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Biomedical subjects

S Kasakura

Publications and source records attributed to S Kasakura.

At least 19 recordsLinked to original sources

Breakdown of self-tolerance by intrathymic injection of a T-cell line inducing autoimmune gastritis in mice.

Autoimmune gastritis (AIG) develops spontaneously in BALB/c mice thymectomized 3 days after birth (3d-Tx). We first confirmed our previous observations that CD4+ splenic T cells in AIG mice induced AIG in nu/nu mice, while those in normal mice suppressed the development of the disease. In addition, we found that a quantitative balance between these effector (Te) and suppressor (Ts) T cells determined either onset or prevention of the disease. Peripheralization of Ts seemed to begin around 3 days after birth, since the incidence of AIG in mice that underwent Tx 6 days after birth (6d-Tx) decreased markedly, compared with that of 3d-Tx mice; 12% in the former, while 79% in the latter. Notably, Ts existed in the 6d-Tx mice that escaped AIG. We next examined the target specificity of such Ts using syngeneic parietal cells known as autoantigens and two kinds of T-cell lines established from an AIG mouse; one is gastritis inducible in vivo, termed A-II, while another is not, named AC-II. Intrathymic injection of parietal cells into mice 3 days after birth followed by 6d-Tx completely prevented the development of AIG. In contrast, injection of irradiated A-II, but not AC-II cells resulted in AIG in 67% of the mice. No autoimmune oophoritis (AIO) was induced in female mice, implying that the breakdown of tolerance is organ specific. Taken together, peripheral tolerance for organ-specific autoantigens seems to be maintained by CD4+ Ts responding to Te, which induces the disease.

Animals

Des-gamma-carboxy prothrombin (PIVKA-II) and alpha-fetoprotein-producing IIc-type early gastric cancer.

We describe the case of a 56-yr-old man with primary gastric adenocarcinoma, who had an extremely high plasma level of des-gamma-carboxy prothrombin (2.45 AU/ml) and of serum alpha-fetoprotein (2810 ng/ml). Histopathologically, the gastric cancer was a IIc type of early cancer which consisted of a combination of a poorly differentiated adenocarcinoma and a well-differentiated tubular adenocarcinoma. The association of a hepatic tumor including hepatocellular carcinoma or liver metastasis was ruled out by ultrasonography, computed tomography, radiocolloid liver scan, magnetic resonance imaging, and angiography. Foci strongly resembling hepatocellular carcinoma (hepatoid differentiation) were noted in the gastric tumor. Localization of des-gamma-carboxy prothrombin and alpha-fetoprotein within the tumor cells, especially within the hepatoid differentiated foci, was demonstrated by the immunohistochemical staining of tissue obtained at biopsy and the resected specimen. This case seems to be the first case reported in which des-gamma-carboxy prothrombin was produced by the gastric cancer. This finding supports the theory of hepatoid differentiation of a gastric cancer.

Adenocarcinoma

[Study for the nature of interfering substances responsible for non-specific reactive phenomena occurred occasionally in EIA determination of CA125].

We studied the nature of IgM-like protein responsible for non-specific reactive phenomena occurred occasionally in EIA determination of CA125. We isolated highly purified IgM-like protein from two patients with non-specifically high CA125 serum values in affinity high performance liquid chromatography (HPLC) using anti-human IgM antibody-TSKgel Tresy15PW column. The isolated IgM-like protein possessed CA125 activity determined in EIA method. SDS-PAGE profiles of this isolated IgM-like protein were compatible with that of normal human IgM, and were distinct from those of CA125 antigen. Moreover, we ruled out the possibility that the Fc region of anti-CA125 monoclonal antibody might be responsible for the non-specific reactive phenomena. Thus, the data obtained from the present study indicate that the IgM-like protein is an anti-idiotypic antibody against the anti-CA125 monoclonal antibody (OC125).

Antibodies, Anti-Idiotypic

[Studies on a serum factor inhibiting lactate dehydrogenase (LDH) activity in a patient's serum].

We found extremely low activity of serum lactate dehydrogenase (LDH, EC. 1.1.1.27) in a 70-year-old female patient. The decrease of LDH activity was observed when the normal serum was incubated with the patient's serum. Inhibition rate of LDH activity by the patient's serum was higher at 4 degrees C than at 37 degrees C. The patient's serum inhibited both subunits of LDH, and inhibited more strongly the M-subunit than the H-subunit LDH isoenzymes. IgG (lambda type) in the patient's serum was found to be responsible for the inhibition of LDH activity. The mechanism why IgG inhibiting LDH activity developed in the patient's serum remain undetermined.

Aged

[Typing of methicillin-resistant Staphylococcus aureus by antibiotic resistance phenotypes as an epidemiological marker in nosocomial infections].

A total of 129 clinical isolates of methicillin-resistant Staphylococcus aureus was tested for the susceptibility to 28 antibiotics, antiseptics and heavy metal salts, according to the method of Gillespie et al. The strains showed resistance ranging from 20% to 80%, to 10 agents, such as amikacin, chloramphenicol, clindamycin, gentamicin, neomycin, streptomycin, tobramycin, acriflavine, cadmium nitrate, ethidium bromide. These agents were finally chosen for typing in this study. Strains resistant to 10 agents were distributed into 55 phenotypes. Most strains isolated from one ward belonged to the specified phenotype, whereas strains isolated from other wards were divided into a variety of phenotypes. It seemed to be the occurrence of nosocomial infection in this hospital. This typing method gives the merit to be easy, economical, rapid and reproducible for the epidemiological investigations in the clinical bacteriological laboratory.

Anti-Bacterial Agents

[Cytokines].

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C-Reactive Protein

[Demonstration of PIVKA-II and AFP production by gastric cancer by indirect immunoenzymatic staining of paraffin sections].

The patient had elevated plasma PIVKA-II and serum AFP levels. However, no tumor was detected with an ultrasonography, angiography, abdominal computed tomography (CT), and magnetic resonance imaging (MR). Gastric endoscopic examination disclosed gastric cancer and then subtotal gastrectomy was done. Shortly after the surgery, both plasma PIVKA-II and serum AFP levels returned to each normal level. The extirpated tumor revealed histologically immature and mature cancer cells. It was pathologically diagnosed as IIc early cancer. The localization of PIVKA-II and AFP in gastric cancer cells was demonstrated by the immunostaining method using monoclonal antibody. Taken together, these results indicate that cancer cells may produce PIVKA-II or AFP in this patient.

Biomarkers

[Plasma PAI-1 levels in patients with various tumors with or without metastasis].

Recently, much interest has focussed on fibrinolysis in malignant tumors. In our previous study, we showed that t-PA antigen was significantly increased in plasma from patients with malignant tumors with metastasis. In our present study, we measured plasminogen activator inhibitor-1 (PAI-1) levels in plasmas from patients with various tumors. PAI-1 antigen was measured by means of enzyme immuno assay in plasma from 64 consecutive patients with a variety of malignant tumors. Patients were subdivided into two groups, one with (n = 47) and without (n = 17) metastasis. In the group with metastasis except for lung cancer, PAI-1 antigen level was increased compared to age-matched control subjects, while in the group without metastasis, PAI-1 antigen level was normal.

Adult

[Early diagnosis of acute myocardial infarction by an immunoinhibition method for analysis of creatine kinase isoforms].

Conventional isoenzyme and enzyme values in serum usually are normal during the first few hours of acute myocardial infarction (AMI). Thus definitive diagnosis may be delayed. Measurement of serum creatine kinase (CK) isoform has begun to attract attention. In this study, we measured CK isoform with an immunoinhibition method in the first available samples from patients with AMI and from healthy subjects. In the 394 healthy subjects, the mean ratio of MM3 to MM1 of CK isoform was 0.494 +/- 0.1495 (SD). The upper limit of the reference values for this ratio was considered to be 0.793 (mean + 2 SD). In 40 of 48 patients, this ratio in the first available samples from patients with AMI was greater than 0.793. In 15 of 20 patients whose total CK activity was less than 260 IU/l, this ratio was greater than 0.793, while CK-MB activity measured with the immunoinhibition method was well within the reference range in all of these patients. Our results show that in the first available samples from patients with AMI, measurement of the ratio of MM3 to MM1 of CK isoform has the highest diagnostic efficiency. Thus, measurement of CK isoform with the immunoinhibition method can be applied for early diagnosis of AMI.

Creatine Kinase

Studies on T-lineage cells in human decidua of first trimester pregnancies.

T-lineage cells in human decidua of early pregnancies were tested for surface markers, proliferative response, interleukin-2 (IL-2) production, and natural killer (NK) activity. T-lineage (CD2+) cells that were obtained from decidua by the use of E-rosette formation contained fewer CD3+ mature T cells and CD4+ cells than those from the peripheral blood of the same donors, while no differences were seen in the frequencies of CD8+ cells. P55 molecules of IL-2 receptor (IL-2R/p55, Tac antigen) were hardly detected on fresh decidual T-lineage cells, though approximately 20% were positive for HLA-DR. More than a half of decidual T-lineage cells expressed CD56 molecules on their surface and killed K562 cells, the prototype target of NK cells, while most of them were negative for CD16 and CD57. Upon stimulation with IL-2, decidual T-lineage cells demonstrated dose-dependent proliferative response. In addition, they were induced to produce high amounts of IL-2 by stimulation with mitogens but not with alloantigens. These results suggest that human decidua contains high numbers of CD2+3-CD16 +/- 56+ lymphocytes and that this population responds to IL-2, produces IL-2 and mediates NK activity.

Decidua

[Study of non specific reactive phenomena in EIA method of CA 125].

We studied the false positive phenomena in immunoassay of CA 125 using mouse monoclonal antibody, and studied the natures of interfering substances. The serum CA 125 level in 405 patients was determined simultaneously by using the EIA and RIA methods. The overall correlation was good between CA 125 levels of the EIA and RIA methods. However, CA 125 levels in 41 cases were remarkably higher in the EIA method as compared with the RIA method. None of these patients had any disease that was known to result in elevation of the serum CA 125 level. The CA 125 activity of sera from five patients with remarkably discrepant values was contained in the column fractions corresponding to a molecular weight of human IgM in gel chromatography of TSK gel G 4000 SWXL that was smaller than the molecular weight of CA 125. To further determine whether IgM was involved in the CA 125 activity, we investigated the effect of adding anti-human IgM serum to discrepant sera. CA 125 activity was markedly reduced by the antiserum, whereas CA 125 activity in non-discrepant sera were not effected by this antiserum. Thus, data obtained from this group of experiments indicate that the interfering material in discrepant serum is IgM.

Antibodies, Monoclonal

[Role of PMN elastase in fibrinolytic activity in patients with acute promyelocytic leukemia].

In order to define a specific acceleration of fibrinolytic activity in acute promyelocytic leukemia (APL), we determined fibrinolytic factors in APL and acute myeloblastic leukemia (AML). An increase in plasma levels of D-dimer was observed in both APL and AML, indicating that there is an acceleration of fibrinolysis in both types of leukemia. The levels of D-dimer/FDP ratio were significantly lower in APL than AML. These findings suggest that fibrinogenolytic activities were higher in APL that in AML. The relationship between the plasma levels of plasmin alpha 2PI complex (PIC) and FDP was investigated to study whether fibrinolysis was induced by plasmin. PIC levels were linearly correlated with FDP levels in AML, while in APL there was no close correlation between the plasma levels of PIC and FDP. Then, we measured PMN elastase-alpha 1 proteinase inhibitor complex (E-alpha 1 PI). There was a correlation between the plasma levels of E-alpha 1PI and FDP in APL but not in AML. Furthermore, PMN elastase activity was detected in leukemic cell lysate in patients with APL but not in AML. These findings suggest that PMN elastase may be an important factor in the induction of fibrinolysis in APL.

Fibrinolysis

Cancer in myelodysplastic syndromes.

Fifty one patients with myelodysplastic syndromes (MDS) treated between September, 1985 and October, 1988 were retrospectively studied. The incidence of cancer was compared with that in the Cancer Registry population of Japan for the same age and sex distribution. In this series, 4 cancers were observed. The risk of cancers developing in patients with MDS was 4.65 times that for an age- and sex-matched population.

Aged

Source of increased plasminogen activators during pregnancy and puerperium.

We investigated the increase of plasminogen activators (tPA and uPA) in the plasma during pregnancy. Both tPA and uPA antigens were found to increase after the third trimester of pregnancy and high levels of PAs persisted through the first stage of labor. The tPA antigen levels rose further for the first few hours post-partum, while the level of uPA antigen returned to normal immediately following childbirth. To clarify whether the uterus and/or placenta are involved in the increased levels of plasma PAs, the levels were measured in uterine venous blood in cases of caesarean sections. During the ante-partum period, the level of uPA antigen in the uterine venous blood was higher than that in the peripheral venous blood, while there was no significant difference between the levels of tPA antigen in peripheral blood and uterine venous blood. The level of tPA antigen in the uterine venous blood rose after delivery. In contrast, the level of uPA antigen declined immediately after delivery. These results suggest that (1) the placenta is the major source of the increased uPA antigen during pregnancy, (2) entire vascular system is involved in the increased tPA antigen during pregnancy, (3) a further increase in tPA after delivery is due to the release of this enzyme from the involuting uterus.

Antigens

Detection of immunoregulatory factors in retroplacental serum in human pregnancy.

Retroplacental serum (RPS) obtained from pregnant women at term deliveries was studied for regulatory effects on T-lymphocyte proliferation and for pregnancy-associated substances and compared with peripheral serum (PS) of the same donor. Proliferative response to phytohemagglutinin and alloantigens in RPS was lower than that in PS. RPS contained higher levels of human placental lactogen, progesterone, estradiol, and prostaglandin E2 than of PS. However, there were no differences in concentrations of pregnancy-associated alpha 2-glycoprotein, pregnancy-specific beta 1-glycoprotein, prostaglandin F2 alpha, alpha-fetoprotein, human chorionic gonadotropin, cortisol, carcinoembryonic antigen, and immunoglobulins between RPS and PS. The amounts of human placental lactogen, progesterone, or prostaglandin E2 seen in RPS did not inhibit T-cell proliferation. Mixtures of various doses of these three substances were still not inhibitory. Thus, the suppressive activity of RPS could not be explained by these pregnancy-associated substances, but a possible involvement of unknown immunoregulatory factors at fetomaternal interface might be suggested.

Dinoprostone

Immunodeficiency associated with selective loss of helper/inducer T cells and hypogammaglobulinaemia in a child with intestinal lymphangiectasia.

A patient with intestinal lymphangiectasia (IL) was studied for his immunological abnormalities. The patient had hypoproteinaemia with severe hypogammaglobulinaemia. The results of lymphocyte subpopulation studies revealed a decrease of CD4+ cells and a decrease of surface immunoglobulin (sIg)-positive B lymphocytes. T cell functions determined by the proliferative responses against Concanavalin A (Con A) or phytohaemagglutinin (PHA) and by delayed type cutaneous hypersensitivity (DTH) response to purified protein derivatives (PPD) and PHA were normal. No immunoglobulin (Ig)-secreting cells were induced when his peripheral blood lymphocytes (PBL) were cultured with pokeweed mitogen (PWM). His T cells showed suppressor function to the PWM-induced differentiation of normal B cells. This suppressor activity was sensitive to 3000 rads irradiation. His B cells also failed to differentiate into Ig-producing cells with the help of normal T cells and PWM. Thus, in this patient, the decrease of Ig-synthesis in vitro could be attributed to suppressor T cells, lack of T helper cells and an intrinsic B cell defect. Therefore, this patient appears to have immunological abnormalities which differ from previously reported IL patients.

Agammaglobulinemia