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Biomedical subjects

L Martin

Publications and source records attributed to L Martin.

At least 91 records · Page 5Linked to original sources

[Expression of p21 WAF1/CIP1 protein in colorectal cancers: study of its relation to p53 mutation and Ki67 antigen expression].

Mutations of the p53 gene are the most common genetic alteration in malignant human tumors. A cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is thought to be an important mediator of p53-induced cell cycle arrest. Although numerous studies have reported p53 expression and mutation in colorectal cancer few of them have correlated p53 expression with that of its downstream effector p21 and with the proliferation index as measured by expression of the Ki67 nuclear antigen. We studied p53, p21 and Ki67 expression by immunohistochemistry and molecular biology in 35 colorectal carcinomas. We compared these findings with each other and with clinical factors. Sixty three percent of tumors expressed p53 whereas seventy one percent expressed p21WAF1/CIP1. In adenocarcinomas, p21 staining was heterogeneous: p21-reactive cells were seen in the most differentiated areas. There was no correlation between p21WAF1/CIP1 and p53 expression, p53 mutation, Ki67 expression or clinical factors such as sex or location of the tumor. On the other hand, there was a statistical relationship between p21 expression and survival: our results indicated an association between high p21 expression and lower stages p21WAF1/CIP1 appears to be induced independently of p53 in these tumors and may be associated with differentiation rather than proliferation.

Adenocarcinoma↗

Influence of steep gradient supporting walls in rock climbing: biomechanical analysis.

This study analyses the reaction forces and variations of rock climbing in vertical and overhanging positions. Subjects voluntarily released their right foot and regained equilibrium. In the overhanging position the quadrupedal state was characterised by a significant involvement of the arms to prevent fall. Moreover, the horizontal forces applied to the holds were less important, which suggests that equilibrium was easier to maintain than in the vertical position. The tripedal state was characterised by less extensive contralateral supporting force transfer on the remaining holds in the overhanging position, which reinforces safety.

Adult↗

Small-cell carcinoma of the esophagus: report of three cases and review of the literature with emphasis on therapy.

Primary small-cell carcinoma (SCC) of the esophagus is rare, with about 200 cases reported up till now in the literature. Like pulmonary SCC, it is an aggressive tumor associated with a poor prognosis. Between 1994 and 1997, three patients with SCC of the esophagus were treated at Besançon University Hospital and this represented 1.85% of all esophageal malignancies diagnosed during this period: one patient had a limited tumor and underwent initial surgical resection, then chemotherapy with cisplatine and etoposide, and radiotherapy for recurrences. The other patients had extensive disease at diagnosis and were treated by the same chemotherapy. This retrospective study reports our experience of patients with this particular tumor and outlines the management strategy based on the available literature.

Aged↗

Solid-phase synthesis of peptides containing the spin-labeled 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC).

2,2,6,6-Tetramethylpiperidine-1-oxyl-4-amino4-carboxylic acid (TOAC) is a nitroxide spin-labeled, achiral Calpha-tetrasubstituted amino acid recently shown to be not only an effective beta-turn and 3(10)/alpha-helix promoter in peptides, but also an excellent rigid electron paramagnetic resonance probe and fluorescence quencher. Here, we demonstrate that TOAC can be effectively incorporated into internal positions of peptide sequences using Fmoc chemistry and solid-phase synthesis in an automated apparatus.

Amino Acids↗

Leptin, body fat content and energy expenditure in intact and gonadectomized adult cats: a preliminary study.

The present study was conducted to assess the body composition, leptin, and energy expenditure changes following gonadectomy in cats. Twenty-one females (12 intact and nine spayed) and 21 males (11 intact and 10 castrated) were used. Body weight was recorded. Serum plasma leptin was measured by radioimmunoassay and body composition and energy expenditure were assessed after injection of doubly labelled water. These results confirmed the gain in body weight and body fat following neutering and demonstrated a strong linear relationship between body fat and serum level of leptin. Energy expenditure decreased in castrated cats in comparison with intact ones. This study underlined the effect of gonadectomy as a major factor of obesity in cats and showed that the increase in circulating leptin reflected the amount of body fat. The present results provide further evidence that the regimen of gonadectomized cats should be carefully controlled to avoid excessive weight gain.

Adipose Tissue↗

Effects of dietary protein restriction and amino acids deficiency on protein metabolism in dogs.

Although stable isotope methods have been used to revisit the protein and amino acid requirements of humans in the last two decades, estimates of the minimum protein requirement of the dog have mainly been based on nitrogen balance studies. The aim of this study was: (i) to assess dog protein metabolism using the (13)C-leucine method, and (ii) to test the effects of protein deprivation and amino acid deficiency on protein metabolism. Eight dogs were fed three consecutive diets: (i) a normoprotein regimen [control; 63 g crude protein (CP)/Mcal metabolizable energy (ME)]; (ii) a protein-restricted diet (PR; 32 g CP/Mcal ME); and (iii) a protein-restricted diet that was, in addition, deficient in lysine and tryptophan (D-PR; 31 g CP/Mcal ME). The energy supply was similar for the three diets. The dogs were adapted to each diet for 2 weeks. After a 24 h fasting period, a 3 h infusion of (13)C-bicarbonate was performed, followed by a 3 h continuous infusion of L-[1-(13)C]leucine. Blood and breath samples were collected before and during the last hour of each isotope infusion for determination of plasma (13)C-alpha-ketoisocaproate and breath (13)CO(2) enrichments by mass spectrometry. Rates of protein breakdown, oxidation, and synthesis were calculated from leucine appearance into plasma, oxidation, and non- oxidative disposal, respectively, and expressed in g N/kg body weight (BW)0.75 per day, assuming body protein contains 0.08 g leucine per g protein. Protein breakdown was 3.71 +/- 0.17, 3.29 +/- 0.16 and 2.73 +/- 0.18 (mean +/- SEM) for control, PR, and D-PR, respectively (p < 0.01 D-PR versus control, and p < 0.05 D-PR versus PR). Protein synthesis was 3.08 +/- 0.13, 2.77 +/- 0.13, and 2.15 +/- 0.18 for control, PR and D-PR, respectively (p < 0.001 D-PR versus control, and p < 0.05 D-PR versus PR). Protein oxidation was 0.63 +/- 0.05, 0.53 +/- 0.05 and 0.58 +/- 0.05 for control, PR and D-PR, respectively (p=NS). These data suggest that: (i) the (13)C-leucine method can be used to assess large variations of protein turnover in dogs; (ii) dogs have the capacity to adapt their protein turnover to the level and to the quality of their protein supplies; and (iii) the dog nitrogen requirement for maintenance may be between 0.41 and 0.55 g N/kg BW(0.75) per day.

Adaptation, Physiological↗

Gastrointestinal transit of solid radiopaque markers in large and giant breed growing dogs.

Observations on food tolerance in dogs have shown that some breeds, especially the giant breeds, have a greater digestive sensitivity. One of the consequences common in these breeds is a higher faecal water content and a poor faecal quality. This could be explained, at least in part, by limited digestive capacity and function in giant breed dogs. In this report, the gastric emptying that represents one parameter of the digestive function was studied in large and giant breed dogs during their growth. Six Great Danes (GD) and six Giant Schnauzers (GS) were fed small radiopaque markers mixed with a test diet at 12, 22 and 36 weeks of age. Abdominal radiographs were made every 30 min for a period of 4 h and then hourly until 12 h. At 12 weeks of age, the gastric emptying pattern was similar in both breeds. However, from 22 weeks of age, the gastric emptying of the GD was significantly more rapid than that of GS. The gastric emptying of small markers tended to slow down in growing dogs, especially in GS. A significant positive correlation between the gastric emptying time of 50% of markers and the body weight was found. These results show that GD have a lower gastric retention time of foods, which could lead to a poor digestion and an altered absorption of nutrients. These could explained why digestive function and sensitivity could be different in dogs from different sizes and breeds.

Age Factors↗

Extraperitoneal approach reduces neutrophil activation, systemic inflammatory response and organ dysfunctionin aortic aneurysm surgery.

OBJECTIVES: to compare the effects of transperitoneal and extraperitoneal approaches on systemic inflammatory response, neutrophil activation and organ dysfunction in elective abdominal aortic aneurysm (AAA) repair. PATIENTS AND METHODS: twenty patients admitted for elective infrarenal AAA repair were prospectively randomised into transperitoneal (n =10) or extraperitoneal ( n =10) groups. Neutrophil activation was assessed by measuring the plasma levels of neutrophil elastase/alpha(1)-anti-trypsin complexes before surgery, intraoperatively and at 6 h, 12 h, 24 h and then daily after surgery. Venous blood samples for estimation of liver function tests, full blood counts, urea and electrolytes and arterial samples for blood gas analysis were taken daily from preoperatively to day 5 after surgery. Multiple organ dysfunction (MOD) and systemic inflammatory response (SIR) scores were calculated daily. RESULTS: the concentrations of neutrophil elastase/alpha(1)-anti-trypsin complexes were significantly higher in the transperitoneal group at 6 h after surgery compared to the extraperitoneal group (799(455-921) ng/ml (median(i.q.r.)) vs 307(171-395) ng/ml, p<0.005), and at 12 h (397(364-936) ng/ml vs 319(134-352) ng/ml, p <0.05). The MOD scores were significantly higher in the transperitoneal group in comparison to the extraperitoneal group at day 1 (2.5(2-3.3) vs 1(0-1), p<0.001) and day 2 (2.5(2-3.3) vs 1(0-1), p <0.001). The SIR scores were also significantly higher at day 1 (1(0-2) vs 0, p <0.01), day 2 (1.5(0-2.3) vs 0, p <0.01), and day 3 (1(0-1) vs 0, p <0.05). CONCLUSIONS: neutrophil activation, systemic inflammatory response and organ dysfunction are increased in elective AAA repair when a transperitoneal approach is used. This may be related to intestinal manipulation and mesenteric traction which are reduced in the extraperitoneal approach.

APACHE↗

Soluble liver antigen: isolation of a 35-kd recombinant protein (SLA-p35) specifically recognizing sera from patients with autoimmune hepatitis.

Autoantibodies to soluble liver antigen (SLA) are considered a specific marker of autoimmune hepatitis. We have performed immunoscreening of a human liver gene expression library with an anti-SLA-positive serum. A reactive clone with a 35-kd open reading frame (ORF) and a 563 base pair (bp) 3' untranslated region (UTR) was isolated (soluble liver antigen [SLA]-p35), showing strong homology to an independently isolated putative SLA/liver-pancreas antigen (LP) sequence (Acc. No. AF146396), and a UGA serine tRNA-protein complex (tRNP)((Ser) Sec) related protein (AJ238617), as well as different expression sequence tag (EST)-clones from lymphatic and oncofetal tissues. Expressed in Escherichia coli, SLA-p35 showed dose-dependent and complete blocking of reactivity to native SLA antigen after preabsorption with the 35-kd recombinant protein. It recognized 67/85 (78.8%) precharacterized anti-SLA-positive sera in dilutions up to 1:40,000 in immunoblot, without detectable cross reactivity in the controls. The commercially available SLA/LP enzymelinked immunosorbent assay (ELISA), by comparison, recognized 63/85 samples (74.1%). Of the negative samples, 18% showed strong inhibition rates (80% and above) in the polyclonal inhibition ELISA. We conlude that the complementary DNA now isolated by 3 independent approaches encodes for the major but not sole antigenic component of soluble liver antigen. Although its truncated form presented here may serve to improve diagnostics based on the new recombinant polypeptide, it currently cannot fully replace the polyclonal inhibition ELISA.

Adolescent↗

Comparison of physiological responses to morning and evening submaximal running.

The aim of this study was to assess the effect of time of day on physiological responses to running at the speed at the lactate threshold. After determination of the lactate threshold, using a standard incremental protocol, nine male runners (age 26.3 +/- 5.7 years, height 1.77 +/- 0.07 m, mass 73.1 +/- 6.5 kg, lactate threshold speed 13.6 +/- 1.6 km x h(-1); mean +/- s) completed a standardized 30 min run at lactate threshold speed, twice within 24 h (07:00-09:00 h and 18:00-21:00 h). Core body temperature, heart rate, minute ventilation, oxygen uptake, carbon dioxide expired, respiratory exchange ratio and capillary blood lactate were measured at rest, after a warm-up and at 10, 20 and 30 min during the run. In addition, the rating of perceived exertion was reported every 10 min during the run. Significant diurnal variation was observed only for body temperature (36.9 +/- 0.9 degrees C vs 37.3 +/- 0.3 degrees C) and respiratory exchange ratio at rest (0.86 +/- 0.01 vs 0.89 +/- 0.07) (P < 0.05). Diurnal variation persisted for body temperature throughout the warm-up (37.1 +/- 0.2 degrees C vs 37.5 +/- 0.3 degrees C) and during exercise (36.2 +/- 0.6 degrees C vs 38.6 +/- 0.4 degrees C), but only during the warm-up for the respiratory exchange ratio (0.85 +/- 0.05 vs 0.87 +/- 0.02) (P < 0.05). The rating of perceived exertion was significantly elevated during the morning trial (12.7 +/- 0.9 vs 11.9 +/- 1.2) (P < 0.05). These findings suggest that, despite the diurnal variation in body temperature, other physiological responses to running at lactate threshold speed are largely unaffected. However, a longer warm-up may be required in morning trials because of a slower increase in body temperature, which could have an impact on ventilation responses and ratings of perceived exertion.

Adult↗

HMR 3647 human-like treatment of experimental pneumonia due to penicillin-resistant and erythromycin-resistant Streptococcus pneumoniae.

An experimental Streptococcus pneumoniae pneumonia model in rabbits was used to assess the efficacy of amoxycillin, erythromycin and a new ketolide, telithromycin (HMR 3647). The MICs of amoxycillin, erythromycin and HMR 3647 for the three clinical S. pneumoniae strains used were, respectively, (mg/L): 0.01, 16 and 0.02 (strain 195); 2, 0.25 and 0.02 (strain 16089); 8, >64 and 0.02 (strain 11724). Antibiotic therapy reproduced human serum pharmacokinetics (amoxycillin 1 g iv tds or erythromycin 500 mg qds or HMR 3647 800 mg bd). Forty-eight hours of therapy with HMR 3647 and amoxycillin resulted in significant bacterial clearance in the lungs and spleen of rabbits infected by S. pneumoniae strain 195 and strain 16089 (at least 3 log(10) cfu/g decrease, P < 0.001). Erythromycin was active against only the erythromycinsusceptible strain (3 log(10) cfu/g decrease at 48 h, P < 0.001). None of the antibiotics showed significant efficacy with strain 11724. All agents produced significant bacterial clearance when time above MBC was >33%, and microbiological failure when it was <25%, whereas MIC was not correlated with microbiological outcome with HMR 3647. Our findings suggest that pharmacodynamic data integrating MBC may be predictive of microbiological success or failure with greater accuracy than with MIC. HMR 3647 produced significant bacterial clearance in both penicillin- and erythromycin-resistant pneumonia, but was less effective against the highly erythromycin-resistant S. pneumoniae strain.

Amoxicillin↗

Advocacy in epidemiology and demography.

This paper is a summary of a panel discussion at the Conference on Epidemiology and Demography held at Georgetown University, in Washington D.C. on February 8-9, 2001. The participants were Al Hermalin, Linda Martin, Mike Stoto, Robert Wallace, Douglas Weed, and Rose Li (who chaired the session). A list of questions similar to the section headings in this paper was prepared in advance of the conference, and each of the participants was asked to address specific issues, although the presentations typically covered a range of topics. This summary also includes comments from the floor.

Consumer Advocacy↗

Seven human immunodeficiency virus (HIV) antigen-antibody combination assays: evaluation of HIV seroconversion sensitivity and subtype detection.

In this study, we evaluated the performance of two prototype human immunodeficiency virus (HIV) antigen-antibody (Ag-Ab) combination assays, one from Abbott Laboratories (AxSYM HIV Ag-Ab) and the other from bioMerieux (VIDAS HIV Duo Ultra), versus five combination assays commercially available in Europe. The assays were Enzygnost HIV Integral, Genscreen Plus HIV Ag-Ab, Murex HIV Ag-Ab Combination, VIDAS HIV Duo, and Vironostika HIV Uniform II Ag-Ab. All assays were evaluated for the ability to detect p24 antigen from HIV-1 groups M and O, antibody-positive plasma samples from HIV-1 groups M and O, HIV-2, and 19 HIV seroconversion panels. Results indicate that although all combination assays can detect antibodies to HIV-1, group M, subtypes A to G, circulating recombinant form (CRF) A/E, and HIV-1 group O, their sensitivity varied considerably when tested using diluted HIV-1 group O and HIV-2 antibody-positive samples. Among combination assays, the AxSYM, Murex, and VIDAS HIV Duo Ultra assays exhibited the best antigen sensitivity (at approximately 25 pg of HIV Ag/ml) for detection of HIV-1 group M, subtypes A to G and CRF A/E, and HIV-1 group O isolates. However, the VIDAS HIV Duo Ultra assay had a lower sensitivity for HIV-1 group M and subtype C, and was unable to detect subtype C antigen even at 125 pg of HIV Ag/ml. The HIV antigen sensitivity of the VIDAS HIV Duo and Genscreen Plus combination assays was approximately 125 pg of HIV Ag/ml for detection of all HIV-1 group M isolates except HIV-1 group O while the sensitivity of Vironostika HIV Uniform II Ag-Ab and Enzygnost HIV Integral Ag-Ab assays for all the group M subtypes was >125 pg of HIV Ag/ml. Among the combination assays, the AxSYM assay had the best performance for detection of early seroconversion samples, followed by the Murex and VIDAS HIV Duo Ultra assays.

AIDS Serodiagnosis↗

Vanadium stimulates human bronchial epithelial cells to produce heparin-binding epidermal growth factor-like growth factor: a mitogen for lung fibroblasts.

The bronchial epithelium is a potential source of growth factors that could mediate airway fibrosis during the progression of diseases such as asthma and chronic bronchitis. We report that conditioned medium (CM) from normal human bronchial epithelial cells (NHBECs) contains mitogenic activity for human lung fibroblasts that is blocked by the epidermal growth factor receptor (EGF-R) tyrosine kinase inhibitor AG1478 and by neutralizing antibodies raised against heparin-binding epidermal growth factor-like growth factor (HB-EGF). Neutralizing antibodies against other EGF-R ligands (EGF and transforming growth factor-alpha) or other antibodies against growth factors (platelet-derived growth factors, insulin-like growth factor-1) had no affect on the mitogenic activity of NHBEC-CM. HB-EGF messenger RNA (mRNA) expression in NHBEC was detected by reverse transcriptase/polymerase chain reaction and Northern blot analysis. HB-EGF protein was detected by enzyme-linked immunosorbent assay. Vanadium pentoxide (V2O5), a fibrogenic metal associated with occupational asthma, caused a several-fold increase in HB-EGF mRNA expression and protein, whereas the inert metal titanium dioxide had no effect on HB-EGF expression. V2O5-induced HB-EGF mRNA expression was inhibited by the EGF-R tyrosine kinase inhibitor AG1478, the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580, and the MAP kinase kinase inhibitor PD98059. Finally, HB-EGF induced the production of fibroblast growth factor (FGF)-2 by human lung fibroblasts and anti-FGF-2 antibody partially blocked the mitogenic activity of NHBEC-CM on fibroblasts. These data suggest that HB-EGF is a fibroblast mitogen produced by NHBECs and that induction of an FGF-2 autocrine loop in fibroblasts by HB-EGF accounts for part of this mitogenic activity.

Blotting, Northern↗