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Biomedical subjects

P Godfrey

Publications and source records attributed to P Godfrey.

15 recordsLinked to original sources
PubMed2000

Regulation of the pituitary somatotroph cell by GHRH and its receptor.

Hormones from the hypothalamus mediate interactions between the nervous and endocrine systems by controlling the activity of specific target cells in the anterior pituitary gland. The hypothalamic peptide, growth hormone-releasing hormone (GHRH), acts on pituitary somatotroph cells to stimulate their proliferation during development and to regulate their ability to produce and secrete growth hormone (GH). These actions are mediated by a recently identified receptor for GHRH that belongs to family B-III of the G protein-coupled receptor superfamily. The rat GHRH receptor is expressed predominantly in the pituitary gland and in somatotroph cells. To investigate this tissue- and cell-specific expression, the receptor gene has been cloned and characterized. The receptor gene promoter is selectively expressed in pituitary cells and is regulated by the pituitary-specific transcription factor Pit-1. There is a sexual dimorphism in GHRH receptor expression in the rat pituitary, suggesting regulation by gonadal steroids. In addition, glucocorticoids are potent positive regulators of GHRH receptor gene expression. Substantial evidence points to an important role for GHRH in regulating the proliferation and functional activity of the somatotroph cell. This is best observed in the dwarf little mouse, which harbors a mutation in the extracellular domain of the GHRH receptor that abolishes the receptor's hormone-binding and signaling properties, resulting in severe somatotroph hypoplasia. Complementary studies in transgenic mice overexpressing the ligand GHRH reveal corresponding somatotroph hyperplasia. Consistent with these observations, GHRH potently activates the MAP kinase pathway in pituitary somatotroph cells. To better understand the hormone-binding and signaling properties of the GHRH receptor, mutant and chimeric receptors have been analyzed to define domains important for GHRH interaction. The GHRH receptor signals predominantly through cAMP-dependent pathways; however, a variant form of the GHRH receptor with an insertion into the third intracellular domain, generated through alternative RNA processing, binds GHRH but fails to signal, suggesting potential modulation of receptor function at a post-transcriptional level. This chapter will integrate these basic investigations of GHRH and its receptor with current information on the involvement of the GHRH signaling system in human diseases of GH secretion and growth.

Animals↗
PubMed1999

Risk stratification in the management of atrial fibrillation in the community.

This study assessed whether risk stratification in patients with atrial fibrillation (AF) in the community had a bearing on the likelihood of receiving aspirin or warfarin therapy. Seven hundred and fifty patients were identified from 14 practices by means of diagnostic READ codes or repeat prescriptions for digoxin from practice computers. The study demonstrates that general practitioners appreciate the importance of antithrombotic therapy in patients who have suffered stroke, but take poor account of increasing age and other independent risk factors. A more proactive approach to risk identification and treatment seems justified.

Aged↗
PubMed1998

EMG signal amplitude assessment during abdominal bracing and hollowing.

Motor pattern re-education is often used by clinicians as part of treatment regimens for chronic low back pain. Such programmes are often validated by the analysis of the electromyographical (EMG) signal from specific muscles. Independent muscles are often compared using the raw amplitude of the EMG signal or comparing the ratio of the amplitudes of two muscles. Statistical inferences from these derived data may depend on minimizing the sources of error when manipulating the EMG signal profile data. This is particularly true for amplitude normalization procedures, their reliability and the subsequent derivation of amplitude ratios. The purpose of the study was first to examine the reliability of five amplitude normalized procedures and second to examine the sensitivity of raw versus ratio amplitude comparisons during two different abdominal muscle exercises. The study demonstrated that maximal effort amplitude normalization techniques reduce the sensitivity of raw data comparisons, but had little influence on the sensitivity of the ratio data in differentiating the two movement patterns. It was concluded that using the EMG signal profile to identify pathological movement strategies, in association with regional pain syndromes, needs special attention to the reliability and validity of the derived variables.

Abdominal Muscles↗
PubMed1993

GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function.

The growth hormone-releasing hormone receptor (GHRHR) is a member of the family of G protein-coupled receptors that is expressed on pituitary somatotrope cells and mediates the actions of GHRH in stimulating growth hormone (GH) synthesis and secretion. We report that the Ghrhr gene is located in the middle of mouse chromosome 6 in the same region as the little mutation. Mice homozygous for this mutation have reduced GH secretion and a dwarf phenotype. A missense mutation was identified in the extracellular domain of the little GHRHR that disrupts receptor function, suggesting that the growth deficit in these mice results from a defect in the GHRHR. Similar alterations in GHRHR might explain some isolated GH deficiencies in humans.

Amino Acid Sequence↗
PubMed1993

In vivo labeling of Escherichia coli cell envelope proteins with N-hydroxysuccinimide esters of biotin.

The primary amine coupling reagents succinimidyl-6-biotinamido-hexanoate (NHS-A-biotin) and sulfosuccinimidyl-6-biotinamido-hexanoate (NHS-LC-biotin) were tested for their ability to selectively label Escherichia coli cell envelope proteins in vivo. Probe localization was determined by examining membrane, periplasmic, and cytosolic protein fractions. Both hydrophobic NHS-A-biotin and hydrophilic NHS-LC-biotin were shown to preferentially label outer membrane, periplasmic, and inner membrane proteins. NHS-A- and NHS-LC-biotin were also shown to label a specific inner membrane marker protein (Tet-LacZ). Both probes, however, failed to label a cytosolic marker (the omega fragment of beta-galactosidase). The labeling procedure was also used to label E. coli cells grown in low-salt Luria broth medium supplemented with 0, 10, and 20% sucrose. Outer membrane protein A (OmpA) and OmpC were labeled by both NHS-A- and NHS-LC-biotin at all three sucrose concentrations. In contrast, OmpF was labeled by NHS-A-biotin but not by NHS-LC-biotin in media containing 0 and 10% sucrose. OmpF was not labeled by either NHS-A- or NHS-LC-biotin in E. coli cells grown in medium containing 20% sucrose. Coomassie-stained gels, however, revealed similar quantities of OmpF in E. coli cells grown at all three sucrose concentrations. These data indicate that there was a change in outer membrane structure due to increased osmolarity, which limits accessibility of NHS-A-biotin to OmpF.

Aminocaproates↗
PubMed1992

Folate deficiency, biopterin and monoamine metabolism in depression.

Seven (21%) of 34 patients with a severe DSM-III diagnosis of major depression had red-cell folate levels below 150 ng/ml. This subgroup with folate deficiency had significantly lower CSF 5-hydroxyindoleacetic acid (5HIAA) compared to neurological controls. For all depressed patients red-cell folate was significantly correlated with CSF 5HIAA and homovanillic acid (HVA). CSF tetrahydrobiopterin (BH4) was significantly correlated with CSF 5HIAA and HVA and red-cell folate. Our observations provide further evidence of the links between folate, biopterin and monoamine metabolism in depression.

Adult↗
PubMed1990

Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine.

Cerebrospinal fluid (CSF) S-adenosylmethionine (SAM) levels were significantly lower in severely depressed patients than in a neurological control group. The administration of SAM either intravenously or orally is associated with a significant rise of CSF SAM, indicating that it crosses the blood-brain barrier in humans. These observations provide a rational basis for the antidepressant effect of SAM, which has been confirmed in several countries. CSF SAM levels were low in a group of patients with Alzheimer's dementia suggesting a possible disturbance of methylation in such patients and the need for trials of SAM treatment.

Administration, Oral↗
PubMed1988

Microvascular revascularization of the tongue.

Revascularization of the tongue, employing microvascular techniques, is useful in cases where the blood supply to this organ must be interrupted to allow for adequate exposure or for adequate margins. A case is presented in which the left lingual artery was divided for purposes of exposure and the right artery was interrupted to encompass the entire tumor. This patient also underwent a total laryngopharyngectomy with jejunal free flap interposition. The blood supply of the tongue was successfully reestablished by anastomosing the right lingual artery to the right facial artery. The patient made an uneventful recovery.

Anastomosis, Surgical↗