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Biomedical subjects

M Saitoh

Publications and source records attributed to M Saitoh.

At least 379 records · Page 21Linked to original sources

Modulation of calmodulin function and of Ca2+-induced smooth muscle contraction by the calmodulin antagonist, HT-74.

The relationship between the functions of calmodulin (CaM) and Ca2+-induced smooth muscle contraction was investigated using a newly synthesized CaM antagonist, 3-(2-benzothiazolyl)-4,5-dimethoxy-N-[3-(4- -phenylpiperidinyl)propyl]benzenesulfonamide (HT-74). We noted a selectivity of HT-74 for CaM, compared to other calcium-binding proteins and target enzymes of CaM. As HT-74 had no significant effect on the intensity of 8-anilino-1-naphthalene-sulfonic acid (ANS) fluorescence in the presence of the Ca2+-CaM complex, the HT-74-binding sites may differ from those of naphthalenesulfonamides and phenothiazines which decrease ANS fluorescence. The Ca2+ binding to CaM was inhibited significantly by 1.0 microM HT-74, in sharp contrast to phenothiazines and naphthalenesulfonamides which increase the extent of the Ca2+ binding to CaM. Increasing CaM concentrations reversed the HT-74-induced inhibition of CaM-dependent enzymes such as myosin light chain kinase and Ca2+-dependent cyclic nucleotide phosphodiesterase, with Ki values of 0.5 microM and 0.4 microM, respectively. In the presence of 0.3 microM HT-74, potassium-depolarized rabbit aortic strips pre-contracted with 0.3 mM CaCl2 relaxed, and this relaxation was completely reversed by the addition of an excess amount of CaCl2 (10 mM). This compound shifted the dose-response curve for CaCl2 to the right, in a competitive manner. However, HT-74 inhibited the phenylephrine-induced contraction elicited in Ca2+-free solution and the calcium ionophore A23187-induced contraction in the presence of calcium ion. Therefore, this agent affects intracellular actions of Ca2+ rather than membrane receptors or the influx of Ca2+. HT-74 is a CaM antagonist which binds to CaM in a manner different from that heretofore reported. It inhibits Ca2+ binding to CaM and produces a competitive inhibition of Ca2+-induced contractions of depolarized vascular smooth muscle.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

[Clinical value of urinary kallikrein determination in obstetrics].

Whether to determine the urinary kallikrein (UKK) level in the second trimester of pregnancy is valuable or not for the prediction of gestosis, especially of hypertension in the third trimester of pregnancy, was studied on 700 cases of pregnant women including 50 cases of gestosis. The main results obtained were as follows. Sixty cases of 610 non-gestotic women were low in UKK, and 17 of these cases later resulted in gestosis or preterm delivery. When a patient with mild gestosis and/or hypertension was admitted, the UKK level was elevated significantly in general by bed rest and a low-salt diet. The UKK level was more significantly lowered in threatened preterm delivery than in normal pregnant women (p less than 0.001). A close positive correlation was seen between UKK levels and prostaglandin E2 in urine in pregnant women (n = 30, r = 0.528). A relatively close correlation was seen between UKK levels and roll-over test results (n = 30). From these results, the authors reached the conclusion that to determine UKK in the second trimester of pregnancy is quite valuable in predicting not only gestosis and/or hypertension in the third trimester of pregnancy but also preterm delivery.

Adult↗

[Two cases of testicular torsion diagnosed by the ultrasonic Doppler method].

Two cases of testicular torsion diagnosed with ultrasonic Doppler method are reported. Case 1. A 17-year-old male noticed pain and swelling of the right intrascrotal contents during sleeping and visited our clinic. A Doppler signal was obtained from the normal testicle, but not from the affected one. Bilateral orchiopexy was therefore done under the diagnosis of right testicular torsion. Case 2. A 20-year-old male visited our clinic with complaints of pain and swelling of the right intrascrotal contents. The ultrasonic Doppler method revealed no blood flow to the right testicle. After manual detorsion, pain improved and Doppler sound was audible. Bilateral prophylactic orchiopexy was performed later.

Adolescent↗

[Electrocardiographic and hemodynamic changes during systemic hyperthermia (42 degrees C)].

During systemic hyperthermia (42 degrees C), depression of ST segments or T wave changes in the left precordial leads were noticed in 56% of patients, and 29% of cases showed right bundle branch block. Supraventricular tachycardia was found in 26% and temporary deviation of mean frontal vector to the left axis was observed in 15%. These changes disappeared following recovery to normal temperature. The ECG findings for any particular patient were similar even during a second period of hyperthermia. Pulse rate became elevated by 1.7 times, and cardiac output became up to 2.4 times higher at 42 degrees C.

Adolescent↗

[Clinical effects of TA-077 in non-Hodgkin's lymphomas].

Ten patients with non-Hodgkin's lymphomas (NHL), six untreated and four with previous chemotherapy, were treated with TA-077, a new derivative of nitrosourea. Partial remission was observed in three untreated cases (30%) of NHL [Case 1: 71-year-old female with B cell lymphoma/diffuse small cell type, Case 2: 79-year-old male with T cell lymphoma/diffuse large cell type, and Case 3: 64-year-old female with adult T cell leukemia lymphoma (ATLL)]. Remission durations were as follows: Case 1; 33 days, Case 2; 38 days and Case 3; 14 days. Side effects were transient anorexia (40%), nausea & vomiting (30%), liver dysfunction (10%) and delayed hematological toxicities (80%). Hematological toxicities consisted of leukocytopenia (80%), thrombocytopenia (60%) and anemia (20%). Our study suggests that TA-077 is a useful agent as one of the drugs used in combination chemotherapy against NHL, since it was effective for refractory T cell malignancies such as ATLL.

Adult↗

[The effects of o,p'-DDD on adrenal steroidogenesis and hepatic steroid metabolism].

O,p'-DDD is used for the treatment of adrenocortical carcinoma and Cushing's disease. The inhibitory effect of this drug on the adrenal steroid biosynthesis has been described by many authors, but there are very few reports about the sites of action of this drug on adrenal steroid synthesis. This paper presents in vitro studies on adrenal steroidogenesis and hepatic steroid metabolism. The effects of o,p'-DDD on adrenal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 11 beta-hydroxylase (11 beta-OHlase) and 18-hydroxylase (18-OHlase) were examined in vitro using mitochondrial and microsomal fractions prepared by standard centrifugation procedures from the homogenate of bovine adrenal cortices. The concentrations of o,p'-DDD inducing 50% inhibition of 3 beta-HSD, 11 beta-OHlase and 18-OHlase were 8 X 10(-6) M, 1 X 10(-5) M and 3 X 10(-6) M, respectively. This study clearly demonstrates the marked inhibitory effects of o,p'-DDD on 3 beta-HSD in vitro, which was not described previously. The inhibitory effects of o,p'-DDD on these 3 enzymes were diminished by an addition of 0.05 approximately 0.5 mM of cofactor (NADPH or NAD). The results indicate that o,p'-DDD may reduce NADPH or NAD utilization, resulting in the inhibition of steroidogenesis. The effects of o,p'-DDD on hepatic 5 beta-reductase were examined in vitro using rat liver homogenate. O,p'-DDD inhibits 5 beta-reductase, resulting in the decrease of conversion of cortisol to dihydrocortisol and tetrahydrocortisol at the concentration of 10(-3) M.

18-Hydroxycorticosterone↗

Percutaneous microexplosion nephrolithotripsy.

We developed the technique of microexplosion for the destruction of bladder stones and have used it since 1981 with good results. The procedure is safe and simple. A renal pelvic stone in a seventy-one-year-old woman was successfully destroyed by microexplosion using a percutaneous approach. We believe this is the first clinical report on the use of microexplosion for upper urinary tract calculi.

Aged↗

Preoperative evaluation of localized prostatic carcinoma by transrectal ultrasonography.

We evaluated 31 patients with clinically localized prostatic carcinoma by transrectal ultrasonography before radical prostatectomy. Results of ultrasonography were reviewed without previous knowledge of the extent of the disease and were compared to the pathological staging obtained by step section of the prostate. Preoperative transrectal ultrasonography was sensitive in detecting capsular and seminal vesicle involvement (89 and 100 per cent, respectively). However, the specificity of the method was low for capsular involvement (50 per cent), probably owing to the inability of this method to detect microscopic disease. This method is a valuable tool in the preoperative evaluation of patients with clinically localized prostatic carcinoma.

Carcinoma↗

Purification and characterization of NADH oxidase from a strain of Leuconostoc mesenteroides.

An NADH oxidase was purified to homogeneity from Leuconostoc mesenteroides with a specific activity 100-fold higher than that of the crude extract. The purified NADH oxidase was an acidic protein having an S0 20,W of 5.49S and a molecular weight of 104,000, consisting of a dimer with 53,000 subunit size. The enzyme could use O2, dichlorophenolindophenol and methylene blue as oxidants, but not H2O2, cytochrome c, or ferricyanide. The physiological substrate was beta-NADH (Km = 0.12 mM) with O2 as the oxidant, probably forming H2O, rather than H2O2. Activity toward alpha-NADH was observed (Km = 0.14 mM), but the maximum velocity was 3 orders of magnitude lower than that with beta-NADH. alpha-NADPH and beta-NADPH were inert for the reaction. The enzyme showed a flavoprotein absorption spectrum with maxima at 273, 379, and 450 nm with a shoulder at 465 nm: the absorption at 450-465 nm disappeared on adding excess NADH or hydrosulfite. One mol of the holoenzyme contained approximately 2 mol of FAD. The apoenzyme was obtained by treatment with EDTA-KBr solution and could be reconstituted partially by adding FAD, but not riboflavin or FMN. The maximum activity of the reaction was observed at pH 6.5 in a temperature range of 35-45 degrees C. The activation energy was estimated to be 3.77 kcal/mol. The enzyme was inhibited by SH reagents, quinacrine, quinine, and Cu2+, but not by EDTA. Adenine and its nucleoside 5'-di- and triphosphates showed competitive inhibitions, while various metabolites, such as H2O2, FDP, acetyl phosphate, lactate, ethanol, and acetate, did not affect the reaction.

Hydrogen-Ion Concentration↗