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Biomedical subjects

E Stein

Publications and source records attributed to E Stein.

At least 37 records · Page 2Linked to original sources
PubMed1998

Nck recruitment to Eph receptor, EphB1/ELK, couples ligand activation to c-Jun kinase.

Eph family receptor tyrosine kinases signal axonal guidance, neuronal bundling, and angiogenesis; yet the signaling systems that couple these receptors to targeting and cell-cell assembly responses are incompletely defined. Functional links to regulators of cytoskeletal structure are anticipated based on receptor mediated cell-cell aggregation and migratory responses. We used two-hybrid interaction cloning to identify EphB1-interactive proteins. Six independent cDNAs encoding the SH2 domain of the adapter protein, Nck, were recovered in a screen of a murine embryonic library. We mapped the EphB1 subdomain that binds Nck and its Drosophila homologue, DOCK, to the juxtamembrane region. Within this subdomain, Tyr594 was required for Nck binding. In P19 embryonal carcinoma cells, activation of EphB1 (ELK) by its ligand, ephrin-B1/Fc, recruited Nck to native receptor complexes and activated c-Jun kinase (JNK/SAPK). Transient overexpression of mutant EphB1 receptors (Y594F) blocked Nck recruitment to EphB1, attenuated downstream JNK activation, and blocked cell attachment responses. These findings identify Nck as an important intermediary linking EphB1 signaling to JNK.

Adaptor Proteins, Signal Transducing↗
PubMed1998

[Treatment of peri-ocular skin lesions with the erbium:YAG laser].

INTRODUCTION: A great number of consmetically disturbing, cutaneous lesions are localized in the periocular region. While various approaches for treatment such as excision, electrocauterization or cryosurgery often show unsatisfactory results, the use of laser technology is of increasing interest. MATERIAL AND METHODS: A total of 104 patients with different cutaneous periorbital lesions (wrinkles, xanthelasma, syringoma) were treated with a new erbium: YAG laser system (wavelength 2940 nm, pulse duration 0.350 ms and pulse energy 0.1-1.7 Joules), which works on the principle of vaporization. RESULTS: The erbium: YAG laser allows athermic ablation of very thin skin layers without scarring and with minimal lateral thermal injury due an extremely short pulse duration. Periorbital lesions can be treated effectively by erbium: YAG laser, and good to excellent cosmetic results can be obtained. CONCLUSIONS: The use of pulsed erbium: YAG laser is an effective and promising new method for treatment of different superficial periorbital cutaneous lesions.

Adult↗
PubMed1998

Cerivastatin in primary hyperlipidemia--a multicenter analysis of efficacy and safety.

Cerivastatin, a novel, synthetic, and enantiomerically pure 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been administered, in clinical trials, to over 2700 patients with primary hypercholesterolemia, of whom over 1000 received treatment for periods of up to 1 year. A global, pooled analysis of the efficacy, safety, and tolerability of cerivastatin was performed on data obtained from all randomized, double-blind studies in which cerivastatin at doses of 0.025-0.4 mg/day were compared with either placebo or active comparators. All studies had a 10-week, diet-controlled run-in period, the last 6 weeks of which included administration of single-blind placebo. Efficacy analysis of the pooled data at 8 weeks post-randomization showed that in comparison with placebo, cerivastatin achieved significant dose-dependent reductions in low-density lipoprotein cholesterol (LDL-C), the primary efficacy parameter, of between 14.2 and 36.1%. Reductions in LDL-C were accompanied by significant reductions in total cholesterol and triglycerides, together with increases in high-density lipoprotein cholesterol (HDL-C). The magnitude of the reduction in plasma triglycerides was strongly related to baseline triglyceride levels. In patients with baseline plasma triglycerides of >250 mg/dl, treatment with 0.4 mg/day cerivastatin decreased these levels by 37%. Cerivastatin was well tolerated, with the type and incidence of clinical adverse effects comparable to that of placebo and comparator drugs. The incidence of biochemical adverse effects was also similar to that seen with either placebo or comparator drugs and was independent of the dose of cerivastatin. Less than 1% of patients treated with cerivastatin at doses of 0.025-0.4 mg/day experienced clinically significant increases in either hepatic transaminases (> 3 x the upper limit of normal) or creatine phosphokinase (CPK) (> 5 x the upper limit of normal). The good tolerability of cerivastatin was reflected in a low rate of premature withdrawal from treatment, below or comparable to that of placebo-treatment. The pooled efficacy and safety analyses have shown that at 1% of the doses of other statins, cerivastatin is a safe, well-tolerated, and highly effective HMG-CoA reductase inhibitor for the treatment of type IIa and IIb hypercholesterolemia.

Adult↗
PubMed1998

Worksite and family education for dietary change: the Treatwell 5-a-Day program.

The National Cancer Institute's '5-a-Day for Better Health Campaign is examining the efficacy of interventions in increasing the consumption of fruits and vegetables to five or more servings a day. This paper presents the study design, intervention and baseline survey results of the Treatwell 5-a-Day project, a randomized, controlled worksite-based intervention study. Twenty-two community health centers were randomly assigned to either a Minimal Intervention, Worksite Intervention or Worksite Plus Family Intervention. The Worksite Intervention included participation of employee advisory boards, programs aimed at individual behavior change and programs aimed at changes in the worksite environment. The Worksite Plus Family Intervention incorporated family-focused interventions into the worksite program, including a learn-at-home program, family newsletter, family festival and materials mailings. A self-administered survey was conducted prior to randomization (mean response rate: 87%, n = 1359). Twenty-three percent reported consuming five or more servings of fruits and vegetables a day. Consumption of fruits and vegetables was directly associated with level of household support for healthy eating. The Treatwell 5-a-Day intervention model has the potential to enhance existing worksite-based intervention through incorporation of its family focus, especially given the association of household support with individual eating habits.

Adult↗
PubMed1997

Comparison of one-year efficacy and safety of atorvastatin versus lovastatin in primary hypercholesterolemia. Atorvastatin Study Group I.

This double-blind study to evaluate long-term efficacy and safety of atorvastatin was performed in 31 community- and university-based research centers in the USA to directly compare a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (reductase inhibitor) to an accepted drug of this class in patients with moderate hypercholesterolemia. Participants remained on a cholesterol-lowering diet throughout the study. One thousand forty-nine patients were randomized to receive atorvastatin 10 mg, lovastatin 20 mg, or placebo. At 16 weeks the placebo group was randomized to either atorvastatin or lovastatin treatment. At 22 weeks, patients who had not met low-density lipoprotein (LDL) cholesterol target levels doubled the dose of reductase inhibitor. Efficacy evaluation was mean percent change from baseline in LDL cholesterol, triglycerides, total cholesterol, high-density-lipoprotein cholesterol, and apolipoprotein B (apoB). Safety profiles as determined by change from baseline in laboratory evaluations, ophthalmologic parameters, and reporting of adverse events were similar for the 2 reductase inhibitors. After 52 weeks, the atorvastatin group maintained a significantly greater reduction in LDL cholesterol (-37% vs -29%), triglyceride (-16% vs -8%), total cholesterol (-27% vs -21%), and apoB (-30% vs -22%) (p <0.05). More patients receiving atorvastatin achieved LDL cholesterol target levels than did lovastatin patients (78% vs 63%, respectively), particularly those with coronary heart disease (37% vs 11%, respectively). Atorvastatin is highly effective and well tolerated in patients with primary hypercholesterolemia with no increased risk of adverse events.

Analysis of Variance↗
PubMed1997

Ethical implications of scientific research on the causes of sexual orientation.

In this article, we evaluate the status of current biological research into sexual orientation and examine the relevance of such research on the legal and social status of gay men and lesbians. We begin with a review of hormonal neuroanatomical and genetic studies of sexual orientation. We argue that the scientific study of sexual orientation is, at best, still in its infancy. We turn then to the ethical and social implications of this research. We argue that even if scientists could explain how sexual orientation develops, no significant ethical conclusions would follow. Further, we suggest that the current emphasis on finding a biological basis for sexual orientation is potentially harmful to lesbians, gay men and other sexual minorities in various ways (although perhaps it is in some ways potentially helpful as well).

Animals↗
PubMed1997

A new culture method for human pancreatic islets using a biopore membrane insert.

The availability of highly purified human islets has increased with the progressive improvement of isolation methods. This has provided opportunities to perform various in vitro studies on human islets. However, when islets are maintained in culture, the overgrowth of fibroblasts results in a reduced islet purity and often has an adverse effect on islet function. To reduce fibroblast growth and to maintain normal islet function, we have investigated a new three-dimensional culture technique using a noncoated transparent Biopore membrane insert (Millicell CM, Millipore). Islets were isolated from seven human pancreata and cultured for 2 months using this membrane insert. At various time intervals, the functional viability of islets was assessed by measurements of insulin released into the culture medium, static incubation assays of basal and stimulated insulin release, islet insulin contents, and insulin biosynthesis. Results were compared to those of islets cultured in hydrophobic plastic petri dishes, our standard procedure. We found that the non-coated membrane does not allow islet attachment to the surface and prevents fibroblast growth, so that islets maintain a three-dimensional structure and remain in a free-floating form. Islets cultured in a membrane insert showed a function similar to or better than that of islets cultured in plastic petri dishes.

Culture Media↗
PubMed1997

Cerivastatin, a New Potent Synthetic HMG Co-A Reductase Inhibitor: Effect of 0.2 mg Daily in Subjects With Primary Hypercholesterolemia.

BACKGROUND: Reduction of serum cholesterol, most notably low-density lipoprotein cholesterol is associated with reductions in cardiovascular morbidity and mortality. Statins have been shown to effectively reduce low-density lipoprotein cholesterol via inhibition of the hydroxymethyl-coenzyme A (HMG-CoA) reductase. Cerivastatin is the most potent HMG-CoA reductase inhibitor currently under study in the United States. METHODS AND RESULTS: A parallel group, randomized, placebo-controlled, double-blind, multicenter study was conducted to compare the efficacy and safety of three different dosing regimens of 0.2 mg/day of cerivastatin, a new HMG-CoA reductase inhibitor, in patients with hypercholesterolemia. After a 10-week diet-placebo lead-in period, 319 patients with low-density lipoprotein cholesterol >160 mg/dL were randomized to 4 weeks of treatment with one of the following regimens: cervastatin 0.1 mg twice daily, cerivastatin 0.2 mg once daily with the evening meal, cerivastatin 0.2 mg once daily at bedtime or placebo. All three active treatment groups produced statistically significant (P <.05) changes compared to aseline and placebo in total cholesterol (0.1 mg twice daily \_18.9%; 0.2 mg once daily with the evening meal: \_21.9%; 0.2 mg once daily at bedtime: \_22.1%; placebo: 0.0%), low-density lipoprotein cholesterol (0.1 mg twice daily: \_25.7%; 0.2 mg once daily with the evening meal: \_29.4%; 0.2 mg once daily at bedtime: \_30.4%; placebo: 1.4%) and high-density lipoprotein cholesterol (0.1 mg twice daily: 5.3%; 0.2 mg once daily with the evening meal: baseline and placebo, were also reduced by all active treatments (0.1 mg twice daily: \_11.6% [P =.05]; 0.2 mg once daily with the evening meal: \_11.6% [P =.05]; and 0.2 mg at bedtime: \_10.9% [P =.07]). The percentage change in total cholesterol and low-density lipoprotein cholesterol after 4 weeks of therapy for the once-daily cerivastatin groups was statistically significantly greater (P <.05) than the cerivastatin twice daily regimen. A treatment responser was seen by 1 week of therapy and was maximal by 3 weeks. The drug was well tolerated in all three dosing regimens and resulted in no significant increase in biochemical or clinical side effects compared to placebo. CONCLUSION: Cerivastatin is a novel, highly potent, well-tolerated HMG-CoA reductase inhibitor that produces low-density lipoprotein cholesterol reductions of approximately 30% when administered at 0.2 mg once a day in the evenings.

Journal Article↗
PubMed1997

Orthodontic extrusion--a new simplified aesthetic technique.

Various techniques have been described to extrude the roots of fractured teeth to facilitate prosthetic restoration. Many of these have the disadvantage of poor aesthetics, they require skill in fabrication and fitting, and there is often inadequate control over the amount of extrusion. With the technique described, root canal therapy is completed initially and a cast gold post is cemented into the root canal. The post has a channel extending from the labial to the palatal aspect. A temporary acrylic crown is fitted to restore aesthetics, and the channel is extended though the palatal and labial surfaces. An orthodontic wire framework with a horizontal strut at the level of the original incisal edge of the fractured tooth is then bonded to the adjacent abutment teeth. The amount of extrusion required is estimated and a corresponding reduction is made in the length of the acrylic temporary crown. An elastic threaded through the channel and looped over the horizontal strut of the framework provides the extrusive force. A 6 week retention period is required following the extrusion. Periodontal surgery is then carried out if necessary, and a new provisional crown is placed. The final porcelain restoration is fitted after 6 months.

Adolescent↗
PubMed1996

Ligand activation of ELK receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells.

ELK is a member of the Eph-related tyrosine kinase family that includes receptors signaling axonal guidance, neuronal bundling, and angiogenesis. We recently identified ELK expression in human renal microvascular endothelial cells and sought to identify intracellular proteins through which it signals responses. The cytoplasmic domain of ELK was used as "bait" in a yeast two-hybrid screen to identify interactive proteins expressed from a randomly primed embryonic murine library (E9.5-10.5). Among interactive products of 76 cDNAs characterized, 10 nonidentical, overlapping clones encoded the SH2 domain of the recently reported Grb10 adapter protein, and an additional 3 encoded Grb2. A self-phosphorylated recombinant, baculovirus-expressed GST-ELKcy fusion protein bound Grb10 and Grb2 from human renal microvascular endothelial cell extracts, while the unphosphorylated fusion form did not. Site-directed mutation identified Tyr-929 as a putative phosphorylation site required for Grb10, but not Grb2, interaction in yeast and recombinant protein assays. The ELK ligand, LERK-2/Fc, stimulated tyrosine phosphorylation of ELK, and recruitment of Grb10 and Grb2 to endothelial ELK receptors recovered by wheat germ agglutinin lectin and immunoprecipitation. These findings define ligand-activated interaction between ELK and the SH2 domains of Grb2 and the newly identified Grb10 protein that shares homology with a Caenorhabditis elegans gene product implicated in neural cell migration.

Adaptor Proteins, Signal Transducing↗
PubMed1996

[Controlled dermabrasion with a newly developed erbium-YAG-laser system. Report of preliminary experiences].

The reasons for the development of pulsed lasers, as well as the differences between them and continuous lasers are discussed. Both the advantages and disadvantages of such lasers, as well as the indications are presented. Furthermore, the erbium-yag laser is contrasted to the ultra-pulsed CO2 laser. Two case reports demonstrate the effectiveness of the erbium-yag laser.

Dermabrasion↗
PubMed1996

Time-related bond strengths of light-cured and chemically cured bonding systems: an in vitro study.

The immediate bond strengths achieved with a light-cured bonding system and those at selected time intervals over a 24-hour period were assessed and compared with the bond strengths produced by a chemically cured system over a similar period. Mesh-backed metal orthodontic brackets were bonded with the light-cured system to 60 teeth, and 50 teeth had similar brackets bonded with a chemically cured system. Shear/peel bond strengths for each were determined with the instron Universal testing machine (Instron Corp., Canton, Mass.) and these were compared statistically. The bond strengths for the chemically cured system were initially low, but these increased with time. The light-cured sample displayed initial bond strengths of sufficient magnitude to withstand the immediate application of orthodontic forces, and these bond strengths also increased with time. There was no significant difference between the bond strengths achieved by the chemically cured and light-cured systems at the 10-minute, 60-minute, and 24-hour intervals.

Bisphenol A-Glycidyl Methacrylate↗
PubMed1996

Orthodontic brackets bonded to glazed and deglazed porcelain surfaces.

Edgewise orthodontic brackets were bonded with a light activated composite resin to 100 glazed and 100 deglazed feldspathic porcelain blocks for an in vitro comparative determination of shear/peel bond strengths. The independent variables studied were porcelain surface preparation and the time interval between activation of the composite resin and the debonding procedure. The initial shear/peel bond strength achieved on bonding to deglazed porcelain was statistically significantly greater than that on bonding to glazed porcelain (p<0.05), but after the 10-minute interval, the bond strength in the glazed porcelain sample was greater than in the deglazed sample. Many more porcelain fractures occurred on deglazed porcelain (71%) than on glazed porcelain (36%) during bond strength determination. Scanning electron microscopy evaluation suggests that deglazing does not substantially increase micromechanical adhesion of the composite resin. Bond strength adequate to withstand the application of orthodontic forces were achieved when bonding to glazed porcelain. This study indicates that deglazing may not be necessary for attachment of orthodontic brackets to porcelain surfaces.

Acrylic Resins↗
PubMed1996

The mental health of children in foster care: a comparison with community and clinical samples.

OBJECTIVE: To determine whether the psychiatric profile of children in foster care is more similar to clinical or community profiles. METHOD: Caregiver and teacher ratings of DSM-III-R externalizing and internalizing symptoms were collected for 3 groups of children: children in foster care, children assessed at a children's mental health centre, and a community sample. RESULTS: Children in foster care approximated the numbers and types of symptoms of the clinical sample. Coming from a family on social assistance, having a parent with a criminal history, and being of the male gender were correlated with higher externalizing and internalizing symptom scores independent of group membership. Group membership accounted for less than 5% of the variance in psychiatric symptom scores. CONCLUSIONS: The high symptom burden of children in care is substantially attributable to their high-risk histories, and treatment should be designed with this in mind.

Adolescent↗
PubMed1996

ELK and LERK-2 in developing kidney and microvascular endothelial assembly.

Eph family receptor tyrosine kinases direct neuronal cell targeting, bundling and intercellular aggregation activity, yet their role in mammalian kidney development has been unexplored to date. We recently identified expression of ELK (Eph-like kinase) receptors in cultured human renal microvascular endothelial cells (HRMEC), and showed that ELK mediates their in vitro assembly into capillary-like structures in response to the exogenous ligand, LERK-2. Here we identify expression of the ELK ligand, LERK-2, in HRMEC and in primitive vascular structures of developing murine kidney. ELK and LERK-2 are expressed on endothelial progenitor cells of primitive microvasculature in a pattern similar to that of the VEGF receptor, flk-1. ELK LERK-2 and flk-1 antigens are also displayed on the branching ureteric bud epithelium; ELK and LERK-2 expression persists in mature collecting ducts, glomeruli and arterioles. To explore whether renal-derived endothelial cells may distinguish LERK-2 from the angiogenic Eck ligand, LERK-1 (B61), and whether endothelial cells from different sources may distinguish among Eph receptor ligands, we compared HRMEC and human umbilical vein endothelial cell (HUVEC) responses in an in vitro capillary-like assembly assay. HRMEC endothelial cells assembled capillary-like structures in response to LERK-2, but not LERK-1, under conditions that promoted HUVEC to assemble in response to LERK-1, but not LERK-2. Therefore, responses mediated through specific Eph family receptors (ELK and Eck) are discriminated by endothelial cells from different vascular bed sources. ELK and its ligand, LERK-2, are spatially and temporally coordinated in expression and may function in morphogenesis of the renal microvasculature.

Animals↗