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Biomedical subjects

A Sinclair

Publications and source records attributed to A Sinclair.

At least 19 recordsLinked to original sources
PubMed1992

Flow resistance of coaxial breathing systems: investigation of a circuit disconnect.

A clinical incident involving an undetected disconnection occurred during the use of a CPRAM coaxial breathing circuit. The flow resistance of this circuit was evaluated and compared with that of a Bain circuit to determine the factors involved. A differential pressure transducer was used to monitor the pressure drop across each circuit during simulation of controlled ventilation with a fresh gas flow of 6 L.min-1. An Ohio V5 anaesthesia ventilator was adjusted to different flow rates and tidal volumes and a test lung simulated an airway resistance of 2.7 cm H2O.L-1.sec and a compliance of 0.05 L.cmH2O-1. Absolute pressure at the ventilator was also monitored when the circuit was disconnected from the test lung. The CPRAM circuit displayed a pressure drop from the ventilator to the endotracheal tube of 6.3 cm H2O at 60 L.min-1, about twice that found with the Bain. A disconnection at the tracheal connector produced an absolute pressure at the ventilator of 9.6 cm H2O with the CPRAM and 5.5 cm H2O with the Bain. Since the ventilator low pressure alarm was preset to 9.2 cm H2O, the alarm provided a warning with the Bain but not the CPRAM. The elevated flow resistance of the CPRAM circuit was attributed to a restriction in the flow area at the patient end of the circuit. Capnographs or adjustable low-pressure alarms provide more reliable monitoring for breathing circuit disconnects.

Anesthesia, Closed-Circuit↗
PubMed1991

Shiverer jimpy double mutant mice. V. Correlation of genotype and myelin proteins.

We have reexamined the levels of myelin basic protein (MBP) and proteolipid protein (PLP) in the brains of mice bred to carry both the shi/shi and jp/Y hypomyelination defects. The genotype of each putative double mutant was confirmed by direct DNA analysis: shi/shi by Southern blot analysis, and jp/Y by restriction enzyme analysis of polymerase chain reaction-amplified fragments. MBP and PLP levels were assessed by immunoblotting. All putative double mutants were found to be shi/shi. However, examination of the PLP locus revealed both jp and wild-type genotypes, the latter produced by an expected crossover. Animals proven to be shi/shi*jp/Y had no detectable MBP or PLP; those proven to be shi/shi*+/Y (the crossover) had no MBP but had PLP. These results differ from an earlier report of both MBP and PLP in the brains of presumed shi*jp animals.

Animals↗
PubMed1991

Search for a retroviral cause for sarcoidosis: no evidence from peripheral blood studies.

Twenty six patients with sarcoidosis of recent onset or with severe progressive disease were studied for evidence of retroviral infection. Peripheral blood mononuclear cells (PBMC) were cultured in vitro and stimulated with phytohaemagglutinin and interleukin-2. Induction of syncytia (SI) and production of reverse transcriptase (RT) were sought as indicators of possible retroviral infection. PBMC from two patients showed syncytia formation and in one of these two there was associated production of low levels of reverse transcriptase. The remaining patients showed neither RT nor SI activity. The predominantly negative results of this study indicate that sarcoidosis is unlikely to be of retroviral aetiology; however, cell populations from sites of active disease should be studied before drawing this conclusion.

Adult↗
PubMed1990

Failure of ADCC to predict HIV-associated disease progression or outcome in a haemophiliac cohort.

Antibody-dependent cell-mediated cytotoxicity (ADCC) has been described in a number of virus infections and occurs in HIV infection. In spite of numerous studies on the ability of HIV-positive sera to mediate ADCC, it remains unclear whether ADCC has any functional significance. Here we examine serial serum samples from a cohort of haemophilia patients who became infected from a common source in 1984, and show that there is no significant difference in ADCC values between those who remained asymptomatic and those who progressed to disease. This study does not compare effector cell function and clinical status and does not exclude activity against different target cell lineages in vivo.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

The epidermal location and possible feeding site of Psorergates ovis, the sheep itch mite.

Skin biopsies from two Merino sheep heavily infested with Psorergates ovis were immersed in liquid nitrogen and cut into vertical frozen sections stained with lipophilic Sudan IV or Oil Red O and haematoxylin. A survey of the lateral distribution of mite sections showed a majority (ca 80%) were in or within 0.2 mm of the follicle mouth. A survey of vertical distribution showed no mite penetration deeper than inner stratum corneum where 57% of mite sections were seen; 30% were within outer stratum corneum or scurf; 13% were on the outer surface and less than 1% were detached. Lipid was the only material seen within stained mites at a location considered to be gut. This was supported by dosing sheep with quinacrine, taking biopsies at Day 6 and Day 14 and examining frozen sections under blue light. Fluorescent lipid was seen at a location considered to be mite gut. From these results it was recommended that acaricide treatments against P. ovis be lipophilic and administered transepidermally because less than 15% of mites were at a superficial location likely to be reached by topical application.

Animals↗
PubMed1988

Butter-enriched diets reduce arterial prostacyclin production in rats.

Rats were fed diets containing 10%, 30% or 50% energy as fat derived predominantly from butter or lard. The protein content of the diets was maintained at 20%. After three weeks on the diets, the rats were killed and the following parameters measured: prostacyclin production in vitro from abdominal aorta and mesenteric artery; platelet aggregation to ADP and thrombin; fatty acid composition of the phospholipids in plasma, thoracic aorta and liver; smooth muscle reactivity and release of endothelial derived relaxing factor (EDRF) from aortic endothelium stimulated by acetylcholine. There was no significant effect of increasing fat content of the diets (neither lard nor butter) on platelet aggregation. In contrast, prostacyclin production in both the mesenteric artery and the abdominal aorta fell in a concentration-dependent manner in the butter-supplemented rats. However, no effect on prostacyclin production was detected in arteries from the lard-supplemented animals. The effects of the diets on prostacyclin (PGI2) production correlated very well with the changes in plasma, aortic and liver phospholipid arachidonic acid (AA) and eicosapentaenoic acid (EPA) contents. AA decreased in a concentration-dependent manner in the rats fed the butter-enriched diets but did not change in those fed the lard-enriched diets, whereas EPA rose in a concentration-dependent manner in the butter-fed rats and was unchanged in the lard-fed animals. The clear-cut effects of the butter-enriched diets on aortic phospholipid fatty acid composition and aortic PGI2 production were accompanied by a significant reduction in smooth muscle relaxation to EDRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

HTLV-1 infection in tropical spastic paraparesis: lymphocyte culture and serologic response.

All 17 patients with tropical spastic paraparesis (TSP) in a series seen in the United Kingdom have antibodies to the human T cell leukemia virus type 1 (HTLV-1). Cultured peripheral blood lymphocytes from these patients formed multinucleated giant cells and reacted with sera and monoclonal antibodies to HTLV-1 in a manner identical to adult T cell leukemia-lymphoma (ATLL) patient lymphocytes. Western blot analysis failed to reveal any marked difference in the antigens recognized by sera from TSP and ATLL patients. The sera from TSP patients, their asymptomatic relatives and ATLL patients were titrated using the following assays: enzyme-linked immunosorbent assays (ELISA), particle agglutination, antibody-dependent cell-mediated cytotoxicity, and pseudotype neutralization. There were significantly stronger serologic responses in the TSP patients than in their relatives or ATLL patients. High antibody titers in the presence of replicating virus often reflect the antigen load; however, these data are also consistent with the suggestion that neurologic damage in TSP may be immunologically mediated.

Adult↗
PubMed1987

Synthetic peptide homologous to beta protein from Alzheimer disease forms amyloid-like fibrils in vitro.

Progressive amyloid deposition in senile plaques and cortical blood vessels may play a central role in the pathogenesis of Alzheimer disease. We have used x-ray diffraction and electron microscopy to study the molecular organization and morphology of macromolecular assemblies formed by three synthetic peptides homologous to beta protein of brain amyloid: beta-(1-28), residues 1-28 of the beta protein; [Ala16]beta-(1-28), beta-(1-28) with alanine substituted for lysine at position 16; and beta-(18-28), residues 18-28 of the beta protein. beta-(1-28) readily formed fibrils in vitro that were similar in ultrastructure to the in vivo amyloid and aggregated into large bundles resembling those of senile plaque cores. X-ray patterns from partially dried, oriented pellets showed a cross-beta-conformation. A series of small-angle, equatorial maxima were consistent with a tubular fibril having a mean diameter of 86 A and a wall composed of pairs of cross-beta-pleated sheets. The data may also be consistent with pairs of cross-beta-sheets that are centered 71-A apart. [Ala16]beta-(1-28) formed beta-pleated sheet assemblies that were dissimilar to in vivo fibrils. The width of the 10-A spacing indicated stacks of about six sheets. Thus, substitution of the uncharged alanine for the positively charged lysine in the beta-strand region enhances the packing of the sheets and dramatically alters the type of macromolecular aggregate formed. beta-(18-28) formed assemblies that had even a greater number of stacked sheets, approximately equal to 24 per diffracting domain as indicated by the sharp intersheet reflection. Our findings on these homologous synthetic assemblies help to define the specific sequence that is required to form Alzheimer-type amyloid fibrils, thus providing an in vitro model of age-related cerebral amyloidogenesis.

Alzheimer Disease↗
PubMed1987

Comparison of electrical measurements on constant voltage and constant current ECT machines.

Electrical measurements were made during treatment of two groups of patients, one group receiving treatment from a constant current ECT machine and the other from a constant voltage machine. The electrical impedance and energy were calculated and compared for the two groups. More energy was delivered by the constant voltage than by the constant current machine, but the spread of energy delivered was comparable. With a consistent technique for applying the electrodes there is little to choose between these machines, but the constant current machine may be preferred where consistency cannot be achieved.

Acute Disease↗
PubMed1986

Stability of XGCGCp, GCGCYp, and XGCGCYp helixes: an empirical estimate of the energetics of hydrogen bonds in nucleic acids.

The stabilizing effects of dangling ends and terminal base pairs on the core helix GCGC are reported. Enthalpy and entropy changes of helix formation were measured spectrophotometrically for AGCGCU, UGCGCA, GGCGCCp, CGCGCGp, and the corresponding pentamers XGCGCp and GCGCYp containing the GCGC core plus a dangling end. Each 5' dangling end increases helix stability at 37 degrees C roughly 0.2 kcal/mol and each 3' end from 0.8 to 1.7 kcal/mol. The free energy increments for dangling ends on GCGC are similar to the corresponding increments reported for the GGCC core [Freier, S. M., Alkema, D., Sinclair, A., Neilson, T., & Turner, D. H. (1985) Biochemistry 24, 4533-4539], indicating a nearest-neighbor model is adequate for prediction of stabilization due to dangling ends. Nearest-neighbor parameters for prediction of the free energy effects of adding dangling ends and terminal base pairs next to G.C pairs are presented. Comparison of these free energy changes is used to partition the free energy of base pair formation into contributions of "stacking" and "pairing". If pairing contributions are due to hydrogen bonding, the results suggest stacking and hydrogen bonding make roughly comparable favorable contributions to the stability of a terminal base pair. The free energy increment associated with forming a hydrogen bond is estimated to be -1 kcal/mol of hydrogen bond.

Calorimetry↗
PubMed1985

Improved free energies for G.C base-pairs.

Thermodynamic parameters of helix formation are reported for seven oligoribonucleotides containing only G.C pairs. These data are used with the nearest-neighbor model to calculate enthalpies and free energies of base-pair formation for G.C pairs. For helix initiation, the free energy change at 37 degrees C, delta G(0)37, is +3.9 kcal/mol; for helix propagation, the delta G(0)37 values are -2.3, -3.2 and -3.3 kcal/mol for C-G, G-G and G-C neighbors, respectively.

Base Composition↗
PubMed1985

Contributions of dangling end stacking and terminal base-pair formation to the stabilities of XGGCCp, XCCGGp, XGGCCYp, and XCCGGYp helixes.

The role of stacking in terminal base-pair formation was studied by comparison of the stability increments for dangling ends to those for fully formed base pairs. Thermodynamic parameters were measured spectrophotometrically for helix formation of the hexanucleotides AGGCCUp, UGGCCAp, CGGCCGp, GCCGGCp, and UCCGGAp and for the corresponding pentanucleotides containing a 5'-dangling end on the GGCCp or CCGGp core helix. In 1 M NaCl at 1 X 10(-4) M strands, a 5'-dangling nucleotide in this series increases the duplex melting temperature (Tm) only 0-4 degrees C, about the same as adding a 5'-phosphate. In contrast, a 3'-dangling nucleotide increases the Tm at 1 X 10(-4) M strands 7-23 degrees C, depending on the sequence [Freier, S. M., Burger, B. J., Alkema, D., Neilson, T., & Turner, D. H. (1983) Biochemistry 22, 6198-6206]. These results are consistent with stacking patterns observed in A-form RNA. The stability increments from terminal A.U, C.G, or U.A base pairs on GGCC or a terminal U.A pair on CCGG are nearly equal to the sums of the stability increments from the corresponding dangling ends. This suggests stacking plays a large role in nucleic acid stability. The stability increment from the terminal base pairs in GCCGGCp, however, is about 5 times the sum of the corresponding dangling ends, suggesting hydrogen bonding can also make important contributions.

Base Composition↗
PubMed1983

External noninvasive cardiac pacing in out-of-hospital cardiac arrest.

External noninvasive cardiac pacing was applied outside the hospital to 19 patients who had experienced cardiopulmonary arrest and 1 patient with life-threatening bradycardia. Seven patients developed electrocardiographic evidence of pacemaker capture, although only 2 had palpable pulses. The patient with bradycardia was successfully paced. This study demonstrates the feasibility of cardiac pacing in out-of-hospital cardiac arrest but confirms the poor prognosis of asystolic cardiac arrest even with the application of pacing.

Adult↗