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Biomedical subjects

J P Meyer

Publications and source records attributed to J P Meyer.

At least 19 recordsLinked to original sources

Comparison of physiological and subjective strains of two protective coveralls in two short physically simulated demanding tasks.

A total of 15 physically active male students carried out a normalised task (T(N)) and a task of access by ladder and scaffolding (T(L)) in two impermeable protective coveralls and a reference sports wear to compare the physiological and subjective strains. Heart rate (HR) was recorded and sweat loss was checked. Subjective evaluations of comfort parameters, acceptable exposure durations and physical exhaustion were recorded at the end of the tasks. Results show that both protective clothing, compared to the sport wear, increase significantly HR, RPE and CR10 in both tasks. However the strains of both protective clothing are not significantly different except in sweat loss and cumbersomeness.

Adult↗

Comparison of physiological and subjective strain in workers wearing two different protective coveralls for asbestos abatement tasks.

The aim of this study was to compare the physiological and subjective strain in workers wearing a disposable "Tyvek" (TYV) and a ventilated "Mururoa" (MUR) coverall in a real working situation. Eleven men performing normal abatement tasks volunteered to participate. Physiological measurements included oral temperature, heart rate and sweat loss. Subjective evaluations of clothing comfort, cooling, robustness, cumbersomness, acceptable exposure duration and physical exertion were carried out at the end of the task. The ventilated MUR reduced heat strain. Indeed, it allowed significantly higher sweat loss than TYV and showed a tendency to reduce the increase in oral temperature. Subjective ratings reveal that MUR was considered better than TYV in terms of clothing comfort, coolness and robustness. On the other hand, MUR is more cumbersome to wear. In this study, where workload and heat stress were moderate, there were few differences between the two coveralls in terms of physiological strains, but far more significant differences in the subjective ratings.

Adult↗

A twenty-year history of alveolar echinococcosis: analysis of a series of 117 patients from eastern France.

OBJECTIVES: Alveolar echinococcosis of the liver is a very rare and severe parasitic disease due to the growth of the larva of Echinococcus multilocularis. The aim of this paper was to describe a 20-year study of the epidemiological, clinical and therapeutic aspects of alveolar echinococcosis in eastern France. DESIGN: One hundred and seventeen consecutive cases, diagnosed and followed in our liver unit, were studied from 1972 to 1993. METHODS: Data from 85 patients followed since 1983 (period B) were compared to data from a first series of 32 patients (period A) collected from 1972 to 1982; 1983 was chosen as the cut-off year because of the numerous changes that occurred in the diagnosis, follow-up and treatment of the disease at this time, in particular the introduction of parasitostatic benzimidazoles. RESULTS: The results of patient follow-up were evaluated in December 1997. The cumulative prevalence was 2.5 per 100,000 persons in period A whereas it reached 6.6 per 100,000 in period B. The annual incidence in period B was 7.3 on average, compared with 2.7 in period A. Twenty-nine per cent of patients from period B were asymptomatic at the time of diagnosis compared with 10% in period A. This change was correlated with less advanced liver lesions, and was related to the extensive use of abdominal ultrasound, and from 1987, serological screening. Curative resections were performed in 24% of the cases in period B versus only 3% in period A. From 1986, liver transplantations were performed in eight patients from period A and 13 patients from period B. In period B, palliative surgery was frequently replaced by radiological non-operative procedures to treat abscesses and jaundice. From 1982, 73 patients received benzimidazoles for a period of time ranging from 4 to 138 months. Stabilization of the lesions was observed in two-thirds of the patients. Episodes of jaundice or digestive haemorrhage due to portal hypertension were 31.5 and 11 times less frequent respectively in patients from period B compared with period A. Actuarial survival at 5 years improved from 67% in period A to 88% in period B in patients of similar age. CONCLUSIONS: Radical changes in the diagnosis and the management of alveolar echinococcosis have occurred during the last decade. Together they have contributed to an improvement in the status of the patients affected by this very severe parasitic disease.

Benzimidazoles↗

Structural model of a cyclic dynorphin A analog bound to dodecylphosphocholine micelles by NMR and restrained molecular dynamics.

The compound c[Cys5,11]dynorphin A-(1-11)-NH2, 1, is a cyclic dynorphin A analog that shows similar selectivity and potency at the kappa-opioid receptor when compared to the native form of the peptide in central nervous system assays. Previous molecular mechanics calculations have shown that the ring portion of the isoform that is trans about the Arg9-Pro10 omega bond contains either a beta-turn from residues Arg6 to Arg9 or an alpha-helical conformation. Our results from solution state NMR indicate that the compound exhibits cis-trans isomerism about the Arg9-Pro10 omega bond in both aqueous solution and when bound to dodecylphosphocholine micelles. Restrained molecular dynamics calculations show that the cis isoform of the peptide contains a type III beta-turn from residues Arg7 to Pro10. Similar calculations on the trans isoform show it to contain a beta-turn from residues Cys5 and Arg8. In this report we describe the generation of three-dimensional models from NMR data for the ring portions of both the cis and trans isoforms of 1 bound to dodecylphosphocholine micelles. Comparison with other dynorphin A structural information indicates that both the cis and trans isoforms of the peptide may be active as kappa-opioid agonists.

Amino Acid Sequence↗

Effects of modifications of residues in position 3 of dynorphin A(1-11)-NH2 on kappa receptor selectivity and potency.

Tyrosine1 and phenylalanine4 in dynorphin A (Dyn A) have been reported to be important residues for opioid agonist activity and for potency at kappa receptors. The glycine residues in the 2 and 3 positions of dynorphin A may affect the relative orientation of the aromatic rings in positions 1 and 4, but their flexibility precludes careful analysis. To examine these effects on dynorphin A, we previously have synthesized the linear analogues [D-Ala3]Dyn A(1-11)-NH2 (2) and [Ala3]Dyn A(1-11)-NH2 (3) and reported their biological activities. Analogues 2 and 3 displayed affinities for the central kappa opioid receptor (IC50 = 0.76 and 1.1 nM, respectively) similar to that of Dyn A(1-11)-NH2 (1) (IC50 = 0.58 nM) and greatly enhanced selectivities for kappa vs mu and kappa vs delta receptors (IC50 ratios of 350 and 1300 for 2, and 190 and 660 for 3, respectively). These results suggest that the structure and lipophilicity of the amino acid present in position 3 of Dyn A(1-11)-NH2 as well as the conformational changes they induce in the message sequence of dynorphin have important effects on potency and selectivity for kappa opioid receptors. To further investigate structure-activity relationships involving the residue at the 3 position of Dyn A(1-11)-NH2, a series of Dyn A analogues with aromatic, charged, and aliphatic side chain substitutions at the 3 position was designed, synthesized, and evaluated for their affinities for kappa, mu, and delta opioid receptors. It was found that analogues with lipophilic amino acids at the 3 position of Dyn A(1-11)-NH2 generally displayed higher affinity but similar selectivities for the kappa receptor than analogues with charged residues at the same position. It is suggested that the structural, configurational, and steric/lipophilic effects of amino acids at position 3 of Dyn A(1-11)-NH2 may play an important role in potency and selectivity for the kappa receptor.

Amino Acid Sequence↗

[A new allergen dibromodicyanobutane. Report of a study in 310 patients January-December 1994].

INTRODUCTION: Methylisothiazolinone chloride (Kathon CG) and its derivatives, used as preservatives in cosmetics, have been shown to be allergenic when used in humans although preliminary studies in Guinea pigs failed to reveal any sensitization. Dibromodicyanobutane, associated with phenoxyethanol in Euxyl K400, has been proposed to replace the isothiazolinone derivatives in cosmetics. Preliminary study has shown that these thiazolinone derivatives are not allergenic in Euxyl K400. The similarity of these situations led us to hypothesize that dibromodicyanobutane could become allergenic. METHODS: We tested 0.1 p. 100 dibromodicyanobutane in vaseline in the additional battery of the ICDRG battery in patients with contact eczema. Among the 310 patients tested, 1.94 p. 100 had a positive test for this allergen (during this same period, 1.29 p. 100 of the patients were positive for isothiazolinones). Three patients were hospitalized because of generalized eczema and 1 patient had changed occupation with no effect because the crems containing the allergen had not been avoided. CONCLUSION: Dibromodicyanobutane is a new allergen. Numerous cases of allergy have developed as use of the product becomes more widespread. The consequences of this sensitization may have an economic impact. Animal experimentation has been unable to predict this allergenic effect. Cosmetic products must be precisely labeled with a single international term for each specific molecule and the name of the preservative added to the active substance.

Adolescent↗

Synthesis using a Fmoc-based strategy and biological activities of some reduced peptide bond pseudopeptide analogues of dynorphin A1.

Eight analogues of Dyn A(1-11)-NH2 incorporating the enzymatically stable psi(CH2-NH) isosteric peptide bond replacement were synthesized and tested for binding affinity at the central opioid mu, delta, and kappa receptors in guinea pig brain (GPB) homogenates and for activity at the peripheral kappa (and mu) receptors in the guinea pig ileum (GPI). The peptidic analogues were synthesized by solid phase techniques using a Fmoc/tert-butyl strategy, and the psi(CH2-NH) bond, or reduced bond, was introduced via reductive alkylation of the N-terminal amino group of the growing peptide with a Fmoc-N(alpha)-protected amino aldehyde. The synthesis of Fmoc-N(alpha)-protected amino aldehydes also is described. Several other peptides have been previously synthesized incorporating this modification and showed for instance increased enzymatic stability and antagonist properties. Results obtained in the GPB show that modifications of the peptide bond in the address site (analogues 4-9) do not affect the binding at the kappa receptor and, with a few exceptions, at the mu and delta receptors. On the other hand, analogues 2 and 3, modified in the message segment of Dyn A(1-11)-NH2, show a decrease in binding affinity at all three receptors. In the GPI, the results are more varied as the influence of the peptide bond modification seems to be more important than in the GPB. Finally, selected analogues were tested with no indication for antagonist activity at the kappa peripheral receptor.

Amino Acid Sequence↗

In vitro stability of some reduced peptide bond pseudopeptide analogues of dynorphin A.

Eight analogues of DYN A(1-11)-NH2 incorporating the nonhydrolyzable psi [CH2-NH] peptide bond surrogate were tested for their in vitro enzymatic stability in mouse brain homogenates. Results show that the Leu(5)-Arg6 and to a lesser extent the Arg(7)-Ile8 and Ile(8)-Arg9 peptide bonds are the more susceptible to enzymatic cleavage in the native peptide. (Leu5 psi[CH(2)-NH]Arg6)DYN A(1-11)-NH2 exhibits an almost complete resistance to enzymatic cleavage with a half-life greater than 500 min in brain, compared to 42 min for the standard peptide, DYN A(1-11)-NH2.

Animals↗

Design, synthesis, and biological properties of highly potent cyclic dynorphin A analogues. Analogues cyclized between positions 5 and 11.

We have recently reported the synthesis of several cyclic disulfide bridge-containing peptide analogues of dynorphin A (Dyn A), which were conformationally constrained in the putative address segment of the opioid ligand. Several of these analogues, bridged between positions 5 and 11 of Dyn A1-11-NH2, exhibited unexpected selectivities for the kappa and mu receptors of the central over the peripheral nervous systems. In order to further investigate the conformational and topographical requirements for the residues in positions 5 and 11 of these analogues, we have synthesized a systematic series of Dyn A1-11-NH2 analogues incorporating the sulfydryl containing amino acids L- and D-Cys and L- and D-Pen in positions 5 and 11, thus producing 16 cyclic peptides. In addition, Dyn A1-11-NH2, [D-Leu5]Dyn A1-11-NH2, and [D-Lys11]Dyn A1-11-NH2 were synthesized as standards. Several of these cyclic analogues, especially c[Cys5,D-Cys11] Dyn A1-11-NH2, c[Cys5, L- or D-Pen11]Dyn A1-11-NH2, c[Pen5, L-Pen11]Dyn A1-11-NH2 and c[Pen5, L- or D-Cys11]Dyn A1-11-NH2, retained the same affinity and selectivity (vs the mu and delta receptors) as the parent compound Dyn A1-11-NH2 in the guinea pig brain (GPB). These same analogues and most others exhibited a much lower activity in the guinea pig ileum (GPI), thus leading to centrally vs peripherally selective peptides, but showed a different structure-activity relationship than found previously. In a wider scope, this series of analogues also provided new insights into which amino acids (and their configurations) may be used in positions 5 and 11 of Dyn A analogues for high potency and good selectivity at kappa opioid receptors. The results obtained in the GPB suggest that requirements for binding are not the same for the kappa, mu, or delta central receptors.

Amino Acid Sequence↗

Seroepidemiologic screening of Echinococcus multilocularis infection in a European area endemic for alveolar echinococcosis.

In a serologic survey for Echinococcus multilocularis infection, we screened sera from 7,884 subjects from the Doubs Departement in France, an area endemic for alveolar echinococcosis (AE) of the liver. An enzyme-linked immunosorbent assay (ELISA) with a highly species-specific antigen (Em2) and an E. multilocularis crude antigen (Emc) was used for screening. An evaluation of the cost/benefit relationship of this screening, followed by therapeutic management of patients, was made and compared with the actual cost of the follow-up and treatment of the disease in symptomatic cases in this endemic area. Antibody reactions to Em2 and/or Emc made possible the detection of eight asymptomatic clinical cases (seroprevalence averaging 1/1,000), with typical lesions of active AE revealed by abdominal ultrasonography and computed tomography. All were seropositive using the Emc ELISA but two were seronegative using the Em2 ELISA. In five additional seropositive cases, the radiologic investigations revealed small calcified lesions similar to the lesions of abortive AE previously found in Alaska. The cost of this serologic screening program per screened subject and per diagnosed case averaged 50.00 French Francs (FF) (U.S. $8.60) and 60,000.00 FF (U.S. $10,909.00), respectively. The cost of diagnosis, follow-up and treatment of the patients was 5,086.00 FF (U.S. $929.00) per patient per month in the case of diseases diagnosed by the screening program and 7,086.00 FF (U.S. $1,288.00) per patient per month for patients with symptomatic AE. This survey indicates a high prevalence of AE in the target area; it confirms the long latency period of the larval growth in human AE and shows that abortive AE is present in Europe. The use of both the Emc and Em2 ELISAs seems to be better than using the Em2 ELISA alone. The cost of the hospitalization and treatment of the eight screened patients would appear to be relatively high. Even though two of them were asymptomatic, they had very severe forms of the disease. In fact, the total cost was much lower than the actual cost of the disease when diagnosed from clinical symptoms.

Adolescent↗

A comparison of operative approaches and parameters predictive of success in multilevel arterial occlusive disease.

BACKGROUND: The correction of abnormal inflow alone in patients with multilevel arterial occlusive disease (MLAOD) may be inadequate to relieve limb-threatening ischemia. This study was undertaken to compare operative approaches and attempt to define preoperative parameters predictive of limb salvage in patients with MLAOD. STUDY DESIGN: The outcome after revascularization for 194 patients with limb-threatening ischemia MLAOD was assessed retrospectively. One hundred fifty-one patients initially underwent an inflow operation alone. Based on whether or not these patients required an outflow operation within one year, they were divided into two groups: group 1, no outflow operation (121 patients, 121 limbs), and group 2, outflow operation required for continued ischemic symptoms (30 patients, 30 limbs). A separate group of forty-three patients (43 limbs) underwent synchronous inflow-outflow operations, or multilevel revascularization, as their initial operative procedure (group 3). RESULTS: Perioperative complications and mortality rates did not differ between groups. Limb salvage rates were similar for groups 1 and 3, whereas in group 2, limb salvage rates were significantly reduced (p = 0.0184). Long-term limb salvage after an isolated inflow procedure was associated with lack of prior vascular reconstructions (p = 0.0002), the absence of tissue loss (p = 0.0019), and an infrageniculate angiographic runoff score of less than 6 (p = 0.054). CONCLUSIONS: In patients with limb-threatening MLAOD, synchronous inflow-outflow operations can be performed with resultant morbidity and mortality rates comparable with inflow alone. After an inflow operation, the approach of "expectant management" may ultimately compromise limb salvage if a subsequent outflow operation is required.

Adult↗

The effects of goal difficulty on physiological arousal, cognition, and task performance.

Two laboratory experiments with 117 undergraduate students were conducted to examine (a) the effect of assigned goal difficulty on arousal (self-report and heart rate), cognition (perceived norm, self-efficacy strength, and personal goal), and behavioral (task performance) measures and (b) the role of heart rate as a mediator of the goal-difficulty-performance relation. All Ss performed a task requiring cognitive and physical responses. Results of both experiments demonstrated that assigned goal difficulty affected heart rate, cognition, and task performance and that heart-rate change was positively related to the cognitive and behavioral measures. Regression analyses suggested that a cognitive-affective mechanism may mediate the goal-difficulty-performance relation. Discussion is focused on the theoretical and practical implications of integrating an arousal concept within goal-setting theory.

Adult↗

Solution structure of salmon calcitonin.

Salmon calcitonin, a 32-residue peptide with a 1-7 disulfide bridge, was synthesized by standard solid-phase techniques, and studied by CD and two-dimensional NMR experiments. The peptide was dissolved in pure trifluoroethanol (TFE) and in aqueous solutions containing various amounts of TFE. CD studies in pure TFE indicated the presence of an alpha-helical structure comprising 40% of the constituent amino acids. This was fully confirmed by nmr. A detailed analysis was performed with the peptide in a 9 : 1 deuterated TFE/H2O mixture. A total of 365 nuclear Overhauser enhancements (154 intraresidual, 112 sequential and 99 long range) were complied from the nuclear Overhauser enhancement spectroscopy spectra and used in the distance geometry calculations. The core of the peptide between residues 8 and 22 assumes an alpha-helix like structure. The Cys 1-Cys 7 ring is well defined and in close association with the helix, while the C-terminal decapeptide folds back toward the core, forming a loose loop.

Amino Acid Sequence↗

A nine-year experience with crossover femoro-femoro-popliteal sequential bypass.

Multisegmental arterial occlusive disease may require a combined inflow and outflow procedure for optimal treatment of limb ischemia. Twenty-one patients with unilateral iliac artery stenosis or occlusion and ipsilateral superficial femoral artery occlusion underwent crossover femoro-femoro-popliteal sequential bypass during a 9-year period. Seventeen operations were for limb salvage. Patency rates were determined separately for each segment of the bypass. Primary patency rates for the femoro-femoral segment were 89%, 83%, and 57% at 1, 2, and 5 years, respectively. Primary patency rates for the femoro-popliteal segments were 68%, 62%, and 40% at 1, 2, and 5 years, respectively. Limb salvage rates were 100%, 90%, and 77% at 1, 2, and 5 years, respectively. This experience indicates that femoro-femoro-popliteal bypass is an effective treatment in selected patients with severe ischemia due to combined iliac artery and superficial femoral artery disease.

Aged↗

2-Diazohistidinyl thyrotropin-releasing hormone (TRH): a photosensitive TRH analog.

We have synthesized a new thyrotropin releasing hormone (TRH) analog, pGlu-2-diazo-His-Pro-NH2 5, which is a potential photoaffinity label for the TRH receptor. Its precursor, pGlu-2-amino-His-Pro-NH2 4, has been synthesized through successive coupling of a 2-aminohistidine derivative 1 with proline and pyroglutamic acid derivatives. Diazotization of the fully deprotected tripeptide 4 gave the photoactivatable TRH analog 5. Compounds 4 and 5 exhibit IC50 values of 2 and 8 microM respectively, to be compared to the 0.02 microM value for native TRH.

Amino Acid Sequence↗