What causes the enhancement of activity of factor VIIa by tissue factor?
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Catalytic Domain↗
Biomedical subjects
R Duke
Publications and source records attributed to R Duke.
Types of Glaucoma and recent trends applied in treatment: Observations from a Glaucoma Training Workshop in the Gambia.
OBJECTIVES: To determine types of glaucoma seen and the recent trends applied in treatment, a retrospective non-comparative case-series study was conducted in the Eye Unit of the Royal Victoria Hospital, Banjul, The Gambia. METHODS: The records of the 88 patients(145 eyes) seen during the glaucoma training workshop(organised by Prof.James Standefer, a clinical ophthalmologist from Minneapolis, U.S.A.) which held between 3rd and 14th of September, 2001, were analysed for types of glaucoma and treatment given. All but one patient who was a baby underwent the following tests: visual acuity measurement using the illiterate E-Chart with multiple optotypes; tonometry using the Schiotz tonometer with the 5.5g weight; oblique flashlight test; Van Herrick's estimation of the angle depth; pupillary reactions to light; Slitlamp biomicroscopy; gonioscopy using the 4-mirror pressure gonioprism; fundoscopy using the +78D Volk lens and confrontational visual field analysis. RESULTS: 27 eyes did not have definite glaucoma. Out of the remaining 118 eyes, 65(55.08%) had POAG;17(14.41%)ACG out of which 8 were CACG and 2 acute ACG. 8 eyes had pseudoexfoliation of the lens capsule with or without glaucoma. In the frail and elderly, guttae Timoptol 0.5% was given once daily. 27 eyes had trabeculectomy; all were with releasable sutures and intraoperative application of 5-Fluorouracil. 3 eyes had laser trabeculoplasty and 5, diode laser transscleral cyclophotocoagulation. CONCLUSIONS: POAG was the commonest type of glaucoma seen. Pseudoexfoliation of the lens capsule with or without glaucoma and ACG are not very rare in The Gambia. In the frail and elderly, guttae Timoptol 0.5% was given once daily and none at all in painless glaucoma-blind eyes. Trabeculectomy with releasable sutures and intraoperative application of 5-FU has a very satisfactory pressure-lowering effect. KEYWORDS: glaucoma; treatment; the Gambia.
Gambia↗
Absence of elevated anti-alpha-synuclein and anti-EBV latent membrane protein antibodies in PD.
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Antibodies, Viral↗
Platelet-derived growth factor stimulation of monocyte chemoattractant protein-1 gene expression is mediated by transient activation of the phosphoinositide 3-kinase signal transduction pathway.
Platelet-derived growth factor (PDGF) stimulates transcription of an immediate-early gene set in Balb/c 3T3 cells. One cohort of these genes, typified by c-fos, is induced within minutes following activation of PDGF receptors. A second cohort responds to PDGF only after a significant time delay, although induction is still a primary response to receptor activation as shown by "superinduction" in the presence of the protein synthesis inhibitor cycloheximide. PDGF-receptor activated signaling pathways for the "slow" immediate-early genes are poorly resolved. Using gain-of-function mutations together with small molecule inhibitors of kinase activity, we show that activation of PI 3-kinase is both necessary and sufficient for the induction of the prototype slow immediate-early gene, monocyte chemoattractant-1 (MCP-1). Following activation of PDGF receptors, MCP-1 mRNA does not begin to accumulate for at least 90 min. However, only a brief (10 min) interval of PI 3-kinase activity is required to trigger this delayed response. The serine/threonine protein kinase, Akt/PKB, likely functions as a downstream affector of PI 3-kinase for this induction.
3T3 Cells↗
Isolation of the human PC6 gene encoding the putative host protease for HIV-1 gp160 processing in CD4+ T lymphocytes.
Production of infectious HIV-1 virions is dependent on the processing of envelope glycoprotein gp160 by a host cell protease. The protease in human CD4+ T lymphocytes has not been unequivocally identified, yet members of the family of mammalian subtilisin-like protein convertases (SPCs), which are soluble or membrane-bound proteases of the secretory pathway, best fulfill the criteria. These proteases are required for proprotein maturation and cleave at paired basic amino acid motifs in numerous cellular and viral glycoprotein precursors, both in vivo and in vitro. To identify the gp160 processing protease, we have used reverse transcription-PCR and Northern blot analyses to ascertain the spectrum of SPC proteases in human CD4+ T cells. We have cloned novel members of the SPC family, known as the human PC6 genes. Two isoforms of the hPC6 protease are expressed in human T cells, hPC6A and the larger hPC6B. The patterns of SPC gene expression in human T cells has been compared with the furin-defective LoVo cell line, both of which are competent in the production of infectious HIV virions. This comparison led to the conclusion that the hPC6 gene products are the most likely candidates for the host cell protease responsible for HIV-1 gp160 processing in human CD4+ T cells.
Amino Acid Sequence↗
Immunologic cytotoxicity in alopecia areata: apoptosis of dermal papilla cells in alopecia areata.
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Alopecia Areata↗
Recurrent subarachnoid hemorrhage due to endometriosis.
A woman with a long history of menstruation-related headaches, at times associated with papilledema and brief episodes of unresponsiveness, was experiencing recurrent cryptogenic subarachnoid hemorrhage. Although the source of hemorrhage was never identified with certainty, strong circumstantial evidence suggested the presence of ectopic endometrial tissue in the spinal canal. Suppression of estrogen levels has prevented further episodes of hemorrhage.
Adult↗
Effect of tetrahydroaminoacridine on cognition, function and behaviour in Alzheimer's disease.
OBJECTIVE: To determine the efficacy of tetrahydroaminoacridine (THA) in Alzheimer's disease. DESIGN: Randomized, double-blind, multiple crossover trial with three treatment periods, each consisting of 3 weeks of active drug therapy and 3 weeks of placebo administration. SETTING: Referral-based geriatric practice in a community hospital. PATIENTS: Thirty-four patients with moderate to severe Alzheimer's disease. Subjects were included if they had stage 3 to 6 disease (as determined by the Reisberg scale) and had not been taking psychotropic drugs for at least 1 month and if informed consent had been obtained from the patients and their next of kin. INTERVENTIONS: Fifty to 100 mg of THA daily and matched placebo. RESULTS: Of the initial 34 patients 14 experienced liver toxicity and 3 gastrointestinal side effects during the study; however, all 22 who completed the study were able to tolerate at least the minimum dose. For the 22 patients there was no clinically or statistically significant effect of THA on cognition, functional status or behaviour. The results for individual patients showed no subgroup of THA-responsive patients. CONCLUSION: THA has no clinically important benefits in Alzheimer's disease and is associated with appreciable toxic effects.
Activities of Daily Living↗
Heparin in the treatment of thromboembolic stroke.
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Clinical Trials as Topic↗
Tumorigenic human squamous lung cancer cells have defined cell surface carbohydrates that are absent from nontumorigenic cells.
Cells of cloned lines derived from human squamous lung carcinomas spontaneously become heterogeneous with respect to several tumor-associated cell surface carbohydrates such as the sialosyl-Lea oligosaccharide antigen or the recently described oligosaccharide recognized by monoclonal antibody 43-9F. Subclones derived from these cultures are initially homogeneous with respect to the presence or absence of a specific cell surface carbohydrate but gradually revert back to a heterogeneous population. Cells of homogeneous subclones having both the sialosyl-LEa and 43-9F cell surface antigens and other subclones lacking them were injected subcutaneously in nude mice. All clones expressing these tumor-associated cell surface carbohydrates were found to be highly tumorigenic, whereas those lacking them were nontumorigenic or, at most, weakly tumorigenic. Clones having the tumor-associated cell surface carbohydrates were more resistant to cytotoxic attack by purified mouse natural killer cells than those clones lacking these carbohydrates, suggesting that the tumorigenicity of the former clones may be influenced by immunoprotective effects of these novel carbohydrates.
Animals↗
Quality assurance review: improving diagnostic accuracy of percutaneous needle biopsy.
Adequate pathologic slide preparation of percutaneous fine-needle biopsy (PFNB) specimens is necessary to maximize sensitivity and yield a tissue diagnosis. We present a quality control review of our biopsy technique and results in 71 aspiration biopsies done in 59 patients. Immediate cytology slide preparation in the radiology suite enabled us to increase our diagnostic yield from 53% to 84%, and allowed us to preserve PFNB, rather than open biopsy, as the primary diagnostic modality. We recommend regular review of biopsy techniques to confirm adequate diagnostic yields of these procedures.
Biopsy, Needle↗
In vivo production of leukotriene B4 and leukotriene C4 in rabbit colitis. Relationship to inflammation.
Leukotriene B4, a proinflammatory compound, recently has been identified as the major metabolite of arachidonic acid in tissue incubations of human and animal colitis. To determine the relationship of inflammation to the in vivo production of leukotrienes, rabbit colitis was induced by formalin enema followed by intravenous infusion of immune complexes, and serial samples were collected by rectal dialysis. Leukotrienes B4 and C4 were measured by radioimmunoassay after high-pressure liquid chromatography. Prostaglandin E2 was assayed after Sephadex chromatography. Leukotrienes were not detected in control animals. Eicosanoid production progressively increased during development of inflammation and correlated with severity of inflammatory cell infiltration (p less than 0.01). Methylprednisolone decreased prostaglandin E2 but did not significantly reduce leukotrienes or inflammation. These data demonstrate that in vivo production of leukotrienes B4 and C4 correlates with indices of inflammation, consistent with the concept that these eicosanoids contribute to the inflammation of colitis.
Animals↗
Assay methods for 6-keto-prostaglandin F1 alpha in human urine. Comparison of chromatographic techniques with radioimmunoassay and gas chromatography-negative-ion chemical-ionization mass spectrometry.
6-Keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in human urine is considered to be a reflection of renal prostacyclin production. Because of the large amounts of unidentified eicosanoid metabolites in urine that may potentially bind to 6-keto-PGF1 alpha antisera, most radioimmunoassays include chromatographic purification of urine. A comparison of chromatographic techniques and of antisera to 6-keto-PGF1 alpha for the assay of human urine is described. Gas chromatography--negative-ion chemical-ionization mass spectrometry (GC--NICI-MS) was used as the reference method. Radioimmunoassays were performed with each of four antisera combined with each of three chromatographic purification systems (silicic acid, Sephadex LH-20, reversed-phase high-performance liquid chromatography). There was marked variability in the results; however, there was at least one chromatographic method for each antiserum that yielded results comparable to GC--NICI-MS. Direct radioimmunoassay of urine without chromatography yielded markedly elevated and variable results for the four antisera. In contrast, the four antisera gave very similar results with direct assay of media from isolated perfused organs. Thus, for the radioimmunoassay of 6-keto-PGF1 alpha in human urine, each antiserum is sensitive to different contaminants in urine and must be individually matched to a chromatographic purification system.
6-Ketoprostaglandin F1 alpha↗
Urinary thromboxane B2 and prostaglandin E2 in the hepatorenal syndrome: evidence for increased vasoconstrictor and decreased vasodilator factors.
Vasodilatory prostaglandins function to maintain renal perfusion in patients with cirrhosis and ascites. To evaluate the potential contribution of the vasodilator prostaglandin E2 and the vasoconstrictor metabolite thromboxane B2 to the development of the hepatorenal syndrome, we measured urinary excretion of these products in 14 patients with hepatorenal syndrome and in control populations with acute or chronic liver or kidney failure. Radioimmunoassay measurements were confirmed by bioassay and by mass spectrometry. Prostaglandin E2 was decreased compared with healthy controls (2.2 +/- 0.3 vs. 6.3 +/- 0.8 ng/h, p less than 0.01) and compared with acute renal failure (9.6 +/- 2.1 ng/h) and with alcoholic hepatitis (9.2 +/- 3.3 ng/h). Thromboxane B2 concentration was normal in patients with alcoholic hepatitis (0.12 +/- 0.02 vs. 0.15 +/- 0.03 ng/ml) and minimally increased in acute renal failure (0.18 +/- 0.15 ng/ml), but markedly elevated in hepatorenal syndrome (0.69 +/- 0.15 ng/ml, p less than 0.001). Urinary thromboxane B2 concentration fell with improved renal function in 3 patients who survived. These data suggest an imbalance of vasodilator and vasoconstrictor metabolites of arachidonic acid in patients with the hepatorenal syndrome.
Acute Disease↗
Dual effects of antidiuretic hormone on urinary prostaglandin E2 excretion in man.
To evaluate the relationship of renal prostaglandin synthesis to urine-concentrating mechanisms, 14 healthy subjects received antidiuretic hormone (ADH) and the nonpressor ADH analog desamino-d-arginine vasopressin (dD'AVP). Endogenous ADH was increased by water deprivation. Urinary prostaglandin E2 (PGE2) was measured by RIA and by bioassay. ADH, dD'AVP, and dehydration each reduced urinary volume by a similar amount (from 582 +/- 66 to an average of 141 +/- 13 ml/4 h) and similarly increased osmolality (from 231 +/- 13 to 721 +/- 31 mosmol/kg). Dehydration and dD'AVP reduced PGE2 from 44 +/- 4 to 25 +/- 5 and 30 +/- 5 ng/4 h, respectively (P less than 0.01), suggesting an inverse correlation of PGE2 with urine osmolality (r = -0.48; P less than 0.005). In contrast, ADH increased urinary PGE2 to 102 +/- 23 ng/4 h (P less than 0.02). Infusions of another vasoconstrictor peptide, angiotensin II, to six of the subjects doubled urine osmolality and also increased urinary PGE2 excretion. These data do not support the theory that the antidiuretic effect of ADH enhances PG synthesis; instead, the data indicate that ADH has two effects on PGE2 excretion: 1) stimulation, presumably by pharmacological pressor activity, and 2) inhibition by antidiuresis.
Adolescent↗
Deoxycorticosterone and aldosterone clearance and binding in normal and hypertensive man.
Deoxycorticosterone (DOC) may play a role in several hypertensive disorders in man, but the dynamics of DOC metabolism are unclear. To characterize DOC binding to plasma proteins and its MCR, 12 patients with essential hypertension and 10 age-matched controls were studied. In control subjects, the DOC MCR was nearly identical to the stimultaneously measured aldosterone MCR (719 +/- 32 vs. 734 +/- 61 liters/m2 x day, respectively), and the MCRs of both steroids were not significantly different in essential hypertension (682 +/- 49 and 672 +/- 50 liters/m2 x day, respectively). Whole blood MCR was also unaltered by hypertension. The DOC whole blood MCRs were 1056 +/- 85 and 1040 +/- 69 liters/m2 x day for control and hypertensive subjects, respectively. The aldosterone whole blood MCRs were 916 +/- 96 and 941 +/- 67 liters/m2 x min. The similarity of the DOC MCR to the aldosterone MCR suggested minimal binding of DOC to high affinity carrier proteins, and this was confirmed by equilibrium dialysis with [3H]DOC at 37 C. In plasma, 6 +/- 1% of DOC is unbound, 84 +/- 3% is bound to albumin, and only 10 +/- 4% is bound to nonalbumin proteins. We conclude that the dynamics of DOC closely resemble those of aldosterone, with minimal plasma binding to specific binding proteins and high MCR that are unaltered in essential hypertension.
Adult↗
Outbreak of hospital infection with a strain of Staphylococcus aureus resistant to gentamicin and methicillin.
A previously unreported strain of Staphylococcus aureus, resistant to both gentamicin and methicillin, as well as other antibiotics, caused an outbreak of hospital infection involving 17 patinets and 8 staff. In this outbreak none of the patients had received previous aminoglycoside therapy. The epidemic strain was eliminated by the use of strict measures for the control of infection.
Cross Infection↗