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Biomedical subjects

J A Schwartz

Publications and source records attributed to J A Schwartz.

At least 19 recordsLinked to original sources
PubMed2001

Vocal cord paralysis as a consequence of peritonsillar infiltration with bupivacaine.

Reduction of postoperative pain is an important goal in the perioperative management of tonsillectomy patients. This is particularly the case for children, who often exhibit resistance to intramuscular or rectal administration of drugs. Peritonsillar bupivacaine infiltration, a relatively safe method of pain control, is in some centers frequently used by otolaryngologists for pain relief. We present the case of a 5-year-old girl who developed bilateral vocal cord paralysis following preoperative peritonsillar bupivacaine infiltration. After an uneventful tonsillectomy and extubation, stridor and respiratory distress developed. Bilateral vocal cord paralysis was seen on laryngoscopy. The patient was reintubated and five hours later was successfully extubated without further sequelae. Anesthesiologists and surgeons should be aware of this uncommon complication than can occur with the use of peritonsillar bupivacaine infiltration for pain control in tonsil surgery.

Anesthetics, Local↗
PubMed2001

Herpes simplex virus type 1 entry is inhibited by the cobalt chelate complex CTC-96.

The CTC series of cobalt chelates display in vitro and in vivo activity against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). The experiments described here identify the stage in the virus life cycle where CTC-96 acts and demonstrate that the drug inhibits infection of susceptible cells. CTC-96 at 50 microg/ml has no effect on adsorption of virions to Vero cell monolayers. Penetration assays reveal that CTC-96 inhibits entry of the virus independent of gC and cellular entry receptors. This observation was supported by the failure to detect the accumulation of virus-specified proteins and alpha mRNA transcripts when CTC-96 is present at the onset of infection. Moreover, virion-associated alphaTIF does not accumulate in the nucleus of cells infected in the presence of CTC-96. CTC-96 targets the initial fusion event between the virus and the cell and also inhibits cell-to-cell spread and syncytium formation. Furthermore, CTC-96 inhibits plaque formation by varicella-zoster virus and vesicular stomatitis virus as efficiently as by HSV-1. Collectively, these experiments suggest that CTC-96 is a broad-spectrum inhibitor of infection by enveloped viruses and that it inhibits HSV-1 infection at the point of membrane fusion independent of the type of virus and cellular receptors present.

Animals↗
PubMed2000

Estrogen receptor protects p53 from deactivation by human double minute-2.

We and others have demonstrated that estrogen receptor alpha (ERalpha) and p53, two important regulatory proteins in breast cancer, bind to each other. In this report, using the glutathione S-transferase pull-down methodology, we show the ligand-independent interaction of ERalpha with the NH2-terminal region of p53, a region known to bind the p300 and human double minute-2 (hdm2) regulatory factors. Furthermore, we have demonstrated that ERalpha is capable of binding hdm2 directly. The interaction of ERalpha and p53 does not interfere with the binding between p53 and hdm2; rather, these proteins form a ternary complex. The effect of ERalpha on the p53-hdm2 regulatory loop has been examined. Our results indicate that ERalpha protects p53 from being deactivated by hdm2. It is evident from these investigations that the ligand-independent protection of p53 by ERalpha is a novel role for this protein in addition to its classic regulatory function as a ligand-inducible transcription factor. This study also describes a new mechanism of cellular regulation of p53 activity.

Breast Neoplasms↗
PubMed2000

Psychological, cognitive, and interpersonal correlates of attributional change in adolescents.

Examined the role of attributional style in adolescent's psychological functioning. Specifically, we examined the cross-sectional correlates of attributional style, as well as the correlates of changes in attributional style over time. A sample of 841 adolescents with either maladaptive or adaptive attributional styles completed a battery of self-report measures at 2 points in time, 1 year apart. Measures assessed depressive symptoms and suicidality, cognitive functioning (self-esteem, pessimism, coping skills), and interpersonal functioning (social competence, conflict with parents, social support from family and friends). Results indicated that attributional style is associated with multiple depression-related variables. In addition, youth experienced significant changes in their attributional styles over time (from adaptive to maladaptive and vice versa). Finally, changes in attributional style were associated with changes in psychological symptoms and other psychosocial variables. Results are discussed in terms of their implications for the prevention and treatment of adolescent depression.

Adaptation, Psychological↗
PubMed1999

p53 down-regulates ER-responsive genes by interfering with the binding of ER to ERE.

Overexpression of the tumor suppressor p53 in HeLa cells leads to loss of the estradiol- and genistein-induced human estrogen receptor (ERalpha) transactivity. The coactivator p300, which binds to both ERalpha and p53, does not prevent this loss of hERalpha function. In this report we demonstrate that p53 physically binds to multiple domains of the hERalpha. This binding did not interfere with either the ERalpha dimerization or the interaction between hERalpha and its coactivator SRC-1. However, p53 did interfere with the hERalpha-ERE binding. These results may explain how p53 down-regulates the expression of some estrogen-responsive genes such as c-fos, c-jun, TPA, and bcl-2. This study supports the cross-talk between the p53 and the ERalpha signaling pathways.

Dimerization↗
PubMed1999

Double-blind comparison of fluoxetine and desipramine in the treatment of depressed women with advanced HIV disease: a pilot study.

A double-blind, placebo-controlled study was conducted to assess the relative efficacy and tolerability of fluoxetine and desipramine in depressed, human immunodeficiency virus (HIV)-positive women. Although difficulty in the recruitment and retention of participants led to insufficient power to detect differences between treatment groups, results indicated that participants experienced improvement in their depression. However, for most women, significant depressive symptoms remained after 6 weeks of treatment. In addition, although most participants reported at least one adverse event after treatment began, most of the side effects, regardless of treatment condition, were mild to moderate in severity. Important barriers to study participation and completion are discussed, as well as suggestions for increasing the involvement of depressed, HIV-positive women in future treatment studies.

Adult↗
PubMed1998

Genistein-mediated attenuation of tamoxifen-induced antagonism from estrogen receptor-regulated genes.

In this study we demonstrate that physiologic concentrations of genistein are sufficient to mediate agonism and to reverse the repressive effects of 4-hydroxytamoxifen on estrogen receptor (ER alpha)-responsive reporter genes. We also show that overexpression of the steroid receptor coactivator (SRC-1) potentiates transactivation by genistein-activated ER alpha and that coexpression of CBP (the cAMP response element binding protein coactivator) synergistically increases this signal. Exogenous expression of a nuclear receptor corepressor (NCoR) was, however, unable to alter genistein-mediated transactivation. In in vitro binding assays, we show that genistein, but not 4-hydroxytamoxifen, induces a direct interaction between radiolabeled ER alpha and a GST-SRC-1 fusion protein. More importantly, coincubation with genistein and 4-hydroxytamoxifen or genistein treatment following preincubation of the ER with 4-hydroxytamoxifen also resulted in a strong physical interaction with SRC-1. These findings imply that genistein-induced shifts in the coregulator status of ER alpha may be involved in transcriptional regulation and suggest that tamoxifen-mediated antagonism at ER-dependent genes is sensitive to attenuation by low levels of genistein.

Drug Synergism↗
PubMed1998

Changes in the structure of the ligand or substitutions to AF2 residues in the estrogen receptor make independent contributions to coactivator sensitivity by SRC-1.

The estrogen receptor (ER) is a ligand-inducible transcription factor which depends, in part, upon the C-terminal activation function (AF2) in order to regulate the expression of target genes. AF2 residues fold into an amphipathic alpha-helix on helix 12 of the ER, with hydrophobic and acidic faces. It is believed that AF2 mediates the gene regulatory activities of ligand-activated ER by interacting with coactivator proteins. We have analyzed the contribution of acidic AF2 residues to the process of ER coactivation by the steroid receptor coactivator, SRC-1. In HeLa cells, SRC-1 coexpression was found to restore transcriptional potency to otherwise inert complexes of wild type ER and 4-hydroxyestratrien-17beta-ol. SRC-1 coexpression also enhanced transcriptional activity of reporter genes induced by an ER mutant with neutral replacements to acidic AF2 residues, in response to E2 or 4-hydroxyestratrien-17beta-ol. By contrast, ER complexes from ICI164,384-treated HeLa cells were both transcriptionally inactive and coactivator insensitive. It is concluded that changes to the structure of the ligand or substitutions to acidic residues in the AF2 region of the receptor contribute independently to the control of coactivator sensitivity in ER.

Amino Acid Sequence↗
PubMed1997

Neutral mutations to three acidic AF2 residues in the mouse estrogen receptor confer agonist activity to A-ring isomers of estradiol.

The ability of the estrogen receptor (ER) to function as a ligand-mediated transcription factor involves the activation function-2 (AF2) in the hormone binding domain (HBD). Although several types of ligand bind to the ER, AF2 functions selectively, as it is activated by estradiol (E2) but not by antiestrogens. The mechanism used by AF2 to interpret the chemical and structural information encoded in the bound ligand, and to transfer this information to other transcriptional regulatory proteins on the promoters of estrogen-regulated genes, is unknown at present. To address this issue, we have examined the activities of two mouse ERs with mutations in the AF2 region. One incorporated changes in three acidic residues (pJ3MOR, D542N/E546Q/D549N) on the polar face of the putative AF2 alpha-helix, whereas the other contained alterations in two hydrophobic amino acids (pJ3MOR, L543D/L544A) on the non-polar face. Transcriptional activity was measured with chloramphenicol acetyltransferase (CAT) reporter genes including a minimal (JA12) or a complex (pS2tkCAT) promoter. In transient cotransfection assays using COS-1 cells, it was found that A-ring isomers of E2, which are inactive or behave as antagonists with the wild-type ER, acted as agonists when the neutral AF2 mutant ER and the pS2tkCAT promoter were tested. On the other hand, when the mutant ER with changes in key hydrophobic residues was used with this same promoter, the estrogen antagonist, ICI 164,384, acted as an agonist. The findings in this report establish a role for acidic AF2 amino acids, and confirm the contributions made by hydrophobic residues, in the interpretation of ligand identity and in the transmission of this information to the transcriptional regulatory apparatus. Critical residues on both sides of the AF2 alpha-helix are, therefore, likely to be involved in distinguishing between ligands with either extensive or subtle alterations in structure, and in mediating this information to the regulatory proteins on estrogen-responsive genes.

Animals↗
PubMed1997

Diagnostic potential of laser-induced autofluorescence emission in brain tissue.

Laser-induced autofluorescence measurement of the brain was performed to assess its spectroscopic properties and to distinguish brain tumors from the normal tissues. The excitation-induced emission spectra were plotted on a 2-dimensional map, the excitation-emission matrix, to determine the excitation wavelengths most sensitive for the spectroscopic identification of brain tumors. The excitation-emission matrices of various types of human brain tumors and normal brain samples lead to the selection of three fluorescence peaks at 470, 520, and 630 nm, corresponding excitation light at 360, 440, and 490 nm, respectively for comparing the autofluorescence signatures of brain tissue. The fluorophores most likely related to each of these peaks are NAD(P)H, various flavins, and porphyrins, respectively. In vivo studies of rat gliomas showed that "NAD(P)H", "flavin", and "porphyrin" fluorescence were lower in gliomas than in normal brain. This finding suggests that there are certain relationship between brain tissue autofluorescence intensity and metabolic activity. In vitro human normal brain tissue fluorescence signals were lower in gray matter than in white matter and "NAD(P)H" fluorescence were lower in all measured human brain tumors than in normal brain. "Flavin" and "porphyrin" fluorescence in the neoplastic tissues was lower or higher than normal tissue depending on their nature. In conclusion, the fluorescence spectroscopic diagnostic system might be able to distinguish brain tumors from the normal brain tissue. The results of this study need to be verified and the investigation extended to human brain tumors in the operating room.

Brain↗
PubMed1997

Influence of nitrous oxide on posterior tibial nerve cortical somatosensory evoked potentials.

The suppressive effect of the halogenated inhalation anesthesia on cortical somatosensory evoked potentials (cSSEPs) has been well documented. Less studied and appreciated is the effect of nitrous oxide often with a narcotic as an alternative to a potent agent for spinal cord monitoring. This study sought to define more clearly the influence of nitrous oxide on cSSEPs elicited to posterior tibial nerve stimulation. A secondary purpose was to demonstrate the advantage of a total intravenous propofol anesthesia in facilitating uncompromised large-amplitude cSSEPs. Fifty adult patients undergoing anterior cervical discectomy served as the study sample. Brainstem and cortical posterior tibial nerve SSEPs were recorded under two independent anesthesia conditions, namely, nitrous oxide and propofol. Results demonstrated a significant amplitude reduction and latency prolongation with the nitrous oxide versus propofol protocol. cSSEP amplitude with propofol was, on the average, approximately two times larger than that with nitrous oxide. Based on these findings, the use of nitrous-oxide anesthesia is not recommended when limited to monitoring cSSEPs that are already amplitude compromised secondary to existing spinal cord disease.

Adult↗
PubMed1997

Changing conceptions of self and world through the spectrum of HIV disease. Implications for psychotherapy.

Individuals with HIV disease face ongoing and phasic challenges that may generate psychological stress or clinically significant distress. Such distress may in part be understood as a response to challenges to fundamental personal conceptions of self and world. The authors describe models generated from social cognition research and the stress response literature and then apply them to common psychological themes that are salient for persons with HIV disease. Implications for psychotherapeutic assessment and intervention are discussed, and a case report is presented to illustrate the use of this approach with HIV and AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1994

A-ring nitro- and amino-substituted estradiol analogs produce a negative cooperative or noncooperative [3H]estradiol-estrogen receptor binding mechanism.

We have investigated the relation between ligand structure and binding mechanism between the calf uterine estrogen receptor. A series of structurally altered estradiol analogs was used in which either an amino- or a nitro group had been added to the 2 or 4 position on the phenolic A-ring. The binding affinity of both amino analogs and the 4-nitro analog for the estrogen receptor was reduced relative to that of estradiol, as measured by competitive binding assay; the values were between 0.008% and 8% of estradiol's affinity. The slope of the displacement curve for the 4-nitro analog was also significantly different from that of estradiol (p < 0.05), indicating that the binding mechanism of these two ligands was different. The affinity of the 2-nitroestradiol ligand for the receptor was too low to be measured. The binding mechanism was then further investigated by measuring the Hill coefficient of [3H]estradiol binding in the presence of the analog. The presence of a nitro group on C4 eliminated the positive cooperativity of the [3H]estradiol-estrogen receptor interaction; the Hill coefficient of [3H]estradiol binding in the presence of the analog was 0.99 compared with 1.7 for [3H]estradiol alone. Most interestingly, the presence of an amino group on either C2 or C4 brought about a switch from a positive to a negative cooperative binding interaction; the Hill coefficients of [3H]estradiol binding in the presence of the analogs were between 0.6 and 0.7. These results provide additional support for an induced-fit mechanism of ligand-estrogen receptor interactions.

Animals↗
PubMed1994

Diuretic and antihypertensive activity of ZENECA ZM224,832: a novel eukalemic diuretic with calcium channel blocking activity.

ZENECA ZM224,832 is a novel eukalemic diuretic from the aminomethylphenol pyrazine series which demonstrated a profile of calcium channel blockers. It produced diuretic and saluretic effects in animals but had only minimal alterations in kaliuresis after oral administration. In contrast to standard diuretics, the plasma K+ concentration was not altered in conscious dogs treated for 14 days with ZENECA ZM224,832 and the concurrent plasma renin activity was also minimally elevated. The isolated rat aorta evaluation indicated that ZENECA ZM224,832, like tiapamil and nifedipine, inhibited vascular smooth muscle tone by inhibiting voltage-dependent calcium channels. ZENECA ZM224,832 produced a dose-dependent decrease of blood pressure in spontaneously hypertensive rats (SHR) in which the antihypertensive activity was not noted with HCTZ. In addition, ZENECA ZM224,832, similar to diltiazem, produced an acute blood pressure lowering effect in nephrectomized SHR which was independent of its diuretic activity. It is concluded that ZENECA ZM224,832 is a potent eukalemic diuretic with calcium channel blocking properties.

Animals↗
PubMed1993

Ligand-mediated modulation of estrogen receptor conformation by estradiol analogs.

The studies presented here show how changing the structure of the ligand can affect the conformation of the receptor. Five different estradiol analogs have been tested for binding to the calf uterine estrogen receptor. In three of the analogs the phenolic hydroxyl group had been moved from the 3 to the 1, 2, or 4 position on the A-ring (1-hydroxyestratrien-17 beta-ol, 2-hydroxyestratrien-17 beta-ol, or 4-hydroxyestratrien-17 beta-ol). In the remaining two analogs either the A- or the D-ring hydroxyl group had been removed altogether (estratrien-17 beta-ol or 3-hydroxyestratriene). Competition binding assay showed that the relative binding affinity for the estrogen receptor had been weakened by all changes in the structure of the ligand. Furthermore, the ligands in which either the 3 beta- or the 17 beta-hydroxyl group was missing produced nonparallel slopes in the linear portions of the displacement curves compared to that of estradiol; the ligands in which the phenolic hydroxyl had simply been moved around the A-ring, however, did not. These observations implied that the receptor binding mechanism used by the monohydroxyl ligands was different from that of estradiol. Saturation binding analysis showed that while the presence of any of the dihydroxyl ligands or that of estratrien-17 beta-ol decreased the positive cooperativity of the [3H]estradiol-estrogen receptor interaction, the presence of the 3-hydroxyestratriene ligand increased it. These results suggest that both the binding mechanism and the affinity of the ligand for the receptor are exquisitely sensitive to the structure of the ligand.

Animals↗
PubMed1993

Depression in stroke rehabilitation.

Despite recent advances in understanding the pathophysiology of poststroke depression, major questions remain. They include the relative importance of lesion location and size and the confounding effects of time since stroke, age, prior history of depression, and cerebral atrophy. To evaluate these issues, we systematically assessed depressive features, functional status, and brain structure with computer tomography scans in 91 men undergoing stroke rehabilitation. Forty percent met DSM-III criteria for major depressive disorder. Mood disturbance was more severe for patients with right than with left hemisphere lesions, correlated with functional disability and lesion size, and was associated with previous history of depression. Age, time since stroke, and atrophy did not correlate with mood. Depression is common in delayed stroke recovery, regardless of lesion location. Because there are no demographic or anatomic features that predict the absence of depression, depression screening should be part of the assessment of all patients undergoing stroke rehabilitation.

Activities of Daily Living↗