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Biomedical subjects

E Martin

Publications and source records attributed to E Martin.

At least 19 recordsLinked to original sources
PubMed1992

Genetic dissection of the transcription cycle. A mutant RNA polymerase that cannot hold onto a promoter.

Deletion of 10 amino acids from a conserved motif in the beta subunit of Escherichia coli RNA polymerase (RNAP) leads to an interrupted transcription cycle and lethal phenotype. RNAP carrying the mutant subunit retains catalytic function and specificity of promoter recognition but is unable to efficiently hold onto DNA in the binary complex, resulting in a diminished initiation frequency. However, inefficient initiation by the mutant enzyme leads to processive and stable ternary elongating complex. Thus, the mutation dissects the traits of promoter selectivity, binary complex stability, and ternary complex processivity reflecting compartmentalization of function within the RNAP molecule.

Amino Acid Sequence↗
PubMed1992

Human recombinant soluble decay accelerating factor inhibits complement activation in vitro and in vivo.

Complement plays a role in activating the inflammatory response and has been implicated in the pathogenesis of some inflammatory diseases. With a view toward controlling unwanted C activation, we evaluated the C regulator, human decay accelerating factor (DAF). Three forms of recombinant DAF were purified from transfected Chinese hamster ovary cells: glycophosphatidylinositol (GPI)-linked membrane DAF (mDAF) extracted from cell membranes; spontaneously shed soluble DAF (sDAF) derived from mDAF; and a novel secreted protein (seDAF), generated by deletion of the signal for GPI attachment. We show that all three molecules inhibit both the classical and alternative pathways of C activation. The following observations indicate that mDAF extracted from Chinese hamster ovary cells reincorporates into RBC membranes via its GPI anchor: 1) cells that are preincubated with mDAF and then washed remain fully protected from C-mediated hemolysis; 2) incubation with phosphatidylinositol-specific phospholipase C abolishes this protection; and 3) sDAF and seDAF, which lack a GPI anchor, do not associate with cell membranes. mDAF is a more potent inhibitor of C-mediated hemolysis than either sDAF or seDAF, suggesting that incorporation into cell membranes greatly enhances the efficiency with which DAF inhibits C activation on the cell surface. In contrast, C activation in the fluid phase is inhibited by sDAF and seDAF, but not by mDAF, possibly due to interference by serum lipoproteins. A reversed passive Arthus reaction in guinea pigs was used to evaluate the ability of recombinant seDAF to inhibit C activation in vivo. When administered at dermal sites, seDAF reduced the severity of immune complex-mediated inflammatory reactions induced by a reversed passive Arthus reaction, as judged by both gross and histologic examination. These data indicate that seDAF may be useful as an anti-inflammatory therapeutic.

Animals↗
PubMed1992

[Elderly patients--perioperative management from the viewpoint of the anesthetist].

FUNDAMENTAL CONSIDERATIONS: The number of elderly people undergoing surgery has increased considerably over the last decades. At the same time, there has been a shift from more minor to major procedures. RANGE OF TOPICS: More intensive diagnostic evaluation (e.g. right heart catheter) during the preoperative phase is required to identify patients with an increased risk. Also in the postoperative phase, mortality can be reduced through intensive and more prolonged monitoring (e.g. Holter monitoring) and appropriate treatment. In the field of anesthesiology, age (greater than 70 years) is a risk factor in its own right, that is, apart from the concomitant diseases seen in the elderly patient. CONCLUSIONS: The elderly patient requires more intensive diagnostic evaluation and care both pre- and postoperatively.

Aged↗
PubMed1992

Flow cytometric assay for estimating fungicidal activity of amphotericin B in human serum.

We describe a simple and rapid bioassay for estimating fungicidal activity of Amphotericin B in human serum using flow cytometry. The method exploits the fact that Candida albicans damaged by Amphotericin B show a decrease in size and take up propidium iodide to exhibit a red fluorescence after deoxycholate treatment. These phenomena display characteristic dose dependencies, and their assessment permits serum fungicidal activity to be broadly grouped into three categories: (1) subfungicidal; (2) fungicidal; and (3) strongly fungicidal. In normal human serum, these three categories correspond to Amphotericin B concentrations of 0 less than or equal to 0.5 micrograms/ml, 0.75-1.5 micrograms/ml, and greater than 2 micrograms/ml, respectively. Pilot analysis of serum samples obtained from four patients undergoing Amphotericin B therapy confirmed the feasibility of using the flow cytometric assay for estimating drug fungicidal activity ex vivo. The method is very simple, generates results within 5 h, and could prove useful for monitoring therapy with this effective but toxic drug.

Amphotericin B↗
PubMed1992

Cortical visual impairment following bacterial meningitis: magnetic resonance imaging and visual evoked potentials findings in two cases.

Cortical visual impairment (CVI) following bacterial meningitis is a very uncommon complication. Two children with CVI following bacterial meningitis are reported. Bacterial agents were Haemophilus influenzae type B in one and meningococci in the other child. Both children showed only insufficient recovery from CVI, mental retardation and residual neurological symptoms. Flash visual evoked potentials (VEP) showed preserved cortical response at onset of CVI. Re-evaluations several months later showed significantly reduced amplitudes, but normal latencies for P100. Thus, flash VEP does not allow prediction of visual outcome. MRI results have not been reported before. MRI at onset of diagnosis showed occipital parenchymal irregularities with enlarged sulci and subarachnoid spaces. Follow up MRI 15 months after onset of CVI in one patient showed marked atrophy of the occipital cortex, hyperintensities of the cortical white matter and no visible optic radiation. The MRI findings indicate hypoxic-ischaemic lesions in the border zone between the distribution of the great cerebral arteries.

Blindness↗
PubMed1992

Antiestrogenic action of 2,3,7,8-tetrachlorodibenzo-p-dioxin: tissue-specific regulation of estrogen receptor in CD1 mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a polychlorinated aromatic hydrocarbon with teratogenic and carcinogenic properties. Previous studies in our and other laboratories have demonstrated that TCDD has antiestrogenic properties. In order to elucidate the mechanism of action of TCDD on estrogen sensitive tissues, we studied its effects on serum estradiol and estrogen receptor (ER) levels in liver and uteri of CD1 mice. Treatment with TCDD did not result in alterations of serum estradiol levels at any of the doses tested (1.0-30 micrograms/kg). In contrast, TCDD treatment induced a dose-dependent decrease in hepatic and uterine ER protein as determined by an enzyme immunoassay and equilibrium binding assays. A decrease in cytosolic and nuclear ER levels in uteri occurred as early as 24 hr after initial treatment with 30 micrograms/kg TCDD and recovery occurred by 14 days. Hepatic cytosolic and nuclear ER also decreased at a dose of 30 micrograms/kg TCDD at 24 hr after treatment, but recovery occurred only by 21 days. Studies in ovariectomized mice indicate that the regulation of hepatic ER by TCDD is independent of ovarian factors, but ovariectomy inhibited the downregulation of uterine ER by TCDD. Furthermore, determination of TCDD-induced cytochrome P-450 levels indicates that the downregulation of uterine ER is uncoupled from induction of hepatic cytochrome P-450. This study indicates that the antiestrogenic effects of low doses of TCDD are mediated through its ability to decrease hepatic and uterine ER and are not due to alterations in serum estradiol levels. Our results on ovariectomized mice indicate that TCDD-induced downregulation of ER is tissue specific and may involve different mechanisms at transcriptional or posttranscriptional levels.

Animals↗
PubMed1992

Myelination of the optic radiation in Leber congenital amaurosis.

We have studied the myelination of the visual pathway by magnetic resonance imaging in seven children (aged 5 months to 16 years) with Leber congenital amaurosis. The corpus geniculatum laterale and the retrogeniculate optic radiation had a normal appearance on MRI in all patients. Therefore we conclude that normal myelination of the optic radiation, as it can be grossly assessed by MRI, can take place even with absent or greatly reduced visual sensory input.

Adolescent↗
PubMed1992

[Anesthesia and acute hepatic porphyrias].

Acute hepatic porphyrias are inherited disorders of heme biosynthesis. A characteristic feature of acute porphyrias is the occurrence of acute attacks which are often precipitated by drugs. Many of the commonly used anaesthetic agents may trigger such a potentially lethal attack. Thus, only safe agents should be administered to predisposed patients. Recommendations given are based on results from animal experiments and on a series of anecdotal reports. Regional anaesthesia is presented as anaesthetic technique of choice. General anaesthesia should be based on a fentanyl-nitrous oxide regimen, with propofol as induction agent. In the case of an acute attack, treatment consists of glucose and haematin administration.

Anesthetics↗
PubMed1992

[Diagnostic imaging of the brain of blind and visually handicapped young children].

In infants with delayed or absent visual maturation a neuroradiological investigation of the brain is commonly performed in addition to neurophysiological examinations. We report our preliminary experience with magnetic resonance imaging (MRI). MRI allows a detailed anatomical assessment and an evaluation of the myelination, including the optic radiation. Following severe perinatal hypoxic-ischemic injury periventricular leukomalacia in the parieto-occipital region was a common finding. The findings in infants with or without ocular abnormalities were heterogeneous, including normal findings, nonspecific delays of cerebral myelination as well as several malformations (such as corpus callosum hypoplasia, Aicardi syndrome, septo-optic dysplasia, migration disorders). In the individual case the neuroradiological findings do not allow to draw conclusions to the visual function and prognosis. In children with Leber congenital retinal amaurosis we have observed a normal myelination of the optic radiation. In many cases, particularly if a syndromic diagnosis is reached, neuro-imaging gives useful information for prognostic and genetic counselling.

Blindness↗
PubMed1992

Biochemical characterization of recombinant human nerve growth factor.

Recombinant human nerve growth factor (rhNGF) was expressed and secreted by Chinese hamster ovary cells and purified to homogeneity using ion-exchange and reversed-phase (RP) chromatography. The isolated product was shown to be consistent with a 120-amino-acid residue polypeptide chain by amino acid composition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), RP-HPLC, and mass spectrometry and with an N-terminal sequence consistent with that expected from the cDNA for human nerve growth factor. By size-exclusion chromatography, rhNGF behaves like a noncovalent dimer. Limited enzymatic digests of the 120-residue monomer produced additional species of 118 (trypsin, removal of the C-terminal Arg119-Ala120 sequence) and 117 (trypsin plus carboxypeptidase B, removal of the C-terminal Arg118-Arg119-Ala120 sequence) residues. Each of these species was isolated by high-performance ion-exchange chromatography and characterized by amino acid and N-terminal sequence analyses, SDS-PAGE, RP-HPLC, and mass spectrometry. All three species were present in the digests as both homodimeric and heterodimeric combinations and found to be equipotent in both the chick dorsal root ganglion cell survival and rat pheochromocytoma neurite extension assays.

Amino Acid Sequence↗
PubMed1992

Flow cytometric assay for quantifying opsonophagocytosis and killing of Staphylococcus aureus by peripheral blood leukocytes.

We describe a novel flow cytometric method for quantifying opsonophagocytosis and killing of Staphylococcus aureus in cell-rich plasma obtained after dextran sedimentation of erythrocytes. To analyze opsonophagocytosis, phagocytes were labeled with a phycoerythrin-conjugated monoclonal antibody and were incubated with viable staphylococci containing carboxyfluorescein as a vital fluorescent dye. Phagocytosing cells assumed a dual, orange-green fluorescence. The relative numbers of bacteria associating with phagocytes could be determined by quantifying the decrease of free green fluorescent particles. A parallel incubation of fluorescent bacteria with unlabeled cell-rich plasma was performed to assess phagocytic killing. Blood cells were lysed with 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propanesulfonate. This detergent spared viable bacteria, and residual green fluorescent particles were counted. The decrease in the number of these particles relative to the controls yielded the degree of killing. At bacteria-to-phagocyte ratios of 1:1 and 10:1, approximately 36 and 75% of the phagocytes participated in opsonophagocytosis, respectively. Over 90% of the staphylococci were phagocyte associated after 30 to 60 min. Killing rates were on the order of 66% +/- 12% and 80% +/- 7% after 1 and 2 h of incubation, respectively. These numbers, which were confirmed by colony countings, were significantly lower than those reported in the majority of past reports.

Antibodies, Monoclonal↗
PubMed1992

Telepathology: a new tool of pathology? Presentation of a French national network.

The field of pathology is constantly growing and the responsibility of the pathologists has progressively increased in the decision of application of some efficient but aggressive therapies. They justify the increasing necessity of discussion between pathologists about the diagnoses of difficult or rare or severe lesions. It is now possible to discuss at distance on good definition digitized images transmitted through I.S.D.N. A French experimental network between 12 workstations has been introduced since 2 years. Difficult or severe diagnoses have been immediately solved in 85% of the discussed cases. It remain legal problems and the necessity of an evaluation protocol which could be discussed at a European level. The increase of technical progress and, above all, the decrease of the costs might favour the development of telepathology. The workstation of the pathologist in the year 2000 could be the combination of a microscope, a HD-TV-camera and a personal computer with many softwares allowing treatment and transmission of numerous pictures.

Equipment Design↗
PubMed1992

[Quantification of nucleolar organizers (NORs) in renal carcinomas. Comparison with the nuclear grade].

Twenty three renal tumours: 6 clear cell carcinomas, 3 granular cell carcinomas, 8 mixed cell carcinomas, 3 tubulopapillary tumours, 2 spindle cell carcinomas and 1 oncocytoma, were retrospectively submitted to a staining technique which reveals argyrophilic proteins related to Nucleolar Organizer Regions (NORs). The semiautomated quantification of the number and mean surface area of the argyrophilic granules was performed by means of a quantimeter. The results were compared to the nuclear grade, which constitutes the reference histological prognostic factor. A very good correlation was observed between NORs and nuclear grade. The mean number of argyrophilic granules per nucleus (n) and more particularly their surface area (s) were very significantly increased in high-grade carcinomas (n = 1.96), s = 3.72) in comparison with low-grade carcinomas (n = 1.50, s = 1.35). Quantification of NORs therefore allowed objective differentiation between a low nuclear grade and a high nuclear grade. The quantification method used emphasised the value of not only measuring the number but also the surface area of the argyrophilic granules.

Cell Nucleus↗
PubMed1992

Genomic organization of the human c-kit gene: evolution of the receptor tyrosine kinase subclass III.

The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor. It belongs to receptor tyrosine kinase subclass III, which also includes the colony-stimulating factor I receptor (c-fms), platelet-derived growth factor receptors A and B (PDGFRA and PDGFRB), as well as FLT1 and FLT3/FLK2. c-kit and PDGFRA, c-fms and PDGFRB, FLT1 and FLT3/FLK2 are grouped by pair in three clusters in man on chromosome 4 band q11-q13, chromosome 5 band q31-q33 and chromosome 13 band q12 respectively. Here, we report the genomic organization of the human c-kit gene, which is composed of 21 small coding exons, distributed over 80 kb. Comparison of the c-kit and c-fms oncogenes shows that they share identified exon/intron boundaries in their two kinase domains, as well as a similar exon/intron organization in the extracytoplasmic domain. Comparison with the kinase domains of tyrosine kinase genes not belonging to subclass III suggests that the exon/intron organization of c-kit and c-fms is a characteristic feature of subclass III. The genomic similarities between c-kit and c-fms, in conjunction with the location in pairs on different chromosomes of the subclass III genes, has led us to hypothesize that cis and trans duplications gave rise to this group of genes.

Amino Acid Sequence↗
PubMed1992

Musculoskeletal trauma: the baseball bat.

Between July 1987 and December 1990 in Washington, DC, 116 patients sustained 146 fractures and seven dislocations due to an assault with a baseball bat. The ulna was the most common site of trauma (61 fractures), followed by the hand (27 injuries) and the radius (14 injuries). Forty-two of the 146 fractures were significantly displaced and required open reduction and internal fixation to restore satisfactory alignment. Twenty-nine of the 146 fractures were open fractures. Treatment protocol for open fractures consisted of irrigation and debridement, antibiotic therapy, and bone stabilization with either internal or external fixation, or casting. Recognition of the severity of the soft tissue and bone damage is important in the management of musculoskeletal trauma secondary to the baseball bat.

Adolescent↗