Identification of Nramp2 as an iron transport protein: another piece of the intestinal iron absorption puzzle

The attitudes of young men and women to breastfeeding were examined including perceived incentives and barriers to the practice in cross sectional survey and focus group discussion. The study involoved 177 (100%) fifth and final year students of both sexes and a subsample of 48 students in 6 focus groups in three post primary schools in an Irish midland town. Overall 28% reported that they themselves were breastfed. The most frequent sources of information were the media rather than home or school. A majority of girls (86%) and boys (77%) agreed that breastfeeding was the best method of feeding, but less intended the practice for their children (54%), girls being significantly less likely than boys. There were no patterns in relation to social class and lifestyle. Reasons for breastfeeding in the focus groups included its naturalness, facility of feeding and adequate nourishment. Reasons against related to embarrassment in public, but mainly related to perceived problems with the practicalities of feeding. Health promotion strategies need to reach young people before they initiate pregnancies. Skills based health education courses would be helpful and girls should be aware of the positive attitudes of boys generally.     

Analysis of health service areas: another piece of the psychiatric workforce puzzle

PURPOSE: To establish the benefit of nonpreserved intracameral lidocaine 1% as an adjunctive anesthetic agent to topical anesthesia for small incision cataract surgery and to determine the agent's safety with respect to corneal toxicity. SETTING: Advanced Vision Care, West Hills, California, USA. METHODS: A retrospective chart review of cataract surgery performed between January 1995 and March 1997 was done. The efficacy of intracameral lidocaine was determined by comparing the number of topical anesthesia cases (Group 1) and of combined topical and intracameral anesthesia cases (Group 2) that required conversion to a more profound level of local anesthesia, determined by patient discomfort, surgeon discomfort, or both. To determine the presence and bias of a surgical learning curve, Group 1 was subdivided chronologically into two subgroups. Corneal toxicity was assayed by the degree of clinical corneal edema noted by slitlamp examination on the first postoperative day. RESULTS: Six hundred thirty-one charts satisfied the criteria for inclusion; 352 cases (Group 1) had topical anesthesia alone and 279 subsequent cases (Group 2), combined topical and intracameral anesthesia. In Group 1, 42.6% of cases required conversion to some form of additional local anesthesia, whereas in Group 2, less than 1.0% required conversion. In the earlier subgroup, 45.8% of cases required conversion and in the latter, 34.3%. On the first day after surgery, 88.2% of Group 2 cases and 76.7% of Group 1 cases were free from corneal edema. The difference was statistically significant but probably resulted from a change in phacoemulsification technique from sculpting to chopping in the latter cases, which were performed under combined topical and intracameral anesthesia. CONCLUSIONS: Intracameral nonpreserved lidocaine 1% appears to be both efficacious and nontoxic as an anesthetic adjunct in small incision cataract surgery.     

Adult sibling expressed emotion and fellow sibling deviance: A new piece of the family process puzzle.

Seventy-three older siblings were assessed in early adulthood with the Five-Minute Speech Sample (FMSS) measure of expressed emotion. Sibling critical expressed emotion was linked with younger brother concomitant and future antisocial behavior, substance use, deviant peer association, increased rate of criminal arrests, and early onset sexual activity. Siblings of younger brothers with behavior problems were also more likely to be critical of, and to report negative relationships with, these brothers than were siblings of well-adjusted brothers. Sibling critical expressed emotion also predicted younger brothers' maladjustment 1-2 years later, after controlling for earlier sibling conflict and parent discipline. The findings accentuate the importance of understanding the influence of intrafamilial processes in the etiology of behavior problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A candidate molecule approach to defining developmental pathology in schizophrenia

The evidence that schizophrenia may have its origins from early in life, possibly during prenatal brain development, is based primarily on a constellation of nonspecific anatomical findings and on the results of surveys of obstetrical complications and of childhood neurological and psychological adjustment. The developmental processes implicated by this evidence are uncertain, but speculation has centered around abnormalities of neuronal proliferation, migration, and connection formation. These developmental milestones are the results of complicated cellular processes involving molecular interactions between cells and between the extracellular and intracellular milieus. To understand how these abnormalities could relate to schizophrenia, it is necessary to characterize the molecular events that define the processes. In this article, we discuss the potential impact of a number of molecules that are important in the sequence of cellular events implicated in schizophrenia. In particular, we focus on molecular mechanisms related to cell proliferation, axonal outgrowth, cell migration, cell survival, synaptic regression, myelination, and developmental aspects of early adult life. These various candidate molecules regulate different aspects of cell growth and cell-cell interactions and are involved in the regulation of deoxyribonucleic acid (DNA) expression. Very few of these molecules have been studied in the schizophrenic brain.     

G proteins and hypertension: an alternative candidate gene approach

Hypertension affects approximately 20 to 30% of individuals in industrialized countries, and is commonly believed to develop on the basis of both genetic and environmental factors. The identification of genes susceptible to the most frequent form of hypertension, commonly referred to as "essential" hypertension, is hampered by the fact that blood pressure is a poorly defined phenotype that is modulated by multiple factors, such as gender, race, body mass etc., and that the definition of hypertension depends on a rather arbitrarily chosen cut-off value. Hence, more progress has been made in the identification of genes responsible for rare autosomal dominant forms of hypertension, such as Liddle's disease. This review focuses on an experimental approach that attempts to define candidate genes for essential hypertension using immortalized cells from well characterized normotensive and hypertensive subjects. From the presently available results, one attractive speculation is that an increased intracellular signal transduction caused by an enhanced reactivity of Gj-type G proteins represents a genetically fixed trait that renders affected individuals susceptible to essential hypertension.     

A candidate recombination modifier gene for Zea mays L

Maize meiotic mutant desynaptic (dy) was tested as a candidate recombination modifier gene because its effect is manifested in prophase I. Recombination rates for desynaptic (dy) and its wild type were compared in two ways: (1) segregation analysis using six linked molecular markers on chromosome 1L and (2) cytogenetic analysis using fluorescence in situ hybridization (FISH)-aided meiotic configurations observed in metaphase I. Chromosome 1L map lengths among the six linked markers were 45-63 cM for five F2 dy/dy plants, significantly lower than the wild-type F2 map distance of 72 cM. Chromosomes 2 and 6 were marked with rDNA FISH probes, and their map lengths were estimated from FISH-adorned meiotic configurations using the expectation-maximization algorithm. Chiasma frequencies for dy/dy plants were significantly reduced for both arms of chromosome 2, for chromosome arm 6L, and for eight unidentified chromosomes. There was a notable exception for the nucleolus-organizing region-bearing arm chromosome arm 6S, where dy increased chiasma frequency. Maize meiotic mutant desynaptic is a recombination modifier gene based on cytogenetic and segregation analyses.     

Structure and dynamics of hydronium in the ion channel gramicidin A

The effects of the hydronium ion, H(3)0+, on the structure of the ion channel gramicidin A and the hydrogen-bonded network of waters within the channel were studied to help elucidate a possible mechanism for proton transport through the channel. Several classical molecular dynamics studies were carried out with the hydronium in either the center of a gramicidin monomer or in the dimer junction. Structural reorganization of the channel backbone was observed for different hydronium positions, which were most apparent when the hydronium was within the monomer. In both cases the average O-O distance between the hydronium ion and its nearest neighbor water molecule was found to be approximately 2.55 A, indicating a rather strong hydrogen bond. Importantly, a subsequent break in the hydrogen-bonded network between the nearest neighbor and the next-nearest neighbor(approximately 2.7 -3.0 A) was repeatedly observed. Moreover, the carbonyl groups of gramicidin A were found to interact with the charge on the hydronium ion, helping in its stabilization. These facts may have significant implications for the proton hopping mechanism. The presence of the hydronium ion in the channel also inhibits to some degree the reorientational motions of the channel water molecules.     

A novel method for structure-based prediction of ion channel conductance properties

A rapid and easy-to-use method of predicting the conductance of an ion channel from its three-dimensional structure is presented. The method combines the pore dimensions of the channel as measured in the HOLE program with an Ohmic model of conductance. An empirically based correction factor is then applied. The method yielded good results for six experimental channel structures (none of which were included in the training set) with predictions accurate to within an average factor of 1.62 to the true values. The predictive r2 was equal to 0.90, which is indicative of a good predictive ability. The procedure is used to validate model structures of alamethicin and phospholamban. Two genuine predictions for the conductance of channels with known structure but without reported conductances are given. A modification of the procedure that calculates the expected results for the effect of the addition of nonelectrolyte polymers on conductance is set out. Results for a cholera toxin B-subunit crystal structure agree well with the measured values. The difficulty in interpreting such studies is discussed, with the conclusion that measurements on channels of known structure are required.     

Antitat gene therapy: a candidate for late-stage AIDS patients

Antitat is an autoregulated gene expressing an inhibitory RNA with dual function: it sequesters the Tat protein by polymeric-TAR and blocks the translation of the Tat messenger RNA by antisense-Tat. Using human T cell lines and peripheral blood lymphocytes as the in vitro target, we have previously shown that antitat is an effective long-term suppressor of HIV-1, including 'field' isolates. To assess the efficacy of this inhibitory gene better in the setting of an infected individual with late-stage AIDS, we examined its antiviral activity in an in vivo established infection. Peripheral blood mononuclear cells isolated from AIDS patients were transduced with replication defective retroviral vectors carrying the antitat gene. In the absence of cell selection, the antitat gene blocked virus replication and allowed infected CD4+ T cells to expand in culture. These results suggest that antitat gene therapy may be beneficial to block HIV-1 replication and reconstitute the immune system of late-phase AIDS patients. We introduced a new parameter, CRF, which defines the effectiveness of the ex vivo gene therapy treatment of AIDS patients. Antitat treatment was efficient in cells of all patients regardless of viral quasispecies, however, it was most potent in severely immunocompromised individuals.     

A negative association of schizophrenia with an allele of the HLA DQB1 gene among African-Americans

The present study investigated the relationship between the time of nocturnal onset of urinary 6-sulfatoxymelatonin (aMT6s) secretion, and the timing of the steepest increase in nocturnal sleepiness ("sleep gate"), as determined by an ultrashort sleep-wake cycle test (7 min sleep, 13 min wake). Twenty-nine men (mean age 23.8 +/- 2.7 years) participated. The ultrashort sleep-wake paradigm started at 0700 hr after a night of sleep deprivation and continued for 24 hr until 0700 hr the next day. Electrophysiological recordings were carried out during the 7-min sleep trials, which were then scored conventionally for sleep stages. Urinary aMT6s was measured every 2 hr. The results showed that the timing of the sleep gate was significantly correlated with the onset of aMT6s secretion. These results are discussed in light of the possible role of melatonin in sleep-wake regulation.