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Biomedical subjects

E Eisenberg

Publications and source records attributed to E Eisenberg.

At least 19 recordsLinked to original sources
PubMed1999

Chronic pain in Holocaust survivors.

There is limited research on the connection between the Holocaust and chronic pain, despite evidence suggesting that medical and psychological sequelae are common in survivors. The goals of this study were: (1) to define Holocaust survivors' (n = 33) chronic pain characteristics as manifested 50 years after the war, (2) to compare survivors with controls (n = 33) who did not experience World War II atrocities, and (3) to investigate the connection between past trauma and chronic pain. Data were collected through questionnaires that included a detailed medical and pain history, visual analog scale (VAS), McGill Pain Questionnaire (MPQ), Beck Depression Inventory (BDI), Symptom Check List-90 (SCL-90), and Pain Disability Index (PDI). A comparison of variables between the two groups was conducted using multivariate analysis of variance (MANOVA) and ANOVA, and canonical discriminant analysis. Results showed that Holocaust survivors reported higher pain levels (73 +/- 18 vs. 56 +/- 21; P < 0.005), more pain sites (4.5 6 2.8 vs. 2.7 6 1.4; P < 0.05), and significantly higher depression scores (17.6 +/- 8.4 vs. 9.2 +/- 4.6; P < 0.001); they tended to utilize more medical services (5.9 +/- 3.0 vs. 5.1 +/- 2.8). Nonetheless, survivors did not regard themselves more disabled as compared with controls. They reported a higher activity level as measured by walking distance capacity, and spent significantly fewer hours resting (4.3 +/- 3.6 vs. 7 +/- 4.6; P < 0.05). This paradoxical combination of high pain intensity, moderate to severe depression, and high activity level characterizes Holocaust survivors' chronic pain. It is conceivable that by remaining active Holocaust survivors fight back their pain, distress, and depression. These findings suggest that Holocaust atrocities affect survivors' chronic pain even years later.

Aged↗
PubMed1999

Leiomyosarcoma presenting as a mandibular gingival swelling: a case report.

We report a case of primary low-grade leiomyosarcoma of the mandible in an otherwise healthy young woman. The neoplasm presented as a painful, pericoronal gingival swelling that mimicked an acute periodontal infection. It was managed accordingly, with curettage, debridement, and antibiotics. When the lesion failed to respond to this treatment approach, a biopsy was performed. Microscopy revealed a malignant mesenchymal neoplasm which, on immunohistochemistry analysis, demonstrated reactivity for smooth muscle actin (SMA) and vimentin. This established the diagnosis of leiomyosarcoma; subsequently, an en bloc resection of mandibular bone and overlying soft tissue was performed. Close follow-up for over 10 years has revealed no evidence of recurrent or metastatic disease. Since the patient was taking oral contraceptives prior to the onset of the lesion, a possible link between estrogen and smooth muscle tumors is considered.

Adult↗
PubMed1998

Characterization of D10S and K71E mutants of human cytosolic hsp70.

To determine the effect of mutations at the nucleotide-binding site of recombinant Hsp70 on its interaction with protein and peptide substrates, point mutations were made at D10 and K71, two residues at the active site. The D10S mutation weakened both ATP and ADP binding, while the K71E mutation weakened only ATP binding. In binding experiments using Hsp70 with no bound nucleotide, the mutated Hsp70s interacted with clathrin and peptide just like the wild-type Hsp70. However, the D10 mutation completely abolished the effects of both ATP and ADP on peptide and clathrin binding. The K71 mutation also abolished the effect of ATP on substrate binding, but ADP, which still bound tightly, had its normal effect on substrate binding. In addition, the D10S and K71E mutants had greatly reduced ability to uncoat clathrin-coated vesicles at pH 7.0, bind to clathrin baskets at pH 6.0, and undergo polymerization induced by YDJ1 in the presence of ATP. We conclude, first, that nucleotides must bind strongly to Hsp70 to affect substrate binding and, second, that interaction of Hsp70 with DnaJ homologues may also require a strongly bound ATP.

Adenosine Diphosphate↗
PubMed1998

Can patients with chronic neuropathic pain be cured by acute administration of the NMDA receptor antagonist amantadine?

The treatment of neuropathic pain remains a challenge as it rarely leads to long-term relief of symptoms. We report three patients with chronic neuropathic pain, in whom acute administration of the N-methyl-D-aspartate (NMDA) receptor antagonist amantadine resulted in complete resolution of symptoms, presumably due to termination the central 'wind-up' phenomenon.

Aged↗
PubMed1998

The NMDA receptor antagonist amantadine reduces surgical neuropathic pain in cancer patients: a double blind, randomized, placebo controlled trial.

Neuropathic pain is often severe, persistent, and responds poorly to analgesic medications. Recent evidence suggests that N-methyl-D-aspartate (NMDA) receptor antagonists may be effective in the treatment of neuropathic pain. The present trial was designed to test the efficacy of acute administration of the NMDA receptor antagonist amantadine in relieving surgical neuropathic pain in patients with cancer. The study sample consisted of 15 cancer patients with the diagnosis of surgical neuropathic pain. Two 500 ml infusions of either 200 mg amantadine or placebo were administered over a 3 h period, in a randomized order, 1 week apart from each other. Spontaneous and evoked pain were measured for 48 h before treatment, during treatment, and for 48 h following treatment. An average pain reduction of 85% was recorded at the end of amantadine infusion vs. 45% following placebo administration. The difference in pain relief between the two treatments was statistically significant (P = 0.009). Mean pain intensity remained significantly lower during the 48 h following amantadine treatment as compared with the 48 h prior to treatment (31% reduction; P = 0.006), whereas no such effect was found with the placebo (6% reduction; P = 0.40). Amantadine, but not the placebo, also reduced 'wind up' like pain (caused by repeated pinpricking) in four patients. We conclude that amantadine infusion is a safe and effective acute treatment for surgical neuropathic pain in cancer patients. Further trials with long-term oral or parenteral amantadine treatment should be conducted.

Adult↗
PubMed1998

The effect of clinical information on the histopathologic diagnosis of oral epithelial dysplasia.

OBJECTIVES: The purpose of this study was to test the hypothesis that clinical information submitted with biopsy specimens helps pathologists be more consistent and accurate in diagnosing oral epithelial dysplasia. STUDY DESIGN: Each of six board-certified oral and maxillofacial pathologists examined the same set of 120 oral biopsies (involving diagnoses ranging from hyperkeratosis to severe epithelial dysplasia); they had examined these same biopsies in a previous study, but this time the clinical information was provided for each case. The examiner's diagnosis was compared to the sign-out diagnosis for each case. RESULTS: Rates of exact agreement with the sign-out diagnosis averaged 38.5%, and there was 85.4% agreement within one histologic grade. The rate of agreement in distinguishing epithelial dysplasia from no dysplasia was 71.4%. These results, when compared to those from a previous study in which the same examiners had evaluated the same slides but without clinical histories, represent a 2.5% to 20% decrease for exact agreement among the six pathologists, a 0% to 8.5% decrease for agreement within one histologic grade, and a 0% to 23.4% decrease for agreement regarding the presence or absence of epithelial dysplasia. CONCLUSIONS: When clinical information was used, accuracy and consistency among board-certified oral and maxillofacial pathologists in the diagnosis of oral epithelial dysplasia was not improved. In fact, there was a decrease in accuracy.

Biopsy↗
PubMed1997

Cloning and characterization of the Aspergillus nidulans DNA topoisomerase I gene.

The topoisomerase I (TOP1) gene was cloned and sequenced from Aspergillus nidulans using the polymerase chain reaction (PCR). Genomic DNA was used as a template to obtain a 2987-bp gene containing five small introns. PCR from a cDNA library yielded a 2613-bp sequence which codes for an 871 amino acid protein. Comparison of the deduced amino acid sequence with other DNA topoisomerase I (topo I) protein sequences shows a somewhat higher degree of identity with other fungal amino acid sequences than with the human enzyme. Topo I is a ubiquitous enzyme which can be converted to a cytotoxic molecule in the presence of drugs that function as topo I poisons. The Aspergillus TOP1 cDNA will be used in an effort to identify novel cytotoxic antifungals which target this enzyme.

Amino Acid Sequence↗
PubMed1997

Effect of yeast and human DnaJ homologs on clathrin uncoating by 70 kilodalton heat shock protein.

We recently found that the DnaJ homolog auxilin is required for Hsc70 to uncoat clathrin baskets. In the present study, we investigated the effect of two other DnaJ homologs, YDJ1 from yeast and HDJ1 from humans, on the uncoating activity of Hsc70. Neither YDJ1 nor HDJ1 substituted for auxilin in supporting uncoating. Rather, in the presence of auxilin, both YDJ1 and HDJ1 strongly inhibited uncoating at pH 7 and also prevented the binding of Hsc70 to clathrin baskets at pH 6. Both YDJ1, as shown previously, and HDJ1 catalytically induce polymerization of Hsc70 into large polymers in ATP, and the YDJ1 concentration required to inhibit uncoating was similar to the concentration required for polymerization. However, uncoating was almost completely inhibited even at low concentrations of Hsc70 where only partial polymerization occurs, suggesting that YDJ1 inhibits uncoating not only by polymerizing the Hsc70 but also by some other mechanism as well. The effects of YDJ1 and HDJ1 were completely reversible; when they were removed, the Hsc70 regained full activity. Since both YDJ1 and HDJ1 inhibited the uncoating of clathrin baskets by brain cytosol as well as by purified Hsc70, this could be a physiological phenomenon which could affect other activities of Hsc70 in addition to uncoating.

Adaptor Proteins, Vesicular Transport↗
PubMed1997

Auxilin-induced interaction of the molecular chaperone Hsc70 with clathrin baskets.

We previously reported that a 100-kDa cofactor, recently identified as auxilin, is a DnaJ homolog which is required for Hsc70 to uncoat clathrin baskets. In the present study we investigated the effect of auxilin on the interaction of Hsc70 with pure clathrin baskets at pH 6, where no uncoating occurs. In a reaction which required auxilin, the baskets activated the Hsc70 ATPase activity more than 100-fold with an apparent dissociation constant of about 0.2 microM. Maximal ATPase activity occurred at a 1 to 1 molar ratio of auxilin to clathrin triskelion independent of the Hsc70 concentration suggesting that auxilin is primarily complexed with the clathrin baskets. The binding of Hsc70 to baskets also required auxilin, but less auxilin was needed for maximum binding than for maximum ATPase activity showing that auxilin can catalytically induce binding of Hsc70. The binding also required ATP; Hsc70 dissociated from baskets with a 6 min half-life when ATP was hydrolyzed to ADP. In contrast to auxilin, the assembly proteins, AP-2 and AP180, did not support activation of the Hsc70 ATPase activity by clathrin baskets nor did soluble clathrin triskelions at pH 7 significantly activate the ATPase activity with auxilin present. Therefore, the interaction of auxilin, clathrin baskets, and Hsc70-ATP is highly specific with auxilin first binding to a clathrin triskelion in the baskets and then Hsc70-ATP strongly binding to the auxilin-clathrin complex; the auxilin can then migrate to another clathrin triskelion before the ATPase cycle is complete.

Adaptor Proteins, Vesicular Transport↗
PubMed1997

Interaction of auxilin with the molecular chaperone, Hsc70.

We have studied the direct interaction of the constitutive isoform of Hsp70 (Hsc70) with the DnaJ homolog, auxilin, a cofactor that binds to clathrin-coated vesicles and is required for their uncoating by Hsc70. Auxilin caused a 5-fold increase in Hsc70 ATPase activity and a corresponding increase in steady-state levels of bound ADP; the dissociation constant for this effect was 0.6 microM. Auxilin also induced polymerization of Hsc70 and bound to the resulting polymer at a 1:1 molar ratio; here too the dissociation constant was 0.6 microM. Both this binding and polymerization required ATP; the Hsc70 depolymerized with a 4-min half-life when ATP was completely hydrolyzed to ADP. Although auxilin induces polymerization stoichiometrically and other DnaJ homologs induce polymerization catalytically, these data show that auxilin is similar to other DnaJ homologs in its ability to activate the Hsc70 ATPase activity, to polymerize Hsc70, and in the nucleotide dependence of this polymerization. Furthermore, the 70-amino acid J-domain of auxilin polymerized Hsc70 with the same nucleotide dependence as intact auxilin. Therefore, although only auxilin and not other DnaJ homologs support uncoating, our data suggest that various DnaJ homologs share a common mechanism of interaction with Hsc70, perhaps because their J-domains interact similarly with Hsc70.

Adaptor Proteins, Vesicular Transport↗
PubMed1997

Mouthwash use and dentures in relation to oral epithelial dysplasia.

This case-control study investigated the potential association between oral epithelial dysplasia (OED) and both mouthwash and denture use. Incident OED cases aged 20-79 years were identified through two oral pathology laboratories. Controls were pair-matched (1:1) to cases on age (+/- 5 years), gender, appointment date and surgeon. A telephone interview was used to obtain exposure information. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were generated using conditional logistic regression. Based upon 127 case-control pairs and after adjusting for smoking, drinking, education and either denture or mouthwash use, the OR for OED and regular mouthwash use (1+ uses/week for 6+ months) was 0.8 (95% CI, 0.4-1.5) while the OR for OED and wearing a denture was 0.7 (95% CI, 0.4-1.3). There were no clear trends of increased OED risk with increased mouthwash use or years of denture wearing. Our findings suggest that neither mouthwash nor denture use are associated positively with OED risk.

Adult↗
PubMed1997

Sonohysterography combined with sonosalpingography: correlation with endoscopic findings in infertility patients.

The diagnostic accuracy of sonohysterography combined with sonosalpingography or sonohysterosalpingography was evaluated in 100 infertility patients who also underwent endoscopic (hysteroscopy with or without laparoscopy) procedures. In patients with normal endometrial biopsy results, single endometrial layer thickness ranged from 3 to 5 mm and varied up to 2 mm in some areas. Diagnostic accuracy was 98% for submucosal fibroids, 96% for polyps, and 81% for synechiae. Missed lesions, were less than 2 mm in diameter. Tubal patency was successfully assessed in 79% of women with saline solution and in 92% of those who received contrast agent. This study demonstrates the efficacy of the combined use of SHG and SSG in infertility patients with uterine or tubal factor disorders.

Fallopian Tube Diseases↗
PubMed1996

Effect of constitutive 70-kDa heat shock protein polymerization on its interaction with protein substrate.

Constitutive 70-kDa heat shock protein (hsc70) is a mixture of monomers and oligomers in ADP, while in ATP it is monomeric unless certain DnaJ homologs are present which induce hsc70 to form large polymers in an ATP-dependent reaction. A key question regarding polymerized hsc70 is whether it is able to bind protein substrates. Polymerized BiP, the hsc70 present in the endoplasmic reticulum, has been found to bind substrates in vitro although substrates appear to bind only to monomeric BiP in vivo. In this study, we investigated whether substrate binds to polymerized cytoplasmic hsc70 in vitro. Although both stoichiometric ATP and high concentrations of cytochrome c peptide monomerized hsc70, direct binding studies provided no evidence that cytochrome c peptide binds to polymerized hsc70. Furthermore, the time course of cytochrome c peptide and clathrin binding to hsc70 suggested that rather than binding to polymerized hsc70, they monomerized it by reducing free monomer, thereby shifting the monomer-polymer equilibrium toward monomer. We conclude that peptide and protein substrates bind at least an order of magnitude more weakly to polymerized hsc70 than to monomer, suggesting that polymerization of hsc70 in vivo, perhaps by DnaJ homologs, may store it in an inactive form.

Adenosine Triphosphate↗
PubMed1996

The peripheral antinociceptive effect of morphine in a rat model of facial pain.

The present study compared the peripheral and systemic antinociceptive effect of morphine on formalin-induced facial pain behavior in the rat. Formalin (5%, 50 microliters) was injected subcutaneously into the vibrissal pad of adult rats (250-300 g). Morphine sulfate at doses of 100-1000 micrograms was subcutaneously injected locally (same area) or systemically (in the neck), 30 min before, or simultaneously with, formalin. The typical biphasic face grooming response, consisting of an early phasic phase (0-6 min) and a delayed tonic phase (12-42 min), displayed by control animals, was suppressed by both local and systemic administration of morphine; this effect was dose dependent. However, the suppression of the early phase with local morphine administration 30 min before formalin could be significantly greater (49-52%) than with systemic administration, depending on the dose used. Administration of local morphine simultaneously with formalin produced up to 34% reduction in the early and an additional 32% reduction of the late phases of face grooming, compared to systemic injections. Local injection of naloxone (10 micrograms) almost completely reversed the antinociceptive effect of 1000 micrograms of morphine (early phase 85 +/- 7%, late phase 100 +/- 26% reduction), whereas the same dose of naloxone applied systemically (i.p.) produced only partial reversal (early phase 29 +/- 16%, late phase 36 +/- 1% reduction). This study further indicates that locally administered morphine can exert an analgesic effect superior to systemic administration in the case of inflammatory and non-inflammatory pain through a peripheral site of action. These results support the clinical use of peripheral opioid administration in the treatment of human painful conditions.

Analgesics, Opioid↗