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Biomedical subjects

J Morris

Publications and source records attributed to J Morris.

At least 253 records · Page 14Linked to original sources

Dexamethasone-mediated induction of MMTV-myf5 in DD3 myoblasts increases endogenous myogenin expression but does not transactivate myf5.

DD3 cells are a myoblast line generated by stable transfection of C3H10T1/2 fibroblasts with the bovine myf5 cDNA (bmyf) fused to the dexamethasone-inducible MMTV promoter. After treating proliferating cells with dexamethasone, bmyf transcripts were induced approximately fivefold within 1.5-2.5 h. Induction of bmyf was followed 4 h later by a similar increase in myogenin transcripts which was dependent on protein synthesis. The elevated level of myogenin transcripts in dividing cells was comparable to that observed in DD3 myoblasts after differentiation. The 4-h lag before the myogenin response suggested involvement of an intermediate factor. However, one possible factor, myocyte-specific enhancer binding factor (MEF-2) (a known enhancer of myogenin promoter activity) was neither detectable nor inducible by dexamethasone in proliferating cells. myoD transcripts were barely detectable and uninducible in proliferating cells but strongly upregulated during differentiation. There was also a transient twofold increase in mrf4 transcripts by dexamethasone treatment in dividing cells, while no changes were detected in the levels of Id, E12, or TnC messages. The mouse myf5 gene was silent and uninducible in DD3 cells under proliferating and differentiating conditions. We conclude that ectopic expression of MMTV-bmyf led to activation of three of the endogenous myogenic factor genes of which only myogenin showed a rapid and sustained response to dexamethasone-mediated induction of bmyf in dividing cells.

Animals↗

Nucleotide sequence analysis and potential environmental distribution of a ferric pseudobactin receptor gene of Pseudomonas sp. strain M114.

The nucleotide sequence of the Pseudomonas sp. strain M114 pbuA gene, encoding the outer membrane receptor for ferric pseudobactin M114, has been determined. The region sequenced spans 2788 bases of plasmid pCUP3, within which the receptor gene had previously been localised. A single open reading frame, potentially encoding 826 amino acids and including a leader peptide of 44 amino acids, is evident and is followed by an inverted repeat segment, which may act as a transcriptional terminator. A 20 bp region of DNA, having significant homology with the E. coli Fur-binding consensus sequence, is located upstream of the open reading frame. PbuA displays characteristics in common with other outer membrane proteins and displays strong homology with the TonB boxes of both E. coli and Pseudomonas receptors. More extensive homologies were found with the PupA receptor of P. putida WCS358 and the FhuE and BtuB receptors of E. coli. It is suggested that areas exhibiting the least homology between these receptors may represent ferric siderophore-specific recognition sites of the PbuA protein. The deduced amino acid sequence of pbuA was compared with that of pupX, encoding the outer membrane receptor for ferric pseudobactin B10, of Pseudomonas sp. strain B 10. A direct alignment of the two proteins gave an identity score of 92.5%. The distribution of PbuA-like receptors among Pseudomonas isolates was investigated by DNA-DNA hybridisation analysis. The results suggest that a PbuA-like receptor may be widely distributed among Pseudomonas rhizosphere isolates.

Amino Acid Sequence↗

An analysis of the corrosion process of the Nova-T IUD.

OBJECTIVE: To measure the copper from Nova-T IUDs that have been used for up to 9 years. To examine the composition and extent of surface deposits on these used IUDs. DESIGN: Nova-T IUDs were randomly collected at normal replacement or removal. The copper, silver and calcium content was quantified by X-ray fluorescence; surface topography and analysis was by scanning electron microscopy and X-ray dispersive analysis. RESULTS: Copper loss slowly increased at an exponential rate over the study period but the copper was stabilized by the silver core and did not show increased fragmentation with extended use. No corrosion of the silver core was detected. Calcium- and sulfur-containing surface deposits built up on the copper but did not modify the rate of copper release. CONCLUSIONS: The mean rate of copper loss was 0.25 mumol/day during the first 40 months of use, which is not significantly different from that of similar IUDs without a silver core. The silver core of the copper coil on the Nova-T IUD prevented its fragmentation. Surface deposits containing calcium and sulfur that built up on the IUD did not affect the rate of copper loss.

Calcium↗

Sedation with midazolam during regional anaesthesia: is there a role for flumazenil?

The aim of this study was to reassess the efficacy of flumazenil for reversal of sedation with midazolam. Twenty-four ASA I or II patients undergoing elective surgery under epidural anaesthesia participated. Following epidural block, midazolam was administered to keep the patient sleepy but still responsive to verbal commands. At the end of surgery the patients were randomly allocated to receive, in a double-blind manner, either flumazenil (0.1 mg.ml-1) or placebo. The study drug (maximum dose: 10 ml) was titrated until the patient became fully awake. Sedation was assessed with the Modified Steward Coma Scale (MSCS), the Trieger test (TT) and Critical Flicker Frequency (CFF). The assessments were done before anaesthesia (baseline), at the end of surgery immediately before administration of study drug, and serially afterwards, at 10, 30, 60, 90, 120, 150 and 180 min. Analyses of variance for repeated measures and pooled t tests were used. The duration of surgery was (mean +/- SD) 0.72 +/- 0.25 hr in the flumazenil group and 0.74 +/- 0.28 hr in the placebo group. The total dose of midazolam was 7.2 +/- 2.2 mg for the flumazenil group and 8.9 +/- 2.7 mg for the placebo group. The volume of study drug administered was 5.5 ml +/- 1.9, equivalent to 0.55 mg, for the flumazenil group and 6.7 +/- 2.2 ml for the placebo group. Critical Flicker Frequency is the only measure which revealed a difference (P < 0.005) between the flumazenil and placebo groups and this occurred only at the ten-minute assessment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Relationships of Na+ and K+ concentrations to GRP, CGRP, and calcitonin immunoreactivities and Na+,K(+)-ATPase (NKA) inhibitory activity in human breast cyst fluid.

BACKGROUND: Although the etiology of gross cystic disease of the breast is unknown, elevated cyst concentrations of potassium (K+) (> 60 mM/L) may be related to symptoms. The purpose of this study was to clarify the mechanism(s) of K+ accumulation in breast cysts. METHODS: We assayed cyst fluids for factors known to exert effects on K+ transport, namely, endogenous digitalis-like inhibitors of Na+,K(+)-ATPase (NKA) and the neuropeptides gastrin-releasing peptide (GRP), calcitonin (CT), and calcitonin gene-related peptide (CGRP). RESULTS: Cyst fluid K+ was directly correlated with cyst volume, cyst NKA inhibitory activity (in ouabain equivalents), and cyst concentrations of calcitonin, GRP, and CGRP. Cyst fluid Na+ was inversely correlated with cyst fluid K+, cyst NKA inhibitory activity, cyst volume, and cyst fluid concentrations of calcitonin, GRP, and CGRP. NKA inhibitory activity correlated directly with GRP and CGRP. Immunocytochemistry localized GRP to breast cyst lining cells and areas of ductal and lobular epithelial hyperplasia in biopsies of 15 of 15 cysts and in 5 of 5 breast carcinomas, but not in (0 of 5) normal breast biopsies. Specificity of GRP staining was demonstrated by total abolition of reactivity after adsorption with synthetic GRP, but not after adsorption with synthetic substance P, neurokinin A, or neurokinin B. CONCLUSIONS: We conclude that both the concentrations of endogenous digitalis-like factors and the neuropeptides calcitonin, GRP, and CGRP in human breast cyst fluids are related to the concentrations of K+ and Na+ in breast cysts and to cyst volume.

Adult↗

Neural-network contributions in biotechnology.

In the mid-1980s, widespread interest in research into artificial neural networks re-emerged following a period of reduced research funding. The much wider availability and the increased power of computing systems, together with new areas of research, is expanding the range of potential application. The main reason for this is that the potential to describe the characteristics of extremely complex systems accurately has been attributed to this methodology. This article examines the contribution of various network methodologies to bioprocess modelling, control and pattern recognition. Industrial processes can benefit from the application of feedforward networks with sigmoidal activation functions, radial basis function networks and autoassociative networks. The contribution that neural networks can make to biochemical and microbiological scientific research is also reviewed briefly.

Animals↗

Relationship between the ability of sunscreens containing 2-ethylhexyl-4'-methoxycinnamate to protect against UVR-induced inflammation, depletion of epidermal Langerhans (Ia+) cells and suppression of alloactivating capacity of murine skin in vivo.

The UVB sunscreen 2-ethylhexyl-4'-methoxycinnamate was evaluated in hairless albino mouse skin for its ability to inhibit UVR-induced (i) oedema, (ii) epidermal Langerhans cell (Ia+) depletion and (iii) suppression of the alloactivating capacity of epidermal cells (mixed epidermal cell-lymphocyte reaction, MECLR). The sunscreen, prepared at 9% in ethanol or a cosmetic lotion, was applied prior to UVB/UVA irradiation. In some experiments there was a second application halfway through the irradiation. Single applications in both vehicles gave varying degrees of protection from oedema and Langerhans cell depletion but afforded no protection from suppression of MECLR. When the sunscreens were applied twice there was improved protection from oedema and Langerhans cell depletion and complete protection was afforded from suppression of MECLR. There was a clear linear relationship between Langerhans cell numbers and oedema with and without sunscreen application. The relationship between Langerhans cell numbers and MECLR was more complex. These data confirm published discrepancies between protection from oedema (a model for human erythema) and endpoints with immunological significance, but show that 2-ethylhexyl-4'-methoxycinnamate can afford complete immunoprotection, although protection is dependent on the application rate and vehicle.

Administration, Topical↗

The role of protein tyrosine phosphorylation in integrin-mediated gene induction in monocytes.

Integrin-mediated cell adhesion, or cross-linking of integrins using antibodies, often results in the enhanced tyrosine phosphorylation of certain intracellular proteins, suggesting that integrins may play a role in signal transduction processes. In fibroblasts, platelets, and carcinoma cells, a novel tyrosine kinase termed pp125FAK has been implicated in integrin-mediated tyrosine phosphorylation. In some cell types, integrin ligation or cell adhesion has also been shown to result in the increased expression of certain genes. Although it seems reasonable to hypothesize that integrin-mediated tyrosine phosphorylation and integrin-mediated gene induction are related, until now, there has been no direct evidence supporting this hypothesis. In the current report, we explore the relationship between integrin-mediated tyrosine phosphorylation and gene induction in human monocytes. We demonstrate that monocyte adherence to tissue culture dishes or to extracellular matrix proteins is followed by a rapid and profound increase in tyrosine phosphorylation, with the predominant phosphorylated component being a protein of 76 kD (pp76). Tyrosine phosphorylation of pp76 and other monocyte proteins can also be triggered by incubation of monocytes with antibodies to the integrin beta 1 subunit, or by F(ab')2 fragments of such antibodies, but not by F(ab) fragments. The ligation of beta 1 integrins with antibodies or F(ab')2 fragments also induces the expression of immediate-early (IE) genes such as IL-1 beta. When adhering monocytes are treated with the tyrosine kinase inhibitors genistein or herbimycin, both phosphorylation of pp76 and induction of IL-1 beta message are blocked in a dose-dependent fashion. Similarly, treatment with genistein or herbimycin can block tyrosine phosphorylation of pp76 and IL-1 beta message induction mediated by ligation of beta 1 integrin with antibodies. These observations suggest that protein tyrosine phosphorylation is an important aspect of integrin-mediated IE gene induction in monocytes. The cytoplasmic tyrosine kinase pp125FAK, although important in integrin signaling in other cell types, seems not to play a role in monocytes because this protein could not be detected in these cells.

Benzoquinones↗

The closure of residential homes: what happens to residents.

A controlled, prospective study is described which demonstrates changes in behaviour and mortality in the residents of two residential homes which were closed. The 59 residents were dispersed to 19 different establishments. Thirteen general practitioners (GPs) received sick elderly people on their lists after relocation. There were delays and other difficulties in communication between GPs. Restlessness, as measured by the Crichton Geriatric Behavioural Rating Scale, was increased soon after moving but no differences in behaviour or dependency between patients and control subjects were demonstrable after 1 year. Although moving in itself did not increase mortality, residents with poor mobility and dressing skills had a high death rate. This pattern of closure with widespread dispersal of residents is likely to become more common after the introduction of the NHS and Community Care Acts. It is associated with psychiatric morbidity which may be preventable by better organization. Medical involvement in the move was minimal, and the special responsibility of medical care of patients living in residential homes should be recognized.

Activities of Daily Living↗

Effects of varying dietary fat, fish, and fish oils on blood lipids in a randomized controlled trial in men at risk of heart disease.

This study aimed to determine the effects of incorporating fish with 40%- or 30%-fat diets and the differences in response to fish or fish oil omega 3 fats. Men with high-normal blood pressure and elevated serum cholesterol were randomly allocated to one of seven diets for 12 wk. Fish or fish oil with a 40%-fat diet increased total cholesterol, HDL cholesterol, HDL2 cholesterol, and LDL cholesterol, and reduced triglycerides. The 30%-fat diet alone reduced cholesterol, LDL cholesterol, and HDL cholesterol, with triglycerides unchanged. Fish with the 30%-fat diet reduced cholesterol, LDL cholesterol, and triglycerides and increased HDL2 cholesterol. This study has shown that plasma lipids are affected similarly by fish or fish oil in men consuming a 40%-fat diet. Adverse effects of omega 3 fats on total and LDL cholesterol are reversed by a 30%-fat diet, whereas one daily fish meal substantially lowers triglycerides and reverses the fall in HDL cholesterol that is usual with a low-fat diet.

Adult↗

HIV-2-infected patients survive longer than HIV-1-infected patients.

OBJECTIVE: To compare survival of patients infected with HIV-1 and HIV-2. DESIGN: Longitudinal follow-up of 175 HIV-1- and 294 HIV-2-infected patients identified in, or referred to a hospital in The Gambia. METHODS: Survival analysis methods were used and the death rate ratios for HIV-2 relative to HIV-1 patients were estimated using proportional hazard regression models that allowed for age, sex and clinical or immunological features. RESULTS: The overall death rate ratio for HIV-2 relative to HIV-1 was 0.67 [95% confidence interval (CI), 0.49-0.91] when adjusted for age, sex and World Health Organization Bangui clinical classification. When allowing for age, sex and three strata of CD4+ count, the rate ratio was 0.64 (95% CI, 0.43-0.94), and for three strata of beta 2-microglobulin levels 0.60 (95% CI, 0.42-0.84). CONCLUSION: Mortality rate in HIV-2-infected patients is approximately two-thirds of that for HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗

Immune response to human papillomavirus type 16 E6 gene in a live vaccinia vector.

Immunization of mice with a recombinant vaccinia virus expressing the human papillomavirus type 16 (HPV-16) E6 gene elicits specific antibody, proliferative and cytotoxic T lymphocyte responses. T and B cell epitopes were mapped by using synthetic peptides. This study provides the background to future investigation aimed at developing prophylactic and therapeutic vaccines against HPV-16 infection and cervical cancer.

Amino Acid Sequence↗

Quality of life as an indicator of outcome in the treatment of cancer patients: the purchaser perspectives.

Evaluation of treatment can be seen as part of a wider concern to measure quality of care, as well as about the need to monitor and improve the effectiveness of services. Quality of life issues will be of increasing interest to those involved in the commissioning of health-care services. Cancer is used to illustrate how the quality of life of patients, both during and after treatment, can be measured and the information used by purchasers to consider the relative effectiveness of different methods of treatment. This in turn can inform the overall purchasing strategy of commissioning agencies.

Health Knowledge, Attitudes, Practice↗

The painful crisis of homozygous sickle cell disease: clinical features.

The details of onset, perceived precipitating factors, associated symptoms, and pain distribution in the painful crisis of homozygous sickle cell (SS) disease have been prospectively recorded in 183 painful crises in 118 patients admitted to a day-care centre in Kingston, Jamaica. Painful crises developed most frequently between 3 p.m. and midnight, most commonly affected patients aged 15-29 years, affected the sexes equally, and were not obviously influenced by menstrual cycle. Of the perceived precipitating factors, skin cooling occurred in 34%, emotional stress in 10%, physical exertion in 7%, and pregnancy in 5% of women of child-bearing age. Cold as a precipitant was not less common in patients with more subcutaneous fat. Pain affected the lumbar spine in 49%, abdomen in 32%, femoral shaft in 30%, and knees in 21%. There was a highly significant excess of bilateral involvement in limb and rib pain. Recurrent painful crises occurred in 40 patients but showed no evidence of involving similar sites on successive occasions. Abdominal painful crises were associated with abdominal distention in 18 (31%) and with referred rib pain in a further 15 (26%) of crises. Fever was common even in apparently uncomplicated painful crises, suggesting that fever is characteristic of the painful crisis itself and not necessarily indicative of infection. Following investigation and treatment in a day-care centre, over 90% of patients returned home.

Adolescent↗

Heterogeneity in the phenotypic expression of the mutation in the mitochondrial tRNA(Leu) (UUR) gene generally associated with the MELAS subset of mitochondrial encephalomyopathies.

BACKGROUND: Point mutations in the mitochondrial (mt) genome underlie a number of neurological disorders. Some are well defined including the myoclonus epilepsy ragged red fibre syndrome (MERRF) and the mitochondrial encephalopathy lactic acidosis stroke like episode syndrome (MELAS). However, other clinical phenotypes are less distinctive and mitochondrial studies are often included in the workup in complex neurological syndromes of uncertain aetiology. AIMS: We investigated 27 consecutive patients with varied clinical phenotypes referred to our laboratory for mtDNA studies to determine the incidence of recognised point mutations in a patient group with a range of phenotypes including many where mt disease was possible but did not fall into a classical syndrome. METHODS: The recognised point mutations were detected by amplification of the appropriate DNA fragment by PCR followed by restriction-endonuclease digestion of the normal and mutant species. RESULTS: The A-G base substitution mutation at nucleotide (nt)3243 in the tRNA(Leu) gene of mtDNA which is present in the majority of cases of MELAS syndrome, was detected in four cases, only one of whom had typical MELAS symptoms. Their clinical manifestations ranged from mild deafness to a mixture of chronic progressive external ophthalmoplegia symptoms (CPEO) and stroke like episodes. The nt3243 mutation was also identified in one of seven mtDNA deletion negative CPEO cases. CONCLUSIONS: The presentation of the mtDNA mutation at nt3243 appears therefore to be quite variable with some mild phenotypes as well as severe phenotypes observed. In general, the chance of finding a mitochondrial point mutation in a patient with an atypical clinical phenotype is small.

Adult↗