Elevated cytosolic calcium levels in human lymphocytes during surface virus infections.

Generalised metabolic and electrolyte disturbances are known to accompany both plasma and surface virus infections. We have investigated whether these infections could impair the transport of Ca2+ from cells under conditions of controlled concentrations of the energy substrate glucose. Thus, cytosolic calcium levels ([Ca2+]i) were measured in single isolated lymphocytes obtained from healthy volunteers or those suffering from coryza. Before making measurements using a Ca(2+)-sensitive fluorescent dye indo 1, we incubated lymphocytes in buffers containing 0 mM-, 5.6 mM- or 11.2 mM-[glucose]. We found that [Ca2+]i of lymphocytes obtained from the sick were significantly higher than those from healthy controls both at 0 mM and 5.6 mM-[glucose], and that [Ca2+]i was inversely related to the media glucose concentration for both groups. These results suggest a diminished capacity of cation pumping in viral infections, such as coryza, in relationship to the available glucose as energy substrate.

Factors in serum and cerebrospinal fluid from children with viral encephalopathies impair glucose transport.

Since glucose transport appears to be inhibited in viral infections, we looked for inhibitors in cerebrospinal fluid (CSF) and serum of children with febrile convulsions (FC) and Singapore syndrome (SS). When incubated with rat and human adipocytes both fluids from FCs inhibited the utilization of glucose supplied in the medium as exhibited by decreased synthesis of triglycerides. Sera in the acute stage of the illness were more inhibitory than those from convalescents. There was competition between 3-0 methyl glucose and the CSF factors suggesting competitive inhibition at the plasma membrane. This may be due to anti-idiotypic antibodies. The likelihood of a second inhibitor is suggested by (1) the inhibitory activity of the larger of two fractions (about 80,000 molecular weight, corresponding to albumin) obtained in gel filtration chromatography of pooled CSF and (2) failure to observe a decrease in inhibitory activity with recovery from SS following management with hyperglycaemia-producing infusions. These observations are consistent with glycated albumin as a possible factor. Further characterization is called for to ascertain the genesis of viral encephalopathies.

Accuracy of anorectal manometry in the diagnosis of Hirschsprung's disease.

The value of anorectal manometry as a diagnostic tool for Hirschsprung's disease (HD) was assessed in 50 children presenting with chronic constipation. Anorectal manometric studies and rectal biopsy were performed on all children. Biopsy specimens were stained with hematoxylin and eosin and serial sections were examined for ganglion cells. Forty-five children had concordant manometric and histologic results, 15 of whom were positive for HD and 30 negative. In five children, the results were discordant. Using histologic aganglionosis as the reference point for the final diagnosis of HD, the overall accuracy of anorectal manometry as a discriminative test was 90.0%. The sensitivity, specificity, and positive and negative predictive values of manometric studies for the diagnosis of HD were 0.79, 0.97, 0.94, and 0.88, respectively. Factors responsible for the inaccuracies of manometric studies are discussed.

The probable mechanisms of brain damage and epilepsy in febrile convulsions, Singapore syndrome and Reye's syndrome.

Current knowledge suggests integration of cerebral perfusion and metabolism as enabling normal neuronal function, and their pertubations explaining the brain damage of hypoxia, hypoglycaemia, hypoperfusion and status epilepticus. Similar mechanisms appear operative in the viral encephalopathies and cause psychomotor dysfunction and epilepsy. A transient inhibition of plasma membrane glucose transport is central to the understanding of the metabolic abnormalities of these encephalopathies, the ensuing cell energy crisis resulting from neuroglycopoenia being evidenced by electroencephalographic changes, lactic and ketoacidosis, hyperuricaemia and ionic aberrations. Failure of Na+ and Ca2+ pumps cause cerebral oedema and neuronal death respectively, the selective nature of the latter being due to alpha-adrenergic vasoconstriction. Management with hyperglycaemia-producing infusions and the judicious use of lactate and steroids can overcome the transport dysfunction and enable complete recovery. The temporal profile of the metabolic aberrations of febrile convulsions, which are the result of adaptation, provide a template supporting this mode of management of the severe encephalopathies.

Hyperpolarization and short-circuiting as mechanisms of seizure prevention following febrile convulsions.

Though children with febrile convulsions only have seizures in the early stage of a febrile illness and not later, these seizures have been attributed to the fever. We studied the serum electrolyte and metabolite profiles in the later stage to see if there were fuel responses resulting in electrophysiological changes which prevented further seizure activity. On admission there was intracellular glucose starvation, as evidenced by increased ketones and lactate, and the possibility of the failure of some electrolyte pumps, as suggested by hyperuricaemia (energy crisis) and decreased serum Na+, Cl- and Ca2+. However, there was adaptive hyperglycemia and decreased serum K+. It seems likely that the hyperglycemia, induced the uptake of K+ by neurones, enabling their repolarization and hyperpolarization, which prevented further seizure activity, while Cl- influx short-circuited depolarizing currents produced by Na+ influx. Studies during recovery showed a gradual return of the metabolic and electrolyte aberrations to normality, suggesting that the provision of energy through adaptation to the stress, enabled recovery of the aforementioned pumps.

Properdin factor B frequencies in four Asian populations.

The distribution of Properdin factor B (Bf) phenotypes and their gene frequencies were investigated in four Asian populations (Chinese, Filipino, Thai and Japanese). The frequency of the BfS phenotype in Filipinos (0.717) was significantly lower than that in Chinese (0.900) and Thai (0.889) (p less than 0.01), but not different from the Japanese (0.840). One variant, BfF 0.65 S, was identified in a Japanese subject. Thus, in the Asian populations studied, Bfs frequencies were high and the frequency of variants other than F and S were low.

Comparative studies on immunological characteristics of IDDM among Asian populations.

Very little information is available related to possible differences in immunological characteristics of IDDM among Asian populations, though it has been reported that IDDM is associated with Bw54-DR4 and B17-DR3 in Japanese and Chinese, respectively. There is virtually no report related to comparative studies on Bf-DM association among Asian populations, while Bf-DM association is reported to be stronger than HLA-DM association in Caucasians. In the present paper, the results of our studies on anti-thyroid antibodies (ATA) of IDDM in Japanese, Chinese and Filipinos are presented. In Japanese, the incidence of ATA positive was higher in IDDM with a duration of less than one year (35.7%) than that in the patients with a duration of one year or more (12.5%). But, there was no such a duration dependent decrease in the incidences of ATA among Chinese or Filipino IDDM. The frequency of BfSS in Filipinos is lower than in Japanese or Chinese. However, no association was found between Bf phenotypes and IDDM in Asian populations. These results indicate that autoimmunity is transient in Japanese IDDM, but persistent in Chinese and Filipinos, and that it is too early to postulate in general that Bf-IDDM association in general populations is stronger than HLA-IDDM association.