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Biomedical subjects

J M Williams

Publications and source records attributed to J M Williams.

At least 55 records · Page 3Linked to original sources
PubMed2001

Characterization of human immunodeficiency virus type 1 in saliva and blood plasma by V3-specific heteroduplex tracking assay and genotype analyses.

The gp120 V3-encoding region of human immunodeficiency virus type 1 (HIV-1) RNA derived from the saliva and blood plasma of 11 individuals was characterized by heteroduplex tracking assay and sequence analyses. R5-like viral variants were identified in both fluids of all subjects. X4-like variants were detected in the plasma and/or saliva of three subjects, indicating that X4-like variants are not excluded from the saliva compartment. Viral subpopulations were similar in both fluids of most subjects, suggesting that HIV-1 in oral fluids and blood may stem from a common source. These findings raise the possibility of using saliva as a noninvasive fluid for evaluating and monitoring viral evolution in infected persons.

Amino Acid Sequence↗
PubMed2001

Developmental changes in ryanodine- and IP(3)-sensitive Ca(2+) pools in ovine basilar artery.

To explore the hypothesis that cerebrovascular maturation alters ryanodine- and inositol 1,4,5-trisphosphate (IP(3))-sensitive Ca(2+) pool sizes, we measured total intracellular Ca(2+) with (45)Ca and the fractions of intracellular Ca(2+) released by IP(3) and/or caffeine in furaptra-loaded permeabilized basilar arteries from nonpregnant adult and term fetal (139-141 days) sheep. Ca(2+) mass (nmol/mg dry weight) was similar in adult (1.60 +/- 0.18) and fetal (1.71 +/- 0.16) arteries in the pool sensitive to IP(3) alone but was significantly lower for adult (0.11 +/- 0.01) than for fetal (1.22 +/- 0.11) arteries in the pool sensitive to ryanodine alone. The pool sensitive to both ryanodine and IP(3) was also smaller in adult (0.14 +/- 0.01) than in fetal (0.85 +/- 0.08) arteries. Because the Ca(2+) fraction in the ryanodine-IP(3) pool was small in both adult (5 +/- 1%) and fetal (7 +/- 4%) arteries, the IP(3) and ryanodine pools appear to be separate in these arteries. However, the pool sensitive to neither IP(3) nor ryanodine was 10-fold smaller in adult (0.87 +/- 0.10) than in fetal (8.78 +/- 0.81) arteries, where it accounted for 72% of total intracellular membrane-bound Ca(2+). Thus, during basilar artery maturation, intracellular Ca(2+) mass plummets in noncontractile pools, decreases modestly in ryanodine-sensitive pools, and remains constant in IP(3)-sensitive pools. In addition, age-related increases in IP(3) efficacy must involve factors other than IP(3) pool size alone.

Animals↗
PubMed2001

Effects of maturation on mechanisms of cGMP-induced cerebral vasodilatation.

In light of observations that cerebrovascular levels of cGMP vary during maturation, the present study examines the possibility that the mechanisms mediating cGMP-induced cerebral vasodilatation also change during maturation. Specifically, these experiments explore age-related changes in the ability of cGMP to both: (1) depress cytosolic calcium concentration, and (2) attenuate contractile protein calcium sensitivity in alpha-toxin and beta-escin permeabilized preparations as well as fura-2 loaded arteries. The present data demonstrate that: (1) cGMP attenuates cytosolic calcium concentration at lower concentrations than required to reduce myofilament calcium sensitivity; (2) both potassium-induced and 5HT-induced contractions were more sensitive to cGMP in fetal than adult arteries; (3) all potassium-induced increases in cytosolic calcium were resistant to the effects of cGMP, but those produced by 5HT were sensitive to attenuation by cGMP, and more so in fetal than in adult basilar arteries, and (4) cGMP attenuated both basal and agonist-enhanced myofilament calcium sensitivity. Overall, these data demonstrate that the mechanisms mediating the multiple vasoactive effects of cGMP are more potent in immature than in mature cerebral arteries and are heavily influenced by both the artery type and the method of contraction.

Animals↗
PubMed2001

Autobiographical memory and parasuicide in borderline personality disorder.

BACKGROUND: Several studies have found that parasuicidal patients are poor at recalling specific autobiographical memories when tested with the word-cueing paradigm and two studies have reported some evidence that over-general recall is a risk factor for repetition of parasuicide. The aim of the present study was to test whether this association could be replicated with a sample of patients suffering from borderline personality disorder (BPD). METHOD: Twenty-three patients with BPD completed a version of the Autobiographical Memory Test (AMT) and self-report measures of depression, anxiety and trait anger. In a structured interview, they also reported the number of times they had engaged in parasuicidal acts during the previous 4 months. RESULTS: The number of general memories produced on the AMT made a significant contribution to the prediction of the frequency of parasuicidal acts in a multiple regression analysis but the partial correlation in the final equation was negative. That is, those who showed greatest over-general recall reported fewest parasuicidal acts. Anxiety and depression, but not trait anger, also made significant independent contributions to the prediction of parasuicide. CONCLUSION: Over-general autobiographical recall may help to protect borderline individuals from parasuicidal acts by helping them to avoid distressing memories.

Adolescent↗
PubMed2001

Effective problem solving in suicide attempters depends on specific autobiographical recall.

The relationship between over-general autobiographical memory and interpersonal problem solving was investigated by comparing a group of suicide attempters with a nonsuicidal psychiatric control group and a normal control group. Results showed that suicide attempters were more over-general in memory and displayed significantly poorer problem solving than the other two groups. Furthermore, suicide attempters who were more over-general displayed greater deficits in problem solving. It was concluded that effective problem solving in suicide attempters depends on specific autobiographical recall.

Adult↗
PubMed2000

Sequential increase in Egr-1 and AP-1 DNA binding activity in the dentate gyrus following the induction of long-term potentiation.

Establishment of long-term potentiation (LTP) at perforant path synapses is highly correlated with increased expression of Egr and AP-1 transcription factors in rat dentate gyrus granule cells. We have investigated whether increased transcription factor levels are reflected in increased transcription factor activity by assessing Egr and AP-1 DNA binding activity using gel shift assays. LTP produced an increase in binding to the Egr element, which was NMDA receptor-dependent and correlated closely with our previously reported increase in Egr-1 (zif/268) protein levels. Supershift analysis confirmed involvement of Egr-1, but not Egr-2 in the DNA binding activity. AP-1 DNA binding was also rapidly elevated in parallel with protein levels, however, the peak increase in activity was delayed until 4 h, a time point when we have previously shown that only jun-D protein was elevated. These data indicate that binding of Egr-1 and AP-1 to their response elements is increased in two phases. This may result in activation of distinct banks of target genes which contribute to the establishment of persistent LTP.

Animals↗
PubMed2000

The retinal nerve fiber layer thickness in ocular hypertensive, normal, and glaucomatous eyes with optical coherence tomography.

OBJECTIVE: To quantitatively assess and compare the thickness of the retinal nerve fiber layer (RNFL) in ocular hypertensive eyes with normal and glaucomatous eyes using the Optical Coherence Tomograph (OCT 2000, software version A4X1; Humphrey Instruments, San Leandro, Calif). METHODS: The mean RNFL thickness of ocular hypertensive (n = 28) eyes was compared with age-matched normal (n = 30) and glaucomatous (n = 29) eyes. Subject eyes were classified into diagnostic groups based on intraocular pressure, stereoscopic disc photographs, and standard automated perimetry. Three circular scans were obtained for each eye at a diameter of 3.4 mm around the optic disc. In each eye, average RNFL thickness measurements were obtained in temporal, superior, nasal, and inferior quadrants. A single index of average RNFL thickness throughout 360 degrees also was obtained. RESULTS: Mean (95% confidence interval) RNFL was significantly thinner in ocular hypertensive eyes than in normal eyes, 72.8 microm (66.4-78.1 microm) and 85.8 microm (80.2-91.7 microm), respectively. More specifically, RNFL was significantly thinner in ocular hypertensive eyes than in normal eyes in the inferior quadrant, 84.8 microm (75.6-94.0 microm) vs 107.6 microm (99.3-115.9 microm); and in the nasal quadrant, 44.1 microm (37.5-51.7 microm) vs 61.8 microm (53.0-65.6 microm). Retinal nerve fiber layer was significantly thinner in glaucomatous eyes than in ocular hypertensive and normal eyes throughout 360 degrees and in all quadrants. CONCLUSION: These findings suggest that quantitative differences in RNFL thickness exist between age-matched ocular hypertensive, normal, and glaucomatous eyes.

Adult↗
PubMed2000

Septohippocampal pathway as a site for the memory-impairing effects of ethanol.

Ethanol affects behavior by interacting with synaptic sites at many levels of the nervous system. However, it targets most readily and at the lowest concentrations those sites mediating higher cognitive functions such as attention and memory. The memory-impairing effects of ethanol are thought to involve the hippocampus, a structure particularly vulnerable to the effects ethanol at low concentrations and early in the rising phase of the blood ethanol concentration curve. One of the early, low-dose effects of ethanol is an interruption of the normal physiological regulation of the hippocampus by the ascending septohippocampal pathway originating in the medial septal area (MSA). Ethanol enhances GABAergic transmission in the MSA, thereby reducing the regularity and vigor with which rhythmically bursting neurons of the MSA drive the hippocampal theta rhythm. Disruption of septohippocampal activity also has consequences on the response of the hippocampus to cortical inputs. Ethanol produces a loss of hippocampal responsivity that reduces the ability of the hippocampus to encode and retrieve relevant stimulus information necessary for accurate memory. This paper examines the behavioral and neural evidence for hippocampal vulnerability to ethanol and explores the hypothesis that these effects are due to ethanol disrupting septohippocampal modulation of the hippocampus, resulting in impairments of memory.

Animals↗
PubMed2000

Platinum-catalysed allylic alkylation: reactivity, enantioselectivity, and regioselectivity.

The use of platinum complexes as catalysts for allylic substitution has been studied. A variety of different complexes catalyse the reaction, and several substrates have been tested. In the alkylation of mono(alkyl)-substituted allylic acetates, regioselectivity is highly dependent on ligand choice. By using tricyclohexylphosphine as the ligand, almost complete formation of branched products is observed. The development of a highly enantioselective (ca. 80-90% ee) reaction that makes use of chiral diphenylphosphinooxazoline ligands (abbreviated as (S)-PN) is also described. The enantioselectivity is highly dependent on the ratio of ligand to platinum (when the ratio ligand/Pt is greater than 1:1, the ee drops off dramatically). This is in contrast to palladium and is interpreted in terms of differing coordination chemistry for the two metals ((S)-PN is hemilabile when complexed to platinum) and should be of significance to future systems that utilise heterobidentate ligands. The crystal structures of two isoelectronic platinum and palladium complexes [[(S)-PN]MCl2] are also described.

Journal Article↗
PubMed2000

Role of nitric oxide in a toxin-induced model of haemolytic uraemic syndrome.

The role of nitric oxide in the pathogenesis of glomerular thrombotic microangiopathy was explored using an established rat model in which ricin with or without lipopolysaccharide induced glomerular thrombosis. Ricin alone caused a small rise in the plasma concentration of nitric oxide (control 9.2+/-0.7 microM, ricin 23.3+/-6.3 microM at 7 h). This increase occurred after the development of glomerular thrombosis. Nitric oxide synthase (NOS) activity in the kidney showed no significant change from control values (control 5.66+/-2.7 pmol/min per ml homogenate, ricin 7.52+/-1.8 pmol/min per ml homogenate, total activity). When ricin and lipopolysaccharide were administered together, calcium-independent NOS activity increased whereas calcium-dependent activity decreased (1.22+/-2.6 pmol/min per ml homogenate). The increase in calcium-independent NOS activity correlated with a high plasma concentration of interleukin-1beta in the ricin plus lipopolysaccharide group (4,036.83+/-1,001.5 pg/ml). These data indicate that thrombus formation in a rat model of haemolytic uraemic syndrome is independent of the effects of nitric oxide.

Animals↗
PubMed2000

Myocardial revascularization in the elderly using beating heart coronary artery bypass surgery.

BACKGROUND: Beating heart or "off-pump" coronary artery bypass (OP-CAB) has become an accepted method of myocardial revascularization by reducing the perioperative morbidity related to cardiopulmonary bypass (CPB). However, the efficacy of OP-CAB has not been well established in the elderly patient population. METHODS: OP-CABs were performed in 53 patients aged 75 years and older, at Pitt County Memorial Hospital from January 1996 to October 1999, either through a median sternotomy or an anterior thoracotomy. These results were compared with 220 patients who underwent standard coronary artery bypass graft (CABG) operation using CPB during the same time period. RESULTS: Mean patient age for both groups was 79+/-0.5 years and preoperative risk factors were similar. There were no differences in postoperative myocardial infarction, atrial fibrillation, bleeding, neurologic complications, or renal failure. There were no deaths after OP-CAB, compared with the 7.6% operative mortality rate after CABG (p<0.05). The OP-CAB group had a significantly shorter postoperative length of stay (4.4+/-0.4 days vs. 8.4+/-0.6 days) and lower transfusion requirements (0.4+/-0.1 units packed red blood cells vs 1.9+/-0.2 units packed red blood cells) than the CABG group. CONCLUSIONS: Our data demonstrate that OP-CAB is a safe and efficacious method of myocardial revascularization in the elderly, and may actually be preferential in these patients when applicable.

Aged↗
PubMed2000

Tyrosine phosphorylation-dependent inhibition of hippocampal synaptic plasticity.

We examined the effects of two protein tyrosine phosphatase inhibitors on the induction of synaptic plasticity in CA1 slices of rat hippocampus. Field potential recordings were made in stratum radiatum in response to stimulation of the Schaffer collateral afferents. Bath application of the tyrosine phosphatase inhibitors sodium orthovanadate or phenylarsine oxide for 30 min had little effect on basal synaptic transmission but blocked the induction of both long-term potentiation (LTP) and homosynaptic long-term depression (LTD). LTP could be partially recovered, and LTD fully recovered, when conditioning stimulation was given in conditions of reduced synaptic inhibition. The block of both forms of synaptic plasticity by the phosphatase inhibitors correlated with a concurrent depression of the N-methyl-D-aspartate (NMDA) receptor-mediated potential, as measured both extracellularly and intracellularly. This depression, which was also induced by peroxyvanadate, required synaptic stimulation to be induced, and was tyrosine kinase-dependent. Our results suggest that tyrosine phosphorylation of as yet unidentified proteins is responsible for a novel activity-dependent depression of NMDA receptor function that inhibits synaptic plasticity.

Animals↗
PubMed2000

Reproducibility of nerve fiber layer thickness measurements by use of optical coherence tomography.

OBJECTIVE: To evaluate the reproducibility of optical coherence tomograph (OCT) retinal nerve fiber layer (RNFL) measurements in normal and glaucomatous eyes by means of the commercially available OCT 2000 instrument (Humphrey Systems, Dublin, CA). DESIGN: Prospective instrument validation study. PARTICIPANTS: One eye each from 10 normal subjects and 10 glaucoma patients. METHODS: Twenty subjects underwent a total of eight scanning sessions during two independent visits. In each session, five circular scans centered on the optic nerve head were performed. The first two sessions were performed by two experienced technicians. Followed by a 30-minute break, a third and a fourth session was completed by the same technicians. This sequence was duplicated on a second visit. Intrasession, intersession, intervisit, and interoperator reproducibility of quadrant and global RNFL measurements were calculated by use of a components of variance model. MAIN OUTCOME MEASURES: RNFL thickness. RESULTS: The coefficient of variation for the mean RNFL thickness was significantly smaller (P = 0.02) in normal eyes (6.9%) than in glaucoma eyes (11.8%). The estimated root mean squared error based on the statistical model using three scans per patient was 5.8 and 8.0 micrometer for normal and glaucoma eyes, respectively. A components of variance model showed most of the variance (79%) to be due to differences between patients. Only a modest contribution to variability was found for session (1%), visit (5%), and operator (2%). CONCLUSION: With the commercially available OCT, our results indicate that the RNFL measurements are reproducible for both normal and glaucomatous eyes.

Adult↗
PubMed2000

Health promotion practices of emergency physicians.

In this article we describe health promotion practices of emergency physicians (EPs). A survey was mailed to members of the West Virginia American College of Emergency Physicians. Main outcomes included the EP's beliefs regarding health promotion, perceived roles in health promotion, and perceived effectiveness in modifying the behavior of patients. Over 90% of respondents routinely asked about cigarette smoking and half about alcohol use. A minority routinely asked about illicit drug use, diet, exercise, domestic violence, or stress. The majority stated they were the main person responsible for patient health education in their emergency department (ED). Most felt prepared to counsel patients about smoking (68%) and alcohol (59%), although very few described themselves as successful in helping patients change their behavior. Although EPs feel responsible for promoting the health of their patients, only a minority reported routinely screening and counseling patients about prevention and most were not confident in their ability to help patients change their health-related behaviors.

Alcohol Drinking↗
PubMed2000

Are infants with autism socially engaged? A study of recent retrospective parental reports.

The purpose of this study was to identify the specific aspects of social engagement that distinguish infants with autism from infants of similar age and developmental level who do not have autism. Ten parents of preschoolers with autism and 10 parents of matched children without autism were given a semistructured interview, the Detection of Autism by Infant Sociability Interview (DAISI), which elicits reports on whether 19 aspects of social engagement characteristic of typically developing infants were present at some time during the child's first 24 months. The reports of infants with autism differed from those of the control group on 16 items. Findings suggest that infants with autism have marked limitation in both person-to-person and person-person-object social engagement, in keeping with the theory that autism involves impairments in primary as well as secondary intersubjectivity (Hobson, 1993a).

Autistic Disorder↗
PubMed2000

Mindfulness-based cognitive therapy reduces overgeneral autobiographical memory in formerly depressed patients.

Previous research on depressed and suicidal patients and those with posttraumatic stress disorder has shown that patients' memory for the past is overgeneral (i.e., patients retrieve generic summaries of past events rather than specific events). This study investigated whether autobiographical memory could be affected by psychological treatment. Recovered depressed patients were randomly allocated to receive either treatment as usual or treatment designed to reduce risk of relapse. Whereas control patients showed no change in specificity of memories recalled in response to cue words, the treatment group showed a significantly reduced number of generic memories. Although such a memory deficit may arise from long-standing tendencies to encode and retrieve events generically, such a style is open to modification.

Adult↗
PubMed2000

Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy.

This study evaluated mindfulness-based cognitive therapy (MBCT), a group intervention designed to train recovered recurrently depressed patients to disengage from dysphoria-activated depressogenic thinking that may mediate relapse/recurrence. Recovered recurrently depressed patients (n = 145) were randomized to continue with treatment as usual or, in addition, to receive MBCT. Relapse/recurrence to major depression was assessed over a 60-week study period. For patients with 3 or more previous episodes of depression (77% of the sample), MBCT significantly reduced risk of relapse/recurrence. For patients with only 2 previous episodes, MBCT did not reduce relapse/recurrence. MBCT offers a promising cost-efficient psychological approach to preventing relapse/recurrence in recovered recurrently depressed patients.

Adult↗