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Biomedical subjects

D Watson

Publications and source records attributed to D Watson.

At least 37 records · Page 2Linked to original sources

Infiltration of canonical Vgamma4/Vdelta1 gammadelta T cells in an adriamycin-induced progressive renal failure model.

We have previously reported an infiltration of renal interstitial gammadelta T cells in Adriamycin-induced progressive glomerulosclerosis in the rat kidney. The TCR repertoire and sequences used by these gammadelta T cells have now been studied. Two injections of Adriamycin 14 days apart caused segmental glomerulosclerosis, massive interstitial infiltration of mononuclear cells, and end-stage renal failure. Flow cytometry of lymphocyte subpopulations with Abs to CD3, the gammadelta TCR, and the alphabeta TCR showed that gammadelta T cells as a proportion of CD3(+) cells were increased in Adriamycin-treated kidneys (8.5 +/- 5.4%), but not in lymph nodes (1.3 +/- 0.4%). A semiquantitative score of glomerular damage (r = 0.65; p < 0.01) and creatinine (r = 0.62; p < 0.01) correlated significantly with the presence of gammadelta T cells. TCR Vgamma repertoire analysis by RT-PCR and Southern blotting showed that Vgamma2 was the dominant subfamily in lymph nodes, whereas Vgamma4 became the predominant subfamily in advanced stages of the rat Adriamycin-treated kidney. Sequencing of the Vgamma4-Jgamma junctional region showed an invariant sequence. The amino acid sequence of the junctional region of the Vgamma4 TCR was the same as the reported mouse canonical Vgamma4 TCR sequence. Analysis of the kidney Vdelta repertoire showed dominant expression of Vdelta1, and sequencing again revealed the selective expression of a canonical Vdelta1 gene. Semiquantitative RT-PCR for cytokine gene expression showed that gammadelta T cells from the kidneys expressed TGF-beta, but not IL-4, IL-10, or IFN-gamma. These results suggest that the predominant gammadelta T cells in the Adriamycin kidney use an invariant Vgamma4/Vdelta1 receptor.

Animals↗

Dependence of the bi-functional nature of a sialyltransferase from Neisseria meningitidis on a single amino acid substitution.

The L1 immunotype strain 126E of Neisseria meningitidis has been shown to have an N-acetyl-neuraminic acid-containing lipooligosaccharide in which an alpha-linked galactose from a P(k) epitope is substituted at the O6 position (Wakarchuk, W. W., Gilbert, M., Martin, A., Wu, Y., Brisson, J. R., Thibault, P., and Richards, J. C. (1998) Eur. J. Biochem. 254, 626-633). Using a synthetic P(k)-epitope containing acceptor in glycosyltransferase reactions, we were able to show by NMR analysis of the reaction product that the 126E(L1)-derived sialyltransferase can make both alpha-2,3 and alpha-2,6 linkages to the terminal galactose. Gene disruption experiments showed that the lst gene in 126E(L1) was responsible for the in vivo addition of the alpha-2,6-linked N-acetyl-neuraminic acid residue. By site-directed mutagenesis it was possible to change the MC58(L3)-derived enzyme into a bifunctional enzyme with a single amino acid change at position 168, where a glycine was changed to an isoleucine. We performed a gene replacement experiment where the 126E(L1) alpha-2,3/6-sialyltransferase was replaced by allelic exchange with the monofunctional MC58(L3) alpha-2,3-sialyltransferase and with the mutant MC58(L3) allele G168I. We observed that the level of LOS sialylation with the G168I allele was very similar to that of the wild type 126E(L1), indicating that residue 168 is the critical residue for the alpha-2,6-sialyltransferase activity in vitro as well as in vivo.

Amino Acid Substitution↗

Circadian and infradian rhythms in mood.

The aim of this study was to assess any variation in positive, negative and total affect recorded longitudinally; to compare the results with those from prior transverse or hybrid population studies, based on the same or a different method of mood rating; and to test for any association of mood with cardiovascular, hormonal and geophysical variables monitored concomitantly. The study approach was as follows. A clinically healthy 34-year-old man filled out the positive and negative affective scale (PANAS) questionnaire five times a day for 86 days. Systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) were also measured automatically at 30-minute intervals with an ambulatory monitor from May 19 to June 29, 2000, while different endpoints of heart rate variability (HRV) were also determined at 5-minute intervals from beat-to-beat electrocardiogram (ECG) monitoring for 42 days between May 3 and June 14, 2000, with only short interruptions while the subject took a shower and changed ECG tapes. Saliva samples were collected at the times of mood ratings for one month for later determination of melatonin and cortisol concentrations. Intervals of 24 hours of the record of each variable displaced in increments of 24 hours were analyzed by chronobiologic serial section at a trial period of 24 hours to assess the circadian characteristics as they changed from one day to another. Estimates of the midline-estimating statistic of rhythm (MESOR) and circadian amplitude and acrophase obtained on consecutive days were correlated among variables to assess any associations. The findings were as follows. Overall, a circadian rhythm was demonstrated for all variables. A positive association was noteworthy between the circadian amplitude of negative affect and the MESOR of both SBP (r= 0.363; P= 0.029) and DBP (r= 0.389; P= 0.019), suggesting that BP is raised in the presence of large swings in negative affect. Needing further validation was a weak association between the MESOR of negative affect and the circadian amplitude of SBP (r= - 0.272; P = 0.108), suggesting a lowering of the circadian SBP amplitude in the presence of a strong negative affect. Of further interest was the lack of a statistically significant relation between positive and negative affect, not only in terms of the MESOR but also in terms of the circadian amplitude.

Adult↗

A prospective randomised concurrent comparison of the COBE Spectra Version 4.7, COBE Spectra Version 6 (auto PBSC) and Haemonetics MCS+ cell separators for leucapheresis in patients with haematological and non-haematological malignancies.

A prospective study of the CD34+ cell collection efficiency of three cell separators was undertaken comparing the mononuclear cell, CD34+ cell and CFU-GM yield. Twenty patients were entered in the study, all had received mobilising chemotherapy and daily G-CSF (5 microg/kg subcutaneously). The first leucapheresis was performed when the peripheral blood absolute CD34+ cell count was > or = 20 cells/microl. All patients underwent two leucaphereses on consecutive days. The patients were randomised to undergo either the first or second leucapheresis using the COBE Spectra Version 4.7 and then randomised to either the COBE Spectra Version 6 or Haemonetics MCS+ for the other leucapheresis. The target durations of the procedure on the COBE Spectra Version 4.7 and Version 6 were 180 min or two total blood volumes (TBV), and for the Haemonetics MCS+ was 20 cycles with four recirculations. All machines were operated on the 1997 software supplied by the respective manufacturers. The time taken for the procedure was significantly longer with both the Haemonetics MCS+ and the COBE Spectra Version 6 than the COBE Spectra Version 4.7. Both COBE Spectra versions processed significantly larger volumes of blood than the Haemonetics MCS+. The absolute yield of mononuclear cells, CFU-GM and CD34+ cells were all significantly lower with the Haemonetics MCS+ compared with both COBE Spectra Versions, as were the yields per unit volume of blood processed. There was no significant difference in the reduction in the platelet count following leucapheresis with any of the machines.

Antigens, CD34↗

The measurement of suicidal ideation.

A four-item suicidal ideation subscale of the GHQ-28 has been used previously to assess suicidal ideation on the basis of its face validity. In order to further validate its use, this study compared scores on this scale with scores on a well-established suicidal intent scale. There was a significant correlation between scores of that subscale and the self-report component as well as the overall score of the suicidal intent scale, thereby confirming its validity in providing a standardized method for comparing suicidal ideation in different populations.

Adult↗

Dissociations of the night: individual differences in sleep-related experiences and their relation to dissociation and schizotypy.

The author examined the associations among sleep-related experiences (e.g., hypnagogic hallucinations, nightmares, waking dreams, and lucid dreams), dissociation, schizotypy, and the Big Five personality traits in 2 large student samples. Confirmatory factor analyses indicated that (a) dissociation and schizotypy are strongly correlated-yet distinguishable-constructs, and (b) the differentiation between them can be enhanced by eliminating detachment/depersonalization items from the dissociation scales. A general measure of sleep experiences was substantially correlated with both schizotypy and dissociation (especially the latter) and more weakly related to the Big Five. In contrast, an index of lucid dreaming was weakly related to all of these other scales. These results suggest that measures of dissociation, schizotypy, and sleep-related experiences all define a common domain characterized by unusual cognitions and perceptions.

Adult↗

Realtime fetal ultrasound by telemedicine in Queensland. A successful venture?

We have established a realtime fetal tele-ultrasound consultation service in Queensland, which has been integrated into our routine clinical practice. The service, which uses ISDN transmission at 384 kbit/s, allows patients in Townsville to be examined by subspecialists in Brisbane, 1500 km away. For the 90 tele-ultrasound consultations performed for the first 71 patients, 90% of the babies have been delivered, and outcome data have been received on all the pregnancies. All significant anomalies and diagnoses have been confirmed. The referring clinicians would have physically referred 24 of the 71 patients to Brisbane in the absence of telemedicine. A crude cost-benefit calculation suggests that the tele-ultrasound service resulted in a net saving of A$6340, and at the same time enabled almost four times the number of consultations to be carried out.

Cost-Benefit Analysis↗

Is there a Persian Gulf War syndrome? Evidence from a large population-based survey of veterans and nondeployed controls.

PURPOSE: Concerns have been raised about whether veterans of the Gulf War have a medical illness of uncertain etiology. We surveyed veterans to look for evidence of an illness that was unique to those deployed to the Persian Gulf and was not seen in comparable military controls. SUBJECTS AND METHODS: A population-based sample of veterans (n = 1,896 from 889 units) deployed to the Persian Gulf and other Gulf War-era controls (n = 1799 from 893 units) who did not serve in the Gulf were surveyed in 1995-1996. Seventy-six percent of eligible subjects, including 91% of located subjects, answered questions about commonly reported and potentially important symptoms. We used factor analysis, a statistical technique that can identify patterns of related responses, on a random subset of the deployed veterans to identify latent patterns of symptoms. The results from this derivation sample were compared with those obtained from a separate validation sample of deployed veterans, as well as the nondeployed controls, to determine whether the results were replicable and unique. RESULTS: One half (50%) of the deployed veterans and 14% of the nondeployed controls reported health problems that they attributed to military service during 1990-1991. Compared with the nondeployed controls, the deployed veterans had significantly greater prevalences of 123 of 137 (90%) symptoms; none was significantly lower. Factor analysis identified three replicable symptom factors (or patterns) in the deployed veterans (convergent correlations > or =0.85). However, these patterns were also highly replicable in the nondeployed controls (convergent correlations of 0.95 to 0.98). The three factors also accounted for similar proportions of the common variance among the deployed veterans (35%) and nondeployed controls (30%). CONCLUSIONS: The increased prevalence of nearly every symptom assessed from all bodily organ systems among the Gulf War veterans is difficult to explain pathophysiologically as a single condition. Identification of the same patterns of symptoms among the deployed veterans and nondeployed controls suggests that the health complaints of Gulf War veterans are similar to those of the general military population and are not consistent with the existence of a unique Gulf War syndrome.

Adult↗

Cognitive avoidance and bulimic psychopathology: the relevance of temporal factors in a nonclinical population.

OBJECTIVE: Previous research has provided evidence of both an attentional bias towards, and a cognitive avoidance of threat cues, by individuals with unhealthy eating attitudes and disorders. It has been suggested that an initial attentional bias might be followed by a later avoidance process. The present study assessed the speed of processing of self-directed ego threat words following different interstimulus intervals (500, 1,000, 1,500, and 2,000 ms). METHOD: Fifty female students completed a computer-driven threat processing task and the Eating Disorders Inventory. RESULTS: Women were significantly slower to process ego-self threat cues following the 2, 000-ms interval than following the other intervals (500, 1,000, and 1,500 ms). Those women with increased levels of bulimic attitudes were slower to process threats following the 1,500-ms interval, but not after the longer or shorter intervals. CONCLUSIONS: The results stress the importance of temporal factors in the processing of threat by individuals with high levels of eating psychopathology. The findings are discussed in terms of an appropriate cognitive model.

Adult↗

Sustained cognitive improvement following treatment of Alzheimer's disease with donepezil.

OBJECTIVES: To audit response to the anticholinesterase inhibitor donepezil in patients referred to a specialist memory clinic, to identify possible means of targeting the drug more accurately. DESIGN: All referrals to the clinic who were assessed and treated against a protocol, with structured follow-up. SUBJECTS: All referrals of any age with the diagnosis of probable Alzheimer's disease, mild to moderately severe. Main outcome measures Cognitive improvement as measured by serial ADAS-cog and MMSE examinations. RESULTS: Two hundred and eight-two patients commenced on treatment, improved cognitive functioning in over 65% of patients reaching 3 months (N=184), 51% on intention to treat analysis (N=231), with significantly greater improvement (p=0.03) in those aged 65 and under. Carer reports of behavioural improvement not always linked to cognitive improvement. Trend to increased response in those on concomitant antidepressants. CONCLUSION: Three-month assessment for response prior to agreeing continuation of treatment selects a group who maintain their response. Younger patients should be targeted for early assessment and treatment.

Activities of Daily Living↗

Prospective randomised concurrent comparison of the COBE spectra version 4.7, COBE spectra version 6 (Auto PBSCtrade mark), and haemonetics MCS+ cell separators for leucapheresis in patients with haematological and non haematological malignancies.

A prospective study of three cell separators was undertaken to compare the mononuclear cell, CD34+ cell and CFU-GM yield. Twenty patients were entered in the study; all had received chemotherapy and daily G-CSF (5 microg/kg subcutaneously) up to and including the first day of leucapheresis. The first leucapheresis was performed on the first day the peripheral blood absolute CD34+ cell count was > or =20 cells/microl. All patients underwent two leucaphereses on consecutive days. The patients were randomised to undergo either the first or second leucapheresis using the COBE Spectra Version 4.7 and then randomised to either the COBE Spectra Version 6 or Haemonetics MCS+ for the other leucapheresis. The target durations of the procedure on the COBE Spectra Version 4.7 and Version 6 were 180 minutes or 2 total blood volumes (TBV), and for the Haemonetics MCS+ was 20 cycles with four recirculations. All machines were operated on the 1997 software supplied by the respective manufacturers. The time taken for the procedure was significantly longer with both the Haemonetics MCS+ and the COBE Spectra Version 6 than the COBE Spectra Version 4.7. Both COBE Spectra versions processed significantly larger volumes of blood than the Haemonetics MCS+. The absolute yield of mononuclear cells, CFU-GM and CD34+ cells were all significantly lower with the Haemonetics MCS+ compared with both COBE Spectra versions, as were the yields per unit volume of blood processed. The product volume was significantly higher with the COBE Spectra Version 4.7 compared to the other two machines. There was no significant difference in the reduction in the platelet count following leucapheresis with any of the machines. The COBE Spectra Version 6 is particularly useful for patients with potentially poor peripheral venous access because of its increased interface stability.

Adult↗

Rapid anxiety assessment in medical patients: evidence for the validity of verbal anxiety ratings.

Rapid assessment of patient anxiety is necessary to insure quality care. A number of self-report measures provide valid and reliable measures of anxiety. These measures can be time-consuming to complete, however, and may be burdensome to medical patients who are in pain or acute anxiety states. Many medical procedures are performed in conditions in which written measures are cumbersome (e.g. patient in supine position), and scoring and interpretation of written measures in a busy clinical setting may be difficult for medical personnel. The present study provides validity data for a verbally administered (0-10) anxiety rating. One hundred and ninety-eight adult interventional radiology patients completed standard measures assessing state anxiety, trait Negative and Positive Affect, and the dimensions of the five-factor model of personality. Verbal anxiety rating was highly correlated with Spielberger's State Anxiety Inventory, showed moderate correlations to the related constructs of neuroticism and trait Negative Affect, and was largely unrelated to theoretically distinct constructs. Verbal anxiety ratings made prior to the invasive procedure also predicted pain and anxiety during the procedure. The verbal anxiety rating also demonstrated sensitivity to changes in anxiety that occurred as a result of changes in situation. Findings support the convergent and discriminant validity of verbal anxiety ratings.

Adolescent↗