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Biomedical subjects

M Sawada

Publications and source records attributed to M Sawada.

At least 343 records · Page 19Linked to original sources

Decreased clastogenicity of dinitropyrenes in Chinese hamster lung (CHL) subclone cells with low NADPH-cytochrome P-450 reductase activity.

Clastogenic potentials of 1,3-, 1,6- and 1,8-dinitropyrenes (DNPs) were compared between Chinese hamster lung (CHL) cells and its subclone MM1 cells, which were recently isolated as menadione-resistant cells after treatment with MNNG. NADPH-cytochrome P-450 reductase activity of the MM1 cells decreased to 50% of that in the parental CHL cells. All 3 DNPs induced chromosomal aberrations without exogenous metabolic activation systems in the CHL cells. 1,6- and 1,8-DNP showed equivalent clastogenic potency: the maximum frequency of cells with chromosomal aberrations was about 50% for both chemicals. The clastogenic potential of 1,3-DNP was lower than that of 1,6- and 1,8-DNP: the maximum frequency of aberrant cells was 10%. In the MM1 cells, in contrast, the frequencies of aberrant cells decreased to about 30% of those observed for the parental CHL cells after treatment with 1,6- and 1,8-DNP, and to the same level as that of the concurrent control after treatment with 1,3-DNP. These results suggest a possibility that the reduced clastogenic effect of 3 DNPs in MM1 cells may correlate with the reduced activity of NADPH-cytochrome P-450 reductase which is thought to contribute to the metabolic conversion of these DNPs to their clastogenic forms in the CHL cells.

Animals↗

Relationship between erythrocyte sorbitol content and diabetic microangiopathy in patients with non-insulin-dependent diabetes mellitus: the study of a diet loading test.

To determine whether erythrocyte sorbitol content could become an indicator of diabetic microangiopathy, we studied the relationship between the changes in erythrocyte sorbitol content in response to diet loading and diabetic microangiopathy in patients with non-insulin-dependent diabetes mellitus. The increase of change in erythrocyte sorbitol content (delta Sor) after diet loading (420 kcal) significantly correlated with that of plasma glucose levels (delta BS). The patients with less than or equal to 40 m/s of motor or sensory nerve conduction velocity (MCV and SCV) had significantly higher delta Sor and delta Sor/delta BS values than those with greater than 40 m/s of MCV and SCV; nevertheless, there were no significant differences in delta BS between the two groups. Furthermore there was a significant negative correlation between nerve conduction velocity and delta Sor and Delta Sor/delta BS values. On the other hand, the patients with nephropathy or retinopathy showed no significant increase in delta Sor or delta Sor/delta BS compared with patients without these complications. The results demonstrated that delta Sor and delta Sor/delta BS could become indicators of the presence or severity of diabetic neuropathy. Furthermore the more significant participation of alteration in the polyol pathway in the pathogenesis of neuropathy than of the other microangiopathies was suggested.

Aged↗

Possible role of tumor necrosis factor and interleukin-1 in the development of diabetic nephropathy.

The possibility that tumor necrosis factor (TNF) and interleukin-1 (IL-1) could participate in the development of diabetic nephropathy was evaluated in streptozocin (STZ)-treated diabetic rats. Diabetic rats were divided into two groups: aminoguanidine treated group (25 mg/kg body wt, daily i.p. injection; DM-AG group) and untreated group (DM group). Non-diabetic age-matched rats were also divided into two groups with the same manner and used as controls. After twelve weeks of treatment, glomerular basement membranes (GBM) were isolated from rats of each experimental group. When thioglycollate-elicited peritoneal macrophages (M phi) from normal rats were incubated with these GBM materials, GBM from DM group induced significantly greater levels of TNF and IL-1 production than did GBM from other three groups with at doses of 2.5 to 10 mg. The TNF and IL-1 production by stimulation of GBM from the DM-AG group were similar to those from each control group. Aminoguanidine treatment significantly decreased the accumulation of advanced glycation end-products (AGEs) in GBM of diabetic rats. These findings suggest that AGE-proteins may be involved in the production of TNF and IL-1 from M phi. AGE-induced cytokines may be implicated in the development of diabetic nephropathy.

Albuminuria↗

Immunologic and immunohistochemical studies on chronic lymphocytic thyroiditis with or without thyroid lymphoma.

The local immunologic phenomena in the thyroid gland of 16 patients with chronic lymphocytic thyroiditis (CLTH) were investigated; 5 of these cases were associated with thyroid non-Hodgkin's lymphomas (NHL). All patients were admitted because of struma, growing slowly in patients with CLTH alone and rapidly in those with associated thyroid NHL. CLTH was confirmed by histologic findings, including the presence of lymphoid follicles or thyroid autoantibodies in the serum in all 16 patients. Immunologic study revealed that all thyroid NHL were of the B cell type. Surface maker study of suspended cells showed that the percentages of E-rosette-forming cells in patient with CLTH and thyroid NHL (38.0 +/- 10.0%) and in patients with CLTH alone (45.0 +/- 11.9%) were between those of B cell NHL of lymph node and B cell hyperplasia reported by others. Immunohistochemical studies confirmed the reactive nature of lymphoid follicles. Subset distribution of T and B lymphocytes in patients with CLTH and thyroid NHL markedly contrasted with that in patients with CLTH alone: an increased ration of CD8+ cells (suppressor/cytotoxic cell) to CD4+ cells (helper/inducer cell). There was a marked increase in the number of immunosuppressive acidic-protein(IAP)-containing macrophages in the thyroid lesion and serum IAP level in patients with thyroid NHL. These findings provide evidence of a difference in the local immunologic conditions in CLTH alone compared to CLTH complicated by thyroid NHL.

Adult↗

Phase IV study and post-marketing surveillance of ofloxacin in Japan.

Data derived from phase IV clinical trials of ofloxacin in 13,850 patients show that the incidence of adverse drug reactions was 2.6%. Gastrointestinal symptoms topped other symptoms in order of frequency, followed by neuropsychiatric and hypersensitivity symptoms. On the other hand, we received 155 spontaneous reports on ofloxacin adverse reactions, including severe convulsions and shock. Examination of various cases of adverse drug reactions suggested that both severe renal dysfunction and a predisposition to epilepsy were risk factors contributing to the onset of convulsions, and a predisposition to allergy was also a risk factor in hypersensitivity reactions including shock. Data from phase IV trials aimed at efficacy analysis show a high efficacy rate. The usefulness of ofloxacin was confirmed by the data obtained after its marketing.

Clinical Trials as Topic↗

Special instruments for laryngeal framework surgery.

Thyroplasties involve a variety of delicate surgical techniques that affect the outcome decisively. In particular, opening a window in the thyroid cartilage, undermining around the window frame and fixation of a window plug in thyroplasty, and passing a suture through the muscular process and thyroid ala are some examples of difficult procedures. Several instruments were devised to facilitate such procedures. They include a special raspatory, an ultrasonic osteotome for cartilage cutting, a narrow polyvinyl tube for suture passing, a suture holder for passing through the muscular process, and a wound retractor for arytenoid adduction. These were found useful in minimizing soft tissue damage and in precise performance of the procedures.

Humans↗

Rapid plasma membrane changes in superoxide radical formation, fluidity, and phospholipase A2 activity in the corpus luteum of the rat during induction of luteolysis.

Early luteolytic changes in the plasma membrane of luteal cells were examined in the rat. Treatment with prostaglandin F2 alpha in vivo caused a rapid transient increase in superoxide radical formation and a decrease in fluidity in plasma membrane samples prepared from luteinized rat ovaries. These alterations preceded detection of a significant fall in plasma progesterone concentration. The rise in superoxide radical was not accompanied by changes in activities of free radical scavenging enzymes. Within the first hour of prostaglandin treatment, there was also a significant increase in the activity of phospholipase A2 and ATP-dependent calcium uptake in the membrane samples. These experiments indicate that one of the initial sites affected by the luteolytic process appears to be the plasma membrane. The changes include a transient rise in production of superoxide radicals, which may cause membrane changes that are responsible for disrupting corpus luteum function in the rat.

Animals↗

Effect of media conditioned by concanavalin A activated spleen cells on pancreatic islet cells.

The effect of media conditioned by concanavalin A-activated spleen cells (C-sup) on insulin release and its islet cell cytotoxicity were studied. In a functional study, C-sup significantly inhibited both basal insulin release and glucose-stimulated insulin release. Morphologically, C-sup had a destructive effect on isolated islets after 72 h incubation. Islet cell cytotoxicity was shown by lactate dehydrogenase (LDH) release assay after 5 days incubation with C-sup in a dose-dependent manner. These results suggest that acceleration of the onset of diabetes in young diabetes prone (DP) Bio-Breeding/Worcester (BB/W) rats following the injection of C-sup may depend on the suppressive and cytotoxic effects of C-sup on pancreatic islet cells.

Animals↗

Induction of diabetes by PolyI:C and anti-RT6.1 antibody treatment in DR-BB rats.

To determine whether environmental factors could affect the incidence of diabetes in RT6.1+ lymphocytes-depleted diabetes resistant (DR) BB rats, we tested polyinosinic-polycytidylic acid (Poly I:C), as an immune activator, in conjunction with anti-RT6.1 antibody in DR-BB rats which were bred in a specific pathogen free (SPF) condition. Diabetes was induced by the combined administration of poly I:C and anti-RT6.1 antibody. The use of poly I:C or anti-RT6.1 antibody alone did not cause diabetes. These results suggest that RT6.1+ T lymphocytes regulate autoimmune diabetes and that non-specific immune activation caused by environmental factors plays a key role in inducing diabetes in DR-BB rats.

Animals↗

[Etiology of left ventricular rupture following mitral valve replacement].

Two uncommon cases of left ventricular rupture that occurred during cardiac surgery were treated successfully. These cases may be useful in understanding the etiology of common left ventricular rupture following mitral valve replacement. One case occurred during coronary bypass surgery. The myocardium which is already abnormal seems to be weak to trauma such as bending, traction and torsion. In the other case, who underwent mitral valve replacement with preservation of the posterior leaflet with its attached chordae, the disruption was localized in the epicardial side of the left ventricular posterior wall, though direct injury by some instrument was excluded as a possibility, with a depth of half the thickness of the wall. In experiments using dogs, shape and movement of the mitral annulus were examined. The length of the annulus attached to the posterior leaflet in end-systole was shortened to 89.0 +/- 4.6% of that in late diastole. Furthermore, the annulus was distorted by the elevation of the heart. We approve of Cobbs' "untethered ventricle theory" and consider moreover as follows: In general, whether with or without preservation of the mitral loop, the mitral annulus and the left ventricular posterior wall after mitral valve replacement are severely constricted by the rigid prosthetic ring and become tense, which limits movement in both circular and longitudinal directions. Then even slight stress may cause a primary tear on the posterior wall of the left ventricle, resulting in rupture. In order to treat the rift, the prosthesis must be removed before the apex of the heart is lifted, to avoid excessive ventricular wall tension.

Aged↗

The effects of overeating on insulin secretion in normal mice.

This study was performed to examine the effect of overeating on in vivo and in vitro insulin secretion in normal mice. Six week old male CRJ-ICR mice were maintained on a cookie and chocolate mashed diet (C.C. diet) until 30 weeks of age; control mice received an ordinary mouse chow. The mice on the C.C. diet (C.C. mice) consumed 125-130% of the daily caloric intake of control mice throughout the study. C.C. mice developed mild hyperglycemia with relative obesity from 16 weeks of age. Fed blood glucose levels at 30 weeks of age for C.C. mice were 158.3 +/- 6.7 mg/dl as opposed to 127.2 +/- 3.1 mg/dl for controls (p less than 0.01). In experimental mice at 18 weeks of age, plasma insulin response after intraperitoneal glucose load (2 mg/g BW) and insulin secretion at 30 mM glucose from the perfused pancreas were similar to those in control mice. However, at 30 weeks of age, insulin secretion at 30 mM glucose from perfused pancreas in C.C. mice was significantly suppressed compared with that of control mice (p less than 0.02). Conversely, in vivo insulin secretory response to intraperitoneal glucose load was significantly increased in C.C. mice (p less than 0.05). There were no differences in insulin secretion at 15 mM glucose from perfused pancreas. These results indicate that impairment of beta-cell secretory capacity develops in impaired glucose tolerant mice with obesity, while in vivo studies show a high insulin response to glucose. This alteration of beta-cell function may be the initial change during the development of the hyperglycemia-induced defect in insulin secretion.

Aging↗

Selective killing of Paneth cells by intravenous administration of dithizone in rats.

Paneth cells are zinc-containing cells widely distributed in Lieberkühn's crypts of intestine in a variety of species. We found that rapid selective killing of Paneth cells took place after the intravenous (i.v.) injection of diphenylthiocarbazone (dithizone), a chelator forming a zinc dithizonate complex, in the rat. As soon as 5 min after the i.v. injection of dithizone, degeneration of Paneth cells occurred. At this stage, zinc dithizonate complexes were observed as purple-red granules in bright field microscopy. Thirty to 60 min later, Paneth cells were detached from the basement membrane and shed into the cryptic lumen. After 6 h, the cell debris in the crypts was no longer seen and the crypts once housing Paneth cells were now occupied by neighbouring crypt base columnar cells. Histochemically demonstrable zinc totally disappeared. After 12-24 h, however, definite Paneth cells began to resume. Histochemical staining for zinc was again positive at the apex of these cells. One week after dithizone administration, the number of Paneth cells increased twice as much as in uninjected control and histochemical staining for zinc was highly positive. After 2 weeks, Paneth cell hyperplasia subsided. X-ray microanalysis revealed that zinc was the most abundant metal in Paneth cells. We concluded that chelation of zinc and formation of zinc-dithizone complexes in Paneth cells' cytoplasm would be responsible for the selective degeneration observed after dithizone administration.

Animals↗

[Case reports on the pectoralis quartus and the pectoralis intermedius muscles].

Each one case of the pectoralis quartus and the pectoralis intermedius muscles was found on the left thoracic wall in a 73 year old male and on the right thoracic wall in a 57 year old female respectively. The pectoralis quartus was a thin muscle of triangular shape, the base of which was the origin arising from the left thoracic wall at the level of the 6th rib between the pectoralis major and the latissimus dorsi, being separated from both margins of the muscles. The aberrant muscle ascended left-upwards about 10 cm to insert to the inner surface of the pectoralis major near its lower margin. The muscle was innervated by the most caudal pectoral nerve, passing around the lower margin of the pectoralis minor. The pectoralis quartus is extremely rare in man, and only two cases were reported by Bluntschli (1906) and Frey (1921). From the comparative anatomical point of view, the pectoralis quartus muscle was supposed to be a remnant of the ventral part of the subcutaneous trunci muscle in lower mammals, differing from the ordinary muscular arch of the axilla which was believed to derive from the dorso-cranial part of the muscle. The pectoralis intermedius was located in the deep layer of the right pectoralis major, lying about 2 cm below the lower margin of the pectoralis minor. It arose in the 4th and 5th ribs and extended right-upwards, running almost parallel with the pectoralis minor. The origin of the pectoralis minor shifted cranially to the 2nd and 3rd ribs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Effect of recombinant human erythropoietin on autologous blood pre-donation in open heart surgery].

We have used recombinant human erythropoietin (EPO) with an autologous blood predonation in open heart surgery looking forward to preventing patient's blood level of hemoglobin and quick recovery in post-operative period. In our results, patient's value of hemoglobin (Hb) and hematocrit (Ht) decreased due to autologous blood predonation. In group A (autologous blood predonation with EPO administration), however, predonated blood volume were larger than in group B (without EPO administration), decreased value of Hb and Ht were smaller than in group B. The counts of reticulocyte were higher in group A at the operative day. Among six cases phlebotomized with EPO administration, five cases required no homologous blood transfusion for their hospital course. Postoperative recovery of patient's Ht value were earlier in preoperative blood donation group. In particular, patients who administered EPO intravenously have showed fair recovery from anemia. EPO is very effective drug to prevent patients from the developing anemia as a complication of autologous blood predonation. We conclude that autologous blood predonation with EPO administration is beneficial method to reduce homologous blood requirement in open heart surgery.

Adolescent↗

[Functional and immunohistochemical studies of cultured rat microglia].

We studied functional and immunohistochemical characteristics of cultured rat microglia. Unstimulated microglia did not proliferate. Microglia stimulated with LCM (L929 conditioned medium: colony stimulating factor-1) had proliferative activity and increased acid phosphatase activity. LPS (lipopolysaccharide) and IFN gamma (interferon-gamma) but did not affect proliferative activity. Immunohistochemically, RCA-1 lectin and GS-1 lectin, which react to beta-D-galactose and alpha-D-galactose respectively, strongly reacted to the cytoplasm and membrane of unstimulated microglia. After stimulation with LCM, microglia elongated processes and decreased response to these lectins. On the other hand, microglia stimulated with LCM showed increased reactivity to monoclonal antibody of vimentin. Microglia stimulated with LPS had round shape and had response to these lectins and vimentin. Microglia stimulated with IFN gamma had adhesive activity and weakly stained with these lectins but not with vimentin. ED-1 (monoclonal antibody of rat monocytes/macrophages) reacted to unstimulated and stimulated microglia. In flow cytometry, unstimulated microglia expressed OX-18 (MHC class I) and W3/25 (CD4) antigen. After stimulation with IFN gamma, microglia were induced to express these antigens. CD4 antigen is a marker of helper/inducer T cells and thought to be a receptor of HIV. The results that microglia had CD4 antigen which was further induced with IFN gamma are important to investigate infection of the CNS with HIV. OX-6 (Ia) antigen was induced with IFN gamma. This indicates that the microglia plays a central role in the CNS immune reaction. These characteristics of cultured rat microglia provide useful informations to investigate the pathogenesis of the CNS disorders.

Animals↗

Stage I epithelial ovarian tumors of low malignant potential.

Clinical and pathological details of 10 patients with stage I low malignant potential tumors of the ovary, between September, 1969, and February, 1988, have been reviewed. The mean age of the patients was 46.6 years. Six patients had serous and four had mucinous tumors. Of the 10 patients, five had a unilateral salpingo-oophorectomy, one had a bilateral salpingo-oophorectomy and four a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The mean duration of follow-up was 12.8 years. All patients have remained alive and disease-free. A recurrence occurred in one patient who has been managed well by additional surgery. Stage I ovarian tumor of low malignant potential appears to carry a favorable prognosis.

Adult↗

Purification and biochemical characterization of statin, a nonproliferation specific protein from rat liver.

The nuclear protein statin, detectable with specific monoclonal antibodies, is found mostly in nonproliferating cells (Wang, E. (1985) J. Cell Biol. 100, 545-551). In the rat liver a 57-kDa protein designated as rat liver protein 57 (RLp57) was recently identified to carry the epitope for the anti-statin-specific monoclonal antibody, S-44 (Sester, U., Moutsatsos, I. K., and Wang, E. (1989) Exp. Cell Res. 182, 550-558). To characterize further the RLp57 protein, in the present study a polyclonal antibody was raised to the RLp57 protein eluted from polyacrylamide gel. Similar to the anti-statin monoclonal antibody, this polyclonal antibody recognizes a nuclear antigen in nonproliferating fibroblasts and reacts with a 57-kDa protein in rat liver and nonproliferating cells strongly suggesting that RLp57 is a statin protein from rat liver. Two isoforms of RLp57 (isoelectric points between 6.5 and 7.0) were detected after two-dimensional gel electrophoresis and immunoblotting. RLp57 was purified using multiple chromatographic steps, including ion-exchange and affinity chromatography followed by chromatofocusing. These results show that RLp57, a statin protein found in liver, has two isoelectric variants and can be purified to apparent homogeneity by sequential steps of chromatographic procedures.

Animals↗