Search PubMed⌕ Search

Biomedical subjects

M J Gibson

Publications and source records attributed to M J Gibson.

At least 73 records · Page 4Linked to original sources
PubMed1988

Positive feedback in hypogonadal female mice with preoptic area brain transplants.

When fetal preoptic area (POA) brain grafts that contain gonadotropin-releasing hormone cells are transplanted into the third ventricle of adult female hypogonadal mice, the animals respond with sexual maturation, persistent estrus, and the ability to ovulate reflexively after mating. However, the absence of normal spontaneous ovulatory cyclicity suggests an impairment in positive feedback. We, therefore, studied the effect of administration of progesterone alone or of sequential estradiol benzoate and progesterone on plasma levels of luteinizing hormone (LH) in groups of hypogonadal (HPG) mice in persistent estrus after receiving POA grafts (HPG/POA). Individual differences in responsivity to progesterone were related in part to the length of time in persistent estrus. Approximately 30% of HPG/POA grafts tested 2 months after graft showed increased levels of plasma LH. This was reduced to 10% when animals were tested 5 months after graft. Sequential administration of estradiol benzoate plus progesterone to intact HPG/POA mice was ineffective in elevating LH. The presence of corpora lutea in ovaries verified that only animals with a progesterone induced LH surge ovulated. Other HPG/POA mice were mated, and the occurrence of reflex ovulation was determined. Four of these mice delivered pups: 3 were previous responders to progesterone. One female mated again during the immediate postpartum period and delivered a second litter. Following weaning of all offspring, this animal displayed spontaneous ovarian cyclicity, confirmed by ovarian histology. This is the first proven example of spontaneous ovulation in a mutant mouse with a brain graft. The results show that some HPB/POA mice are capable of positive feedback responses, and rarely, of becoming spontaneous ovulators.

Animals↗
PubMed1987

Plasma LH rises rapidly following mating in hypogonadal female mice with preoptic area (POA) brain grafts.

Hypogonadal female mice, genetically deficient in gonadotropin releasing hormone (GnRH), respond to preoptic area (POA) grafts obtained from normal fetal or neonatal mice with increased gonadotropin levels, ovarian and uterine development and continual vaginal estrus rather than spontaneous ovulatory cyclicity. Previous studies showed that such mice became pregnant following one overnight pairing with a normal male, indicating reflex ovulation. The present study evaluated plasma LH concentrations in relation to mating. Plasma LH levels in the hpg females with POA grafts were significantly elevated 10 min following the male partner's ejaculation, but were no different than baseline at 30, 60 or 120 min following the male's ejaculation. The post-copulatory plasma LH levels of 3.0 +/- 0.6 ng/ml (mean +/- S.E.M.) were considerably lower than the proestrous LH surge seen in the normal females in the colony (16.8 +/- 4.8 ng/ml), but in at least 4 of 10 hpg mice the levels were sufficient to induce ovulation as proved by pregnancy following this single mating. Grafts contained GnRH-reactive cells and fibers that projected to the median eminence of the host brains.

Animals↗
PubMed1987

Accessory olfactory bulb transplants correct hypogonadism in mutant mice.

Transplantation of normal fetal gonadotropin-releasing hormone (GnRH) neurons from the accessory olfactory bulb (AOB) to the third ventricle of GnRH-deficient adult mutant mice reverses the genetically determined reduction in pituitary hormones and poorly developed gonads. The transplanted heterotopic AOB neurons adapt their morphology and secretory functions to what is observed with preoptic GnRH neurons when transplanted into deficient mice and in the normal intact mature animal. This suggests the presence of median eminence trophic factors affecting the growth, terminal sprouting, and functional behavior of the transplanted neurons.

Animals↗
PubMed1987

Female sexual behavior in hypogonadal mice with GnRH-containing brain grafts.

Hypogonadal female mice respond to GnRH-containing fetal preoptic area (POA) implants in the third ventricle with vaginal opening and persistent vaginal estrus, ovarian, and uterine development and increased gonadotropin secretion. When these females are mated with normal males, reflex ovulation results in pregnancy. In the present study, POA implants derived from neonatal pups, whether male or female, were also capable of supporting reproductive development in the hypogonadal female mice. Evaluation of female sexual behavior in the mice with grafts showed that these mice responded to normal males with comparable levels of lordosis as are seen in normal female mice on the proestrous days of their cycles.

Animals↗
PubMed1987

Implantation of fetal preoptic area into the lateral ventricle of adult hypogonadal mutant mice: the pattern of gonadotropin-releasing hormone axonal outgrowth into the host brain.

Transplantation of fetal preoptic area tissue containing gonadotropin-releasing hormone neurons into the third ventricle of male hypogonadal mice resulted in an elevation of pituitary gonadotropin levels and correction of hypogonadism. This reversal of the neuroendocrine deficit was correlated with innervation of the median eminence by gonadotropin-releasing hormone axons. The specificity of fiber outgrowth suggested that local neuromodulatory factors might guide these axons to the nearby median eminence. To test this hypothesis, 14 adult hypogonadal males received unilateral fetal preoptic area grafts into the lateral ventricle, a site distant from the median eminence. After four months, healthy grafts containing numerous gonadotropin-releasing hormone neurons were seen in 9 hosts. However, none of these grafts corrected the hypogonadism of the host and there was no gonadotropin-releasing hormone innervation of the median eminence in any of these animals, thus demonstrating that the presence of gonadotropin-releasing hormone neurons in the ventricular space is itself not sufficient to stimulate the pituitary-gonadal axis. Instead, gonadotropin-releasing hormone axons coursed in the host fimbria, fornix, corpus callosum, and stria terminalis. These fibers could be traced into the anterior hippocampal area, medial and lateral septum, and the anterior hypothalamus. The distribution of these fibers included a number of regions which receive gonadotropin-releasing hormone fiber input in the normal mouse. These findings show that gonadotropin-releasing hormone neurons transplanted into the lateral ventricle can survive and extend processes into the host brain, often projecting to sites of normal gonadotropin-releasing hormone innervation. Their success in contacting these sites suggests that gonadotropin-releasing hormone fiber outgrowth may be influenced by regionally specified trophic and/or guidance factors.

Animals↗
PubMed1987

The effects of the age of intracerebroventricular grafts of normal preoptic area tissue upon pituitary and gonadal function in hypogonadal (HPG) mice.

Hypogonadal mice are deficient in the hypothalamic gonadotrophic hormone releasing hormone and as a consequence postnatal testicular development does not occur. Grafting preoptic area tissue from normal mice directly into the hypogonadal third ventricle dramatically reverses the hypogonadism; however, the age of the grafted preoptic area tissue is crucial to the survival and function of the graft. Grafting embryonic tissue (E16-18) resulted in 69% of the hypogonadal mice increasing testis weight some sevenfold within 30 days (5.6 to 35 mg). Postnatal day 1 (P1) tissue grafts elicited a similar rise in testis weight in 77% of recipients, whereas P5 tissue was only successful in 22% of cases. In this experimental group, however, testis weight also increased sevenfold compared with hypogonadal untreated mice. Stimulation of testicular growth in the E16-18 and P1 experimental groups was accompanied by an increase in pituitary gonadotrophic hormone content. P10 tissue did not stimulate testis growth nor was pituitary gonadotrophic hormone control elevated and the majority of grafts failed to survive over the 30 day period of the experiment. The present study has shown that the age of grafted tissue is critical in the restoration of physiological function in hypogonadal mice, and that gonadotrophic hormone releasing hormone neurons from E16-18, P1 and P5 preoptic area grafts that survive the 30 day period of the experiment and whose axons reach the median eminence portal vessels are equipotent in stimulating pituitary gonadotrophin synthesis and secretion.

Age Factors↗
PubMed1987

The long-term effect of chemonucleolysis on the intervertebral disc as assessed by magnetic resonance imaging.

With Magnetic Resonance Imaging (MRI) it is possible to monitor the changes in water content of the nucleus pulposus after intradiscal injection of chymopapain. In this prospective study the changes that occurred in 20 patients undergoing single-level chemonucleolysis were monitored. A constant pattern of gradual reduction of nuclear signal was seen in all cases. Complete loss of signal took at least 6 weeks and corresponded to the maximum reduction in disc space height. Seventeen patients were scanned at more than 1 year after treatment. Of these, 13 had been treated by chemonucleolysis alone. No significant return of signal from the nucleus pulposus was noted despite a slight reconstitution in disc space height. Chymopapain produced irreversible changes analogous to gross premature disc degeneration. No similar changes were noted in a control group of 12 patients (31 discs) undergoing diagnostic discography without injection of the enzyme.

Adolescent↗
PubMed1987

Magnetic resonance imaging of adolescent disc herniation.

Magnetic resonance imaging (MRI) was used to compare the appearance of the spine in 20 adolescents with proven symptomatic intervertebral disc herniations with that in 20 asymptomatic patients who acted as controls. Abnormality in the signal from the nucleus pulposus of one or more discs was present in all patients, while only four of the 20 controls had any abnormal signals. In all the patients the symptomatic disc produced an abnormal signal and in most a herniated fragment of the nucleus pulposus was identified. Fifteen of the 20 patients had multiple-disc abnormality: six had three abnormal discs and nine had two. This suggests there was an underlying diathesis in patients who later developed disc herniation.

Adolescent↗
PubMed1987

The penetration of antibiotics into the normal intervertebral disc.

The role of antibiotics in the treatment of disc-space infection is controversial. This study assessed the tissue penetration of flucloxacillin and cephradine into the normal intervertebral disc after intravenous administration of a bolus dose of antibiotic. Twenty-five discs were removed from 12 adolescent patients having anterior spinal surgery to correct scoliosis; antibiotic had been administered between 30 minutes and four hours before operation. Despite high blood levels, no antibiotic could be detected by bioassay or by high-pressure liquid chromatography (h.p.l.c.) in any of the specimens from the nucleus pulposus or the annulus fibrosus.

Absorption↗
PubMed1986

Role of the preoptic area in the neuroendocrine regulation of reproduction: an analysis of functional preoptic homografts.

In conclusion, POA grafts that contain GnRH cell bodies are capable of correcting many of the reproductive deficiencies that are associated with a genetic failure to produce GnRH. The previously infertile animals exhibit steroidogenesis and gametogenesis. Ovulations associated with mating suggest that the grafted GnRH cells are responding to some environmental cues and may be under some regulation by the host brain. Although the grafts contain tissue that may have sexually dimorphic characteristics, the studies with the hpg mice have not yet revealed any effects of the grafts that could be related to the sex of the donor.

Animals↗
PubMed1986

Magnetic resonance imaging and discography in the diagnosis of disc degeneration. A comparative study of 50 discs.

The lumbar spines of 22 patients were examined for disc degeneration by magnetic resonance imaging (MRI) and by discography. The results from 50 intervertebral discs visualised by both techniques were independently assessed and graded on a five-point scale from normality to gross degeneration and then compared. In 44 discs the results agreed. Of the six discs which gave differing results, four discrepancies were due to observer error and two to incorrect placement of the discographic needle. MRI was shown to be more accurate than discography in the diagnosis of disc degeneration. It has several major advantages, which should make it the investigation of choice.

Adult↗
PubMed1986

Weakness of foot dorsiflexion and changes in compartment pressures after tibial osteotomy.

Weakness of dorsiflexion of the foot is a common complication of proximal tibial osteotomy and it has been suggested that this may be caused by an anterior tibial compartment syndrome. A prospective study of 20 patients undergoing tibial osteotomy was undertaken, in which compartment pressures were recorded and related to clinical signs. In 10 of the patients, the operation site was drained, and in 10 no drainage was employed. The undrained group showed significant elevation (greater than 45 mmHg) of the anterior compartment pressure in seven patients, and five of these had transient clinical signs. Only one patient had any permanent deficit, a minor asymptomatic weakness of extensor hallucis longus. In the drained group the pressures remained below 30 mmHg in all except two patients, who both had only a minor pressure rise and no significant early clinical signs. However, two patients from this group later developed weakness of dorsiflexion, probably due to common peroneal nerve injury, the cause of which is not clear.

Compartment Syndromes↗
PubMed1986

The changes in the intervertebral disc after chemonucleolysis demonstrated by magnetic resonance imaging.

Magnetic resonance imaging (MRI) of the spine produces images which reflect the chemical composition of the intervertebral disc. We have conducted a prospective study of the serial changes in the MRI appearance of the intervertebral disc after chemonucleolysis with the enzyme chymopapain. Fourteen patients were studied after single-level chemonucleolysis and the results compared with a control group of 17 discs in six patients who had diagnostic discography without enzyme insertion. A consistent pattern of gradual loss of signal from the nucleus pulposus culminating in complete loss of nuclear signal was seen in all cases after chemonucleolysis. Chymopapain therefore produced MRI changes analogous with premature gross disc degeneration. The rate at which this occurred varied; complete loss of signal took at least six weeks. Transitory minor end-plate changes were present in five patients, probably representing a mild chemical discitis. No similar changes were seen in the discography group.

Acute Disease↗
PubMed1986

Relationships between behavioral rhythms, plasma corticosterone and hypothalamic circadian rhythms.

Circadian rhythms in physiological processes and behaviors were compared with hypothalamic circadian rhythms in norepinephrine (NE) metabolites, adrenergic transmitter receptors, cAMP, cGMP and suprachiasmatic nucleus (SCN) arginine vasopressin (AVP) in a single population of rats under D:D conditions. Eating, drinking and locomotor activity were high during the subjective night (the time when lights were out in L:D) and low during the subjective day (the time when lights were on in L:D). Plasma corticosterone concentration rose at subjective dusk and remained high until subjective dawn. Binding to hypothalamic alpha 1- and beta-adrenergic receptors also peaked during the subjective night. Cyclic cGMP concentration was elevated throughout the 24-hr period except for a trough at dusk, whereas DHPG concentration peaked at dawn. Arginine vasopressin levels in the suprachiasmatic nucleus peaked in the middle of the day. No rhythm was found either in binding to the alpha 2-adrenergic receptor, or in MHPG or cAMP concentration. Behavioral and corticosterone rhythms, therefore, are parallel to rhythms in hypothalamic alpha 1- and beta-receptor binding and NE-release. Cyclic GMP falls only at dusk, suggesting the possibility that cGMP inhibits activity much of the day and that at dusk the inhibition of nocturnal activity is removed. SCN AVP, on the other hand, peaking at 1400 hr, may play a role in the pacemaking function of the SCN that drives these other rhythms.

Animals↗
PubMed1986

Magnetic resonance imaging of the spine in adolescents.

The appearances of the spine in 14 adolescents with symptomatic intervertebral disc herniations and in 20 asymptomatic controls were compared at magnetic resonance imaging. Abnormality in the signal from the nucleus pulposus of one or more discs was present in all the patients, while only 4 of the 20 controls had any abnormal discs. Ten of the 14 patients had multiple-level disc abnormality. Five had three abnormal discs and five two-level abnormality. This suggests that there was an underlying diathesis in these patients towards the development of disc herniation.

Adolescent↗
PubMed1986

Ultrastructure of gonadotropin-releasing hormone neuronal structures derived from normal fetal preoptic area and transplanted into hypogonadal mutant (hpg) mice.

The hpg mutant mouse lacks the neurohormone gonadotropin-releasing hormone (GnRH) and hence has a reproductive deficit. This deficit can be corrected by placement of normal fetal preoptic area into the third ventricle (see Krieger et al., 1985). We have now used ultrastructural immunocytochemistry to investigate the morphology of GnRH neurons in such intraventricular grafts, the routes that their axons take as they exit into the host, and the neurosecretory terminations that they make in the host median eminence. The GnRH cells in the transplant were similar in morphology to that reported for such cells in the preoptic area of other rodents. There was a large central nucleus, frequently indented and containing 1 or 2 nucleoli. The thin rim of cytoplasm was filled with rough endoplasmic reticulum, Golgi stacks, and mitochondria. Both dendritic and axonal profiles were identified, and a modest synaptic input to the former was found. Between the host and the implant a complex multilayered ependymal zone developed, and it was through this region that GnRH axons exited into the host arcuate nucleus and median eminence, usually surrounded by ependymal or glial elements. Within the median eminence, GnRH terminals were in close association with fenestrated blood vessels forming a normal neurosecretory terminus.

Animals↗
PubMed1985

The effects of the GnRH agonist, [(imBzl)-D-His6, Pro9-NEt]-GnRH, on the response to stress in rats.

The antigonadal activity of potent gonadotropin-releasing hormone (GnRH) analogs may be associated with undesirable secondary effects on other aspects of the endocrine system. In preliminary studies, rats treated with GnRH agonists were noted to have altered adrenal weights. To determine whether this was associated with alterations in the pituitary-adrenal axis we have studied male and female rats treated with the GnRH agonist [(imBzl)-D-His6, Pro9-NEt]-GnRH (GnRH-A). Animals receiving daily doses of this peptide showed normal adrenal corticosteroid responsivity to both ether and immobilization stress. Brain, pituitary, and plasma concentrations of immunoreactive (IR) beta-endorphin and ACTH were unaffected in treated animals after four weeks of daily injections, although after one week plasma levels of the two hormones were transiently elevated in female rats. Adrenal, thyroid, and pituitary lobe weights were unchanged with treatment, except for an increase in anterior pituitary weight in males receiving the lowest dose of GnRH-A. In conclusion, long-term treatment with GnRH-A, while significantly affecting gonadal and secondary sexual tissue, had little impact on the hypothalamo-pituitary-adrenal system or on stress responsivity in rats.

Adrenal Glands↗