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Biomedical subjects

A Meyer

Publications and source records attributed to A Meyer.

At least 289 records · Page 16Linked to original sources

Mutations in p53 produce a common conformational effect that can be detected with a panel of monoclonal antibodies directed toward the central part of the p53 protein.

Human p53 displays two immunodominant regions localized in the amino and carboxy termini of the protein. Using a truncated p53 (residues 66 to 361), we selected eight new monoclonal antibodies directed to the central part of the protein. We identified the epitopes recognized by seven out of eight antibodies with a set of overlapping peptides. One of these antibodies had an epitope similar to PAb240, whereas the others recognized novel and diverse antigenic determinants. Using a series of 19 p53 mutants, we show that the behavior of several of the new monoclonal antibodies is similar to that of PAb240 despite their various epitope localizations. This suggests that different mutations in the p53 protein induce an overall conformational change that can be detected by various monoclonal antibodies directed toward the central part of the protein.

Amino Acid Sequence↗

[Primary leiomyosarcoma of the femoral vein. Therapeutic aspects].

Leiomyosarcomas are exceptional in peripheral veins. Clinical signs are not specific, secondary to effects of the tumoural mass. Computed tomography and MRI give a precise topographic diagnosis. Pathology examination on biopsy or surgical specimens establishes the histological diagnosis. Therapeutic management must take into account local tumour recurrence and metastasis. Surgical exeresis should be wider than the tumour's pseudocapsule to include micrometastases neighbouring the primary tumour. Post-operative radiotherapy (55 to 70 Gy) and chemotherapy should follow. With this management scheme, local disease is controlled in 85% of the cases with a 5-year follow-up. Local or metastatic extension usually occurs within the first 3 years. Management of venous sarcomas thus requires a multidisciplinary cooperation between the surgeon, the radiotherapists and the chemotherapist.

Adult↗

[Linkage between juvenile glaucoma and chromosome 1q in 2 French families].

Primary open-angle glaucoma is a major cause of irreversible blindness in Western countries for which there is presently no curative treatment. Linkage of hereditary juvenile glaucoma with chromosome 1q21-q23 was recently described in 2 American families. Here we have studied two large French pedigrees with a similar form of familial autosomal dominant juvenile-onset glaucoma. Linkage of glaucoma with chromosome 1 was confirmed in these 2 families. Maximal lod-score of 7.60 was reached at the D1S212 marker for a recombination fraction of 4.4%. The typing of this marker should facilitate the screening of glaucoma families and the identification of individuals at risk for the disease. It will also provide a reference to evaluate the genetic heterogeneity of glaucoma.

Adolescent↗

Wilson's disease. Psychiatric manifestations may be the clinical presentation.

It is important to consider Wilson's disease in patients with psychiatric signs and symptoms who also have abnormal liver function test results or neurologic findings, or both. Thorough evaluation of emotionally disturbed persons, including complete history taking, careful physical examination, and appropriate laboratory profile, generally rules out or arouses suspicion of Wilson's disease during routine screening. Laboratory abnormalities necessitate repeated studies and additional family and personal history taking with emphasis on possible Wilson's disease. Further workup may then be indicated. Prompt recognition and vigorous, consistent treatment can minimize symptoms and tissue damage. Identifying a case of Wilson's disease and seeing clinical aspects improve with appropriate therapy is gratifying.

Clonazepam↗

The evolution of copulatory organs, internal fertilization, placentae and viviparity in killifishes (Cyprinodontiformes) inferred from a DNA phylogeny of the tyrosine kinase gene X-src.

Cyprinodontiforms are a diverse group of approximately 900 pantropical and temperate fishes, mostly found in freshwater. Whereas the vast majority of fishes lay eggs (i.e. are oviparous), this group is unusual in that four groups of cyprinodont fishes give birth to living young (i.e. are viviparous). A molecular phylogenetic hypothesis was based on partial DNA sequences of the tyrosine kinase gene X-src. The study included the major lineages of fishes of the suborder Cyprinodontoidei, order Cyprinodontiformes. Our phylogeny agrees with some but not all of the conclusions of a previous morphological cladistic analysis (Parenti (Bull. Am. Mus. nat. Hist. 168, 335 (1981)). The differences are: (i) the Profundulidae are the sister group to the Goodeidae, not the sister group to all other cyprinodontoids; (ii) Fundulidae are the sister group to the Profundulidae and Goodeidae; (iii) Cubanichthys and the Cyprinodontinae might not be sister taxa; (iv) Cubanichthys, and not the Profundulidae, might be the most basal member of the cyprinodontoids; and (v) the Anablepinae and Poeciliinae might be sister groups. The molecular phylogeny was used to reconstruct the evolution of major life-history traits such as internal fertilization, copulatory organs, livebearing and placentas. Internal fertilization, modifications of the male's anal fin to form a copulatory organ, and viviparity probably evolved independently three times in cyprinodontiform fishes: in the subfamilies Goodeinae, Anablepinae and Poeciliinae (sensu Parenti 1981). The evolution of bundled sperm, spermatozeugmata, is probably not a prerequisite for internal fertilization because at least one species with internal fertilization has free spermatozoa. Livebearing (viviparity), which takes the form of ovoviviparity (where embryos are nourished by their yolk sac only), evolved only in the subfamily Poeciliinae. Advanced forms of viviparity, in which the mother provides additional nourishment to the embryos through placenta-like structures, apparently evolved at least three times from egg-laying ancestors: in the subfamilies Goodeinae, Anablepinae, and more than once in the Poeciliinae.

Animals↗

Mitochondrial cytochrome b: evolution and structure of the protein.

Cytochrome b is the central redox catalytic subunit of the quinol: cytochrome c or plastocyanin oxidoreductases. It is involved in the binding of the quinone substrate and it is responsible for the transmembrane electron transfer by which redox energy is converted into a protonmotive force. Cytochrome b also contains the sites to which various inhibitors and quinone antagonists bind and, consequently, inhibit the oxidoreductase. Ten partial primary sequences of cytochrome b are presented here and they are compared with sequence data from over 800 species for a detailed analysis of the natural variation in the protein. This sequence information has been used to predict some aspects of the structure of the protein, in particular the folding of the transmembrane helices and the location of the quinone- and heme-binding pockets. We have observed that inhibitor sensitivity varies greatly among species. The comparison of inhibition titrations in combination with the analysis of the primary structures has enabled us to identify amino acid residues in cytochrome b that may be involved in the binding of the inhibitors and, by extrapolation, quinone/quinol. The information on the quinone-binding sites obtained in this way is expected to be both complementary and supplementary to that which will be obtained in the future by mutagenesis and X-ray crystallography.

Amino Acid Sequence↗

The phylogenetic position of the zebrafish (Danio rerio), a model system in developmental biology: an invitation to the comparative method.

The zebrafish, Danio (Brachydanio) rerio, has become one of the most widely studied model systems in developmental biology. We present a DNA-based phylogeny of zebrafish and other species of the genus Danio, and the genera Rasbora, Puntius and Cyprinus. Homologous regions of the large (16S) mitochondrial ribosomal RNA gene were amplified by the polymerase chain reaction and directly sequenced. The phylogeny revealed: (i) the zebrafish, Danio (Brachydanio) rerio, is identical in its 16S sequence to its aquarium breeding morph, the leopard danio; (ii) the pearl danio (Danio albolineatus) is more closely related to the zebrafish than the giant danio (Danio aequipinnatus); and (iii) species of the genus Rasbora (hetermorpha, trilineata, elegans, pauciperforata, dorsiocellata) are more closely related to the danios than members of the genus Puntius (tetrazona, conchonius) and Cyprinus, the carp. All of these species are readily available in the aquarium trade, easily kept and bred in captivity, and amenable to developmental work. It is hoped that this molecular phylogeny will invite developmental biologists to use the comparative method to ask questions about function (e.g. cellular and genetic aspects) and evolution of zebrafish developmental biology in a phylogenetic context.

Animals↗

Revised phylogeny of whales suggested by mitochondrial ribosomal DNA sequences.

Living cetaceans are subdivided into two highly distinct suborders, Odontoceti (the echolocating toothed whales) and Mysticeti (the filter-feeding baleen whales), which are believed to have had a long independent history. Here we report the determination of DNA sequences from two mitochondrial ribosomal gene segments (930 base pairs per species) for 16 species of cetaceans, a perissodactyl and a sloth, and construct the first phylogeny for whales and dolphins based on explicit cladistic methods. Our data (and earlier published myoglobin sequences) confirmed that cetaceans are closely related to artiodactyls and that all families and superfamilies of cetaceans are monophyletic. A surprising finding was that one group of toothed whales, the sperm whales, is more closely related to the baleen whales than to other odontocetes. The common ancestor of baleen whales and sperm whales might have lived only 10-15 million years ago. The suggested paraphyly of toothed whales has many implications for classification, phylogeny and our understanding of the evolutionary history of cetaceans.

Animals↗

Culprit lesion morphology and stenosis severity in the prediction of reocclusion after coronary thrombolysis: angiographic results of the APRICOT study. Antithrombotics in the Prevention of Reocclusion in Coronary Thrombolysis.

OBJECTIVES: In the APRICOT study (Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis), we sought to determine whether angiographic characteristics of the culprit lesion could predict reocclusion after successful thrombolysis and to analyze the influence of three antithrombotic treatment regimens. BACKGROUND: After successful thrombolysis, reocclusion is a major problem. Prediction of reocclusion by angiographic data and choice of antithrombotic treatment would be important for clinical management. METHODS: After thrombolysis, patients were treated with intravenous heparin until initial angiography was performed within 48 h. Patients with a patent infarct-related artery were eligible. Three hundred patients were randomly selected for treatment with coumadin, aspirin (300 mg once daily) or placebo. Patency on a second angiographic study after 3 months was the primary end point of the study. RESULTS: Reocclusion rate was 25% with aspirin, 30% with coumadin and 32% with placebo (p = NS). Lesions with > 90% stenosis reoccluded more frequently (42%) than did those with < 90% stenosis (23%) (p < 0.01). Reocclusion rate of smooth lesions was higher (34%) than that of complex lesions (23%) (p < 0.05). In lesions with < 90% stenosis, the reocclusion rate was lower with aspirin (17%) than with coumadin (25%) or placebo (30%) (p < 0.01). In complex lesions, the reocclusion rate was lower with aspirin (14%) than with coumadin (32%) or placebo (25%) (p < 0.02). Multivariate analysis showed only stenosis severity > 90% to be an independent predictor of reocclusion (odds ratio 2.31, 95% confidence interval 1.28 to 4.18, p = 0.006). CONCLUSIONS: Angiographic features of the culprit lesion after successful coronary thrombolysis significantly predict the risk of reocclusion: high grade (> 90%) stenoses reoccluded more frequently. Aspirin was effective only in complex and less severe lesions (< 90% stenosis). These findings should prompt investigation of the effects of an aggressive approach to patients with severe residual stenosis.

Aspirin↗

Comparison of APACHE II, Trauma Score, and Injury Severity Score as predictors of outcome in critically injured trauma patients.

Trauma Score (TS), APACHE II score, and Injury Severity Score (ISS) have been utilized to quantitate severity of illness in various groups of patients. The purpose of this study was to compare the relationship of the APACHE II score, TS, and "computer-derived" ISS with outcome in critically injured trauma patients. Data were recorded prospectively in a computer database for 428 consecutive trauma admissions. Stepwise discriminate analysis was utilized to determine the best predictor of both intensive care unit (ICU) and hospital outcome. Forty-two patients died in the ICU (10%), and another 18 patients died after leaving the ICU (4%), for a total mortality rate of 14%. The mean p value and partial R2 value obtained from stepwise discriminant analysis of the relationships between APACHE II score, TS, and ISS to ICU and hospital survival are shown. APACHE II score was the best predictor of both ICU and hospital outcome in these critically ill trauma patients. However, when combining all three measures (APACHE II score, TS, and ISS), only a portion of the variance in outcome is explained by the scores (R2 < 0.05). We conclude that scoring systems for outcome prediction should be utilized only as an adjunct to clinical assessment in the evaluation of the severity of illness and mortality risk in critically ill trauma patients.

Female↗

Mitochondrial phylogeny of the endemic mouthbrooding lineages of cichlid fishes from Lake Tanganyika in eastern Africa.

Of the three cichlid species flocks in eastern Africa, Lake Tanganyika harbors the oldest species assemblage, which is also the most diverse morphologically and behaviorally. For 12 species (20 individuals) of 12 genera of the tribe Ectodini, 852 bp from two segments (cytochrome b and control region) of the mitochondrial genome were sequenced. In addition, orthologous sequences were obtained from eight species (11 individuals) representing other mouthbrooding lineages from Lake Tanganyika. Comparisons of sequence divergences revealed that the single Tanganyikan tribe Ectodini appears to be approximately five times older than the whole Lake Malawi cichlid species flock, suggesting that the radiation of the Tanganyikan mouthbrooding lineages took place long before the species flocks of Lakes Malawi and Victoria evolved. Seven of nine surveyed tribes of Tanganyikan cichlids appear to be approximately equally divergent, and this seems to corroborate the hypothesis of a rapid simultaneous formation of lineages at an early stage in the history of the Lake Tanganyika species flock. The close genetic relationship between the endemic Tropheus lineage and a nonendemic "Haplochromine," Astatotilapia burtoni, indicates that members of the tribe Tropheini may be the sister group of the cichlid flocks of Lakes Malawi and Victoria. The phylogenetic analyses demonstrate the monophyly of the Ectodini and identify the Cyprichromini as their sister group among the Tanganyikan cichlids. Within the tribe Ectodini the molecular data suggest both a branching pattern different than that previously proposed and a subdivision of the Ectodini into four clades, instead of the two originally described. The previously postulated model of morphological transformations believed to be responsible for the drastically different types of ecological specialization found among the Ectodini might therefore be in need of reinterpretation. Characters immediately related to foraging and nutrition seem to be particularly prone to homoplasy, even among members of a single lineage of cichlid fishes.

Africa, Eastern↗

An analysis of the association of trauma centers with per capita hospitalizations and death rates from injury.

OBJECTIVE: This study used population-based data bases to assess the association of trauma centers with per capita county hospitalization and trauma death rates in the State of North Carolina. SUMMARY BACKGROUND DATA: The current study extended previous work using two North Carolina data bases to assess the association of the presence of a trauma center with per capita county trauma death rates. METHODS: Data on per capita county trauma hospitalizations and deaths were obtained from the state hospital discharge data base and the North Carolina Medical Examiner's data base. Bivariate and multivariate analysis techniques were used. The dependent variables of interest were prehospital, hospital, and total trauma death rates and hospitalization rates for injury. RESULTS: Bivariate analysis identified a number of factors associated with per capita county hospitalizations and trauma death rates. These included the per cent unemployment, racial distribution, county alcohol tax receipts, and advanced life support certified emergency medical services providers. The per capita trauma death rates were significantly lower in counties with trauma centers compared with those without trauma centers (4.0 +/- 0.5 and 5.0 +/- 1.1 deaths per 10,000 population, p = 0.0001, respectively). The per capita hospitalizations for trauma were also lower in counties with trauma centers. Multivariate modeling showed that the presence of a trauma center and advanced life support providers were the best predictors of decreased per capita county trauma death rates. CONCLUSIONS: The study showed that the presence of a trauma center and advanced life support training were the two medical system factors that were the best predictors of the per capita county prehospital and total trauma death rates. These findings are consistent with the hypothesis that trauma centers are associated with a decrease in trauma death rates.

Adolescent↗

[Pancreatic hypernephroma manifested by a duodenal hemorrhage].

Clear cell carcinoma are known to be disseminated in 40% of cases once diagnosis is made. We describe a patient presenting with a proximal gastrointestinal hemorrhage four years after nephrectomy for a left renal carcinoma. Investigations showed a solitary pancreatic mass and we performed cephalic duodenopancreatectomy which confirmed the presence of metastasis of the clear cell carcinoma. Gastrointestinal hemorrhage in cancer patients generally suggests delayed metastatic dissemination. Pancreatic localization is present in nearly 20% of metastatic renal carcinomas but it is the only site in less than 1% of cases. Evidence of lymphatic spread of renal tumor is sustained by our report. Attitudes concerning the step-by-step process of metastasis, growth pattern of renal cancer and the role of surgery are discussed.

Aged↗

[A rare cause of hypercalcemia: familial hypocalciuric hypercalcemia].

BACKGROUND: Familial hypocalciuric hypercalcemia is a rare disease with autosomal dominant transmission. Its basic defect is unknown and it requires no treatment. CASE REPORT: A 4 month-old girl was admitted for unexplained crying. She was found to have hypercalcemia (2.8 mmol/l) and later values of blood calcium were 3, 3.1 and 3 mmol/l. The serum free ionic calcium level was also elevated. The serum concentrations of protein, phosphorus, magnesium and the alkaline phosphatase activity were all normal. Serum concentrations of 25-(OH)-D3, 1.25-(OH)-2-D3 and PTH were also normal. The urinary calcium/creatinine ratio was normal and the urinary calcium excretion was 1.08 mg/kg/d. Screening of family members showed hypercalcemia in the father (2.8 mmol/l) and a brother aged 7 years (2.9 mmol/l). Short-term treatment with disodium etidronate lowered the serum calcium level to normal, but hypercalcemia reappeared once the treatment was discontinued. CONCLUSIONS: This asymptomatic familial hypercalcemia has the characteristics of familial hypocalciuric hypercalcemia. There was no associated endocrine disorder. Screening of family members is worthwhile.

Calcium↗