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K Taga

Publications and source records attributed to K Taga.

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Dissociated production of interleukin-2 and immune (gamma) interferon by phytohaemagglutinin stimulated lymphocytes in healthy infants.

Cord blood lymphocytes were stimulated with phytohaemagglutinin (PHA) to produce interleukin-2 (IL-2) and immune interferon (IFN-gamma). On PHA stimulation, cord blood lymphocytes produced efficiently IL-2 as much as adult ones. Antiviral activity generated on PHA stimulation was shown to consist mainly of IFN-gamma as assessed by the sensitivity to pH 2.0 treatment and neutralization with anti-human IFN-gamma antibody. In contrast to IL-2 production, cord blood lymphocytes released extremely low levels of IFN-gamma following PHA stimulation. The producing ability of IFN-gamma by lymphocytes on PHA stimulation gradually increased with child growth, but was significantly low at 1-2 years of age as compared with adult controls. Around 3 years of age or later, the producing ability of IFN-gamma by lymphocytes on PHA stimulation attained levels comparable to those of adult cells. These results suggested that IL-2 producing ability of lymphocytes appeared to be at a mature stage at birth, whereas lymphocytes in the early human life might be relatively deficient in their ability to produce IFN-gamma.

Adolescent↗

Differential effects of recombinant human interferon-gamma and interleukin 2 on natural killer cell activity of peripheral blood in early human development.

Ontogenic development and the lymphokine responsiveness of human NK cell activity against K562 target cells in peripheral blood lymphocytes were evaluated in fetuses, premature infants, and term neonates by using a 4-hr 51Cr-release assay. Basal NK activity and NK boosting by lymphokines were comparatively assayed after an 18-hr incubation with medium alone, recombinant human IFN-gamma (1000 U/ml), and recombinant human IL 2 (25 U/ml), respectively. Lymphocytes from 20-wk-old fetuses lacked NK cell activity even after the pretreatment with IFN-gamma. Low, but significant levels of NK activity and NK boosting by IFN-gamma were observed in premature infants after 27 wk of gestation, with a progressive intrauterine maturation of these activities. Both basal NK activity and NK boosting by IFN-gamma in term neonates were still lower than those of adult controls. The grade of NK boosting by IFN-gamma appeared to depend on the development of basal NK activity. Contrary to IFN-gamma, IL 2 could induce marked NK activity even in 20-wk-old fetuses who lacked both basal and IFN-gamma inducible NK activities. NK boosting by IL 2 was much more efficient than that by IFN-gamma at any period of human life. The facts that IL 2-induced NK boosting could occur without any appreciable production of IFN-gamma in neonatal lymphocytes, and that ample neutralizing doses of anti-IFN-gamma antibody hardly suppressed IL 2-mediated NK boosting even in adult lymphocytes, indicated that the effect of IL 2 on NK boosting might be independent of IFN-gamma production. On the basis of the ontogenic differences in the development of the lymphokine responsiveness of NK cell activity and on the different NK boosting mechanisms of these lymphokines it was suggested that so-called human "pre-NK cells" might be divided into IFN-gamma sensitive and IL 2-sensitive cells. Whether these cell populations belong to different cell lineages or different maturation stages of the same cell line, however, remains unsettled.

Adult↗

Mode of in vitro augmentation of natural killer cell activity by recombinant human interleukin 2: a comparative study of Leu-11+ and Leu-11- cell populations in cord blood and adult peripheral blood.

Human newborn natural killer (NK) cell activity against K562 target cells was observed to be low compared with adult controls. Although Leu-7 (HNK-1)+ cells were negligible in cord blood, the proportions of Leu-11+ cells were equal to those of adult peripheral blood. Leu-11+ cells sorted from cord blood lymphocytes, as well as from adult lymphocytes exhibited the morphology of granular lymphocytes. In this study, we have investigated the phenotypic characterization of recombinant interleukin 2 (rIL 2)-induced cytotoxic lymphocytes against K562 cells by using anti-Leu-11 monoclonal antibody. Spontaneous cytotoxicity of lymphocytes was restricted to Leu-11+ cells in cord blood, as well as in adult blood, but this activity was low in cord blood Leu-11+ cells as compared with that of adult ones. NK cell activity of adult Leu-11+ cells could not be additionally enhanced after an 18-hr incubation with rIL 2(25 U/ml), whereas rIL 2 could potentiate the cytotoxicity of cord blood Leu-11+ cells approximately to the adult levels. It should be noted that cytotoxic activity of both Leu-11- cells from cord blood and adult blood that had no basal NK cells activity could be significantly potentiated by rIL 2. On the other hand, lymphokine-activated killer cells cytotoxic for HL-60 cell line could not be generated, and no proliferation of the lymphocytes was detected after an 18-hr incubation with rIL 2. It was shown that rIL 2 could not enhance the ability to bind to target cells in Leu-11+ and Leu-11- cells by means of a single cell conjugate assay, but the rate of target lysis of Leu-11+ cells from cord blood was significantly enhanced by rIL 2. These results suggested that rIL 2-induced cytotoxic effector cells were heterogeneous, and rIL 2 might potentiate the cytotoxicity of functionally immature NK cells or NK precursor cells.

Adult↗

[Biventriculographic and clinicopathologic evaluation of apical hypertrophy: with reference to asymmetrical septal hypertrophy with hypertension].

To clarify the pathogenesis of apical hypertrophy with asymmetrical septal hypertrophy (ASH), left ventriculography in the right anterior oblique projection (LVG), biventriculography (BVG), and endomyocardial biopsy of the right ventricle were performed for patients with ASH. The patients were categorized in four groups according to ECG, LVG and BVG. Patients with hypertrophic cardiomyopathy (HCM) were divided into two subsets; (A) Apical hypertrophy group (AH: nine patients), with ECG showing left ventricular hypertrophy (LVH) and giant negative T waves (GNT), and with LV configurations showing the S or SR form at end-diastole on LVG. (B) Non-apical hypertrophy group (non-AH: 12 patients), with ECG showing LVH without GNT and LV configuration showing R form at end-diastole on LVG (cf: Fig. 1). Patients with ASH and hypertension (ASH-HT) were also divided into two subsets; (A) AH: seven patients. (B) non-AH: nine patients. Analysis of LVG and BVG: In HCM, the septal configuration showed the TS X S form in both two subset groups. The septal configuration in ASH-HT was divided into the NH form, which was clearly distinguishable from the septal configuration in HCM, and the TS X S form as in cases with HCM. In both HCM and ASH-HT, the diastolic thickness of the anterior apical wall was significantly thicker in all patients with AH than that in non AH. In HCM, the diastolic thickness of the septum and the percent systolic thickening did not significantly differ between AH and non-AH groups. In ASH-HT, the NH form showed similar diastolic thickness of the septum and % systolic thickening in AH and non-AH groups. On the other hand, the TS X S form in non-AH group showed greater thickness and lower % systolic thickening similar to those of HCM. Histological analysis of endomyocardial biopsy; In HCM, the transverse diameters of the myocytes and the biopsy scores did not differ significantly between AH and non-AH groups. In ASH-HT, the TS X S form in non-AH group had longer diameters and higher biopsy scores similar to those of HCM compared to the NH form in AH group. In conclusion, both HCM and ASH-HT may have apical hypertrophy manifested by giant negative T waves in the EKG and spade like form of left ventriculogram. In addition, apical hypertrophy in ASH-HT with the NH form of septal configuration seemed to be caused by hypertension.

Adult↗

Interferon-gamma can augment expression ability of HLA-DR antigens on pokeweed mitogen-stimulated human T lymphocytes.

The effect of natural interferon (IFN)-gamma on HLA-DR molecule expression of pokeweed mitogen (PWM)-stimulated T cells from cord blood and adult peripheral blood was assessed by direct immunofluorescence with fluorescein-labeled monoclonal anti-HLA-DR antibody on a flow cytometer. Although cord blood T cells showed only weak expression of HLA-DR antigens on PWM stimulation, IFN-gamma could enhance HLA-DR expression of PWM-stimulated cord blood T cells to levels comparable to those of adult ones. A similar, but slight, increase in HLA-DR expression was inducible in PWM-stimulated adult T cells by the addition of IFN-gamma, but at higher doses. This increased expression of HLA-Dr antigens on PWM-stimulated T cells was almost completely abolished by both acid treatment of IFN-gamma and neutralization of IFN-gamma with specific antiserum. In contrast to IFN-gamma, neither recombinant IFN-alpha nor IFN-beta showed any effect on HLA-DR expression of PWM-stimulated T cells. These results suggested a possible function of IFN-gamma that might modulate HLA-DR expression ability of T cells in their activation process.

Adult↗

Immunohistologic localization and immune phenotypes of lymphocytes expressing Tac antigen in human lymphoid tissues.

A monoclonal anti-Tac antibody has been identified as a putative antibody against the human interleukin 2 (IL 2) receptor. In the present study, anti-Tac antibody was used to determine the location of cells expressing IL 2 receptors in frozen sections of human lymph nodes and tonsils by means of an immunoperoxidase technique. It was found that a substantial number of lymphoid cells reactive with anti-Tac antibody were present in these tissues. The majority of the Tac-positive cells were located in the paracortical and interfollicular regions of lymph nodes and tonsils, whereas only a few Tac-positive cells were scattered in the mantle zones and germinal centers of the secondary follicles. In contrast, no Tac-positive cells were demonstrated on cytocentrifuge preparations of peripheral blood lymphocytes from some of tissue donors, as evaluated by the same technique. In some experiments, a double-marker immunofluorescence analysis with the use of different fluorochromes, fluorescein isothiocyanate (FITC), and tetramethylrhodamine isothiocyanate (TRITC) was applied to characterize the phenotypes of cells expressing Tac antigen. Double staining with TRITC and FITC, respectively, for the identification of Tac-positive cells and T cells, showed that Tac-positive cells in lymph nodes and tonsils almost exclusively co-expressed a pan-T cell marker, Leu-1 antigen, that probably does not belong to non-T cell lineages. About 80% of Tac-positive cells were Leu-3 (helper/inducer) positive, and 20% of them Leu-2 (suppressor/cytotoxic) positive. These observations imply the plausible notion that an IL 2-mediated immune activation of T cells may actually occur in local lymphoid organs.

Adult↗

[Evaluation of septal hypertrophy and wall dynamics by biventricular cineangiography and endomyocardial biopsy].

To clarify clinically the pathogenesis of septal hypertrophy in terms of its morphology and wall dynamics, simultaneous biventricular cineangiography (BVG) and endomyocardial biopsy of the left ventricle were performed for patients with left ventricular hypertrophy. The patients were categorized in four groups according to their clinical and BVG findings; 1) 24 normal control subjects (C), 2) 39 patients with hypertension and symmetrical septal hypertrophy (SH-HT), 3) 17 patients with hypertension and asymmetrical septal hypertrophy characterized by the ratio (IVS/PW) greater than or equal to 1.3 by BVG, and 4) 25 patients with hypertrophic cardiomyopathy (HCM). The BVG's configuration of the septum in SH-HT showed a normal form of septal hypertrophy (NH form) essentially similar to that of the control subjects (N form), except for septal thickness increases of more than 10 mm. In HCM, a triangle or shell (TS) form or spindle (S) form of the septum was demonstrated by BVG. The TS form was characterized by straight or convex thickening of the septum from its center to its base toward the left ventricle. The S form was characterized by convex thickening localized to the central part and a relatively thin base. However, the configuration in ASH-HT was either the NH form (7 cases) or the TS or S form (10 cases). The configuration in ASH-HT with the NH form was not distinguishable from that of SH-HT, nor was the configuration in ASH-HT with the TS or S form distinguishable from that of HCM. Systolic thickening (%) of the septum and systolic shortening (%) of the septal length decreased significantly in this order: C, SH-HT, ASH-HT with the NH form, and ASH-HT with the TS or S form. Those of HCM were similar to those of ASH-HT with the TS or S form. In the cases of the N or NH form, there was a negative correlation between systolic thickening (%) and thickness of the septum in diastole. In cases with the TS or S form, systolic thickening (%) was not affected by the thickness of the septum in diastole, and a lower value was observed in all cases. Histological studies of endomyocardial biopsies revealed a positive correlation between the transverse diameters of the myocytes and the total systemic peripheral resistance (TSPR) in 25 patients with SH-HT. In 12 patients with HCM, there was no correlation, and severe hypertrophy of the myocytes was observed despite a lower TSPR.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Circadian changes of T lymphocyte subsets in human peripheral blood.

The circadian variations in circulating T cell subsets defined by monoclonal antibodies in eight healthy male volunteers were evaluated in whole blood using a flow cytometry. In all subjects, the number of lymphocytes showed a clear rhythmicity with high values at night and low values during the day. This circadian variation in circulating lymphocytes appeared to reflect largely a change in the number of T cells rather than B cells. The percentage of OKT3+ and OKT11+ cells showed a similar fluctuation with a peak at night and a depression during the day. It was found that the percentage of OKT4+ cells varied in parallel with that of T cells, particularly of OKT3+ cells, but the OKT8+ subset was not appreciably altered over a 24 h period. Thus, a circadian variation of T cells could be largely accounted for by a circadian change of OKT4+ cells. Plasma cortisol levels showed an expected circadian variation. It was also shown that there might be an intimate relationship between these circadian changes of T cell subsets and plasma cortisol levels.

Adult↗

Clinical evaluation of biventriculo-cineangiographic findings in hypertensive left ventricular hypertrophy.

In the present study, we demonstrated that hypertensive left ventricular hypertrophy can be divided angiographically into symmetrical (SH) and asymmetrical septal hypertrophy (ASH) groups. In the SH group, the dynamics of the septal wall and the free wall were almost the same as those of the control group. On the other hand, the ASH group rather resembled the HCM group in the thickness and dynamics of the septal wall and the free wall as well as in the septal configuration. The most characteristic difference of the ASH and HCM groups from the SH group was in the significantly greater thickness of the septal wall at end diastole. However, in view of the developmental mechanism of hypertensive heart, it is interesting to note that the more the septal-free wall ratio increases, the more the thickness of the septal wall increases in the SH group.

Adult↗

Mitral valve prolapse syndrome with early diastolic click.

An instance of mitral valve prolapse syndrome demonstrating early diastolic click was reported. From the phonographic analysis of the cardiac sounds with simultaneous recording of apexcardiogram or echocardiogram, the production mechanism of the diastolic click was discussed.

Adult↗

Relation between spinal cord and epidural blood flow.

To test applicability of monitoring regional spinal cord blood flow by measuring regional epidural blood flow, both were simultaneously measured by the hydrogen clearance method in response to changes in PaCO2 and mean arterial blood pressure in rats anesthetized with pentobarbital. An excellent correlation was found between regional spinal and epidural blood flow over a physiological range of PaCO2 (27.8-66.7 torr) and blood pressure (30-130 torr), while a poor correlation was demonstrated between regional spinal or epidural blood flow and regional muscle blood flow in response to these same physiological parameters. Moreover, the rates of change in regional spinal and epidural blood flows were almost the same in response to both PaCO2 and blood pressure. These results suggest that both regional spinal and epidural blood flow are regulated by a similar mechanism and suggest that regional spinal cord blood flow can be monitored by regional epidural blood flow.

Animals↗