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Biomedical subjects

K Ohno

Publications and source records attributed to K Ohno.

At least 523 records · Page 29Linked to original sources

[Intra-arterial chemotherapy with cis-diamminedichloroplatinum (CDDP) for primary mediastinal seminoma].

Primary mediastinal malignant germinoma is a rare disease, and only about 15 patients have been reported in Japan. We treated a patient with this disease by intra-arterial CDDP infusion and observed good effects. A 29 year-old male was admitted to our hospital due to SVC syndrome in 1980. A right mediastinal tumor was detected, and the resection of this tumor was performed. Histological examination showed seminoma. Though postoperative Co irradiation was performed, radiation pneumonitis developed in the right lung. Subsequently, the tumor metastasized to the right kidney and spinal cord. After removal of the right kidney followed by Co irradiation, the clinical course was good. In 1987, a mass (10 x 6 cm) was detected in the left mediastinum, suggesting recurrence. Four courses of CDDP infusion into the left bronchial artery and left internal thoracic artery (1 course: 45-70 mg) were performed, and good effects were obtained. No side effects were observed, and the clinical course has been good until now. This case is of interest in evaluating the multidisciplinary treatment for mediastinal seminoma.

Adult↗

Quantitative determination of deleted mitochondrial DNA relative to normal DNA in parkinsonian striatum by a kinetic PCR analysis.

Deleted mitochondrial DNA (mtDNA) was accumulated in the parkinsonian striatum, but the same deleted mtDNA was also detectable in the control striatum when cycles of polymerase chain reaction were increased. To discriminate between these pathological and physiological conditions, we quantitatively analyzed the proportion of deleted mtDNA to normal mtDNA by measuring the incorporation of alpha-[32P]deoxycytosine triphosphate into mtDNA fragments by using a laser image analyzer. To estimate the molar ratio of the deleted mtDNA to normal mtDNA, the radioactivity was normalized by each fragment size. By plotting logarithms of normalized radioactivities against PCR amplification cycles, straight lines were obtained with different slopes. By extrapolation of the line to the zero amplification, the proportion of mutant mtDNA to normal mtDNA in the original sample from the parkinsonian striatum was estimated to be ca. 5%, which was at least ten times higher than the proportion of ca. 0.3% in the control striatum. These results indicate that phenotype of the mutant mtDNA as Parkinson's disease is expressed when the proportion of deleted mtDNA to normal mtDNA exceeds a threshold of ten times higher value than in the normal subject.

Base Sequence↗

Increase of deleted mitochondrial DNA in the striatum in Parkinson's disease and senescence.

A mutant mitochondrial DNA (mtDNA) with a 4,977-bp deletion was detected in the parkinsonian brain by using the polymerase chain reaction. Although the deleted mtDNA was detectable even in the brain of aged controls, the proportion of deleted mtDNA to normal mtDNA in the striatum was higher in the parkinsonian patients than in the controls. In both the parkinsonian patients and the aged controls, the proportion was higher in the striatum than in the cerebral cortex. These results indicate that age-related accumulation of deleted mtDNA is accelerated in the parkinsonian striatum and suggest that the deletion contributes to pathophysiological processes underlying Parkinson's disease.

Adult↗

Multiple mitochondrial DNA deletions exist in cardiomyocytes of patients with hypertrophic or dilated cardiomyopathy.

Genetic impairment was revealed in idiopathic cardiomyopathy and the responsible DNA locus was estimated. Mitochondrial DNA were amplified from autopsied cardiac specimens from three patients who died from hypertrophic or dilated cardiomyopathy by using polymerase chain reaction (PCR). By using two novel methods for PCR gene amplification, the pleioplasmic existence of multiple populations of differently deleted mitochondrial DNA in all specimens from the patients was confirmed. Mitochondrial DNA with a 7,436 bp deletion which commonly existed among the specimens was sequenced and the direct repeat at each edge of deletion was identified as (CATCAACAACCG) which was located in ATPase 6 gene and in the D-loop region. From our results mitochondrial DNA mutations could also be an important contributory factor to cardiomyopathy.

Adenosine Triphosphatases↗

Production of granulocyte/macrophage colony-stimulating factor by cultured astrocytes.

We investigated the production of interleukin-3 (IL-3)-like factor by murine astrocytes. Supernatants from lipopolysaccharide (LPS)-stimulated astrocytes induced proliferation of IC-2, an IL-3- and granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent cell line. This activity was completely neutralized by the antibody against GM-CSF but not by the anti-IL-3 monoclonal antibody. Northern blot analysis revealed the expression of GM-CSF mRNA, but not of IL-3 mRNA, in cultured astrocytes. These results indicate that with proper stimuli murine astrocytes produce GM-CSF.

Animals↗

Responses of regional cerebral blood flow following focal electrical stimulation of the nucleus basalis of Meynert and the medial septum using the [14C]iodoantipyrine method in rats.

The effects of focal electrical stimulation of the nucleus basalis of Meynert (NBM) and the medial septum (MS) on regional cerebral blood flow (rCBF) of the 14 brain regions were examined in halothane-anesthetized rats using the [14C]iodoantipyrine ([14C]IAP) method. The stimulation of the unilateral NBM (with parameters of 200 microA, 0.5 ms, 50 Hz for 60 s) produced significant increases in frontal, parietal and occipital cortical blood flows in the hemisphere ipsilateral to the stimulated NBM; no rCBFs in all other brain regions examined were influenced by the stimulation. The stimulation of the MS produced significant increases in bilateral hippocampal rCBFs, but rCBFs in other brain regions were not influenced by the stimulation. In summary, the response of increase in rCBF following focal electrical stimulation of the NBM or MS is restricted to regions that receive cholinergic nerve projections from the NBM or MS.

Animals↗

Induction of gamma-glutamylcysteine synthetase by prostaglandin A2 in L-1210 cells.

Effects of prostaglandin A2 (PGA2) on glutathione (GSH) status in L-1210 cells were examined. When the cells were cultured in the presence of PGA2, a persistent rise of cellular GSH concentration was observed 6 h after the addition of PGA2. This stimulatory effect of PGA2 was abolished if the cells were pretreated with an enzyme inhibitor of GSH synthesis, buthionine sulfoximine. Subsequent study with cell free extract of cultured L-1210 has revealed that PGA2 stimulated the biosynthesis of gamma-glutamylcysteine synthetase (EC 6.3.2.2). Actinomycin D inhibited this stimulatory effect of PGA2 on cultured cells. The optimal pH, Km value for glutamic acid and sensitivity to inhibitors of gamma-glutamylcysteine synthetase from PGA2 treated and nontreated cells were virtually the same. Thus, our findings suggest that PGA2 induced gamma-glutamylcysteine synthetase in cultured L-1210 cells which is responsible for the elevated level of GSH in these cells.

Animals↗

Assessment of the intrapulmonary ventilation-perfusion distribution after the Fontan procedure for complex cardiac anomalies: relation to pulmonary hemodynamics.

In 12 patients who underwent the Fontan procedure for complex cardiac anomalies, lung scanning with xenon-133 was performed to assess the intrapulmonary ventilation-perfusion distribution, and comparison was made with a control group. All data were then analyzed in relation to either pre- or postoperative pulmonary hemodynamic data. In ventilation scans, the intrapulmonary distribution in the right lung was almost normal. In perfusion scans, an abnormal increased upper to lower lobe perfusion ratio greater than the normal value found in the control group was noted in seven patients (58.3%). There was a significant correlation (p less than 0.02) between the upper to lower lobe perfusion ratio and postoperative pulmonary vascular resistance. Furthermore, this perfusion ratio correlated inversely with the preoperative (p less than 0.005) and postoperative (p less than 0.02) right pulmonary artery area index, defined as the ratio of cross-sectional area to the normal value. Of five patients with less than 90% arterial oxygen saturation, four showed an abnormal distribution of pulmonary blood flow greater than the normal perfusion ratio. No patient had evidence of a pulmonary arteriovenous fistula by the echocardiographic contrast study. These results suggest that abnormal distribution of pulmonary blood flow to the upper lung segment may develop in patients after the Fontan procedure, and that insufficient size of the pulmonary artery before operation and the consequent postoperative elevation of pulmonary vascular resistance may be responsible for this perfusion abnormality.

Child↗

A new point mutation within exon 5 of beta-hexosaminidase alpha gene in a Japanese infant with Tay-Sachs disease.

A new point mutation within exon 5 of beta-hexosaminidase alpha subunit gene (guanine509----adenine; arginine170----glutamine) has been identified as being responsible for the typical clinical and enzymological phenotype of infantile Tay-Sachs disease in a Japanese infant. Expression of the mutant enzyme protein in the COS I cell system indicated that it is catalytically inactive and also is unstable. The patient is a compound heterozygote, and the exact abnormality in the other allele could not be identified except that it is not any of the other nine known mutations of the beta-hexosaminidase alpha. The data collectively suggest that the other allele is not producing stable messenger RNA (mRNA). The rapidly increasing number of mutations responsible for clinical and enzymological phenotypes and the very large number of statistically possible combinations among them for compound heterozygosity pose a serious pragmatic problem for classification and nomenclature of this group of rare genetic disorders.

Amino Acid Sequence↗

Mental outcome following encephaloduroarteriosynangiosis in children with moyamoya disease with the onset earlier than 5 years of age.

The mental prognosis of children with moyamoya disease, in whom the onset was when they were younger than 5 years of age, has been reported to be very poor. We studied the mental outcome of these patients after encephaloduroarteriosynangiosis (EDAS) in relation to the age at the onset of the disease and the age at operation. For patients in whom the onset of moyamoya disease occurs when they are younger than 2 years of age, the prognosis is very poor with regard to mental abilities even if they have an operation within a year after the onset. Slight hope remains if the operation is within 3 months of the onset. For patients in whom the disease begins when they are 2-5 years of age, EDAS performed before the age of 9 years may result in a good outcome with regard to mental ability, as well as resolution of the paroxysmal symptoms and cerebral revascularization.

Adolescent↗

Mapping of the Hox-3.1 and Myc-1.2 genes on chromosome 15 of the mouse by restriction fragment length variations.

Restriction endonuclease fragment length variations (RFLV) were detected by use of the cDNA probe Hox-3.1 for the homeo box-3.1 gene and also the c-myc oncogene probe for exon 2. RFLV of Hox-3.1 were found in HindIII restriction patterns, and RFLV of the Myc-1.2 gene in EcoRV patterns. From the RFLV, the Hox-3.1 and Myc-1.2 genes were mapped on chromosome 15. Three-point cross test data showed that the frequency of recombination is 26.4% between Myc-1.2 and Gpt-1, 30.2% between Gpt-1 and Gdc-1, and 9.4% between Gdc-1 and Hox-3.1. The following order of these genes is proposed, Myc-1.2--Gpt-1--Gdc-1--Hox-3.1. All laboratory strains carry the Hox-3.1a and Myc-1.2a alleles. Among strains of wild origin, domesticus strains carry only the Hox-3.1a and Myc-1.2a alleles, as do the laboratory strains. One strain of brevirostris carries the Hox-3.1a and Myc-1.2b alleles. Other wild subspecies from Europe and Asia, M. m. musculus, M. m. castaneus, M. m. molossinus, Chinese mice of wild origin, and M. m. yamashinai carry the Hox-3.1b and Myc-1.2b alleles.

Alleles↗

Specific role of an alpha,beta-unsaturated carbonyl group in gamma-glutamylcysteine synthetase induction by prostaglandin A2.

The effects of prostaglandins (PGs) on cellular glutathione (GSH) status in L-1210 cells were examined. PGA2 and J2, which have an alpha,beta-unsaturated carbonyl group in the cyclopentane ring, elevated the GSH content, but PGB2, D2, E2 and F2 alpha did not show the effect. When L-1210 cells were incubated with various 2-cyclopentenone derivatives, 4-hydroxy-2-cyclopentenone and some of related compounds elevated cellular GSH levels. Subsequent study with cell-free extract of cultured L-1210 cells revealed that PGA2 and 4-hydroxy-2-cyclopentenone induced gamma-glutamycysteine synthetase activity at the transcriptional level. This induction was also found in other cultured mammalian cells such as HeLa S3, NIH/3T3 and porcine aorta endothelial cells. When L-1210 cells were incubated with PGA2 in the presence of 4-hydroxy-2-cyclopentenone and its analogues, they inhibited the accumulation of PGA2 in cell nuclei. Our findings thus suggest that an alpha,beta-unsaturated carbonyl moiety is responsible for enhancing the biosynthesis of gamma-glutamylcysteine synthetase in cultured cells.

Animals↗

Cytoplasmic body and mitochondrial DNA deletion.

A patient with chronic progressive external ophthalmoplegia (CPEO) who had abundant cytoplasmic bodies in muscle fibers and a deletion of mitochondrial DNA is reported. The patient was a 26-year-old male suffering from ophthalmoplegia from age 21. He had a marfanoid skeletal abnormality and perceptive hearing loss, but had neither retinopathy, ataxia, nor dementia. In the mitochondria isolated from the biopsied skeletal muscle, NADH-ubiquinone oxidoreductase activity was slightly decreased, succinate-cytochrome c reductase activity was slightly increased, and cytochrome c oxidase activity remained normal. Southern blot analysis of the muscle DNA identified heteroplasmy composed of a normal-sized mitochondrial DNA and a mutant mitochondrial DNA with a 4.2-kilobase deletion. The PCR plus S1 analysis showed that the deletion extended from nucleotide position 7860 +/- 60 to 12,090 +/- 70. The histological studies of the biopsied muscle revealed ragged-red fibers and cytochrome c oxidase-negative fibers in 15.7% and 18.6% of the muscle fibers, respectively. Other conspicuous histological change was abundant cytoplasmic bodies surrounded by clusters of abnormal mitochondria. The cytoplasmic bodies were found preferentially in type 1 fibers, and exclusively in cytochrome c oxidase-negative fibers and in ragged-red fibers. Focal existence of cytoplasmic bodies in muscle fibers with abnormal mitochondria suggests that segregated distribution of the abnormal mitochondria with deleted mitochondrial DNA is involved in the pathogenesis of cytoplasmic bodies.

Adult↗

Cavernous angioma with encapsulated intracerebral hematoma: report of two cases.

Two cases of a cavernous angioma with an encapsulated intracerebral hematoma are presented. In both instances, computed tomography scan showed a ringlike appearance with a nodular lesion. Cerebral angiograms of the two cases, however, were normal. The preoperative diagnosis for both cases was a brain neoplasm. The diagnostic problems that this type of vascular malformation presents and its role in the development of the encapsulated hematoma are discussed.

Adult↗

Symptoms and their pattern of progression in childhood moyamoya disease.

In the series of 81 childhood moyamoya patients, the common pattern of clinical progression seen in 77 patients was revealed to be no more than four. The characteristics of each type of clinical progression were presented for a better understanding of the disease and for an initiation of early treatment of this rather rare and insidiously progressive disease. Type I (21 cases) and type II (15 cases) are cases without infarction, even in those types there are cases with poor IQ. Type III (17 cases) and type IV (24 cases) are cases with infarction and an early operation is mandatory. Types I and II are also good candidates for early operation, for IQ deterioration insidiously progress in these types and there is no way of knowing them from type III before infarctions occur. We now have effective surgical measures to improve the ischemic conditions of this disease.

Age Factors↗

Retrobulbar optic neuritis in a two-year-old boy.

We report a 2-year-4-month-old boy with retrobulbar optic neuritis. He had a sudden onset of impaired vision, which progressed to total blindness within a day. The visual evoked potential (VEP) showed no activity, but the electroretinogram was normal. Computed tomography (CT) and magnetic resonance imaging (MRI) showed no abnormal findings in the visual tract. The cerebrospinal fluid (CSF) myelin basic protein (MBP) level was elevated and serum anti-myelin antibody was positive. These findings suggested that optic neuritis in our patient was induced by retrobulbar demyelination, perhaps as a result of an autoimmune process. His visual impairment recovered gradually, but not completely, following oral prednisolone therapy. We have followed him for one year since discharge and have found neither recurrence of optic neuritis nor any other neurological disorders. Optic neuritis in children is rare and, to our knowledge, this patient is one of the youngest to be reported. This case suggests that autoimmune mechanisms may induce optic neuritis even in early childhood. In addition to VEP and MRI studies, the CSF MBP and serum anti-myelin antibody can be useful in the diagnosis and follow-up the patients with optic neuritis.

Child, Preschool↗

Factors contributing to skeletal relapse after surgical correlation of mandibular prognathism.

Postoperative follow-up and multiple regression analysis of skeletal relapse following mandibular setback were carried out to clarify the timing and causes of the relapse. The subjects were 24 mandibular prognathism patients. All patients underwent intraoral oblique sagittal splitting osteotomy with circumferential wiring and intermaxillary fixation for 8 weeks. Occlusal splints were not used. Postoperative positional changes of segments were evaluated by lateral cephalograms taken at appropriate intervals. Horizontal relapse was most evident within six months after surgery; vertical relapse seldom occurred. Multiple regression analysis revealed little association between preoperative morphological patterns and postoperative relapse. Although spatial changes of the proximal segment at operation and age of the patient were the best predictors for postoperative horizontal relapse, analysis indicated unsatisfactory prediction of vertical relapse because of its rare occurrence. Based on these results, the aetiology of relapse is discussed and two proposals are suggested for its prevention.

Adolescent↗

Functional effects of intraoral reconstruction with a free radial forearm flap.

Postoperative articulation was investigated in patients who underwent glossectomy and reconstruction with free radial forearm flaps. The methods of evaluation consisted of scores for intelligibility of 100 Japanese syllables and 3 groups of glossal sounds. The glossal sounds, based on palato-lingual contact (lingogram), were useful to evaluate function of the respective parts of the tongue. One patient who had had a partial glossectomy and resection of the floor of the mouth achieved an overall score of 80.5% one year postsurgery, and his glossal sounds were also excellent. Three patients who underwent removal of the floor of the mouth and hemiglossectomy, excluding the root of the tongue, had overall scores ranging from 45.6% to 82.1%. Two of these had particularly low scores for the glossal sounds produced with the rear part of the tongue, and this suggested the necessity for suspension slings to prevent depression of the reconstructed tongue and the floor of the mouth. The hemiglossectomy with partial mandibulectomy had an acceptable score of 68.7%. Chronologically, the glossal sounds produced with the rear part and the blade of the tongue often tended to improve postsurgery.

Aged↗