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Biomedical subjects

K Ohno

Publications and source records attributed to K Ohno.

At least 487 records · Page 27Linked to original sources

Mitochondrial DNA mutations in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).

The total sequences of mitochondrial DNA were determined in two patients with juvenile-onset mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) due to Complex I deficiency. Patients 1 and 2 had three and two unique point mutations, respectively, causing replacement of phylogenically conserved amino acids. A transition from G to A was found at nucleotide position 5601 in the alanine tRNA gene of Patient 2, and a transition from A to G was found at 3243 in the leucine (UUR) tRNA gene of both patients. The latter mutation located at the phylogenically conserved 5' end of the dihydrouridine loop of the tRNA molecule, and was present in two patients with adult-onset MELAS and absent in controls. These results indicate that a mass of mtDNA mutations including the A-to-G transition in the tRNA(Leu) gene is a genetic cause of MELAS.

Adolescent↗

Mitochondrial DNA deletions in inherited recurrent myoglobinuria.

We describe two brothers with inherited recurrent exertional myoglobinuria and alcohol intolerance associated with distinct morphological abnormalities of muscle mitochondria and multiple deletions of muscle mitochondrial DNA. Patient 1 (26 years old) and Patient 2 (21 years old) had recurrent episodes of myoglobinuria provoked by strenuous exercise or alcohol intake, from the age of 18 years. Although their serum lactate and pyruvate levels were normal at rest, they were significantly elevated by aerobic exercise. Histochemistry of their biopsied limb muscles showed ragged-red fibers and cytochrome c oxidase-negative fibers as well as degenerating and regenerating fibers. Electron microscopy showed pronounced accumulation of abnormal mitochondria containing paracrystalline inclusions and moderate increases of glycogen particles. The enzyme activities of the electron-transfer complexes in the isolated muscle mitochondria of Patient 2 were within normal ranges. Southern blot analysis revealed multiple deletions of mitochondrial DNA, some of which were common between the patients. Polymerase chain reaction of their muscle mitochondrial DNA detected multiple abnormal fragments indicating mitochondrial DNA deletions. We propose that a defect of the mitochondrial energy-transducing system due to multiple mitochondrial DNA deletions is a novel genetic cause of inherited recurrent myoglobinuria.

Adult↗

Stimulation of human fetal astrocyte proliferation by bacterial lipopolysaccharides and lipid A.

This report concerns the effect of bacterial endotoxin [lipopolysaccharide(LPS) and lipid A] on cultured human fetal astrocytes. Exposure to 1 micrograms/ml LPS or lipid A caused a striking stimulation of the rate of proliferation of the cells. The effect was most pronounced with exponentially growing cultures. Stimulation was associated with enhance DNA synthesis as ascertained by [3H]thymidine incorporation. These findings at the cellular level may be of relevance in the elucidation of the effects of bacterial endotoxins on the developing human brain.

Astrocytes↗

A molecular genetic linkage map of mouse chromosome 19, including the lpr, Ly-44, and Tdt genes.

The mouse lpr gene, which is an autosomal recessive gene causing autoimmune disease with features of human systemic lupus erythematosus and eventually death from severe immune-complex glomerulonephritis, has been mapped on chromosome 19. To determine its exact chromosomal location, a three-point backcross was carried out by mating (MRL/MpJ-lpr/lpr x MOL-MIT)F1 x MRL/MpJ-lpr/lpr using the genes Ly-44 (lymphocyte differentiation antigen-44) and Tdt (terminal deoxynucleotidyl transferase) as markers. The following order of genes is proposed, with the distances between genes given in parentheses: centromere-Ly-44 (19.3 cM)-lpr (6.1 cM)-Tdt-telomere. The Ly-44a and Tdta alleles are found in all laboratory strains and in the wild Western European subspecies, domesticus and brevirostris. In contrast, the Ly-44b and Tdtb alleles are found in some Asian subspecies, Chinese mice of wild origin, yamashinai and molossinus. Furthermore the third Tdt allele, Tdtc, is detected in castaneus.

Animals↗

A molecular genetic linkage map of mouse chromosome 18, including spm, Grl-1, Fim-2/c-fms, and Mbp.

Restriction endonuclease fragment length variations (RFLV) were detected in mice with DNA probes for myelin basic protein (Mbp), glucocorticoid receptor-1 (Grl-1), and Friend MuLV integration site-2 (Fim-2). RFLV of the Mbp gene were found in SacI restriction patterns, RFLV of the Grl-1 gene were found in EcoRV patterns, and RFLV of the Fim-2 were found in BglII patterns. A three-point backcross was carried out by the backcross mating (C57BL/KsJ-spm/spm x MOL-MIT)F1 males x C57BL/KsJ-spm/spm; spm is an autosomal recessive gene causing sphingomyelinosis. From the results, spm, Grl-1, Fim-2, and Mbp loci were mapped on chromosome 18, and the following order of genes is proposed, with distances between genes in parentheses: centromere--spm--(7.8 cM)--Grl-1--(7.8 cM)--Fim-2--(39.1 cM)--Mbp--telomere. All laboratory strains and two European subspecies (Mus mus domesticus and M. m. brevirostris) carry the Grl-1a, Fim-2a, and Mbpa alleles. In contrast, another wild subspecies from Europe (M. m. musculus) and some Asian subspecies (M. m. molossinus, Chinese mice of wild origin, and M. m. yamashinai) carry the Grl-1b, Fim-2b, and Mbpb alleles. Only castaneus strains carry the intermediate combination of the Grl-1b, Fim-2a, and Mbpb alleles.

Animals↗

Symptomatic cerebral vasospasm of unusually late onset after aneurysm rupture.

An unusually late occurrence of symptomatic cerebral vasospasm is reported. The case involves a 50-year-old male who was uneventfully operated on for a ruptured anterior communicating artery aneurysm, with no symptom of cerebral vasospasm, 17 days after sustaining the subarachnoid haemorrhage. Two days after surgery, a right hemiparesis developed and angiography disclosed severe cerebral vasospasm. This case history and the aetiological factors of symptomatic vasospasm are discussed.

Cerebral Angiography↗

Protective effect of prostaglandin A2 against menadione-induced cell injury in cultured porcine aorta endothelial cells.

Prostaglandin A2 (PGA2) stimulates the biosynthesis of gamma-glutamylcysteine synthetase and elevates glutathione (GSH) contents in cultured mammalian cells. To clarify the importance of gamma-glutamylcysteine synthetase induction in the defence of endothelial cells against oxidative stress, the effect of PGA2 on menadione (2-methyl-1,4-naphthoquinone)-induced cell injury was examined. Incubation of porcine aorta endothelial cells with menadione produced marked loss of cellular GSH and protein sulfhydryl groups, followed by leakage of lactic dehydrogenase (LDH) into the culture medium. The LDH leakage and modification of protein thiol was, however, completely prevented by pretreatment of the cells with PGA2. The protective effect of PGA2 was more potent than that of cysteine delivery agents such as methionine, N-acetylcysteine or 2-oxo-4-thiazolidine carboxylic acid (OTC). The results suggest that cellular GSH plays an important role in the defence against oxidative stress, and induction of gamma-glutamylcysteine synthetase is effective for protecting vascular endothelial cells.

Animals↗

Histologic findings of apatite-titanium complex dental implants in the jaws of dogs.

This study concerns the histologic examination of apatite-titanium complex dental implants (two-piece, cylindrical type) in dogs. There was no plaque control. One to 3 months after implantation, the surface of the apatite root was directly bound to newly formed, woven bone. Seven-and-a-half months to 1 year after implantation, the apatite root was directly bound to the newly formed lamellar bone, which provided strong bone bonding (apatite-bone bonding). There appear to be two types of mechanisms for the resorption of apatite ceramics: first, cellular-type resorption by both multinuclear and mononuclear macrophages; and second, a noncellular, fluid mechanism (dissolution). The gingival sulcus around implants and downward growth of the epithelial cells could be observed in almost all of the implants. There was no cellular inflammation in the tissue around the implants, in the nasal cavity, or in the maxillary sinus. From this study we concluded that clinical application of this dental implant system would be practical.

Animals↗

Perioperative complications of encephalo-duro-arterio-synangiosis: prevention and treatment.

We performed encephalo-duro-arterio-synangiosis on 169 sides of 81 Moyamoya and 8 non-Moyamoya patients in the past 10 years. The advantage of this operation is its minimal operative invasion, giving rise to few operative complications. During 10 years of practice, however, we encountered some perioperative problems. Perioperative cerebral infarction of varying severity was seen in six Moyamoya patients. Severe hyperventilation with crying was the main trigger of infarction. Two patients developed wound infection with Gram-negative rods. Removal of an infected bone flap was necessary. One Moyamoya patient developed malignant hyperthermia during the operation. One acute epidural hematoma necessitated an emergency hematoma removal. Five patients showed a temporary aggravation of involuntary movements. Prolonged mild fever and temporary and limited hair loss around the wound were often observed. Cases and their treatment are presented with discussion of preventive measures.

Adolescent↗

A case of bipartite median nerve at the wrist.

We report a case of bipartite median nerve at the wrist associated with contracture of the flexor muscles in the forearm and anterior interosseous nerve palsy. The possibility of a bipartite median nerve must be borne in mind during operations on the distal forearm.

Child, Preschool↗

An experimental study of healing around hydroxylapatite implants installed with autogenous iliac bone grafts for jaw reconstruction.

The purpose of this study was to evaluate the use of hydroxylapatite implants (HA) with autogenous bone grafts for jaw reconstruction. After autogenous iliac bone grafts were transplanted to 36 rabbit mandibles, an HA implant was installed into the graft immediately (IM group), or 90 days (90D group), or 180 days (180D group) later. The animals were killed 7, 14, 30, 60, 90, and 180 days after the HA implant placement. The healing process was examined histologically, and histomorphometric measurements were made with a computer-based image analyzer to quantify the percentage of HA-bone bonding and trabecular bone in the medullary cavity. In the IM group, the HA-bone bonding tended to be deterred by fibrous tissue, and the rate of HA-bone bonding (BBSR) was less than that of the other groups. The trabecular bone around the implants tended to decrease after 30 days in all groups. However, the average of the trabecular bone specific volume (tVsp) in the 90D group was about 10% higher than that in the other groups. From these results, it is concluded that in clinical use of HA-coated dental implants with autogenous bone grafts, the time of installation should not be immediately after the bone graft, but when there is sufficient newly formed trabecular bone to enhance HA-bone bonding.

Animals↗

Familial hypobetalipoproteinaemia complicated by cerebellar ataxia and steatocystoma multiplex.

A 55-year-old man with cerebellar ataxia and steatocystoma multiplex was found to have reduced serum concentrations of total cholesterol, betalipoprotein and apolipoprotein B. Computed tomography revealed atrophy of the cerebellum and brain stem. Of the six family members examined, four had hypobetalipoproteinaemia, and one had mild ataxia. Similar skin lesions were noted in five male relatives. This case represents a rare combination of familial hypobetalipoproteinaemia, cerebellar ataxia and steatocystoma multiplex.

Cerebellar Ataxia↗

Autosomal recessive polycystic kidney in rats.

We evaluated the characteristics of renal lesions in rat autosomal recessive polycystic kidney (ARPK). In rat ARPK, small cysts appeared primarily in the medulla 2 months after birth and gradually extended to the cortex, forming large cysts involving the entire layer after 8 months. By immunofluorescence microscopy, type IV collagen was more strongly stained in the epithelial basement membrane of the rat ARPK than in the normal rat tubular basement membrane (TBM). Electron microscopy demonstrated a marked thickening, slight splitting and lamination of the TBM in the ARPK. As peroxidase-labeled lectins, dolichos biflorus very strongly stained the cyst epithelium whereas lens culinaris did not. These findings indicate that cysts in rat ARPK originate in the collecting duct.

Age Factors↗

Extracellular ATP stimulates interleukin-dependent cultured mast cells and eosinophils through calcium mobilization.

We examined the effect of ATP and related nucleotides on the changes in intracellular calcium ([Ca2+]i) in murine bone marrow-derived mast cells (BMMC) and human cord blood-derived eosinophils (EO) cultured in the presence of interleukins. ATP, ADP and AMP released a substantial amount of histamine and leukotriene C4 from BMMC, and EO showed locomotive activity in response to ATP, ADP and GTP. These reactions were accompanied with an increase in [Ca2+]i in BMMC and in EO. The rise in [Ca2+]i in BMMC induced by ATP or antigen at optimal concentrations was inclined to be persisting. On the other hand, these nucleotides induced a rapid and transient rise in [Ca2+]i in EO. Purified human peripheral EO also exhibited locomotive activity and an increase in [Ca2+]i in response to ATP. These results indicate that extracellular ATP activates interleukin-dependent cultured mast cells and EO through Ca2+ mobilization, and suggest that ATP, which is known to be released from activated platelets or autonomic nerves, may stimulate in vivo counterparts of these cultured inflammatory cells.

Adenosine Triphosphate↗

Effects of encephalo-duro-arterio-synangiosis on childhood moyamoya patients--swift disappearance of ischemic attacks and maintenance of mental capacity.

The effect of encephalo-duro-arterio-synangiosis (EDAS) upon chronic cerebrovascular ischemia in 65 pediatric moyamoya patients was evaluated by the postoperative interval before complete disappearance of ischemic attacks and changes in pre- and postoperative intelligence (IQ) or development quotients (DQ). The ischemic attacks disappeared after a mean period of 239 days, in three-fourths of patients within a year and in about one-fourth within the second year. This was very fast compared with the natural course of the disease. There was no significant difference in DQ/IQ before and after the operation. The mentally normal (IQ/DQ greater than or equal to 86) population in the postoperative patients was greater than in the natural course of the disease, although fewer in the preoperative group. This shows that EDAS delayed or prevented the deterioration in mental capacity usually present but often overlooked in the natural course of pediatric moyamoya disease.

Adolescent↗