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Biomedical subjects

B Marks

Publications and source records attributed to B Marks.

At least 37 records · Page 2Linked to original sources
PubMed1996

The structure of the prostaglandin EP4 receptor gene and related pseudogenes.

The EP4 prostaglandin receptor (EP4R) is a member of the seven transmembrane receptor superfamily. We have obtained the human EP4 receptor gene sequence and determined its structure relative to EP4R cDNA synthesized from peripheral blood lymphocytes. The EP4R gene spans approximately 22 kb and consists of three exons separated by two introns. The first exon (530 bp) is noncoding. After an intron of 472 bp, the second exon contains a short (43 bp) 5' sequence before a 289-amino-acid open reading frame (ORF). An 11.5-kb intron is found at the end of transmembrane 6, and the rest of the ORF is in exon 3. The gene structure is analogous to those of the thromboxane, PGI, and PGD receptors. The deduced initiation site does not contain a conventional TATA box but is 70% GC-rich and contains CCAAT boxes, SP1 and AP2 motifs, and motifs consistent with activation by proinflammatory cytokines. Southern blot analysis of human genomic DNA shows two genes with homology to the EP4R gene. Both appear to be pseudogenes with 70% amino acid identity to the EP4R up to the "ERY" sequence at the end of transmembrane 3, where an Alu-like repetitive sequence element was found. The ORF sequence is also interrupted by a stop codon. The pseudogenes differ in that one contains a second "repetitive element" (a line 1 repeat) in the 5' end of the ORF. Northern blot analysis of human mRNA using a pseudogene probe showed hybridization only to the EP4 receptor transcript. PCR also failed to detect expression of either pseudogene. This study defines the gene structure of EP4R and suggests the existence of two related pseudogenes.

Amino Acid Sequence↗
PubMed1996

Vaginal wall sling for anatomical incontinence and intrinsic sphincter dysfunction: efficacy and outcome analysis.

PURPOSE: A prospective cohort study was done to determine the efficacy and clinical outcome of a new technique for anterior vaginal wall sling construction to treat urinary incontinence due to intrinsic sphincter dysfunction or anatomical incontinence. MATERIALS AND METHODS: Preoperative evaluation included lateral cystography, video urodynamics, cystoscopy and incontinence staging. Postoperative subjective and objective staging outcome measures were prospectively assigned at predetermined regular intervals by a third party. RESULTS: Of the patients 95 had intrinsic sphincter dysfunction and 65 had anatomical incontinence. The repair failed in 7% of the 160 patients who had recurrent incontinence during followup and 9% had de novo urgency incontinence. Time to failure comparing patients with intrinsic sphincter dysfunction and anatomical incontinence was modeled using Kaplan-Meier survival curves, and the log rank test showed no significant difference between the groups (p > 0.05). Logistic regression covariates revealed no significant predictive factors for postoperative failures. Preoperative patient age was the only predictive factor for de novo instability (logistic regression model p < 0.05). CONCLUSIONS: Our initial results indicate that the 2 groups are indistinguishable to date based on current clinical and experimental statistics except for time to full recovery of postoperative voiding and incidence of postoperative instability (regression model p < 0.05).

Adult↗
PubMed1993

High-dose chemotherapy-induced platelet defect: inhibition of platelet signal transduction pathways.

Patients receiving high-dose chemotherapy and autologous bone marrow transplantation acquire a platelet secretion defect. The role of chemotherapeutic agents and their metabolites in mediating this platelet defect was investigated. 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU), but not cyclophosphamide or cis-platinum, was found to inhibit platelet aggregation in vitro in response to activation by either ADP, thrombin, or collagen. Inhibition by BCNU was dose dependent and required preincubation of platelets with BCNU. After a 60-min preincubation, 30 microM BCNU produced 50% inhibition of platelets in platelet-rich plasma. The cyclophosphamide metabolites acrolein and 4-hydroperoxycyclophosphamide also inhibited platelet aggregation in a dose-dependent manner, with a requirement for preincubation. Platelet inhibition occurred at clinically relevant concentrations of BCNU and metabolites of cyclophosphamide. The effects of acrolein were totally prevented by coincubation with the sulfhydryl-protecting agents N-acetylcysteine and 2-mercaptoethanesulfonic acid, whereas the effects of BCNU were incompletely prevented. The mechanism of platelet inhibition was investigated next by examining protein phosphorylation in response to platelet agonists. Acrolein inhibited thrombin- and phorbol ester-induced phosphorylation of a 40-kDa polypeptide and other substrates, indicating a cellular defect in protein kinase C signaling. BCNU did not interfere with protein phosphorylation, indicating preservation of initial signaling pathways. Thus, chemotherapeutic agents and their metabolites inhibit platelet function by inhibiting distinct components of the intracellular activation pathways.

Acrolein↗
PubMed1992

The insertion of monoamine oxidase A into the outer membrane of rat liver mitochondria.

Human monoamine oxidase A that had been synthesized in a reticulocyte lysate translation system was capable of binding to and inserting into either rat liver mitochondria or isolated mitochondrial outer membranes. The inserted form was as resistant to proteinase K as endogenous mitochondrial monoamine oxidase A. The insertion, but not the binding, of monoamine oxidase A was prevented by depleting the reaction mixture of either ATP (with apyrase) or ubiquitin (with purified antibodies against this polypeptide). Addition of ATP or ubiquitin, respectively, to these depleted mixtures restored the insertion of the enzyme. In the absence of mitochondria, in vitro synthesized monoamine oxidase A did not catalyze its own alkylation by the mechanism-based inhibitor, [3H]clorgyline. However, both monoamine oxidase A that had been membrane-inserted in vitro and monoamine oxidase A that had been bound to the mitochondria under conditions of ATP depletion catalyzed adduct formation. Furthermore, reaction of either clorgyline or another mechanism-based inhibitor, pargyline, with the membrane-bound enzyme during ATP depletion inhibited the insertion of monoamine oxidase A when ATP was restored. These observations indicate that monoamine oxidase A acquired a catalytically active conformation on interaction with the mitochondrial outer membranes prior to its ATP and ubiquitin-dependent insertion into the membrane.

Adenosine Triphosphate↗
PubMed1992

Empty sella syndrome associated with partial hypopituitarism (visualized on MRI scan).

The empty sella syndrome has become a rather frequent finding in magnetic resonance imaging (MRI) scanning. The usual presentation of empty sella syndrome involves an incidental finding on a computed tomography scan or an MRI scan. It is unusual to find empty sella syndrome associated with hypopituitarism. The authors describe such an unusual finding in a 54-year-old nulliparous woman.

Empty Sella Syndrome↗
PubMed1989

Perception of eating and exercise in children as a function of child and parent weight status.

The present study assessed the effects of child body weight (obese/lean) and familial loading for obesity (two obese parents/two lean parents) on the psychophysics of sweetness, fatness and exercise workloads, as well as subjective ratings of foods varying in sugar and fat and activities varying in energy expenditure. Children were measured in a baseline state and at 6 months after the obese children had participated in a family-based behavioral weight control program. No differences between obese and lean children in perceptual ratings were observed. However, offspring of obese or lean parents differed on intensity rating, food palatability and activity enjoyment ratings. Intensity ratings for sweetness in offspring of obese parents was increased, with a similar trend for intensity ratings for fatness. Offspring of obese parents rated all foods and activities with lower palatability and enjoyment ratings than offspring of lean parents. After a 6 month family-based behavioral weight loss treatment, obese children had significant decreases in percent overweight while lean children remained stable. Changes in the pattern of food ratings were observed for the obese children, with a reduction in liking for foods high in fat and/or sugar, and an increase in ratings for food slower in fat and sugar. The effects of parental obesity on food and exercise intensity ratings and hedonic ratings were maintained. Overall, these results suggest parental weight influences behavioral factors related to obesity in children.

Body Weight↗
PubMed1989

Resting metabolic rate in lean and obese children: relationship to child and parent weight and percent-overweight change.

Two studies were conducted to assess differences in metabolic rate as a function of child weight (study I); and the interaction of child and parent weight (study II). In both studies obese children had higher resting metabolic rates (RMRs) than lean children (p less than 0.05). Child weight accounted for 72 and 78% of the variance in RMR in studies 1 and 2, respectively. Including parental weight did not improve the prediction of RMR. After 6 mo of treatment, obese children decreased percent overweight, whereas lean children showed no change (p less than 0.01). RMR in both groups remained unchanged after 6 mo. These results indicate that the RMR is higher in obese than in lean children, that changes in percent overweight that result from increases in height and no change in weight do not decrease RMR over 6 mo, and parent weight does not improve the prediction of child RMR.

Basal Metabolism↗
PubMed1989

Liaison psychiatry in general practice: a comparison of the liaison-attachment scheme and shifted outpatient clinic models.

Most psychiatrists who visit health centres use the shifted outpatient clinic model, the main aim of which is to improve secondary care by providing it in the primary care setting. For five years we have employed a liaison-attachment scheme in which support and advice from the psychiatrist enables general practitioners to improve their care of patients with psychiatric and psychological problems. One of the advantages of the latter model is that the psychiatrist can contribute to the care of patients not seen by the specialist psychiatric service and also to the development of the primary care team. The scheme is cost effective as psychiatrists can advise on the care of far more patients than they could see in formal referrals, fewer patients are taken on for a course of psychiatric treatment that could be provided by general practitioners and the skills of general practitioners and their trainees are enhanced. It is hoped that more general practitioners will adopt this pattern of working so that it can be fully developed and evaluated.

Consultants↗
PubMed1988

Survey of patients' satisfaction with access to general practitioners.

The north west England faculty patients' liaison group, supported by community health councils and family practitioner committees, surveyed patients' perceptions of accessibility to general practitioners in seven districts in 1985 and 1986. Findings on appointment systems, telephone access and out-of-hours calls are compared with those from other surveys. The results show that patients' satisfaction with appointment systems is related to the efficiency of their own general practitioner's system. The results also show higher levels of dissatisfaction with waiting times for outof- hours visits than in studies 10 years ago and that a large proportion of patients would like direct telephone access to their general practitioner.

Consumer Behavior↗
PubMed1986

Periodontal disease as a function of life events stress.

Studies relating stress and oral pathology have been limited to animal experiments or clinical studies of personality and psychological health that have ignored the role of specific life events. The present study related measurements of life events stress to measurements of periodontal disease. Subjects were fifty male volunteers recruited from a pool of dental patients from the Brooklyn VA Outpatient Dental Clinic. Oral examinations were given to determine the degree of periodontitis and gingivitis. Evidence of other somatic symptomatology was assessed by the somatization subscale of the Brief Symptom Inventory. The degree of life events stress was assessed with the Life Experience Survey. Measurements of life events stress were found to be significantly correlated with measures of periodontal disease. Periodontal disease was more severe and widespread as stressors increased. Subjects were found whose general physical health was unrelated to their life situation.

Adult↗
PubMed1985

Persistence of polybrominated biphenyls (PBB) in human post-mortem tissue.

Polybrominated biphenyl (PBB), a fire retardant, was accidentally substituted for an animal feed supplement in Michigan 10 years ago. This led to widespread livestock contamination and ultimately to contamination of virtually every human residing in the State at that time. In order to evaluate the extent of PBB persistence and distribution in human tissues 10 years after this accidental poisoning, a study was conducted on a series of autopsy cases from the Grand Rapids ("high" exposure) area of the State. No attempt was made to relate cause of death to PBB exposure or tissue concentration. Samples of 196 tissues from 15 subjects were analyzed for PBB content, and levels were determined by measurement of the hexabromobiphenyl peak using electron capture gas chromatography. Only 4 of the 196 samples analyzed did not have PBB concentration above the limit of detection (0.5 ng/g). As expected, fat and fat-rich tissue had the highest PBB concentration. Perirenal fat had the highest mean concentration (475 ng/g). Adrenal, atheromatus aorta and thymus had mean concentrations about half that of perirenal fat; all other tissues had mean concentrations one-tenth or less of perirenal fat. The results document that PBB is still present in human tissue and that PBB was distributed in all tissues examined. The PBB fat elimination half-time was estimated to be at least 7.8 years. If this is approximately correct, PBB will persist in tissues throughout the lifetime of humans so contaminated.

Adipose Tissue↗
PubMed1985

Regulatory factors specific for adult and embryonic globin genes may govern their expression in erythroleukemia cells.

In order to test if trans-acting regulatory factors specific for globin genes of the adult and embryonic stages of development exist in erythroid cells, transcriptionally active embryonic and adult globin genes on the same chromosome were transferred by cell fusion from the human leukemia cell K562 into phenotypically adult mouse erythroleukemia cells. Restriction-fragment-length polymorphisms of the K562 zeta (embryonic) globin genes were used to establish that all three copies of human chromosome 16 present in the K562 cell showed the same pattern of human globin gene expression after transfer to the mouse erythroleukemia cell. Adult (alpha) but not embryonic (zeta) human globin mRNA was detected in all nine of the independently derived mouse erythroleukemia hybrid cells, each of which contained human chromosome 16. Restriction endonuclease studies of the K562 alpha- and zeta-globin genes after transfer into the mouse erythroleukemia cell showed no evidence of rearrangements or deletions that could explain this loss of zeta-globin gene expression. These data suggest that regulation of globin gene expression in these erythroleukemia cells involves trans-acting regulatory factors specific for the adult and embryonic stages of development.

Animals↗
PubMed1984

The role of actors in teaching communication.

This paper describes a series of communication workshops designed to improve the consultation skills of third-year clinical medical students during their period of attachment in general practice, and to enable them to understand the differences in perspective and attitude existing between doctor and patient and their effect on the process and outcome of the clinical interview. The workshops involve a group of professional actors as simulated patients. The advantages of this method are discussed in terms of increased lay participation in the teaching.

Attitude of Health Personnel↗