Polymorphism of apolipoprotein E influences levels of serum apolipoproteins E and B in the human neonate

To gain more insight into the genetic vs. environmental influence of the apoE phenotypes on plasma lipoprotein variation we studied human umbilical cord sera at birth. Apolipoprotein E genetic phenotypes were determined in 110 individuals by immunoblotting and shown to be identical to the adult human isoforms with six phenotypes present and occurring at a similar frequency as reported previously for the adult population in the same area. Total serum cholesterol and triglyceride levels were low in the neonates and did not differ significantly between apoE phenotypes. On the other hand as in the adult, levels of apoE and B differed significantly between the phenotypes. ApoE was highest in individuals with the epsilon 2 allele and lowest in individuals expressing apoE4, and vice versa for apoB. We conclude that apoE phenotypes in human umbilical cord blood serum are already associated with pronounced differences in apoE and B levels in the newborn. The study demonstrates that the association of apoE and apoB levels with the apoE polymorphism occurs independently of significant enteral nutrition in the relatively constant in utero environment.     

Blood polymorphonuclear dysfunction in patients with alcoholic cirrhosis

Polymorphonuclear leucocyte function was investigated in twenty patients with alcoholic cirrhosis and three patients with cryptogenic cirrhosis. Bacterial ingestion, oxygen-dependent bactericidal capacity, and chemotactic response were measured. Serum dependent abnormalities were common; they included deficiencies of ingestion and of all subsequent oxygen-dependent metabolic events (three patients), all oxygen-dependent metabolic events (one patient), cytochrome c reduction and iodination deficiencies (six patients), isolated cytochrome c reduction deficiency (ten patients), and chemotactic deficiencies (fourteen out of eighteen patients). Serum-independent abnormalities were much less common; they included increased ingestion rate (four patients), decreased stimulated reduction of nitroblue tetrazolium (three patients), and decreased myeloperoxidase content (eight patients). Polymorphonuclear leucocyte abnormalities are frequent in cirrhosis and may account in part for increased susceptibility to infection in that disease.     

Interactions Among DUI Offender Characteristics and Traditional Intervention Modalities: a long-term recidivism follow-up

Using long-term DUI (Driving Under the Influence of Alcohol) arrest recidivism data from a controlled study of DUI intervention effectiveness, interactions among DUI interventions, age, race, education, and alcohol severity were estimated using logit analysis. Data were collected in a 9-year follow-up study of the Mississippi DUI Probation Project. The effects of short-term interventions (alcohol education schools for low alcohol severity offenders and structured group interventions for high alcohol severity offenders) were specified by educational level. Short-term rehabilitation was modestly effective for those with less than 12 years of education, but less effective or detrimental for the more highly educated. The effects of probation were specified by age and education, being more effective for those under 30 years and 55 years or older than for the middle aged group. Probation was most effective for well-educated older (55 +) offenders. An analysis of the under 30 years group also suggested that probation was especially effective for young well-educated Minority offenders.     

DNA analysis by flow cytometry in cutaneous T-cell lymphomas

DNA histograms of skin and blood specimens from 64 patients with known or suspected cutaneous T-cell lymphoma (CTCL) have been examined and compared with normal blood mononuclear cells and skin biopsy samples from 50 patients with various benign cutaneous conditions (i.e. patch test infiltrates, eczema, psoriasis, lichen planus, atopic dermatitis) in an attempt to establish whether DNA measurements by flow cytometry may improve the early recognition of CTCL. The results indicate that right-skewed G0/G1 peaks are seen frequently in both benign disorders and known and suspected CTCL. Such peaks may reflect increased stainability of DNA due to chromatin dispersion during cell activation and/or cell proliferation and do not constitute reliable evidence of malignancy. In contrast, discrete aneuploid DNA peaks are confined to malignant lesions, but are seen almost exclusively in the advanced stages in which the diagnosis can be established easily based on routine histological criteria. These data indicate that DNA measurements by flow cytometry is of only limited help in the early recognition of CTCL and support the view that the lymphoid infiltrate in early CTCL may be reactive (rather than neoplastic) or alternatively may contain only minor reactive (rather than neoplastic) or alternatively may contain only minor populations of abnormal (malignant) cells which cannot be detected by currently available DNA measurement techniques.     

Sleep deprivation reduces the citalopram –induced inhibition of serotoninergic neuronal firing in the nucleus raphe dorsalis of the rat

SUMMARY Sleep deprivation (SD) for one night induces mood improvement in depressed patients. However, relapse often occurs on the day after deprivation subsequently to a sleep episode. In light of the possible involvement of central serotonin (5–hydroxytryptamine, 5-HT) neurotransmission in both depression and sleep mechanisms, we presently investigated, in the rat, the effects of SD and recovery sleep on the electrophysiological response of 5–HT neurons in the nucleus raphe dorsalis (NRD) to an acute challenge with the 5–HT reuptake blocker citalopram. In all rats, citalopram induced a dose–dependent inhibition of the firing of NRD neurons recorded under chloral hydrate anaesthesia. After SD, achieved by placing rats in a slowly rotating cylinder for 24 h, the inhibitory action of citalopram was significantly reduced (with a concomitant 53% increase in its ED5, value). After a recovery period of 4 h, a normal susceptibility of the firing to citalopram was restored. The decreased sensitivity of 5-HT neuronal firing to the inhibitory effect of citalopram after SD probably results in an enhancement of 5-HT neurotransmission. Such an adaptive phenomenon (similar to that reported after chronic antidepressant treatment), and its normalization after recovery sleep, parallel the mood improvement effect of SD and the subsequent relapse observed in depressed patients. These data suggest that the associated changes in 5–HT autocontrol of the firing of NRD serotoninergic neurons are relevant to the antidepressant action of SD.     

Intradermal immunization of rats with plasmid DNA encoding Schistosoma mansoni 28 kDa glutathione S-transferase

Direct administration of plasmid DNA encoding an antigen represents an attractive approach to vaccination against infectious diseases, particularly in developing countries where easy-to-handle and cost-effective vaccines are needed. We have investigated the potential of DNA immunization to induce a specific antibody response against Schistosoma mansoni , using plasmid-DNA encoding the protective antigen, S. mansoni 28 kDa glutathione S-transferase (Sm28GST). Since S. mansoni parasite penetrates into its host through the skin, this tissue was chosen for plasmid DNA delivery. Following plasmid DNA administration into the skin of rats, the parasite antigen was detected in skin cells by immunohistochemistry. Three administrations of 200 μg plasmid at 14 day intervals led to the induction of a long-lasting specific IgG antibody response in the sera of immunized rats, with a predominance of IgG2a and IgG2b subclasses. Sera of immunized animals were able to mediate antibody-dependent cellular cytotoxicity in vitro , leading to the specific killing of parasite larvae. A parasite challenge performed on plasmid DNA-immunized animals induced a strong and rapid boosting effect on the specific IgG antibody response. These results demonstrate the potential of genetic immunization via the skin with plasmid DNA encoding Sm28GST for inducing immune responses with protective patterns against an S. mansoni infection .     

Evaluation of a New Sensor-Based Algorithm to Protect Against Atrial Arrhythmias

The SmarTracking (ST) algorithm (Marathon 294–09, Intermedics Inc.) uses the sensor-calculated rate (SCR) to define a "variation band" for the intrinsic sinus rate. If the sinus rate exceeds the upper limit of the band, the ventricular pacing rate is limited by the ST rate (STR) and Wenckebach behavior is observed. The present study was aimed at evaluating the behavior of the ST mechanism in patients with healthy sinus node, during exercise and at rest. Methods: Twenty-one patients (15 men; mean age 67.8 ± 9.7 years) with normal sinus function were studied. Heart rate was recorded via the rate profile of the implanted pacemaker (Relay 294–03, Intermedics Inc.), and STR and SCR were obtained via a previously calibrated strap-on pacemaker. A 15-minute protocol was used during which subjects alternated periods of walking with periods of rest. Results: The relative difference between the average STR and the average sinus rate (DST) was calculated for each phase of the protocol as well as the maximum number of patients showing inappropriate Wenckebach behavior (#W). At nominal settings, DST was always positive and did not fall below 20%. #W was maximum at rest (5) and during heavy exercise (3). By increasing the STR at rest to 95 ppm and the maximum pacing rate to 150 ppm, the #W was reduced to zero for all types of activity except during very fast walk where #W was 1. Conclusion: In general, there was no competition observed between the STR and the intrinsic rhythm. In some cases, the STR at rest and the maximum pacing rate had to be reprogrammed for optimal performance.