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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 775 records · Page 43Linked to original sources
PubMed1991

[Neoadjuvant therapy of stage III non-small cell lung cancer].

Locally advanced stage III disease constitutes 30 to 40% of the entire group of non-small cell lung cancer. Surgery is the only curable modality in this stage disease, but resection rate is less than 40%. Even in completely resected patients 5-year survival is only 30%. Several reports have evaluated postoperative chemotherapy and radiotherapy. Prospective randomized studies, however, have failed to demonstrate a survival advantage from adjuvant therapy. Neoadjuvant therapy is under investigation in attempt to improve survival of stage III patients. Preliminary data show that neoadjuvant therapy could increase resection rate and improve survival with moderate toxicities. However, there are many problems in study design such as the use of single-arm studies with short duration of follow-up, lack of accurate staging of selected patients and no precise definitions of resectability for stage III disease. Therefore, there is an urgent need for well designed randomized trial to confirm whether neoadjuvant therapy offers a survival advantage on locally advanced stage III disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Embryonic expression of beta-actin-lacZ hybrid gene injected into the fertilized ovum of the domestic fowl.

An experiment was carried out to investigate the expression of cloned DNA injected into the germinal disc of the chick fertilized ovum. The beta-actin-lacZ hybrid gene, MiwZ, was injected, in the closed circular form, into the cytoplasm of the germinal disc at the single-cell stage. The embryos were cultured in vitro, then in recipient eggshells up to day 4 of incubation. The survival rate of the embryos at day 4 was 42% (55/130), and the rate of embryos expressing MiwZ was 64% (35/55). Twenty-two embryos expressed the MiwZ in both embryonic and extraembryonic tissues, while the remainder expressed the MiwZ in only extraembryonic tissues. Mosaic expression was observed in most of the embryos expressing MiwZ in embryonic tissues. Expression throughout all tissues of the embryo including blood cells occurred in one case. In this case, the injected DNA was assumed to have integrated at an earlier stage. The results indicate that it is now possible to investigate the promoter activities of introduced exogenous genes as well as the effect of introduced genes on embryogenesis in early chick embryos. This technique may also facilitate the production of transgenic chicks.

Actins↗
PubMed1991

[Regeneration of bone marrow tissue. Growth and differentiation of hematopoietic stem cells and the role of bone marrow microenvironment on hematopoiesis].

Hematopoietic stem cell proliferation and differentiation is regulated by a multistep process involving stem cell self-renewal, commitment, differentiation and maturation. Each process is controlled by a variety of humoral factors and cell-cell interactions, i.e., (i) growth factor and growth inhibitor acting toward the cascade of stem cell proliferation and differentiation, (ii) cytokine network involving cytokine-producing hematopoietic cells and stromal cells, (iii) interaction between hematopoietic cells and bone marrow microenvironment that is consisted of stromal cells and extracellular matrix. Recent advances in cell biology and cell physiology enabled us to understand the roles of these marrow microenvironments on hematopoiesis in molecular basis. We here discuss the complexities of hematopoietic system and the mechanism of the regeneration of hematopoietic tissues in special reference to bone marrow transplantation.

Animals↗
PubMed1991

Differences in tolerance to hypoxia/anoxia in mice of different ages.

Tolerance to hypoxic stress was examined in male C57BL mice of different ages through use of a hypoxic chamber (4% oxygen, 96% nitrogen). The basal survival times in a hypoxic chamber did not significantly differ between mice of different ages (6 wks, 8 wks, 10 months, 28 months). The pretreatment of antihypoxic prostaglandin I2 (PGI2) significantly prolonged the survival time in both adult (10-month-old and aged (30-month-old) mice, but the effect tended to be smaller in aged mice. The effect of sublethal hypoxia treatment on survival time in a hypoxic chamber was minimal in both adult and aged mice, but the effect tended to be smaller in aged mice. IP injection of sublethal doses of potassium cyanide (3.0 mg/kg) significantly prolonged the survival time in a hypoxic chamber when examined 10 min after the pretreatment in immature mice (6 wks), but in adult and aged mice, the survival time tended to be slightly shorter at that time than respective control values without pretreatment. The maximal survival time after KCN pretreatment was longest in immature mice and shortest in aged mice. The results suggest that the basal tolerance to hypoxic stress in mice is little affected by aging. However, the potential antihypoxic mechanisms appear to be progressively affected by aging.

Aging↗
PubMed1991

Immunological detection of the dystrophin molecule with antibody directed against the synthetic peptide.

We synthesized a peptide designated R8 (amino acid residues 1157-1201) based on the primary structure presumed from the nucleotide sequence of the cDNA clone from the gene for Duchenne muscular dystrophy. Antibody to the synthetic R8 generated by immunization of rabbits was tested on human and mouse skeletal muscle by Western blotting analysis. The antibody reacted with a component of the 400K dystrophin of normal human and mouse skeletal muscles, but not with components of the muscles of Duchenne muscular dystrophy patients and mdx mice. Thus we established that this peptide sequence is in fact missing in the protein product 'dystrophin' encoded by the DMD gene. The antibody may prove useful for the diagnosis of the Duchenne types of muscular dystrophy.

Amino Acid Sequence↗
PubMed1991

Aspirin injection test to predict angioplasty outcome in unilateral renovascular hypertension: preliminary report.

We examined the usefulness of aspirin DL-lysine for prediction of the outcome of renal artery angioplasty in renovascular hypertension. The study was carried out in eight hypertensive patients with unilateral renal artery stenosis: six were free from azotemia and two had slight azotemia. Before and 30 min after an intravenous injection of aspirin DL-lysine (18 mg/kg), renal venous and abdominal aortic plasma was sampled and assayed for prostaglandin E2 and plasma renin activity. Blood pressure and heart rate were serially measured at this time. Renal angioplasty was later performed and was technically successful in all patients. In the six patients without azotemia, aspirin inhibited renal prostaglandin E2 synthesis and suppressed renin release from the ischemic kidney, resulting in lowered blood pressure. Renal angioplasty caused plasma renin activity to become normal and lowered high blood pressure. The reduction in blood pressure by angioplasty was correlated with the responses of blood pressure and renin release to aspirin. However, in the two patients with azotemia, aspirin neither suppressed renin release nor lowered blood pressure. Their hypertension was not reduced by the angioplasty. These results indicate that an aspirin injection test could be useful for prediction of the outcome of angioplasty in unilateral renovascular hypertension.

Adult↗
PubMed1991

[Prevention of scald injury due to intraperitoneal hyperthermic perfusion for far-advanced gastric cancer].

In an attempt to prevent scald injury on the peritoneo-serosal surface due to intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastric cancer patients, a histamine H2-receptor antagonist, cimetidine, was prescribed for 9 patients. The IPHP treatment was carried out with a closed circuit using a heated perfusate, and intra-abdominal temperature was kept over 44 degrees C throughout IPHP, for 120 minutes. Of 18 patients given IPHP, 9 were administered intravenously cimetidine at a dose of 50 mg/kg just before IPHP (cimetidine group) and the remaining 9 were prescribed IPHP and not given cimetidine (control group). Amounts of exudate and protein from peritoneal cavity and serum histamine were compared between the two groups. The amount of intra-abdominal exudate was 768 +/- 95 ml for 24 hours in the control group, against 408 +/- 75 ml in the cimetidine group. The protein amounts in exudate throughout IPHP were 62.5 +/- 23.5 g in the control group, against 15.9 +/- 5.4 g in teh cimetidine group. Both the exudate and protein amounts were significantly decreased in the cimetidine group, compared with the controls (p = 1.416 x 10(-7), p = 5.358 x 10(-5)). Serum histamine levels in the cimetidine group increased 2.5 to 6.5 fold for over 12 hours after IPHP, compared to those in the control group. These findings suggest that cimetidine suppresses scald injury on the peritoneo-serosal surface by competitive inhibition with histamine. Consequently, histamine originated from the scald region was released into the circulating blood. Thus, cimetidine helped to prevent thermal injury due to the IPHP.

Body Temperature↗
PubMed1991

[A case of angiomatous meningioma near the geniculate ganglion].

A 57-year-old male was admitted with pulsatile tinnitus and hearing disturbance of the right ear and right peripheral facial palsy. Otological examination revealed a pulsatile red mass in his right ear and right conductive hearing disturbance. CT and MRI showed the mass lesion at his right middle fossa near the geniculate ganglion. Right external carotid angiogram disclosed a tumor stain fed by the middle meningeal artery. The tumor was removed via a combination of subtemporal and transmastoidal approaches. Histologically, this tumor was diagnosed as angiomatous meningioma partly with meningotheliomatous meningioma. Meningioma in this region is very rare. We discussed its clinical and radiological characteristics in comparison with chemodectoma and facial neurinoma at the geniculate ganglion.

Angiography↗
PubMed1991

Carbonic anhydrase III in serum in muscular dystrophy and other neurological disorders: relationship with creatine kinase.

We measured with a radioimmunoassay the concentrations of carbonic anhydrase III (CA-III, EC 4.2.1.1) in sera from 68 patients with muscular dystrophy, 10 carriers of Duchenne muscular dystrophy (DMD), and 63 patients with other neurological disorders. The values obtained were compared with those for creatine kinase (CK, EC 2.7.3.2). Serum CA-III was strikingly increased in patients with DMD (mean, 274.4 micrograms/L) and congenital (Fukuyama-type) (182.8 micrograms/L) and limb-girdle (203.7 micrograms/L) dystrophies and positively correlated with the activities of CK in patients with DMD. CA-III concentration decreased with the subjects' age and the severity of the disease, similar to the tendency observed between age or severity and the concentration of CK. We found moderately increased CA-III in patients with polymyositis, myotonic dystrophy, amyotrophic lateral sclerosis, spinal progressive muscular atrophy, or Kugelberg-Welander disease and in carriers of DMD.

Adolescent↗
PubMed1991

[Clinical evaluation of intra-peritoneal hyperthermic perfusion under hypothermic general anesthesia for advanced gastric cancer].

Right after surgery, intra-peritoneal hyperthermic perfusion (IPHP) was performed under hypothermic general anesthesia for 41 gastric cancer patients with peritoneal dissemination or serosal invasion. The control group consisted of 40 patients given surgery alone. With respect to the direct antitumor efficacy of IPHP, there were no cancer cells in the peritoneal lavage from Douglas' pouch and, ascitic effusion disappeared in all patients with peritoneal dissemination. The 1- and 3-year survival rates for the IPHP group were 68% and 39%, whereas those of the control group were 30% and 0%, respectively. The survival rates for the IPHP group were better than those for the control group, with a statistically significant difference of p = 8.1 x 10(-7). As to prevention of recurrence, the incidence of peritoneal dissemination for the IPHP group was lower at p = 0.002 than the control group.

Anesthesia, General↗
PubMed1991

Serotonin (5-HT)3 receptor blocking activities of YM060, a novel 4,5,6,7-tetrahydrobenzimidazole derivative, and its enantiomer in anesthetized rats.

YM060 [(R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimida zol e hydrochloride], is structurally independent of other 5-HT3 receptor antagonists. We investigated in vivo 5-HT3 receptor blocking activity of YM060 and compared results with those of its enantiomer (S-form), ondansetron (GR38032F), granisetron (BRL43694), ICS205-930 [(3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester], LY277359 [endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclo[3.2.1] oct-3-yl)-7-benzofuran-carboxamide-(Z)-2-butenedioate (1:1)], Y25130 [(+-)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-oxo-3,4- dihydro-2H-1,4-benzoxazine-8-carboxamide hydrochloride] and zacopride [(R,S)4-amino-N-[1-azabicyclo (2.2.2)oct-3-yl]-5-chloro-2-methoxybenzamide(E)-2-butenedioat e]. YM060 injected i.v. dose-dependently inhibited the reduction in heart rate induced by 5-HT (30 micrograms/kg i.v.) in rats (von Bezold-Jarisch reflex) with an ED50 value of 0.036 (0.031-0.041) micrograms/kg (n = 3-5). Based on these values, YM060 was 53, 18, 23, 16, 11 and 4 times as potent as ondansetron, granisetron, ICS205-930, LY277359, Y25130 and zacopride, respectively. The S-form of YM060 also inhibited 5-HT-induced bradycardia, but with a potency approximately 250 times less than that of YM060 (R-form). YM060 dosed p.o. also inhibited 5-HT-induced bradycardia with an ED50 value of 0.59 (0.44-0.80) micrograms/kg (n = 3-5), indicating the drug to be 387, 66, 97, 6 and 16 times more potent than ondansetron, granisetron, ICS205-930, LY277359 and Y25130, respectively, but 2 times less potent than zacopride. Bioavailability of YM060 based on the p.o.-to-i.v. ED50 ratio (p.o./i.v. = 16) was lower than those of zacopride (2) and LY277359 (6), similar to that of Y25130 (22) and better than those of ondansetron (109), granisetron (60) and ICS205-930 (71).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Oxygen and temperature dependence of stimulated insulin secretion in isolated rat islets of Langerhans.

The effects of lowered O2 tension on insulin secretion and changes in cellular energy parameters were investigated in isolated rat pancreatic islets perifused with buffers equilibrated with 21, 9, 5, and 1% oxygen and containing 5 mM glucose. Decreasing the external [O2] reduced the amount of insulin released in response to 16 mM glucose, 20 mM alpha-ketoisocaproic acid, and 40 mM KCl. Secretion elicited by high glucose or KCl had declined significantly at 9% oxygen, whereas that caused by alpha-ketoisocaproic acid became inhibited below 5% O2. Lowering the oxygen tension also decreased the ability of islets to respond with a rise in [ATP]/[ADP] upon stimulation with metabolic secretagogues. This reduction in the evoked increase in the nucleotide ratios paralleled the inhibition of stimulated insulin secretion. Addition of 2 mM amytal markedly decreased the islet energy level and eliminated the secretory response to 16 mM glucose. The results suggest that enhancement of B-cell energy production and a consequent rise in [ATP] (or [ATP]/[ADP]) are a necessary event for the hormone release elicited by high glucose and alpha-ketoisocaproic acid. A decrease in temperature inhibited insulin secretion with all three secretagogues tested. The energies of activation were similar for high glucose and KCl-induced secretion, about 20 kcal/mol, but were higher for alpha-ketoisocaproic acid, about 35 kcal/mol. At 28 degrees C, the [ATP]/[ADP] was larger than that at 38 degrees C (8 versus 5) and was not increased further upon addition of 16 mM glucose. It is suggested that a decrease in the rate of energy production at lowered temperatures may contribute to the inhibition of insulin release caused by metabolic secretagogues.

Animals↗
PubMed1990

Influence of chemotherapeutic agents on superoxide anion production by human polymorphonuclear leukocytes.

The effects of 11 chemotherapeutic agents on superoxide anion (O2-) production were examined in human polymorphonuclear leukocytes (PMNL). All drugs, except predonine, were found to suppress O2- production in PMNL. Adriamycin (doxorubicin), mitomycin C, vindesine, cisplatin, etoposide, nimustine, and pepleomycin suppressed O2- production at relatively low drug concentrations, whereas methotrexate, 5-fluorouracil and vincristine suppressed O2- production at high drug concentrations. Time-dependent suppression of O2- production was evaluated in four drugs, namely Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cisplatin, vindesine, and methotrexate. Only Adriamycin showed suppressive effect on PMNL-derived O2- production in a time-dependent manner. Production of O2- by PMNL is a fundamental element for its bactericidal activity. The authors' results showed suppression of O2- production in PMNL in the presence of chemotherapeutic agents. This indicates a relationship between chemotherapy drugs and susceptibility to infection. The influence of chemotherapeutic agents on O2- production by PMNL should thus be taken into consideration when assessing defense mechanisms and susceptibility to infection of patients treated with these drugs.

Anions↗
PubMed1990

Isolation and characterization of a tumor-derived human protein related to chromogranin A and its in vitro conversion to human pancreastatin-48.

A protein with pancreastatin-like immunoreactivity has been isolated and purified from liver metastasis of a patient with insulinoma. NH2-terminal residue analysis, in conjunction with the use of antibodies that are specific for the C-terminal amide peptide of porcine pancreastatin, identified this protein as a 186-amino-acid protein corresponding to human chromogranin A-116-301 (the fragment corresponding to the positions from 116 to 301 of human chromogranin A). Digestion of this protein with trypsin yielded a 48-amino-acid peptide with the retention of full pancreastatin activity. Serum from patient with insulinoma contains a peptide specie(s) that comigrates with the 48-amino-acid pancreastatin, suggesting that this peptide might be a physiologically important circulation form of pancreastatin in humans. A sensitive radioimmunoassay was established using antibody developed against a synthetic 29-amino-acid peptide amide of pancreastatin. Immunocytochemical staining revealed that a major population of human pancreatic islet cells were immunoreactive to the antiserum but with varying intensity of staining. Pancreastatin-like immunoreactivity was not observed in exocrine acinar cells.

Adenoma, Islet Cell↗
PubMed1990

The complete amino acid sequence of the shorter form of human basic fibroblast growth factor receptor deduced from its cDNA.

We have isolated a full-length cDNA for human basic fibroblast growth factor (bFGF) receptor-like protein from a human placenta cDNA library. Determination of the nucleotide sequence of the cDNA allows elucidation of the complete amino acid sequence of the receptor (731 amino acids) which has two extracellular immunoglobulin-like domains, a transmembrane domain and an intracellular tyrosine kinase domain. The receptor has remarkable amino acid similarity (98% identity) to the shorter form of murine bFGF receptor reported recently (H.H. Reid et al. (1990) Proc.Natl.Acad.Sci. USA 87, 1596-1600). The receptor described here is expected to be the shorter form of human bFGF receptor.

Amino Acid Sequence↗
PubMed1990

Age-dependent decrease in the hepatic uptake of taurocholic acid resembles that for ouabain. A possible role of surface membrane protein mobility.

Isolated hepatocytes were prepared from Wistar-derived male rats of different ages (4, 12 and 27-29 months) by the collagenase perfusion method. The hepatic uptake rate of taurocholate (TC) for the saturable fraction was calculated by subtracting the non-saturable fraction from the total hepatic uptake. The Vmax and the apparent affinity constant Km were computed for the saturable fraction by means of non-linear regression. The Vmax (nmol/mg protein/min, mean +/- SE) for young rats (N = 6) was 2.15 +/- 0.11, whereas in old rats (N = 4) the value was 50% lower (1.16 +/- 0.11, P less than 0.005). In contrast, Km (microM) values were not significantly different between young (25.88 +/- 1.90) and old (30.34 +/- 4.96) rats. There was a significant inverse linear relationship (r = 0.79; P less than 0.01) between the age of rats and the uptake velocity (nmol/mg/mg protein/min) at 1 microM of TC, suggesting a steady and almost linear decrease of TC uptake velocity with age. The rate of decrease per month (2.1%) was quite close to the value for ouabain uptake (2.8%) previously found by the authors. Furthermore, a marked linearity was observed between the average values for TC uptake rates for three age groups and corresponding lateral diffusion constants of hepatocyte plasma membrane proteins previously obtained by the authors using the fluorescence recovery after photobleaching method. The results support our previous proposal that protein mobility within the hepatocyte surface membrane may play at least a partial role in regulation of carrier-mediated hepatocyte uptake functions for various materials.

Age Factors↗