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Biomedical subjects

J D Gough

Publications and source records attributed to J D Gough.

16 recordsLinked to original sources

Probing protein function with small molecules.

The interface of chemistry and biology offers many opportunities to explore different aspects of cell biology. The emerging field of chemical genetics is providing the chemical means to understand biological systems not easily accessible using classical genetic manipulations. In this article, we will discuss how natural product mode of action studies and novel bio-organic manipulation of intracellular protein levels are proving useful in the exploration of cell biology.

Animals↗

Ionic blockade of the rat connexin40 gap junction channel by large tetraalkylammonium ions.

The rat connexin40 gap junction channel is permeable to monovalent cations including tetramethylammonium and tetraethylammonium ions. Larger tetraalkyammonium (TAA(+)) ions beginning with tetrabutylammonium (TBA(+)) reduced KCl junctional currents disproportionately. Ionic blockade by tetrapentylammonium (TPeA(+)) and tetrahexylammonium (THxA(+)) ions were concentration- and voltage-dependent and occurred only when TAA(+) ions were on the same side as net K(+) efflux across the junction, indicative of block of the ionic permeation pathway. The voltage-dependent dissociation constants (K(m)(V(j))) were lower for THxA(+) than TPeA(+), consistent with steric effects within the pore. The K(m)-V(j) relationships for TPeA(+) and THxA(+) were fit with different reaction rate models for a symmetrical (homotypic) connexin gap junction channel and were described by either a one- or two-site model that assumed each ion traversed the entire V(j) field. Bilateral addition of TPeA(+) ions confirmed a common site of interaction within the pore that possessed identical K(m)(V(j)) values for cis-trans concentrations of TPeA(+) ions as indicated by the modeled I-V relations and rapid channel block that precluded unitary current measurements. The TAA(+) block of K(+) currents and bilateral TPeA(+) interactions did not alter V(j)-gating of Cx40 gap junctions. N-octyl-tributylammonium and -triethylammonium also blocked rCx40 channels with higher affinity and faster kinetics than TBA(+) or TPeA(+), indicative of a hydrophobic site within the pore near the site of block.

Animals↗

Moderate hypothermic versus normothermic total cardiopulmonary bypass for coronary artery surgery: a retrospective study.

A retrospective analysis of 200 patients who underwent coronary artery bypass surgery between 1987 and 1990 was performed to ascertain whether there was any difference in morbidity or mortality with normothermic versus moderate hypothermic perfusion. Total cardiopulmonary bypass was used in all patients. 100 patients (Group H) were perfused using moderate (28-32 degrees C) hypothermia and the remaining 100 patients (Group N) were perfused at normothermia (37 degrees C). Both groups were comparable for age, weight, BSA, and perfusion time (Group H-mean 64 years, 82 Kg., 1.92 m2, 94 minutes; Group N-mean 63 years, 82 Kg., 1.90 m2, 90 minutes). Mean perfusate temperature in Group H was 31 degrees C, while the normothermic group was maintained at 37 degrees C. Both groups were perfused to maintain a venous oxygen saturation between 65-70 percent and arterial pressure between 60-70 mmHg. The cardiac index during bypass for Group H was lower (2.32 +/- .19 L/m2/min) than Group N (2.55 +/- .11 L/m2/min) (p less than 0.001). Mean arterial pressure for Group H was 69 +/- 12.4 mmHg and for Group N was 63 +/- 7.8 mmHg (p less than 0.001). Oxygen transfer for Group N (159 +/- 43 cc/min) was higher than Group H (113 + 31cc/min) (p less than .001). Metabolic acidosis was not observed in either group. Group H required vasodilators while Group N required vasoconstriction to maintain pressures on total bypass between 60-70 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The control of post-thoracotomy pain. A comparative evaluation of thoracic epidural fentanyl infusions and cryo-analgesia.

This is a comparative study of two methods to relieve postoperative thoracotomy pain. Continuous thoracic epidural infusion of fentanyl produced superior analgesia when compared with cryo-analgesia of the relevant thoracic nerves. Linear analogue pain scores were consistently lower in the epidural group reaching significance (p less than 0.05) at 32 and 40 hours after operation. All 36 patients in the cryo-analgesia group required additional analgesia, while 12 out of the 32 patients in the epidural group did not. This difference was significant at p less than 0.001. Respiratory and cardiovascular measurements were similar in both groups and the only side effect attributable to the epidural fentanyl was itching but this was not a problem.

Analgesia↗

Lectin-stimulated lymphocyte responses: use and misuse in clinical research.

The use of mitogen stimulation assays in clinical research has increased rapidly during the last 25 years. However, little is understood about the mechanisms of action of mitogens. This, coupled with the complexity of the mitogen stimulation assay, has led to much misuse and abuse of this assay system. Data are presented that demonstrate the inherent variability of the assay system due to diurnal variation in the response of human lymphocytes to mitogen stimulation and to the variation in response between patients. It is argued that the use of the assay should be confined to rigorously controlled studies using either animal lymphocytes or paired samples from humans, one of which should be treated in vitro with test material.

Adult↗

The obstetric management of non-immunological hydrops.

During the past 8 years, non-Rhesus hydrops has been observed in 31 pregnancies extending beyond 28 weeks gestation. Only three of the babies survived. Antenatal diagnosis is possible by ultrasound examination and although 27 of our patients had at least one indication for this procedure, only 22 were so investigated and in 13, fetal hydrops was demonstrated. Twenty-three were delivered before 36 weeks gestation, 10 by caesarean section of whom none survived; 16 babies were stillborn. Fourteen infants had major cardiovascular anomalies and six had other major malformations. In five infants, infection was thought to be causally related to fetal hydrops and in only four could no cause for the hydrops be found. In five pregnancies the cause of hydrops was discovered antenatally; this influenced subsequent management and two of the five survived. The unexpected appearance of a very abnormal fetal heart rate pattern requires the exclusion of fetal anomaly and non-immunological hydrops. When a diagnosis of non-immune hydrops is made its underlying cause should be sought without delay so that specific treatment may be instituted in the few cases where this is appropriate. A high incidence of complications of the third stage of labour should be anticipated. Subsequent pregnancies are likely to be normal.

Adolescent↗

Non-immunologic hydrops fetalis: a review of 27 cases.

Twenty seven babies with severe non-haemolytic hydrops fetalis were born during a 7 1/4 year period (1/1400 total births). Thirteen were live born and admitted to the intensive care nursery, but only three survived. The survivors differed from those live born infants who died in the neonatal period in that the cause of the hydrops was discovered antenatally, their serum concentrations of total protein and albumin were normal, and they had no structural anomaly. A scheme of investigation of the severely hydropic fetus in the antenatal period is outlined and the role of active obstetric management is evaluated.

Blood Proteins↗

Raised maternal serum AFP, oligohydramnios and poor fetal outcome.

Six women who had an ultrasound scan examination in early pregnancy on account of a high serum alpha-fetoprotein level were noted to have little or no amniotic fluid. This paper gives details of the six pregnancies, two of which were extrauterine; only one of the six infants survived.

Adolescent↗

Doppler ultrasound method for detecting human fetal breathing in utero.

An audible Doppler ultrasound method for detecting human fetal breathing movements in utero has been developed. The frequencies synchronous with fetal breathing movements probably originate from the lung rather than the chest wall. This method is much cheaper and simpler than the ultrasound A-scan method and is suitable for screening large numbers of people.

Costs and Cost Analysis↗

Modeling antileukemic activity of carboquinones with electrotopological state and chi indices.

The antileukemic activity (medium effective dose, MED) of a set of 37 carboquinones was modeled using a combination of the electrotopological state (E-state) and molecular connectivity indices with multiple linear regression. A four-variable model gave good statistics: r2 = 0.90, s = 0.21. Using the leave-one-out method, the cross-validation statistics indicate a model useful for prediction: r2press = 0.85, spress = 0.26. The same variables were used to model the optimum effective dose (OD): r2 = 0.88, s = 0.19. The cross-validation statistics indicate a model useful for prediction: r2press = 0.83, spress = 0.23. The descriptor variables are interpreted in terms of the molecular structure.

Animals↗