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Biomedical subjects

L Weir

Publications and source records attributed to L Weir.

47 records · Page 3Linked to original sources

Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation.

We have developed a general method for introducing cloned genes into mammalian cells that affords substantial benefits over current technology. It is simple, rapid, and applicable to many (perhaps all) cell types, including those that are refractory to traditional transfection procedures. The method involves exposure of a suspension of cells and cloned DNA to a high-voltage electric discharge. In a model application of this transfection procedure, we have studied the expression of cloned human and mouse Ig kappa genes stably introduced into mouse pre-B cells and fibroblasts. We find that there is a B-cell-specific enhancer-activator region in the J-C intron of the human kappa gene that is necessary for efficient transcription of the cloned gene in mouse pre-B lymphocytes. This suggests that both the DNA element and the proteins required for its regulatory activity have been highly conserved in evolution and that these elements operate at the pre-B-cell stage of immunocyte development, a stage that precedes productive kappa gene rearrangement.

Animals↗

Mandatory sublingual buprenorphine for postoperative pain.

This study examined the analgesic effect, vital signs and side effects when 0.4 mg doses of buprenorphine were given pre-emptively for the treatment of postoperative pain after elective total hip replacement. Pain intensity, pain relief, retrospective peak pain intensity and pain relief, sedation, vital signs and side effects were measured 1 hour after surgery and then in the morning and evening of the first 2 postoperative days. There was a significant improvement in pain measured over the 3 days, with concomitant reduction in side effects and sedation. However, there was a significant increase in the number of patients with a pulse rate greater than 100 beats per minute. No particular benefit for postoperative pain relief was observed in patients receiving buprenorphine premedication in comparison with those who had received morphine or placebo.

Administration, Oral↗

Comparison of effects of intraoperative and postoperative methadone: acute tolerance to the postoperative dose?

The effects of methadone 10 mg administered in two different clinical contexts, at induction of anaesthesia and following operation, were studied in two groups of patients undergoing elective total hip replacement. The intraoperative group received methadone 10 mg i.v. at induction of anaesthesia as part of a balanced anaesthetic technique. The postoperative group received methadone 10 mg i.v. following operation, extradural bupivacaine being used for the operative period. A demand analgesia system delivering methadone i.v. was used after operation in both groups. Arterial blood-gas tensions, cortisol and glucose concentrations, analgesic effects and plasma methadone concentrations were compared in the two groups. The only major difference between the two groups was in analgesic requirement. At the time of connection to the demand system the two groups had the same plasma methadone concentrations. Subsequently, the postoperative group had a significantly greater analgesic requirement which resulted in significantly greater plasma methadone concentrations the following morning. Thus, the administration of methadone following operation appeared to exert less analgesic effect than the same dose given during operation. The reasons for this are discussed.

Adult↗

A comparison of intramuscular and sublingual buprenorphine, intramuscular morphine and placebo as premedication.

Buprenorphine premedication by two routes, 0.4 mg sublingual and 0.3 mg intramuscular was compared double-blind, double-dummy with intramuscular morphine 10 mg and placebo in 74 patients undergoing elective total hip replacement. Anxiety, depressive mood, sedation, vital signs and side-effects were measured before surgery. All patients then received a standardised general anaesthetic using a muscle relaxant and ventilation. The effects of the premedication on the anaesthetic were assessed by a scoring system. Intra- and postoperative blood gases, plasma cortisol and glucose were measured and the 1 hour postoperative pain intensity, side-effects and sedation were assessed. No differences between the premedications were seen on any of the pre-, intra- or postoperative measurements, suggesting that even with adequate measurement sensitivity it is difficult to distinguish opiate from placebo premedication.

Administration, Oral↗

A model for comparison of local anesthetics in man.

Ten patients scheduled for bilateral arm surgery were given general anesthesia plus, on one side, an axillary brachial plexus block. Ten additional patients scheduled for bilateral foot surgery were similarly given general anesthesia plus an ankle block on one side. A within-patient blind comparison of postoperative analgesia between blocked and unblocked side was performed. An additional 10 patients scheduled for bilateral foot surgery had one side blocked with lidocaine and the other side blocked with bupivacaine for comparison of postoperative analgesia. Postoperative analgesia recorded by a nurse observed was significantly better on the blocked side compared with the unblocked side. This difference was greater for ankle blocks. There were no differences between the analgesic measures for lidocaine and bupivacaine ankle blocks over the 6-hour study period.

Adolescent↗

An oral buprenorphine and paracetamol combination compared with paracetamol alone: a single dose double-blind postoperative study.

1 An oral combination of buprenorphine and paracetamol was compared with paracetamol alone in a single dose, double-blind postoperative study. One hundred and twenty patients undergoing elective minor orthopaedic operations were allocated to four groups of 30 patients. The four treatments were 1,1.5 or 2 mg of buprenorphine with paracetamol 1,000 mg or paracetamol 1,000 mg alone. 2 There were no significant differences between the groups in analgesia measured by the observer over the 6 h period of direct observations. The oral opiate produced a significant increase in duration of analgesia beyond the 6 h study period. A significant increase in side-effects was seen only at the highest buprenorphine dose compared with paracetamol. 3 The problems of trial design for analgesic combinations are considered. Drug mixtures create additional complexities which decrease the certainty of the conclusion that no real benefits result from such mixtures.

Acetaminophen↗

Some endocrine changes associated with the post-partum period of the suckling beef cow.

Seven Hereford cows with single calves were bled by jugular venepuncture, daily from parturition until 63-79 days post partum; 6 of the cows were also bled through jugular cannulae every 15 min for 8 h every 10 days. The average post-partum interval to first oestrus was 59.8 +/- 3.7 days for 5 of the cows. In cows returning to oestrus, plasma concentrations of progesterone were low until 55.5 +/- 3.0 days post partum, rose to exceed 0.5 ng/ml plasma for 4.0 +/- 0.4 days, declined for 5.0 +/- 0.5 days and then rose again to normal luteal-phase levels. First oestrus preceded the initial rise in progesterone in 1 cow and followed it is 4. Ovarian palpation revealed considerable follicular development before the initial rise in progesterone, but no clearly discernable corpus luteum until normal luteal-phase progesterone levels were detected. Plasma concentrations of oestradiol-17 beta fell after parturition and, although very variable, showed no apparent trend thereafter. Plasma concentrations of LH varied in an episodic manner, with an apparent increase in frequency and magnitude of peaks up to 10-33 days before the first elevation in plasma progesterone. Subsequently there was little change, except for a decline in peak LH concentrations after the initial elevation in plasma progesterone.

Animals↗

A conserved sequence in the immunoglobulin J kappa-C kappa intron: possible enhancer element.

Several functionally important genetic elements (such as the TATA box, mRNA splice sequences, poly(A) addition signal) were first detected as short segments of unexplained sequence homology within non-coding regions of different genes. A short region of unknown sequence in the intron between the human J kappa and C kappa immunoglobulin coding regions was found to be sufficiently homologous to the corresponding segment of the mouse gene to form stable heteroduplexes. Although no specific function has yet been definitely ascribed to this region (which we call the kappa intron conserved region, or KICR), some functional significance has been inferred from the findings that (1) activation of B lymphocytes induces a DNase hypersensitivity site in this region and (2) deletions including this region reduce expression of kappa genes introduced into lymphoid cells. To delineate the KICR more precisely and to test the generality of the sequence conservation in a third species, we have sequenced this region of the human and mouse genes and have examined the corresponding region of a recently cloned rabbit kappa gene. We find a segment of about 130 base pairs (bp) that shows striking conservation in all three species, demonstrating homology significantly higher than within the C kappa coding region itself. Two short sequences from the J kappa-C kappa intron that were noted by other investigators to be homologous to proposed 'enhancer' sequences both lie within the conserved region.

Animals↗