Search PubMed⌕ Search

Biomedical subjects

R Drake

Publications and source records attributed to R Drake.

At least 37 records · Page 2Linked to original sources

Earliest Homo.

The origin of our own genus, Homo, has been tentatively correlated with worldwide climatic cooling documented at about 2.4 Myr (million years). It has also been conjectured that members of Homo made the first stone tools, currently dated at 2.6-2.4 Myr. But fossil specimens clearly attributable to Homo before about 1.9 Myr have been lacking. In 1967 a fossil hominoid temporal bone (KNM-BC1) from the Chemeron Formation of Kenya was described as family Hominidae gen. et sp. indet. Although a surface find, its provenance within site JM85 (BPRP site K002) was established and a stratigraphic section provided indicating the specimen's position. This evidence has been affirmed but the exact age of the fossil was never determined, and the absence of suitable comparative hominid material has precluded a more definitive taxonomic assignment. Here we present 40Ar/39Ar age determinations on material from the hominid site indicating an age of 2.4 Myr. In addition, comparative studies allow us to assign KNM-BC1 to the genus Homo, making it the earliest securely known fossil of our own genus found so far.

Animals↗

Evidence for the involvement of a 35-kDa membrane protein in the synthesis of glucosylphosphoryldolichol.

Photoactivatable (beta-32P)5-azidoUDPGlc binds to two proteins in rat liver microsomes. As determined by SDS-PAGE electrophoresis, the molecular masses of the 32P-labeled proteins were found to be 62- and 35-kDa. Binding of the photoprobe to both proteins was inhibited by addition of unlabeled UDPGlc. Labeling of the higher molecular weight protein occurred in the absence of photoactivation. In contrast, formation of the 32P-labeled 35-kDa protein was dependent on exposure of the membranes to UV light (250 nm). Moreover, labeling of the 35-kDa protein required the intact sugar nucleotide and divalent cations and was affected by the level of the endogenous and exogenous dolichylphosphate. All of these results are consistent with the possibility that the 35-kDa membrane protein is a component of glucosylphosphoryldolichol synthase.

Animals↗

Evidence that the synthesis of glucosylphosphodolichol in yeast involves a 35-kDa membrane protein.

In an effort to identify the polypeptide chain of glucosylphosphodolichol synthase (EC 2.4.1.117), yeast microsomal membranes were allowed to react with 5-azido[beta-32P]UDPGlc, a photoactive analogue of UDPGlc, which is a substrate for this enzyme. Upon photolysis the 32P-labeled probe was shown to link covalently to a 35-kDa protein present in microsomal membranes prepared from several wild-type yeast strains. Binding was either reduced or absent in the microsomal membranes from two yeast mutants (alg5 and dpg1) that are known to be defective in the synthesis of glucosylphosphodolichol. The microsomes isolated from a heterozygous diploid strain alg5::dpg1 generated from these two mutants exhibited partial restoration of both the ability to photolabel the 35-kDa protein and the ability to catalyze the synthesis of glucosylphosphodolichol. Microsomal membranes from a mutant strain that synthesized glucosylphosphodolichol but lacked the ability to transfer the glucosyl residue to the growing lipid-linked oligosaccharide (alg6) exhibited labeling with 5-azido[beta-32P]UDPGlc comparable to that found in microsomes from the wild-type strain. In all cases photoinsertion of the probe into the 35-kDa protein correlated with the level of synthase assayed in the microsomal membranes. These results strongly support the conclusion that the 35-kDa protein labeled in these experiments is a component of glucosylphosphodolichol synthase.

Affinity Labels↗

Cyanide and arsenic poisoning by intravenous injection.

A 29-year-old man was found unresponsive a few minutes after self-injecting undetermined amounts of potassium cyanide and sodium arsenite intravenously in a suicide attempt. Treatment with the Lilly Cyanide Antidote kit rapidly resolved the initial coma, despite a whole blood cyanide level of 4.4 micrograms/mL. A 12-hour urine arsenic collection begun on admission showed 10,065 micrograms arsenic/12 hr. The patient received intramuscular BAL initially, which was followed by two ten-day courses of oral D-penicillamine. Complications included upper gastrointestinal tract bleeding requiring transfusion, transient elevations of liver function tests, self-limited complaints of decreased vision with conjunctival hyperemia and photophobia, and an abscess at the injection site. Although specific antidote therapy completely resolved the cyanide toxicity, early and prolonged arsenic chelation did not prevent a mild sensory peripheral neuropathy from developing with onset about 17 days after self-injection.

Adult↗

Left atrial hypertension causes pleural effusion formation in unanesthetized sheep.

We studied the effect of left atrial pressure (LAP) elevation on the formation of pleural effusion in unanesthetized sheep. We prepared the animals by placing catheters in the left atrium, pulmonary artery, femoral artery, and vein. We also placed a balloon catheter in the left atrium. After a recovery period of at least 1 wk, we measured LAP, pulmonary artery pressure (PAP), systemic arterial pressure, systemic venous pressure, cardiac output, plasma protein concentration, and plasma colloid osmotic pressure (pi c). We calculated capillary pressure (Pc) as 0.5(PAP - LAP). We then elevated LAP such that Pc-pi c was between -10 and 19.5 mmHg for 6-24 h. At the end of the experiment, we killed the sheep and measured the volume and protein concentration of the right pleural effusion. We also determined the extravascular fluid to blood free dry weight of the right lung. We found that pleural effusions and pulmonary edema formed when Pc-pi c greater than 5 mmHg. We also found that the pleural effusion volume correlated with the amount of pulmonary edema. Our data show that elevated LAP may cause pleural effusions, but only after pulmonary edema has developed.

Animals↗

Effect of outflow pressure on lung lymph flow in unanesthetized sheep.

Studies in anesthetized animals have shown that the flow rate from lung lymphatics (QL) depends on the pressure at the outflow end of the vessels (Po). We tested this in unanesthetized sheep prepared with chronic lung lymph cannula. We measured QL with the lymph cannula held at various heights above the olecranon and calculated Po as the height + QL X cannula resistance. QL decreased with increases in Po (delta QL/delta Po = -8.2 +/- 6.4 microliter X min-1 X cmH2O-1, mean +/- SD). We increased QL by raising left atrial pressure or infusing Ringer solution or Escherichia coli endotoxin and found that QL was even more sensitive to Po (delta QL/delta Po = -32 +/- 22). Cannula resistance caused a 9-70% reduction in QL. Changes in QL caused by increasing Po were not associated with changes in lymph protein concentration for up to 330 min. This indicates that increases in Po shunt lymph away from cannulated vessels but do not substantially effect microvascular filtration rate. The shunted lymph may flow into other vessels or collect in the lung. We conclude that QL does not accurately represent microvascular filtration rate because it depends on the cannula resistance and position at which the investigator chooses to place the cannula.

Animals↗

An assessment of the schedule for schizotypal personalities and the DSM-III criteria for diagnosing schizotypal personality disorder.

The authors assessed the reliability and validity of the DSM-III criteria for schizotypal personality disorder (SPD) and their measurement by the Schedule for Schizotypal Personalities (SSP) developed by Baron. Additional criteria not in DSM-III were also explored. Consensual clinical ratings of videotaped interviews of subjects were used to validate item content of the SSP and the schizotypal diagnosis. The SSP assessments, with the exception of odd speech, were found to be reliable and valid. Higher cutoff scores than those recommended by Baron may be helpful in discriminating schizotypal from other psychiatric patients. Six of eight DSM-III criteria and all experimental criteria were highly specific for SPD cases but varied widely in their sensitivities. Based on these pilot data, the authors recommend combining all of the criteria into four conceptual categories: 1) self-report cognitive-perceptual disturbances, 2) observable disorders of thought and communication, 3) deficits in drive or affect, and 4) interpersonal difficulties. When three of these were required to make the SPD diagnosis, all of the subjects in the present data set were correctly identified.

Affective Symptoms↗

Contamination of caudal mediastinal node efferent lymph in sheep.

Many investigators have used the chronic sheep lung lymph preparation to collect caudal mediastinal node (CMN) efferent lymph. These investigators have assumed that the lymph collected with the preparation is almost pure lung lymph. We examined 17 sheep for possible systemic contamination to the lymph, and in each sheep we found one to five lymph vessels that ran from the diaphragm to the CMN. Contamination from these vessels would not be eliminated in the chronic sheep preparation. We estimated the flow rate from these vessels to be 3.0 +/- 2.6 (SD) ml/h in anesthetized sheep. This represents 25-60% of the lymph flow rate in the chronic lymph preparation. In five sheep, we also located 1-4 esophageal lymph vessels that entered th CMN. These results show that lymph collected with the chronic sheep lung lymph preparation contains a significant nonpulmonary contamination.

Animals↗

Estimation of the filtration coefficient of pulmonary exchange vessels.

Filtration characteristics of the exchange vessels in isolated dog lung were studied by calculating the volume conductance (LP,C) with use of different components of the weight-gain curve following changes in capillary pressure. In one series of lungs, capillary pressure was elevated to levels that produced alveolar edema (29.4 +/- 5.3 (mean +/- SD) mmHg), and total alveolar capillary membrane conductances (LP,T) were calculated using different components of the accumulated weight-gain measurements. These conductance values are similar to those found in the literature for studies in which alveolar edema developed and LP,T was calculated using wet-to-dry weight ratios as a measure of filtered volume. In another series of lungs, capillary pressure was altered by only 5.8 +/- 2.5 mmHg, and LP,C was calculated by estimating the initial filtration rate by an extrapolation method LP,C calculated by use of the extrapolation method (0.71 X 10(-11) cm3/dyn-s) was larger than the LP,T reported in the literature, because LP,T is an estimate of the conductance of the alveolar plus the capillary membrane. Also, for the most calculations of LP,T, tissue forces have changed which causes an overestimation of the filtration driving pressure and thus an underestimate of the capillary volume conductance. After estimating both LP,C and LP,T, the maximum volume conductance of the alveolar membrane (LP,a) was calculated to be 0.13 X 10(-11) cm3/dyn-s.

Animals↗

Nuclear magnetic resonance studies of anaesthetic interactions with haemoglobin.

The use of 270 MHz Fourier Transform nuclear magnetic resonance (NMR) spectrometer, combined with signal processing techniques to improve resolution, enabled proton resonances from the individual aromatic residues of haemoglobin to be distinguished. In the presence of clinical concentrations of the general anaesthetic drugs halothane and methoxyflurane, specific changes in the NMR spectrum can be distinguished which probably reflect local changes of conformation. When higher concentrations of anaesthetic are used, extensive changes in the NMR spectrum occur which are consistent with non-specific binding of the anaesthetic to the hydrophobic parts of the haemoglobin molecule.

Chemical Phenomena↗

Control of RNA content of developing human placenta.

Human placentae obtained early in pregnancy or at full term were examined for RNA content per cell, RNA polymerase types and activities, and chromatin template availability. The RNA:DNA ratio fell from 0.7 at 15 to 20 weeks to 0.4 at 40 weeks of pregnancy. Since RNase activities were similar at both times, the reduction in RNA content was attributed not to increased degradation, but to reduced synthesis. At both stages of pregnancy, about 55 to 60 per cent of the RNA polymerase activity in isolated placental nuclei was accounted for by RNA polymerase II, as judged by suppression of activity with alpha-amanitin and by separation of the extracted polymerases on DEAE-Sephadex. The relative roles of changes in polymerase activity and template availability were measured in nuclei from 20- and 40-week placentae. Nuclei showed 20 per cent greater polymerase activity in full-term than in early placentae, but the template availability of isolated chromatin for transcription by RNA polymerase II was 70 per cent less at full term. We conclude that the reduced amount of RNA per cell in the full-term placenta is due to reduced template availability that more than offsets the slight increase in polymerase activity.

Cell Nucleus↗