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Biomedical subjects

R Hayashi

Publications and source records attributed to R Hayashi.

At least 55 records · Page 3Linked to original sources

Production of IL-10 and IL-12 in CD40 and interleukin 4-activated mononuclear cells from patients with Graves' disease.

We investigated the effect of T cell-dependent B cell activation on the production of IL-10 and IL-12 by peripheral blood mononuclear cells (PBMCs) obtained from patients with Graves' disease vs Hashimoto's thyroiditis, type 1 diabetes or normal controls. Incubation of PBMCs, from each of the subject groups, with a combination of anti-CD40 monoclonal antibodies and interleukin 4 (IL-4)-activated B cells, as shown by an increased level of soluble CD23. There was also a notable increase in the number of CD23(+)cells in PBMCs from patients with Graves' disease as compared to the other subject groups. This combination of B cell stimulants increased production of IL-10 in PBMCs obtained from patients with Graves' disease relative to those patients with Hashimoto's thyroiditis, type 1 diabetes, or the control subjects. The production of IL-12 showed wide variation that depended on the basal IL-12 level. In subjects with a low basal IL-12 level there was a positive correlation between the production of IL-12 and that of IL-10 from PBMCs stimulated with anti-CD40 antibodies plus IL-4. On the contrary, in the patients with a high basal IL-12 level, no change or a decrease of IL-12 production was observed after the stimulation. Thus, T cell-dependent B cell activation via a CD40 pathway triggers the overproduction of IL-10 and overcome the effect of IL-12 to shift the Th(1)/Th(2)balance to Th(2)dominance in patients with Graves' disease but not in Hashimoto's thyroiditis or type 1 diabetes.

Adult↗

Reduction of blood loss using tranexamic acid in total knee and hip arthroplasties.

There have been several attempts to reduce postoperative blood loss in patients undergoing total arthroplasty. Benoni et al. reported the usefulness of tranexamic acid in total knee arthroplasty (TKA). We investigated its effect in TKA and total hip arthroplasty (THA). Blood loss was significantly reduced in patients given tranexamic acid in both the TKA and THA groups, and no severe complications, such as venous or pulmonary thrombosis, were noted in any of the patients who received the agent. Administration of tranexamic acid seems to be useful for reducing postoperative blood loss in TKA and THA.

Antifibrinolytic Agents↗

Scavenging effect of nicorandil on free radicals and lipid peroxide in streptozotocin-induced diabetic rats.

Free radicals and lipid peroxide (LPO), easily formed in the diabetic state, play an important role in the development of diabetic complications. Potentially, nicorandil may reduce the production of free radicals and LPO in various organs. In fact, increased LPO levels in the serum, kidney, and cardiac muscle of diabetic (DM) rats were reduced by nicorandil treatment (N treatment). Xanthine oxidase (XOD), which produces free radicals, was decreased in the liver and increased in the kidney of DM rats compared with control rats, and these changes were prevented by N treatment. The concentration of Cu, Zn-superoxide dismutase (SOD) decreased in the cardiac muscle and increased in the kidney of DM rats, and these changes returned to normal after N treatment. The decreased concentration of Mn-SOD in the liver, kidney, and cardiac muscle from DM rats was also reversed by N treatment. The changes in catalase and glutathione peroxidase (GSH-PX) activities in DM rats were not improved effectively by N treatment. Another K-adenosine triphosphate (K-ATP) channel opener, tilisolol hydrochloride, had an effect similar to that of nicorandil. The effects of nicorandil and tilisolol were studied only in DM rats. These data imply that N treatment, as an antioxidative therapy, may be beneficial in preventing diabetic complications due to lipoperoxidation and free radicals in DM rats.

Animals↗

Bradykinin stimulates IL-6 and IL-8 production by human lung fibroblasts through ERK- and p38 MAPK-dependent mechanisms.

Bradykinin (BK) is a major kinin with well-documented pharmacological properties including vascular leakage and induction of a variety of cytokines. However, the intracellular signalling mechanisms by which BK induced proinflammatory cytokine production have not been fully elucidated. This study investigated the role of the extracellular signal-regulated protein kinase 1/2 (ERK 1/2) and p38 mitogen-activated protein kinase (p38 MAPK) in the BK-induced interleukin (IL)-6 and IL-8 production by human lung fibroblasts. Lung fibroblasts were stimulated with BK in the presence or in the absence of PD98059, a specific MAPK/ERK kinase-1 inhibitor, or SB203580, a specific p38 MAPK inhibitor, and IL-6 or IL-8 production and their gene expression was examined. BK-induced ERK 1/2 or p38 MAPK phosphorylation was also analysed by Western blot analysis. BK at nanomolar concentrations stimulated lung fibroblasts to produce IL-6 and IL-8 along with increased ERK 1/2 and p38 MAPK phosphorylation. BK-induced IL-6 and IL-8 synthesis was inhibited by a B2-type BK receptor antagonist. Furthermore, PD98059 or SB203580 significantly suppressed BK-induced IL-6 and IL-8 production and their gene expression. These results indicate that bradykinin-induced interleukin-6 and interleukin-8 production are at least partly mediated through the extracellular signal-related protein kinase 1/2 and p38 mitogen-activated protein kinase pathway-dependent activation in human lung fibroblasts, and suggest that bradykinin appears to be involved in the inflammatory reaction leading to acute lung injury through stimulating interleukin-6 and interleukin-8 production by lung fibroblasts.

Blotting, Northern↗

Radiographic evaluation of bioactive glass-ceramic grafts in postero-lateral lumbar fusion.

STUDY DESIGN: Follow-up study of bioactive glass-ceramic graft for postero-lateral fusion (PLF) in the lumbar spine was performed using plain radiography. OBJECTIVES: To investigate the fusion state of the porous stick type of bioactive glass-ceramic which has been used in PLF in the lumbar spine, by plain radiography, and to evaluate the usefulness of this technique. METHODS: Fourteen patients who underwent PLF using apatite and wollastonite-containing glass-ceramic (A-W. GC) were followed-up for more than 1 year and 6 months by plain radiography. RESULTS: Six patients who were followed up for more than 2 years were considered to have obtained subtotal or total fusion. CONCLUSION: PLF using A-W. GC mixed with autologous grafted bone can preserve bone stock without the need to harvest a bone graft from the iliac crest and will be useful for PLF in the lumbar spine.

Bone Transplantation↗

Ovarian yolk sac tumor with virilization during pregnancy: immunohistochemical demonstration of Leydig cells as functioning stroma.

A case is reported of yolk sac tumor occurring in the left ovary and complicated by pregnancy. The 22-year-old patient presented at 28 weeks gestation with virilization and elevated serum levels of testosterone and alpha-fetoprotein. The tumor showed the typical features of yolk sac tumor with a mixture of islands of Leydig cells. The accumulations of Leydig cells were well demarcated from the cellular components of the yolk sac tumor and were distributed throughout the tumor, although with predominant localization at the periphery. By immunohistochemistry the Leydig cells were intensely positive for vimentin and negative for cytokeratins, allowing clear distinction from the cell components of the yolk sac tumor, which were positive for cytokeratins and negative for vimentin. Testosterone was also identified in the cytoplasm of the Leydig cells. After tumor resection the testosterone and alpha-fetoprotein levels declined simultaneously; this, together with the immunohistochemical demonstration of testosterone, indicates that the Leydig cells were responsible for the endocrine manifestations. Furthermore, antibodies against inhibin alpha-subunit and calretinin could be used to detect the Leydig cells. The present case, a combination of yolk sac tumor and Leydig cells acting as a functioning stroma and causing virilization during pregnancy, is very rare.

Adult↗

Effect of mutagenic replacement of the carboxyl terminal amino acid, val124, on the properties and regeneration of bovine pancreatic ribonuclease A.

An important role of C-terminal amino acid residues of bovine pancreatic ribonuclease A (RNase A) in the formation of the three-dimensional structure was previously implied. In this study, we replaced the C-terminal amino acid, Val124, with amino acid residues with different properties by site-directed mutagenesis. The recombinant mutant enzymes were purified and subjected to a refolding study after being converted to a fully reduced and denatured state. There was a significant difference among the mutant enzymes in the rate of recovery of the activity when air oxidation was performed: the rate decreased in the order of V124E, V124L, V124G, V124K, V124A, and V124W. On the other hand, the recovery rates for all the mutant RNase A in the presence of GSH and GSSG were almost the same. The recovered activity of V124E after 24 h incubation reached approximately 90% of that of the wild type enzyme, followed by V124L 80%, V124A and V124W 65%, and V124K and V124G 50%. The duration of the initial lag phase became shorter in the order of V124W, V124A, V124K or V124G, V124E, or V124L. The results imply that the C-terminal amino acid significantly influences the formation of correct disulfide bonds during the refolding process and that the hydrophobic interaction of Val124 is important for efficient packing of the RNase A molecule.

Animals↗

Postoperative complications and functional results after total glossectomy with microvascular reconstruction.

Microsurgical reconstruction after total glossectomy can greatly improve quality of life; however, postoperative functional results are often unstable, and the effectiveness of total glossectomy remains questionable. To determine the problems of reconstruction after total glossectomy with laryngeal preservation and to examine the functional results of swallowing and speech, 30 patients who had undergone total glossectomy and reconstruction with free flaps were reviewed for this study. The patients ranged in age from 20 to 73 years, and 23 of the 30 had undergone reconstruction with a rectus abdominis musculocutaneous flap. Wider and thicker flaps were designed and transferred and were sutured to suspend the larynx. To maintain physiologic swallowing function after surgery, the extent of laryngeal suspension and cricopharyngeal myotomy was limited. Of the 30 patients, 21 (70 percent) could be decannulated with laryngeal preservation; 20 of these 21 could tolerate a normal/soft/pureed diet, and 1 was limited to a fluid diet. Speech was intelligible in 16 of the 19 patients evaluated. In 9 of the 30 patients, laryngeal function could not be preserved. In four of these nine patients, additional resection combined with total glossectomy caused severe aspiration and recurrent pneumonia. Two patients with preoperative cerebral dysfunction were also poor candidates for laryngeal preservation. Additionally, the transferred flap's lack of bulk in the oral cavity and the advanced age (73 years) of one patient and the poor motivation of another may have contributed to postoperative aspiration. Aspiration occurred in one patient because of local recurrence of a tumor. The presence of preoperative cerebral dysfunction (p = 0.025), resection of the epiglottis (p = 0.005), and postoperative orocutaneous fistulas (p = 0.04) were significantly associated with the failure of laryngeal preservation. However, because of the difficulty of enrolling a sufficient number of patients in the study and the inherent limitations of retrospective studies, multivariate analysis in this study showed that no factors, such as patient age, flap volume, and the type of neck dissection, were significant predictors of laryngeal preservation. Although prospective studies are necessary, the function of individual patients must be assessed so that the study experiences discussed here can be applied to subsequent patients.

Adult↗

High incidence of posttransplant lymphoproliferative disease in pediatric patients with cystic fibrosis.

A major cause of morbidity and mortality following lung transplantation is posttransplant lymphoproliferative disease (PTLD). In a retrospective cohort analysis of pediatric patients, we evaluated the risk factors associated with PTLD in 128 first-time lung transplant recipients from 1990 to 1997. The greatest risk factor for PTLD was a diagnosis of cystic fibrosis (CF). Of the 16 patients in our analysis who had PTLD, 13 had a diagnosis of CF (odds ratio [OR]: 5.8; confidence interval 95% [CI]: 1.6 to 21.4). Because of the high frequency of PTLD in patients with CF (13 of 61; 23%), we performed a retrospective cohort analysis in which patients with CF and PTLD were designated as cases and patients with CF and without PTLD served as controls. In patients with CF, the only risk factor associated with PTLD was two or more episodes of acute rejection within 3 mo after transplantation (OR: 11.0; 95% CI: 2.7 to 55.7). Age, recipient Epstein-Barr virus or cytomegalovirus status, induction with antilymphocyte globulin or antithymocyte globulin (ATG), or use of ATG or OKT3 for acute rejection episodes were not risk factors for PTLD. The high frequency of PTLD in the subgroup of patients with two or more episodes of graft rejection within 2 mo after lung transplantation was unexpected, and warrants further investigation in prospective clinical studies and basic laboratories.

Adolescent↗

Optically active antifungal azoles. X. Synthesis and antifungal activity of N.

New optically active antifungal azoles, N-14-(azolyl)phenyl]- and N-14-(azolylmethyl)phenyl]-N'-[(IR,2R)-2(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(IH-1,2,4-triazol-1-yl)propyllazolones (1, 2, 3), were prepared in a stereocontrolled manner. Compounds 1-3 showed strong antifungal activity against Candida albicans in vitro. Among them, the imidazolidinones 3 showed a broad antifungal spectrum in vitro as well as potent in vivo activity against candidiasis and aspergillosis in mice. The imidazolidinones (3i, j, k) having 1H-1,2,3-triazol-1-yl, 2H-2-tetrazolyl and IH-1-tetrazolyl moieties were found to exert strong protective effect against aspergillosis.

Antifungal Agents↗

Expression of soluble bovine pancreatic ribonuclease A in Pichia pastoris and its purification and characterization.

A Pichia pastoris expression system for bovine pancreatic RNase A was constructed: the RNase A sequence was fused to the PHO1 signal and the AOX1 promoter was used for efficient secretion. Approximately 5 mg of soluble enzymes were secreted per liter of the culture, but one half of them were glycosylated. After a series of purifications by cation-exchange chromatography, the glycosylated enzyme was removed and the pure recombinant soluble unglycosylated RNase A was obtained in the final yield of 1 mg per liter of the culture. N-Terminal sequence, molecular weight, secondary structure, thermal stability, and activity were completely identical with those of commercial RNase A. Glycosylated RNase A had a decreased kcat, 60-70% of the activity of wildtype RNase A, as in the case of RNase B. Its carbohydrate moiety seemed to destabilize the enzyme differently from RNase B since Tm of the glycosylated RNase A was decreased by 6 degrees C. The carbohydrate moiety of the glycosylated enzyme contained no GlcNAc. The N34A mutant RNase A, in which the only potential N-glycosylation site, Asn34, is mutated to alanine, was also glycosylated, implying that glycosylation is not N-linked but O-linked.

Animals↗

Lipid peroxidation levels in rat cardiac muscle are affected by age and thyroid status.

Free radicals, hydroxyperoxides and H(2)O(2) are all known to damage cell components. This study was designed to compare the concentrations of hydroxyperoxide and free radical scavengers in the cardiac muscles of old rats in the hyper- or hypothyroid condition, to determine whether rates of peroxidation would differ with age, thyroid status, or both. Rats were rendered hyper- or hypothyroid by administration of l-thyroxine or methimazole for 4 weeks. Among the old rats, the lipid peroxide (LPO) concentrations, measured as thiobarbituric acid (TBA) reactants, were significantly greater in the hyperthyroid than in the euthyroid state and the LPO concentrations measured as TBA+Fe(3+) reactants, which may be precursors of LPO, were significantly greater in the hyperthyroid state, whereas in young rats, the LPO concentrations measured by TBA or TBA+Fe(3+) methods did not differ significantly in the hyperthyroid state. In the euthyroid state, the concentration of LPO measured as TBA+Fe(3+) reactants was significantly reduced with age. Xanthine oxidase (XOD) activity also was markedly increased with age, being more pronounced in the hyperthyroid than in the euthyroid state. The Mn and Cu/Zn superoxide dismutase activities were greater in the hyperthyroid than in the euthyroid state. Glutathione peroxidase activity decreased with age in the euthyroid and, particularly, in the hyperthyroid state. Catalase activity was not affected in the old rats. Concentrations of alpha-tocopherol in the old rats were high in the hyperthyroid state and low in the hypothyroid state, whereas the levels of beta- and gamma-tocopherols in these rats were unchanged in both conditions as compared with the euthyroid state findings. Data suggest that the site of free radical generation differs in older rats, with additional shifts in the location of intracellular lipid peroxidation being noted during hyperthyroidism. Thus, as rats age, the reduction of the free radical scavenger system and the increase in LPO and XOD activities might induce myocardial dysfunction.

Aging↗

Effect of exercise on blood pressure in pregnant women with a high risk of gestational hypertensive disorders.

OBJECTIVE: To prospectively determine whether moderate exercise during pregnancy lowers blood pressure. STUDY DESIGN: A randomized, controlled trial with one test group and one control group. All subjects have a history of mild hypertension, gestational hypertensive disorders or a family history of hypertensive disorders. Subjects were recruited before 14 weeks' gestation. After four weeks of observation, the subjects were randomly assigned to either the exercise or control group. The exercise group visited the laboratory three times a week for 10 weeks (18-28 gestation weeks) to perform 30 minutes of exercise at Rating of Perceived Exertion level 13. RESULTS: A total of 16 pregnant women (mean age, 30 years) participated. The mean metabolic equivalent during exercise sessions was 4.7 (SD = 0.8). Blood pressure measurements were compared before and after the 10-week exercise period in the two groups. Systolic blood pressures did not change significantly, but diastolic blood pressure (DBP) in the exercise group decreased by 3.5 mm Hg, while that in the control group increased by 1.1 mm Hg. Thus, the pre-post change in DBP differed by 4.6 mm Hg between groups. Exercise treatment reduced the diastolic blood pressure to a near-significant level in the exercise group (t = 2.34, df = 7, P = .052). Percent body fat did not differ between the exercise and control groups either before or after exercise treatment. ANOVA revealed that pregnancy had a significant effect (F(1, 14) = 5.7, P = .03) on increasing the percentage of fat, but exercise treatment did not (F(1, 14) = .18, P = .68). Estimated energy expenditure in overall daily physical activities during the intervention did not differ between the two groups despite the inclusion of exercise. CONCLUSION: This study detected a strong trend that 10 weeks of moderate exercise lowered the diastolic blood pressure among pregnant women at risk of hypertensive disorders. The reductions were probably due to the effect of exercise itself, not to weight or overall daily physical activity levels.

Adult↗

[Rheumatoid arthritis-associated bronchiolitis successfully treated with erythromycin].

A 52-year-old man with a 4-year history of rheumatoid arthritis, and who had an episode of suspected BOOP in early 1994, was admitted to our hospital because of cough and fever. A chest X-ray film on admission showed small patchy infiltrates, and a computed tomographic (CT) scan showed centrilobular nodules and patchy infiltrates with thickened broncho-vascular bundles in both lungs. Transbronchial and thoracoscopic lung biopsies disclosed the coexistence of interstitial pneumonia with BOOP pattern, follicular bronchiolitis, and diffuse panbronchiolitis-like purulent and obliterative bronchiolitis. Due to findings of chronic sinusitis, the patient was treated with erythromycin for 8 weeks, and the abnormal CT shadows regressed. This was an interesting case of various pulmonary lesions associated with rheumatoid arthritis, and successfully treated with erythromycin.

Anti-Bacterial Agents↗

Potential role of microvessel density in predicting radiosensitivity of T1 and T2 stage laryngeal squamous cell carcinoma treated with radiotherapy.

Curative radiotherapy is the first choice of therapy for T1 and T2 stage laryngeal squamous cell carcinoma (LSCC) patients to preserve their phonation. Patients with recurrent tumors who undergo salvage surgery require prolonged nasal feeding. Therefore, clinical interest has been focused on elucidating a predictive factor indicating which tumors are likely to be radiosensitive before radiotherapy. We analyzed the relations between radiosensitivity and clinicopathological factors (gender, tumor location, histological factors, and clinical tumor-node-metastasis stage), expression of apoptosis-related proteins (p53, bax, bcl-2), apoptotic index using the terminal deoxynucleotidyltransferase-mediated nick end labeling method, expression of cell proliferation-related proteins (Ki-67-labeling index and epidermal growth factor receptor overexpression) and microvessel density (MVD, vessels/field = 0.391 mm2) in biopsy specimens from 31 LSCC patients given radiotherapy (total radiotherapy dose of 52-70 Gy over 4-6.5 weeks). Univariate analysis revealed that tumors with a high MVD (> or =35 vessels/field) showed better radiosensitivity than those with a low MVD (<35 vessels/field, P = 0.008) and that a high Ki-67-labeling index (> or =40%) was weakly associated with radiosensitivity (P = 0.056). Multivariate analysis and Kaplan-Meier analysis showed that MVD alone had significant predictive power for radiosensitivity in T1 and T2 stage LSCCs after radiotherapy (P = 0.012, 0.0003, respectively). No significant association between clinicopathological factors, or of overexpression of p53, bax, bcl-2, epidermal growth factor receptor, or apoptotic index, with radiosensitivity was found. These results indicate that MVD is a potentially useful clinical factor predicting radiosensitivity for patients with early stage LSCCs before treatment.

Aged↗

[Acute eosinophilic pneumonia induced by cigarette smoking: positive lymphocyte stimulation test of a cigarette extract].

A 21-year-old man was admitted to our hospital with high fever, general fatigue and dyspnea. Chest radiography on admission showed diffuse bilateral infiltrate shadows with Kerley's B lines, and a CT scan showed patches of infiltrates with thickened interlobular septa in both lungs. Examination of the bronchoalveolar lavage fluid and the clinical course led to a diagnosis of acute eosinophilic pneumonia. The patient improved without steroid therapy. We suspected that the disease was related to smoking because the patient had started smoking seven days before the onset of the symptoms. Because a lymphocyte stimulation test gave a positive reaction to a cigarette extract, a challenge test was done. After this, the patient had fever and hypoxemia. These findings suggest that cigarette smoking induces acute eosinophilic pneumonia.

Acute Disease↗

[A case of primary Sjögren's syndrome with interstitial pneumonia showing bronchiolitis obliterans organizing pneumonia pattern and lymphofollicular formation].

A 46-year-old woman with a 2-year history of xerostomia, who had had an episode of suspected Sjögren's syndrome in 1995, was admitted to our hospital because of a dry cough. Chest radiography on admission showed ground-glass infiltrates and reticular shadows in both lower lung fields. Primary Sjögren's syndrome was diagnosed by lip biopsy. Video-assisted thoracoscopic lung biopsies revealed the co-existence of interstitial pneumonia with the BOOP pattern and follicular bronchiolitis. Treatment with oral prednisolone improved the symptoms, and reduced the abnormal chest shadows. This was an interesting case of the BOOP pattern in a lung lesion associated with primary Sjögren's syndrome.

Administration, Oral↗