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Biomedical subjects

S Sakamoto

Publications and source records attributed to S Sakamoto.

At least 433 records · Page 24Linked to original sources
PubMed1991

Increased activities of thymidylate synthetase and thymidine kinase in human thyroid tumors.

Thymidylate synthetase (TS) is known to catalyse the methylation of deoxyuridine monophosphate (dUMP) for the de novo synthesis of deoxythymidine monophosphate (dTMP). Thymidine kinase (TK) catalyzes the formation of dTMP by the phosphorylation of thymidine via the pyrimidine salvage pathway. High TS and TK activities have been observed in rapidly proliferating tissues. Both TS and TK activities in human thyroid adenocarcinoma increased to approximately 2-fold that in normal thyroid tissue. The thyroid TK isozymes can be separated into two types by DEAE-cellulose column chromatography. One of them is associated with the cytosol cell fraction of rapidly proliferating cells, such as fetal or neoplastic cells. Its activity is not affected by low concentration of deoxycytidine triphosphate (dCTP), and its molecular weight and Km value for thymidine are 120 kD and 0.5 x 10(-6) M, respectively. The average activity of this cytosol-associated isozyme in thyroid adenocarcinoma was increased slightly to 2.3-fold that of normal thyroid tissue. These results obtained from the activities of TK and its isozyme may be indicative of the slow-growing property of thyroid adenocarcinoma compared to mammary or colonic adenocarcinoma, which has high activities of TK and its isozyme.

Adenocarcinoma↗
PubMed1991

Relationship between fetal hypoxia and endothelin-1 in fetal circulation.

The role of endothelin-1 (ET-1), a potent vasoconstrictor peptide secreted by endothelial cells, in fetal circulation was investigated in relation to fetal hypoxia. Umbilical venous blood was obtained from 23 subjects who delivered between 36 and 41 weeks of gestation. In all cases, pH of umbilical venous blood was measured immediately after the delivery of placenta. ET-1 was extracted from the umbilical venous plasma by an Amprep C2 column and determined by a specific radioimmunoassay. Immunoreactive ET levels in the umbilical cord plasma (pg/ml, mean +/- SEM) from subjects with umbilical venous blood pH levels below 7.30 (n = 9) were 12.53 +/- 2.03, significantly higher than those with pH levels above 7.30 (6.44 +/- 1.11, n = 14). These results indicate that ET-1 in the fetal circulation may be involved in the regulation of the circulation in response to changes in acid-base balance related to fetal hypoxia.

Adult↗
PubMed1991

Inhibitory effect of inhaled procaterol on anaphylactic bronchoconstriction and thromboxane A2 production in guinea-pigs.

This study was designed to examine whether an inhaled beta 2-agonist, procaterol, inhibits thromboxane A2 (TXA2) production induced by antigen challenge in passively sensitized guinea-pigs in vivo. Antigen-induced bronchoconstriction was markedly inhibited by pre-treatment with procaterol. Inhaled procaterol significantly reduced in a dose-dependent manner the increment in TXB2 concentration in bronchoalveolar lavage fluid obtained 5 min after antigen challenge. Aerosol administration of procaterol significantly inhibited bronchoconstriction induced by inhaled histamine. These results suggest that inhalation of procaterol has an inhibitory effect on antigen-induced TXA2 production as well as a protective effect against bronchoconstriction induced by bronchoactive agents.

Administration, Inhalation↗
PubMed1991

Inhibitory effect of inhalation of a thromboxane synthetase inhibitor on bronchoconstriction induced by aerosolized leukotriene C4 and thromboxane A2 analogue in anesthetized guinea pigs.

Effect of aerosol administration of a thromboxane synthetase inhibitor (OKY-046) on bronchoconstriction induced by aerosol leukotriene C4, histamine and a thromboxane A2 analogue (STA2) was studied in anesthetized, artificially ventilated guinea pigs in order to evaluate the effectiveness of inhalation of OKY-046 on an unfavorable mechanism of secondary release of thromboxane A2. 0.01-1.0 micrograms/ml leukotriene C4, 25-400 micrograms/ml histamine and 0.033-1.0 micrograms/ml STA2 inhaled from an ultrasonic nebulizer developed for small animals caused a dose-dependent increase of pressure at the airway opening (Pao), which is considered to be an index representing bronchial response. Pretreatment of the animals with aerosol OKY-046 (0.035 and 0.35 mg/animal) significantly reduced the airway responses produced by inhalation of leukotriene C4 and STA2, in a dose-dependent manner, while the pretreatment did not affect the histamine dose-response curve. These findings suggest that aerosol leukotriene C4 and STA2 activate thromboxane synthesis in the airway, and inhalation of OKY-046 may be useful for preventing the secondary release of thromboxane A2, which is an unfavorable mechanism in asthma.

Administration, Inhalation↗
PubMed1991

Perinatal morbidity of infants of diabetic mothers.

Along with the recent progress in controlling the diabetic state during pregnancy, the number of diabetic pregnancies in our country has been increasing. It is not appropriate to apply White's classification to Japanese pregnant women, because more than two-thirds are NIDDM and it is not easy to clarify their duration of illness. Neonatal complications were analyzed in 160 infants of diabetic mothers (IDMs) who were admitted to Tokyo Women's Medical College over the past five years. All were inborn except four. Neonatal outcomes of IDDM and NIDDM were not statistically different. The overall incidence of neonatal complications in IDMs was 66%, and there were no neonatal deaths. Offspring whose mothers had been suffering from retinopathy were likely to be premature and light-for-date infants. A planned pregnancy in diabetic women is likely to decrease neonatal complications. The cooperative total care of diabetic mothers and their offspring by respective specialists, namely endocrinologists, obstetricians and neonatologists is essential for the better prognosis of infants of diabetic mothers.

Female↗
PubMed1991

Clinicopathological analysis of alcoholic liver disease complicating chronic type C hepatitis.

Seventy-six chronic alcoholics in Japan were evaluated for histological changes of liver needle biopsies, Chiron C100 antibody (C-100) for hepatitis C virus, as well as clinical and laboratory data. In biopsies, the presence of necroinflammations within the parenchyma, lymphocytic reaction in the portal tracts, or both, might indicate non-A, non-B (NANB) chronic hepatitis. Using these histological criteria, the patients were previously classified into two groups: alcoholic liver disease (ALD) alone and ALD complicating NANB chronic hepatitis. The C100-positive ratio was found to be 12% in the former group and 69% in the latter. Further clinical and laboratory comparison revealed that there were significant differences in gamma-glutamyl transpeptidase, gamma-globulin, and adenosine deaminase levels in the sera between the ALD alone and the ALD complicating NANB chronic hepatitis groups. Since some chronic alcoholics are also affected by chronic type C hepatitis, detailed evaluations of the liver biopsy and C-100 assay are required for the differentiation of these hepatic disorders.

Antigens, Viral↗
PubMed1991

Anticancer effects of a Chinese herbal medicine, juzen-taiho-to, in combination with or without 5-fluorouracil derivative on DNA-synthesizing enzymes in 1,2-dimethylhydrazine induced colonic cancer in rats.

Juzen-taiho-to (JTT; [Shi-quan-da-bu-tang], a Japanese modified Chinese herbal prescription) in combination with an anticancer drug UFT (5-fluorouracil derivative) prevented the body weight loss and the induction of the colonic cancer in rats treated with a chemical carcinogen 1,2-dimethylhydrazine (DMH), and suppressed markedly the activity of thymidylate synthetase (TS) involved in the de novo pathway of pyrimidine synthesis in colonic cancer induced by DMH.

Adenocarcinoma↗
PubMed1991

Chronic beta-adrenoceptor blockade prevents the development of beta-adrenergic subsensitivity in experimental right-sided congestive heart failure in dogs.

BACKGROUND: The reductions of myocardial beta-adrenergic receptor density and responsiveness to catecholamines in congestive heart failure are associated with excessive sympathetic stimulation. The purpose of this study was to determine whether the myocardial changes could be prevented by beta-receptor blockade. METHODS AND RESULTS: We administered the oral beta-receptor blocking agent nadolol (40 mg/day) to dogs during an early stage of experimental right heart failure and to sham-operated dogs for 5 weeks. Animals receiving no nadolol were studied concurrently. Nadolol treatment did not prevent right ventricular hypertrophy or elevated concentrations of plasma norepinephrine that occurred in right heart failure, nor did it affect the decrease in myocardial norepinephrine content and norepinephrine uptake activity, suggesting that the hemodynamic stress imposed on the right ventricle of dogs with right heart failure was similar regardless of the presence or absence of beta-receptor blockade. Resting heart rate, right atrial pressure, aortic pressure, cardiac output, right ventricular dP/dt, and left ventricular dP/dt and dP/dt/P measured 5 days after discontinuation of nadolol did not differ significantly from those without nadolol treatment in either right heart failure or sham-operated animals. Sham-operated dogs also showed no changes in myocardial beta-receptor or adenylate cyclase activity after nadolol treatment. However, nadolol treatment prevented the reduction of myocardial beta-receptor density and attenuated the decrease in the cardiac beta-adrenergic sensitivity that occurred in right heart failure. CONCLUSIONS: Excessive sympathetic stimulation may play an important role in the development of beta-receptor downregulation and beta-adrenergic subsensitivity in right heart failure.

Adenylyl Cyclases↗
PubMed1991

Effects of short-term, diet-induced hypercholesterolemia on systemic hemodynamics, myocardial blood flow, and infarct size in awake dogs with acute myocardial infarction.

BACKGROUND: Short-term cholesterol feeding has been shown to affect vasomotor tone and increase infarct size in anesthetized rabbits. The purpose of the study was to determine whether acute hypercholesterolemia reduced collateral flow to ischemic myocardium and increased infarct size in the awake dog. METHODS AND RESULTS: Acute myocardial infarction was produced in awake dogs by a 4-hour left anterior descending coronary artery occlusion followed by 6-hour reperfusion after either a cholesterol-supplemented diet (n = 14) or a control diet of dog chow (n = 15) for 10 days. Infarct size was determined using nitroblue tetrazolium staining. In two subgroups, a 15-minute transient occlusion of the left anterior descending coronary artery was produced before the diet treatments and was compared with occlusion after diet treatments, so that the effects of hypercholesterolemia of collateral flow could be determined by paired comparisons. Cholesterol feeding increased plasma cholesterol to 288 +/- 52 mg/dl, which was twofold to threefold that in the control group (127 +/- 35 mg/dl), but had no effects on baseline systemic hemodynamics and myocardial blood flow. Coronary artery occlusion produced similar increases in heart rate, mean aortic pressure, left atrial pressure, and plasma norepinephrine in both groups of animals. However, cholesterol feeding reduced collateral flow to ischemic myocardium and increased infarct size, compared with the control group. The infarct size correlated with ischemic myocardial blood flow in both groups, but the slopes of regression lines relating the two variables did not differ between the two groups. CONCLUSIONS: Short-term, diet-induced hypercholesterolemia increased infarct size in awake dogs. This change results, at least in part, from a decrease in collateral blood flow to ischemic myocardium during coronary artery occlusion.

Animals↗
PubMed1991

Phorbol ester-induced LH release in pituitary gonadotrophs: effects of antagonists of calmodulin and GnRH.

The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of Ca(2+)- and phospholipid-dependent protein kinase (C kinase), stimulates luteinizing hormone (LH) release from rat pituitary cells. The actions of TPA upon LH release were compared with those of the GnRH superagonist [D-Ala6] des-Gly10-GnRH N-ethylamide (GnRHa) in cultured pituitary cells. LH release was stimulated by 0.1 nM TPA and the maximum response at 10 nM TPA was 50% of the LH response to GnRHa. The ED50 values for TPA and GnRHa were 1.2 and 0.037 nM, respectively, and the maximum stimulatory effects of TPA and GnRHa on LH release were not additive. GnRHa-stimulated LH release was decreased by calmodulin (CaM) antagonists including pimozide, trifluoperazine, W5 and W7, being most effectively reduced (by 70%) by 10 microM pimozide. In contrast to their inhibition of GnRH action, these antagonists enhanced TPA-stimulated LH release, so that 10 microM pimozide and W7 doubled the maximum LH response. The potent GnRH antagonist [Ac-D-p-Cl-Phe1.2, D-Trp3, D-Lys6, D-Ala10]GnRH, which completely inhibited GnRHa-stimulated LH release with ID50 of 6.8 nM, also reduced maximum TPA-stimulated LH release by about 50%. These results suggest that both Ca2+/CaM and C kinase pathways are involved in the LH release mechanism, and indicate that C kinase plays a major role in the action of GnRH upon gonadotropin secretion. The synergism between CaM antagonists and TPA suggests that blockade of CaM-mediated processes leads to enhanced activation of the C kinase pathway, possibly by removal of an inhibitory influence. Furthermore, the partial inhibition of TPA-stimulated LH release by a GnRH antagonist suggests that the pathway(s), specifically connected with LH release in the diverse effects of C kinase, might be locked by the continuous receptor inactivation by antagonist and indicates the complicated pathways which diverge from the receptor and converge into specific cellular response.

Animals↗
PubMed1991

Immunocytochemical study of phenobarbital- and 3-methylcholanthrene-inducible cytochrome P450 isozymes in primary cultures of porcine ciliary epithelium.

We found in the previous study that the induction of 7-pentoxyresorufin O-dealkylase and 7-ethoxyresorufin O-dealkylase activities by phenobarbital and 3-methylcholanthrene, respectively, is more pronounced in porcine ciliary nonpigmented epithelial cells than in pigmented epithelial cells. In order to determine whether cytochrome P450 isozymes that mediate the O-dealkylase activities are also induced in nonpigmented cells under the conditions, primary cultures of porcine ciliary processes were treated with phenobarbital and 3-methylcholanthrene and the expression and localization of cytochrome P450 isozymes induced by these compounds were investigated by immunocytochemical methods using antibodies against the individual P450 isozymes. Intense labeling of nonpigmented epithelial cells was observed when ciliary processes treated with phenobarbital were reacted with anti-P450 (phenobarbital) antibody and when the processes treated with 3-methylcholanthrene were incubated with anti-P450 (methylcholanthrene) antibody. The labeling patterns supported the conclusion that the O-dealkylase activities and P450 isozymes specific for these activities are co-induced in and localized to the endoplasmic reticulum. This study is the first report presenting direct evidence of cytochrome P450 induction in primary cultures of ocular tissues and demonstrates the usefulness of porcine ciliary epithelial cells for studying the induction of ocular drug metabolizing enzymes.

Animals↗
PubMed1991

[DNA-synthesizing enzyme activities and the immunohistochemistry in proliferation of bone marrow cells in rats].

Thymidylate synthetase (TS) and thymidine kinase (TK) are know to catalyze the methylation of dUMP for the de novo synthesis of dTMP and the phosphorylation of thymidine for the salvage synthesis of dTMP in the pyrimidine pathway, respectively, and both enzyme activities are high in rapidly proliferating tissues. In the present study, these enzyme activities and the immunohistochemistry using monoclonal anti-bromodeoxyuridine (BrdU) were investigated during the period of proliferation of bone marrow cells after the hypoplastic period induced by cyclophosphamide (Cy) treatment in rats. Right after Cy treatment, nucleated cell count (NCC) of bone marrow cells, BrdU labelling ratio and TK activity were abruptly decreased. On the other hand, TS activity peaked at day 5 followed by an increase of TK activity, NCC and BrdU labelling ratio from day 7 after Cy treatment. These results indicate that, in the proliferation of bone marrow cells, the DNA de novo synthesis rises at first, and secondly, the DNA salvage synthesis predominantly increases with the increase of bone marrow cells labelled with BrdU, i.e., increase of the cells in the S phase.

Animals↗
PubMed1991

Serum factor from patients with cirrhosis and hepatocellular carcinoma enhances production of prostaglandin E2 by U937 cells.

The effect of serum from patients with cirrhosis and hepatocellular carcinoma on the release of prostaglandin E2 by the human histiocytic lymphoma cell line U937 was investigated to explain the mechanism underlying the immunoregulatory dysfunction of monocytes in cirrhosis and hepatocellular carcinoma. Prostaglandin E2 production by U937 cells cultured with serum from cirrhosis patients (5.9 +/- 2.7 ng/ml, p less than 0.01) and hepatocellular carcinoma patients (5.4 +/- 2.6 ng/ml, p less than 0.01) was significantly higher than that of control cultures (2.0 +/- 1.0 ng/ml). This activity was decreased after heating and after freezing and thawing. By size exclusion fast protein liquid chromatography, the probable factor was eluted in the fraction with a molecular weight of 150 kD. By anion exchange chromatography with a stepwise increase of the NaCl concentration, the peak activity augmenting prostaglandin E2 production by U937 cells was eluted in the 0.05 to 0.1 mol/L NaCl fraction. The high level of this factor (monocyte-regulating factor) in patient serum might be one cause of abnormal monocyte immunoregulatory function in cirrhosis and hepatocellular carcinoma.

Blood Physiological Phenomena↗
PubMed1991

[An immunohistochemical study on cellular infiltration of bronchial walls in bronchial asthma].

Inflammatory cell reactions in bronchial asthma have been considered to contribute directly to asthmatic attacks. Therefore, attention has been focused on the role of inflammatory cells in the airway wall. In this study, we investigated inflammatory cells in the airway wall of bronchial asthma histologically and immunohistologically using 20 autopsy cases who died of the asthma attacks (Group A) and 11 autopsy cases who died of other causes (Group B). Six autopsy cases were treated as controls (Group C). A significantly larger number of eosinophils in the bronchi and bronchioles were found in Group A. The majority of eosinophils were found to be stained with EG2. Parts of the bronchial epithelium with marked infiltration of EG2 positive eosinophils were detached from the basal layer. Immunoelectron microscopically, the matrix of EG2 positive areas within the eosinophils corresponded to that of eosinophil granules. A significantly larger number of lymphocytes in the bronchi and bronchioles was observed in Groups A and B. Almost all of these lymphocytes were determined to be activated T lymphocytes. There were significantly more IgE positive cells in cases with bronchial asthma, especially in Group A. The majority of IgE positive cells were determined to be mast cells. These results suggest that eosinophils, lymphocytes and mast cells play an important role in the pathogenesis of bronchial asthma.

Adolescent↗
PubMed1991

Long-term bone marrow failure accompanied by skin pigmentation.

A rare case of long-term bone marrow failure with skin pigmentation is presented. The patient was a female with a long history of anemia and skin pigmentation since childhood, although she had no malformations nor chromosomal abnormalities. Hematological improvement has been maintained by the administration of prednisolone. This case may differ from other disorders known as congenital aplastic anemia.

Addison Disease↗
PubMed1991

[Endophthalmitis in Japan--a nationwide study with reference to type and etiology].

A nationwide clinical study on bacterial and fungal endophthalmitis was done with special reference to their type and etiology. Two hundred and eighty cases of endophthalmitis were reviewed. All cases were divided into two categories such as exogenous (trauma, surgery, and ulcer) and endogenous (metastasis). Penetrating trauma was responsible for 93 cases (33.2%), surgery for 88 cases (31.4%), ulcer for 11 cases (3.9%) and metastasis for 88 cases (31.4%). Out of the 280 cases, 79 cases (28.2%) were microbiologically diagnosed through aqueous or vitreous tap or biopsy. The total numbers of isolated organisms amounted to 87 consisting of 43 Gram-positive bacteria, 30 Gram-negative bacteria and 14 fungi. The positive isolation was 31 out of 86 (36%) from the aqueous and 52 out of 103 (50%) from the vitreous. Exogenous types associated with trauma, surgery or ulcer were mainly caused by Gram-positive bacteria of 37 strains, led by coagulase-negative staphylococci in 14 cases. On the other hand, endogenous cases were mainly due to Gram-negative bacteria of 14 strains including Klebsiella pneumoniae in 5 cases, E. coli in 4 cases and fungi of 11 strains including candida spp in 9 cases.

Adolescent↗
PubMed1991

[Clinicopathological study of meningiomas of the tentorium and its surrounding structures].

We report the clinical features, radiological studies, operative procedures and results, and follow-up data in 29 patients with meningiomas of the tentorium and its surrounding structures. The cases represented 22.5% of all the intracranial meningiomas operated on in a 15 year period and were divided into three groups, depending on their main attachments, tentorial, cerebellopontine angle (dorsal aspect of the petrous ridge) and others. Tumor size was generally large and 13 cases were larger than 5 cm. The most common tumor site was along or near the superior petrosal sinus and transverse-sigmoid junction in cases involving the tentorium, and medial to the porus acousticus in cases involving the cerebellopontine angle. Different operative approaches to these tumors were carried out, depending on their location. The tumors in the lateral or medial petrous ridge were approached mainly with a suboccipital craniectomy using a retromastoid incision. Total removal was carried out in 80% of the tentorial cases, in 46.2% of cerebellopontine angle cases, and in the 83.3% in the others. Total operative mortality rate was zero. Follow-up periods ranged up to 5 years 5 months in the tentorial cases, 4 years 6 months in cerebellopontine angle cases, and 7 years 1 month in the others. Long-term results were good in 21 cases (72.4%), fair in 3 cases (10.3%) and poor in 2 (6.9%). Three patients died due to tumor recurrence. One of them suffered lung metastasis, and two of them suffered extensive local recurrences. We recommend the retromastoid approach combined with the petrosal approach, if the CPA tumor is large enough and extends to the retroclival region.

Adult↗