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Biomedical subjects

M David

Publications and source records attributed to M David.

At least 289 records · Page 16Linked to original sources

Hypertonic saline treatment of hemorrhagic shock in awake rats.

Hypertonic saline solution (HTS) treatment of uncontrolled hemorrhagic shock (UCHS) in anesthetized animals leads to increased bleeding, fall in mean arterial pressure (MAP), and increased mortality. To rule out the effect of anesthetic drugs on this response, HTS infusion in UCHS was studied in awake rats. 24 h prior to the experiment, the animals were cannulated under neurolidal-ketalar anesthesia and two major branches of the ileo-colic artery were encircled with a silk suture. On the next day the awake animals were randomly divided into two groups: in group 1 (n = 16) controlled hemorrhagic shock (CHS) was induced by arterial bleeding of 20 mL/kg; in group 2 (n = 16) UCHS was induced by transcutaneous tear of two branches of the ileo-colic artery. The animals in each group were then divided into two subgroups: group A was untreated and group B was treated with 5 mL/kg 7.5% NaCl (HTS) after 10 min. Arterial bleeding in group 1A was followed by a fall in MAP to 63 +/- 2 mmHg (p < .001), and the hematocrit decreased to 37 +/- 3% (p < .01) in 10 min. Injury to two branches of the ileo-coli artery was followed by intra-abdominal bleeding, fall in MAP to 87 +/- 6 mmHg (p < .01), and a decrease in hematocrit to 32 +/- 2% (p < .01) in 10 min. Infusion of HTS in group 1B was followed by an increase in MAP to 84 +/- 4 mmHg (p < .01) and a fall in hematocrit to 22 +/- 2% (p < .01) after 60 min, while in the untreated group 1A, the MAP was 65 +/- 4 mmHg (p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Localization of the gene for Darier disease to a 5-cM interval on chromosome 12q.

Darier disease is an autosomal dominant abnormality of epidermal differentiation characterized clinically by the presence of hyperkeratotic papules on the skin and histologically by the loss of cell cohesion and by disorderly keratinization. Two groups recently found evidence that the gene whose mutations underlie this disease is located at chromosome 12q23-q24.1, a site on chromosome 12 that clearly is distal to the type II keratin gene cluster. We report here evidence for sublocalization to a 5-cM region of that site in an additional ten families of European and Middle Eastern ancestry with a combined lod score in excess of 20.

Adult↗

Study of final height in Turner's syndrome: ethnic and genetic influences.

In understanding Turner's syndrome, spontaneous adult height is a prerequisite for an accurate assessment of the therapeutic efficiency of growth hormone treatment. The heights described in the literature reveal significant differences (136-147 cm). Our collaborative study pooled results from 16 pediatric endocrinology centers and obtained a large number of spontaneous adult heights (n = 216). The selective criteria were: chronological age (CA) > 18 years, bone age (BA) > 16 years, typical karyotype, no treatment with growth hormone or anabolic steroids. Mean CA was 23.3 +/- 5.6 years. Chromosomal anomalies were: monosomy X 56%; mosaicism 37.2%; structural aberration 10.6%. Mean final height in the whole group was 141.5 (129-160) cm. There was no significant difference in height between the three groups: monosomy X (n = 121: 141.1 +/- 6.4 cm); mosaicism (n = 72: 141.5 +/- 7.5 cm); X anomaly (n = 23: 141.4 +/- 5.0 cm). Mean parental height was 170.4 +/- 7.1 cm (father) and 160.1 +/- 6.2 cm (mother). Parental height and patients' heights correlated significantly, but more so with fathers' heights (r = 0.50) than with mothers' (r = 0.42). The correlation was still apparent with the target height (r = 0.55). The results of different series in the literature show the existence of significant variations as mean final heights are between 136 and 147 cm. These differences can be explained by the variations in normal female heights in each country. We have found in these different countries a very strong correlation (r = 0.91) between normal height and final height in Turner's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

FixL of Rhizobium meliloti enhances the transcriptional activity of a mutant FixJD54N protein by phosphorylation of an alternate residue.

In Rhizobium meliloti, transcription of nitrogen fixation genes is induced in oxygen-depleted conditions under the control of the two-component regulatory system FixLJ. FixJ is a transcriptional activator whose activity is dramatically enhanced by phosphorylation, whereas FixL is a hemoprotein kinase that controls the level of phosphorylated FixJ in response to oxygen availability. We have found that a mutant FixJ protein, FixJD54N, in which the presumed site of phosphorylation (aspartate 54) was changed to an asparagine, is strongly affected for phosphorylation by FixL and is not detectably phosphorylated from the low-molecular-weight phosphate donor, acetyl-phosphate. Unexpectedly, FixL strongly enhances the transcriptional activity of the FixJD54N protein both in vivo and in vitro. We present evidence that FixJD54N transcriptional activity is enhanced by phosphorylation of an alternate residue in a reaction that requires FixL and ATP and is not affected by oxygen. We also demonstrate the key role of Asp-54 of FixJ in oxygen signal transduction.

Bacterial Proteins↗

Human cancer cell lines express a negative transcriptional regulator of the interferon regulatory factor family of DNA binding proteins.

Members of the interferon regulatory factor (IRF) family of DNA binding transcription factors have roles in growth regulation, antiviral responses, and transcriptional induction of interferon (IFN)-activated early response genes. The IRF family member ISGF3 gamma is the DNA binding component of IFN-stimulated gene factor 3 (ISGF3), a multicomponent complex responsible for the stimulation of IFN-alpha-responsive genes. IFN-alpha-stimulated formation of ISGF3 and subsequent gene expression can be inhibited by phorbol esters or expression of the adenovirus E1A protein. We have investigated IFN signaling in human malignant tumor cell lines of the lung, colon, ovary, cervix, and hematopoietic organs and found some of these cells to be defective for IFN-alpha-induced formation of ISGF3. In many cases, an inhibitory activity termed transcriptional knockout (TKO) correlated with nonresponsiveness. TKO purified from a human papillomavirus-negative cervical carcinoma cell line has a molecular size of 19 kDa. The purified protein interacted with the ISGF3 gamma component of ISGF3, preventing binding of ISGF3 to DNA. Purified TKO displaced ISGF3 from its DNA binding site in vitro and prevented ISGF3 gamma, IRF-1, and IRF-2 from interacting with the IFN-stimulated response element. Partially purified TKO can also directly interact with ISGF3 gamma in the absence of DNA. This protein may be involved with the development of malignancies and the inability of IFN to exert its antiproliferative and antiviral effects.

Base Sequence↗

Growth hormone and erythropoietin differentially activate DNA-binding proteins by tyrosine phosphorylation.

Binding of growth hormone (GH) and erythropoietin (EPO) to their respective receptors results in receptor clustering and activation of tyrosine kinases that initiate a cascade of events resulting not only in the rapid tyrosine phosphorylation of several proteins but also in the induction of early-response genes. In this report, we show that GH and EPO induce the tyrosine phosphorylation of cellular proteins with molecular masses of 93 kDa and of 91 and 84 kDa, respectively, and that these proteins form DNA-binding complexes which recognize an enhancer that has features in common with several rapidly induced genes such as c-fos. Assembly of the protein complexes required tyrosine phosphorylation, which occurred within minutes after addition of ligand. The activated complexes translocated from the cytoplasm to the nucleus. The protein activated by GH is antigenically similar to p91, a protein common to several transcription complexes that are activated by interferons and other cytokines. In contrast, the proteins activated by EPO are distinct from p91. These findings establish the outlines for a cytokine-induced intracellular signaling pathway, which begins with ligand-induced receptor clustering that activates one or more tyrosine kinases. These data are the first to demonstrate that GH- and EPO-activated tyrosine-phosphorylated proteins can specifically recognize a well-defined enhancer and therefore provide a mechanism for rapidly transducing signals from the membrane to the nucleus.

Base Sequence↗

Toxic effects of systemic retinoids on meibomian glands.

Systemic use of retinoids is common in the treatment of various dermatological disorders. Blepharitis and conjunctivitis have been reported in 20-45% of the patients following systemic treatment with 13-cis-retinoic acid. Our purpose was to study the histopathological changes in the eyelids caused by long-term systemic treatment of female New Zealand rabbits with isotretinoin (2 mg/kg) and etretinate (2 mg/kg). The histopathological evaluation showed degenerative changes in the meibomian gland acini, leading to cell necrosis and a decrease in the basaloid cells lining the acini walls. No evidence of acute or chronic inflammatory reaction was noted.

Administration, Oral↗

[A pioneer in surgical gynecology. On the 55th anniversary of the death of Paul Ferdinand Strassmann (23 October 1866 to 15 August 1938)].

This year (1993) we want to commemorate the 55th anniversary of the death of the Berlin gynecologist Prof. Paul Ferdinand Strassmann. In the first half of the 20th century, Strassmann was one of the leading specialists of plastic surgery of the female genital tract. Famous gynecologists and surgeons, e.g. the Mayo brothers, visited the Strassmann clinic in the Schumannstrasse with the aim of learn new surgical techniques. The present paper aims to outline particularly the life of Paul F. Strassmann but also his importance in the creation of modern gynecological surgery.

Germany↗

Origins of hyperphenylalaninemia in Israel.

Mutations and polymorphisms at the phenylalanine hydroxylase (PAH) gene were used to study the genetic diversity of the Jewish and Palestinian Arab populations in Israel. PAH mutations are responsible for a large variety of hyperphenylalaninemias (HPAs), ranging from the autosomal recessive disease phenylketonuria to various degrees of nonclinical HPA. Seventy-two Jewish and 36 Palestinian Arab families with various HPAs, containing 115 affected genotypes, were studied by haplotype analysis, screening for previously known PAH lesions and a search for novel mutations. Forty-one PAH haplotypes were observed in this sample. Four mutations previously identified in Europe (IVS10nt546, R261Q, R408W and R158Q) were found, and were associated with the same haplotypes as in Europe, indicating possible gene flow from European populations into the Jewish and Palestinian gene pools. Of particular interest is a PAH allele with the IVS10nt546 mutation and haplotype 6, that might have originated in Italy more than 3,000 years ago and spread during the expansion of the Roman Empire. These results, together with previous identification of three PAH mutations unique to Palestinian Arabs [IVSnt2, Edel(197-205) and R270S], indicate that the relatively high genetic diversity of the Jewish and Palestinian populations reflects, in addition to genetic events unique to these communities, some gene flow from neighboring and conquering populations.

Amino Acid Metabolism, Inborn Errors↗

Heparin therapy in pediatric patients: a prospective cohort study.

Current guidelines for heparin therapy in pediatric patients have been extrapolated from trials in adult patients without rigorous evaluation of efficacy and safety. We prospectively monitored consecutive pediatric patients receiving systemic doses of heparin over 10 mo at one institution using a predetermined nomogram to monitor maintenance therapy. Sixty-five consecutive children; 38 males and 27 females, received systemic doses of heparin. Thirty children had deep venous thrombosis and/or pulmonary embolism; 11 had arterial thrombi, most frequently after diagnostic angiography; and the remaining 24 received heparin prophylactically, for congenital heart disease. Twenty-nine (45%) of the 65 patients were less than 1 y of age and 22 (34%) were 10 y or older. Congenital heart disease was the predominant diagnosis under 1 y and deep venous thrombosis in older children. After a bolus dose of 50 U/kg, 39% of children (n = 30) achieved a minimal level activated partial thromboplastin time (APTT). Sixty-eight percent of children achieved a minimal level APTT by 24 h and 81% by 48 h. For all 65 children, APTT values were within the therapeutic range 43% of the time. APTT values outside the therapeutic range were twice as likely to be low as high. The average amount of heparin required to maintain therapeutic APTT values for children was 22 U/kg/h: 28 U/kg/h for infants < 1 y and 20 U/kg/h for the rest. Bleeding was rare (2%) and mild. Documented recurrent thrombotic disease was more common (7%) with associated morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Angiosarcoma of the pericardium. Apropos of a case].

Malignant primary cardio-pericardial tumours are rare and difficult to diagnose because of the diversity of their clinical expression. The authors report a case of pericardial angiosarcoma and review the literature, underlining the value of new non-invasive imaging techniques in the diagnosis and surgical approach to obtaining histological confirmation. Magnetic resonance imaging is a valuable tool in this context as it allows scanning of the tumoral extension in all spatial planes and the visualisation of the haemorrhagic signs of malignancy the pericardial effusion related to this pathology.

Heart Neoplasms↗

Seborrheic keratoses of the areola.

A patient noted the appearance of a few asymptomatic lesions on both areolae eighteen months after delivery of her last son. Histologic examination showed typical seborrheic keratosis. A brief review of the differential diagnosis of skin problems of the nipple and the areola is provided.

Adult↗