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Biomedical subjects

T Misawa

Publications and source records attributed to T Misawa.

At least 37 records · Page 2Linked to original sources

Establishment and characterization of acquired resistance to platinum anticancer drugs in human ovarian carcinoma cells.

To investigate differences in resistance to cis-diamminedichloroplatinum(II) (CDDP) and diammine (1,1-cyclobutanecarboxylato)platinum(II) (CBDCA), and their newly developed derivative, ((-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato)platinum (II) (DWA2114R), four types of resistant cell lines were established from a parental cell line (NOS2) of a serous cystadenocarcinoma of the ovary. The cross-resistance of CDDP-resistant cells (NOS2CR1 and NOS2CR2) to DWA2114R was slight (only 25% of the resistance to CDDP), and no cross-resistance was observed to anticancer drugs other than the CDDP derivative, except to camptothecin (CPT-11) in the case of NOS2CR2 cells. The cross-resistance of CBDCA-resistant cells (NOS2CBR) to DWA2114R was slight (only about 1/3 of the resistance to CBDCA), and no cross-resistance was observed among anticancer drugs other than the CDDP derivative. On the other hand, DWA2114R-resistant cells (NOS2DR) showed a high cross-resistance to CDDP, CBDCA, etoposide (VP-16), and CPT-11. Intracellular accumulations of CDDP and CBDCA were markedly reduced in NOS2CR1, NOS2CR2, and NOS2CBR cells compared to those in NOS2 cells, but were reduced only slightly in NOS2DR cells. Intracellular accumulation of DWA2114R was reduced somewhat in the four types of resistant cells. Glutathione S-transferase activity was not increased in any of the four types of resistant cells, and intracellular GSH concentration was increased only in NOS2CR2 cells (by 2.6 fold). From these results, we consider that the resistance mechanisms against CDDP and CDBCA are similar, and reduction of intracellular drug accumulations is a significant factor. Resistance to DWA2114R differed from resistance to CDDP and CBDCA in both cross-resistance spectrum and resistance mechanism, indicating that reduction in intracellular drug accumulation is not the major resistance mechanism.

Camptothecin↗

Direct contractile effect of endothelin-1 on isolated circular smooth muscle cells of guinea pig caecum.

Smooth muscle cells isolated from the circular muscle layers of the guinea pig caecum were used to determine whether endothelin-1 (ET-1) can cause contraction by exerting a direct action on smooth muscle cells. In addition, the inhibitory effects of 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an inhibitor of intracellular Ca2+ release, verapamil, a Ca2+ channel blocker, and removal of extracellular Ca2+ on the ET-1-induced muscle contraction were examined. ET-1 elicited a contractile response of isolated smooth muscle cells in a dose-dependent manner (ED50: 2 nM). TMB-8, verapamil, and removal of extracellular Ca2+ significantly inhibited the contraction produced by ET-1. These results strongly suggest that ET-1 has a direct contractile effect on circular smooth muscle cells of the guinea pig caecum, and that this contraction depends on both intracellular and extracellular Ca2+.

Animals↗

Regional medical information network using optical memory cards and integrated services for digital network.

Since 1986, we have been developing a regional health and welfare system using optical memory cards. We have expanded the system and performed model experiments and evaluations this time. There are approximately 3000 card-holders and 23 card-reader terminals in use. They cover 50 percent of the medical facilities in the city of Isehara. Two medical clinics within neighboring cities have joined our project. Standard Deviation Index (SDI) has been introduced to standardize the numeric results of examinations. The terminals are connected with Integrated Services for Digital Network (ISDN) allowing remote access to the optical memory cards. This enhanced connectivity has allowed greater cooperation in delivering quality medical services.

Aged↗

[Establishment of a human colon cancer-derived cell line (KC-1) which produces CEA, CA 19-9 and sialyl SSEA-1(SLX)].

A human colon cancer-derived cell line, KC-1, was established from the surgical specimen of mucinous adenocarcinoma of the colon. The cells grew as monolayers, showing formation of irregular aggregation of cells and pleomorphic nuclei. The doubling time in vitro was 56.6 hours. The cells produced CEA, CA19-9 and sialyl SSEA-1(SLX). Chromosome numbers were distributed between 79 and 83 with many structural abnormalities. A point mutation of the Ki-ras gene in codon 61 (CAA-->CAT) was found. The cells have been subcultured 13 times during these three years. This cell line can be useful for investigations of colon cancer.

Adenocarcinoma, Mucinous↗

Characteristics of anemia in patients with nephrotic syndrome.

Primary nephrotic syndrome can, although infrequently, cause severe anemia. However, the mechanisms of the anemia remain unknown. We investigated the mechanism of anemia in nephrotic syndrome by measuring parameters of nephrotic syndrome and anemia in 44 nephrotic patients (male: female; 21:23, average age; 43.6 +/- 20.3 years). Nephrotic patients had significantly lower hematocrits than did healthy controls (43.3 +/- 3.7 vs. 46.8 +/- 3.4% in males, 37.4 +/- 3.5 vs. 40.8 +/- 2.8% in females). Serum erythropoietin (Epo) concentrations were correlated inversely with hemoglobin (Hb), hematocrit (Hct), and red blood cell corpuscle (RBC) counts. Furthermore, serum Epo correlated with the serum iron concentration, but not with the other parameters, such as reticulocytes, serum protein and proteinuria. However, the maximum Epo concentration was less than 100 mU/ml in spite of severe anemia, and this was thought to be inappropriate. On the contrary, urine Epo was not detected by the same method of serum Epo determination in spite of aggressive dialysis with distilled water. When four patients with severe anemia were subcutaneously administered recombinant Epo 6,000 unit two times a week, they showed marked improvement in Hb/Hct/RBC. The precise mechanism of anemia in NS was not elucidated by this investigation, but further study should clarify the causes of the inappropriately low concentration of serum Epo in patients with primary nephrotic syndrome.

Adult↗

[Pregnancy and delivery in patients with lupus nephritis].

To investigate some of the problems associated with pregnancy and delivery in lupus nephritis, 13 pregnancies in 7 patients with inactive lupus nephritis and 5 pregnancies in one patient with primary antiphospholipid syndrome (PAPS) were compared with 36 pregnancies in 22 patients with primary nephrotic syndrome (NS). Furthermore, a follow-up survey during 0-8 years was made with 12 babies born to mothers with lupus nephritis. Some pregnancies during lupus nephritis were accompanied by disease exacerbation and worsening of renal function. There was a higher incidence of babies born with a low birth weight, and the incidences of fetal loss or premature birth and toxemia were higher in lupus nephritis than in NS. The number of babies with a low birth weight was significantly higher in patients with pregnancy-induced hypertension or skin lesion due to lupus erythematosus. The presence of antibodies against SSA/RO in the mother was associated with the occurrence of congenital heart block. Birth weight of babies born to mothers with lupus nephritis was low, but there were no statistical differences in the growth of babies after 6 months of age compared with babies born to normal women.

Adult↗

Effect of Sairei-to on gentamicin nephrotoxicity in rats.

The effect of Sairei-to, an oriental traditional medicine, against gentamicin nephrotoxicity was examined in gentamicin nephrotoxicity rat models. Gentamicin nephrotoxicity was induced by s.c. injection of gentamicin (100 mg/kg/day, for 3 days) in male Sprague-Dawley rats. Renal functions of two rat groups were compared, one eating rat chow containing 2.5% Sairei-to, the other eating normal rat chow. Sairei-to administration reduced the increase of urinary N-acetyl-beta-D-glucosaminidase (NAG) and protein excretion, and decreased creatinine clearance induced by gentamicin. Gentamicin increased renal cortical malondialdehyde (MDA) concentration in normal diet group but not in the Sairei-to diet group. The renal cortical gentamicin concentration was not different between the two groups. In conclusion, Sairei-to shows reno-protective action against gentamicin nephrotoxicity, possibly through its anti-oxidant action.

Acetylglucosaminidase↗

Rectal carcinoid tumor: endoscopic ultrasonographic detection and endoscopic removal.

Eight patients with rectal carcinoid tumors were examined by endoscopic ultrasonography (EUS) to assess the depth of invasion of the rectal wall. All resected tumors were contained within the submucosa and their depth of invasion was correctly diagnosed by EUS before treatment. Perirectal lymph nodes were not delineated by EUS. Four patients who were treated only with endoscopic polypectomy were completely cured as were four patients who had a surgical resection. EUS is useful in selecting the candidates for endoscopic removal or local resection and thus may help to avoid unnecessary radical surgery.

Aged↗

Comparison of plasma pancreastatin and GAWK concentrations, presumed processing products of chromogranin A and B, in plasma of patients with pancreatic islet cell tumors.

Plasma pancreastatin (PST) and GAWK, peptides processed from chromogranin A and B, were elevated in patients with various neuroendocrine tumors. In the present study, we measured plasma PST- and GAWK-like immunoreactivity (LI) concentrations in 12 patients with pancreatic islet cell tumors and evaluated them as a marker for these tumors. We also performed the gel filtration of the plasma from a gastrinoma patient and investigated the processing of PST and GAWK in plasma. Elevation of plasma PST-LI was found in 4 of 12 patients (33%) and elevation of plasma GAWK-LI was found in 6 of 12 patients (50%). A significant correlation was not found between plasma PST- and GAWK-LI concentrations of the patients. In the gel permeation chromatography of the plasma from a gastrinoma patient, PST-LI composed of a single peak but GAWK-LI composed of several components with wide range molecular weights.

Adenoma, Islet Cell↗

A case of pheochromocytoma of the urinary bladder in a long-term hemodialysis patient.

The development is reported of a pheochromocytoma of the urinary bladder in a 33-year-old patient with systemic lupus erythematosus who had undergone long-term hemodialysis. A hypertensive episode followed by defecation was demonstrated by the monitoring of blood pressure with a portable automated sphygmomanometer without elevation of plasma catecholamines. The tumor was surgically removed and normalization of the patient's blood pressure followed. Thus, monitoring of blood pressure for 24 h proved useful for the diagnosis of pheochromocytoma and, in particular, of paroxysmal hypertension.

Adult↗

Direct inhibitory effect of neurotensin on isolated gastric smooth muscle cells of guinea pig via the cyclic GMP system.

Smooth muscle cells isolated from the gastric muscle layers of the guinea pig were used to determine whether neurotensin can inhibit the contractile response produced by 10(-6) M carbachol by exerting a direct action on muscle cells. In addition, the inhibitory effect of 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, and methylene blue, an inhibitor of guanylate cyclase, on the neurotensin-induced relaxation of gastric smooth muscle cells were examined. Neurotensin inhibited the contractile response produced by carbachol in a dose-dependent manner, with an IC50 value of 5 nM. 2',5'-Dideoxyadenosine did not have any significant effect on the neurotensin-induced relaxation. On the other hand, methylene blue significantly inhibited the relaxation produced by neurotensin. These results strongly suggest that the action of neurotensin is mediated by cyclic GMP.

Animals↗

The first pediatric Japanese case to undergo heart transplantation in the Utah Cardiac Transplant Program in the United States.

A seven-year-old girl underwent heart transplantation because of progressive congestive heart failure resulting from familial dilated cardiomyopathy. Her parents were second cousins to each other and her brother had died of dilated cardiomyopathy. Her symptoms of congestive heart failure began four months before the transplantation and became gradually worse. Left ventricular ejection fraction was 10 to 20% echocardiographically, and mitral and tricuspid valve regurgitation were present. Her condition of NYHA IV was not improved by treatment with dobutamine infusion and isosorbide dinitrate. She was transported to the Primary Children's Medical Center in Utah, USA, on July 22, 1991 in critical condition to undergo heart transplantation. Despite treatment with amrinone and additional catecholamines, she became semicomatose due to ischemic liver injury on July 24, 1991. A donor became available on July 25, 1991, and the transplantation was performed. Cardiac ischemic time was 97 min. Although she had transient OKT3 monoclonal antibody-related encephalopathy on her fifth postoperative day, she recovered normally. She had moderate rejection on the 20th postoperative day and mild rejection on the 79th and 149th postoperative days. She has had no significant infectious diseases. The baseline examination performed three months after heart transplantation revealed no abnormal findings on her coronary arteriogram. She returned to Japan and has been attending elementary school. The annual examination of her transplanted heart showed neither stenosis nor occlusion in her coronary angiogram. She has been receiving cyclosporine, azathioprine, and a low dose of prednisone as an immunosuppressive regimen. If she does not exhibit rejection, the use of steroids will be decreased or discontinued.

Cardiomyopathy, Dilated↗

Effects of prenatal aluminum treatment on development and behavior in the rat.

Developmental and behavioral effects of aluminum administration were studied in THA rats. To three groups of pregnant rats were administered single dose of 0, 900 or 1,800 mg/kg of aluminum chloride on the day 15 of gestation by gavage. Significant differences were observed between the aluminum treated offspring and controls in terms of body weight, timing of pinna detachment and eye opening, and appearances of auditory startle. Slower learning acquisition was observed in treated groups. The longer latency and more rearings in the open field test were observed in 1,800 mg/kg treated females. These results suggest that single dose of aluminum chloride during prenatal period affects the development and behavior in rats.

Aluminum↗

Evaluation of acetic acid-induced gastric ulcers in dogs by endoscopic ultrasonography.

To clarify the ability of endoscopic ultrasonography (EUS) to diagnose gastric ulcer, we induced gastric ulcer (19 open ulcers and 11 ulcer scars) by injecting acetic acid into the stomach via an endoscope in 15 dogs. The stomachs were resected and scanned by EUS in a water bath, and the findings were compared with the histologic observations. The ulcer depth was correctly diagnosed in 29 of 30 instances (96.7%). In active, open ulcers the width and depth of the ulcer crater and the thickness of the gastric wall around the crater measured in the photographs obtained by EUS corresponded with those observed in histologic photographs. In the ulcers disrupting the muscularis propria layer the distance between the disrupted muscularis propria layer in EUS also corresponded to the histologic observations. In all ulcer lesions the low-echoic area below the ulcer in EUS corresponded to the histologic area of granulation or fibrosis. However, it was difficult to distinguish granulation from fibrosis by EUS. EUS is thus considered useful for evaluating gastric ulcers quantitatively in the clinical setting.

Acetates↗