Search PubMed⌕ Search

Biomedical subjects

F Schwartz

Publications and source records attributed to F Schwartz.

At least 19 recordsLinked to original sources

DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells.

BACKGROUND: The glucagon-like peptides-1 and -2 (GLP-1 and -2) are co-secreted after food intake from intestinal L cells. Since both peptides are rapidly degraded by dipeptidyl peptidase-IV (DPPIV), research is focused on the development of DPPIV inhibitors or DPPIV resistant. AIMS: In this study we investigated, whether the inhibition of DPPIV activity and the resulting increased half-life of DPPIV substrates may influence cancer development and progression. METHODS: We examined proliferation and migratory activity of two human colon cancer cell lines (SW480, HT29) after stimulation with GLP-2 in combination with or without DPPIV inhibitors. RESULTS: Migratory activity was increased by 25% from 20% matrix induced activity to a maximum of 45% (100 nM GLP-2). In cells expressing CD26, migration was prolonged by addition of DPPIV inhibitors in a concentration dependent manner. After treatment with GLP-2 doubling time decreased from 2.4 to 1.5 days - and addition of DPPIV inhibitors enhanced the effect of GLP-2. CONCLUSIONS: The use of DPPIV inhibitors together with GLP-2 led to increased proliferation as well as elevated migratory activity. Therefore, the use of DPPIV inhibitors could increase the risk of promoting an already existing intestinal tumour and may support the potential of colon cancer cells to metastasize.

Adenosine Deaminase Inhibitors↗

Maternal component in the familial aggregation of hypertension.

To assess maternal versus paternal contributions to the familial aggregation of hypertension, we examined family history data from 344 hypertensive probands (69 African American, 153 US Caucasian, 122 Greek Caucasian) ascertained without respect to parental hypertension status. The proportion of hypertensive mothers (81.7, 65.0 and 84.8% for African Americans, US Caucasians and Greek Caucasians, respectively) of these probands was significantly greater than the proportion of hypertensive fathers (50.0, 44.9 and 48.3%, respectively) in all three ethnic groups. The lifetime risk of hypertension was significantly greater for mothers compared with fathers of these hypertensive probands (p<0.001). Examination of the proband's siblings indicated that maternal history of hypertension was associated with greater lifetime risk for hypertension than paternal history (p<0.01). In conclusion, we observe a consistent maternal component in the inheritance of hypertension. Although we cannot separate a maternal genetic from epigenetic or environmental effect, our findings suggest that genetic research should include studies of the mitochondrial as well as nuclear genome. Furthermore, when assessing a patient's risk for hypertension, particular attention should be paid to the maternal family history.

Adult↗

Multisite regional telephone care.

A multisite, regional telephone-care program staffed by advance practice and critical care nurses has improved patient care and reduced unnecessary clinic and emergency room visits. It allows patients to access the health care system and receive expert advice through the use of the telephone, 24 hours per day, 7 days per week. Computerized patient medical records from eight hospitals and 31 clinics are available to a registered nurse so that informed decisions can be made. The RN records the patient's concern and intervention directly into the patient's medical record, which is transmitted to the primary care provider in real time.

Continuity of Patient Care↗

Mitochondrial DNA mutations in patients with orthostatic hypotension.

We determined the entire sequence of the mitochondrial genome in affected individuals from three families with idiopathic orthostatic hypotension. The disorder in two of these families was recently linked to chromosome arm 18q, while the third family remains unlinked. In all three families, orthostatic hypotension is inherited through the females, suggesting the existence of additional contributing factors, such as genomic imprinting or a mitochondrial modifier. We now report the presence of multiple point mutations in the mitochondrial DNA (mtDNA) in all three families. While most of the changes are common polymorphisms, several novel mutations were found that merit further consideration. In one individual, we detected a T-to-C transition at position 1243 in the 12SrRNA, a change from threonine to alanine at position 67 of the ND1 protein, and from valine to isoleucine at position 197 of the ND2 protein. A second individual harbored a novel substitution of threonine with serine at position 536 of the ND5 protein. Two previously unreported amino acid replacements were detected in a third individual: amino acid 193 of cytochrome b was changed from alanine to threonine, and amino acid 88 of COIII was changed from threonine to alanine. Further studies are required to assess the role of these mutations in blood pressure homeostasis.

DNA, Mitochondrial↗

Identification of a polymorphic glutamic acid stretch in the alpha2B-adrenergic receptor and lack of linkage with essential hypertension.

Essential hypertension, a clinically significant elevation in blood pressure with no recognizable cause, is believed to be attributable to the collective effect of genetic predisposing factors in combination with specific environmental factors, such as diet and stress. Of the genetic causes, genes coding for proteins involved in blood pressure regulation, such as the alpha- and beta-adrenergic receptors, are obvious candidates. The alpha2-adrenergic receptor plays a key role in the sympathetic nervous system by mediating the effects of epinephrine and norepinephrine. To evaluate the potential role between the alpha2B receptor and essential hypertension, we scanned the alpha2B-receptor gene for genetic variation in 108 affected sibling pairs. The screening revealed two major forms of the receptor. They differ by the presence of either 9 or 12 glutamic acid residues in the acidic domain of the third cytoplasmic loop of the protein. Investigation of the pattern of this variation in hypertensive sibling pairs suggests that the alpha2B receptor locus does not contribute substantially to genetic susceptibility for essential hypertension.

Alleles↗

Evidence for linkage between essential hypertension and a putative locus on human chromosome 17.

Several clinical and animal studies indicate that essential hypertension is inherited as a multifactorial trait with a significant genetic and environmental component. In the stroke-prone spontaneously hypertensive rat model, investigators have found evidence for linkage to blood pressure regulatory genes (quantitative trait loci) on rat chromosomes 2, 10, and X. In 1 human study of French and UK sib pairs, evidence for linkage has been reported to human chromosome 17q, the syntenic region of the rat chromosome 10 quantitative trait loci (QTL). Our study confirms this linkage (P=0.0005) and refines the location of the blood pressure QTL.

Aged↗

Autosomal dominant orthostatic hypotensive disorder maps to chromosome 18q.

Familial orthostatic hypotensive disorder is characterized by light-headedness on standing, which may worsen to syncope, palpitations, and blue-purple ankle discoloration, and is accompanied by a marked decrease in systolic blood pressure, an increase in diastolic pressure, and tachycardia, all of which resolve when supine. We ascertained three families in which this disorder is inherited as an autosomal dominant trait with reduced penetrance. A genomewide scan was conducted in the two largest families, and three regions with multipoint LOD scores >1.5 were identified. Follow-up of these regions with additional markers in all three families yielded significant evidence of linkage at chromosome 18q. A maximum multipoint LOD score of 3.21 in the three families was observed at D18S1367, although the smallest family had negative LOD scores in the entire region. There was significant evidence of linkage in the presence of heterogeneity at 18q, with a maximum LOD score of 3.92 at D18S1367 in the two linked families. Identification of the gene responsible for orthostatic hypotensive disorder in these families may advance understanding of the general regulatory pathways involved in the continuum, from hypotension to hypertension, of blood pressure.

Blood Pressure↗

The 239AB gene on chromosome 22: a novel member of an ancient gene family.

A novel family of genes expressed in human brain has recently been identified. Gene 239FB, transcribed extensively in fetal brain, was isolated from the chromosome 11p13 region associated with mental retardation component of the WAGR (Wilms tumor, aniridia, genitourinary anomalies, mental retardation) syndrome. This report presents a cDNA sequence and expression profile of a related gene, 239AB, isolated from adult brain library, that was mapped to chromosome 22. While similar in structure, the two genes differ in their expression pattern and may have different roles in central nervous system development and function. In contrast to the 239FB, which is expressed predominantly in fetal brain, the 239AB gene is transcribed in adult tissues. Both human genes encode novel proteins of unknown function that are highly conserved from Caenorhabditis elegans to birds and mammals. Phylogenetic analysis suggested that the two lineages of the ancient gene family represented by 239FB and 239AB have been in existence prior to the emergence of modern animals.

Adult↗

Improving self-efficacy in nursing research.

THE PURPOSE OF this project was to increase research activities of practicing nurses at one large healthcare facility. The members of the nursing research committee at this institution planned a participatory learning experience with the goal of increasing the nurses' self-efficacy toward conducting research. Increased self-efficacy was the impetus for stimulating increased research activities by the nurses. Measurable outcomes of this project included a significant increase in the participants' self-efficacy and implementation of a number of research projects. The Delphi technique proved useful in identifying nursing research priorities as well as in stimulating nurses to initiate and conduct clinical research. Project implementation and evaluation are described to help practicing nurses and their employers in pursuit of the same goal.

Clinical Competence↗

EGb 761 in control of acute mountain sickness and vascular reactivity to cold exposure.

METHOD: We recruited 44 subjects to participate in a study of the preventive effect of Ginko biloba extract (EGb 761) on acute mountain sickness (AMS) and vasomotor changes of the extremities during a Himalayan expedition. After giving their written informed consent, the subjects were randomized to two groups. One group received 160 mg of EGb 761 per day in two divided doses and the other group received placebo. Assessment was based on the course of the Environmental Symptom Questionnaire (ESQ) score and the cold gradient measured by photoplethysmography. RESULTS: The prophylactic efficacy of treatment with EGb 761 was clearly demonstrated in this study. In terms of factor 1 (AMS-Cerebral), no subject in the EGb 761 group developed acute mountain sickness versus 40.9% of subjects in the placebo group; this difference was very significant (p < or = 1.4 x 10(-3)). In terms of factor 2 (AMS-Respiratory), 3 subjects (13.6%) in the EGb 761 group developed acute mountain sickness versus 18 (81.8%) in the placebo group; this difference was very significant (p = 1.2 x 10(-5)). CONCLUSION: Due to its multiple pharmacological actions, EGb 761 provides an interesting response to the prevention of mountain sickness for moderate altitude (5400 m) with gradual exposure. It also decreased vasomotor disorders of the extremities, as demonstrated by plethysmography (p < 10(-8)) and a specific questionnaire (p < 10(-9)).

Adult↗

cDNA sequence, genomic organization, and evolutionary conservation of a novel gene from the WAGR region.

A new gene (239FB) with predominant and differential expression in fetal brain has recently been isolated from a chromosome 11p13-p14 boundary area near FSHB. The corresponding mRNA has an open reading frame of 294 amino acids, a 3' untranslated region of 1247 nucleotides, and a highly GC-rich 5' untranslated region. The coding and 3' UT sequence is specified by 6 exons within nearly 87 kb of isolated genomic locus. The 5' end region of the transcript maps adjacent to the only genomically defined CpG island in a chromosomal subregion that may be associated with part of the mental retardation of some WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome patients. In addition to nucleotide and amino acid similarity to an EST from a normalized infant brain cDNA library, the predicted protein has extensive similarity to two Caenorhabditis elegans polypeptides of, as yet, unknown function. The 239FB locus is, therefore, likely part of a family of genes with two members expressed in human brain. The extensive conservation of the predicted protein suggests a fundamental function of the gene product and will enable evaluation of the role of the 239FB gene in neurogenesis in model organisms.

Amino Acid Sequence↗

Oral health in adolescents from a small French town.

In France, caries are more prevalent in rural areas than in large cities. This study analyzed the relationship between number of oral health indices and some known risk factors (toothbrushing, sugar consumption, saliva components) and sociodemographic factors in adolescents from a small town. The sample included 112 children aged 12-14 in the north-east of France. School marks was found to be better linked with dental caries indices than the socio-occupational category of parents: gingival index (GI), DMFS, DMFT and caries severity (CS) significantly increased with decreasing school marks; oral plaque was related to socio-occupational of parents. The analysis using the regression method showed that the variance explained by the various factors studied was modest (between 23 and 30%) for GI, initial caries sites (IS), DS, DMFS, DMFT and CS, and was small for plaque (5%) and calculus (3%). This would be due in part to the wide dispersion of these indices. The sex had a non-significant regression coefficient for all oral health indices investigated. For GI, only mutans streptococci (MS) and plaque had a significant regression coefficient. Calculus was explained by any factor considered. Only MS had a significant part in plaque. IS was explained by MS, toothbrushing and age. For DS, only toothbrushing, MS and sweet drinks during meals had a significant part. DMFS and DMFT were explained only by MS and age. CS was explained by MS, age, salivary buffer pH, salivary flow rate, and toothbrushing.

Adolescent↗

A WAGR region gene between PAX-6 and FSHB expressed in fetal brain.

Developmental delay or mental retardation is a frequent component of multi-system anomaly syndromes associated with chromosomal deletions. Isolation of genes involved in the mental dysfunction in these disorders should define loci important in brain formation or function. We have identified a highly conserved locus in the distal part of 11p13 that is prominently expressed in fetal brain. Minimal expression is observed in a number of other fetal tissues. The gene maps distal to PAX-6 but proximal to the loci for brain-derived neurotrophic factor (BDNF) and the beta subunit of follicle stimulating hormone (FSHB), within a region previously implicated in the mental retardation component of some WAGR syndrome patients. Within fetal brain, the corresponding transcript is prominent in frontal, motor and primary visual cortex as well as in the caudate-putamen. The characteristics of this gene, including the striking evolutionary conservation at the locus, suggest that the encoded protein may function in brain development.

Blotting, Northern↗

Study of the antiischemic action of EGb 761 in the treatment of peripheral arterial occlusive disease by TcPo2 determination.

In a randomized, placebo-controlled, double-blind, parallel study of 20 patients, the antiischemic effect of EGb 761 (Ginkgo biloba Extract) was studied by measuring the transcutaneous partial pressure of oxygen (TcPo2) during exercise. Transcutaneous oximetry during exercise provides a good, noninvasive estimation of local arterial perfusion and constitutes a real index of local and regional capillary perfusion. Twenty patients between the ages of forty-four and seventy-three years suffering from claudicating atherosclerotic arterial occlusive disease in stage II according to the Leriche and Fontaine classification, diagnosed for more than a year and stable for three months, were included. The eligible patients received placebo for fifteen days under single-blind conditions. At the end of this preinclusion period, the eligibility criteria were checked and the patients were randomized to two treatment groups. The first group received 320 mg per day of EGb 761 for four weeks and the second group received placebo. The treadmill walking test was performed under standardized conditions at the same time of day and by the same investigator. In a comparison of the differences before and after treatment, the areas of ischemia decreased by 38% in the EGb 761 group but remained essentially stable (+5%) in the placebo group. This difference between groups is significant (F [1.18] = 4.91; P = 0.04) and the 95% confidence interval for the difference ranges from 0.89 to 3.87. This study confirmed significantly the rapid antiischemic action of EGb 761 and its value in the management of peripheral arterial occlusive disease at the stage of intermittent claudication.

Adult↗

Eupergit C-coated membranes as solid support for a sensitive immunoassay of human albumin.

A number of commercially available membranes preactivated by coating with oxirane-containing Eupergit C beads were used for diagnostic immunoassay applications. These membranes possess a higher capacity for protein binding than the respective unmodified membranes as measured with fluorescently labelled antibodies. Immobilization of antigens or antibodies as the first step of the assay was achieved by covalent binding of amino groups of proteins to the oxirane moieties introduced onto the membranes. The high performance of the newly developed membranes bearing covalently bound antibodies, was demonstrated by a dot enzyme-linked microalbuminuria immunoassay as compared to unmodified membranes.

Albumins↗

Obesity in adult females: the relationship among personality characteristics, dieting, and weight.

1. The author studied 225 employed women in the New York Metropolitan area between the ages of 25 and 55 years. The Disinhibited Dieters in this study were overweight, depressed, anxious, and had a low self esteem. The Cognitive Controlled Dieters were not depressed or anxious, had a positive self esteem, and were not overweight. 2. The only significant variable between successful Cognitive Controlled Dieters and Disinhibited Dieters was exercise. 3. Nurses must examine their own beliefs and feelings concerning weight and eating and the connection with depression, anxiety, and self esteem before they can successfully relate to clients. 4. Attitude, cognitive changes, involvement in sports and exercise, and healthy eating are primary prevention interventions to be utilized by the nurse.

Adult↗

The role of personality in the treatment of schizophrenic and schizoaffective disorder inpatients: a pilot study.

As a prelude to a prospective study of personality functioning in chronically psychotic patients, the medical records of 736 hospitalized schizophrenic and schizoaffective disorder patients were retrospectively reviewed. The authors found much higher rates of Axis II personality disorder (PD) diagnoses among patients on extended-care inpatient units, which was consistent with their belief that clinicians on these units were using Axis II labels to document concurrent as well as premorbid personality factors. In addition, patients with PD diagnoses had significantly different courses of inpatient treatment, as documented by length-of-stay data. Level of function at discharge did not differ between those with and without PD diagnoses. The authors posit various hypotheses about these findings and discuss difficult conceptual and methodological issues regarding the influence of personality factors in schizophrenia.

Comorbidity↗