The effects of FK-506 and cyclosporin A on the proliferation of PHA-stimulated T cells in response to IL-2, IL-4 or IL-6.

Stimulated by PHA, the T cells responded well to exogenous IL-2, IL-4 or IL-6, but the responses were inhibited by FK-506 or cyclosporin A (Cs A). In contrast, when stimulated by PMA, the T cells responded to IL-2 and IL-4, but not to IL-6 and the responses were not inhibited by FK-506 and Cs A. Kinetic studies showed that FK-506 and Cs A had no inhibitory effects on T cell proliferation in response to IL-2 and IL-4 after the resting T cells were pulsed with PHA alone for a certain time. However, the response of the PHA-pulsed T cells to IL-6 was still inhibited by FK-506 or Cs A, but the inhibitory effect gradually decreased as the time in which the PHA-pulsed T cells interacted with IL-6 was prolonged. In a control system, the proliferation of the T cells that were treated with FK-506 or Cs A for 3 h and washed 3 times was not inhibited when the T cells were stimulated with PHA in combination with either IL-2, IL-4 or IL-6. Our data suggest that FK-506 and Cs A interfere with the early steps of T cell proliferation after stimulation of PHA, but not PMA. It is likely that the two drugs inhibit the expression of lymphokine receptors, by interfering Ca(2+)-related signals and that IL-6 induces T cell proliferation in a different way than IL-2 and IL-4, which are FK-506- and Cs A-sensitive.

Cells, Cultured

Longitudinal study of regional cerebral blood flow changes in depression after stroke.

BACKGROUND: We studied 60 patients longitudinally to examine relations between regional cerebral blood flow and depressive states after stroke. METHODS: Poststroke depressive states were assessed by the Zung Self-Rating Depression Scale (SDS). Regional cerebral blood flow was measured using the 133xenon inhalation method with patients in the resting state on the same day as the SDS assessment. All patients were followed for an average of 14 months after the initial assessment. RESULTS: Severity of depression was inversely correlated with regional cerebral blood flow values in the parieto-occipital regions of the right hemisphere and in the anterior temporal region of the left hemisphere at the initial evaluation. Patients with lesions in left frontal or right parieto-occipital regions were more depressive in comparison with those with other brain lesions. Follow-up study showed significant inverse correlations between changes in SDS score and changes in regional cerebral blood flow at all scalp sites. Furthermore, higher inverse correlations were observed at specific brain regions in each hemisphere, including the parietal and parieto-occipital regions of the right hemisphere and the anterior temporal and inferior frontal regions of the left hemisphere. This relation was independent of recovery from neurological deficits. CONCLUSIONS: These results suggest that dysfunction of specific cortical and subcortical regions in both hemispheres asymmetrically contributes to depressive state after stroke.

Affect

Effect of single oral administration of nilvadipine on cerebral blood flow in chronic cerebral infarction.

UNLABELLED: The effect of nilvadipine, a newly developed calcium antagonist, on regional cerebral blood flow (rCBF) was investigated in 7 patients with chronic cerebral infarction. rCBF was measured by the 133Xenon inhalation method. Patients were given a single dose of 4 mg of nilvadipine after the first measurement of rCBF, and the second measurement was done one hour after the administration. All patients had hemiparesis and 2 of them had mild to moderate mental deterioration, but all patients could walk to the outpatient clinic by themselves. RESULTS: (1) rCBF of the affected side significantly increased by 22.7% after single oral administration of nilvadipine (p < 0.05). The increase of rCBF was significantly marked in frontal regions of the affected hemispheres. (2) No significant changes in blood pressure or end tidal partial pressure of carbon dioxide were observed during the examination. These results indicate that nilvadipine has a potent selective vasodilatory action on the cerebral arteries in patients with cerebral infarction.

Administration, Oral

[Depressed mood and subjective sensation well-being in the elderly living alone on Oki island in Shimane prefecture].

In order to clarify the influence of living alone on depressed mood and subjective sensation of well-being in the elderly, we studied 113 elderly (60 years old or more) living in Chibu village on Oki island. The subjects were divided into two groups, 33 subjects (Single group) who were living alone (mean age 74.1 years) and 80 subjects (Married group) who were married and lived with their spouses (mean age 69.0 years). For the measurement of depressed mood and subjective sensation of well-being the Zung Self-Rating Depression Scale (SDS) and Morale Scale were used. The SDS score of the Single group was significantly higher than that of the Married group. The incidence of depression was higher in the Single group than in the Married group, but the difference was not of statistical significance. The Morale Scale score in the Single group was significantly higher than in the Married group. Subjects in the Single group felt more lonely than those in the Married group, but not significantly so. There was a highly significant correlation between the SDS score and the Morale scale score. We concluded that, in the elderly, living alone is more depressing and less satisfying than living with a partner.

Affect

P300 event-related potentials correlated with cerebral blood flow in nondemented patients with lacunar infarction.

We have studied the relationship between the P300 latency and regional cerebral blood flow (rCBF) in 25 nondemented patients who had lacunar infarctions in the territory of the deep perforating branches of the internal carotid artery system. A significant prolongation of the P300 latency with advancing age was observed. There was a negative correlation between the P300 latency and the rCBF. These results indicate that a combination of P300 latency and rCBF measurements might prove more sensitive in detecting mental decline than rCBF studies alone in nondemented patients with lacunar infarctions.

Adult

Preliminary criteria for classification of adult Still's disease.

We have attempted to design classification criteria for adult Still's disease by analyzing the data obtained through a multicenter survey of 90 Japanese patients with this disease and of 267 control patients. The proposed criteria consisted of fever, arthralgia, typical rash, and leukocytosis as major, and sore throat, lymphadenopathy and/or splenomegaly, liver dysfunction, and the absence of rheumatoid factor and antinuclear antibody as minor criteria. Requiring 5 or more criteria including 2 or more major criteria yielded 96.2% sensitivity and 92.1% specificity. However, an exclusion process will be needed for an accurate classification, since this disease is relatively rare.

Adolescent

[Studies on clinical subsets and severity of systemic lupus erythematosus based on a 1987 questionnaire conducted in Japan--clinical analysis of the outcome and treatments in clinical subsets].

A 1987 questionnaire sponsored by the Health and Welfare Ministry concerning the clinical subsets and severity of systemic lupus erythematosus (SLE) was distributed to 93 medial facilities. A clinical analysis of the outcome and treatments was accomplished on one thousand six hundred and fourteen SLE patients fulfilling ARA criteria. The outcome was evaluated into 6 categories, namely; complete remission, incomplete remission, no change, gradual worsening, rapid worsening and unknown. Treatments included (1) anti-inflammatory drugs, (2) initial dose of prednisolone (PSL) below 29 mg/day, (3) initial dose of PSL from 30 to 59 mg/day, (4) initial dose of PSL above 60 mg/day, (5) pulse therapy, (6) immunosuppressants, (7) plasmapheresis, and (8) hemodialysis. Statistical significances were determined with ridit analysis. The severity of the disease for 1,614 SLE patients was evaluated by the judgement of each medical facility independently, separating it into 3 grades. As a result, 16.8% was evaluated as severe, 54.6% was evaluated as moderate, and 28.6% was evaluated as mild. Clinical subsets were divided into 3 categories according to the outcome; (1) those with high complete remission rates (serositis, convulsion, oral ulcers, unconsciousness, hemolytic anemia and so on), (2) those with high incomplete remission rates (lupus nephritis, digital gangrene, hypertension, peripheral neuropathy, erythema, Raynaud's phenomenon and so on), and (3) those with high rates of no change or worsening (aseptic bone necrosis, pulmonary hypertension, pneumonitis, chronic renal failure and so on). SLE patients with persistent proteinuria below 3.4 g/day, pulmonary hypertension, or pneumonitis treated with large doses of PSL such as an initial dose of PSL above 60 mg/day and/or pulse therapy had a significantly higher remission rate than those treated with small dosages of PSL. Hereafter, the establishment of modes of treatments for increasing the remission rates of intractable clinical subsets in highly desired.

Adolescent