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Biomedical subjects

M Levine

Publications and source records attributed to M Levine.

At least 361 records · Page 20Linked to original sources

Recruitment for an efficacy study in chemoprevention--the Concerned Smoker Study.

Efficacy studies are important for the development of long-term cancer prevention strategies. Recruitment aims for a highly motivated group of participants. The Concerned Smoker Study is aimed at smokers with at least a 15 pack-year history and bronchial atypia on sputum sampling Recruitment has been primarily through use of the media. During the first year of randomization 905 potential participants expressed interest. Of these, 80 were eventually randomized. With over 60 participants having completed the study only one has defaulted and compliance with the study protocol has been high. Participants became aware of the study through the following sources: daily newspaper 36.6%, weekly newspaper 16.2%, television 14.9%, radio 13.8%, community television 1.3%, other sources 13.3%. Over 90% of potential participants who initially express interest in such a chemoprevention project may not ultimately be suitable. The population chosen for such studies may not be very representative of the more general population; however, a high degree of compliance can be obtained which will provide valuable information on treatment efficacy.

Advertising↗

Complications of reduction mammaplasty: comparison of nipple-areolar graft and pedicle.

A retrospective study of breast reductions in 268 patients by two plastic surgeons was performed. Particular attention was paid to those patients treated by inferior pedicle techniques; these patients were compared with those treated by free nipple grafts. According to our findings, patients with skin loss were heavier and had longer suprasternal notch-to-nipple distances. Patients who had free nipple grafts were older and heavier and had larger specimen weights and longer suprasternal notch-to-nipple distances. Fifty-four of the original 268 patients were included in a substudy of larger breasts, defined as those with a specimen weight of over 700 g. Nineteen patients underwent free nipple grafts, and 35 underwent inferior pedicle techniques. None of the 19 patients having free nipple grafts developed complications, whereas 6 of the 35 undergoing inferior pedicle techniques sustained significant complications. We conclude that free nipple grafts should be considered over inferior pedicles in heavier patients with breast ptosis.

Adult↗

Spatial regulation of zerknüllt: a dorsal-ventral patterning gene in Drosophila.

zerknüllt (zen) is one of approximately 10 zygotically active genes that control the differentiation of the dorsal-ventral (D/V) pattern during early embryogenesis in Drosophila. Past genetic analyses suggest that maternal factors repress the expression of zen in ventral regions, thereby restricting zen products to dorsal and dorsal-lateral regions of precellular embryos. Subsequent interactions with other zygotic D/V regulatory genes refine the zen pattern, restricting expression to the dorsal-most ectoderm. Here we describe the use of zen promoter fusions and P-element transformation to identify cis elements that are responsible for the complex spatial pattern of zen expression. The zen promoter shows a two-tier organization: Distal sequences mediate its initial response to maternal factors, whereas proximal sequences are responsible for the refinement of the pattern in older embryos. The distal regulatory element has the property of a silencer (or anti-enhancer) element and can act over a distance to repress ventral expression of a heterologous promoter. Also, we discuss evidence that proximal promoter sequences interact with factors that may be modulated by a cell-cell communication pathway.

Animals↗

Psychotherapy and mandated reporting of child abuse.

Seventy-six percent of 65 psychotherapy cases seen in a child guidance clinic either did not change or improved following a mandated report of suspected child abuse. In a significant minority of cases, the therapy relationship deteriorated when the report was made about a client in treatment, and improved when the report was made about a third party not in treatment.

Adolescent↗

Identification of mar mutations in herpes simplex virus type 1 glycoprotein B which alter antigenic structure and function in virus penetration.

Analysis of six monoclonal antibody-resistant (mar) mutants in herpes simplex virus type 1 glycoprotein B identified two type-common (II and III) and two type-specific (I and IV) antigenic sites on this molecule. To derive additional information on the location of these sites, mar mutations were mapped and nucleotide alterations were identified by DNA sequencing. Each mutant carried a single amino acid substitution resulting from a G-to-A base transition. Alterations affecting antibody neutralization were identified at residues 473, 594, 305, and 85 for mutants in sites I through IV, respectively. Two clonally distinct site II antibodies each selected mar mutants (Gly to Arg at residue 594) that exhibited a reduction in the rate of entry (roe) into host cells. A site II mar revertant that regained sensitivity to neutralization by site II antibodies also showed normal entry kinetics. DNA sequencing of this virus identified a single base reversion of the site II mar mutation, resulting in restoration of the wild-type sequence (Arg to Gly). This finding demonstrated that the mar and roe phenotypes were the result of a single mutation. To further define structures that contributed to antibody recognition, monoclonal antibodies specific for all four sites were tested for their ability to immune precipitate a panel of linker-insertion mutant glycoprotein B molecules. Individual polypeptides that contained single insertions of 2 to 28 amino acids throughout the external domain were not recognized or were recognized poorly by antibodies specific for sites II and III, whereas no insertion affected antibody recognition of sites I and IV. mar mutations affecting either site II or III were previously shown to cause temperature-sensitive defects in glycoprotein B glycosylation, and variants altered in both these sites were temperature sensitive for virus production. Taken together, the data indicate that antigenic sites II and III are composed of higher-order structures whose integrity is linked with the ability of glycoprotein B to function in virus infectivity.

Amino Acid Sequence↗

Prevention of venous thrombosis in patients undergoing major orthopaedic surgical procedures.

A summary of the relative effectiveness of the various prophylactic approaches is shown in Table 13. From this it can be seen that for studies comparing active prophylaxis with no prophylaxis, aspirin was relatively ineffective, while dextran, oral anticoagulants and low dose heparin were approximately equally effective, each being associated with a risk reduction of approximately 50 per cent. Low dose heparin and DHE showed a risk reduction of 52 per cent in one study, while LMWH showed a risk reduction of 72 per cent.

Anticoagulants↗

Characterization of encephalitis in adult mice induced by intracerebral inoculation of herpes simplex virus type 1 (KOS) and comparison with mutants showing decreased virulence.

The spread of herpes simplex virus type 1 (HSV-1) strain KOS, and two less neurovirulent mutants of the strain was studied in female DBA/2 mice during the 1- to 5-day postinoculation period after intracerebral inoculation. Immunohistopathology showed that wild-type KOS virus first infected the meninges and ependymal cells but did not infect cells at the inoculation sites. The virus continued to spread to some cells directly adjacent to ventricles; however, the most extensive and severe lesions were found in the pyriform lobes and other structures associated with the limbic system. The pattern of spread suggested that direct cell to cell viral spread is important but that retrograde axonal transport to distant sites probably accounts for the more severe lesions associated with the limbic system. Both less neurovirulent mutant viruses multiplied to a much lesser degree in the brain and spread less extensively than the wild type virus when equivalent doses were given; however, when a large dose of the least neurovirulent mar C10.1 mutant virus was inoculated, infection spread rapidly to the same regions of the brain affected by KOS. Studies of mar C10.1 showed that thymidine kinase deficiency, rather than a mutation in the gene coding for glycoprotein C, probably accounted for the decreased neurovirulence of this mutant. This mouse model of HSV-1 virus-induced encephalitis, in combination with appropriate studies of the molecular biology of the HSV-1 KOS strain, should be useful for the study of neurovirulence factors contributing to the pathogenesis of HSV-1.

Animals↗

A randomized trial of less intense postoperative warfarin or aspirin therapy in the prevention of venous thromboembolism after surgery for fractured hip.

A randomized trial was carried out with 194 patients to compare the effectiveness of sodium warfarin or aspirin with that of placebo in the prevention of venous thromboembolism after surgery for fractured hip. Prophylaxis was commenced postoperatively and continued for 21 days or until patient discharge, whichever was earlier. All patients underwent surveillance with iodine 125-fibrinogen leg scanning and impedance plethysmography, with subsequent venography. Venous thromboembolism occurred in 13 patients (20.0%) in the warfarin group, 27 patients (40.9%) in the aspirin group, and 29 patients (46.0%) in the placebo group. Proximal vein thrombosis or pulmonary embolism occurred in 6 patients (9.2%) in the warfarin group, 7 patients (10.6%) in the aspirin group, and 19 patients (30.2%) in the placebo group. The results of this study show that sodium warfarin therapy is safe and effective in preventing thromboembolic complications in patients undergoing surgery for fractured hip, and that aspirin therapy is an equally safe and effective method for preventing proximal vein thrombosis or pulmonary embolism.

Adult↗

A diagnostic algorithm for osteonecrosis of the femoral head.

For patients considered at risk for osteonecrosis (ON) of the femoral head, an algorithm for the efficient and appropriate use of diagnostic tests can be developed. Such an algorithm requires a clear idea of the evolution of the disease process and an understanding of the limitations of each of the modalities by which the disease process can be identified. The role of each of the diagnostic tests available for the diagnosis of ON and the results of prospective evaluations to assess their sensitivity, specificity, and predictive values are reviewed. No single diagnostic test is 100% accurate in the diagnosis of the disease. Thus, one must consider an algorithm that accounts for the variable nature of the disease presentation. The goal of such an algorithm is the accurate identification and staging of the disease. For disease not roentgenographically apparent, an approach using magnetic resonance imaging and bone scanning is recommended. For disease that is apparent roentgenographically, tomography is used to define the extent of the disease and the presence or absence of subchondral fracture. The accuracy of diagnosis is critical to understanding the role of the various treatment modalities prescribed for ON. For this purpose, it is necessary to reach a consensus as to what constitutes a successful outcome of treatment. Once diagnosis of the disease is accepted, clinical success of treatment outcomes should be reported in three ways: by a standard hip rating system, by ability to prevent roentgenographic deterioration, and by survival of the femoral head (the absence of further treatment intervention).(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Multimodality approach to osteonecrosis of the femoral head.

Treatment of osteonecrosis of the femoral head appears to be effective when the disease is identified and treated early. Forty-one patients were evaluated with prospective laboratory assessment, anteroposterior and frog-lateral roentgenograms of both hips, intraosseous pressure measurements (IOP), magnetic resonance imaging (MRI), and 99mTc methylene diphosphonate planar and single-photon emission computerized tomographic (SPECT) bone imaging. Pathologic specimens were obtained in most patients. Preradiographic disease was identified in 26 hips and 11 of these were asymptomatic. Fifteen clinically symptomatic hips had normal plain roentgenograms, but abnormal protocol studies. Evaluation of sensitivity, specificity, and predictive value (positive and negative), respectively, in diagnosing osteonecrosis of the femoral head revealed the following percentages: 83%, 83%, 96%, and 48% for planar bone scanning; 91%, 78%, 94%, and 70% for SPECT; 87%, 83%, 96%, and 55% for MRI; 80%, 60%, 95%, and 25% for IOP; and 88%, 100%, 100%, and 25% for core biopsy. (There were few true negatives, thus specificity values are approximations.) The identification of preradiographic stages is possible, but difficult. MRI appears appealing at present, particularly in identifying disease in asymptomatic hips. However, there is no definitive method for noninvasive diagnosis. Pathologic confirmation in early stages is difficult.

Adolescent↗

Ascorbic acid and Mg-ATP co-regulate dopamine beta-monooxygenase activity in intact chromaffin granules.

Ascorbic acid and Mg-ATP were found to regulate norepinephrine biosynthesis in intact secretory vesicles synergistically and specifically, using the model system of isolated bovine chromaffin granules. Dopamine uptake into chromaffin granules was shown to be unrelated to the presence of Mg-ATP and ascorbic acid at external dopamine concentrations of 7.5 and 10 mM. Under these conditions of dopamine uptake, norepinephrine biosynthesis was enhanced 5-6-fold by Mg-ATP and ascorbic acid compared to control experiments with dopamine only. Furthermore, norepinephrine formation was enhanced approximately 3-fold by ascorbic acid and Mg-ATP together compared to norepinephrine formation in granules incubated with either substance alone. The action of Mg-ATP and ascorbic acid together was synergistic and independent of dopamine content of chromaffin granules as well as of dopamine uptake. The apparent Km of norepinephrine formation for external ascorbic acid was 376 microM and for external Mg-ATP was 132 microM, consistent with the larger amounts of cytosolic ascorbic acid and ATP that are available to chromaffin granules. Other physiologic reducing agents were not able to increase norepinephrine biosynthesis in the presence or absence of Mg-ATP. In addition, maximum enhancement of norepinephrine biosynthesis occurred only with the nucleotide ATP and the cation magnesium. The mechanism of the effect of ascorbic acid and Mg-ATP on norepinephrine biosynthesis was investigated and appeared to be independent of a positive membrane potential. The effect was also not mediated by direct action of ADP, ATP, or magnesium on the activity of soluble or particulate dopamine beta-monooxygenase. These data indicate that Mg-ATP and ascorbic acid specifically and synergistically co-regulate dopamine beta-monooxygenase activity in intact chromaffin granules, independent of substrate uptake. Although the mechanism is not known, the data are consistent with the possibility that the chromaffin granule ATPase mediates these effects.

Adenosine Triphosphate↗