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Biomedical subjects

S Schwartz

Publications and source records attributed to S Schwartz.

At least 271 records · Page 15Linked to original sources
PubMed1995

Predictors of sunscreen use in childhood.

OBJECTIVE: To identify risk factors predictive of sunscreen use in children. DESIGN: Cross-sectional review of convenience sample. SETTING: Emergency department of a regional referral pediatric hospital. SUBJECTS: Nine hundred twenty-five parents of children presenting to the emergency department in August 1993. MAIN OUTCOME MEASURES: Parental risk factors assessed were use of sunscreen, tanning behaviors, previous blistering sunburn, knowledge of cancer risk related to sunburn and sun protection factor definition, education level, and other health-promoting behaviors. The parents were asked about perceived risk for their child's being sunburned in the next month or development of skin cancer in their lifetime, as well as an estimation of safe sun exposure time for their child. Child risk factors included a history of previous painful sunburn and parental assessment of their child's skin type based on susceptibility to sunburn. RESULTS: Eighty-four percent of parents reported that their children had used sunscreen at least once in the previous 2 months. The use of sunscreen in children younger than 1 year was 54%, from 1 to 12 years of age was 91%, and older than 12 years was 68%. Factors associated with increased likelihood of sunscreen use were age of 1 to 12 years, parental use of sunscreen, estimation of safe sun exposure of less than 30 minutes, description of child skin type as burns "sometimes," "easily," or "always," and correct definition of sun protection factor. Application of a multivariate model yielded a sensitivity of 96%, specificity of 36%, and positive predictive value of sunscreen use of 89%. CONCLUSIONS: Sunscreen use in parents is predictive of use in their children and relates more to experience with sunburn than with concerns about future skin cancer risk.

Adolescent↗
PubMed1995

Promoter demethylation in MMTV/N-rasN transgenic mice required for transgene expression and tumorigenesis.

We studied demethylation within the transgene promoter in transgenic mice carrying the N-ras proto-oncogene driven by the mouse mammary tumor long terminal repeat (MMTV/N-rasN) and the relationship of demethylation to transgene overexpression and tumorigenesis. Demethylation at Fspl or Clal sites correlated with age of the animal and transgene expression in nontumorous mammary gland. Demethylation preceded expression in this tissue. In lymphomas and mammary tumors, the promoter Fspl and Clal sites were significantly more demethylated than in nontumorous control tissues. The Aval, Cfol, and Hpall sites were also found to be undermethylated in older animals and showed differences between tumor and control tissues. Two additional sites (Eagl and Narl) remained fully methylated in all tissues. In contrast with normal tissue, demethylation at the Fspl and Clal sites and expression were not correlated in tumor tissue. An increase in expression in normal tissue initially occurred and was correlated with the level of promoter demethylation; this increase was followed by a further increment in transgene expression when tumors developed. Thus, promoter demethylation leading to transgene overexpression was associated with long-latency tumorigenesis in MMTV/N-rasN transgenic mice. Demethylation of proto-oncogene promoters may therefore be a mechanism of carcinogenesis that requires further investigation in human tumors.

5-Methylcytosine↗
PubMed1995

Aerosol amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in neutropenic cancer patients.

To determine the value of aerosol amphotericin B inhalations for prevention of invasive pulmonary aspergillosis (IPA), we initiated a prospective randomized multicenter trial. The scheduled intent-to-treat interim analysis included 115 patients (30%) with prolonged neutropenia after chemotherapy for acute myeloid leukemia, acute lymphoblastic leukemia/high-grade non-Hodgkin's lymphoma, or solid tumors undergoing autologous stem cell transplantation. Sixty-five patients had been randomized to receive prophylactic aerosol amphotericin B inhalations at a dose of 10 mg twice daily (group A); for the remaining 50 patients no aerosol amphotericin B prophylaxis was used (group B). No serious side effects from amphotericin B inhalations occurred, but coughing (54%), bad taste (51%), and nausea (37%) caused early cessation of aerosol amphotericin B prophylaxis in 23% (15/65) of courses. In group A, the incidence of proven, probably, or possible IPA was 5% (3/65) as compared with 12% (6/50) in group B (p > 0.05). Microbiologically documented bacterial pneumonias were observed in 5/65 (8%) patients in group A and in 1/50 (2%) patients in group B (p > 0.05). Thus, no reduction in incidence of IPA from use of prophylactic aerosol amphotericin B inhalations was found in this interim analysis. As there were no serious side effects from aerosol amphotericin B prophylaxis, accrual in the study will continue for a total of 380 patients.

Administration, Inhalation↗
PubMed1995

Public knowledge, attitudes, and beliefs about homeless people: evidence for compassion fatigue.

Media reports suggest that the public is becoming impatient with the homeless--that so-called "compassion fatigue" has gripped the nation. This characterization of public sentiment could have important policy consequences-- restrictive measures can be justified by growing public impatience, and progressive housing policies seem feasible within a hostile climate of opinion. But evidence to support the compassion fatigue notion is anecdotal. We examine the issue by tracking the results of public opinion polls and by reporting detailed evidence from a nationwide random-digit dial telephone survey (N = 1,507) concerning knowledge attitudes and beliefs about homeless people. To be sure, the public sees homelessness as an undesirable social problem and wants something done about it. However, although the homeless are clearly stigmatized, there is little evidence to suggest that the public has lost compassion and is unwilling to support policies to help homeless people.

Adolescent↗
PubMed1995

Efficacy and safety of pravastatin in the treatment of patients with type I or type II diabetes mellitus and hypercholesterolemia.

PURPOSE: Patients with type I and type II diabetes mellitus have an increased risk of coronary heart disease. In many diabetics, hypercholesterolemia is present and further exacerbates this risk. We investigated the efficacy and safety of pravastatin in the treatment of patients with type I or type II diabetes mellitus and hypercholesterolemia. PATIENTS AND METHODS: In this 24-week, multi-center, double-blind, placebo-controlled study, 94 patients (45 men, 49 women), 18 to 70 years of age, with type I or type II diabetes mellitus and hypercholesterolemia (fasting plasma low-density lipoprotein cholesterol [LDL-C] levels > 150 mg/dL and above the 75th percentile for the US population by age and gender) were randomized to receive pravastatin 20 mg hs or matching placebo. Two patients were randomized to treatment with drug for every 1 randomized to placebo. The dose could be doubled after 10 weeks, and cholestyramine or colestipol could be added after 18 weeks, as needed, to attempt to lower the LDL-C levels to below the 50th percentile for the US population. RESULTS: Significant reductions in LDL-C (-27.6%), total cholesterol (-22.1%), very-low-density lipoprotein cholesterol (-22.6%), and triglycerides (-12.8%) (P < or = 0.001 versus placebo for all reductions), and significant increases in high-density lipoprotein cholesterol (4.4%) (P < or = 0.05 versus placebo) were noted in the pravastatin treatment group (average dose 29.5 mg) at 16 weeks. The beneficial lipid-lowering effects of pravastatin were maintained throughout the 24 weeks of the study. Pravastatin was well tolerated, and the frequency of side effects was similar in the pravastatin and placebo groups. No clinically significant changes in the control of diabetes, as assessed by fasting blood glucose levels and glycosylated hemoglobin measurements, were seen during this study. CONCLUSION: The results of this study demonstrate that pravastatin is well tolerated and effective in lowering total cholesterol and LDL-C in patients with type I or type II diabetes mellitus and hypercholesterolemia.

Adult↗
PubMed1995

Ewing's sarcoma of the mandible: a case report.

Ewing's sarcoma is an uncommon malignancy that usually occurs in childhood and is rare in the mandible. A case of Ewing's sarcoma of the mandible is presented and discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15.

A subset of patients with Angelman and Prader-Willi syndrome have apparently normal chromosomes of biparental origin, but abnormal DNA methylation at several loci within chromosome 15q11-13, and probably have a defect in imprinting. Using probes from a newly established 160-kb contig including D15S63 (PW71) and SNRPN, we have identified inherited microdeletions in two AS families and three PWS families. The deletions probably affect a single genetic element that we term the 15q11-13 imprinting centre (IC). In our model, the IC regulates the chromatin structure, DNA methylation and gene expression in cis throughout 15q11-13. Mutations of the imprinting centre can be transmitted silently through the germline of one sex, but appear to block the resetting of the imprint in the germline of the opposite sex.

Angelman Syndrome↗
PubMed1995

Identification of centromeric antigens in dicentric Robertsonian translocations: CENP-C and CENP-E are necessary components of functional centromeres.

Robertsonian translocations are the most common structural dicentric rearrangements in humans. The stability of these dicentrics is attributed to the inactivation of one centromere by mechanisms which are currently unknown. The presence and amounts of centromeric proteins (CENPs) differ between the centromeres of the few dicentrics which have been studied, providing a limited understanding of the protein components necessary for centromeric function. However, CENP-C previously has been observed only at the active centromeres in two dicentric chromosomes. In the present investigation, the presence and localizations of several centromeric antigens, CENP-B, -C and -E, have been determined in 12 dicentric Robertsonian translocations. Each translocation was studied initially using in situ hybridization with alpha-satellite DNA probes to determine the active centromere. Subsequent immunofluorescence of monoclonal and polyclonal antibodies generated to various centromeric antigens demonstrated that the protein composition differs at the two centromeres of these dicentric translocations. While CENP-B was present at both active and inactive centromeres, CENP-C and -E were located at active centromeres only in the majority of translocations. These results confirm previous observations of CENP-C at active centromeres and provide the first evidence that CENP-E correlates with active centromeres as well, demonstrating that at least two specific centromeric proteins are required for human centromeric function.

Autoantigens↗
PubMed1995

Analysis of cross reactivity of retrovirus proteases using a vaccinia virus-T7 RNA polymerase-based expression system.

We have used the vaccinia virus-T7 RNA polymerase-based expression system for studies on the activity of proteases from various retroviruses on homologous and heterologous Gag polyproteins in eukaryotic cells. Proteases from human immunodeficiency virus (HIV) types 1 and 2, equine infectious anaemia virus, human T cell leukaemia virus type 1 and human spumavirus were produced and were shown to cleave their cognate Gag substrates produced in trans. Analysis of cross reactivity revealed that lentivirus proteases cleaved only lentivirus Gag proteins and oncovirus proteases acted primarily on oncovirus Gag proteins. The HIV-2 protease cleaved the HIV-1 Gag precursor almost as efficiently as HIV-1 protease. Expression of the 5' end of the human spumavirus pol gene revealed that it encodes a functional protease that acts specifically on the human spumavirus Gag polyprotein. This assay will allow further investigation on the activity and specificity of retrovirus proteases in eukaryotic cells.

Amino Acid Sequence↗
PubMed1995

The Rev protein of human immunodeficiency virus type 1 counteracts the effect of an AU-rich negative element in the human papillomavirus type 1 late 3' untranslated region.

We have identified a sequence in the late 3' untranslated region of human papillomavirus type 1 mRNAs that acts posttranscriptionally to repress gene expression. Deletion analysis localized the inhibitory element to an AU-rich sequence between nucleotides 6958 and 6984 on the human papillomavirus type 1 genome. This sequence inhibits gene expression in an orientation-dependent manner. Upon transfection of eucaryotic cells with plasmids containing this sequence, approximately 4-fold-lower cytoplasmic mRNA levels and 64- to 128-fold-lower protein levels were produced compared with those produced by plasmids lacking the inhibitory sequence. Interestingly, providing the constitutive transport element of simian retrovirus type 1 in sense orientation counteracted inhibition exerted by the human papillomavirus type 1 sequence. Inhibition could also be overcome by the presence of human immunodeficiency virus type 1 Rev protein in trans and its target sequence, the Rev-responsive element, in cis. Rev is a nuclear protein and acts by promoting nuclear export of human immunodeficiency virus type 1 mRNAs encoding structural proteins. Our results are consistent with a model for human papillomavirus type 1 late-gene expression in which mRNAs containing human papillomavirus type 1 inhibitory sequences enter a nonproductive route in the nucleus, resulting in inefficient mRNA utilization. Rev directs mRNA containing inhibitory sequences to a productive route by interacting with the Rev-responsive element.

Base Composition↗
PubMed1995

Efficiency of reinitiation of translation on human immunodeficiency virus type 1 mRNAs is determined by the length of the upstream open reading frame and by intercistronic distance.

In this study, we examined the mechanism of translation of the human immunodeficiency virus type 1 tat mRNA in eucaryotic cells. This mRNA contains the tat open reading frame (ORF), followed by rev and nef ORFs, but only the first ORF, encoding tat, is efficiently translated. Introduction of premature stop codons in the tat ORF resulted in efficient translation of the downstream rev ORF. We show that the degree of inhibition of translation of rev is proportional to the length of the upstream tat ORF. An upstream ORF spanning 84 nucleotides was predicted to inhibit 50% of the ribosomes from initiating translation at downstream AUGs. Interestingly, the distance between the upstream ORF and the start codon of the second ORF also played a role in efficiency of downstream translation initiation. It remains to be investigated if these conclusions relate to translation of mRNAs other than human immunodeficiency virus type 1 mRNAs. The strong inhibition of rev translation exerted by the presence of the tat ORF may reflect the different roles of Tat and Rev in the viral life cycle. Tat acts early to induce high production of all viral mRNAs. Rev induces a switch from the early to the late phase of the viral life cycle, resulting in production of viral structural proteins and virions. Premature Rev production may result in entrance into the late phase in the presence of suboptimal levels of viral mRNAs coding for structural proteins, resulting in inefficient virus production.

Base Sequence↗
PubMed1995

Efficient expression of the human papillomavirus type 16 L1 protein in epithelial cells by using Rev and the Rev-responsive element of human immunodeficiency virus or the cis-acting transactivation element of simian retrovirus type 1.

Production of the human papillomavirus (HPV) late gene products L1 and L2 is limited to terminally differentiated keratinocytes. Here, we demonstrate that mRNA encoding the HPV-16 L1 capsid protein contains cis-acting RNA elements that inhibit expression at the posttranscriptional level. While cytoplasmic L1 mRNA is detectable in transfected HeLa cells, L1 protein is not produced. We have identified at least one major inhibitory element that is located within the L1 open reading frame, whereas another negative element had been reported to lie in the 3'-untranslated region of L1. The presence of these elements may explain the lack of HPV late gene expression in undifferentiated epithelial cells. Efficient production of HPV-16 L1 could be achieved with posttranscriptional regulatory elements of human immunodeficiency virus type 1 or simian retrovirus type 1. L1 protein was expressed in the presence of human immunodeficiency virus type 1 Rev from hybrid mRNAs containing the RNA binding site for Rev (Rev-responsive element). In addition, we have achieved efficient expression of L1 from hybrid mRNAs containing a cis-acting transactivation element from simian retrovirus type 1. Our data show that HPV-16 L1 protein production is regulated posttranscriptionally. This regulated expression may allow virus production in terminally differentiated epithelial cells and is probably a conserved and important mechanism for HPV expression.

Base Sequence↗
PubMed1995

Diode laser contact transscleral retinal photocoagulation: a clinical study.

AIM: To examine the clinical efficacy of contact transscleral retinal photocoagulation with a diode laser. METHODS: Transscleral retinal photocoagulation was performed on 36 eyes. The conditions treated included peripheral retinal breaks associated with retinal detachments (30 eyes) and giant retinal tears (six eyes). Of the 30 eyes with retinal detachments, 28 underwent transscleral photocoagulation to the site of drainage of subretinal fluid in an attempt to reduce the risk of hemorrhage. RESULTS: Threshold lesions were obtained with irradiances of between 95.4 W/cm2 and 191 W/cm2. Satisfactory chorioretinal adhesion was achieved in all eyes with retinal breaks and giant retinal tears. The only significant complications of treatment encountered were punctate choroidal haemorrhages (three eyes). Drainage related choroidal haemorrhage following earlier photocoagulation occurred in two of 28 eyes. CONCLUSIONS: This study confirms the clinical potential of transscleral diode laser photocoagulation in the therapy of surgical retinal conditions.

Adolescent↗
PubMed1995

Protein synthesis in specific tissues during sepsis.

BACKGROUND: The hypothesis that fractional protein synthesis rates (Ks) are tissue-specific and bidirectional during sepsis was tested in an animal model. MATERIAL AND METHODS: Ks in liver, triceps muscle, and diaphragm were measured in septic (n = 27) and control rats (n = 26). Sepsis was induced by a reproducible model established in our laboratory (intraperitoneal injection of sterile NaOH 0.75 N at 0.075 ml/100 g of body weight). Ks were measured using the flooding-dose method in tissue obtained from the diaphragm, liver, and from the triceps muscle. RESULTS: In hepatic and diaphragmatic tissue, Ks were significantly higher in the septic animals (Ks: 112.2 +/- 8 and 5.4 +/- 1.9, respectively) than in control animals (Ks: 78.5 +/- 13 and 2.9 +/- 1.7, respectively). In the triceps, Ks were significantly lower in septic animals (Ks: 2.9 +/- 1.4) than in control animals (Ks: 5 +/- 1.8). CONCLUSION: The results suggest that in septic animals the rate of protein synthesis is enhanced in tissues of priority, such as the liver, and varies in response to differences in muscle activity.

Animals↗
PubMed1995

Age and family relationship accentuate the risk of insulin-dependent diabetes mellitus (IDDM) in relatives of patients with IDDM.

The international community of diabetologists is rapidly becoming involved in intervention trials aimed at preventing insulin-dependent diabetes in high risk relatives. Whereas age and relationship to a proband with insulin-dependent diabetes mellitus interacting with detected islet cell autoantibodies (ICA) are risk factors, their independent contribution to that risk remains unclear. In a prospective study of 6851 nondiabetic relatives of 2742 probands conducted between 1979-1993, we found age, but not relationship, to be a dramatic risk variable in ICA-positive persons as estimated by the Cox regression model. The 5-yr risk of insulin-dependent diabetes mellitus was 66% for those found to have ICA detectable before age 10 yr, falling progressively to less than 16% for ICA-positive relatives over age 40 yr. In ICA-negative relatives, age and relationship are independent prognostic variables.

Adolescent↗
PubMed1995

Alveolar cleft bone grafts: results and imprecisions of the dental radiograph.

Alveolar cleft bone grafts customarily have been evaluated by one-dimensional dental radiographic measurements. Based on the dental radiograph, remarkable successes with just a single bone graft have been reported in the literature. At the Montreal Children's Hospital, the experience with 101 alveolar bone grafts in 62 cleft lip and palate patients was retrospectively reviewed to determine (1) the precision of dental radiographs at evaluating the clinical outcome, (2) the effect of dental maturation on alveolar bone grafts, and (3) the effect of augmentation bone grafts. The dental radiograph significantly overestimated the number of clefts that could be managed orthodontically (p < 0.01, McNemar's test) and thus poorly prognosticated the ability to achieve bony obliteration of the alveolar cleft and orthodontic closure of the dental gap. Bone grafts performed during the preeruptive canine dentition yielded significantly better results (p < 0.05, chi-squared test). With each subsequent augmentation bone-graft procedure performed, there existed a trend toward improved dental arch stability and radiographic and clinical outcomes.

Adolescent↗