Centronuclear Myopathy with Abundant Nemaline Rods in a Japanese Black and Hereford Crossbred Calf.

Histopathological examination was performed on skeletal and diaphragmatic muscles from an 8-month-old male crossbred calf showing abnormal gait and tremor of the hindlimbs. There were numerous round fibres with centrally placed nuclei forming nuclear chains in longitudinal sections, associated with interstitial fibrosis or adipose tissue infiltration. On nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) staining, some muscle fibres in severe lesions showed a spoke-like appearance due to a radial arrangement of sarcoplasmic strands. Additionally, increased NADH-TR activity in the subsarcolemmal structures, appearingas ring-like or necklace-like forms, were observed. Transmission electron microscopy revealed dilated sarcoplasmic reticulum and variably shaped electron-dense inclusions consisting of myofibrillar streams. Another prominent feature was the existence of numerous nemaline rods within muscle fibres; these were stained red by Gomori's trichrome stain. Immunohistochemistry revealed that the nemaline rods showed strong immunoreactivity with α-actinin and desmin antibodies. Electron microscopically, these structures were composed of dense-homogeneous material and continuous with the Z disk. The case was diagnosed as centronuclear myopathy with increased nemaline rods.

Sphingosylphosphorylcholine induces α-smooth muscle actin expression in human lung fibroblasts and fibroblast-mediated gel contraction via S1P2 receptor and Rho/Rho-kinase pathway.

Chronic airway diseases like COPD and asthma are usually accompanied with airway fibrosis. Myofibroblasts, which are characterized by expression of smooth muscle actin (α-SMA), play an important role in a variety of developmental and pathological processes, including fibrosis and wound healing. Sphingosylphosphorylcholine (SPC), a sphingolipid metabolite, has been implicated in many physiological and pathological conditions. The current study tested the hypothesis that SPC may modulate tissue remodeling by affecting the expression of α-SMA in human fetal lung fibroblast (HFL-1) and fibroblast mediated gel contraction. The results show that SPC stimulates α-SMA expression in HFL-1 and augments HFL-1 mediated collagen gel contraction in a time- and concentration-dependent manner. The α-SMA protein expression and fibroblast gel contraction induced by SPC was not blocked by TGF-ß1 neutralizing antibody. However, it was significantly blocked by S1P2 receptor antagonist JTE-013, the Rho-specific inhibitor C3 exoenzyme, and a Rho-kinase inhibitor Y-27632. These findings suggest that SPC stimulates α-SMA protein expression and HFL-1 mediated collagen gel contraction via S1P2 receptor and Rho/Rho kinase pathway, and by which mechanism, SPC may be involved in lung tissue remodeling.

Familial interstitial pneumonia in an adolescent boy with surfactant protein C gene (Y104H) mutation.

Recent studies have suggested that some cases of familial interstitial pneumonia are associated with mutations in the gene encoding surfactant protein C (SFTPC). We report here a case of familial interstitial pneumonia in an adolescent boy whose paternal grandfather and father suffered from idiopathic interstitial pneumonia (IIP). The patient was asymptomatic but showed an abnormal shadow in the chest at his medical check-up. The surgical biopsy of the patient revealed non-specific interstitial pneumonia and showed pathological findings similar to those in his father's autopsy. Genomic DNA from blood leucocytes of the patient was sequenced for the Thy104His (Y104H) SFTPC mutation. Based on these results, he was diagnosed with SFTPC mutation-associated familial interstitial pneumonia. There has been no clinical, physiologic and radiologic progression for 4 years since the diagnosis. The relation between clinical manifestation and the mutation site of the patient may broaden the spectrum of SFTPC mutation-associated interstitial pneumonia.

Resolution of D- and L-glucoses by chiral N-octyl-beta-D-glycoside-Cu(II) complex adsorbed at the gas/liquid interface of small bubbles.

A new technique of the jet drop method (JDM) was applied to a chiral molecular discrimination of optically active D- or L-glucose (guest) by chiral N-octyl-beta-D-glycoside (ObetaDG)-Cu(II) complex (host) at the gas/liquid interface of small bubbles. The discrimination of glucoses as the guests is possible using ObetaDG adsorbed at the gas/liquid interface of bubbles where it acts as the host, either in the presence or the absence of Cu(II) ions. In order to make clear the host-guest interaction at the gas/liquid interface, the composition of 5000 top jet drops periodically collected onto a slide glass receiver was analyzed. The relative concentration (eta(i)-1) and the surface excess amount, Gamma(i)(0) of species i such as D- and L-glucoses, and ObetaDG were determined as a function of bubble size, d(b) and bulk concentration C(b). The partition coefficient, Pi(i)=Gamma(i)(0)/C(b) was also evaluated for each component. The adsorption of these materials either in the presence or absence of Cu(II) ions, was assigned to the Freundlich type, and the discrimination of D- and L-glucoses with ObetaDG was evaluated in terms of the Freundlich constant, k(i) and 1/n. The discrimination ability of ObetaDG was also evaluated by determining the equilibrium constants, K(c) of complex formations for the respective glucoses in the presence and absence of Cu(II) ions. It was found that L-glucose can form a more stable complex with ObetaDG-Cu(II).

Statins inhibit matrix metalloproteinase release from human lung fibroblasts.

Pleiotropic effects of statins have been reported to include inhibition of matrix metalloproteinase (MMP) release from macrophages and endothelial cells. We evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodelling processes. Monolayer and three-dimensional (3D) collagen gel cultures of fibroblasts were used. Cytokines (tumour necrosis factor-alpha and interleukin-1alpha) were used to induce MMP release and mRNA expression. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. Atorvastatin inhibited MMP-1 and -3 release and mRNA expression in both culture systems. Similar results were obtained with simvastatin and fluvastatin. In 3D cultures where cytokines also stimulated MMP-9 release, atorvastatin also inhibited MMP-9 release. In 3D cultures, cytokines together with NE induced collagen degradation, which was also inhibited by atorvastatin. The effect of atorvastatin was reversed by mevalonate and geranylgeranyl-pyrophosphate but not by farnesyl-pyrophosphate. The current data suggest that statins may modulate remodelling processes mediated by fibroblasts by inhibiting MMP release.

[Platelet activation in obstructive sleep apnea syndrome].

The incidences of cardiovascular and cerebrovascular diseases are reportedly higher in patients with obstructive sleep apnea (OSA) than in OSA-free subjects, though the mechanism remains unknown. Recently, the contribution of activated platelets to a number of pathological conditions such as stroke or ischemic heart disease has been suggested. We hypothesized that the expression of activated platelet markers resulting from OSA might be higher than in healthy subjects. By flow cytometry using monoclonal antibodies, we measured two such markers, PAC-1 and CD 62 P, in OSA patients and healthy subjects. Twelve healthy men (age, 52.7 +/- 12.8 y/o; and body mass index (BMI), 22.2 +/- 16.1 kg/m2; mean +/- S.D.) and 20 male patients with OSA (age, 50 +/- 7.96 y/o; BMI, 28.1 +/- 3.3 kg/m2; apnea hypopnea index (AHI), 38.2 +/- 21.2 times/hr; and lowest SpO2, 75.6 +/- 11.3%) were enrolled in this study. PAC-1 expression was significantly higher in OSA patients (65.1 +/- 17.8%) than in healthy subjects (16.8 +/- 7.4%), as was CD 62 P expression (8.5 +/- 8.8% vs. 0.88 +/- 0.57%). The increase in PAC-1 expression was correlated with AHI and the arousal index. These findings suggest that activated platelet markers could be good indicators for untreated OSA.

[Crescent moon-type tracheobronchial malacia alleviated by placement of stents in trachea and main bronchi].

We encountered a case of crescent-type tracheobronchomalacia in a 54-year-old male smoker. The patient experienced extreme obstructive pulmonary changes but his FVC and DLco findings were within the normal ranges. Plain chest X-ray films indicated tracheal narrowing, a diagnosis that was confirmed by fiberoptic bronchoscopy. Two Z-stents were implanted in the trachea but the patient's symptoms did not subside. Thoracic computed tomography (CT) elucidated stenosis of both main bronchi at end-expiration. The implantation of Z-stents in the main bronchi remarkably alleviated the symptoms and improved peak expiratory flow. Six months after implantation, the tracheal stents broke. A favorable course was obtained by inserting an ultraflex stent inside the broken Z-stents. DLco is important to the diagnosis of tracheobronchomalacia, whereas peak expiratory flow and thoracic CT findings are useful in evaluating the effectiveness of treatment. We concluded that ultraflex stents should be the first choice for treatment of tracheal stenosis, and that Z-stents are appropriate for the treatment of bronchial obstruction.

[A case of idiopathic tracheal stenosis].

A 44-year-old woman who had been treated for bronchial asthma for 5 years was admitted for further evaluation of progressive dyspnea. Physical examination revealed wheezing originating in the neck. A flow-volume curve suggested upper-airway stenosis. The patient had no history of trauma, endotracheal intubation, granulomatous diseases, or any other severe respiratory tract infections. Chest radiography and laboratory examination showed no abnormalities. Tracheal X-P, computed tomography and magnetic resonance imaging of the neck, and bronchoscopy demonstrated circumferential subglottic tracheal stenosis extending for 40 mm. The diameter of the lumen was 5 mm at its narrowest. The trachea distal to the lesion was normal. Bronchoscopic biopsy revealed thickened tracheal mucosa and submucosa with increased fibrous tissue and chronic inflammatory cell infiltration, suggesting a nonspecific inflammatory process. These findings are compatible with idiopathic tracheal stenosis, which was reported by Bhalla et al. The patient was treated with Nd-YAG laser surgery via a fiberoptic bronchoscope, which resulted in a great improvement in respiration. Regression of the lesion has not occurred in the 40 months since the laser surgery. The majority of patients with this condition have been treated by surgical resection of the stenotic lesion and reconstruction. However, the success of Nd-YAG laser surgery in the present case suggests that this approach would be a satisfactory alternative procedure for treatment of idiopathic tracheal stenosis.

Rapid response to inhaled frusemide in severe acute asthma with hypercapnia.

We report 7 patients with severe acute asthma unresponsive to standard medication, including sympathomimetic agents, aminophylline and corticosteroids, who responded to inhaled frusemide. All were hypercapneic with a mean PaCO2 of 7.7 kPa (57.7 mm Hg) [range 6.2-8.8 kPa (46.2-66.3 mm Hg)]. Following nebulization of 20 mg frusemide, clinical response was rapid, and the mean PaCO2 fell significantly to 5.4 kPa (40.6 mm Hg) [range 5.0-6.2 kPa (37.5-46.5 mm Hg)] within 20-60 min. No adverse effect was recognized. Inhaled frusemide should be considered for treatment of acute asthma refractory to conventional therapy.

Pyridoxal 5'-phosphate binds to a lysine residue in the adenosine 3'-phosphate 5'-phosphosulfate recognition site of glycolipid sulfotransferase from human renal cancer cells.

In the course of characterization of glycolipid sulfotransferase from human renal cancer cells, the manner of inhibition of sulfotransferase activity with pyridoxal 5'-phosphate was investigated. Incubation of a partially purified sulfotransferase preparation with pyridoxal 5'-phosphate followed by reduction with NaBH4 resulted in an irreversible inactivation of the enzyme. When adenosine 3'-phosphate 5'-phosphosulfate was coincubated with pyridoxal 5'-phosphate, the enzyme was protected against this inactivation. Furthermore, pyridoxal 5'-phosphate was found to behave as a competitive inhibitor with respect to adenosine 3'-phosphate 5'-phosphosulfate with a Ki value of 287 microM. These results suggest that pyridoxal 5'-phosphate modified a lysine residue in the adenosine 3'-phosphate 5'-phosphosulfate-recognizing site of the sulfotransferase.

[Efficacy and assessment of patient education as related to morbidity from asthma].

Asthmatic patients are sometimes ignorant of their treatment and of the pathophysiology of their disease. In such patients, anxiety about the disease may worsen their condition. We studied the effects of an educational program for bronchial asthma. In 45 patients, the Severity of Asthma Scores before and after the program were measured. Sixty percent of the patients were assessed as "improved". On self-administered questionnaires concerned with asthma, most of the patients indicated that the program significantly improved their condition, reduced apprehension about the disease, and increased their trust in the hospital. In 24 patients, three psychological tests were done. Results of the comprehensive asthma inventory indicated that the program was useful for dependent and self-disciplined patients, but was not useful for resigned and depressed patients. The Y-G test showed that most of the patients who were helped by the program were introverted. Results of the Edwards Personal Preference Schedule revealed a difference in desire between the group that benefitted from the program and the group that did not. These results suggest that each group had a certain inclination toward psychogenic symptoms. Therefore, psychological tests are useful for predicting the effects of education. In conclusion, educational programs for patients with bronchial asthma may affect morbidity from asthma. Possible mechanisms include relief of anxiety about the disease and improvement in the patient's compliance with prescribed therapy.

Ocular findings in patients with autosomal dominant retinitis pigmentosa and transversion mutation in codon 244 (Asn244Lys) of the peripherin/RDS gene.

OBJECTIVE: To identify phenotypic characteristics of a certain mutation in the peripherin/RDS gene. DESIGN: Case reports with clinical features and results of fluorescein angiography, electroretinography, kinetic visual field testing, dark adaptometry, and DNA analysis. SETTING: University medical center. PATIENTS: We studied the ocular findings in eight members of a Japanese family with autosomal dominant retinitis pigmentosa and cytosine-to-adenine transversion at the third nucleotide in codon 244 of the peripherin/RDS gene. This mutation resulted in a substitution of lysine for asparagine in amino acid 244 of peripherin/RDS, a photoreceptor-specific glycoprotein. RESULTS: Clinical findings of each affected member in this family showed a marked intrafamilial similarity, which may provide the natural course of the phenotype produced by the Asn244Lys mutation. Characteristic features include diffuse pigmentary retinal degeneration in the midperipheral and peripheral fundi associated with macular degeneration in the later stage, starting with bull's-eye maculopathy, and severely deteriorated electroretinographic findings in both rods and cones, even in the early stage. CONCLUSION: The mutation at codon 244 of the peripherin/RDS gene causes both rod and cone degeneration, although the precise mechanism of retinal degeneration is currently unknown.

Changes in diaphragmatic EMG activity during sleep in space.

It remains unknown how increased upper airway resistance (UAR) during sleep could be a function of gravity. We therefore conducted quantitative evaluation of the gravitational influence on diaphragmatic EMG activity (EMGdi) in an astronaut to estimate the effect of UAR in space. EMGdi was recorded by paired surface electrodes on the ground (control, C) and abroad a short-term space mission (space, S) for 30 consecutive h. Mean EMGdi recorded during quiet breathing in wakefulness was assigned the value of 100. EMGdi in C was significantly enhanced in all sleep stages compared with that while awake in the supine position (mean +/- SD, 230 +/- 23.2% in non-rapid eye movement (non-REM) Stage II, 233 +/- 13.8 in slow-wave sleep, and 233 +/- 40.0 in REM sleep versus 100 +/- 17.3 in wakefulness, p < 0.001). In contrast, there was no statistical difference in EMGdi in S between awake and any non-REM sleep stage (mean +/- SD, 100 +/- 20.5% in wakefulness versus 103 +/- 16.9 in non-REM Stage II and 100 +/- 14.8 in slow-wave sleep; NS). However, EMGdi in REM sleep in S was statistically greater (132 +/- 28.3%) than that during wakefulness or any other sleep stage in space (p < 0.001). Therefore, gravity may play a much more significant role in the normal healthy human in the increased upper airway resistance during sleep than the relative atonia of the upper airway muscles.

[Successful treatment of diaphragm pacing-induced obstructive sleep apnea syndrome with nasal CPAP].

We report a 71-year-old female patient with primary alveolar hypoventilation syndrome who received diaphragm pacing (DP) and developed obstructive sleep apnea syndrome (OSAS). Application of nCPAP markedly improved her nocturnal hypoxemia. The monitored polygrams before and after the application strongly suggested that the main mechanism of OSAS was an imbalance of activity between upper airway dilator muscles and pump muscles. Moreover, paradoxical movement of the rib cage is not necessarily due to upper airway obstruction. Monitoring of tidal volume and arterial oxygen saturation is essential for the diagnosis of DP-induced OSAS.