Search PubMed⌕ Search

Biomedical subjects

S Weiss

Publications and source records attributed to S Weiss.

At least 109 records · Page 6Linked to original sources
PubMed2000

Laboratory, clinical, and kindergarten test of a new eccentric infrared photorefractor (PowerRefractor).

PURPOSE: Photorefraction is a convenient way to determine refractive state from a distance. It is, therefore, useful for measuring infants and noncooperative subjects. However, its reliability (or precision) and accuracy (or validity) has been questioned. In a study in subjects without cycloplegia, we have tested whether, after complete automatization, eccentric photorefraction at a 1-m distance can be as reliable as a common autorefractor. METHODS: In a laboratory study of 15 student subjects without the use of cycloplegia (30 eyes, refractive errors ranging from -6 D to +6 D), age 25 to 31 years, the photorefractive measurements were compared with spectacle prescriptions. In a clinical study, photorefraction, autorefraction, and subjective refraction were performed in 40 patients without cycloplegia (refractive errors ranging from -4 D to +4 D), most of them with various ocular pathologies. Subjective refractions were obtained by an experienced clinical ophthalmologist but were not accessible to the examiner who used the two refractors. Visual acuity was 20/20 or better except for five subjects. Ages ranged from 6 to 75 years. In the kindergarten screening study, 108 children aged 3 to 6 years were screened for refractive errors. RESULTS: In the laboratory study, it was found that the mean difference between spectacle prescription and PowerRefractor measurements was < 0.6 D for spheres and below 0.4 D for cylinders. In the clinical study, data were obtained by all three procedures in 78 eyes. The photorefractor and the autorefractor performed similarly for spheres (mean absolute dioptric difference between refractor and subjective measure: 0.593 D and 0.696 D) and cylinders (mean absolute dioptric differences: 0.399 D and 0.389 D). However, the photorefractor was superior with regard to the measurement of the magnitude and axis of astigmatism (mean weighted difference between objective and subjective axis 0.644 D and 0.769 D, respectively). In the kindergarten study, it was found that the PowerRefractor was very convenient to handle. The autorefractor measured more myopic refractions than the PowerRefractor (mean of the left eyes 0.11 +/- 1.1 D vs. 0.62 +/- 0.53 D, p < 0.001). There was no indication that the PowerRefractor failed to detect hyperopia, because all but one child with more than 2 D of hyperopia measured with autorefractor (n = 7) was also hyperopic with the PowerRefractor. Furthermore, presenting an interesting fixation target at a 3-m distance did not cause more hyperopic refractions, indicating that the camera of the PowerRefractor at a 1-m distance was not a significant stimulus to accommodation. CONCLUSIONS: The PowerRefractor was shown to have comparable or slightly better reliability and accuracy than a modern autorefractor; however, it has major advantages over current autorefractors in that it is faster, measures both eyes at once, and gives interpupillary distance, pupil size, and information on the alignment of the eyes at the same time.

Adolescent↗
PubMed2000

Oral delivery of DNA vaccines using attenuated Salmonella typhimurium as carrier.

The efficacious delivery of eukaryotic expression plasmids to inductive cells of the immune system constitutes a key prerequisite for the generation of effective DNA vaccines. Here, we have explored the use of bacteria as vehicles to orally deliver expression plasmids. Attenuated Salmonella typhimurium aroA harbouring eukaryotic expression plasmids that encoded virulence factors of Listeria monocytogenes were administered orally to BALB/c mice. Strong cytotoxic and helper T cell responses as well as antibody production were elicited even after a single administration. Mice immunised four times with Salmonella that carried a eukaryotic expression plasmid encoding the secretory listerial protein listeriolysin were protected against a subsequent lethal challenge with this pathogen. A single dose was already partially protective. The efficiency of this vaccination procedure was due to transfer of the expression plasmid from the bacterial carrier to the mammalian host. Evidence for such an event could be obtained in vivo and in vitro. Expression of the desired antigen in various lymphoid tissues was already detectable 1 day after administration of the DNA vaccine and persisted for at least 1 month in spleen and mesenteric lymph nodes. Induction of cytotoxic and helper T cell responses was observed in all mouse strains tested including outbred strains whereas antibodies were mainly detected in BALB/c. Furthermore, we could show that immunogenicity could be improved by increasing the invasiveness of the bacterial carrier.

Administration, Oral↗
PubMed2000

Second generation to Holocaust survivors: enhanced differentiation of trauma transmission.

"Second generation to Holocaust Survivors" is a description of a segment of society, as well as an attempt at characterizing these individuals. It is common to speak of mechanisms of transmission of trauma as characterizing the dynamics of the second generation. This paper intends to advance differentiation between two kinds of transmission of trauma: direct transmission (also called transposition) and indirect transmission. There seems to be some confusion in this realm, since there is some discrepancy between clinical and the experimental publications: Whereas the first usually presents evidence of direct transmission of trauma in the second generation, the second mostly demonstrates indirect transmission. We shall present a clinical account of group therapy demonstrating indirect transmission, proposing a distinction between second-generation individuals owing to the relative dominance of each of the mechanisms in their mental structuring. This distinction has significant clinical consequences.

Adult↗
PubMed2000

Biological variability of serum and urinary N-telopeptides of type I collagen in postmenopausal women.

Measurement of N-telopeptides of type I bone collagen (NTX) provides a specific indicator of the current level of bone resorption. The biological intrasubject variability of NTX in urine and serum was studied in 277 postmenopausal women, mean age, 63.6 years +/- 10.2 (+/-SD) years. Second-morning void urine and serum specimens were collected at baseline and for two consecutive days to determine short-term variability (% CV). Long-term variability was determined by comparing NTX results at baseline and two consecutive months. Subjects were instructed to maintain current diet, lifestyle, and medications during the study. The median short-term %CV was 13.1% for urine NTX. This compared with 6.3% for serum NTX. Calculation of long-term %CV showed similar trends, with the %CV for NTX measured in serum (7.5%) lower than when measured in urine (15.6%). Using the least significant change (LSC) calculation, our data show that to be 90% confident that a decrease in NTX after initiation of antiresorptive therapy in an individual patient is not caused by variability alone, a 31 % decrease in urine NTX and a 14% decrease in serum NTX is required. As reported changes in NTX caused by antiresorptive therapy are greater than these calculations; our results support the use of either specimen to measure NTX to monitor the effect of therapy.

Aged↗
PubMed2000

LHRH might act as a negative autocrine regulator of proliferation of human ovarian cancer.

OBJECTIVE: More than 80% of human ovarian cancers express LHRH and its receptor. The proliferation of human ovarian cancer cell lines is reduced by both LHRH agonists and antagonists. This study was designed to further clarify the possible biological function of this LHRH system. DESIGN: As LHRH agonists and antagonists uniformly reduce proliferation of human ovarian cancer in a dose-dependent way, the effect of low concentrations of authentic LHRH was studied. In addition, longer periods of treatment (up to 9 days) were analyzed. To assess the physiological role of LHRH produced by ovarian cancer cells it was neutralized by adequate concentrations of a specific LHRH antiserum. METHODS: Human ovarian cancer cells EFO-21 and EFO-27, which express LHRH and its receptor, were incubated for 1-9 days with increasing concentrations (1pmol/l to 10 micromol/l) of authentic LHRH or with concentrations of LHRH antiserum capable of neutralizing at least 1nmol/l LHRH. Proliferation was assessed by counting cells. RESULTS AND CONCLUSIONS: Authentic LHRH reduced time- and dose-dependently proliferation (by maximally mean+/-s.e.m. 32.7 +/- 4.4%, Newman-Keuls, P < 0.001) of both ovarian cancer cell lines. At very low concentrations (1pmol/l) a marginal reduction of proliferation or no effect was observed. A mitogenic effect of authentic LHRH was never detected. Treatment of ovarian cancer cell cultures with antiserum to LHRH significantly increased (up to mean+/-s.e.m. 121.0 +/- 2.8% of controls, Newman-Keuls P <0.001) proliferation of EFO-21 and EFO-27 cells. These findings suggest that LHRH produced by human ovarian cancer cells might act as a negative autocrine regulator of proliferation.

Adenocarcinoma, Mucinous↗
PubMed2000

Effect of low level lead exposure on hyperuricemia and gout among middle aged and elderly men: the normative aging study.

OBJECTIVE: To determine whether longterm lead accumulation is associated with hyperuricemia and gouty arthritis among middle aged and elderly men. METHODS: In a retrospective cohort study, 777 male participants were evaluated between August 1991 and October 1996 in the Department of Veterans Affairs Normative Aging Study, a 35 year longitudinal study of aging. We examined the development of gout and an increased uric acid level in relation to lead, adjusting for other known risk factors. Lead levels were measured in blood and by K x-ray fluorescence (K-XRF) technique in tibial (cortical) and patellar (trabecular) bone. RESULTS: Blood lead levels in this mostly Caucasian (97%) population were low (mean 5.9 microg/dl, SD 3.5). Bone lead levels were comparable to those described in other general populations. In a multivariate analysis adjusting for the risk factors, age, body mass index, diastolic blood pressure, alcohol intake, and serum creatinine level, there was a positive association between patellar bone lead and uric acid levels (p = 0.02). Of 777 participants, 52 (6.7%) had developed gouty arthritis. In logistic regression of similar covariates, body mass index (p < 0.0001) and serum creatinine level (p = 0.005) were the strongest determinants of gout; neither bone nor blood lead levels predicted gout in this cohort. CONCLUSION: The longterm accumulation of lead is associated with an increased uric acid level in middle aged and elderly men. However, this study shows no association between lead and gouty arthritis at the levels arising from community exposure.

Age Factors↗
PubMed1999

Adaptive phase estimation and its application in EEG analysis of word processing.

Oscillations are a general phenomenon of neuronal activity during information processing. Mostly, widespread networks are involved in brain functioning. In order to investigate network activity coherence analysis turned out to be a useful tool for examining the functional relationship between different cortical areas. This parameter allows the investigation of synchronisation phenomena with regard to defined frequencies or frequency bands. Coherence and cross phase are closely connected spectral parameters. Coherence may be understood as a measure of phase stability. Whereas coherence describes the amount of information transfer, the corresponding phase, from which time delays can be computed, hints at the direction of information transfer. Mental processes can be very brief and coupling between different areas may be highly dynamic. For this reason a two-dimensional approach of adaptive filtering was developed to estimate coherence and phase continuously in time. Statistical and dynamic properties of instantaneous phase are discussed. In order to demonstrate the value of this method for studying higher cognitive processes the method was applied to EEG recorded during word processing. During visual presentation of abstract nouns an information transfer from visual areas to frontal association areas in the Alpha1 frequency band could be verified within the first 400 ms. The Alpha1 band predominately seems to reflect sensory processing and attentional processes. In addition to conventional coherence analyses during word processing phase estimations may yield valuable new insights into the physiological mechanisms during word processing.

Adult↗
PubMed1999

The conserved undecapeptide shared by thiol-activated cytolysins is involved in membrane binding.

Thiol-activated cytolysins share a conserved hydrophobic, Trp-rich undecapeptide that is suggested to be involved in membrane binding and intercalation. The neutralizing monoclonal antibody PLY-5 recognizes all members of this toxin family and peptide mapping assigned its epitope to the undecapeptide motif. This antibody inhibited binding of the toxins to host cell membranes and the epitope was no longer available for binding when a preformed toxin/membrane complex was tested. These results confirm the model of cytolysin binding suggested by structural data.

Amino Acid Sequence↗
PubMed1999

Carotenoid-binding sites of the major light-harvesting complex II of higher plants.

Recombinant light-harvesting complex II (LHCII) proteins with modified carotenoid composition have been obtained by in vitro reconstitution of the Lhcb1 protein overexpressed in bacteria. The monomeric protein possesses three xanthophyll-binding sites. The L1 and L2 sites, localized by electron crystallography in the helix A/helix B cross, have the highest affinity for lutein, but also bind violaxanthin and zeaxanthin with lower affinity. The latter xanthophyll causes disruption of excitation energy transfer. The occupancy of at least one of these sites, probably L1, is essential for protein folding. Neoxanthin is bound to a distinct site (N1) that is highly selective for this species and whose occupancy is not essential for protein folding. Whereas xanthophylls in the L1 and L2 sites interact mainly with chlorophyll a, neoxanthin shows strong interaction with chlorophyll b, inducing the hyperchromic effect of the 652 nm absorption band. This observation explains the recent results of energy transfer from carotenoids to chlorophyll b obtained by femtosecond absorption spectroscopy. Whereas xanthophylls in the L1 and L2 sites are active in photoprotection through chlorophyll-triplet quenching, neoxanthin seems to act mainly in (1)O(2)(*) scavenging.

Binding Sites↗
PubMed1999

Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects.

OBJECTIVES: To compare colesevelam hydrochloride (Cholestagel), a nonabsorbed hydrogel with bile acid-sequestering properties, with placebo for its lipid-lowering efficacy, its effects on laboratory and clinical safety parameters, and the incidence of adverse events. METHODS: Following diet and placebo lead-in periods, placebo or colesevelam was administered at 4 dosages (1.5, 2.25, 3.0, or 3.75 g/d) for 6 weeks with morning and evening meals to men and women with hypercholesterolemia (low-density lipoprotein cholesterol level >4.14 mmol/L [>160 mg/dL]). Patients returned to the clinic every 2 weeks throughout the treatment period for lipid parameter measurements and adverse event assessments. Samples were collected for serum chemistry profiles, hematologic studies, coagulation studies, and vitamin level assessment at baseline and after 6 weeks of treatment. RESULTS: Among the 149 patients randomized, 137 completed the study. Low-density lipoprotein cholesterol concentrations decreased in a dosage-dependent manner by 0.11 mmol/L (4.2 mg/dL) (1.8%) in the 1.5-g/d colesevelam treatment group and up to 1.01 mmol/L (39 mg/dL) (19.1%) in the 3.75-g/d colesevelam treatment group. Low-density lipoprotein cholesterol concentrations at the end of treatment were significantly reduced from baseline levels in the 3.0- and 3.75-g/d colesevelam treatment groups (P = .01 and P<.001, respectively). Total cholesterol levels demonstrated a similar response to colesevelam treatment, with an 8. 1% decrease from baseline in the 3.75-g/d treatment group (P<.001). High-density lipoprotein cholesterol levels rose significantly in the 3.0- and 3.75-g/d colesevelam treatment groups, by 11.2% (P=.006) and 8.1% (P=.02), respectively. Median triglyceride levels did not change from baseline, nor were there any significant differences between treatment groups. The incidence of adverse events was similar among all groups. CONCLUSIONS: Colesevelam therapy is effective for lowering low-density lipoprotein cholesterol concentrations in persons with moderate hypercholesterolemia. It lacks the constipating effect of other bile acid sequestrants, demonstrating the potential for increased compliance.

Adult↗
PubMed1999

Generation of tyrosine hydroxylase-producing neurons from precursors of the embryonic and adult forebrain.

We have explored the plastic ability of neuronal precursors to acquire different identities by manipulating their surrounding environment. Specifically, we sought to identify potential signals involved in the specification of forebrain dopaminergic neurons. Here we describe culture conditions under which tyrosine hydroxylase (TH) expression is induced in neuronal precursors, which were derived directly from the embryonic striatum and adult subependyma (SE) of the lateral ventricle or generated from multipotent forebrain stem cells. TH was successfully induced in all of these cell types by 24 hr exposure to basic fibroblast growth factor (FGF2) and glial cell conditioned media (CM). The greatest magnitude of the inductive action was on embryonic striatal precursors. Although FGF2 alone induced limited TH expression in striatal cells (1.1 +/- 0.2% of neurons), these actions were potentiated 17.5-fold (19.6 +/- 1.5% of neurons) when FGF2 was coadministered with B49 glial cell line CM. Of these TH-immunoreactive cells, approximately 15% incorporated bromodeoxyuridine (BrdU), indicating that they were newly generated, and 95% coexpressed the neurotransmitter GABA. To investigate whether precursors of the adult forebrain subependyma were competent to respond to the instructive actions of FGF2+CM, they were first labeled in vivo with a pulse of BrdU. Although none of the cells expressed TH in control, 0.2% of total cells showed TH immunoreactivity in FGF2+CM-treated cultures. Under these same conditions only, in vitro-generated precursors from epidermal growth factor-responsive stem cells exhibited TH expression in 10% of their total neuronal progeny. Regulation of neurotransmitter phenotype in forebrain neuronal precursors, by the synergistic action of FGF2 and glial-derived diffusible factors, may represent a first step in understanding how these cells are generated in the embryonic and adult brain and opens the prospect for their manipulation in vitro and in vivo for therapeutic use.

Animals↗
PubMed1999

Complex behavioral strategy and reversal learning in the water maze without NMDA receptor-dependent long-term potentiation.

Successful performance of the water maze task requires that rats learn complex behavioral strategies for swimming in a pool of water, searching for and interacting with a hidden platform before its spatial location can be learned. To evaluate whether NMDA receptor-dependent long-term potentiation (NMDA-LTP) is required for learning the required behavioral strategies, rats with NMDA-LTP blocked by systemic pharmacological treatment were trained in the behavioral strategies using simplified and stepwise training methods. Despite the blockade of NMDA-LTP in the dentate gyrus and hippocampal area CA1, rats learned the required behavioral strategies and used them to learn both initial and reversed platform locations. This is the first evaluation of the role of NMDA-LTP specifically in behavioral strategy learning. Although hippocampal NMDA-LTP might contribute to the water maze task, this form of LTP is not essential for learning complex behavioral strategies or multiple hidden platform locations.

Animals↗
PubMed1999

Single-pair fluorescence resonance energy transfer on freely diffusing molecules: observation of Förster distance dependence and subpopulations.

Photon bursts from single diffusing donor-acceptor labeled macromolecules were used to measure intramolecular distances and identify subpopulations of freely diffusing macromolecules in a heterogeneous ensemble. By using DNA as a rigid spacer, a series of constructs with varying intramolecular donor-acceptor spacings were used to measure the mean and distribution width of fluorescence resonance energy transfer (FRET) efficiencies as a function of distance. The mean single-pair FRET efficiencies qualitatively follow the distance dependence predicted by Förster theory. Possible contributions to the widths of the FRET efficiency distributions are discussed, and potential applications in the study of biopolymer conformational dynamics are suggested. The ability to measure intramolecular (and intermolecular) distances for single molecules implies the ability to distinguish and monitor subpopulations of molecules in a mixture with different distances or conformational states. This is demonstrated by monitoring substrate and product subpopulations before and after a restriction endonuclease cleavage reaction. Distance measurements at single-molecule resolution also should facilitate the study of complex reactions such as biopolymer folding. To this end, the denaturation of a DNA hairpin was examined by using single-pair FRET.

DNA↗
PubMed1999

Fluorescence spectroscopy of single biomolecules.

Recent advances in single-molecule detection and single-molecule spectroscopy at room temperature by laser-induced fluorescence offer new tools for the study of individual macromolecules under physiological conditions. These tools relay conformational states, conformational dynamics, and activity of single biological molecules to physical observables, unmasked by ensemble averaging. Distributions and time trajectories of these observables can therefore be measured during a reaction without the impossible need to synchronize all the molecules in the ensemble. The progress in applying these tools to biological studies with the use of fluorophores that are site-specifically attached to macromolecules is reviewed.

DNA↗
PubMed1999

Single-molecule fluorescence spectroscopy of enzyme conformational dynamics and cleavage mechanism.

Fluorescence resonance energy transfer and fluorescence polarization anisotropy are used to investigate single molecules of the enzyme staphylococcal nuclease. Intramolecular fluorescence resonance energy transfer and fluorescence polarization anisotropy measurements of fluorescently labeled staphylococcal nuclease molecules reveal distinct patterns of fluctuations that may be attributed to protein conformational dynamics on the millisecond time scale. Intermolecular fluorescence resonance energy transfer measurements provide information about the dynamic interactions of staphylococcal nuclease with single substrate molecules. The experimental methods demonstrated here should prove generally useful in studies of protein folding and enzyme catalysis at single-molecule resolution.

Base Sequence↗
PubMed1999

A role for the POU-III transcription factor Brn-4 in the regulation of striatal neuron precursor differentiation.

Both insulin-like growth factor-I (IGF-I) and brain-derived neurotrophic factor (BDNF) induce the differentiation of post-mitotic neuronal precursors, derived from embryonic day 14 (E14) mouse striatal multipotent stem cells. Here we ask whether this differentiation is mediated by a member of the POU-III class of neural transcription factors. Exposure of stem cell progeny to either IGF-I or BDNF resulted in a rapid upregulation of Brn-4 mRNA and protein. Indirect immunocytochemistry with Brn-4 antiserum showed that the protein was expressed in newly generated neurons. Other POU-III genes, such as Brn-1 and Brn-2, did not exhibit this upregulation. Basic FGF, a mitogen for these neuronal precursors, did not stimulate Brn-4 expression. In the E14 mouse striatum, Brn-4-immunoreactive cells formed a boundary between the nestin-immunoreactive cells of the ventricular zone and the beta-tubulin-immunoreactive neurons migrating into the mantle zone. Loss of Brn-4 function during the differentiation of stem cell-derived or primary E14 striatal neuron precursors, by inclusion of antisense oligonucleotides, caused a reduction in the number of beta-tubulin-immunoreactive neurons. These findings suggest that Brn-4 mediates, at least in part, the actions of epigenetic signals that induce striatal neuron-precursor differentiation.

Animals↗