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Biomedical subjects

A Gartner

Publications and source records attributed to A Gartner.

At least 19 recordsLinked to original sources
PubMed2006

Determinants of nutrition improvement in a large-scale urban project: a follow-up study of children participating in the Senegal Community Nutrition Project.

OBJECTIVE: To study individual determinants of differential benefit from the Senegal Community Nutrition Project (CNP) by monitoring improvement in children's weight-for-age index (WA) or underweight status (WA < -2 Z-scores) during participation. DESIGN: A follow-up study using the CNP child monitoring data. Linear general models compared variations in WA according to 14 factors describing the beneficiaries and CNP services. SETTING: Poor neighbourhoods of Diourbel, a large city in Senegal, West Africa. Over a 6-month period, the CNP provided underweight or nutritionally at-risk 6-35-month-old children with monthly growth monitoring and promotion and weekly food supplementation, provided that mothers attended weekly nutrition education sessions. SUBJECTS: All the children who participated in the first two years of the project (n=4084). RESULTS: Mean WA varied from -2.13 (standard deviation (SD) 0.82) to -1.58 (SD 0.81) Z-scores between recruitment and the end of the follow-up. The lower the child's initial WA, the greater was their increase in WA but the lower was the probability of recovery from underweight. Only 61% of underweight children recovered. Six months of CNP services may not be sufficient for catch-up growth of severely underweight children. The number of food supplement rations received was not a direct indicator of the probability of recovery. After adjustment for services received and initial WA, probability of recovery was lower in girls, in younger children, in twins and when mothers belonged to a specific ethnic group. CONCLUSIONS: Determinants of benefit from CNP differed from the risk factors for underweight. Identification of participants with a lower probability of recovery can help improve outcome. Moreover, an explanation for the lack of recovery could be that many underweight children are stunted but not necessarily wasted.

Adult↗
PubMed2005

C. elegans ced-13 can promote apoptosis and is induced in response to DNA damage.

The p53 tumor suppressor promotes apoptosis in response to DNA damage. Here we describe the Caenorhabditis elegans gene ced-13, which encodes a conserved BH3-only protein. We show that ced-13 mRNA accumulates following DNA damage, and that this accumulation is dependent on an intact C. elegans cep-1/p53 gene. We demonstrate that CED-13 protein physically interacts with the antiapoptotic Bcl-2-related protein CED-9. Furthermore, overexpression of ced-13 in somatic cells leads to the death of cells that normally survive, and this death requires the core apoptotic pathway of C. elegans. Recent studies have implicated two BH3-only proteins, Noxa and PUMA, in p53-induced apoptosis in mammals. Our studies suggest that in addition to the BH3-only protein EGL-1, CED-13 might also promote apoptosis in the C. elegans germ line in response to p53 activation. We propose that an evolutionarily conserved pathway exists in which p53 promotes cell death by inducing expression of two BH3-only genes.

Amino Acid Sequence↗
PubMed2004

Use of hand-to-hand impedancemetry to predict body composition of African women as measured by air displacement plethysmography.

OBJECTIVES: To test the validity of a simple, rapid, field-adapted, portable hand-held impedancemeter (HHI) for the estimation of lean body mass (LBM) and percentage body fat (%BF) in African women, and to develop specific predictive equations. DESIGN: Cross-sectional observational study. SETTINGS: Dakar, the capital city of Senegal, West Africa. SUBJECTS: A total sample of 146 women volunteered. Their mean age was of 31.0 y (s.d. 9.1), weight 60.9 kg (s.d. 13.1) and BMI 22.6 kg/m(2) (s.d. 4.5). METHODS: Body composition values estimated by HHI were compared to those measured by whole body densitometry performed by air displacement plethysmography (ADP). The specific density of LBM in black subjects was taken into account for the calculation of %BF from body density. RESULTS: : Estimations from HHI showed a large bias (mean difference) of 5.6 kg LBM (P<10(-4)) and -8.8 %BF (P<10(-4)) and errors (s.d. of the bias) of 2.6 kg LBM and 3.7 %BF. In order to correct for the bias, specific predictive equations were developed. With the HHI result as a single predictor, error values were of 1.9 kg LBM and 3.7 %BF in the prediction group (n=100), and of 2.2 kg LBM and 3.6 %BF in the cross-validation group (n=46). Addition of anthropometrical predictors was not necessary. CONCLUSIONS: The HHI analyser significantly overestimated LBM and underestimated %BF in African women. After correction for the bias, the body compartments could easily be estimated in African women by using the HHI result in an appropriate prediction equation with a good precision. It remains to be seen whether a combination of arm and leg impedancemetry in order to take into account lower limbs would further improve the prediction of body composition in Africans.

Adipose Tissue↗
PubMed2004

Perceptions of healthy and desirable body size in urban Senegalese women.

OBJECTIVE: To examine the cultural ideals for body size held by urban Senegalese women; to determine the body size that women associate with health; and to estimate the change in prevalence of female obesity in an urban neighbourhood of Dakar. DESIGN: Cross-sectional, population-based study in the subject's home, using a structured interviewer-administered questionnaire, conducted in the same Dakar neighbourhood as that of a previous survey conducted in 1996. SUBJECTS: A total of 301 randomly selected women, aged 20-50 y, living in a specific Dakar neighbourhood, Senegal. MEASUREMENTS: A total of 32 items concerning body satisfaction, social status, health and individual attributes to associate with one of six photographic silhouettes; body mass index (BMI), waist circumference, waist-to-hip ratio by anthropometry; and measures of economic status. RESULTS: In all, 26.6% of women were overweight (BMI 25-29.9 kg/m2) and 18.6% were obese (BMI > or =30 kg/m2) compared with 22.4 and 8.0% respectively in 1996. Overweight was the most socially desirable body size, although obesity itself was seen as undesirable, associated with greediness and the development of diabetes and heart disease. Lay definitions of overweight and normal weight differed substantially from health definitions, as one-third of the sample saw the 'overweight' category as normal. Over a third of women with BMI > or =25 kg/m2 wanted to gain more weight. CONCLUSION: There has been a sharp rise in the prevalence of obesity in Senegalese women living in a Dakar neighbourhood over the last 7 y. In general, overweight body sizes (but not obese) were seen in a positive light. The finding that the term 'overweight' made little sense to these Senegalese women could have important implications for developing public health policies.

Adult↗
PubMed2003

Change in body water distribution index in infants who become stunted between 4 and 18 months of age.

OBJECTIVE: To evaluate body composition changes using bioelectrical impedance analysis and skinfold thickness measurements in infants from tropical areas who become stunted between 4-18 months of age. DESIGN AND MEASUREMENTS: Follow-up study. Extracellular water to total body water ratio index (length(2)/resistance at low to high frequency), peripheral fat (tricipital and subscapular skinfold thickness), and length-for-age index were studied at 4 and 18 months of age. SETTINGS: Low-income areas in four tropical regions (Congo, Senegal, Bolivia and New Caledonia). SUBJECTS: Infants were included in the analysis provided they were neither stunted nor wasted at 4 months. Two groups of infants were compared, those that were stunted at 18 months (n=61) or not (n=170). RESULTS: The extracellular water to total body water ratio index and the sum of skinfold thickness measurements were similar in the two groups at 4 months, and only the extracellular water to total body water ratio index was significantly different at 18 months. When no stunting appeared between 4 and 18 months, the change in the extracellular water to total body water ratio index was not linked with variations in length-for-age, and presented the expected pattern of variation in body water compartments. When stunting occurred, variation in length-for-age was related to significant changes in the extracellular water to total body water ratio index, the biggest increase in the proportion of extracellular water being found in the most stunted infants. Variations in the sum of the two skinfold thickness measurements presented the expected pattern for the 4-18 months growth and did not differ between the two groups. CONCLUSIONS: Multifrequency resistances suggested that stunting was associated with a lack of the expansion of the intracellular compartment that is expected during normal growth of cell mass, together with preserved fat mass. SPONSORSHIPS: Supported by grant 92L0623 from the French Ministry of Research, and by Institut de Recherche pour le Développement (IRD).

Adipose Tissue↗
PubMed2001

C. elegans RAD-5/CLK-2 defines a new DNA damage checkpoint protein.

BACKGROUND: In response to genotoxic stress, cells activate checkpoint pathways that lead to a transient cell cycle arrest that allows for DNA repair or to apoptosis, which triggers the demise of genetically damaged cells. RESULTS: During positional cloning of the C. elegans rad-5 DNA damage checkpoint gene, we found, surprisingly, that rad-5(mn159) is allelic with clk-2(qm37), a mutant previously implicated in regulation of biological rhythms and life span. However, clk-2(qm37) is the only C. elegans clock mutant that is defective for the DNA damage checkpoint. We show that rad-5/clk-2 acts in a pathway that partially overlaps with the conserved C. elegans mrt-2/S. cerevisiae RAD17/S. pombe rad1(+) checkpoint pathway. In addition, rad-5/clk-2 also regulates the S phase replication checkpoint in C. elegans. Positional cloning reveals that the RAD-5/CLK-2 DNA damage checkpoint protein is homologous to S. cerevisiae Tel2p, an essential DNA binding protein that regulates telomere length in yeast. However, the partial loss-of-function C. elegans rad-5(mn159) and clk-2(qm37) checkpoint mutations have little effect on telomere length, and analysis of the partial loss-of-function of S. cerevisiae tel2-1 mutant failed to reveal typical DNA damage checkpoint defects. CONCLUSIONS: Using C. elegans genetics we define the novel DNA damage checkpoint protein RAD-5/CLK-2, which may play a role in oncogenesis. Given that Tel2p has been shown to bind to a variety of nucleic acid structures in vitro, we speculate that the RAD-5/CLK-2 checkpoint protein may act at sites of DNA damage, either as a sensor of DNA damage or to aid in the repair of damaged DNA.

Adenosine Triphosphatases↗
PubMed2001

The C. elegans homolog of the p53 tumor suppressor is required for DNA damage-induced apoptosis.

In mammals, one of the key regulators necessary for responding to genotoxic stress is the p53 transcription factor. p53 is the single most commonly mutated tumor suppressor gene in human cancers. Here we report the identification of a C. elegans homolog of mammalian p53. Using RNAi and DNA cosuppression technology, we show that C. elegans p53 (cep-1) is required for DNA damage-induced apoptosis in the C. elegans germline. However,cep-1 RNAi does not affect programmed cell death occurring during worm development and physiological (radiation-independent) germ cell death. The DNA binding domain of CEP-1 is related to vertebrate p53 members and possesses the conserved residues most frequently mutated in human tumors. Consistent with this, CEP-1 acts as a transcription factor and is able to activate a transcriptional reporter containing consensus human p53 binding sites. Our data support the notion that p53-mediated transcriptional regulation is part of an ancestral pathway mediating DNA damage-induced apoptosis and reveals C. elegans as a genetically tractable model organism for studying the p53 apoptotic pathway.

Amino Acid Sequence↗
PubMed2001

Body composition unaltered for African women classified as 'normal but vulnerable' by body mass index and mid-upper-arm-circumference criteria.

OBJECTIVE: To test the hypothesis that 'normal but vulnerable' adults, as defined by body mass index (BMI) in combination with mid-upper-arm-circumference (MUAC), are closer to normal than to malnourished ones. For that purpose body composition measurements were compared between normal and low BMI categories and according to MUAC value in an African context and for different age groups. DESIGN: Reanalysis of data from a previous cross-sectional cluster sample nutrition survey. SETTING: A rural area of the Republic of Congo, Central Africa. SUBJECTS: A representative sample (n=544) of non-pregnant women. MAIN OUTCOME MEASURES: Arm muscle area was calculated from measurements of triceps skinfold thickness and MUAC. Peripheral body fat was assessed by the sum of four skinfold thicknesses. The ratio of resistance at high and low frequencies was derived from whole body measurement of multifrequency bioelectrical impedance analysis and used as the extracellular to total body water ratio index. RESULTS: The prevalence of thinness decreased from 18.7% as defined by BMI alone to 9.0% as defined by BMI and MUAC. This difference was due to the group of subjects classified as 'normal but vulnerable' (9.7%). Prevalence of thinness increased with age when assessed by BMI alone, but no longer when assessed by BMI and MUAC. Comparison with the BMI> or =18.5 kg/m(2) category showed that in 'normal but vulnerable' subjects lower BMI was accompanied by lower both fat and lean compartments, in absolute values, but the equilibrium of body water compartments was not altered. In BMI<18.5 women, low MUAC was associated with altered lean tissues, at peripheral and whole body level, whereas fat tissue did not differ. CONCLUSIONS: 'Normal but vulnerable' subjects appeared as 'thin but healthy' rather than malnourished, at all ages, even though their BMI was lower than 18.5 kg/m(2). The new classification of thinness based on BMI and MUAC provides a more specific index of nutritional status when restricting the thin category to more at-risk subjects.

Adipose Tissue↗
PubMed2000

A conserved checkpoint pathway mediates DNA damage--induced apoptosis and cell cycle arrest in C. elegans.

To maintain genomic stability following DNA damage, multicellular organisms activate checkpoints that induce cell cycle arrest or apoptosis. Here we show that genotoxic stress blocks cell proliferation and induces apoptosis of germ cells in the nematode C. elegans. Accumulation of recombination intermediates similarly leads to the demise of affected cells. Checkpoint-induced apoptosis is mediated by the core apoptotic machinery (CED-9/CED-4/CED-3) but is genetically distinct from somatic cell death and physiological germ cell death. Mutations in three genes--mrt-2, which encodes the C. elegans homolog of the S. pombe rad1 checkpoint gene, rad-5, and him-7-block both DNA damage-induced apoptosis and cell proliferation arrest. Our results implicate rad1 homologs in DNA damage-induced apoptosis in animals.

Animals↗
PubMed2000

Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group.

BACKGROUND & AIMS: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade. METHODS: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection. RESULTS: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001). CONCLUSIONS: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.

Adult↗
PubMed1998

Pheromone-dependent G1 cell cycle arrest requires Far1 phosphorylation, but may not involve inhibition of Cdc28-Cln2 kinase, in vivo.

In yeast, the pheromone alpha-factor acts as an antiproliferative factor that induces G1 arrest and cellular differentiation. Previous data have indicated that Far1, a factor dedicated to pheromone-induced cell cycle arrest, is under positive and negative posttranslational regulation. Phosphorylation by the pheromone-stimulated mitogen-activated protein (MAP) kinase Fus3 has been thought to enhance the binding of Far1 to G1-specific cyclin-dependent kinase (Cdk) complexes, thereby inhibiting their catalytic activity. Cdk-dependent phosphorylation events were invoked to account for the high instability of Far1 outside early G1 phase. To confirm any functional role of Far1 phosphorylation, we undertook a systematic mutational analysis of potential MAP kinase and Cdk recognition motifs. Two putative phosphorylation sites that strongly affect Far1 behavior were identified. A change of serine 87 to alanine prevents the cell cycle-dependent degradation of Far1, causing enhanced sensitivity to pheromone. In contrast, threonine 306 seems to be an important recipient of an activating modification, as substitutions at this position abolish the G1 arrest function of Far1. Only the phosphorylated wild-type Far1 protein, not the T306-to-A substitution product, can be found in stable association with the Cdc28-Cln2 complex. Surprisingly, Far1-associated Cdc28-Cln2 complexes are at best moderately inhibited in immunoprecipitation kinase assays, suggesting unconventional inhibitory mechanisms of Far1.

Animals↗
PubMed1996

Effect of early, short-term supplementation on weight and linear growth of 4-7-mo-old infants in developing countries: a four-country randomized trial.

The effect of supplementation on growth was tested by means of four similar controlled randomized trials in the Congo (n = 120), Senegal (n = 110), Bolivia (n = 127), and New Caledonia (n = 90). Four-month-old infants were randomly allocated to supplement or control groups. A cereal-based precooked porridge was offered twice daily for 3 mo and consumption was monitored. Both groups were free to eat local food. At 7 mo of age, all infants were still breast-fed in the Congo, Senegal, and Bolivia compared with 47% in New Caledonia. Mean daily consumption of the supplement varied among countries (558-790 kJ/d). Mean length at 4 mo was lowest in Bolivia, higher in Senegal and the Congo, and near the National Center for Health Statistics reference in New Caledonia. The mean 4-7 mo length increment was 0.48 cm higher for supplemented than for control infants in Senegal (P < 0.05), whereas weight increments did not differ. No significant effect was found in the other countries.

Body Height↗
PubMed1994

MSG5, a novel protein phosphatase promotes adaptation to pheromone response in S. cerevisiae.

Pheromone-stimulated yeast cells and haploid gpa1 deletion mutants arrest their cell cycle in G1. Overexpression of a novel gene called MSG5 suppresses this inhibition of cell division. Loss of MSG5 function leads to a diminished adaptive response to pheromone. Genetic analysis indicates that MSG5 acts at a stage where the protein kinases STE7 and FUS3 function to transmit the pheromone-induced signal. Since loss of MSG5 function causes an increase in FUS3 enzyme activity but not STE7 activity, we propose that MSG5 impinges on the pathway at FUS3. Sequence analysis suggests that MSG5 encodes a protein tyrosine phosphatase. This is supported by the finding that recombinant MSG5 has phosphatase activity in vitro and is able to inactivate autophosphorylated FUS3. Thus MSG5 might stimulate recovery from pheromone by regulating the phosphorylation state of FUS3.

Adaptation, Physiological↗
PubMed1994

Bioelectrical impedance analysis in small- and appropriate-for-gestational-age newborn infants.

OBJECTIVE: To determine the reliability of bioelectrical impedance analysis, and to compare and contrast the anthropometric and BIA status of newborns. DESIGN: BIA and anthropometric parameters were compared in the few days after birth and at about 3 weeks of age. SETTING: At the maternity hospital or in a paediatric care unit. SUBJECTS: Small- or appropriate-for-gestational-age newborns, with birth weight below or above the 10th percentile of the reference value, respectively. Measurements were performed on 36 and 47 newborns at birth, and for a subgroup (21 and 11) again about 3 weeks later, respectively. RESULTS: At birth, length2/resistance was 4.3 +/- 0.6 and 6.1 +/- 1.2 cm2/omega (P = 10(-7)), and at 3 weeks of age length2/resistance was 5.0 +/- 0.6 and 5.7 +/- 0.8 cm2/omega (P = 0.11), for small- and appropriate-for-gestational-age newborns, respectively. Percentage reliability was 2.2% and 2.6% for intra- and inter-observer measurements of resistance. Importance of a correct placement of the sensor electrode was demonstrated. CONCLUSIONS: Ease of measurement and reliability of BIA in neonates were shown. Evolution of BIA values is in agreement with the known increase in total body water linked to regrowth of cell mass in small-for-gestational-age infants. Additional study is required before BIA should be used in usual clinical setting in newborns due to the lack of prediction equation.

Age Factors↗
PubMed1993

FAR1 links the signal transduction pathway to the cell cycle machinery in yeast.

Alpha factor induces arrest of yeast a cells in G1 and transcription of genes involved in mating. Prior work indicates that FUS3, a member of the MAP kinase family, and FAR1, whose molecular activity is unknown, contribute to cell cycle arrest by inhibiting G1 cyclins. Here we show that FAR1 is a substrate for FUS3 and that this phosphorylation regulates association of FAR1 with CDC28-CLN2 kinase. We show also that FAR1 is phosphorylated in vitro by the CDC28-CLN2 complex and in vivo in a CDC28-dependent manner. Mutational analysis of FAR1 reveals a correlation between its ability to associate with CDC28-CLN2 and to arrest the cell cycle. These results suggest that FAR1 protein is the link between the signaling pathway and the cell cycle machinery.

Amino Acid Sequence↗
PubMed1993

MAP kinase-related FUS3 from S. cerevisiae is activated by STE7 in vitro.

Pheromone-stimulated haploid yeast cells undergo a differentiation process that allows them to mate. Transmission of the intracellular signal involves threonine and tyrosine phosphorylation of the redundant FUS3 and KSS1 kinases, which are members of the MAP kinase family. FUS3/KSS1 phosphorylation depends on two additional kinases, STE11 and STE7 (refs 2, 5, 6). Genetic analyses predict an ordered pathway where STE11 acts before STE7 and FUS3/KSS1 (refs 2, 7). Here we report that STE7 is a dual-specificity kinase that modifies FUS3 at the appropriate sites and stimulates its catalytic activity in vitro. From these data and previous genetic results, we argue that STE7 is the physiological activator of FUS3. Recent indications that MAP kinase activators are related to STE7 suggest that signal transduction pathways in many, if not all, eukaryotic organisms use homologous kinase cascades.

Calcium-Calmodulin-Dependent Protein Kinases↗