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Biomedical subjects

J Morgan

Publications and source records attributed to J Morgan.

At least 37 records · Page 2Linked to original sources
PubMed2004

Expression of the peripheral benzodiazepine receptor is decreased in skin cancers in comparison with normal skin.

BACKGROUND: The peripheral benzodiazepine receptor (PBR) is an 18-kDa protein receptor mainly found on the outer mitochondrial membrane of cells. The PBR plays a role in several cellular functions including haem synthesis, steroidogenesis, DNA synthesis, cell growth and differentiation, and apoptosis. PBR expression in normal skin correlates with proliferating, secretory and differentiated cellular structures. Increased or aberrant expression of PBR has been associated with aggressive behaviour in several tumour types including ovarian, colon and breast adenocarcinomas and glioblastoma. OBJECTIVES: To determine whether changes in normal PBR distribution would be useful as markers for skin cancers or possible target sites for therapies such as photodynamic therapy (PDT), we used immunohistochemistry to evaluate PBR expression and distribution in normal and photodamaged skin (actinic keratoses), skin cancers (in situ and invasive squamous cell carcinomas and superficial, nodular, morphoeiform and mixed pattern basal cell carcinomas) and several benign epithelial proliferations. METHODS: A rabbit polyclonal antibody to a synthetic peptide fragment of the PBR was developed and characterized by enzyme-linked immunosorbent assay and Western blot analysis. The antibody was used to stain formalin-fixed and paraffin-embedded tissue samples (n = 157) by a routine avidin-biotin immunohistochemical technique. Sections were evaluated for antibody localization, distribution (0-4+) and reaction intensity (negative to strong). RESULTS: Normal skin stained with a strong homogeneous positive reaction (3-4+) in the spinous and granular layers (with a gradient corresponding to increasing differentiation), the pilosebaceous units, eccrine gland ducts, endothelial cells and pilar muscle. In cutaneous neoplasms and other skin diseases, a heterogeneous pattern (0-4+) of PBR expression at lower intensity was seen depending on tumour type and degree of differentiation. PBR expression was greatest in well-differentiated tumours, synonymous with the PBR expression gradient seen in normal skin; and least in poorly differentiated and infiltrative tumour types. CONCLUSIONS: The haem biosynthetic pathway has been harnessed for PDT of skin carcinomas by application of exogenous aminolaevulinic acid to generate the endogenous photosensitizer protoporphyrin IX (PpIX). Owing to the role of PBR as a transporter of haem precursors in haem synthesis, PBR density and distribution in skin cancers could be a predictor of the capacity for PpIX production and subsequent response to PDT in skin cancers.

Biomarkers, Tumor↗
PubMed2004

Pilot study of dermal and subcutaneous fat structures by MRI in individuals who differ in gender, BMI, and cellulite grading.

BACKGROUND/AIMS: Puckered, dimply skin on the thighs, hips, and buttocks is known as cellulite. The cause of cellulite is not known, although there are a number of different hypotheses. In this study, we use magnetic resonance (MR) micro-imaging to study cellulite skin. To the best of our knowledge, this is the first reported MR study of cellulite. METHODS: High-resolution in vivo MR images of the postlateral thigh skin of two male groups and four female groups were obtained. Subjects were grouped according to their body mass index (BMI) and cellulite grade. A qualitative assessment of how MRI can be used to differentiate skin tissue at different levels of cellulite grading was performed. RESULTS: We found that changes in skin architecture with cellulite can be visualized by in vivo MR micro-imaging. The skin fat layers beneath the dermis and down to the level of muscles are well visualized in the images. Also, the diffuse pattern of extrusion of underlying adipose tissue into dermis is clearly imaged, and was found to correlate with cellulite grading. We also show that other skin tissue parameters such as (a) the percentile of adipose vs. connective tissue in a given volume of hypodermis and (b) the percentile of hypodermic invaginations inside the dermis are correlated with cellulite grade. CONCLUSION: MR images can be interpreted to measure tissue parameters correlated with cellulite. Considering that we had only three subjects in each group, the achievements of this pilot study were highly satisfactory. We have shown that the in vivo micro-MR is a technique able to detect the effects of cellulite and gender. This study can be extended for further investigations of drugs and/or medical devices for cellulite treatment.

Adipose Tissue↗
PubMed2004

Eczema and early solid feeding in preterm infants.

AIMS: To establish whether development of eczema is influenced by feeding practices in preterm infants, while taking account of confounding factors. METHODS: Data were assembled from 257 infants born prematurely and studied to 12 months post-term. Logistic regression analysis was performed to establish the association between feeding practices and eczema, allowing for potential confounding factors including the infants' gender, parental atopic status, social background, and parental smoking habits. RESULTS: For the development of eczema (with or without other symptoms) by 12 months post-term, the introduction of four or more solid foods by or before 17 weeks post-term was a significant risk (odds ratio 3.49). Male infants were at significantly higher risk (odds ratio 1.84). In addition, having non-atopic parents who introduced solid foods before 10 weeks post-term or having at least one atopic parent represented a significant risk scenario (odds ratio 2.94). CONCLUSIONS: Early introduction of a diverse range of solid foods may predispose the preterm infant to eczema development by 12 months post-term. Furthermore, non-atopic parents who practice early as opposed to late introduction of solid foods may be exposing preterm infants to a greater risk of eczema by 12 months post-term.

Adolescent↗
PubMed2003

Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms.

BACKGROUND: Mutations in SCN1A, the gene encoding the alpha1 subunit of the sodium channel, have been found in severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). Mutations in SMEI include missense, nonsense, and frameshift mutations more commonly arising de novo in affected patients. This finding is difficult to reconcile with the family history of GEFS+ in a significant proportion of patients with SMEI. Infantile spasms (IS), or West syndrome, is a severe epileptic encephalopathy that is usually symptomatic. In some cases, no etiology is found and there is a family history of epilepsy. METHOD: The authors screened SCN1A in 24 patients with SMEI and 23 with IS. RESULTS: Mutations were found in 8 of 24 (33%) SMEI patients, a frequency much lower than initial reports from Europe and Japan. One mutation near the carboxy terminus was identified in an IS patient. A family history of seizures was found in 17 of 24 patients with SMEI. CONCLUSIONS: The rate of SCN1A mutations in this cohort of SMEI patients suggests that other factors may be important in SMEI. Less severe mutations associated with GEFS+ could interact with other loci to cause SMEI in cases with a family history of GEFS+. This study extends the phenotypic heterogeneity of mutations in SCN1A to include IS.

Amino Acid Sequence↗
PubMed2003

The measurement and comparison of jet characteristics of surgical pulse lavage devices.

The characteristics of pulse waveform, pulse duration, pulse frequency, impact force/pressure, and flow rate of 4 commercially available pulse lavage devices are measured and compared. Validation of the measurements obtained is provided by a laboratory system that generates and measures precise jet waveforms. However, the value of the devices studied awaits clinical trials.

Equipment Design↗
PubMed2003

Investigation of the role of CD8+ T cells in bovine tuberculosis in vivo.

Mycobacterium bovis is the causative agent of bovine tuberculosis (TB), and it has the potential to induce disease in humans. CD8(+) T cells (CD8 cells) have been shown to respond to mycobacterial antigens in humans, cattle, and mice. In mice, CD8 cells have been shown to play a role in protection against mycobacterial infection. To determine the role of CD8 cells in bovine TB in vivo, two groups of calves were infected with the virulent M. bovis strain AF2122/97. After infection, one group was injected with a CD8 cell-depleting monoclonal antibody (MAb), and the other group was injected with an isotype control MAb. Immune responses to mycobacterial antigens were measured weekly in vitro. After 8 weeks, the animals were killed, and postmortem examinations were carried out. In vitro proliferation responses were similar in both calf groups, but in vitro gamma interferon (IFN-gamma) production in 24-h whole-blood cultures was significantly higher in control cattle than in CD8 cell-depleted calves. Postmortem examination showed that calves in both groups had developed comparable TB lesions in the lower respiratory tract and associated lymph nodes. Head lymph node lesion scores, on the other hand, were higher in control calves than in CD8 cell-depleted calves. Furthermore, there was significant correlation between the level of IFN-gamma and the head lymph node lesion score. These experiments indicate that CD8 cells play a role in the immune response to M. bovis in cattle by contributing to the IFN-gamma response. However, CD8 cells may also play a deleterious role by contributing to the immunopathology of bovine TB.

Animals↗
PubMed2002

The role of CD55 in protecting the tumour environment from complement attack.

CD55 is a complement regulatory protein expressed by cells to protect them from bystander killing by complement. CD55 is over-expressed 2-100-fold on tumour cells and is deposited in large amounts within tumour matrix. Vascular endothelial growth factor (VEGF) produced by tumours to stimulate angiogenesis, also up-regulates endothelial cell surface expression of CD55 and stimulates the release of matrix degrading metalloproteinases. This study investigated the effects of VEGF on CD55 deposition into matrix and the release of CD55 by metalloproteinases. In contrast to inflammatory cytokines, CD55 was up-regulated by VEGF at the cell surface and within the extracellular matrix (ECM). Interestingly, human umbilical vein endothelial cells (HUVEC) exposed to VEGF released similar amounts of CD55 into the ECM as a tumour cell line expressing 50-fold higher level of CD55 on its cell surface. Furthermore, in contrast to earlier studies, both tumour and HUVEC-derived CD55 was functionally active. However, in contrast to papain that degrades CD55, and collagenase that fails to release CD55, MMP-7 released intact CD55 from ECM. This suggests that it may have a further role to play in protecting cells during inflammation and invasion.

CD55 Antigens↗
PubMed2002

Association of British Clinical Diabetologists (ABCD): survey of specialist diabetes care services in the UK, 2000. 3. Podiatry services and related foot care issues.

AIM: To examine the provision of, and variations in, podiatry and other services for diabetic foot care in the UK. METHOD: A postal survey of secondary care providers of diabetes services in the UK in 2000. RESULTS: Following two reminders a 77% response rate was achieved. The responses indicated that 97% had a state-registered podiatrist attached to the service, providing three (median) sessions each week for diabetes care, although only 44% had availability at all diabetic clinics, and only 3% had availability at paediatric diabetic services. Podiatry access at all diabetic clinics increased the likelihood of associated preventative as opposed to reactive ('trouble shooting') care (P < 0.05). All individuals with feet at 'high risk' of ulceration had access to 'at least 2 monthly review' in 15% of trusts, and with active foot ulceration at least weekly in 43%. Over 70% used at least one form of equipment to assess peripheral neuropathy, but peripheral blood flow was only formally measured in 13%. Although podiatry input to patient education was common (84%), only 6% had received formal training in education. Guidelines and strategies for management of active foot problems were available in 50-74% of cases. Orthotic input was highly variable, and absent in 15% of responses. Podiatrist fitting and application of foot protective apparatus was only recorded in 22-61% of responses. Access to isotopic and/or MR foot imaging and peripheral angiography and angioplasty was recorded in 75-83% of responses. Separate specialist foot clinics were available in 49%, and where this was the case the use of newer foot ulcer healing applications was higher (P < 0.01). Clear regional differences were apparent in the nature of the service, the use of newer treatments, and in access to an orthotist, a local 'dedicated' foot surgeon or a separate diabetic foot clinic. Of 245 documented bids for service improvements, only 19 related to foot care and only 21% of bids were successful. CONCLUSIONS: Despite an increase in podiatry support to diabetes care over the last 10 years, the level of access and the nature of the services provided is much less than recommended in many advisory documents. The strategy of a co-ordinated 'team' approach to foot care still takes place in less than 50% of centres. There are clear regional differences in diabetes foot care services. Both providers and purchasers of diabetes services may not have given sufficient attention to this area, given the relatively small number of documented bids for service improvements in this area, and the very low success rate of such bids.

Diabetes Mellitus↗
PubMed2002

Costs of aspirin and statins in general practice.

BACKGROUND: Aspirin and statins are the two drugs most commonly indicated for secondary prevention of atherosclerotic disease in the UK. Statin treatment, which is more expensive, is under-prescribed. AIM: To assess the expenditure in Greater Manchester general practices on aspirin and statins. DESIGN: Survey of general practice records. METHODS: Practice registers were searched for patients receiving regular prescriptions for aspirin. For each patient, the next patient of the same sex, aged within +/- 5 years, not on aspirin, acted as a control. Details of all medications were recorded. In a sub-study, records of 100 patients on aspirin were studied to determine indications for aspirin prescription. RESULTS: There were 1003 (511 men, 492 women) in each group; mean age was 70 years in both groups. In the sub-study, 79% of patients received aspirin for established vascular disease, 9% for hypertension, 5% for diabetes mellitus, 5% for unknown reasons and 2% for arthritis. Of the patients on aspirin, 67% received dispersible aspirin 75 mg/day. The rest were on higher doses (10%) or on more expensive preparations (22%), costing up to 22.4 p/day. The mean daily cost of aspirin was 1.7p. Dyspepsia treatment was received by 266 patients and 194 controls (p<0.001). There was a wide range of dyspepsia medications (10-306p/day), averaging in the groups as a whole 15.5p/day in patients and 12.5p/day in controls. Of the patients on aspirin, 28% received statins, compared to 4% of controls. Mean daily expenditure on statins in patients was 23.4p. CONCLUSION: Assuming the difference in the use of medication for dyspepsia between patients and controls was due to aspirin, the full cost of aspirin treatment was 4.7p/day. Statins were probably under-prescribed in aspirin-takers, many of whom would have been at high CHD risk.

Aged↗
PubMed2002

Vitreoretinopathy with phalangeal epiphyseal dysplasia, a type II collagenopathy resulting from a novel mutation in the C-propeptide region of the molecule.

A large family with dominantly inherited rhegmatogenous retinal detachment, premature arthropathy, and development of phalangeal epiphyseal dysplasia, resulting in brachydactyly was linked to COL2A1, the gene encoding proalpha1(II) collagen. Mutational analysis of the gene by exon sequencing identified a novel mutation in the C-propeptide region of the molecule. The glycine to aspartic acid change occurred in a region that is highly conserved in all fibrillar collagen molecules. The resulting phenotype does not fit easily into pre-existing subgroups of the type II collagenopathies, which includes spondyloepiphyseal dysplasia, and the Kniest, Strudwick, and Stickler dysplasias.

Adult↗
PubMed2002

SALL1 expression in the human pituitary-adrenal/gonadal axis.

SALL1 was originally identified on the basis of its DNA sequence homology to the region-specific homeotic gene Sal, in Drosophila melanogaster, which acts as a downstream target of hedgehog/tumor growth factor-beta-like decapentaplegic signals. The SALL1 gene has been associated with the Townes-Brocks Syndrome (TBS), a disorder characterized by multiorgan dysgenesis including renal and genital malformations. In this study, SALL1 message production was evaluated in association with the tissue localization of the protein product of SALL1, p140. SALL1 protein expression was observed in various adult and fetal tissues which elaborate reproductive endocrine hormones. The p140 was localized in specific microanatomic sites of the pituitary, adrenal cortex and the placenta. In the human pituitary, SALL1 protein expression was limited to the adenohypophysis, where it colocalized to those cells producing GH and the gonadotropins, LH and FSH. SALL1 expression was also found in most of the fetal and adult adrenal cortex in addition to the trophoblastic cells of the placenta. This pattern of expression complements prior studies demonstrating p140 in testicular fetal Leydig cells, adult Leydig and Sertoli cells, and granulosa cells of the ovary. The SALL1 protein was also shown here to be highly expressed in trophoblast tumors, which overproduce sex hormones. The expression patterns of SALL1 at multiple levels of the reproductive endocrine axis and the phenotypic effects associated with TBS suggest that SALL1 may have an important role in the interaction of the pituitary-adrenal/gonadal axis during reproduction.

Adrenal Glands↗
PubMed2001

Impaired cardiac functional reserve and left ventricular hypertrophy in adult sheep after prenatal dexamethasone exposure.

We have shown that exposure of pregnant ewes to dexamethasone (11.5 mg/d for 2 days) at 27 days of gestation (term, 150 days) led to increased blood pressure and cardiac output in adult offspring. In this study, we hypothesized that dexamethasone-induced hypertension is associated with left ventricular hypertrophy and a reduced cardiac functional reserve (CO(max-0)). Six control animals (group C) and five dexamethasone-exposed animals (group D) were volume-loaded with Hemaccel until the wedge pressure was 13 mm Hg (baseline). The wedge pressure was held constant during an infusion of dobutamine at incremental doses (0.4 to 12 microgram/kg/min) while blood pressure and cardiac output were measured. The same protocol was repeated in each animal 5 days later under mild general anesthesia (1.5% isoflurane), when transthoracic echocardiography (M-mode) was obtained. Group D showed a reduced CO(max-0) in response to dobutamine during both conscious (89+/-22 versus 150+/-25 mL/kg/min in control; P<0.01) and anesthetized states (91+/-38 versus 156+/-56 mL/kg/min in control; P<0.05). Reduced CO(max-0) in group D was associated with higher left ventricular mass index compared with group C (2.6+/-0.67 versus 1.8+/-0.51 g/kg; P<0.05). In addition, group D showed a reduced cardiac contractility reserve (FS(max-0)) in response to dobutamine (21+/-22% versus 54+/-34% in group C; P<0.05). An impaired cardiac functional reserve in group D was associated with increased left ventricular type I collagen content. In conclusion, brief prenatal exposure to dexamethasone led to the development of hypertension, left ventricular hypertrophy, and reduced cardiac functional reserve in adult life.

Animals↗
PubMed2001

Cloning and characterization of two promoters for the human HSAL2 gene and their transcriptional repression by the Wilms tumor suppressor gene product.

HSAL2 is a member of a gene family that encodes a group of putative developmental transcription factors. The HSAL gene complex was originally identified on the basis of DNA sequence homology to a region-specific homeotic gene (SAL) in Drosophila. This study reveals a novel, functional 5' exon for HSAL2 and demonstrates that two distinct HSAL2 gene transcripts arise from two overlapping transcription units, resulting in proteins that differ by 25 amino acids. By utilizing functional luciferase reporter assays, two distinct promoters for HSAL2, P1 for the proximal promoter (upstream of exon 1) and P2 for the distal promoter (upstream of exon 1A), were identified. Evaluation of mRNA prevalence and tissue specificity, with particular focus on adult tissues, revealed that production of mRNA from P1 was selective and relatively rare. Production of mRNA from P2 was demonstrably higher and was expressed by a greater number of tissues. In contradistinction, HSAL2 expression directed by P2 was undetectable in some malignant populations as opposed to their normal human counterparts, suggesting a potential role as a tumor suppressor gene. Consensus-binding sites were identified for several transcriptional factors, with multiple sites for WT-1, and Hox-1.3 present within both the P1 and P2 regions. In transient transfection assays, transcription from both HSAL2 P1 and P2 was strikingly repressed by the WT-1 tumor suppressor protein. These findings suggest that an intracellular WT-1/HSAL2 pathway may play a role in development and hematopoiesis.

Amino Acid Sequence↗