The non-genetic determinants of central adiposity

Central adiposity carries an increased risk of non-insulin dependent diabetes mellitus (NIDDM), cardiac disease, hypertension and death, and is closely related to insulin resistance. Genetic factors explain a large proportion of the population variance in central adiposity, although the genotypic characteristics remain obscure. Hormonal factors such as endogenous sex steroid levels, the menopause, hormone replacement therapy and cortisol may influence body fat partitioning. The link between dietary factors and central adiposity is controversial, with contradictory results in the literature. Smoking is associated with lower total body fat, but investigations of its influence on central adiposity have also yielded contradictory results. Higher levels of physical activity are associated with lesser amounts of central fat, both cross-sectionally and in intervention studies. Some of the contradictory results regarding putative influences on central adiposity may be due to limitations of some of the anthropometric parameters of central adiposity, such as the waist-hip ratio. Further research is required to clarify the relationships between many of these factors and with both compartments of central adiposity: subcutaneous abdominal and intraabdominal adipose tissue.     

The determinants of pay satisfaction.

Conducted a study to test empirically (a) the utility of a model of the determinants of pay satisfaction developed by E. E. Lawler (1971) and (b) the value of adding to this model a category of variables not previously included: perceptions of pay-system administration. The study was conducted among 180 US, 133 French-Canadian, and 79 English-Canadian managers. Results provide some support for the utility of Lawler's model and additional support for the value of adding the administrative-type variables. Results of this and other studies are used to develop a modified model of the determinants of pay satisfaction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The determinants of pelvic brim morphology in the female

There is a significant positive correlation between the brim index and the conjugate dimension (r = 0,66). The latter also shows a high degree of correlation with stature (r = 0,58). The inverse covariability between the transverse inlet diameter and the brim index is weak (r = -0,17). The larger brim areas and brim indices of taller women are due to their greater sagittal inlet measurements.     

Structural determinants present in the C-terminal binding protein binding site of adenovirus early region 1A proteins

The C-terminal binding protein (CtBP) has previously been shown to bind to a highly conserved six-amino acid motif very close to the C terminus of adenovirus early region 1A (Ad E1A) proteins. We have developed an enzyme-linked immunosorbent assay that has facilitated the screening of synthetic peptides identical or similar to the binding site on Ad E1A for their ability to bind CtBP and thus inhibit its interaction with Ad12 E1A. It has been shown that amino acids both C-terminal and N-terminal to the original proposed binding site contribute to the interaction of peptides with CtBP. Single amino acid substitutions across the binding site appreciably alter the Kd of the peptide for CtBP, indicative of a marked reduction in the affinity of the peptide for CtBP. The solution structures of synthetic peptides equivalent to the C termini of both Ad5 and Ad12 E1A and two substituted forms of these have been determined by proton NMR spectroscopy. Both the Ad12 and Ad5 peptides dissolved in trifluoroethanol/water mixtures were found to adopt regular secondary structural conformations seen as a series of beta-turns. An Ad12 peptide bearing a substitution that resulted in only very weak binding to CtBP (Ad12 L258G) was found to be random coil in solution. However, a second mutant (Ad12 V256K), which bound to CtBP rather more strongly (although not as well as the wild type), adopted a conformation similar to that of the wild type. We conclude that secondary structure (beta-turns) and an appropriate series of amino acid side chains are necessary for recognition by CtBP.     

The etiology and determinants of hospital closure

This article examines the etiology of hospital closure and the correlates of hospital closure and the extent of similarity in this organizational outcome between pre- and post-Prospective Payment System (PPS) implementation. It also replicates a study from an earlier time period. Findings support the study's main hypotheses: in more stringent and turbulent markets, institutional and strategic variables are more important determinants of hospital closure. Merger acquisitions are found to be similar to both system acquisitions and autonomous hospitals. Standard Metropolitan Statistical Area (SMSA) status and regulation show an effect on hospital closure and merger acquisition. While many similarities exist when compared to the replicated study and findings prior to PPS implementation, it appears that sufficient differences exist to support the hypothesis that the PPS has an impact upon hospital organizational outcome.     

Identification of HLA class II-restricted determinants of Mycobacterium tuberculosis-derived proteins by using HLA-transgenic, class II-deficient mice

T helper 1 cells play a major role in protective immunity against mycobacterial pathogens. Since the antigen (Ag) specificity of CD4(+) human T cells is strongly controlled by HLA class II polymorphism, the immunogenic potential of candidate Ags needs to be defined in the context of HLA polymorphism. We have taken advantage of class II-deficient (Ab0) mice, transgenic for either HLA-DRA/B1*0301 (DR3) or HLA-DQB1*0302/DQA*0301 (DQ8) alleles. In these animals, all CD4(+) T cells are restricted by the HLA molecule. We reported previously that human DR3-restricted T cells frequently recognize heat shock protein (hsp)65 of Mycobacterium tuberculosis, and only a single hsp65 epitope, p1-20. DR3.Ab0 mice, immunized with bacillus Calmette-Guérin or hsp65, developed T cell responses to M. tuberculosis, and recognized the same hsp65 epitope, p1-20. Hsp65-immunized DQ8.Ab0 mice mounted a strong response to bacillus Calmette-Guérin but not to p1-20. Instead, we identified three new DQ8-restricted T cell epitopes in the regions 171-200, 311-340, and 411-440. DR3.Ab0 mice immunized with a second major M. tuberculosis protein, Ag85 (composed of 85A, 85B, and 85C), also developed T cell responses against only one determinant, 85B p51-70, that was identified in this study. Importantly, subsequent analysis of human T cell responses revealed that HLA-DR3+, Ag85-reactive individuals recognize exactly the same peptide epitope as DR3.Ab0 mice. Strikingly, both DR3-restricted T cell epitopes represent the best DR3-binding sequences in hsp65 and 85B, revealing a strong association between peptide-immunodominance and HLA binding affinity. Immunization of DR3.Ab0 with the immunodominant peptides p1-20 and p51-70 induced T cell reactivity to M. tuberculosis. Thus, for two different Ags, T cells from DR3.Ab0 mice and HLA-DR3+ humans recognize the same immunodominant determinants. Our data support the use of HLA-transgenic mice in identifying human T cell determinants for the design of new vaccines.     

The determinants of respiratory rate during mechanical ventilation

The independent and interactive effect of feedback related to volume, CO2, inspiratory flow, and arousal state on the regulation of respiratory rate in mechanically ventilated humans is not well characterized. We examined the rate response of eight normal volunteers during both quiet wakefulness and non-rapid-eye-movement (NREM) sleep, while mechanically ventilated through a nasal mask in an assist/control mode with a machine back-up rate of 2 breaths/min. Tidal volume (VT) was set slightly above spontaneous VT and then increased by 0.2 L every 3 min up to 1.8 L or 25 ml/kg. Either an inspiratory flow of 40 L/min or an inspiratory time of 2 s (iso-T(I)) was set, with CO2 added (F(I)CO2 > 0) or F(I)CO2 = 0. Measurements were made during both quiet wakefulness and NREM sleep. We found that as VT increased, the respiratory rate decreased; the rate decline was observed during wakefulness and sleep, and under isocapnic as well as hypocapnic conditions. Increasing inspiratory flow raised the respiratory rate during wakefulness and NREM sleep. During NREM sleep, hypocapnia resulted in wasted ventilator trigger efforts. In summary, both VT and inspiratory flow settings affect the respiratory rate, and depending on state, can affect CO2 homeostasis. Ventilator settings appropriate for wakefulness may cause ventilatory instability during sleep.     

The stability of proteins in extreme environments

Three complete genome sequences of thermophilic bacteria provide a wealth of information challenging current ideas concerning phylogeny and evolution, as well as the determinants of protein stability. Considering known protein structures from extremophiles, it becomes clear that no general conclusions can be drawn regarding adaptive mechanisms to extremes of physical conditions. Proteins are individuals that accumulate increments of stabilization; in thermophiles these come from charge clusters, networks of hydrogen bonds, optimization of packing and hydrophobic interactions, each in its own way. Recent examples indicate ways for the rational design of ultrastable proteins.     

The Dienes phenomenon: identification of the determinants of compatibility

Two hundred and four isolates of swarming strains of Proteus species which had been typed for their ability to produce bacteriocin (proticine) and also their proticine sensitivity (P/S typing) were tested in all combinations for their Dienes compatibility with each other. Ninety-eight distinct Dienes compatibility groups were found. Physiological and genetic experiments supported the evidence of typing results that, irrespective of species, both the type of proticine a strain produces (P type) and the sensitivity of the strain to proticine (S type) were determinants of Dienes compatibility. Strains showing compatibility in the Dienes test were of the same P/S type, whereas those of different P/S types were incompatible.     

The structure of iron-sulfur proteins

Ferredoxins are a group of iron-sulfur proteins for which a wealth of structural and mutational data have recently become available. Previously unknown structures of ferredoxins which are adapted to halophilic, acidophilic or hyperthermophilic environments and new cysteine patterns for cluster ligation and non-cysteine cluster ligation have been described. Site-directed mutagenesis experiments have given insight into factors that influence the geometry, stability, redox potential, electronic properties and electron-transfer reactivity of iron-sulfur clusters.     

Socioeconomic determinants of health. The contribution of nutrition to inequalities in health

Social class differences in health are seen at all ages, with lower socioeconomic groups having greater incidence of premature and low birthweight babies, heart disease, stroke, and some cancers in adults. Risk factors including lack of breast feeding, smoking, physical inactivity, obesity, hypertension, and poor diet are clustered in the lower socioeconomic groups. The diet of the lower socioeconomic groups provides cheap energy from foods such as meat products, full cream milk, fats, sugars, preserves, potatoes, and cereals but has little intake of vegetables, fruit, and wholewheat bread. This type of diet is lower in essential nutrients such as calcium, iron, magnesium, folate, and vitamin C than that of the higher socioeconomic groups. New nutritional knowledge on the protective role of antioxidants and other dietary factors suggests that there is scope for enormous health gain if a diet rich in vegetables, fruit, unrefined cereal, fish, and small quantities of quality vegetable oils could be more accessible to poor people.     

Biochemical determinants in Gender identity

The purpose of this communication is to report cognate studies which suggest that the nature of the peripheral metabolism of testosterone may impart gender direction to thought construction and motive. In patients with the complete testicular feminizing syndrome [4], the XO/XY syndrome [4], female trans-sexualism [4] and testicular agenesis [5] HCG-tests of 3 days duration were performed, and plasma and urinary testosterone, urinary excretion of 5 alpha-androstane, 3 alpha, 17 beta-diol (5 alpha-diol), 5 beta-androstane, 3 alpha, 17 beta-diol (5 beta-diol) and epiandrosterone before and after stimulation were measured. In addition steroid transformation was examined by incubation studies with human fetal brain tissue. The results of the latter method presented here are in agreement with published work. It seems clear therefore that the peripheral levels of androgens, oestrogens and their metabolites combine with cerebral steroid transformation, metabolism and possible also synthesis in order to establish gender identity. Exploration of the role of peripheral hormones as stimulators of both gender identity and gender function has dictated the need for a new approach to therapy for gender abnormalities in psyche and soma.     

The determinants of user satisfaction with community psychiatric nursing care

A 70-year-old diabetic woman with sensory polyneuropathy presented with osteonecrosis of the toes and a plaque-like lesion on the dorsum of the ipsilateral foot. Histological diagnosis of eccrine syringofibroadenoma (ES) was made. A review of the literature reveals several cases of solitary ES of the foot in diabetic patients with peripheral neuropathy. This variant of ES seems to be an eccrine sweat duct hyperplasia during the restoration of skin structures damaged by traumas in a situation of peripheral neuropathy. Diabetes and polyneuropathy should be searched for in patients with ES, particularly in acral locations.     

The common nodABC genes of Rhizobium meliloti are host-range determinants

Symbiotic bacteria of the genus Rhizobium synthesize lipo-chitooligosaccharides, called Nod factors (NFs), which act as morphogenic signal molecules on legume hosts. The common nodABC genes, present in all Rhizobium species, are required for the synthesis of the core structure of NFs. NodC is an N-acetylglucosaminyltransferase, and NodB is a chitooligosaccharide deacetylase; NodA is involved in N-acylation of the aminosugar backbone. Specific nod genes are involved in diverse NF substitutions that confer plant specificity. We transferred to R. tropici, a broad host-range tropical symbiont, the ability to nodulate alfalfa, by introducing nod genes of R. meliloti. In addition to the specific nodL and nodFE genes, the common nodABC genes of R. meliloti were required for infection and nodulation of alfalfa. Purified NFs of the R. tropici hybrid strain, which contained chitin tetramers and were partly N-acylated with unsaturated C16 fatty acids, were able to elicit nodule formation on alfalfa. Inactivation of the R. meliloti nodABC genes suppressed the ability of the NFs to nodulate alfalfa. Studies of NFs from nodA, nodB, nodC, and nodI mutants indicate that (i) NodA of R. meliloti, in contrast to NodA of R. tropici, is able to transfer unsaturated C16 fatty acids onto the chitin backbone and (ii) NodC of R. meliloti specifies the synthesis of chitin tetramers. These results show that allelic variation of the common nodABC genes is a genetic mechanism that plays an important role in signaling variation and in the control of host range.     

Residues at the carboxy terminus of T4 DNA polymerase are important determinants for interaction with the polymerase accessory proteins

Three T4 DNA polymerase accessory proteins (44P/62P and 45P) stimulate the polymerase (pol) activity and the 3'-5' exonuclease (exo) activity of T4 DNA polymerase (43P) on long, double-stranded DNA substrates. The 44P/62P "clamp loader" facilitates the binding of 45P, the "sliding clamp", to DNA that is primed for replication. Using a series of truncated 43P mutants, we identified a region at the extreme carboxy terminus of the DNA polymerase that is required for its interaction with accessory proteins. Truncation mutants of 43P lacking the carboxy-terminal 3, 6, or 11 residues retained full pol and exo activity on short synthetic primer-templates. However, the ability of the accessory proteins to enhance these activities on long double-stranded DNA templates was drastically reduced, and the extent of the reduction in activity was greater as more residues were deleted. One of the truncation mutants (N881), which had 17 residues removed from the carboxy terminus, showed reduced binding affinity and diminished pol activity but enhanced exo activity upon incubation with a small primer-template. The exo activity of the N881 mutant, on short, single-stranded DNA was unchanged, however, compared to the wild-type enzyme. These results are consistent with inferences drawn from the crystal structure of a DNA polymerase from a related T-even phage, RB69, where the carboxy-terminal 12 residues (equivalent to the 11 residues of 43P from phage T4) protrude from the thumb domain and are free to interact with complementary surfaces of the accessory proteins. The structural integrity of the thumb region in the N881 mutant is probably perturbed and could account for its reduced binding affinity and pol activity when incubated with short, double-stranded DNA substrates.