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Biomedical subjects

E Khan

Publications and source records attributed to E Khan.

6 recordsLinked to original sources
PubMed1991

Retroviral integrase domains: DNA binding and the recognition of LTR sequences.

Integration of retroviral DNA into the host chromosome requires a virus-encoded integrase (IN). IN recognizes, cuts and then joins specific viral DNA sequences (LTR ends) to essentially random sites in host DNA. We have used computer-assisted protein alignments and mutagenesis in an attempt to localize these functions within the avian retroviral IN protein. A comparison of the deduced amino acid sequences for 80 retroviral/retrotransposon IN proteins reveals strong conservation of an HHCC N-terminal 'Zn finger'-like domain, and a central D(35)E region which exhibits striking similarities with sequences deduced for bacterial IS elements. We demonstrate that the HHCC region is not required for DNA binding, but contributes to specific recognition of viral LTRs in the cutting and joining reactions. Deletions which extend into the D(35)E region destroy the ability of IN to bind DNA. Thus, we propose that the D(35)E region may specify a DNA-binding/cutting domain that is conserved throughout evolution in enzymes with similar functions.

Amino Acid Sequence↗
PubMed1991

Chronic morphine therapy for cancer pain: plasma and cerebrospinal fluid morphine and morphine-6-glucuronide concentrations.

Morphine-6-glucuronide (M-6-G) is an active metabolite that may contribute to the clinical effects produced by systemic administration of morphine. To help clarify the extent to which M-6-G may cross the blood-brain barrier and exert effects, we employed high-performance liquid chromatography with electrochemical detection to measure the concentrations of M-6-G and morphine in the plasma and either ventricular (three patients) or lumbar (eight patients) CSF of cancer patients receiving chronic morphine therapy. The mean ratio of morphine in ventricular CSF:morphine in plasma was 0.71; the same ratio for M-6-G was only 0.077. The average molar ratio of M-6-G: morphine in ventricular CSF was 0.207, and the average molar ratio in plasma was 1.89. Although sampling problems render the lumbar CSF results less reliable, they were very similar. Thus, plasma contained approximately twice as much M-6-G as morphine, whereas CSF contained only one-fifth to one-third as much. These data confirm that M-6-G in plasma is distributed into CSF, but to a far lesser extent than morphine. They help explain animal data demonstrating much higher potency of M-6-G on administration into CSF than systemic administration and indicate that the degree to which M-6-G contributes to morphine effects in humans remains an unresolved question.

Adult↗
PubMed1987

Propranolol increases oxygen utilization during hypoxia.

The effects of propranolol on whole body oxygen consumption and blood oxygen content were measured in the dog during extreme hypoxic conditions. At 9% inspired oxygen four of eight control animals died within 40 min. An identical second group was pretreated with propranolol and none died during the same hypoxic stress. Hypoxia decreased oxygen consumption in both groups, but the decrease was less in the propranolol-pretreated dogs. A second set of 16 dogs was ventilated with 10% oxygen and all animals survived. A similar, although less pronounced, effect on oxygen consumption was noted and propranolol once again lessened the hypoxia-induced decrease in oxygen consumption. With hypoxaemia, metabolic acidosis developed in all animals and the arterio-venous oxygen content difference decreased; however, propranolol lessened the acidosis and the decrease in arterio-venous oxygen content difference. We conclude that, during hypoxia, propranolol increases oxygen utilization by the tissues and this might account for better survival.

Animals↗
PubMed1979

Hypertension during anesthesia on discontinuation of sodium nitroprusside-induced hypotension.

The authors had observed that on intraoperative discontinuation of sodium nitroprusside being administered to induce hypotension, mean arterial pressure increased to above the pre-hypotension level. Twelve patients who recieved hypotensive anesthesia for surgical correction of cerebral aneurysms were studied to evaluate the role of the renin-angiotensin system in this phenomenon. In the awake state, mean arterial pressure was 100 +/- 2 torr and plasma renin activity 3.0 +/- 0.1 ng/ml/hr. Thirty minutes after the establishment of stable halothane-nitrous oxide anesthesia, mean arterial pressure decreased to 85 +/- 1 torr and plasma renin activity increased to 4.4 +/- 0.1 ng/ml/hr. No appreciable change in either occurred over the next two hours of operation. During sodium nitroprusside-induced hypotension, mean arterial pressure decreased to 49 +/- 2 torr and plasma renin activity increased to 15.2 +/- 0.2 ng/ml/hr. Thirty minutes after discontinuation of sodium nitroprusside administration, mean arterial pressure increased to 112 +/- 2 torr, which was not only higher than the prehypotension level, but also significantly higher than that recorded in the awake state. Plasma renin activity at that time was 10.9 +/- 0.1 ng/ml/hr. As the half-life of plasma renin is 15 min, the data suggest that the persistently increased plasma renin activity is probably responsible for the increase of arterial pressure following sodium nitroprusside-induced hypotension.

Adolescent↗