Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis

During the last 10 years, we have demonstrated morphological and biochemical abnormalities of skin extracellular matrices in amyotrophic lateral sclerosis (ALS). However, currently little is known concerning collagen of the spinal cord in ALS. We measured the amount of collagen and characterized collagen at light and electron microscopic levels in posterior funiculus, posterior half of lateral funiculus and anterior horn of cervical enlargement of the spinal cord obtained from ten patients with ALS, 11 patients with other neurologic diseases (control group A), and ten patients without neurologic ones (control group B). In posterior half of lateral funiculus and anterior horn, (1) by light microscopy, there was no significant difference in vessel wall area between ALS patients and control groups A and B; (2) ultrastructurally, collagen bundles were more fragmented and widely separated, and the fibrils were randomly oriented in the perivascular space of capillaries in ALS patients, which were not observed in any areas of control groups or in posterior funiculus of ALS patients; and (3) the collagen contents in ALS were significantly lower (P<0.001 and P<0.001, respectively) than those in control groups A and B. Fragmented and widely separated collagen bundles in the interstitial tissue surrounding capillaries and markedly decreased amount of collagen in posterior half of lateral funiculus and in anterior horn of ALS could be related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS, that is, selective neuronal vulnerability in ALS.     

Nebivolol induces endothelium-dependent relaxations of canine coronary arteries.

Nebivolol is a new beta 1-antagonist that acutely reduces arterial blood pressure without depressing cardiac function. The present study was designed to determine the effect of nebivolol on coronary arteries. Rings of canine left anterior descending coronary (LAD) artery with or without endothelium were suspended in organ chambers and the isometric tension was recorded. In some experiments, the transmembrane potential of the smooth muscle cells was recorded by electrophysiological methods. During contractions to prostaglandin F2 alpha, nebivolol induced concentration-dependent relaxations of the coronary arteries. The enantiomer, l-nebivolol, also induced comparable relaxations; however, d-nebivolol induced smaller relaxations. The relaxations induced by nebivolol and its enantiomer were significantly larger in tissues with than in those without endothelium. The differences between tissues with and without endothelium were abolished by nitro-L-arginine (3 x 10(-5) M) or methylene blue (10(-5) M). The nebivolol-induced relaxations were not affected by indomethacin (10(-5) M), phentolamine (5 x 10(-6) M), propranolol (5 x 10(-6) M), or methysergide (3 x 10(-6) M). Nebivolol at a subthreshold concentration for inducing relaxation (3 x 10(-7) M) did not significantly affect endothelium-dependent relaxations to acetylcholine but potentiated ADP-induced endothelium-dependent relaxations. The potentiation is stereoselective for l-nebivolol. Nebivolol induced a small hyperpolarization of the coronary smooth muscle with endothelium (1 mV).(ABSTRACT TRUNCATED AT 250 WORDS)     

AMP deaminase activity of skeletal muscle in neuromuscular disorders in childhood. Histochemical and biochemical studies

We studied the histochemical staining and biochemical activity of AMP deaminase in biopsied muscle in Becker-type muscular dystrophy (BMD), Fukuyama-type congenital muscular dystrophy (FCMD), Duchenne-type muscular dystrophy (DMD), Werdnig-Hoffmann disease (WH) in order to elucidate the change of AMP deaminase activity in muscle with neuromuscular disorders in childhood. The intensity of AMP deaminase staining did not decrease in BMD with mild pathologic change, but in DMD, FCMD and WH it decreased in parallel with the severity of the pathologic change. The biochemical activity of AMP deaminase did not decrease in muscle with mild pathologic change in patients with DMD and tended to decrease according to the progress of the disease. The activity of AMP deaminase in muscle of patients with FCMD and WH which showed severe pathologic change was remarkably low. It was demonstrated that the decrease in the activity of AMP deaminase was related to the intensity of pathologic change rather than diagnosis of a neuromuscular disorder.     

Immunohistochemical localization and dynamics of paraquat in the stomach and esophagus of rats

Summary The dynamics of paraquat in the stomach and esophagus of rats were demonstrated using immunohistochemical techniques. The Rats were killed 3 h, 12 h, 24 h, 3 days, 7 days and 10 days after intravenous administration of paraquat. In the stomach, paraquat was localized in the epithelial cells between 24h and 10 days after injection, whereas in the esophagus, paraquat was localized in epithelial cells and the lamina propria mucosa between 12 h and 10 days after administration. Although these findings were similar to those observed in the intestine of rats, no clear changes in the distribution of paraquat with time were observed; suggesting that the stomach and esophagus are important reservoirs for the redistribution of paraquat.     

An Autopsy Case of Dermatomyositis with Rapidly Progressive Diffuse Alveolar Damage

A 47-year-old woman visited a clinic with dyspnea which had continued for two months and was followed by general fatigue and fever. Antibiotics were not effective. Edematous erythema occurred on her face, elbows, knees and feet, and she entered our hospital. A skin biopsy revealed interface dermatitis with severe edema and mucinosis in dermis. Diffuse bilateral infiltration was observed in the chest X-ray, and laboratory findings showed increased LDH, GPT, GOT and CPK. No antinuclear factor was detected. Her respiratory condition rapidly worsened, and she died eight days after hospitalization in spite of corticosteroid pulse therapy. The autopsy revealed that the main cause of death was diffuse alveolar damage (DAD). Interstitial pneumonia related to dermatomyositis is not histologically uniform; the response to the therapy depends on its histological type. The patients with dermatomyositis who have poor prognosis are clinically characterized by acute onset with general symptoms and less pronounced muscle weakness; they generally show DAD in their lungs. We need to establish a simple method for distinguishing histological types of interstitial pneumonia and adequate therapy for each one.     

The kinesin superfamily protein Rab6KIFL is not involved in the pathophysiology of Charcot-Marie-Tooth disease type 4C

Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive peripheral neuropathy reported in several Algerian families. The gene locus of this disease has been narrowed to 5q31-33. Recently, a missense mutation in the gene for the kinesin superfamily KIF1B was reported as the cause of Charcot Marie Tooth disease type 2A (CMT2A). We suspected that Rab6KIFL, one of the kinesin superfamily proteins, might be involved in the pathophysiology of CMT4C, because Rab6KIFL gene is located in 5q31. The coding regions of the Rab6KIFL gene of genomic DNA derived from one Algerian family with CMT4C were analyzed by direct sequencing. No mutation in Rab6KIFL gene was found in this family. Further investigation is necessary to identify the causative gene for CMT4C.     

Immunosuppressive effect of restraint stress on the initiation of allergic rhinitis in mice

BACKGROUND: Exposure to acute stressors modulates both innate and acquired immune function. However, little is known about whether stress has the potential to modulate the pathogenesis of allergic rhinitis. OBJECTIVES: To determine the effects of acute restraint stress on the initiation of allergic rhinitis in a murine model. METHODS: CBA/J mice were repeatedly intranasally sensitized with phospholipase A2 (PLA2) from honeybee venom without adjuvant. Restraint stress was applied using uniform cylinders once a week for a continuous 8-hour period, on five occasions in total. Production of PLA2-specific antibodies and degree of nasal and blood eosinophilia were compared between stressed and control mice. RESULTS: Repeated intranasal sensitization with PLA2 induced PLA2-specific IgE and marked eosinophilia in both the nose and blood in CBA/J mice. Exposure to restraint stress significantly inhibited production of PLA2-specific IgE, IgG1 and IgG2a. Conversely, the stress exerted no significant effect on eosinophilia. CONCLUSIONS: Exposure to acute restraint stress inhibits antigen-specific antibody production, but not local or systemic eosinophilia. The results of this study suggest that acute stress has the potential to modulate the initiation of allergic rhinitis.     

Mutational screening of APP gene in patients with early-onset Alzheimer disease utilizing mismatched PCR-RFLP

To elucidate the frequency of mutations of the β/A4 amyloid protein precursor (APP) gene in early-onset Alzheimer disease, we designed a mismatched PCR-RFLP that can identify all kinds of missense mutations at codon 717 in addition to the seven kinds of known mutations at exon 17. When we screened mutations at exon 17 utilizing this method and the double missense mutations at exon 16 of the APP gene by PCR-RFLP, no cases revealed mutations of the APP gene among 13 familial and 54 sporadic cases, except one family (OS-1) that had previously been reported and used as a positive control of APP717(Val → Ile). Our results support the hypothesis that mutations in the APP gene are not major causes in early-onset Alzheimer disease.     

Cytoarchitectonic subdivisions of the parabrachial nucleus in the Japanese monkey (Macacus fuscatus) with special reference to spinoparabrachial fiber terminals

The cytoarchitectonic subnuclear organization of the parabrachial nucleus (PB) surrounding the brachium conjunctivum (BC) in the monkey was examined using the Nissl method and the anterograde axonal flow method. PB of the monkey could be divided into the following subnuclei: the dorsal area (DPBM) along the medial surface of the medial three-fourths of BC in the caudal half of medial PB (PBM), the ventral area (VPBM) along the medial surface of the lateral one-fourth of BC in the rostral two-thirds of PB, the ventrolateral part of lateral PB (PBL) lateral to BC throughout PB (EL), the ventral part of the rostral half of PBL ventral to EL (EXL), the medial part of middle PBL along the dorsal surface of BC (VL), the dorsal and lateral marginal part of PBL in the rostral two-thirds of PB (DL), the cell cluster in the dorsomedial part of the rostral half of PBL between VL and DL (CL), the dorsocentral part appearing at the level of root exit of the trochlear nerve between DL and CL and extending to the rostral end of PBL (IL), the area between DL and IL in the rostral one-seventh of PBL (SL), and K?lliker-Fuse nucleus (KF) ventral to EL and BC in the middle one-third of PB and lateral to the lateral pontine tegmentum. After the injection of biotinylated dextran amine into the upper cervical segments, labeled fibers terminated in each subdivision of PB with different densities; most heavily in IL, more heavily in DL and KF, moderately in EL and VPBM, and scarcely in the rest of PB. The present study demonstrated for the first time the subdivisions of PB in the monkey, which were essentially common to those of the rat based on the cytoarchictecture of PB and spinal fiber terminals in it.     

Different immunosuppresive effects of anti-red blood cell sera and their fractions obtained from various animal species

Sheep red cells (RC) were coupled with HSA by means of an HSA—anti-SRBC IgG conjugate. The coupled RC were used to prepare rosettes with spleen cells of mice immunized to HSA in Freund's complete adjuvant. The rosettes were fractionated on discontinuous Ficoll gradients and the rosette-rich and rosette-poor fractions were tested for ability to transfer adoptively secondary responsiveness to HSA. Efficiency of transfer was measured in terms of haemagglutination titres. Memory of HSA was shown to be associated with rosette-forming cells, i.e. with cells carrying receptors for HSA. Several parameters of the adoptive transfer system employed were studied. The HSA-coupled RC proved to be very efficient in stimulating secondary responses to HSA. High titres of haemagglutinating antibodies (up to 1/80,000) were obtained with 10 × 10⁶ spleen cells transferred and 2 × 10⁶ spleen cells consistently gave titres of the order of 1/10,000.