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Biomedical subjects

D Stein

Publications and source records attributed to D Stein.

At least 19 recordsLinked to original sources
PubMed2006

Factors associated with self-evaluated severity of illness and quality of life in male Israeli asthmatic soldiers.

OBJECTIVE: To evaluate whether the asthmatic condition and quality of life of male asthmatic Israeli soldiers deteriorate during army service. METHOD: We retrospectively assessed 178 asthmatic soldiers during service using an adapted version of the Mini Asthma Quality of Life Questionnaire, and compared it to their condition before service. The participants responded additionally to questionnaires assessing psychosocial resources and adjustment to illness. RESULTS: The self-evaluated degree of asthma disease severity (SEDOAD) of the participants deteriorated in the army compared to before service. Soldiers with mild SEDOAD during service, compared to soldiers with severe (and in most cases also moderate) SEDOAD, had less severe medically evaluated and self-evaluated asthma before service. Mild SEDOAD participants showed, additionally, lower inclination towards active seeking of asthma-related information, more favorable health care-related attitudes, less unfavorable effects of their illness on military and extra-military functioning, greater reported pre-enlistment optimism, and a greater belief in their ability to cope successfully with their asthma during service. CONCLUSION: SEDOAD and the quality of life during service are associated not only with pre-enlistment asthma severity, but also with the manner in which the soldier perceives the influence of the illness on his health condition, and the manner in which he copes with this influence.

Adult↗
PubMed2006

Continuous renal replacement therapy in patients following traumatic injury.

In critically injured patients, the incidence of acute renal failure has been reported to occur in as many as 31% of patients. The use of CRRT modalities for patients following traumatic injuries is becoming more common, albeit slowly, and this therapy may impact upon long-term recovery of renal function and mortality. Historical studies investigating the early use of intermittent dialysis reported significant improvement in survival in patients who were dialyzed earlier and more vigorously than in control subjects. Early trauma patients also showed improved survival following war injuries when dialyzed prophylactically. Although there is a growing acceptance in favor of earlier renal replacement therapy, the published consensus and the practice in many centers has been to dialyze/filter relatively ill rather than relatively healthy patients. The R Adams Cowley Shock Trauma Center (STC) in Baltimore, Maryland, USA, admits over 8,000 trauma patients each year. Within the STC, a program of continuous renal replacement therapy was established in the early 1980's. We review both historical and current literature on the use of renal replacement therapies after traumatic injury, and suggest some future areas of investigation and indications for these modalities.

Acute Kidney Injury↗
PubMed2005

Circulatory neurosteroid levels in underweight female adolescent anorexia nervosa inpatients and following weight restoration.

Nineteen female adolescent inpatients diagnosed with anorexia nervosa, restricting type (AN-R) and 16 non-eating disordered (ED) controls were assessed for plasma dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulphate (DHEA-S), and cortisol levels, and for eating-related and non-eating-related psychopathology. AN-R patients were assessed at admission, 1 month and 4 months following hospitalization. The non-ED controls were assessed once. No baseline between-group differences were found in plasma cortisol, DHEA, and DHEA-S levels, whereas the patient group had a significantly lower Cortisol/DHEA-S ratio and elevated scores on most psychopathological parameters. A significant increase was found in the body mass index of the AN-R patients at 4 months post-hospitalization, accompanied by a decrease in plasma cortisol levels and a trend towards decreased Cortisol/DHEA and Cortisol/DHEA-S ratios, whereas no change occurred in psychopathology. The difference in Cortisol/DHEA-S ratio between AN-R patients and non-ED controls, and the different patterns of change in cortisol vs. DHEA(-S) levels following weight restoration, may in part account for the feeding difficulties in AN, particularly during refeeding.

Adolescent↗
PubMed2003

[Cyclic psychosis associated with the menstrual cycle].

Cyclic psychosis associated with the menstrual cycle is an uncommon disorder, not included under the accepted definitions of functional psychoses. We present three female adolescents who developed an acute psychosis a few days before menstruation, which resolved completely upon bleeding or several days later, only to reappear in the same form in subsequent cycles. The clinical presentation was not in line with that of the typical functional psychoses. An extensive medical work-up did not show any significant disturbances, with the exception of anovulatory cycles in one youngster. Psychotropic treatment had no effect on the course of the psychosis. Treatment with progesterone in the second half of the cycle in one case, and with a combined progesterone/estrogen contraceptive agent in another, resulted in full recovery within several cycles. The third girl showed a spontaneous remission within four cycles. Remission continued in all cases after discontinuation of the hormonal treatment, and with no need to reintroduce any psychotropic agent, for a period of 2-4 years. We discuss several possible etiologic mechanisms for cyclic psychosis associated with the menstrual cycle, including it being a cycloid non-specific affective disorder, and its association with a temporary functional hypothalamic-pituitary dysfunction, and with anovulation. We also discuss the role of psychotropic and hormonal treatment in this disorder.

Adolescent↗
PubMed2002

Eating-related concerns, mood, and personality traits in recovered bulimia nervosa subjects: a replication study.

OBJECTIVE: Limited data suggest that eating-related concerns and behaviors, disturbances in mood, and altered temperament persist following recovery from bulimia nervosa (BN). METHOD: In order to replicate and extend such findings, 11 women who were long-term recovered from BN (>1 year with no binging, purging, or restricting behaviors, normal weight, and regular menstrual cycles) were compared with 15 healthy volunteer women on the Eating Disorders Invertory-2 (EDI-2), the Beck Depression Inventory, the State Trait Anxiety Inventory, and the Multidimensional Personality Questionnaire (MPQ). RESULTS: Compared with the control women, the recovered BN women showed elevated levels of the EDI-2 subscales of Drive for Thinness, Body Dissatisfaction, Ineffectiveness, Perfectionism, and Social Insecurity, greater depression and anxiety, elevated levels of the MPQ Stress Reaction dimension and the higher-order factor of Negative Emotionality, and lower levels of the MPQ Well Being and Closeness dimensions. DISCUSSION: Core eating and weight-related concerns, dysphoric affect, social discomfort, and personality traits indicative of perfectionism persist following long-term recovery from BN.

Adult↗
PubMed2002

Association between anorexia nervosa and the hsKCa3 gene: a family-based and case control study.

Familial and twin studies have suggested that anorexia nervosa (AN) is a multifactorial disorder with a substantial genetic contribution. The hSKCa3 potassium channel gene, which contains polymorphic CAG repeats in the coding region and is involved in the regulation of neuronal activity, may be a candidate gene for AN because alleles with longer repeats have been found to be associated with mental disorders. Forty Israeli AN family trios were genotyped for the hSKCa3 CAG repeat polymorphism using the haplotype relative risk (HRR) method. The distribution of alleles transmitted to the patients was found to be significantly different from that of the non-transmitted parental alleles, with the longer alleles being over-represented in the patients (Wilcoxon rank test, P = 0.008). The transmission disequilibrium test (TDT) revealed that longer (>19) repeat alleles were preferentially transmitted to AN patients (McNemar's chi(2) = 10.31, P = 0.0013). These results were corroborated by comparing the distribution of alleles between patients and healthy controls (Mann-Whitney test, P = 0.005). Our study suggests that the longer repeat alleles of the hSKCa3 gene may contribute to the genetic susceptibility to AN.

Adolescent↗
PubMed2001

The torso ligand, unmasked?

When a transmembrane receptor protein tyrosine kinase (RTK) is expressed throughout the plasma membrane, yet only a specific handful of them must be activated, what's a ligand to do? During the development of the anterior and posterior termini of the Drosophila embryo, uniformly secreted ligand precursors are activated by proteolysis near the location of the receptors that must be activated. Stein and Stevens discuss the recent publication by Casali and Casanova that describes the mechanism of activation of the Drosophila RTK called Torso. In addition, Casali and Casanova may have identified a physiologically relevant ligand for Torso called Trunk. Proteolytic cleavage of the Trunk precursor can activate Torso-dependent signaling, but the existence of cleaved Trunk has not yet been demonstrated in vivo for Drosophila. Stein and Stevens discuss the ramifications of such a highly regulated process of ligand activation, and also prefer alternative scenarios for Torso activation.

Animals↗
PubMed2001

Ion-beam sculpting at nanometre length scales.

Manipulating matter at the nanometre scale is important for many electronic, chemical and biological advances, but present solid-state fabrication methods do not reproducibly achieve dimensional control at the nanometre scale. Here we report a means of fashioning matter at these dimensions that uses low-energy ion beams and reveals surprising atomic transport phenomena that occur in a variety of materials and geometries. The method is implemented in a feedback-controlled sputtering system that provides fine control over ion beam exposure and sample temperature. We call the method "ion-beam sculpting", and apply it to the problem of fabricating a molecular-scale hole, or nanopore, in a thin insulating solid-state membrane. Such pores can serve to localize molecular-scale electrical junctions and switches and function as masks to create other small-scale structures. Nanopores also function as membrane channels in all living systems, where they serve as extremely sensitive electro-mechanical devices that regulate electric potential, ionic flow, and molecular transport across cellular membranes. We show that ion-beam sculpting can be used to fashion an analogous solid-state device: a robust electronic detector consisting of a single nanopore in a Si3N4 membrane, capable of registering single DNA molecules in aqueous solution.

Biosensing Techniques↗
PubMed2001

Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels.

BACKGROUND: Prospective studies indicate that baseline levels of C-reactive protein (CRP), the prototypic marker of inflammation, are associated with an increased risk for cardiovascular events. Limited studies have examined therapies that influence high-sensitive CRP (hs-CRP) levels, especially in hyperlipidemic patients. Thus, we tested the effects of 3 hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins), simvastatin (20 mg/d), pravastatin (40 mg/d), and atorvastatin (10 mg/d), on levels of hs-CRP in a randomized, double-blind, crossover trial of 22 patients with combined hyperlipidemia (LDL cholesterol >130 mg/dL and triglycerides of 200 to 600 mg/dL). METHODS AND RESULTS: After 6 weeks of an American Heart Association Step 1 diet, fasting blood samples were drawn at baseline and after 6 weeks of therapy with each drug. hs-CRP levels were significantly decreased after treatment with all 3 statins compared with baseline (median values: baseline, 2.6 mg/L; atorvastatin, 1.7 mg/L; simvastatin, 1.7 mg/L; and pravastatin, 1.9 mg/L; P<0.025). The reductions obtained with the 3 statins were similar. In addition, there was no significant effect on either plasma interleukin-6 or interleukin-6 soluble receptor levels. There was no relationship between reductions in hs-CRP and LDL cholesterol. CONCLUSIONS: Pravastatin, simvastatin, and atorvastatin significantly decreased levels of hs-CRP. These data support an anti-inflammatory effect of these drugs.

Atorvastatin↗
PubMed2001

Local delivery of c-myc neutrally charged antisense oligonucleotides with transport catheter inhibits myointimal hyperplasia and positively affects vascular remodeling in the rabbit balloon injury model.

Myointimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA) is a key component of the process of restenosis. The c-myc is a critical cell-cycle division protein involved in the formation of neointima. We evaluated the long-term impact of local delivery of c-myc neutrally charged antisense oligonucleotides (Resten-NG) on myointimal hyperplasia after PTCA in a rabbit model. PTCA was performed in the iliac arteries of 25 New Zealand white rabbits, using a Transport catheter at 8 atm for 30 sec, three times; 500 microg Resten-NG (n = 11) or saline (n = 14) was delivered to the PTCA site at 2 atm with the outer balloon for 2 min. The diet was supplemented with 0.25% cholesterol for 10 days before and 60 days after PTCA. Angiography was performed at harvest, and vessels were fixed in formalin, processed, and stained with hematoxylin and eosin (H&E) and Movat. Quantitative angiography showed that local delivery of antisense c-myc at PTCA reduced late luminal loss from 1.8 +/- 0.30 mm in control animals to 0.90 +/- 0.30 mm in the treatment group (P = 0.001). Histological analysis by planimetry showed that intimal areas were 1.67 +/- 0.44 mm(2) and 0.82 +/- 0.32 mm(2) in the control and antisense delivery groups, respectively (P < 0.05). We conclude that local delivery of Resten-NG inhibited myointimal hyperplasia after PTCA in cholesterol-fed rabbits for up to 60 days.

Angioplasty, Balloon, Coronary↗
PubMed2001

Decreased interferon-alpha production in HIV-infected patients correlates with numerical and functional deficiencies in circulating type 2 dendritic cell precursors.

Peripheral blood mononuclear cells from patients with human immunodeficiency virus (HIV) infection exhibit a progressively marked decrease in the production of virus-induced interferon (IFN)-alpha, a finding that correlates with and is highly predictive of disease progression and opportunistic infections. The major IFN-alpha producing population has recently been defined as the precursor to type 2 dendritic cells (pDC2) or plasmacytoid DC (pDC). Using four-color flow cytometry, we have enumerated the pDC2 vs non-IFN-alpha producing myeloid DC1 in peripheral blood from HIV-infected patients and healthy controls and related these values to CD4 cell numbers, viral load, and functional activity. The patients had reductions in the numbers of both pDC2 (lin-/HLA-DR+/CD123(bright)) and DC1 (lin1-/HLA-DR+/CD123(dim)/CD11c+), both at an absolute level and as a percentage of cells. The decreases were most evident in patients with decreased CD4 levels. Viral load correlated with the functional frequency of the IFN producing cells but not with absolute pDC2 levels. Using intracellular flow cytometric analysis for IFN-alpha, the patients were demonstrated to have fewer pDC2, as well as a lower percentage of responding cells among those remaining. We conclude that deficient production of IFN-alpha by pDC2 from HIV-infected patients results from both selective loss of these cells and their qualitative dysfunction. Given the central role of DC, and in particular, DC2, in linking innate and adaptive immune responses, these qualitative and quantitative changes in pDC2 are likely to be key contributors to HIV pathogenesis.

CD4 Lymphocyte Count↗
PubMed2001

Association of anorexia nervosa with the high activity allele of the COMT gene: a family-based study in Israeli patients.

Anorexia nervosa (AN) is a common, severe and disabling psychiatric disorder, characterized by profound weight loss and body image disturbance. Family and twin studies indicate a significant genetic contribution and pharmacological data suggest possible dysfunction of the serotonergic and dopaminergic pathways. Catechol-O-methyltransferase (COMT) is a candidate gene for mediating susceptibility to AN since it is involved in the dopamine catabolism and because its functional polymorphism (Val/Met 158) determines high (H) and low (L) enzymatic activity alleles. Fifty-one Israeli AN patients and their parents were genotyped with the COMT polymorphism. Using the haplotype relative risk (HRR) method it was found that the frequency of the H allele among alleles transmitted to AN patients from their parents was significantly higher than in those not transmitted (68% vs 51% chi(2) = 5.20, df = 1, P = 0.023, odds ratio: 2.01). Transmission disequilibrium test (TDT) revealed that out of 49 heterozygote parents the H allele was transmitted to AN patients 33 times while the L allele was transmitted only 16 (McNemar's chi(2) = 5.90, df = 1, P = 0.015). Our study suggests that the COMT gene is associated with genetic susceptibility to AN, and that individuals homozygous for the high activity allele (HH) have a two-fold increased risk for development of the disorder.

Adolescent↗
PubMed2001

Inhibition of human immunodeficiency virus type 1 transcription by chemical cyclin-dependent kinase inhibitors.

Cyclin-dependent kinases (cdk's) have recently been suggested to regulate human immunodeficiency virus type 1 (HIV-1) transcription. Previously, we have shown that expression of one cdk inhibitor, p21/Waf1, is abrogated in HIV-1 latently infected cells. Based on this result, we investigated the transcription of HIV-1 in the presence of chemical drugs that specifically inhibited cdk activity and functionally mimicked p21/Waf1 activity. HIV-1 production in virally integrated lymphocytic and monocytic cell lines, such as ACH(2), 8E5, and U1, as well as activated peripheral blood mononuclear cells infected with syncytium-inducing (SI) or non-syncytium-inducing (NSI) HIV-1 strains, were all inhibited by Roscovitine, a purine derivative that reversibly competes for the ATP binding site present in cdk's. The decrease in viral progeny in the HIV-1-infected cells was correlated with a decrease in the transcription of HIV-1 RNAs in cells treated with Roscovitine and not with the non-cdk general cell cycle inhibitors, such as hydroxyurea (G(1)/S blocker) or nocodazole (M-phase blocker). Cyclin A- and E-associated histone H1 kinases, as well as cdk 7 and 9 activities, were all inhibited in the presence of Roscovitine. The 50% inhibitory concentration of Roscovitine on cdk's 9 and 7 was determined to be approximately 0.6 microM. Roscovitine could selectively sensitize HIV-1-infected cells to apoptosis at concentrations that did not impede the growth and proliferation of uninfected cells. Apoptosis induced by Roscovitine was found in both latent and activated infected cells, as evident by Annexin V staining and the cleavage of the PARP protein by caspase-3. More importantly, contrary to many apoptosis-inducing agents, where the apoptosis of HIV-1-infected cells accompanies production and release of infectious HIV-1 viral particles, Roscovitine treatment selectively killed HIV-1-infected cells without virion release. Collectively, our data suggest that cdk's are required for efficient HIV-1 transcription and, therefore, we propose specific cdk inhibitors as potential antiviral agents in the treatment of AIDS.

Cell Line↗
PubMed2001

Separable and redundant regulatory determinants in Cactus mediate its dorsal group dependent degradation.

Dorsal-ventral polarity within the Drosophila syncytial blastoderm embryo is determined by the maternally encoded dorsal group signal transduction pathway that regulates nuclear localization of the transcription factor Dorsal. Nuclear uptake of Dorsal, a Rel/NFkappaB homolog, is controlled by the interaction with its cognate IkappaB inhibitor protein Cactus, which is degraded on the ventral side of the embryo in response to dorsal group signaling. Previous studies have suggested that an N-terminally located kinase target motif similar to that found in IkappaB proteins is involved in the spatially controlled degradation of Cactus. We report studies of the in vivo function and distribution of fusion proteins comprising segments of Cactus attached to Escherichia coli beta-galactosidase (lacZ). Full-length Cactus-lacZ expressed in vivo normalizes the ventralized phenotype of embryos that lack Cactus and faithfully reconstitutes dorsal group-regulated degradation, while fusion protein constructs that lack the first 125 amino acids of Cactus escape dorsal group-dependent degradation. Furthermore, Cactus-lacZ constructs that lack only the putative IkappaB-dependent kinase target-like motif can nevertheless undergo spatially regulated dorsal group-dependent degradation and we have identified the regulatory determinant responsible for dorsal group-dependent degradation of Cactus in the absence of this motif. Taken together, our studies indicate the presence of two distinct redundantly acting determinants in the N terminus of Cactus that direct dorsal group-dependent degradation. Strikingly, the regulatory domain of human IkappaBalpha can also direct polarized degradation of Cactus-lacZ fusion protein.

Amino Acid Motifs↗