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Biomedical subjects

M Sheppard

Publications and source records attributed to M Sheppard.

At least 37 records · Page 2Linked to original sources
PubMed1996

Sandostatin LAR: a promising therapeutic tool in the management of acromegalic patients.

A stable and sustained suppression of growth hormone (GH) secretion was noted in 101 patients treated long term with individual doses (20 and 30 mg in 89 patients, 40 mg in 12 patients) of Sandostatin LAR (Sandoz Pharma Ltd, Basel, Switzerland). Doses of 20 mg and 30 mg at 4-week intervals delivered average octreotide concentrations of 1,348 +/- 483 ng/L and 2,631 +/- 1,026 ng/L, respectively, in steady-state conditions and provided adequate control of patients who had been well controlled during treatment with 0.1 mg and 0.2 mg thrice-daily subcutaneous (SC) Sandostatin. Suppression of GH serum concentrations to less than 5 micrograms, 2 micrograms, and even 1 microgram/L was recorded in more patients and more consistently during long-term treatment with Sandostatin LAR than Sandostatin. A marked decrease or even a normalization of insulin-like growth factor-1 (IGF-1) serum concentrations was observed after the first double-blind 10-, 20-, or 30-mg dose of Sandostatin LAR. A progressive improvement was recorded during long-term treatment, with normalization of IGF-1 serum concentrations in 65.3% of patients. A marked clinical improvement was observed in parallel, with 36 of 101 patients (35.6%) becoming asymptomatic after the nineteenth injection of Sandostatin LAR. A greater than 20% shrinkage of the GH-secreting adenoma was also recorded in 12 of 14 patients treated with Sandostatin LAR after receiving only 2 to 4 weeks of treatment with SC Sandostatin and in 11 of 18 patients receiving Sandostatin LAR as adjuvant therapy after failure of surgery. The systemic tolerability of Sandostatin LAR was good, and most adverse events were mild and short term (1 to 2 days). No impairment of thyroid function was detected. Newly occurring gallstones were recorded in four of 101 patients and microlithiasis in four of 101 after up to 30 months of treatment with Sandostatin LAR. Due to its excellent efficacy, good tolerability, convenience of administration, and acceptability by patients, Sandostatin LAR is considered a promising therapeutic tool in the management of acromegalic patients.

Acromegaly↗
PubMed1996

Immunopathogenesis and physical maps of fowl adenovirus serotype 9.

Restriction endonuclease maps of the genome of fowl adenovirus (FAV) serotype 9 have been constructed for the restriction endonucleases NdeI, NotI and XbaI. The total size of the FAV-9 genome was estimated to be 44.5 kb pairs, consistent with previous reports that FAV genomes are approximately 10 kb larger than human adenovirus (HAV). The pathogenicity of this virus in day-old chickens was intermediate between the pathogenicity of the non-pathogenic and the highly pathogenic FAVs.

Adenoviridae Infections↗
PubMed1996

Depression in the work of British health visitors: clinical facets.

The primary health care setting has been established as a key venue for identifying and working with depression. Despite this, and the high risk of depression experienced by women in the post-natal period, maternal depression has been little examined in the work of health visitors. This study focuses on clinical facets of this work, including the rate and content of depression amongst health visitor attenders, the capacity of health visitors to identify accurately the presence of depression, the relationship between depression and child abuse and child behavioural issues, variations in the practice of health visitors and work with other professionals. In a cohort of 701, 11% of women were depressed, with distinguishing symptoms including fatigability, disgust/hate of herself and a sense of failure. Health visitors were not generally accurate in their identification of depression, were significantly more likely to see depressed women at home (than at clinic), but there was little difference in mean frequency of consultations according to whether or not the women were depressed. Urban health visitors had a higher mean frequency of consultations, but rural health visitors showed a rather greater tendency to increase frequency of consultation with the presence of depression. Child abuse concerns and behavioural problems were significantly associated with depression and these were three times as frequent amongst depressed women with no children aged under one compared with women in their post-natal year. Depressed women were far more likely to be involved with other agencies, but the GP was by far the most likely other professional to be involved. Health visitors are in a strategic position to help women with depression, and it is important that they are able to identify its presence. The association with child abuse is very important and indicates the need for multi-professional involvement, particularly with social workers, to a greater degree than was evident. The higher rate of depression in women beyond the post-natal year, was a surprising finding, and particularly in view of its relationship with child abuse concerns, suggests that this is a group of attenders who should be carefully monitored.

Adult↗
PubMed1996

A single gene encoding the fiber is responsible for variations in virulence in the fowl adenoviruses.

Intertypic recombinant fowl adenoviruses (FAVs) were generated to determine regions of the viral genome involved in virulence. Recombinants were produced with two serotype 8 FAVs, mildly virulent CFA 3 and hypervirulent CFA 40. Restriction endonuclease fragments from the genomes of the two FAVs were used to transfect primary chicken kidney cells. Virulence testing of these recombinants located the region responsible for differences in virulence to an 8.4-kb fragment of the genome located between kb 26.6 and 35.0. According to data available for a serotype 10 FAV that had been partially characterized in the laboratory, this segment of the genome contained three genes of known identity (100K, 33K, and pVIII) and a region between kb 31 and 35 with unknown coding potential (although this information subsequently became available for a serotype 1 FAV, CELO). Therefore, the region between kb 30.5 and 34.5 was sequenced. The results revealed that the unknown region encoded a fiber gene on the right strand and several small open reading frames of unknown identity on the left strand. Further recombinant viruses containing defined exchanges within the 4-kb fragment were constructed, and virulence testing of these viruses indicated that the fiber was responsible for differences in virulence for CFA 40 and CFA 3.

Adenoviridae↗
PubMed1996

Nucleotide and amino acid sequence analysis of the porcine adenovirus 23K protein.

The genomic location of the viral encoded protease (23K) of porcine adenovirus serotype 3 (PAV3) was determined and the appropriate fragment cloned and sequenced. An open reading frame (ORF) coding for a polypeptide of 203 amino acids and a calculated molecular weight of 23.3 kDa was found. The ORF was situated in a position similar to that of the human adenovirus 23K, that is, between a putative stop codon for the hexon gene and the polyadenylation signal, AATAAA, for the late region 3. Amino acid sequence alignment of the predicted polypeptide with the sequences of the 23K proteins from other mammalian adenoviruses revealed homology of between 50% and 60% for all except the bovine adenovirus type 7, which displayed appreciable variance from the PAV3 putative 23K with an overall sequence homology of approximately 35%. Conserved cysteine, histidine and proline residues believed to be important in the activity of the 23K protein of human adenoviruses were also present in the PAV3 protein. The genomic location and amino acid sequence of the characterised reading frame suggests that this gene is that of the 23K protein of PAV3.

Adenoviruses, Human↗
PubMed1995

Nucleotide sequence analysis of an infectious laryngotracheitis virus gene corresponding to the US3 of HSV-1 and a unique gene encoding a 67 kDa protein.

The DNA sequence of 4005 nucleotides from the Kpnl O and part of Kpnl K fragments in the short unique region of infectious laryngotracheitis virus (ILTV) was determined. The sequence contained two complete and one partial open reading frames (ORFs). The partial ORF was open at the 5' end of the sequence and represented the NH2-terminal 118 amino acids (aa) of a polypeptide. Its partial predicted protein product exhibited significant homology to the US2 gene product of HSV-1 (herpes simplex virus type 1) and it homologs in other herpesviruses. ORF 2 is 471 aa long and could encode a protein of 53.8 kDa which shared aa homology with the protein kinases encoded by HSV-1 US3 and its gene homologs. Analysis of the ORF 2 aa sequence revealed domains characteristic of protein-serine/threonine (S/T) kinases of cellular and viral origin. The ORF 3 encoded a predicted protein of 601 aa (M(r) 67.5 kDa) which exhibited limited homology (18% overall identity) with the UL47 protein (major tegument protein) of HSV-1. Northern (RNA) blot hybridization and metabolic inhibitors were used to characterize the ILTV protein kinase and the 67K mRNAs. The data revealed that protein kinase is a gamma-1 gene encoding a 1.6 mRNa, while the 67K ORF is a gamma-2 gene encoding a 2 kb mRNA.

Amino Acid Sequence↗
PubMed1995

ICP27 immediate early gene, glycoprotein K (gK) and DNA helicase homologues of infectious laryngotracheitis virus (gallid herpesvirus 1) SA-2 strain.

A 4.8 kilobase segment located at the left-terminal in the unique long (UL) region of infectious laryngotracheitis virus (ILTV) SA-2 strain contained three open reading frames (ORFs). The first of 421 amino acids (aa) was located at map units 0.065 to 0.07, and its predicted 48 kiloDaltons (kDa) protein product has significant homology to the immediate early regulatory protein ICP27 (UL54) of herpes simplex virus type-1 (HSV-1), to varicella-zoster virus (VZV) ORF4 and to equine herpesvirus 1 (EHV-1) ORF5. The zinc finger conserved in the C-terminal of the proteins from HSV-1, VZV and EHV-1, is poorly conserved in ILTV homologue. The second ORF of 336 aa, located at map units 0.075 to 0.08, has a predicted molecular weight (MW) of 38 kDa with significant homology to glycoprotein K (gK) of HSV-1 (UL53), ORF5 of VZV and ORF6 of EHV-1. ILTV gK has features characteristic of a membrane-bound glycoprotein. The 3' region of a third ORF was located at map units 0.08 to 0.095. Translation of the sequence revealed significant homology to the 3'-region of the DNA helicase-primase complex protein (UL52) of HSV-1, ORF6 of VZV and ORF 7 of EHV-1. Northern blot analyses were used to characterize the ILTV ICP27, gK and DNA helicase mRNAs. The data revealed that ILTV ICP27 is an immediate early gene that encodes a 1.6 kb mRNA, ILTV gK encodes a late transcript of 1.8 kb, while ILTV DNA helicase encodes a late transcript of 3.7 kb.

Amino Acid Sequence↗
PubMed1995

Immunological and molecular comparison of fowl adenovirus serotypes 4 and 10.

Some discussion has centered on whether fowl adenovirus (FAV) serotypes 4 and 10 are distinct serotypes or in fact should be reclassified as a single serotype. We have undertaken a detailed characterisation of representatives of both serotypes in order to determine if types 4 and 10 should be grouped together or retained as distinct serotypes. Examination at the genomic level has revealed considerable similarities and few differences between these 2 serotypes. DNA cross-hybridization failed to distinguish between them and restriction enzyme analysis demonstrated limited sequence differences. In vivo studies demonstrated the cross-protection afforded by a natural route vaccination with serotype 4 FAV when chickens were challenged with serotype 10 FAV. On the basis of these studies it is suggested that these FAV serotypes be combined in future FAV classification. Physical maps for both serotype 4 and 10 have been constructed using the restriction enzymes Hpa I, Dra I, Nde I, Xba I and Not I for both serotypes and in addition Eco RI, Sfi I, Sma I and BglII for serotype 10.

Animals↗
PubMed1995

Nucleotide sequence of infectious laryngotracheitis virus (gallid herpesvirus 1) ICP4 gene.

The infectious laryngotracheitis virus (ILTV) gene encoding a homologue to the ICP4 protein of herpes simplex virus (HSV) has been mapped to the inverted repeat region. The complete nucleotide sequence of ILTV ICP4 has been determined. The ILTV ORF encoding ICP4 is 4386 nucleotides long, calculated from the first of four ATG codons, and has an overall G+C content of 59%. The ILTV ICP4 contains two domains of high homology which have been reported in other studies to be conserved in the ICP4 homologues of alphaherpesviruses, and to be functionally important. Several regulatory features were identified including a serine-rich domain in region one. A more extensive serine-rich domain was located in region five which is also found in varicella-zoster virus (VZV) and bovine herpesvirus 1. A 5.4 kb immediate early transcript was identified in infected primary kidney cells.

Amino Acid Sequence↗
PubMed1995

Genomic mapping and sequence analysis of the fowl adenovirus serotype 10 hexon gene.

The gene for the major capsid protein (hexon) of fowl adenovirus serotype 10 (FAV-10) has been identified by the use of the expression vector pGEX and rabbit polyclonal antisera raised against FAV-10. The nucleotide sequence of the entire hexon gene has been determined. Sequence analysis revealed an open reading frame of 2808 bp coding for a putative polypeptide 936 amino acids long with a molecular mass of 105.5 kDa. The translation initiation codon has a local sequence which conforms with the optimal translation start sequence of CC(A/G)CCATGG. The location of the hexon gene in the FAV genome was from 46.85 to 52.81 map units, which is to the left of the hexon gene in the genomes of both bovine and human adenovirus (52.4 to 60.5 map units.). A splice acceptor site was identified 12 bp upstream of the initiation codon by using mRNA and PCR. It had the sequence TAGG which conforms to the consensus sequence of (C/T)AGG. Comparison of the amino acid sequence of the FAV-10 hexon with those of the bovine, human and murine hexon gene products revealed highest levels of identity occurring in the regions corresponding to the pedestals which form the base region of the hexon, and the lowest levels of identity in the regions corresponding to the loops which are exposed to the external environment.

Amino Acid Sequence↗
PubMed1995

Sequence characteristics of a gene in infectious laryngotracheitis virus homologous to glycoprotein D of herpes simplex virus.

An infectious laryngotracheitis virus (ILTV, gallid herpesvirus 1) gene homologous to glycoprotein D of herpes simplex virus (HSV) was identified and characterized by its nucleotide and derived amino acid sequence. The ILTV gD gene is located in the unique short region (U(s)) and contains an open reading frame capable of specifying a polypeptide of 380 amino acids, including N- and C- terminal hydrophobic domains consistent with signal and anchor regions respectively, and no potential sites for N-glycosylation. Alignment of the amino acid sequence with those published for HSV gD, equine herpesvirus type 1 (EHV-1) gD, pseudorabies virus (PRV) gp50, Marek's disease virus (MDV) gD, herpesvirus of turkeys (HVT) gD and bovine herpesvirus type 1 (BHV-1) gD showed similarities over the N-terminal region, with the greatest differences occurring in the C-terminal. The identical positioning of 6 cysteine residues supports the hypothesis of common ancestry of herpesvirus family (McGeoch, 1990) and is consistent with the essential role of this glycoprotein.

Amino Acid Sequence↗
PubMed1994

Dispensing surgical gloves onto the open surgical gown pack does not increase the bacterial contamination rate.

In implant surgery air and surface contamination have become important factors in post-operative wound infection. We established the rate of contamination of surgical gown packs and found that dropping gloves onto the open gown pack prior to scrubbing had no effect on it. Ninety-six contact plates were used for this study, which was carried out during clean orthopaedic operations in one operating room. The overall rate of contamination was 65%. Most of the contaminants were skin commensals. The rate of contamination was 67% when gloves were dropped onto the gown pack compared with 63% when opened and presented to the scrubbed and gowned theatre staff. However this difference was statistically not significant. The high rate of contamination was probably due to the gown packs having been left opened for too long. This delay arose because each gown pack had three gowns and would have been avoided if single gown packs had been used.

Environmental Microbiology↗
PubMed1994

Cloning and sequencing of the chicken anaemia virus (CAV) ORF-3 gene, and the development of an ELISA for the detection of serum antibody to CAV.

Chicken anaemia virus (CAV) is a small, unclassified virus involved in anaemia and suspected of causing immunosuppression in young chickens. We have developed an ELISA for the detection of serum antibody to CAV based on cloned antigen. The gene for ORF-3 (the putative capsid protein) was cloned, sequenced and expressed in a bacterial expression system, pGEX. An ORF-3 fusion protein was used to produce an indirect ELISA.

Amino Acid Sequence↗
PubMed1994

Audit of pleural biopsies: an argument for a pleural biopsy service.

We audited 203 consecutive pleural biopsies performed by medical and geriatric firms over a 3-yr period in our hospital (1987-9). For firms without a special respiratory interest only two to three biopsies per yr were performed, compared with 23 per yr for a respiratory team. Twenty percent of biopsies failed to obtain pleural tissue, 50% revealed normal or non-diagnostic pleural changes and 30% provided a diagnosis. For the respiratory team that performed a third (68) of the biopsies the failure rate for obtaining pleura was 9% compared with 27% for other teams. In view of this disparity a pleural biopsy service was offered by the respiratory team during routine bronchoscopy lists. A repeat audit (1990-2) following the introduction of this service revealed that 60% (84) of 141 biopsies were performed by the respiratory team with their failure rate for obtaining pleura being lower at 6% as compared to 16% for the general physicians. Thirty-one percent of biopsies provided a definitive diagnosis, being higher for those performed by the respiratory team (37%) as opposed to 23% for general physicians.

Biopsy, Needle↗
PubMed1994

Bone mineral density in thyroxine treated females with or without a previous history of thyrotoxicosis.

OBJECTIVE: The results of studies examining the influence of T4 therapy upon bone mineral density (BMD) are conflicting. This conflict may, in part, reflect inclusion of patients with varying thyroid disorders. We have therefore examined the influence of preceding thyroid history and T4 therapy on BMD. DESIGN: Case-control studies of patients on long-term T4 therapy who have or have not previously received radioiodine treatment for thyrotoxicosis, as well as previously thyrotoxic patients who have not required T4 replacement. PATIENTS: Twenty-seven premenopausal and 60 postmenopausal females with a past history of thyrotoxicosis and subsequent T4 treated hypothyroidism (group 1), 39 post-menopausal females with a past history of radioiodine treated thyrotoxicosis not receiving T4 (group 2) and 22 post-menopausal females with primary hypothyroidism on T4 (group 3). Female controls individually matched to patients by age and menopausal status. MEASUREMENTS: BMD measured by dual-energy X-ray absorptiometry. Serum biochemistry and tests of thyroid function. RESULTS: No significant differences were found in femoral or lumbar spine BMD measurements between premenopausal patients and controls in group 1 or between group 2 patients and controls. Measurements of BMD at all sites were lower in post-menopausal patients in groups 1 and 2 than in controls; when allowance was made for differences in BMD due to body mass index by analysis of variance, significant reductions in femoral trochanter BMD (3.9%, P < 0.05) and lumbar spine (5.6-8.5%, P < 0.01) BMD results were found in post-menopausal females in group 1 and reductions in femoral trochanter (3.9%, P < 0.01), Ward's triangle (5.6%, P < 0.05) and lumbar spine (8.5%, P < 0.01) BMD results in group 2. Separate analysis of BMD results of those with normal or reduced serum TSH did not affect outcome. BMD measurements were not significantly correlated with duration of T4 therapy, T4 dose, or serum free T4 or TSH in any patient group. CONCLUSIONS: Thyroxine therapy alone does not represent a significant risk factor for loss of bone mineral density but there is a risk of bone loss in post-menopausal (but not premenopausal) females with a previous history of thyrotoxicosis treated with radioiodine.

Absorptiometry, Photon↗
PubMed1994

Lung metastasectomy in patients with soft tissue sarcoma.

Metastases develop in 50-60% of patients with high grade soft tissue sarcomas despite primary treatment. Between 1970 and 1990, 189 patients with soft tissue sarcoma referred to the Royal Marsden Hospital Sarcoma Unit developed lung metastases as the sole first site of disseminated disease. 44 of these 189 cases have been treated by pulmonary metastasectomy. In an attempt to determine which patients benefit from this surgery the medical records, radiology and pathology of these cases have been reviewed. Both the overall 5 year survival (70% vs 19%) and the subsequent survival from the time lung metastases developed (52% vs 7.5%) of those selected for thoracotomy were better than in the 145 patients not undergoing surgery. On multivariate analysis, survival and control of lung disease following resection were not related to the number of metastases resected, completeness of excision, use of adjuvant chemotherapy or presence of bilateral disease. The most important factor was the use of lung resection itself as treatment, for which the risk of death was 0.2 compared with those not having metastasectomy. Age less than 40 years and primary tumour in a lower limb site were also factors associated with a reduced risk of death. Pulmonary metastasectomy should be considered in selected patients with soft tissue sarcoma after primary local cure. However, without collection of prospective data on all patients developing lung metastases or a randomized trial the true role of lung metatasectomy will never be clarified.

Adult↗
PubMed1993

Expression of endothelin-1 in lungs of patients with cryptogenic fibrosing alveolitis.

The vasoconstrictor and mitogenic peptide endothelin-1 (ET-1) is believed to play a part in fibrosis and collagen production. We examined expression of ET-1 in lung tissue from 52 patients with interstitial lung fibrosis, of whom 45 had cryptogenic fibrosing alveolitis (CFA), 10 had CFA and concomitant pulmonary hypertension, and 7 had non-specific focal fibrosis. 17 normal unused donor lungs were studied as controls. Immunohistochemistry and in-situ hybridisation were done with polyclonal antisera to ET-1 and its precursor big ET-1, and complementary RNA probes for preproET-1. Normal lung tissue and that from patients with focal fibrosis expressed very little ET-1. By contrast, there was striking expression of ET-1 in lung tissue from patients with CFA. Immunostains for ET-1 and big ET-1 and expression of ET-1 mRNA were most prominent in airway epithelium and type II pneumocytes, particularly those lining areas of young granulation tissue. ET-1-like immunoreactivity and mRNA were also present in pulmonary vascular endothelial cells, particularly in specimens from patients with pulmonary hypertension. In all patients, there was a significant correlation between ET-1-like immunoreactivity and histological parameters of disease activity (r = 0.78, 95% CI 0.65-0.87, p < 0.001). These findings suggest a possible role for cell-specific expression of ET-1 in the pathogenesis of CFA and associated pulmonary hypertension.

Biomarkers↗