Search PubMed⌕ Search

Biomedical subjects

K Tsuji

Publications and source records attributed to K Tsuji.

At least 397 records · Page 22Linked to original sources

Studies on antiinflammatory agents. II. Synthesis and pharmacological properties of 2'-(phenylthio)methanesulfonanilides and related derivatives.

The structure of the previously reported new antiinflammatory agent (1, FK3311) was chemically modified in an attempt to find novel compounds with more potent and broader-spectrum activities. Some 2'-(phenylthio) and 2'-(phenylamino)methanesulfonanilides (2 and 3), in particular those bearing an electron-attracting substituent at the 4'-position, potently inhibited adjuvant arthritis in rats as well as collagen-induced arthritis in mice when administered orally. 4'-Carbamoyl-2'-(2,4-difluorophenylthio)methanesulfonanilide (3b), which was selected as a candidate for further development from among the compounds synthesized herein, exhibited activity in reducing arthritis in a spontaneous autoimmune disease model (MRL/lpr mice) within the dose range of 10-100 mg/kg (p.o.).

Anilides↗

Circulating levels and bone contents of bone gamma-carboxyglutamic acid-containing protein in rat models of non-insulin-dependent diabetes mellitus.

In order to investigate the pathophysiology of the diabetic osteopenia observed in non-insulin-dependent diabetes mellitus, the circulating levels and the bone contents of bone gamma-carboxyglutamic acid-containing protein (osteocalcin) were determined in rat models of non-insulin-dependent diabetes mellitus, neonatally streptozotocin-induced rats and in genetic Wistar fatty rats. In Wistar fatty rats the plasma level of osteocalcin was 8.1 +/- 0.8 nmol/l, significantly lower than the value of 17.3 +/- 0.9 nmol/l in their lean littermates (p < 0.001). Bone length, bone strength, and weight of powdered bone in Wistar fatty rats were significantly decreased compared to control rats (p < 0.001, p < 0.02 and p < 0.001, respectively). Bone content of osteocalcin per femur in Wistar fatty rats was also significantly decreased compared to controls (p < 0.001). In addition, plasma osteocalcin in neonatally streptozotocin-induced diabetic rats was 2.9 +/- 0.3 nmol/l, which was also significantly decreased compared to the value of 5.6 +/- 0.5 nmol/l in their controls (p < 0.001). Since it has been established that the plasma level of osteocalcin is well related to bone formation and turnover, the low plasma values in these animal models suggest that bone formation and turnover are decreased in non-insulin-dependent diabetes mellitus. Low bone formation and turnover are, therefore, postulated to be one of the pathophysiological characteristics of the skeletal tissue in non-insulin-dependent diabetes mellitus, and to be at least in part responsible for the occurrence of this complication.

Animals↗

Intramural rupture of the esophagus: a rare complication associated with nasobiliary catheter placement.

Intramural rupture of the esophagus developed after short-term nasobiliary catheter placement in an 87-year-old female with choledocholithiasis and suppurative cholangitis. Endoscopy revealed bleeding accompanied by circumferential disruption of the mucosa along the lower third of the esophagus. Withdrawal of the catheter and conservative treatment resulted in recovery of the lesion and relief of symptoms. This rare complication should be kept in mind during the placement of nasobiliary catheter.

Aged↗

Protothecosis in a patient with systemic lupus erythematosus.

A rare case of protothecosis in a 40-year-old Japanese woman with systemic lupus erythematosus, under long-term prednisolone treatment is presented. The patient developed extensive ulcerative skin lesions after injury. The characteristic histopathological findings and biochemical sugar assimilation tests indicated infection by Prototheca wicherhamii. The lesions improved following treatment with amphotericin B. The immunodeficient state of this patient seemed to contribute to the infection with Prototheca.

Abscess↗

Association of HLA-A24 with complete beta-cell destruction in IDDM.

A sensitive C-peptide immunoreactivity radioimmunoassay demonstrated the presence of subtle, but definite residual beta-cell function in patients with IDDM of long duration. Although HLA antigens are known to influence susceptibility to IDDM, their contribution to the extent of pancreatic beta-cell destruction has not yet been examined extensively. We studied the relationship between residual beta-cell function and HLA class I and class II antigens in 111 unrelated Japanese IDDM patients. Using the sensitive C-peptide immunoreactivity radioimmunoassay, the presence or absence of residual beta-cell function was evaluated by the C-peptide immunoreactivity response to a 100-g oral glucose load. DNA typing for HLA-DQA1 and HLA-DQB1 antigens was performed in addition to serological typing of HLA-A, HLA-B, HLA-C, and HLA-DR antigens. A C-peptide immunoreactivity response > 0.033 nM was regarded as an indication of the presence of residual beta-cell function, not the assay error. Surprisingly, 35 of 37 (94.6%) patients without residual beta-cell function had HLA-A24, whereas only 39 of 74 (52.7%) patients with residual beta-cell function had this antigen (corrected P = 9.795 x 10(-6). Any other HLA antigens, including the DR and DQ loci, showed no difference in the frequency with regard to residual beta-cell function. The duration of diabetes was similar between the groups with and without residual beta-cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Peptidyl carbamates as novel elastase inhibitors: structure-activity relationship studies.

Twenty-six novel peptidyl carbamates and thiocarbamates were synthesized and evaluated as elastase inhibitors. Eighteen compounds inhibited porcine pancreatic elastase, whereas only eleven of the newly synthesized compounds inhibited human leukocyte elastase. Neither of the other serine dependent proteases, trypsin or chymotrypsin, were affected by any of the active inhibitors. Structure-activity relationship studies indicated that inhibition was dependent on P1 and P'1 substitution as well as on the presence of the carbamate functionality. Placement of an isostere of valine at P1 and a 1-(phenyl mercaptotetrazole at P'1 resulted in the most active human leukocyte elastase inhibitor within this series of compounds (Ki - 3.0 x 10(-7) M).

Amino Acid Sequence↗

Human space experiments in SL-J: preparation and conducted.

This experiment investigated how human beings achieve visual stability during body movements, including fine motion on the ground. When humans are exposed to an environment with different gravity vectors, the programmed behavior on the ground must be changed, that is, it is reprogrammed. This is called habituation or familiarization. This experiment focuses on visual, vestibular and somatosensory perception coordination and how it changes in microgravity as compared to a 1-G environment. We examined these issues under microgravity during the mission Spacelab Japan [correction of Japane] (SL-J) mission with the cooperation of the Japanese Payload Specialist (PS), Dr. Mohri. In this paper we describe how the first human life science experiments were conducted and how the data processed is being.

Adaptation, Physiological↗

Evaluation of prognoses of patients with gastric cancer by the responsiveness of peripheral blood lymphocyte to OK432 in vitro.

The response of peripheral blood lymphocytes to the streptococcal preparation OK432 was examined in vitro in 193 gastric cancer patients. When the patients were divided by stimulation index (SI) into two groups, SI > or = 20 and SI < 20, the response rate of SI > or = 20 group of stage IV was 37.5%, and higher than those of the other stages (p < 0.05). In the relationship between SI and the survival period in stage III, the SI > or = 20 group showed longer survival than the SI < 20 group (p < 0.05). There was no statistically significant difference in survival between SI > or = 20 and SI < 20 in stage IV, but no member of the SI < 20 group survived more than 2 years, whereas the five-year survival of the SI > or = 20 group was 38.9%. In the overall survival of stage III and IV, the SI > or = 20 group showed longer survival than the SI < 20 group (p = 0.001). The lymphoproliferative responses to OK432 decreased in very advanced gastric cancer patients and this might lead to poor prognosis.

Cell Division↗

CD7, CD4 and myeloid antigen-positive acute lymphoblastic leukemia.

We report a case of acute lymphoblastic leukemia (ALL, FAB-L2) with unique cellular characteristics. Leukemic cells were negative for various cytochemical stainings except acid phosphatase. Immunophenotypic studies revealed CD7+, CD4+, CD8-, CD2+, CD3-, CD13+, CD25+, CD33+ and CD34+. The immunoglobulin heavy chain and T-cell receptor beta, gamma and delta chain genes were germline configurations. This patient had a karyotype of complex abnormalities involving Nos. 5 and 7. Leukemic cells showed a prominent response to interleukin-3, granulocyte macrophage colony stimulating factor (GM-CSF) and G-CSF with partial granulocytic differentiation in a colony assay. A binding assay confirmed the presence of both high and low affinity receptors for GM-CSF. These findings suggest that CD7+CD4+CD8-CD3- putative T-cell precursors may retain the capacity to differentiate to myeloid lineage.

Antigens, CD↗

Clinical significance of serum soluble HLA class I antigens in systemic lupus erythematosus.

Serum soluble HLA (SHLA) class I antigens in patients with systemic lupus erythematosus (SLE) were examined by enzyme-linked immunosorbent assay. The primary antibody used was W6/32, anti-HLA class I mouse monoclonal antibody, and the secondary antibody was peroxidase-conjugated anti-mouse IgG antibody. The reactivity of SHLA class I antigens, the number of peripheral lymphocytes, and the clinical state of SLE were compared. The results were as follows; 1) Sixteen of 55 samples from SLE patients were SHLA class I antigen-positive (29%). 2) The reactivity of SHLA class I antigens was closely related to disease activity. 3) The number of lymphocytes and the reactivity of SHLA class I antigens were negatively correlated. 4) Nine of 23 samples from the active SLE patients were SHLA class I antigen-negative. Of these, 7 were from patients with a nephrotic syndrome due to lupus nephritis. It is concluded that SHLA class I antigens can be an useful marker for monitoring the clinical state of SLE.

Biomarkers↗

Non-obstructive hypertrophic cardiomyopathy with mitral regurgitation requiring valve replacement.

Non-obstructive hypertrophic cardiomyopathy (HCM) is rarely associated with mitral regurgitation severe enough to require valve replacement. A 39-year-old man, previously diagnosed as having non-obstructive HCM with mitral regurgitation, developed atrial fibrillation with tachycardia and congestive heart failure. Echocardiography and cardiac catheterization, including left ventriculography, documented an unusual type of non-obstructive HCM with severe mitral regurgitation. The patient underwent successful mitral valve replacement.

Adult↗

Overexpression of HLA class I antigen reduces insulin secretion in pancreatic beta cells (RINM5F): evidence for a non-immune mechanism.

Our recent observation indicated that overexpression of HLA-class I antigen on pancreatic beta cells is one of the features of insulin-dependent diabetes mellitus (IDDM). To analyze the effect of class I antigen overexpression, we have introduced human HLA class I (HLA-Cw3) gene into rat pancreatic beta cell lines, RINm5F. Several stable transformants with various levels of surface expression of class I antigens have been cloned. The insulin secretion of these transfectants was analyzed to evaluate the functions of beta cells. Highly negative correlation between the level of insulin secretion and that of class I expression (correlation coefficiency: r = 0.89) has been observed. These data suggest that the overexpression of HLA class I antigen itself may impair pancreatic beta cells through a nonimmune mechanism.

Animals↗

[Unrelated match bone marrow transplantation for severe aplastic anemia].

The results of unrelated bone marrow transplantation (BMT) is poor because of the rejection of bone marrow graft and graft versus host disease (GVHD). However, the rate of rejection has been reported to be decreased by intensive immuno-suppressive preconditioning regimens combined with total body irradiation (TBI). We report a case of an 18-year-old male with severe aplastic anemia who received a matched BMT from an unrelated donor. The pre-conditioning regimen included cyclophosphamide (50mg/kg) for 4 days, total lymphoid irradiation (TLI: 6Gy) and TBI (5Gy). GVHD (grade 1), hemorrhage cystitis and varicella occurred after BMT but were cured. His performance status is now 100% on the Karnofsky score at 10 months after BMT.

Adolescent↗

[Expression of LFA-1 and ICAM-1 on peripheral blood T-cells and soluble CD2 levels in serum during acute Kawasaki disease].

To clarify the activation of peripheral blood T-cells in Kawasaki Disease (KD) patients, we investigated whether the expression of lymphocyte function-associated antigen-1 (LFA-1) and/or intercellular adhesion molecule-1 (ICAM-1) on peripheral blood T-cells and serum levels of soluble CD2 (sCD2) increase during the acute stage. Expression of cellular adhesion molecules was analyzed using flow cytometry. sCD2 levels in serum were measured by a sandwich enzyme immunoassay. There was a decrease in the number of CD3+ T-cells in the bright LFA-1 alpha and LFA-1 beta population and a concomitant increase in the dim population of LFA-1 alpha and LFA-1 beta during the acute stage, in comparison with the convalescent stage. In addition, we observed no significant differences in ICAM-1 expression between the acute stage and the convalescent stage. There were no significant differences in sCD2 levels among the acute stage, the convalescent stage and the control subjects. In our view the present data, in conjunction with previous reports on T-cell function during acute KD, suggest that sequestration of activated peripheral blood T-cells may be a feature of this disease.

Antigens, CD↗

[Can ulinastatin be an effective inhibitor of human polymorphonuclear granulocyte elastase under severe stressed state?].

The inhibitory effect of ulinastatin (UST), an intrinsic human trypsin inhibitor was investigated on the activity of polymorphonuclear granulocyte elastase (PMNE) with or without alpha 1-protease inhibitor (alpha 1-PI) using the in vitro models. The results of the dodecyl-sulfate-electrophoresis (SDS-PAGE), indicated that splitting-action of crude granulocyte enzyme solution on the plasma fibronectin was inhibited by concentration-dependent UST of an equivalent value for treatment of stressed state. The PMNE-UST complex was competitively replaced by PMNE-alpha 1-PI complex in vitro models of inflammatory focus and circulation, hence UST was weaker than alpha 1-PI in its binding-affinity for PMNE. The PMNE activity was directly inhibited by UST in the inflammatory focus and circulation with or without alpha 1-PI.

Binding, Competitive↗

[Urgent mitral valve replacement for acute mitral regurgitation due to ruptured chordae tendineae in systemic lupus erythematousus].

We reported a successful surgical treatment of mitral regurgitation (MR) due to ruptured chordae tendineae in a 44-year-old man with systemic lupus erythematosus (SLE) who had received the steroid therapy. He had signs of acute congestive heart failure with severe pulmonary hypertension due to MR, and underwent urgent mitral valve replacement. The postoperative course was uneventful. When replacing valve in SLE, a careful manipulation should be taken because of friability of cardiovascular tissue. Patients are usually administered steroid agents, and the agents ought to be discontinued in perioperative period, but it seems to be better to resume as soon as possible. We conclude that the surgical treatment for valvular diseases should be considered, even in the patient with SLE.

Acute Disease↗

[Immunogenetic studies of spina bifida--sibling cases in three families].

We reported sibling cases of spina bifida in three families. In the first family, three boys were the products of one mother and different two fathers. They all suffered from spina bifida cystica with various degrees of hydrocephalus. Cyst closure and ventriculo-peritoneal shunt were performed. Elder boys had more severe neurological deficits. In the second family, two boys and one girl were affected. The elder boy had minimum neurological deficit but the younger boy had a severe neurological deficit and hydrocephalus. Cyst closure was performed on both of them but the shunting procedure was not. The girl was normal. In the third family, three girls were affected. The second girl suffered from spina bifida cystica with hydrocephalus and cyst closure was performed. After that ventriculo-peritoneal shunt was done. Other two girls were spina bifida occulta without any neurological deficit. HLA typing, red blood cell antigen typing and chromosome test were studied in three families. There was no evidence of linkage between spina bifida and HLA antigens. Also no relationship between spina bifida and red blood cell antigens. They all had normal chromosomes. We could not make as one material for genetic counseling from above studied three methods.

ABO Blood-Group System↗