What is the right operation for stress incontinence? A urologist's view.
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Algorithms↗
Biomedical subjects
C Evans
Publications and source records attributed to C Evans.
Multiple gamma-Aminobutyric acid plasma membrane transporters (GAT-1, GAT-2, GAT-3) in the rat retina.
gamma-Aminobutyric acid (GABA) plasma membrane transporters (GATs) influence synaptic neurotransmission by high-affinity uptake and release of GABA. The distribution and cellular localization of GAT-1, GAT-2, and GAT-3 in the rat retina have been evaluated by using affinity-purified polyclonal antibodies directed to the C terminus of each of these GAT subtypes. Small GAT-1-immunoreactive cell bodies were located in the proximal inner nuclear layer (INL) and ganglion cell layer (GCL), and processes were distributed to all laminae of the interplexiform layer (IPL). Varicose processes were in the optic fiber layer (OFL) and the outer plexiform layer (OPL). Weak GAT-1 immunostaining surrounded cells in the INL and GCL, and it was found in the OFL and OPL and in numerous processes in the outer nuclear layer (ONL) that ended at the outer limiting membrane. GAT-1 is therefore strongly expressed by amacrine, displaced amacrine, and interplexiform cells and weakly expressed by Müller cells. GAT-2 immunostaining was observed in the retina pigment epithelium and the nonpigmented ciliary epithelium. GAT-3 immunoreactivity was distributed to the OFL, to all laminae of the IPL, GCL and INL, and to processes in the ONL that ended at the outer limiting membrane. Small GAT-3-immunoreactive cell bodies were in the proximal INL and GCL. GAT-3 is therefore strongly expressed by Müller cells, and by some amacrine and displaced amacrine cells. Together, these observations demonstrate a heterologous distribution of GATs in the retina. These transporters are likely to take up GABA from, and perhaps release GABA into, the synaptic cleft and extracellular space. This suggests that GATs regulate GABA levels in these areas and thus influence synaptic neurotransmission.
Amino Acid Sequence↗
Agonist-selective endocytosis of mu opioid receptor by neurons in vivo.
Opiate alkaloids are potent analgesics that exert multiple pharmacological effects in the nervous system by activating G protein-coupled receptors. Receptor internalization upon stimulation may be important for desensitization and resensitization, which affect cellular responsiveness to ligands. Here, we investigated the agonist-induced internalization of the mu opioid receptor (MOR) in vivo by using the guinea pig ileum as a model system and immunohistochemistry with an affinity-purified antibody to the C terminus of rat MOR. Antibody specificity was confirmed by the positive staining of human embryonic kidney 293 cells transfected with epitope-tagged MOR cDNA, by the lack of staining of cells transfected with the delta or kappa receptor cDNA, and by the abolition of staining when the MOR antibody was preadsorbed with the MOR peptide fragment. Abundant MOR immunoreactivity (MOR-IR) was localized to the cell body, dendrites, and axonal processes of myenteric neurons. Immunostaining was primarily confined to the plasma membrane of cell bodies and processes. Within 15 min of an intraperitoneal injection of the opiate agonist etorphine, intense MOR-IR was present in vesicle-like structures, which were identified as endosomes by confocal microscopy. At 30 min, MOR-IR was throughout the cytoplasm and in perinuclear vesicles. MOR-IR was still internalized at 120 min. Agonist-induced endocytosis was completely inhibited by the opiate antagonist naloxone. Interestingly, morphine, a high-affinity MOR agonist, did not cause detectable internalization, but it partially inhibited the etorphine-induced MOR endocytosis. These results demonstrate the occurrence of agonist-selective MOR endocytosis in neurons naturally expressing this receptor in vivo and suggest the existence of different mechanisms regulating cellular responsiveness to ligands.
Animals↗
Presumed Pott's disease.
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AIDS-Related Opportunistic Infections↗
Chromosomal assignment of 79 cDNAs from a range of human tissues.
Single-pass DNA sequencing of cDNAs selected at random from a human mixed tissue cDNA library have generated a series of more than 2000 expressed sequence tags. One hundred twenty-eight unique cDNA fragments with little or no known protein or nucleic acid homologies have been selected for further analysis. Oligonucleotide primer pairs have been designed from the cDNAs and used in PCR amplification in combination with genomic DNA from a panel of monochromosomal somatic cell hybrids. This has allowed us to assign 70 of these transcribed genes to a single chromosome, and a further 9 have been located on two or three chromosomes. Additionally, 3 cDNAs contain short tandem repeats that may allow them to be further localized by linkage analysis.
Animals↗
HLA-A2-restricted peripheral blood cytolytic T lymphocyte response to HPV type 16 proteins E6 and E7 from patients with neoplastic cervical lesions.
The DNA from human papillomavirus (HPV) can be detected in 90% of cervical carcinomas. To address whether patients infected with HPV can mount efficient T cell responses to this pathogen we examined the cytotoxic T lymphocyte (CTL) response of peripheral blood mononuclear cells (PBMC) from patients with abnormal genital epithelial cells. PBMC from 11 HLA-A2+ patients were stimulated with CaSki, a cervical carcinoma cell line that is HPV 16+ and HLA-A2+. The CTL were screened for reactivity to the cervical carcinoma cell line C33A (HPV-, HLA-A2+) transfected with the HPV 16 E6 or E7 genes or the plasmid without insert. The CTL of 1 patient showed particularly strong CaSki and HPV E6 or E7 protein-specific cytotoxicity in a HLA-A2+-restricted fashion. In contrast, these CTL lysed neither a vector-only transfectant, the natural killer cell (NK) target, K562 nor the lymphokine-activated killer cell (LAK) target, Daudi. HLA-A2 restriction was demonstrated by the lack of recognition of a HLA-A2- CaSki cell line developed in our laboratory. The CTL line was cloned and 99 clones were harvested and screened; 51 clones lysed CaSki, of which 17 did not lyse the A2- CaSki. Of these HLA-A2- restricted clones, 8 did not lyse C33A transfectants, 6 lysed all C33A transfectants, 3 lysed C33A-E7 only and none lysed C33A-E6 only. These data imply that, within the bulk CTL line, HLA-A2-restricted recognition of antigens was restricted to CaSki antigens, antigens common to cervical carcinoma (CaSki plus C33A), or HPV-16-E7-derived antigen on the clonal level. The E7-restricted clones were negative for recognition of known HLA-A2-binding peptides from E7.
Base Sequence↗
Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice.
In nonobese diabetic (NOD) mice, beta-cell reactive T-helper type 1 (Th1) responses develop spontaneously and gradually spread, creating a cascade of responses that ultimately destroys the beta-cells. The diversity of the autoreactive T-cell repertoire creates a major obstacle to the development of therapeutics. We show that even in the presence of established Th1 responses, it is possible to induce autoantigen-specific anti-inflammatory Th2 responses. Immune deviation of T-cell responses to the beta-cell autoantigen glutamate decarboxylase (GAD65), induced an active form of self-tolerance that was associated with an inhibition of disease progression in prediabetic mice and prolonged survival of syngeneic islet grafts in diabetic NOD mice. Thus, modulation of autoantigen-specific Th1/Th2 balances may provide a minimally invasive means of downregulating established pathogenic autoimmune responses.
Adoptive Transfer↗
Isolation and mapping of three new polymorphic markers to chromosomes 3, 20 and 21.
Screening of single human chromosome plasmid libraries using a digoxygenin labelled (AAAT)15 oligonucleotide probe led to the identification of several positive clones. DNA sequence analysis of these was carried out and showed the presence of a number of simple DNA repeats. Oligonucleotide primers were designed from the sequences flanking these repeats and tested in PCR amplification reactions of human genomic DNA. Three of the markers tested were shown to be polymorphic with heterozygosities ranging from 40% to 69%. The markers were assigned to chromosomes using a panel of monochromosomal somatic cell hybrids combined with linkage analysis using DNA from the CEPH panel of families. The markers designated (AAAT)11, (AAAT)12 and (CA)19 were thus assigned to chromosomes 3, 21 and 20 respectively.
Base Sequence↗
Elevated endoxin-like factor complicating a multifetal second trimester pregnancy: treatment with digoxin-binding immunoglobulin.
We report a case of a second trimester multifetal pregnancy with preeclampsia associated with an elevated digoxin-like immune factor. Due to the remoteness from viability the patient was offered therapy with digoxin-binding immunoglobulin. No untoward maternal effects were noted.
Adult↗
Marfan syndrome and retroperitoneal fibrosis.
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Aortic Aneurysm, Abdominal↗
The conserved aspartate residue in the third putative transmembrane domain of the delta-opioid receptor is not the anionic counterpart for cationic opiate binding but is a constituent of the receptor binding site.
Opioids are cationic compounds that mediate their biological action through three highly homologous receptors (mu, delta, and kappa) known to belong to the G protein-coupled receptor (GPR) family. The third putative transmembrane domain of opioid receptors contains a conserved aspartate residue that is typically found in biogenic amine binding GPRs and is generally believed to form an ion pair with the cationic neurotransmitters. Using site-directed mutagenesis, we investigated the possibility of an identical role for this residue (Asp128) in the mouse delta-opioid receptor. Removal of the carboxylate group via an aspartate-to-alanine mutation did not modify binding affinity of a representative set of opioid compounds, including bremazocine, diprenorphine, naloxone, Tyr-D-Thr-Gly-Phe-Leu-Thr, [D-Ala2,D-Leu5]enkephalin, cyclic[D-penicillamine2,D-penicillamine5]enkephalin, deltorphin II, (+/-)-4-[(a-R*)-a-[(2S*,5R*)-4-allyl-2,5-di-methyl-1- piperazinyl]-3-hydroxybenzyl]-N,N-diethylbenzamide, and naltrindole. It nevertheless decreased receptor expression level and affected the binding of three agonists ([D-Ala2,D-Leu5]enkephalin, Tyr-D-Thr-Gly-Phe-Leu-Thr, and (+/-)-4-[(a-R*)-a-[(2S*,5R*)-4-allyl-2,5-di- methyl-1-piperazinyl]-3-hydroxybenzyl]-N,N-diethylbenzamide) when the receptor was under Na(+)-induced low affinity state. On the other hand, the aspartate-to-asparagine mutation strongly impaired the binding of all of the above ligands and highlighted differential modes of interaction for alkaloids and peptides. Finally, removal of the homologous carboxylate group in the mouse mu receptor had distinct effects because it dramatically reduced the binding potency of some, but not all, tested ligands. Taken together, these results demonstrate that (i) the direct ligand/receptor interaction previously demonstrated for the beta-adrenergic receptor does not take place in the delta receptor, (ii) Asp128 nevertheless contributes to stabilization of the spatial conformation of the binding pocket, and (iii) these conclusions cannot be extended to the closely related mu receptor.
Amino Acid Sequence↗
The problem with weighing: effects on mood, self-esteem and body image.
OBJECTIVE: To examine the effect of weighing and comparison with social norms on self-esteem, mood and body dissatisfaction. DESIGN: An experimental design was used. SUBJECTS: Seventy-four normal weight individuals took part in the study. PROCEDURE: Subjects completed a set of measures before and after being weighed and sequentially allocated to either the under, average or over weight conditions according to a fictional height-weight chart. RESULTS: The results showed that subjects allocated to the overweight group showed an increase in depression and a decrease in self esteem following the manipulation, compared to subjects in the average weight group who reported improvements in these measures and the underweight group who similarly showed decreased depression, but showed some deterioration of their self-esteem. CONCLUSION: Weighing and comparison with height weight charts of weight norms is used both to detect and treat overweight and obesity. The results from this study indicate that this procedure may not be as benign as believed and may contribute to the negative psychological state of the individual.
Adolescent↗
Problematic renal calculi presenting during pregnancy.
Urinary tract calculi presenting during pregnancy are rare, with less than 0.1% of pregnancies being associated with stones, the vast majority being asymptomatic and a chance finding. We outline six cases treated over an 8-year period. They presented with combinations of pain, sepsis and obstruction. Intervention was required in four cases: insertion of antegrade nephrostomy, double-J stent, Dormia basket stone extraction, open pyelolithotomy and induction of labour. In each case the pregnancy had a successful outcome. Renal colic can precipitate premature labour. Delayed diagnosis and intervention can result in permanent renal impairment. Ionising radiation and anaesthetic agents may be harmful during pregnancy. The problem is rarely encountered and we therefore present information on the relative risks in each trimester of exposure to the mother and fetus and present a clinical algorithm for the management of these patients.
Adult↗
Ocular lens gap junctions: protein expression, assembly, and structure-function analysis.
Recent advances in understanding lens fiber gap junction formation are reviewed. These include studies of junctional protein expression in the embryonic lens, and of age related changes affecting gap junction structure and composition in the adult lens. An in vitro assembly system based on detergent solubilized pore complexes and endogenous lipids has been developed to provide information on the molecular interactions involved in gap junction formation and to provide material for structure analysis. Important information on the electrical properties of lens gap junction channels is obtained using electrophysiological techniques including planar lipid bilayer analysis and patch clamping.
Animals↗
Comparison of the haemodynamic effects of dopamine and dobutamine in young children undergoing cardiac surgery.
Nineteen children, aged 2-54 months, requiring high-dose inotropic support after cardiac surgery, were given either dopamine or dobutamine in a blinded, double crossover, study. Using a pulmonary artery thermistor, right and left atrial cannulae, and pulmonary and femoral arterial catheters, conventional haemodynamic variables were measured hourly over three consecutive 4 h dopamine-dobutamine-dopamine or dobutamine-dopamine-dobutamine exchanges. No significant differences in haemodynamics occurred during dopamine therapy compared with the same dose of dobutamine in 14 patients receiving phenoxybenzamine 2 mg kg-1, four of whom had also received enoximone. In five patients, neither enoximone nor phenoxybenzamine was used and significant increases in pulmonary artery pressure and pulmonary vascular resistance (P = 0.04) occurred when patients were given dopamine rather than dobutamine. We conclude that dobutamine and dopamine are equipotent inotropes in children and that dopamine in doses > 7 micrograms kg-1 min-1, caused pulmonary vasoconstriction, an effect mediated by alpha adrenergic receptors.
Cardiac Surgical Procedures↗
Involvement of the inferior vena cava by renal tumour: surgical excision using hypothermic circulatory arrest.
OBJECTIVE: To evaluate the immediate and long-term results of a radical surgical technique in the treatment of renal tumours with extensive involvement of the inferior vena cava (IVC). PATIENTS AND METHODS: Seven patients with extensive involvement of renal tumours into the IVC were operated upon using a cardiopulmonary by-pass, hypothermia and cardiac arrest to facilitate surgery. Wide exposure of the IVC in a bloodless field permitted complete removal of all visible tumour in each case. Histological sections confirmed renal cell cancer in six patients and Wilms tumour in a 15-year-old girl. RESULTS: All patients recovered well from their surgery with no major complications and spent one or two days in the Intensive Treatment Unit and an average of 13 days in hospital after the operation. Of the seven patients, four are alive and well with no obvious disease after an average follow-up time of 30 months (range 8-54). The other three patients have died from disseminated renal cancer. CONCLUSION: This procedure provides good local control of the tumour and offers the only hope of cure in patients with this disease. In collaboration with the surgical cardiac team it can be safely carried out with acceptable morbidity and mortality.
Adolescent↗
The elusive factor structure of the Inventory of Interpersonal Problems.
This paper reports data on the psychometric properties of the Inventory of Interpersonal Problems (IIP; Horowitz, Rosenberg, Baer, Ureño & Villaseñor, 1988) obtained from a UK inner city sample of 286 out-patient clients presenting for cognitive analytic therapy or treatment in a sexual dysfunction clinic. The results are compared with those of Barkham, Hardy & Startup (1994): only moderate replication of their eight components in the raw data, and four bipolar components from analysis of ipsatized data were found. Split halves of the data were analysed and compared in order to explore the possible influences of clinical and demographic variables on the component structure.
Adult↗
Multiple axis-II diagnoses of personality disorder.
BACKGROUND: Simultaneous diagnosis of more than one personality disorder (PD) has been termed 'comorbidity' or 'co-occurrence' implying that single diagnoses are the norm and multiple diagnoses interesting exceptions. Surveys of PD subjects in fact show 1.5-5.6 diagnoses per subject. Our study explores the hypothesis that multiple PD diagnosis is common and increases with increasingly personality disordered populations. METHOD: The PDQ-R questionnaire was administered to three UK samples: referrals for specialist PD in-patient treatment (n = 275); high tariff offenders attending a probation centre (n = 57); and undergraduate students (n = 274). RESULTS: Means of 6.0 (95% CI 5.7-6.3), 4.0 (3.1-5.0) and 3.4 (3.0-3.8) PDQ-R diagnoses per subject were found respectively. High rates of PD diagnosis in individual subjects suggest that multiple diagnosis is the norm rather than the exception. CONCLUSIONS: Multiple diagnosis of PD is better construed as 'breadth' of psychopathology rather than comorbidity and is a function of sampling frame. High rates of multiple diagnoses question the interpretation of studies of any single PD. The graded construct of 'breadth' of axis-II pathology may further our understanding of PD.
Adolescent↗