Decrease in glutamate in the jugular vein after head injury.
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Biomedical subjects
Publications and source records attributed to A Ogawa.
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Protein breakdown was monitored in C2C12 myotubes as the rate of release of radioactivity after prelabeling cell protein with [3H] tyrosine. IGF-1 (13 nM) and insulin (100 nM) prolonged the half-life of long-lived proteins. Enzymatic activities of cathepsins B and B+L were inhibited by the addition of IGF-1 or insulin. Immunoblotting of cathepsins B and L revealed extensive degradation of heavy chain forms by IGF-1. However, neither expression of cathepsins B and L genes nor expression of cystatin beta, an intrinsic inhibitor for cathepsins, was influenced. The addition of E-64, L-3-carboxy-trans-2,3-epoxypropionyl-leucylamide-(4-guanidin o) butane, a inhibitor of cathepsins B and L, increased protein contents of heavy chains of cathepsins B and L in the IGF-1 treated cells. Inhibition of protein breakdown by IGF-1 is mediated by autocatalytic inactivation of lysosomal cathepsins B and L.
Interleukin(IL)-6 transgenic mice were produced by microinjection of human IL-6 cDNA fused with H-2Ld promoter into the pronucleus of fertilized eggs from C57BL/6J mice. At 16 weeks old, the gastrocnemius muscles of the IL-6 transgenic mice became atrophic as compared to those of the normal mice, while the body weights increased significantly. The activities and mRNA levels of lysosomal cathepsins B and L were increased in the muscles of the transgenic mice. Immunohistochemical study on the muscles showed increased staining of both cathepsins B and L in the transgenic mice. IL-6 is responsible for enhanced muscle catabolism by activating the lysosomal cathepsin (B and L) system.
To elucidate the mechanism of the basal hyperinsulinemia of obesity, we perfused pancreata from obese Zucker and lean Wistar rats with substimulatory concentrations of glucose. Insulin secretion at 4.2 and 5.6 mM glucose was approximately 10 times that of controls, whereas beta-cell volume fraction was increased only 4-fold and DNA per islet 3.5-fold. We therefore compared glucose usage at 1.4, 2.8, and 5.6 mM. Usage was 8-11.4 times greater in Zucker islets at 1.4 and 2.8 mM and 4 times greater at 5.6 mM; glucose oxidation at 2.8 and 5.6 mM glucose was > 12 times lean controls. To determine if the high free fatty acid (FFA) levels of obesity induce these abnormalities, normal Wistar islets were cultured with 0, 1, or 2 mM long chain FFA for 7 days. Compared to islets cultured without FFA insulin secretion by FFA-cultured islets (2 mM) perifused with 1.4, 3, or 5.6 mM glucose was increased more than 2-fold, bromodeoxyuridine incorporation was increased 3-fold, and glucose usage at 2.8 and 5.6 mM glucose was increased approximately 2-fold (1 mM FFA) and 3-fold (2 mM FFA). We conclude that hypersecretion of insulin by islets of obese Zucker fatty rats is associated with, and probably caused by, enhanced low Km glucose metabolism and beta-cell hyperplasia, abnormalities that can be induced in normal islets by increased FFA.
OBJECTIVE: To investigate the characteristics of HLA-B27 that render susceptibility to seronegative spondylarthropathies. METHODS: Serologic HLA class I typing of Japanese patients with ankylosing spondylitis (AS), juvenile rheumatoid arthritis (JRA), and healthy controls, was performed. HLA-B39 subtypes were determined by polymerase chain reaction-sequence-specific oligohybridization. RESULTS: HLA-B27 was present in 40 of 48 patients with AS (83%), and in only 1 of 210 healthy controls (0.5%). Three of 8 patients (37.5%) who were negative for HLA-B27 were positive for HLA-B39, which was significantly higher compared with the HLA-B27-negative controls (6.2%; P = 0.01). Significant association with HLA-B39 was also noted in the JRA patients (16.7%; P < 0.01), especially in those patients with pauciarticular-onset disease (33.3%; P < 0.01). Ten of 13 HLA-B39-positive patients had subtype B*3901 and 3 had B*3902. CONCLUSION: Because HLA-B27 and HLA-B39 share Glu at position 45 and Cys at position 67, both of which constitute components of the peptide-anchoring B pocket, and because they possess similar peptide-ligand motifs, our results may support either the role of the peptides presented by class I antigens or the importance of Cys at position 67, in the development of spondylarthropathies and pauciarticular-onset JRA.
We examined immunohistochemically 123 autopsy brains from patients aged between 30 to 59, who died as a result of malignant neoplasms. Using antiserum to amyloid beta protein (A beta), we found that cerebral A beta deposits began in the subjects' fifth decade; its prevalence was 0%, 9.8% and 21.5% in the fourth, fifth and sixth decades, respectively. The major form of A beta deposition was diffuse-type plaques, although one third of the brains with A beta deposition showed amyloid angiopathy. Subpial A beta deposition is frequently associated with amyloid angiopathy. The prevalence of cerebral A beta deposits was about two times higher in the patients who had received brain radiation therapy (27.8%) compared to non-radiated patients (14.8%). Amyloid angiopathy was much more prominent (P < 0.05) with radiation therapy (22.2%) than without (8.0%). We found that cerebral A beta-deposition is dependent on aging, even in patients with malignant tumors and at beginning in their forties, and that brain radiation therapy is a possible risk factor of A beta deposition, especially in the form of amyloid angiopathy.
In order to achieve complete irrigation, reduce air in the hematoma cavity, and obtain rapid reduction of the cavity without drainage, we use burr-hole evacuation of the hematoma followed by irrigation using physiologic saline solution and replacement of the hematoma with carbon dioxide (CO2) gas. We have treated 19 cases between the ages of 41 and 84. With the exception of one case with dementia of 5 years' duration, all cases were asymptomatic postoperatively. Computed tomography (CT) scans obtained immediately postoperatively showed the gas to fill the hematoma cavity, but on the following day, the gas and the hematoma cavity had nearly disappeared. There was no surgical mortality nor morbidity and there were no side effects of the CO2 gas. Recurrence was found in one case (5.3%). By filling the hematoma cavity with CO2, disappearance of the cavity is rapid and drainage is not needed. Moreover, this technique implies no restrictions on postoperative motility, and is thus suitable for elderly patients.
An allele encoding an HLA-C antigen, tentatively called CX44, associated with HLA-B44 was identified as a new member of the Cw14 group, Cw*1403. The nucleotide sequence of Cw*1403 was closest to that of Cw*1401: five bases were different between the two alleles, in which three bases in Cw*1403 (two in exon 3 and one in exon 4) were the same as those of most HLA-C alleles. Two substitutions from guanine to adenine were found in the new allele, both of which are in exon 2, one at position 134 (61 of exon 2) and the other at position 201 (128 of exon 2). The former nucleotide substitution leads to the substitution of amino acid residue 21 from Arg to His, and the other substitution was synonymous. The former substitution was shared with Cw2, 3, 5, 13, and 15 alleles, and the latter was shared with Cw2, 4, 5, 8, 12, 13, 15 and 16 alleles. The other seven unrelated Japanese samples with CX44 were analyzed by a PCR-SSO method. It was confirmed that all the seven samples have the same substitutions as the sequenced allele, and the allele demonstrates a strong association with A33, B44, DR13, and DQ1, which are known to form a common haplotype in Japanese and Koreans.
We created a new continent urinary valve in 6 dogs by placing an ileal segment between the anterior rectus sheath and rectus muscle in an antiperistaltic fashion. This ileal segment maintained urinary continence sufficiently and was readily catheterizable. Since it is easy to construct, the subfascial ileal valve will be applicable to construction of continent urinary reservoirs.
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HLA-DQA1 and -DQB1 genes were investigated in 30 Japanese children with idiopathic nephrotic syndrome (INS) using the polymerase chain reaction-restriction fragment length polymorphism method. Compared with control children, there was a significant increase in the HLA-DQA1*0501, DQB1*0301 and DQB1*0601 alleles, whereas the frequency of DQB1*0501 showed a significant decrease in the patients. The increase of DQA1*0501 can be explained as being a result of a linkage disequilibrium with DQB1*0301. The previous result demonstrating a positive association of DRw6 and DRw8 with INS is also assumed to be attributable to a linkage disequilibrium with DQB1*0301 and 0601. A total of 83% of patients compared with 37% of controls possessed DQB1*0301 and/or DQB1*0601 allele (P < 0.001, RR = 8.6). Only these alleles have alanine at residue 13 and tyrosine at residue 26 in the hypervariable region in the Beta 1 domain of DQB1 gene. These findings suggest that the unique amino acid residues in the DQB1 gene may contribute to disease susceptibility in Japanese children with INS.
We constructed a continent, catheterizable urinary conduit using a smooth muscle graft in dogs. One end of an isolated vascularized ileal segment was anastomosed to the bladder dome, and the other end was opened in the abdominal wall. The ileal conduit was tightly encircled with a free seromuscular flap of the ileum in 6 dogs and with a similar flap of colon in 6 other dogs. All smooth muscle grafts were alive 6 months after the operation. Pressure study showed that all but one ileal conduit had a pressure of more than 30 cm of water. Two dogs with a free ileal graft leaked urine when the bladder pressure increased, whereas all dogs with a colonic graft never leaked urine from the stoma. This smooth muscle graft will be available to reinforce the continent action of a plicated or narrowed intestinal tube for a urinary reservoir.
A buccal mucosa graft from the lower lip was used for meatal reconstruction in 3 patients. The buccal mucosa graft was combined with a bladder mucosa graft for urethral substitution in 1 adult and 1 child, and was anastomosed to a skin tube for creating a glanular urethra in 1 child. The buccal mucosa graft obtained was approximately twice as wide as the desired urethra. Postoperatively the buccal mucosa graft became shrunken at the proximal anastomosis and urethral stricture developed in 2 children. The graft did not shrink at the meatus, but the meatus became widened in 2 patients. These results suggest that a buccal mucosa graft is useful for meatal reconstruction, but further technical improvement is necessary to avoid postoperative complications.
A rare case of persistent primitive trigeminal artery variant (PTAV) with cerebellar ischemia is reported. A 23-year-old male complained of sudden dizziness and nausea after playing valley ball. CT scan and MRI on admission revealed no abnormal findings. Left carotid angiography demonstrated a PTAV anastomoting precavernous portion of left internal carotid artery to the left superior cerebellar artery. The 37 cases reported in literature were reviewed to characterise PTAV. Ninety-seven% of the cases arising from precavernous portion of internal carotid artery, and terminated in anterior inferior cerebellar artery in 73%, posterior inferior cerebellar artery in 13.5% and superior cerebellar artery in 13.5%. Approximately 22.2% of patients with PTAV have cerebral aneurysms. The hypotension or mechanical compression of PTAV on playing valley ball with poor vascular supply to the part of cerebellum possibly caused cerebellar ischemia in this case.
A 75-year-old female, born in Tochigi Prefecture, was admitted because of lumbago in August of 1991. The leukocyte count was 11,800/microliters with 22.5% atypical lymphocytes. We demonstrated a lymphocyte surface marker, ATL-associated antigen, and proviral DNA. We also identified 2.60 g/dl of serum monoclonal protein, found to be IgG, lambda type, and punched out lesions in the skull. We made a diagnosis of ATL. She was also a HBV carrier. The patient was treated with a modification of CHOP therapy, because of increasing atypical lymphocytes in the peripheral blood in November of 1992. She died of acute hepatitis, suddenly, in March of 1993. Autopsy revealed multiple myeloma, fulminant hepatitis and occult thyroid cancer in addition to ATL.
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Tectal glioma is rare and difficult to diagnose, and the tumor has been known as the tumor that gives no indication of the need for direct surgery because of its anatomical location. At present, MR imaging is available to detect the tumor and its location. We present two patients who underwent direct surgery. Case 1: A 18-year-old female was admitted with headache and nausea. MRI showed signs of stenosis of the aqueduct and a tumor of the tectal region. The tumor was removed partially. Histological examination of this tumor demonstrated a low grade astrocytoma. After surgery, hydrocephalus improved. Case 2: A 12-year-old boy was admitted with hydrocephalus detected by CT. MRI demonstrated a tumor of the midbrain without confirmation. He underwent a V-P shunt for hydrocephalus, and was discharged without any complaints. After 2 years, he was admitted again with shunt malfunction. After shunt revision, his consciousness recovered. However, Parinaud's sign appeared and patency of the shunt was unstable. MRI revealed a tumor of the tectal region and signs of stenosis of the aqueduct of Sylvius. The tumor was removed directly by the occipital transtentorial approach. The aqueduct was opened and a catheter was inserted from the 3rd to the 4th ventricle. Histological examination revealed a low grade astrocytoma. The patient followed a satisfactory postoperative course except for slight Parinaud's sign, and the V-P shunt was no longer necessary.