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Biomedical subjects

G Lawrence

Publications and source records attributed to G Lawrence.

At least 55 records · Page 3Linked to original sources

The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution.

The complete DNA sequence was determined for strain U1102 of human herpesvirus-6, a CD4+ T-lymphotropic virus with disease associations in immunodeficient settings and a possible complicating factor in AIDS. The genome is 159,321 bp in size, has a base composition of 43% G + C, and contains 119 open reading frames. The overall structure is 143 kb bounded by 8 kb of direct repeats, DRL (left) and DRR (right), containing 0.35 kb of terminal and junctional arrays of human telomere-like simple repeats. Since eight open reading frames are duplicated in the repeats, six span repetitive elements and three are spliced, the genome is considered to contain 102 separate genes likely to encode protein. The genes are arranged colinearly with those in the genome of the previously sequenced betaherpesvirus, human cytomegalovirus, and has a distinct arrangement of conserved genes relative to the sequenced gammaherpesviruses, herpesvirus saimiri and Epstein-Barr virus, and the alphaherpesviruses, equine herpesvirus-1, varicella-zoster virus, and herpes simplex virus. Comparisons of predicted amino acid sequences allowed the functions of many human herpesvirus-6 encoded proteins to be assigned and showed the closest relationship in overall number and similarity to human cytomegalovirus products, with approximately 67% homologous proteins as compared to the 21% identified in all herpesviruses. The features of the conserved genes and their relative order suggested a general scheme for divergence among these herpesvirus lineages. In addition to the "core" conserved genes, the genome contains four distinct gene families which may be involved in immune evasion and persistence in immune cells: two have similarity to the "chemokine" chemotactic/proinflammatory family of cytokines, one to their peptide G-protein-coupled receptors, and a fourth to the immunoglobulin superfamily.

AIDS-Related Opportunistic Infections↗

Blockade by botulinum neurotoxin B of catecholamine release from adrenochromaffin cells correlates with its cleavage of synaptobrevin and a homologue present on the granules.

Botulinum neurotoxin type B blocks transmitter release via a selective endoproteolysis of the small clear vesicle membrane protein synaptobrevin that is essential for neuro-exocytosis. In view of the distinct characteristics of exocytosis of adrenochromaffin granules and considering the controversy over the presence of synaptobrevin on the latter, this study aimed to determine the molecular basis of the inhibition by this toxin of secretion from chromaffin cells. Thus, affinity-purified antibodies against a synaptobrevin synthetic peptide were used to quantify its concentrations in subcellular fractions of bovine adrenal medulla. The latter, as well as density gradient centrifugation and size-exclusion chromatography, showed that > 70% of the protein copurifies with the granules and their marker, dopamine beta-hydroxylase. Notably, much lower concentrations of synaptobrevin and synaptophysin were found in chromaffin granules than in synaptic small clear vesicles (approximately 9% and approximately 2%, respectively); however, isolated granule membranes exhibited greater enrichments (approximately 35% and approximately 9%). A second immunoreactive protein was colocalized with synaptobrevin on chromaffin granules; in view of its susceptibility to the toxin and lower M(r), it is assumed to be cellubrevin and, also, because of its high homology. Involvement of synaptobrevin and cellubrevin in Ca(2+)-triggered granule exocytosis was established by the demonstrated correlation between the extent of botulinum neurotoxin B-induced inhibition of secretion and their selective proteolysis following introduction of the toxin into intact chromaffin cells. On the basis of these collective findings, it is concluded that these proteins occur on chromaffin granules and one or both are essential for exocytosis.

Adrenal Cortex↗

The detection of latency-associated transcripts of equine herpesvirus 1 in ganglionic neurons.

Neural tissues from specific pathogen-free ponies that had been experimentally infected with equine herpesvirus 1 (EHV-1) were analysed by in situ hybridization. Digoxigenin-labelled EHV-1 BamHI fragments spanning almost the entire EHV-1 genome were hybridized to RNA in tissue sections from latently infected trigeminal ganglia. The BamHI E fragment detected EHV-1 RNA antisense to gene 63 (HSV-1 homologue ICP0) in a small number of neurons. Sixteen other BamHI fragments gave negative results in 20 sections tested with each fragment. Latency associated transcripts (LATs) were localized to the neuronal nuclei. EHV-1 nucleotide sequence data in the region reveals the presence of a putative EHV-1 LAT promoter that shares a similar motifs with the HSV-1 LAT promoter, including the LAT promoter-binding factor, and may have a role in EHV-1 LAT expression.

Amino Acid Sequence↗

Asthma self-management programs can reduce the need for hospital-based asthma care.

UNLABELLED: Mortality from asthma and its complications is increasing as is the expense associated with treating this disease. We hypothesized that an asthma-education program, already in place, had reduced hospitalizations (HOS) and emergency-department (ED) visits for asthmatic patients who participated. METHODS: We compared asthmatic patients' ED visits and HOS for the 12-month periods immediately before and after treatment in our center. METHODS: All patients received physician-directed medical management based upon the National Asthma Education Panel recommendations. One group (PART, n = 13) received instruction in self-management using the peak-flow meter (PFM) and an action plan (AP) to adjust medication dosages in response to changing post-bronchodilator peak-flow meter readings. Average cost for this intervention was $820 (2 visits, each with 60-90 minutes of instruction). The other group (FULL, n = 13), in addition to receiving a PFM and AP, completed a multidisciplinary education program stressing trigger identification and avoidance, environmental control, proactive adjustment of anti-inflammatory agents, and stress management. Average cost for this intervention was $1,700 (multidisciplinary evaluations and 12 hours of instruction). Those who did not enter the education program did so by choice or circumstance (ie, transportation problems, inability to commit the required time for the program, insurance denial). RESULTS: Of the 13 PART-group subjects, 8 experienced all 31 ED and/or HOS in the year prior to our program. Four of 13 accounted for the 15 ED and/or HOS after discharge from the program (50% improvement, p < 0.05). Of the 14 patients in the FULL group, 7 accounted for 25 ED and/or HOS prior to the program. There were no ED and/or HOS after the program (100% improvement, p < 0.05). CONCLUSION: Based on this sample, it is evident that both PART and FULL programs can significantly impact the frequency with which hospital-based asthma care is required and thus reduce the overall cost of caring for patients with asthma.

Asthma↗

Correlation of thyroid histopathology with fine needle aspiration of thyroid nodules: the St. Agnes Hospital experience.

Fine needle aspiration (FNA) cytology results were compared with thyroid tissue pathology reports in 44 patients who underwent thyroidectomy. Benign (12) and malignant (10) thyroid cytology interpretations correlated with the final thyroid histopathology. Of 22 thyroid aspirate samples that were considered suspicious or indeterminate, 5 were malignant and 17 were benign. The data obtained support the efficacy of FNA in the evaluation of thyroid nodular disease.

Adenocarcinoma, Papillary↗

Beauty and the beast--a medical essay.

Breast cancer is the most common cancer among women, and the incidence of the cancer is on the rise. However, public education and screening have permitted the detection of this disease at an early stage. This early presentation has open opportunities for physicians to offer therapeutic options tailored both to the individual's disease process and the patient's desires. There is an increased responsibility on the doctor (s) to view an individual's breast cancer as a subset of the disease, for which one or more treatment modalities may be combined. The combination is designed to deliver the best cure rates with the least risk of acute complications and late morbidity. This paper outlines the pathological determinants of breast cancer and their impact on the behavior of the disease. Algorithms are presented to view and manage the patient's overall disease process. The subtleties in the medical literature on the management and clinical results of breast cancer are discussed.

Beauty↗