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R Weiss

Publications and source records attributed to R Weiss.

At least 73 records · Page 4Linked to original sources
PubMed1999

Immune responses after immunization with plasmid DNA encoding Bet v 1, the major allergen of birch pollen.

BACKGROUND: Immunization with plasmid DNA encoding various antigens is a promising method in vaccine research. Recent studies also indicate that DNA-based immunization might represent a potential approach in allergen-specific immunotherapy. OBJECTIVE: In this study we have characterized the immune responses induced by recombinant Bet v 1a and plasmid DNA encoding for Bet v 1a, the major allergen of birch pollen in a mouse system. METHODS: Balb/c mice were injected intraperitoneally with recombinant Bet v 1a and intradermally with plasmid DNA encoding for the gene of Bet v 1a (pCMV-Bet). In addition, the effect of immunostimulatory DNA sequences was investigated by appending CpG motifs to the gene of Bet v 1a, coinjecting CpG-oligodeoxynucleotides together with the pCMV-Bet construct, or both. IgE and IgG antibody responses, as well as IgG subclasses, were measured by ELISA in sera after each immunization. IFN-gamma and IL-4 levels were also measured by ELISA in sera and supernatants of allergen-stimulated spleen cells. RESULTS: The primary humoral response to a single treatment with pCMV-Bet was very weak, but the reaction could be boosted to higher levels by 2 additional injections. On the other hand, proliferation assays of spleen cells and measurements of cytokine levels already indicated a cellular response after the first injection of plasmid DNA. After 2 immunizations with pCMV-Bet, the ratio of IgG1 to IgG2a pointed to a TH1 subclass profile. IgE was not detectable in any group at any time during the immune reaction. Accordingly, IL-4 levels were markedly reduced in the serum, as well as in the supernatants, of stimulated spleen cells. Animals immunized with pCMV-Bet containing appended CpG motifs at the 3' end of the Bet v 1a gene and/or with the CpG-ODN GCTAGACGTTAGCGT plus pCMV-Bet displayed reduced humoral responses against Bet v 1a when compared with animals injected with pCMV-Bet alone. The levels of IFN-gamma measured after allergen stimulation of isolated spleen cells were significantly higher in animals immunized with pCMV-Bet plus CpG motifs than with pCMV-Bet alone. Immunization with recombinant Bet v 1a protein elicited a strong TH2 -type response, including IgE production, a high titer of IgG1, and IL-4 production in both serum and supernatants of proliferation cultures. CONCLUSION: In contrast to immunization with protein, DNA immunization induces a strong TH1 -type response against a relevant inhalant allergen. Our data support the concept of developing a novel type of allergen immunotherapy based on plasmid DNA immunization.

Allergens↗
PubMed1999

Options for managing psychotropic medications in drug-abusing patients participating in behavioral therapies clinical trials.

This manuscript reviews strengths and weaknesses of common design options for managing non-study medications in randomized clinical trials of behavioral treatments for drug abusers. While the principal focus of these trials is on the relative efficacy of different behavioral interventions, drug abusers entering these trials are often either using or in need of prescribed psychotropic medications, which can have a major independent impact on treatment outcome. Options reviewed range from tight to minimal restriction on use of ancillary medications. Generally, major tradeoffs pertain to the balance between internal validity and generalizability. However, experimental rigor can be maintained while allowing subjects to use ancillary medications if steps are taken to monitor and minimize the variability in treatment delivery.

Behavior Therapy↗
PubMed1999

Cocaine-induced mood disorder: prevalence rates and psychiatric symptoms in an outpatient cocaine-dependent sample.

This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-induced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD), other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. The prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication.

Adult↗
PubMed1999

Distinctive RR dynamics preceding two modes of onset of spontaneous sustained ventricular tachycardia. (ESVEM) Investigators. Electrophysiologic Study Versus Electrocardiographic Monitoring.

INTRODUCTION: We hypothesized that autonomic activity preceding spontaneous sustained monomorphic ventricular tachycardia (VTsm) as assessed by heart rate (HR) and RR interval variability (RRV) differs between type 1 VTsm which is initiated by morphologically distinct, early cycle, possibly triggering premature ventricular complexes (PVCs) and type 2 VTsm in which the initial complex has a QRS waveform identical to subsequent complexes. METHODS AND RESULTS: Baseline Holter tapes (1,646) from a clinical trial were scanned for VTsm. QRS complexes of VTsm were compared by two-lead cross-correlation to distinguish type 1 and type 2 VTsm. Frequency domain RRV index were estimated over 5 minutes, 15 minutes, and 24 hours. Type 1 and type 2 VTsm were present in 15 (group 1) and 33 (group 2) of 48 patients, respectively. HR did not change in group 1 (88.4+/-15.2 to 89.7+/-13.0 beats/min, P = 0.89), but increased before the onset of VTsm in group 2 (74.3+/-16.3 to 81.2+/-18.0 beats/min, P < 0.001). RRV index were severely depressed in both groups. No RRV index changed significantly before the onset of type 1 VTsm, whereas significant changes occurred before type 2 VTsm from 24-hour average to 30 minutes before VTsm in very low (very low-frequency power [VLFP]: 6.62+/-1.53 to 6.20+/-2.07 ln msec2, P = 0.036), low (low-frequency power [LFP]: 5.61+/-1.43 to 5.28+/-1.59 ln msec2, P = 0.004), normalized low (normalized low-frequency power [LFPn]: -0.48+/-0.58 to -0.55+/-0.64 normalized units [nu], P = 0.05) and the ratio of LFP to high-frequency power (HFP) (LFP/HFP: 4.20+/-3.47 to 3.45+/-2.53, P = 0.017). Declines in RRV index between 2 hours to the 30-minute period before VTsm occurred in group 2 but not group 1 in LFP (5.85 +/- 1.42 to 5.28 +/- 1.59 In msec, P = 0.043) and HFP (4.94 +/- 5.14 to 3.46 +/- 2.52 In msec2, P = 0.008), with a downward trend in LFP/HFP (4.94+/-5.14 to 3.45+/-2.53, P = 0.127) and LFPn (-0.38+/-0.36 to -0.55+/-0.64, P = 0.15), while HFPn tended to rise (-1.47+/-0.65 to -1.27+/-0.64, P = 0.15). CONCLUSIONS: HR and RRV did not change before type 1 VTsm, suggesting that short-term changes in autonomic activity were not essential to initiation of apparent PVC-triggered VTsm. In contrast, RR interval dynamics before type 2 VTsm suggested that short-term changes in neurohormonal activity contributed to arrhythmia initiation. Heterogeneities in arrhythmia onset may reflect distinct triggers and substrate properties that could provide a basis for effective therapeutic targets.

Autonomic Nervous System↗
PubMed1999

Purification and molecular characterization of the tungsten-containing formaldehyde ferredoxin oxidoreductase from the hyperthermophilic archaeon Pyrococcus furiosus: the third of a putative five-member tungstoenzyme family.

Pyrococcus furiosus is a hyperthermophilic archaeon which grows optimally near 100 degreesC by fermenting peptides and sugars to produce organic acids, CO2, and H2. Its growth requires tungsten, and two different tungsten-containing enzymes, aldehyde ferredoxin oxidoreductase (AOR) and glyceraldehyde-3-phosphate ferredoxin oxidoreductase (GAPOR), have been previously purified from P. furiosus. These two enzymes are thought to function in the metabolism of peptides and carbohydrates, respectively. A third type of tungsten-containing enzyme, formaldehyde ferredoxin oxidoreductase (FOR), has now been characterized. FOR is a homotetramer with a mass of 280 kDa and contains approximately 1 W atom, 4 Fe atoms, and 1 Ca atom per subunit, together with a pterin cofactor. The low recovery of FOR activity during purification was attributed to loss of sulfide, since the purified enzyme was activated up to fivefold by treatment with sulfide (HS-) under reducing conditions. FOR uses P. furiosus ferredoxin as an electron acceptor (Km = 100 microM) and oxidizes a range of aldehydes. Formaldehyde (Km = 15 mM for the sulfide-activated enzyme) was used in routine assays, but the physiological substrate is thought to be an aliphatic C5 semi- or dialdehyde, e.g., glutaric dialdehyde (Km = 1 mM). Based on its amino-terminal sequence, the gene encoding FOR (for) was identified in the genomic database, together with those encoding AOR and GAPOR. The amino acid sequence of FOR corresponded to a mass of 68.7 kDa and is highly similar to those of the subunits of AOR (61% similarity and 40% identity) and GAPOR (50% similarity and 23% identity). The three genes are not linked on the P. furiosus chromosome. Two additional (and nonlinked) genes (termed wor4 and wor5) that encode putative tungstoenzymes with 57% (WOR4) and 56% (WOR5) sequence similarity to FOR were also identified. Based on sequence motif similarities with FOR, both WOR4 and WOR5 are also proposed to contain a tungstobispterin site and one [4Fe-4S] cluster per subunit.

Aldehyde Oxidoreductases↗
PubMed1999

Identification of human herpesvirus 8-specific cytotoxic T-cell responses.

Human herpesvirus 8 (HHV-8) (or Kaposi's sarcoma-associated herpesvirus) is implicated in the etiopathogenesis of Kaposi's sarcoma (KS) and certain lymphoproliferations. The introduction of more effective therapies to treat human immunodeficiency virus infection has led to a decline in the incidence of KS and also in the resolution of KS in those already affected. This suggests that cellular immune responses including cytotoxic T lymphocytes (CTLs) could play a vital role in the control of HHV-8 infection and in KS pathogenesis. Here we elucidate HLA class I-restricted, HHV-8-specific cellular immune responses that could be important in the control of HHV-8 infection and subsequent tumor development. We show the presence of CTLs against HHV-8 latent (K12), lytic (K8.1), and highly variable (K1) proteins in infected individuals.

AIDS-Related Opportunistic Infections↗
PubMed1999

Isoforms of the major allergen of birch pollen induce different immune responses after genetic immunization.

BACKGROUND: Recent publications indicate that immunization with plasmid DNA encoding allergens might represent a potential approach in allergen-specific immunotherapy. OBJECTIVE: In the present study we have compared the immune responses induced by plasmid DNA encoding for two isoforms of Bet v 1, the major allergen of birch pollen. METHODS: BALB/c mice were injected intradermally with plasmid DNA encoding for the genes of Bet v 1a (pCMV-Beta) and Bet v 1d (pCMV-Betd). In addition, the effect of immunostimulatory DNA sequences was investigated by appending and/or coinjecting CpG motifs. Antibody responses and IFN-gamma and IL-4 levels were measured by ELISA. Allergen-specific proliferation was determined by incorporation of [(3)H]-thymidine. RESULTS: The two isoforms induced a similar humoral response. The lack of any IgE production and the ratio of IgG1 to IgG2a clearly indicated a Th-1-type response. The antisera against both isoforms were highly cross-reactive, which was supported by the energy plot indicating similar folding of the two protein isoforms. However, determination of IFN-gamma and IL-4 in the serum elicited a strikingly different cytokine profile during the course of the immune response. In contrast to pCMV-Beta, pCMV-Betd caused no significant allergen-specific proliferation and induced only marginal levels of the key cytokines. CONCLUSIONS: Based on the assumption that the induction of a strong Th-1 type response is a prerequisite for successful treatment of allergy, our results favor the use of isoform Bet v 1a in combination with CpG motifs for a novel type of allergen immunotherapy based on plasmid DNA immunization. Additionally, the data also confirm the assumption that the antigen itself can have a marked influence on the immune response after genetic immunization.

Allergens↗
PubMed1999

Rhizopusmycosis in a harbor porpoise from the Baltic Sea.

A case of systemic mycosis due to a Rhizopus sp. infection is described in a dead-stranded, 10-yr-old, male harbor porpoise (Phocoena phocoena) found on the beach of Neustadt, Schleswig-Holstein on the Baltic Sea (Germany). At necropsy, granulomatous mycotic lesions in brain, lung, kidneys, testis, and draining lymph nodes were found. In addition, a focal ulcerative gastritis of the first stomach, due to a nematode infection, was present and is suspected to be the portal of entry for the fungus.

Animals↗
PubMed1999

Serum antibodies against particular antigens of Borrelia burgdorferi sensu stricto and their potential in the diagnosis of canine Lyme borreliosis.

Dog sera (n = 118) were tested for antibodies recognizing Borrelia (B.) burgdorferi sensu stricto strain B31 (ATCC 35210) antigens. In total, 18 of the dog sera gave positive results in a whole cell sonicate ELISA (WCS ELISA). These positive sera were further evaluated by immunoblot assay, utilizing a whole bacterial lysate as antigens. 94.4% (17 of 18) of the dog sera reacted with immunodominant antigens at 20-22 kDa (protein C, pC), 31 kDa (outer surface protein A, OspA), 34 kDa (outer surface protein B, OspB), 41 kDa (flagellin), 60 kDa ("common antigen"), and/or 100 kDa (presumably p100). Sera recognizing pC (20-22 kDa) and antigens > 94 kDa always detected the highest number of antigen bands, indicating the specificity of those antigens in serological diagnosis. The results clearly demonstrate that the WCS ELISA is a useful tool for testing sera of dogs for antibodies against B. burgdorferi. However, positive results should be confirmed by immunoblot, using WCS as antigen. According to the presented data, we recommend criteria for B. burgdorferi immunoblots using dog sera as follows: sera have to be considered as positive if they detect the 41 kDa flagellin, and two of the 5 immunodominant antigens, namely > 94 kDa (presumably p100), 60 kDa ("common antigen"), 34 kDa and 29-31 kDa (OspB and OspA, respectively) and 20-22 kDa (pC). If sera only recognize the 41 kDa flagellin, this result is equivocal, requiring testing a second serum sample 4 to 8 weeks later.

Animals↗
PubMed1998

Acute changes in spontaneous echo contrast and atrial function after cardioversion of persistent atrial flutter.

With use of transesophageal echocardiography, the short-term effects of transthoracic electrical cardioversion of atrial flutter (AFI) on atrial mechanical function and spontaneous echo contrast were determined. Thirty patients who had AFI for a mean of 6.4 +/- 12.2 months underwent transthoracic cardioversion. A transesophageal echocardiogram was recorded immediately before cardioversion, and left atrial appendage emptying velocity and spontaneous contrast were assessed serially at 1, 3, and 5 minutes after cardioversion in 28 patients, and also at 8, 10, and 15 minutes after cardioversion in a subgroup of 13 patients. Cardioversion was deferred in 2 patients (7%) because a thrombus was found in the left atrial appendage. Before cardioversion, spontaneous contrast was present in the left atrium in 7 of 28 patients (25%) who underwent cardioversion. The mean left atrial appendage emptying velocity of 54 +/- 22 cm/s before cardioversion fell by 26% to 40 +/- 25 cm/s at 1 minute after restoration of sinus rhythm (p <0.01). There were no significant changes in the mean left atrial appendage-emptying velocity between 1 and 15 minutes after cardioversion. Within 5 minutes after conversion to sinus rhythm, left atrial spontaneous echo contrast developed de novo or worsened in 12 of the 28 patients (43%). In conclusion, the results of this study demonstrate that persistent AFI may be associated with left atrial thrombi before cardioversion and that cardioversion of AFI is associated with a significant degree of atrial stunning and formation of spontaneous echo contrast.

Adult↗
PubMed1998

Effectiveness of three different doses of carvedilol for exertional angina. Carvedilol-Angina Study Group.

Carvedilol is a nonselective beta-receptor antagonist with vasodilating properties primarily due to selective alpha-1 antagonism. This 4-treatment, 5-period, double-blind, crossover study evaluated the efficacy and safety of 3 doses of carvedilol (12.5, 25, and 50 mg given twice daily) versus placebo in 122 patients with chronic stable angina. Carvedilol in doses of 25 mg twice daily and 50 mg twice daily was statistically superior to placebo with respect to time to angina (placebo: 316 seconds; 25 mg carvedilol: 337 seconds, p = 0.0039; 50 mg: 345 seconds, p <0.0001) and time to 1-mm ST-segment depression (placebo: 301 seconds; 25 mg: 313 seconds; 50 mg: 323 seconds; p <0.0001). The percentage of patients reporting any adverse experience was slightly less in those receiving placebo (placebo: 28.4%; 12.5 mg: 33.1%; 25 mg: 34.5%; 50 mg: 31.9%). Carvedilol is effective and safe in treating patients with chronic stable angina.

Aged↗
PubMed1998

Predictors of dropout from psychosocial treatment of cocaine dependence.

The current study assessed demographic, drug and psychiatric predictors of dropout in the pilot/training phase of a large, multi-site psychotherapy outcome study for patients with cocaine dependence. The different predictors of dropout were assessed throughout the phases of the study: screening, intake, stabilization and assessment phase, and following randomization to treatment. Results showed that (1) younger patients were less likely to keep their intake appointment. (2) Of the patients who had an intake visit, those who did not complete high school and with more days of cocaine use in the previous month were less likely to complete an initial stabilization and assessment phase requiring 1 week of abstinence from all drugs. A survival analysis was used to examine time to dropout for the 286 patients randomized to individual treatment. (3) Again, younger age was associated with dropout after randomization. (4) Drug use variables did not predict time to dropout. (5) Presence of any current Axis I disorder was associated with later dropout from treatment. Minority treatment information seekers and treatment initiators were less likely to go on to complete the full treatment program.

Adult↗
PubMed1998

The relationship between cardiothoracic ratio and left ventricular ejection fraction in congestive heart failure. Digitalis Investigation Group.

BACKGROUND: Left ventricular ejection fraction (EF) is a valuable prognostic index in patients with congestive heart failure (CHF). Although EF can be readily measured, many clinicians use roentgenographic heart size as a clue to differentiate systolic from diastolic dysfunction, even in the absence of solid supportive data. OBJECTIVE: To test the hypothesis that the cardiothoracic ratio (CTR) measured from the chest roentgenogram can be used to estimate left ventricular EF in individuals with CHF. METHODS: To answer this question, the database of the Digitalis Investigation Group trial was used. The CTR, determined using the Danzer method, and quantitative EF, measured locally using angiographic, radionuclide, or 2-dimensional echocardiographic techniques, were compared in 7476 patients with clinical CHF (New York Heart Association functional classes I-IV) due to acquired left-sided cardiac disease of ischemic, hypertensive, idiopathic, and alcohol-related causes. RESULTS: Mean (+/-SD) CTR for the cohort was 0.53+/-.07. Mean (+/-SD) EF was 31.7%+/-12.2%. A weak, negative correlation between CTR and EF was observed (r=-0.176). Similar findings were obtained when the results were stratified by cause of CHF, presence of clinically defined right ventricular dysfunction, and method of EF measurement. Categorical analysis failed to yield a CTR cutoff point that facilitated useful segregation of individuals with an EF greater than 35% or 35% and below; greater than 40% or 40% and below; and greater than 45% or 45% and below in any patient group. CONCLUSIONS: Although a weak, negative correlation exists between CTR and EF, this relationship does not allow for accurate determination of systolic function in individual patients with CHF. Considering the morbidity and mortality associated with CHF, and the clinical implications of systolic function in this syndrome, direct measurement of EF is recommended.

Aged↗
PubMed1998

Smoking in adult survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Health-related behaviors are of particular concern in survivors of childhood cancer as they are at increased risk for second cancers and long-term organ dysfunction. The purpose of this study was to compare the smoking behavior and associated factors in young-adult survivors of childhood acute lymphoblastic leukemia (ALL) with those in sibling controls. METHODS: A telephone interview that surveyed smoking behavior was conducted with 592 young-adult survivors, treated before age 20 years on Children's Cancer Group ALL protocols, and 409 sibling controls. Using stratified chi-squared analyses and Cox proportional hazards models, we compared the rates of smoking initiation and smoking cessation between survivors and control subjects. Demographic characteristics (age, sex, race, and education) and psychological factors (mood and self-concept) were examined as predictors interacting with survivorship in logistic regression analyses to try to distinguish a subgroup of survivors who may be at greater risk for smoking. RESULTS: Survivors were significantly less likely to have ever smoked (23.0% versus 35.7%; P<.0001) and thus were less likely to ever be regular, daily smokers than sibling controls (19.1% versus 31.3%; P<.0001). Survivors were less likely to quit smoking than sibling controls (26.6% versus 35.2%), although this result was not statistically significant. There were no interactions between survivor status and either demographic or psychological features on smoking behavior. CONCLUSIONS: Young-adult survivors of childhood ALL are less likely to experiment with smoking but, once having started, are at similar risk for becoming habitual, persistent smokers as sibling controls.

Actuarial Analysis↗
PubMed1998

[Asylum seekers and refugees in general practice: problems and possible developments].

Health and health services provided to asylum seekers and refugees by the Swiss National Health System have so far not been systematically investigated. The aim of this cross-sectional study was to describe the attending asylum seekers and refugees demographically and clinically, to identify main problem areas as perceived by general practitioners and to highlight options and venues for improvements. 272 questionnaires have been filled in by GPs of eight "federal districts" (Kantone) and the consultations of 1477 asylum seekers and refugees have been documented during one month in 193 surgeries. The documented asylum seekers and refugees reflected the distribution of this population in Switzerland. Low consultation rates of asylum seekers and refugees in the majority of surgeries and high diversity of this population in respect to places of origin, education and proficiency in languages appear to be the major determinants of the difficulties in providing adequate health services to them. Readily available information on the past medical history and on the ethnic background of these patients and continuing education on specific topics concerning health care for asylum seekers and refugees were thought to be particularly useful. This needs to be considered in the planning of services for this group. General practitioners specialized in health care for asylum seekers and refugees is an option for providing improved specific services (interpreters, institutional links, culturally adapted medical care).

Adolescent↗
PubMed1998

Cardiac electrophysiologic effects of norepinephrine in human beings.

BACKGROUND: The electrophysiologic effects of norepinephrine (NE) in human beings have not been previously described. METHODS: The electrophysiologic effects of NE infused at a rate of 25 ng/kg/min were determined in 21 patients with a mean age of 41 +/- 11 years and without structural heart disease who underwent an electrophysiology procedure. In a subgroup of 10 patients electrophysiologic parameters were measured at baseline, after the infusion of NE, and after administration of beta-blockade while in continuous NE infusion. RESULTS: The baseline NE plasma concentration of 298 +/- 153 pg/ml increased to 708 +/- 419 pg/ml after the infusion of NE. NE significantly increased the mean blood pressure, sinus cycle length, corrected sinus node recovery time, ventriculoatrial block cycle length, and the atrial and ventricular effective refractory periods. In a subset of 10 patients 0.2 mg/kg propranolol administered during continued infusion of NE resulted in a further increase in sinus cycle length, atrial-His interval, and ventricular refractoriness. CONCLUSION: A physiologic elevation in the plasma NE concentration results in a depression of sinus node function and atrioventricular conduction and in prolongation of atrial and ventricular refractoriness. Some of NE's effects are partially offset by beta-adrenergic stimulation.

Adrenergic alpha-Agonists↗
PubMed1998

Effect of isoproterenol on QRS complex morphology during ventricular pacing: implications for pace mapping.

Ventricular pace mapping may be used to identify the site of origin of idiopathic ventricular tachycardia. Isoproterenol is often required to induce this type of ventricular tachycardia, but its effect on QRS morphology during pace mapping is unknown. Therefore, this study was performed to evaluate the effect of isoproterenol on QRS morphology during ventricular pacing. The study population consisted of 20 patients (mean age 38 +/- 14 years) undergoing a clinically indicated electrophysiology procedure. Ventricular overdrive pacing was performed in trains of 12 stimuli at cycle lengths of 400, 350, 300, and 250 ms, first in the baseline state during an infusion of isoproterenol, and again after isoproterenol washout. Pacing was performed at the right ventricular apex in 10 patients, in the right ventricular outflow tract in 6 patients, and in the left ventricle in 4 patients. Visual evaluation revealed no apparent effects of isoproterenol on QRS morphology at any of the three pacing sites or at any of the pacing cycle lengths. It was concluded that QRS morphology during ventricular pacing is not affected by isoproterenol infusion. Therefore, in patients with idiopathic ventricular tachycardia, even if the induction of tachycardia requires infusion of isoproterenol, successful pace mapping may be performed in its absence.

Aged↗