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Biomedical subjects

K Mills

Publications and source records attributed to K Mills.

At least 91 records · Page 5Linked to original sources
PubMed1993

The South London Somatisation Study. I: Longitudinal course and the influence of early life experiences.

In a two-year longitudinal study, a two-stage screening procedure was used to identify subjects in primary care with emotional disorder presenting with a recent onset of physical symptoms and a comparison sample of patients presenting with physical symptoms only. Somatisers (n = 44) were defined as subjects who had an emotional disorder but who presented with physical symptoms that could not be attributed to organic disease. The course and outcome of these conditions were compared with those of pure emotional disorder (n = 11), pure physical disorder (n = 90) and 'mixed' conditions (n = 39). The physical symptoms of somatisers were less likely to improve and lagged behind those of the other groups, and 16 of these acute somatisers went on to develop chronic somatoform disorders. Among somatisers, changes in physical symptom levels throughout the follow-up closely mirrored changes in emotional arousal. Emotionally disordered subjects reported more instances of parental lack of care, but somatisers were also more likely than other groups to report parental physical illness and to have had more physical illness themselves in childhood. A logistic regression suggests that adult somatisation is best modelled by parental lack of care followed by childhood illness.

Adolescent↗
PubMed1993

The ability of the acoustic energy/stone burden ratio to predict gallstone clearance in biliary lithotripsy.

The relationship between acoustic energy, stone burden, and stone clearance in biliary extracorporeal shock wave therapy (ESWL) is unclear. We hypothesized that there is a consistent relationship between these parameters that enables gallstone clearance to be predicted. Using a porcine model and various gallstone burdens, we performed biliary ESWL with varying energy levels and number of shock waves. The acoustic energy/stone burden ratio (AE/SB) was calculated that incorporated these variables. Stone clearance increased with higher energy settings and fewer stones present (p less than 0.005). The relationship between AE/SB ratio and stone clearance was logarithmic (r 2 = 0.82). The plateau of this curve showed optimal stone clearance at approximately 20 joules/g, beyond which point the benefit of further ESWL may not outweigh the risks. This relationship between AE/SB ratio and stone clearance may be able to predict the optimal energy required and probable outcome of biliary ESWL prior to the procedure.

Cholelithiasis↗
PubMed1992

Relationship between the debrisoquine hydroxylase polymorphism and cancer susceptibility.

There have been a series of reports on the association of a genetic polymorphism at the cytochrome P450 CYP2D6 gene locus with cancer susceptibility. Many of these reports have remained contradictory either because of small numbers of patients studied or because of the limitations and controversy surrounding the pharmacokinetic assay used to identify affected individuals (poor metabolizers; PMs). We have recently developed a DNA-based assay that will allow the unequivocal identification of poor metabolizers and have applied this to the study of 1635 patients with different forms of cancer. Out of 361 lung cancer patients studied no statistically significant change in the proportion of PMs relative to controls was found. However, a significant increase in the proportion of poor metabolizers or heterozygotes was seen in leukaemia, bladder cancer and melanoma patients. This could be explained by a role for CYP2D6 in carcinogen detoxification or by linkage to another cancer-causing gene.

Amino Acid Sequence↗
PubMed1992

Macrophage activation and immunomodulation by myeloperoxidase.

Myeloperoxidase (MyPo) is an enzyme found in neutrophils and monocytes that plays an important role in the microbicidal and cytocidal activities of these cells. The present studies show that this enzyme can also affect both capacities and functions of macrophages. When resident peritoneal macrophages from C57BL/6 mice were exposed to preparations of either human or canine enzyme in vitro, tumor necrosis factor (TNF) was released. The amount of TNF produced was dose dependent and could be neutralized with polyclonal anti-TNF. Low levels of interferon were also produced by these cells. In addition, exposure of murine macrophages in vitro to this enzyme resulted in increased ability to destroy 3T12 target cells. Intravenous injection of mice with myeloperoxidase induced the production of both TNF and interferon, which could be detected in the sera. Possible mechanisms of TNF induction include radical production by myeloperoxidase or ligand-receptor interaction by the binding of this enzyme to the mannosyl-fucosyl receptor. These results, when taken in their entirety, suggest that this enzyme can modulate the immune response through effects on macrophage function.

Analysis of Variance↗
PubMed1992

Continuing medical education for general practitioners--a Northern Ireland plan.

Following the introduction of the 1990 contract for general practitioners and the new postgraduate education allowance, the Northern Ireland Continuing Medical Education Group, comprising the clinical tutors from four Belfast hospitals and members of the University department of general practice, was established to provide high quality co-ordinated continuing medical education for general practitioners. A questionnaire was sent to all general practitioners in Northern Ireland to find out their needs and preferences with regard to continuing education. The responses indicate the value of small group discussion as well as the traditional lecture and the important role of local hospital consultants in providing education. Therapeutics, recent advances in medicine and learning new skills are all desirable topics. The group intends to use this information in the provision of courses for general practitioners in the province.

Education, Medical, Continuing↗
PubMed1991

Autoimmune aetiology for acquired neuromyotonia (Isaacs' syndrome)

Neuromyotonia is a rare disorder of unknown cause in which hyperexcitability of peripheral motor nerves leads to incapacitating muscle twitching, cramps, and weakness. We investigated an antibody-mediated mechanism for neuromyotonia in a 24-year-old man with a 7-year history of severe disease unresponsive to pharmacological treatment. Two periods of plasma exchange each produced almost complete disappearance of symptoms for 2-3 weeks, and a highly significant decrease in recorded neuromyotonic discharges. Injection of the patient's plasma or purified IgG into mice significantly enhanced in-vitro resistance to d-tubocurarine at the neuromuscular junction of phrenic nerve-diaphragm preparations. This finding suggests that an increase in neurotransmitter release might result from an antibody-mediated reduction in the number of functional potassium channels that normally regulate nerve excitability. The demonstration of pathogenic IgG autoantibodies in acquired neuromyotonia suggests that immunosuppressive treatment may be helpful in severe cases.

Adolescent↗
PubMed1991

Induction of tumor necrosis factor and macrophage-mediated cytotoxicity by horseradish peroxidase and other glycosylated proteins: the role of enzymatic activity and LPS.

Recent studies by these investigators have shown that horseradish peroxidase (HRP) can cause murine thioglycollate-induced peritoneal macrophages (M phi) to produce both tumor necrosis factor (TNF) and enhance macrophage-mediated cytotoxicity (MMC) to 3T12 target cells. The present study identifies the roles of both enzymatic activity and contaminating lipopolysaccharides (LPS) (less than or equal to 1 ng) on these activities. The addition of 100 ng/ml of polymyxin B (PB) to enzymatically active HRP significantly reduced TNF production but did not affect MMC. Enzymatically inactive HRP (DHRP) was more effective than HRP in both TNF production and MMC but was not affected by PB. The inability of PB to modify DHRP-induced TNF suggests that LPS was not required. The induction of TNF and MMC in the absence of LPS was also corroborated by similar studies using M phi from endotoxin-resistant C3H/HeJ mice. Glycosylated proteins such as HRP, DHRP, and mannosylated bovine serum albumin (M-BSA) are known to bind to mannose receptors (mannosyl-fucosyl receptor [MFR]) on the surface of M phi. In the present studies, M-BSA behaved similarly to DHRP in that it induced both TNF secretion and MMC. These results suggest that binding to the MFR may be sufficient to induce TNF secretion and MMC. In addition, the data suggest that neither enzymatic activity nor LPS was required for DHRP-induced TNF.

Animals↗
PubMed1991

Comparison of two enzyme-linked immunosorbent assays for detection of herpes simplex virus antigen.

Two enzyme-linked immunosorbent assays (ELISAs) for herpes simplex virus (HSV) detection were compared with culture in a prospective, blinded study with 153 patients with suspected recurrent oral or genital HSV. A subset of 15 of these subjects were studied daily until symptom resolution during a single episode of recurrent HSV. Direct-site specimens were collected and either placed in viral transport media (for Ortho ELISA and fresh inoculation into primary rabbit kidney cells) or frozen in ELISA collection media (DuPont). One hundred eighty-six culture-ELISA comparisons were analyzed. On the basis of culture positivity, the DuPont and Ortho ELISAs differed substantially with regard to sensitivity (93 versus 35%) but had similar specificities (95 versus 100%) and positive (85 versus 100%) and negative (98 versus 85%) predictive values. There were seven DuPont ELISA-positive, culture-negative samples which were confirmed positive for HSV by blocking antibody test (revised specificity, 100%; positive predictive value, 100%). Six of these discrepant samples were from previously culture-positive subjects. These results demonstrate that currently available ELISA kits vary substantially as to their sensitivities in detecting HSV antigen from direct-site specimens. In addition, antigen detection, by ELISA technology, is not always synonymous with state of viral infectivity as judged by tissue culture cytopathic effect.

Antigens, Viral↗
PubMed1991

Immunological evidence for the co-existence of the Lambert-Eaton myasthenic syndrome and myasthenia gravis in two patients.

Two patients are described in whom a clinical and electromyographic diagnosis of the Lambert-Eaton myasthenic syndrome (LEMS) was made. Serum antibodies to voltage-gated calcium channels (VGCCs), the antigenic target in LEMS and to acetylcholine receptors (AChRs), the antigen in myasthenia gravis, were detected at raised titres in both cases, using radioimmunoassays based on 125I-omega-Conotoxin labelled VGCCs and 125I-alpha-Bungarotoxin labelled AChRs. These data provide immunological evidence for the coexistence of the two disorders in these patients.

Adult↗
PubMed1990

A sensitive method of screening for dominant T cell clones by amplification of T cell gamma gene rearrangements with the polymerase chain reaction.

A sensitive method of screening for dominant T cell clones in small samples of DNA has been developed using the polymerase chain reaction to amplify and identify T cell gamma receptor gene rearrangements. It can detect such rearrangements in nanogram quantities of DNA from cultured T cell clones, even in the presence of 20-100 parts of polyclonal lymph node DNA, and works with DNA extracted from paraffin sections of cloned T cells which have been fixed in formalin. Presumptive clonal reactions have been obtained in preliminary tests on 8 of 10 unfixed T cell lymphomas but in 0 of 10 reactive lymph nodes.

Base Sequence↗
PubMed1990

Induction of tumor necrosis factor and cytotoxicity by macrophages exposed to lactoperoxidase and microperoxidase.

Peroxidases are involved in a number of cytotoxic reactions. Murine thioglycollate-induced peritoneal macrophages were exposed to either lactoperoxidase or microperoxidase in vitro. At a concentration of 17.7 microM, both of these enzymes induced between 100 and 200 units of tumor necrosis factor (TNF) per 0.1 ml. Furthermore, these substances were able to stimulate macrophages to kill 3T12 target cells in a dose dependent manner at concentrations of 0.177 microM to 17.7 microM. Per cent cytotoxicity varied from 20% up to 75% at the higher concentrations. It was concluded that these enzymes can induce macrophages to secrete TNF and become activated to the cytotoxic state.

Animals↗
PubMed1990

The production and purification of PCR-derived recombinant simian immunodeficiency virus p27 gag protein; its use in detecting serological and T-cell responses in macaques.

The polymerase chain reaction (PCR) was used to amplify a region of the gag gene, encompassing the core protein p27, from genomic DNA of cells infected with SIVmac251 (32H isolate). The 767 base pair PCR product was cloned into the bacteriophage M13 and fully sequenced before sub-cloning into the expression vector pUC19. The 30 kilodalton (kDa) fusion protein of lacZ-p27 was expressed as a soluble protein in E. coli JM101 cells and purified to greater than 90% purity by affinity chromatography. The affinity purified product was used in serological and T-cell assays to assess immune function in cynomolgus macaques immunised or challenged with immunodeficiency virus derived material. This reagent and accompanying methods provide valuable assays for monitoring the efficacy of vaccines for SIV as a model for human AIDS.

Animals↗
PubMed1990

Late lower arch crowding: the effect of second molar extraction.

Mesial drift and change in crowding over a 5-year period were compared in 30 subjects whose lower second molars were extracted between ages 11 and 17 years and 30 subjects whose lower second molars were not extracted. Significant differences were found. The nonextraction subjects showed an average forward movement of first molars and an increase in crowding. The extraction group showed slight distal movement of first molars and a decrease in crowding. It is concluded that lower second molar extraction reduces the tendency to forward movement of buccal segments and increased crowding by relieving eruptive pressure from third molars and that the presence of a developing lower third molar with insufficient space can be one cause of late lower arch crowding.

Adolescent↗
PubMed1989

Peroxidases enhance macrophage-mediated cytotoxicity via induction of tumor necrosis factor.

Tumor necrosis factor (TNF) is a monokine which is involved in macrophage-mediated cytotoxicity (MMC). We have previously reported that peroxidases can activate thioglycollate-induced macrophages to the tumoricidal state in vitro. The present study was undertaken in an attempt to correlate peroxidase-induced MMC with production of TNF. Horseradish peroxidase (HRP) was used as the principal model for these studies. Resident and thioglycollate-induced macrophages exposed to peroxidases were examined for both MMC against 3T12 cells and production of TNF. Thioglycollate-induced macrophages exposed to HRP, bovine lactoperoxidase, or human myeloperoxidase demonstrated enhanced secretion of TNF. When exposed to HRP, both resident and thioglycollate-induced macrophages secreted significant amounts of TNF and acquired the ability to lyse 3T12 cells. However, resident macrophages were considerably less efficient in both their cytotoxic activity and TNF secretion. Macrophage-mediated cytotoxicity was eliminated by the addition of specific antisera to TNF. In addition, replacement of culture supernatants within 24 hr after exposure of the macrophages to HRP increased tumor cell killing in the absence of additional detectable TNF production, suggesting that other factors may be involved in peroxidase-induced MMC. These results indicate that TNF is intimately associated with peroxidase-induced MMC and suggest a possible role for peroxidases as immunomodulators via augmentation of macrophage capacities and functions.

Animals↗