Search PubMed⌕ Search

Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 595 records · Page 33Linked to original sources

A flower-specific Myb protein activates transcription of phenylpropanoid biosynthetic genes.

Synthesis of flavonoid pigments in flowers requires the co-ordinated expression of genes encoding enzymes in th phenylpropanoid biosynthetic pathway. Some cis-elements involved in the transcriptional control of these genes have been defined. We report binding of petal-specific activities from tobacco and Antirrhinum majus (snapdragon) to an element conserved in promoters of phenylpropanoid biosynthetic genes and implicated in expression in flowers. These binding activities were inhibited by antibodies raised against Myb305, a flower-specific Myb protein previously cloned from Antirrhinum by sequence homology. Myb305 bound to the same element and formed a DNA-protein complex with the same mobility as the Antirrhinum petal protein in electrophoretic mobility shift experiments. Myb305 activated expression from its binding site in yeast and in tobacco protoplasts. In protoplasts, activation also required a G-box-like element, suggesting co-operation with other elements and factors. The results strongly suggest a role for Myb305-related proteins in the activation of phenylpropanoid biosynthetic genes in flowers. This is consistent with the genetically demonstrated role of plant Myb proteins in the regulation of genes involved in flavonoid synthesis.

Base Sequence↗

Cloning and molecular analysis of structural genes involved in flavonoid and stilbene biosynthesis in grape (Vitis vinifera L.).

Genes involved in flavonoid and stilbene biosynthesis were isolated from grape (Vitis vinifera L.). Clones coding for phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), dihydroflavonol 4-reductase (DFR), leucoanthocyanidin dioxygenase (LDOX) and UDP glucose:flavonoid 3-O-glucosyl transferase (UFGT), were isolated by screening a cDNA library, obtained from mRNA from seedlings grown in light for 48 h using snapdragon (Antirrhinum majus) and maize heterologous probes. A cDNA clone coding for stilbene synthase (StSy) was isolated by probing the library with a specific oligonucleotide. These clones were sequenced and when the putative products were compared to the published amino acid sequence for corresponding enzymes, the percentages of similarity ranged from 65% (UFGT) to 90% (CHS and PAL). The analysis of the genomic organization and expression of these genes in response to light shows that PAL and StSy genes belong to large multigene families, while the others are present in one to four copies per haploid genome. The steady-state level of mRNAs encoded by the flavonoid biosynthetic genes as determined in young seedlings is coordinately induced by light, except for PAL and StSy, which appear to be constitutively expressed.

Anthocyanins↗

Whole blood concentrations of mefloquine enantiomers in healthy Thai volunteers.

We studied the pharmacokinetics of the enantiomers of mefloquine in whole blood in healthy Thai volunteers after administration of a single oral dose of 750 mg of the racemic mixture. Mefloquine pharmacokinetics were stereoselective. The peak concentrations and areas under the curve of the (-) enantiomer were significantly higher than those of its antipode (0.79 versus 0.46 microgram.ml-1 and 402 versus 94 micrograms.h.ml-1). The half-lives of (-)MQ were significantly longer than those of (+)MQ (531 versus 206 h). No stereoselectivity was observed for tmax values.

Adult↗

Prognostic values of serum cytokines in septic shock.

OBJECTIVE: To prospectively evaluate the prognostic values of two serum cytokine levels, TNF alpha and IL6 serially measured at predetermined intervals in septic shock patients unresponsive to correction of hypoxaemia and plasma volume expansion and treated according to a strict protocol designed to meet specific therapeutic goals (goal-directed therapy). The evolution of serum lactate levels and oxygen-derived parameters was also investigated. DESIGN: A prospective case series study. Patients were followed-up until they were discharged from the hospital, or died. SETTING: ICU of a university hospital. PATIENTS: 30 consecutive patients with septic shock of various origins. INTERVENTIONS: The therapy was aimed at achieving and maintaining for at least 24 h supranormal values CI (> or = 4.0 l.min-1.m-2), oxygen delivery (DO2 > or = 550 ml.min-1.m-2) and oxygen uptake (VO2 > or = 150 ml.min-1.m-2) using a combination of fluid loading, norepinephrine, dobutamine and dopamine. A significant decrease in TNF alpha levels was associated with a favourable outcome while TNF alpha levels remained elevated in the patients who died in shock or of multiple organ failure. No prognostic value was associated with changes in IL 6 concentrations. In a stepwise logistic regression analysis, only TNF alpha levels contributed significantly to prediction of patients' outcome. A significant decrease in serum lactate concentrations was observed both in survivors and in patients who survived the episode of septic shock, but subsequently died of multiple organ failure. A positive DO2/VO2 relationship was observed only in survivors but did not contribute significantly to prediction of patient outcome. CONCLUSIONS: TNF alpha is a major mediator involved in the pathogenesis of septic shock and its decrease was significantly associated with a favourable outcome. IL 6 is certainly involved in the pathophysiology of septic shock but further studies are required to determine whether or not it is directly involved in the mediation of late and lethal complications of septic shock. Serum lactate levels and oxygen-derived variables were of less interest as prognostic factors.

Adult↗

Effects of norepinephrine on right ventricular function in septic shock patients.

OBJECTIVE: To study the effects of norepinephrine on right ventricular function in patients with hyperdynamic septic shock. DESIGN: Prospective, open study. SETTING: A 15 bed ICU in a university hospital. PATIENTS: 9 patients with hyperdynamic septic shock (SBP < 90 mmHg, Cl > or = 4 l.min-1.m-2, SVRI < or = 850 dynes.s.cm-5m-2 and oliguria). INTERVENTIONS: Plasma volume expansion was used to correct a suspected volume deficit and then, norepinephrine infusion was started and titrated to restore systemic blood pressure to the normal range (mean infusion rate: 1.1 +/- 0.2 mcg.kg-1.min-1). Norepinephrine was the only vasoactive agent used in these patients. MEASUREMENTS AND RESULTS: A modified Swan-Ganz catheter mounted with a fast response thermistor was inserted in each patient, allowing repeated measurements of RVEDVI and RVEF. At time of inclusion to the study, all but one patient had elevated MPAP (23 +/- 4 mmHg) and RVEF < or = 50%, and all patients had RVEDVI > or = 90 ml.m-2. During norepinephrine infusion, MAP increased from 51 +/- 9 to 89 +/- 10 mmHg (p < 0.0001), PVRI increased from 204 +/- 35 to 286 +/- 63 dynes.s.cm-5.m-2 (p < 0.05), and despite this increase in right ventricular afterload, no detrimental effect in RVEF (36 +/- 11 to 36 +/- 10%) or in RVEDVI (116 +/- 30 to 127 +/- 40 ml.m-2) was observed. A Frank-Starling relationship for the right ventricle was constructed by plotting an index of ventricular performance (RVSWI) against an index of ventricular preload (RVEDVI). A significant upward shift to the right of the relationship was observed during norepinephrine infusion. CONCLUSION: It was concluded that norepinephrine exerted a favourable effect on right ventricular function.

Adult↗

[Selective digestive decontamination in patients under reanimation].

Nosocomial infections increase morbidity and mortality in hospitalized patients. ICU patients are at high risk of sustaining them, due to the high rate of invasive procedures and their poor health state. Conventional methods for decreasing the incidence of infection in ICU patients include handwashing, catheter care, strict antibiotic policy, and reduction of environmental sources of infection. Despite these measures, the colonization in these patients is always high, because of the presence of pathogens in the own patients' flora. Nosocomial pneumonia which is a major cause of mortality in ICU patients arises from retrograde colonization of the lung by pathogens originating from oro-pharyngeal and gastric secretions. Since 1984, selective decontamination of the digestive tract (SDD) has been advocated in ICUs to prevent from bacterial and fungal gastrointestinal/oropharyngreal colonization, nosocomial infection, subsequent multiple organ failure (MOF) and death. The SDD regimen is usually an extemporaneously prepared suspension of antimicrobial agents. Appropriate antibiotics for this regimen should ideally be nonabsorbable, to prevent from the development of resistant pathogens and avoid systemic toxicity. They should also be able to selectively eliminate enterobacteriaceae and yeasts, without decreasing the protective anaerobic flora. The most used combination is a suspension of colistin, amphotericin B and aminoglycoside, administered four times day through the nasogastric tube, in association with a paste consisting of 2 p. 100 colistin/amphotericin B/aminoglycoside, applied to the oropharynx. A parenteral antibiotic is also often co-administered during the first four days to prevent from early infections until the SDD regimen reaches its full effect; cefotaxime is usually used for this. SDD significantly decreases colonization rates in the oropharynx, gastrointestinal (GI) tract and trachea. This effects is primarily attributable to a decrease of Gram-negative bacilli (GNB) and yeasts, although several studies also reported decreased isolates of Gram-positive cocci (GPC). Oropharyngeal and GI colonization significantly decrease after four days of such a regimen, but tracheal decontamination in uncertain. Several studies recognized an emergence of GPC during or after SDD and resistance occurrence in GNB (especially against aminoglycosides). Recolonization occurs rapidly, about 4 to 8 days after the discontinuation of SDD. SDD decreases significantly the nosocomial infections, especially Gram-negative pneumonia. This benefit is most obvious in trauma patients, severely burned patients and after orthopic liver transplantation. Several studies reported a significant decrease in the overall rate of infections, especially extrapulmonary infections, including blood, urinary tract, wounds, abdominal, and catheter related infections. Despite a major decrease in infection rates with SDD, most studies did not show lowered mortality rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

The mottled gene is the mouse homologue of the Menkes disease gene.

The mottled mouse has been proposed as an animal model for Menkes disease, an X-linked disorder of copper transport. The recent isolation of a copper-transporting ATPase gene responsible for Menkes disease has allowed us to test this hypothesis. Here we report the isolation and sequence of the mouse homologue of this gene. We show that two mottled (Mo) alleles, dappled (Modp) and blotchy (Moblo), have abnormalities in the murine mRNA and that Modp has a partial gene deletion. These studies prove that the mottled mouse is the murine model for Menkes disease, providing the basis for future biochemical and therapeutic studies.

Adenosine Triphosphatases↗

Antimicrobial prophylaxis in surgery: general concepts and clinical guidelines. French Study Group on Antimicrobial Prophylaxis in Surgery, French Society of Anesthesia and Intensive Care.

Bacteria are found in 90% of surgical incisions, regardless of surgical technique or environment. Initially, the number of pathogens is low, but proliferation is facilitated by favorable local conditions and weakened host defense mechanisms. The principles of presurgical administration of antibiotics are well defined, but a few controversies persist. An ideal antimicrobial agent would not induce bacterial resistance in pathogenic organisms, would penetrate tissues effectively, would have a long enough half-life so that a single injection could guarantee protection throughout the operation, would have a low toxicity, would not interfere with anesthetics, would be easy to administer, and would be cost-effective.

Anti-Bacterial Agents↗

A study of peripheral tolerance through embryonic grafts of the bursal epithelial rudiment between MHC-distinct chick embryos.

We report here that different organ grafts are not equally competent to induce tolerance of the host even if they are performed early in development, i.e. before the host's immune system has started to develop. We have grafted the epithelio-mesenchymal rudiment of the bursa of Fabricius between histoincompatible chicken embryos at E5 and found that the transplant is normally colonized by hemopoietic cells from the host and that a normal contingent of B cells is eventually produced. The grafted bursa is tolerated after birth for a few weeks (> or = 4-8) but is in all cases rejected by an immune mechanism which cannot be assimilated to the physiological involution process which occurs at 4-5 months of age. Moreover, even in the first month after birth, when the bursa is still healthy, skin grafts of the same MHC haplotype are promptly rejected. These observations are in contrast with the outcome of allogeneic limb bud grafts which are permanently tolerated after birth although in an unperfect manner. We show in addition that, as was the case in xenogeneic grafts of limb buds and bursas of Fabricius from quail and chick embryos, the allogeneic in situ graft to thymic epithelium of the MHC haplotype of the bursal implant induces tolerance of the bursa. One common point of xenogeneic and allogeneic embryonic grafts of limb bud, bursa and even thymic rudiments is that none of them induced a complete state of tolerance, since proliferation responses were always obtained in vitro in one-way host-donor mixed leucocyte cultures.

Animals↗

Insertion sequence IS1137, a new IS3 family element from Mycobacterium smegmatis.

A new insertion sequence (IS) has been isolated from Mycobacterium smegmatis. It is 1361 bp long and possesses characteristics of the IS3 family elements. It harbours 32 bp imperfect inverted repeats at its extremities and a 3 bp direct repeat flanks the element, possibly as the result of a transposition event. This IS, IS1137, contains three major ORFs. Two of them, ORF A and ORF B show homologies both at the amino acid sequence level and at the organization level with the ORFs encoding the transposase of the IS3 family elements. IS1137 has a narrow host range and was found only in M. smegmatis and M. chitae. The fact that IS1137 is not present in the M. tuberculosis complex strains makes this element a new candidate for transposon mutagenesis in mycobacteria.

Amino Acid Sequence↗

Autoimmune haemolytic anaemia presenting 9 years prior to Castleman's disease.

Castleman's disease (CD) is a rare disease of unknown aetiology and pathogenesis. We present an unusual case of abdominal CD in whom the first manifestation was an autoimmune haemolytic anaemia presenting 9 years before the diagnosis. The Coombs test became negative 2 months after surgical resection of the mass, suggesting that the mass was the source of the autoantibody. CD may be present in autoimmune haemolytic anaemia in patients with no evidence of any other disease.

Adult↗

Waldeyer ring lymphomas. A clinicopathological study of 79 cases.

Waldeyer ring lymphomas belong to a category of tumours which has not yet been fully defined. Their relation to mucosa-associated lymphoid tissue (MALT) and other extranodal lymphomas remains largely unknown. We performed a clinicopathological retrospective study of 79 patients, and compared them with a series of MALT and nodal lymphomas. Tumours from the nasopharynx and palatine tonsil showed similar histological profiles, with a predominance of large B-cells. Centroblastic lymphomas constituted the largest group (n = 45), followed by those of centrocytic type (9) with smaller groups of centroblastic-centrocytic (5) and Hodgkin's lymphomas (2). Three monocytoid B-cell lymphomas were identified. Only one case could be classified as MALT lymphoma. The frequency of bcl-2 expression in large B-cell tumours of Waldeyer's ring has an intermediate range between large B-cell lymphomas occurring in mucosal and nodal locations. Epitheliotropism was present in all low-grade cases, and was therefore not a useful marker in the identification of potential MALT lymphomas in contrast with other mucosal sites. Comparative survival studies showed significant overall differences between Waldeyer ring lymphomas, MALT and nodal cases. These disappeared after taking stage and histological grade into account. We conclude that Waldeyer ring lymphomas show distinctive features, mainly in terms of histological distribution and immunophenotype. The key factor determining their behaviour could be their different spreading capability. These findings suggest that extranodal lymphomas are heterogeneous, and indicate the need for additional efforts to clarify this.

Adolescent↗

Mosaic pbpX genes of major clones of penicillin-resistant Streptococcus pneumoniae have evolved from pbpX genes of a penicillin-sensitive Streptococcus oralis.

Penicillin-resistant clinical isolates of Streptococcus pneumoniae contain mosaic penicillin-binding protein (PBP) genes that encode PBPs with decreased affinity for beta-lactam antibiotics. The mosaic blocks are believed to be the result of gene transfer of homologous PBP genes from related penicillin-resistant species. We have now identified a gene homologous to the pneumococcal PBP2x gene (pbpX) in a penicillin-sensitive Streptococcus oralis isolate M3 from South Africa that diverged by almost 20% from pbpX of penicillin-sensitive pneumococci, and a central sequence block of a mosaic pbpX gene of Streptococcus mitis strain NCTC 10712. In contrast, it differed by only 2-4% of the 1 to 1.5 kb mosaic block in pbpX genes of three genetically unrelated penicillin-resistant S. pneumoniae isolates, two of them representing clones of serotype 6B and 23F, which are prevalent in Spain and are also already found in other countries. With low concentrations of cefotaxime, transformants of the sensitive S. pneumoniae R6 strain could be selected containing pbpX genes from either S. mitis NCTC 10712 or S. oralis M3, demonstrating that genetic exchange can already occur between beta-lactam-sensitive species. These data are in agreement with the assumption that PBPs as penicillin-resistance determinants have evolved by the accumulation of point mutations in genes of sensitive commensal species.

Amino Acid Sequence↗

Right ventricular end-systolic pressure-volume relation during propofol infusion.

The effects of propofol on right ventricular function were studied in 11 ICU patients who needed sedation for acute respiratory failure or neurological diseases. Right ventricular function was studied using a thermodilution method at patients' bedside. Right ventricular ejection fraction (RVEF), cardiac output (CO), right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), right ventricular end-systolic pressure (RVESP) and pulmonary capillary wedge pressure (PCWP) were obtained from a modified Swan-Ganz catheter. Calculation of right ventricular end-systolic pressure-volume relation (ESPVR) allowed to assess changes in right ventricular inotropic state. A baseline ESPVR was obtained before propofol infusion: RVESP = 0.21 RVESV + 2.4, r = 0.83, P < 0.0001. Then, patients were given an induction dose of 1 to 2.5 mg.kg-1 propofol over 1 min followed by a continuous infusion of 3 mg.kg-1.h-1. During propofol infusion heart rate, mean arterial pressure, PCWP, CO, systemic vascular resistance and RVEF significantly decreased. No change in RVEDV and RVESV was observed. ESPVR was significantly altered with a dramatic decrease in the slope of the relation: RVESP = 0.12 RVESV + 6.9 (P < 0.001 from baseline). Dobutamine was used in five patients with clinically significantly cardiac dysfunction and restored the slope of the ESPVR to the baseline value: RVESP = 0.22 RVESV + 6.3 (NS from baseline). In the study patients, propofol altered the inotropic state of the right ventricle.

Anesthesia, Intravenous↗

Penetration of vancomycin into mediastinal and cardiac tissues in humans.

Vancomycin penetration into heart tissues (valves, myocardium, auricles, and pericardium) and mediastinal tissues (fat and sternal bone) was evaluated after two regimens of vancomycin administration. Ten patients were given 15 mg of vancomycin per kg of body weight before anesthesia. Ten other patients received the same dose and then a second 7.5-mg/kg dose at the time of initiation of cardiopulmonary bypass. Similar and satisfactory vancomycin tissue penetrations were observed in both groups. However, for some patients in the two groups, vancomycin levels in tissue were less than the MICs for potential pathogens (Staphylococcus aureus and Staphylococcus epidermidis).

Adipose Tissue↗