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Biomedical subjects

D Turner

Publications and source records attributed to D Turner.

At least 73 records · Page 4Linked to original sources

Increased intracellular macrophage inflammatory protein-1beta correlates with advanced HIV disease.

The objective of this study was to correlate between macrophage inflammatory protein-1beta (MIP1beta) and viral loads in untreated, HIV-infected individuals. For that purpose, HIV-positive patients were tested for number of copies of HIV-RNA in plasma and for intracellular MIP1beta in freshly explanted CD8 and CD4 lymphocytes and monocytes. Results demonstrate that the levels of MIP1beta in the various cell populations were significantly higher in the HIV group than in age-matched healthy individuals. Moreover, patients with low CD4 cell counts (<500/microl) and relatively high viral loads exhibited much higher levels of intracellular MIP1beta than patients with lower viral loads and CD4 counts >500/microl. We conclude therefore that although MIP1beta is induced in the various cell populations as a result of HIV infection in vivo, a high intracellular level of MIP1beta appears to be linked to a deterioration in the immune status of the patients.

CD4 Lymphocyte Count↗

Localization of an insulin-like growth factor (IGF) binding site of bovine IGF binding protein-2 using disulfide mapping and deletion mutation analysis of the C-terminal domain.

We have investigated which region(s) of bovine insulin-like growth factor binding protein-2 (bIGFBP-2) interact with insulin-like growth factors (IGFs) using C-terminally truncated forms of bIGFBP-2. Initially to aid in mutant design, we defined the disulfide bonding pattern of bIGFBP-2 C-terminal region using enzymatic digestion. The pattern is Cys186-Cys220, Cys231-Cys242, and Cys244-Cys265. In addition, cyanogen bromide cleavage of bIGFBP-2 revealed that the N- and C-terminal cysteine-rich domains were not linked by disulfide bonds. Taking the disulfide bonding pattern into consideration, C-terminal truncation mutants were designed and expressed in COS-1 mammalian cells. Following IGF binding assays, a region between residues 222 and 236 was identified as important in IGF binding. Specifically, mutants truncated by 14, 36, and 48 residues from the C terminus bound IGFs to the same extent as wild type (WT) bIGFBP-2. Removal of 63 residues resulted in a greatly reduced (up to 80-fold) ability to bind IGF compared with WT bIGFBP-2. Interestingly this mutant lacked the IGF-II binding preference of WT bIGFBP-2. Residues 236-270 also appeared to play a role in determining IGF binding specificity as their removal resulted in mutants with higher IGF-II binding affinity.

Amino Acid Sequence↗

Antibiotic resistance pattern of enterotoxigenic Escherichia coli isolated from infants and young adults in Israel.

The aim of this study was to describe antibiotic resistance rates of enterotoxigenic Escherichia coli in Israel in order to facilitate the empirical choice of antibiotic treatment or prophylaxis for traveler's diarrhea and infantile diarrhea in our region. A total of 281 enterotoxigenic Escherichia coli isolates were tested: 144 from Bedouin infants and 137 from Israeli soldiers. Antibiotic-resistant isolates were prevalent in both groups, but higher resistance rates were found in the pediatric group. Strains producing heat-labile toxin showed higher resistance rates than strains producing heat-stable toxin. The results obtained in Israel preclude the use of many commonly used antibiotics for the treatment of traveler's diarrhea. Quinolones, however, are still effective.

Adolescent↗

Links between social network and quality of life: an epidemiologically representative study of psychotic patients in south London.

Quality of life has been found to be associated with social networks in patients with psychiatric disorders. We aimed to determine whether quality of life was related to social network size in group of severely mentally ill subjects living in the community. In a population-based, prospective controlled study of two sector mental health teams in South London, a random sample of representative 1-year prevalent cases of non-organic psychosis was identified. Patients were interviewed at baseline, and associations between quality of life and social network size were analyzed cross-sectionally. For average quality of life there was increase up to a certain level of social network size (about 20 social contacts). For the quality of life subscore on social relations there appeared to be an optimal middle level of network size (10-12), with lower subscores for smaller and larger networks. Multivariate analysis confirmed the associations between quality of life and social network size. In analyses of network subgroups the importance of confiding contacts was underlined.

Adolescent↗

CENP-G: a new centromeric protein that is associated with the alpha-1 satellite DNA subfamily.

A new constitutive centromere-specific protein (CENP) has been identified as a result of its recognition as an autoantigen by serum from a patient with gastric antral vascular ectasia disease. Conventional immunoblotting and two-dimensional double blotting with both this antiserum and a known anti-centromere antiserum showed that this antiserum predominantly recognized a Mr 95,000 protein that is different from all known CENPs. We have named this new protein CENP-G. This protein was detected at the centromeric region throughout the cell cycle. In mitosis, it was restricted to the kinetochore inner plate as shown by immunogold labeling and electron microscopy. The centromeres of some human chromosomes are known to contain two subfamilies of alpha-satellite DNA. Using immunofluorescence combined with fluorescent in situ hybridization with subfamily-specific DNA probes, we revealed that CENP-G was specifically associated with one of the subfamilies, which we have named alpha-1, but not the other. The localization and the alpha-1-specific association suggested that CENP-G may play a role in kinetochore organization and function. Like CENP-B and C, but unlike CENP-A, this protein remained with the nuclear matrix after intensive extraction. While CENP-B is absent from the human Y chromosome, the existence of CENP-G on the Y chromosome has been proven by immunofluorescence and whole chromosome painting. CENP-G was also detected in CHO, Indian muntjac and Chinese muntjac cells, suggesting that it is conserved in evolution.

Animals↗

Neuropeptide Y2 receptors on nerve endings from the rat neurohypophysis regulate vasopressin and oxytocin release.

Neuropeptide Y and peptide YY are important central and peripheral modulators of cardiovascular and neuroendocrine functions, that act through multiple receptor subtypes, Y1 through Y5. A neuropeptide Y-binding site of the Y2 type was characterized by ligand-binding studies in isolated nerve terminals from the rat neurohypophysis. Functionally, neuropeptide Y and peptide YY dose-dependently triggered arginine 8-vasopressin and oxytocin release from perfused isolated terminals, and potentiated the arginine-8-vasopressin release induced by depolarization. Osmotic stimulation by salt loading of rats for two and seven days caused a more than three-fold increase in the neuropeptide Y content of the nerve endings. However, the Y2 receptor expression and arginine-8-vasopressin content declined, showing that the neuropeptide Y system is dynamic and suggesting that it plays a physiological role in salt and water homeostasis. Two sets of observations suggest the arginine-8-vasopressin release by neuropeptide Y may not be explained by neuropeptide Y effects on intracellular Ca2+. First, absence of Ca2+ from the perfusion medium did not affect the arginine-8-vasopressin release, and secondly neuropeptide Y did not change intraterminal Ca2+ concentrations. Pretreatment with pertussis toxin blocked arginine-8-vasopressin secretion by neuropeptide Y, suggesting activation of Gi or Go heterotrimeric G-proteins are required for secretion. It is concluded, that the nerve endings of the neurohypophysis contain a complete neuropeptide Y system with ligand and receptors. Neuropeptide Y may act in an autocrine fashion via activation of Y2 neuropeptide Y receptors to stimulate the release of vasopressin and oxytocin via a Gi/Go dependent secretory mechanism.

Animals↗

Effects of depolarization evoked Na+ influx on intracellular Na+ concentration at neurosecretory nerve endings.

Electrophysiological measurements of voltage-dependent Na+ influx using patch-clamp methodology were combined with optical monitoring of the free intracellular Na+ concentration in isolated rat neurohypophysial nerve endings to determine the relationship between Na+ influx generated by repetitive stimulation and change in [Na+]i. Application of step depolarizations under voltage-clamp-evoked tetrodotoxin-sensitive inward currents that were dependent upon extracellular Na+ and that exhibited rapid activation and inactivation properties. These characteristics substantiated the evoked current as a voltage-dependent Na+ current. Application of stimulus trains consisting of step depolarizations that mimick in frequency and duration those of action potentials were found to result in increases in [Na+]i. The induced change in [Na+]i was found to be related to the frequency and period of stimulation. Changes in [Na+]i were greatest at frequencies of 40 Hz and gave maximal changes with 30 s of continuous stimulation of approximately 2.4 mM. Sodium influx expressed as a molar quantity resulted in a nearly directly proportional increase in [Na+]i during the initial period of stimulation at low Na+ loads. When expressed as a charge density (pC/microm2) Na+ influx was found to increase with smaller diameter nerve endings as did the rate of change in [Na+]i in response to applied repetitive step depolarizations. Repetitive step depolarizations which simulate impulse activity that invade neuroendocrine nerve endings in vivo in response to physiological demand for hormone secretion resulted in an increased [Na+]i. It is postulated that this increased [Na+]i may provide a modulatory influence on the secretory response indirectly via alteration of intracellular calcium regulation or, perhaps, via a direct action on the secretory mechanism.

Animals↗

Pulmonary function threshold for distinguishing ventilatory- and nonventilatory-limited patients with airflow obstruction.

Patients with chronic obstructive pulmonary disease (COPD) may demonstrate great variability between results on the pulmonary function test (PFT) compared to those on the cardiopulmonary exercise test (CPXT). The purpose of this study was to correlate PFT and CPXT indices and to identify PFT threshold values for predicting exercise capacity in patients with airflow limitation. Fifty-seven patients (48 men and 9 women) of mean age 66.4 +/- 4.8 years with COPD and 40 age-matched control patients underwent PFT and CPXT. Based on the CPXT results, the patients were divided into ventilatory-limited (VL) and nonventilatory-limited (NVL), and the findings were correlated with the PFT indices. Linear regression analysis was used to determine the relationship between dyspnea index (VEmax/MVV) and forced expiratory volume in one second (FEV1). The cutoff value for VL was FEV1 < 38% and for NVL FEV1 > 68%. The prominent limiting symptom (61%) in the VL group was dyspnea sensation, with leg discomfort presenting in only 14%; corresponding rates in the NVL group were 38% and 31%. We conclude that the FEV1 is a reliable index for distinguishing VL from NVL COPD patients during CPXT at two extremes: below 38% of the predicted value (VL) and above 68% of the predicted value (NVL).

Aged↗

Two novel biallelic polymorphisms in the IL-2 gene.

We have detected two novel single nucleotide polymorphisms in the IL-2 gene, at positions -330 and +166 relative to the transcription start site. The +166 change occurs within the leader peptide and does not affect amino acid sequence. The -330 polymorphism has two common alleles, making it an ideal marker for genetic association studies.

5' Untranslated Regions↗

IL-10 gene promoter polymorphisms in rheumatoid arthritis.

IL-10 is an anti-inflammatory cytokine which may modulate disease expression in RA. Three dimorphic polymorphisms within the IL-10 gene promoter have recently been identified and appear to influence regulation of its expression. The 1082*A allele has been associated with low and the 1082*G allele with high in vitro IL-10 production. We have analysed 117 unrelated Caucasoid RA patients and 119 ethnically matched controls. No significant differences in the allele frequencies of the three polymorphisms were found between controls and RA patients. In contrast, a significant association between the 1082*A allele and the (-1082*A/-819*C/-592*C) haplotype and IgA RF+ve/IgG RF-ve patients was observed. The association of genotypes encoding low IL-10 production with IgA RF in RA is incompatible with its suggested role in antibody isotype switching. IgA RF has been associated with severe RA and may thus be indirectly correlated with a genotype encoding low IL-10 production.

Alleles↗

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome.

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.

Arthritis, Rheumatoid↗

Cytokine gene polymorphism and heart transplant rejection.

BACKGROUND: Allograft rejection is mediated by cytokines. As polymorphism in cytokine genes can result in interindividual differences in cytokine production, we hypothesize that some patients may have an increased risk of rejection. METHODS: We have related polymorphisms that influence cytokine production in the tumor necrosis factor (TNF)-A and interleukin (IL)-10 genes to early graft rejection in 115 heart transplant recipients. RESULTS: Certain combinations of TNF-A and IL-10 gene polymorphisms are associated with rejection. Five of 19 patients who had high levels of rejection typed as high TNF-alpha/low IL-10 producers compared with 4 of 96 patients with lower levels of rejection (P<0.005). CONCLUSIONS: We have identified a particular cytokine genotype that may confer susceptibility to increased levels of early rejection. Patients with a worse prognosis may be able to be identified pretransplant by DNA analysis of TNF-A, IL-10, and other gene polymorphisms.

Cytokines↗

Expression and regulation of alpha1beta1 integrin in Schwann cells.

The interaction of cells with the extracellular matrix plays a critical role in morphogenesis and cell differentiation. To define how Schwann cells might interact with the extracellular matrix, we chose to study the expression of the laminin/collagen receptor alpha1beta1 integrin during nerve development in the rat from embryonic day 14 to maturity. We found that this integrin is expressed predominantly on mature non-myelin-forming cells and only at very low levels on myelin-forming cells. Significant levels of this integrin were not detected on Schwann cell precursors or embryonic Schwann cells in vivo. Experiments using transected and crushed sciatic nerve showed that alpha1beta1 integrin expression is regulated at least in part by axonal contact. Furthermore, Schwann cell culture experiments showed that alpha1beta1 integrin levels are strongly upregulated by transforming growth factor-beta(s) and phorbol esters.

Animals↗

Using British trial procedures in American cases: a more civil trial?

A number of attorneys, judges, and legal scholars have asserted that the overly combative nature of American trials may impact on the actual quality of justice and bring the legal system into disrepute. In contrast, many who witness criminal and civil trials conducted in Great Britain are struck by the greater apparent civility of the courtroom atmosphere. Closer examination of the English system reveals seven specific procedural differences that may contribute to this perceived change in atmosphere. In this study, these procedural differences were manipulated and their effect on verdict and on perceptions of trial participants measured. In addition, opinions about these differences were elicited. Results showed that while the trial was perceived as more civil, and the judge viewed more positively, participants tended to indicate preferences for the American style. Implications of these results are discussed.

Adult↗

Social networks and service use among representative cases of psychosis in south London.

BACKGROUND: Large social networks in patients with severe mental illness have been reported to be associated with a low rate of hospitalisation. We aim to determine whether social network size is related to the likelihood of hospitalisation and the amount of service use. METHOD: As part of a prospective controlled study, baseline interview data for a random sample of one-year prevalent cases with non-organic psychosis were analysed with respect to social network characteristics and service use during a six-month period. RESULTS: The likelihood of hospitalisation decreased with an increase in network size, while the number of services used by patients grew as the social network size increased. CONCLUSIONS: While larger social networks may be associated with a lower likelihood of hospitalization, they may also be related to wider use of non-hospital services.

Adolescent↗

The Notch ligand, X-Delta-2, mediates segmentation of the paraxial mesoderm in Xenopus embryos.

Segmentation of the vertebrate embryo begins when the paraxial mesoderm is subdivided into somites, through a process that remains poorly understood. To study this process, we have characterized X-Delta-2, which encodes the second Xenopus homolog of Drosophila Delta. Strikingly, X-Delta-2 is expressed within the presomitic mesoderm in a set of stripes that corresponds to prospective somitic boundaries, suggesting that Notch signaling within this region establishes a segmental prepattern prior to somitogenesis. To test this idea, we introduced antimorphic forms of X-Delta-2 and Xenopus Suppressor of Hairless (X-Su(H)) into embryos, and assayed the effects of these antimorphs on somite formation. In embryos expressing these antimorphs, the paraxial mesoderm differentiated normally into somitic tissue, but failed to segment properly. Both antimorphs also disrupted the segmental expression of X-Delta-2 and Hairy2A, a basic helix-loop-helix (bHLH) gene, within the presomitic mesoderm. These observations suggest that X-Delta-2, via X-Notch-1, plays a role in segmentation, by mediating cell-cell interactions that underlie the formation of a segmental prepattern prior to somitogenesis.

Animals↗