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Biomedical subjects

A Sinclair

Publications and source records attributed to A Sinclair.

At least 55 records · Page 3Linked to original sources

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

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

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

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

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

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

Effect of vagotomy on the quantitative histological distribution of histamine and histidine decarboxylase in the rat stomach.

Determinations were made of the quantitative histological distribution of histamine and histidine decarboxylase in the body of the glandular stomach of fed and 14-hr fasted rats subjected to pyloroplasty and to pyloroplasty with vagotomy for comparison with untreated rats. Pyloroplasty on fasted rats had no significant effect on the concentration of histamine which was localized predominantly in the chief cell zone. However, the superimposed vagotomy was associated with some increase in the concentration. With the fed rats, the concentration was essentially unchanged from normal in either group of operated animals and it also was about the same as that in the normal fasted group. Histidine decarboxylase activity, which was also localized predominantly in the chief cell zone, underwent an increase in concentration following pyloroplasty of the fasted rats; no additional effect was observed with added vagotomy. The higher concentration of the enzyme activity in the fed rats was markedly further elevated in both groups of operated animals but these groups did not differ significantly from one another. An explanation of the elevation of histidine decarboxylase activity following pyloroplasty requires further investigation, but the lack of effect of the superimposed vagotomy on the enzyme activity would appear to rule out direct vagal control as the sole factor in determining the enzyme function at this site.

Animals

The measurement of radiant temperature in neonatal thermal environments.

Heat exchange through radiation is recognized as the dominant mode of heat transfer for an infant nursed in an incubator or warmer. A radiometer was constructed to measure the planar radiant temperature experienced by the infant. Two heat-flow sensors of different emissivities were mounted onto a heat sink such that one measured principally convective heat exchange while the other measured convective and radiant heat exchange. The radiant heat exchange was obtained from the difference between these values, from which the planar radiant temperature could be calculated. The spatial variation in planar radiant temperatures within an incubator and warmer was determined by orienting the instrument towards the five orthogonal hemispheres sensed by the infant abdomen, sides, head, and feet. In the incubator, the spatial variation in radiant temperatures exceeded 2 degrees C, or four times the spatial variation in air temperatures (0.5 degrees C). The radiant warmer had a spatial variation of 18 degrees C in radiant temperature at three-fourths of maximum power, corresponding to a variation in heat flux over the infant's surface of 100 W/m2. This thermal asymmetry would be expected to influence the variation in surface skin temperature, and thus the thermal stimuli to the infant thermoregulatory system. Further research is needed to understand the clinical significance of this asymmetry. Furthermore, the precise control over air temperature in modern incubators provides a false sense of thermal control and stability. Radiant temperature needs to be measured in addition to air temperature if the thermal performances of incubators and warmers are to be fully understood.

Calibration