Search PubMed⌕ Search

Biomedical subjects

I Jones

Publications and source records attributed to I Jones.

At least 55 records · Page 3Linked to original sources

Tumour necrosis factor alpha and bipolar affective puerperal psychosis.

The macrophage theory of depression proposes that an excessive secretion of monocyte/macrophage cytokines causes symptoms of depression. It has been suggested that changes in immune function that accompany pregnancy and childbirth could contribute to the affective symptoms suffered by many puerperal women. Tumour necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine that has been implicated in inflammatory infections and immune diseases. Production of TNFalpha has been shown to be regulated by oestrogen, which suggests it as a potential candidate for susceptibility to post-partum mood disorders. Several polymorphisms have been identified in the TNFalpha gene. The -308 promoter polymorphism has been associated with elevated production of TNFalpha and has been found to influence the neurological outcome of various infections. In a case-control association study, we have examined the frequency of this polymorphism in groups of parous DSM-IV Bipolar females with (N = 116) and without (N = 56) puerperal psychosis, and a female non-psychiatric comparison group (N = 72). We provided no support for the hypothesis that this polymorphism influences susceptibility to bipolar disorder, or acts as a trigger for puerperal psychosis. However, variation at other polymorphisms within TNFalpha or in other oestrogen-regulated genes involved in immune function remain interesting candidates for study in post-partum mood disorders.

Adult↗

CTG18.1 and ERDA-1 CAG/CTG repeat size in bipolar disorder.

Several groups have reported association between large CAG/CTG repeat sequences in the genome and bipolar disorder using the Repeat Expansion Detection (RED) method. Unfortunately, the RED method cannot identify the specific repeat(s) responsible for these findings but it has recently been proposed that around 90% of the large CAG/CTG repeats detected by RED can be explained by repeat size at either CTG18.1, which maps to 18q21.1, or ERDA-1 (also known as Dir 1), which maps to 17q21.3. These data suggest that the previous associations between bipolar disorder and large CAG/CTG repeats might be explained at least in part by a specific association between bipolar disorder and either or both of these loci. However, using a case control study design, we find no evidence for such associations. Thus we conclude that in our sample, the previous RED associations are not a result of large CAG/CTG repeats at CTG18.1 or ERDA-1.

Adult↗

Bipolar disorder and the serotonin transporter gene: a family-based association study.

BACKGROUND: The human serotonin transporter gene (5-HTT) is a strong candidate for involvement in the pathogenesis of mood disorders. Two common polymorphisms have been identified in the gene: a VNTR in intron 2 and a functional deletion/insertion in the promoter region. In previous studies we proposed that allele 12 of the VNTR might increase susceptibility for bipolar disorder. METHODS: We have genotyped 122 parent-offspring trios of British Caucasian origin where the proband had DSM-IV Bipolar I disorder (BPI). The results were analysed with the transmission/ disequilibrium test (TDT), which examines whether particular alleles are preferentially transmitted from heterozygous parents to affected offspring. RESULTS: The 12 repeat in the VNTR in intron 2 was transmitted 72 times and not transmitted 56 times (chi2 = 2.0, 1 df, P = 0.16). If we exclude 24 families in which the proband was a case in our published case-control studies (Collier et al. 1996a; Rees et al. 1997), the excess transmission of allele 12 reaches conventional levels of statistical significance: chi2 = 3.85, 1 df, P < 0.05. The deletion/insertion polymorphism in the promoter region was not associated with BPI: 66 parents transmitted the inserted (L) allele and 59 parents transmitted the deleted (S) allele (chi2 = 0.39, 1 df, P = 0.53). CONCLUSIONS: The 12 repeat of the VNTR in intron 2 of the serotonin transporter gene might be a susceptibility factor in bipolar affective disorder. The genetic effect, if true, is likely to be small, and requires confirmation in further studies using parental controls.

Adult↗

Family-based association studies of bipolar disorder with candidate genes involved in dopamine neurotransmission: DBH, DAT1, COMT, DRD2, DRD3 and DRD5.

The dopaminergic system has been implicated in the aetiology of mood disorders. We conducted family-based association studies for polymorphisms at three genes involved in the metabolism of dopamine: dopamine transporter (DAT1), dopamine-beta-hydroxylase (DBH) and catechol-O-methyl transferase (COMT); and three dopamine receptors: DRD2, DRD3 and DRD5. We used a sample of 122 parent-offspring trios of British Caucasian origin where the proband had bipolar disorder I (BPI), and analysed the results with the transmission/disequilibrium test (TDT) which is robust to hidden population stratification. No statistically significant differences were found between transmitted and not transmitted alleles for any of the polymorphisms studied.

Adult↗

The effect of route of immunization on mucosal immunity and protection.

In macaques, the route of immunization has a profound effect on the immune response. Augmenting rectal or vaginal immunization with oral or nasal immunization enhanced the secretory IgA, serum IgG, and T cell responses. However, targeted iliac lymph node (TILN) immunization with recombinant simian immunodeficiency virus (SIV) gp120 and p27 elicited the most consistent mucosal antibody responses in the rectum, vagina, urine, seminal fluid, and blood. Both mucosal and TILN immunization induced specific CD4+ T cell proliferative responses in the iliac lymph nodes, which drain these mucosal surfaces, and in the splenic and circulating T cells. Rectal mucosal challenge with cell-free SIV induced total protection in 4 of 7 macaques that were immunized by the TILN route, and, compared with unimmunized macaques or those immunized by the mucosal route (P<.001), it induced a >90% decrease in virus load in 3 of them. Protection from mucosal rectal infection with SIV was significantly associated with an increase in the CD8 suppressor factor (which was generated by the iliac lymph node), RANTES, and MIP-1beta (P<.01).

Animals↗

Genetics of bipolar disorder.

Bipolar disorder (also known as manic depressive illness) is a complex genetic disorder in which the core feature is pathological disturbance in mood (affect) ranging from extreme elation, or mania, to severe depression usually accompanied by disturbances in thinking and behaviour. The lifetime prevalence of 1% is similar in males and females and family, twin, and adoption studies provide robust evidence for a major genetic contribution to risk. There are methodological impediments to precise quantification, but the approximate lifetime risk of bipolar disorder in relatives of a bipolar proband are: monozygotic co-twin 40-70%; first degree relative 5-10%; unrelated person 0.5-1.5%. Occasional families may exist in which a single gene plays the major role in determining susceptibility, but the majority of bipolar disorder involves the interaction of multiple genes (epistasis) or more complex genetic mechanisms (such as dynamic mutation or imprinting). Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest identified in linkage studies include 4p16, 12q23-q24, 16p13, 21q22, and Xq24-q26. Chromosome 18 is also of interest but the findings are confusing with up to three possible regions implicated. To date most candidate gene studies have focused on neurotransmitter systems influenced by medication used in clinical management of the disorder but no robust positive findings have yet emerged. It is, however, almost certain that over the next few years bipolar susceptibility genes will be identified. This will have a major impact on our understanding of disease pathophysiology and will provide important opportunities to investigate the interaction between genetic and environmental factors involved in pathogenesis. This is likely to lead to major improvements in treatment and patient care but will also raise important ethical issues that will need to be addressed.

Bipolar Disorder↗

The influence of fresh water pollutants and interaction with Asellus aquaticus (L.) on the feeding activity of Gammarus pulex (L.).

The feeding response of juvenile amphipod Gammarus pulex (L.) was investigated following exposure to freshwater pollutants. The method employed is nondestructive, provides a rapid indication of the status of groups of individuals, and is based on a time-response analysis of the consumption of the eggs of Artemia salina and the determination of median feeding times or FT50s. The feeding activity of juvenile G. pulex was found to be a sensitive response criterion for use in assessing the sublethal toxicity of copper, lindane, and 3,4-dichloroaniline (3,4-DCA). Reductions in gammarid feeding activity were identified following 96 hours exposure at 12.1 microg/L copper or 8.4 microg/L lindane and 240 hours exposure at 918 microg/L 3,4-DCA. However, a significant increase was observed in the feeding rate of gammarids that had been exposed for 240 h at 0.09 microg/L lindane in comparison with control values. The increase in feeding rate may be interpreted as a possible stimulatory effect associated with the toxicant action of lindane. Increases in gammarid feeding activity were not determined during the experiments conducted with either copper or 3,4-DCA. A sustained reduction in G. pulex feeding rates may cause growth inhibition and impaired reproduction which have previously been identified as sublethal responses of other freshwater organisms exposed to comparable concentrations of lindane, 3,4-DCA, or copper. The feeding bioassay was also used as a tool in an investigation of species interactions in toxicant systems. The feeding responses of G. pulex, which had been maintained in the presence of Asellus aquaticus (as interacting pairs) and exposed to a range of concentrations of lindane or 3,4-DCA, were recorded and compared. The findings illustrate the complex nature of test systems that integrate the stresses of toxicant and competition. In the lindane test system a reduction in gammarid feeding activity was observed following a 96-h exposure with A. aquaticus at 3.8 and 6.0 microg/L lindane (mean measured concentrations). After a 240-h exposure period a decrease in feeding rate was recorded only for gammarids that had been exposed to 6.5 microg/L lindane, however exposure to very low concentrations of lindane (0.1 and 0.9 microg/L) resulted in a significant increase in gammarid feeding activity. In the experiment conducted with 3,4-DCA the calculation of median feeding times or FT50s of gammarids that had been exposed for 96 and 240 h in the toxicant treatment groups with A. aquaticus was largely precluded (in most groups less than 50% of the A. salina eggs were eaten). However, control group FT50 values were determined on each occasion the bioassay was performed, indicating that a substantial reduction in gammarid feeding activity had occurred in the majority of the 3,4-DCA treatment groups.

Aniline Compounds↗

Low activity allele of catechol-O-methyltransferase gene associated with rapid cycling bipolar disorder.

Catechol-O-methyltransferase (COMT) plays a major role in the breakdown of catecholamines. An amino acid polymorphism (val-108-met) determines high and low activity of the enzyme. A recent study in a small sample of patients with velo-cardio-facial syndrome who had bipolar affective disorder suggested that the Met (low activity) COMT allele might be associated with rapid-cycling in this population. We therefore tested the hypothesis that the Met allele might be associated with rapid cycling bipolar disorder in the wider population. We studied a sample of British Caucasian DSM-IV bipolar patients, of whom 55 met criteria for rapid cycling at some time during the illness and 110 met stringent criteria for a definite non-rapid cycling course. The COMT genotype was determined using a PCR assay. The low activity allele was more frequent in the group of rapid cyclers: 0.55 vs 0.42 (one-tailed chi 2 = 5.12, d.f. = 1, P = 0.012), and bearers of low activity alleles showed a dose-dependent increased risk of lifetime occurrence of rapid cycling: chi 2 test of linear association = 4.84, d.f. = 1, P = 0.014. Our data support the hypothesis that variation in the COMT gene modifies the course of bipolar disorder.

Alleles↗

Bacterial or crystal-associated arthritis? Discriminating ability of serum inflammatory markers.

A retrospective study of patients with culture-verified septic arthritis (n = 54) and polarizing microscopy verified crystal-associated arthritis (n = 34) was conducted with the objective to identify discriminating laboratory parameters in serum. Serum CRP levels (p = 0.002) and ESR (p = 0.03) were significantly higher on admission in patients with septic arthritis than in those with crystal-associated arthritis. The peripheral WBC counts did not differ between the two groups, nor did the lactoferrin or procalcitonin (PCT) levels. Serum TNFalpha concentrations on admission were higher in patients with septic arthritis than in those with crystal-associated arthritis (p = 0.0008). Significant differences were also found for IL-8 (p = 0.01) and G-CSF (p = 0.002), but not for IL-6 (p = 0.5). However, extensive overlap between the groups was present, resulting in low sensitivity, specificity and predictive value for each test. Determining serum levels of acute phase reactants, including cytokines, does not replace careful synovial fluid examination, including direct microscopy and cultivation.

Acute-Phase Proteins↗

Urinary growth hormone excretion in post-menarcheal adolescent girls with type 1 diabetes.

The aim of the present study was to compare measurements of urinary growth hormone (GH), serum insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP3) between two groups of post-menarcheal girls, 13-18 y of age, one comprising 64 type 1 diabetic patients and the other 64 healthy girls matched for age and stage of puberty. GH was determined on two occasions in nocturnal urine samples by using a modification of an immunoradiometric method for serum. Significantly higher urinary GH concentrations but lower IGF-I and IGFBP3 levels were found in diabetic girls than in controls (p < 0.001). A significant correlation was found between urinary GH concentrations and the daily dose of insulin (U kg[-1]) (r = 0.426, p = 0.003). Urinary GH concentrations were also significantly related to HbA1c (r = 0.380, p = 0.003). In conclusion, disturbances of the GH-IGF-I axis may be evaluated by the use of non-invasive urinary GH measurements, which is a simple alternative to frequent sampling of serum GH. Increased GH secretion seems to be related to a great need for insulin and poor metabolic control. More knowledge about underlying causal factors in the disturbed GH-IGF-I axis is required.

Adolescent↗

A truly knotted cord.

SUMMARY: A case of 4 true knots in an umbilical cord, which did not cause any detectable harm, is presented. Careful examination of the placenta, membranes and umbilical cord continues to be encouraged.

Adult↗

Use of an electric ear syringe in the emergency department.

OBJECTIVES: To introduce an electric ear syringe into an emergency department and evaluate its use in the removal of foreign bodies from the external auditory canal. METHODS: Report of the use of a new device (the Propulse electric ear syringe) in an emergency department with a retrospective audit of the management of all cases of aural foreign bodies during one year. RESULTS: Almost 60% of the 84 patients who presented with foreign bodies in the auditory canal were children. Staff chose to treat over half of all patients with aural foreign bodies with the electric ear syringe. The overall success rates for the removal of the foreign bodies were: electric syringe, 93% in adults and 88% in children and instrumentation, 68% in adults and 50% in children. CONCLUSIONS: Irrigation with an electric ear syringe is an effective method of removing foreign bodies from the external auditory canal. The device tested was safe, inexpensive, easy to use, and readily acceptable to both adults and children. The availability of an electric ear syringe in an emergency department can avoid the need for specialist referral and the subsequent removal of foreign bodies under general anaesthesia.

Adult↗