Gendered experiences of unemployment, suicide and self-harm: a population-level record linkage study.

BACKGROUND: Unemployment and being not in the labour force (NILF) are risk factors for suicide, but their association with self-harm is unclear, and there is continuing debate about the role of confounding by prior mental health conditions. We examine associations between employment status and self-harm and suicide in a prospective cohort, taking into account prior mental-health-related factors. METHODS: We used linked data from the New Zealand Integrated Data Infrastructure. The outcomes were chosen to be hospital presentation for self-harm and death by suicide. The exposure was employment status, defined as employed, unemployed, or NILF, measured at the 2013 Census. Confounders included demographic factors and mental health history (use of antidepressant medication, use of mental health services, and prior self-harm). Logistic regression was used to model effects. Analyses were stratified by gender. RESULTS: For males, unemployment was associated with an increased risk of suicide [odds ratio (OR): 1.48, 95% confidence interval (CI): 1.20-1.84] and self-harm (OR: 1.55, 95% CI: 1.45-1.68) after full adjustment for confounders. NILF was associated with an increased risk of self-harm (OR: 1.43, 95% CI: 1.32-1.55), but less of an association was seen with suicide (OR: 1.19, 95% CI: 0.94-1.49). For females, unemployment was associated with an increased risk of suicide (OR: 1.30, 95% CI: 0.93-1.80) and of self-harm (OR: 1.52, 95% CI: 1.43-1.62), and NILF was associated with a similar increase in risk for suicide (OR: 1.31, 95% CI: 0.98-1.75) and self-harm (OR: 1.32, 95% CI: 1.26-1.40). DISCUSSION: Exclusion from employment is associated with a considerably heightened risk of suicide and self-harm for both men and women, even among those without prior mental health problems.

Pharmacological properties of cannabinoid receptors in the avian brain: similarity of rat and chicken cannabinoid1 receptor recognition sites and expression of cannabinoid2 receptor-like immunoreactivity in the embryonic chick brain.

The pharmacological properties of brain cannabinoid receptors were investigated in brains of 35 day-old chickens, since little is known about the avian cannabinoid system. The cannabinoid1 receptor-selective antagonist ligand [3H]SR 141716A bound to chicken brain membranes with K(D) and Bmax values of 0.92+/-0.28 nM and 790+/-58 fmol/mg protein, respectively. The binding was inhibited by CP 55,940 with a pI50 value of 7.63+/-0.14 and by a series of compounds with the order of potency CP 55,940>R(+)WIN 55,212-2>R-1 methanandamide approximately DAK. S(-)WIN 55,212-3 and AM404 were without inhibitory effect at 1 microM. Similar results were found for rat brain membranes. For both rat and chicken brain membranes, addition of the non-hydrolysable GTP analogues Gpp[NH]p and GTPgammaS shifted the CP 55,940 inhibition curve to the right, consistent with an intact coupling to G-proteins in the preparations. Fatty acid amidohydrolase in chicken brain membranes was less sensitive to inhibition by phenylmethylsulphonyl fluoride and arachidonoyl serotonin than its rodent equivalent. However, when fatty acid amidohydrolase activity in the preparations was reduced by use of a lower assay membrane concentration, anandamide was found to inhibit the binding of [3H]SR 141716A to chicken membranes with a pI50 value of 6.39+/-0.16. Using a novel antibody raised to amino acids 346-359 from the C-terminal tail of the human cannabinoid2 receptor, it was found that embryonic chick brain tissue (and embryonic chick neurones in primary culture) expressed a approximately 53 kDa immunoreactive band. This immunoreactivity, which was prevented by preincubation of the antibody with the immunising peptide, was also seen in cells expressing the recombinant human cannabinoid, receptor, but was not seen in adult chicken brain homogenates or in rat cerebellar homogenates. However, a "classical" cannabinoid2-receptor component of [3H]WIN 55212-2 binding (i.e. a fraction inhibited by low concentrations of the cannabinoid2-receptor-selective antagonist SR 144528) was not found.

GABA(B) receptor heterodimer-component localisation in human brain.

In recombinant cell lines, functional GABA(B) receptors are only formed by the heterodimerisation between two related G-protein coupled receptor proteins GABA(B)R1 (GBR1) and GABA(B)R2 (GBR2), whilst the individual GBR1 or GBR2 do not produce fully functional receptors. To determine whether the heterodimerisation occurs in vivo, novel polyclonal antibodies targeting the C termini of GBR1 and GBR2, were raised in different species, characterised, and used to determine the relative localisation of the reported heterodimer components in human brain tissue, using immunohistochemistry. The use of different species for the raising of the antisera allowed double immunofluorescent labelling of the receptors as an indication of GBR1/GBR2 receptor co-localisation in human brain. The presence of both proteins is reported in cerebellum, hippocampus, cortex, thalamus and basal ganglia. Regions of the brainstem including pons and medulla, also express GBR1 and GBR2 protein. The double immunofluorescence demonstrated that GBR1 and GBR2 are co-localised in the human cerebellar cortex. Together these results suggest the widespread distribution of GABA(B) receptors in human brain, and that GABA(B) receptors GBR1 and GBR2 can exist in the same cell, and therefore may function as a heterodimer in the human brain.

Heterodimerization is required for the formation of a functional GABA(B) receptor.

GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the mammalian central nervous system, where it exerts its effects through ionotropic (GABA(A/C)) receptors to produce fast synaptic inhibition and metabotropic (GABA(B)) receptors to produce slow, prolonged inhibitory signals. The gene encoding a GABA(B) receptor (GABA(B)R1) has been cloned; however, when expressed in mammalian cells this receptor is retained as an immature glycoprotein on intracellular membranes and exhibits low affinity for agonists compared with the endogenous receptor on brain membranes. Here we report the cloning of a complementary DNA encoding a new subtype of the GABAB receptor (GABA(B)R2), which we identified by mining expressed-sequence-tag databases. Yeast two-hybrid screening showed that this new GABA(B)R2-receptor subtype forms heterodimers with GABA(B)R1 through an interaction at their intracellular carboxy-terminal tails. Upon expression with GABA(B)R2 in HEK293T cells, GABA(B)R1 is terminally glycosylated and expressed at the cell surface. Co-expression of the two receptors produces a fully functional GABA(B) receptor at the cell surface; this receptor binds GABA with a high affinity equivalent to that of the endogenous brain receptor. These results indicate that, in vivo, functional brain GABA(B) receptors may be heterodimers composed of GABA(B)R1 and GABA(B)R2.

The product of varicella-zoster virus gene 62 autoregulates its own promoter.

Varicella-zoster (VZV) gene 62 encodes a protein with a predicted Mr of 140,000 (140K) which has considerable amino acid identity with the major immediate early (IE) protein Vmw175 (ICP4) of herpes simplex virus type I (HSV-1). Vmw175 is an essential virus polypeptide with a pivotal role in the activation of early and late viral gene expression and also in the repression of IE gene expression. The VZV 140K protein has been shown to function as a strong transcriptional activator in transfection assays and largely complements for the loss of Vmw175 function in HSV-1. We report the results of cotransfection experiments which demonstrate that the 140K protein strongly represses expression from its own promoter, that of gene 62, thus establishing further functional similarity between it and Vmw175. However, whereas Vmw175 can substitute for the 140K protein in repression of the gene 62 promoter, the 140K protein does not repress the HSV-1 IE3 promoter in the reciprocal experiment. The integrity of a domain of Vmw175 (designated region 2), previously shown to be crucial for repression of the HSV-1 IE3 promoter, is also required for repression of the gene 62 promoter. Moreover, a similar requirement for the highly similar region 2 of the 140K protein for repression is demonstrated, suggesting that VZV 140K protein and HSV-1 Vmw175 autoregulate IE gene expression by a related mechanism.

A herpes simplex virus type 1 recombinant with both copies of the Vmw175 coding sequences replaced by the homologous varicella-zoster virus open reading frame.

Varicella-zoster virus (VZV) gene 62 encodes a protein with a predicted Mr of 140,000 (VZV 140K) that shares considerable amino acid homology with the immediate early (IE) regulatory protein Vmw175 of herpes simplex virus type 1 (HSV-1) and is believed to be its functional equivalent. We have tested this hypothesis by insertion of VZV gene 62 (expressed from the HSV-1 IE3 promoter) into both IE3 gene loci in the short region repeats of the HSV-1 genome. The parent virus used for this manipulation was D30EBA, which is a variant of HSV-1 from which the majority of the Vmw175 coding sequences have been deleted. Like other HSV-1 viruses lacking Vmw175 functions, D30EBA is able to grow only in cell lines which express Vmw175 constitutively. The resulting recombinant virus. HSV-140, is able to propagate (but unable to form obvious plaques) on normal cell lines. The properties of HSV-140 were studied by monitoring the time course of polypeptide expression and DNA replication during normal infection. We found that at high multiplicity HSV-140 synthesized apparently normal amounts of many viral polypeptides but that the expression of certain late genes was reduced; this slight defect may be related to less efficient DNA replication by HSV-140. At low multiplicity HSV-140 expressed viral proteins inefficiently. Surprisingly, VZV 140K was produced in large amounts at later times of a normal infection, indicating that the polypeptide fails to autoregulate the IE3 promoter. The results strongly suggest that VZV 140K is able to perform most of the functions of Vmw175 during growth of HSV-1, but that differences in detail lead to less efficient virus growth.

Control of expression of the varicella-zoster virus major immediate early gene.

The cis-acting DNA sequences and trans-acting proteins that control the expression of the major immediate early (IE) gene of varicella-zoster virus (VZV) were investigated. The location of the IE mRNA 5' terminus was determined by primer extension and S1 nuclease analyses and the functional activities of DNA sequences upstream of this site were analysed by a transfection assay. The VZV IE promoter exhibited low activity in BHK and HeLa cells, but was transactivated by the herpes simplex virus type 1 (HSV-1) virion protein Vmw65. DNA sequences between positions -131 and +57 were responsible for promoter activity, whereas sequences between -410 and -131 mediated the response to Vmw65. Two short elements in the -410 to -131 region formed protein-DNA complexes with HeLa cell nuclear proteins and formed a ternary complex when Vmw65 was added. One of the elements, ATGTAAATGAAAT, possessed a strong similarity to the HSV-1 TAATGARAT. The VZV homologue of Vmw65, encoded by open reading frame (ORF) 10, failed to trans-activate expression from HSV-1 or VZV IE promoters and did not form a ternary complex with functional TAATGARAT elements and HeLa cell proteins. Therefore, stimulation of VZV IE transcription by Vmw65 can occur by a mechanism similar to that employed by HSV-1, but VZV ORF 10 does not function as a trans-activator of IE gene expression.

Nutrients supplied by food groups in diets of teenaged girls.

Sources of nutrients were determined in diets of teenaged girls, a group generally thought to be at nutritional risk. This study of Southern adolescent girls of two races examines intakes of energy, energy-yielding nutrients, vitamins, minerals, and other components of various food groups. Effects of race, age, place of residence, and per capita income on nutrients furnished by food groups were determined from two 24-hour dietary recalls from each of 1,195 girls, aged 12, 14, or 16. Of the food groups examined, foods of low nutrient density provided the most energy, fat, and carbohydrate. The meat group provided the most protein. Dairy products, which supplied the largest amounts of six vitamins and minerals of any food group, were used less by black, rural, or older teenagers than by white, urban, or younger girls. Blacks obtained more vitamin A from vegetables and more thiamin from meat than whites. Amounts of meat, starchy, and low-nutrient-density subgroups also varied with race, age, and/or place of residence. As income increased, consumption of starches (especially breakfast cereals) and eggs decreased and that of fruit increased.

Factors related to blood pressure in a biracial adolescent female population.

Blood pressure levels, anthropometric parameters, and dietary intakes were assessed in 1981 and 1983 in a population of black (n = 236) and white (n = 296) adolescent girls, aged 14 and 16 years in 1983. The 14-year-old black girls exhibited significantly higher mean systolic and diastolic blood pressures than whites in both years. Body weight and Quetelet index were more strongly associated with blood pressure than were height and triceps skinfold thickness. Correcting blood pressures for weight, Quetelet index, 2-year changes in height, and age at menarche decreased in each case (but did not negate) the observed race differences in blood pressure. Dietary calcium and potassium intakes were inversely related to blood pressure, and a race difference in the intake of these nutrients (whites greater than blacks) was observed. Covariate adjustment for calcium, but not for potassium, decreased the magnitude of race differences in blood pressure. Family type (single-parent vs nuclear) and place of residence (urban vs nonurban) appeared to be the most important confounding variables for race differences in blood pressure, since differences largely were eliminated by controlling for these factors. Conflicting reports in the literature regarding the age range during which race differences in blood pressure become apparent may be partially attributed to the complex interrelationships among these factors and the potential influence of other genetic-environmental interactions that may also play a role in blood pressure regulation.

Nutrient intakes of female adolescents from eight southern states.

Nutrient intakes were calculated from two 24-hour recalls for 1,247 adolescent black and white girls. Whites consumed more vitamins E, C, and B-12, niacin, folacin, calcium, phosphorus, magnesium, and zinc and had higher intakes per 1,000 kcal of those nutrients, protein, vitamin D, and iron than blacks. Intakes of calcium (whites) and magnesium (both races) decreased with age. Urban girls consumed more energy and magnesium than rural ones. Folacin intake increased with income. Folacin intakes were most frequently below 67% RDAs, followed by intakes of iodine, vitamin D, iron, calcium, vitamin B-6, zinc, magnesium, and vitamin A. The majority of diets met or exceeded RDAs for protein, vitamins E, C, and B-12, riboflavin, and thiamin. Intakes are reported for most nutrients for which safe ranges have been set.

The iron status of Black and white female adolescents from eight Southern states.

Hb, hematocrit, plasma iron, and transferrin saturation were measured in approximately 1000 girls aged 12, 14, or 16 yr in eight southern states. The iron status parameters did not differ significantly among the three age groupings or between menstruating and nonmenstruating girls. Blacks had significantly lower mean Hb (p less than 0.0001), hematocrit (p less than 0.0001), and transferrin saturation (p less than 0.05) levels than whites and a greater proportion of Blacks exhibited low Hb (p less than 0.05) and low hematocrit levels (p less than 0.01). Adjusting for dietary iron intakes and per capita income levels did not adequately account for significant race differences for iron status parameters. These findings support the contention that genetic as well as environmental factors are responsible for the frequently reported Black-white differences in Hb and hematocrit levels.

Relationships among anthropometric indices of growth and creatinine and hydroxyproline excretion in preadolescent black and white girls.

Relationships among anthropometric indices of growth and creatinine and hydroxyproline excretion were studied over a 2-year longitudinal period in 124 preadolescent girls. Four groups of girls were selected: low-income white (LIW), middle-income white (MIW), low-income black (LIB) and middle-income black (MIB). Changes in body height, weight, subcapsular skinfold, bone density of the phalanx and bone mineral of the radius and ulna were used as indices of growth in relation to creatinine and hydroxyproline excretion. There were no significant differences in subcapsular skinfold among the groups. Bone density of the phalanx and bone mineral of the radius and ulna were significantly greater in blacks than whites at each age. Mean values for urinary creatinine concentration ranged from 0.115 to 0.209 g/dl from 9 to 11 years of age and tended to be greater for the middle-income than the low-income girls. Urinary hydroxyproline (g)/creatinine (g) ranged from 0.072 at 9 to 0.128 at 11 years of age with no significant differences between groups. All measurements showed significant increases with age. Significant positive correlations were seen among several indices in both racial groups and are discussed. INDEX WORDS: Growth, height/weight, hydroxyproline/creatinine excretion, race-income groups, subscapular skinfold, bone density, bone mineral content, preadolescent girls.