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Biomedical subjects

R A Williams

Publications and source records attributed to R A Williams.

At least 55 records · Page 3Linked to original sources

Sequences of the ribonucleotide reductase-encoding genes of felid herpesvirus 1 and molecular phylogenetic analysis.

The felid herpesvirus 1 (FHV-1) genes encoding the two ribonucleotide reductase (RR) subunits (RR1, large subunit and RR2, small subunit) were cloned and their nucleotide (nt) sequence determined. The RR1 open reading frame (ORF) is 2358 nts long and is predicted to encode a protein of 786 amino acids (aa). In common with herpesviruses in the Varicellovirus genus of the alphaherpesvirus subfamily, FHV-1 RR1 lacks the N-terminal serine threonine protein kinase region present in herpes simplex virus (HSV)-1 and -2. FHV-1 RR1 has a predicted aa identity of 47-64% with other alphaherpesvirus RR1 peptides, falling to 26-29% for gammaherpesviruses. The RR2 ORF is 996 nts long, predicted to encode a protein of 332 aa and has aa identities of 64-70% with alphaherpesviruses and 38-39% with gammaherpesviruses. Molecular phylogenetic analysis groups FHV-1 with equid herpesviruses 1 and 4 (EHV 1 and 4), pseudorabies virus (PRV) and bovid herpesvirus 1 (BHV 1) within the genus Varicellovirus.

Alphaherpesvirinae↗

Prodromal symptoms of recurrent major depressive episodes: a qualitative analysis.

In four focus groups, 16 people with major depressive or bipolar disorder were asked to describe the onset of an acute depressive episode. Findings indicate that those entering a major depressive episode often have difficulty identifying prodromal symptoms, although they experience early warning phases. These phases and described, and implications for clinical intervention are outlined.

Adult↗

Permanent atrial pacing in cardiac transplant patients.

Thirteen out of 223 consecutive cardiac transplant patients required permanent pacemaker implantation; 11 for sinus node dysfunction and 2 for complete AV block. Patients with sinus node dysfunction were considered for AAIR mode pacemakers if they had intact AV conduction defined as a Wenckebach point of > 120 beats/min. Ten of 11 patients with sinus node dysfunction had a single atrial lead placed. Atrial lead placement was most easily accomplished with a straight, active fixation lead and the use of manually curved stylets to find an optimal position in the donor atrium, although active fixation leads with a preformed atrial J were used as well. Two leads dislodged requiring revision. In contrast, only 1 of 250 atrial leads implanted in nontransplanted hearts dislodged (P < 0.0001). Transvenous endomyocardial biopsies have not caused atrial lead dislodgment. Most transplant recipients requiring permanent pacing have intact AV nodal function and require only atrial pacing. Atrial lead dislodgment requiring lead revision occurs more frequently in heart transplant recipients than in native hearts. Use of a straight active fixation lead with a manually formed curve in the stylet is useful in order to find the optimal position for pacing.

Adult↗

Transsphenoidal surgery for pituitary tumours.

OBJECTIVES: Transsphenoidal surgery (TSS) is the preferred method for the excision of pituitary microadenomas in adults. This study was carried out to establish the long term efficacy and safety of TSS in children. STUDY DESIGN: A 14 year retrospective analysis was carried out on 23 children (16 boys and seven girls), all less than 18 years of age, who had undergone TSS at our centre. RESULTS: Twenty nine transsphenoidal surgical procedures were carried out. The most common diagnosis was an adrenocorticotrophic hormone (ACTH) secreting adenoma (14 (61%) patients). The median length of follow up was 8.0 years (range 0.3-14.0 years). Eighteen (78%) patients were cured after the first procedure. No death was related to the operation. The most common postoperative complication was diabetes insipidus, which was transient in most patients. Other complications were headaches in two patients and cerebrospinal fluid leaks in two patients. De novo endocrine deficiencies after TSS in children were as follows: three (14%) patients developed panhypopituitarism, eight (73%) developed growth hormone insufficiency, three (14%) developed secondary hypothyroidism, and four (21%) developed gonadotrophin deficiency. Permanent ACTH deficiency occurred in five (24%) patients, though all patients received postoperative glucocorticoid treatment until dynamic pituitary tests were performed three months after TSS. CONCLUSIONS: TSS in children is a safe and effective treatment for pituitary tumours, provided it is performed by surgeons with considerable experience and expertise. Surgical complications are minimal. Postoperative endocrine deficit is considerable, but is only permanent in a small proportion of patients.

Adenoma↗

Hazard analysis and critical control point systems applied to public health risks: the example of seafood.

The authors describe the way in which the two components of risk analysis--risk assessment and risk management--can be used in conjunction with the hazard analysis and critical control points concept to determine the allocation of resources at potential critical control points. This approach is examined in the context of risks to human health associated with seafood, and in particular with regard to ciguatera poisoning.

Animals↗

Exploring the possibility of DNA ploidy measurements in tissue sections using liver as a model.

OBJECTIVE: To evaluate DNA image cytometry (ICM) in tissue sections, human and rat liver was used as a model. These tissues have distinct DNA ploidy histograms of mainly diploid (human) and predominantly tetraploid (rat) plus octaploid nuclei. STUDY DESIGN: Section thickness varied from 4 to 12 microns in rat liver and 4 to 10 microns in human liver, in steps of 2 microns. The measurements were made using a commercially available ICM system, strictly following a measurement protocol. RESULTS: Four-micrometer-thick sections gave very broad histograms. Six-micrometer-thick sections gave better results, but with increasing DNA PLOIDY (> 4c), modal peaks were broad and increasingly shifted to the left. Sections of 8-10 microns gave linear results of the 2c, 4c and 8c peaks and also the narrowest peaks. The 12-micron sections of rat liver were more difficult to measure, and the results were not improved. CONCLUSION: The 8-micron sections gave the best results and were easiest to measure. These results are promising, but since liver is a fairly simple model, further studies are required to elucidate whether DNA ploidy measurements can be performed reliably on tissue sections of human tumors.

Animals↗

African-American physicians and smoking cessation counseling.

While African American physicians can play a key role in encouraging black patients who smoke to quit, little is known about the views and activities of these physicians with respect to antitobacco programming. In the process of developing a protocol for encouraging physicians' smoking cessation intervention, 96 African-American physicians completed a survey indicating their knowledge, attitudes, and practices relating to stop smoking counseling. Few physicians reported patient help-seeking behavior and 47.9% cited lack of patient motivation as a key barrier to intervention. Only 46.8% believed that it is possible to accomplish a lot of cessation help in a few minutes time, and 34.4% believed that setting up and maintaining an office protocol would require a great deal of effort. Explaining health risks (71.9%) and enrolling patients in programs (66.6%) were perceived as keys to patient cessation; fewer than half of the physicians surveyed discuss specific strategies for quitting with their patients. Physicians indicated a willingness to offer more counseling in the future and were open to a range of strategies for learning more about effective approaches. Our findings support the need for dissemination of such information, particularly among specialists, to support antitobacco efforts among African-American physicians.

Adult↗

Tsp49I (ACGT/), a thermostable neoschizomer of the Type II restriction endonuclease MaeII (A/CGT), discovered in isolates of the genus Thermus from the Azores, Iceland and New Zealand.

One hundred and forty eight isolates of the genus Thermus, from neutral and alkaline hot water springs on four continents, have been screened for the presence of restriction endonuclease activity. An isolate (SM49) from the island of Sao Miguel, in the Azores, showed a high level of restriction endonuclease activity when a cell-free extract was incubated with lambda phage DNA at 65 degrees C. A Type II restriction endonuclease (Tsp49I) has been partially purified from this isolate and the recognition and cleavage site determined. Tsp49I recognizes the four base sequence ACGT, which is the same as the recognition sequence of the mesophilic Type II restriction endonuclease MaeII. However, unlike MaeII, which cleaves DNA between the first and second bass of the recognition sequence (A/CGT), Tsp49I hydrolyses the phosphodiester bond in both strands of the substrate after the last base of the recognition sequence 5'-ACGT/-3', producing four base 3'-OH overhangs (sticky ends). The enzyme has a pH optimum of 9.0, requires 2 mM MgCl2 for maximum activity and retains full enzyme activity following incubation for 10 min at temperatures up to 8O degrees C. Two further examples of the same restriction endonuclease specificity as Tsp491 were detected in Thermus isolates from Iceland (TspIDSI) and New Zealand (TspWAM8AI). The three MaeII neoschizomers, Tsp49I, TspIDSI and TspWAM8AI, exhibit similar pH optima, heat stabilities and MgCl2 requirements, but differ in their requirements for NaCl and KCl.

Bacteriophage lambda↗

Microbial transformations of steroids--X. Cytochromes P-450 11 alpha-hydroxylase and C17-C20 lyase and a 1-ene dehydrogenase transform steroids in Nectria haematococca.

Nectria haematococca contains four enzymes that metabolise exogenous steroids. Two of these are microsomal cytochromes P-450 which act sequentially on progesterone producing firstly, by side-chain cleavage, the C19 steroid androstenedione (C17-C20 lyase), and then, in a subsequent set of transformations, 11 alpha-hydroxylated derivatives (11 alpha-hydroxylase). Two other conversions occur after side-chain cleavage. Unsaturation, in the form of a double bond at C1-C2, is introduced into the A ring by a catalytically self-sufficient microsomal 1-ene dehydrogenase. This enzyme is specific for C19 substrates. A C17-specific oxidoreductase is also involved in the production of androstenedione and testosterone from progesterone. The lyase, 11 alpha-hydroxylase and 1-ene dehydrogenase were purified to homogeneity.

Androstenedione↗

Sense of belonging and indicators of social and psychological functioning.

Sense of belonging has recently been described and defined as one specific interpersonal process that influences health. The purpose of this study was to examine the relationships between sense of belonging and personal characteristics and selected indicators of social and psychological functioning in men and women. Using a sample of 379 community college students, sense of belonging was examined in relation to social support, conflict, involvement in community activities, attendance at religious services, loneliness, depression, anxiety, history of psychiatric treatment, and suicidality. Results indicated that sense of belonging is closely related to indicators of both social and psychological functioning. These relationships were generally stronger for women than for men. It appears that sense of belonging is a useful concept pertinent to exploration of social and psychological functioning.

Adaptation, Psychological↗

Loss of heterozygosity and microsatellite instability at the retinoblastoma locus in osteosarcomas.

Studies of osteosarcoma cell lines or frozen tissue have detected loss of heterozygosity (LOH) at the retinoblastoma (RB) locus by Southern blot analysis or restriction fragment length polymorphism. Most archived clinical specimens cannot be analyzed by these techniques. We analyzed formalin-fixed, paraffin-embedded samples from 19 cases of osteosarcoma for molecular changes at the RB locus using polymerase chain reaction amplification of polymorphic short tandem repeat sequences (microsatellite repeats). Four repeat sequences, two within and two flanking the RB gene, were analyzed. Fourteen of 18 informative cases (78%) showed molecular changes at the RB locus. LOH was identified in 13 cases (72%). Unexpectedly, microsatellite instability (MI) was found in eight cases (44%). All of the cases of MI involved alterations of more than one repeat unit, and six of eight were associated with LOH. LOH was identified at three unlinked loci in one case and at a single locus in another Microsatellite analysis of archival tissue yields prevalence rates of LOH comparable to those found by other methods and has the added advantage of showing MI. The ability to use formalin-fixed, paraffin-embedded tissue extends genetic analysis to routinely processed surgical material and may permit molecular confirmation of challenging cases of osteosarcoma.

Bone Neoplasms↗

Thermus oshimai sp. nov., isolated from hot springs in Portugal, Iceland, and the Azores, and comment on the concept of a limited geographical distribution of Thermus species.

We examined aerobic, thermophilic, gram-negative bacteria that were isolated from hot springs in Portugal and were identified as Thermus strains and placed in phenetic groups on the basis of their phenotypic characteristics. We determined the composition of the peptidoglycan, identified the respiratory quinones, and determined the mean base composition of the DNA, and the levels of DNA-DNA homology were determined by both the filter hybridization and reassociation rate methods. Thermus aquaticus, Thermus brockianus, and Thermus filiformis were not detected in this collection of organisms, although three Thermus thermophilus strains were identified. We propose that the isolates that belonged to phenetic clusters E and F are members of a new species, Thermus oshimai; the type strain of T. oshimai is strain SPS17.

Azores↗

Further testing of the value of a measurement protocol for DNA ploidy studies using image cytometry. Comparison of results obtained from cytologic and paraffin section preparations.

OBJECTIVE: To apply DNA image cytometry (ICM) to 53 tissue sections of breast cancer and skin melanomas. STUDY DESIGN: DNA ICM was performed on 6-microns-thick sections with a commercially available ICM system, strictly following a previously developed measurement protocol. The histograms were classified according to Auer. RESULTS: In 48 of the 53 cases (90.6%, kappa = .84) there was complete agreement in the Auer class. Discrepancies were one class 1-2 and one class 1-3 shifts (cytocentrifuge samples class 1); one case was class 2 in the section and class 3 in the cytocentrifuge sample, and two cases were class 4 in the cytologic and class 3 in the histologic specimen. CONCLUSION: By paying careful attention to the measurement protocol and technical quality of the material, for certain tumors with relatively small nuclei and limited nuclear overlap, reliable DNA ICM results can be obtained in most cases from 6-microns-thick tissue sections that are comparable to those from single-cell preparations.

Breast Neoplasms↗