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Biomedical subjects

K Suda

Publications and source records attributed to K Suda.

At least 181 records · Page 10Linked to original sources
PubMed1993

Continuous 5-fluorouracil infusion causing acute gastric mucosal lesions.

A 59-year-old woman with advanced gastric cancer was treated with continuous 5-fluorouracil infusion for thirty-five days. Endoscopy of the upper gastrointestinal tract was performed due to continuing nausea seven days after the cessation of 5-fluorouracil infusion and revealed multiple erosions in the antrum which were absent before chemotherapy. Continuous 5-fluorouracil infusion was probably the cause of acute gastric mucosal lesions and should be included in the differential diagnosis of dyspepsia in 5-FU-treated patients.

Adenocarcinoma↗
PubMed1993

Molecular form of islet amyloid polypeptide (amylin) released from isolated rat islets of Langerhans.

Islet amyloid polypeptide (IAPP) is a 37-amino acid residue polypeptide, originally isolated from the pancreatic amyloid deposits of patients with type II diabetes mellitus. Subsequently, IAPP was found to be colocalised with insulin in beta-cell secretory granules of the normal mammalian pancreas. Recently, IAPP has been reported to inhibit glucose-stimulated insulin release from isolated rat islets and to be released in response to glucose and arginine. To investigate further the regulation of IAPP release from the islet, we used a previously developed specific radioimmunoassay for IAPP and measured IAPP secretion from isolated rat islets of Langerhans. Release of IAPP-like immunoreactivity (-LI) was stimulated by glucose: 3.3 +/- 0.3, 3.9 +/- 0.3, and 11.1 +/- 1.5 (n = 5, mean +/- SEM) fmol/islet/60 min at 2, 7, and 20 mM, respectively. Carbachol (0.1 mM) increased the release of IAPP-LI at the lower glucose concentrations: 8.1 +/- 0.9, 8.7 +/- 0.6, and 11.7 +/- 1.8 fmol/islet/60 m in at 2, 7, and 20 mM glucose. Somatostatin (1 microM) suppressed glucose-stimulated IAPP-LI release (17.5 +/- 1.5 vs. 5.1 +/- 0.5 fmol/islet/60 min). Chromatographic characterisation of the IAPP-LI released into the incubation medium revealed two immunoreactive forms: The major peak (74% of the total IAPP-LI) corresponded to synthetic IAPP-37, while a smaller form, comprising 26% IAPP-LI, eluted later. In acid extracts of islets, all (> 95%) immunoreactivity co-eluted with the synthetic IAPP.

Amyloid↗
PubMed1993

Radionuclide assessment of left ventricular performance on exercise after external conduit operation.

Only limited information is available concerning left ventricular (LV) response to exercise after an external conduit operation for cyanotic congenital heart disease. Sixteen patients who had undergone external conduit repair (EC group) were studied with multi-gated cardiac pool imaging using a supine bicycle ergometer on 20 occasions. Six patients with a history of Kawasaki disease without coronary artery stenosis served as controls (control group). Myocardial imaging and cardiac catheterization were also performed in the EC group. There was no significant difference in left ventricular ejection fraction (LVEF) at rest between the groups. However, on exercise, LVEF of the EC group was significantly lower than that of the control group. Nine patients in the EC group showed a perfusion defect (PD) on 12 occasions. LVEF on exercise of the patients with PD was significantly lower than that of the patients without PD. Furthermore, only the patients with PD showed a LVEF decrease of 5% or more in response to exercise. In the EC group, a significant inverse relationship was demonstrated between right ventricular systolic pressure (RVP) and LVEF response to exercise. However, two out of four patients who underwent external conduit replacement improved their LVEF response to exercise with successful reduction of RVP. These findings indicate that an impaired left ventricular response to exercise was common in patients after external conduit operations. Myocardial damage and right ventricular outflow tract obstruction could be the causes of this left ventricular dysfunction.

Adolescent↗
PubMed1993

Intralysosomal pH and release of lysosomal enzymes in the rat liver after exhaustive exercise.

The mechanism underlying exhaustive exercise-induced release of lysosomal enzymes was studied in the rat liver. Exhaustive exercise resulted in the release of beta-glucuronidase and cathepsin D, but not beta-glucosidase and acid phosphatase, into the blood and cytosol, suggesting that the release of lysosomal enzymes is not due to disruption of lysosomal membranes. The intralysosomal pH of the liver, which was approximately 5.5 at the resting level, rose significantly after exhaustive exercise to pH 6.3. In vitro, beta-glucuronidase and cathepsin D were released at an intralysosomal pH exceeding 6.2. In contrast, beta-glucosidase and acid phosphatase were not released. The elevation of intralysosomal pH reduced the aggregation of beta-glucuronidase and cathepsin D. The rate of ammonia accumulation increased markedly in the lysosome-enriched subcellular fraction after exercise. There was a positive relationship between the rate of ammonia accumulation and the elevation of intralysosomal pH in vitro. Lysosomes isolated after exhaustive exercise showed significantly increased osmotic fragility. Our findings suggest that, during exhaustive exercise, the accumulation of ammonia in lysosomes leads to the elevation of intralysosomal pH, resulting in the reduced aggregation of certain lysosomal enzymes. Thus, less aggregated lysosomal enzymes may be released into the cytosol through the lysosomal membrane, the permeability of which has been increased.

Acid Phosphatase↗
PubMed1993

Effect of insulin on adipocyte lipolysis in exercise-trained rats.

The effect of exercise training on the antilipolytic action of insulin was studied in rat adipocytes. Exercise training enhanced lipolysis induced by norepinephrine. Insulin dose dependently inhibited norepinephrine- (1 microM) stimulated lipolysis in both groups. Its inhibition rate was significantly greater in the trained than in the control group. Thus, exercise training enhanced the antilipolytic action of insulin. In the control group, insulin (1,000 microU/ml) reduced the displacement rate of [3H]CGP-12177 binding to adipocytes by low concentrations of (-)-norepinephrine. The slope factor without insulin was 0.76, whereas that with insulin was 0.95. In the trained group, insulin did not affect the competition binding of (-)-norepinephrine for [3H]CGP-12177. The displacement rate of [3H]CGP-12177 binding from adipocytes by low concentrations of (-)-norepinephrine was significantly greater in the trained than in the control group. The number of surface beta-adrenergic receptors per adipocyte was smaller in the trained than in the control group. Cilostamide, which blocks the antilipolytic action of insulin, restored lipolysis in both groups. The recovery rate was significantly greater in the trained than in the control group. These findings suggest that the enhanced antilipolytic action by insulin in the trained group occurs at a site distal to the binding of norepinephrine to beta-adrenergic receptors and that it is due to the increased activity of particulate low-Michaelis constant phosphodiesterase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Mechanism of isoprenaline-stimulated diacylglycerol formation in rat parotid acinar cells.

The kinetics and mechanism of sn-1,2-diacylglycerol (DAG) formation induced by isoprenaline were studied in rat parotid acinar cells. DAG accumulation induced by 100 microM isoprenaline reached its maximum at 1 min, rapidly decreased (about 50%) at 5 min and then remained constant for 30 min. DAG accumulation 1 min after isoprenaline treatment was dose-dependent. Either propranolol or phentolamine inhibited isoprenaline-stimulated DAG accumulation in a dose-dependent manner. Addition of a vasoactive intestinal polypeptide, forskolin, or dibutyryl cyclic AMP had no effect on DAG accumulation. Isoprenaline did not cause the release of [3H]choline or [3H]ethanolamine metabolites into the medium. Based on the kinetics of DAG formation and [32P]phosphoinositide breakdown, we conclude that isoprenaline-induced DAG formation was mainly related to the hydrolysis of [32P]phosphatidylinositol 4,5-bisphosphate ([32P]PIP2). These results suggest that the effect of isoprenaline on DAG formation is mediated by alpha 1-adrenoceptor activation, that it is not related to the increase in cyclic AMP, and that it is closely related to PIP2 hydrolysis.

Alkaloids↗
PubMed1993

Expression of ras-P21 and ras gene alteration in pleomorphic adenomas.

The expression of ras-P21 protein and gene alteration of the K-ras gene were examined in 12 cases of pleomorphic adenoma of the salivary gland. The tumor cells in all 12 cases were strongly stained for ras-P21 protein by the indirect immunoperoxidase method, suggesting the enhanced expression of ras-P21 protein in pleomorphic adenomas. Analysis of the PCR products for the K-ras gene by temperature-gradient gel electrophoresis (TGGE) revealed that gene alterations such as point mutations occurred in 4 out of 12 pleomorphic adenoma tissues examined.

Adenoma, Pleomorphic↗
PubMed1993

Pancreatic fibrosis in patients with alcoholic dependence syndrome.

Pancreatic fibrosis in patients with alcoholic dependence syndrome was studied histopathologically. In 30 of 41 autopsied patients with alcoholic dependence syndrome, fibrosis was observed despite the absence of clinical pancreatitis. The fibrosis was categorized into three types, according to Martin's classification: intralobular sclerosis in 15 cases, perilobular sclerosis in seven cases, and a mixed intralobular and perilobular sclerosis in the remaining eight cases. The type of the fibrosis was not related to the duration of alcohol abuse. Alcoholic liver cirrhosis was coexistent in 23 of the 30 cases of pancreatic fibrosis. These cases were also divided into categories according to the three types, as follows: intralobular sclerosis in 12 (80%) of 15 cases, perilobular sclerosis in four (57%) of seven cases, and mixed sclerosis in seven (88%) of eight cases. That is, intralobular and mixed sclerosis were frequently coexistent with alcoholic liver cirrhosis. When the pancreases from the 19 subjects with intralobular sclerosis and mixed sclerosis coexistent with liver cirrhosis in alcoholic dependence syndrome were compared with 20 pancreases from patients with nonalcoholic liver cirrhosis, periacinar (or intralobular) fibrosis was found in all cases of the former, but in none of the latter. Hence, it was concluded that periacinar fibrosis occurred as a result of alcohol abuse. Pancreatic fibrosis in patients with alcoholic dependence syndrome was distributed mainly in the intralobular areas and was frequently coexistent with alcoholic liver cirrhosis.

Adult↗
PubMed1993

[A 66-year-old man with backache and progressive difficulty of gait].

We report a 66-year-old man with progressive spinal paraplegia. He was well until June of 1991 when he had an onset of backache and right chest pain. On August 25, he lost sensation to void and he became unable to urinate. On the same day, he noted weakness in his legs which became progressively worse, and he was admitted to our hospital. Past medical history included diabetes mellitus which was found 3 years previously. He had upper gastrointestinal series 2 months before, which revealed a normal study. On admission, he was alert and general physical examination was unremarkable. Neurological examination revealed a mentally sound man with normal higher cerebral functions. Cranial nerves were also intact. He was unable to walk. No muscle atrophy was noted, but he had moderate to marked (2/5) weakness in both legs. No ataxia was noted in the upper extremities. Jaw jerk was normal, however, deep reflexes in the upper extremities were decreased, and absent in the lower extremities Babinski sign was present bilaterally. All sensory modalities were diminished below the Th 6 dermatome. No meningeal sign was present. Emergency myelography was performed on the day of admission, which revealed complete block from the Th4 to Th8 segments. CSF taken at that time was xanthochromic, positive Queckenstedt test containing 1,133 mg/dl of protein, 54 mg/dl of sugar and 1/3 microliters of lymphocyte. On August 31, laminectomy was performed from Th5 to Th7. The spinal bones in this area was very fragile and hemorrhagic. A soft yellowish vascular-rich tissue was surrounding the spinal cord in the epidural space. Despite surgery his weakness in legs worsened, and he became paraplegic by September 10th. He became somnolent with disorientation to time. In the subsequent course, he developed metabolic acidosis on September 26. On September 28, he became anuric and hypotensive. He expired later on that day.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1993

[A 79-year-old man with rapidly progressive tetraparesis].

We report a 79-year-old man who developed progressive gait disturbance and sensory loss. He had been doing well except for hepatitis B virus hepatitis until 72 years of age when he developed angina pectoris for which aorto-coronary bypass operation was performed when he was 73-year-old (1986). In 1990, he developed pulmonary fibrosis for which prednisolone was prescribed. His liver function deteriorated, and the liver function tests suggested liver cirrhosis. He noted an onset of gait disturbance in the middle of June in 1992 when he was 79-year-old. His gait disturbance deteriorated progressively, and he developed edema and loss of sensation in his both legs. He became unable to walk unassisted in the beginning of July. He fractured his right external malleolus after falling down from a chair. He became unable to stand by himself, and he was admitted to the cardiology service of our hospital on July 18, 1992, and the neurology service was asked to see the patient on July 30 of the same month. The patient was well developed and well nourished man in no acute distress. General physical examination revealed slight jaundice, left carotid bruit, and slight pitting pretibial edema. His temperature was 37.3 degrees C. On neurologic examination, he was alert and mentally sound without dementia. He showed a slight weakness in the facial muscles bilaterally and mild dysarthria and dysphagia, however, the other cranial nerves appeared intact. He was unable to stand unassisted. The muscle tone was hypotonic, however, no focal muscle atrophy was noted, nor was observed fasciculatory twitches.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

[Etoposide, doxorubicin, cisplatin and 5-FU (EAP-F) therapy of advanced gastric cancer--its antitumor effect and evaluation of quality of life].

Fourteen patients with advanced gastric cancer were treated with EAP-F therapy. The regimen was CD DP 40 mg/m2 day 1 and 6, 5-FU 600 mg/m2 day 2 and 4, leucovorin 20 mg/m2 day 2 and 4, etoposide 60 mg/m2 day 3 and 5, and doxorubicin 20 mg/m2 day 7, with repetition every 28 days. Thirteen patients were evaluable; one patient was CR, four were PR, five were NC and three were PD. The response rate was 38.5% and median survival was 7 months. Hematologic toxicities were moderate to severe but tolerable, gastrointestinal toxicities were mild and renal toxicity was absent. Quality of life (QOL) of the patients was evaluated by means of symptom-free ratio (duration of symptom-free to survival time) and outpatient ratio (duration at home in relation to survival time). Patients with lymph node metastasis showed a higher symptom-free ratio and outpatient ratio than those with liver metastasis or peritoneal dissemination. All high-QOL patients were chemotherapy responders. In conclusion, EAP-F therapy is effective for advanced gastric cancer and its side effects are tolerable. CR or PR is necessary to achieve a high QOL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Investigation of the interaction of VIP binding sites with VIP and PACAP in human brain.

We have compared the binding of [125I]vasoactive intestinal polypeptide (VIP) to human brain membranes with that of [125I]PACAP27. [125I]VIP was displaced by PACAP27, VIP and two synthetic peptides, peptide-1 (N-terminal PACAP27/C-terminal VIP) and peptide-2 (N-terminal VIP/C-terminal PACAP27), but the IC50 of PACAP27 and peptide-1 were 10-20 times lower than those of VIP and peptide-2. [125I]PACAP27 was readily displaced by PACAP27 and peptide-1, with an IC50 of less than 1 nM, but poorly by VIP and peptide-2. Chemical cross-linking revealed that both labels were bound to polypeptides of Mr 66,000 and Mr 50,000. The results indicate that in human brain membranes both binding sites have a higher affinity to the N-terminal sequence of PACAP27, and VIP binding sites prefer PACAP27 to VIP itself.

Adenylyl Cyclases↗
PubMed1992

Mechanism of carbachol-stimulated diacylglycerol formation in rat parotid acinar cells.

We studied the relationship between phosphoinositide hydrolysis, phosphatidylcholine hydrolysis, and sn-1,2-diacylglycerol (DAG) formation in response to carbachol stimulation in rat parotid acinar cells. Previously, we demonstrated that DAG formation stimulated with 1 microM carbachol was biphasic: the first peak occurred at 5 min and the second one at 20 min. It was also demonstrated that the second peak was regulated in part by a calmodulin/protein kinase C-dependent mechanism. Based on the kinetic analysis of DAG formation and [32P]phosphoinositide breakdown, the first peak of carbachol (1 microM)-stimulated DAG accumulation was found to be related to the breakdown of [32P]phosphatidylinositol 4-monophosphate ([32P]PIP) and [32P]phosphatidylinositol 4,5-bisphosphate ([32P]PIP2). The second peak was found to be related to [32P]PIP2 breakdown. Carbachol stimulated the release of [3H]phosphocholine into the medium, indicating that the predominant pathway for phosphatidylcholine hydrolysis was via phospholipase C. Moreover, carbachol stimulated the release of [3H]choline metabolites in a time- and dose-dependent manner. This agonist slightly stimulated the release of [3H]ethanolamine metabolites. A calmodulin/protein kinase C-dependent mechanism was also studied and was found to be involved in carbachol-stimulated phosphatidylcholine hydrolysis; W-7, a calmodulin inhibitor and staurosporine, a protein kinase C inhibitor, inhibited the carbachol (1-microM)-induced release of [3H]choline metabolites at 20 min in a dose-dependent manner, but did not have inhibitory effects at 5 min. These results suggest that the first peak of DAG accumulation induced by carbachol is predominantly associated with the breakdown [32P]PIP and of [32P]PIP2 and that the second peak is predominantly associated with [32P]PIP2 breakdown and phosphatidylcholine hydrolysis.

Alkaloids↗
PubMed1992

Effects of CPT-11 in combination with other anti-cancer agents in culture.

CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy camptothecin, is a newly developed water-soluble camptothecin derivative now undergoing phase-II evaluation. In an attempt to establish whether the combination of CPT-11 with other standard anti-cancer agents would be of any benefit, we studied the effects of CPT-11 in combination with 11 other anti-cancer agents on a human T-cell leukemia cell line, MOLT-3, in culture. We used both CPT-11 and SN-38 (active substance of CPT-11 in vivo), for our study. Cells were incubated for 3 days in the presence of 2 drugs (CPT-11 or SN-38 and another drug) and cytotoxic effects were determined by MTT assay. The effects of drug combinations on ID50 were analyzed by an improved isobologram method. Supra-additive and marginal supra-additive effects (synergism) were observed for CPT-11 in combination with cisplatin, cytosine arabinoside and mitomycin C. Additive effects were observed for its combination with amsacrine, bleomycin, doxorubicin, etoposide, 5-fluorouracil, mitoxantrone and vincristine. Alternate sub-additive and protective effects (antagonism) were observed for CPT-11 in combination with methotrexate. Similar tendencies were observed for SN-38 in combination with other agents. These results suggest that CPT-11 in simultaneous administration with a majority of anti-cancer agents has an advantage for cytokilling. Of these agents, cisplatin, cytosine arabinoside and mitomycin C are most suitable for simultaneous administration with CPT-11.

Antineoplastic Agents, Phytogenic↗
PubMed1992

Surgical treatment of primary carcinoma of the gallbladder based on the histologic analysis of 48 surgical specimens.

During the past 5 years, extended cholecystectomy and/or more radical procedures, including pancreatoduodenectomy and extended hepatic lobectomy, were performed on 48 patients with carcinoma of the gallbladder in an attempt to cure the disease. It was retrospectively proven from microscopic analysis of the surgical specimens taken from the 48 patients that 28 patients had received curative resections. The 28 consisted of all 4 patients with stage I carcinoma, all 9 with stage II, 6 of 8 with stage III, and 9 of 27 with stage IV. We reached the following conclusions: (1) extended cholecystectomy with resection of the bile duct in the hepatoduodenal ligament is the optimum procedure for patients with stage I and stage II carcinomas, and (2) for patients with stage III carcinoma, more radical procedures, including pancreatoduodenectomy and/or wider resection of the liver, might result in curative resection of the disease. For some patients with stage IV tumors, such as duodenal invasion or direct invasion of the liver, curative resection may be achieved by pancreatoduodenectomy or extended hepatic lobectomy.

Adult↗
PubMed1992

Ca2+ potentiates corticotropin-induced, but not isoproterenol-induced, [3H]guanosine diphosphate release in rat adipocyte membranes.

EGTA abolished corticotropin (ACTH)-stimulated adenylate cyclase in rat adipocyte membranes. In contrast, the potency of guanosine triphosphate (GTP) stimulation of adenylate cyclase activated with ACTH was greater in the presence of Ca2+ (1 mmol/L). EGTA (1 mmol/L) powerfully inhibited ACTH-stimulated [3H]guanosine diphosphate (GDP) release from membranes prelabeled with [3H]GTP in the presence of isoproterenol (ISO) or ACTH, whereas Ca2+ significantly increased it. In contrast, neither EGTA nor Ca2+ affected ISO-stimulated [3H]GDP release. These data clearly show that Ca2+ is necessary for the binding of ACTH to its receptor, and that Ca2+ stimulates the interaction of the ACTH-occupied receptor with GTP-binding proteins.

Adenylyl Cyclases↗
PubMed1992

The effects of ICRF-154 in combination with other anticancer agents in vitro.

We studied the effects of ICRF-154 in combination with 11 anticancer agents on four human leukaemia cell lines. Cells were incubated for 3 days in the presence of two drugs (ICRF-154 and one other), and cell growth inhibition was determined by MTT assay. Effects of drug combinations at the ID50 level were analysed using the isobologram method (Steel). In the lymphoblastic leukaemia cell lines, MOLT-3, HSB, and B-ALL, supra-additive effects were observed for ICRF-154 in combination with amsacrine, bleomycin, doxorubicin, and etoposide. Additive effects were observed for its combinations with cisplatin, CPT-11, cytosine arabinoside, 5-fluorouracil, mitomycin C, and vincristine. Sub-additive to protective effects were observed in combination with methotrexate. In an erythroleukaemia cell line, K-562, no drug showed supra-additive effects with ICRF-154, while sub-additive to protective effects were observed for ICRF-154 in combination with cisplatin and methotrexate. The other drugs showed additive effects with ICRF-154. These results indicate that the combined effects of ICRF-154 with other agents vary, depending on the cell line. Against lymphoid malignancies, ICRF-154 would be advantageous when administered simultaneously with many anticancer agents. Of such agents, amsacrine, bleomycin, doxorubicin, and etoposide are the most suitable, while methotrexate is least suitable for such combined treatment.

Antineoplastic Agents↗