Biomedical subjects
Publications and source records attributed to K Yoshioka.
We report a case of systemic sclerosis (SSc) associated with mediastinal lymphadenopathy. A 77-year-old woman was admitted because of general fatigue. Mediastinal lymphadenopathy was diagnosed by chest computed tomography before the skin and lung involvements of SSc was discovered. The mediastinal lymphadenopathy declined with the development of lung fibrosis.
We report a case of acute renal failure occurring about 90 days after extracorporeal shock wave lithotripsy (ESWL) for a right renal stone. On left renal needle biopsy, immunofluorescence demonstrated linear fixation of IgG and C3 along the glomerular basement membrane (GBM). Serum circulating antitype IV collagen NC1 domain antibody was detected after ESWL, while it was not detected in the serum taken before ESWL. Based on these findings, the diagnose of anti-GBM antibody-mediated glomerulonephritis was made. Circulating antibodies against several GBM components (type IV collagen NC1 domain, laminin, fibronectin and heparan sulfate proteoglycan) was consistently negative in 9 randomly selected patients who underwent ESWL for renal stones. These findings suggest that the production of these autoantibodies associated with irradiation of shock waves to the kidney was not frequent, but, after ESWL, patients deserve close follow-up.
In order to clarify the insulin-release mechanism of beta 3-adrenoceptor agonist, we examined the effect of CL 316,243, a highly specific beta 3-adrenoceptor agonist having a relative potency of beta 1:beta 2:beta 3 = 0:1:100,000, on insulin secretion in perfused mouse pancreas. The application of 0.2 mM and 0.5 mM CL 316,243 produced significant insulin secretion from within 1 min, which lasted until 2 min after its withdrawal. DL-propranolol and ICI 118551 at 0.2 mM partially inhibited the insulin secretion induced by the 0.2 mM CL 316,243, but 0.2 mM metoprolol had no effect on the insulin release produced by 0.2 mM CL 316,243. We conclude that beta 3-adrenoceptor agonist stimulates insulin secretion via beta 3-action in the perfused mouse pancreas.
A 52-year-old woman was admitted to our hospital with a fever and swelling of the tonsils and lymph nodes. A tonsillectomy was performed and she was diagnosed as having non-Hodgkin's lymphoma of T-cell phenotype. Genotypic analysis revealed a rearrangement of the T-cell receptor gene, but not of the immunoglobulin genes. The neoplastic cells of the tonsils also expressed the Ki-1 antigen. The clinical course was aggressive with peripheralization of the neoplastic cells, and the patient died of respiratory failure.
Our previous studies showed that 54 kD and 48 kD tubular basement membrane (TBM) proteins were the major form of the target antigen involved in anti-TBM antibody-mediated tubulo-interstitial nephritis in humans. In those studies, we isolated the 54 kD glycoprotein (named gp54) from collagenase-digested bovine TBM. NH2-terminal amino acid sequencing indicated that gp54 represented a newly defined glycoprotein. In this study, we further characterized the target antigen, using mouse monoclonal antibodies to gp54 and polyclonal anti-gp54 peptide antibody. Two monoclonal antibodies (H79 and H80) were established, and they reacted, by immunofluorescence, predominantly with the proximal TBM of humans, rabbits, and Wistar, Sprague-Dawley, and Brown-Norway rats, but not with that of Lewis rats. They were also fixed by blotting intensely to the 54 kD component and weakly to the 48 kD component of collagenase-digested human TBM. In vivo transfer of H79 to Wistar rats showed extensive linear binding of mouse IgG to the TBM and the basal membrane of the small intestine; however, no pathologic changes were seen by light microscopy. The anti-gp54 peptide antibody reacted with both the 54 kD and 48 kD TBM components of human TBM. mRNA was prepared from rabbit kidneys, and fractionated to enrich mRNA encoding the 54 kD and 48 kD peptides. On in vitro translation experiments with the mRNA fraction, the 54 kD and 48 kD peptides were immunoprecipitated with anti-gp54 antibodies. These findings indicate that the 54 kD and 48 kD components are encoded with different mRNA, but that they share the same antigenic epitope.(ABSTRACT TRUNCATED AT 250 WORDS)
We have found previously that arotinolol, an alpha/beta-adrenergic blocker, increases blood flow in brown adipose tissue (BAT) in a similar extent as BRL 26830A, a beta 3-adrenoceptor agonist. We tested the hypothesis that arotinolol activates thermogenesis in BAT, leading to weight loss in monosodium-L-glutamate-induced (MSG-induced) obese mice and saline-treated controls. Six weeks of standard animal feed (CE-2) containing arotinolol hydrochloride (350 mg/kg CE-2), which reduced mean blood pressure in MSG-treated mice, significantly increased the mitochondrial protein content in BAT, and activated the specific and total binding of guanosine-5'-diphosphate (GDP) in BAT mitochondria, leading to a reduction of obesity in both MSG- and saline-treated mice vs. the control groups fed with CE-2 diet alone. However, six weeks of CE-2 diet containing propranolol hydrochloride (525 mg/kg CE-2) a non-selective beta-blocker, markedly reduced the specific and total binding of GDP in BAT mitochondria, leading to weight gain in both MSG- and saline-treated mice. These findings support the hypothesis, that arotinolol activates BAT thermogenesis, leading to weight loss.
The predictive factors in the efficacy of interferon therapy were analyzed on the patients with chronic hepatitis C by multivariate analysis, and HCV genotype and histological diagnosis were found useful for predicting the response to interferon therapy. Of the patients, 57% were found to be infected with HCV II, 27% were with HCV III, and 3% were with HCV IV. HCV I was not found in our patients. The complete response rate of the patients with HCV II (21%) was significantly lower than that of HCV III (63%). The concentration of HCV RNA was significantly larger in the patients with HCV II than in those with HCV III. When the patients with equal concentrations of HCV RNA were compared, the complete response rate was also significantly lower in the patients with HCV II than in those with HCV III. On histological diagnosis, the patients with mild disease were significantly more responsive than those with severe disease. The complete response rate of the patients with HCV II who have severe histological lesions (severe CAH) was 7%. On the other hand, the complete response rate of the patients with HCV III and a histological diagnosis of mild disease (CPH or mild CAH) was 80%. Our findings suggest that the outcome of interferon therapy can be predicted to some degree from the pretreatment data.
We conducted a double-blind test to examine whether or not the addition of mazindol, an appetite suppressor, to combined diet therapy [low-calorie diet + Optifast: 4600-3928kj(1100-940 kcal)/day] enhances the weight-reduction effect and reduces dropout from treatment in women with severe obesity. All of the patients were enrolled in the combined diet therapy and exercise [1255kj(300 kcal/day)] for 7 months. At the end of the first month, the patients were given, at random, three tablets of either 0.5 mg mazindol (18 women) or placebo (18 women) per day, in three doses for three months, in addition to the diet and exercise therapies. At 7 months, the key for the double-blind test was opened by the controller. Four of the 18 patients in the placebo group dropped out of the programme at 2 months after drug treatment, because they could not endure the intense hunger. Therefore, data for these 4 patients were excluded from evaluation. However, none of the patients treated with mazindol + combined diet therapy dropped out. The body weight and body-fat ratio showed marked reduction (p < 0.01 vs. premedication weight). The percent weight loss and percent reduction in body-fat ratio in the mazindol group was significantly (p < 0.01) greater than those found in the placebo group, which also showed a significant decrease in body weight and body-fat ratio (p < 0.01 vs. pre-medication weight) during the same period.(ABSTRACT TRUNCATED AT 250 WORDS)
We reported here a case of Langer-Giedion syndrome (tricho-rhino-phalangeal syndrome (TRPS) type II) associated with epilepsy. TRPS type II is an uncommon genetic disease characterized by sparse, slowly growing scalp hair, pear-shaped nose, multiple cartilagenous exostosis and mental retardation associated with delayed speech development. This patient displayed typical features of this syndrome. He also showed arachnoid cyst in the frontal area on computer tomography of the brain, and paroximal activities on EEG. Chromosomal analysis revealed a partial deletion of the long arm of chromosome 8. He had afebrile convulsion which is a rare complication of this syndrome.
We retrospectively evaluated renal outcome in a total of 38 children and adolescents with IgA nephropathy who were selected for 6-month therapy for clinical (proteinuria > 1 g/m2/24 hour) and pathologic (mesangial proliferation, crescent formation, and tubulo-interstitial changes) features suggestive of progressive renal failure. Seventeen patients (group A) were treated with a combination of prednisolone, cyclophosphamide and dipyridamole, and the remaining patients (21; group B) were treated with the same drugs plus warfarin. All the patients were followed-up for more than 2 years (range 2-10 years, mean 4.8). In both groups, the mean urinary protein excretion value was significantly reduced after the therapy, compared with that at entry into the therapy. The significant reduction continued for up to 6 years in group A and up to 5 years in group B. Creatinine clearance was stable until 5-6 years after the trial in both groups, but 4 patients progressed to end-stage renal failure after that period. Post-therapy biopsy was performed in 14 patients, and was compared with the pre-therapy biopsy. The activity score had improved in both groups, but the chronicity score did not. These results indicate that there was a temporary effect and limited benefit with this treatment of combined drugs for children and adolescents with IgA nephropathy. The additive effect of warfarin was not substantiated.
OBJECTIVE: To examine the efficacy of the addition of small doses of additional disease modifying antirheumatic drugs (DMARD) to ongoing DMARD treatment [additive DMARD therapy (ADT)]. METHODS: A 3-month prospective, double blind, randomized, placebo controlled study was performed using either 100 mg/day of bucillamine (Buc) or an inactive placebo (P1). Two groups of 12 patients each who had experienced an insufficient benefit from gold sodium thiomalate (GSTM) alone were enrolled in the study. RESULTS: The addition of Buc proved more beneficial than P1 regarding improvement in disease activity (p = 0.0032) and drug usefulness (p = 0.0025). A significant within group improvement was observed in joint swelling count, the Lansbury activity index, erythrocyte sedimentation rate and C-reactive protein. However, the difference in the clinical variables between the 2 groups was minimal. CONCLUSION: The usefulness of ADT was suggested by this trial; however, further confirmation by additional studies is still needed.
Although the evidence indicates that mutation of the gene for the alpha 5 chain of type IV collagen, alpha 5-(IV), is the primary defect in X-linked Alport syndrome, protein data for the alpha 5(IV) chain with regard to its normal distribution and its distribution in patients with Alport syndrome is lacking. We produced a rat monoclonal antibody (H51) by immunizing rats with a synthetic peptide corresponding to the nonconsensus amino acid sequence of alpha 5(IV) NC1 domain. H51 reacted by Western blotting with 26-kd cationic monomers and associated dimers of human type IV collagen NC1 domain. Immunohistochemical studies demonstrated that in normal human kidney alpha 5(IV) was present in the glomerular basement membrane and basement membranes of the Bowman's capsule and in some tubules (collecting ducts). The alpha 5(IV) chain was also detected in the basement membranes of normal skin, eye, and lung. Male patients with X-linked Alport syndrome revealed no reactivity of renal and epidermal basement membranes with H51, whereas alpha 5(IV) staining was normal in the glomerular basement membrane of patients with other types of glomerular diseases, including benign familial hematuria. The staining was also normal in the skin of nonaffected males in X-linked Alport families. Female heterozygous for Alport syndrome exhibited a discontinuous or mosaic pattern in the immunofluorescent staining of the epidermal basement membrane. These findings confirm that in patients with X-linked Alport syndrome there are abnormalities in alpha 5(IV) in renal and epidermal basement membranes at the protein level. Immunofluorescent staining of skin biopsies with this antibody may be of value in making a diagnosis of Alport syndrome, and, furthermore, may aid in detecting carrier females in whom urinary abnormalities are often mild or silent.
OBJECTIVES: Studies were undertaken to determine whether intrahepatic lymphocytes have a greater cellular immune response specific for hepatitis B virus (HBV) antigen than peripheral blood lymphocytes in HBV-infected man. METHODS: HB nucleocapsid antigen-stimulated interferon-gamma (IFN-gamma) production of lymphocytes was measured in acute self-limited hepatitis (AH) (eight cases) and chronic hepatitis (CH) (14 cases). RESULTS: In both patient groups, basal IFN-gamma levels without any stimulation were higher in the hepatic T cells than in the peripheral T cells. The values in cultures from blood and liver were larger in AH than in CH. Alternatively, IFN-gamma response to HBcAg and HBeAg was less in hepatic T cells than in the corresponding blood cultures; T cell response was HLA class II restricted. Cell flow cytometry study showed that in all patient groups, percentages of CD3+, CD8+, and HLA-DR+ cells were significantly greater in liver than in peripheral blood, whereas the proportion of hepatic CD4+ cells was decreased, compared with that in peripheral CD4+ cells. CONCLUSIONS: These findings suggest that liver infiltrates are already activated in vivo to produce IFN-gamma, particularly in patients with AH. The changes in the proportion of lymphocyte subsets may be responsible for the altered IFN-gamma response of hepatic T cells.
A seven-year-old boy with a 15p tetrasomy: [47, XY, + inv dup (15) (pter-->q13: :q13-->pter)] was reported. The clinical manifestation were as follows; infantile spasms, delayed development and slightly brownish coloured skin. But there were no other abnormal findings in neurological or physical examinations. This was the first case with 15p tetrasomy and infantile spasms.
The pharmacological profiles of tachykinin receptors mediating the release of acetylcholine were examined in the isolated spinal cord of the neonatal rat. The acetylcholine release evoked by neurokinin A or acetyl-[Arg6,Pro9]substance P-(6-11) was depressed by the tachykinin antagonists, spantide and GR71251 at 10 microM, whereas the release evoked by substance P (0.3 microM) or neurokinin B (0.3 microM) was not affected by these tachykinin antagonists. Polymerase chain reaction amplification of rat spinal cord cDNA and sequence analysis revealed the presence of a substantial amount of fragments having sequences identical to that of the NK1 or NK3 receptor, but only a few having a sequence identical to that of the NK2 receptor. These results suggest that in the neonatal rat spinal cord a novel subtype of tachykinin receptor similar but not identical to the classical NK1 receptor is involved in tachykinin-evoked acetylcholine release.
The chemical nature of urinary stone protein is poorly understood. We have sequenced a cDNA of urinary calcium oxalate stone protein extracted with EDTA. cDNA sequences showed complete identity between urinary stone protein and human osteopontin. Osteopontin protein was detected by staining with Stains-All, which specifically stains phosphoproteins, and by digestion with the highly specific protease thrombin, demonstrating that urinary calcium oxalate stones consist of osteopontin protein. We used a technique of in situ hybridization to detect osteopontin mRNA in the kidney. In control rats, distal tubular cells were sporadically positive, and proximal tubular cells and glomeruli were negative for osteopontin mRNA. A rat model of stone formation was induced with glyoxylic acid. In stone-forming rats, staining of distal tubular cells was remarkably increased, but proximal tubular cells and glomeruli were still negative. Immunostaining for the osteopontin protein also revealed that epithelial cells of distal tubules were weakly positive in control rats and significantly increased in stone-forming rats, although proximal tubular cells and glomeruli were negative. Northern blot analysis showed a significant increase of osteopontin mRNA in stone-forming rats in proportion to the dosage and the duration of the stone-inducing drugs. These results show that osteopontin in the kidney is presumably involved in urinary stone formation as the stone matrix.