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Biomedical subjects

Y Sakaguchi

Publications and source records attributed to Y Sakaguchi.

At least 73 records · Page 4Linked to original sources

Acute left ventricular failure with pulmonary edema following pericardiocentesis for cardiac tamponade--a case report.

We describe the complications of pericardiocentesis and their management in an 18 year-old man. This patient was admitted because of dyspnea and was found on echocardiogram to have cardiac tamponade with coexisting left ventricular dysfunction. He developed acute left ventricular failure with severe pulmonary edema immediately after pericardiocentesis. This complication may have been caused by an abrupt increase in venous return to the failing left ventricle following the release of the pericardial compression. Therefore, pericardial fluid must be drained with caution in pericardiocentesis, especially in cardiac tamponade patients with left ventricular dysfunction, and hemodynamics should be monitored both during and after this procedure.

Acute Disease↗

Beta-adrenergic stimulation induces ST-segment elevation in dogs with healing myocardial infarction.

There is controversy with regard to the mechanism of the exercise-induced ST-segment elevation in myocardial infarction. The purpose of the present study was to investigate the mechanism of ST-segment elevation through pharmacologic interventions. Transmural anterior myocardial infarction was produced by gelatin sponge embolization of the left anterior descending artery in seven closed-chest dogs. One and four weeks after myocardial infarction, the dogs underwent the following three interventions: right atrial pacing, norepinephrine infusion (3.75, 7.5, and 15 micrograms/min) with the pacing, and methoxamine injection (2.5 and 5.0 mg) with the pacing. All dogs had transmural infarction with a mean infarct size of 12.0 +/- 4.2% of the left ventricular weight. Right atrial pacing did not induce significant changes in ST-segment. Norepinephrine induced a marked elevation of ST-segment at leads V1 to V4, while methoxamine did not. Norepinephrine induced a significant increase in left ventricular ejection fraction, while methoxamine produced a marked decrease in the ejection fraction and an increase in ventricular volume. The mean percent radial shortening of the non-infarct ventricular wall showed a significant increase with norepinephrine, but a decrease with methoxamine. In conclusion, myocardial ischemia and wall motion abnormality may be excluded as possible mechanisms of ST-segment elevation and an enhanced beta-adrenergic mechanism in the non-infarct myocardium is suggested to be responsible for ST-segment elevation.

Adrenergic beta-Agonists↗

Male reproductive toxicity study of nefiracetam in rats.

Sprague-Dawley male rats were administered nefiracetam orally at daily doses of 500 and 1500 mg/kg/day for 4 or 9 weeks. Although the copulation index was not affected by nefiracetam treatment, the fertility index was extremely low in the 1500 mg/kg/day group for both treatment periods. This high dose group consistently exhibited decreased testicular weights. Epididymal and prostate weights were also reduced in the 1500 mg/kg/day group after both 4- and 9-week treatments and in the 500 mg/kg/day group after the 9-week treatment. Severe degenerative changes such as degeneration of germ cells, loss of germ cells and atrophy of seminiferous tubules were observed in all rats of the 1500 mg/kg/day groups after both 4 and 9 weeks of treatment. Retention of spermatids in stage IX, X and XI seminiferous tubules was also noted after the 4- and 9-week treatments at 500 mg/kg/day. The testicular sperm head counts were markedly decreased following the 4- and 9-week treatments at 1500 mg/kg/day, and mildly reduced after the 4-weeks treatment at 500 mg/kg/day. From these results it is concluded that histopathological examination and the testicular sperm head count method are highly useful for detecting testicular toxicity and that testicular lesions caused by nefiracetam can be detected after 4 weeks of exposure.

Animals↗

[Reproductive toxicity of iodixanol, a new non-ionic, iso-tonic contrast medium in rats and rabbits].

The reproductive toxicity of iodixanol, a non-ionic isotonic contrast medium, was investigated in rats and rabbits. Iodixanol was administered intravenously to male rats at doses of 0.3, 1.0 or 2.0 gI/kg/day for 80 days or more until successful copulation. Female rats were treated with iodixanol at the same dose levels for at least 14 days prior to and in the early stage of pregnancy. No remarkable adverse effects on fertility were noted at any dose level. Increased water consumption and swollen paws/face were observed among male rats receiving > 1.0 gI/kg/day. In addition, decreased food consumption was observed in males of the 2.0 gI/kg/day group. In female rats, no remarkable adverse effects were noted at any dose level. Iodixanol elicited no evidence of teratogenicity when administered during the fetal organogenesis period to pregnant rats and rabbits at doses of 0.3, 1.0 or 2.0 gI/kg/day. No remarkable changes were observed in rat or rabbit fetuses, nor in dams of any dose group. In a perinatal and postnatal dosing study in rats using doses of 0.3, 1.0 or 2.0 gI/kg/day, iodixanol did not adversely affect the reproductive performance of the treated parent animals and pre- and postnatal development of their offspring.

Abnormalities, Drug-Induced↗

[Anesthetic management of Seckel syndrome: a case report].

Seckel syndrome is a rare syndrome of chromosome aberration, in which bird-headed dwarfism, microcephalus and other minor deformities are recognized. A 24-year-old male patient with Seckel syndrome underwent both abdominal and orthopaedic surgeries in 1 year under general anesthesia. The first operation was an emergent operation under preshock state and enterostomy was performed. The second was arthrodesis of the hip joint. Before the second operation, laryngeal CT, tomography and fiberscopy revealed stenosis just below his vocal cord. During the second operation, the anesthesia was unsatisfactory with inhalation of nitrous oxide and sevoflurane and intravenous vecuronium, because of intraoperative abnormal hypertension. But the recovery from the anesthesia was prompt. Although we experienced no difficulty in intubation except for intraoperative abnormal hypertension, preoperative laryngeal and renal examinations are necessary in the anesthetic management of this syndrome.

Abnormalities, Multiple↗

[DNA ploidy pattern and p53 overexpression in gastric cancer].

DNA ploidy pattern was determined by flow cytometry and p53 overexpression was investigated immunohistochemically in 145 primary gastric cancers. Aneuploid patterns were found in 78 (65%) and diploid patterns in 67 (46%). Metastasising to lymph nodes was observed more frequently in cases with aneuploid tumors, as compared to those with diploid tumors (p < 0.01). DNA ploidy patterns were related to overexpression of p53. The incidences of overexpression of p53 in aneuploid tumors and diploid ones were 65% and 33%, respectively (p < 0.05). Thus, we suggest that gastric carcinomas with the aneuploid pattern have mutation of tumor suppressor gene p53 and high potential to metastasize to lymph nodes.

Cell Cycle↗

[Two-color flow cytometry analysis of lymphocyte subsets in patients with acute myocardial infarction and post-myocardial infarction syndrome].

Serial changes in lymphocyte subsets were analyzed in 37 patients with acute myocardial infarction (AMI), in 2 patients with postmyocardial infarction syndrome (PMIS), and in healthy subjects (control group) using two-color flow cytometry to investigate cellular immunity after AMI and PMIS. Peripheral blood lymphocyte subsets were measured on admission and at weeks 2, 4, 8, and 16 after the onset of AMI. The white blood cell count was significantly higher on admission and at week 2 in the AMI group compared with the control group. The percentage of CD4-positive helper T cells was significantly higher on admission and at weeks 2 and 4 in the AMI group compared with the control group, and the percentage of CD8-positive suppressor T cells was significantly lower in the AMI group at week 2 than in the control group. The ratio of helper-to-suppressor T cells peaked 2 weeks after the AMI and then decreased gradually. There were no significant changes in the CD4/CD8 ratio, the percentage of cytotoxic T cells, or the percentage of inducer T cells, throughout the observation period. There were no significant differences in the percentage of T cells, B cells, CD4-positive T cells, CD8-positive T cells, and natural killer cells between AMI patients and control subjects. The percentage of activated CD4- and CD8-positive cells was higher in the AMI group at weeks 4 and 8 than in the control group. There was no significant correlation between changes in lymphocyte subsets and infarct size. The percentage of activated CD8-positive cells was consistently higher in the PMIS group compared with the control and AMI groups. The percentage of cytotoxic T cells in one of the PMIS patients was significantly higher than in the AMI group. There were no significant differences in the proportions of other subsets between PMIS and AMI patients. The changes in lymphocyte subsets observed in patients with AMI suggested that immunological competence was enhanced in these patients. Abnormalities in humoral immunity, such as the appearance of anticardiac antibody, have been observed in patients with PMIS. Our results suggest that PMIS is also associated with changes in cellular immunity.

Adult↗

Clinicopathologic characteristics and outcome of adenocarcinoma of the human gastric cardia in comparison with carcinoma of other regions of the stomach.

BACKGROUND: Carcinoma arising in the cardioesophageal junction is a distinct clinical entity compared with tumors located in other regions of the stomach. This study was done to analyze the biologic characteristics of carcinoma of the gastric cardia compared with other gastric carcinomas. STUDY DESIGN: Clinicopathologic features and postoperative prognosis of 68 cases of carcinoma of the cardia were evaluated, in comparison with findings of tumors in other regions of the stomach. RESULTS: From 1975 to 1992, 68 (6.5 percent) of 1,042 patients with carcinoma of the stomach had adenocarcinoma of the cardia. Carcinoma of the cardia was characterized by a more advanced stage compared with carcinoma of other regions of the stomach. The incidence of early stage carcinoma (limited to the submucosal layer) was 11.8 percent in the cardia, 15.8 percent in the upper one-third, and 42.2 percent in the remaining middle and lower thirds of the stomach. When compared to carcinoma in other regions of the stomach, tumors of the cardia had a significantly poorer prognosis and there was a higher incidence of lymph node and hepatic metastasis. The five-year survival rates in patients with adenocarcinoma in the cardia, the upper one-third, and the remaining middle and lower thirds of the stomach were 35.3, 43.7, and 61.9 percent, respectively. Especially for patients with stage II and stage III disease, the prognosis was significantly worse with adenocarcinoma of the cardia than with carcinomas of the other regions of the stomach. CONCLUSIONS: Early detection is crucial to improve the survival of patients with carcinoma of the gastric cardia. Extended dissection of lymph nodes and aggressive postoperative chemotherapy in an attempt to prevent hepatic metastasis are highly recommended.

Adenocarcinoma↗

[Immunohistochemical study of the endomyocardial biopsy of systemic lupus erythematosus].

The mechanisms of cardiac involvement in systemic lupus erythematosus (SLE) were studied using immunohistochemical staining of endomyocardial biopsy specimens from 14 patients with SLE and normal coronary arteriograms. All 14 specimens showed mild interstitial edema, 11 showed mild cardiac fibrosis, and another two cases showed moderate cardiac fibrosis with myocardial derangements. Four specimens showed moderate cell infiltration in the interstitium. Area of fibrosis, diameter of myocardium and area of interstitial edema were increased in the SLE patients compared to the control cases. Immunofluorescence showed IgG and fibrinogen deposition in the membrane of cardiac myocytes and in the interstitium. Immunohistochemistry found no B lymphocytes in any of the seven SLE cases. T lymphocytes were observed in all seven SLE cases, and OKT 8 lymphocytes were increased significantly in the interstitial tissue as compared with OKT 4 lymphocytes. At endomyocardial biopsy, all 14 patients were receiving corticosteroid therapy and had low activity disease. The results suggest that cardiac tissue damage was associated with immunological abnormalities and might progress silently under conditions in which the disease activity was suppressed by corticosteroid therapy.

Adult↗

[A case of desmoplastic malignant mesothelioma].

A 43-year-old man was admitted to Nara Medical University Hospital because of right-sided chest pain. Computed tomographic examination revealed a right pleural effusion and diffuse pleural thickening. Malignant mesothelioma was diagnosed from the results of a percutaneous pleural biopsy, and the patient then underwent right pleuro-pneumonectomy. The resected specimen was examined by light and electron microscopy, which revealed scattered sarcoma-like malignant cells with some epithelial differentiation, in abundant extracellular collagen with storiform derangement. Therefore, desmoplastic malignant mesothelioma (mixed type) was diagnosed. This is a rare histological subgroup of malignant mesotheliomas. The patient died 2 months after the operation, due to multiple and rapidly growing metastases. After lung tissue was dissolved, ferruginous (asbestos) bodies were counted, and the results were consistent with occupational exposure to asbestos (413 asbestos bodies per 5 g of lung tissue).

Adult↗

Therapeutic efficacy of long duration-low temperature whole body hyperthermia when combined with tumor necrosis factor and carboplatin in rats.

This study examines the effects of a combined modality regimen of long duration-low temperature whole body hyperthermia (6 h at 40.0 degrees C; LL-WBH), recombinant human tumor necrosis factor-alpha (TNF) and carboplatin (CBDCA) on a transplantable fibrosarcoma as well as normal tissue. We compare LL-WBH with short duration-high temperature whole body hyperthermia (2 h at 41.5 degrees; SH-WBH). LL-WBH alone had no significant effect on tumor growth. Tumor growth delay (TGD) with TNF alone (0.1 days) and that with CBDCA alone (1.3 days) were significantly increased to 2.6 days (P < 0.05) and 2.8 days (P < 0.05), respectively, when combined with LL-WBH. Although TNF+CBDCA produced minimally increased TGD of 1.9 days, the combination of LL-WBH+TNF+CBDCA produced a significantly greater TGD of 5.6 days, compared to the other dual combinations (P < 0.01). There was no difference between TGDs for SH-WBH and LL-WBH in combination with TNF+CBDCA. Trimodality treatment-induced normal tissue toxicities, characterized by body weight loss, diarrhea, foot edema, and myelosuppression, were significantly greater in rats treated with SH-WBH+TNF+CBDCA, compared to LL-WBH+TNF+CBDCA. Histopathological examination also demonstrated that SH-WBH+TNF+CBDCA caused severe damage to the lymphoid tissues, intestinal tract, and peripheral microvasulature. We observed minimal histopathological changes observed in rats treated with LL-WBH+TNF+CBDCA. These data suggest that LL-WBH in combination with TNF and CBDCA has a greater therapeutic efficacy than SH-WBH.

Animals↗

Laser flow cytometric studies on the intracellular accumulation of anthracyclines when combined with heat.

The effects of heat on intracellular accumulation of anthracyclines were investigated by laser flow cytometry analysis. Sarcoma-180 cells were exposed to Adriamycin (ADM), epirubicin (EPIR), daunomycin (DM), THP-Adriamycin (THP), ME-2303 (ME) and KRN-8602 (KRN) at 37 degrees C and at higher temperatures. There was a dose-dependent increase in the fluorescence intensity of all drugs at 37 degrees C, but heat varied the fluorescence intensity of each drug. At 43 degrees C the cellular fluorescence of ADM and EPIR increased by approximately 200%, but for DM the increase was 110-130%. The cellular fluorescence of THP and ME was little affected by heat, and heat reduced that of KRN to 80-90%. Each drug showed was unique in the relationship between drug exposure time and the fluorescence intensity at 37 degrees C and 43 degrees C. Cytotoxicity determined by the MTT assay was enhanced with heat in the cases of ADM and EPIR, but not with DM, THP, ME, or KRN. Thus, ADM and EPIR are expected to show enhanced antitumor activities when given in combination with hyperthermia.

Animals↗

Absence of anti-trifluoroacetate antibody after halothane anaesthesia in patients exhibiting no or mild liver damage.

It has been shown that the circulating antibodies, which bind to rat hepatic microsomal proteins obtained after in vivo exposure to halothane, are detectable by immunoblotting in patients with "halothane hepatitis (HH)," and that rabbit immunized anti-sera against trifluoroacetylated rabbit serum albumin (TFA-RSA) recognizes rat microsomal distorted polypeptides in almost the same way as do sera from patients with HH. In this paper, we report first the development of a novel method of synthesizing TFA-RSA using p-nitrophenyl TFA, and second the results of tests for circulating anti-TFA antibodies in the serum of 86 patients who had received halothane anaesthesia and developed no (67 patients) or mild (19 patients, the maximum activity of serum alanine aminotransaminase 519 IU.L-1) liver damage. Serum was selected from stored sera of post-transfusion patients. The new method of synthesizing TFA-RSA was convenient and was able to be done at neutral pH. Rabbit sera obtained after immunization with the newly synthesized TFA-RSA recognized the same polypeptides (109 kDa, 92 kDa, 80 kDa, 76 kDa, 64 kDa and 59 kDa) as the established anti-sera against TFA-RSA, and these reactions were inhibited in the presence of TFA-lysine. Circulating antibodies were not detected in our patients who had developed no or mild liver damage. The present finding supports the hypothesis that the appearance of circulating antibodies against microsomal distorted proteins are specific to patients with HH. Furthermore, we have shown here that the halothane-induced mild increase in ALT activity is not associated with the appearance of those circulating antibodies, supporting the pathophysiological difference between HH and halothane-induced mild hepatic damage.

Adolescent↗

Exercise-induced ST-segment elevation and hemodynamic responses one month after myocardial infarction.

Changes in hemodynamics and plasma norepinephrine levels during supine bicycle exercise after myocardial infarction were measured to investigate the mechanism of exercise-induced ST-segment elevation. Seventy-eight patients were divided into groups which showed either ST elevation (STE), ST depression (STD), or no ST changes (STU). Most of the STE group had anterior myocardial infarction (90.6%) and single-vessel disease (76.7%). The STE group achieved a significantly higher workload (119.5 +/- 4.0 watts, mean +/- SEM) than the STD group (82.3 +/- 2.8, p < 0.01). Heart rate and cardiac output at maximal workload were significantly higher in the STE group (136.6 +/- 3.4 beats/min, 7.44 +/- 0.28 l/min/m2) than in the STD group (110.0 +/- 3.9, 4.83 +/- 0.36, p < 0.01). Pulmonary artery pressures were less elevated in STE than STD patients. Plasma norepinephrine levels increased significantly at maximal workload in STE patients, as compared to the other groups. In conclusion, the STE group achieved a higher exercise level associated with augmented sympathetic activity, which may be a possible mechanism of exercise-induced ST elevation after myocardial infarction.

Cardiac Output↗

Angiotensin II receptor antagonist, TCV-116, prevents myocardial hypertrophy in spontaneously hypertensive rats.

Recently, it has been suggested that angiotensin II (AII) might be associated with cardiac hypertrophy and fibrosis. We investigated the preventive effect of an AII receptor antagonist, TCV-116, on the development of cardiac hypertrophy and fibrosis in spontaneously hypertensive rats (SHR) at 24 weeks of age through histopathological study and an AII receptor assay. Treatment with TCV-116, enalapril (an angiotensin-converting enzyme inhibitor, ACEI), and hydralazine for 20 weeks lowered systolic blood pressure (SBP) significantly (-39 mmHg, -45 mmHg, and -45 mmHg, respectively). The heart weight/body weight ratio, cardiac myocyte diameter, and percent cardiac fibrosis were significantly reduced by treatment with TCV-116 and enalapril as compared with hydralazine treatment or no treatment. The AII receptor density was significantly increased by treatment with TCV-116 and enalapril as compared with hydralazine treatment or no treatment. The results of this study suggest that AII receptors are involved in the development of cardiac hypertrophy and fibrosis in SHR. It was demonstrated that the AII receptor antagonist, TCV-116, was comparable to the ACEI, enalapril, in inhibiting the progression of cardiac hypertrophy and fibrosis via the AII receptor.

Angiotensin II↗