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Biomedical subjects

T Gray

Publications and source records attributed to T Gray.

At least 37 records · Page 2Linked to original sources
PubMed1999

The effects of anxiety on psychiatric morbidity in patients with multiple sclerosis.

Our objective was to assess the point prevalence and effects of clinically significant anxiety in patients with Multiple Sclerosis (MS). One hundred and fifty two consecutive patients with MS attending an outpatient clinic underwent neurological examination and were assessed for psychopathology with the Hospital Anxiety and Depression Scale, the 28 item General Health Questionnaire and a questionnaire probing suicidal thoughts or intent. Clinically significant anxiety, either with or without depression, was endorsed by 25% of patients, three times the rate for depression. Females were significantly more anxious than males. Anxiety co-morbid with depression, rather than anxiety or depression alone, was associated with increased thoughts of self harm, more somatic complaints and greater social dysfunction. Patients with increased psychopathology were not more likely to be taking psychotropic medication. The results provide preliminary evidence that anxiety, which may be often overlooked clinically, is a frequent accompaniment to depression, thereby adding to the morbidity associated with MS. The implications of the findings to MS patients' quality of life are emphasised.

Adult↗
PubMed1999

Nursing in genitourinary medicine: 10 years on from the Monks Report. The membership of GUNA. Genito-Urinary Nurses Association.

Various reports and surveys since 1988 have highlighted differences in gradings and diversity of roles and responsibilities of nurses in genitourinary medicine (GUM). In addition there was no method of defining how many nurses work in the speciality. Therefore the Genito-Urinary Nurses Association (GUNA) undertook a survey last year to establish how many nurses, of what grade, undertaking what roles are working in GUM clinics. Over half the clinics in the UK responded, from full-time busy London clinics to small part-time rural clinics. The results suggest approximately 2000 nurses working in GUM nationally, with a wide diversity of grades, roles and responsibilities still apparent 10 years after the Monks Report. Further analysis of the data obtained by the survey is given in the report.

Female Urogenital Diseases↗
PubMed1998

Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency.

OBJECTIVE: To examine whether amniotic membrane transplantation (AMT), in preparing the perilimbal stroma, enhances the success of allograft limbal transplantation (ALT). METHODS: Thirty-one eyes of 26 consecutive patients had cytologically proven limbal deficiency resulting from chemical burns (14 eyes); Stevens-Johnson syndrome, toxic epidermal necrolysis, or pseudopemphigoid (5 eyes); contact lens-induced keratopathy (3 eyes); aniridia (3 eyes); multiple surgical procedures (2 eyes); atopy (2 eyes); or an unknown cause (2 eyes). Based on the severity of limbal deficiency, group A (mild), comprising 10 eyes, received AMT alone; group B (moderate), comprising 7 eyes, received AMT and ALT; and group C (severe), comprising 14 eyes, received AMT, ALT, and penetrating keratoplasty. All patients except those in group A received continuous oral cyclosporine. RESULTS: Except for the 2 eyes with atopy, all amniotic membrane-covered surfaces showed rapid epithelialization (in 2 to 4 weeks) and reduced inflammation, vascularization, and scarring, and the surfaces became smooth and wettable. For the mean follow-up period of 15.4 months, 25 (83%) of 30 eyes showed visual improvement, consisting of 6 or more lines (13 eyes), 4 to 5 lines (6 eyes), or 1 to 3 lines (6 eyes). Visual improvement decreased with the severity of limbal deficiency from 8 (100%) of 8 eyes in group A to 5 (71%) of 7 eyes in group B and 11 (79%) of 14 eyes in group C. In group C, corneal graft rejection occurred in 9 (64%) of 14 eyes, and reversible early limbal allograft rejection was noted in 3 (14%) of 21 eyes of groups B and C. CONCLUSIONS: For partial limbal deficiency with superficial involvement, AMT alone is sufficient and hence superior to ALT because there is no need to administer cyclosporine. For total limbal deficiency, additional ALT is needed, and AMT helps reconstruct the perilimbal stroma, with reduced inflammation and vascularization, which collectively may enhance the success of ALT.

Adult↗
PubMed1998

Differential lamina propria cell migration via basement membrane pores of inflammatory bowel disease mucosa.

BACKGROUND & AIMS: In active inflammatory bowel disease (IBD), the intestinal mucosa is infiltrated by polymorphonuclear cells (PMNs), lymphocytes, and monocytes from the systemic circulation. Using an ex vivo model, we have investigated luminally directed migration of cells out of the lamina propria. METHODS: Fresh untreated and deepithelialized mucosal samples were studied by electron microscopy. Cells migrating out of the lamina propria were investigated by immunohistochemistry and fluorescence-activated cell sorter analysis. RESULTS: In intact IBD mucosal samples, tunnels containing cells were prominent in the lamina propria matrix, and PMNs, but not other cell types, were prominent in the epithelium. In deepithelialized mucosal samples, the basement membrane was either destroyed or contained numerous large pores. During culture of deepithelialized mucosal samples, many cells (3.3 [+/-0.8] x 10(5) . g tissue-1 . h-1) migrated out of the lamina propria via basement membrane pores. PMNs and eosinophils were prominent during the first 3 hours of culture, but T cells predominated thereafter. Macrophages also migrated, but B cells were the minority population (<2%) at all times. CONCLUSIONS: In active IBD mucosa with an intact epithelium, luminally directed migration of lamina propria cells is restricted mainly to PMNs. After loss of the epithelium, other cell types also migrate into the lumen via numerous, large, basement membrane pores.

Basement Membrane↗
PubMed1998

Serial magnetic resonance imaging findings for a spontaneously resolving spinal subdural hematoma: case report.

OBJECTIVE AND IMPORTANCE: Spinal subdural hematoma (SSDH) is a rare entity, and cases are usually managed as surgical emergencies. We describe a patient with a SSDH who demonstrated incomplete clinical resolution with nonsurgical management, despite continued anticoagulation treatment. We provide the most complete demonstration of the magnetic resonance imaging (MRI) characteristics of a large SSDH from its initiation to its radiological resolution. CLINICAL PRESENTATION: A 61-year-old woman developed a large SSDH as a complication of a lumbar puncture. Her only neurological deficit was urinary retention. INTERVENTION: Because of the extensiveness of the hematoma and the relative neurological preservation of the patient, she was treated conservatively. Serial MRI scans were obtained at 4, 7, 13, and 25 days. The evolution of deoxyhemoglobin in the hematoma to methemoglobin was observed. By 25 days, MRI scans showed virtual resolution. CONCLUSION: SSDHs undergo MRI signal changes that are similar to those of brain hematomas. In certain cases, even large SSDHs demonstrate swift and dramatic spontaneous resolution, despite continued anticoagulation treatment. This report suggests that there is a role for conservative management for selected cases of SSDHs.

Female↗
PubMed1998

Production of proinflammatory cytokines and inflammatory mediators in human intestinal epithelial cells after invasion by Trichinella spiralis.

Epithelial cells are the first point of host contact for invasive intestinal pathogens and may initiate mucosal inflammatory responses via production of proinflammatory cytokines and mediators. The aim of the present study was to investigate in vitro the initial invasion of a parasitic nematode (Trichinella spiralis), to measure the early production of specific epithelial cytokines and inflammatory mediators after invasion, and to compare these responses with those to invasive bacteria. Monolayers of human colonic epithelial cell lines (HT29, T84, and Caco-2) were infected by T. spiralis or Listeria monocytogenes. Bile-activated infective larvae of T. spiralis invaded and migrated into the epithelial cell monolayers, leaving trails of dead cells. Transmission electron microscopy studies of damaged cells along the trail showed a progressive increase in size, disruption of cell membranes, loss or dilution of cytoplasmic proteins, and swelling of mitochondria and nuclei. However, no nuclear fragmentation was observed. With reverse transcription-PCR and an enzyme-linked oligonucleotide chemiluminescent assay, mRNA transcripts of interleukin-1beta (IL-1beta), IL-8, and epithelial neutrophil-activating peptide 78 were shown to increase in epithelial cells invaded by T. spiralis or L. monocytogenes, but only L. monocytogenes elicited increased inducible nitric oxide synthase (iNOS) mRNA. No increase in tumor necrosis factor alpha or transforming growth factor beta mRNA was seen after T. spiralis invasion. Increased levels of IL-8 were also released from the basolateral surfaces of infected monolayers as detected by sandwich enzyme-linked immunosorbent assay. Induction and secretion of proinflammatory cytokines in epithelial cells after nematode or bacterial invasion may initiate the acute inflammatory response of the small intestine. The upregulation of iNOS in bacterial infections may contribute to mucosal defense and may also be associated with subsequent cell death, whereas different mechanisms appear to operate after nematode invasion.

Animals↗
PubMed1997

Prevalence and neurobehavioral correlates of pathological laughing and crying in multiple sclerosis.

OBJECTIVES: To establish the point prevalence of pathological laughing and crying (PLC) in multiple sclerosis (MS). To define associated neurological, emotional, and cognitive correlates of PLC. DESIGN: A consecutive sample of 152 patients with clinically or laboratory definite MS were screened for PLC, defined as sudden, involuntary displays of laughing or crying or both, without associated subjective feelings of depression or euphoria. Thereafter, a case-control design was followed with patients with PLC matched to patients with MS without PLC on age, gender, physical disability (Expanded Disability Status Scale), duration of MS, and premorbid IQ. SETTING: An MS outpatient clinic, the population representative of a large urban catchment area. PATIENTS: Fifteen of 152 patients had PLC, 11 of whom (mean [SD] age, 43.7 [8.3] years, 7 women) agreed to further testing. Thirteen patients with MS without PLC acted as controls. MAIN OUTCOME MEASURES: Neurological examination, Pathological Laughter and Crying Scale, Hospital Anxiety and Depression Scale, 28-item General Health Questionnaire, and the Wechsler Adult Intelligence Scale-Revised. RESULTS: The point prevalence of PLC in MS was 10%. Patients had a mean Expanded Disability Status Scale score of 6.5, had had MS for a mean (SD) of 10 (5.8) years, and had entered a chronic-progressive phase of their illness. Pathological laughing and crying was not associated with disease exacerbations. Compared with controls, patients were not more depressed or anxious, but had a greater decline in IQ. CONCLUSIONS: Pathological laughing and crying as distinct from emotional lability affects 1 in 10 patients with MS. It occurs in severely physically disabled patients, generally with long-standing disease. The presence of cognitive deficits relative to controls implies more extensive brain involvement.

Adult↗
PubMed1997

Screening for depression on continuing care psychogeriatric wards.

The performance of the Depressive Signs Scale (DSS) completed by the nursing staff, in detecting significant clinical depression among continuing care psychogeriatric inpatients was examined. A cutoff score of 5/6 gave the best sensitivity (70%) and specificity (72%) in the whole sample. The same cutoff value gave the best sensitivity (62%) and specificity (72%) in the dementia subsample.

Adult↗
PubMed1997

Melanoma of the hand.

Melanomas of the hand are relatively rare, and much confusion exists concerning their pathology and treatment. We reviewed our experience with 39 patients diagnosed with melanoma of the hand. The data were categorized by site, histology, and type of treatment. Most primaries were on the digits, with a few tumors arising on the palm. The most common histology was superficial spreading melanoma, even in the subungual location. Acral lentiginous melanoma accounted for only 8 of 39 cases. Most patients could be treated without radical amputations, even for melanomas on the digits. Review of our patients emphasized the need for early diagnosis. Biopsy of all unexplained pigmented lesions on the hands can lead to early diagnosis, relatively nondeforming treatment, and good survival.

Adolescent↗
PubMed1997

A single dose of intravenously injected poloxamine-coated long-circulating particles triggers macrophage clearance of subsequent doses in rats.

1. Adsorption of the block copolymer non-ionic surfactant poloxamine-908 on to the surface of polystyrene nanospheres (60 nm in diameter) produced 'phagocyte-resistant' particles (otherwise known as long-circulating particles). This was reflected by a profound reduction in uptake of such engineered nanospheres by macrophages of the reticuloendothelial system and extended blood circulation time, after intravenous administration to rats. 2. A single intravenous administration of poloxamine-908-coated particles dramatically affected the circulation half-life and body distribution of a second subsequent dose. The degree of alteration depended on the interval between the two doses. At 3 days after a single intravenous injection of poloxamine-coated particles, Kupffer cells and spleen macrophages could clear a second dose of long-circulating beads from the blood. When tested at day 14, the second dose of intravenously injected poloxamine-coated particles avoided rapid uptake by liver and spleen macrophages and remained in the blood. 3. The coating polymer (poloxamine-908) apparently triggered bead clearance by resident Kupffer cells and certain sub-populations of spleen macrophages, since a single intravenous dose of an endotoxin-free solution of poloxamine 3 days before the administration of long-circulating particles induced similar effects. When the interval between the two injections was 2 weeks, poloxamine-coated particles again exhibited long circulation half-life. This cycle could be repeated after intravenous administration of a second poloxamine dose 2 weeks after the first poloxamine injection. 4. The mechanism of particle recognition by resident tissue macrophages was found to be independent of opsonization processes. 5. These studies could have important implications in biomedical application, design and engineering of poloxamine-based long-circulating drug carriers for repeated intravenous administration.

Animals↗
PubMed1997

Migration of human intestinal lamina propria lymphocytes, macrophages and eosinophils following the loss of surface epithelial cells.

Lymphocytes and macrophages are present in the normal intestinal lamina propria, separated from the epithelial monolayer by the basement membrane. There is evidence for movement of mononuclear cells through the lamina propria, entering from the systemic circulation and exiting via lymphatic channels. The goal of our studies was to investigate the capacity of cells to migrate out from the lamina propria into the lumen following the loss of surface epithelial cells. An in vitro model was therefore established in which normal human intestinal mucosal samples, denuded of the surface epithelium, were maintained in culture. Electron microscopy showed that during culture, large numbers (>2 x 10(6)/g tissue per 24 h) of cells migrated out of the lamina propria via discrete 'tunnels' which were in continuity with pores (diameter <4 microm) in the basement membrane. The emigrating cells were T cells (68.5 +/- 5.1%), macrophages (10.5 +/- 1.3%) and eosinophils (7.1 +/- 1.3%). Our studies have therefore demonstrated, for the first time, the capacity for large numbers of lymphocytes, macrophages and eosinophils to migrate out of the lamina propria, via basement membrane pores. We postulate that such emigration of cells occurs in vivo following the loss of surface epithelial cells due to injury, and could represent an important form of host defence against luminal microorganisms and also facilitate wound repair by enhancing restitution by neighbouring epithelial cells, via peptide factors.

Antigens, CD↗
PubMed1997

Response to prejunctional adenosine receptors is dependent on stimulus frequency.

PURPOSE: To characterize the adenosine receptor modulation of norepinephrine (NE) release from sympathetic neurons in the isolated rabbit iris/ciliary body. METHODS: Iris/ciliary bodies were isolated from New Zealand White rabbits and incubated in the presence of 3H-NE. Norepinephrine release was elicited by field stimulation with varied frequencies from 5 to 30 Hz. The effects of adenosinergic and alpha 2 adrenergic compounds on NE release were determined and compared. RESULTS: At a stimulation frequency of 5 Hz, the addition of the adenosine A1 agonist CHA did not significantly alter 3H-NE release. However, in the presence of the alpha 2 adrenergic antagonist yohimbine, the addition of CHA produced a dose-related reduction in 3H-NE release. The EC50 for this reduction was 14 nM. At a stimulus frequency of 20 Hz, the addition of CHA alone (10(-6) M) produced a significant reduction in 3H-NE release of 41%. The EC50s for the adenosine A1 agonists CHA- and R-PIA-induced suppression of 3H-NE release at 20 Hz were 32 and 24 nM, respectively. The adenosine A2 agonist CV-1808 did not alter 3H-NE release at stimulation frequencies of 5 or 20 Hz. Pretreatment of tissues with the adenosine A1 antagonist CPT or pertussis toxin reversed the suppression of 3H-NE release induced by CHA. Comparison of the inhibitory responses of CHA to the alpha 2 adrenergic agonist UK-14,304 at stimulus frequencies of 5 to 30 Hz demonstrated that this adenosine A1 agonist was effective only in suppressing NE release at frequencies of 20 Hz or greater. In contrast, the alpha 2 adrenergic agonist UK-14,304 was most effective in reducing NE release at 5 Hz. CONCLUSIONS: These results provide evidence that adenosine agonists inhibit 3H-NE release in the iris/ciliary body via prejunctional adenosine A1 receptors linked to Gi/o-protein. However, the expression of this response was dependent on the frequency of neuronal stimulation. Hence, prejunctional adenosine A1 receptors may act to selectively limit high-frequency neurotransmission.

Adenosine↗
PubMed1997

Adult human colonic subepithelial myofibroblasts express extracellular matrix proteins and cyclooxygenase-1 and -2.

Interactions between epithelial cells and subepithelial myofibroblasts are increasingly recognized as important in the regulation of epithelial cell function. We have established primary cultures of subepithelial myofibroblasts from adult human colonic mucosal samples denuded of epithelial cells and maintained in culture. During culture of mucosal tissue, subepithelial myofibroblasts migrated out via basement membrane pores before establishment in culture. Despite prolonged culture and passage, the myofibroblasts maintained their phenotype, as demonstrated by expression of alpha-smooth muscle actin and vimentin. The cells expressed transcripts and protein for cyclooxygenase (COX)-1 and -2 enzymes, and their release of prostaglandin E2 (PGE2) was inhibited by selective COX-1 and -2 inhibitors. The myofibroblasts also expressed the extracellular matrix (ECM) proteins collagen type IV, laminin-beta 1 and -gamma 1, and fibronectin. Adult human colonic subepithelial myofibroblasts may influence epithelial cell function via products of COX-1 and -2 enzymes, such as PGE2 and secreted ECM proteins.

Actins↗
PubMed1997

Regulation of the secretory phenotype of human airway epithelium by retinoic acid, triiodothyronine, and extracellular matrix.

The purpose of our studies was to identify factors which regulate the composition of airway secretions produced by normal human tracheobronchial epithelial (NHTBE) cells. Individual factors were removed from the culture media of NHTBE cells grown in air-liquid interface (ALI) cultures (which support mucociliary differentiation) and the effects on mucin, lysozyme (LZ), and secretory leukocyte protease inhibitor (SLPI) secretion and gene expression were examined. Deletion of hydrocortisone, epinephrine, transferrin, or gentamycin-amphotericin from the media had no reproducible effects; deletion of insulin was incompatible with culture growth. We identified 3 factors, namely retinoic acid (RA), triiodothyronine (T3) and collagen gel substratum, which had a major impact on the profile of NHTBE secretions. Removal of RA from the media caused a drastic decrease in mucin secretion and a decrease in expression of the mucin genes MUC2 and MUC5AC.LZ and SLPI secretions were increased in these cultures. Paradoxically LZ mRNA was decreased, while SLPI mRNA levels were increased. Removal of T3 selectively increased mucin secretion, MUC2 gene expression was not affected, but MUC5AC mRNA levels reproducibly increased, suggesting that the expression of these two mucin genes is differentially regulated. LZ and SLPI secretion levels were not significantly affected by deletion of T3 from the culture media; however, LZ mRNA levels were increased in the absence of T3 while SLPI transcript levels were not affected. Omission of the attachment substratum, type I collagen gel, resulted in significant increases in all 3 secretory products. MUC2 and MUC5AC steady state mRNA levels were not consistently affected. In contrast LZ and SLPI gene expression were reproducibly increased. Our studies show that individual factors in the epithelial environment can regulate expression of specific secretory cell gene products in a highly selective manner.

Anti-Infective Agents↗
PubMed1996

Evolutionary strategies for the elucidation of cis and trans factors that regulate the developmental switching programs of the beta-like globin genes.

We describe three strategies for the identification of specific cis and trans factors that regulate globin gene expression, all three of which are based on the evolution of the globin genes and their expression patterns. The first approach, phylogenetic footprinting, relies on a search for sequence similarities and is designed to elucidate the factors that control those expression patterns which are shared by orthologous globin genes of all eutherian mammals (e.g., the expression of the epsilon globin genes in the embryonic yolk sac and its repression in fetal and adult hematopoietic tissues). The second approach, differential phylogenetic footprinting, relies on a search for sequence differences. This approach may be of value in identifying the mechanisms underlying the generation of novel expression patterns in specific lineages (e.g., the expression of gamma as a fetal gene in the simian primates in contrast with the embryonic expression of gamma in all other mammals). Finally, motif-based phylogenetic analysis takes into consideration the fact that many transcription factors are quite flexible in the recognition of their cognate sites. The approach allows the detection of functionally conserved binding sites despite their sequence variation.

Adult↗
PubMed1996

A full genome search in multiple sclerosis.

The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.

Chromosome Mapping↗
PubMed1996

Effect of Clostridium difficile toxin A on human intestinal epithelial cells: induction of interleukin 8 production and apoptosis after cell detachment.

Clostridium difficile is the aetiological agent of pseudomembranous colitis, and animal studies suggest the essential role of secreted toxin A in inducing disease. This study examined the biological responses to toxin A by human intestinal epithelial cells. Confluent monolayers of Caco2, HT29, and T84 cells and primary epithelial cells in organ cultures of human colonic biopsy specimens and after detachment with EDTA were studied. Interleukin 8 was assayed using enzyme linked immunosorbent assay (ELISA). Purified C difficile toxin A induced cell rounding and detachment of monolayers of the epithelial cell lines. Cells in detached monolayers initially remained viable while adherent to each other. Subsequently, an increasing number of apoptotic cells appeared in suspension. Exposure to toxin A for 24 hours induced interleukin 8 production in T84 and HT29 cells. Toxin A also induced epithelial cell rounding, detachment, and apoptosis in organ cultures of human colonic biopsy specimens. During culture (in medium only), EDTA detached colonic epithelial cells produced interleukin 8 and cell death occurred by apoptosis. Colonic disease by C difficile may be initiated by toxin A mediated induction of epithelial cell interleukin 8 production and apoptosis after cell detachment from the basement membrane. Studies on isolated (toxin untreated) colonic epithelial cells suggest that interleukin 8 production and apoptosis occur as a consequence of cell injury and detachment.

Apoptosis↗