Enterotoxigenic Escherichia coli in central Canada.

During epidemiological studies carried out in urban and rural areas of the midwestern Canadian province of Manitoba, we cultured enterotoxigenic Escherichia coli (ETEC) from 16 (1.7%) of 945 diarrheal stools and 4 (0.3%) of 1,282 normal stools. ETEC was found in not more than 2.3% of diarrheal stools obtained from any population during any season. Diarrhea associated with ETEC persisted for a mean of 9 days. Two children were dehydrated and required intravenous fluid therapy, and one adult suffered a cholera-like syndrome. Half of the children required hospitalization for management of their diarrhea. Two adults and two children who harbored ETEC were completely asymptomatic. The pattern of toxin production correlated with serotype and the serotypes encountered were (with a few exceptions) similar to those found in other areas. We conclude that ETEC is an uncommon cause of diarrhea, both in rural and urban areas of central Canada. However, the possibility that ETEC might cause severe sporadic cases or epidemics of gastroenteritis remains.     

Plasma immunoglobulin concentrations in twins

A study has been made of the similarity of concentrations of IgG, IgA and IgM in twins. The results provide evidence for the genetic control of all three immunoglobulins in adolescence, but in adults genetic control was demonstrable only for IgG in males. The findings suggest that although genetic factors regulating all classes of immunoglobulin levels in adults cannot be excluded by this study, if such factors do exist their effects are relatively small or are confined to certain individuals. This conclusion suggests that immunoglobulin concentrations in healthy adults will not form useful indices of future susceptibility to genetically determined diseases of immunity.     

Biology of Mouse Thymic Virus, a Herpesvirus of Mice, and the Antigenic Relationship to Mouse Cytomegalovirus

Mouse thymic virus (TA) is a herpesvirus which produces extensive necrosis of the thymus of newborn mice 7 to 14 days after infection. Infectious virus can be recovered from the thymus for only 10 days after infection, with highest titers occurring between days 5 and 7. In mice 5 days old or less, TA infects thymus cells and produces massive necrosis. TA also infects the salivary glands and persists as a chronic infection. Newborn mice infected with TA have no detectable humoral immune response. Infected adult mice respond, and humoral antibody is detected 7 days after infection. Titers are maintained for months thereafter. Regardless of the age of the mice inoculated with TA, persistent infection was established in the salivary glands, but no evidence for thymus involvement was observed when adults were infected. TA does not cross-react serologically by immunofluorescent, complement fixation, or virus neutralization tests with mouse cytomegalovirus; however, interestingly, the epidemiology of the two herpesviruses are similar. Both mouse cytomegalovirus and TA were isolated from the same animals in populations of laboratory and wild mice. Evidence of infection with mouse cytomegalovirus and TA were most apparent by virus isolations, since humoral antibody responses are rarely observed. All strains of mice tested were susceptible to TA infection. However, in some strains maximum necrosis occurred at 7 days, compared with 10 to 14 days for other strains. The difference in age susceptibility and the target tissue of thymus in newborn mice suggests that TA is a model herpesvirus for studying the effects of viral infections on humoral and cell-mediated immunological functions.     

Detection of N-myc gene amplification by fluorescence in situ hybridization. Diagnostic utility for neuroblastoma.

We assessed fluorescence in situ hybridization (FISH) as an alternative to Southern blot analysis for determination of N-myc gene amplification in neuroblastoma. In the 44 pediatric solid tumor cell lines examined (20 neuroblastomas), the mean number of N-myc copies determined by FISH correlated closely with Southern blot results. There was wide intercellular variability in gene copy number in tumors that had evidence of amplification; however, tumors judged to be non-amplified completely lacked any cells with high N-myc copy number. FISH provided reliable estimates of N-myc amplification in 12 clinical samples even when the percentage of tumor was low. The other advantages of FISH over Southern blot analysis were speed and technical simplicity, ability to discern heterogeneous gene amplification among tumor cells in the same specimen, and capacity to determine the source of the amplified N-myc signal, whether extrachromosomal double-minute chromosomes, expanded intrachromosomal regions, or chromosome 2 aneuploidy. We conclude that FISH would refine the analysis of N-myc amplification in neuroblastoma and thus improve the assignment of patients to prognostic groups based on this unfavorable risk factor.     

Plasmodium falciparum rosetting is associated with malaria severity in Kenya.

Rosette formation in 154 fresh Plasmodium falciparum isolates from Kenyan children with mild (n = 54), moderate (n = 64), or severe (n = 36) malaria was studied to determine whether the ability to form rosettes in vitro is correlated with malaria severity. There was a wide distribution of rosette frequencies within each clinical category; however, a clear trend towards higher rosette frequency with increasing severity of disease was seen, with the median rosette frequency of the mild-malaria group (1%; range, 0 to 82%) being significantly lower than those of the moderate-malaria group (5%; range, 0 to 45%; Mann-Whitney U test, P < 0.02) and the severe-malaria group (7%; range, 0 to 97%; Mann-Whitney U test, P < 0.003). Within the severe-malaria category there was no difference in rosetting among isolates from cerebral malaria patients or those with other forms of severe malaria. We also examined the ABO blood groups of the patients from whom isolates were obtained and found that isolates from group O patients (median rosette frequency, 2%; range 0 to 45%) rosetted less well than those from group A (median, 7%; range 0 to 82%; Mann-Whitney U test, P < 0.01) or group AB (median, 11%; range 0 to 94%; Mann-Whitney U test, P < 0.03). We therefore confirm that rosetting is associated with severe malaria and provide further evidence that rosetting is influenced by ABO blood group type. Whether rosetting itself plays a direct role in the pathogenesis of severe malaria or is a marker for some other causal factor remains unknown.     

Antigenic relationships between the enteroinvasive Escherichia coli O antigens O28ac, O112ac, O124, O136, O143, O144, O152, and O164 and Shigella O antigens

Enteroinvasive Escherichia coli strains have been found in the following O serogroups: O28ac, O112ac, O124, O136, O143, O144, O152, and O164. The biochemical reactions of these enteroinvasive E. coli strains are often similar to those of Shigella strains, and identification may be difficult. The problem of differentiation and identification is further complicated by the sharing of antigenic components. The antigenic relationships between these O antigens and those of all the established and provisional Shigella serovars were examined. O antigen identity was demonstrated between E. coli O124 and Shigella dysenteriae 3 and between E. coli O152 and provisional Shigella serovar 3341:55. Reciprocal relationships were found between E. coli O112ac and S. dysenteriae 2, S. boydii 1, S. boydii 15, between E. coli O136 and S. dysenteriae 3, and between E. coli O164 and S. dysenteriae 3. A one-way relationship was demonstrated between E. coli O136 and S. boydii 1. The remaining enteroinvasive E. coli O serogroups showed no significant antigenic relationships with any Shigella serovar.     

Potassium homeostasis during hyperinsulinemia: effect of insulin level, beta-blockade, and age

The euglycemic glucose clamp technique was used to evaluate the influence of level and duration of hyperinsulinemia, presence of beta-adrenergic blockade, and subject age on insulin-mediated changes in plasma potassium. In 16 young subjects, 2-h insulin infusions at 20 (n = 6), 80 (n = 13), and 200 (n = 8) mU.m-2.min-1 resulted in dose-dependent declines in plasma potassium (P less than 0.001 at all doses) during the 1st h. During the 2nd h plasma potassium declined during the 20 mU.m-2.m-1 infusions, was stable during the 80 mU.m-2.m-1 infusions, and rose slightly during the 200 mU.m-2.min-1 infusions. There was a significant reciprocal relationship between the changes in plasma potassium during the 1st and 2nd h of study (r = 0.99, P less than 0.01). During 4-h infusions (80 mU.m-2.min-1, n = 6) plasma potassium declined during the first 90 min (p less than 0.001) and rose thereafter until the end of the infusion (P less than 0.05). Studies with and without propranolol infusion at two insulin dose levels (20 and 80 mU.m-2.min-1) in six young subjects showed no effect of beta-blockade, and studies at three insulin dose levels [20 (n = 5), 80 (n = 6), and 200 (n = 6) mU.m-2.min-1 in 10 older males (63-77 yr] showed no effect of age on the changes in plasma potassium during hyperinsulinemia. These results suggest the presence of a regulatory mechanism influencing insulin-mediated alterations in plasma potassium. This mechanism appears uninfluenced by age or beta-adrenergic blockade.