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Biomedical subjects

T Ohkubo

Publications and source records attributed to T Ohkubo.

At least 307 records · Page 17Linked to original sources

Further characterization of the biological properties of human hematopoietic survival and growth factor.

Human hematopoietic survival and stem cell growth factor (SCGF), derived from the KPB-M15 myeloid cells, is a heat- and pH-stable protein. Chemical modification with various denaturing agents and proteolytic enzymes abrogated SCGF activity. The granulocyte-macrophage colony-potentiating and erythroid burst-promoting activities of SCGF were proportional to the density of the bone marrow (BM) cells cultured, the optimal BM cell density for delta granulocyte- and delta burst-promoting activities being 5 to 10 X 10(5)/ml. These data could be important in enabling the use of SCGF to induce proliferation of human hematopoietic stem cells in vitro.

Bone Marrow Cells↗

[Studies on the relationship between therapeutic schedule and antitumor effect of etoposide and cytosine arabinoside in murine L1210 leukemia].

The sequence dependency of the antitumor effect of etoposide and ara-C was investigated against the L1210 ascites tumor in BDF1 mice. Etoposide (7.5 mg/kg or 15 mg/kg) and ara-C (25 mg/kg or 500 mg/kg) were administered intraperitoneally on days 1, 4 and 7 after inoculation of L1210 with or without time interval of 3 or 6 h. Antitumor effect was decided for cure rate and post inoculation survival time of the mice died of tumor. Six hours pretreatment with 15 mg/kg of etoposide followed by 500 mg/kg of ara-C yielded 100% of cure rate, but only 20% of cure rate was obtained with the reverse sequence. Simultaneous administration of etoposide and ara-C produced 70% of cure rate. At every dosage examined, pretreatment with etoposide given 6 hr before ara-C was the most effective antitumor schedule in L1210 leukemia.

Animals↗

[Randomized-controlled study of treatment with UFT-MMC or UFT-ACR in advanced gastric cancer. Tohoku Study Group of Cancer Treatment for the Digestive Organs].

The effect of UFT-MMC- or UFT-ACR-therapy on the unresectable or recurrent gastric cancer was studied by a multicenter, randomized-controlled trial. All the patients who were randomly divided into the two groups were administered orally with 400 or 600 mg/day of UFT everyday. In addition, the UFT-MMC group was intravenously injected weekly for three weeks and then triweekly after six weeks with 6 or 8 mg/body of MMC, while the UFT-ACR group was intravenously injected with 20 mg/body of ACR for 5 serial-days every three weeks. Out of 88 cases registered, 75 (85.2%) were evaluable, consisting of 40 (31 complete cases) in UFT-MMC and 35 (27 complete cases) in UFT-ACR. There was no difference in various background factors between the two groups. PR, NC and PD was 10/31, 15/31 and 6/31 in the UFT-MMC group, whereas 0/27, 22/27 and 5/27 in the UFT-ACR group, respectively. The efficacy in the former group was higher, though not significant (U-test, p = 0.052), than that in the latter group. However, there was no difference in the 50% survival time (4.9 months in UFT-MMC vs. 5.4 months in UFT-ACR) of the either group.

Aclarubicin↗

[Local analgesic action and tissue irritability of nishika thesirol, a root canal disinfectant].

Local analgesic action and tissue irritability of nishika thesirol made newly, which was one of the root canal disinfectants, were investigated. 1) Nishika thesirol was less irritative than any other drugs such as formocresol, champhophenique and creodon, and there was a significant difference between nishika thesirol and formocresol. 2) Marked local analgesic action of nishika thesirol was observed by means of formalin method in mice. Formalin-induced pain response was also inhibited significantly, when nishika thesirol was directly applied to the sciatic nerve 3 days before the experiment. 3) Thesit, one of the effective ingredients of nishika thesirol, had a long lasting local anesthetic action as compared with the same dose of lidocaine.

Analgesics↗

[A case of primary pulmonary cryptococcosis].

A 53-year-old male was admitted because of an abnormal chest roentgenogram showing a solitary tumor shadow in the right upper lung field. Laboratory data was normal. Although examination with the bronchoscope and sputum cytology showed no abnormal findings, a partial resection of the right upper lobe was performed. Microscopic examination of the lesion was cryptococcosis. As another focus was not found by systemic examination, the lesion was disclosed primary pulmonary cryptococcosis. Cryptococcosis is rare but we must think of it when we meet a solitary tumor shadow on the chest roentgenogram.

Cryptococcosis↗

[Exercise-induced precordial ST depression in patients with prior inferior myocardial infarction with single vessel disease].

We investigated the mechanisms of exercise-induced precordial ST depression in prior inferior myocardial infarction in single vessel disease, and attempted to differentiate ST depression in single vessel from multivessel disease. Subjects were categorized as; Group I (n = 18), with inferior myocardial infarction and single vessel disease without (n = 11; Ia) and with (n = 7; Ib) exercise-induced precordial ST depression and group II (n = 10), inferior myocardial infarction with multivessel disease. The subjects were examined using 12-lead exercise ECG, stress T1-201 myocardial imaging and stress radionuclide ventriculography. Compared to group Ia, exercise-induced precordial ST depression in group Ib was associated with extensive infarction extending into the inferoseptal left ventricular wall by T1-201 myocardial imaging. Worsening of septal wall motion was also more frequently observed on stress radionuclide ventriculography. For detecting multivessel disease in prior inferior myocardial infarction, exercise ECG and radionuclide ventriculography had poor specificity and predictive value compared to stress T1-201 myocardial imaging. We conclude that exercise-induced precordial ST depression observed in patients with prior inferior myocardial infarction due to single vessel disease reflects a peri-infarction ischemia in the inferoseptal wall of the left ventricle. Great caution is necessary when predicting multivessel disease in prior inferior myocardial infarction using exercise ECG. Stress T1-201 myocardial imaging is the most accurate diagnostic means for this purpose.

Aged↗

The production of anorexigenic substances by intestinal flora.

The role of intestinal flora in the production of anorexigenic substance was investigated. Proteus mirabilis (P. mirabilis) and Escherichia coli (E. coli) were found to produce an anorexigenic substance, while Enterococcus faecalis (E. faecalis, type 1 and 2) and Staphylococcus intermedius (S. intermedius) did not. The anorexigenic substance was purified and was detected as, a single though broad band by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The specific activity of the final form of the purified substance was 120 units/mg carbohydrate. The substance contained no protein residue and appeared to be a lipopolysaccharide. The evidence that intestinal flora produces an anorexigenic substance leads to an interesting assumption that the intestinal flora may be responsible for regulating food intake.

Animals↗

Immunohistochemical demonstration of steroid C-21 hydroxylase in normal and neoplastic salivary glands.

The presence of steroid C-21 hydroxylase in normal and neoplastic salivary glands was investigated immunohistochemically with the use of antibody against cytochrome P-450 specific for steroid 21-hydroxylation (P-450C21). In normal salivary glands, P-450C21 was exclusively present in the excretory duct system (intercalating, striated and large excretory ducts), and not observed in acini. In salivary gland tumors, P-450C21 was observed in most epithelial cells of duct origin within pleomorphic adenomas including cells of amorphous groups scattered in myxoid areas, and in adenolymphoma. Some mucous cells in mucoepidermoid tumor also were positive for this enzyme. These findings in the normal and neoplastic salivary gland suggest that the expression of P-450C21 is closely related to ductal differentiation.

Adenocarcinoma↗

Exercise-induced precordial ST-segment depression in prior inferior myocardial infarction with single-vessel disease; with special reference to its mechanisms and distinction from multi-vessel disease.

We investigated the mechanisms of exercise-induced precordial ST-segment depression on the electrocardiogram in prior inferior myocardial infarction with single-vessel disease and attempted to differentiate the ST-segment depression between single- and multi-vessel disease. Subjects included three groups: group Ia (n = 11), inferior myocardial infarction with single-vessel disease that showed no precordial ST-segment depression; group Ib (n = 7), inferior myocardial infarction with single-vessel disease accompanied by precordial ST-segment depression; and group II (n = 10), inferior myocardial infarction with multi-vessel disease. The subjects underwent 12-lead exercise electrocardiography, stress Tl-201 myocardial imaging and stress radionuclide ventriculography. Exercise-induced precordial ST-segment depression observed in group Ib was associated with large infarction and infarction extending into the inferoseptal wall of the left ventricle on myocardial image. On stress ventriculography, worsening of the septal wall motion was more frequently observed in group Ib than in group Ia. Coronary arteriography revealed a higher rate of rich collateral vessels to the infarcted zone in group Ib than in group Ia. When we compared the diagnostic ability for detecting multi-vessel disease in prior inferior myocardial infarction, although sensitivity was not different among three tests, both exercise electrocardiography and radionuclide ventriculography had poor specificity and predictive value compared to stress Tl-201 myocardial imaging. Thus we concluded that exercise-induced precordial ST-segment depression observed in prior inferior myocardial infarction with single-vessel disease should reflect a peri-infarctional ischemia located in the inferoseptal wall of the left ventricle, and that stress Tl-201 myocardial imaging is the most accurate method for diagnosing multi-vessel disease in prior inferior myocardial infarction.

Cardiac Output↗

Sequence-dependent antitumor effect of VP-16 and 1-beta-D-arabinofuranosylcytosine in L1210 ascites tumor.

The sequence-dependence of the antitumor effect of etoposide (VP-16) and 1-beta-D-arabinofuranosylcytosine (ara-C) was investigated against the L1210 ascites tumor in BDF1 mice. Treatment with VP16 (7.5 or 15 mg/kg) and ara-C (25 or 500 mg/kg) was administered intraperitoneally on days 1, 4 and 7 after tumor inoculation. Six hour pretreatment with 15 mg/kg VP16 followed by 500 mg/kg ara-C yielded a 100% cure rate, but only a 20% cure rate was obtained with the reverse sequence. Simultaneous administration of 15 mg/kg of VP-16 and 500 mg/kg ara-C interacted synergistically, producing a 70% cure rate. In contrast with the results obtained with VP-16 and 500 mg/kg ara-C, simultaneous administration of 25 mg/kg ara-C neither antagonized nor potentiated the antitumor effect of VP-16. Twenty-five mg/kg ara-C was too low to produce any antitumor effect with VP-16 in simultaneous administration. At every dose investigated, pretreatment with VP-16 followed by ara-C was the most effective antitumor schedule in L1210 leukemia. This sequence of drug administration did not cause greater toxicity as measured by weight loss or toxic death.

Animals↗

The conformation of alpha-human atrial natriuretic polypeptide in solution.

The three-dimensional structure of alpha-human ANP in solution was determined through the combined use of nuclear magnetic resonance spectroscopy and distance geometry. The results are based on distance constraints determined by nuclear Overhauser effect measurements and one disulfide bond. The structure is as follows. Three separate regions, which are Ser1-Cys7, Arg11-Ile15, and Gln18-Tyr28 each have some ordered structure. The remaining parts in the sequences of Gly9-Gly10 and Gly16-Ala17 act as hinges. And the C-terminal part is folded back toward the cyclic moiety. The conformation of alpha-hANP reported here is expected to give a better understanding of the relationships between its biological activities and three-dimensional structure.

Amino Acid Sequence↗

Myocardial mechanical and myosin isoenzyme alterations in streptozotocin-diabetic rats.

Fifteen week old male Wistar rats (n = 7) were made diabetic by intravenous injection of streptozotocin (50 mg/kg). Age-matched, untreated male Wistar rats (n = 9) served as controls. Hearts were removed after 5-6 weeks of diabetes, and the isometric developed tension (T) of isolated left ventricular papillary muscles and its first derivative (dT/dt) were measured at a frequency of 0.2 Hz. During testing, the muscles were perfused with Tyrode's solution (Ca2+ concentration was half of normal Tyrode's solution, pH 7.4, 32 degrees C, bubbled with 95% O2 and 5% CO2). In addition, the left ventricular isoenzyme pattern, which is related to myocardial energetics, was determined by pyrophosphate gel electrophoresis. There was no significant difference in isometric developed tension between diabetic and control rats (DM: 2.90 +/- 0.89 vs controls: 2.87 +/- 0.85 g/mm2, mean +/- SD), but in diabetic rats, dT/dtmax decreased significantly as compared with controls (DM: 23.5 +/- 4.2 vs controls: 31.9 +/- 7.9 g/mm2.s, p less than 0.05). Myocardial mechanical responses to isoproterenol (10(-7)M) and dibutyryl cyclic AMP (10(-5)M) also decreased in diabetic rats. The left ventricular myosin isoenzyme pattern shifted toward VM-3 in diabetic rats (VM-3: DM: 74.9 +/- 10.7 vs controls: 9.5 +/- 4.1%, p less than 0.001). These results indicate that diabetes influences myocardial contractility and changes cardiac energetics. Post-receptor processes may play a role in myocardial mechanical responses to catecholamines in streptozotocin-diabetic rats.

Animals↗

[Blood reflux into cartridge in dental anesthesia. Detection of total protein and human hemoglobin in residual anesthetic solution].

The present study was designed to elucidate the blood reflux into cartridge under infiltration anesthesia. When imitation examination was carried out using pontamine blue dye solution in 7 kinds of syringes for the use of cartridge, dye reflux was observed in all of them. Compared 4 kinds of cartridges on the market, dye reflux was observed in all except one. The amounts of protein in residual anesthetic solution of cartridges after infiltration anesthesia were quantitatively measured by dye binding method. Human hemoglobin was also measured by enzyme immunoassay (EIA). The detection rates of protein and human hemoglobin were 26.2% (85/324) and 24.2% (24/99), respectively. From these facts that blood reflux cannot be avoided in the cartridge system, it is necessary to prohibit the reuse of residual anesthetic solution of cartridge as quickly as possible to avert the risk of cross infection of HB and AIDS virus.

Acquired Immunodeficiency Syndrome↗

Incorporation of N4-behenoyl-1-beta-D-arabinofuranosylcytosine into DNA as 1-beta-D-arabinofuranosylcytosine.

BHAC is a newly synthesized lipophilic derivative of ara-C. To clarify its pharmacological mode of action, P388 murine leukemic cells were incubated with two different types of 14C-labeled BHAC, [cytosine-2-14C]BHAC and [acyl-1-14C]BHAC, and DNA was extracted with phenol. The phenol-extracted DNA was then hydrolyzed by nuclease P1 and analyzed with high-performance liquid chromatography (HPLC). The radioactivity of DNA, from the cells incubated with [cytosine-2-14C]BHAC, was detected as ara-CMP. But the radioactivity of DNA, from the cells incubated with [acyl-1-14C]BHAC, was hardly detected. On the other hand, the main radioactivity of the acid soluble fraction was determined as ara-CTP. On the basis of our results, BHAC is not phosphorylated directly to produce N4-behenoyl-ara-CTP, but is mainly converted to ara-C which subsequently produces ara-CTP, the active metabolite of the drug, and which is then incorporated into DNA.

Animals↗

Effects of bunitrolol on myocardial contractility and left ventricular myosin isoenzyme pattern.

Effects of long term treatment of hypertension with bunitrolol on myocardial contractility and left ventricular myosin isoenzyme pattern were examined. Male 22-week-old spontaneously hypertensive rats were treated with bunitrolol (30-40 mg/kg/d, p.o.) for 8-10 weeks. The blood pressure of the bunitrolol-treated group did not differ from that of the untreated group, but ratio of ventricular weight to body weight was significantly lower in the treated group. There were no significant differences in isometric developed tension and dT/dtmax of isolated left ventricular papillary muscles between bunitrolol-treated and control groups. Myocardial mechanical responses to isoprenaline (isoproterenol) also showed no differences between the two groups. Left ventricular myosin isoenzyme pattern obtained by pyrophosphate gel electrophoresis was significantly shifted to VM-1 by bunitrolol treatment.

Animals↗