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Biomedical subjects

H Seki

Publications and source records attributed to H Seki.

At least 271 records · Page 15Linked to original sources

Some evidence for the in vivo functional activation of suppressor T cells in asymptomatic patients with hemophilia A receiving Factor VIII concentrates.

Of 14 asymptomatic hemophilia A patients receiving factor VIII concentrates, 11 severe hemophilia patients had an inverted T-helper/suppressor ratio but 3 moderate patients had a normal ratio. Most hemophilia patients showed poor lymphocyte proliferative responses to mitogens and diminished in vitro immunoglobulin-producing ability of lymphocytes. One important finding was that most patients were found to have increased numbers of Ia-like antigen-positive suppressor T cells, suggesting that circulation activated suppressor T cells. In addition, OKT8+ suppressor T cells from severe hemophilia patients showed strong suppressor activity on B-cell differentiation in a Nocardia delipidated cell mitogen-driven system, whereas those from normal age-matched controls showed no suppressor function. These results suggested that suppressor T cells in hemophilia patients treated with factors might be already activated in vivo by undetermined mechanisms, implying the presence of a peculiar immunoregulatory status in this disease.

Adolescent↗

Impaired natural killer cell activity in Bloom's syndrome could be restored by human recombinant IL-2 in vitro.

Natural killer (NK) activity against K562 tumor cells was evaluated in peripheral blood nonadherent mononuclear cells (PBMNC) obtained from four patients with Bloom's syndrome. NK activity of PBMNC from all patients was found to be depressed to less than half of age-matched control values. However, all patients showed the normal percentages of large granular lymphocytes and of cells expressing the NK-cell-associated determinants (OKM1, Leu-7, and Leu-11). Although recombinant interferon-beta or -gamma augmented NK activity of patients' PBMNC in a manner similar to their effects on NK activity of normal individuals, impaired NK activity of PBMNC from Bloom's patients could be restored to normal ranges only by recombinant interleukin 2 (IL-2). These results suggested that IL-2 and interferons might participate in boosting NK activity of Bloom's syndrome in different ways.

Adolescent↗

Unilateral hydrocephalus combined with occlusion of the ipsilateral internal carotid artery.

The authors encountered a rare case of a patient who developed a mild hemiparesis on the right side at age 8 months with marked enlargement of the left lateral ventricle and occlusion of the ipsilateral internal carotid artery. In computed tomography scans and nuclear magnetic resonance scans 8 years after an operation to install a ventricular shunt, there was marked enlargement of the left lateral ventricle and almost no left basal ganglion. In this case, the differentiation between hydranencephaly and severe hydrocephalus presented a problem because no biopsy had been performed. Diagnosis was difficult, but it appeared that occlusion of the ipsilateral internal carotid artery played a major role.

Arterial Occlusive Diseases↗

Use of balloon occlusion and substances to protect ischemic brain during resection of posterior fossa AVM. Case report.

The successful resection of a large posterior fossa arteriovenous malformation (AVM) is reported. A balloon catheter was used for temporary intraoperative occlusion of the basilar artery and feeding vessels of the AVM. Prior to occlusion of these arteries, newly tested substances to protect the ischemic brain were administered to prolong occlusion time. Resection of the AVM was completed without complication, and the patient returned to normal life. This is a useful intraoperative procedure for the resection of AVM's considered inoperable by conventional approaches.

Adolescent↗

[Preclinical and clinical studies on aztreonam in obstetrics and gynecology].

Aztreonam (AZT), a new monobactam antibiotic, was studied in obstetrics and gynecology with the following results. The tissue concentration of AZT in the female genital organs was relatively high at the portio vaginalis and the cervix uteri followed by at the ovary and the myometrium, but the distribution to the endometrium and the oviduct was a little poor. The concentration of AZT in the pelvic dead space exudate was highest at 2 hours after intravenous injection whereas it was highest at 5 hours after intravenous drip infusion. However, there was no significant difference in the concentration between intravenous injection and intravenous drip infusion and the distribution to the pelvic dead space exudate was relatively good. AZT was clinically administered to pyometra (3 cases), puerperal endometritis (3), adnexitis and endometritis (3), pelvioperitonitis (1), Bartholin's abscess (4) and purulent vulvitis (1), a total of 15 cases with an overall effective rate of 93.3%. AZT was microbiologically effective for Gram-negative bacteria such as E. coli and K. pneumoniae, but also effective for anaerobes and some Gram-positive bacteria, etc., for which MIC of AZT is high. With regard to safety of AZT, neither side effects nor abnormal laboratory findings were reported.

Adult↗

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↗

Treatment of multiple sclerosis with anti-measles cow colostrum.

Previous virological and immunological studies have suggested that multiple sclerosis (MS) is an auto-immune disease triggered by a virus infection. In order to inhibit the growth of measles virus in the patient's jejunum, we obtained an IgA-rich cow colostrum containing anti-measles lactoglobulin resistant to proteases. This colostrum was orally administered to patients with MS to investigate its effect on the course of the disease. Measles-positive antibody colostrum was orally administered every morning to 15 patients with MS at a daily dosage of 100 ml for 30 days. Similarly, measles-negative antibody (less than 8) control colostrum was orally administered to 5 patients. As a clinical assessment, disability scores developed by the International Federation of Multiple Sclerosis Societies were used. As a result, of 7 high NT titre (512-5120) anti-measles colostrum recipients 5 patients improved and 2 remained unchanged. Among 8 low NT titre (8-32) anti-measles colostrum recipients 5 patients improved and 3 remained unchanged. However, of 5 negative NT titre (less than 8) colostrum recipients 2 patients remained unchanged and 3 worsened. No side-effects were observed in colostrum recipients. These findings suggest the efficacy of orally administered anti-measles colostrum in improving the condition of MS patients (P less than 0.05).

Adolescent↗

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↗