Cytoskeletal protein abnormalities in patients with olivopontocerebellar atrophy — an immunocytochemical and Gallyas silver impregnation study

A highly sensitive silver technique for glial cytoplasmic inclusions (GCI) in olivopontocerebellar atrophy (OPCA) was applied to tissues from 15 patients with neurodegenerative disorders including OPCA, Joseph disease, Alzheimer's disease (AD), Huntington's chorea, Pick disease and three control non-neurological subjects. Brain tissue from both OPCA and AD impregnated positively. Neurons, astroglia and oligodendroglia in the putamen, pontine nucleus and inferior olivary nucleus all impregnated in addition to white matter oligodendroglia. Neuronal inclusions in the pontine nucleus appeared as compact or fibrillary masses, and GCI-bearing oligodendroglia and astrocytes showed homogeneously impregnated somata. The myelinated pontocerebellar tract and the white matter surrounding the inferior olivary nucleus contained a small number of impregnated nerve fibres with a hollow structure, which resembled the myelin sheath. Immunocytochemical studies to clarify these argyrophilic structures in the OPCA subjects employed paired helical filament (PHF), microtubule associated proteins (MAPs), MAP1, MAP2, MAP5, tau, ubiquitin, neurofilament (200 or 70 kilodaltons) and myelin basic protein (MBP) antisera. GCI-bearing white matter oligodendroglia expressed PHF, tau, MAP5 and ubiquitin immunoreactives and non-argyrophilic astroglia were positive for MAP5 antiserum alone. In the putamen, pontine nuclei and inferior olivary nuclei, impregnated neurons as well as the GCI-bearing oligodendroglia immunostained with PHF, tau, MAP5 and ubiquitin antisera and impregnated astroglia were also immunoreactive to these antisera except for being tau negative in the putamen. Silver impregnated nerve fibres showed only MBP immunoreactivity. These findings indicate that the argyrophilia in the OPCA subjects closely correlates with PHF and tau immunoreactivities.     

Steroid Therapy in IgA Nephropathy: A Prospective Pilot Study in Moderate Proteinuric Cases

Forty-three patients with IgA nephropathy whose proteinuriapersisted between 1.0 and 2.0 g/day were assessed in an uncontrolledpilot study of steroid treatment. Fourteen patients receivean initial dose of 40 mg/day of prednisolone, followed by gradualreduction of the dose over an average period of about 19 months.After discontinuation of corticosteroids, they were treatedwith non-steroid anti-inflammatory drugs and/or anti-thrombocytedrugs to the end of the study. Another 29 patients receivednon-steroid anti-inflammatory drugs and/or anti-thrombocytedrugs throughout the study. Fourteen patients treated with steroidsexperienced considerable reduction in proteinuria and maintainedrenal function over 81 months. In 29 patients treated with non-steroidanti-inflammatory drugs and/or anti-thrombocyte drugs alone,proteinuria did not decrease and renal function deterioratedsignificantly during 60 months. At the end of the study, differencesin degree of proteinuria and in levels of renal function betweenthe steroid and non-steroid groups were statistically significant.In addition, these differences became more distinct in patientswith initial creatinine clearance values 70 ml/min or more inboth groups. These results suggest that treatment with steroidsin IgA nephropathy may be beneficial, especially in the earlystage of the disease.     

Impact of Androgen Deprivation Therapy on Volume Reduction and Lower Urinary Tract Symptoms in Patients with Prostate Cancer

Objective

To evaluate the impact of androgen deprivation therapy (ADT ) on prostate volume, lower urinary tract symptoms (LUTS ), and LUTS ‐related quality of life (QOL ) in patients with prostate cancer.

Methods

Patients with prostate cancer (PCa ) were treated with goserelin and bicalutamide for 24 weeks. Changes in the total prostate volume (TPV ), International Prostate Symptom Score (IPSS ), and QOL score for urinary symptoms were assessed every 12 weeks. Of the 42 patients enrolled, 8 patients withdrew and 2 were excluded, so 32 patients were analyzed.

Results

The median age, PSA levels, and TPV were 77.5 years, 22.0 ng/mL, and 29.5 cm³, respectively. TPV showed a significant decrease from baseline in weeks 12 and 24, with the mean percent decreases being ?37.5 ± 4.25 and ?7.5 ± 3.84%, respectively. The IPSS decreased from baseline to weeks 12 and 24 (from 11.7 ± 1.6 to 9.3 ± 1.0 and 9.3 ± 1.0; P = 0.15 and 0.2, respectively). The IPSS voiding score showed a significant decrease from baseline to weeks 12 and 24 whereas the IPSS storage score did not. In patients with moderate to severe LUTS , the IPSS and the QOL score showed a significant decrease in weeks 12 and 24. In patients with mild LUTS , nocturia increased significantly from baseline and there was approximately one additional episode of nocturia at 24 weeks.

Conclusions

In this study, we observed that ADT significantly reduced TPV and improved LUTS in patients with PCa and moderate to severe LUTS , but increased nocturia in patients with mild LUTS .

     

Intestinal mast cell response and mucosal defence against Strongyloides venezuelensis in interleukin-3-hyporesponsive mice

Recently several inbred strains of mice were found to be hyporesponsive to Interleukin (IL)-3 because of a 5-bp deletion in the intron 7 of the gene that encodes IL-3 receptor α subunit (IL-3Rα). Due to this mutation, mast cells were not generated in vitro from bone marrow cells of these mice under the presence of IL-3. Intestinal mucosal mast cells, of which growth/differentiation is dependent on IL-3, are important effector cells in immune-mediated expulsion of intestinal nematodes, Strongyloides spp. In the present study, therefore, we examined intestinal mast cell response and mucosal defence against Strongyloides venezuelensis in IL-3-hyporesponsive C58/J and A/J mice. After subcutaneous inoculation with 10 000 infective larvae, C58/J and IL-3-responsive C57BL/6 mice showed identical kinetic patterns of daily faecal egg output and intestinal mast cell response. When these mice were infected with 3000 L3 and, five weeks later, they were challenged by intraduodenal implantation of 800 S. venezuelensis adult worms, the timing of logarithmic decline of faecal egg count as well as intestinal mastocytosis was delayed for two days in C58/J mice. Kinetics of intestinal mastocytosis and faecal egg excretion after a primary and challenge infection in A/J mice, another IL-3-hyporesponsive strain, were identical with those seen in C58/J mice. These results suggest that intestinal mast cell response and mucosal defence against S. venezuelensis of the mutant mice were almost completely compensated in vivo . Possible mechanisms of induction of intestinal mast cell response in IL-3Rα-defective mice are discussed .     

Suppression of Torsades de Pointes by Biventricular Pacing in a Patient with Long QT Syndrome

This report describes a case of a patient with long QT syndrome (LQTS) with recurrent episodes of torsades de pointes (TdP). Use of biventricular pacing (BiVP) resulted in a shorter QT interval and a shorter T‐peak‐end interval and prevented further episodes of TdP. These findings suggest that BiVP may be helpful in patients with LQTS and refractory TdP.     

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) as a Direct-Acting Teratogen in Micromass in vitro Tests

3-Chloro-4-(dichloromethyl)-5-hydroxy-2( 5H )-furanone (MX) causes complete inhibition of rat embryonic midbrain (CNS) cell differentiation in the micromass in vitro test when applied at a concentration of 5 μ g/ml under conditions where MX is rapidly degraded in culture medium with a half-life of 56 min. This study investigated whether or not degradation products of MX have inhibitory effects on CNS cell differentiation following pre-incubation of MX in culture medium for 0.5, 1 or 2 hr. When MX was pre-incubated for 0.5 hr, the mean number of differentiated foci was 0.2 against 62.5 for the control. However, the number increased to 44.7 when pre-incubation time was extended to 2 hr. These results suggest that MX, but not its degradation products, is a teratogen in vitro. MX manifested almost complete inhibitory effects on CNS cell differentiation by 0.5 hr of exposure.     

Lack of Teratogenicity of 3-Chloro-4-(Dichloromethyl)-5-Hydroxy-2 (5H)-Furanone (MX) in Embryonic Mouse Palate Culture in vitro

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5 H )-furanone (MX) is known as a by-product of wood pulp manufacture and a contaminant of chlorinated drinking water. Since our previous studies (Teramoto et al., 1998, 1999) demonstrated in a micromass in vitro test a strong inhibitory effect of MX on rat embryo cell differentiation, the potential teratogenicity was investigated in this study by using a suspension organ culture system. Twelve-day mouse embryo palatal explants were cultivated for 72 hr in the MX-containing medium at a concentration of 0, 1, 10, 100 or 300 μg/ml and examined for closure of the palatal shelves. All control explants showed almost complete closure of the palatal shelves. Similar results were also obtained in the MX-treated explants at concentrations up to and including 100 μg/ml. Immunohistochemistry revealed no difference between the control and MX-treated explants in distribution of PCNA-and TUNEL-positive cells in the palatal mesenchyme and medial edge epithelium, respectively. When the MX concentration was raised to 300 μg/ml, palatal shelves remained wide open. However, histopathology revealed extensive pyknosis of the mesenchymal cells and loss of the epithelium. These results may indicate that MX is cytotoxic against the mouse palate at a high concentration, and that it has no cleft-palate inducing effects in mice.     

Colonic Mucosal Blood Flow in Ischemic Colitis

Altered colonic mucosal blood flow (CMBF) is thought to be involved in the onset mechanism of ischemic colitis (IC). This study was designed to clarify the features of CMBF in six patients with IC (average age, 61 yr) and 10 control subjects (44.6yr). In the IC patients, CMBF was measured at both the affected site (ulcer margin and surrounding mucosa) and at a normal appearing site, during the active, healing, or recovery phase, by the laser doppler method. In the control group, CMBF was measured in various segments of the colon. The CMBF around the ulcer site during the active phase was significantly lower than that at the homologous segment in normal controls, while CMBF at normal sites in IC patients did not differ markedly from that of normal controls. CMBF in reddened portions of the ulcer margin in IC patients was significantly higher than that of the surrounding mucosa. A significant increase in CMBF was also observed during PGEi administration as compared to that before administration. This evidence clearly indicates that decreased CMBF is involved in the pathogenic mechanism of IC. The CMBF at sites of active mucosal restoration was somewhat increased. Continuous intravenous administration of PGEi was found to increase CMBF in IC patients.     

Effects of the timing of exercise on the night sleep

Abstract The effects of physical exercises taken at different times in the day upon subjective sleep feeling were examined in five healthy university students (aged 20–22 years); morning exercise, evening exercise, and late evening exercise. The late evening exercise with the strength of 50–60% VO₂max of 1 h has the effect of getting better subjective sleep feeling in the morning and the effect of the decreased daytime sleepiness.