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Biomedical subjects

M Yoshioka

Publications and source records attributed to M Yoshioka.

At least 199 records · Page 11Linked to original sources

Melanin-laden macrophages in cerebrospinal fluid in Vogt-Koyanagi-Harada syndrome.

OBJECTIVE: To identify basophilic granules in the cytoplasm of macrophages in cerebrospinal fluid (CSF) smears from patients with Vogt-Koyanagi-Harada (VKH) syndrome as melanin pigment. DESIGN: Morphological and immunocytochemical studies were performed on CSF smears obtained from 7 patients with VKH syndrome. Specimens were stained with May-Grünwald and evaluated by a silver impregnation method (Fontana-Masson staining). For immunocyto-chemical study, the smear was reacted with mouse anti-human melanoma cell (HMB-45) monoclonal antibody. RESULTS: Basophilic granules were detected in the cytoplasm of macrophages in CSF cell smears obtained from 6 of 7 patients with VKH syndrome in the early stages (within 25 days). Using the silver impregnation method, these basophilic granules were strongly stained black. Moreover, they were identified as melanin by positive immunocytochemical staining. The total number of cells containing cytoplasmic granules ranged from 3 to 8 per 10,000 total cells in CSF. In contrast, no cells containing cytoplasmic granules were found in control CSF cell smears from patients with viral, bacterial, or noninflammatory diseases. CONCLUSION: The identification of melanin-laden macrophages in the CSF of patients with VKH syndrome suggests that these cells are responsible for pleocytosis in the immunopathologic process of VKH syndrome.

Adult↗

Upregulation of Bcl-2 protein in the myasthenic thymus.

We examined the expression of Fas antigen and Bcl-2 protein in thymic tissue surgically resected from 10 patients with myasthenia gravis, using immunocytochemical techniques. Histologically, thymic tissues from 7 myasthenia gravis patients showed hyperplasia, while 3 other patients had thymomas. In hyperplastic thymic tissue, immunoreactivity for Fas antigen was observed mainly in the network of medullary epithelial cells. In contrast, expression of Fas antigen was rare in the cortex. Fas antigen was also detected to some degree in thymoma tissue from 3 patients. Bcl-2 protein was highly expressed in the medullary thymocytes in the hyperplastic thymic tissue, whereas its staining was quite low in myasthenia gravis thymomas. The number of Bcl-2-positive thymocytes in the medulla was significantly greater in the hyperplastic myasthenia gravis thymic tissue than in the control thymic tissue. These findings suggest that Bcl-2 protein may be upregulated in the myasthenia gravis thymus and that this phenomenon may be related to impaired apoptotic cell death of autoreactive thymocytes in myasthenia gravis.

Adult↗

Functional regulation by dopamine receptors of serotonin release from the rat hippocampus: in vivo microdialysis study.

The functional regulation by dopamine (DA) receptors of serotonin (5-HT) release from the rat hippocampus was investigated by use of in vivo microdialysis. Dialysate 5-HT levels were reduced by co-perfusion of 10 microM tetrodotoxin (TTX) and were elicited by K+ (60 and 120 mM) stimulation in a concentration-dependent manner. Local perfusion (10 microM) and peripheral administration (20 mg/kg, i.p.) of fluoxetine produced increases in 5-HT levels. These results indicate that the spontaneous 5-HT levels in the rat hippocampus can be used as indices of neuronal origin from the serotonergic nerve terminals. The nonselective dopamine (DA) receptor agonist apomorphine (1, 10 and 100 microM), when perfused through the probe over a period of 40 min, increased 5-HT release in a concentration-dependent manner. Apomorphine-induced (100 microM) increases in 5-HT release was abolished by pretreatment with the selective D2 receptor antagonist, S(-)-sulpiride (1 and 10 microM), but not prevented by pretreatment with the selective D1 receptor antagonist, R(+)-SCH-23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine) (1 microM). S(-)-Sulpiride and R(+)-SCH-23390 by themselves did not alter the spontaneous 5-HT levels. The 5-HT release was elevated by perfusion of the selective DA reuptake inhibitor GBR 12909 (1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenyl-propyl]piperazine) (1, 10 and 100 microM), indicating the possibility of not only exogenous but also endogenous DA-mediated facilitatory effects on 5-HT release in vivo. The 5-HT release was also elevated by perfused (+/-)-PPHT ((+/-)-2-(N-phenylethyl-N-propyl)-amino-5-hydroxytetralin) (1, 10 and 100 microM), the selective D2 receptor agonist, in a concentration-dependent manner. On the other hand, (+/-)-PPHT (100 microM) failed to increase 5-HT release in catecholamine (CA)-lesioned rats pretreated with 6-hydroxydopamine (6-OHDA)(200 micrograms/rat, i.c.v.). The (+/-)-PPHT-induced (100 microM) increase in 5-HT release was prevented not only by pretreatment with 10 microM S(-)-sulpiride but also by pretreatment with the alpha 2-adrenoceptor antagonist idazoxan (10 microM). These findings suggest that the functional regulation of 5-HT release via D2 receptors exists in the rat hippocampus. Furthermore our results indicate that the facilitatory effect of 5-HT release via D2 receptors may be mediated indirectly by noradrenergic neurons, but not mediated directly through D2 receptors located on serotonergic nerve terminals.

Adrenergic alpha-Antagonists↗

Successful treatment of bronchial mucoepidermoid carcinoma in an 11-year-old boy by bronchoplasty: report of a case.

We report herein the rare case of an 11-year-old boy in whom mucoepidermoid carcinoma of the right upper lobe bronchus was successfully treated by bronchoplasty. The patient underwent bronchoscopy to investigate the cause of relapsing respiratory infections over the past 2 years, which revealed a tumor at the orifice of the right upper lobe bronchus. Thus, a right upper sleeve lobectomy was effectively carried out, preserving right pulmonary function. The tumor was observed to partially invade the bronchial wall, but not the lung parenchyma. Histological examination confirmed a diagnosis of mucoepidermoid carcinoma, classified as grade 2 by Conlan's classification. The patient has been well and free of recurrence for 3 years postoperatively.

Anastomosis, Surgical↗

Increased NADPH-diaphorase reactivity and cytokine expression in dorsal root ganglia in acquired immunodeficiency syndrome.

We studied lumbosacral dorsal root ganglia (DRGs) from 10 patients with acquired immunodeficiency syndrome (AIDS) and five controls using immunocytochemistry, in situ hybridization and NADPH-diaphorase (NADPHd) histochemistry. Human immunodeficiency virus (HIV)-1 RNA was detected in five AIDS cases, and HIV-1 p24 antigen was found in four of these patients. The densities of nodules of Nageotte (nN), macrophages and major histocompatibility complex-class II-positive cells were significantly increased in the DRGs of AIDS patients compared to controls. Cytomegalovirus antigen was observed in the DRGs of four AIDS cases and one control, but without its presence being related to neuronal degeneration. Furthermore, we detected tumor necrosis factor, interferon-gamma, interleukin (IL)-1 beta, and IL-6 in the DRGs from AIDS patients. Using NADPHd histochemistry, we showed that the number of NADPHd-positive neurons was significantly increased in the DRGs of AIDS patients compared to controls, implying upregulation of nitric-oxide (NO) production in AIDS DRGs. Generally, there were increased numbers of nN in DRGs which contained more NADPHd-positive neurons. Additionally, immunoreactivity for an inducible form of NO synthase was detected in interstitial cells in AIDS DRGs. These results suggest that reactive inflammation, including the production of cytokines, occurs in the DRGs of AIDS patients and that excessive production of NO may be related to neuronal degeneration in AIDS DRGs.

Acquired Immunodeficiency Syndrome↗

A comparative study of the effects of alpha 1-adrenoceptor antagonists on sympathetic function in rats.

alpha 1-Adrenoceptor antagonists were comparatively evaluated in terms of their acute and long-term effects on sympathetic function in rats. In the first study, the effects of alpha 1-adrenoceptor antagonists on cardiovascular sympathetic nerve activity were electrophysiologically determined in anesthetized normotensive rats. Intravenous administration of four alpha 1-antagonists-prazosin, bunazosin, SM-2470, and YM-617-produced no changes or decreases in heart rate, in spite of the expected reflex tachycardia resulting from their marked hypotensive effect. Among the alpha 1-antagonists examined, some also produced a significant decrease in inferior cardiac nerve activity. All except prazosin decreased renal nerve activity, while prazosin showed an opposite tendency to increase the renal nerve activity. On the other hand, preganglionic adrenal nerve activity, an index of central sympathoinhibitory activity, underwent a significant decrease after SM-2470 and YM-617 administration, and a dose-dependent increase was observed in response to prazosin and bunazosin. In the second study, the long-term (4 weeks) effects of alpha 1-antagonists on plasma and urinary catecholamine levels and urinary electrolyte excretions were evaluated in stroke-prone spontaneously hypertensive rats (SHRSP). Prazosin and bunazosin did not exert any consistent changes on plasma and urinary catecholamine concentrations. SM-2470, however, significantly decreased both plasma and urinary epinephrine concentrations. In addition, bunazosin and SM-2470 produced increases in urinary sodium and potassium excretions. Urine volume tended to increase after bunazosin administration. Prazosin, on the other hand, produced decreases in urinary sodium and potassium excretions as well as in urine volume. These findings demonstrate that alpha 1-antagonists differentially affected cardiovascular sympathetic tone in anesthetized rats. These varied sympathoinhibitory profiles might be in part explainable as different effects on urinary electrolyte metabolism after long-term administration of alpha 1-antagonists in SHRSP.

Adrenergic alpha-Antagonists↗

Effects of portal venous inoculation with donor splenocytes on lung allograft survival in dogs.

The effects of portal venous inoculation with donor splenocytes on lung allograft survival were evaluated in dogs. Within the dose range examined, portal venous inoculation with donor splenocytes alone did not affect the graft survival time. Although the mean graft survival time was prolonged by FK 506 treatment for 14 days, the transplanted lungs were rejected within 12 days after termination of FK 506 administration. However, when the recipients were given portal venous inoculation with donor splenocytes at the time of transplantation, the graft survival time after termination of FK 506 administration was significantly prolongated. In the recipients that received combined therapy of portal venous inoculation with donor splenocytes and FK 506 treatment, arterial oxygen tension and histologic architecture of the transplanted lungs remained within the normal range for a longer period than these measures did in control animals that received FK 506 treatment alone. Dose-response experiments revealed that 1 x 10(8) cells/recipient was most effective in causing prolonged graft survival after termination of FK 506 treatment. On the basis of these results, perioperative portal venous inoculation with donor splenocytes can enhance the immunosuppressive effect of FK 506 in the canine lung transplantation model.

Animals↗

Spouse enabling of alcohol abuse: conception, assessment, and modification.

This article presents a conception of spouse enabling of partner alcohol abuse, a review of its dysfunctions, and an approach to assessment and modification to reduce spouse enabling behavior. Based on experience with its use in unilateral family therapy with many spouses of treatment-refusing alcohol abusers, procedural guidelines, treatment methods, two case examples from a crossover experimental dyad, and clinical results for the two cases in the dyad are described. Also presented are practice issues, characteristics of spouse enabling as they relate to disenabling intervention, and areas of possible application of the disenabling program.

Adult↗

Characterization of a model of osteoarthritis in the rabbit knee.

A new computerized method of histomorphometry was used to assess the development of osteoarthritis (OA) in a rabbit model. Three groups of 10 New Zealand White rabbits with closed epiphyses underwent unilateral anterior cruciate ligament transection (ACLT) and contralateral arthrotomy (sham). Groups were killed at 4, 8 and 12 weeks. At the time of death the femoral condyles were assessed grossly following the application of India ink using the following grading scale. Grade 1: intact surface; grade 2: minimal fibrillation; grade 3: overt fibrillation; grade 4: erosion. All histological sections were assessed using a color image analysis system. The mean thickness and area were measured for a defined cartilage region. The root mean square surface roughness (based on deviations from an idealized smooth surface) was calculated to assess the surface profile of the articular cartilage. The results were as follows. After ACLT, no full-thickness ulceration was noted at 4 weeks. Four of the medial femoral condyles at 8 weeks and six at 12 weeks showed full-thickness ulceration of the articular cartilage. The per cent cartilage area and cartilage thickness (ACLT divided by sham) in almost all regions showed decreases with time, indicating progressive erosion. The surface of the ACLT knees was much rougher than that of sham of the knees. These results demonstrate the usefulness of a quantitative methodology using a computerized video analysis system to assess the articular cartilage following ACLT in a rabbit model for the development of OA.

Animals↗

Predictors of fall-related injuries among community-dwelling elderly people with dementia.

To determine the annual incidence of fall-related injuries among community-dwelling elderly people with dementia and to identify the factors predicting those likely to sustain such injuries, we conducted a cohort study with a one-year follow-up. As predicting factors, we paid particular attention to behavioural problems and difficulties in helping with activities of daily living based on the Assessment of Basic Care for the Demented (ABCD) scale. Thirty-five of 86 final study subjects and nine of 98 final control subjects sustained fall-related injuries. Significant factors associated with fall-related injuries to demented elderly subjects were ABCD score (adjusted odds ratio 0.73, 95% confidence interval 0.60-0.89), history of falls in the past year (3.65, 1.34-9.95), and Barthel index score (1.04, 1.00-1.08). This highlights the predictive value of better physical function but more difficult care status in relation to ADL for fall-related injuries.

Accidental Falls↗

Purification and refolding of recombinant human proMMP-7 (pro-matrilysin) expressed in Escherichia coli and its characterization.

Human matrix metalloproteinase-7 (MMP-7 = matrilysin) was overproduced in Escherichia coli as a recombinant zymogen (31 kDa), the C-terminus of which bears artificial hexa-histidines. Most of the enzyme was isolated from the insoluble fraction of the cell lysate and purified by a single step using Ni-NTA resin after solubilization of the precipitates with 8 M urea solution. The resin-bound recombinant protein was refolded into a form that is activatable by p-amino-phenylmercuric acetate in an autocatalytic manner. The activated enzyme cleaved a synthetic peptide substrate at the reported site for MMP-7. Digestion of carboxymethylated transferrin (a natural substrate of MMP-7) by the recombinant proteinase generated fragments with the same peptide map as in the case of native purified MMP-7. The autocatalytic activation and enzyme reaction were entirely dependent on the presence of calcium and zinc ions. The enzyme activity to cleave carboxymethylated transferrin was inhibited by tissue inhibitors of metalloproteinases-1 and -2, MMP-specific inhibitors. The activity of the recombinant MMP-7 was also inhibited by a synthetic peptide derived from a part of the cysteine switch that maintains the zymogen in an inactive state. Thus, we report here a simple means of preparing a large quantity of recombinant proMMP-7 that can be used to study the activation mechanism and to screen synthetic inhibitors.

Amino Acid Sequence↗

Parvalbumin and calbindin D-28 k immunoreactivity in dorsal root ganglia in acquired immunodeficiency syndrome.

Various degrees of neuronal degeneration have been found in lumbosacral dorsal root ganglia of patients with acquired immunodeficiency syndrome (AIDS). To characterize the subpopulations of primary sensory neurons affected in AIDS, we immunostained dorsal root ganglion tissues from 11 AIDS patients and six controls using antibodies to the calcium binding proteins, parvalbumin and calbindin D-28 k. In controls, the proportion of neurons containing parvalbumin and calbindin was 18.0% and 22.4%, respectively. The majority of parvalbumin-positive neurons, which are thought to be proprioceptive neurons, were of medium to large size, while calbindin was found in both large- and small-sized neurons. The density of parvalbumin-immunoreactive neurons was reduced by 7.3% in AIDS patients, but the density of calbindin-immunoreactive neurons was preserved. Furthermore, in AIDS cases, the number of parvalbumin-positive neurons was reduced more in dorsal root ganglia in which human immunodeficiency virus (HIV) antigen was detected than in HIV-negative ganglia. These results suggest that specific subpopulations of sensory neurons positive for parvalbumin may be differentially affected over the course of AIDS, and that this could be related to peripheral neuropathy which frequently occurs in the late stages of AIDS.

Acquired Immunodeficiency Syndrome↗

Biological and antigenic characterization of three BApNA-hydrolyzing proteases from the culture supernatant of Porphyromonas gingivalis.

Biological and antigenic distinction of 3-N-alpha-benzoyl-DL-arginine p-nitroanilide (BApNA)-hydrolyzing proteases (Pase-B, Pase-C and Pase-S) isolated from the culture supernatant of Porphyromonas gingivalis were determined. Immunoblotting analysis of these enzymes using a polyclonal antibody against Pase-S, which is a soluble, clostripain-like protease, revealed immunological distinction from Pase-C, a vesicle-associated thiol-protease. Pase-B, a vesicle-associated clostripain-like protease, reacted with the antibody and was also found to contain a considerable amount of carbohydrates in its structure, as compared with the others. Analysis of N-terminal amino acids of Pase-B provided a sequence not found in the SwissProt data bank or previously reported as N-terminal sequences of proteases from P. gingivalis. Pase-S, resembling Pase-B in its hydrolytic specificity, cleaved only arginine residues of peptides and degraded type IV and denatured type I collagen. Pase-C hydrolyzed N-alpha-benzoyl-DL-lysine p-nitroanilide and showed the strongest capacity of degrading native type I collagen. This enzyme was also the only one to possess hemagglutinating activity. Our findings suggest that Pase-S from P. gingivalis is less active than Pase-C and that the enzyme may be an isozyme of Pase-B.

Affinity Labels↗

Cholinergic changes in the hippocampus of stroke-prone spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: We investigated age-related changes in the central cholinergic systems in stroke-prone spontaneously hypertensive rats (SHRSP) to examine whether the regional and progressive cholinergic changes occur and are correlated with behavioral changes in the passive avoidance task. METHODS: Tissue levels of choline (Ch) and acetylcholine (ACh) were determined in the cerebral regions, including the hippocampus, of SHRSP (at two ages: 15 to 20 and 30 to 40 weeks) that had been tested in a passive avoidance task and were compared with those of age-matched controls, Wistar-Kyoto rats (WKY). With the use of in vivo microdialysis, high K+-stimulated release of hippocampal ACh, a functional parameter of the cholinergic system, was also determined in 15- to 20-week-old SHRSP. RESULTS: We found that 15- to 20-week-old SHRSP demonstrated a markedly lower level of hippocampal Ch than age-matched WKY. The decrease in the Ch level in 15- to 20-week-old SHRSP was observed in all regions examined; however, in the hippocampus a significant difference from WKY was subsequently observed at the age of 30 to 40 weeks. The hippocampal ACh release was markedly decreased by repetitive stimulation with high K+ in 15- to 20-week-old SHRSP. Behavioral impairment in the passive avoidance task was observed in the two age groups of SHRSP, with significant and positive correlations between the hippocampal ACh levels and the response latency. CONCLUSIONS: A decrease in hippocampal Ch level was observed in both 15- to 20-week-old and 30- to 40-week-old SHRSP, accompanied by performance failure in the passive avoidance task. The abnormal release of hippocampal ACh in response to the repetitive K+ stimulation was also noted in 15- to 20-week-old SHRSP. Thus, cholinergic dysfunction in the hippocampal system may be responsible for behavioral abnormality in the passive avoidance task in SHRSP.

Acetylcholine↗

Marinoic acid, a novel bufadienolide-related substance in the skin of the giant toad, Bufo marinus.

We found a novel substance, 3 beta-hydroxy-11,12-seco-5 beta, 14 beta-bufa-20,22-dienolide-11,14-olide-12-oic acid (1), which we called marinoic acid, in the skin of the toad, Bufo marinus. The structure was established from NMR and MS data. Like bufadienolides, marinoic acid contained an A/B ring structure in the cis configuration and a D/alpha-pyrone ring structure, but the structure of the C ring differed considerably from that of bufadienolides. Marinoic acid exhibited biological activity, as demonstrated by inhibition of Na+, K(+)-ATPase enzymatic activity, and by inhibition of [3H]ouabain binding to the digitalis receptor site on Na+, K(+)-ATPase, although marinoic acid was a less effective inhibitor than typical bufadienolides. Although marinoic acid cannot be classified as a bufadienolide, its chemical structure and its Na+, K(+)-ATPase inhibitory activity suggest that it is bufadienolide-related.

Animals↗

Functional interaction between serotonin and other neuronal systems: focus on in vivo microdialysis studies.

In this review, the functional interactions between serotonin (5-HT) and other neuronal systems are discussed with the focus on microdialysis studies in the mammalian brain (mainly rats). 5-HT release is negatively regulated not only by somatodendritic 5-HT1A and terminal 5-HT1B (5-HT1D) autoreceptors but also by alpha 2-adrenergic and mu-opioid heteroreceptors that are located on serotonergic nerve terminals. 5-HT by itself is involved in the inhibitory effects of noradrenaline release and the facilitatory regulation of dopamine release via multiple 5-HT receptors. Acetylcholine release appears to be regulated by inhibitory 5-HT1B heteroreceptors located on cholinergic nerve terminals. Long-term treatment with 5-HT-uptake inhibitors and noradrenaline-uptake inhibitor produces desensitization of 5-HT1A autoreceptors and alpha 2-heteroreceptors, respectively, which may be related therapeutically to the delayed onset of the effects of antidepressants. Some microdialysis studies have predicted that the combination of a 5-HT-uptake inhibitor and 5-HT1A-autoreceptor antagonist might produce much greater availability of 5-HT in the synaptic cleft in terms of much faster induction of subsensitivity of 5-HT1A autoreceptors. Clinical trials based on this hypothesis have revealed that combination therapy with a 5-HT-uptake inhibitor and 5-HT1A-autoreceptor antagonist ameliorated the therapeutic efficacy in depressive patients. Taken together, neurochemical approaches using microdialysis can contribute not only to clarification of the physiological role of the serotonergic neuronal systems but also might be a powerful pharmacological approach for the development of therapeutic strategies.

Animals↗

Capsaicin in diet does not affect glycogen contents in the liver and skeletal muscle of rats before and after exercise.

Effects of capsaicin, a pungent principle of hot red pepper, on glycogen contents in the liver and skeletal muscle at rest and during exercise were studied in rats. The contents of glycogen in the liver and soleus muscle, and the concentrations of serum glucose, lactate, free fatty acid and glycerol were examined. Capsaicin was supplemented at 0.014% of the experimental diet. Each group of rats was fed the capsaicin-diet ad libitum for 7 days, and then both groups of rats were fed isoenergetic diets with or without capsaicin for 7 days. Rats were trained running with a treadmill for 14 days. At the final stage of the experiments, 1 h running was loaded after the capsaicin diet or the control diet. The glycogen contents in the liver and soleus muscle were not significantly different between the capsaicin-diet group and the control-diet group after the meal and during exercise. The concentrations of serum glucose, lactate, free fatty acid and glycerol were not significantly different between the two dietary groups after the meal and during exercise. The results in this study suggest that the intake of capsaicin have little effect on glycogen contents in the liver and soleus muscle at rest and during exercise in rats previously fed a capsaicin-diet ad libitum for 1 week.

Animals↗