A 44,000 glycoprotein is involved in the attachment of echovirus-11 onto susceptible cells.

Cellular receptors play an important role in viral pathogenesis. Until now little was known on echovirus (EV) receptor. Using detergent-treated KB cell extracts as immunogen, a mouse monoclonal antibody (Mab 143) was produced that selectively blocks the attachment of EV-11 to KB and other susceptible cells. By immunoblotting, Mab 143 detected a 44,000 protein on susceptible cell lines but not on cell lines from nonprimate origin. The receptor protein complex, purified from KB cell membranes by immunoaffinity using Mab 143 as ligand, was shown to contain a single glycoprotein with apparent molecular weight of 44,000 (gp44). The role of gp44 in the attachment of EV-11 onto KB cells was demonstrated by the ability (i) of affinity-purified gp44 to reduce the infectivity of EV-11 and (ii) of rabbit polyclonal antisera raised against gp44 to protect cells from the replication of various EV, as did Mab 143.     

Detection of neutralizing IgM antibodies in the diagnosis of enterovirus infections

Data are presented of IgM detection by a neutralization test used routinely in 1,062 patients. Antigens isolated during the period of investigation were EV4, EV7, EV11, EV18, EV21, EV24, EV33, CA9, CB2, CB4, and CB5. No difference was observed in the distribution of IgM-positive sera according to age and sex. Total antibodies are at higher titres when IgM antibodies are present. Polytypic IgM responses are not frequent (less than 10%). The frequency of the IgM-positive sera for a given serotype correlated with the frequency of isolates for the serotype except for CA9. Other than for babies under age 6 months, IgM detection is more frequent than is isolation. The susceptibility of the elderly and the frequency of IgM-positive sera among adults over age 40 years suggests possible underestimation of enterovirus infections in adults. The duration of IgM remains a major question.     

Autonomic and peripheral nerve function in early diabetic neuropathy. Possible influence of a novel aldose reductase inhibitor on autonomic function

Autonomic and peripheral nerve functions as well as the possible short-term effect of a novel aldose reductase inhibitor (ARI) on neuropathy were evaluated in 30 male type I diabetics (age 25-44 years, mean 34; duration of diabetes 10-20 years, mean 34) with neurographic signs of peripheral neuropathy (PN). Autonomic neuropathy (AN) was established by the heart rate reactions to deep breathing (E/I ratio = vagal function) and to tilt (acceleration index = sympathetic and vagal functions; the brake index = vagal function). Twenty-nine patients, 13 with AN, completed the study. Among neurographic variables, only sural nerve function tests correlated with autonomic functions. Patients with AN showed significantly lower mean sensory action potential amplitudes (SAPA) sural, indicating axonal losses, than patients without AN (3.58 +/- 0.79 microV v. 7.34 +/- 1.12 microV; p less than 0.01). PN as measured by neurography did not improve during ARI treatment. On the other hand, vagal function (brake indices) improved (p less than 0.05) during ARI in AN patients.     

Pneumococcus observatory data in the Rhône-Alps region. Results from 1996

Throughout 1996, 22 hospital-based laboratories in the Rh?ne-Alpes region of France collected pneumococcal strains and used a standardized protocol to record the following data; patient age and sex; type of specimen; and determination of susceptibility to at least the following antibiotics: oxacillin 1 microgram and 5 micrograms, erythromycin (Ery), tetracycline (Tet), chloramphenicol (Chl), rifampin (Rmp), and loracarbef. For penicillin-nonsusceptible strains (PNSSs), which were identified based on results with oxacillin, MICs for penicillin G, amoxicillin (Amx), and cefotaxime (Ctx) were determined using the E Test, at the study site and agar dilution at the coordinating center. Of the 1153 strains, 65.5% were from adults and 31.8% from children; patient age was unknown in 2.7% of cases. PNSPs (MIC > 0.06 mg/l) contributed 32.9% of strains (I: 23.3%; R: 9.6%) and were more common in children (41.1%) than in adults (28.1%). The frequency of PNSSs varied across specimen types: 27.9% in blood cultures (305 strains), 15.6% in cerebrospinal fluid (32), 38.7% in protected bronchopulmonary specimens (31), 31.5% in unprotected bronchopulmonary specimens (434), 50.8% in acute otitis media (118), and 34.4% in other specimens (221). Among PNSSs, nonsusceptibility (I + R) to other antibiotics was variable: Ery, 62.1%; Tet, 41.5%; Chl, 40.4%; Rmp, 1.1%. Corresponding figures for the overall strain population were Ery, 33.3%; Tet, 22.7%; Chl, 22.8%; Rmp, 0.9%. In addition, 56.5% of PNSSs exhibited multiple drug resistance. Resistance to amoxicillin (MIC > 2 mg/l) was demonstrated for only 5 strains. No strains were resistant to loracarbef or cefotaxime. Serotypes of the 379 PNSSs were as follows: 23F, 26.6%; 14 (25.6%); 9V (18.2%), 6 (8.7%), 15 (5%), 19 (4.5%).     

The vigilance-promoting drug modafinil counteracts the reduction of tyrosine hydroxylase immunoreactivity and of dopamine stores in nigrostriatal dopamine neurons in the male rat after a partial transection of the dopamine pathway

We studied the ability of the vigilance-promoting drug modafinil to modulate the anterograde and retrograde changes in tyrosine hydroxylase (TH) immunoreactivity and in dopamine (DA) stores in the nigro-neostriatal DA neurons, following a partial hemitransection of this ascending DA system, using a combined morphometrical, biochemical and behavioural analysis. Modafinil was given daily i.p. in doses of 10–100 mg/kg, starting 15 min after the lesion, and the partially hemitransected rats were killed 2 weeks later. Changes in TH-immunoreactive nerve cell bodies and nerve terminals induced by the partial hemitransection were studied in the substantia nigra and neostriatum in combination with image analysis. The substantia nigra and neostriatum were also subjected to biochemical analysis of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels. Modafinil treatment dose-dependently (10–100 mg/kg) counteracted the hemitransection-induced disappearance of nigral TH-immunoreactive nerve cell body profiles and neostriatal TH-immunoreactive nerve terminal profiles. A 2-week treatment with 100 mg/kg of modafinil also counteracted the hemitransection-induced depletion of DA stores in the neostriatum and the ventral midbrain. Moreover, the repeated daily treatment with modafinil (100 mg/kg) protected against the hemitransection-induced disappearance of striatal 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and noradrenaline levels. Striatal DA function was analysed by studying apomorphine-induced (1 mg/kg, s.c.) ipsilateral rotational behaviour 4 and 11 days after the operation. A marked dose-dependent reduction of ipsilateral rotational behaviour was demonstrated after the daily modafinil treatment in the partially hemitransected rats. In another model involving unilateral nigral microinjections of 6-hydroxydopamine, acute (one single dose) modafinil (100 mg/kg) did not affect the contralateral rotational behaviour induced by apomorphine (0.05 mg/kg s.c.), when given 30 min before the apomorphine. Taken together, morphological, neurochemical and behavioural evidence has been obtained that anterograde and retrograde changes induced in the DA stores and TH immunoreactivity of the nigro-neostriatal DA neurons by a partial hemitransection are counteracted by modafinil in a dose dependent way with 100 mg/kg producing a significant protective action against impairment of DA transmission. The results of this study open up the possibility that modafinil may protect against the anterograde and retrograde degeneration of nigrostriatal DA neurons seen after mechanically induced injury.     

Identification of a new locus for autosomal dominant non-syndromic hearing impairment (DFNA7) in a large Norwegian family

Hereditary hearing impairment affects about 1 in 1000 newborns. In most cases hearing loss is non-syndromic with no other clinical features, while in other families deafness is associated with specific clinical abnormalities. Analysis of large families with non-syndromic and syndromic deafness have been used to identify genes or gene locations that cause hearing impairment. The present report describes a large Norwegian family with autosomal dominant non-syndromic, progressive high tone hearing loss with linkage to 1q21-q23. A maximum LOD score of 7.65 (theta = 0.00) was obtained with the microsatellite marker D1S196. Analysis of recombinant individuals maps the deafness gene (DFNA7) to a 22 cM region between D1S104 and D1S466. The region contains several attractive candidate genes. This report supports the idea of extensive genetic heterogeneity in hereditary hearing impairment and represents the first localization of a deafness gene in a Norwegian family.      

Monoclonal antibodies against Vibrio cholerae lipopolysaccharide.

A cell line producing monoclonal antibodies directed against the core region of Vibrio cholerae lipopolysaccharide has been established. These antibodies were inhibited by lipopolysaccharide preparations of both O-group 1 vibrios and some non-O-group 1 vibrios as detected in enzyme-linked immunosorbent assay-inhibition experiments. Coagglutination experiments with monoclonal and polyclonal antibodies adsorbed to protein A-carrying staphylococci were performed. All V. cholerae strains tested, regardless of serotype, were agglutinated when mixed with staphylococci coated with the monoclonal antibodies, whereas staphylococci coated with group-specific (O1) polyclonal antibodies only agglutinated with O-group 1 vibrios.     

Respiratory mortality among firefighters.

Although firefighters have been shown in some studies to suffer chronic respiratory morbidity from their occupational exposures, an increased risk for dying from non-malignant respiratory diseases has not been documented in any previous retrospective cohort mortality study. In order to assess the possibility that an unusually strong "healthy worker effect" among firefighters might mask this increased risk, a mortality analysis of firefighters was carried out in three cities in relation to the United States population and also to a comparison cohort of police officers. The firefighters were employed between 1945 and 1980 and experienced 886 deaths by 1 January 1984; compared with the United States population they had a significantly reduced risk of dying from all causes (SMR = 82, 95% confidence interval, 77-87), and from non-malignant circulatory diseases (SMR = 81, 95% confidence interval 73-89), but no significant difference in risk of non-malignant respiratory diseases (SMR = 88, 95% confidence interval 66-117). Compared with police, the firefighters experienced a trend toward improved mortality outcomes for all causes investigated (SMR = 82), but they had an excess of deaths from non-malignant respiratory diseases (SMR = 141). The results indicate that firefighters are probably at increased risk for dying from non-malignant respiratory diseases; this increased risk may have been missed in previous studies because of the limitations of using a general reference population.     

Abnormal sweat test in patient with Diabetes Insipidus unresponsive to ADH

Increased sweat concentrations (92, 76 and 80 mEq/l) were observed in a 7-year-old boy with pitressin-resistant diabetes insipidus. All previous observations of elevated sweat electrolytes in diabetes insipidus have been in infants less than 10 months of age. The sweat test is an exceptionally reliable, sensitive and specific test for the diagnosis of Cystic Fibrosis. Pitressin-resistant diabetes insipidus is one of the diseases associated with elevated sweat test results.