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Biomedical subjects

E Levin

Publications and source records attributed to E Levin.

At least 19 recordsLinked to original sources
PubMed1996

Receptors characterization of intraperitoneally N-nitroso-N-methylurea-induced mammary tumors in rats.

Mammary adenocarcinomas induces in female Sprague-Dawley rats by three intraperitoneal injections of N-nitroso-N-methylurea were studied in order to characterize their estrogen (ER), progesterone (PgR), prolactin (PRLR) and epidermal growth factor (EGFR) receptors. All samples evaluated showed the presence of ER and PgR in the cytosol fraction and PRLR amd EGFR in the membrane fraction. Q (fmol/mg) and K(d) (nM) values were as follows: ER, 56 +/- 11 and 0.5 +/- 0.1; PgR, 109 +/- 25 and 2.2 +/- 0.5 and PRLR, 335 +/- 75 and 0.5 +/- 0.2, respectively. In all tumors studied, two specific sites were found for EGFR, one with Q(1) = 22 +/- 9 and K(d1) = 0.6 +/- 0.3, and the other with Q(2) = 125 +/- 33 and K(d2) = 2.1 +/- 0.5. Receptor content was found to be independent of tumor histopathological variety. Displacement index (DI) with estradiol and tamoxifen of [I(3)H]E2-ER binding showed great heterogeneity, with values ranging from 0.01 to1.54. No correlation between ER content and DI values was found. Antiestrogenic binding sites were not found in the microsomal fraction of ten mammary tumors examined. Proliferation of this experimental mammary tumor may be regulated by a complex interaction of steroid and polypeptide hormones, as well as growth factors.

Animals↗
PubMed1996

Effect of tamoxifen on intraperitoneal N-nitroso-N-methylurea induced tumors.

The effect of tamoxifen (TAM) was evaluated on a mammary tumor model induced in Sprague-Dawley rats by intraperitoneal administration of three N-nitroso-N-methylurea (NMU) doses. Animals received TAM (1 mg/kg per day) from 10 days before the first NMU dose up to 140 days later. Thereafter, treatment was discontinued and the observation period was extended 60 days longer. Mean overall latency period, tumor number per rat and tumor incidence were recorded. Significant differences between treated and control batches were observed in tumor number per rat (1.8 +/- 1.1 versus 5.2 +/- 1.6; P < 0.05) and in tumor incidence (50% versus 100%; P < 0.05), respectively. No significant difference in latency period between both batches was recorded. All lesions induced in the control batch were malignant, whereas only 45% of those induced in TAM-treated animals were malignant and the remaining 55% were preneoplastic. At 60 days after treatment discontinuance, tumor incidence increased to 90% and also tumor number per rat increased to 4.6 +/- 1.5. TAM effect was also evaluated in rats with NMU-induced tumors by treatment with 1 mg/kg per day during 60 days starting when tumors reached a 1.5-cm diameter. Regression to less than 80% of initial size in 49% of the tumors was observed, while in ovariectomized rats, 33% of tumors regressed. Estrogen receptor content, ER (fmol/mg protein) and Kd (nM) in control tumors were: 56 +/- 10 and 0.5 +/- 0.1. In tumors of TAM-treated animals, ER was less than 5 fmol/mg protein. Findings demonstrate that TAM significantly decreased the appearance of tumors induced in rats by i.p. injection of NMU and when TAM treatment was initiated after tumor induction, some tumors failed to respond to hormonal manipulation. Differential tumor growth response after TAM or oophorectomy in each tumor indicates that in the same rat it is possible to distinguish hormone-dependent and hormone-autonomous tumor populations. Hormonal regulation of tumor growth can be under intrinsic control, regardless of the hormonal status of the whole organism.

Animals↗
PubMed1995

Acute and long-term beta-adrenergic blockade for patients with neurocardiogenic syncope.

OBJECTIVES: This study was designed to prospectively evaluate the long-term outcome of drug therapy guided by head-up tilt testing for the management of unexplained syncope and near syncope. BACKGROUND: Head-up tilt testing is used to evaluate patients with unexplained syncope. The validity of acute drug testing and the efficacy of long-term oral therapy for prevention of recurrent syncope have not been investigated in large patient groups. METHODS: We studied 296 consecutive patients with unexplained syncope or near syncope who underwent 80 degrees head-up tilt testing with and without isoproterenol challenge. The efficacy of intravenous and oral beta-blocker therapy was evaluated by repeat testing. Patients with both positive and negative responses to therapy were followed up for rates of recurrence of syncope. RESULTS: A total of 193 patients (65%) had a positive tilt test response; 89% of these 193 required isoproterenol challenge to elicit this response. Patients with a positive tilt test result had lower values for heart rate at rest (mean +/- SD 69 +/- 13 vs. 74 +/- 14 beats/min, p = 0.046) and systolic blood pressure (137 +/- 28 vs. 145 +/- 30 mm Hg, p = 0.0018) at baseline than did the patients with a negative tilt test result. Intravenous propranolol blocked the positive response in 163 (90%) of 181 patients retested. Oral beta-blockers were effective by tilt test criteria in 118 (94%) of 125 patients; 12 (10%) had recurrent clinical symptoms while taking beta-blockers. Eight (42%) of 19 patients who had a negative tilt test response during beta-blocker therapy had recurrent symptoms when they stopped therapy. Three (23%) of 13 patients receiving empiric beta-blocker therapy had recurrent symptoms. The follow-up period for the patients with a positive tilt test result was 28 +/- 11 months (range 5 to 48). CONCLUSIONS: Intravenous propranolol is effective in preventing neurocardiogenic syncope diagnosed during head-up tilt testing and predicts the response to oral beta-blocker therapy. Oral beta-blocker therapy prevents recurrent syncope in the majority of patients. Recurrence of syncope is lowest when efficacy of oral beta-blocker therapy is confirmed by repeat head-up tilt testing.

Administration, Oral↗
PubMed1995

Opposite effect of a cAMP analogue on tumoral growth related to hormone dependence of a murine mammary tumor.

Interactions among transcription factors are one of the mechanisms that regulate gene expression. Through protein-protein associations different signaling pathways become connected and the message triggered by each of the molecules involved can modify other related routes. In a murine mammary tumor induced by medroxyprogesterone acetate (MPA), further treatment with this agent showed a different response on tumor growth. In one group of tumors, growth rate was increased (hormone dependent, HD), whereas in the other group the progestin agent failed to modify the rate of tumor development (hormone autonomous, HA). Progesterone receptors (PgR) and estrogen receptors (ER) were expressed in both groups. Administration of 8-CI-cAMP, a cAMP analogue, stimulated tumor growth in the HD subline and inhibited growth in the HA subline. Simultaneous administration of 8-CI-cAMP and MPA resulted in suppression of inhibitory 8-CI-cAMP action in the HA tumor subline attributable to changes in molecular configuration of protagonic members of each signaling pathway, whereas in the HD subline growth was additive as if each of the pathways were acting separately. MPA induced down regulation of PgR in both tumor sublines and up regulation of ER in the C4-HD subline. The effect of 8-CI-cAMP alone or associated with MPA was more complex and variations in PgR and ER content by themselves are insufficient to explain changes in tumoral growth. A model consistent with our experimental findings is presented.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Probing to bone in infected pedal ulcers. A clinical sign of underlying osteomyelitis in diabetic patients.

OBJECTIVE: To assess a bedside technique for diagnosing osteomyelitis. DESIGN: We prospectively assessed infected pedal ulcers for detectable bone by probing with a sterile, blunt, stainless steel probe. We then examined the relationship between detection of bone and the presence or absence of osteomyelitis that was defined histopathologically and/or clinically. SETTING: A tertiary care center. PATIENTS: Seventy-five hospitalized diabetic patients with a total of 76 infected foot ulcers were studied. RESULTS: Osteomyelitis was diagnosed in 50 instances (66%) and was excluded in 26 instances. Bone was detected by probing in 33 of 50 ulcers with contiguous osteomyelitis; in contrast, bone was probed in only four of 26 ulcers without contiguous osteomyelitis (P < .001). Bone detected on probing was visible in only three instances. Palpating bone on probing the pedal ulcer had a sensitivity of 66% for osteomyelitis, a specificity of 85%, a positive predictive value of 89%, and a negative predictive value of 56%. CONCLUSIONS: Palpation of bone in the depths of infected pedal ulcers in patients with diabetes is strongly correlated with the presence of underlying osteomyelitis. If bone is palpated on probing, specialized roentgenographic and radionuclide tests to diagnose osteomyelitis are unnecessary. Probing for bone should be included in the initial assessment of all diabetic patients with infected pedal ulcers.

Aged↗
PubMed1995

Serological evidence for hepatitis E virus infection in Israel.

Israel is suspected to be endemic for hepatitis E virus (HEV) because of its geographic location and the large-scale immigration from endemic countries. Although no cases of local HEV infection have been diagnosed, a serological survey would provide indirect evidence for such infection. We examined sera from 1,416 healthy subjects, including 1,139 Jews from various regions of Israel and 277 Arabs, most of whom reside in the West Bank of the Jordan River. In addition, we tested 13 non-A, non-B, and non-C viral hepatitis patients. Sera were screened for antibody to hepatitis E virus (anti-HEV) by a newly developed enzyme immunoassay (EIA) and by immunoblots for both IgG and IgM anti-HEV activity. Positive samples were confirmed by neutralization. The seroprevalence found by EIA was 2.81% and 1.81% in the Jewish and Arab populations, respectively. More than a 2-fold higher prevalence in males compared to females and an increase with age were found in both populations. However, these differences were nonsignificant. The geographical distribution was even throughout the country, except for two clusters of 3 and 4 seropositive individuals possibly reflecting past foci of infection. Eight of 37 EIA-positive sera were positive for IgG, and 3 were positive for IgM by the immunoblot assay. Among hepatitis patients (9 acute and 4 chronic), one patient with chronic hepatitis was positive for both IgG and IgM. Our study provides indirect evidence that Israel is endemic for HEV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Hepatitis E virus infection in hemophiliacs.

Israel is endemic for hepatitis E virus (HEV), the causative agent of enteric non-A, non-B hepatitis. Transmission is via the feco-oral route but the possibility of transmission through blood transfusion has been raised. This question was addressed by examining sera from 188 hemophilic patients in Israel, screening was performed with an enzyme immunoassay (EIA) for antibody against hepatitis E virus (anti-HEV) and confirmed with a neutralization test. Sixteen patients (9%) were seropositive for anti-HEV. A statistically significant difference was not found between the seroprevalence in this group and that of a healthy Israeli control population, matched for sex and age. The anti-HEV-seropositive hemophiliacs had the same seroprevalence of antibodies to hepatitis B and C virus and to HIV and the same number of cases with chronic hepatitis as among the anti-HEV-seronegative patients. The seroprevalence of antibodies to hepatitis A virus (anti-HAV) was, on the other hand, higher in the anti-HEV-seropositive group. This study indicates that HEV is not transmitted by cryoprecipitate or lyophilized factor concentrates. High prevalence of coinfection with hepatitis A supports our conclusion that HEV infection in Israeli hemophiliacs was due mainly to feco-oral transmission.

Adolescent↗
PubMed1995

Increased capillary permeability induced by human follicular fluid: a hypothesis for an ovarian origin of the hyperstimulation syndrome.

OBJECTIVE: To examine the effect of follicular fluid (FF) and peritoneal fluid (PF) from patients undergoing assisted reproductive technology procedures on endothelial barrier function. This was determined in vitro by measuring the permeability of filter-grown bovine aortic endothelial cell monolayers to a permeability marker. DESIGN: Endothelial cells obtained from bovine thoracic arotas were treated with collagenase solution and plated on millicell filters, on which they formed confluent monolayers. Flux rate was determined at 60 minutes by measuring the radioactive tracer (3H mannitol) permeating from the apical to the basolateral part of the filter. Fifty-eight samples of FF and PF, both from stimulated and natural cycles were analyzed and grouped according to the number of eggs retrieved. Follicular fluid and PF samples from natural cycles were used as controls. RESULTS: There was an augmentation in the permeability rate of both FF and PF from patients undergoing controlled ovarian hyperstimulation (COH) who responded with an increasing number of eggs compared with controls (51% and 39%, respectively). When analyzing samples from patients who responded with a low number of oocytes, no significant increase was observed. CONCLUSIONS: It is known that in OHSS, the increase in capillary permeability is related to the administration of gonadotropins, and is believed to be mediated by a vasoactive substance of ovarian origin. In this study, FF and PF from patients undergoing COH showed a significant increase in the permeability rate through endothelial cells in vitro. Based on these findings, it could be hypothesized that if the same events took place in vivo, the isolation of this factor from ovarian source could be of significant importance to elucidate the pathogenesis of OHSS.

Adult↗
PubMed1994

Estrogen receptor isoforms and progestin hormone dependence in a mouse mammary tumor model.

The close interaction between receptors and other transcription factors suggests that their corresponding transducing signals can trigger functional and structural changes in other related molecules. The effect of a progestinic agent, medroxyprogesterone acetate (MPA), on some of the estrogen-receptor (ER) parameters was studied in 2 murine mammary tumor sublines with different progestin hormone dependence for their respective growth. The relative binding affinity of estradiol and tamoxifen for the ER, the receptor content and the ER isoforms studied by HPLC were determined in the hormone-autonomous (HA) and the hormone-dependent (HD) tumor sublines. In the HA subline administration of MPA did not modify the tumor growth rate, whereas this was accelerated in the HD subline. The ER content was clearly increased in the HD tumor subline, but not in the HA subline, compared with the untreated controls. In contrast, the E2 and tamoxifen relative binding affinity for the ER and the isoform profiles were affected by MPA treatment in the HA, but not in the HD tumor subline. The functional change (decrease in relative binding affinity) can be attributed to the appearance of a lower-molecular-size ER isoform under the progestinic treatment. Modifications in one receptor molecule by the action of ligands corresponding to another type of receptor show the interconection between transcription factors and the necessity of broadening conventional concepts regarding hormone dependence in mammary tumorigenesis.

Animals↗
PubMed1994

Use of ampicillin/sulbactam versus imipenem/cilastatin in the treatment of limb-threatening foot infections in diabetic patients.

In a double-blind randomized trial, imipenem/cilastatin (I/C; 500 mg every 6 hours) and ampicillin/sulbactam (A/S; 3 g every 6 hours) were compared in regard to their efficacy for initial empirical and definitive parenteral treatment of limb-threatening pedal infection in diabetic patients. The major endpoints of treatment were cure (resolution of soft-tissue infection), failure (inadequate improvement, necessitating a change in antibiotic therapy), and eradication (clearance of all pathogens from the wound and any bone cultures). Patients in the two treatment groups were similar in regard to the severity of diabetes; presence of neuropathy and peripheral vascular disease; site and severity of infection; pathogen isolated; and frequency of osteomyelitis (associated with 68% of the 48 A/S-treated infections and 56% of the 48 I/C-treated infections). After 5 days of empirical treatment, improvement was noted in 94% of the A/S and 98% of the I/C recipients. At the end of definitive treatment (days' duration [mean +/- SD]: 13 +/- 6.5 [A/S], 14.8 +/- 8.6 [I/C]), outcomes were similar: cure, 81% (A/S) vs. 85% (I/C); failure, 17% (A/S) vs. 13% (I/C); and eradication, 67% (A/S) vs. 75% (I/C). Treatment failures were associated with the presence of antibiotic-resistant pathogens and possible nosocomial acquisition of infections. The number of adverse events among patients in the two treatment groups was similar: 7 in the A/S group (4 had diarrhea and 3 had rash) and 9 in the I/C group (5 had diarrhea, 2 had severe nausea, 1 had rash, and 1 had seizure). Efficacy of A/S and I/C is similar for initial empirical and definitive treatment of limb-threatening pedal infection in patients with diabetes.

Adult↗
PubMed1994

[Transcription factors and proliferative diversity of neoplastic cells].

Cancer is a multistage process with sequential steps: initiation, promotion, progression. However, the distinction between the agents that can trigger any of these processes is less clear, depending on doses, biological stage of the tissue, molecular interactions, genomic and somatic mutation, etc. Thus, steroid receptors, classically considered as promoters, could be acting as initiators under different alterations. On the other hand, chemical carcinogens that can produce DNA damage leading to cellular transformation, in lower dosage are able to alter nuclear proteins which in turn favor the action of other agents triggering the initiation process. Transcription factors (TF) are nuclear proteins with particular structural configurations for their interaction with DNA. There are families of TF with specificity for certain nucleotide sequences called "response elements". The association TF-DNA response elements modulate the genomic transcription and synthesis of proteins, many of which are related to cellular proliferation. The transcriptional message can also be influenced by TF protein-protein interactions, besides their association with the response elements. This "cross-talk" or "side regulation" becomes an important genomic regulatory mechanism. Certain biochemical signals acting on particular proteins (receptors, enzymes) can then trigger biological effects attributable to other proteins. Another transcriptional regulatory mechanism is the cytoplasm-nucleus shuttling of TF according to the cellular replication rhythm and other metabolic cellular requirements. These recent advances open new vistas for the pharmacological attack to the proliferative diversity of neoplastic cells.

Animals↗
PubMed1993

A shared pathway in atrioventricular nodal reentrant tachycardia and atrial flutter: implications for pathophysiology and therapy.

Atrioventricular (AV) nodal reentrant tachycardia and atrial flutter are considered 2 distinct supraventricular tachycardias. Recent clinical and experimental data suggest that both these tachycardias include an area in the lower right atrial septum in their reentrant pathways. This study was designed to test the hypothesis that there is an association between the mechanisms of AV nodal reentrant tachycardia and atrial flutter because of a shared pathway of reentry. Consecutive patients referred for evaluation and management of supraventricular tachycardia, thought to be due to AV nodal reentry, underwent electrophysiologic testing protocols designed to induce both AV nodal reentrant tachycardia and atrial flutter, if present. Fifteen of 29 patients (52%) had both AV nodal reentrant tachycardia and atrial flutter induced during electrophysiologic testing. Seven of these 15 patients (47%) underwent transcatheter radiofrequency current application (mean power 34 +/- 4 W) against the tricuspid annulus above the coronary sinus. In each patient, neither AV nodal reentrant tachycardia nor atrial flutter could be induced after the procedure. Repeat study after successful ablation (mean 6 days) showed no inducible supraventricular arrhythmia of either type at baseline study or during isoproterenol infusion. Atrial flutter occurs frequently (15 of 29 patients; 52%) in patients with AV nodal reentrant tachycardia, because of a shared pathway in their reentry circuits. Because of this shared pathway, both arrhythmias can be ablated at the same site. These observations promote new insights into the mechanism and therapeutics of supraventricular tachycardias.

Adult↗
PubMed1993

Anticoagulant activity of Hirulog, a direct thrombin inhibitor, in humans.

Hirulog (BG8967) is a direct thrombin inhibitor built by rational design using the protein hirudin as a model (Maraganore et al. [1990]; Biochemistry 29: 7095-101). In order to evaluate the therapeutic potential for hirulog in the management of thrombotic disease, the tolerability and anticoagulant activity of the agent were examined in a study of human volunteers. In a randomized, placebo-controlled study (n = .54), the intravenous infusion of hirulog over 15 min showed a rapid, dose-dependent prolongation of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). There was a corresponding dose-dependent increase in plasma hirulog levels. The peptide was rapidly cleared with a half-life of 36 min and a total body clearance rate for the peptide of 0.43 l kg-1 h-1. Similar activity was observed following subcutaneous injection but with sustained pharmacodynamic and pharmacokinetic behavior. There was a significant correlation between pharmacokinetic and pharmacodynamic variables for both intravenous (r = 0.8, p < 0.001) and subcutaneous administration (r = 0.7, p = 0.002). To evaluate the possible interactions of aspirin on the tolerability and anticoagulant activity of intravenous hirulog, a cross-over design was employed in eight subjects. Aspirin administration did not modify the peptide's activity. At the administered dose of 0.6 mg kg-1 h-1 for 2 h, hirulog infusion prolonged APTT from 230 to 260% baseline. The infusion of hirulog in subjects who had received aspirin was not associated with any significant changes in the template bleeding time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Characterization of rat uterine estrogen receptors in vivo.

In vivo binding of [3H]estradiol ([3H]E2) in the rat uterus was performed by an intraluminal perfusion of the ligand for different time periods. In this way the binding takes place in the intact organ before processing the tissue. In 10 min, with 10 nM [3H]E2 apparent saturation or steady state incorporation of the [3H]E2 was achieved with a similar distribution of the label between cytosol and nuclear fractions. In vitro, the subcellular localization of the estrogen receptor (ER) is influenced by the extent of tissue damage. With the intact organ the ER subcellular distribution approaches that of the in vivo perfusion. With increasing [3H]E2 in the perfusate it was possible to obtain a "saturation" curve and to derive the kinetic parameters. For cytosol: Kd 16 nM; Bmax 235 fmol/mg prot. For nucleus: Kd 2.7 nM; Bmax 103 fmol/mg prot. To follow the time course of the ER movement in vivo, "pulse and wait" experiments were designed. Both uterine horns were perfused for 1 min. One of the horns was immediately processed (0 time) and the other was left in place after the perfusion for different periods. At 0 time 90% of the bound label appeared in the cytosol. At 5, 15 and 30 min, the label in the cytosol decreased and that of the nucleus increased approx. to 50%. Thus, translocation of the bound label from cytosol to nucleus was apparent. The role of the cytoplasm-nucleus ER traffic in the regulation of gene transcription by estrogens is discussed.

Animals↗
PubMed1991

The Norwegian, Danish and Dutch version of the Appraisal of Self-care Agency Scale; comparing reliability aspects.

This study was designed to test reliability aspects of a scale that was developed to measure the theoretical concept of self-care agency (Orem 1985). Equivalence and internal consistency of the scale were studied with populations of elderly patients and their nurses in The Netherlands, Norway and Denmark. Data was provided by 120 patients and 233 nurses. Not all criteria for reliability could be met for the Danish and the Norwegian versions of the scale. Nevertheless it is concluded that the results are indications for the reliability of the Dutch, as well as the Danish and Norwegian versions of the scale.

Denmark↗
PubMed1991

Brain and atrial natriuretic peptides bind to common receptors in brain capillary endothelial cells.

The recent discovery of brain natriuretic peptides (BNP) that stimulates natriuresis, diuresis, and vascular smooth muscle relaxation in a manner similar to that of atrial natriuretic peptide (ANP) suggests the possibility that these endocrine hormones function via some common mechanism. Indirect evidence from several laboratories suggests that BNP and ANP may bind to the same receptors. We examined whether ANP and BNP bind to a common set of receptors in cultured bovine brain capillary endothelial cells and in bovine aortic endothelial cells. Scatchard plot analysis of binding data shows a similar dissociation constant (KD) of approximately 0.3 nM and a maximal binding capacity (Bmax) of 50 fmol/mg protein for both natriuretic peptides in brain capillary cells and 0.6 nM and 80 fmol/mg protein, respectively, in the aortic endothelial cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the affinity cross-linked receptor-ligand complex shows a strongly labeled 65-kDa receptor and a 125-kDa band that is likely to be a receptor of the guanylate cyclase type. ANP and BNP cross compete equally for binding to the two receptors identified on the gels. ANP and BNP also stimulate guanosine 3', 5'-cyclic monophosphate production in these cells, consistent with the presence of a functional guanylate cyclase-linked B receptor. We conclude that ANP and BNP share common receptors in brain capillary and aortic endothelial cells.

Animals↗