COMT Gene Polymorphism Is Associated with Declarative Memory in Adulthood and Old Age

Variation in memory performance is to a large extent explained by genes. In the prefrontal cortex, the catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine, a neurotransmitter implicated in cognitive functions. The present study examined the effect of a polymorphism in the COMT gene on individual differences and changes in memory in adulthood and old age. Tests assessing episodic and semantic memory were administered to 286 men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula prospective cohort study) at two occasions followed over a 5-year period. Carriers of the Met/Met genotype (with low enzyme activity) performed better on episodic and semantic memory, as compared to carriers of the Val allele (with higher enzyme activity). Division of episodic memory into its recall and recognition components showed that the difference was specific to episodic recall, not recognition tasks; an effect that was observed across three age groups (middle-age, young-old, and old-old adults) and over a 5-year period. The COMT gene is a plausible candidate gene for memory functioning in adulthood and old age.     

CP-64131, an aminobenzazepine with cytokine-like properties, stimulates human neutrophil functions through the p38-MAPK pathway

CP-64131 (CP), an aminobenzazepine with cytokine-like, physiologic effects similar to granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage (GM)-CSF, increases the number of neutrophils and stimulates marrow recovery after doxirubicin ablation. CP can also function as a neutrophil agonist, like formyl-Met-leu-Phe (fMLP). In these studies, we show that CP is unique in that it stimulates the p38-mitogen-activated protein kinase (MAPK) pathway but not extracellular signal-regulated kinase (ERK)1/2 or c-jun N-terminal kinase MAPKs in human neutrophils from peripheral blood. This is in contrast to other neutrophil agonists such as fMLP, interleukin (IL)-8, or GM-CSF, which stimulate multiple MAPK pathways. Like fMLP and IL-8, CP is capable of stimulating superoxide (O2-) production, CD11b expression, and cell polarization in human neutrophils. CP-stimulated O2- production is completely dependent on p38-MAPK activation, as determined by sensitivity to the p38-MAPK inhibitor SB203580. In contrast, SB203580 only partially inhibits expression of CD11b and has no effect on cell polarization stimulated by CP. Therefore, CP treatment of neutrophils activates p38-MAPK but has effects independent of p38-MAPK activation. In human embryonic kidney 293 cells, a human kidney epithelial cell line CP stimulates p38-MAPK and modestly activates ERK1/2. The findings define CP as a novel, small molecule, which has little cellular toxicity in vitro. CP has the ability to activate specific MAPK pathways in different cell types and should prove to be an effective agonist in combination with inhibitors to study biological responses regulated by MAPKs.     

Neurobehavioral phenotype in carriers of the fragile X premutation

There have been contradictory findings in the fragile X (fraX) literature about possible neurocognitive and psychological symptoms due to the fraX premutation (pM). The purpose of the present study was to investigate the relationship between CGG repeat length and neurobehavioral functioning in carriers of the fraX pM. Eighty‐five female carriers of the pM with allele sizes ranging from 59–166 were administered a comprehensive IQ test (WAIS‐III) and completed a questionnaire designed to measure psychopathology (Symptom Checklist (SCL)‐90‐R). No relationship between allele size and cognition was identified. A significant negative relationship between allele size and age was found, as well as a positive relationship between allele size and depression. Follow‐up analyses separating small and large allele sizes (below and above 100 CGG repeats) indicated that individuals with larger allele sizes scored significantly higher on the Interpersonal Sensitivity and Depression subscales of the SCL‐90‐R. Despite the limitation of few individuals with high CGG repeat lengths, our findings suggest that females with larger premutated alleles (≥ 100 repeats) display some clinical manifestations of fraX syndrome. © 2001 Wiley‐Liss, Inc.     

Sleep need in adolescents: a longitudinal approach

A sample of 190 male and female "high school" students completed a sleep questionnaire for the first time when they were 10 to 14 years old. The survey was repeated five times at 2 year intervals. Ninety-three subjects answered the questionnaire each time. Subjective sleep need was assessed by the indicated wish for more sleep. The wish for more sleep was very pronounced, varying between 54.3% and 74.5% across the years. Individual consistency, however, was low since only 14.5% of the adolescents indicated the wish for more sleep in each survey, emphasizing the state dependency of this variable. Within each total sample, subjects with the wish for more sleep (MSL) and with sufficient sleep (SSL) were compared. Subjective sleep need was consistently validated by a syndrome of morning-tiredness. In the last two surveys, there was reduced time in bed (TIB) on weekdays in MSL subjects and longer TIB during vacation in surveys 2 through 5. Furthermore, MSL subjects more often showed irregular sleep habits. The previous sleep history of the MSL subjects in the last survey indicated that concomitants of the wish for more sleep were already experienced earlier in adolescence. The desired sleep duration of these subjects was 1.7 h longer than their current sleep on weekdays, an amount they had not obtained on weekdays since early adolescence. It is concluded that a substantial proportion of the adolescents seem to have had difficulties adapting to the general sleep time reduction occurring in adolescence.     

A short-term quantitative XC assay for murine leukemia virus.

A syncytial-plaque (SXC) assay for murine leukemia virus is described which utilizes a single cycle of infection, thus allowing quantitation of virus-producing mouse cells in 3 to 4 days. Depending upon the Fv-1 genotype of infected mouse cells, the assay will reflect single or multiple “hitness” after infection by N- or B-tropic MuLV. The test is equally sensitive to the uv-XC plaque assay for tissue culture adapted MuLV, but is less sensitive to in vivo derived MuLV from an AKR/J mouse. Newly isolated AKR MuLV requires a longer latent period than the in vitro adapted Moloney strain of MuLV.     

Craniofacial serial dimensions related to age, sex, and cleft-type from six months of age to two years.

The first two postnatal years are a time of rapid craniofacial growth. We selected 30 cleft lip/palate children, each seen at 6, 12, 18, 24 months, at which time lateral X-ray headfilms were taken. There were five boys, five girls, in each of three cleft-types: cleft palate only (CP), unilateral cleft lip/palate (UCLP), and bilateral cleft lip/palate (BCLP). Three dimensions were selected: 1) anterior cranial base (S-N); 2) upper face height (N-Pt.A); 3) maxillary depth (Pt.A-Ptm). All were in the midsagittal plane. This is a repeated measures study on the factor patient age, so that for each combination of sex and cleft-type the same subject was measured at the four levels of patient age. The multiple comparison technique utilized was the Newman-Keuls Procedure. There is no significant joint effect in the 6-24 months period. The factors seem to operate singly. There is no main effect due to the factor sex. Dimensions N-Pt.A. and Pt.A-Ptm show a significant main effect due to the factor cleft-type. There is a highly significant main effect due to the patient age factor.     

Increasing access to medical education for students from medically underserved communities: one program's success.

The Premedical Honors College (PHC) is an eight-year, BS-MD program created in 1994 by Baylor College of Medicine (BCM) and The University of Texas-Pan American (UT-PA) to increase the number of physicians addressing the health care needs of underserved populations in Texas. The PHC targets South Texas, a 13-county, medically underserved area with a population that is 82% Hispanic. To date, the PHC has had 159 matriculants and 71 graduates, of whom 60 (84.5%) have matriculated into medical school. These results are significant considering that in 1996, only four students from all five South Texas colleges (combined enrollment of 30000 students) were accepted to medical school. An outcomes study comparing PHC matriculants with students of similar academic ability, ethnicity, and interest in medicine revealed that the odds of medical school matriculation were seven times higher for PHC students than for non-PHC students. The PHC's initial success has been acknowledged by the Texas legislature, which recently passed a bill to promote the PHC's replication. In addition, the number of PHC students-of whom 95% are Mexican American-who matriculate into medical school annually is significant nationally. In 2001, only 386 U.S. medical school matriculants (2.3% of all matriculants) were Mexican American; 17 of these students (4.4%) were PHC graduates. If current trends continue, the PHC could significantly expand the number of physicians serving minority and medically underserved populations in Texas and the nation. Also, the PHC provides an opportunity for research on programs designed to create pathways from high school to medical school.     

Zur darstellung tritiummarkierter polymethacrylsäuremethylester

A method is described for the preparation of identical fractions of tritium marked and unmarked fractions of polymethacrylate of higher molecular weights. The labeling is done by TOH on polymethacrylic acid and does not change the molecular weight distribution. Further the influence of labeling by the method of WILZBACH on fractionated polymethacrylate is reported. The molecular weight distributions before and after the exposing to tritium gaz of 3 curie are determined. These data make it is possible to gain information concerning the number of bonds broken and of the position of the active hydrogen atoms in the polymer chain.