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Biomedical subjects

Y Kawase

Publications and source records attributed to Y Kawase.

At least 109 records · Page 6Linked to original sources
PubMed1989

Effects of cyclosporine A on thymocyte differentiation in fetal thymus organ culture.

During the course of differentiation in the thymus, precursor T cells are negatively selected by a self-tolerance mechanism or positively selected to acquire restriction specificity to self major histocompatibility complexes. We investigated the process of T cell differentiation and those selections using a fetal thymus organ culture with or without cyclosporine A. The agent blocked the maturation step from CD4+8+ double positive cells to mature CD4-8+ or CD4+8- single positive cells. On the other hand, the agent did not inhibit the development of CD3+4-8- T cell receptor (TCR)alpha beta- cells, which were supposed to be T cells bearing gamma delta-TCR chains. These results suggest that the development of thymocytes bearing alpha beta- or gamma delta-TCR chains differ in requirement for thymocyte-stromal cell interaction.

Animals↗
PubMed1989

Hereditary macular dystrophy without visible fundus abnormality.

We found an unusual form of macular dystrophy in three patients from two generations of the same family. The fundi of these patients appeared normal by ophthalmoscopy and fluorescein angiography, even in an older patient and in patients with poor visual acuity. Results of full-field electroretinograms were also normal in both cone and rod components. Focal macular electroretinograms were severely affected, however, indicating retinal impairment in the macular region. Results of Tübingen perimetry were consistent with electroretinographic findings. Since the condition was progressive, this disease is thought to be a hereditary macular dystrophy without visible fundus abnormality.

Adult↗
PubMed1989

Destruction of pancreatic islet cells by cytotoxic T lymphocytes in nonobese diabetic mice.

Proliferation of islet-associated leukocytes occurred when isolated islets from 20-wk-old female nonobese diabetic (NOD) mice were cultured with 10 U/ml rIL-2 for 7 days. Co-culture of these leukocytes with freshly isolated islets from 6- to 8-wk-old NOD donors in the presence of 1 U/ml rIL-2 produced islet structural deformation within 24 h and islet cytolysis within 48 h. Three lines of evidence suggest that these leukocytes were composed mainly of CTL specific for islet cells. First, morphologically, these proliferating cells adhered to NOD islets at 6 h and killed islets within 48 h of culture, but these phenomena could not be observed in the other tissues from NOD mice. These islet-derived cells were cytotoxic to NOD islet cells in a 51Cr-release assay, whereas no appreciable cytotoxicity was observed when NOD Con A-induced splenic blasts or fibroblasts were used as targets. Second, a flow cytometric analysis showed that these cells consisted of 97% Thy-1.2, 69% Lyt-2, 8% L3T4, and 4% asialo-GM1-positive cells, whereas Mac-1-positive cells could not be seen in these assays. After treatment with anti-Thy-1.2 or Lyt-2 mAb and C, these cells lost their activity to lyse NOD islet cells. However, these cells still had a full killing activity after the depletion of L3T4 or asialo GM1-positive cells. Third, islet cells from BALB/c, DBA/2, and B10.GD mice which share the same H-2K Ag with NOD mice were susceptible to cytolytic activity of these cells, whereas islet cells from NON, C57BL/6, C57BL/10, and C3H mice remained intact. Furthermore, anti-Kd antibody was capable of blocking this cytolysis. These results suggest that CTL expressing Thy-1.2 and Lyt-2 phenotypes appear to recognize the islet cell Ag with the restriction of MHC class I Kd, and then destroy NOD islet cells.

Animals↗
PubMed1989

[Cellular immune dysfunction in the NOD mouse: suppression of concanavalin A-induced responses in spleen cells by activated macrophages].

It is generally accepted that T lymphocyte-mediated autoimmunity contributes to the pathogenesis of Type 1 diabetes in humans and animals. Using spleen cells from nonobese diabetic (NOD) mice, a model of human Type 1 diabetes, we have analyzed the subset of T lymphocytes by flow cytometry and investigated concanavalin A (Con A)-induced interleukin 2 (IL-2) production and cell proliferation. NOD mice showed a higher percentage of Thy1.2+, L3T4+, and Lyt2+ T lymphocytes than did control ICR mice through the whole age examined. Spleen cells from a large majority of NOD mice were found to generate very low IL-2 production and cell proliferation in response to Con A. However, a few mice preserved their responsiveness to Con A. The following reasons may indicate that macrophage-mediated suppression participates in the deficient function of NOD spleen cells. (a) Macrophage depletion from NOD spleen cells retrieved Con A-induced IL-2 production. (b) Thioglycollate-induced peritoneal exudate cells containing many activated macrophages could completely suppress cell proliferation. (c) Prostaglandin synthetase inhibitor indomethacin reversed the suppression of IL-2 production by macrophages. (d) Conversely, exogenous prostaglandins could show the partial suppression of IL-2 production. These results suggest that activated macrophages suppress the response of NOD spleen cells to Con A mostly through prostaglandins. This impairment may contribute to the pathogenesis of Type 1 diabetes in NOD mice.

Animals↗
PubMed1989

Suppressor T-cell abnormality in NOD mice before onset of diabetes.

To investigate the pathological role of suppressor T-cells in non-obese diabetic (NOD) mice, we stimulated splenic T-lymphocytes from diabetes-prone NOD mice with concanavalin A (ConA) and then evaluated their ability to suppress the lymphocyte-proliferative responses to mitogen and allogenic cells. Lymphocytes from NOD mice showed significantly less suppressor ability than did those from BALB/c mice and non-obese non-diabetic (NON) mice, the corresponding non-diabetic sister strain of the NOD mouse, both in the mitogen response and in the mixed lymphocyte reaction (MLR). We used monoclonal antibodies and flow cytometry to analyze the lymphocytic surface phenotypes, and found markedly fewer Lyt2+ T-lymphocytes (suppressor/cytotoxic T-lymphocyte) in the NOD mice than in both controls after exposure to ConA. These results suggest that suppressor T-cell activity is already depressed in NOD mice before diabetes begins and that a substantial decrease in the number of suppressor T-cells induced by ConA may explain this depressed suppressor activity. This impairment may contribute to the pathogenesis of type 1 diabetes in NOD mice.

Animals↗
PubMed1989

Split tolerance in nude mice transplanted with 2'-deoxyguanosine-treated allogeneic thymus lobes.

To elucidate the acquisition of self tolerance in the thymus, full-allogeneic thymic chimeras were constructed. Athymic C3H and BALB/c nude mice were reconstituted with the thymic lobes of BALB/c and B10.BR fetuses, respectively, that were organ cultured for 5 days in the presence of 2'-deoxyguanosine. T cells in these chimeras were tolerized to the host MHC in both MLR and CTL assays. In contrast, T cells in the chimeras exhibited split tolerance for the thymic MHC haplotype. CTL specific for class I MHC of the thymic haplotype were generated not only from the peripheral T cells of the chimeras but also from thymocytes re-populated in the engrafted thymic lobes. However, T cells in these chimeras responded poorly to the class II MHC of the thymic haplotype in a standard MLR assay. In a syngeneic MLR culture upon stimulation with enriched APC of the thymic haplotype, only 22 to 48% of the responses were mediated by CD4+ cells, and proliferations of CD4- cells were prominent. There were no haplotype-specific suppressor cells detected which would cause the unresponsiveness to the thymic class II MHC. These results indicated that the thymic lobes treated with 2'-deoxyguanosine were defective in the ability to induce the transplantation tolerance for the class I MHC expressed on the thymus, although the same thymic lobes were able to induce the transplantation tolerance for the thymic class II MHC.

Animals↗
PubMed1989

[Ultrasonographic diagnosis of mild fatty infiltration of the liver with the difference between liver and kidney echolevels].

At the same dynamic range (DR) a constant difference of echolevels was found between two materials with different acoustic impedance in any gain-setting by the phantom study. Our retrospective study in which we compared the difference between liver-kidney echolevels with the US-findings of fatty liver indicated that the difference over 10 in echoleveled by our equipment with 3.5 MHz phased array sector scan and 42 dB DR had a possibility of the fatty infiltration of the live. In our prospective study of 1452 abdominal US-studies we found 93 cases (6.5%) with the difference over 10 in echolevel. In all these patients the difference of liver-spleen CT-numbers and liver-kidney echolevels was compared. Although the liver CT-number is normally higher than the spleen, 75 of 93 patients showed the lower liver CT-number than that of the spleen, indicating fatty infiltration of the liver. The abnormal difference of echolevels were independent from the severity of fatty infiltration. Concerning the US-findings, "bright liver" (77.4%) and "masking sign" (66.7%) were more sensitive than "vascular blurring" (44.1%) and "deep attenuation" (44.1%). But for the severe fatty infiltration with the difference over -20 H.U. between liver-spleen CT numbers, the last two findings seemed very credible. The abnormal difference between liver-kidney echolevels was most sensitive (80.7%), especially in mild cases with 0 to -19 H.U. (53 in 75 cases), and very objective than the other US-findings.

Fatty Liver↗
PubMed1989

Tolerance induction in the organ-cultured thymus lobes upon intimate contact with allogeneic thymus lobes.

In an organ-cultured murine fetus thymus, precursor cytotoxic T lymphocytes (pCTL) specific for alloantigens developed successfully but those reactive with self antigens were eliminated. In attempting to dissect the mechanism of self tolerance, intrathymic chimera was made by culturing two genetically disparate thymuses in close contact with each other (parabiosis of thymuses). This maneuver resulted in the induction of specific and mutual CTL tolerance. It seems that CTL tolerance was induced by clonal deletion but not by active suppression. Since 2'-deoxyguanosine treatment abolished the tolerogenic capability of the thymus, hemopoietic cells capable of migrating to and fro in the parabiotic thymuses are thought to be responsible for tolerance induction. Induction of CTL tolerance was dependent on the maturation stages of T cells in the thymus: T cells in 5-day-, but not in 7-day-cultured thymuses were susceptible to tolerance induction, indicating that T cells expressing T cell receptors at low density are susceptible to tolerance induction.

Age Factors↗
PubMed1989

Suppression of concanavalin A-induced responses in splenic lymphocytes by activated macrophages in the non-obese diabetic mouse.

Spleen cells from non-obese diabetic mice were found to generate low interleukin 2 production and cell proliferation in response to concanavalin A. However, some of non-obese diabetic mice maintained in the same environment preserved their responsiveness to this T cell mitogen. Non-obese diabetic mice at every age had a higher percentage of Thyl.2, L3T4, and Lyt2-positive spleen cells than did control mice, suggesting that the dysfunction of spleen cells did not depend on the number of T cells or the ratio of these subpopulations. Evidence for macrophage-mediated suppression participating in the deficient function of splenic lymphocytes in this mouse model of insulin-dependent diabetes includes: 1) the restoration of mitogen-induced interleukin 2 production after the macrophages have been depleted by silica absorption form spleen cells; 2) the complete suppression of the cell proliferation by thioglycollate-stimulated peritoneal exudate cells from non-obese diabetic and control mice, and the partial suppression by spleen macrophages from non-obese diabetic mice; 3) the reversal of the suppression of interleukin 2 production by the prostaglandin synthetase inhibitor indomethacin (0.1-1 microgram/ml); 4) the partial suppression of interleukin 2 production, conversely, by the exogenous prostaglandins E1 and E2 (2.5 x 10(-6) mol/l). These results indicate that the activated macrophages existing among the spleen cells suppress the response of splenic T cells to concanavalin A. This impairment may contribute to the pathogenesis of insulin-dependent diabetes in non-obese diabetic mice.

Aging↗
PubMed1989

A kinetic study on secretion and elimination of endogenous thyrotropin in the thyrotropin-releasing hormone test.

Serum thyrotropin (TSH) concentrations in normal young men were measured by a high-sensitivity immunoradiometric assay before and after intravenous administration of 500 micrograms of TSH-releasing hormone (TRH). A kinetic model was applied to evaluate the secretion rate both before (V0) and after (V0 + V* at maximum rate) the administration of TRH, the elimination constant (K), the latent time (L) between TRH administration and start of the stimulated secretion, and the total amount of TSH (T) released in response to TRH. V0, V* and T varied widely from individual to individual, but correlated well with TSH before TRH administration (r = 0.93, 0.80 and 0.87, respectively). A few minutes (1.89 +/- 1.30 min) after the administration of TRH, the secretion of TSH (0.025 +/- 0.016 microU/min ml) was stimulated, and the total release over about 1 h was 12.5 +/- 5.6 microU/ml. Serum TSH was maximum at 31.5 +/- 5.7 min. The half-time of disappearance of TSH was 42 +/- 9 min. These data confirm that the stimulated secretion continues for more than 30 min, and that the pituitary releases 43.2 +/- 22.9 mU of TSH (assuming the distribution volume of TSH is 5.8% of body weight) in response to TRH, an amount which correlates closely (r = 0.91) with TSH before TRH administration.

Adult↗
PubMed1989

Biological properties of an initial degradation product of insulin by insulin-degrading enzyme.

We previously reported on the degradation of monocomponent porcine insulin by affinity-purified pig skeletal muscle insulin-degrading enzyme (IDE) and on the detection and HPLC separation of the initial degradation product (peak VI). Using relatively high concentration of insulin, peak VI appeared rapidly at 30 sec of incubation, whereas other peaks were not detected within 5 min of incubation. Performate oxidation studies suggested that peak VI is composed of a cleaved A-chain and an intact B-chain. To assess whether the initial degradation product of insulin generated by IDE preserves biological properties, we analyzed several insulin-like activities of peak VI. It had a hypoglycemic effect on rats. In vitro, it bound to the insulin receptors of rat adipocytes and stimulated glucose oxidation there. It also strengthened insulin receptor kinase activity in insulin receptors from rat liver and human placenta. Its biological potency, however, was 1/40th to 1/160th that of insulin itself. This is probably due to reduced affinity for the insulin receptor, since it had 2.5% of insulin's ability to both bind to the receptor and stimulate glucose oxidation. Moreover, peak VI had all of insulin's agonistic effect on glucose oxidation when used at a higher concentration. On the other hand, cross-linking analysis suggested that peak VI preserves almost the same affinity for IDE as does insulin. These results suggest that pig skeletal muscle IDE may cleave peptide bonds within the A-chain early in insulin degradation, generating peak VI; this then serves as the next substrate of IDE while exerting reduced insulin-like activity, and peak VI is converted to several relatively low mol wt products.

Adipose Tissue↗
PubMed1989

The complement system in the acute phase of myocardial infarction.

Although some studies suggest that complement activation is involved in the development of acute myocardial infarction, there has been little convincing evidence of a change in the complement system in patients suffering from myocardial infarction. In this study circulating levels of C3a, C3, C4 and the total hemolytic complement titer (CH50) were serially measured in 12 patients with acute myocardial infarction up to 10 days after an attack. The plasma C3a level was greatly elevated throughout the post-attack observation period. The C3, C4 and CH50 levels were significantly increased above those controls on days 8, 9 and 10 after infarction. These findings indicate that there is complement activation in patients with acute myocardial infarction, and suggest a pathogenetic role for complement activation in the development of myocardial damage after infarction.

Acute-Phase Reaction↗
PubMed1989

Multiple myeloma in alcoholic liver cirrhosis.

A case of multiple myeloma (Bence Jones, lambda) associated with alcoholic liver cirrhosis is reported. A 56-year-old Japanese male died of hepatic failure and hypercalcemia. Autopsy revealed alcoholic liver cirrhosis and plasma cell myeloma. Immunoelectrophoretic analysis of his reserved serum disclosed the presence of M component of lambda Bence Jones protein. IgA and lambda light chain were demonstrated in the cytoplasm of the myeloma cells. Complications such as generalized amyloidosis, metastatic calcification, myeloma kidney and hemorrhagic pancreatitis were noted. The coexistence of multiple myeloma and liver cirrhosis has rarely been reported. On the basis of a review of the reported cases, a possible association between both diseases was discussed.

Humans↗
PubMed1989

The role of the sympathetic nervous system in cysteamine-induced gastric lesions in rats.

Cysteamine.HCl, when administered subcutaneously at 350 mg/kg, consistently induced severe gastric lesions in Wistar Kyoto rats (WKY), but not in spontaneously hypertensive rats (SHR). In both WKY and SHR, visible ulcers could not be induced in the duodenum in response to cysteamine. It appears that the stomach and duodenum of SHR are resistant to cysteamine due to hyperfunctioning of the sympathetic nervous system.

Animals↗
PubMed1989

[Female urethral diverticulum calculi: a case report].

A case of urethral diverticulum with calculus in a 53-year-old woman is reported. She was admitted to Isahaya General Hospital complaining of a localized swelling in the external genitalia. We found a urethral diverticular calculi by urethrography. Urethral diverticulectomy was carried out without any complications. The removed stones were in 2 pieces and they were composed of calcium phosphate and ammonium urate.

Diverticulum↗