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Biomedical subjects

J Wild

Publications and source records attributed to J Wild.

At least 73 records · Page 4Linked to original sources

Survey provides data on practice acquisition activity.

In an effort to assess trends in the number and type of physician practices being acquired by healthcare organizations throughout the country and to gather information on related costs, HEALTHCARE FINANCIAL MANAGEMENT and Physician Services of America, Louisville, Kentucky, cosponsored the first national survey on trends in practice acquisition and integration. More than 5,300 senior financial executives in healthcare organizations and systems were surveyed. Thirty-six percent of respondents said that their healthcare organization had acquired practices in the past five years. Most practice acquisitions were in primary care; family practice physicians and groups were in high demand, with the Midwest the most active region in the country regarding family practice acquisitions. In addition, the survey gathered information about the considerations involved in acquisitions. Respondents cited strategic planning, communicating with medial staff, negotiating compensation packages, and managing productivity as reasons to pursue acquisition opportunities.

Data Collection↗

The methylfolate axis in neural tube defects: in vitro characterisation and clinical investigation.

We have investigated various micronutrients important to folate metabolism in women with two previous neural tube defect (NTD)-affected pregnancies. Results suggest the disposition of plasma 5-methyltetrahydrofolate (5CH3-H4PteGlu) with respect to dietary intake may differ from that of the control population. It appears that to achieve a given plasma level of 5CH3-H4PteGlu, the population with a history of NTD pregnancies needs to take in more dietary folate than controls. We discuss this in the context of a potential lesion at or upstream from 5,10-methylenetetrahydrofolate reductase (MTHFR). This metabolic axis, which is responsible for the multienzymic conversion of PteGlu to 5CH3-H4PteGlu, has been investigated in a rat model using liver homogenate. The anticonvulsant drug (ACD) carbamazepine was found to inhibit the reaction in terms of a reduced Vmax and increased Km. Inhibition approaching maximal was found to occur at therapeutic levels of ACD. Various potential inhibitory sites along the methylfolate axis are considered and possible relationships to congenital malformations discussed. We describe folate and one carbon metabolism in relation to potential NTD lesion sites, not only in the light of present findings, but with respect to the published findings of other workers. Based on our hypothesis that an NTD lesion exists upstream from MTHFR, we expound how pteroylmonoglutamate supplementation may protect against NTD (i) by reducing endotoxic homocysteine and (ii) through inhibiting MTHFR (as do dihydrofolates) and thus diverting one carbon units into DNA thymine.

Animals↗

Investigation of folate intake and metabolism in women who have had two pregnancies complicated by neural tube defects.

OBJECT: To investigate folate intake and blood levels of folic acid and vitamin C in women with and without a history of two NTD-affected pregnancies and to measure the increase in serum folate following ingestion of orange juice. SUBJECTS: Sixteen women with a history of two NTD-affected infants and 16 controls with no such history, none of whom were either pregnant or taking vitamin supplements. The orange juice loading test was carried out on eight matched pairs. MAIN OUTCOME MEASURES: Dietary intake of folate was assessed by questionnaire and blood levels of folate and vitamin C were measured. RESULTS: There was no evidence of decreased intake of folate in subjects who had had two NTD-affected pregnancies. In controls, both serum and red cell folate showed significant correlation with dietary folate, while in subjects there was no such correlation. Subjects also had smaller increases in serum folate following an oral load than controls, although the differences were not significant. CONCLUSION: Women who have had two NTD-affected pregnancies may have defective folate metabolism. Further investigations on short term utilisation of ingested food folates in these women are required.

Adult↗

Organization and expression of the Escherichia coli K-12 dad operon encoding the smaller subunit of D-amino acid dehydrogenase and the catabolic alanine racemase.

A fragment of the Escherichia coli K-12 chromosome complementing the D-amino acid dehydrogenase and catabolic alanine racemase deficiency of a dad operon deletion mutant was cloned in a mini-Mu plasmid. The dadA and dadX genes were localized to a 3.5-kb part of the plasmid insert. The nucleotide sequence of this fragment revealed two open reading frames encoding 432- and 356-amino-acid-long proteins. We show here that they correspond to the dadA and dadX genes. The dadA gene can encode only the smaller of the two subunits of D-amino acid dehydrogenase. A computer search revealed the presence of a flavin adenine dinucleotide-binding motif in the N-terminal domain of the deduced DadA protein sequence. This is in agreement with biochemical data showing that the D-amino acid dehydrogenase contains flavin adenine dinucleotide in its active center. The predicted dadX gene product appeared to be 85% identical to a dadB-encoded catabolic alanine racemase of Salmonella typhimurium. The organization of the dadA and dadX genes confirmed our previous conclusion based on the genetic data (J. Wild, J. Hennig, M. Lobocka, W. Walczak, and T. Kłopotowski, Mol. Gen. Genet. 198:315-322, 1985) that these genes form an operon. The main transcription start points of the dad operon were determined by primer extension. They are preceded by a putative sigma 70 promoter sequence and two cyclic AMP-cyclic AMP receptor protein (cAMP-CRP) binding sites, one of higher and one of lower affinity to CRP. We propose that the high-affinity site, centered 59.5 bp upstream of the main transcription start point, plays a role in cAMP-CRP-mediated activation of dad operon expression in the absence of glucose.

Alanine Racemase↗

Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated pre-term babies.

A sick premature baby who requires intensive care will undergo many uncomfortable procedures. It is now accepted that such babies perceive pain and need adequate analgesia, but little is known about the effects of sedation in these patients. We investigated the use of morphine to provide analgesia and sedation for ventilated preterm babies in a randomised, double-blind, placebo-controlled trial. 41 mechanically ventilated babies who had been treated with surfactant (Curosurf) for hyaline membrane disease were randomly assigned morphine in 5% dextrose (100 micrograms/kg per h for 2 h followed by 25 micrograms/kg per h continuous infusion) or 5% dextrose (placebo). Plasma catecholamine concentrations were measured 1 h after the first dose of surfactant and 24 h later. Blood pressure was measured at study entry and after 6 h. The morphine and placebo groups showed no differences in method of delivery, Apgar scores, birthweight, gestation, or catecholamine concentrations at baseline. Morphine-treated babies showed a significant reduction in adrenaline concentrations during the first 24 h (median change -0.4 [95% CI -1.1 to -0.3] nmol/L p < 0.001), which was not seen in the placebo group (median change 0.2 [-0.6 to 0.6] nmol/L, p = 0.79). There was a non-significant reduction in noradrenaline concentration in the morphine group. Blood pressure showed a slight but non-significant fall (median -4 mm Hg) in morphine-treated babies. The incidence of intraventricular haemorrhage, patent ductus arteriosus, and pneumothorax, the number of ventilator days, and the numbers of deaths did not differ significantly between the groups. Morphine, in the dose regimen we used, is safe and effective in reducing adrenaline concentrations in preterm ventilated babies.

Analgesia↗

Physical attractiveness of boys with gender identity disorder.

University students blind to group status rated boys with gender identity disorder and clinical control boys regarding their physical attractiveness. Ratings were made of the face and upper torso from photographs taken at the time of clinical assessment (mean age, 8.1 years). On all five adjectives (attractive, beautiful, cute, handsome, and pretty), boys with gender identity disorder were judged to be more attractive than were the clinical control boys. Attractiveness correlated with extent of behavioral femininity in the clinical control group, but not in the group of boys with gender identity disorder. The extent to which the group differences in attractiveness were due to objective, structural differences in facial attractiveness vs. socially created, or subjective, processes is discussed.

Beauty↗

[Recurrent episcleritis with hyperemia of the external ear As an early symptom of chronic polychondritis].

A 49-year-old patient with relapsing polychondritis, who presented in the first instance to an eye department, is described. The patient had episcleritis, papilloedema and posterior scleritis. Both auricles were red, swollen and tender under pressure. The patient responded well to systemic steroid therapy for two weeks. Relapsing polychondritis is a rare connective tissue disorder. Early diagnosis is important, as progressive disease may cause lesions of vital organs (lung, heart).

Cartilage Diseases↗

Investigation of factors influencing folate status in women who have had a neural tube defect-affected infant.

OBJECTIVE: To investigate folate intake and blood levels of vitamins in women with and without a history of neural tube defect (NTD)-affected infant and to explore the relation between red cell and serum folate in those women. SUBJECTS: Twenty-nine women with a history of NTD-affected infant, who had taken periconceptional vitamin supplements one year or more prior to the study and twenty-nine controls with no such history. MAIN OUTCOME MEASURES: Dietary intake of folate was assessed by questionnaire and blood levels of folate, vitamin B12 and vitamin C were measured. RESULTS: Neither dietary intake of folate nor any of the blood vitamins measured were lower in the women with a history of NTD infant. The majority of women who had received periconceptional vitamin supplementation subsequently had adequate folate intakes and red blood cell folates greater than 160 micrograms/l. Smokers had lower plasma Vitamin C levels than nonsmokers. Multiple regression analysis suggested that the relation between red blood cell (RBC) and serum folate may differ between women with and without a history of NTD. CONCLUSIONS: Women with a history of NTD-affected infants may have different folate metabolism from those who have not.

Adult↗

Accumulation of secretory protein precursors in Escherichia coli induces the heat shock response.

The accumulation of secretory protein precursors, caused either by mutations in secB or secA or by the overproduction of export-defective proteins, results in a two- to fivefold increase in the synthesis of heat shock proteins. In such strains, sigma 32, the alternative sigma factor responsible for transcription of the heat shock genes, is stabilized. The resultant increase in the level of sigma 32 leads to increased transcription of heat shock genes and increased synthesis of heat shock proteins. We have also found that although a secB null mutant does not grow on rich medium at a temperature range of 30 to 42 degrees C, it does grow at 44 degrees C. In addition, we found that a secB null mutant exhibits greater thermotolerance than the wild-type parental strain. Elevated levels of heat shock proteins, as well as some other non-heat shock proteins, may account for the partial heat resistance of a SecB-lacking strain.

Bacterial Proteins↗

Prediction of adjustment from preschool to middle childhood.

This study identified predictor variables associated with outcome in middle childhood in a clinical preschool sample. These variables were examined in relation to functional level at outcome. At Time 1 the sample consisted of 129 children admitted to a psychiatric preschool program; 82 of these children comprised the follow-up sample at Time 2. The results indicated that the variables significantly associated with each child's outcome were IQ, the presence of diagnosis at Time 1 and the length of time each child was in the treatment program. Different predictors were important for different outcomes and a given predictor variable was not equally salient across all levels of outcome.

Adolescent↗

Partial loss of function mutations in DnaK, the Escherichia coli homologue of the 70-kDa heat shock proteins, affect highly conserved amino acids implicated in ATP binding and hydrolysis.

A set of 37 mutations in DnaK, the Escherichia coli homologue of the 70-kDa heat shock proteins, was isolated using a selection for high constitutive expression of heat shock proteins. Of these, 11 mutants were able to carry out some but not all functions of DnaK. These partial function mutants were divided into two classes. Class I mutants are recessive and permit replication of bacteriophage lambda and growth of cells up to 40 degrees C. Class II mutants are dominant, do not permit growth of lambda, and are temperature-sensitive for growth above 34 degrees C. Mutations in both classes alter amino acids that are highly conserved in the 70-kDa heat shock protein family. The dominant negative mutations provide strong genetic evidence that at least one form of DnaK is multimeric. Moreover, every dominant negative mutation occurs at an amino acid that has been hypothesized to be intimately involved in the process of ATP binding and hydrolysis. Our findings provide strong support for the hypothesis that such mutations are excellent tools for identifying amino acids that play critical roles in protein function.

Amino Acid Sequence↗

Effect of morphine and pancuronium on the stress response in ventilated preterm infants.

Ninety-five premature newborns who had hyaline membrane disease and were struggling against the ventilator were randomised to one of three treatment groups: morphine (group M), pancuronium (group P) or morphine with pancuronium (group M+P). The dose of morphine was 50 micrograms/kg per h but was increased to 100 micrograms/kg per h in group M infants if they continued to struggle. The dosage of pancuronium was 100 micrograms/kg given as required to inhibit spontaneous respiration. Plasma catecholamine levels were measured on entry and at 24 h. Blood pressure and ventilatory requirements were determined on entry and at 6 h. The clinical outcome of the infants was documented. Group M infants (n = 29) showed a significant reduction in noradrenaline levels (median change -2.2 nmols/l (range -47.2 to +7.2 nmols/l), although seven were withdrawn from this group because of failure to settle. Group P (n = 28) and group M+P (n = 38) showed no significant change in noradrenaline levels. Comparison between the groups showed that group M infants had a significant reduction in noradrenaline levels compared with group P. The immediate effects of treatment on blood pressure and ventilatory requirements were similar in the three groups. The clinical outcome did not differ for any of the measured parameters. When adequate sedation is achieved, morphine may reduce the stress of newborn intensive care.

Blood Pressure↗

DnaK and DnaJ heat shock proteins participate in protein export in Escherichia coli.

In Escherichia coli secreted proteins must be maintained in an export-competent state before translocation across the cytoplasmic membrane. This function is carried out by a group of proteins called chaperones. SecB is the major chaperone that interacts with precursor proteins before their secretion. We report results indicating that the DnaK and DnaJ heat shock proteins are also involved in the export of several proteins, most likely by acting as their chaperones. Translocation of alkaline phosphatase, a SecB-independent protein, was inhibited in dnaK- and dnaJ- mutant strains, suggesting that export of this protein probably involves DnaK and DnaJ. In addition, DnaK and DnaJ play a critical role in strains lacking SecB. They are required both for viability and for the residual processing of the SecB-dependent proteins LamB and maltose-binding protein (MBP) seen in secB null strains. Furthermore, overproduction of DnaK and DnaJ permits strains lacking SecB to grow in rich medium and accelerates the processing of LamB and MBP. These results suggest that under conditions where SecB becomes limiting, DnaK and DnaJ probably substitute for SecB and facilitate protein export. This provides the cell with a mechanism to overcome a temporary imbalance in the secretion process caused by an abrupt expansion in the pool of precursor proteins.

Alkaline Phosphatase↗