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Biomedical subjects

K Ohno

Publications and source records attributed to K Ohno.

At least 595 records · Page 33Linked to original sources
PubMed1989

Extended operation for lung cancer invading the aortic arch and superior vena cava.

Extended operation for lung cancer and mediastinal carcinoma involving the aortic arch or superior vena cava was performed in six patients. In three patients with lung cancer invading the right side of the mediastinum, sleeve pneumonectomy (two patients) or sleeve lobectomy was followed by resection and reconstruction of the superior vena cava with ringed polytetrafluoroethylene grafts. One patient with squamous cell carcinoma and T4 N1 M0 disease was alive and free of disease more than 34 months after the operation. The other patients with adenocarcinoma (T4 N1 M0) and adenosquamous cell carcinoma (T4 N2 M0) died 18 and 5 months after the operation of systemic metastases. In two patients with invasion of lung cancer into the left side of the mediastinum, resection and reconstruction of the aortic arch and left common carotid artery were performed by a femoro-femoral bypass. These patients had adenocarcinoma (T4 N2 M0) and large cell carcinoma (T4 N1 M0) and died of systemic metastases and bleeding during reoperation 12 and 4 months after the initial operation. In one patient with mediastinal squamous cell carcinoma, resection and reconstruction of the aortic arch and left subclavian artery were performed by application of a temporary bypass graft between the ascending and descending aorta. This patient was alive and free of disease more than 17 months after the operation.

Adult↗
PubMed1988

Induction of 68,000-dalton heat shock proteins by cyclopentenone prostaglandins. Its association with prostaglandin-induced G1 block in cell cycle progression.

Cyclopentenone prostaglandins (PGs) such as PGA2 and delta 12-PGJ2 act specifically on cells in the G1 phase and induce block of cell cycle progression (Ohno, K., Sakai, T., Fukushima, M., Narumiya, S., and Fujiwara, M. (1988) J. Pharmacol. Exp. Ther. 245, 294-298). In this study, we characterized proteins induced by these PGs in HeLa S3 cells of synchronized growth and examined its association with the cell cycle block. HeLa S3 cells transiently expressed two 68-kDa proteins of isoelectric points of 5.5 and 5.6 in the G1 phase of cell cycle. When G1-enriched cells were incubated with either PGA2 or delta 12-PGJ2, synthesis of these proteins was markedly enhanced. Enhancement by delta 12-PGJ2 was persistent and irreversible, whereas that by PGA2 was reversible. delta 12-PGJ2 also enhanced the synthesis of two additional 68-kDa proteins with isoelectric points of 5.8 and 5.9. On two-dimensional gel electrophoresis, these proteins overlapped exactly with the 68-kDa heat shock proteins induced in cells treated at 43 degrees C for 90 min. They were also indistinguishable from the heat shock proteins in limited proteolysis. When delta 12-PGJ2 was incubated with G2/M phase cells, it induced only a small and transient increase in the 68-kDa proteins. These results suggest that cyclopentenone PGs extensively induce 68-kDa heat shock proteins in the G1 phase HeLa S3 cells and this induction is closely associated with the G1 block of cell cycle progression caused by these PGs.

Cell Cycle↗
PubMed1988

Multiple abnormal beta-hexosaminidase alpha chain mRNAs in a compound-heterozygous Ashkenazi Jewish patient with Tay-Sachs disease.

Abnormal beta-hexosaminidase alpha chain cDNA clones were isolated from fibroblasts of an Ashkenazi Jewish patient with Tay-Sachs disease. Four abnormal cDNA clones were sequenced in their entirety. We showed previously that three of these mRNAs retained intron 12 with a mutation from G to C at the 5' donor site and that the patient was heterozygous with respect to this splicing defect (Ohno, K., and Suzuki, K., (1988) Biochem. Biophys. Res. Commun. 153, 463-469). One clone retained, in addition to intron 12, intron 13, which was truncated and polyadenylated due to a polyadenylation signal within intron 13. The fourth clone did not contain intron 12 and was missing exon 12. Some of these abnormal mRNAs were also missing one or more of upstream exons. The regions of exon 12-intron 12 and of upstream exons were evaluated in a total of 30 clones, including those completely sequenced, by restriction mapping and Southern analysis with appropriate probes. Of the 25 cDNA clones that included the exon 12-intron 12 region, 11 contained the exon 12-intron 12 sequence with the junctional transversion, and 11 were missing both exon 12 and intron 12. Among the 12 clones that included the region of exon 3-exon 9, 7 were missing one or more of upstream exons. Three clones gave results expected of normal cDNA in the region of exons 12 and 13. One of the three, furthermore, was 3.6-kilobases long and contained the completely normal beta-hexosaminidase alpha chain mRNA sequence on the 3' side and an abnormal 1.7-kilobase segment at the 5' end. These findings suggest that the splicing defect results in either retention of intron 12 or skipping of exon 12 in approximately equal proportions and that remote upstream exons are also frequently excised out. The three clones that were normal in the exon 12-intron 12 region could have derived from the other yet-to-be-characterized mutant allele. However, we were unable to obtain firm evidence that the abnormal upstream sequence is directly related to Tay-Sachs disease.

Base Sequence↗
PubMed1988

GM2-gangliosidosis B1 variant: a wide geographic and ethnic distribution of the specific beta-hexosaminidase alpha chain mutation originally identified in a Puerto Rican patient.

A point mutation within exon 5 of beta-hexosaminidase alpha chain gene was identified earlier in a Puerto Rican patient with GM2-gangliosidosis B1 variant (the DN-allele) [K. Ohno and K. Suzuki: J. Neurochem. 50:316-318, 1988]. Oligonucleotide probes designed to detect either the normal or the DN-allele showed that four additional patients carried the same mutation. These patients were of Italian, French, Spanish, and English/Italian/Hungarian origin. Three of them, as well as our original patient, were compound heterozygotes with positive signals for both the mutant and normal probes, while the Spanish patient was positive only for the DN-allele. A patient from Czechoslovakia was negative for the DN-allele. Thus, the specific mutation originally found in the Puerto Rican patient has a surprisingly wide geographic and ethnic distribution. This mutation can account for the B1 variant phenotype in five of the six B1 variant patients so far examined.

Alleles↗
PubMed1988

Maternal inheritance of deleted mitochondrial DNA in a family with mitochondrial myopathy.

Skeletal muscles from a mother and her daughter both with chronic progressive ophthalmoplegia were analyzed. Histological and biochemical analyses of their muscle samples showed typical features of this type of mitochondrial myopathy. Southern blot analysis revealed that, in both patients, there were two species of mitochondrial DNA (mtDNA): normal one and partially deleted one. The sizes of the deletion were different; the mutant mtDNAs from the mother and the daughter had about 2.5- and 5-kilobase deletions, respectively. The two mutant mtDNAs shared a common deleted region of 1.2-kilobase. However, both the start and the end of deletion were different between them, implying a novel mode of inheritance. This is the first report that the mutant mtDNA is responsible for the maternal inheritance of a human disease.

Adolescent↗
PubMed1988

A splicing defect due to an exon-intron junctional mutation results in abnormal beta-hexosaminidase alpha chain mRNAs in Ashkenazi Jewish patients with Tay-Sachs disease.

Abnormal beta-hexosaminidase alpha chain mRNAs from an Ashkenazi Jewish patient with the classical infantile Tay-Sachs disease contained intact or truncated intron 12 sequences. Sequence analysis showed a single nucleotide transversion at the 5' donor site of intron 12 from the normal G to C. This provides the first evidence that this junctional mutation, also found independently in two other laboratories by analysis of genomic clones, results in functional abnormality. Analysis with normal and mutant oligonucleotides as probes indicated that our patient was a compound heterozygote with only one allele having the transversion. The patient studied in the other two laboratories was also a compound heterozygote. Another Ashkenazi Jewish patient was normal in this region in both alleles. Thus, the splicing defect is the underlying genetic cause in some but not all Ashkenazi Jewish patients with Tay-Sachs disease.

Base Sequence↗
PubMed1988

Contribution of cholinergic vasodilators on the increase in cerebral cortical blood flow responses to the intravenous administration of thyrotropin releasing hormone in anesthetized rats.

The effect of an intravenous administration of thyrotropin-releasing hormone (TRH) on the regional cerebral blood flow in the sensory cortex was studied in halothane-anesthetized adult Wistar rats. The regional cerebral blood flow was continuously monitored with the laser Doppler flowmetry. The cerebral blood flow increased dose-dependently following the administration of 3 x 10(2) and 3 x 10(3) microns/kg TRH. The systemic blood pressure also increased simultaneously. After maintaining the systemic blood pressure at a constant level via a pressure reservoir system, the TRH-induced increases in the cerebral blood flow continued to be observed. In atropinized animals, the blood pressure increased as high as that indicated in non-atropinized animals following TRH administration, but the responses of the cerebral blood flow in the latter were much attenuated. It was suggested that the cholinergic vasodilative system contributed to the TRH-induced increase in cerebral blood flow.

Animals↗
PubMed1988

Subcellular distribution and isoelectric heterogeneity of the substrate for ADP-ribosyl transferase from Clostridium botulinum.

When the homogenate of bovine adrenal gland was subjected to subcellular fractionation, an Mr 21,000 substrate for botulinum ADP-ribosyl transferase was found not only in the membrane fractions but also in the cytosol; the amounts in the 10,000 x g precipitates and the 100,000 x g supernatant were about 21 and 56% of the total amount, respectively. Each fraction gave a single ADP-ribosylated protein band on SDS-polyacrylamide gel electrophoresis, but yielded on isoelectric focusing at least three bands between pH 5.5 and 6.0, suggesting the presence of multiple forms of the substrate of a similar molecular weight but different isoelectric points. ADP-ribosylated protein bands from the membrane and cytosol overlapped each other on both electrophoreses. After ammonium sulfate fractionation, the substrate from the cytosol showed requirement of divalent cations or guanine nucleotides for the reaction. Among cations tested, calcium, magnesium and manganese stimulated, whereas cadmium and lanthanum inhibited the reaction. Guanine nucleotides such as GTP, GDP and GTP-gamma-S also stimulated the substrate activity in the cytosol as that in the membrane fraction. However, no additive effects were observed when the nucleotides and cations were added together.

ADP Ribose Transferases↗
PubMed1988

A review of 102 consecutive patients with intracranial aneurysms in a community hospital in Japan.

One hundred and two consecutive non selected patients with intracranial aneurysms were reviewed. The incidence of ruptured aneurysm was 17.5 per population of 100,000 per year. The patients were divided into two groups, according to a change of policy that reversed the timing of operations from delayed to early surgery. The overall mortality and occurrence rate of neurological deficits due to vasospasm in patients in Hunt and Kosnik grades I through III were found to be lower during the period with a policy of early surgery. Elderly patients over 70 years old constituted 19% of the cases and those in poor condition (grade IV and V) 31%. These figures in this study are high, which may reflect the fact that these are common problems inherent in the treatment of ruptured aneurysms without patient selection at most community hospitals in the forefront of primary medical care.

Adult↗
PubMed1988

Experimental study on diaphragm fatigue during diaphragm pacing.

An experimental study was performed to determine the main site of fatigue associated with diaphragm pacing. Using 24 mature mongrel dogs, weighing 7.5 to 12.7 kg, direct phrenic nerve pacing was conducted from the right cervical area at three different respiration rates, 37 (Group 1, n = 6), 25 (Group 2, n = 6) and 12 (Group 3, n = 6) times per minute, under fixed stimulation conditions (pulse duration, 200 microseconds; frequency, 25 Hz; pulse train repetition time, 1.2 sec). Diaphragm fatigue was defined as the reduction in transdiaphragmatic pressure (Pdi) to less than or equal to 60% of the initial value. In each animal, tidal volume (Vt), induced muscle action potential (Edi), conduction time (CT) and electrical current (E) between two electrodes were examined at various periods until fatigue. In addition, after fatigue, aminophylline (10 mg/kg) was injected and each parameter was observed for an additional 45 min. In 10 animals, the polarity of stimulation was changed from anodal to cathodal current after fatigue and changes in Pdi and Edi were examined. The time to fatigue was 70 +/- 20 min for Group 1, 149 +/- 48 min for Group 2, and 371 +/- 97 min for Group 3, showing a significant stimulation rate dependency (P less than 0.05). Vt and Edi showed a significant decrease (P less than 0.05) at fatigue in all of the groups. However, no significant differences of CT and E were seen between pre- and postfatigue values. Pdi and Edi did not change even when polarity was changed after fatigue. Following administration of aminophylline, Pdi showed a significant (P less than 0.05) increase over time in all groups: 19.8 +/- 13.5% at 5 min, 23.0 +/- 13.5% at 15 min, and 16.2 +/- 14.9% at 30 min for Group 1; 23.6 +/- 11.6% at 5 min, 27.3 +/- 15.5% at 15 min, and 19.0 +/- 16.1% at 30 min for Group 2; and 29.9 +/- 21.1% at 5 min, 29.5 +/- 18.6% at 15 min, 22.3 +/- 13.8% at 30 min, and 15.5 +/- 13.4% at 45 min for Group 3. In contrast, administration of aminophylline caused no significant changes in Edi. Based upon the finding that aminophylline was significantly effective at the time of diaphragm fatigue, it is concluded that fatigue of the muscle itself constitutes one of the contributing factors for the fatigue phenomenon associated with diaphragm pacing.

Action Potentials↗
PubMed1988

Prediction of postoperative respiratory failure in patients undergoing lung resection for lung cancer.

To evaluate the correlation between predicted postoperative lung function and postoperative respiratory morbidity, 156 patients with lung cancer who underwent resection were classified into four groups based on the degree of postoperative problems: Group 1--no problems (116 patients); Group 2--retention of sputum or atelectasis requiring bronchofiberscopy two or more times (17 patients); Group 3--tracheostomy or mechanical ventilation for more than 2 days or both (14 patients); and Group 4--postoperative death (9 patients). The mean ages of Groups 2, 3, and 4 were significantly (p less than 0.05) higher than the mean age of Group 1. The predicted postoperative lung function (F) was assessed by the formula F = [1-(b-n)/(42-n)] x f, where f is the preoperative vital capacity or forced expiratory volume in one second, b is the number of subsegments of the resected lung lobe, and n is the number of subsegments obstructed by the tumor, which was assessed by the findings on the chest tomogram, on the bronchogram, at bronchofiberscopy, or a combination of these. The total number of subsegments was assumed to be 42. The predicted postoperative % FEV1 was 65.1 +/- 19.3% in Group 1,55.3 +/- 10.6% in Group 2,37.6 +/- 12.1% in Group 3, and 42.3 +/- 18.4% in Group 4. It was significantly (p less than 0.05) different between all the groups except between Groups 3 and 4. All 10 patients with a predicted postoperative % FEV1 of less than 30% were in Groups 3 and 4. We conclude that special attention to postoperative management is needed for patients whose predicted postoperative %FEV1 is lower than 30%.

Aged↗
PubMed1988

A point mutation in the coding sequence of the beta-hexosaminidase alpha gene results in defective processing of the enzyme protein in an unusual GM2-gangliosidosis variant.

cDNA clones were isolated from cultured fibroblasts of a patient previously reported as having GM2-gangliosidosis due to defective processing of the precursor beta-hexosaminidase alpha chain. Sequence analysis of a clone containing the entire protein coding sequence showed a single nucleotide substitution, from G to A, at nucleotide residue no. 1444, which resulted in a change in amino acid residue no. 482, from the normal glutamic acid to lysine. This transversion was confirmed in two other cDNAs from the same unamplified library. The results collectively indicate that the change from the strongly negative to strongly positive charge at amino acid residue no. 482 is responsible for the defective processing of the enzyme in this patient.

Amino Acid Sequence↗
PubMed1988

Mutation in GM2-gangliosidosis B1 variant.

Fibroblasts from a patient with GM2-gangliosidosis B1 variant contained mRNA of normal size but in reduced quantity for the beta-hexosaminidase alpha subunit. The nucleotide sequence of a cDNA clone that included the entire protein coding sequence was completely normal except for a single base substitution from G to A at no. 533, resulting in a change from arginine to histidine at amino acid no. 178. The same mutation was found in two other cDNA clones. The position of the mutation is approximately 90 amino acids from the N-terminus of the mature, processed enzyme. Computer analysis predicted substantial alterations in the secondary structure of the enzyme protein. These results provide new insight into functional domains of this enzyme.

Amino Acid Sequence↗
PubMed1988

Comparative subjective evaluation and prevalence study of TMJ dysfunction syndrome in Japanese adolescents based on clinical examination.

The purpose of this report was to investigate the actual need, as opposed to patient demand, for treatment of TMJ dysfunction syndrome in adolescents. For this investigation, 2198 Japanese schoolchildren, aged 10-18 yr (1095 boys and 1103 girls), were examined by questionnaire. In addition, each subject was given a clinical examination. The results of the subjective evaluations were compared with the frequency of actual occurrence of TMJ dysfunction syndrome. The results were: 1) Subjective recognition of TMJ dysfunction syndrome symptoms involved 253 students (11.5%): 129 boys (11.8%) and 124 girls (8.2%), with no significant difference in number between the sexes, 2) by comparing subjective assessment with clinical examination, the junior high school age was found to be the proper age for the introduction of preventive medical care, because these pupils were able to recognize the symptoms of TMJ dysfunction syndrome as accurately as adults, 3) the results obtained from the questionnaire and the clinical examination showed evidence of higher frequency of accurate recognition on the part of girls.

Adolescent↗
PubMed1988

Serial changes in focal hyperemia associated with hypertensive putaminal hemorrhage.

Seventeen separate xenon-enhanced computed tomographic images were performed in seven patients with hypertensive putaminal hemorrhage. Regional cerebral blood flow maps were then computed and assessed. All patients were categorized as being of good recovery potential, with moderate-sized hematomas, and all were treated conservatively. The regional cerebral blood flow assessments were scheduled within 4 days after, 2 weeks after, and less than 25 days after the ictus. The initial decrease in hemispheric blood flow ipsilateral to the side of the hematoma was calculated as the ratio of ipsilateral to contralateral hemispheric blood flow and was correlated with the size of the hematoma; that is, the larger the hematoma, the greater the decrease in the ratio of ipsilateral to contralateral hemispheric blood flow. The decrease persisted for 1 month. The mean of the ratio at 2 weeks after onset was 70%, the lowest during follow-up. All cases examined within 4 days after onset demonstrated perihematomatous focal hyperemia, or "luxury perfusion," which accounted for the delayed decrease. The same tissue that had previously shown hyperemia showed decreased regional cerebral blood flow 2 weeks after onset. Our results demonstrate that the luxury perfusion syndrome caused the secondary brain damage even in the cases that were in relatively good condition. The feasibility of treatment can be assessed by considering these results.

Cerebral Hemorrhage↗
PubMed1988

Diaphragm function after pulmonary resection. Relationship to postoperative respiratory failure.

We studied the lung mechanics and respiratory muscle function in 20 patients undergoing pulmonary resection. Transdiaphragmatic pressure (delta Pdi) during quiet breathing did not show any remarkable change after the operation (9.5 +/- 1.1 to 10.9 +/- 1.0 cm H2O), while the ratio of abdominal to transdiaphragmatic pressure changes (delta Pab/delta Pdi) revealed a significant difference between the preoperative and the early postoperative periods (0.32 +/- 0.06 to 0.00 +/- 0.11, p less than 0.05). The postoperative delta Pab/delta Pdi correlated significantly with the work of breathing (r = -0.60, p less than 0.01). The maximal transdiaphragmatic pressure (Pdimax) decreased significantly after operation (75.0 +/- 15.8 to 32.8 +/- 12.4 cm H2O, p less than 0.05), with no significant change in the maximal inspiratory mouth pressure (MIP) (74.2 +/- 16.8 to 39.5 +/- 11.6 cm H2O). Four of 20 patients developed respiratory failure postoperatively and required mechanical ventilation. delta Pab/delta Pdi in these patients was significantly lower than in the other patients (-0.62 +/- 0.24 versus 0.16 +/- 0.09, p less than 0.005). Our results suggested that during quiet breathing diaphragmatic function was preserved and intercostal/accessory muscles recruitment increased, but maximal strength of the diaphragm might be reduced in patients undergoing pulmonary resection.

Adult↗