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Biomedical subjects

R Briggs

Publications and source records attributed to R Briggs.

At least 37 records · Page 2Linked to original sources

Forearm vascular responsiveness to prolonged venous occlusion in normal subjects.

Fourteen normal subjects (18-42 y) were studied using venous occlusion plethysmography to investigate the characteristics and reproducibility of the forearm vasoconstrictor response following a prolonged venous occlusion stimulus. Upon release of the stimulus, a transient vasodilation is followed by a vasoconstriction. As the stimulus of venous occlusion pressure increased (40, 60, 80, and 100 mmHg for 5 min), there was a significant increase in maximum flow (p = 0.01). Minimum relative flow (minimum divided by control) was unchanged except at the highest occlusion pressure (0.49 +/- 0.05, 0.38 +/- 0.04, 0.47 +/- 0.07, 0.66 +/- 0.12, p = 0.04). As venous occlusion duration increased (3, 4, 5, and 6 min at 80 mmHg), there was no significant change in minimum relative flow (p = 0.73). With increasing ambient temperature (18, 23, and 28 degrees C), there were no significant changes in maximum or minimum relative flows (p = 0.40 and 0.25, respectively). Minimum relative flow was not significantly altered following occlusion with a 2.5-cm cuff vs. a 10-cm cuff (p = 0.77). Thus, the vasoconstriction response was reproducible over a range of venous occlusion stimuli and experimental conditions. We conclude that dynamic vascular responsiveness to prolonged venous occlusion can be measured by venous plethysmography and that calculation of the minimum flow relative to control flow is an appropriate and reproducible index of the vasoconstrictor response. Based on our studies and to conveniently measure these changes, we recommend a 10-cm venous occlusion cuff, with a pressure < or = 80 mmHg, for durations < or = 5 min, in an ambient temperature of 23 degrees C.

Adolescent↗

Different requirements for productive interaction between the active site of HIV-1 proteinase and substrates containing -hydrophobic*hydrophobic- or -aromatic*pro- cleavage sites.

The sequence requirements for HIV-1 proteinase catalyzed cleavage of oligopeptides containing two distinct types of junctions (-hydrophobic*hydrophobic- or -aromatic*Pro-) has been investigated. For the first type of junction (-hydrophobic*hydrophobic-) the optimal residues in the P2 and P2' positions were found to be Val and Glu, respectively, in accord with recent statistical analysis of natural cleavage sites [Poorman, R. A., Tomasselli, A. G., Heinrikson, R. L., & Kézdy, F. J. (1991) J. Biol. Chem. 266, 14554-14561]. For the -aromatic*Pro- type of junction, in the specific sequence context studied here, the value of Glu in the P2' position was again observed. An explanation for the inefficient cleavage observed for peptides with the sequence -Val-Tyr*Pro- has been provided from molecular modeling of the putative enzyme-substrate complex. A significant effect upon cleavage rates due to the amino acid in the P5 position has also been documented. While lysine in the P5 position in one sequence of the -hydrophobic*hydrophobic- type produces a peptide cleaved very efficiently (kcat greater than 15 s-1 for Lys-Ala-Arg-Val-Nle*p-nitrophenylalanine-P2'-Ala-Nle-NH2, for P2' = Glu, Gln, Ile, Val, or Ala), for substrates of the -aromatic*Pro- type, the P5 residue can exert either a positive or negative effect on cleavage rates. These results have again been interpreted in light of molecular modeling. We suggest that interaction of the substrate sequence on the periphery of the active site cleft may influence the match of the enzyme-substrate pair and, hence, control the efficiency of catalysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Comet Halley as an aggregate of interstellar dust and further evidence for the photochemical formation of organics in the interstellar medium.

Photolysis of mixtures of CO:NH3:H2O at 12 K results in the formation of an organic residue which is not volatile in high vacuum at room temperature. Analysis of this fraction by GC-MS resulted in the detection of C2-C3 hydroxy acids and hydroxy amides, glycerol, urea, glycine, hexamethylene tetramine, formamidine and ethanolamine. Use of isotopically labeled gases made it possible to establish that the observed products were not contaminants. The reaction pathways for the formation of these products were determined from the position of the isotopic labels in the mass spectral fragments. The significance of these findings to the composition of comets and the origins of life is discussed.

Dust↗

Instrumentation control and automation in the control of biological effluent treatment.

The role of instrumentation, control, and automation (ICA) in the management, operation, and control of domestic and industrial wastewater treatment works is examined following an historical account of developments in the UK over the past two decades. Included also are aspects of process optimization and process selection, taking into account size and types of works and populations served. The particular ICA requirements of individual unit processes are examined and the effects of unattended operation and remote supervision are considered. Particular attention is paid to measurement technology, the shortcomings of available instruments and systems, and recent developments of relevance, with particular emphasis being placed on microelectronic and fibre- and electro-optic-based sensors and on the role of advanced commenting methods including expert systems. Progress with biologically based sensors is also discussed.

Automation↗

Conjunctival mast cells and the allergic late phase reaction.

An active model of ocular anaphylaxis was developed in guinea pigs to evaluate the histopathology of the early (EPR) and late (LPR) phase reaction, focusing on the role of mast cells. Five groups (n = 6) of animals were actively immunized by first injecting into each of the axillary and inguinal lymph node areas, 0.25 ml of an emulsion containing 1 mg dinitrophenyl bovine gamma-globulin (DNP-BCG) with 0.5 ml complete Freund's adjuvant. After two weeks, an intramuscular injection of 0.5 ml of an emulsion containing 1 mg DNP-BGG with 0.5 ml of incomplete adjuvant was administered. One month after the first injection, animals were sacrificed after topical ocular challenge with 10 microliters of 1 mg/ml divalent hapten, di-DNP-lysine, in one eye and phosphate buffered saline (PBS) in the fellow eye as control. Clinical reactions were graded over time and histology evaluated at the endpoint (time 0, 0.5, 3, 9, and 24 h). Results showed that all animals clearly developed both an EPR and an LPR, as either a biphasic, multiphasic or prolonged clinical response. A small percentage of mast cells were degranulated at baseline, whereas, at 0.5 h, 95% of mast cells were degranulated in the eyes treated with specific hapten and 25% in the control eyes treated with PBS. At 3 h, 84% of the mast cells were degranulated. This value rose to 89% at 9 h, and remained unchanged at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Management of the facial nerve in skull base surgery.

The facial nerve presents a significant obstacle to adequate surgical exposure of lesions involving the skull base. The evolution of various surgical approaches to the jugular foramen, petrous apex, and lateral facial approaches to the skull base aimed at preserving the seventh cranial nerve are reviewed. Methods and techniques in management of the intratemporal and extratemporal facial nerve are discussed.

Facial Nerve↗

Interaction of lymphocytes and high endothelial venules in irradiated lymph nodes.

After total-body exposure to various doses of ionizing radiation, the ability of lymphocytes to interact specifically with high endothelial venules of rat cervical and mesenteric lymph nodes was analyzed in frozen sections. Following a radiation dose of 1.5 Gy, high endothelial venules remained intact and the binding of unirradiated lymphocytes to the venules was enhanced relative to unirradiated controls. At radiation doses above 5.0 Gy, damage to high endothelial venules was observed histologically as well as assessed functionally. There was a significant decrease in specific lymphocyte-venule binding and a significant increase in nonspecific binding. These findings suggest that radiation-induced damage to high endothelial venules might play a role in radiation-induced immunosuppression by interfering with the normal passage of lymphocytes from the blood into lymph nodes via a specific interaction between lymphocytes and high endothelial venules.

Animals↗

Comparison of bretylium and lidocaine in the prevention of ventricular fibrillation after aortic cross-clamp release in coronary artery bypass surgery.

The authors compared bretylium and lidocaine for reducing the incidence and persistence of ventricular fibrillation following aortic cross-clamp release performed during coronary artery bypass surgery. Thirty-three adult patients scheduled for elective bypass surgery were randomly assigned in a double-blind fashion to receive a bolus of bretylium, 10 mg/kg, lidocaine, 2 mg/kg, or saline, in equal volumes prior to the release of the aortic cross-clamp. Coronary artery bypass surgery was conducted using standard cardiopulmonary bypass (CPB) procedures with systemic cooling to 24 degrees to 28 degrees C. Temperature, arterial blood gases, and electrolytes were recorded. After clamp release, the first electrical rhythm was noted. Abnormal rhythms (ventricular fibrillation) were allowed to persist for 1 to 2 minutes, and if spontaneous conversion to a supraventricular rhythm did not occur, defibrillation with internal DC countershocks was applied. Patients were compared with respect to occurrence of ventricular fibrillation, need for DC countershocks, antiarrhythmic drugs, and inotropic support. There was no significant difference among the groups with respect to age, sex, preoperative medications, past medical histories, ejection fractions, average number of bypasses, cross-clamp times, or temperatures during bypass. The incidence of ventricular fibrillation after aortic cross-clamp removal was: saline 91%, lidocaine 64% (P less than 0.01), and bretylium 36% (P less than 0.01). The number of countershocks required to defibrillate, while lower in the bretylium group, did not reach statistical significance. After cardiopulmonary bypass, cardiac output and systemic vascular resistance were comparable. Bretylium warrants further study in this setting.

Aged↗

Selective isolation of human breast carcinoma cells resistant to the growth-inhibitory effects of retinol.

The anchorage-dependent and anchorage-independent growth of the human mammary carcinoma cell line MDA-MB-231 is inhibited by vitamin A (retinol). Clones resistant to growth inhibition by retinol were isolated from this cell line in soft agar without the use of mutagens. This paper describes the isolation and characterization of the resistant lines. The clones were selectively resistant to retinol. There was significant growth inhibition after treatment with retinoic acid and 13-cis-retinoic acid. The resistant clones maintain their resistance to retinol through multiple passages. Resistance is specific for inhibition of growth, because treatment of the resistant clones results in stimulation of plasminogen activator activity without alteration of proliferation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows no significant qualitative or quantitative difference in the clones when compared with the MDA-MB-231 parent line. Although the clones do not regrow in soft agar, they are tumorigenic in athymic mice. Tumors are produced at a rate similar to the parent line. The advantage of this isolation method is that sensitive and resistant malignant cells derived from the same parent cell line are now available to study the molecular events involved in the inhibition of cellular proliferation after treatment with retinol.

Animals↗

Histology of ocular late-phase reaction in guinea pigs passively sensitized with IgG1 antibodies.

The ocular late-phase reaction (LPR) is a mast cell-dependent, delayed inflammatory reaction developing 4-12 h after the early-phase reaction (EPR). We developed a passive IgG1 antibody-dependent guinea pig model that clinically reproduced the biphasic reaction of ocular EPR and LPR. An EPR was observed in all animals; a biphasic, multiphasic or prolonged inflammation was observed in the animals maintained for 9 and 24 h. The substantia propria of eyes undergoing EPR (0.5 h) showed intense edema, mast cell degranulation (88%), and 4-fold increase in eosinophils. At 9 h, the neutrophils and eosinophils had increased 11- and 25-fold, respectively. The number of basophils and lymphocytes was significantly increased compared to the controls (p less than 0.05). Of the mast cells, 45% were degranulated compared with 19% for controls. Cellular reactions had subsided by 24 h. Conjunctival epithelium also accumulated inflammatory cells as did the stroma of the lid skin. These histologic changes in ocular tissues undergoing anaphylaxis demonstrated that mast cell degranulation was most severe in the early phase, whereas neutrophil, eosinophil, and basophil accumulation was most marked in the late phase.

Animals↗

Altered binding of human histone gene transcription factors during the shutdown of proliferation and onset of differentiation in HL-60 cells.

Two sites of protein-DNA interaction have been identified in vivo and in vitro in the proximal promoter regions of an H4 and an H3 human histone gene. In proliferating cells, these genes are transcribed throughout the cell cycle, and both the more distal site I and the proximal site II are occupied by promoter-binding factors. In this report we demonstrate that during the shutdown of proliferation and onset of differentiation of the human promyelocytic leukemia cell line HL-60 into cells that exhibit phenotypic properties of monocytes, histone gene expression is down-regulated at the level of transcription. In vivo occupancy of site I by promoter factors persists in the differentiated HL-60 cells, but protein-DNA interactions at site II are selectively lost. Furthermore, in vitro binding activity of the site II promoter factor HiNF-D is lost in differentiated cells, and nuclear extracts from differentiated cells do not support in vitro transcription of these histone genes. Our results suggest that the interaction of HiNF-D with proximal promoter site II sequences plays a primary role in rendering cell growth-regulated histone genes transcribable in proliferating cells. It appears that while cell-cycle control of histone gene expression is mediated by both transcription and mRNA stability, with the shutdown of proliferation and onset mRNA stability, with the shutdown of proliferation and onset of differentiation, histone gene expression is regulated at the transcriptional level.

Base Sequence↗

Muscle acidosis during static exercise is associated with calf vasoconstriction.

In this study we measured (n = 6) the phosphocreatine-to-inorganic phosphate ratio (PCr/Pi), Pi, and pH with 31P-nuclear magnetic resonance (31P-NMR) in the human forearm during static work at 30% of maximal voluntary contraction (MVC) for 2 min followed immediately by 3 min of circulatory arrest (forearm arterial occlusion). Static exercise, with its central volitional and skeletal muscle metabolic and mechanical afferent components, caused a rise in heart rate (HR, 32%), blood pressure (BP, 29%), and calf vascular resistance (calf R, 30%). During forearm occlusion after static exercise, HR returned to base line, the increase in BP was attenuated by 30%, and calf R remained elevated and unchanged. The percent change in calf R was correlated with forearm cellular pH (R = 0.56, P less than 0.001) but only weakly associated with PCr/Pi (R = 0.33, P less than 0.042). 30% MVC for 1 min followed by arterial occlusion (3 min) reduced PCr/Pi by 65% and pH by 0.16 U (P less than 0.05). Calf R was unchanged. Circulatory arrest alone (20 min) caused no change in either pH or calf R but large changes in PCr/Pi (50% reduction). We conclude that 1) there is an association between forearm cellular acidosis and calf vasconstriction during static forearm exercise and 2) large changes in PCr/Pi without concomitant changes in pH are not associated with changes in calf R.

Acidosis↗

Phlegmasia cerulea dolens and its association with hypercoagulable states: case reports.

Six patients who developed phlegmasia cerulea dolens are described. All patients had associated hypercoagulable states: heparin-induced thrombocytopenia (2 patients), congenital deficiency of protein C (1 patient), and antithrombin III deficiency (3 patients). Their clinical course and management are discussed. Previous reports have failed to show a definite correlation between phlegmasia cerulea dolens and hypercoagulable states because of an unavailability of appropriate diagnostic techniques. Phlegmasia cerulea dolens is a life- and limb-threatening complication. An appreciation of underlying hypercoagulable states is essential to proper management, prophylaxis, and treatment of this disorder.

Adult↗

Monitoring and evaluating psychotropic drug use for persons with mental retardation: a follow-up report.

Psychotropic drug use in a large Massachusetts public facility for mentally retarded adults was reduced and maintained at approximately 20% over an 8-year period during which a monitoring and evaluating procedure (including interdisciplinary team review, identification of target behaviors, and concurrent alternative forms of treatment) was in effect. Average daily dosages for antipsychotics were lower than usually reported in institutional settings. Follow-up of 225 individuals receiving psychotropics showed that of 130 withdrawn, 69% remained off drugs, demonstrating sustained effectiveness of the review process.

Adult↗

Regional distribution of pre- and postsynaptic glutamatergic function in Alzheimer's disease.

Ca2+/Cl- -independent L-[3H]glutamate- and sodium-dependent D-[3H]aspartate binding assays were used to assess the integrity of N-methyl-D-aspartate (NMDA) receptors and glutamate uptake sites in a number of areas from control and Alzheimer's diseased brain. NMDA receptor densities were unchanged in all areas tested. In contrast, significant reductions in the number of glutamate terminals were seen in the hippocampus of the Alzheimer's samples. A smaller reduction was seen in the caudate nucleus but this failed to reach significance. No such reductions were seen in either the frontal or parietal cortices.

Aged↗

Presynaptic and postsynaptic glutamatergic function in Alzheimer's disease.

Sodium dependent D-aspartate and Ca2+/Cl-independent L-glutamate binding assays were used to assess the integrity of glutamate uptake sites and postsynaptic NMDA receptor levels in control and Alzheimer's disease temporal cortex. The number of glutamate uptake sites was significantly and substantially reduced in accordance with previous findings. However, NMDA receptor levels were unchanged. This finding suggests that glutamatergic presynaptic elements are severely reduced in Alzheimer's disease, whilst postsynaptic elements remain intact.

Aged↗

Boom in private rest homes in Southampton: impact on the elderly in residential care.

A survey in 1986 of 450 elderly people in 51 private rest homes and 206 residents of seven local authority (part III) homes in the Southampton area showed no significant difference in overall dependency between the two populations. Although age and sex distributions of the residents of part III homes had remained the same between 1982 and 1986, the average level of dependency had fallen significantly. Since the provision of places increased because of expansion in the private sector residential care institutions are generally catering for a more independent population.

Activities of Daily Living↗