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Biomedical subjects

J Hunt

Publications and source records attributed to J Hunt.

At least 19 recordsLinked to original sources

Purification and properties of milk xanthine dehydrogenase.

Milk xanthine oxidase (XO) has been prepared in a dehydrogenase form (XDH) by purifying the enzyme in the presence of 2.5 mM dithiothreitol. Unlike XO, which reacts rapidly only with oxygen and not with NAD, the XDH form of the enzyme reacts rapidly with NAD. XDH has a turnover number for the NAD-dependent conversion of xanthine to urate of 380 mol/min/mol at pH 7.5, 25 degrees C, with a Km = < or = 1 microM for xanthine and a Km = 7 microM for NAD, but has very little O2-dependent activity. There is evidence that the two forms of the enzyme have different flavin environments: XDH stabilizes the neutral form of the flavin semiquinone and XO does not. Further, XDH binds the artificial flavin 8-mercapto-FAD in its neutral form, shifting the pK of this flavin by 5 pH units, while XO binds 8-mercapto-FAD in its benzoquinoid anionic form. XDH can be converted back to the XO form by the addition of three to four equivalents of the disulfide-forming reagent 4,4'-dithiodipyridine, suggesting that, in the XDH form of the enzyme, disulfide bonds are broken; this may cause a conformational change which creates a binding site for NAD and changes the protein structure near the flavin.

Animals

Asthma under-recognition and under-treatment in an Australian community.

In a study in south-western Sydney, we examined asthma symptoms in a random sample of 4239 schoolchildren aged five-12 years. The prevalence of current wheeze and cough was 17.1% (95% CI 16.0-18.2%). Interviews were conducted with the parents of all 214 symptomatic children from two of the six schools. Only 60% of these children had ever been labelled as asthma, and only 20% were using appropriate asthma treatment. Fewer than 6% had ever had their airway function assessed. There was a socio-economic difference, with better levels of asthma recognition and management in children attending the school in the more affluent region. The findings suggest that asthma recognition, assessment and management in the Australian community, as in New Zealand and the UK, may need to be improved.

Asthma

Coexisting macrophage-associated fibrin formation and tumor cell urokinase in squamous cell and adenocarcinoma of the lung tissues.

Mechanisms of coagulation activation in situ were studied by means of immunohistochemical techniques applied to surgically resected primary adenocarcinomas and squamous cell carcinomas of the lung. Findings in these two histologic types were similar. Double-labeling techniques using macrophage-specific antibody together with antibody to either tissue factor, factor VII, factor X, or factor V revealed coincident staining for each of these coagulation factors on tumor-associated macrophages. Staining of tumor cells for these factors was rare and inconsistent. Both macrophages and fibroblasts in the tumor connective tissue stained for the a subunit of factor XIII. Fibrinogen was abundant throughout the tumor connective tissue, but staining for fibrin and D-dimer cross-linked sites of fibrin was restricted to areas adjacent to macrophages, indicating that thrombin was generated in association with tumor macrophages but not with tumor cells. By contrast, tumor cells stained diffusely for urokinase-type plasminogen activator and focally for thrombomodulin. These findings contrast with those reported previously for small cell carcinoma of the lung and suggest that coagulation activation in adenocarcinoma and squamous cell carcinoma of the lung may occur indirectly through activation of certain host cells such as macrophages. By contrast, tumor cell plasminogen activator may mediate certain aspects of the malignant phenotype in these tumor types.

Adenocarcinoma

Cellular localization of activated factor X by Xa-specific probes.

A probe, recombinant antistasin, that reacts specifically with the activated form of factor X (Xa) was used in immunohistochemical procedures to detect cellular sites of Xa generation within intact tissues. Factor Xa was detected on tumor cells in small cell carcinoma of the lung, renal cell carcinoma, and malignant melanoma. Tumor-associated macrophages (but not tumor cells) expressed Xa in adenocarcinoma and squamous cell carcinoma of the lung, and Hodgkin's disease. Factor Xa in these locations corresponded to evidence reported previously for an intact coagulation pathway and thrombin formation associated with these tumor cells and macrophages. By contrast, only rare connective tissue cells stained for Xa in breast and colon cancer, tumor types shown previously to lack an intratumoral coagulation pathway and thrombin generation, and in normal liver, lung, breast, kidney, and placental tissues. Hepatocytes did not stain. These results suggest that such probes may be useful for studying the activation state of cell-associated factor X in situ within intact tissues.

Factor Xa

The emotional phases of marital separation: an empirical investigation.

The emotional process of marital separation was investigated via the application of Bowlby's theory of loss. Physical separation was found to entail the three phases--wish to recover the lost object, disorganization, and reorganization--proposed by Bowlby. Length of time separated appeared the most powerful factor in emotional resolution. The clinical implications of the findings are discussed.

Adaptation, Psychological

The cytological recognition of African siderosis on bone smears.

Eight cases of African siderosis primarily recognized on cytological smears are presented and discussed. All the smears were obtained from Jamshidi needle biopsies of vertebral bodies. Six cases showed siderosis only, while a seventh showed two pathological processes on one slide, namely metastatic keratinizing squamous carcinoma and siderosis. The remaining case showed cytological evidence of tuberculosis and siderosis. All cases were histologically confirmed, an additional feature in two cases being osseous tuberculosis which was not evident on the cytological smears. A search of the literature failed to reveal any report on the cytological recognition of this disease, or its association with tuberculosis.

Adult

Attitudes towards gamete donation among couples undergoing in vitro fertilization.

The attitudes of 234 anonymous couples undergoing in vitro fertilization toward sperm and oocyte donation were explored by questionnaire. All the questionnaires were returned of which 222 (95%) were complete and analysed. A high proportion of couples found the use of donor sperm acceptable for therapeutic, diagnostic and treatment purposes (77%, 90% and 97% respectively) and 72%, 84% and 90% respectively were willing to donate oocytes for these purposes. Of potential oocyte donors 41% would agree to nonanonymous donation, 12% would wish to meet the recipient couple and although only 4% wanted to choose the recipient, a quarter of the couples would prefer a relative or friend as the recipient. Provision of nonidentifying information about the donor to the recipient couple was acceptable to almost 70% whereas 40% found giving the same information to the child acceptable.

Adult

Comparative and interactive in vivo effects of tumor necrosis factor alpha and endotoxin.

A comparative and interactive analysis of the effects of tumor necrosis factor alpha (TNF) and endotoxin (ETX) on selected hemodynamic and glucoregulatory alterations was performed in conscious, unrestrained, adult male Holtzman rats. Rats with indwelling carotid artery and jugular vein cannulae were administered intravenous (i.v.) bolus injections of either (1) ETX at 1.55 or 30 mg/kg; (2) TNF at 0.1, 0.5, or 1.0 mg/kg; or (3) TNF plus ETX as a low dose co-treatment at 0.1 mg/kg plus 1.55 mg/kg, respectively. Control groups received either saline or heat-inactivated TNF. TNF induced a lethal response such that 1.0 mg/kg resulted in five out of six deaths within 6 hr. Elevated pulse rates, early hyperglycemia, late hypoglycemia, hyperlactacidemia, hypoinsulinemia, and elevated catecholamine concentrations were evident after injection of 1.0 mg/kg TNF. The pathophysiological alterations observed after 1.0 mg/kg TNF were comparable to the changes observed after the administration of a highly lethal, 30 mg/kg dose of ETX (six out of six deaths within 24 hr). Co-treatment with low doses of TNF plus ETX resulted in the rapid demise of the rats, resulting in six out of six deaths within 4 hr. The resultant shocklike state was accompanied by significant hypotension, hyperglycemia and hyperlactacidemia, similar to the changes induced by highly lethal doses of TNF or ETX alone. This study supports the involvement of TNF in the pathogenesis of gram-negative septic shock and documents the hemodynamic and glucoregulatory alterations which accompany the exacerbated shocklike state induced after co-treatment with separately, minimally lethal doses of TNF plus ETX.

Animals

Isolation of four forms of acetone-induced cytochrome P-450 in chicken liver by h.p.l.c. and their enzymic characterization.

The purpose of this study was to purify and characterize the forms of cytochrome P-450 induced in chicken liver by acetone or ethanol. Using high performance liquid ion-exchange chromatography, we were able to isolate at least four different forms of cytochrome P-450 which were induced by acetone in chicken liver. All four forms of cytochrome P-450 proved to be distinct proteins, as indicated by their N-terminal amino acid sequences and their reconstituted catalytic activities. Two of these forms, also induced by glutethimide in chicken embryo liver, appeared to be cytochromes P450IIH1 and P450IIH2. Both of these cytochromes P-450 have identical catalytic activities towards benzphetamine demethylation. However, they differ in their abilities to hydroxylate p-nitrophenol and to convert acetaminophen into a metabolite that forms a covalent adduct with glutathione at the 3-position. Another form of cytochrome P-450 induced by acetone is highly active in the hydroxylation of p-nitrophenol and in the conversion of acetaminophen to a reactive metabolite, similar to reactions catalysed by mammalian cytochrome P450IIE. Yet the N-terminal amino acid sequence of this form has only 30-33% similarity with cytochrome P450IIE purified from rat, rabbit and human livers. A fourth form of cytochrome P-450 was identified whose N-terminal amino acid sequence and enzymic activities do not correspond to any mammalian cytochromes P-450 reported to be induced by acetone or ethanol.

Acetaminophen

The transposable element Uhu from Hawaiian Drosophila--member of the widely dispersed class of Tc1-like transposons.

We report the complete nucleotide sequence of the transposable element Uhu from the vicinity of the alcohol dehydrogenase (Adh) gene of Drosophila heteroneura (an endemic Hawaiian Drosophila). The complete element is about 1650 base-pairs (bp) long, has 46-50 base-pair inverse imperfect repeats at it's ends, and contains a large open reading frame potentially encoding a 192 amino acid protein. We demonstrate that Uhu belongs to a class of transposable elements which includes Tc1 from Caenorhabditis elegans, Barney from Caenorhabditis briggsae, and HB1 from Drosophila melanogaster. All of these elements share significant sequence similarity, are approximately 1600 base pairs long, have short inverse terminal repeats (ITRs), contain open reading frames (ORFs) with significant sequence identity, and appear to insert specifically at TA sequences generating target site duplications.

Alcohol Dehydrogenase

Subtyping aggression in children and adolescents.

To document the existence of "predatory" (goal-oriented, planned, hidden, or controlled) and "affective" (impulsive, unplanned, overt, or uncontrolled) subtypes of aggression, this study assessed 73 aggressive child and adolescent psychiatric patients for the presence of theoretically predatory and affective behaviors. Cluster analysis, using the reliable items, confirmed the predicted partition, yielding a "predatory" and an "affective" cluster. The scale, with a total score from +5 (fully predatory) to -5 (fully affective), had good internal consistency (alpha = .73). The score distribution tended to be bimodal, with peaks at -3 (predominantly affective) and 1 (mixed). Patients with "affective" aggression were more likely to have lower IQ, to receive neuroleptics or lithium, and to have a chart diagnosis of schizophrenia. History of drug abuse was more frequent among the "predatory" patients.

Adolescent

Systemic lupus erythematosus and miliary tuberculosis in a prepubertal girl--a case report.

A 13 year old girl presented with miliary tuberculosis and active systemic lupus erythematosus (S.L.E.). She responded to a combination of antituberculous drugs and systemic steroids. This case illustrates the fact that S.L.E. presenting in childhood may be rare but not unknown and exemplifies the need for vigilance in detecting life threatening infections in this group of patients.

Adolescent

Clinical experience with a hypotonic oral rehydration solution for treatment of pediatric gastroenteritis in the United Kingdom.

Animal and human perfusion studies suggest that water absorption can be optimized by glucose-electrolyte solutions with low total osmolality. A new oral rehydration solution (ORS), reformulated Dioralyte (RD), containing 60 mmol/L of sodium and 90 mmol/L of glucose with an osmolality of 240 mosm/kg, was tested for safety and efficacy in children in the United Kingdom with acute gastroenteritis. In a double-blind, controlled trial, RD was compared with standard Dioralyte (SD), a widely used low-sodium, high-glucose solution containing 35 mmol/L of sodium and 200 mmol/L of glucose, with an osmolality of 310 mosm/kg. Infants and children aged 2 weeks to 3 years admitted with acute gastroenteritis of less than five days' duration and mild to moderate dehydration were randomized to receive either RD or SD. Clinical and laboratory assessments were made on admission and 12, 24, and 48 hours after treatment. Thirty-two children were enrolled in the study; 14 received RD and 18 SD. No adverse effects from either ORS were reported. Efficacy was evaluated in 24 patients, of whom eight received RD and 16 SD. Total ORS intake and intake in milliliters per kilogram were similar in both treatment groups. Mean fluid balance, mean percentage weight change, and median stool frequency did not differ between the groups at 12, 24, and 48 hours after onset of treatment. Three (12.5%) patients had greater than or equal to 0.05% reducing substances in the stool during treatment, and the incidence was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool