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Biomedical subjects

J Frost

Publications and source records attributed to J Frost.

At least 19 recordsLinked to original sources
PubMed2002

Five year results of a prospective very low calorie diet or conventional weight loss programme in type 2 diabetes.

AIMS: To complete 5-year follow-up of an intensive weight loss programme in established type 2 diabetic subjects. METHODS: Forty-five obese type 2 diabetic subjects, Body mass index (BMI) > 30, expressed interest in an intensive weight loss programme. Group 1 comprised 15 who selected very low calorie diet (VLCD), Group 2, 15 selected intensive conventional diet and exercise (ICD), 15 failed to follow either programme. Group sessions of eight to 15 subjects continued weekly for 6 months, then monthly for 12 months with prospective recording at 3, 6 and 12 months and then annually of quality of life, BMI, waist/hip ratio, blood pressure, fasting blood glucose, serum fructosamine and serum lipids. RESULTS: Weight loss was slower in the intensive conventional diet group than in the VLCD group, but better maintained at 5 years: group 1, 4.8 +/- 6 kg; group 2, 8.9 +/- 4 kg. In the intensive conventional diet group, 5 year high-density lipoprotein cholesterol was increased 1.78 +/- 0.26 mmol L-1 vs. 1.10 +/- 0.32 mmol L-1 at baseline, and diastolic blood pressure reduced 74.5 +/- 13.3 vs. 85.5 +/- 13.3 at baseline, both P < 0.05. CONCLUSIONS: Out-patient VLCD treatment proved safe and effective in overweight diabetic subjects but those who chose conventional diet and exercise had a slower but more sustained weight loss. Diabetic patients willing to attempt VLCD may safely lose sufficient weight to allow major surgery, but weight regain is inevitable. Patients willing to undertake a long-term group programme of conventional diet can sustain significant weight loss for 5 years, but still require antidiabetic medication.

Adult↗
PubMed2001

From genome to vaccine: in silico predictions, ex vivo verification.

Bioinformatics tools enable researchers to move rapidly from genome sequence to vaccine design. EpiMer and EpiMatrix are computer-driven pattern-matching algorithms that identify T cell epitopes. Conservatrix, BlastiMer, and Patent-Blast permit the analysis of protein sequences for highly conserved regions, for homology with other known proteins, and for homology with previously patented epitopes, respectively. Two applications of these tools to epitope-driven vaccine design are described in this review. Using Conservatrix and EpiMatrix, we analyzed more than 10000 HIV-1 sequences and identified peptides that were potentially immunostimulatory and highly conserved across HIV-1 clades. MHC binding assays and CTL assays have been carried out: 50 (69%) of the 72 candidate epitopes bound in assays with cell lines expressing the corresponding MHC molecule; 15 of the 24 B7 peptides (63%) stimulated gamma-interferon release in ELISpot assays. These results lend support to the bioinformatics approach to selecting novel, conserved, HIV-1 CTL epitopes. EpiMatrix was also applied to the entire 'proteome' derived from two Mycobacterium tuberculosis (Mtb) genomes. Using EpiMatrix, BlastiMer, and Patent-Blast, we narrowed the list of putative Mtb epitopes to be tested in vitro from 1600000 to 3000, a 99.8% reduction. The pace of vaccine design will accelerate when these and other bioinformatics tools are systematically applied to whole genomes and used in combination with in vitro methods for screening and confirming epitopes.

AIDS Vaccines↗
PubMed2001

Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease.

Cross-sectional positron emission tomography (PET) studies find that cognitively normal carriers of the apolipoprotein E (APOE) epsilon4 allele, a common Alzheimer's susceptibility gene, have abnormally low measurements of the cerebral metabolic rate for glucose (CMRgl) in the same regions as patients with Alzheimer's dementia. In this article, we characterize longitudinal CMRgl declines in cognitively normal epsilon4 heterozygotes, estimate the power of PET to test the efficacy of treatments to attenuate these declines in 2 years, and consider how this paradigm could be used to efficiently test the potential of candidate therapies for the prevention of Alzheimer's disease. We studied 10 cognitively normal epsilon4 heterozygotes and 15 epsilon4 noncarriers 50-63 years of age with a reported family history of Alzheimer's dementia before and after an interval of approximately 2 years. The epsilon4 heterozygotes had significant CMRgl declines in the vicinity of temporal, posterior cingulate, and prefrontal cortex, basal forebrain, parahippocampal gyrus, and thalamus, and these declines were significantly greater than those in the epsilon4 noncarriers. In testing candidate primary prevention therapies, we estimate that between 50 and 115 cognitively normal epsilon4 heterozygotes are needed per active and placebo treatment group to detect a 25% attenuation in these CMRgl declines with 80% power and P = 0.005 in 2 years. Assuming these CMRgl declines are related to the predisposition to Alzheimer's dementia, this study provides a paradigm for testing the potential of treatments to prevent the disorder without having to study thousands of research subjects or wait many years to determine whether or when treated individuals develop symptoms.

Aged↗
PubMed2000

Recruitment experience in the first phase of the African American Hereditary Prostate Cancer (AAHPC) study.

The African American Hereditary Prostate Cancer (AAHPC) Study is an ongoing multicenter genetic linkage study organized by Howard University and the National Human Genome Research Institute (NHGRI), with support from the Office for Research on Minority Health and the National Cancer Institute. The goals of the study are to: (i) look for evidence of involvement of chromosome 1q24-25 (HPC1) in African American men with hereditary prostate cancer (HPC) and (ii) conduct a genome-wide search for other loci associated with HPC in African American men. To accomplish these goals, a network has been established including Howard University, the NHGRI, and six Collaborative Recruitment Centers (CRCs). The CRCs are responsible for the identification and enrollment of 100 African American families. To date, 43 families have been enrolled. Recruitment strategies have included mass media campaigns, physician referrals, community health-fairs/prostate cancer screenings, support groups, tumor registries, as well as visits to churches, barber shops, and universities. By far, the most productive recruitment mechanisms have been physician referrals and tumor registries, yielding a total of 35 (81%) families. Approximately 41% (n = 3400) of probands initially contacted by phone or mail expressed interest in participating; the families of 2% of these met the eligibility criteria, and 75% of those families have been enrolled in the study, indicating a 0.5% recruitment yield (ratio of participants to contacts). As the first large-scale genetic linkage study of African Americans, on a common disease, the challenges and successes of the recruitment process for the AAHPC Study should serve to inform future efforts to involve this population in similar studies.

Black or African American↗
PubMed1999

The prevalence and etiology of impotence in 101 male hypertensive outpatients.

Erectile dysfunction and impotence has a high prevalence among male hypertensive patients. Whether this relates mainly to specific drug side effects or to primary pathogenic disorders is unknown. In the present study 101 male patients from our outpatient hypertension clinic answered detailed questionnaires about hypertension and sexual function. Patients with perceived impotence were offered a thorough penile evaluation and examination performed by specialists in the urology department. Twenty-seven (27%) men had impotence. The main cause of impotence was an arterial dysfunction (89%). The prevalence of impotence was related to the degree of secondary organ manifestation, reflected by World Health Organization (WHO) classification I-III (P = .01). Intermittent claudication (P = .001) and ischemic heart disease (P = .005) were the best determinants in this respect. Twelve impotent patients (44%) ascribed onset of impotence to drug initiation. A variety of drugs were incriminated in the occurrence of drug-induced impotence. In summary our results indicate that impotence in hypertensive men is caused mainly by penile arterial vascular changes, probably atherosclerosis. Drug-induced impotence could well be the result of blood pressure reduction itself and not specific drug side effects.

Adult↗
PubMed1999

Regions of the human brain affected during a liquid-meal taste perception in the fasting state: a positron emission tomography study.

BACKGROUND: The sensation of taste provides reinforcement for eating and is of possible relevance to the clinical problem of obesity. OBJECTIVE: Positron emission tomography (PET) was used to explore regions of the brain that were preferentially affected during the taste perception of a liquid meal by 11 right-handed, lean men in the fasting state. DESIGN: After subjects had fasted for 36 h, 2 measurements of regional cerebral blood flow (rCBF) obtained immediately after subjects retained and swallowed 2 mL of a flavored liquid meal (the taste condition) were compared with 2 measurements of rCBF obtained immediately after subjects retained and swallowed 2 mL of water (the baseline condition). RESULTS: Compared with the baseline condition, taste was associated with increased rCBF (P < 0.005) in the left dorsolateral prefrontal cortex and superior temporal gyrus; the right ventrolateral prefrontal cortex, supramarginal gyrus, and anterior thalamus; and bilaterally in the hippocampal formation, posterior cingulate, midbrain, occipital cortex, and cerebellum. Taste was also associated with decreased rCBF (P < 0.005) in the right dorsolateral prefrontal cortex, superior temporal gyrus, and supplementary motor area, and bilaterally in the medial prefrontal cortex and inferior parietal lobule. CONCLUSIONS: This exploratory study provides additional evidence that the temporal cortex, thalamus, cingulate cortex, caudate, and hippocampal formation are preferentially affected by taste stimulation. The asymmetric pattern of activity in the dorsolateral prefrontal cortex and superior temporal gyrus may contribute to the taste perception of a liquid meal perceived as pleasant. Additional studies are required to determine how these regions are affected in patients with obesity or anorexia.

Adult↗
PubMed1998

An intensive weight loss programme in established type 2 diabetes and controls: effects on weight and atherosclerosis risk factors at 1 year.

The efficacy, safety, and effect on cardiovascular risk factors of two intensive weight loss programmes in overweight Type 2 diabetic subjects were studied. The patients were recruited from hospital diabetic clinics and control obese subjects from the community. Obese (BMI >30) patients with Type 2 diabetes mellitus and controls were offered intensive conventional diabetic advice or a very low calorie diet. Weekly 2 h sessions were conducted in two day-room areas of adjacent medical wards of Torbay Hospital. Non-diabetic and diabetic very low calorie diet groups reduced BMI by 6 and 5 kg m(-2), respectively, at 1 year. Waist-hip ratios (-0.06 and -0.05) were also reduced (p = 0.04 and p = 0.01), while HDL/total cholesterol ratios increased (+0.04 and +0.06, p = <0.01). Transient changes in blood pressure and antioxidant vitamin status occurred in the intensive conventional diet group. Fourteen of diabetic very low calorie diet subjects discontinued insulin and oral hypoglycaemic agents for the whole year, and psychological well-being transiently improved. Substantial weight loss and improvement in cardiovascular risk factors could be maintained for 1 year in Type 2 diabetic patients by the use of a very low calorie diet.

Adult↗
PubMed1996

The highly conserved skb1 gene encodes a protein that interacts with Shk1, a fission yeast Ste20/PAK homolog.

The Shk1 protein kinase, a homolog of Saccharomyces cerevisiae Ste20 and mammalian p21Cdc42/Rac-activated kinases, is an essential component of a Ras- and Cdc42-dependent signaling cascade required for cell viability, normal morphology, and mitogen-activated protein kinase-mediated sexual responses in the fission yeast, Schizosaccharomyces pombe. To identify S. pombe proteins that modulate or mediate Shk1 functions, we conducted a two-hybrid screen for Shk1-interacting proteins. One of the genes identified as a result of this screen was skb1. We show that Skb1 interacts with a region of the N-terminal regulatory domain of Shk1 distinct from that to which Cdc42 binds, and that Shk1, Cdc42, and Skb1 are able to form a ternary complex in vivo. S.pombe cells carrying an skb1 null mutation are less elongate in morphology than wild-type cells and exhibit a moderate growth defect. The morphology defect of the skb1 deletion mutant is suppressed by overexpression of Shk1. Overexpression of Skb1 causes wild-type S. pombe cells to become hyperelongated. Additional genetic analyses described herein suggest that Skb1 is a component of the morphology control branch of the Ras signaling cascade in S. pombe and that it positively modulates Shk1 function. Homologs of Skb1 are encoded by open reading frames in the genomes of S. cerevisiae and Caenorhabditis elegans and by an uncharacterized human cDNA sequence. Thus, skb1 may be the first well-characterized member of a highly conserved family of genes encoding potential p21Cdc42/Rac-activated kinase regulators.

Amino Acid Sequence↗
PubMed1996

[Blood loss during transurethral resection of the prostate].

Measurement of the perioperative blood loss during transurethral resection of the prostate was performed using the modern HemoCue photometer in 100 men. The measurement lasts only 5-10 minutes. The median weight of the removed prostate was 28 grams and the operating time 60 minutes. The median blood loss was 393 ml (range 8-1843 ml) and was positively correlated to operating time, change in the peroperative blood pressure, volume of the irrigating fluid and the drop in the postoperative serum sodium. Perioperative measurements of the blood loss draw the surgeons' attention to the haemostasis, provide an objective measure of the most important factor for morbidity during TURP and allow a rational policy for blood transfusion. It is an advantage to place this measurement in the hands of professionals, i.e. laboratory technicians, who are trained to quality-secure the measurement and preserve the photometer.

Aged↗
PubMed1996

Antagonist properties of the stereoisomers of ifenprodil at NR1A/NR2A and NR1A/NR2B subtypes of the NMDA receptor expressed in Xenopus oocytes.

The NMDA receptor antagonist ifenprodil contains two asymmetric centres which give rise to four stereoisomeric forms of this molecule. The inhibitory effects of each of these stereoisomers on recombinant NMDA receptors expressed from NR1A/NR2A and NR1A/NR2B subunit combinations were studied in Xenopus oocytes by voltage-clamp recording. All four ifenprodil stereoisomers were potent antagonists at NR1A/NR2B (IC50 < 0.8 microM), but weak antagonists at NR1A/NR2A receptors (IC50 > 100 microM). In heteromeric NR1A/NR2B receptors, (+) erythro- and (-) threo-ifenprodil (IC50 0.21 and 0.22 microM, respectively) were about 4 times more potent than (-) erythro- and (+) threo-ifenprodil (IC50 0.81 and 0.76, respectively). These results show that the stereoisomers of ifenprodil exhibit a weak though significant stereoselectivity at the NR1A/NR2B NMDA receptor subtype.

Animals↗
PubMed1995

Activation of mitogen-activated protein kinase cascades by p21-activated protein kinases in cell-free extracts of Xenopus oocytes.

In the evolutionarily distant yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, genetic evidence suggests that activation of pheromone-induced mitogen-activated protein kinase (MAPK) cascades involves the function of the p21cdc42/racl-activated protein kinases (PAKs) Ste20 and Shk1, respectively. In this report, we show that purified Ste20 and Shk1 were each capable of inducing p42MAPK activation in cell-free extracts of Xenopus laevis oocytes, while a mammalian Ste20/Shk1-related protein kinase, p65pak (Pak1), did not induce activation of p42MAPK. In contrast to p42MAPK, activation of JNK/SAPK in Xenopus oocyte extracts was induced by both the yeast Ste20 and Shk1 kinases, as well as by mammalian Pak1. Our results demonstrate that MAPK cascades that are responsive to PAKs are conserved in higher eukaryotes and suggest that distinct PAKs may regulate distinct MAPK modules.

Animals↗
PubMed1995

MEKK1 phosphorylates MEK1 and MEK2 but does not cause activation of mitogen-activated protein kinase.

A constitutively active fragment of rat MEK kinase 1 (MEKK1) consisting of only its catalytic domain (MEKK-C) expressed in bacteria quantitatively activates recombinant mitogen-activated protein (MAP) kinase/extracellular signal-regulated protein kinase (ERK) kinases 1 and 2 (MEK1 and MEK2) in vitro. Activation of MEK1 by MEKK-C is accompanied by phosphorylation of S218 and S222, which are also phosphorylated by the protein kinases c-Mos and Raf-1. MEKK1 has been implicated in regulation of a parallel but distinct cascade that leads to phosphorylation of N-terminal sites on c-Jun; thus, its role in the MAP kinase pathway has been questioned. However, in addition to its capacity to phosphorylate MEK1 in vitro, MEKK-C interacts with MEK1 in the two-hybrid system, and expression of mouse MEKK1 or MEKK-C in mammalian cells causes constitutive activation of both MEK1 and MEK2. Neither cotransfected nor endogenous ERK2 is highly activated by MEKK1 compared to its stimulation by epidermal growth factor in spite of significant activation of endogenous MEK. Thus, other as yet undefined mechanisms may be involved in determining information flow through the MAP kinase and related pathways.

Animals↗
PubMed1995

[Clinical symptoms and diagnosis of feline infectious peritonitis].

Body effusions from 197 cats and blood serum samples from 252 cats, where Feline Infectious Peritonitis (FIP) was part of the differential diagnosis, were analysed. The diagnoses were confirmed by clinical follow up or histopathology. The final diagnosis FIP was always confirmed by histopathology. The median age of cats with FIP was 1.6 years. FIP was responsible for 41% of the body effusions, whereas malignomas caused 24%, cardial insufficiencies 14% and purulent serositis 12% of the body effusions. The rivalta test was highly sensitive for FIP. Predictive value of a negative result was 100%, predictive value of a positive result was 84%. In half of the cases with purulent serositis and in 20% of malignomas rivalta reacted positive. The cardial insufficiencies were negative for rivalta. Coronavirus antigen could be demonstrated by immunofluorescence in 34 of 49 body effusions caused by FIP, whereas in the 50 body effusions caused by other diseases no coronavirus antigen was detected. An albumin globulin ratio of < 0.6 was highly diagnostic for an inflammatory process, nearly exclusively for FIP. An albumin globulin ratio of > or = 0.8 almost excluded FIP. Only a negative or very high (1:1600) FIP titer could contribute to confirm diagnosis. Low and medium titers, however, should not be interpreted.

Aging↗
PubMed1994

Effects of an advanced surgical nursing module on clinical practice.

1. Innovation and changes in practice can be developed through continuing education. 2. By adapting appropriate change strategies, theories learned in class can be applied in practice. 3. Excellence in quality can be achieved by all qualified nurses by applying theory to practice.

Education, Nursing, Continuing↗
PubMed1994

Regulation of the MAP kinase cascade.

The MAP kinase cascade is regulated by many hormones and growth factors and its activation leads to changes in properties of cytoplasmic, membrane-associated, and nuclear proteins. The MAP kinases themselves are activated by MEKS. MEKs lie at a point of convergence for multiple upstream signals, mediated by distinct protein kinases, Raf, MEK kinase, and Mos, all of which have MEK kinase activity. Additional inputs that stimulate the MAP kinase pathway are the activation of protein kinase C and the yeast protein kinase STE20. Mechanisms of regulation of some of the upstream components of this cascade have not yet been fully elucidated.

Animals↗
PubMed1994

Complementary treatments for eczema in children.

1. Complementary therapies are just that and not an alternative to routine therapies. 2. The growing use of complementary therapies for eczema reflects a renewed interest in self-medication and a declining belief in orthodox medicine. 3. Prior to using essential oils, nurses should check for sensitivity to certain oils. 4. Herbalism offers a number of approaches to the treatment of eczema.

Child↗