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Biomedical subjects

A M Farrell

Publications and source records attributed to A M Farrell.

At least 55 records · Page 3Linked to original sources
PubMed1997

Permeability barrier disruption coordinately regulates mRNA levels for key enzymes of cholesterol, fatty acid, and ceramide synthesis in the epidermis.

The extracellular lipids of the stratum corneum, which are comprised mainly of cholesterol, fatty acids, and ceramides, are essential for epidermal permeability barrier function. Moreover, disruption of the permeability barrier results in an increased cholesterol, fatty acid, and ceramide synthesis in the underlying epidermis. This increase in lipid synthesis has been shown previously to be due to increased activities of HMG-CoA reductase, acetyl-CoA carboxylase, fatty acid synthase and serine palmitoyl transferase, key enzymes of cholesterol, fatty acid, and ceramide synthesis, respectively. In the present study, we determined whether the mRNA levels for the key enzymes required for synthesis of these three classes of lipids increase coordinately during barrier recovery. By northern blotting, the steady-state mRNA levels for HMG-CoA reductase, HMG-CoA synthase, farnesyl pyrophosphate synthase, and squalene synthase, key enzymes for cholesterol synthesis, all increased significantly after barrier disruption by either acetone or tape stripping. Additionally, the steady-state mRNA levels of acetyl-CoA carboxylase and fatty acid synthase, required for fatty acid synthesis, as well as serine palmitoyl transferase, the rate-limiting enzyme of de novo ceramide synthesis, also increased. Furthermore, artificial restoration of the permeability barrier by occlusion after barrier disruption prevented the increase in mRNA levels for all of these enzymes, except farnesyl pyrophosphate synthase, indicating a specific link of the increase in mRNA levels to barrier requirements. The parallel increase in epidermal mRNA levels for the enzymes required for cholesterol, fatty acid, and ceramide synthesis may be due to one or more transcription factors that regulate lipid requirements for permeability barrier function in keratinocytes.

Acyltransferases↗
PubMed1997

Constitutive endothelial and inducible nitric oxide synthase in inflammatory dermatoses.

We have used immunohistochemistry to localize the expression of the constitutive endothelial and inducible forms of the enzyme nitric oxide synthase (NOS) in skin from involved and uninvolved sites in patients with atopic dermatitis (AD) and allergic contact dermatitis (CD). Endothelial NOS (eNOS) immunoreactivity was localized to vascular endothelium in the dermis of both involved and uninvolved skin from all patients. Inducible NOS (iNOS) immunoreactivity was found to be closely associated with the upper dermal microvasculature in all the involved AD biopsies, but only in two of 10 uninvolved AD biopsies. CD biopsies were taken from 10 positive skin patch test sites and iNOS immunoreactivity was detected in all of these. iNOS immunoreactivity was detected in only one of the negative patch test biopsies. Both the extent and intensity of iNOS immunoreactivity was lower in CD than in AD skin lesions. The presence of eNOS in the skin is necessary for constitutive NO-mediated dilatation of the dermal vasculature. Induction of iNOS in the dermal endothelium and in perivascular inflammatory cells may be significant with respect to the roles of NO in both the vasodilatory component of the inflammatory response and in the modulation of immune responses in the skin.

Dermatitis, Allergic Contact↗
PubMed1996

Staphylococcal scalded skin syndrome in an HIV-1 seropositive man.

The staphylococcal scalded skin syndrome (SSSS) is very rare in adults. Renal impairment and immunocompromise are predisposing causes. We report a 38-year-old HIV-1 seropositive intravenous drug abuser who developed SSSS due to staphylococcal pneumonia. An exfoliating toxin-releasing Staphylococcus aureus, phage type II type 3C, was isolated from the sputum and from blood cultures. This is the third case of adult SSSS to be reported in the context of HIV disease.

AIDS-Related Opportunistic Infections↗
PubMed1996

Scleredema diabeticorum of Buschke confined to the thighs.

We describe a patient with insulin-dependent diabetes without vascular complications in whom scleredema was confined to the thighs. Electron microscopy demonstrated heterogeneity in both the size and density of the collagen fibrils and the presence of filamentous material between them.

Adult↗
PubMed1996

Ectopic cutaneous schistosomiasis: extragenital involvement with progressive upward spread.

The ectopic deposition of ova of Schistosoma haematobium within the dermis is very rare, even in countries where infection with this trematode is widespread. When it does occur, it usually affects the genital area. We report a patient who developed ectopic genital and extragenital cutaneous involvement 4 months after swimming in Lake Malawi. The lesions appeared sequentially and spread from the genitalia in a caudocephalic manner. Doppler imaging of the pelvic veins did not reveal any anomalous venous drainage to account for the distribution of these lesions.

Adult↗
PubMed1996

Cutaneous lymphocytic vasculitis in acute myeloid leukaemia.

We report a 63-year-old woman who presented with an 8-week history of widespread indurated, purpuric lesions associated with weight loss of 7 kg and several episodes of epistaxis. A skin biopsy demonstrated a lymphocytic vasculitis with haemorrhage and parakeratosis. A blood film and bone marrow examination showed features of a myelodysplastic syndrome in transformation to acute myeloid leukaemia. Leucocytoclastic vasculitis and polyarteritis nodosa occur in association with acute myeloid leukaemia, but the association with lymphocytic vasculitis is new.

Acute Disease↗
PubMed1995

Cloning, nucleotide sequence determination and expression of the Staphylococcus aureus hyaluronate lyase gene.

The Staphylococcus aureus 8325-4 hyaluronate lyase gene (hysA) was identified after detecting hyaluronate lyase activity expressed by phages from a genomic library. The hysA open reading frame, capable of encoding a protein of 91 980 Da, was identified by Tn5 mutagenesis and nucleotide sequencing. HysA shares 35 and 36% amino acid sequence identity with group B streptococcal hyaluronate lyase and pneumococcal hyaluronidase, respectively. A 94-kDa protein was expressed in Escherichia coli minicells, a result consistent with the coding capacity of hysA. Identification of the S. aureus 8325-4 hyaluronate lyase gene will allow the regulation of this putative virulence determinant to be studied.

Amino Acid Sequence↗
PubMed1995

Arthropathy, leucopenia and recurrent infection associated with a TcR gamma delta population.

This report documents the presence of clonal gamma delta T-cell receptor (TcR) population in the blood of a patient who presented with an arthropathy of undetermined cause, leucopenia and splenomegaly. There was no evidence for lymphoid malignancy clinically or at post-mortem. The phenotype and genotype of the clonal T-cell population were not associated with the predominant TcR delta rearrangement found in peripheral blood gamma delta cells, but were similar to those found in gamma delta TcR cells infiltrating rheumatoid synovium. The data indicate the presence of a monoclonal population of gamma delta cells TcR cells which in the face of continued immunosuppression behaved benignly. The case may represent a cytomorphologically atypical example of the large granular lymphocytes, neutropenia and arthropathy syndrome/lymphoproliferative disease of granular lymphocytes and, although the patient's clinical features were not 'classical', rheumatoid arthritis (RA) may have been the underlying primary disorder.

Arthralgia↗
PubMed1994

Parainfluenza virus type 3 induced alterations in tachykinin NK1 receptors, substance P levels and respiratory functions in guinea pig airways.

We have investigated the effects of parainfluenza virus type 3 (PI-3) on sensory neuropeptide levels, tachykinin receptors and their functions in guinea pig airways during the course of respiratory viral infection. PI-3 infected guinea pigs were hyperresponsive to methacholine and substance P aerosols as determined by earlier onset of dyspnea in these animals as compared with control on post-inoculation day (PID) 7 but not 19. In addition, plasma protein extravasation produced in response to the tachykinin was increased in infected airways during the first week post inoculation. Infected guinea pig trachea did not respond any differently to methacholine when smooth muscle contraction and [3H]inositol phosphate accumulation were measured although the magnitude of substance P effects using in vitro tests was significantly greater than control on post-inoculation day 7 but not 19. Trachea from PI-3 infected animals were characterized by reductions in substance P-like immunoreactivity, tachykinin NK1 receptor number and agonist affinity during the first post-inoculation week. Substance P levels or tachykinin NK1 receptor numbers or affinity were not altered in trachea of guinea pigs 4 days after treatment with lipopolysaccharide. These data suggest substance P release occurs during critical periods of respiratory viral infection which are temporally correlated with airway hyperresponsiveness. Despite apparent down-regulation of tachykinin NK1 receptors, substance P-mediated functions remained enhanced suggesting some alterations in post-receptor mechanisms.

Animals↗
PubMed1994

The effect of glycerol monolaurate on growth of, and production of toxic shock syndrome toxin-1 and lipase by, Staphylococcus aureus.

The effects of glycerol monolaurate on the growth of, and production of Toxic Shock Syndrome Toxin-1 (TSST-1) and lipase by, Staphylococcus aureus FRI 1187 were investigated in batch and continuous culture models using a defined synthetic medium. The growth and yield of S. aureus depended on glycerol monolaurate concentration, pH of the environment and the inoculum size. The MICs for glycerol monolaurate of 29 S. aureus isolates, determined in a complex medium, were between 10 and 20 mg/L with a 10(3) to 10(4) cfu inoculum; a 1000-fold increase in inoculum size increased the MIC five-fold. In continuous culture, glycerol monolaurate increased the cell yield of S. aureus. In batch cultures with 17 mg/L glycerol monolaurate, TSST-1 and lipase production by S. aureus was delayed and their specific production was not decreased compared with cultures without glycerol monolaurate. At 150 mg/L glycerol monolaurate, growth and toxin production were decreased. The lipase of S. aureus hydrolyzed glycerol monolaurate. The reduction of toxin production was associated with effects on S. aureus growth, and these effects might have been relieved after lipase had been produced.

Bacterial Toxins↗
PubMed1994

Complement activation by cellulosic dialysis membranes.

AIMS: To assess the effect of cellulosic dialysis membranes on the production of complement degradation products to determine to the role of the classical pathway. METHOD: Complement activation was studied in 33 patients during a single haemodialysis session using cellulosic membranes. Pre- and post-dialysis plasma EDTA valves of C3, C4, C3dg, C4d and C reactive protein (CRP) were measured. Statistical analysis was done using the Wilcoxon signed rank test. RESULTS: Post-dialysis C4 (p = 0.0003), C3dg (p < 0.0001), and C4d (p = 0.003) concentrations were increased compared with pre-dialysis values. There was no significant change in C3 (p = 0.095) and CRP (p = 0.13) values. Post-dialysis C3dg and C4d concentrations correlated significantly (p = 0.007). IgG, an undialysed molecule, was quantified and post-dialysis valves were significantly higher than those before dialysis (p = 0.0002), indicating a degree of haemoconcentration. To remove this effect, the C3:IgG, C4:IgG, C3dg:IgG, C4d:IgG and CRP:IgG ratios were calculated. Compared with pre-dialysis values, post-dialysis C3dg:IgG and C4d:IgG ratios were increased and C3:IgG decreased significantly. No change was observed in C4:IgG and CRP:IgG ratios. CONCLUSION: This study confirms that significant complement activation takes place following dialysis with cellulosic membranes. This is denoted by an increase in C3dg. This was paralleled by a rise in C4d, implying a contributory role for the classical pathway. Concomitant post-dialysis increases in IgG and C4 indicate a degree of haemoconcentration; but removal of this effect shows that C3dg and C4d are increased following dialysis--suggesting classical, in addition to alternative, pathway activation.

Adult↗
PubMed1993

Tachykinin-mediated respiratory effects in conscious guinea pigs: modulation by NK1 and NK2 receptor antagonists.

Tachykinins, in particular neurokinin A and substance P, produce a number of airway effects which may contribute to respiratory diseases such as asthma. We examined the ability of aerosolized substance P, neurokinin A or capsaicin to produce respiratory alterations in conscious guinea pigs using modified whole body plethysmography. Substance P-mediated dyspnea and significant respiratory events were inhibited by the NK1 receptor antagonist, CP-96,345. Neurokinin A-mediated respiratory effects were ablated by the NK2 receptor antagonists: MEN 10207, MDL 29,913 and SR 48,968, the latter being the most potent. The peptide-based antagonist, MEN 10207, produced respiratory effects itself suggesting partial agonist activity. The cyclic hexapeptide, MDL 29,913, relaxed airway smooth muscle via mechanisms other than tachykinin antagonism. NK2 but not NK1 receptor antagonists were able to delay the onset of capsaicin-induced dyspnea, although alone they did not usually (in approximately 10% of the animals) eliminate the response. However, when NK2 receptor antagonists were combined with CP-96,345, the incidence of dyspnea induced by capsaicin decreased significantly (40%) suggesting that both tachykinins contribute to dyspnea in this system.

Aerosols↗