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Biomedical subjects

D S Weiss

Publications and source records attributed to D S Weiss.

At least 73 records · Page 4Linked to original sources
PubMed1995

Predicting symptomatic distress in emergency services personnel.

This study identified predictors of symptomatic distress in emergency services (EMS) personnel exposed to traumatic critical incidents. A replication was performed in 2 groups: 154 EMS workers involved in the 1989 Interstate 880 freeway collapse during the San Francisco Bay area earthquake, and 213 counterparts from the Bay area and from San Diego. Evaluated predictors included exposure, social support, and psychological traits. Replicated analyses showed that levels of symptomatic distress were positively related to the degree of exposure to the critical incident. Level of adjustment was also related to symptomatic distress. After exposure, adjustment, social support, years of experience on the job, and locus of control were controlled, 2 dissociative variables remained strongly predictive of symptomatic response. The study strengthens the literature linking dissociative tendencies and experiences to distress from exposure to traumatic stressors.

Adaptation, Psychological↗
PubMed1995

Zinc is a mixed antagonist of homomeric rho 1 gamma-aminobutyric acid-activated channels.

The transition metal Zn2+ is differentially distributed in the central nervous system, where it is proposed to be a neuromodulator. One of the documented effects of Zn2+ is the antagonism of gamma-aminobutyric acid (GABA)-mediated synaptic inhibition. This antagonism is presumed to result from a direct interaction of Zn2+ with the GABA receptor/ionophore complex, although the characteristics of Zn2+ sensitivity are dependent on the particular GABA subunit combination. In this study, we examined the effects of Zn2+ on homomeric rho 1 GABA-activated channels expressed in Xenopus oocytes. Zn2+ was found to be a mixed antagonist of these recombinant rho 1 GABA receptors. The antagonism was predominantly competitive at low Zn2+ concentrations (< or = 100 microM), whereas at high Zn2+ concentrations (> 100 microM) a noncompetitive antagonism was apparent. Evidence is presented showing that the antagonism was not due to an interaction of GABA and Zn2+ in solution but, rather, resulted from interactions of these two ligands with the GABA-activated channel. A mechanism is proposed for Zn(2+)-mediated antagonism in which GABA and Zn2+ bind to distinct sites on the GABA complex. The apparent mixed antagonism may arise from different Ki values for the binding of Zn2+ to non-agonist-bound or agonist-bound receptors. However, two distinct Zn2+ binding sites, one competitive and one noncompetitive, could also give rise to the dual antagonism.

Animals↗
PubMed1995

Point mutations in the M2 region of the alpha, beta, or gamma subunit of the GABAA channel that abolish block by picrotoxin.

Site-directed mutagenesis and the two-electrode voltage-clamp techniques were used to evaluate the site of action of picrotoxin on rat alpha 1 beta 2 gamma 2 containing GABAA receptors expressed in Xenopus oocytes. Following a sequence comparison between GABAA subunits and the picrotoxin-insensitive glycine beta subunit, the following mutations were made near the center of the M2 region of the alpha 1, beta 2, and gamma 2 GABAA subunits: alpha 1(T261F/T267A), beta 2(T246F/T252A), and gamma 2(T271F/T277A). Wild type (alpha 1 beta 2 gamma 2) GABA channels had an IC50 for picrotoxin of 1.3 +/- O.3 microM. In contrast, alpha 1 beta 2 gamma 2 channels that contained any one of the mutated alpha 1, beta 2, or gamma 2 subunits produced currents that were insensitive to picrotoxin (0.1-100 microM). The single mutant beta 2(T246F), in combination with wild type alpha and gamma subunits, also conferred picrotoxin-insensitivity. In contrast, combinations containing beta 2(T252A) were blocked by picrotoxin with an IC50 of 1.4 +/- 0.4 microM. In some instances, the EC50 to GABA was slightly altered in the mutant receptors; but no change was observed in EC50 or potentiation by the allosteric modulator, alprazolam. The data in this study suggest that picrotoxin's site of action is within the channel pore; however the mechanism by which picrotoxin blocks current remains unknown.

Amino Acid Sequence↗
PubMed1994

The energetics and sodium-ion dependence of N5-methyltetrahydromethanopterin:coenzyme M methyltransferase studied with cob(I)alamin as methyl acceptor and methylcob(III)alamin as methyl donor.

N5-Methyltetrahydromethanopterin:coenzyme M methyltransferase from methanogenic Archaea is a membrane-associated enzyme complex that uses a methyl-transfer reaction to drive an energy-conserving sodium-ion pump. Methyl transfer occurs in two steps, first from N5-methyltetrahydromethanopterin (CH3-H4MPT) to an enzyme-bound cob(I)amide prosthetic group, and secondly from the methylated cobamide to coenzyme M (H-S-CoM). In this study, we report that methyltransferase can also use exogenous cob(I)alamin and methylcob(III)alamin as methyl acceptor and methyl donor, respectively. The enzyme catalyzes methylcob(III)alamin formation from CH3-H4MPT and cob(I)alamin (reaction a), and methyl-coenzyme M formation from methylcob(III)alamin and H-S-CoM (reaction b). Both reactions were shown to be reversible. Reaction a was catalyzed at approximately the same rate (3 U/mg) and reaction b at approximately 10% the rate (0.3 U/mg) of the physiological reaction, namely methyl transfer from CH3-H4MPT to H-S-CoM. The free energy changes (delta G0') associated with reactions a and b were both between -10 kJ/mol and -20 kJ/mol, consistent with a free energy change of approximately -30 kJ/mol determined for the physiological reaction. Reaction b but not reaction a was sodium-ion dependent. Assuming that methylation of exogenous cob(I)alamin and demethylation of exogenous methylcob(III)alamin mimic methylation and demethylation of the enzyme-bound corrinoid prosthetic group, it can be inferred that methyl transfer from the methylated cobamide prosthetic group to H-S-CoM is a site of coupling with sodium-ion translocation.

Energy Metabolism↗
PubMed1994

N5-methyltetrahydromethanopterin:coenzyme M methyltransferase from Methanobacterium thermoautotrophicum. Catalytic mechanism and sodium ion dependence.

N5-Methyltetrahydromethanopterin:coenzyme M methyltransferase from methanogenic Archaea is a membrane associated, corrinoid-containing enzyme complex which uses a methyl-transfer reaction to drive an energy-conserving sodium ion pump. The purified methyltransferase from Methanobacterium thermoautotrophicum (strain Marburg) exhibited a rhombic EPR signal indicative of a base-on cob(II)amide. In this form, the enzyme was almost completely inactive. Upon addition of Ti(III)citrate, which is a one-electron reductant known to reduce corrinoids to the cob(I)amide form, the EPR signal was completely quenched. In the reduced form, the enzyme was active. When the purified complex was incubated in the presence of both Ti(III) and N5-methyltetrahydromethanopterin (CH3-H4MPT), enzyme-bound Co-methyl-5'-hydroxybenzimidazolyl cob(III)amide was formed. Upon incubation of the methylated enzyme with either tetrahydromethanopterin or coenzyme M, the enzyme was demethylated with the concomitant formation of CH3-H4MPT and methylcoenzyme M, respectively. Enzyme demethylation, in contrast to enzyme methylation, was not dependent on the presence of Ti(III). Methyl transfer from the methylated enzyme to coenzyme M was essentially irreversible. These results are interpreted to that the purified enzyme complex is active only when the enzyme-bound corrinoid is in the reduced cob(I)amide form, and that methyl transfer from CH3-H4MPT to coenzyme M proceeds via nucleophilic attack of the cobalt(I) on the N5-methyl substituent of CH3-H4MPT, forming an enzyme-bound CH3-corrinoid as intermediate. Methyl-coenzyme M formation from CH3-H4MPT and coenzyme M, as catalyzed by the purified methyltransferase, was stimulated by sodium ions, half-maximal activity being obtained at approximately 50 microM Na+. We therefore infer that the methyltransferase, as isolated, is capable of vectorial sodium ion translocation.

Catalysis↗
PubMed1994

Does trauma-linked dissociation vary across ethnic groups?

This investigation assessed the relationship between traumatic stress exposure and dissociation in male Vietnam theater veterans from three ethnic groups. Subjects were African-American (N = 61), Caucasian (N = 91), and Hispanic (N = 73) veterans who completed the Dissociative Experience Scale and a measure of war zone stress exposure, and who were rated on the Peritraumatic Dissociative Experiences Questionnaire-Rater Version. Greater exposure to war zone stress was associated with reports of more dissociation at the time of trauma and with more general dissociative experiences both when the data were pooled and when examined separately for each group. After controlling for the effects of war zone stress exposure, the significant differences found in peritraumatic and general dissociative experiences across the three ethnic groups no longer were evident. This investigation demonstrated that among American Vietnam veterans, greater exposure to traumatic stress is related to more dissociative experiences, regardless of ethnicity.

Adult↗
PubMed1994

Inhibition of adenosine-induced coronary vasodilation by block of large-conductance Ca(2+)-activated K+ channels.

The aim of the present study was to investigate the contribution of large-conductance calcium-activated potassium (large-conductance KCa) channels to adenosine (Ado)- and nitroprusside-mediated relaxation in small coronary arteries. Canine subepicardial arteries (170 +/- 23 microns at 120 mmHg) were studied as in vitro pressurized vessels. Pressure-diameter experiments showed myogenic tone over a physiological range of pressures. Tone was increased with the thromboxane A2 analogue 9,11-dideoxy-11 alpha,9 alpha-epoxy-methanoprostaglandin F2 alpha (U-46619). Tetraethylammonium (TEA+; 1 mM) significantly inhibited Ado-induced [and by implication, adenosine 3',5'-cyclic monophosphate (cAMP)-induced] relaxations at Ado concentrations ranging from 0.1 to 10 microM with maximal inhibition (61 +/- 8%) at 1 microM Ado. The large-conductance KCa-channel blocker iberiotoxin (IbTX; 0.01-0.1 microM) inhibited Ado-mediated relaxation in a concentration-dependent manner. Inhibition by IbTX increased with increasing vessel pressure (i.e., 45 +/- 12% at 40 mmHg and 83 +/- 20% at 120 mmHg). TEA+ had a minimal effect (8 +/- 3%) on relaxation induced by nitroprusside. Similar results were found with acetylcholine and bradykinin. These results suggest that (in dog coronary arteries with diameter < 200 microns) large-conductance KCa-channel modulation may play a major role in cAMP-mediated relaxation but is not significant in guanosine 3',5'-cyclic monophosphate-mediated relaxation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Peritraumatic dissociation and posttraumatic stress in male Vietnam theater veterans.

OBJECTIVE: The aim of this study was to determine the reliability and validity of a proposed measure of peritraumatic dissociation and, as part of that effort, to determine the relationship between dissociative experiences during disturbing combat trauma and the subsequent development of posttraumatic stress disorder (PTSD). METHOD: A total of 251 male Vietnam theater veterans from the Clinical Examination Component of the National Vietnam Veterans Readjustment Study were examined to determine the relationship of war zone stress exposure, retrospective reports of dissociation during the most disturbing combat trauma events, and general dissociative tendencies with PTSD case determination. RESULTS: The total score on the Peritraumatic Dissociation Experiences Questionnaire--Rater Version was strongly associated with level of posttraumatic stress symptoms, level of stress exposure, and general dissociative tendencies and weakly associated with general psychopathology scales from the MMPI-2. Logistic regression analyses supported the incremental value of dissociation during trauma, over and above the contributions of level of war zone stress exposure and general dissociative tendencies, in accounting for PTSD case determination. CONCLUSIONS: These results provide support for the reliability and validity of the Peritraumatic Dissociation Experiences Questionnaire--Rater Version and for a trauma-dissociation linkage hypothesis: the greater the dissociation during traumatic stress exposure, the greater the likelihood of meeting criteria for current PTSD.

Adult↗
PubMed1994

The agonist binding site of the gamma-aminobutyric acid type A channel is not formed by the extracellular cysteine loop.

The amino-terminal extracellular domain of the subunits comprising the gamma-aminobutyric acid (GABA) receptor contains two cysteine residues (designated at relative positions 1 and 15) separated by 13 amino acids. These two cysteines (presumably disulfide bonded) are located approximately 150 amino acids from the amino terminus. There is significant homology in the amino acid sequence of this cysteine loop both between the different subunits of the GABA receptor and with subunits of other members of this ligand-gated ion channel superfamily (nicotinic acetylcholine- and glycine-activated ion channels). A number of highly conserved amino acids within the cysteine loop have been postulated to play a role in agonist binding. Here, using site-directed mutagenesis and oocyte expression, we have examined the effects of mutating amino acids comprising the cysteine loop on the activation of recombinant GABA channels composed of rat alpha 1, beta 2 and gamma 2 subunits. Preventing the formation of the putative cysteine-cysteine disulfide bond in any of the subunits, by mutating the cysteine at position 15 to serine, prevented the functional expression of that subunit. For example, coexpression of gamma C15S with wild-type alpha and beta subunits resulted in GABA-activated currents with properties identical to those of GABA-activated currents from coexpression of alpha and beta subunits alone. These properties included sensitivity to activation by GABA (similar EC50 values), blockade by Zn2+, and lack of modulation by the benzodiazepine diazepam. We also mutated conserved amino acids in the beta subunit that had been specifically proposed to form the GABA binding site (beta R6, beta Y8, and beta D11). These mutations (as well as several others within or adjacent to the cysteine loop) produced either a very moderate effect or no effect on GABA sensitivity, suggesting that these particular amino acids do not play a key role in activation of the GABA channel. The data presented in this study support a role for the cysteine loop in subunit assembly, rather than channel activation.

Amino Acid Sequence↗
PubMed1994

The relationship between heavy metal and rap music and adolescent turmoil: real or artifact?

Adolescents and their parents were surveyed to investigate the association between heavy metal and rap music and adolescent psychosocial turmoil. Subjects were asked about current and past psychosocial functioning, as well as their music preferences. Adolescents who preferred heavy metal and rap music were compared with those who preferred other types of music. Results indicated that adolescents who preferred heavy metal and rap had a higher incidence of below-average school grades, school behavior problems, sexual activity, drug and alcohol use, and arrests. However, when gender was controlled, only below-average current and elementary school grades and a history of counseling in elementary school for school problems remained significant. Implications of these findings are discussed.

Adolescent↗
PubMed1994

Homomeric rho 1 GABA channels: activation properties and domains.

Expression of human rho 1 subunits in Xenopus laevis oocytes forms homomeric GABA-activated chloride channels with activation and pharmacological properties distinct from those of typical heteromeric GABA channels (e.g., alpha 1 beta 2 gamma 2). Here, we describe these rho 1 activation features and use site-directed mutagenesis to identify amino acids involved in GABA-mediated activation. In comparison to heteromeric GABA channels (alpha 1 beta 2 gamma 2), GABA channels comprised of rho 1 subunits are approximately 40-fold more sensitive to GABA, activate 8.3-fold more slowly (at a GABA concentration equal to their respective EC50S), do not desensitize with maintained agonist application, and close approximately 8-fold more slowly after agonist removal. Site-directed mutagenesis of rho 1 GABA channels has identified five amino acids (Y198, Y200, Y241, T244, and Y247) located between the N-terminal extracellular cysteine loop and first membrane spanning domain, that when conservatively mutated, significantly impaired GABA-mediated activation. These five residues are grouped in two domains that correspond in position to the putative agonist-binding domains previously identified for the beta 2 subunit of alpha 1 beta 2 gamma 2 GABA channels. Y198, T244, and Y247 correspond directly to crucial amino acids identified in the beta 2 subunit; Y200 and Y241 do not. These differences may account, in part, for the unique activation and pharmacological features of homomeric rho 1 GABA channels.

Amino Acid Sequence↗
PubMed1993

GABAA receptor needs two homologous domains of the beta-subunit for activation by GABA but not by pentobarbital.

The predominant inhibitory neurotransmitter of the brain, GABA (gamma-aminobutyric acid), activates chloride-selective ion pores integral to the receptor complex. Subunits comprising the presumed hetero-pentameric GABA channel have been cloned, but little information is available on the domains important for activation. Rat wild-type or mutated alpha 1-, beta 2- and gamma 2-subunits (designated alpha, beta and gamma) were coexpressed in Xenopus oocytes and examined electrophysiologically. We report here the identification of two separate and homologous domains of the beta-subunit, each of which contributes a tyrosine and threonine essential for activation by GABA. Conservative substitution of each of these four amino acids dramatically decreased GABA channel sensitivity to activation by GABA and the GABA agonist muscimol. These substitutions, however, did not impair activation by the barbiturate pentobarbital, indicating these two different classes of agonists activate GABA channels through distinct mechanisms. We also present evidence suggesting that the two identified domains of the beta-subunit contribute a major component of the GABA receptor.

Amino Acid Sequence↗
PubMed1993

Glutamate at the site of phosphorylation of nitrogen-regulatory protein NTRC mimics aspartyl-phosphate and activates the protein.

The NTRC protein of enteric bacteria is an enhancer-binding protein that activates transcription by the sigma 54-holoenzyme form of RNA polymerase under nitrogen-limiting conditions. In vitro NTRC must be phosphorylated to catalyze ATP hydrolysis and activate transcription. The site of phosphorylation of NTRC from Salmonella typhimurium is Aspartate 54, which lies in the amino-terminal regulatory domain of the protein. We used site-directed mutagenesis to make "conservative" substitutions at residue 54 to alanine, asparagine, and glutamate, and examined the properties of the mutant NTRC proteins in vitro and in vivo. In vitro none of them was detectably phosphorylated, as expected if D54 is, in fact, the sole site of phosphorylation. D54A and D54N did not activate transcription of glnA but, interestingly, D54E activated constitutively. Activation by D54E was partial compared to that by phosphorylated wild-type NTRC. Combining D54A or D54N with S160F, a change in the central domain of NTRC that partially bypasses the requirement for phosphorylation, yielded doubly mutant proteins that were as active as a form carrying S160F alone, indicating that the changes in D54 did not adversely affect the function of the remainder of NTRC. Combining D54E with S160F increased the levels of constitutive ATPase activity and transcriptional activation above those of mutant NTRC proteins carrying either single change alone. We conclude that phosphorylation of aspartate 54 is required to activate NTRC and postulate that the D54E mutation mimics phosphorylation, thereby allowing NTRC to hydrolyze ATP and activate transcription. Phenotypes of mutant strains encoding NTRC proteins with substitutions at D54 indicated that phosphorylation of NTRC at position 54 was necessary for normal growth in the absence of glutamine and that such phosphorylation occurred to some extent even in the absence of NTRB.

Aspartic Acid↗
PubMed1993

The relationship of cortical activation to alternating autonomic activity.

It has been proposed that it is possible to selectively activate the cerebral hemispheres, thereby enhancing lateralized cognitive abilities. A proposed method of achieving selective activation is by altering nasal congestion/decongestion (nasal cycle), which is believed to effect a contralateral change in hemispheric activation through the autonomic nervous system (ANS). This hypothesis was tested in 4 right-handed male and 6 right-handed female undergraduate students. Subjects were untrained in specific breathing techniques but were aware of the experimental hypothesis. Four 1 min samples of EEG were recorded in each of 4 experimental conditions in which nasal decongestion was altered by having subjects lie in the lateral recumbent position and occluding the contralateral nare. Cortical activation and laterality were examined using ratios of the low beta (12-18 Hz) and high alpha (10-12 Hz) bandwidths relative to each other and between hemispheres. Repeated measures ANOVAs showed non-significant changes in the alpha and beta bandwidths across the 4 experimental conditions. Although changes in hemispheric activation have been postulated for all subjects, this study does not support such changes in subjects untrained in breathing techniques.

Adult↗
PubMed1992

Method of analysis of local neuronal circuits in the vertebrate central nervous system.

Although a considerable amount of knowledge has been accumulated about the activity of individual nerve cells in the brain, little is known about their mutual interactions at the local level. The method presented in this paper allows the reconstruction of functional relations within a group of neurons as recorded by a single microelectrode. Data are sampled at 10 or 13 kHz. Prominent spikes produced by one or more single cells are selected and sorted by K-means cluster analysis. The activities of single cells are then related to the background firing of neurons in their vicinity. Auto-correlograms of the leading cells, auto-correlograms of the background cells (mass correlograms) and cross-correlograms between these two levels of firing are computed and evaluated. The statistical probability of mutual interactions is determined, and the statistically significant, most common interspike intervals are stored and attributed to real pairs of spikes in the original record. Selected pairs of spikes, characterized by statistically significant intervals between them, are then assembled into a working model of the system. This method has revealed substantial differences between the information processing in the visual cortex, the inferior colliculus, the rostral ventromedial medulla and the ventrobasal complex of the thalamus. Even short 1-s records of the multiple neuronal activity may provide meaningful and statistically significant results.

Animals↗
PubMed1992

Problems in families of male Vietnam veterans with posttraumatic stress disorder.

Interviews were conducted with a nationally representative sample of 1,200 male Vietnam veterans and the spouses or co-resident partners of 376 of these veterans. The veteran interview contained questions to determine the presence of posttraumatic stress disorder (PTSD) and items tapping family and marital adjustment, parenting problems, and violence. The spouse or partner (S/P) interview assessed the S/P's view of these items, as well as her view of her own mental health, drug, and alcohol problems and behavioral problems of school-aged children living at home. Compared with families of male veterans without current PTSD, families of male veterans with current PTSD showed markedly elevated levels of severe and diffuse problems in marital and family adjustment, in parenting skills, and in violent behavior. Clinical implications of these findings are discussed.

Adaptation, Psychological↗