Cell fusion induced by scrapie and Creutzfeldt-Jakob virus-infected brain preparations.

Cell fusion was induced by brain extracts containing the scrapie virus and the virus of Creutzfeldt-Jakob disease. The assay involved quantitation of colony-forming ability in a double selection system, strandardized against fusion induced by Sendai virus. Correlation between the logarithm of virus dilution and the hybrid colony number gave similar curves for scrapie virus and Sendai virus. Fusion induction may explain some aspects of pathogenesis in these diseases and provide a potential in vitro assay.     

Monoclonal antibody specific for myelin glycoprotein P0: derivation and characterization.

A monoclonal antibody was produced against the major structural glycoprotein (P0) of human peripheral nervous system myelin. The hybridomas were generated by fusion of mouse myeloma line NS-1 with spleen cells of C3H mice immunized with purified human peripheral nervous system myelin. Hybridomas were screened by a two-step solid-phase radioimmunoassay, with P0 adsorbed on microtiter plates and with addition of 125I-labeled rabbit anti-mouse IgG as the second step. One derived clone, designated 41G10, bound P0 in the radioimmunoassay 4-fold over the background value obtained by using bovine serum albumin as the negative control antigen. Clone 41G10 was shown by immunofluorescence to bind to frozen sections of human intercostal nerve. Diffuse fluorescent staining occurred uniformly over the entire myelin sheath. The cylindrical axons were unstained. The same pattern of immunofluorescence was noted on rat, hamster, mouse, and rabbit sciatic nerve. Immunofluorescence was abolished when 41G10 was absorbed by P0. The monoclonal antibody 41G10 was absorbed by P0. The monoclonal antibody 41G10 is of the IgM class and activated complement in the presence of myelin vesicles or P0 liposomes but not in their absence.     

Creutzfeldt-Jakob disease: possible medical risk factors

To explore possible risk factors in the past medical history of patients with Creutzfeldt-Jakob disease (CJD), we conducted a case-control study among 26 cases and 40 matched controls. Statistically significant odds ratios were obtained for intraocular pressure testing; injury to or surgery on the head, face or neck; and trauma to other parts of the body. The odds ratios were nearly significant for head trauma and procedures requiring sutures. These data suggest that the CJD agent may be acquired by inoculation through injury or during surgery, and perhaps on certain absorbable sutures of animal origin. The tonometer used for glaucoma testing may also be a vehicle of transmission.     

Creutzfeldt-Jakob disease in France: II. Clinical characteristics of 124 consecutive verified cases during the decade 1968--1977.

One hundred twenty-four consecutive cases of Creutzfeldt-Jakob disease (CJD) in France, verified by biopsy or autopsy between 1968 and 1977, were analyzed with respect to their clinical characteristics. The series comprised equal numbers of men and women, with the most frequent age at onset being 60 to 64 years and the most frequent duration, two to three months. A prodromal illness was observed in more than one-third of the patients. Clinical presentations and symptom frequencies are tabulated, and a multifactor analysis has been performed to obtain those combinations of symptoms and signs which occurred at least as often as the triad of dementia, myoclonus, and a positive electroencephalogram. Two groups of atypical cases are also emphasized: one with sudden, strokelike presentation and rapidly evolving illness of less than 2 months' duration, and the other with a long clinical course of between 2 and 10 years.     

Disappearance of high-incidence amyotrophic lateral sclerosis and parkinsonism-dementia on Guam

The high incidence rates of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) occurring among the Chamorros of Guam have declined to rates only slightly higher than those observed in the continental United States. This decline has occurred principally among males, especially those born after 1920 and living in areas where calcium and magnesium levels are low in soil and water. The male-to-female ratio among affected patients now approaches unity, compared with ratios of 2 to 1 for ALS and 3 to 1 for PD three decades ago. These changes are consistent with the hypothesis that the previously high incidence resulted from defects in mineral metabolism and secondary hyperparathyroidism, provoked by nutritional deficiencies of calcium and magnesium, with resultant deposition of calcium and aluminum in neurons.     

Creutzfeldt-Jacob disease in continental France. Retrospective study from 1968 to 1977]

During the decade 1968-1977, 170 cases of Creutzfeldt-Jakob disease were found in France. The clinical features of 124 neuropathologically-verified cases are summarized and a multi-factor analysis performed to obtain the most frequent combinations of signs and symptoms. Certain exceptional features are discussed. The annual mortality rate during this period was 0.32 cases per million for the whole of France, and 0.69 cases per million for the Paris metropolitan area. Preliminary totals for 1978 suggest that these figures may possibly be doubled, with 30-40 new cases occurring annually. No temporal-spatial clustering of cases was observed, and no contact between patients could be established, except for familial cases (9% of the total). No risk factors were identified; in particular, iatrogenic surgical or neurosurgical transmission did not occur, nor was any relationship apparent between CJD in man, and scrapie in sheep or goats. These data furnish a base of comparison for prospective studies in France, with a view towards discovering the natural mode of transmission of the virus of CJD.