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Biomedical subjects

B Weiss

Publications and source records attributed to B Weiss.

At least 37 records · Page 2Linked to original sources
PubMed2000

Differential gene expression by endothelial cells in distinct angiogenic states.

Angiogenesis is a complex process that can be regarded as a series of sequential events comprising a variety of tissue cells. The major problem when studying angiogenesis in vitro is the lack of a model system mimicking the various aspects of the process in vivo. In this study we have used two in vitro models, each representing different and distinct aspects of angiogenesis. Differentially expressed genes in the two culture forms were identified using the suppression subtractive hybridization technique to prepare subtracted cDNA libraries. This was followed by a differential hybridization screen to pick up overexpressed clones. Using comparative multiplex RT-PCR we confirmed the differential expression and showed differences up to 14-fold. We identified a broad range of genes already known to play an important role during angiogenesis like Flt1 or TIE2. Furthermore several known genes are put into the context of endothelial cell differentiation, which up to now have not been described as being relevant to angiogenesis, like NrCAM, Claudin14, BMP-6, PEA-15 and PINCH. With ADAMTS4 and hADAMTS1/METH-1 we further extended the set of matrix metalloproteases expressed and regulated by endothelial cells.

Base Sequence↗
PubMed2000

Seeking care for nonurgent medical conditions in the emergency department: through the eyes of the patient.

INTRODUCTION: The policy goal of shifting nonurgent visits from the emergency department to nonemergency health care settings is commonly devised, planned, and implemented without considering patients' perspectives. The purpose of this study was to gain an understanding of the context in which patients choose to seek health care in an emergency department. Human science provided the framework for this exploratory descriptive research study. METHODS: This study was conducted at an urban, university emergency department in Denver, Colo. Uninsured adult patients triaged as nonurgent who were being discharged home were eligible to participate. Eligible patients from 15 randomly selected shifts were asked to participate. Following their ED visit, open-ended interviews began with the question, "Can you tell me the story, or the chain of events, that led to your coming to the emergency department today?" Each interview was audiotaped. Transcripts were analyzed to identify common themes. Patients also rated their severity of illness from 1 (not severe) to 5 (life-threatening), and they rated their satisfaction with the health care they received from 1 (not satisfied) to 5 (extremely satisfied). RESULTS: The 30 study participants ranged in age from 17 to 60 years; 22 participants (73%) were women. Most patients (73%) rated their severity of illness as 3 or less and their satisfaction with the health care they received as 4 or more (83%). Five themes for seeking care were identified: (1) toughing it out, (2) symptoms overwhelming self-care measures, (3) calling a friend, (4) nowhere else to go, and (5) convenience. Despite the fact that the patients had nonurgent medical problems, their stories revealed that distress in their lives had influenced their need for emergency care. CONCLUSIONS: Access was prominent in the minds of uninsured patients seeking ED care for nonurgent medical diagnoses. Typically, patients did not perceive themselves as having an urgent problem, had been unsuccessful in gaining access to alternative non-ED health care settings, and found the emergency department to be a convenient and quality source of health care. The patients' stories relayed a context for ED visits that goes beyond medical diagnoses. This perspective has important implications for quality care delivery and for including patients in planning ways to access emergency health care.

Adolescent↗
PubMed2000

Flavodoxin mutants of Escherichia coli K-12.

The flavodoxins are flavin mononucleotide-containing electron transferases. Flavodoxin I has been presumed to be the only flavodoxin of Escherichia coli, and its gene, fldA, is known to belong to the soxRS (superoxide response) oxidative stress regulon. An insertion mutation of fldA was constructed and was lethal under both aerobic and anaerobic conditions; only cells that also had an intact (fldA(+)) allele could carry it. A second flavodoxin, flavodoxin II, was postulated, based on the sequence of its gene, fldB. Unlike the fldA mutant, an fldB insertion mutant is a viable prototroph in the presence or absence of oxygen. A high-copy-number fldB(+) plasmid did not complement the fldA mutation. Therefore, there must be a vital function for which FldB cannot substitute for flavodoxin I. An fldB-lacZ fusion was not induced by H(2)O(2) and is therefore not a member of the oxyR regulon. However, it displayed a soxS-dependent induction by paraquat (methyl viologen), and the fldB gene is preceded by two overlapping regions that resemble known soxS binding sites. The fldB insertion mutant did not have an increased sensitivity to the effects of paraquat on either cellular viability or the expression of a soxS-lacZ fusion. Therefore, fldB is a new member of the soxRS (superoxide response) regulon, a group of genes that is induced primarily by univalent oxidants and redox cycling compounds. However, the reactions in which flavodoxin II participates and its role during oxidative stress are unknown.

Bacterial Proteins↗
PubMed2000

FISH deletion mapping defines a single location for the Y chromosome stature gene, GCY.

At least 1 in 1000 males lacks part of the long arm of the Y chromosome. This chromosomal aberration is often associated with short stature and infertility. Deletion mapping and genotype-phenotype analysis have previously defined two non-overlapping critical regions for growth controlling gene(s), GCY(s), on the euchromatic portion of the Y chromosome long arm. These initial mapping assignments were based on the analysis of patients carrying a pure 46,XYq- karyotype as defined by classical cytogenetic karyotyping. Four genes have been assigned to the distal one of the two critical regions. To determine whether one or both of these two critical regions harbours GCY and whether one of the four genes assigned to the distal region is involved in determination of stature, nine adult patients with Yq chromosomal abnormalities were studied in detail. By PCR and FISH analysis, we showed that all patients with a previously defined pure 46,XYq- karyotype are actually mosaics with cells containing an idic(Y) or ring(Y) chromosome in association with 45,X0 cells. This leads us to conclude that (1) FISH is an absolute prerequisite for the correct identification of Y chromosomal rearrangements and (2) only patients with interstitial Y deletions are reliable predictors for the physical location of stature gene(s) on Yq. Our molecular analyses of chromosomes from patients with interstitial Yq deletions finally establishes the proximal interval between markers DYZ3 and DYS11 as the only GCY critical interval. No functional gene has so far been identified in this region adjacent to the centromere.

Adult↗
PubMed2000

The developing brain and the environment: an introduction.

mental retardation: timing and thresholds; (italic)b(/italic)) endocrine dysfunction and developmental disabilities: dose and target implications; (italic)c(/italic)) attention-deficit disorder-ADHD and learning disabilities; and (italic)d(/italic)) new horizons: extending the boundaries. Support for the Rochester conference came from both public and private sources. The National Institute of Environmental Health Sciences (NIEHS), the National Institute of Child Health and Human Development, and the EPA represented the federal government. The conference also received grants from several foundations: the Jennifer Altman Foundation, the Heinz Family Foundation, the National Alliance for Autism Research, the Violence Research Foundation, the Wacker Foundation, and the Winslow Foundation. The second of these conferences helped launch a new Center for Children's Health and the Environment at the Mount Sinai School of Medicine. It was held in New York City on 24-25 May 1999, and was convened specifically to consider the intersection between neurodevelopmental impairment, environmental chemicals, and prevention. Over 300 health scientists, pediatricians, and public health professionals examined the growing body of evidence linking environmental toxins to neurobehavioral disorders. The conference title was Environmental Influences on Children: Brain, Development, and Behavior. The conference began by reviewing well-known examples of deleterious effects of environmental chemicals, including lead and PCBs, on children's brains. The conferees then considered the potential impact of environmental chemicals on neurological disorders with particular focus on ADHD, autism, and Parkinson's disease. The inclusion of Parkinson's disease was intended to signal the notion that exposures in early life may have an influence on the evolution of neurological disease in later life. Support for the Mount Sinai conference came from the Superfund Basic Research Program (NIEHS); The Pew Charitable Trusts; the Institute for Health and the Environment at the University of Albany School of Public Health; the Agency for Toxic Substances and Disease Research (ATSDR); the Ambulatory Pediatric Association; Myron A. Mehlman, PhD; the National Center for Environmental Assessment (EPA); the National Center for Environmental Health (CDC); the National Institute of Child Health and Human Development; the Office of Children's Health Protection (EPA); Physicians for Social Responsibility; The New York Academy of Medicine; The New York Community Trust; and the Wallace Genetic Foundation. The impact of environmental toxins on children's health has become a topic of major concern in the federal government. Eight new research centers in children's environmental health have been established in the past 2 years with joint funding from EPA and NIEHS. Clinical units that specialize in the treatment of children with environmentally induced illness have been developed across the nation with grant support from ATSDR. The American Academy of Pediatrics has just published its (italic)Handbook of Pediatric Environmental Health (/italic)((italic)17(/italic)), the "Green Book," which is available to pediatricians throughout the Americas. Children's environmental health has climbed to a critical position as we launch the new millennium. This monograph marks a significant milestone in the evolution of this emerging discipline.

Brain↗
PubMed2000

Vulnerability of children and the developing brain to neurotoxic hazards.

For much of the history of toxicology, the sensitivity of the developing organism to chemical perturbation attracted limited attention. Several tragic episodes and new insights finally taught us that the course of early brain development incurs unique risks. Although the process is exquisitely controlled, its lability renders it highly susceptible to damage from environmental chemicals. Such disturbances, as recognized by current testing protocols and legislation such as the Food Quality Protection Act, can result in outcomes ranging from death to malformations to functional impairment. The latter are the most difficult to determine. First, they require a variety of measures to assay their extent. Second, adult responses may prove an inadequate guide to the response of the developing brain, which is part of the reason for proposing additional safety factors for children. Third, neuropsychological tests are deployed in complex circumstances in which many factors, including economic status, combine to produce a particular effect such as lowered intelligence quotient score. Fourth, the magnitude of the effect, for most environmental exposure levels, may be relatively small but extremely significant for public health. Fifth, changes in brain function occur throughout life, and some consequences of early damage may not even emerge until advanced age. Such factors need to be addressed in estimating the influence of a particular agent or group of agents on brain development and its functional expression. It is especially important to consider ways of dealing with multiple risks and their combinations in addition to the prevailing practice of estimating risks in isolation.

Brain↗
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↗