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Biomedical subjects

S Sawada

Publications and source records attributed to S Sawada.

At least 307 records · Page 17Linked to original sources
PubMed1991

Impaired tumour necrosis factor-alpha (TNF-alpha) production and abnormal B cell response to TNF-alpha in patients with systemic lupus erythematosus (SLE).

We examined the TNF-alpha activity in culture supernatants of monocytes isolated from the peripheral blood of patients with SLE and of normal individuals. The monocytes from patients with SLE stimulated with silica particles, lipopolysaccharide or Staphylococcus aureus Cowan 1 secreted significantly lower amounts of TNF-alpha than did normal monocytes. A decreased TNF mRNA expression was observed in peripheral blood mononuclear cells stimulated by mitogens from patients with SLE. Furthermore, we examined the effect of recombinant TNF-alpha (rTNF-alpha) on the B cell function in SLE patients. rTNF-alpha inhibited the spontaneous B cell proliferation of SLE, but tended to enhance the normal B cell proliferation. Spontaneous IgM production from SLE B cells was inhibited by rTNF-alpha, but that from normal B cells was not. Spontaneous IgG production was unaffected by rTNF-alpha. Also, rTNF-alpha did not affect the viability of B cells. These findings suggest that an impaired TNF-alpha production and an abnormal B cell response to TNF-alpha play a role in the immunological dysfunction in patients with SLE.

B-Lymphocytes↗
PubMed1991

Mechanism of calcium ionophore and phorbol ester-induced T-cell activation. Accessory cell requirement for T-cell activation.

We examined the role of monocytes in T-cell activation induced by phorbol myristate acetate (PMA) and calcium ionophore ionomycin. Depletion of monocytes from peripheral blood mononuclear cells (PBMC) was associated with the loss of interleukin-2 (IL-2) production, IL-2 receptor (IL-2R) expression and proliferation, in response to either PMA or ionomycin. Addition of monocytes to highly purified T cells resulted in the complete reconstitution of IL-2 production, IL-2R expression and proliferation by PMA-stimulated lymphocytes. Exogenous IL-2, but not interleukin-1 (IL-1), could reconstitute the T-cell responsiveness. Addition of monocytes to highly purified T cells stimulated with ionomycin resulted in partial reconstitution of IL-2 production, IL-2R expression and proliferation. Similarly, the addition of exogenous IL-2 to ionomycin-stimulated T cells only partially reconstituted the response compared with PBMC. These results suggest that monocyte-T-cell interactions contribute to IL-2 production and IL-2R expression and are crucial events for PMA-induced T-cell proliferation. With ionomycin, monocytes play a role, in part, in inducing IL-2 production, IL-2R expression and proliferation. However, IL-2 is not a sufficient signal to induce T-cell proliferative response to ionomycin, suggesting that an IL-2-independent mechanism may exist in ionomycin-induced T-cell proliferation.

Cell Division↗
PubMed1991

Identification and characterization of a T-cell-specific enhancer adjacent to the murine CD4 gene.

Expression of the CD4 and CD8 glycoproteins is a tightly regulated process tied to the maturation of functionally distinct classes of thymocytes. Therefore, understanding of the mechanism of expression of the genes encoding CD4 and CD8 is likely to yield important insight into regulation of the differentiated functions of T cells. Here, we report the identification of a T-cell-specific enhancer in a DNase I-hypersensitive region about 13 kb 5' of the transcription initiation site of the murine CD4 gene. Within the minimal enhancer element, at least three nuclear protein binding sites were identified by DNase I footprint analysis. One site contains the consensus motif for TCF-1 alpha/LEF-1, a recently identified HMG box transcription factor primarily expressed in pre-B and T cells. By Southwestern (DNA-protein) blotting and binding competition analyses, the protein binding to this site was found to be indistinguishable from TCF-1 alpha/LEF-1. Mutagenesis of this site resulted in loss of factor binding but had a relatively minor effect on enhancer activity. In contrast, mutations in another site, containing two consensus binding motifs for basic helix-loop-helix proteins, abolished factor binding and dramatically reduced enhancer activity. None of the protein binding sites had activity on its own, suggesting that the CD4 enhancer requires the interaction of multiple regulatory sites.

Animals↗
PubMed1991

Relocatable Gianturco expandable metallic stents.

The authors modified Gianturco expandable metallic stents to make them relocatable. Two tandem designs were made. The first design had long struts and, thus, more evenly distributed expansive force; the second had short struts and more flexibility and was better suited for use in curved strictures. Both designs (two to four in tandem, 0.012-, 0.014-, and 0.018-inch wire) were tested successfully in vitro, and both designs (two to four in tandem, 0.012-inch wire) were successfully placed, retrieved, and relocated in the inferior vena cava of five dogs.

Animals↗
PubMed1991

Synthesis and antitumor activity of 20(S)-camptothecin derivatives: carbamate-linked, water-soluble derivatives of 7-ethyl-10-hydroxycamptothecin.

Novel 36 derivatives (6), bonding the phenolic hydroxyl group of 7-ethyl-10-hydroxycamptothecin (4) with diamines through a monocarbamate linkage, were synthesized and their antitumor activity was evaluated in vivo. The derivatives were soluble in water as their HCl salts with the E lactone ring intact and exhibited significant antitumor activity. One of the derivatives, 6-27 showed excellent activity against L1210 leukemia and other murine tumors. The structure of its hydrochloride trihydrate (CPT-11) was determined by spectroscopic and crystallographic methods.

Animals↗
PubMed1991

Chemical modification of an antitumor alkaloid camptothecin: synthesis and antitumor activity of 7-C-substituted camptothecins.

A radical substitution reaction of 20(S)-camptothecin (1) with methanol furnished 7-hydroxymethylcamptothecin (2). Reaction of 1 with primary alcohols higher than methanol gave 7-alkylcamptothecins (4), of which alkyl groups were one carbon less than the alcohols used and also 7-hydroxyalkylcamptothecins (5). For the preparation of 7-alkylcamptothecin (4), aldehydes were used as a radical source and several alkylated derivatives were synthesized. 7-Acyloxymethyl derivatives (6), 7-carbaldehyde (7), iminomethyl derivatives (10), acid (11), esters (12) and amides (13) were synthesized starting from 2. 7-Ethyl- (4b) and 7-propylcamptothecin (4c), acyloxymethyl compounds 6a, 6c and ethyl ester (12b) exhibited higher antitumor activity than 1 against L1210 in mice.

Animals↗
PubMed1991

Synthesis and antitumor activity of 20(S)-camptothecin derivatives: A-ring modified and 7,10-disubstituted camptothecins.

20(S)-Camptothecin derivatives having nitro, amino, chloro, bromo, hydroxyl and methoxyl groups in the A-ring were synthesized. B-Ring hydrogenated camptothecin (2a) was converted into 10-hydroxycamptothecin (6e) by treatment with lead tetraacetate in trifluoroacetic acid. 10-Substituted derivatives (6) were obtained by a photoreaction of N-oxides (9). The cytotoxicity of the A-ring modified camptothecins was evaluated against KB cells in vitro and leukemia L1210 in mice. 7-Ethyl-10-hydroxycamptothecin (6i) was identified as a potential derivative for further modification.

Animals↗
PubMed1991

Effect of cyclic GMP and sulfhydryl on prostacyclin production by human vascular endothelial cells.

The relationship between sulfhydryls and cGMP has been observed in several biological processes. Captopril is a sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor, that decreases PGI2 production in cultured human vascular endothelial cells. Enalapril does not appear to have this property. The role of cyclic GMP (cGMP) and sulfhydryls in the regulatory mechanisms in captopril-induced PGI2 production and Ca++ kinetics was investigated. Bradykinin and Ca ionophore A23187 enhanced PGI2 production, and increased the cytosolic free Ca++ concentration ([Ca++]i). It was observed that 8-bromo cGMP increased intracellular cGMP concentration ([Ca++]i), and decreased PGI2 production without changing [Ca++]i. Sulfhydryl containing compounds such as captopril, N-acetylcysteine and glutathione decreased PGI2 production via increased [cGMP]i. Enalapril, an ACE inhibitor without sulfhydryls, has no effect on PGI2 production, [Ca++]i and [cGMP]i. These results suggested that the presence of sulfhydryl groups is an important factor in the ability of vasoactive substances to induce PGI2 production.

Acetylcysteine↗
PubMed1991

Organ doses received by atomic bomb survivors during radiological examinations at the Radiation Effects Research Foundation.

When evaluating the risks of oncogenesis and cancer mortality following exposure to the radiations of the atomic bombs (A-bombs), the medical X-ray doses received by the A-bomb survivors must also be estimated and considered. Using a human phantom, dosimetry was performed to estimate the X-ray doses received by A-bomb survivors during medical examinations at the Radiation Effects Research Foundation (RERF) as part of the long-term follow-up on the Adult Health Study (AHS). These examinations have been estimated to represent nearly 45% of the survivors' cumulative medical irradiation dose. Doses to the salivary glands, thyroid gland, lung, breast, stomach and colon were measured using thermoluminescent dosimeters. The results, which are reported here, will aid in estimating organ doses received by individual AHS participants.

Abdomen↗
PubMed1991

Organ doses to atomic bomb survivors during photofluorography, fluoroscopy and computed tomography.

Doses to the salivary glands, thyroid gland, breast, lung, stomach and colon during mass radiological gastric screening, mass radiographic chest screening, upper gastrointestinal series and computed tomography were determined by exposing a female human phantom to simulated radiological X-ray examinations as performed in community hospitals. The doses were measured using thermoluminescent dosimeters, and the results will be used to document organ doses received by participants in the Atomic Bomb Casualty Commission/Radiation Effects Research Foundation Adult Health Study.

Adult↗
PubMed1991

Gamma-ray- and fission neutron-induced micronuclei in PHA stimulated and unstimulated human lymphocytes.

Two groups of normal human blood cells, one stimulated with phytohaemagglutinin (PHA) for 24 hr (G1-S phase of the cell cycle) and one unstimulated (G0 phase), were irradiated with 60Co gamma rays or 252Cf radiation. A comparison of radiation-induced micronucleus frequencies showed that the high-dose-rate gamma rays were more effective in inducing micronuclei than low-dose-rate gamma rays. In the cells exposed to low-dose-rate irradiation, there was little difference between the frequency of micronuclei in the G0 phase and the G1-S phase. However, cells in the G1-S phase were more sensitive than G0-phase cells to high-dose-rate gamma rays. The relative biological effectiveness of 252Cf neutron irradiation measured in micronucleus assays was consistent with the value obtained for the lethal effect of 252Cf on cultured cells.

Adult↗
PubMed1991

Medical X-ray doses' contributions to the ionizing radiation exposures of atomic-bomb survivors.

Doses from diagnostic radiological examinations were measured in order to evaluate the radiation risks of atomic-bomb survivors in Hiroshima and Nagasaki. Using a phantom human, doses to the active bone marrow, gonads, salivary glands, thyroid gland, lung, breast, stomach and colon were determined by type of examination and by examination site. The results of this dosimetry program will aid in estimating the diagnostic exposure doses received by each participant in the Adult Health Study of the Radiation Effects Research Foundation. The current results of these dosimetry studies also indicate that the effects of A-bomb exposure cannot be reliably assessed unless medical X-ray doses are carefully incorporated into these long-term evaluations.

Humans↗
PubMed1991

Anti-thyroid antibodies in patients with hyperprolactinemia.

To clarify the possible role of prolactin in the regulation of immune responses in man, we measured circulating anti-thyroid antibodies in 172 normal subjects, 84 patients with prolactinoma and 63 patients with acromegaly with normal thyroid and adrenocortical functions. Frequencies of positive thyroidal microsome and thyroglobulin antibodies were significantly (p < 0.05 and p < 0.01, respectively) higher in women with prolactinoma (20.6% and 20.6%) than in normal women (7.5% and 4.7%). Men with prolactinoma had a significantly (p < 0.05) higher frequency of positive thyroglobulin antibody (18.8%) than normal men (1.5%). When the subjects were divided by decade, women with prolactinoma in the 4th decade had significantly (p < 0.05) higher frequencies of positive thyroidal microsome and thyroglobulin antibodies (30.8% and 30.8%) than normal women of corresponding age (3.7% and 3.7%). In contrast, there was no significant difference in the frequencies of positive anti-thyroid antibodies in patients with acromegaly and in normal subjects. Analysis of the peripheral lymphocyte population revealed that patients with prolactinoma had a higher percentage of B cells than normal subjects, while there was no significant difference in the percentages of total T lymphocytes or in the helper and suppressor T cell ratios in the two groups of subjects. These results suggest that prolactin regulates humoral immune responses in man directly by stimulating B lymphocytes or indirectly by inhibiting suppressor T lymphocyte activity.

Acromegaly↗
PubMed1991

Correlations between IL-2 enhancing activity and clinical parameters in patients with rheumatoid arthritis and systemic lupus erythematosus.

In a previous paper (Tomura, K. et al. Tohoku J. Exp. Med., 1989, 159, 171-183), we discovered IL-2 enhancing factor(s) designated B cell derived-growth enhancing factor-2 (BGEF-2), which enhanced IL-2 dependent cell proliferation, and reported that BGEF-2 was produced by B cells of the patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) only when they were in the active stage of the disease. In this paper, we studied relationship between each IL-2 enhancing activity from B cell supernatant of the patients with these diseases and clinical parameters. IL-2 enhancing activities did not correlate with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), but correlated with plasma concentrations of gamma-globulin from the patients with RA and SLE in the active stages. IL-2 enhancing activities correlated with hypocomplementemia and leukocytopenia in the patients with SLE, and also correlated with RAHA titer in the patients with RA. Moreover, on several patients with RA or SLE in the active stages, diminution of IL-2 enhancing activity was found when they were in the remission stage after treatments. These findings suggested that IL-2 enhancing activity (i.e., BGEF-2 activity) correlated with activity of these diseases and supported the hypothesis that BGEF-2 played an important role in the polyclonal B cell activation and autoantibody production in patients with these diseases.

Adult↗
PubMed1991

Bialaphos poisoning with apnea and metabolic acidosis.

A 64-year-old man with ethanol intoxication, ingested a bottle of Herbiace (100 ml, 32 w/v% of bialaphos, CAS #35597-43-4, Meiji Seika Kaisha, Tokyo, Japan). He had severe metabolic acidosis and was treated with infusions of sodium bicarbonate and furosemide, plus gastric lavage and enema. The metabolic acidosis improved 15 hours after treatment but nystagmus, apnea and convulsions were progressive. Although his sensorium was clear, spontaneous respirations were not observed for 64 hours. The electroencephalographic findings of atypical triphasic waves and slow waves suggest a unique response to bialaphos poisoning. His clinical course indicates that the management of apnea is critically important to recovery from bialaphos poisoning.

Acidosis↗
PubMed1991

Cell-cycle dependence of heat-induced interphase death in mouse L5178Y cells.

Cell lysis and eosin staining were observed in L5178Y cells within the first 3 h of post-hyperthermia incubation at 37 degrees C, after which both leveled to a plateau. Lysis and eosin staining were proportional to the severity of heat in asynchronous cells, whereas it was maximum in the most heat-sensitive M phase, intermediate in S, and least in heat-resistant G1 for the same heat treatment. Further, leakage of labeled [3H]thymidine and a decrease in radioactivity retained within heated cells coincided with an increase in eosin staining, indicating that the dye uptake was due to membrane damage. It was presumed that the eosin-stained fraction represented dead cells. The percentage eosin-stained cells reached a plateau, and this level was used to determine survival; when the results were compared with those obtained by the colony formation method, they were identical. By comparing the two survival assay methods we concluded that cell death after hyperthermia in L5178Y cells is mainly by interphase death in all phases of the cell cycle. The reasons for this conclusion are that a reduction in survival could be detected within one generation of L5178Y cells by the eosin staining method, and the survival values obtained by this method were identical to those obtained by the colony formation method.

Acclimatization↗
PubMed1991

Prevention of gastric complications in hepatic arterial chemoembolization. Balloon catheter occlusion technique.

Gastric complications may be a problem in transcatheter arterial chemoembolization, if the right gastric artery branches distally from the proper hepatic artery or its branch, or the accessory left gastric artery arises from the left hepatic artery. We occluded the proper hepatic artery with a balloon catheter to redirect blood flow in these gastric branches toward the liver. This procedure prevented chemoembolic agents from flowing into the gastric branches, and accordingly protected against gastric complications even when chemoembolization was performed by injecting the agents proximally to the gastric branches.

Carcinoma, Hepatocellular↗