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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 559 records · Page 31Linked to original sources
PubMed1995

Starch branching enzymes belonging to distinct enzyme families are differentially expressed during pea embryo development.

cDNA clones for two isoforms of starch branching enzyme (SBEI and SBEII) have been isolated from pea embryos and sequenced. The deduced amino acid sequences of pea SBEI and SBEII are closely related to starch branching enzymes of maize, rice, potato and cassava and a number of glycogen branching enzymes from yeast, mammals and several prokaryotic species. In comparison with SBEI, the deduced amino acid sequence of SBEII lacks a flexible domain at the N-terminus of the mature protein. This domain is also present in maize SBEII and rice SBEIII and resembles one previously reported for pea granule-bound starch synthase II (GBSSII). However, in each case it is missing from the other isoform of SBE from the same species. On the basis of this structural feature (which exists in some isoforms from both monocots and dicots) and other differences in sequence, SBEs from plants may be divided into two distinct enzyme families. There is strong evidence from our own and other work that the amylopectin products of the enzymes from these two families are qualitatively different. Pea SBEI and SBEII are differentially expressed during embryo development. SBEI is relatively highly expressed in young embryos whilst maximum expression of SBEII occurs in older embryos. The differential expression of isoforms which have distinct catalytic properties means that the contribution of each SBE isoform to starch biosynthesis changes during embryo development. Qualitative measurement of amylopectin from developing and maturing embryos confirms that the nature of amylopectin changes during pea embryo development and that this correlates with the differential expression of SBE isoforms.

1,4-alpha-Glucan Branching Enzyme↗
PubMed1995

Biochemical and molecular characterization of a novel starch synthase from potato tubers.

An isoform of starch synthase from potato tubers which is present both in the stroma of the plastid and tightly bound to starch granules has been identified biochemically and a cDNA has been isolated. The protein encoded by the cDNA is 79.9 kDa and has a putative transit peptide and a distinct N-terminal domain which is predicted to be highly flexible. It is similar in both amino acid sequence and predicted structure to the granule-bound starch synthase II (GBSSII) of pea embryos. When expressed in Escherichia coli, the mature protein has starch synthase activity. The importance of the isoform has been assessed by biochemical measurements and antisense transformation experiments in which the amount of the isoform in the tuber is severely and specifically reduced. Both approaches indicate that the isoform contributes a maximum of 15% of the total starch synthase activity of the tuber. It is suggested that this isoform and the GBSSII of pea embryos represent a widely distributed class of isoforms of starch synthase. The contribution to total starch synthase activity of members of this class probably varies considerably from one type of storage organ to another.

Amino Acid Sequence↗
PubMed1995

beta-Endorphin and blood pressure in multiple trauma victims.

In addition to pain and stress, endogenous opiates and in particular beta-endorphin could be involved in the modulation of cardiovascular parameters. Several studies have thus shown increases in plasma beta-endorphin levels in the course of septic or hypovolemic shock. Our study involving 44 multiple trauma patients indicates that even in the absence of any hemodynamic disorders, there is a correlation between systolic blood pressure and plasma beta-endorphins. These results argue in favor of the existence of feedback between systolic blood pressure and plasma beta-endorphins.

Adult↗
PubMed1995

Mutations of the presenilin I gene in families with early-onset Alzheimer's disease.

We analyzed 12 families with autosomal dominant early-onset Alzheimer' s disease (EOAD)for mutations in the coding region of the presenilin I (PSNLI) gene corresponding to the AD3 locus on chromosome 14q24.3. A total of eight missense mutations at codons 82, 115, 139, 163, 231, 264, 392, and 410 including six novel mutations, were identified in eight families. Cosegregation of the mutations with EOAD was confirmed in three families, one including 36 affected individuals. This study underlines the great allelic heterogeneity and the large distribution of the mutations within the PSNLI coding region. Our results support the notion that PSNLI is the major gene involved in autosomal dominant EOAD.

Age of Onset↗
PubMed1995

Safety profile of gemcitabine.

This paper reviews the toxicity profile of gemcitabine in a large group of patients (up to 790) from pivotal phase II studies, in which the drug was given intravenously as a 30 min infusion, in a schedule once a week for 3 weeks followed by a week of rest. The safety profile of gemcitabine is unusually mild for such an active agent in solid tumours. Haematological toxicity is mild and short-lived with modest WHO grades 3 and 4 for haemoglobin (6.4% and 0.9% of patients), leukocytes (8.1% and 0.5%), neutrophils (18.7% and 5.7%) and platelets (6.4% and 0.9%). The incidence of grade 3 and 4 infection associated with this level of myelosuppression was low (0.9% and 0.2%). Transaminase elevations occurred frequently, but they were usually mild, and rarely dose limiting. Mild proteinuria and haematuria were seen but were rarely clinically significant. There was no evidence of cumulative hepatic or renal toxicity. Nausea and vomiting was mild, rarely dose limiting, and generally well controlled with standard antiemetics. Flu-like symptoms were experienced in a small proportion of patients but were of short duration. Where oedema/peripheral oedema was experienced there was no evidence of any association with cardiac, hepatic or renal failure. Hair loss was rare, with WHO grade 3 alopecia reported in 0.5% of patients. There was no grade 4 alopecia. Furthermore, gemcitabine displayed minimal toxicity in elderly patients, and the side-effect profile does not seem to be affected by patient age. The adverse events typically experienced with cytotoxic agents, namely myelosuppression, nausea and vomiting and alopecia, are not seen to such a degree with gemcitabine, and this nonoverlapping toxicity profile suggests that gemcitabine is a promising agent for incorporation into combination chemotherapy regimens.

Age Factors↗
PubMed1995

CDP571, a humanized antibody to human tumor necrosis factor-alpha: safety, pharmacokinetics, immune response, and influence of the antibody on cytokine concentrations in patients with septic shock. CPD571 Sepsis Study Group.

OBJECTIVES: To determine the safety of a "humanized" antibody to human anti-tumor necrosis factor-alpha (TNF-alpha) in patients with septic shock, and to examine the pharmacokinetics, immune response, and influence of the antibody on cytokine concentrations in this patient group. DESIGN: Prospective, randomized, placebo-controlled, phase II multicenter clinical trial, with escalating doses of a fully humanized anti-TNF-alpha antibody (CDP571). SETTING: Seven academic intensive care units in Europe. PATIENTS: Forty-two patients with rapidly evolving septic shock who received CDP571 in addition to standard supportive care. INTERVENTIONS: Patients received intravenously either placebo or one of four single doses of CDP571: 0.1, 0.3, 1.0, or 3.0 mg/kg. MEASUREMENTS AND MAIN RESULTS: The humanized anti-TNF-alpha antibody was well tolerated. The overall all-cause 28-day mortality rate was 62%. Mortality rate was similar in the placebo and treatment groups, except that all six patients who received 0.3 mg/kg of CDP571 died within 7 days. This outcome, which was not dose-related, is consistent with the poorer prognostic characteristics of this group at baseline. The peak CDP571 concentrations and area under the curve increased proportionately with the dose. The low level of the immune response detected had little effect on the ability of circulating CDP571 to bind TNF-alpha and on the pharmacokinetics of the antibody. An abrupt reduction in circulating TNF-alpha concentration was observed 30 mins after CDP571 administration at all active dosage levels. While interleukin-1 beta and interleukin-6 plasma concentrations decreased with time in all dosage groups, these cytokine concentrations decreased more rapidly during the initial 24 hrs in the treatment groups than in the placebo group. CONCLUSIONS: The humanized anti-TNF-alpha antibody, CDP571, is well tolerated and able to cause a dose-dependent reduction in circulating TNF-alpha concentrations in patients with septic shock. Further studies are needed to determine the efficacy of this antibody to improve the survival rates of critically ill patients with severe sepsis.

APACHE↗
PubMed1995

Comparison of concentrations of two doses of clavulanic acid (200 and 400 milligrams) administered with amoxicillin (2,000 milligrams) in tissues of patients undergoing colorectal surgery.

The concentrations of clavulanic acid and amoxicillin were determined in sera and different abdominal tissues of 17 patients who underwent elective colorectal surgery. Patients were randomly allocated to two groups. At the time of induction of anesthesia, patients in group 1 were given 200 mg of clavulanic acid with 2,000 mg of amoxicillin and patients in group 2 received 400 mg of clavulanic acid with 2,000 mg of amoxicillin. In both groups, the initial dose was administered again after 2 h. Blood samples were collected to determine peak and trough antibiotic levels. Serial blood samples were also collected at predetermined periods (opening and closure of the abdominal cavity and surgical anastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously. Antibiotic concentrations were determined by high-performance liquid chromatography. Increasing the dose of clavulanic acid to 400 mg resulted in significantly higher peak and trough levels in serum (P < 0.03). Following the injection of 400 mg, mean concentrations of clavulanic acid in the fatty tissues were significantly increased at the time of opening (P < 0.02). The concentrations of clavulanic acid and amoxicillin in fatty tissues were 17 to 52% and 12 to 23% of the levels in sera, respectively. In the colonic wall, the concentrations of clavulanic acid and amoxicillin were 52 to 63% and 49 and 27% of the levels in sera, respectively. In sera, clavulanic acid given at a dose of 200 or 400 mg reached or exceeded the concentrations found to be effective in vitro to reduce the MICs of amoxicillin from the resistant to the susceptible category for 90% of the potential pathogens. In most of the tissues investigated, increased the dose of clavulanic acid to 400 mg resulted in a significantly higher number of samples with concentrations found to be effective in vitro (72 versus 11%; P < 0.05). In conclusion, increasing the dose of clavulanic acid to 400 mg resulted in higher levels in sera and improved penetration into the abdominal tissues in patients undergoing colorectal surgery.

Adipose Tissue↗
PubMed1995

Genetic diversity of Pseudomonas aeruginosa strains isolated from patients with cystic fibrosis revealed by restriction fragment length polymorphism of the rRNA gene region.

The restriction fragment length polymorphism patterns of rDNAs from Pseudomonas aeruginosa strains isolated from the respiratory tracts of patients suffering from cystic fibrosis were obtained to evaluate the genetic polymorphism of this population of strains. Eighty-seven P. aeruginosa strains isolated from 87 patients from diverse areas of France and the ATCC 10145 strain were examined. Four restriction enzymes were used: BamHI, ClaI, EcoRI, and PstI. Forty-nine strains (56%) were in the three most frequent ribotypes (ribotypes R1 to R3). In addition, hierarchical clustering analysis of the data showed that 71 of the 88 strains (81%) clustered at a distance of less than one-third of the greatest distance observed in the total population. This indicates that clinical isolates implicated in the pathology of cystic fibrosis present a low degree of heterogeneity of rRNA operons, in contrast to the heterogeneity of strains of P. aeruginosa isolated from patients with various other pathologies. This relative homogeneity of rRNA genes was observed independently of the clinical status of the patient and the colony morphology.

Adolescent↗
PubMed1995

Chromosomal DNA fingerprinting analysis using the insertion sequence IS6110 and the repetitive element DR as strain-specific markers for epidemiological study of tuberculosis in French Polynesia.

The polymorphism of Mycobacterium tuberculosis strains was evaluated in French Polynesia, an area with a low incidence of tuberculosis and a population which has been geographically stable during recent decades. Nonrepetitive strains isolated from 64 patients during 1991 and 1992 were subjected to DNA restriction fragment length polymorphism (RFLP) analysis, using the insertion sequence IS6110 and the repetitive element DR as probes. Thirty-eight different IS6110 RFLP types were identified. They could be clustered in 11 groups. All the members of each group are identical or differ by one to three bands. All the other strains are gathered in the miscellaneous group. In some cases, transmission of strains with identical RFLP types between patients of the same family or between patients living in the same area was identified. Strains exhibiting similar IS6110 RFLP types also exhibited identical DR RFLP patterns, confirming that strains with similar types were genetically linked. Strains belonging to two different IS6110 clusters exhibited the same DR RFLP type. These data may also indicate a common origin for these strains and evolution to new IS6110 types. The results obtained in this study suggest that not only reactivation of latent tuberculous infections but also active transmissions are still occurring in French Polynesia.

Adolescent↗
PubMed1995

Pulmonary fibrosis correlates with outcome in adult respiratory distress syndrome. A study in mechanically ventilated patients.

STUDY OBJECTIVE: The present study was carried out to evaluate the prognostic value of pulmonary fibrosis diagnosed on the basis of pulmonary samples obtained by fiberscopic transbronchial lung biopsy (TBLB) in patients treated for severe established adult respiratory distress syndrome (ARDS). DESIGN: Prospective cohort study. SETTING: Intensive Care Unit of a University Hospital. PATIENTS: Consecutive patients with a diagnosis of established ARDS. INTERVENTIONS: Samples of pulmonary tissue (3 to 6 in each patient) were obtained by fiberoptic TBLB. Severity of pulmonary fibrosis was assessed based on pathologic changes. Hematoxylin and eosin and Masson's trichrome stains were performed on each tissue sample. MAIN RESULTS: Twenty-two lung specimens were obtained from 25 consecutive patients with ARDS of various origin (postsurgical complications, 7 patients; multiple trauma, 8 patients; medical problems, 7 patients). Transbronchial lung biopsy was complicated by small or moderate hemorrhage in three patients. No case of pneumothorax was identified. Pathologic findings showed that 14 patients (64%) had pulmonary fibrosis, either mild (9 patients) or moderate to severe fibrosis (5 patients). In the patients with pulmonary fibrosis, mortality rate was 57% (8 out of 14 patients), which was significantly different (p < 0.02) from the 0% mortality rate observed in patients without pulmonary fibrosis. Severity of pulmonary fibrosis (mild vs moderate and severe) did not influence outcome. With the exception of pathologic findings, characteristics of patients with and without pulmonary fibrosis (PaO2, PaCO2, the ratio of PaO2 to fraction of inspired oxygen, and positive end-expiratory pressure) were not different. CONCLUSION: In the study patients, pulmonary fibrosis diagnosed on the basis of TBLB was closely related to fatality in established ARDS.

Adult↗
PubMed1995

Comparing two heat and moisture exchangers with one vaporizing humidifier in patients with minute ventilation greater than 10 L/min.

STUDY OBJECTIVE: To evaluate in patients submitted to minute ventilation > 10 L/min the ability to preserve patients' heat and humidity of two heat and moisture exchangers (HMEs) and one vaporizing humidifier (VH). DESIGN: Prospective, randomized, comparative, non-blinded study. SETTING: Intensive care unit of a university hospital. PATIENTS: Nine tracheally intubated, mechanically ventilated patients, sedated and submitted to mechanical ventilation with minute ventilation > 10 L/min. INTERVENTIONS: Using the psychrometric method, relative humidity (RH) and absolute humidity (AH) of inspired gas were obtained as well as temperature of inspired gas and tracheal temperatures (maximal and minimal). Following a randomized order, each patient was ventilated for two 24-h periods with a vaporizing humidifier (Bennett Cascade 2, Bennett; France) and one of two HMEs: Pall Ultipor filter BB50 (Pall Biomedical; France) or DAR Hygroster filter (Peters; France). Both were first tested for a 45-min period and then the HME that achieved the best performance in terms of temperature and water preservation was tested for 24 h. MEASUREMENTS AND RESULTS: During the 45-min test period, the Pall Ultipor HME achieved a lower performance than the other two systems for any of the studied parameters (p < 0.05 to p < 0.0001). The DAR Hygroster HME achieved lower temperature of inspired gas (29.9 vs 32.0 degrees C, p < 0.005) and lower absolute humidity (29.3 vs 33.2 mg H2O/L, p < 0.005) than the Bennett Cascade 2. After 24 h of use, lower values of temperature of inspired gas (28.5 vs 32.0 degrees C, p < 0.002) and of AH (28.0 vs 33.6 mg H2O/L, p < 0.001) were obtained with the DAR Hygroster HME than with the Bennett Cascade 2. No differences were found between the two systems for the other tested parameters. At that time, no patients had RH lower than 97% and absolute humidity lower than 23 mg H2O/L with the use of the DAR Hygroster HME. CONCLUSIONS: In patients with minute ventilation > 10 L/min, the DAR Hygroster HME showed a thermic and humidification capability similar to the reference system, the Bennett Cascade 2 VH. In these patients, the Pall Ultipor HME had a significantly lower capability.

Adolescent↗
PubMed1995

Clinical pharmacokinetics of zopiclone.

Zopiclone is a cyclopyrrolone hypnotic agent. It possesses a chiral centre and is commercially available as a racemic mixture. Methods involving high performance liquid chromatography (HPLC), gas chromatography, capillary electrophoresis (CE) and high performance thin layer chromatography have been developed for the quantitation of zopiclone and its 2 main metabolites in biological samples. For the chiral determination of the enantiomers of zopiclone and its metabolites, HPLC and CE methods are available. After oral administration, zopiclone is rapidly absorbed, with a bioavailability of approximately 80%. The plasma protein binding of zopiclone has been reported to be between 45 and 80%. Zopiclone is rapidly and widely distributed to body tissues including the brain, and is excreted in urine, saliva and breast milk. Zopiclone is partly metabolised in the liver to form an inactive N-demethylated derivative and an active N-oxide metabolite. In addition, approximately 50% of the administered dose is decarboxylated and excreted via the lungs. Less than 7% of the administered dose is renally excreted as unchanged zopiclone. In urine, the N-demethyl and N-oxide metabolites account for 30% of the initial dose. The terminal elimination half-life (t1/2z) of zopiclone ranges from 3.5 to 6.5 hours. The pharmacokinetics of zopiclone in humans are stereoselective. After oral administration of the racemic mixture, Cmax (time to maximum plasma concentration), AUC (area under the plasma time-concentration curve) and t1/2z values are higher for the dextrorotatory enantiomer owing to the slower total clearance and smaller volume of distribution (corrected by the bioavailability), compared with the levorotatory enantiomer. In urine, the concentrations of the dextrorotatory enantiomers of the N-demethyl and N-oxide metabolites are higher than those of the respective antipodes. The pharmacokinetics of zopiclone are altered by aging and are influenced by renal and hepatic functions. Drug interactions have been observed with erythromycin, trimipramine and carbamazepine.

Azabicyclo Compounds↗
PubMed1995

Circadian changes in energy expenditure in the preruminant calf: whole animal and tissue level.

A study was conducted using four preruminant calves to determine the contribution of portal-drained viscera, liver, and hindquarters to circadian changes in total energy expenditure, after removing variations due to behavioral patterns. Indirect calorimetry and in vivo arterio-venous techniques were used. Standing time was longer (P < .01) after the meals and shorter (P < .01) at night. These variations were associated with higher (P < .01) energy cost of standing immediately after the meals and lower (P < .01) ones at night. When these behavioral effects were removed, total energy expenditure of lying calves was shown to be stable between the morning and evening meal, to increase by 11.5% and remained elevated during the 6 h after the evening meal, and to reach the lowest values at night. Portal-drained viscera and liver contributed 32.8 to 53.7% and 29.1 to 32.2%, respectively, to the circadian variations calculated for calves that were always standing. Changes in splanchnic tissue energy expenditure resulted from combined modifications in blood flow and O2 extraction rate. The contribution of hindquarters could not be clearly established. Overall, portal-drained viscera, liver, and hindquarters contributed 17.2, 12.8, and 18.0%, respectively, to total energy expenditure of standing calves. Their respective in vivo metabolic activities averaged 1.08, 2.10, and .25 mumol of O2 consumed.min-1.g-1 of fresh tissue.

Animals↗
PubMed1995

Molecular heterogeneity in childhood precursor B acute lymphoblastic leukemia with immunoglobulin heavy chain gene in germline configuration.

Four childhood acute leukemias with morphological, cytochemical and immunological characteristics correlating to precursor B lymphocyte and with germline configuration of the immunoglobulin heavy chain joining region were studied for the organization of the C mu segment. Two of the four lymphoblast samples retained the germline configuration of both JH and C mu regions. The other two samples showed delection of the entire JH region resulting in the rearrangement of the C mu region. In contrast to patients with C mu rearrangement, patients with C mu in germline form were not able to achieve complete remission after induction therapy. Study of the C mu region in patients with JH segment in germline configuration could separate subgroups in childhood precursor B acute lymphoblastic leukemia with different prognoses.

Adolescent↗