Racial differences in vitamin B12 levels in the United States

Studies from Africa have demonstrated that black people have higher vitamin B12 (cobalamin) levels than do white people. The authors compared healthy white people, black people, and Latin-Americans in the United States. Their study is also the largest in which the effect of race and sex on the cobalamin levels has been examined. Analysis of 233 healthy subjects showed that black people had significantly higher (P less than 0.0001) vitamin B12 levels than did white people. Latin-Americans had levels intermediate between those of white and black people, although their levels were significantly different only in comparison with white people (P = 0.0029). Based on the study of 305 healthy subjects, no sex difference in vitamin B12 levels was noted. Conflicting claims have been made on sex difference in the past. The authors conclude that there is a racial but not a sex difference in vitamin B12 levels in the United States. Like African black people, black people and Latin-Americans in this country have significantly higher vitamin B12 levels than do white people. This finding supports the thesis that genetic factors contribute to the racial differences in vitamin B12 levels.     

Single-column thalamocortical network model exhibiting gamma oscillations, sleep spindles, and epileptogenic bursts

To better understand population phenomena in thalamocortical neuronal ensembles, we have constructed a preliminary network model with 3,560 multicompartment neurons (containing soma, branching dendrites, and a portion of axon). Types of neurons included superficial pyramids (with regular spiking [RS] and fast rhythmic bursting [FRB] firing behaviors); RS spiny stellates; fast spiking (FS) interneurons, with basket-type and axoaxonic types of connectivity, and located in superficial and deep cortical layers; low threshold spiking (LTS) interneurons, which contacted principal cell dendrites; deep pyramids, which could have RS or intrinsic bursting (IB) firing behaviors, and endowed either with nontufted apical dendrites or with long tufted apical dendrites; thalamocortical relay (TCR) cells; and nucleus reticularis (nRT) cells. To the extent possible, both electrophysiology and synaptic connectivity were based on published data, although many arbitrary choices were necessary. In addition to synaptic connectivity (by AMPA/kainate, NMDA, and GABA(A) receptors), we also included electrical coupling between dendrites of interneurons, nRT cells, and TCR cells, and--in various combinations--electrical coupling between the proximal axons of certain cortical principal neurons. Our network model replicates several observed population phenomena, including 1) persistent gamma oscillations; 2) thalamocortical sleep spindles; 3) series of synchronized population bursts, resembling electrographic seizures; 4) isolated double population bursts with superimposed very fast oscillations (>100 Hz, "VFO"); 5) spike-wave, polyspike-wave, and fast runs (about 10 Hz). We show that epileptiform bursts, including double and multiple bursts, containing VFO occur in rat auditory cortex in vitro, in the presence of kainate, when both GABA(A) and GABA(B) receptors are blocked. Electrical coupling between axons appears necessary (as reported previously) for persistent gamma and additionally plays a role in the detailed shaping of epileptogenic events. The degree of recurrent synaptic excitation between spiny stellate cells, and their tendency to fire throughout multiple bursts, also appears critical in shaping epileptogenic events.     

Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3

Genetic linkage studies have indicated that chromosome 14q24.3harbours a major locus for early-onset (onset age <65 years)Alzheimer's disease (AD3). Positional cloning efforts have identifieda novel gene S182 or presenilin 1 as the AD3 gene. We have mappedS182 in the AD3 candidate region between D14S277 and D14S284defined by genetic linkage studies in the two chromosome 14linked, early-onset AD families AD/A and AD/B. We have shownthat S182 is expressed in lymphoblasts and have determined thecomplete cDNA in both brain and lymphoblasts by RT-PCR sequencing.S182 is alternatively spliced in both brain and lymphoblastswithin a putative phosphorylation site located 5' in the codingregion. We identified two novel mutations, Ile143Thr and Gly384Alalocated in, respectively, the second transmembrane domain andin the sixth hydrophilic loop of the putative transmembranestructure of S182. As families AD/A and AD/B have a very similarAD phenotype our observation of two mutations in functionallydifferent domains suggest that onset age and severity of ADmay not be very helpful predictors of the location of putativeS182 mutations.     

Development of enhanced blood flow responses to prostaglandin E1 in carrageenan-induced granulation tissue

The distribution of cardiac output (c.o.) was measured by the radioactive microsphere method in rats at different time intervals after the implantation of carrageenanimpregnated sponges. The amount of blood distributed to the developing granulomata increased from day 5 after sponge implantation to day 7, but showed no further increase at day 10. A similar pattern in blood flow was observed in the skin covering the granulomata. Injection of PGE₁ (100 ng) into the sponges led to an increase in blood flow, the magnitude of which became gradually larger between days 5 and 10. A similar, though less marked increase in sensitivity to PGE₁ was observed in the skin covering the granulomata, PGE₁ causing a significant increase in blood flow to the skin on day 10. These changes in sensitivity to exogenous PGE₁ may be due to decreasing levels of endogenous PGE and/or maturation of the newly formed blood vessels in the granulation tissue.     

N-myristoyltransferase: A potential novel diagnostic marker for colon cancer

Background  

Colon cancer is the second leading cause of cancer deaths in the western world. If detected early, colorectal cancer is one of the most treatable forms of cancer. Unfortunately, very few people are screened. N-myristoyltransferase (NMT) catalyzes myristoylation of various proteins including oncoproteins. We have demonstrated earlier the alteration of NMT activity during the progression of colorectal cancer and established NMT as a putative therapeutic target for cancer.     

Lack of PTEN expression in endometrial intraepithelial neoplasia is correlated with cancer progression

We tested the hypothesis that PTEN inactivation may stratify cancer progression risk among putative endometrial hyperplasias, classified prognostically by means of the morphometric D score (DS). The DS, calculated from 3 morphometric variables measured in routine hematoxylin-eosin-stained endometrial biopsy slides, is the most sensitive and specific method of endometrial cancer risk prediction currently available. Clinical outcomes of 103 women with endometrial hyperplasia on biopsy were tallied according to the DS. Seven (7/103; 7%) patients with carcinoma during follow-up were all distributed within the high-risk prognostic group (ie, DS <1 = endometrial intraepithelial neoplasia [EIN]) (7/21; 33% progression). None of the 82 cases with a DS higher than 1 progressed. All cases that progressed were PTEN null, indicating that this genotype is capable of further stratifying cancer progression risk in hyperplasias irrespective of histological categorization. However, only 16% of the PTEN-null cases progressed. When PTEN expression pattern was combined with EIN, the prognostic power was greatly increased (specificity from 63% for PTEN and 85% for EIN to 93% when combined; positive predictive value from 16% and 33% to 50%). We conclude that loss of PTEN expression is the first biomarker in EIN that increases the accuracy of the prognostic DS to predict cancer progression risk. Unless endometrial hyperplasias are stratified by histological morphometric D-Score, PTEN has a low positive predictive value.     

Fibrin as a cell carrier in cardiovascular tissue engineering applications

In cardiovascular tissue engineering approaches, efficient seeding methods are essential. To achieve this and to save time, cells can be encapsulated in gels. Combining the advantages of a gel as a cell carrier with the advantages of a fiber-based scaffold, providing structural integrity to the developing tissue, might offer several advantages. In this study, seeding by using fibrin as a cell carrier is compared to the conventional static seeding method with regard to tissue development. Seeding with fibrin resulted in less loss of soluble collagen into the medium and a more mature extracellular matrix in a shorter period of time. The use of fibrin degradation inhibitors was shown to inhibit extracellular matrix formation, although it did not hamper cell proliferation. The use of fibrin as a cell carrier to seed cells into a fiber-based scaffold may represent a promising, timesaving approach in cardiovascular tissue engineering applications.     

Age,experience, and rare-male mating advantages inDrosophila pseudoobscura

Because published experiments documenting frequency-dependent sexual selection have exclusively used young virgins, we endeavored to test for this same phenomenon in females who differed in age and in previous mating experiences. Direct observation tests were conducted employingDrosophila pseudoobscura females of the previously described Arrowhead (AR) and Chiricahua (CH) homokaryotypes. Four-day-old virgin females confer mating advantages on all tested rare males, i.e.,or. AR, and CH. Females who had a previous mating experience when younger award a rare-male advantage only when the rare male is of the same genotype of karyotype as their first mate, and matings are random when the first-mate type males are common. Equivalently aged (11 days) virgin females mate significantly more than expected with minority males if they are of the same karyotype as the females themselves. whereas matings are near random when the males are different. Frequency-dependent mating, therefore, is both age and experience dependent.A. P. is supported by funds from the Biopsychology Program, Hunter College and C.U.N.Y. L.F. is the recipient of USPHS Career Award 2KO3 HD 0903308: work supported by NIH Grant 5RO1 18907-02.Paper presented at the third annual meeting of the Behavior Genetics Association, Chapel Hill, North Carolina, April 7, 1973.     

Escherichia coli Isolated from Domestic Animals Pathogenic for Gnotobiotic Piglets

Three strains of Escherichia coli isolated from infectious processes in a calf, a dog, and a cat were examined for their capacity to produce disease or death, or both, in newborn gnotobiotic piglets. The O groups represented by these particular strains of E. coli were O4: (canine origin), O6: (feline origin), and O39: (bovine origin). All three isolates upon oral administration proved to be pathogenic. Infection with the E. coli O4: (canine) or O39: (bovine) consistently produced signs of enteric coli-bacillosis and death in all 1- and 3-day-old piglets within 24 to 48 hr. The O6: (feline) isolate, on the other hand, produced a marked polyserositis and generally required 6 to 7 days to kill a piglet. Only the respective type of E. coli used in the particular trial was recovered from the diseased piglets. These findings suggest the possible role of domestic animals and household pets in the spread of potentially pathogenic E. coli to other species.