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Biomedical subjects

N Yoshimura

Publications and source records attributed to N Yoshimura.

At least 451 records · Page 25Linked to original sources

Heterogeneous response in calcium signaling by adrenergic and cholinergic stimulation in cultured bovine trabecular cells.

Adrenergic and cholinergic drug-dependent Ca(2+)-signaling in cultured bovine trabecular cells was studied using a fluorescent calcium dye, fura-2, and digital video-imaging system. The resting calcium concentration in the cultured cell was 178.7 +/- 1.8 nM. Upon stimulation with norepinephrine, isoproterenol and carbachol trabecular cells responded heterogeneously. Many types of reaction to the stimuli were found; about 25% of the cells responded to the stimuli and about 30% showed no response to all of the stimuli. Carbachol induced response was blocked with pretreatment of atropine, and timolol inhibited the isoproterenol-induced response. Ca2+ signaling in trabecular cells may mediate the action of adrenergic and cholinergic drugs and possibly play significant roles in the regulation of intraocular pressure.

Adrenergic beta-Agonists↗

Influence of the ultrasonic surgical aspirator on the dura and spinal cord. An electrohistologic study.

The influence of the ultrasonic surgical aspirator on the dura and underlying spinal cord was examined. Spinal-cord-evoked potential was simultaneously recorded. In a test of identical time, the degree of influence on the dura, the pia mater, and the spinal cord increased according to the increase of energy of the ultrasonic surgical aspirator. With 60% energy at 20 seconds and 80% energy at both 10 and 20 seconds, spinal-cord-evoked potential showed wave changes. In light of these results, it is suggested that in using the ultrasonic surgical aspirator on the dura, the electrohistologic safety limit be set at 60% energy and the maximum time duration at one point less than 10 seconds.

Aged↗

Sequential determinations of serum interleukin 6 levels as an immunodiagnostic tool to differentiate rejection from nephrotoxicity in renal allograft recipients.

Serum interleukin 6 (IL-6) levels were utilized as an immunologic marker of activation of T cells and macrophages in renal allograft recipients treated with a cyclosporine and prednisone immunosuppressive regimen. IL-6 concentrations were estimated in serum samples selected to correspond to similar timepoints in the clinical courses of renal transplant recipients suffering four types of events: group I, quiescent patients without rejection or infectious disease (n = 16, 147 samples); group II, patients with only rejection episodes (n = 26, 291 samples); group III, patients with only infectious episodes (n = 10, 87 samples); and group IV, patients with CsA-induced nephrotoxicity (n = 15, 117 samples). Serum IL-6 activity measured using an IL-6-dependent cell line (MH60.BSF-2) was specific for this lymphokine based upon the capacity of monoclonal anti-IL-6 antibodies to block target cell proliferation. The control group displayed uniformly elevated IL-6 levels during the first posttransplant day (mean 20.1 +/- 4.1 U/ml range 6.4-64 U/ml), thereafter decreasing by 10-14 days to a mean level of 3.4 +/- 0.9 U/ml (range 1.0-4.2 U/ml). The rejection group showed increased IL-6 levels ranging from 5.3 +/- 0.4 U/ml (range 1.0-64 U/ml) to 56.2 +/- 13.3 U/ml (range 10-300 U/ml, P less than 0.01), occurring at a mean of 2 days (range 0-10 days) before the diagnosis of rejection was established by clinical criteria. Interestingly, all three recipients treated with OKT3 and 5/11 treated with antilymphocyte globulin displayed further significant increases in serum IL-6 levels (OKT3: 46.0 +/- 12.9 U/ml; ALG: 34.6 +/- 7.8 U/ml) one day after inception of treatment. Five of 10 recipients displaying septic events showed elevated serum IL-6 activity--namely, 5.0 +/- 1.2 U/ml to 47.5 +/- 16.2 U/ml, beginning at a mean of 1.2 days before diagnosis. Contrariwise, recipients afflicted with CsA-induced nephrotoxicity displayed reduced IL-6 levels (mean = 1.4 +/- 0.18 U/ml). The ratio (IL-6 activity/CsA trough level) proved to be even more useful than the serum IL-6 level itself to discriminate acute rejection from nephrotoxicity--namely, 0.53 versus 0.006, respectively (P less than 0.01).

Antibodies, Monoclonal↗

The immunosuppressive antagonism of low doses of FK506 and cyclosporine.

Clinical immunosuppression with potentially toxic agents may be optimized by combining drugs that act synergistically at low doses. The studies presented herein attempted to apply this strategy to the macrolide FK506 and the endecapeptide cyclosporine, which similarly inhibit T cell responses but display distinctive arrays of toxic side effects. The interaction between these agents was subjected to rigorous pharmacologic analysis using the median effect and combination index equations to determine synergistic, antagonistic, or additive drug interactions. FK506 and CsA showed pharmacologic antagonism in inhibiting in vitro proliferation upon phytohemagglutinin, anti-CD3 antibody, and mixed lymphocyte reaction (MLR) stimulation, and interleukin 2 generation by activated normal human peripheral blood lymphocytes. The antagonistic relationship was confirmed in vivo using low doses of FK506 in combination with CsA to treat Wistar-Furth recipients of heterotopic Buffalo rat cardiac allografts, a major plus minor histocompatibility barrier. This antagonistic relation suggests that FK506/CsA combination therapy does not permit dose reduction of the individual drugs to mitigate toxic complications.

Animals↗

Prolongation of renal allograft survival in the rat treated with amniotic fluid.

To assess the role of amniotic fluid (AMF) in the maintenance of pregnancy, immunosuppressive effects of AMF were studied in vivo, and the mechanisms of suppressor activity were analyzed immunologically in vitro in the rat. Female Lewis (LEW, RT-1l) rats mated with Brown-Norway (BN, RT-1n) rats for 14 days were sacrificed and cell-free AMF was obtained. AMF was diafiltered with PBS (PH 7.2) and reconstituted to 2 OD units measured at 280 nm. Untreated LEW hosts rejected BN renal grafts at 7.8 +/- 0.2 days (n = 10). Five days of intravenous inoculation of AMF into LEW hosts remarkably enhanced BN graft survivals (MST = 20.3 +/- 4.4 days, n = 12) compared with controls (P less than 0.01), and slightly prolonged third-party DA (RT-1a) graft survivals (MST = 9.4 +/- 0.8 days, n = 7) compared with control LEW hosts engrafted with a DA kidney (MST = 7.6 +/- 0.2 days, n = 6). Five days of intravenous inoculation of pregnant sera into LEW hosts had no effect on BN graft survival. The AMF suppressed the proliferative response of LEW lymphocytes against not only irradiated BN stimulator cells but also irradiated third-party DA stimulators. The AMF also suppressed allokiller T cell generation of normal LEW lymphocytes against BN cells by 70.1% and 51.3%, and against DA cells by 64.9% and 38.9% at concentrations of 25% and 12.5%, respectively (P less than 0.01). To dissect the immunosuppressive activity of AMF, the effect of AMF on cytokine production and interleukin 2 (IL-2) receptor expression of concanavalin A-stimulated lymphocytes were investigated. AMF suppressed interferon and IL-2 production. Interestingly, however, AMF did not suppress interleukin 3 (IL-3) and interleukin 6 (IL-6) production, as well as IL-2 receptor expression. These results demonstrated that rat AMF displayed a strong immunosuppression in vivo as well as in vitro, and that AMF might play an important role in the maintenance of pregnancy.

Amniotic Fluid↗

Interleukin-2 receptor gene expression in kidney transplant recipients treated with cyclosporin A.

We examined the effects of cyclosporin A (CsA) administered in vivo on the capacity of peripheral blood mononuclear cells (PBMC) from kidney transplant recipients to express IL-2 receptor (IL-2R) gene at the level of mRNA after mitogen stimulation in vitro. There were no differences in the percentage of IL-2R+ cells among the groups of normal individuals, azathioprine-prednisolone treated, and CsA-prednisolone-treated recipients, using FITC-labelled monoclonal anti-IL-2R antibody (anti-alpha chain): 40.3 +/- 10.1% and 62.8 +/- 11.1% of normal PBMC (n = 18), 37.0 +/- 9.3% and 61.7 +/- 5.8% of PBMC from azathioprine-prednisolone-treated recipients (n = 20), and 37.7 +/- 9.6% and 60.7 +/- 12.7% of PBMC from CsA-prednisolone-treated recipients (n = 20) expressed IL-2R after 24 h and 48 h of phytohaemagglutinin stimulation, respectively. However, in a study of Northern blotting using cDNA for IL-2R (anti-alpha chain specific), both the 3500 and 1400 bp families of IL-2R mRNA were remarkably decreased in PBMC from CsA-prednisolone-treated recipients compared with azathioprine-prednisolone-treated recipients and normal individuals. These studies demonstrated that CsA could inhibit IL-2R gene expression at the level of mRNA at physiological concentration.

Adult↗

[An adult case of virus-associated hemophagocytic syndrome (VHAS) and a review of this syndrome in adults in Japan].

An adult case of Virus-associated hemophagocytic syndrome (VAHS) was reported and a review of this syndrome in adults in Japan was also made. A 79 year-old woman was referred to our hospital for detailed examination for sustained generalized fatigue lasting for about two weeks. Other clinical manifestations of this patient included fever, generalized lymphadenopathy, hepatosplenomegaly, anemia and mild liver dysfunction. The biopsy of the lymph node revealed hyperplasia of histiocyte with hemophagocytosis. There was also an elevation of IgG antibody against EB virus and the patient was therefore diagnosed to have VAHS. The prednisolone therapy was then initiated and the patient responded to this treatment very well. By the review of the Japanese literatures, seven adult cases of VAHS were found. Based on the descriptions on these cases, the prognosis of this syndrome appeared to be extremely poor which is totally different from VAHS in children. Our case showed a very favourable clinical course following steroid therapy and this suggested that steroid therapy should be considered even at the early stage of this syndrome in adults.

Aged↗

[Diffuse panbronchiolitis in two brothers with different clinical courses].

Diffuse panbronchiolitis in two brothers is reported. The elder brother aged 46, was admitted in May 1983 due to severe dyspnea and productive cough, which had gradually worsened over several years. He had severe hypoxemia and hypercapnia. He died at age 47 of respiratory failure due to pseudomonas infection despite antibiotic therapy. The younger brother, at age 41, was admitted in March 1983 due to fever, productive cough, and abnormal shadows on chest X-ray films. He showed mild hypoxemia and his symptoms improved with antibiotic treatment. Since then he has been followed as an outpatient for over 7 years while taking 400 mg of Erythromycin per day, and he has had no exacerbation. These two cases had different clinical courses despite the facts that both had similar conditions of chronic sinusitis and appeared to be exposed to no special environmental or occupational hazards. These facts suggest that not only intrinsic factors, such as defenselessness of airways, but extrinsic factors such as viral, mycoplasmal, or bacterial infection may act together on the mechanisms of the onset and progression of diffuse panbronchiolitis.

Adult↗

[Intrascrotal and seminal vesicular granuloma probably induced by propionibacterium acnes].

A case of right intrascrotal and seminal vesicular granuloma probably induced by Propionibacterium acnes is reported. A 62-year-old man was admitted to our department because of low grade fever and the right intrascrotal and retrovesical masses without tenderness. Ultrasonography computed tomography, magnetic resonance imaging and vesiculography suggested a neoplasm. However, leukocytosis and high erythrocyte sedimentation rate (ESR) and c-reactive protein level (CRP) suggested inflammatory disease. He was treated for 1 week with parenteral cefazolin (CEZ) (4 g/day), and the intrascrotal mass was remarkably reduced in size. To rule out neoplasms, right orchiectomy and needle biopsy of the right seminal vesicle were performed and nonspecific chronic granuloma was identified histologically. On the 5th postoperative day he developed fever (39.2 degrees C) and P. acnes was isolated from blood culture. Gram stain revealed gram-positive rods in the specimen. Further chemotherapy normalized levels of ESR and CRP and white blood cell count and reduced the right seminal vesicle to its normal size. Recently several cases of infection induced by P. acnes have been reported, but this is the first report in the genitourinary tract.

Genital Diseases, Male↗

[Histochemical and biochemical investigations of monoamine oxidase activity level in the brain of the brindled mouse].

In order to make clear the degree of brainstem affection in Menkes disease, it is important to investigate morphological and enzymatic changes of monoamine oxidase (MAO)-containing neurons in the brain in this disease. For this purpose, MAO activity levels in brain tissue from normal and brindled mice were examined histochemically and biochemically. A coupled peroxidatic oxidation method for the histochemistry and a rapid microfluorimetric method for the biochemical assay were adopted. Animals aged 3 days, 8 days, 13 days, 3 months and 12 months were used for the histochemical study. Three-, 7-, and 12-day-old mice were used for the biochemical study. Histochemical examinations showed no significant differences in the stainability, morphology and distribution of MAO positive neurons in the brain between normal and brindled mice at the same age. Biochemical assays revealed that MAO activity levels in the brain of the postnatal brindled mice rose with age as highly as those in the normal control mice. There were no significant differences in them between normal and brindled mice at the same age. The results indicate that in Menkes disease in mice the brainstem affection, if there is, is not so severe as to influence the morphology and enzyme activity of MAO-containing neurons.

Animals↗

[The effects of perioperative administration of donor lymphocytes via portal vein in rat skin transplant model].

The effects of perioperative portal venous (P.V.) administration of donor lymphocytes on skin allograft survival were investigated in rat skin transplant model. Heterotopic skin transplantations were performed form Brown-Norway (BN, RT-1n) to Lewis (LEW, RT-1(1] male rats. P.V. administration of donor BN lymphocytes (1 x 10(8] resulted in significant prolongation of BN skin graft survival (MST = 13.4 +/- 3.9 days, p less than 0.05) compared with I.V. administration of same number of donor lymphocytes (8.6 +/- 1.2 days) or with PV administration of third party DA (RT-1a) rat's lymphocytes (7.4 +/- 0.8 days) or with untreated controls (9.0 +/- 1.4 days). These results suggested that this effect was antigen specific. P.V. administration of donor lymphocytes prevented recipient which received BN skin graft form developing delayed-type hypersensitivity responses to donor antigen. Serum from LEW recipients which induced unresponsiveness by PV administration with donor BN lymphocytes had significant antigen specific suppressor effect (77.0 +/- 5%) on the MLR proliferative reaction of LEW responder cells toward donor BN cells, but not third party DA stimulation. Moreover, this immunological unresponsiveness was transferable by the serum in kidney transplant model. These results indicate that PV administration of donor lymphocytes induces recipient's unresponsiveness to donor alloantigen in rat skin transplant model, and this effect is transferable by the suppressor factor in the serum.

Animals↗

[The effect of trabeculotomy on the day-time variation of intraocular pressure of the primary open-angle glaucoma].

We selected 34 eyes with primary open-angle glaucoma cases having glaucomatous visual field loss, but with relatively low base-line intraocular pressure (average intraocular pressure at normal office hour, below 20mmHg) and with one or more episodes of intraocular pressure over 21mmHg in a diurnal fluctuation estimated at 8:30, 9:30, 11:30, 13:30, 15:00 and 17:00. They were treated with trabeculotomy ab externo and we compared the pre- and postoperative diurnal fluctuation pattern of the intraocular pressure. The mean of the base-line intraocular pressure decreased from 18.4 to 16.3mmHg. The mean values of the maximal pressure of the diurnal estimation and of the diurnal difference (maximum minus minimum) also decreased, from 23.4 to 17.9 and from 7.4 to 3.9mmHg, respectively. In 31 eyes (91%) the individual maximal value did not exceed 20mmHg postoperatively. From these findings, it was speculated that trabeculotomy can be effective on primary open-angle glaucoma with relatively low intraocular pressure.

Circadian Rhythm↗

[Management of voiding dysfunction in geriatric general hospital: clinical experience of 315 cases with indwelling urethral catheter or diapers].

In a geriatric general hospital, 157 patients with an indwelt urethral catheter and 158 patients using diapers were evaluated by detailed interview, urinalysis, measurement of residual urine, and cystometry during a period of 16 months from July, 1988, when the Department of Urology was established. As a result of therapeutic modalities, 94% of the patients were freed from the catheter or diapers. The indwelling catheter was found to be unnecessary in one-third of the patients. In addition, among the patients wearing diapers, one-third were capable of urinating only with the appropriate assistance of paramedical staff. It took less than 1 month for half but more than 1 year for 10% of the patients to be freed from the catheter or diapers. On the contrary, 19 patients could not be freed from the catheter or diapers, not due to bladder dysfunction but rather to mental, physical and social disabilities. These findings indicate that accurate diagnosis and management in collaboration with paramedical staff are required to solve urinating problems in the elderly.

Aged↗

Growth factor-induced cytosolic calcium ion transients in cultured human retinal pigment epithelial cells.

Growth factor-induced changes of cytosolic free calcium ion concentration ([Ca2+]i) and phosphatidylinositol (PI) turnover in cultured human retinal pigment epithelial (RPE) cells were studied, and their temporal relationship was compared. After a 24-hr serum depletion, RPE cells were loaded with fura-2/AM, and [Ca2+]i was analyzed using a digital imaging microscopy system. The resting [Ca2+]i in a single cultured human RPE cell was 153 +/- 1.5 nM (mean +/- the standard error of the mean [SEM], n = 105). The percentage of reactive cells that had Ca2+ transients induced by various growth factors were: epidermal growth factor, 18%; basic fibroblast growth factor (bFGF), 5%; nerve growth factor, 15%; platelet-derived growth factor (PDGF), 70%; insulin-like growth factor, 0%; fibronectin, 0%; insulin, 3%; and fetal bovine serum (FBS), 100%. The PDGF showed a peak concentration of 237 +/- 4.7 nM (mean +/- SEM, n = 67) and FBS, 774 +/- 34.5 nM (mean +/- SEM, n = 52). Chelation of the extracellular Ca2+ by EGTA made the resting and peak concentration lower. The Ca2+ transients occurred within 60 sec and lasted less than 5 min after the application of the growth factors. However, measurements of phosphoinositides in 24-hr serum-starved RPE cells revealed that growth factor-induced PI turnover was much slower than Ca2+ transients. In addition, FBS, bFGF, and PDGF increased the contents of inositol phosphate, inositol biphosphate, and inositol triphosphate (IP3) in RPE cells slowly up to 60 min except that PDGF showed a peak of IP3 at 15 min after stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

[Evaluation of urinary incontinence among the nursing home elderly].

We assessed the prevalence of urinary incontinence and contributory factors such as senile dementia, impaired mobility, medication, associated disorders and urinary tract infection in 98 elderly residents of a nursing home. The residents' mean age was 79 years, and 78% were women. Urinary incontinence was found in 47 (48%), of whom 21 had severe urinary incontinence for which they needed to wear diapers. Senile dementia and impaired mobility were observed in 53 (54%) and 45 (46%), respectively. We also found that those with both dementia and impaired mobility had significantly (p less than 0.01) precipitated urinary incontinence. However, no significant effects on urinary incontinence were observed for associated disorders, medication or urinary tract infection. A cystometrogram performed in 73 of the 98 residents revealed detrusor overactivity in 47%. In addition, there were significant correlations between the incidence of detrusor overactivity, and the prevalence of dementia or urinary incontinence. These results suggest that senile dementia and immobility are independent risk factors for urinary incontinence in the elderly, and that detrusor overactivity, which was found to be associated with senile dementia, is a possible cause of urinary incontinence.

Aged↗