Antineuronal antibody in Sjögren's syndrome masquerading as paraneoplastic cerebellar degeneration.
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Biomedical subjects
Publications and source records attributed to K Ishida.
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The cellular binding sites of an antineuronal antibody were characterized in an autopsy case of the paraneoplastic encephalo-myelo-ganglionitis. A 61 year-old woman developed a subacute sensorimotor polyneuropathy and, later, multiple involvement of cranial nerves, disturbance of consciousness, and generalized seizure. An autopsy revealed a small cell lung carcinoma and neuropathological changes that included disseminated encephalitis, spinal anterior horn lesions, severe loss of dorsal root ganglion neurons, and secondary degeneration and loss of the nerve fibers in the spinal posterior column and peripheral nerves. The serum IgG from the patient contained antineuronal antibody(s) including an antibody to 35- to 37-kDa neuronal antigens called anti-Hu as demonstrated in Western blot. In immunohistochemical studies, the serum IgG immunostained neurons of the brains, spinal cords, and dorsal root ganglia of humans or rats. Confocal laser-scanning microscopy revealed binding of the patient's IgG in the neuronal nuclei and cytoplasm, but not in the nucleoli. In immunoelectron microscopic studies, immunolabelling with the IgG was found diffusely in the karyoplasm, excluding nucleoli, and in the cytoplasmic matrix between the cisternae of the reticulums, Golgi apparatus, and mitochondria. Encephalo-myeloganglionitis is a clinicopathological entity frequently associated with the presence of neoplasm and antineuronal antibody, however, the role of the antibody in the pathogenesis remains to be elucidated.
The present study addresses to determine whether hemoglobin within red blood cells can be utilized as a spin-trap agent for nitric oxide. We demonstrate the diazotization method coupled with a gel filtration chromatography, which is simply due to the separation of nitrosylhemoglobin from nitrite, nitrate or other low molecular nitroso-compounds in biological systems and to the liberation of nitric oxide from nitrosyl heme-complexes in the acidic condition. The amount of nitric oxide can be estimated by the difference of absorbances at 542 nm between diazo-compounds formed by Griess reagent and hemichrome by phosphoric acid. Our results indicate that hemoglobin in red cells as a spin-trap agent would be useful for monitoring nitric oxide in the circulation under the several disease states.
The incidence of non-insulin-dependent diabetes mellitus in a model rat (Otsuka-Long-Evans-Tokushima Fatty [OLETF]) has been shown to be much higher in males than in females. To evaluate the role of sex hormones in the development of diabetes in this model, we performed biochemical and morphological studies on the effects of castration and sex hormones on the development of non-insulin-dependent diabetes mellitus in these rats. The rats were randomly assigned to six groups of 10 rats each, three groups of males and three of females. Two of the male groups and two of the female groups were castrated at 5 weeks of age, and the third male and female groups received sham operations. From 9 to 30 weeks of age, one group of castrated males received testosterone enanthate (1 mg-wk-1) and one group of castrated females received estradiol valerate (1 mg.wk-1). The other castrated groups received an equal volume of vehicle only. At 30 weeks of age, the cumulative incidences of diabetes mellitus in the sham-operated male and female rats were 100% and 0%, respectively. Orchiectomy reduced the incidence of diabetes to 20%, whereas ovariectomy increased it to 30%. Administration of sex hormones restored the incidence to 89% in males and 0% in females. In vivo insulin-stimulated glucose uptake as measured with a euglycemic clamp was reduced in sham-operated males, castrated males with hormone replacement (HR), and castrated females without HR as compared with sham-operated females and castrated females with HR.(ABSTRACT TRUNCATED AT 250 WORDS)
Induction of bradykinesia by SM-9018, a novel 5-HT2 and D2 antagonist, was compared with that of other neuroleptics using the pole test in mice. Neuroleptics including SM-9018, haloperidol, chlorpromazine, and thioridazine dose dependently induced bradykinesia in the pole-descending behavior of mice with relative potencies consistent with those for catalepsy induction. SM-9018 was about 70 times weaker than haloperidol and twice as weak as thioridazine in inducing bradykinesia. Other CNS drugs such as barbiturates and antidepressants had no effects. Haloperidol-induced bradykinesia was significantly attenuated by a cholinergic muscarinic antagonist (i.e., trihexyphenidyl) and 5-HT2 antagonists (i.e., ritanserin and cyproheptadine) whereas that caused by SM-9018 was relatively resistant to the 5-HT2 antagonists. These findings suggest that SM-9018 is weaker than other neuroleptics in inducing extrapyramidal side effects and that the 5-HT2 blocking activity of SM-9018 may contribute to its atypical neuroleptic property.
Exercise training every day has been shown to be effective in preventing the development of non-insulin-dependent diabetes mellitus (NIDDM) in a model rat (Otsuka Long Evans Tokushima Fatty (OLETF)). For determination of whether less vigorous exercise training also has a protective effect against the development of NIDDM in this model, seven male OLETF rats each were assigned to training every other day, every 3 days and every 7 days from 6 to 30 weeks of age. At 30 weeks of age, rats trained every other day, 3 days, 7 days and sedentary rats weighed averages of 547, 548, 603 and 695 g and had abdominal fat deposits of 28, 24, 32 and 72 g, respectively. The mean meterages of running of rats trained every other day, 3 days and 7 days over the whole experimental period were 9630, 5166 and 1685 m/week, respectively. At 30 weeks of age, the cumulative incidence of NIDDM in sedentary rats was 85.7% (6/7), while none of the trained rats became diabetic except for one of rats trained every 7 days. The glucose infusion rate (GIR), an index of insulin sensitivity, in the group trained every 7 days, 60.6 +/- 5.0 mumol.kg-1.min-1, was significantly greater than that in the sedentary group, 21.7 +/- 1.7 mumol.kg-1.min-1. Morphological studies on the pancreas of rats trained every other day and every 3 days showed minimal changes of islets, whereas sections of islets from rats trained every 7 days appeared enlarged and fibrotic, though significantly less so than the islets of sedentary rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiostrongylus cantonensis is the causative agent of human eosinophilic meningoencephalitis in the Pacific Islands and Southeast Asia. Prominent eosinophilia in the cerebrospinal fluid (CSF) of the patients has been used as one of the diagnostic criteria for the disease but the role(s) of the CSF eosinophils has remained to be elucidated. In this article, Kentaro Yoshimura, Hiroko Sugaya and Kazuto Ishido discuss the involvement of CSF eosinophils in the killing of intracranial worms and the damage of the central nervous system of the hosts, and consider why eosinophils in A. cantonensis infection play a more important role in nonpermissive hosts (including humans) than in the permissive rat host.
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We investigated the in-vitro and in-vivo activity of a new quinolone AM-1155 against Mycoplasma pneumoniae, and compared it with ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin and minocycline. AM-1155 was the most potent agent in vitro of the quinolones tested. Its pre-treatment minimal inhibitory concentrations for 90% of the 41 strains (MIC90) was 0.06 mg/L. In contrast, pre-treatment MIC90 values for ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin, and minocycline were 1, 1, 2, 0.5, 0.0156, and 0.5 mg/L, respectively. Post-treatments MIC90s, which may reflect mycoplasmacidal potency, of AM-1155, ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin and minocycline were 0.125, 1, 2, 4, 0.5, 0.125 and 4 mg/L, respectively. In-vitro activities of antimicrobial agents were assessed in an experimental pulmonary infection model in Syrian golden hamsters. AM-1155 was the most effective agent among five antimicrobial agents (AM-1155, ofloxacin, tosufloxacin, erythromycin, minocycline) tested in terms of reduction in viable M. pneumoniae cells and in reducing macroscopic lung lesions. These results suggest that AM-1155 will be a useful antimicrobial agent for the treatment of M. pneumoniae infections.
This study was undertaken to elucidate whether phase I appeared at the onset of voluntary and passive arm movements and to compare these results with those of similar leg movements. Instead of the conventional cranking exercise, seven male subjects performed alternately flexion-relaxation of both arms, extension-relaxation of both legs, and combined arm and leg exercise at the rate of about 60 min-1 for four breaths in a sitting position. Similar movements were accomplished passively by the experimenters. In all experiments, minute ventilation increased rapidly within the first breath after the onset of exercise. The difference of ventilation (delta value) between the mean of the first two breaths at the onset of voluntary exercise and that of five breaths during rest was significantly (P < 0.05) greater in arm (7.75 l min-1) than in leg (5.19 l min-1). Passive movement showed a similar tendency. Arm delta ventilation correlated highly (r = 0.74-0.91) with leg delta ventilation and the slope of the regression lines was about 1.2. Heart rate increased abruptly while cardiac output did not always increase rapidly at the onset of locomotion. Oxygen uptake in the voluntary leg exercise continued for 3 min was slightly but nonsignificantly higher than in the arm exercise, indicating the equality of the exercise intensity. In conclusion, ventilatory responses at the onset of the arm exercise are larger than those of the leg in both voluntary and passive conditions regardless of the muscle mass, suggesting the different neurogenic mechanism between arm and leg.
The inhibitory effects of azithromycin (AZM), a new 15-membered macrolide antibiotic, on the production of exotoxin A, total protease, elastase, and phospholipase C by Pseudomonas aeruginosa were determined, and the virulence-suppressing effects of AZM were compared with those of erythromycin (EM), roxithromycin (RXM), and rokitamycin (RKM). The effect of exposure of P. aeruginosa PA103 or B16 in cultures to sub-MICs of these macrolide antibiotics on the production of exoenzymes was determined. AZM suppressed the in vitro production of extracellular and intracellular exotoxin A by P. aeruginosa PA103 more than did EM, even at a concentration of only 2 micrograms/ml. At concentrations of between 4 and 32 micrograms/ml, AZM also inhibited total protease, elastase, and phospholipase C production by P. aeruginosa B16 more than did EM, RXM, and RKM. AZM was effective in suppressing exotoxin A and total protease production through 24 h of incubation in the presence of drug at sub-MICs, but it had no significant effect on either the growth of P. aeruginosa or its total protein production. Moreover, at a concentration of 4 micrograms/ml, AZM suppressed exoenzyme production by other strains of P. aeruginosa more than did EM. These findings indicate that AZM, EM, RXM, and RKM each has an inhibitory effect on exoenzyme production separate from the antimicrobial effect and that, of these macrolides, AZM has the strongest virulence-suppressing effect.
The in vitro and in vivo activities of sparfloxacin against Mycoplasma pneumoniae were compared with those of erythromycin, levofloxacin, ofloxacin, and minocycline. The MICs of sparfloxacin, erythromycin, levofloxacin, ofloxacin, and minocycline for 90% of the 43 M. pneumoniae strains tested were 0.063, 0.016, 0.5, 1, and 0.5 microgram/ml, respectively. In the experimental pulmonary M. pneumoniae infection model in Syrian golden hamsters, sparfloxacin was as effective as erythromycin when orally administered at 15 mg/kg twice daily for 5 days and more effective than erythromycin when orally administered at 10 mg/kg once daily for 5 days. Sparfloxacin was more effective than levofloxacin and ofloxacin in both dosing regimens. The peak concentrations of sparfloxacin in hamster sera after administration of single oral doses of 15 mg/kg were almost the same as those in human sera after administration of single oral doses of 200 mg (the usual clinical dose), and the half-life of sparfloxacin in hamster serum was shorter than that in human serum after administration of a single oral dose of 200 mg. These results suggest that sparfloxacin may be clinically useful for the treatment of M. pneumoniae infections.
We investigated the in vitro and in vivo activities of macrolides against Mycoplasma pneumoniae. In vitro MICs of azithromycin, erythromycin, clarithromycin, and roxithromycin were determined. Azithromycin was the most potent antimicrobial agent tested in vitro. Its MIC for 90% of the strains was 0.00024 micrograms/ml. MICs for 90% of the strains of erythromycin, clarithromycin, and roxithromycin were 0.0156, 0.0078, and 0.03125 micrograms/ml, respectively. In vivo activities were assessed in a pulmonary infection model with Syrian golden hamsters. We evaluated the in vivo effects on reduction of viable M. pneumoniae cell counts and on reduction of microscopic and macroscopic histopathologies for azithromycin, erythromycin, and clarithromycin given at 10 mg/kg once daily for 1 and 3 days and given at 15 mg/kg twice daily for 2.5 and 5 days. Azithromycin was significantly more effective than erythromycin or clarithromycin in the same regimens. Especially at 10 mg/kg once daily for 1 day, only azithromycin was significantly effective in the reduction of viable M. pneumoniae cells and histopathologies. These results show that azithromycin is more efficacious than the other drugs tested against M. pneumoniae pneumonia in hamsters. These data suggest that clinical studies of macrolides in human patients are warranted.
We report the case of a 42-year-old woman with autosomal dominant polycystic kidney disease complicated by primary aldosteronism. She had a history of hypertension for 12 years and was found to have hypokalemia and polycystic renal and hepatic disease. Endocrinological tests revealed hyporeninemia and hyperaldosteronemia. Adrenal scintigraphy and venography demonstrated a left adrenal adenoma. Blood sampled from the adrenal veins confirmed hyperaldosteronemia originating from the left adrenal gland. Left adrenalectomy was performed. After surgery, plasma renin activity, plasma aldosterone titer, and serum potassium level normalized. The mechanism for the development of primary aldosteronism with autosomal dominant polycystic kidney disease may be related to the activation of the renin-angiotensin system. Four years after left adrenalectomy, hepatic but not renal cysts showed a remarkable increase; the improvement in hypokalemia may have delayed the progression of kidney cysts.
We evaluated the effect of chronic tobacco smoke exposure on the function of the alveolar macrophage (AM) in mice. Tumor necrosis factor-alpha production of the AM triggered by lipopolysaccharides was smaller in smoke-exposed mice as compared to control mice but did not reach statistical significance (27.3 +/- 4.0 vs. 34.8 +/- 4.9 U/ml). The percentage of AM which did not phagocytize latex particles in the smoke-exposed mice was significantly larger than that in control mice (33.9 +/- 2.3 vs. 20.8 +/- 2.1%; p < 0.05). Ia antigen expression of the AM was significantly larger in smoke-exposed mice (cytotoxicity index: 0.180 +/- 0.033 vs. 0.038 +/- 0.0118; p < 0.01). The asialo-GM1 antigen expression was similar in both groups (0.949 +/- 0.007 vs. 0.961 +/- 0.011). Although the precise mechanisms of these functional changes of the AM by tobacco smoke exposure are not clear, they may have some immunological effects on the alveolar space.
BACKGROUND: The mechanism of ventricular tachycardia (VT) after correction of tetralogy of Fallot (TF) is poorly understood. The purpose of this study was to examine the histopathology of the arrhythmogenic area detected by intraoperative mapping. METHODS AND RESULTS: The patients were three men who underwent radical surgery for TF at age 3, 3, or 5 years, respectively. VT developed at 8, 9, or 11 years, respectively, after surgery, and shock developed during VT in every case. The ECG revealed monomorphic VT in two cases and polymorphic VT in one case. Induction of VT resulted in a wide left-axis deviation-pattern QRS with cycle lengths varying between 260 and 330 milliseconds. The VT origin was identified at the right ventricular outflow tract (RVOT). A radical operation was performed with the patient under cardiopulmonary bypass. On epicardial mapping, delayed activation of the RVOT was recorded during sinus rhythm, and clockwise circus movement of the macroreentry current during VT on the right ventricular free wall was documented in each case. The VTs were treated successfully by surgical resection and cryoablation of the myocardium. In every patient, histology of the myocardial specimens showed degeneration, adiposis, fibrosis, inflammatory cell infiltration, and scattered myocyte islets. These lesions corresponded anatomically to the area of myocardium in which delayed activation was evident during epicardial mapping. CONCLUSIONS: The results of this study indicate that patients with VT after radical correction of the TF have abnormal histopathological findings at the site of the prior right ventriculotomy scar. These lesions were noted within the region of delayed activation found during epicardial mapping and were found to be a part of the reentrant circuit.