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Biomedical subjects

S Liddle

Publications and source records attributed to S Liddle.

7 recordsLinked to original sources

A large-scale evaluation of amnio-PCR for the rapid prenatal diagnosis of fetal trisomy.

OBJECTIVE: Traditional chromosome preparation from amniotic fluid samples often involves lengthy culture procedures in order to obtain cells for analysis. Multiplex quantitative fluorescent polymerase chain reaction (PCR) is a new molecular biological technique capable of quantifying in-situ DNA without the need for cell culture. Our objective was to test the reliability of PCR using fetal DNA from amniotic fluid (amnio-PCR) for the rapid prenatal diagnosis of the common trisomies. DESIGN: This was a large prospective study of 5000 amniocentesis specimens. Multiplex quantitative fluorescent PCR was performed specifically for short tandem repeat sequences within chromosomes 21, 18, 13, X and Y. All amniocentesis samples were subsequently analyzed by traditional karyotyping methods. RESULTS: Amnio-PCR detected all 89 major autosomal trisomies in this cohort. Diagnosis of sex chromosome anomalies was accurate for cases involving first meiotic division nondisjunction. However, further markers were necessary to detect sex chromosome anomalies arising from second meiotic division nondisjunction, highlighting the importance of using specific markers that enable the quantification of both the X and the Y chromosomes simultaneously. CONCLUSIONS: Rapid prenatal diagnosis of trisomies 21, 18, and 13 and the sex chromosome anomalies using amnio-PCR is a reliable technique that aids the clinical management of pregnancy. The speed of the methodology will help to minimize the period of parental anxiety in the wait for a diagnostic test result.

Amniotic Fluid↗

Identification of domains responsible for signal recognition and transduction within the QUTR transcription repressor protein.

QUTR (qutR-encoded transcription-repressing protein) is a multi-domain repressor protein active in the signal-transduction pathway that regulates transcription of the quinic acid utilization (qut) gene cluster in Aspergillus nidulans. In the presence of quinate, production of mRNA from the eight genes of the qut pathway is stimulated by the activator protein QUTA (qutA-encoded transcription-activating protein). Mutations in the qutR gene alter QUTR function such that the transcription of the qut gene cluster is permanently on (constitutive phenotype) or is insensitive to the presence of quinate (super-repressed phenotype). These mutant phenotypes imply that the QUTR protein plays a key role in signal recognition and transduction, and we have used deletion analysis to determine which regions of the QUTR protein are involved in these functions. We show that the QUTR protein recognizes and binds to the QUTA protein in vitro and that the N-terminal 88 amino acids of QUTR are sufficient to inactivate QUTA function in vivo. Deletion analysis and domain-swap experiments imply that the two C-terminal domains of QUTR are mainly involved in signal recognition.

Base Sequence↗

Interruption of parturition in rats by morphine: a result of inhibition of oxytocin secretion.

Oxytocin secretion is inhibited by opioids, and oxytocin is important in parturition. The effects on parturition of morphine, a relatively selective mu-opioid receptor agonist, were studied in the rat. Morphine or vehicle with or without the opiate antagonist naloxone were administered immediately after the birth of the second pup and the subsequent course of parturition was recorded in a total of 80 rats. Both s.c. morphine (10 mg/kg) and intracerebroventricular (i.c.v.) morphine (18 micrograms through a previously implanted cannula) interrupted parturition, delaying the birth of the sixth pup after treatment to 187.3 +/- 35.9 (S.E.M.) min and 195.4 +/- 19.5 min respectively, compared with 46.4 +/- 3.7 and 66.1 +/- 17.5 min after vehicle alone. The dose of morphine given i.c.v. had no effect when given s.c. Naloxone given concurrently prevented the effects of morphine. Eventually the rate of parturition in the morphine-treated groups recovered. Perinatal pup mortality rate was not increased when morphine was given to the mothers, but it did inhibit the expression of normal intrapartum maternal behaviour. Pup mortality was increased 48 h post partum by morphine given during parturition, and it reduced the proportion of rats with normal maternal behaviour 24 h post partum. Morphine did not affect spontaneous or oxytocin-stimulated contractile activity of the parturient uterus in vitro. The concentration of oxytocin in trunk blood plasma was decreased 40 min after i.c.v. morphine (24.3 +/- 3.9 vs 39.3 +/- 6.5 pmol/l in controls), as was vasopressin (7.2 +/- 1.5 vs 19.7 +/- 4.5 pmol/l in controls). Intravenous infusion of oxytocin (2-5 mU/min for 144.3 +/- 8.2 min; total infused 448.5 +/- 61.9 mU) after i.c.v. morphine re-started parturition; all pups were born to these rats (mean time to pup 6, 110.3 +/- 12.7 min) before the i.v. vehicle-infused rats given i.c.v. morphine re-started (mean time to pup 6, 406.3 +/- 125.2 min). It is concluded that morphine given during parturition acts centrally through opioid receptors to inhibit oxytocin secretion, and impairs the expression of maternal behaviour. Reversal of the effects of morphine on parturition by i.v. oxytocin demonstrates the important role of oxytocin in fetus ejection and expulsion.

Animals↗

Tendon grafting with glutaraldehyde fixed material.

An evaluation of 0.2% buffered glutaraldehyde fixed tendon as a potential tendon replacement prosthesis was evaluated in rabbit and chicken models. In vivo implantations were done to determine compatability, function, and strength of grafts. Autogenous fresh grafts were used as controls in the strength evaluations. The fixed tendon elicits no cellular rejection response, is invaded and replaced by host tissues, and anastomosis strength in tension compares favorably to a fresh autogenous control. These preliminary evaluations indicate a useful potential for this fixed biomaterial as a tendon prosthesis.

Aldehydes↗

Laboratory evaluation of various cold therapy modalities.

An attempt to evaluate the potential of four modalities to cool soft tissue mass has been done under laboratory conditions using canines. The cooling of deep soft tissues within the thigh after application of various cooling devices was recorded over a 60-min exposure period. Under these circumstances, ice performed best, a frozen gel pack performed in a parallel but slightly less efficient manner. Two other modalities, an inflatable bladder filled with refrigerant gas and an endothermic chemical reaction, were least efficient in cooling.

Acute Disease↗

Conditioning program for competitive figure skating.

To test the feasibility that traditional interval training methods could be adapted to the needs of competitive figure skaters, an interval skating program was conducted during a 3-month period for a group of skaters at diverse levels of proficiency. The program required only a small portion of the total ice time utilized by the skaters on a daily basis, i.e., 1/2 hr, three times a week. On alternate days, the skaters used the same amount of time in a strength training program. A flexibility-stretching facet was to be done by the skaters on a daily basis. Progress was evaluated by treadmill oxygen consumption determinations and ability to perform a 1/2-mile skate effort. Over the course of the 3-month period, the skaters in the program showed an average increase in oxygen consumption of 9% from 44.73 cc per kg per min to 55.51 cc per kg per min. This was accompanied by an average 10-sec reduction in the timed effort at the 1/2-mile skate. Subjectively, the skaters were less fatigued during their freestyle skating programs and were able to improve consistency at skilled maneuvers in the last minute of their performances. This initial effort to evaluate the efficacy of this type of a training program for competitive figure skating seems to have proven to be beneficial to the skaters. Currently, we are continuing our efforts to expand the program.

Adolescent↗

Cryotherapy influence on posttraumatic limb edema.

The potential of local cooling to reduce posttraumatic swelling has been assessed on rabbits. A standard crush injury to a forelimb was used as a control model. In a treatment regimen of one hour of cooling following the injury, 30 degrees C proved to perform best, this group having less residual swelling at 24 hours than the 20 degrees C group. Repeated applications of cooling in 3 cycles of one hour of cooling followed by one hour exposure to ambient room air showed residual swelling at 24 hours in both 20 degrees C and 30 degrees C groups. Although no clear-cut clinical directives can be made from the data, it does appear that too much cold or too long application may be deleterious. For these reasons, discretion in the utilization of cold therapy is warranted. Within limits of physiologic conditions, there is empirical evidence for the use of icing treatment of local musculoskeletal trauma.

Animals↗