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Biomedical subjects

A Sinclair

Publications and source records attributed to A Sinclair.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1984

Relative stability of guanosine-cytidine diribonucleotide cores: a 1H NMR assessment.

Proton NMR was used to study the secondary structure and melting behavior of six self-complementary oligoribonucleotide tetramers, each containing two guanosine and two cytidine residues (GGCC, CCGG, GCCG, CGGC, GCGC, and CGCG). GGCC and CCGG formed perfect duplexes containing four G.C base pairs with Tms of 54 and 47.8 degrees C, respectively; GCCG and CGGC formed staggered duplexes with two G.C base pairs and four 3' double-dangling bases, with Tms of 35.5 and 29.2 degrees C, respectively; GCGC formed a perfect duplex with a Tm of 49.9 degrees C, while CGCG formed a staggered duplex with a Tm of 36.9 degrees C. From these results, an order of stability of the cores containing two G.C base pairs was proposed: GC:GC is more stable than GG:CC which is more stable than CG:CG. The RY model for secondary structure stability prediction was applied to the above tetramers with reasonable success. Suggestions for refinements are discussed.

Base Sequence↗
PubMed1984

Prehospital advanced life support: benefits in trauma.

The Boston Emergency Medical Service system was studied to determine the effects of Advanced Life Support (ALS) prehospital trauma care compared to Basic Life Support (BLS) treatment. The severity of injury and clinical status of patients was defined and monitored using the Trauma Score (TS) described by Champion. The TS on arrival at the hospital increased significantly more for patients receiving field ALS care than for patients transported by BLS ambulances (p = 0.01). ALS resuscitation had most influence on patients with TS 4-13 and did not delay transport time. Furthermore, a positive change in prehospital TS was significantly related to an increased chance of long-term survival for any given severity of injury (p = 0.0002). From these data we conclude that the TS is useful for prehospital triage and that appropriate field ALS resuscitation results in more favorable outcomes following major trauma.

Adult↗
PubMed1984

A three-frequency audiogram for use in industry.

Some form of audiometric screening forms part of any comprehensive hearing conservation programme, but because of the large numbers of workers exposed to noise, it is suggested that routine audiometry using an 8-frequency test preceded by history and examination makes undue demands on limited resources. It is proposed that a simple 3-frequency test without prior preparation of subjects is adequate for the purposes of industrial audiometry. Men whose hearing threshold was worse than 20 dB at 1, 2, or 4 kHz were considered to have failed the 3-frequency test and 150 such cases were randomly selected and subjected to a full 8-frequency audiogram. The results were then assessed for numerical accuracy and diagnostic reliability. The results of the 3-frequency test were marginally worse than the 8-frequency audiogram by 2.33 to 4.98 dB, and the comparison of the two tests as a diagnostic tool gave a concordance rate of 79%-80% (p = 0.00001) between the two physicians who examined the results and a level of interpersonal agreement of 87% for the 3-frequency test and 89% for the full audiogram. If audiometric screening is to be offered to the whole population at risk it should be simple, rapid, and accurate enough to detect hearing loss before disability develops so that those individuals may be counselled. It is suggested that the 3-frequency test fulfils this purpose, demonstrates the "reasonably practicable" approach of recent legislation, and does not unnecessarily divert resources from other key tasks in the practice of occupational medicine.

Audiometry↗
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↗
PubMed1978

Roux-Y intestinal bypass for administration of sorbents in uremia.

In order to minimize interaction of sorbents with food and digestive secretions, an intestinal bypass was created for sorbent administration in normal and uremic rats (N = 18) and goats (N = 5). Two separate limbs of small intestine were fashioned, one for food absorption and one for sorbent function, which joined at a Roux-Y anastomosis before the cecum. Particulate sorbent suspensions were injected into the intestine via a cutaneous stoma, and were excreted with food wastes in the feces. In animals with normal kidneys, sorbent function was calculated from changes in fecal and urinary excretion. Nitrogen clearance by the intestinal bypass was 20 to 40% of normal renal clearance in rats and goats. Potassium clearance was 40% of normal renal clearance in rats, and over 100% in goats. Sorbent treatment in anephric animals caused serum urea nitrogen concentrations to stabilize at 210 mg/dl in rats, and 110 mg/dl in goats. Serum potassium concentrations stabilized at 4.5 mEq/liter in rats, and fell to 2 mEq/liter in goats. Water balance was maintained by producing a mild osmotic diarrhea. At least three substances which accumulate in renal failure--urea, potassium, and water--were removed in therapeutically significant amounts.

Animals↗