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Biomedical subjects

M Hooks

Publications and source records attributed to M Hooks.

7 recordsLinked to original sources

The Arabidopsis acyl-CoA oxidase gene family.

A family of acyl-CoA oxidase isozymes catalyse the first step in the peroxisomal fatty acid beta-oxidation spiral. Our group and others have recently characterized four genes from this family in the model oilseed Arabidopsis. These genes encode isozymes with different acyl-CoA substrate specificities, which together encompass the full range of fatty acid chain lengths that exist in vivo. Here we review the biochemical properties and physiological roles of the acyl-CoA oxidase isozymes.

Acyl-CoA Oxidase↗

Differentiating pervasive developmental disorder not otherwise specified from autism and language disorders.

Features useful in distinguishing children with pervasive developmental disorder (PDD) from those with autism or language disorder were developed from a retrospective chart review using groups of children with PDD-NOS and MA- and sex-matched autistic and language-disordered groups. Charts were reviewed using a list of 80 items compiled from various sources. Items that had adequate interrater reliability and significantly discriminated the PDD-NOS cases from the language-disordered or autistic cases were then evaluated using a second set of cases and signal detection methods. Fewer items significantly discriminated cases with autism from those with PDD-NOS as compared to cases with language disorder. Clinical implications are discussed.

Autistic Disorder↗

Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues.

The frizzled (fz) locus of Drosophila encodes a protein (Fz) with a seven-transmembrane-domain profile characteristic of G-protein-coupled receptors. In Drosophila, genetic evidence suggests that Fz functions to transmit and transduce polarity signals in epidermal cells during hair and bristle development. We have isolated from a UMR 106 rat osteosarcoma cell library a cDNA (fz-1) encoding a predicted 641-residue protein (Fz-1) with 46% homology with Drosophila Fz. We also identified a second cDNA (fz-2) encoding a protein (Fz-2) of 570 amino acids that is 80% homologous with Fz-1, with divergence most evident in the extracellular domains. Southern blots of rat genomic DNA indicated that fz-1 and fz-2 represent distinct genes. Northern analysis revealed the presence of a single fz-1 mRNA (4.7 kilobases) and two fz-2 mRNAs (2.5 and 4.5 kilobases) in rat tissues. The fz-1 and fz-2 genes are widely expressed in rat tissues with the highest steady-state levels of mRNA in kidney, liver, heart, uterus, and ovary. fz-1 and -2 mRNA levels were greater in neonatal than in corresponding adult tissues. Treatment of UMR 106 cells with bone resorbing agents including parathyroid hormone, epidermal growth factor, and 1,25-dihydroxyvitamin D3 produced increases in fz-1 and -2 mRNA levels. We suggest that hormonal induction of Fz proteins in osteoblasts serves to promote intercellular signaling required for functional responses such as increased bone resorption. Fz-1 and Fz-2 may represent products of a gene family whose members serve as transducers or intercellular transmitters of signals required for normal morphogenesis and/or differentiated function in diverse tissues.

Amino Acid Sequence↗

High cardiac output of advanced liver disease persists after orthotopic liver transplantation.

This study measured cardiac output before and 1 or 2 yr after orthotopic liver transplantation in 23 patients. Cardiac output was measured by thermodilution before transplantation and by first-pass radionuclide angiocardiography at follow-up. Study patients were selected as those doing well clinically and by standard laboratory tests at 1-yr and 2-yr reevaluations with no evidence of rejection: six had mild recurrent hepatitis shown on biopsy samples. Hepatocyte function was normal at the time of the study as shown by galactose elimination capacity of 442 +/- 90 mg/min. Medications were cyclosporine and prednisone in all patients, azathioprine in 10 patients and a combination of antihypertensive therapy to maintain diastolic blood pressure less than 90 mm Hg in 20 patients. Mean (+/- S.D.) pretransplantation cardiac output was 9.1 +/- 3.1 L/min and remained elevated at 8.3 +/- 2.1 L/min 1 yr, and 9.6 +/- 2.6 L/min (n = 13) 2 yr after transplantation. A significant (p less than 0.001) correlation was found between pretransplant and follow-up cardiac output. End diastolic, end systolic and stroke volumes are all increased in a pattern similar to that seen in end-stage cirrhosis. These data show that the high cardiac output of the hyperdynamic state of advanced liver disease persists after liver transplantation. The mechanisms and consequences of this require further study.

Cardiac Output↗

Increased galactose clearance after liver transplantation: a measure of increased blood flow through the denervated liver?

This study measured the liver blood flow-dependent index of galactose clearance in patients after liver transplantation, to test the hypothesis that liver blood flow is increased in the denervated liver. Eight normal subjects and 16 patients 1 to 8 months after liver transplant were studied. All patients were stable with no evidence of severe rejection at the time of study. Galactose clearance was measured at steady state during continuous infusion of 75 mg per min of 5% galactose. The results show a statistically significant (p less than 0.01) higher average galactose clearance in the transplant patients (1,187 +/- 316 ml per min per m2) compared to the control group (709 +/- 121 ml per min per m2). The major limiting factor in galactose clearance at low concentrations is liver blood flow, and we interpret these data as evidence for increased blood flow in the transplanted liver. Possible mechanisms for the increased galactose clearance are (i) loss of normal vasomotor tone in the denervated liver, or (ii) persistence of abnormal systemic hemodynamics after transplantation. Elucidation of these mechanisms awaits further study.

Adult↗

Perturbation of red cell membrane structure during intracellular maturation of Plasmodium falciparum.

An experimental approach, which in this study was applied to the malarial system, can be used to analyze the molecular structure and organization of individual phospholipids in a wide variety of biological membranes. Electron spin resonance spectroscopy was used to investigate the structural modifications of the major red cell phospholipids that occur in erythrocyte membranes infected with the human malarial parasite, Plasmodium falciparum. These modifications were correlated with the intracellular developmental stage of the parasite. Phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine were increasingly disordered (fluidized) as infection progressed. This disordering occurred at different rates and to varying extents.

Animals↗