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N Fukuma

Publications and source records attributed to N Fukuma.

34 records · Page 2Linked to original sources
PubMed1991

Severe combined immunodeficient (SCID) mice: a model for investigating human thyroid autoantibody synthesis.

We have studied the ability of lymphocytes from the blood, thyroid and lymph nodes of patients with autoimmune thyroid disease (AITD) to produce autoantibodies to thyroglobulin (Tg) and/or thyroid peroxidase (TPO) in SCID mice. Human IgG class Tg and/or TPO antibodies were detectable in plasma from SCID mice 7 days after transfer of 15-25 x 10(6) cells/mouse and the highest levels were recorded 2-3 weeks later. In contrast, Tg and/or TPO antibodies were undetectable in recipients of lymphocytes from thyroid antibody negative controls. AITD thyroid lymphocytes produced the most antibody in recipient mice and lower levels were observed in recipients of AITD blood and lymph node lymphocytes. The amounts of Tg and/or TPO antibody detected were in accordance with the ability of thyroid and lymph node lymphocytes to secrete these autoantibodies spontaneously in culture (indicating the presence of cells activated in the patient) and with the capacity of blood lymphocytes (probably B memory cells) to secrete Tg and/or TPO antibodies in culture in response to pokeweed mitogen. Tg antibodies in plasma from SCID recipients of thyroid lymphocytes were of subclasses IgG1, IgG2 and IgG4 and the proportions closely resembled those of the donor's serum Tg antibodies. Blood lymphocytes transferred to SCID recipients were also able to produce Tg antibodies of subclasses 1, 2 and 4 but the subclass distribution varied between mice and the reason for this is not clear at present. Since SCID mice provide an environment in which B lymphocytes from patients with AITD can be activated without mitogen to secrete thyroid antibodies, this model will provide a powerful system for elucidating the mechanisms regulating the secretion of human antibodies to Tg and TPO.

Animals↗
PubMed1991

Role of perceptive threshold in myocardial infarction patients without previous angina.

The purpose of this study is to clarify the mechanism of sudden onset myocardial infarction (MI) without previous angina and the relationship of MI without previous angina to the mechanism of onset of postinfarction asymptomatic myocardial ischemia. The mean initial time of ischemic pain in the upper arm under the tourniquet test was significantly prolonged in the MI patients without previous angina, compared with that for the MI patients with previous angina and normal control subjects, although there are some overlapping cases (74 +/- 37 sec versus 52 +/- 20 sec (p less than 0.01), and versus 56 +/- 15 sec (p less than 0.05), respectively). The tolerance time for ischemic pain also was similarly prolonged. There was no significant difference between the groups of MI patients (with and without previous angina) with respect to age, frequency of complications of diabetes mellitus, severity of coronary artery lesions or site of MI. The incidence of post-infarction myocardial ischemia was 50% for the previous angina group and 39.5% for the group without previous angina, but the frequency of asymptomatic ischemia was significantly higher in patients without previous angina, at 66.7%, than in those with previous angina, 32.3% (p less than 0.05). These results suggest that there is a close relationship between the mechanism of MI with sudden onset and that of asymptomatic myocardial ischemia during the pre- and post-infarction periods in patients with low sensitivity to pain.

Angina Pectoris↗
PubMed1991

Attachment of Vibrio parahaemolyticus strains to estuarine algae.

Attachment of Vibrio parahaemolyticus strains to estuarine microalgae was examined in artificial seawater by viable counts of the organism and direct counts of the bacterial cells after immunoperoxidase staining. Thermostable direct hemolysin (TDH)-producing and TDH-non-producing strains of V. parahaemolyticus were found to attach to five estuarine strains of Navicula (diatom alga) in similar levels. The level of the bacterial attachment depended on salinity and temperature of the water, in which the maximum attachment was observed in 15% artificial seawater at 25 degrees C, a typical condition of Hashizu estuary in Japan during summer months. The attachment was inhibited by pectinase digestion of the algal cells. These evidences confirmed the participation of the microalgae to the ecological cycle of V. parahaemolyticus at the estuary.

Chlorella↗
PubMed1991

Human monoclonal thyroglobulin autoantibodies of high affinity. I. Production, characterisation and interaction with murine monoclonal thyroglobulin antibodies.

Four hybridomas secreting human thyroglobulin (Tg) autoantibodies of different IgG subclasses and light chain types (IgG1 lambda, IgG1 kappa, IgG2 lambda and IgG2 kappa) were obtained by direct fusion of Hashimoto thyroid lymphocytes with the mouse myeloma X63-Ag.653. The autoantibodies were specific for human Tg and the functional affinities were high (only 2.6-3.9 log10 pM Tg required to give 50% inhibition of binding in ELISA). Using thyroid lymphocytes, 4 lines secreting Tg autoantibodies were obtained from 11 fusions compared with 1 line from 32 fusions of Epstein Barr virus infected blood lymphocytes, which emphasises the importance of using lymphocytes derived from a tissue known to be enriched in thyroid autoantibody secreting precursor B cells. These 4 human Tg autoantibodies, as well as an IgG2 lambda Tg antibody previously derived from Hashimoto blood B cells and an IgG4 kappa monoclonal Tg antibody present in a Hashimoto serum, were used in attempts to probe the interaction between human Tg autoantibodies and the Tg molecule (2 polypeptides of 330 KD). The binding to 125-I Tg by 3/7 murine monoclonal antibodies was inhibited (36-78%) by an IgG2 lambda and an IgG4 kappa human monoclonal Tg autoantibody, indicating an overlap between the epitopes recognised by these 3 murine monoclonal Tg antibodies and 2 monoclonal human Tg autoantibodies. None of the human Tg autoantibodies (or the murine monoclonal Tg antibodies) bound to Tg denatured by reduction and alkylation. Although the number of observations is limited, our study demonstrates that high affinity human monoclonal Tg autoantibodies, like polyclonal serum Tg autoantibodies, recognise non-linear B cell epitopes on conformationally intact human Tg.

Animals↗
PubMed1990

Thyroid autoantigens and human T cell responses.

We investigated the ability of T cells from patients with Hashimoto's thyroiditis and with Graves' disease as well as control donors to proliferate in response to thyroid peroxidase (TPO) and thyroglobulin using (i) lymphoid cells from different lymphoid organs; (ii) unfractionated or CD8- depleted lymphoid suspensions or T cells + autologous low density cells (LDC); (iii) 200-microliters well cultures and 20-microliters hanging-drop microcultures; and (iv) intact TPO and thyroglobulin, denatured thyroglobulin and 12 synthetic peptides predicted on the basis of the amino acid sequence of TPO to be T cell epitopes. In 200-microliters well cultures, proliferative responses (assessed in terms of 3H-thymidine uptake) to intact TPO or thyroglobulin, digested thyroglobulin or synthetic TPO peptides were not significantly different in unfractionated or CD8-depleted lymphoid suspensions from blood, thyroid or lymph nodes of TPO/thyroglobulin autoantibody-positive patients, autoantibody-negative patients or control donors. In contrast, blood T cells from some high titre patients with Hashimoto's thyroiditis (but not from healthy individuals) proliferated in response to intact thyroglobulin or TPO presented by autologous LDC in hanging-drop microcultures. Heat denatured thyroglobulin (with which thyroglobulin autoantibodies do not interact) did not stimulate proliferation and this observation, together with the ability of T cells from some patients to respond to intact thyroglobulin in the absence of LDC, indicated that thyroglobulin-specific B cells may be involved in antigen presentation. As we were unable to demonstrate proliferation by blood T cells + LDC from all thyroglobulin antibody-positive patients with Hashimoto's thyroiditis, our studies suggest that the presence of sufficient precursor T cells, as well as the number and type of antigen-presenting cells, are critical for T cell proliferative responses to human TPO and thyroglobulin.

Antigen-Presenting Cells↗
PubMed1990

Evaluation of a new vasodilating beta-blocking agent, carvedilol, in exertional angina using holter monitoring.

Antianginal and antiischemic effects and clinical pharmacologic actions of carvedilol, a novel beta-blocking agent with a vasodilator action, were determined by Holter electrocardiographic monitoring in 13 patients with exertional angina. The patients were observed for 1 week prior to entry into the study, followed by 1 to 2 weeks of treatment with carvedilol. During the observation period the patients received one placebo tablet daily, and during the treatment period one 20 mg tablet of carvedilol daily. Before and after the treatment 24-hour Holter electrocardiographic tracings were obtained. The mean interval of Holter monitoring was 11.2 +/- 4.5 days for the observation and treatment periods, and the mean time of drug administration was 8:25 a.m. (+/- 30 min). The Holter electrocardiographic tracings which were obtained twice in 9 patients during the observation period showed a high degree of reproducibility with respect to the frequency, magnitude and duration of ST-segment depression. The total frequency of ST depression per patient was 4.5 +/- 3.4 events/day pre-drug and 2.1 +/- 2.1 events/day post-drug. There was a significant reduction in total frequency of ST depression post-drug (p less than 0.01). The frequency of asymptomatic ST depression was similarly decreased post-drug (p less than 0.01), and the total magnitude and duration of ST depression were significantly improved post-drug (p less than 0.01 and p less than 0.05, respectively). These effects of carvedilol lasted for 24 hours after administration. Considering that the heart rate was not excessively reduced during the night, and nocturnal myocardial ischemic episodes were not exacerbated, the mode of action of this drug seems to be based on not only a beta-blocking action but also on a vasodilator action. Carvedilol benefits exertional angina when used in a 20 mg s.i.d. regimen.

Adrenergic beta-Antagonists↗
PubMed1990

Relationship between thyroid autoantibody spectrotype and IgG subclass.

The relationship between spectrotype and IgG subclass of autoantibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO) has been investigated using sera from Hashimoto and Graves' patients. Isoelectric focussing (IEF) was carried out in gels over the range pI 3.5-9.5 followed by transblotting to nitrocellulose and probing the filters using 125I-labelled TPO and Tg. As has been shown previously for Tg antibodies, TPO antibody focussed over different pI values in different patients but the spectrotypes for individuals were constant over 2-5 years. Further, the pI values for TPO and Tg autoantibodies appeared to be related to IgG subclass, for example IgG1 Tg antibodies tended to focus nearer the cathode (pI 8.0-9.5) than IgG4 antibodies (pI 6.5-8.5) while antibodies of subclasses IgG1 + 2 + 4 produced spectrotypes covering a broad pI range (5.7-9.5). Consequently, it seems likely that the characteristic spectrotypes described by others for Tg autoantibodies, and those we now report for TPO antibodies, reflect the IgG subclass "fingerprints" which we suggest may be a measure of the ability of an individual to respond to different epitopes on these two thyroid antigens.

Autoantibodies↗
PubMed1990

Potential role of PHA in producing human monoclonal thyroid autoantibodies of different subclasses.

A human monoclonal autoantibody to thyroglobulin (Tg) of subclass IgG2 was developed by fusing a mouse myeloma with Tg antibody secreting Epstein-Barr virus (EBV)-infected B lymphocytes from a Hashimoto patient. Subsequent studies showed that EBV-infected B lymphocytes from this patient synthesized IgG2 Tg antibody while unfractionated blood lymphocytes cultured with pokeweed mitogen secreted IgG1, IgG2, and IgG4 Tg antibodies in amounts proportional to those present in the patient's serum. To investigate this discrepancy further, we cultured EBV-infected lymphocytes from blood, lymph nodes, and thyroid tissue in medium alone and with increasing concentrations of PHA. In individuals with thyroid autoantibodies predominantly of subclass IgG1, PHA enhanced the levels of total Tg antibody synthesis without affecting the IgG subclass distribution. However, in patients with serum autoantibodies of subclasses IgG1, 2, and 4, the increased levels of total Tg antibody synthesis were associated with increased amounts of thyroid autoantibodies of all of these subclasses; in some instances IgG1 and IgG4 autoantibodies were only synthesized in cultures containing PHA. These observations suggest that addition of the T-cell mitogen PHA to cultures of EBV-infected lymphocytes may ensure activation of B-cell precursors committed to synthesizing the IgG subclasses characteristic of serum antibody in the lymphocyte donor. Since Tg antibodies of subclasses IgG2 and IgG4 recognize different epitopes on Tg, the ability to produce human monoclonal antibodies of different IgG subclasses may simultaneously ensure the development of antibodies to different epitopes on the same antigen.

Animals↗
PubMed1989

Clinical significance and management of silent myocardial ischemia in patients with angina pectoris and myocardial infarction.

The present study was canued out to clarify the relationship between silent myocardial ischemia in patients with angina pectoris and onset of myocardial infarction, and the former's prognostic significance. The peak incidences of onset of myocardial infarction in patients were at 2 a.m., 9 a.m., 2 p.m., 8 p.m., and 9 p.m., and the peak onsets of transient silent myocardial ischemia in angina pectoris patients were at 9 a.m., 2 p.m., 8 p.m., and 9 p.m. Thus the most likely onset times were almost the same with both events. Of 169 patients with coronary artery disease admitted for treatment, 128 patients had no anginal attacks during follow-up and the remaining 41 had persistent angina despite adequate medical treatment. Holter monitoring electrocardiography was performed twice with the non-angina patients, during admission. Of these 128 patients, 54 showed no silent myocardial ischemia on either of the electrocardiographic recordings, 34 showed silent ischemia with the first Holter monitoring but not with the second one, and the remaining 41 showed silent myocardial ischemia on both tests. The subsequent incidences of "cardiac events" were 9.4%, 14.7%, and 36.6%, respectively for these three groups. Therefore, it is concluded that the presence of silent myocardial ischemia is closely related to onset of myocardial infarction and is an important prognostic factor in patients with coronary artery disease.

Adult↗
PubMed1989

A human-mouse hybridoma which secretes monoclonal thyroglobulin autoantibody with properties similar to those of the donor patient's serum autoantibody.

Human monoclonal antibodies produced by Epstein Barr (EB) virus transformation and/or cell fusion are frequently IgM antibodies which tend to cross react with a range of antigens and often bear little relationship to the highly specific IgG antibodies associated with human autoimmune disease. By fusing EB virus transformed B lymphocytes from a Hashimoto patient with a mouse myeloma line and selecting for synthesis of IgG class thyroglobulin (Tg) antibody, we have developed a hybridoma (VB/5) secreting Tg antibody of IgG2 subclass and lambda light chain type which has the characteristics of a monoclonal antibody on isoelectric focussing. The antibody has a high affinity for human Tg and recognises Tg from other primates but not non-primate Tg. However, it does not react with human thyroid peroxidase or a panel of other autoantigens. In terms of affinity constant, functional affinity and affinity heterogeneity, the antibody closely resembles the IgG2 lambda Tg antibody present in the serum of the Hashimoto patient whose B lymphocytes were used to develop the hybridoma. In addition to providing a useful reference standard for Tg antibody IgG subclass assays, VB/5 antibody and the hybridoma line provide a valuable starting point for detailed studies of Tg autoantibodies and the genes coding for the variable regions of their heavy and light chains.

Animals↗
PubMed1989

Human thyroglobulin autoantibodies of subclasses IgG2 and IgG4 bind to different epitopes on thyroglobulin.

IgG autoantibodies to thyroglobulin (Tg) in the serum of patients with autoimmune thyroid disease only recognize a very limited number of epitopes, probably between four and six (Nye, Pontes De Carvalho & Roitt, 1980) on the large Tg molecule (660,000 MW), but attempts to characterize the epitopes have been unsuccessful so far (Male et al., 1985). The distribution of Tg autoantibodies between the IgG subclasses also tends to be restricted and individual patients possess characteristic 'fingerprints' of high affinity IgG1 and/or IgG4 Tg antibodies with smaller amounts of IgG2 Tg antibody (McLachlan et al., 1987, 1988). We have therefore investigated the possibility that Tg autoantibodies of different IgG subclasses interact with different epitopes on Tg.

Autoantibodies↗
PubMed1986

Studies on thyrotropin releasing hormone in cerebellar ataxia mutant mouse brain.

The effects of cathecholamine on the regional TRH distribution in the brain was studied in rolling mouse Nagoya (RMN) and non-affected C3H mice. TRH was extracted from the hypothalamus, brain stem, cerebellum, and cerebrum one hour after i.p. injection of the precursor or inhibitors of cathecholamine. TRH was distributed throughout the brain of both affected and non-affected mice; however, in RMN, TRH levels were lower in the hypothalamus and higher in other areas. 1-Dopa caused a decrease of TRH in the brain stem but no change in other regions in the RMN brain, whereas it caused an increase in TRH levels in all areas of the C3H brain. Fusaric acid increased TRH in the hypothalamus of RMN and decreased it in the cerebellum; alpha-MPT also caused a decrease in the TRH level in the cerebellum. Reserpine increased the TRH level in the hypothalamus and decreased it in the cerebrum. From these results, it appears that cerebellar ataxia in RMN does not result from a decrease in the TRH, which is actually increased in the cerebellum. Catecholamine had different effects on TRH levels in RMN and the controls; this might be due to the excess accumulation of noradrenaline in the RMN brain.

Animals↗
PubMed1984

Abnormal lymphocyte function precedes hyperglycaemia in mice treated with multiple low doses of streptozotocin.

To investigate early immunological disturbances at the onset of diabetes, lymphocyte function and islet cell surface antibodies were studied in streptozotocin-treated C57BL/10 and B10.BR mice. In C57BL/10 mice, streptozotocin given in multiple low doses depressed lymphoblastic transformation to phytohaemagglutinin and pokeweed mitogen, but not to concanavalin A on day 6 after the first administration. On day 20, the transformation remained suppressed with phytohaemagglutinin, but recovered to the control level with pokeweed mitogen. In the early phase after treatment, the islet cell surface antibodies were elevated and then declined. Single high dose administration depressed responses to phytohaemagglutinin with no detectable islet cell surface antibodies. In B10.BR mice transformations to pokeweed mitogen and concanavalin A were suppressed in the early phase. The strain of mice may be a factor to be considered. Thus, it was suggested that the deterioration of immunological function with the formation of islet cell surface antibodies preceded the onset of hyperglycaemia in mice treated with multiple low doses of streptozotocin.

Animals↗
PubMedDate not supplied

Combination of ambulatory electrocardiographic monitoring and psychological testing in coronary artery disease patients.

Ambulatory electrocardiographic monitoring and psychological testing were performed in 100 patients with chronic stable myocardial infarction. These patients were divided into four groups according to their chest pain and transient ST-segment depression by Holter monitoring during the follow-up period: group A, 40 patients without complications; group B, 20 patients with silent myocardial ischemia; group C, 14 patients with episodes of chest pain alone; and group D, 26 patients with postinfarction angina. Whereas group B had silent myocardial ischemia and extroversion, groups C and D were characterized by introversion and neuroticism. The frequency of multi-vessel disease was 41% for group A, 53% for group B, 8% for group C and 70% for group D. The patients of group B not only received treatment for coronary artery disease but also behavioral counseling and those of group C received psychotherapy. The results support the view that a combination of Holter monitoring and psychological testing is clinically useful for the development of therapeutic strategies for coronary artery disease.

Aged↗