Polyglutamine tracts: no evidence of a major role in bipolar disorder.
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Base Sequence↗
Biomedical subjects
A Duffy
Publications and source records attributed to A Duffy.
The vagaries of self-reports of physical activity: a problem revisited and addressed in a study of exercise promotion in the over 65s in general practice.
BACKGROUND: The assessment of levels of physical activity relies upon suitable measurement tools. OBJECTIVE: We aimed to investigate whether a practice nurse, using a motivational interview technique, could encourage older patients to increase their physical activity. METHODS: Health and well-being were monitored at baseline and 8 weeks following intervention. Physical activity levels were ascertained using both a self-report measure and ambulatory heart-rate monitoring. RESULTS: Whilst patients reported higher levels of physical activity at follow-up, this finding was not confirmed by the heart-rate data. CONCLUSION: The study concludes that patients tend to overestimate the amount of physical activity undertaken and that ambulatory heart-rate monitoring may be more useful for verifying actual behaviour.
Aged↗
MAOA: association and linkage studies with lithium responsive bipolar disorder.
A number of association studies have investigated the role of the monoamine oxidase A (MAOA) gene in the susceptibility to bipolar disorder. Although some studies have reported positive findings, there remains some controversy, because results from different studies have not been consistent. A common explanation for inconsistencies between studies is genetic heterogeneity. We have focused on lithium responsive bipolar disorder as a way to reduce heterogeneity. In this study, we investigated the role of MAOA in lithium responsive bipolar patients using association and linkage study designs. The investigation used 138 patients and 108 normal controls. In addition, 25 families were also studied. Our results were not supportive of a major role of MAOA in the predisposition to bipolar disorder.
Alleles↗
Mitogen-activated protein kinases signal inhibition of apoptosis in lipopolysaccharide-stimulated neutrophils.
BACKGROUND: Neutrophil (PMN) apoptosis is critical to the resolution of infection and the limitation of inflammation. Bacterial endotoxin (lipopolysaccharide [LPS]) inhibits PMN apoptosis and activates the p38 mitogen-activated protein kinase (MAPK) signal cascade. The role of p38 and other MAPKs (ERK and SAPK/JNK) in regulating PMN apoptosis after LPS stimulation is unknown. We hypothesize that MAPK activation by LPS signals inhibition of PMN apoptosis. METHODS: PMNs were isolated from the blood of healthy human volunteers and incubated with PD98059 (ERK inhibitor), SB203580 (p38 inhibitor), or 0.1% dimethyl sulfoxide (vehicle) for 1 hour before treatment with LPS (0, 10, or 1000 ng/mL). Neutrophil MAPK activation was determined by Western blot analysis for phosphorylated p38, ERK, and SAPK/JNK. Apoptosis was quantified by flow cytometry with use of propidium iodide and annexin V. RESULTS: LPS inhibited PMN apoptosis and activated p38 and ERK in a dose- and time-dependent fashion. SAPK/JNK was not activated by LPS. Treatment of cells with ERK inhibitor before LPS stimulation abrogated LPS signaled inhibition of PMN apoptosis. Conversely, p38 inhibition with SB203580 augmented inhibition of apoptosis by LPS. CONCLUSIONS: These data demonstrate opposing roles of MAPKs in mediating PMN apoptosis after LPS stimulation. We conclude that LPS signal transduction by ERK inhibits PMN apoptosis while activation of p38 promotes apoptosis.
Apoptosis↗
Evidence supporting the independent inheritance of primary affective disorders and primary alcoholism in the families of bipolar patients.
BACKGROUND: This study explored the nature of the association between bipolar disorder and alcoholism. METHODS: The authors studied 814 first-degree relatives of 121 bipolar patients, divided on the basis of response to lithium prophylaxis. Logistic regression analysis was used to analyze the contribution of demographic, familial and clinical variables to the risk of primary alcoholism in the relatives. RESULTS: The risk of primary alcoholism in relatives was not related to the degree of affective loading in the family or to the proband's lithium response. CONCLUSION: This study does not support a shared genetic liability between bipolar disorder and alcoholism. LIMITATIONS: This study lacked a control group, but the analysis accounted for this. CLINICAL RELEVANCE: These disorders are not alternative forms of the same illness.
Adult↗
Evidence for a role of phospholipase C-gamma1 in the pathogenesis of bipolar disorder.
Several studies have indicated that patients with bipolar disorder (BD) who respond well to lithium prophylaxis constitute a biologically distinct subgroup. Lithium is thought to stabilize mood by acting at the phosphoinositide cycle. We have investigated a polymorphism located in the gene (PLCG1) that codes for a gamma-1 isozyme of phospholipase (PLC), an enzyme that plays an important role in the phosphoinositide second messenger system. A population-based association study and a family-based linkage study were carried out on patients who were considered excellent responders to lithium prophylaxis. Response to lithium was evaluated prospectively with an average follow-up of 14.4 +/- 6.8 years. The PLCG1 polymorphism was investigated in 136 excellent lithium responders and 163 controls. In addition, the segregation of this marker was studied in 32 families ascertained through lithium-responsive bipolar probands. The allele distributions between lithium-responsive bipolar patients and controls were different, with a higher frequency of one of the PLCG1 polymorphisms in patients (chi2 = 8.09; empirical P = 0.033). This polymorphism, however, confers only a small risk (OR = 1.88, CI 1.19-3.00). Linkage studies with the same marker yielded modest support for the involvement of this gene in the pathogenesis of BD when unilineal families were considered (Max LOD = 1.45; empirical P = 0.004), but not in the whole sample. Our results provide preliminary evidence that a PLC isozyme may confer susceptibility to bipolar disorder, probably accounting for a fraction of the total genetic variance. Whether this polymorphism is implicated in the pathogenesis of BD or in the mechanism of lithium response remains to be determined.
Adult↗
Psychiatric symptoms and syndromes among adolescent children of parents with lithium-responsive or lithium-nonresponsive bipolar disorder.
OBJECTIVE: The purpose of this pilot study was to describe the initial course of psychiatric illness in the adolescent children of parents with bipolar disorder who were divided into two groups on the basis of their response to long-term lithium monotherapy. METHOD: Proband parents met Research Diagnostic Criteria for bipolar illness and predetermined criteria for a clear response or nonresponse to lithium prophylaxis. All adolescent offspring were interviewed by a blinded interviewer using the Schedule for Affective Disorders and Schizophrenia for School-Age Children, and final diagnosis was made by blinded consensus. RESULTS: Psychiatrically ill children of lithium-responsive parents tended to have affective disorders that remitted and followed a recurrent course. Psychiatrically ill children of lithium-nonresponsive parents, however, manifested a broad range of psychopathology, had high rates of comorbid illnesses, and experienced nonremitting affective illnesses. CONCLUSIONS: These results suggest that family history and course of illness are important factors to consider in the diagnosis and pharmacological treatment of affective disorders.
Adolescent↗
Can practice nurses increase physical activity in the over 65s? Methodological considerations from a pilot study.
There is ample evidence of the benefits of exercise for older people. Less is known about the most effective strategies for promoting the participation of older people in exercise regimes. An approach whereby practice nurses used motivational interviewing, based on Prochaska and Di Clemente's model of behaviour change, was piloted in two general practices. The strategy appeared feasible and will be tested further in a large controlled trial.
Aged↗
Autosomal recessive inheritance of affective disorders in families of responders to lithium prophylaxis?
In this paper we report the results of a study of the mode of inheritance in affective disorders responsive to lithium. Earlier we described a series of 71 families in which the genetic transmission was compatible with a single-gene model. We have now carried out an independent replication study on 25 newly recruited families in a different geographical location. The autosomal recessive model from our original study could not be rejected with the new data. In a subsequent analysis of the pooled sample of 96 families, a recessive model with a common predisposing allele (q = 0.16) and sex-specific penetrance (0.35 in males, 0.66 in females) fitted the data best. On the other hand, X-chromosome and polygenic models could be rejected. The finding of a major-gene effect represents a specific hypothesis that can be tested by molecular genetic techniques.
Adult↗
Survey on the treatment of non-small cell lung cancer (NSCLC) in England and Wales.
As an adjunct to a meta-analysis of chemotherapy for non-small cell lung cancer (NSCLC), a survey was conducted in England and Wales of clinicians' views on the role of chemotherapy in NSCLC and the benefits it would have to offer to lead them to change their practice. Radiotherapists, medical oncologists, surgeons and physicians specializing in thoracic medicine, and physicians of palliative medicine were asked their views on the treatment of three case histories of 65 yr old men: Case 1, resected tumour involving a hilar lymph node (tumour (T)2, node (N)1, metastasis (M)0); Case 2, tumour that had spread to mediastinal lymph nodes bilaterally (T2, N3, M0); and Case 3, metastatic cancer (M1) accompanied by minor haemoptysis. Six hundred and ninety eight (85%) of the 821 clinicians responded. For Case 1, 74% would not recommend any adjuvant treatment, 24% would recommend radiotherapy, and <1% chemotherapy, and there was little expectation that adjuvant treatment would improve survival. For Case 2, 68% would recommend radiotherapy, 11% chemotherapy, and 1% surgery, 7% recommending a combination. Adjuvant treatment, regardless of modality, was expected to improve survival. For Case 3, only 11% would recommend chemotherapy, but 26% if the patient was aged < or = 50 yrs. There was little expectation of survival beyond 1 yr, or of improving survival with chemotherapy. For all three cases, most of those not recommending chemotherapy would require it to achieve substantially improved survival for them to use it routinely. Surgery alone is currently considered sufficient for resectable non-small cell lung cancer. Chemotherapy is rarely recommended for disease of any stage.
Aged↗
Lithium-responsive affective disorders: no association with the tyrosine hydroxylase gene.
Family, adoption, and twin studies have demonstrated the involvement of genetic factors in the etiology of major affective disorders. In an attempt to identify the involved genes, several linkage and association studies have focused on the gene coding for tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. The discrepant results to date could be explained by etiological heterogeneity, which may be substantially reduced by selecting patients according to lithium response. Therefore, we investigated 54 patients who had shown definite long-term response to lithium monotherapy in spite of a high risk of recurrence as indicated by the previous clinical course. All the subjects suffered from major affective disorder by Research Diagnostic Criteria (48 bipolar, 6 recurrent unipolar). They were compared to 94 population controls of similar ethnic background to test for association with a penta-allelic microsatellite marker found within the tyrosine hydroxylase gene. No significant differences in allele and genotype frequencies were observed between the two groups, providing further evidence against a major role for the tyrosine hydroxylase gene in the etiology of major affective disorders.
Adult↗
No association between chromosome-18 markers and lithium-responsive affective disorders.
An allelic association study of excellent responders to lithium was conducted with a candidate gene (Golf, a G-protein receptor gene) and five other chromosome-18p markers. Golf is of special interest because it maps to a region of chromosome 18 where two independent groups (Berrettini et al., 1994; Stine et al., 1995) have found linkage to bipolar disorder. It has been proposed that G proteins are involved in the pathogenesis of bipolar disorder, and lithium, an effective prophylactic agent, is known to impair G-protein activation. To reduce heterogeneity--a common obstacle to genetic investigation--only patients who showed excellent response to lithium prophylaxis were studied. Fifty-five genetically unrelated excellent responders to lithium prophylaxis were compared with 94 normal subjects of similar ethnic background. The groups did not differ in either allele or genotype frequency for the tested markers. The data do not support the hypothesis that the tested loci confer a major susceptibility for affective disorders.
Adult↗
Case study: withdrawal syndrome in adolescent chronic cannabis users.
Cannabis use is common among adolescents and has recently been increasing, especially among young teenagers. Whether the reduction of cannabis in chronic heavy users results in a clinically significant withdrawal syndrome is controversial. This article presents three case vignettes supporting the view that chronic cannabis use by adolescents may result in a clinically significant withdrawal syndrome and that the associated physiological symptoms directly contribute to the persistent use of the substance.
Adolescent↗
Effects of various dietary animal and vegetable proteins on serum and biliary lipids and on gallstone formation in the hamster.
The objective of this study was to determine the effects of various dietary animal (casein, bovine albumin and egg albumin) and vegetable (soy, cottonseed and peanut) proteins on serum and biliary constituents and gallstone formation in the hamster. Eighty-four hamsters (60 +/- 5 g) were assigned to either a control group (Purina rat chow) or to one of the 6 experimental groups. Experimental diets contained 20.0% protein. With the exception of hamsters fed egg albumin, gallstone incidence was greater among hamsters fed animal proteins. Hamsters fed egg albumin exhibited a lower concentration of total serum cholesterol and HDL-cholesterol than most of the other experimental groups. There were no significant differences between experimental groups for either HDL3-cholesterol concentration or VLDL-LDL-cholesterol concentration. Bile acid concentrations within the vegetable Protein-fed groups were significantly higher than within the animal protein-fed groups. Casein- and bovine albumin-fed hamsters showed a significantly higher percentage of biliary cholesterol in the bile fluid. As the percentage of biliary cholesterol increased, the percentage of bile acids was found to decrease.
Animals↗
Indirect induction of a Staphylococcus aureus prophage by P11de a plasmid phage hybrid.
The ability to mediate indirect induction of staphylococcal prophages was found to be a property of the cryptic high frequency transducing phage P11de but not of three other phages tested. P11de is the product of a recombination between a P11 phage and a gamma plasmid. Irradiated P11de preparations could not induce prophage development in strains which contained either a P11 prophage or a gamma plasmid. The establishment of P11de in a strain was not, however, inhibited by the presence of a P11 prophage. It is inferred that the inhibition of indirect induction exerted by the resident P11 prophage occurs at a stage other than the establishment of the P11de replicon.
Plasmids↗
Distinct effects of high-glucose conditions on endothelial cells of macrovascular and microvascular origins.
Recent studies implicate hyperglycemia as an important cause of macrovascular and ocular complications in diabetes mellitus. In this study, the authors examined the effect of high glucose on macrovascular and microvascular endothelial cell viability and apoptosis in culture. Human aortic endothelial cells (HAECs) and human retinal endothelial cells (HRECs) were exposed to normal-glucose conditions (NG) and high-glucose conditions (NG supplemented with 25 mM D-glucose) for 72 h in vitro. D-Mannitol was used as an osmotic control. Cell viability was assessed by methlythiazolydiphenyltetrazolium bromide (MTT) assay, and induction of apoptosis was assessed by Hoechst staining. Statistics were analyzed by paired t tests. In HAECs, cell viability was decreased by 12.9% in high-glucose conditions, and apoptotic cells were significantly increased by 77%. However, in HRECs, cell viability was increased by 14.9% in high-glucose conditions, and apoptotic cells were significantly decreased by 33.3%. Mannitol did not show any effect on cell survival or apoptosis ruling out an osmotic effect. High-glucose conditions reduce cell viability and induce apoptosis in HAECs, which may contribute to macrovascular complications associated with diabetes. In contrast, high-glucose increases viability in HRECs and inhibits apoptosis, which may contribute to the development of diabetic retinopathy.
Aorta↗