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Biomedical subjects

S Weiss

Publications and source records attributed to S Weiss.

At least 127 records · Page 7Linked to original sources
PubMed1999

B cells are programmed to activate kappa and lambda for rearrangement at consecutive developmental stages.

Kappa and lambda, the two types of immunoglobulin light (L) chains present in mammals, contribute differently to the L chain pool of each species. Here we show that the extreme preponderance of kappa in the mouse results from programmed sequential activation of the kappa and lambda loci. Activation--a prerequisite of rearrangement--was monitored by analyzing transcription of unrearranged J-C clusters. Upon in vitro differentiation of a rearrangement-deficient pro/pre-B line, germ-line transcripts of the lambda J-C clusters, that are newly described here, became detectable 2 days later than their counterparts of J-C kappa. Clear differences could also be observed in vivo: germ-line transcripts of kappa were already present in large B220+ CD25+ pre B-II cells whereas germ-line lambda transcripts first became detectable at the consecutive developmental stage of small B220+ CD25+ pre-B-II cells. This activation pattern was found to be identical in mice which can not rearrange kappa due to a targeted deletion or inactivation of kappa. This suggests that pre-B-II cells follow a hit-and-run mechanism of development which includes programmed transitions and differential activation of the L chain loci, i.e. kappa first, then lambda. Thus, privileged activation of kappa might be the decisive factor in setting the 10:1 ratio of kappa to lambda present in the mouse.

Animals↗
PubMed1999

Magnetoencephalographic localization in pediatric epilepsy surgery: comparison with invasive intracranial electroencephalography.

The object of this study was to determine the concordance of the anatomical location of interictal magnetoencephalographic (MEG) spike foci with the location of ictal onset zones identified by invasive ictal intracranial electroencephalographic recordings in children undergoing evaluation for epilepsy surgery. MEG was performed in 11 children with intractable, nonlesional, extratemporal, localization-related epilepsy. Subsequently, chronic invasive intracranial electroencephalographic monitoring was performed by using subdural electrodes to localize the ictal onset zone and eloquent cortex. Based on the invasive monitoring data, all children had excision of, or multiple subpial transections through, ictal onset cortex and surrounding irritative zones. In 10 of 11 patients, the anatomical location of the epileptiform discharges as determined by MEG corresponded to the ictal onset zone established by ictal intracranial recordings. In all children, the anatomical location of the somatosensory hand area, determined by functional mapping through the subdural electrode array, was the same as that delineated by MEG. Nine of 11 patients became either seizure-free or had a greater than 90% reduction in seizures after surgery, with a mean follow-up of 24 months. MEG is a powerful and accurate tool in the presurgical evaluation of children with refractory nonlesional extratemporal epilepsy.

Adolescent↗
PubMed1999

[Fully implantable intramedullary distraction nail in shortening deformity and bone defects. Spectrum of indications].

Since the first clinical experiences with the fully implantable programmable distraction nail nearly ten years ago, the system has been improved in Munich and meanwhile used in 26 patients. During the first 10 cases there has been highest interest in the reliability of the system, while in the following the expansion of indications was more important. At the thigh a good indication beside shortening is the combination of shortening and axis deviation, even if the center of deviation is located near to the knee joint in the supracondylar area. According to preoperative planing the deformity correction can be done acutely while the lengthening procedure follows postoperatively automatically at night-time. If the stabilization with an intramedullary nail is possible, large bone defects can be treated by bone transport using this system also. The fully implantable intramedullary nail has proved its variable functions in cases of large bone defects combined with shortening of the femur. The system is able to perform the bone transport at first and the lengthening procedure automatically without any further operation thereafter.

Accidental Falls↗
PubMed1999

Can subretinal microphotodiodes successfully replace degenerated photoreceptors?

The idea of implanting microphotodiode arrays as visual prostheses has aroused controversy on its feasibility from the moment it appeared in print. We now present results which basically support the concept of replacing damaged photoreceptors with subretinally implanted stimulation devices. Network activity in degenerated rat retinae could be modulated through local electrical stimulation in vitro. We also investigated the long term stability and biocompatibility of the subretinal implants and their impact on retinal physiology in rats. Ganzfeld electroretinograms and histology showed no significant side effect of subretinal implants on retinal function or the architecture of the inner retina.

Animals↗
PubMed1999

Relationships between duration of asthma and asthma severity among children in the Childhood Asthma Management Program (CAMP)

BACKGROUND: Many factors, including heredity, atopic status, and environment, have been implicated in the determination of asthma severity. Relatively little is known about the degree to which asthma duration influences asthma severity. OBJECTIVE: The Childhood Asthma Management Program (CAMP), consisting of 1041 children (age 8. 9 +/- 2.1 years at enrollment) with mild-to-moderate asthma, offers an opportunity to examine the relationship between asthma duration and asthma severity. METHODS: By using the extensive CAMP baseline cross-sectional data on asthma duration, spirometry, bronchial responsiveness, symptomatology, and markers of atopy, univariate and multivariate regression models were used to evaluate whether asthma duration is associated with asthma severity. RESULTS: Duration of asthma in the study cohort from time of diagnosis until randomization into CAMP ranged from 0.3 to 12.1 years (mean, 5.0; SD, 2.7; median, 4.8). Asthma duration is associated in univariate analyses both with lower levels of several lung functions (P <.001), including methacholine bronchial reactivity (natural log [ln] FEV1 PC20, mg/mL; r = -0.112), prebronchodilator and postbronchodilator percent predicted FEV1 (r = -0.176 and r = -0.130, respectively), and prebronchodilator and postbronchodilator FEV1 /forced vital capacity (FVC) (%) (r = -0.237 and r = -0.211, respectively), as well as higher levels of symptoms (symptom score: r = 0.147, P <. 001) and borderline greater use of albuterol for symptoms (r = 0.058, P =.064) during a 28-day screening period before randomization. Simple linear regression detected the following differences in lung functions per year of asthma duration: ln FEV1 PC20, -0.050 mg/mL/y; prebronchodilator FEV1, -0.907 percent predicted/y; and prebronchodilator FEV1 /FVC, -0.729 percent predicted/y. After controlling for potential explanatory variables (atopy, inflammatory markers, household Der p 1 levels, anti-inflammatory medication use, and clinical center), regression models revealed that the duration of asthma remained significantly and independently associated with ln FEV1 PC20 (P =.004), prebronchodilator percent predicted FEV1 (P =.043), and prebronchodilator and postbronchodilator FEV1 /FVC (%) (P <.001), as well as being positively associated with mean daily symptom score (P <.001) and albuterol use for symptoms (P =.003) during a 28-day screening period. Duration was also found to be significantly associated with physician/nurse assessment of asthma severity and other historical measures of medication use. CONCLUSIONS: These data demonstrate that asthma duration is associated with lower lung function, greater methacholine responsiveness, more asthma symptomatology, and greater use of as-needed albuterol, which are all measures of asthma severity. As such, early diagnosis and intervention may be necessary to ameliorate these adverse effects of persistent asthma.

Adrenergic beta-2 Receptor Agonists↗
PubMed1999

Projection-reconstruction reduced [correction of reduces] FOV imaging.

Reduced field-of-view (rFOV) imaging was introduced recently as a rapid imaging technique that improves temporal resolution while maintaining spatial resolution. It is based on undersampling in k-space and utilizes the fact that the dynamics of an evolving process are often confined to a local area within the full FOV. In the work presented here the reduced FOV approach is applied to projection-reconstruction MRI and compared to the original spin-warp implementation. Results are presented that clearly demonstrate the increased robustness of the projection-reconstruction version of rFOV imaging. The technique is successfully applied to an MR-guided biopsy scenario (ex-vivo) and to cine cardiac imaging. Finally an algorithm is proposed that uses the intrinsic advantages of radial k-space sampling to evaluate the projection data to control the adjustment of position and size of the reduced FOV window.

Algorithms↗
PubMed1999

Rapid onset of control with budesonide Turbuhaler in patients with mild-to-moderate asthma.

BACKGROUND: Budesonide (Pulmicort) is an inhaled corticosteroid with high topical potency but low systemic activity. Turbuhaler is a novel breath-actuated, multi-dose, dry-powder inhaler. OBJECTIVES: This study was conducted to determine the efficacy and safety of two different dose regimens of budesonide Turbuhaler, compared with placebo, in adult patients with mild-to-moderate asthma not well-controlled with bronchodilator therapy. METHODS: This double-blind, randomized, placebo-controlled, parallel-group, multicenter study compared the efficacy and safety of 200 microg and 400 microg of budesonide, administered twice daily via Turbuhaler, with placebo, in 273 adult patients (aged 19 to 70 years) with mild-to-moderate asthma (FEV1 67% of predicted normal), not well-controlled with bronchodilator therapy. Efficacy was assessed by pulmonary function tests and patient assessments of asthma symptom control. Safety was assessed in terms of adverse events, laboratory evaluations, and physical examinations. RESULTS: Two hundred and 400 microg of budesonide bid were significantly more effective than placebo at improving morning PEF (mean differences from placebo of 43.63 L/min and 40.10 L/min, respectively; P < .001) and FEV1 (mean differences from placebo of 0.44 L, and 0.50 L, respectively; P < .001) over the 12-week treatment period. Onset of action as assessed by morning PEF was within two days. Basal and stimulated plasma cortisol concentrations were not significantly affected by budesonide treatment compared with placebo. CONCLUSIONS: Treatment of adults suffering from mild-to-moderate asthma with budesonide Turbuhaler is well tolerated and results in a rapid onset of asthma control which is maintained over time.

Administration, Inhalation↗
PubMed1999

Role of the 37 kDa laminin receptor precursor in the life cycle of prions.

Prions are thought to consist of infectious proteins that cause, in the absence of detectable nucleic acid, a group of fatal neurodegenerative diseases, called transmissible spongiform encephalopathies (TSE). Among these diseases are bovine spongiform encephalopathy (BSE), scrapie of sheep and Creutzfeldt-Jakob disease (CJD) in humans. They occur as sporadic, infectious or genetic disorders and have in common the accumulation of an abnormal, pathogenic isoform of the cellular prion protein PrPc which is converted in a post-translational process into PrPSc concomitant with conformational changes of the protein. During this process PrPc acquires a high beta-sheet content and becomes partially resistant to proteases. The mechanism of this conversion as well as the physiological function of the cellular prion protein PrPc are poorly understood, but studies employing PrP knock-out mice demonstrated that PrPc is required for the development of prion diseases. The involvement of co-factors such as chaperones, receptors or an unknown protein, designated "protein X" in the conversion process are discussed. In a yeast two-hybrid screen we have identified the 37 kDa laminin receptor precursor (LRP) as an interactor of the cellular prion protein and this interaction could be confirmed by co-infection and co-transfection studies in mammalian and insect cells. LRP evolved from the ribosomal protein p40 essential for protein synthesis lacking any laminin binding activity to a cell surface receptor binding laminin, elastin and carbohydrates. The gene encoding 37 kDa LRP/p40 has been identified in a variety of species including the sea urchin Urechis caupo, Chlorohydra viridissima, the archaebacterium Haloarcula marismortui, the yeast Saccharomyces cerevisiae as well as in mammals where it is highly conserved. LRP works as a receptor for alphaviruses and is associated with the metastatic potential of solid tumors where it was first identified. The 37 kDa LRP forms its mature 67 kDa isoform with high laminin binding capacity by an unknown mechanism involving acylation. The multifunctionality of LRP as a ribosomal protein and a cell surface receptor for infectious agents such as viruses and prions might be extended by additional properties.

Animals↗
PubMed1999

Substance abuse studies and prevention efforts among Arabs in the 1990s in Israel, Jordan and the Palestinian Authority--a literature review.

This paper is the result of a collaborative project of Israeli, Jordanian and Palestinian scientists gathered to reveal the current extent of substance abuse and efforts at prevention among Arabs in Israel, Jordan and the Palestinian Authority territories, in order to identify needs and suggest future collaborative activities and directions for regional cooperation. The article provides data and covers the current state of substance abuse prevention and research among Moslems, Christians and Druze in the trilateral region in the 1990s by reviewing prevention materials and studies published in the professional literature, as well as in reports and Doctoral and Master's theses in Arabic, which have been located in academic libraries and other institutions, in the framework of a comprehensive search. This manuscript is the first to summarize Jordanian and Palestinian findings in the substance abuse domain. The review shows that most of the Israeli research in the Arab sector deals with alcohol use among youth, that the majority of Jordanian studies focus on illicit drug use, that the research among Palestinians is in its infancy, and that comprehensive prevention programs are lacking in the trilateral region. It describes the key results of most of the 12 Israeli studies among Arabs, 11 Jordanian studies and four Palestinian studies. It reveals that drug abuse among Israeli Arab students is probably more prevalent than among Jewish adolescents, that the typical Jordanian drug addict has a higher level of education than the typical Palestinian drug addict, and that the Palestinian is more likely to be a multiple drug user. Recommendations for future activities include organization of a regional collaborative workshop in order to establish data collection systems for basic statistics relevant to drug abuse and development of comprehensive prevention programs, as well as studies in the substance abuse domain concerning knowledge, attitudes and behavior among the general Arab population.

Arabs↗
PubMed1999

How good is the match between the plane of the text and the plane of focus during reading?

Because results from animal models demonstrate that retinal image defocus is a crucial factor in the visual control of eye growth, we have measured the precision of accommodation during reading at 1 m and at 30 cm distance. A newly developed photorefractor was used to sample both the refraction in the vertical meridian and direction of gaze at 25 Hz. Using these two parameters, a three-dimensional "refraction map" of the visual field was plotted. It showed the optic disc as an area with more myopic refractions and the course of refractions across a visual field of about +/- 25 deg. A special calibration scheme was employed to ensure that the precision of the refractions was 0.2 dpt or better (as estimated from the standard deviations of repeated measurements and the noise in the calibration curve). Twelve young adults (students from the lab) served as subjects. We found considerable inter-individual variability in the off-axis refractions but little variability among repeated measurements in the same subjects. Inter-individual variability reached a minimum in the foveal region. Both myopes wearing their spectacle corrections (n = 6) and emmetropes (n = 6) under-accommodated by about 0.3 D during reading at 30 cm distance but, at 1 m distance, only the emmetropes under-accommodated. Since both refraction groups under-accommodated similarly during reading at close distance, it remains unclear whether the small amount of defocus is critical for their future myopia development. Either accommodation errors differ at earlier times when myopia first appears (as suggested by the literature), or the subjects' eye growth was differently sensitive to defocus, or our simple protocol did not pick up existent differences in accommodation among the two groups.

Accommodation, Ocular↗
PubMed1999

An extreme-sib-pair genome scan for genes regulating blood pressure.

Hypertension, a risk factor for many cardiovascular, cerebrovascular, and renal diseases, affects one in four Americans, at an annual cost of>$30 billion. Although genetic mutations have been identified in rare forms of hypertension, including Liddle syndrome and glucocorticoid-remediable aldosteronism, the abundance of plausible candidate genes and potential environmental risk factors has complicated the genetic dissection of more prevalent essential hypertension. To search systematically for chromosomal regions containing genes that regulate blood pressure, we scanned the entire autosomal genome by using 367 polymorphic markers. Our study population, selected from a blood-pressure screen of >200,000 Chinese adults, comprises rare but highly efficient extreme sib pairs (207 discordant, 258 high concordant, and 99 low concordant) and all but a single parent of these sibs. By virtue of the sampling design, the number of sib pairs, and the availability of genotyped parents, this study represents one of the most powerful of its kind. Although no regions achieved a 5% genomewide significance level, maximum LOD-score values were >2.0 (unadjusted P<.001) for regions containing five markers (D3S2387, D11S2019, D15S657, D16S3396, and D17S1303), in our primary analysis. Other promising regions identified through secondary analyses include loci near D4S3248, D7S2195, D10S1423, D20S470, D20S482, D21S2052, PAH, and AGT.

Adolescent↗
PubMed1999

Distribution of dinucleotide microsatellites in the Drosophila melanogaster genome.

Microsatellites, a special class of repetitive DNA, have become one of the most popular genetic markers. The progress of various genome projects has made it possible to study the genomic distribution of microsatellites and to evaluate the potential influence of several parameters on their genesis. We report the distribution of dinucleotide microsatellites in the genome of Drosophila melanogaster. When considering only microsatellites with five or more repeat units, the average length of dinucleotide repeats in D. melanogaster is 6.7 repeats. We tested a wide range of parameters which could potentially influence microsatellite density, and we did not detect a significant influence of recombination rate, number of exons, or total length of coding sequence. In concordance with the neutral expectation for the origin of microsatellites, a significant positive correlation between AT content and (AT/TA)n microsatellite density was detected. While this pattern may indicate that microsatellite genesis is a random process, we also found evidence for a nonrandom distribution of microsatellites. Average microsatellite density was higher on the X chromosome, but extreme heterogeneity was observed between different genomic regions. Such a clumping of microsatellites was also evident on a more local scale, as 38.9% of the contiguous sequences analyzed showed a deviation from a random distribution of microsatellites.

Animals↗
PubMed1999

Ketorolac versus acetaminophen for treatment of acute fever in the emergency department.

BACKGROUND: The purpose of this preliminary study was to compare acetaminophen to ketorolac for treating patients with fever in the emergency department (ED). METHODS: In this prospective, randomized, double-blind pilot study, patients were enrolled as a convenience sample during a 6-month study period. All subjects 18 years or older with a temperature of 100.4 degrees F or higher were eligible. Investigators gave patients 10 mg of oral ketorolac or 750 mg of oral acetaminophen. The temperature and pulse were rechecked at 30, 60, and 90 minutes. Patients recorded discomfort on a visual analog scale (VAS) at 30, 60, and 90 minutes. RESULTS: A total of 17 patients were enrolled. A t test showed no difference in temperatures, and the Mann-Whitney nonparametric test showed no difference in VAS scores. CONCLUSION: In this preliminary study comparing ketorolac with acetaminophen for febrile illness in the ED, we found no difference in efficacy between the two medications.

Acetaminophen↗
PubMed1999

Role of Listeria monocytogenes exotoxins listeriolysin and phosphatidylinositol-specific phospholipase C in activation of human neutrophils.

Polymorphonuclear leukocytes (PMN) are essential for resolution of infections with Listeria monocytogenes. The present study investigated the role of the listerial exotoxins listeriolysin (LLO) and phosphatidylinositol-specific phospholipase C (PlcA) in human neutrophil activation. Different Listeria strains, mutated in individual virulence genes, as well as purified LLO were used. Coincubation of human neutrophils with wild-type L. monocytogenes provoked PMN activation, occurring independently of phagocytosis events, with concomitant elastase secretion, leukotriene generation, platelet-activating factor (PAF) synthesis, respiratory burst, and enhanced phosphoinositide hydrolysis. Degranulation and leukotriene formation were noted to be solely dependent on LLO expression, as these features were absent when the LLO-defective mutant EGD- and the avirulent strain L. innocua were used. These effects were fully reproduced by a recombinant L. innocua strain expressing LLO (INN+) and by the purified LLO molecule. LLO secretion was also required for PAF synthesis. However, wild-type L. monocytogenes was more potent in eliciting PAF formation than mutants expressing LLO, suggesting the involvement of additional virulence factors. This was even more obvious for phosphoinositide hydrolysis and respiratory burst: these events were provoked not only by INN+ but also by the LLO-defective mutant EGD- and by a recombinant L. innocua strain producing listerial PlcA. We conclude that human neutrophils react to extracellularly provided listerial exotoxins by rapid cell activation. Listeriolysin is centrally involved in triggering degranulation and lipid mediator generation, and further virulence factors such as PlcA apparently contribute to trigger neutrophil phosphoinositide hydrolysis and respiratory burst. In this way, listerial exotoxins may influence the host defense against infections with L. monocytogenes.

Bacterial Toxins↗
PubMed1999

Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K protein.

Pycnodyostosis, an autosomal recessive osteosclerosing skeletal disorder, has recently been shown to result from mutations in the cathepsin K gene. Cathepsin K, a lysosomal cysteine protease with an abundant expression in osteoclasts, has been implicated in osteoclast-mediated bone resorption and remodeling. DNA sequence analysis of the cathepsin K gene in a nonconsanguineous family demonstrated compound heterozygozity for mutations in two affected siblings. We have identified a missense mutation with a single base G-->A transition at cDNA nucleotide 236, resulting in conversion of a conserved glycine to a glutamine residue (G79E). The other mutation is an A-->T transition at nucleotide 154, leading to the substitution of a lysine residue by a STOP codon (K52X) predicting premature termination of the precursor cathepsin K polypeptide. Sequencing of genomic and cDNAs from the parents demonstrated that the missense mutation was inherited from the father and the nonsense mutation from the mother. Protein expression in both affected children was virtually absent, while in the parents was reduced by 50-80% compared with controls. The protein studies demonstrate that even significantly reduced cathepsin K levels do not have any phenotypic effect, whereas absent cathepsin K results in pycnodysostosis.

Cathepsin K↗
PubMed1999

Attitudes of Israeli Jewish and Arab high school students toward alcohol control measures.

This article describes a study carried out in the winter of 1997 in order to determine the attitudes of 2,186 adolescents of four religions in the north of Israel toward eight alcohol control measures: Taxation on alcohol, age limit for buying alcohol, restrictions on types of outlets which are allowed to sell alcohol to minors, restrictions on opening hours of pubs, restrictions on advertising of alcohol, limit of blood level of alcohol when driving, the authority of policemen concerning the testing of drunk drivers, and restrictions on roadside alcohol outlets. Findings indicate that the majority of the respondents tend to enhance alcohol control measures pertaining to alcohol and driving issues, but only about a third of the participants tend to enhance alcohol control measures in the other domains. In addition, Arabs tend to favor restrictive attitudes toward alcohol control measures in comparison with Jews, and Arab females tend to favor such attitudes more than Arab males. Implications for prevention and effective alcohol policy are discussed.

Adolescent↗