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Biomedical subjects

B Weiss

Publications and source records attributed to B Weiss.

At least 55 records · Page 3Linked to original sources
PubMed2000

Evaluation of techniques for assessing neurobehavioral development in children.

A battery of tests has been designed to explore functional disabilities in children 10-12 years of age arising from adverse conditions during early development. At these ages, it becomes possible to use more complex and challenging tests than those typically used at earlier ages. Although the battery was prompted originally by questions arising from methylmercury exposure, it was also designed for applicability to neurotoxicant exposures arising from pesticides, solvents, persistent organic pollutants such as PCBs and dioxins, other metals, and nutrient excesses and deficiencies as well. The test battery includes the following categories: (1) neuropsychological tests with established psychometric properties not widely exploited in studies of developmental neurotoxicity; (2) electrophysiological and behavioral tests of sensory functioning spanning a broader range of indices than those used generally in studies of neuropsychological development; and (3) adaptations of performance tasks used previously only in animals. The battery was developed in Rochester, New York, and then field-tested on a group of 61 children in the Republic of the Seychelles, where the Ministry of Health had established the Child Development Center. Our findings suggest a number of tests and procedures with the potential for inclusion in test batteries aimed at the exploration of adverse neurodevelopmental effects.

Adolescent↗
PubMed1999

Endonuclease V protects Escherichia coli against specific mutations caused by nitrous acid.

Endonuclease V (deoxyinosine 3'-endonuclease) of Escherichia coli K-12 is a putative DNA repair enzyme that cleaves DNA's containing hypoxanthine, uracil, or mismatched bases. An endonuclease V (nfi) mutation was tested for specific mutator effects on a battery of trp and lac mutant alleles. No marked differences were seen in frequencies of spontaneous reversion. However, when nfi mutants were treated with nitrous acid at a level that was not noticeably mutagenic for nfi(+) strains, they displayed a high frequency of A:T-->G:C, and G:C-->A:T transition mutations. Nitrous acid can deaminate guanine in DNA to xanthine, cytosine to uracil, and adenine to hypoxanthine. The nitrous acid-induced A:T-->G:C transitions were consistent with a role for endonuclease V in the repair of deaminated adenine residues. A confirmatory finding was that the mutagenesis was depressed at a locus containing N(6)-methyladenine, which is known to be relatively resistant to nitrosative deamination. An alkA mutation did not significantly enhance the frequency of A:T-->G:C mutations in an nfi mutant, even though AlkA (3-methyladenine-DNA glycosylase II) has hypoxanthine-DNA glycosylase activity. The nfi mutants also displayed high frequencies of nitrous acid-induced G:C-->A:T transitions. These mutations could not be explained by cytosine deamination because an ung (uracil-DNA N-glycosylase) mutant was not similarly affected. However, these findings are consistent with a role for endonuclease V in the removal of deaminated guanine, i.e., xanthine, from DNA. The results suggest that endonuclease V helps to protect the cell against the mutagenic effects of nitrosative deamination.

DNA Glycosylases↗
PubMed1999

Hyperactive Ras as a therapeutic target in neurofibromatosis type 1.

The NF1 gene encodes neurofibromin, a GTPase-activating protein (GAP) for members of the p21(ras) (Ras) family, which negatively regulates Ras output by accelerating the conversion of active Ras. GTP to inactive Ras.GDP. Analysis of tumors from patients with neurofibromatosis type 1 (NF1) has shown biochemical evidence of hyperactive Ras as well as frequent loss of the normal NF1 allele, consistent with its role as a tumor suppressor gene. Taken together, these data suggest that novel therapeutics directed against components of the Ras signaling cascade might provide effective treatments for certain pathological complications of NF1. Here we summarize data that support a role for hyperactive Ras in NF1 disease, including Ras processing, activation, and down-regulation. We review targets for rational drug design, provide preliminary results, and discuss implications for future studies. Am. J. Med. Genet. (Semin. Med. Genet.) 89:14-22, 1999.

Drug Design↗
PubMed1999

Antisense RNA gene therapy for studying and modulating biological processes.

Agents that produce their effects through an antisense mechanism offer the possibility of developing highly specific alternatives to traditional pharmacological antagonists, thereby providing a novel class of therapeutic agents, ones which act at the level of gene expression. Among the antisense compounds, antisense RNA produced intracellularly by an expression vector has been used extensively in the past several years. This review considers the advantages of the antisense RNA approach over the use of antisense oligodeoxynucleotides, the different means by which one may deliver and produce antisense RNA inside cells, and the experimental criteria one should use to ascertain whether the antisense RNA is acting through a true antisense mechanism. Its major emphasis is on exploring the potential therapeutic use of antisense RNA in several areas of medicine. For example, in the field of oncology antisense RNA has been used to inhibit several different target proteins, such as growth factors, growth factor receptors, proteins responsible for the invasive potential of tumor cells and proteins directly involved in cell cycle progression. In particular, a detailed discussion is presented on the possibility of selectively inhibiting the growth of tumor cells by using antisense RNA expression vectors directed to the individual calmodulin transcripts. Detailed consideration is also provided on the development and potential therapeutic applications of antisense RNA vectors targeted to the D2 dopamine receptor subtype. Studies are also summarized in which antisense RNA has been used to develop more effective therapies for infections with certain viruses such as the human immunodeficiency virus and the virus of hepatitis B, and data are reviewed suggesting new approaches to reduce elevated blood pressure using antisense RNA directed to proteins and receptors from the renin-angiotensin system. Finally, we outline some of the problems which the studies so far have yielded and some outstanding questions which remain to be answered in order to develop further antisense RNA vectors as therapeutic agents.

Animals↗
PubMed1999

[Cardiovascular disease in pregnancy].

There is a heterogeneous population of young women with cardiovascular disease contemplating pregnancy. Many of the conditions are rare and require teams with expertise in the management of such patients. A specific congenital or acquired cardiovascular anomaly and its physiology must be understood. The nature of prior surgical procedures and the residua and sequelae following therapy are essential to manage a pregnant woman with cardiovascular disease. Physiologic changes during pregnancy and after delivery must be known. Counseling includes maternal and fetal risk stratification and genetic counseling regarding inherited disorders. The outcome of pregnancy is favourable in many women with good functional class. These patients can be reassured. A multidisciplinary approach may be crucial to manage this population during pregnancy, labour, delivery and in the postpartum period to avoid serious maternal and fetal complications. Women with intermediate and high risk pregnancy must be followed and managed in a high risk pregnancy unit and a team from obstetricians, cardiologists, anesthetists, pediatricians, neonatologists and cardiac surgeons who are skilled in high risk pregnancies. Vaginal delivery is the method of choice in many women (class 1 woman) and cesarean section is seldom a cardiac indication. Contraindications for pregnancy are: poor maternal functional class, poor ventricular function, severe cyanosis without pulmonary hypertension (oxygen saturation < or = 85%), pulmonary vascular disease, severe mitral stenosis, severe left ventricular outflow tract obstruction, Marfan syndrome with aortic dilatation (> 40 mm) and aortic valve involvement (moderate to severe aortic regurgitation), symptomatic hypertrophic obstructive cardiomyopathy. Preconception counseling must be offered if unfavourable outcome is likely. Tubal ligation is probably the safest and most appropriate method of sterilization if there is a high risk pregnancy.

Adult↗
PubMed1999

The effectiveness of traditional child psychotherapy.

This study used a randomized design to evaluate the effectiveness of child psychotherapy as typically delivered in outpatient settings. Overall results were similar to the results of nonrandomized studies of traditional child psychotherapy: Little support was found for its effectiveness, with treatment producing an overall effect size of -.08. Despite the lack of significant differences between treatment and control groups in regard to changes in child functioning, parents of children who received treatment reported higher levels of satisfaction with services than control group parents whose children received academic tutoring. Overall, the findings highlight the importance of developing, validating, and transporting effective treatments to clinical settings.

Black or African American↗
PubMed1999

The critical region of overlap defining the AZFa male infertility interval of proximal Yq contains three transcribed sequences.

The position of deletion breakpoints in a series of four AZFa male infertility patients has been refined using new markers derived from BAC clone DNA sequence covering the AZFa male infertility interval. The proximal half of the AZFa interval is occupied by pseudogene sequences with homology to Xp22. The distal half contains an anonymous expressed sequence tag (named AZFaT1) found transcribed in brain, testis, and skeletal muscle and the DFFRY and DBY genes. All the patients have AZFaT1 and DFFRY deleted in their entirety and three patients additionally have DBY deleted. The three patients with AZFaT1, DFFRY, and DBY deleted show a severe Sertoli cell only syndrome type I phenotype, whereas the patient that has retained DBY shows a milder oligozoospermic phenotype. The expression of DBY in a cell line from this latter patient is unaltered; this shows that it is the loss of genes lying within the deletion that is responsible for the observed oligozoospermia. RT-PCR analysis of mouse testis RNA from normal and XXSxr(a) mice (devoid of germ cells) has shown that Dby is expressed primarily in somatic cells and that the level of expression is unaltered during germ cell differentiation. This contrasts with Dffry where no transcripts are detectable in XXSxr(a) mouse testis and expression occurs specifically in testis mRNA in a germ cell dependent fashion.

Adult↗
PubMed1999

Middle molecules in peritoneal equilibration test as a marker of peritoneal stress in children on continuous peritoneal dialysis.

At 1 month, 3 months, 6 months, and more than 6 months after healed peritonitis, we evaluated repeated peritoneal equilibration tests (PETs) for small molecules such as urea, and middle molecules such as cystatin C, beta 2-microglobulin, and alpha 1-microglobulin. We analyzed a total of 104 PETs in 21 children aged 1.7-18.6 years (median: 9.9 years). Equilibration quotients (D/P)--that is, substrate concentration in dialysis fluid (D) divided by substrate concentration in plasma (P)--were calculated after a dwell time of 4 hours. The D/P for urea did not change after healed peritonitis. In a cross-sectional study, the D/P for middle molecules showed an increase in peritoneal permeability between 3 months and 6 months after a healed peritonitis. In a consecutive follow-up of 4 patients for more than 6 months, beta 2-microglobulin and, more impressively, alpha 1-microglobulin showed a statistically significant increase in D/P (p < 0.05) 3 months after a healed peritonitis. All differences seen were completely reversible after more than 6 months, showing that peritoneal function is rather stable if peritonitis is healed. It is noteworthy that peritoneal dysfunction lasts for up to 6 months after a completely healed peritonitis. This period might be a vulnerable phase in continuation of peritoneal dialysis.

Adolescent↗
PubMed1999

[Sensitivity and resistance of Helicobacter pylori to antibiotic treatment].

Resistance to antibiotics is considered the main reason for failure to eradicate Helicobacter pylori (HP). Resistance rates are different in developed and developing countries and are not known for Israel. We studied HP resistance rates in 40 patients who underwent esophagoduodenoscopy for various indications and were found to have gastric HP colonies. Sensitivity was determined by E-test, using clarythromycin, amoxycillin, clindamycin, erythromycin and metronidazole. The resistance rate for metronidazole was up to 67% but that for clindamycin was only 10%. HP was very sensitive to both macrolide antibiotics, erythromycin and clarythromycin.

Anti-Bacterial Agents↗
PubMed1998

Common and specific features of childhood psychopathology.

This article describes a conceptual and data-analytic model for characterizing different levels of common and specific features of child psychopathology: common features, which differentiate psychopathology from normality; broadband-specific features, which differentiate internalizing problems (e.g., anxiety, somatization) from externalizing problems (e.g., aggression, hyperactivity); and narrowband-specific features, which differentiate different narrowband syndromes (e.g., anxiety from somatization, hyperactivity from aggression) within each of the broadband syndromes. As an illustration of the model, data for 6 cognitive variables (e.g., global self-worth, causal attributions) are related to 6 psychopathology domains (e.g., aggression, depression) in a sample of 204 children. It is suggested that common features may be related to severity of psychopathology, whereas specific features may be more related to differentiation of psychopathology.

Child↗
PubMed1998

Effect of antisense oligodeoxynucleotides directed to individual calmodulin gene transcripts on the proliferation and differentiation of PC12 cells.

Calmodulin (CaM) is encoded by three different genes that collectively give rise to five transcripts. In the present study, we used antisense oligodeoxynucleotides targeted to unique sequences in the transcripts from the individual CaM genes to selectively block the expression of the different genes and to investigate the roles these individual genes play in the proliferation and nerve growth factor (NGF)-induced differentiation of PC12 cells. Culturing PC12 cells in the presence of oligodeoxynucleotide antisense to the transcripts from CaM genes I and II caused a significant decrease in the proliferation and a significant delay in the NGF-induced differentiation of PC12 cells when compared with untreated cells and with cells treated with the corresponding randomized oligodeoxynucleotides. However, an oligodeoxynucleotide antisense to CaM gene III did not significantly alter the proliferation or the NGF-induced differentiation of PC12 cells. The inhibition of cell proliferation could be reversed by washing out the antisense oligodeoxynucleotides. The levels of CaM in cells treated with oligodeoxynucleotides antisense to CaM genes I or II were reduced 52% or 63%, respectively, of the levels found in the control cells. However, the levels of CaM were not significantly reduced in PC12 cells treated with CaM gene III antisense oligodeoxynucleotide. None of the randomized oligodeoxynucleotides had any effect on the levels of CaM in PC12 cells. The reduced levels of CaM in PC12 cells treated with an oligodeoxynucleotide antisense to CaM gene I were accompanied by a reduction in the levels of the CaM gene I mRNAs, supporting a true antisense mechanism of action for these oligodeoxynucleotides. These results suggest that altering the level of CaM by using antisense oligodeoxynucleotides targeted to the dominant CaM transcripts in a particular cell type will specifically inhibit their proliferation and, in the case of neuronal cells, alter the course of their differentiation.

Animals↗