[Latin-American collaborative study on congenital malformations].
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Adult↗
Biomedical subjects
E Harris
Publications and source records attributed to E Harris.
Arthroscopic distal clavicle excision. Technique and early results.
Since 1941, distal clavicle excision has been a reliable technique for alleviating pain caused by acromioclavicular joint arthritis. Disadvantages of the procedure include permanent shoulder weakness, a lengthy recovery time ranging from weeks to months before useful function of the extremity returns, and lack of cosmesis. By modifying the standard portals used to perform arthroscopic subacromial decompression, the authors have successfully excised the distal clavicle of ten consecutive patients. Using this arthroscopic technique, the surgical time averaged approximately one hour 40 minutes, blood loss was negligible, and there were no complications. Operations were performed in an outpatient setting. Five of ten patients missed work only on the day of surgery, and seven of ten patients required no formal physical therapy. All ten patients achieved a good or excellent result on the UCLA. Shoulder Scale for short-term follow-up evaluation. Postoperative radiographs documented adequate bone resection in all cases. In experienced hands, arthroscopic distal clavicle excision is an excellent substitute for the "open" procedure.
Acromioclavicular Joint↗
A developmentally regulated microsomal protein specific for the pigment epithelium of the vertebrate retina.
In the vertebrate retina, the retinal pigment epithelium (RPE) performs specific functions critical to the normal process of vision. Although some of these functions are well documented, molecular data are still scarce. Using the RPE-specific monoclonal antibody RPE9, raised against human RPE cells, we have identified a novel 65 kD protein, conserved in mammals, birds, and frogs. This RPE-specific protein was found to be nonglycosylated. It was most effectively solubilized in the presence of detergent suggesting that it is associated with the RPE cell membranes. Its partitioning in the detergent phase of Triton X-114 and its solubilization in 0.75 M and 1.0 M KCl suggest that it interacts with the membrane either through a polypeptide anchor or charged amino acids. Cell fractionation by differential solubilization and differential centrifugation demonstrated that the protein was preferentially associated with the microsomal membrane fraction, where it is the major protein. Developmental expression of this 65 kD protein was examined in neonatal rats. Morphologically well-differentiated RPE cells did not express the 65 kD protein at birth. However, expression was detectable at postnatal day 4, that is, one to two days before the photoreceptors develop their outer segments, suggesting that the expression of the 65 kD protein may be coordinated with other developmental events in the intact retina. This is further supported by the fact that RPE cells in confluent culture lose the expression of this protein within two weeks, while they maintain their characteristic epithelial morphology. Because of its specificity, its evolutionary conservation, and its timing of expression, it is possible that this protein may be involved in one of the key roles of RPE and as such is an important molecular marker for RPE differentiation.
Animals↗
Degradation of human and rat surfactant apoprotein by neutrophil elastase and cathepsin G.
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Animals↗
Heartwater in Guadeloupe and in the Caribbean.
A sero-epidemiological survey for heartwater was organized in 1992 in the Lesser Antilles, from Grenada to Saint Martin. Blood from about one percent of the ruminant livestock of the islands was randomly sampled and the sera were tested with an indirect ELISA. The percentage of positive sera was found to be 30% in Guadeloupe, 25% in Antigua, 2.2% in St.Martin, 1.3% in St. Kitts & Nevis, 3.8% in Montserrat, 1.7% in Dominica, 1.5% in St.Lucia, 1.5% in St.Vincent, 3.5% in Barbados, 2.9% in Grenada and 7% in Martinique. Ruminants from Guadeloupe and Antigua are known to be infected with heartwater. The low percentage of positive sera and the absence of clinical cases in the other islands strongly suggest that positive sera in these islands are probably due to non-specific cross reactions between Cowdria and other micro-organisms (possibly Ehrlichia) which remain to be isolated. In particular, the high percentages of positive sheep sera in Martinique (15%) and Montserrat (11%) should be further investigated.
Animals↗
The homeodomain: a new face for the helix-turn-helix?
The discovery of conserved protein domains found in many Drosophila and mammalian developmental gene products suggests that fundamental developmental processes are conserved throughout evolution. Our understanding of development has been enhanced by the discovery of the widespread role of the homeodomain (HD). The action of HD-containing proteins as transcriptional regulators is mediated through a helix-turn-helix motif which confers sequence specific DNA binding. Unexpectedly, the well conserved structural homology between the HD and the prokaryotic helix-turn-helix proteins contrasts with their divergent types of physical interaction with DNA. A C-terminal extension of the HD recognition helix has assumed the role that the N-terminus of the prokaryotic helix plays for specification of DNA binding preference. However, the HD appears also capable of recognizing DNA in an alternative way and its specificity in vivo may be modified by regions outside the helix-turn-helix motif. We propose that this intrinsic complexity of the HD, as well as its frequent association with other DNA binding domains, explains the functional specificity achieved by genes encoding highly related HDs.
Amino Acid Sequence↗
Early degenerative joint disease simulating impingement syndrome: arthroscopic findings.
Eighteen patients who underwent shoulder arthroscopy for impingement syndrome were shown at operation to have coexisting glenohumeral degenerative joint disease (DJD) which was not apparent during preoperative clinical and radiographic evaluation. Because traditional ("open") techniques of anterior acromioplasty do not allow inspection of the glenohumeral joint, it is almost certain that this pathology would have been missed at operation if open acromioplasty had been performed. We conclude that arthroscopic subacromial decompression (ASD), by allowing easy inspection of the glenohumeral joint, offers a distinct advantage over traditional acromioplasty. Furthermore, arthroscopic evaluation of some of these patients' glenohumeral joints provided us with evidence supporting the existence of subluxation arthropathy. We have also developed a new clinical test, the "compression-rotation" test, which has been helpful in distinguishing patients with both impingement syndrome and early DJD syndrome from those with isolated impingement syndrome. Although patients in this study appeared to be doing well at short-term follow-up status post-ASD and glenohumeral debridement, no long-term results are yet available.
Adult↗
An in vitro investigation of the action of lamotrigine on neuronal voltage-activated sodium channels.
Lamotrigine (LTG), 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine, is a novel antiepieptic drug structurally unrelated to the major anticonvulsants in current use. Previous studies of LTG in rodents revealed efficacy in maximal electroshock test, pentylenetetrazol test and kindling models of seizures suggesting potential utility in the treatment of partial and generalized (tonic-clonic) seizures. In the present study, LTG was found to block sustained repetitive firing of sodium-dependent action potentials in mouse spinal cord cultured neurons and inhibit [3H]batrachotoxinin A 20-alpha-benzoate binding in rat brain synaptosomes suggesting a direct interaction with voltage-activated sodium channels.
Action Potentials↗
Acetaminophen overdose as a suicidal gesture: a survey of adolescents' knowledge of its potential for toxicity.
Acetaminophen is a popular nonprescription analgesic that is often taken in overdose by adolescents during suicidal gestures. The authors hypothesized that most adolescents are naive about the toxic and lethal potential of acetaminophen in overdose. A one-page, 12-item questionnaire was administered to 169 high school students to evaluate their perceptions and knowledge in this area. Whereas only 22% of the sample underestimated the dose of acetaminophen necessary to cause harm, 40.5% underestimated the potential lethality of acetaminophen in overdose. Moreover, 17% of the sample did not believe one could ingest enough acetaminophen to cause death. The lack of knowledge about acetaminophen's potential dangerousness, its widespread availability, and an absence of early symptoms of hepatotoxicity make this medication highly dangerous to those adolescents who take it in overdose during parasuicidal behavior.
Acetaminophen↗
Development of enzymes of glycolysis and gluconeogenesis in human fetal liver.
The activities of two key enzymes of glycolysis and two key enzymes of gluconeogenesis were measured in liver samples from 44 human fetuses ranging in gestational age from 20 weeks to term, from infants to 10 years and from adults from 21 to 58 years. Specific activities of both gluconeogenic enzymes, fructose-1,6-biphosphatase and phosphoenolpyruvate carboxykinase, increased throughout the period of fetal development examined, and rose to near adult levels after birth. The activities of both glycolytic enzymes, phosphofructokinase 1 and pyruvate kinase, were lower in fetal than in pediatric and adult samples. For both of these enzymes, there was a significant reduction in activity of livers from fetuses of 34-37 weeks' gestation. Both enzymes showed hyperbolic kinetics at 24 weeks' gestation, but this changed to sigmoid kinetics during the 34-37 weeks' period of low activity. The data indicate that during the last weeks of gestation, inhibition of the activities of these two glycolytic enzymes, coupled with the rise in the two gluconeogenic enzymes, may reflect a change in liver from a primarily glycolytic role in the first two trimesters to a gluconeogenic role shortly before birth.
Adult↗
A normal level of beta-globin expression in erythroid cells after retroviral cells transfer.
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Animals↗
Benzylated 1,2,3-triazoles as anticoccidiostats.
Substituted 5-amino-4-carbamoyl-1,2,3-triazoles 3a-w were prepared by two synthetic schemes and evaluated in vivo for anticoccidial activity. Both schemes proceeded by brominating appropriately substituted toluenes 4a-s,v to 5a-s,v. In Scheme I, the brominated benzyl analogues 5 were converted to the corresponding benzyl azides 6, which were treated with cyanoacetamide to yield 1-substituted-5-amino-4-carbamoyl-1,2,3-triazoles 3. In Scheme II, the benzyl halides 5 were employed to alkylate the sodium salt of 5-amino-4-carbamoyl-1,2,3-triazole (7). Preliminary screening data against Eimeria acervulina and E. tenella in chickens suggested structural requirements for maximizing activity. Further evaluation against a relatively resistant series of eight Eimeria field isolates revealed L-651,582 (3a) to be a highly effective coccidiostat. However, unacceptable tissue residues precluded further development. Mechanistic studies on this series of 5-amino-4-carbamoyl-1,2,3-triazoles and, in particular, on L-651,582 (3a) revealed that its mode of action does not involve inhibition of IMP dehydrogenase, but probably interferes with host cell calcium entry. In addition, L-651,582 has been found to have antiproliferative activity in several disease models and was recently reported to possess antimetastatic activity in a model of ovarian cancer progression.
Alkylation↗
The paired box encodes a second DNA-binding domain in the paired homeo domain protein.
The homeo box, which encodes the DNA-binding homeo domain, is a DNA sequence motif present in several Drosophila developmental genes; it has been used to identify many homologous genes involved in mammalian development. The paired box is another conserved sequence motif, first identified in the paired (prd) and gooseberry (gsb) Drosophila homeo domain genes. It encodes a 128-amino-acid domain, the paired domain, which has since been found in other fly and mouse gene products, in association with the homeo domain or in its absence. We show that the paired box of the prd gene encodes a DNA-binding activity, independent of the DNA-binding activity of the Paired (Prd) homeo domain and with a different sequence specificity. The amino-terminal region of the paired domain, including one of the three predicted alpha-helices, is necessary and sufficient for binding. We investigate the binding of the Prd protein to two sites in the even-skipped promoter, which are composed of overlapping sequences bound by the homeo domain and by the paired domain. We also show that a mutation in the paired box of Prd, corresponding to the mutation in the paired box of the mouse Pax-1 gene thought to cause the undulated skeletal phenotype, destroys the ability of the Prd protein to bind to the paired domain-specific site. This supports the view that the undulated phenotype results from the inactivation of the DNA-binding activity of the paired domain of Pax-1.
Animals↗
Survival of patients with breast cancer attending Bristol Cancer Help Centre.
The Bristol Cancer Help Centre (BCHC) was set up in 1979 to offer various alternative therapies and treatments for patients with cancer. It attracted much public interest and a high demand for its services--and profound medical scepticism. In a study beginning in 1986 of 334 women with breast cancer attending the centre for the first time between June, 1986, and October, 1987, information about the diagnosis was obtained from case notes. Controls were a sample of 461 women with breast cancer attending a specialist cancer hospital or two district general hospitals. The same information was obtained for the control group as for the BCHC group. All patients have been followed up to June, 1988. 85% of patients with breast cancer attending the BCHC were aged under 55 at diagnosis. More than half had experienced recurrence of their disease before entry. For patients metastasis-free at entry, metastasis-free survival in the BCHC group was significantly poorer than in the controls (relapse rate ratio 2.85). Survival in relapsed cases was significantly inferior to that in the control group (hazard ratio 1.81). For cases metastasis-free at entry to the BCHC there was a significant difference in survival between cases and controls, confirming the difference in metastasis-free survival. There was no significant difference in survival or disease-free survival between the cancer hospital controls and other controls.
Adult↗
A randomized clinical trial of inpatient family intervention. V. Results for affective disorders.
This paper reports the results at follow-up of a randomized clinical trial of combining family intervention with drug treatment during hospitalization for patients with affective disorder. The results suggest that female bipolar patients and their families benefited from family intervention, whereas unipolar patients and families did not. Patient outcome was positively correlated with the achievement of the goals of family intervention.
Adolescent↗
The evolution of antibody response in armadillos inoculated with Mycobacterium leprae.
Plasma from 30 armadillos (Dasypus novemcinctus) was collected prior to inoculation and at approximately 3-month intervals for a period of 1-3 years. These animals were inoculated intravenously with 6.1 x 10(8) +/- 2 x 10(8) (x +/- SD) armadillo-derived Mycobacterium leprae. These samples were analysed for antibodies of IgM and IgG class to phenolic glycolipid-I (PGL-I) and to sonicated M. leprae components using ELISA and immunoblotting techniques, respectively. We had previously observed among a group of 11 armadillos, that some animals produced and maintained a high IgG antibody response to PGL-I. In this study, an animal's ability to produce and maintain an elevated IgG anti-PGL-I response was significantly correlated with their ability to delay dissemination of the infection and their ability to survive longer. When the animals were moribund, a significant decrease in the IgG anti-PGL-I absorbance value was observed. The detection of PGL-I in the plasma samples collected from moribund armadillos suggested that high concentrations of PGL-I in the plasma may have contributed to a drop in absorbance values by the formation of non-lattice-type immune complexes in vivo. As detected by immunoblotting, the IgM and IgG response to antigens derived from sonically disrupted M. leprae was directed towards molecules with broad bands of immunoreactivity ranging from 21- to 45-kDa. There were no distinguishing features of these antibody responses among armadillos as was evident with the IgG anti-PGL-I responses.
Animals↗
A single amino acid can determine the DNA binding specificity of homeodomain proteins.
Many Drosophila developmental genes contain a DNA binding domain encoded by the homeobox. This homeodomain contains a region distantly homologous to the helix-turn-helix motif present in several prokaryotic DNA binding proteins. We investigated the nature of homeodomain-DNA interactions by making a series of mutations in the helix-turn-helix motif of the Drosophila homeodomain protein Paired (Prd). This protein does not recognize sequences bound by the homeodomain proteins Fushi tarazu (Ftz) or Bicoid (Bcd). We show that changing a single amino acid at the C-terminus of the recognition helix is both necessary and sufficient to confer the DNA binding specificity of either Ftz or Bcd on Prd. This simple rule indicates that the amino acids that determine the specificity of homeodomains are different from those mediating protein-DNA contacts in prokaryotic proteins. We further show that Prd contains two DNA binding activities. The Prd homeodomain is responsible for one of them while the other is not dependent on the recognition helix.
Amino Acid Sequence↗
Pulmonary blood vessels and endocrine cells in subacute infantile mountain sickness.
A male infant of 16 months, of the Han race, died from subacute infantile mountain sickness in Lhasa (3600 m). At necropsy there was right ventricular hypertrophy secondary to muscularization of the pulmonary arteries and arterioles thought to have been induced by hypobaric hypoxia. In addition, there was intimal proliferation of myofibroblasts in the pulmonary arterioles, venules and veins. There were increased numbers within the bronchioles of pulmonary endocrine cells, containing calcitonin and bombesin, which could be related to hypoxia or trophic effects on the pulmonary vasculature. The relation of delayed effects of hypoxia to primary pulmonary hypertension is considered in this study.
Altitude Sickness↗