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Biomedical subjects

L Murphy

Publications and source records attributed to L Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1994

Abnormal Leydig cell development at puberty in the androgen-resistant Tfm mouse.

Leydig cells are the major source of androgens in the male, and it is likely that these cells are also targets for androgen action. The role of androgen action in regulating the development of Leydig cell function has been determined using the testicular feminized (Tfm/Y) mouse, which lacks androgen receptors. In Tfm mice, the testes fail to descend at the normal time (25 days), and testicular descent was, therefore, surgically prevented in control (+/Y) animals. The activity of 3 beta-hydroxysteroid dehydrogenase increased during development from 5-40 days in control and Tfm mice, with no significant difference between the groups. In control animals, 17 alpha-hydroxylase activity was low from 5-25 days, at which time there was a 26-fold increase up to 40 days. In the Tfm group, 17 alpha-hydroxylase activity was 4-fold higher than that in controls on day 5, but showed no change in activity after 25 days and remained at neonatal levels up to 40 days. The activity of 17-ketosteroid reductase in the control animals showed a developmental pattern similar to that of 17 alpha-hydroxylase, with a marked increase in activity after 25 days. In the Tfm group, 17-ketosteroid reductase was normal on day 5, but failed to show any significant change thereafter and remained at neonatal levels on day 40. Serum LH levels in control animals increased from 5 days to a peak at 30 days. In Tfm mice, LH levels were significantly increased on days 20 and 40, but did not differ from controls on days 5, 25, and 30. In control +/Y animals, in which normal testicular descent was allowed to proceed at 25 days, the pattern of development was similar to that in the cryptorchid +/Y animals, although the increase in 17 alpha-hydroxylase activity at 30 and 40 days was significantly greater. The results show 1) that fetal Leydig cell steroidogenesis is enhanced in the absence of androgen receptors, but 2) that adult Leydig cells require receptor-mediated androgen activity around day 25 for normal functional development. In addition, 3) the lack of testicular descent at 25 days reduces the pubertal rise in 17 alpha-hydroxylase activity.

3-Hydroxysteroid Dehydrogenases↗
PubMed1993

Cytochrome P-450 17 alpha-hydroxylase protein and mRNA in the testis of the testicular feminized (Tfm) mouse.

The testicular feminized (Tfm) mouse lacks functional androgen receptors and develops with a female external phenotype and internal testes. The testes of these animals contain normal, or close to normal, numbers of Leydig cells but secrete very low amounts of androgen due to a lack of 17 alpha-hydroxylase activity. To determine whether this loss of activity is due to a lack of enzyme synthesis or a change in catalytic activity we have examined 17 alpha-hydroxylase cytochrome P-450 (P-450(17 alpha)) protein and mRNA levels in the testes of Tfm mice. Levels of P-450(17 alpha) protein were measured by immunoblotting, while mRNA was measured following reverse transcription (RT) and amplification by the polymerase chain reaction (PCR). Conditions for RT-PCR were determined which allowed semiquantification of P-450(17 alpha) mRNA relative to beta-actin mRNA. In extracts of Tfm testes P-450(17 alpha) protein was undetectable using antiserum against porcine P-450(17 alpha). In contrast, a protein of around 54 kDa was clearly detectable in extracts of control cryptorchid testes. Using RT-PCR, P-450(17 alpha) mRNA was detectable in both control and Tfm testes but, expressed in terms of beta-actin mRNA, levels of P-450(17 alpha) mRNA in control testes were 40-fold higher than those in Tfm testes. If the total amount of RNA extracted from each testis is taken into account then P-450(17 alpha) mRNA levels per testis were up to 400-fold higher in control testes. These results show that the reduced level of 17 alpha-hydroxylase activity in Tfm testes is related to reduced protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Cost/benefit study of reusable and disposable OR draping materials.

A large metropolitan teaching hospital in Canada wanted to know if it should continue to use disposable drapes or return to reusables. In order to determine which choice would be more cost-effective, which would be more environmentally friendly and which would best meet the surgical team's needs while meeting infection control guidelines and other pertinent standards a study was conducted of the then present draping practices and costs. The study was done on the operating room, including inpatient and same day surgery drape usage. It included drape types, patterns of usage, volume of usage and draping practices. An analysis was made based on the actual costs and number of cases for 1990 and the estimated needs for the next year. Drape expenses included handling, storage, removal from user areas and disposal. The study resulted in the conclusion that, at that time, reusable surgical drapes were a viable alternative from an environmental perspective, but based on the information available, they were not considered to be financially competitive.

Bedding and Linens↗
PubMed1992

Evaluation of four commercial automatic endoscope washing machines.

Four commercially available endoscope washing machines (Pyser System 83, Wolf Fiberscope Disinfector, Olympus EW20, Keymed Auto-Disinfector) were evaluated. In most cases the machines were expensive, immobile and noisy, and could only wash one endoscope per cycle. Daily use involved repetitive chores and contact with glutaraldehyde. Disinfection procedures were flawed; no machine auto-disinfected adequately. In conclusion, these machines are unsatisfactory and represent a potential source of serious infection.

Disinfection↗
PubMed1991

Effects of delta-9-tetrahydrocannabinol exposure on adrenal medullary function: evidence of an acute effect and development of tolerance in chronic treatments.

Previous studies have shown that the secretion of several stress-related hormones can be altered by exposure to marihuana or its purified constituents. The purpose of this study was to examine changes in adrenal medullary function caused by acute, subchronic and chronic treatments with two different doses of delta-9-tetrahydrocannabinol (THC). Acute exposure to THC caused a significant decrease in the adrenal medulla contents of both norepinephrine (NE) and epinephrine (E) and a significant increase in the E/NE ratio. These effects were mainly observed with the highest dose of THC, but they were not accompanied by a statistically significant decrease in adrenal medulla tyrosine hydroxylase activity, the rate-limiting enzyme in the catecholamine (CA) synthesis. These effects disappeared after seven or fourteen days of a daily THC treatment, which suggests the development of tolerance to this drug. Analysis of plasma PRL, ACTH and corticosterone levels showed some THC-related changes in these hormones. THC-induced modifications in ACTH and corticosterone were not in parallel to the changes in the adrenal medulla function, whereas those effects of acute THC on PRL release were statistically correlated with decreases of CA contents following acute THC. In conclusion, acute exposure to THC caused an alteration in the adrenal medullary function, reflected by a fall in endogenous stores of both CAs which could influence the adrenal medullary response to stress situations. This acute effect of THC could be mediated by the pituitary secretion of PRL, although the possibility of an effect directly exerted on the adrenal medulla chromaffin cells should be also considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1991

Effect of cryptorchidism on testicular and Leydig cell androgen production in the mouse.

Unilateral cryptorchidism was induced surgically in adult mice and the effects on testicular and Leydig cell steroidogenesis were studied after 7 weeks. There was a 60% reduction in weight of the cryptorchid testis and this was associated with a significant reduction in intratesticular androgen content, both under basal conditions and following an injection of hCG. Testicular androgen production in vitro was also significantly lower in the cryptorchid testis compared to the scrotal testis, again under both basal conditions (29 +/- 6% of control) and in the presence of hCG (46 +/- 9% of control). Scrotal testes from the unilaterally cryptorchid animals did not show any significant difference in steroidogenic capacity compared to testes from untreated control animals. The decrease in steroidogenic capacity of the cryptorchid testis was due, at least in part, to a reduction in activity for each Leydig cell. In four experiments, androgen production by Leydig cells isolated from cryptorchid testes was 48 +/- 9% of cells from scrotal testes in the presence of a saturating dose of hCG. Under basal conditions the effect was more variable between experiments with steroid secretion by Leydig cells from cryptorchid testes being 58 +/- 32% of that for cells from scrotal testes. Leydig cell steroidogenesis in the scrotal testes of unilaterally cryptorchid animals did not differ significantly from untreated controls. These results show that induced cryptorchidism in the mouse causes a significant reduction in Leydig cell activity. This is apparently different from the effects of this procedure on the rat and raises the possibility that intratesticular regulation differs between the two species.

Androgens↗
PubMed1991

First metatarsophalangeal joint reaction forces during high-heel gait.

First metatarsophalangeal (MTP) joint reaction forces were calculated for 11 normal females during the toe-off phase of gait while walking in bare feet and in high heeled shoes. A biomechanical model was used to calculate the forces utilizing kinematic, kinetic, footprint, and radiographic data. The results showed that the MTP joint reaction forces (FJ), the metatarsal-sesamoid forces (FS), and the resultant of these forces (FRES), were twice as large in high heels compared to barefoot walking. The average peak forces for barefoot and high-heeled gait were FJ: 0.8 and 1.58 times body weight, FS: 0.44 and 1.03 times body weight, and FRES: 0.93 and 1.88 times body weight. Also, the kinematics changed when wearing high heels, making angles of application of forces and sesamoidal articulations less favorable.

Adult↗
PubMed1991

Testicular steroidogenesis in the testicular feminized (Tfm) mouse: loss of 17 alpha-hydroxylase activity.

Testicular feminized (Tfm) mice are totally insensitive to androgen and may be used to study the role of the androgen receptor in normal development and function. We have examined testicular and Leydig cell steroidogenesis in Tfm mice. Serum bioactive LH was high in Tfm mice but serum testosterone was low and this was associated with a severe reduction in testicular testosterone production in vitro. Examination of [3H]pregnenolone metabolism by testes of Tfm mice indicated that progesterone, rather than testosterone, was the major steroid produced. Leydig cells were isolated from normal and Tfm mice and from normal mice in which testicular descent was surgically prevented before puberty. As in whole testes, androgen production in response to human chorionic gonadotrophin was severely reduced in Leydig cells from testes of Tfm mice compared with normal or cryptorchid groups. In contrast, progesterone production by Leydig cells from testes of Tfm mice was markedly increased in comparison with other groups. Total steroid production (progesterone plus androstenedione plus testosterone), however, was only 24% of normal in Leydig cells from Tfm mice. The pattern of steroid production by Leydig cells from cryptorchid testes was similar to control, although total steroid production was reduced to about 50% (this was significantly higher than the Tfm group, P less than 0.05). The high progesterone/androgen ratio in testes from Tfm mice suggested that 17 alpha-hydroxylase was depleted in these animals. To confirm this, activity of the four major steroidogenic enzymes associated with the smooth endoplasmic reticulum was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

17-Hydroxysteroid Dehydrogenases↗
PubMed1991

Steroidogenic enzyme activity in the rat testis following Leydig cell destruction by ethylene-1,2-dimethanesulphonate and during subsequent Leydig cell regeneration.

Ethylene-1,2-dimethanesulphonate (EDS) rapidly destroys Leydig cells in the rat testis, although repopulation occurs within 5-7 weeks. In this study we have examined the activity of testicular steroidogenic enzymes after Leydig cell destruction and during regeneration. This was designed to measure the contribution of cells, other than Leydig cells, to steroidogenic activity in the testis, and to determine whether changes in steroidogenic enzyme activity during Leydig cell regeneration after EDS parallel those which occur during normal Leydig cell development. The enzymes studied are those responsible for androgen synthesis and metabolism in the testis. Adult male Wistar rats (300-350 g) were injected with EDS (100 mg/kg, i.p.) and testicular steroidogenic enzyme activity was measured on days 0, 3, 7, 14, 21 and 35. On day 3, when no Leydig cells remain in the testis, cholesterol side-chain cleavage (CSCC) activity, per testis, declined to undetectable levels, while 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) and 17 alpha-hydroxylase retained only 0.04 and 0.15% of control activity respectively. In contrast, 17-ketosteroid reductase (17-KSR) and 5 alpha-reductase retained 33 and 10% of control activity respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

17-Hydroxysteroid Dehydrogenases↗
PubMed1990

Joint reaction forces at the first MTP joint in a normal elderly population.

The calculation of net ankle, knee, and hip joint reaction forces is an often applied procedure in the analysis of gait. Except for very few studies, joint reaction forces have not been measured in other joints such as the fingers, wrist, elbow, shoulder and toes. In this study the joint reaction forces between the metatarsal head and the proximal phalanx and the metatarsal head and the sesamoids are calculated for the push off phase during gait. The results of ten normal elderly subjects show that the maximum resultant loads of the two articulations lie close to the longitudinal axis of the metatarsal. The knowledge of the magnitude and direction of the joint reaction forces of a normal elderly population will be essential for the design of an optimal fixation of an artificial anatomical first MTP joint.

Aged↗
PubMed1989

Alignment of the first metatarsal-phalangeal joint: important criteria for a new joint replacement.

Joint replacement is one of many options for the treatment of the first metatarsophalangeal (MTP) joint. Studies of the geometry of that joint have shown that it consists of two distinct articulations, the metatarsophalangeal and the MT-sesamoidal. Both are important, but the MT-sesamoidal tolerates only small deviations from an ideal alignment. The aim of this study was to investigate the alignment of the first MTP joint of a potential patient population, in order to design an optimal surface replacement. One measurement, the extension angle between the MT and the proximal phalanx was found to be the most important alignment criterion for the successful design of an implant and the necessary instruments. This angle controls the delicate interplay between the metatarsal head and the sesamoids and tolerates only small deviations from the normal range before the chance of sesamoidal subluxation increases significantly. The pre-operative knowledge of this and other alignment criteria is important for the ideal placement of an anatomical implant.

Humans↗