Immunoreactivity of PMP-22, P0, and other 19 to 28 kDa glycoproteins in peripheral nerve myelin of mammals and fish with HNK1 and related antibodies

Mammalian peripheral nervous system (PNS) myelin contains several glycoproteins with molecular weights of 19 to 28 kDa, including the major 28 kDa P0 glycoprotein and a recently cloned protein called PMP-22. Some glycoproteins in this M(r) range in humans, cats and some other mammals react with HNK1, a mouse monoclonal antibody that identifies a carbohydrate epitope shared between the immune system and a number of adhesion proteins in the nervous system. A variety of antibodies to P0, PMP-22, and the carbohydrate determinants reacting with HNK1 were used to characterize immunochemically these 19 to 28 kDa glycoproteins of cat PNS myelin. The HNK1-reactive components include P0 and two slightly smaller 23 to 26 kDa proteins that are immunologically related to P0. However, HNK1 reacts most strongly with a lower molecular weight glycoprotein that does not react with the antibodies to P0 and was identified as PMP-22. Since the carbohydrate structure reacting with HNK1 is generally expressed on adhesion molecules, this result suggests that PMP-22 may function in cell-cell or membrane-membrane interactions. Furthermore, the related human anti-MAG monoclonal IgM antibodies from patients with neuropathy also react strongly with PMP-22, suggesting that it may be a target antigen in the pathogenesis of this disease. Purified PNS and CNS myelin from bony fish (toadfish and trout) were also shown to contain major glycoproteins, in the same 19 to 28 kDa M(r) range, that react very strongly with HNK1. It is shown that fish myelin has major proteins of this size that are immunologically and structurally related to mammalian P0, and it is demonstrated here that one of the strongly HNK1-positive proteins reacted well with an antiserum raised to bovine P0. The presence of high levels of the adhesion-related HNK1 epitope on these major myelin proteins of fish suggests that this carbohydrate structure may have played a role in the molecular evolution of myelin.     

Molecular analysis and genetic mapping of the rhodopsin gene in families with autosomal dominant retinitis pigmentosa

Eighty-eight patients/families with autosomal dominant retinitis pigmentosa (RP) were screened for rhodopsin mutations. Direct sequencing revealed 13 different mutations in a total of 14 (i.e., 16%) unrelated patients. Five of these mutations (T4K, Q28H, R135G, F220C, and C222R) have not been reported so far. In addition, multipoint linkage analysis was performed on two large families with autosomal dominant RP due to rhodopsin mutations by using five DNA probes from 3q21-q24. No tight linkage was found between the rhodopsin locus (RHO) and D3S47 (theta max = 0.08). By six-point analysis, RHO was localized in the region between D3S21 and D3S47, with a maximum lod score of 13.447 directly at D3S20.     

Preliminary report on videothoracoscopy in the evaluation and treatment of thoracic injury

A prospective trial of videothoracoscopy was conducted at an urban trauma center between February 1992 and February 1993 to determine the efficiency of this less invasive method of evaluation and treatment. Twenty-four consecutive patients with chest trauma (penetrating, n = 22; blunt, n = 2) were examined thoracoscopically for clotted hemothorax that otherwise would have been treated with thoracotomy (n = 9), suspected diaphragmatic injury (n = 10), and continued bleeding (n = 5). To ensure maximal exposure, general anesthesia with a double-lumen endotracheal tube was used in each patient. Clotted hemothorax was successfully evacuated in eight of nine patients (89%). Diaphragmatic laceration was suspected in 10 patients (2 abnormal chest radiographs, 8 proximity penetrating wounds) and confirmed thoracoscopically in 5. In four patients, diaphragmatic lacerations were successfully repaired with thoracoscopic techniques. Five patients underwent thoracoscopy for continued hemorrhage (greater than 1,500 mL per 24 hours) after tube thoracostomy. Intercostal artery injury was confirmed in all patients, and diathermy provided hemostasis in three patients without thoracotomy. No complications occurred. These data suggest the following: (1) Videothoracoscopy is an accurate, safe, and minimally invasive method for the assessment of diaphragmatic injuries, control of continued chest wall bleeding, and early evacuation of clotted hemothorax. (2) This technique should be used more frequently in patients with thoracic trauma. (3) Technical advances may expand the therapeutic role of thoracoscopy.     

Drug-resistant strains of Mycobacterium tuberculosis exhibit a range of virulence for mice

A panel of clinical isolates of Mycobacterium tuberculosis, several of which were resistant to one or more antimycobacterial drugs, were tested for their capacity to give rise to active disease following aerogenic infection of normal immunocompetent mice. The panel exhibited a range of virulence in this model, which followed no clear trend in terms of geographical source, degree of drug resistance, or rate of growth in vitro. Several isolates grew very quickly over the first 20 days in mouse lungs before being contained by emerging immunity. In view of this latter observation, we hypothesize that it is possible that such so-called fast growers may be responsible for the rapid fatality sometimes seen in immunocompromised patients with tuberculosis. Moreover, the results of the study do not support the belief that increased drug resistance usually associates with loss of virulence of the isolate.