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Showing papers by "St Thomas' Hospital published in 1995"


Journal ArticleDOI
TL;DR: Turk, Melzack, and Katz as discussed by the authors proposed the McGill Pain Questionnaire: Appraisal and current status to assess patients with chronic pain, and used it to measure the dimensions and stages of pain.

1,492 citations


Journal ArticleDOI
TL;DR: The risk of recurrent thrombosis in patients with the antiphospholipid-antibody syndrome is high and long-term anticoagulation therapy in which the international normalized ratio is maintained at or above 3 is advisable in these patients.
Abstract: Background The antiphospholipid-antibody syndrome is a thrombophilic disorder in which venous or arterial thrombosis, or both, may occur in patients with antiphospholipid antibodies. The optimal treatment of these patients is unclear. We assessed the efficacy of warfarin, low-dose aspirin, or both in the secondary prevention of thrombosis in patients with the syndrome. Methods One hundred forty-seven patients (124 [84 percent] of whom were female) with the antiphospholipid-antibody syndrome and a history of thrombosis were studied retrospectively. The syndrome was primary in 62 patients and was associated with systemic lupus erythematosus in 66 patients and lupus-like disease in 19. Each patient's history was reviewed. Results One hundred one patients (69 percent) had a total of 186 recurrences of thrombosis. The median time between the initial thrombosis and the first recurrence was 12 months (range, 0.5 to 144 months). Treatment with high-intensity warfarin (producing an international normalized ratio o...

1,336 citations


Journal ArticleDOI
TL;DR: This work reviews how currently available delivery systems, both plasmid and viral, can be manipulated to improve their targeting to specific cell types and suggests how gene therapy delivery systems of the future will be composites of the best features of diverse vectors already in use.
Abstract: Successful gene therapy requires not only the identification of an appropriate therapeutic gene for treatment of the disease, but also a delivery system by which that gene can be delivered to the desired cell type both efficiently and accurately. Reductions in accuracy will inevitably also reduce efficiency since fewer particles will be available for delivery to the correct cells if many are sequestered into nontarget cells. In addition, the therapy will have net benefit to the patient only if gene delivery is sufficiently restricted such that normal cells are left unaffected by any detrimental affects of bystander cell transduction. Here we review how currently available delivery systems, both plasmid and viral, can be manipulated to improve their targeting to specific cell types. Currently, targeting is achieved by engineering of the surface components of viruses and liposomes to achieve discrimination at the level of target cell recognition and/or by incorporating transcriptional elements into plasmid or viral genomes such that the therapeutic gene is expressed only in certain target cell types. In addition, we discuss emerging vectors and suggest how gene therapy delivery systems of the future will be composites of the best features of diverse vectors already in use.

423 citations


Journal ArticleDOI
TL;DR: The first mutations in the gene encoding the 180-kD bullous pemphigoid antigen (BPAG2) are described, a transmembranous hemidesmosomal collagen, also known as type XVII collagen (COL17A1)8, a rare variant of JEB, and isacompound heterozygote for premature termination codons on both alleles are described.
Abstract: Junctional epidermolysis bullosa (JEB) is a heterogeneous autosomal recessively inherited blistering skin disorder associated with fragility at the dermal-epidermal junction1. Characteristic ultrastructural findings in JEB are abnormalities in the hemidesmosome-anchoring filament complexes1,2. These focal attachment structures, which extend from the intracellular compartment of the basal keratinocytes to the underlying basement membrane, have been shown to be hypoplastic or rudimentary in different forms of JEB2. Previously, in different JEB phenotypes, mutations have been found in the three genes for the anchoring filament component laminin5 (LAMA3, LAMBS, and LAMC2)3–6 and in the gene for the hemidesmosome-associated integrin β4 subunit7. Here, we describe the first mutations in the gene encoding the 180-kD bullous pemphigoid antigen (BPAG2), a transmembranous hemidesmosomal collagen, also known as type XVII collagen (COL17A1)8.The patient is affected with generalized atrophic benign epidermolysis bullosa (GABEB)9, a rare variant of JEB, and isacompound heterozygote for premature termination codons on both alleles. These novel findings emphasize the molecular heterogeneity of this group of genodermatoses, and attest to the importance of BPAG2 in maintaining adhesion between the epidermis and the dermis.

351 citations


Journal Article
TL;DR: The histogenic and genetic relatedness of myxoid and round cell liposarcomas is apparent from these data.
Abstract: Translocation t(12;16)(q13;p11) is regarded as a diagnostic marker for myxoid liposarcoma. Cytogenetic data on round cell liposarcomas and combined myxoid and round cell tumors is scarce, and the genetic basis of progression of myxoid tumors to high grade, round cell lesions is unknown. We have accumulated six round cell, four combined myxoid and round cell, and three myxoid liposarcomas for analysis. t(12;16)(q13;p11) was present in three round cell lesions and was detectable in all of the tumors by DNA analysis. In each tumor type, the CHOP gene in 12q13 was rearranged and fused to the TLS gene in 16p11. A variant TLS-CHOP RNA transcript was detected by polymerase chain reaction but did not correlate with clinicopathological data. No distinguishing cytogenetic or molecular markers for round cell or mixed lesions were found. The histogenic and genetic relatedness of myxoid and round cell liposarcomas is apparent from these data.

192 citations


Journal ArticleDOI
TL;DR: It is confirmed that CNS disease in SLE is significantly associated with the presence of aPL antibodies, and the CNS manifestations can occur in about half of SLE patients without any other evidence of lupus activity.

185 citations


Journal ArticleDOI
TL;DR: These findings provide the first evidence that nonsense mutations within the LAMA3 gene are also involved in the pathogenesis of JEB, and indicate that mutations of all three genes of laminin 5 can result in the JEB phenotype.
Abstract: The inherited mechanobullous disorder, junctional epidermolysis bullosa (JEB), is characterized by extensive blistering and erosions of the skin and mucous membranes. The diagnostic hallmarks of JEB include ultrastructural abnormalities in the hemidesmosomes of the cutaneous basement membrane zone, as well as an absence of staining with antibodies against the anchoring filament protein, laminin 5. Therefore, the three genes encoding alpha 3, beta 3 and gamma 2 chains of laminin 5, known as LAMA3, LAMB3 and LAMC2, are candidate genes for JEB. We have previously demonstrated mutations in the LAMB3 and LAMC2 genes in several families with JEB. We initiated mutation analysis from an affected child by PCR amplification of individual LAMA3 exons, followed by heteroduplex analysis. Nucleotide sequencing of heteroduplexes identified a homozygous nonsense mutation within domain I/II of the alpha 3 chain. These findings provide the first evidence that nonsense mutations within the LAMA3 gene are also involved in the pathogenesis of JEB, and indicate that mutations of all three genes of laminin 5 can result in the JEB phenotype.

175 citations


Journal ArticleDOI
TL;DR: Treatment with 6.00-mm ablation diameters precipitated less initial overcorrection, greatly improved the predictability of photorefractive keratectomy, and was associated with a reduction in complications impairing postoperative visual performance.
Abstract: Objective: To determine the effects of the ablation diameter on the outcome of excimer laser photorefractive keratectomy. Design: Eighty patients were randomized to either a 5.00-mm or a 6.00-mm treatment group and within these groups underwent either a −3.00-diopter (D) ora −6.00-D correction based on their preoperative refraction. A Summit Omnimed excimer laser was used throughout the study. Results: In eyes treated with a 6.00-mm-diameter ablation, the initial hyperopic shift was reduced, with significant differences at 1 week with −3.00-D corrections and at 1 and 4 weeks with −6.00-D corrections (P Conclusions: Treatment with 6.00-mm ablation diameters precipitated less initial overcorrection, greatly improved the predictability of photorefractive keratectomy, and was associated with a reduction in complications impairing postoperative visual performance.

139 citations


Journal ArticleDOI
TL;DR: London-born black Caribbean children appear to be at an increased risk of having atopic dermatitis, according to a cross-sectional prevalence survey of junior school children in three schools.
Abstract: Background: Previous reports suggest that atopic dermatitis is more common in black Caribbean children born in the United Kingdom than in white children. It is unclear whether these differences are caused by selection bias or variations in the use of the word "eczema" in the groups studied. Objective: Our objective was to explore ethnic group differences in the prevalence of atopic dermatitis in London schoolchildren. Methods: A cross-sectional prevalence survey of 693 junior school children in three schools was performed. Atopic dermatitis was defined in three ways: (1) by a dermatologist, (2) by visible flexural dermatitis as recorded by an independent observer, and (3) by a history of flexural dermatitis according to the child's parents. Results: The prevalence of atopic dermatitis according to examination by a dermatologist was 16.3% in black Caribbean children and 8.7% in white children. This increased risk was present for different methods of defining of atopic dermatitis and persisted after adjustment for potential confounders. Conclusion: London-born black Caribbean children appear to be at an increased risk of having atopic dermatitis.

137 citations


Journal ArticleDOI
TL;DR: Preliminary results from this small sample suggest that E-cadherin expression may be a useful prognostic marker in colorectal cancer patients.
Abstract: A series of colorectal carcinomas (n = 49) resected from patients with known clinical outcomes were analysed for E-cadherin expression using in situ hybridisation to measure mRNA. Patients surviving 5 years or longer (n = 31) exhibited significantly higher levels of E-cadherin mRNA than those surviving less than 5 years (n = 18, P = 0.003). These preliminary results from this small sample suggest that E-cadherin expression may be a useful prognostic marker in colorectal cancer patients.

135 citations


Journal ArticleDOI
TL;DR: Investigation of whether HPV‐16 and ‐18 DNA in infants contaminated at delivery persists until they are 6 months of age found bimodal distribution of IgM seropositivity peaked between 2 and 5 and 13 and 16 years of age, suggesting that two distinct modes of transmission may occur.
Abstract: Perinatal transmission of genital human papillomaviruses (HPVs), including HPV-16 and -18 which are associated with anogenital carcinomas have been described previously [Pakarian et al. (1994): British Journal of Obstetrics and Gynaecology 101:514-517; Kaye et al. (1994) Journal of Medical Virology 44:415-421]. A study was undertaken to investigate whether HPV-16 and -18 DNA in infants contaminated at delivery persists until they are 6 months of age. Of 61 pregnant women recruited, 42 (68.8%) were HPV-16 and 13 (21.3%) were HPV-18 DNA positive. At 24 hr there were transmission rates from HPV DNA positive mothers to their infants of about 73% (HPV-16: 69%; HPV-18: 76.9%). Ten mothers who were both HPV-16 and -18 DNA positive produced six (60%) infants who were also doubly positive at 24 hr. HPV DNA persisted to 6 weeks in 79.5% (HPV-16: 84%; HPV-18: 75%) of those infants who were positive at birth. At 6 months of age, persistent HPV-16 DNA was detected in 83.3% of cases, but HPV-18 DNA persistence at this time was 20%. To extend these observations over a greater age range of children HPV-16 L1 and L2 proteins were expressed in insect cells via recombinant baculoviruses and sera from 229 children were examined to determine at what age IgM antibodies to HPV were acquired. There was a bimodal distribution of IgM seropositivity which peaked between 2 and 5 and 13 and 16 years of age, suggesting that two distinct modes of transmission may occur. The observation that infection with high cancer risk genital HPVs may occur in early life and persist is of considerable importance for HPV vaccine strategies.

Journal ArticleDOI
TL;DR: Findings suggest that truncated trkB may modulate neuronal responses to neurotrophins which act via trkB in adult motor neurons.
Abstract: Localization of mRNA encoding trkB indicates that two truncated isoforms of trkB, T1trkB and T2trkB, are differentially distributed in the rodent nervous system, and that each of these transcripts is co-expressed with catalytic trkB (TK+trkB) in adult motor neurons. In contrast to the prominent expression of T1trkB by non-neuronal cells, T2trkB expression appeared to be restricted to neurons and demonstrated significant overlap with the pattern of TK+trkB distribution. In developing spinal cord ventral horn, an age-related increase in hybridization was observed for truncated isoforms. These findings suggest that truncated trkB may modulate neuronal responses to neurotrophins which act via trkB.

Journal ArticleDOI
TL;DR: There is increased hepatic secretion of VLDL apoB which may partly explain the dyslipoproteinaemia seen in the non-insulin-dependent diabetes mellitus (NIDDM), and it is suggested that increased secretion of this apolipoprotein may be a consequence of resistance to the inhibitory effect of insulin.
Abstract: We measured the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 (VLDL apoB) using a stable isotope gas-chromatography mass-spectrometry method in six patients with non-insulin-dependent diabetes mellitus (NIDDM) (four males, two females, age 57.5±2.2 years (mean±SEM), weight 88.2±5.5 kg, glycated haemoglobin (HbA1) 8.5±0.5%, plasma total cholesterol concentration 5.7±0.5 mmol/l, triglyceride 3.8±0.9 mmol/l, high-density lipoprotein (HDL) cholesterol 1.0±0.1 mmol/l) and six non-diabetic subjects matched for age, sex and weight (four males, two females, age 55.7±2.8 years, weight 85.8±5.6 kg, HbA1 6.5±0.1%, plasma total cholesterol concentration 5.7±0.5 mmol/l, triglyceride 1.2±0.1 mmol/l, HDL cholesterol 1.4±0.1 mmol/l). HbA1, plasma triglyceride and mevalpnic acid (an index of cholesterol synthesis in vivo) concentrations were significantly higher in the diabetic patients than in the non-diabetic subjects (p=0.006, p=0.02 and p=0.004, respectively). VLDL apoB absolute secretion rate was significantly higher in the diabetic patients compared with the non-diabetic subjects (2297±491 vs 921±115 mg/day, p<0.05), but there was no significant difference in the fractional catabolic rate of VLDL apoB. There was a positive correlation between VLDL apoB secretion rate and (i) fasting C-peptide (r=0.84, p=0.04) and (ii) mevalonic acid concentration (r=0.83, p<0.05) in the diabetic patients but not in the non-diabetic subjects. There was also a significant positive association between plasma mevalonic acid and plasma C-peptide (r=0.82, p<0.05) concentrations in the diabetic patients. We conclude that in NIDDM, there is increased hepatic secretion of VLDL apoB which may partly explain the dyslipoproteinaemia seen in this condition. We suggest that increased secretion of this apolipoprotein may be a consequence of resistance to the inhibitory effect of insulin on VLDL apoB secretion. Insulin resistance may also be the mechanism by which cholesterol synthesis, a regulator of apoB secretion, is increased in NIDDM.

Journal ArticleDOI
TL;DR: The results of the present study provide further support for the hypothesis that reading disability may, to some extent, result from dysfunction of the visual and oculomotor systems.
Abstract: Most individuals interested in reading disability favor the view that disordered language processing is the main cause of children's reading problems and that visual problems are seldom, if ever, responsible. Nevertheless, in a preliminary study (Eden, Stein, & Wood, 1993) we showed that visuospatial and oculomotor tests can be used to differentiate children with reading disabilities from nondisabled children. In the present study we investigated a larger sample of children to see if these findings held true. Using 93 children from the Bowman Gray Learning Disability Project (mean age = 11.3 years; 54 boys, 39 girls), we compared the phonological and visuospatial abilities of nondisabled children (children whose reading at fifth grade rated a Woodcock-Johnson reading standardized score between 85 and 115), and children with reading disability (whose reading standardized score was below 85 on the Woodcock-Johnson). In addition to performing poorly on verbal tests, the children with reading disability were ...

Journal ArticleDOI
TL;DR: There is still great scope (and need) for the development of new, improved retroviral vectors and packaging systems to fuel further advances in the field of human gene therapy.
Abstract: Recombinant retroviruses have long been used to deliver heterologous genes to mammalian cells. Convenient packaging cell lines and vector plasmids have been distributed widely and 'home-made' retroviral vectors have now become a useful research tool in many laboratories. Compared to more traditional methods of gene transfer, retroviral vectors are extraordinarily efficient gene delivery vehicles which cause no detectable harm as they enter their target cells. In the nucleus the retroviral necleic acid becomes integrated into chromosomal DNA, ensuring its long-term persistence and stable transmission to all future progeny of the transduced cell. Up to 8 kilobases of foreign gene sequence can be packaged in a retroviral vector and this is more than enough for most gene therapy applications. Retroviral vectors can also be manufactured in large quantities to meet very stringent safety specifications. They have therefore been selected as the vectors of choice in 80% of the clinical gene therapy trials that have been approved to date. So far there have been no reported short- or long-term toxicity problems associated with their use in human gene therapy trials, now dating back to 1989. However, despite this impressive record, there is still great scope (and need) for the development of new, improved retroviral vectors and packaging systems to fuel further advances in the field of human gene therapy. In the following discussion, existing retroviral vectors are reviewed and current areas of technological development are emphasised.

Journal ArticleDOI
TL;DR: It is believed that careful monitoring and management of the lupus pregnancy has substantially improved the fetal outcome.


Journal ArticleDOI
TL;DR: Corrosion is continually changing the shape, size and chemical composition of the implanted alloy, which may alter the biochemical environment of the tissue surrounding an implant to favour bone resorption.
Abstract: Tissue reaction to wear particles from metal implants may play a major role in the aseptic loosening of implants. We used electron microprobe elemental analysis to determine the chemical composition of wear particles embedded in the soft tissues around hip and knee implants from 11 patients at revision surgery for aseptic loosening. The implants were made of cobalt-chromium-molybdenum alloy or titanium-aluminium-vanadium alloy. Histological examination showed a widespread giant-cell reaction to the particles. Elemental analysis showed that the chemical composition of the particles was different from that of the implanted alloys: cobalt and titanium were reduced, often down to zero, whereas chromium and aluminium persisted. Our findings indicate that corrosion is continually changing the shape, size and chemical composition of the implanted alloy. This may alter the biochemical environment of the tissue surrounding an implant to favour bone resorption.

Journal ArticleDOI
TL;DR: In this paper, the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy remains obscure and the placoid lesions and characteristic findings on fluorescein angiography have been interpreted as representing either primary disease or disease of the Choroidal vasculature.

Journal ArticleDOI
TL;DR: The biphasic morphologic pattern and tumor immunophenotype are discussed in relation to increasing evidence of immunophenotypic and morphologic heterogeneity of normal follicular dendritic cells.
Abstract: Tumors showing differentiation toward follicular dendritic cells are rare and usually occur in lymph nodes. Their occurrence at extranodal sites was recognized recently. This report documents two further extranodal cases, one arising in the small intestine of a 23-year-old woman and the second in periduodenal retroperitoneal soft tissue of a 63-year-old man. Both neoplasms displayed a typical biphasic morphologic pattern, composed of large cells with indistinct cytoplasmic borders creating a syncytial appearance, admixed with spindle cell areas resembling malignant fibrous histiocytoma, and infiltrated by numerous small T lymphocytes. Expression of CD21 and CD35, together with ultrastructural demonstration (in one case) of long cytoplasmic processes connected by desmosomes, confirmed follicular dendritic cell differentiation. One case also expressed HLA-DR, and both showed aberrant epithelial membrane antigen staining. Neither tumor showed CD45 expression. In both cases the tumors were treated by local excision. Case 1 has shown an unusually aggressive course with extensive intraperitoneal recurrence. The biphasic morphologic pattern and tumor immunophenotype are discussed in relation to increasing evidence of immunophenotypic and morphologic heterogeneity of normal follicular dendritic cells.

Journal ArticleDOI
TL;DR: Bone formation appears to be reduced, partly reflecting disease activity, whereas resorption is increased only in steroid users, and bone metabolism may be uncoupled in chronic RA.
Abstract: Objective. To investigate bone metabolism in postmenopausal women with rheumatoid arthritis (RA) treated with or not treated with corticosteroids, and the response to hormone replacement therapy (HRT). Methods. One hundred six RA patients were divided into those taking low-dose steroids (RA+; n = 35) and those not (RA–; n = 71) and randomly allocated to receive HRT or calcium for 2 years. Bone formation markers included serum osteocalcin (OC) and bone-specific alkaline phosphatase, and resorption markers included urinary deoxypyridinoline (DPyr) and CrossLaps (XL). Bone mineral density (BMD) was measured annually using dual x-ray absorptiometry. Results. OC levels were significantly lower in both the RA+ and RA– groups compared with 112 healthy control subjects (P < 0.01 and P < 0.05, respectively), but were similar in the 2 RA groups. DPyr and XL levels were elevated in the RA+ group compared with the RA– group (P < 0.05) but were similar between the RA– group and controls. OC was negatively correlated with parameters of disease activity (P < 0.05). After HRT, XL excretion decreased significantly in the overall RA group. Three-month changes in XL correlated with 2-year changes in spinal BMD (P < 0.01). Conclusion. Bone metabolism may be uncoupled in chronic RA. Bone formation appears to be reduced, partly reflecting disease activity, whereas resorption increased only in steroid users. HRT reduces resorption in RA irrespective of steroid usage, emphasizing its value in the treatment of postmenopausal women with RA.

Journal ArticleDOI
TL;DR: It is concluded that isolation of lymphocytes by density gradient centrifugation and of granulocytes and monocytes by dextran-sedimentation and centrifuge using Histopaque gradients, but avoiding washing and the use of hypotonic erythrocyte lysis, are appropriate techniques for studying the expression and function of adhesion molecules.

Journal ArticleDOI
TL;DR: Nerve growth factor ameliorates some of the changes seen in sensory neurones in animal models of diabetic neuropathy and small fibre cytostatic drug neuropathy, whereas neurotrophin-3 has been found to reverse some changes in large sensory neurone associated with cisplatin neurotoxicity.

Book ChapterDOI
TL;DR: A number of compounds of widely differing chemical structure have been developed in an attempt to alter the open probability of what has become known as the adenosine triphosphate-sensitive potassium channel (KATP channel).
Abstract: A number of compounds of widely differing chemical structure have been developed in an attempt to alter the open probability of what has become known as the adenosine triphosphate-sensitive potassium channel (KATP channel). They include channel openers (such as pinacidil, aprikalim, nicorandil, bimakalim, cromakalim and its active enantiomer levcromakalim) and channel blockers such as glibenclamide, tolbutamide and 5-hydroxydecanoate. They all are able to override the actions of an array of biochemical regulators of channel activity including ATP (an inhibitor of channel opening), adenosine diphosphate, adenosine, fatty acids, lactate, pyruvate and pH (for detailed reviews on the nature of the KATP channel and its biological and pharmacological control see (1–6)

Journal ArticleDOI
TL;DR: It is confirmed that patients with CF are susceptible to oxidative-induced DNA damage, although this appears to be independent of clinical status.

Journal ArticleDOI
TL;DR: It is affirm that PUVA is generally not an effective treatment for alopecia areata.
Abstract: Our 10-year experience with PUVA treatment for alopecia areata, partialis, totalis and universalis was retrospectively reviewed using charts and follow-up questionnaires for 70 patients at St John's Institute of Dermatology. In all cases, several previous therapies were judged to be unsatisfactory prior to starting PUVA, and many cases were already deemed clinically refractory prior to referral for PUVA. If cases of vellus hair growth are excluded, and those who lost their PUVA-induced regrowth rapidly on follow-up, the effective success rate was at best 6.3% for alopecia areata partialis, 12.5% for alopecia areata totalis and 13.3% for alopecia areata universalis. We affirm that PUVA is generally not an effective treatment for alopecia areata.

Journal ArticleDOI
TL;DR: Radiological site-specific definition of the disease is now recognized as the major tool available in defining OA, and there is general consensus that the grading of osteophytes and joint space narrowing at the major sites using validated atlases is an important step forward.
Abstract: Osteoarthritis is the commonest rheumatic disease, but despite its high prevalence in the elderly, associated disability and public health costs, there is little understanding of the aetiology of the disease. Questions still remain unanswered: 'what do we mean by the term osteoarthritis?; how do we define it?; how do we classify patients with the disease?; how do we differentiate between cases for population studies, and clinically relevant disease the physician wishes to treat?'. This chapter has demonstrated the considerable advances that have been made over the last thirty years in solving these issues, but we are still lacking a universal definition and classification of the disease. Defining and classifying OA is not an easy task, as it is not a single disease, but rather a spectrum of diseases that are the end result of a number of different processes. However, in order to understand the aetiology and natural course of the disease, and to devise appropriate treatment strategies, correct definition of OA at distinct sites is vital. Radiological site-specific definition of the disease is now recognized as the major tool available in defining OA. There is general consensus that the grading of osteophytes and joint space narrowing at the major sites using validated atlases is an important step forward.

Journal ArticleDOI
01 Jul 1995-Gut
TL;DR: Findings suggest that the histological changes seen previously in the mucosa of coeliac patients after wheat peptide challenge may be caused by increased expression of cytokines within the mucosal.
Abstract: This study investigated the presence of mRNA coding for interferon gamma (IFN gamma), tumour necrosis factor alpha (TNF alpha), and interleukins 2 (IL2) and 6 (IL6), in the mucosa of four coeliac patients in remission who had been challenged with either gliadin or synthetic gliadin oligopeptides. Jejunal biopsy specimens from these patients, taken before and at two, four, and six hours after challenge, were hybridised with specific 35S-labelled DNA oligonucleotide probes. The lamina propria of all the patients contained significantly increased numbers of cytokine mRNA expressing cells four hours after challenge with gliadin or an oligopeptide corresponding to amino acids 31-49 of A-gliadin (peptide A). No significant changes were seen with the peptides corresponding to aminoacids 202-220 (peptide B) or 3-21 (peptide C) of A-gliadin, with the exception of one patient who showed a significant increase in the number of TNF alpha mRNA expressing cells four hours after challenge with peptide B. In vivo studies in coeliac disease have shown that significant histological changes occur in the mucosa of treated coeliac patients four hours after challenge with either gliadin or peptide A. These findings suggest that the histological changes seen previously in the mucosa of coeliac patients after wheat peptide challenge may be caused by increased expression of cytokines within the mucosa.

Journal ArticleDOI
TL;DR: In this article, the incidence of malignancies in recipients of renal transplants was compared to that in nongrafted patients on maintenance dialysis as reported to the EDTA-ERA Registry and in the general population as recorded by the cancer registries of England and Wales, of Sweden, of the (former) German Democratic Republic, and of Lombardy and Varese in Northern Italy.
Abstract: The incidence of malignancies in recipients of renal transplants was compared to that in nongrafted patients on maintenance dialysis as reported to the EDTA-ERA Registry and in the general population as recorded by the cancer registries of England and Wales, of Sweden, of the (former) German Democratic Republic, and of Lombardy and Varese in Northern Italy. For tumours known to be associated with immunosuppression, namely Kaposi's sarcoma, non-Hodgkin lymphoma and the common malignancies of the skin (except melanoma), an increased incidence was confirmed for the transplanted population. Thyroid carcinoma and hepatoma were found to be more frequent in non-grafted patients on dialysis as well as after renal transplantation. An increased incidence of cancer of the cervix and of the body of the uterus was recorded only for young cohorts with a functioning graft but not for women after menopause. Most of the other malignancies had similar incidences in grafted and non-grafted populations which did not differ from those in the general populations of the cancer registries except cancer of the colon which was slightly more frequent, particularly at 10-20 years after the first transplant operation. Survival after diagnosis of cancer at the most frequent sites, such as bronchopulmonary, breast, oesophagogastric and colorectal cancer, did not differ between non-grafted patient groups on dialysis and those who developed the tumour while carrying a functioning renal transplant. Although certain specific malignancies such as non-Hodgkin lymphoma and skin tumours occur more frequently in recipients of renal grafts, the risk of developing cancer has been exaggerated and survival after diagnosis of the common cancers does not appear to be affected to any great extent by immunosuppressive therapy

Journal ArticleDOI
TL;DR: The results demonstrate that the first phase of the hypoxic constriction is associated with a transient rise in [Ca2+]i via either Ca2+ influx and/or release, and may have a PKC-dependent component, whereas the second phase involves aPKC-independent sensitization of the contractile machinery to Ca2+.
Abstract: The effect of hypoxia on intracellular Ca2+ ([Ca2+]i) and tension in small intrapulmonary arteries (IPA) of the rat was examined using the Ca2+ fluorophore fura 2. Induction of hypoxia in IPA preconstricted with 3 microM prostaglandin F2 alpha (PGF2 alpha) resulted in a biphasic contractile response, the first phase of which was associated with a transient rise in [Ca2+]i. No additional rise in [Ca2+]i was observed during the more slowly developing second phase constriction. Upon reoxygenation [Ca2+]i and tension returned to prehypoxic levels. Ro-31-8220 [a specific protein kinase C (PKC) inhibitor] reduced the first phase in IPA preconstricted with PGF2 alpha or 20 mM KCl, but had no effect on the second phase constriction in either of these groups. These results demonstrate that the first phase of the hypoxic constriction is associated with a transient rise in [Ca2+]i via either Ca2+ influx and/or release, and may have a PKC-dependent component, whereas the second phase involves a PKC-independent sensitization of the contractile machinery to Ca2+.