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D Freeman

Publications and source records attributed to D Freeman.

At least 37 records · Page 2Linked to original sources
PubMed1999

Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family.

We have identified a cytokine of the IL-6 family and named it novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3). NNT-1/BSF-3 cDNA was cloned from activated Jurkat human T cell lymphoma cells. Its sequence predicts a 225-aa protein with a 27-aa signal peptide, a molecular mass of 22 kDa in mature form, and the highest homology to cardiotrophin-1 and ciliary neurotrophic factor. The gene for NNT-1/BSF-3 is on chromosome 11q13. A murine equivalent to NNT-1/BSF-3 also was identified, which shows 96% homology to human NNT-1/BSF-3. NNT-1/BSF-3 mRNA is found mainly in lymph nodes and spleen. NNT-1/BSF-3 induces tyrosine phosphorylation of glycoprotein 130 (gp130), leukemia inhibitory factor receptor beta, and signal transducer and activator of transcription 3 in the SK-N-MC human neuroblastoma cells. NNT-1/BSF-3 shows activities typical of IL-6 family members. In vitro, it supports the survival of chicken embryo motor and sympathetic neurons. In mice, it induces serum amyloid A, potentiates the induction by IL-1 of corticosterone and IL-6, and causes body weight loss and B cell hyperplasia with serum IgG and IgM increase. NNT-1/BSF-3 is a gp130 activator with B-cell stimulating capability.

Amino Acid Sequence↗
PubMed1999

Effect of usual doses of folate supplementation on elevated plasma homocyst(e)ine in hemodialysis patients: no difference between 1 and 5 mg daily.

Hyperhomocyst(e)inemia is a probable contributor to the excess atherosclerosis of patients with chronic renal failure on dialysis. Although treatment with folate 2 mg daily is usually effective in normalizing plasma homocyst(e)ine (H(e)) in patients with normal renal function, higher doses of folate or other approaches to treatment may be necessary in renal failure. There is no agreement among dialysis units regarding the 'correct' dose of folate supplementation; routine doses range from 1 to 5 mg daily. To determine whether one of these doses is more effective, we compared H(e) in 55 hemodialysis taking 1 mg folate versus 73 patients taking 5 mg folate daily at two dialysis units. In the group as a whole, mean H(e) was 28.23 +/- 17.49, significantly higher than in a group of 290 volunteers with normal renal function 12.31 +/- 6.17 (p = 0. 0001). H(e) levels were 28.93 +/- 16.79 micromol/l on 5 mg folate and 27.31 +/- 18.49 on 1 mg; p = 0.61. There was no significant relationship between adequacy of dialysis (Kt/V) and H(e). In a small group of peritoneal dialysis patients, H(e) was significantly lower at 18.8 +/- 7.89 (p = 0.026), but further study is required in a larger sample to confirm that observation. It appears that routine doses of folate in use in dialysis units are not sufficient to reduce H(e) to levels associated with average cardiovascular risk; new approaches to treatment of hyperhomocyst(e)inemia in dialysis patients are required.

Aged↗
PubMed1999

Plasma homocyst(e)ine concentration, but not MTHFR genotype, is associated with variation in carotid plaque area.

BACKGROUND AND PURPOSE: Elevated plasma homocyst(e)ine [H(e)] concentration is associated with premature atherosclerosis. A common cause of elevated plasma H(e) concentration is a thermolabile mutation (677T) in the gene encoding methylenetetrahydrofolate reductase (MTHFR). We sought to determine whether plasma H(e) concentration or MTHFR genotype would be more strongly associated with carotid plaque area (CPA), a potential intermediate phenotype of atherosclerosis. METHODS: In 307 subjects who were ascertained through a premature atherosclerosis clinic, we measured CPA with 2-dimensional ultrasound and also determined traditional atherosclerosis risk factors, in addition to plasma H(e) concentration and MTHFR genotypes. RESULTS: We found that the frequency of the MTHFR 677T allele was 0.363 in this sample. Mean plasma H(e) concentration was significantly higher in 677T/T homozygotes than in 677T/C heterozygotes and 677C/C homozygotes (17. 1+/-13.7 versus 13.5+/-6.1 versus 12.6+/-5.9 micromol/L, respectively, P<0.001). Analysis of variance showed that CPA was significantly associated with age, sex, smoking, diabetes, hypertension, and hyperlipidemia (each P<0.05). When plasma H(e) concentration was included in the model, it was significantly associated with CPA (P<0.05). However, when the MTHFR genotype was included in the model, it was not associated with CPA (P=0.50). Furthermore, there was a significant correlation of CPA with plasma H(e) (r=0.23, P<0.0001). However, the mean CPA did not differ between subjects according to genotype. CONCLUISONS: Thus, plasma H(e), but not MTHFR genotype, is significantly associated with carotid atherosclerosis, suggesting that the biochemical test may be sufficient to identify patients who may be at increased risk of atherosclerosis through this mechanism.

Adult↗
PubMed1999

Cognitive approaches to delusions: a critical review of theories and evidence.

PURPOSE: To review critically the evidence for three contemporary theories of delusions. METHODS: The theoretical approaches to delusions proposed by Frith and colleagues ('theory of mind' deficits), Garety and colleagues (multi-factorial, but involving probabilistic reasoning biases) and Bentall and colleagues (attributional style and self-discrepancies) are summarised. The findings of empirical papers directly relevant to these proposals are critically reviewed. These papers were identified by computerised literature searches (for the years 1987-1997) and a hand search. RESULTS: The evidence does not unequivocally support any of the approaches as proposed. However, strong evidence is found to support modifications of Garety and colleagues' and Bentall and colleagues' theories. Studies have replicated a 'jumping to conclusions' data-gathering bias and an externalising attributional bias in people with delusions. There is preliminary evidence for a 'theory of mind' deficit, as proposed by Frith, although possibly related to a more general reasoning bias. Evidence for an underlying discrepancy between ideal and actual self-representations is weaker. CONCLUSIONS: A multi-factorial model of delusion formation and maintenance incorporating a data-gathering bias and attributional style, together with other factors (e.g. perceptual processing, meta-representation) is consistent with the current evidence. It is recommended that these findings be incorporated into cognitive therapy approaches. However, there are limitations to existing research. Future studies should incorporate longitudinal designs and first episode studies, and should not neglect the co-morbidity of delusions, including affective processes, or the multi-dimensional nature of delusions.

Cognition Disorders↗
PubMed1998

The maize retinoblastoma protein homologue ZmRb-1 is regulated during leaf development and displays conserved interactions with G1/S regulators and plant cyclin D (CycD) proteins.

Recent discoveries of plant retinoblastoma (Rb) protein homologues and D-type cyclins suggest that control of the onset of cell division in plants may have stronger parallels with mammalian G1/S controls than with yeasts. In mammals, the Rb protein interacts specifically with D-type cyclins and regulates cell proliferation by binding and inhibiting E2F transcription factors. However, the developmental role of Rb in plants and its potential interaction with cell cycle regulators is unknown. We show that the maize Rb homologue ZmRb-1 is temporally and spatially regulated during maize leaf development. ZmRb-1 is highly expressed in differentiating cells, but almost undetectable in proliferating cells. In vitro, both ZmRb-1 and human Rb bind all classes of plant D-type cyclins with the involvement of a conserved N-terminal Leu-x-Cys-x-Glu (LxCxE) Rb-interaction motif. This binding is strongly reduced by mutation of the conserved Cys-470 of ZmRb-1. ZmRb-1 binds human and Drosophila E2F, and inhibits transcriptional activation of human E2F. We also show that ZmRb-1 is a good in vitro substrate for all human G1/S protein kinases. The functional conservation of proteins that control the G1/S transition in mammals and plants points to the existence of plant E2F homologues. We conclude that evolution of Rb and cyclin D proteins occurred after separation of the fungi from the higher eukaryotic lineage, but preceded the divergence of plant and animal kingdoms.

Arabidopsis↗
PubMed1998

The use of intraoperative nitrous oxide leads to postoperative increases in plasma homocysteine.

UNLABELLED: Hyperhomocysteinemia is an independent risk factor for coronary artery and cerebrovascular disease, but its significance in the perioperative period is unknown. Nitrous oxide inhibits methionine synthase, which aids in the conversion of homocysteine to methionine. In this prospective, controlled, randomized study, we determined the effect of intraoperative nitrous oxide exposure on postoperative plasma homocysteine concentrations. Twenty ASA physical status I-III patients, aged >18 yr, presenting for elective craniotomy, were randomized to receive general anesthesia with or without nitrous oxide (inspired nitrous oxide >50%). Plasma was sampled before the induction of anesthesia, on arrival in the postanesthesia care unit (PACU) after discontinuation of nitrous oxide, and 24 h after induction. There was a significant increase (22.6+/-11.4 vs 13.0+/-4.7 micromol/L; P = 0.0038 for postoperative versus preinduction values) in plasma homocysteine concentrations in the nitrous oxide group on arrival in the PACU and for 24 h. In the nonnitrous oxide group, mean plasma homocysteine concentrations did not change (9.5+/-1.9 vs 9.8+/-1.6 micromol/L; P = 0.86 for postoperative versus preinduction values). The change in plasma homocysteine concentrations in the nitrous oxide group was significantly different from that in the nonnitrous group (P = 0.0031). We conclude that the use of intraoperative nitrous oxide leads to significant increases in perioperative plasma homocysteine concentrations. IMPLICATIONS: Short-term exposure to nitrous oxide led to significant increases in plasma homocysteine. Further investigations are required to determine the clinical significance of this change.

Adult↗
PubMed1998

The London-East Anglia randomized controlled trial of cognitive-behaviour therapy for psychosis. IV: Self-esteem and persecutory delusions.

OBJECTIVES: There has been a resurgence of interest in the view that persecutory delusions serve a function of defending self-esteem. An alternative account of levels of self-esteem in individuals with persecutory delusions is that they result from processes similar to those studied in people with depression (i.e. from the occurrence of a range of life experiences and how the individual interprets and copes with them). This study aimed to examine both hypotheses together for the first time, and, as the literature indicates that delusions may not share a common cause, attention was given to the possibility of the presence of subgroups. DESIGN: Data were examined cross-sectionally and longitudinally from a randomized controlled trial of cognitive behaviour therapy for 60 people with drug-resistant psychosis. METHOD: The study is based on the initial assessment of all participants on self-esteem, delusional conviction and a large number of demographic, clinical and cognitive measures. Longitudinal analyses were also carried out, and are reported separately for those who received the therapy intervention and those in the control group. RESULTS: Almost three-quarters of participants with persecutory delusions reported low self-esteem. Changes over time in total self-esteem correlated with changes in measures of mood and social functioning, but not conviction in persecutory delusions. The individuals who initially had normal levels of self-esteem displayed a different pattern of results from the majority of participants. CONCLUSION: Low self-esteem in people with drug-resistant persecutory delusions is common and, in most cases, can best be understood in terms of normal emotional processes. There was evidence that the majority of persecutory delusions do not fit either strong or weak formulations of the delusion-as-defence explanation and that there may be subgroups with differing aetiologies. These results need to be replicated, and extended to groups in which symptoms are not resistant to medication.

Adaptation, Psychological↗
PubMed1998

London-east Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. III: Follow-up and economic evaluation at 18 months.

BACKGROUND: A randomised controlled trial of cognitive-behavioural therapy (CBT) for people with medication-resistant psychosis showed improvements in overall symptomatology after nine months of treatment; good outcome was strongly predicted by a measure of cognitive flexibility concerning delusions. The present paper presents a follow-up evaluation 18 months after baseline. METHOD: Forty-seven (78% of original n = 60) participants were available for follow-up at 18 months, and were reassessed on all the original outcome measures (see Part I). An economic evaluation was also completed. RESULTS: Those in the CBT treatment group showed a significant and continuing improvement in Brief Psychiatric Rating Scale scores, whereas the control group did not change from baseline. Delusional distress and the frequency of hallucinations were also significantly reduced in the CBT group. The costs of CBT appear to have been offset by reductions in service utilisation and associated costs during follow-up. CONCLUSIONS: Improvement in overall symptoms was maintained in the CBT group 18 months after baseline and nine months after intensive therapy was completed. CBT may be a specific and cost-effective intervention in medication-resistant psychosis.

Adult↗
PubMed1998

Geographic variations in breast cancer mortality: do higher rates imply elevated incidence or poorer survival?

OBJECTIVES: Mortality rates from breast cancer are approximately 25% higher for women in the northeastern United States than for women in the South or West. This study examined the hypothesis that the elevation is due to decreased survival rather than increased incidence. METHODS: Data on breast cancer incidence, treatment, and mortality were reviewed. RESULTS: The elevated mortality in the Northeast is apparent only in older women. For women aged 65 years and older, breast cancer mortality is 26% higher in New England than in the South, while incidence is only 3% higher. Breast cancer mortality for older women by state correlates poorly with incidence (r = 0.28). CONCLUSIONS: Those seeking to explain the excess breast cancer mortality in the Northeast should assess survival and should examine differences in cancer control practices that affect survival.

Adult↗
PubMed1997

Budesonide, a locally acting steroid, prevents graft rejection in a rat model of intestinal transplantation.

BACKGROUND: The requirement for potent systemic immunosuppression to prevent intestinal graft rejection has resulted in high rates of infection and post-transplant lymphoproliferative disease. Budesonide (BUD) is a locally acting steroid that is almost completely metabolized during its first pass through the intestinal wall and liver. The present study examined whether BUD could prevent small bowel allograft rejection without causing the adverse systemic effects associated with prednisolone. METHODS: Orthotopic Brown Norway to Lewis rat small bowel allotransplants were randomly assigned to treatment with low-dose BUD (0.1 mg/kg/day, p.o.) and high-dose BUD (1.0 mg/kg/day, p.o.) with and without cyclosporine (CsA; 2 mg/kg/day s.c.). The following parameters were assessed: allograft survival, recipient plasma adrenocorticotrophic hormone (ACTH) levels, recipient adrenal, splenic and thymic weights, recipient CsA levels, and graft histopathology. RESULTS: Low- and high-dose BUD alone did not prolong graft survival compared with the untreated group (9.1+/-0.4 days vs. 11+/-0.8 days vs. 9.7+/-0.4 days, respectively). However, when low-dose BUD and high-dose BUD were given in combination with CsA, the mean graft survival times were prolonged to 27.6+/-5.3 and 36.6+/-8.0 days, respectively (P<0.01). ACTH levels, adrenal weights, and thymic weights were not significantly different in the treatment and control groups receiving intestinal transplants. CONCLUSIONS: BUD enhances the immunosuppressive effects of CsA and prolongs small bowel allograft survival in rats without inhibiting normal ACTH release. These data suggest that BUD may be a useful immunosuppressive agent for clinical intestinal transplantation.

Adrenocorticotropic Hormone↗
PubMed1997

London-East Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. I: effects of the treatment phase.

BACKGROUND: A series of small, mainly uncontrolled, studies have suggested that techniques adapted from cognitive-behavioural therapy (CBT) for depression can improve outcome in psychosis, but no large randomised controlled trial of intensive treatment for medication-resistant symptoms of psychosis has previously been published. METHOD: Sixty participants who each had at least one positive and distressing symptom of psychosis that was medication-resistant were randomly allocated between a CBT and standard care condition (n = 28) and a standard care only control condition (n = 32). Therapy was individualised, and lasted for nine months. Multiple assessments of outcome were used. RESULTS: Over nine months, improvement was significant only in the treatment group, who showed a 25% reduction on the BPRS. No other clinical, symptomatic or functioning measure changed significantly. Participants had a low drop-out rate from therapy (11%), and expressed high levels of satisfaction with treatment (80%). Fifty per cent of the CBT group were treatment responders (one person became worse), compared with 31% of the control group (three people became worse and another committed suicide). CONCLUSIONS: CBT for psychosis can improve overall symptomatology. The findings provide evidence that even a refractory group of clients with a long history of psychosis can engage in talking about psychotic symptoms and their meaning, and this can improve outcome.

Adaptation, Psychological↗
PubMed1997

London-East Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. II: Predictors of outcome.

BACKGROUND: Despite growing evidence of the effectiveness of cognitive-behavioural therapy (CBT) for psychosis, typically only about 50% of patients show a positive response to treatment. This paper reports the first comprehensive investigation of factors which predict treatment outcome. METHOD: In a randomised controlled trial of CBT for medication-resistant psychosis (see Part I) measures were taken at baseline of demographic, clinical and cognitive variables. Changes over time were assessed on the Brief Psychiatric Rating Scale and the relationship between potential predictor variables and outcome was investigated using analysis of variance and covariance. RESULTS: A number of baseline variables were identified as predictors of good outcome in the CBT group. Key predictors were a response indicating cognitive flexibility concerning delusions (P = 0.005) and the number of recent admissions (P = 0.002). Outcome was less predictable in the control group and was not predicted by any cognitive variable. CONCLUSIONS: Good outcome is strongly predicted in patients with persistent delusions by a cognitive measure, while this was not the case in controls. Thus we argue that positive outcome in CBT is due in part to specific effects on delusional thinking.

Adult↗
PubMed1996

Plant cyclins: a unified nomenclature for plant A-, B- and D-type cyclins based on sequence organization.

The comparative analysis of a large number of plant cyclins of the A/B family has recently revealed that plants possess two distinct B-type groups and three distinct A-type groups of cyclins. Despite earlier uncertainties, this large-scale comparative analysis has allowed an unequivocal definition of plant cyclins into either A or B classes. We present here the most important results obtained in this study, and extend them to the case of plant D-type cyclins, in which three groups are identified. For each of the plant cyclin groups, consensus sequences have been established and a new, rational, plant-wide naming system is proposed in accordance with the guidelines of the Commission on Plant Gene Nomenclature. This nomenclature is based on the animal system indicating cyclin classes by an upper-case roman letter, and distinct groups within these classes by an arabic numeral suffix. The naming of plant cyclin classes is chosen to indicate homology to their closest animal class. The revised nomenclature of all described plant cyclins is presented, with their classification into groups CycA1, CycA2, CycA3, CycB1, CycB2, CycD1, CycD2 and CycD3.

Amino Acid Sequence↗
PubMed1996

The Diagnostic Interview Schedule for Children (DISC-2.1) in Spanish: reliability in a Hispanic population.

The reliability across time, informants and interviewers of the Spanish translation of the DISC-2.1 was tested on a Puerto Rican Hispanic sample using a test-retest design. Levels of reliability between clinic and community samples and between younger and older children were compared to explore the sources of low reliability for certain psychiatric disorders. Parents' reports tended to be more reliable than those of their children, although the difference was less obvious with older children. Reliability was generally higher for the externalizing disorders and when the second interviewer was a psychiatrist rather than a lay interviewer.

Adolescent↗
PubMed1996

Effectiveness of an abdominal obesity reduction programme in men: the GutBuster "waist loss' programme.

OBJECTIVE: To examine the long term (1-2 year), as well as immediate effectiveness of a "waist loss' programme for men. DESIGN: Two preliminary studies are reported; one following a small group of 42 men over two years after a 6 week "GutBuster' course, the second following men for 1 year after having completed the initial 6 week programme (n = 83), or the initial course plus an additional six fortnightly "advanced' course (n = 37). MEASUREMENTS: Waist, hip and weight measures were reported for the 2 year group; waist and hip only in study 2. Dietary fat, exercise and alcohol intake were also recorded in study 2 through the use of questionnaires. The goal for the initial course was a 1% waist loss per week. RESULTS: All groups achieved an average waist loss > 1%/week during the initial programme. Waist sizes reported in study 1 were significantly less after 2 years (t = 8.28, p < 0.001) averaging a 6% loss in the group. This equated with an average weight loss of 5.5 kg. A repeated measures ANOVA also showed a significant main effect (F = 85.35; p < 0.0001) for waist losses and an interaction effect (F = 16.53; p < 0.0001) between initial and advanced groups after 1 year in study 2. Average waist losses were 4% and 10% respectively. There were also significant changes in dietary fat intake, exercise and alcohol consumption. CONCLUSION: Reductions in waist size in men appear to be more feasible than weight losses in women. "Waist loss' may also be a more valid measure of fat loss in men that body mass measures.

Abdomen↗
PubMed1996

Expansion of the cerebral ventricles and correlation with acquired immunodeficiency syndrome neuropathology in 232 patients.

BACKGROUND: Expansion of the cerebral ventricles is highly prevalent in patients with the acquired immunodeficiency syndrome (AIDS). The mechanism remains unclear. The purpose of this study was to correlate the volume of the cerebral ventricles with histopathologic abnormalities in the brain. METHODS: At autopsy, the volume of the cerebral ventricles in brain slices was estimated planimetrically in 232 patients with AIDS and 77 age-appropriate controls. Estimated volumes were compared with the neuropathologic results using multiple regression analysis. RESULTS: Multiple regression analysis demonstrated a significant relationship between ventricular volume and cerebral cytomegalovirus infection (P < .0004). When human immunodeficiency virus (HIV) encephalitis with multinucleated cells was present, median volume did not differ significantly from other subjects with AIDS. In 11 patients who had HIV-1 proviral DNA detected using the polymerase chain reaction, average volume was not different from 22 patients who tested negatively using polymerase chain reaction. Ventricular expansion did not have a clear-cut neuropathologic substrate in many instances. CONCLUSIONS: In some subjects with AIDS, cytomegalovirus encephalitis was the underlying neuropathologic lesion associated with ventricular expansion. Key indicators of brain HIV-1 infection were related either weakly or not at all, and the role of HIV-1 remains uncertain in most cases.

Acquired Immunodeficiency Syndrome↗