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M J Gibson

Publications and source records attributed to M J Gibson.

At least 55 records · Page 3Linked to original sources
PubMed1991

Effects of N-methyl-D,L-aspartic acid on luteinizing hormone secretion in normal mice and in hypogonadal mice with fetal preoptic area implants.

Many aspects of reproductive function are corrected in hypogonadal mice with preoptic area grafts (HPG/POA). Gonadotropin release and gonadal development are dependent on the presence of GnRH cells within the grafts and GnRH innervation of the median eminence. This study examined the effect of a known modulator of GnRH secretion, N-methyl-D,L-aspartic acid (NMA), in adult normal and HPG/POA male and female mice. All HPG/POA males had significant testicular development after graft surgery, and most HPG/POA females were in constant vaginal estrus and showed ovarian and uterine development; a few also demonstrated ovulatory cyclicity after pregnancies initiated by reflex ovulation. Groups of normal and HPG/POA males that were intact (INT) or castrated (CX) 7 days before testing were challenged with saline, NMA (20 mg/kg), and GnRH (100 ng/0.1 ml). Sequential blood samples from awake animals were obtained via intracardiac catheters for evaluation of plasma LH. There were significant increases in plasma LH after NMA challenge in normal INT [n = 15; 0 min, 0.26 +/- 0.02 (mean +/- SE); 10 min, 1.20 +/- 0.10 ng/ml; P less than 0.05] and normal CX (n = 13; 0 min, 0.36 +/- 0.06, 10 min, 3.25 +/- 0.27). Plasma LH secretion in response to NMA was significantly correlated (r = 0.786; P less than 0.001) with plasma LH release after the GnRH challenge in normal males. In contrast, only 3 of 17 HPG/POA (1 INT and 2 CX) showed increased circulating LH after NMA challenge, despite heightened pituitary sensitivity to GnRH. Normal and HPG/POA female mice were ovariectomized (OX) or OX and estrogen primed (OXE2) 7 days before testing. Intact cycling normal and cycling HPG/POA mice were tested in estrus (EST). There was a greater response to NMA in normal OX (n = 8; 0 min, 0.39 +/- 0.02; 10 min, 1.44 +/- 0.28) than in OXE2 (n = 13; 0 min, 0.29 +/- 0.01; 10 min, 0.52 +/- 0.07) despite similar gonadotroph sensitivity to GnRH. There was also a significant increase in plasma LH in response to NMA in HPG/POA-OX (n = 7; 0 min, 0.50 +/- 0.10; 10 min, 1.62 +/- 0.22) and HPG/POA-OXE2 (n = 12; 0 min, 0.39 +/- 0.04; 10 min, 1.31 +/- 0.26). Plasma LH levels after NMA treatment were significantly correlated with responses to GnRH in female HPG/POA (r = 0.58; P less than 0.03), but not in normal females. Neither normal-EST nor HPG/POA-EST had increased LH release after NMA challenge, perhaps due to the low gonadotroph sensitivity in this state.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Dislocation after primary arthroplasty for subcapital fracture of the hip. Wide range of movement is a risk factor.

Dislocation is the most frequent serious complication following total hip replacement for subcapital femoral fracture. We report a prospective study, using matched groups, which compared the range of hip movement following hip replacement for arthritis and for fracture. The range of movement was significantly greater in the fracture group. We suggest that this is a predisposing factor for dislocation.

Aged↗
PubMed1990

Modulation of gonadotropin-releasing hormone neuronal activity as evidenced by uptake of fluorogold from the vasculature.

Peripheral injections of the tracer fluorogold (FG) and immunocytochemistry were used to study the modulation of gonadotropin-releasing hormone (GnRH) cell secretory activity in adult mice. Intraperitoneal administration of FG would make it available to all GnRH terminals outside the blood-brain barrier. The degree of capture of the dye would be linked to exocytotic (e.g., secretory) events at the nerve terminal. Single injections of tracer were made into intact mice of both sexes, and this resulted in the retrograde labeling of two-thirds of the GnRH cell bodies. Administration of identical doses to 3 week castrate mice revealed a reduction in the percentage of GnRH cells, with detectable FG, to 40% of the total. Castration did not diminish the number of GnRH cells visualized. When castrate animals received two doses of FG, the number of GnRH cells with tracer was increased to slightly greater than intact levels. This suggests that the secretory rate of individual GnRH cells might be reduced under conditions of castration. In addition, when ovariectomized females treated with estrogen and progesterone to induce luteinizing hormone (LH) surge were injected with FG just prior to that surge, over 80% of the GnRH neurons were robustly labeled with FG. These latter data are interpreted as representing GnRH neurons at maximally synchronized activity. This study suggests that peripheral administration of FG can be used in this species to follow alterations in neurosecretory rates.

Animals↗
PubMed1990

Are neurons of the arcuate nucleus necessary for pathfinding by GnRH fibers arising from third ventricular grafts?

The hypogonadal (hpg) mouse lacks GnRH due to a severe truncation of the gene by which it is encoded. This results in an infertile animal with an infantile reproductive system. When fetal or 1-day postnatal septal/preoptic area of a normal mouse is grafted into the third ventricle of an hpg mouse, GnRH-containing fibers grow out of the grafts and innervate the host median eminence (ME), a normal target of these fibers. GnRH axons exiting the graft course follow a very stereotyped pathway through host tissue. They are observed passing through the ependymal wall of the ventricle directly into the ME or arching through the host arcuate nucleus to terminate in the host ME. Given the fixed pattern of outgrowth, we wanted to determine if the neurons of the arcuate nucleus, which lie between the graft and its target, are exerting an influence on the growth and direction of these fibers. The excitotoxin monosodium glutamate (MSG) has been shown to destroy the vast majority of arcuate neurons when administered neonatally. Mutant host animals treated with MSG received fetal grafts of normal septal/preoptic area. Brains were examined for GnRH fiber outgrowth 30 days later to assess early outgrowth which preferentially uses the arcuate route. We report here that the pattern of outgrowth is virtually identical to that observed in saline-injected, grafted animals. There is also no difference in the success rate of grafts placed in control vs MSG-treated hosts nor in the stimulation of testicular growth. The results of this experiment imply that axonal outgrowth to the ME does not rely on arcuate neurons for guidance information or trophic substances. These functions may be subserved by glia, tanycytes/ependyma, or the target.

Animals↗
PubMed1990

Repair of reproductive deficits by neural transplantation.

Transplantation of brain tissue has been used to ameliorate the genetic lesion of the hypogonadal mutant mouse. This animal does not synthesize gonadotropin-releasing hormone (GnRH) and so has an infantile reproductive system. Implantation of normal fetal or neonatal preoptic area containing GnRH neurons reverses many aspects of the reproductive deficiency. Pituitary and plasma levels of gonadotropins rise, followed by growth of the gonads and sexual organs. Pituitary release of gonadotropins is episodic, suggesting that the grafted tissue is integrated into the "pulse generator." The vast majority of grafted animals do not show castration-induced elevations of luteinizing hormone (LH) nor respond to exogenous steroids with a depression in circulating LH. Negative feedback of gonadal steroids seems to be inoperative. In contrast, some females can show ovulatory surges of LH in response to mating (reflex ovulation), after administration of exogenous steroid (progesterone), and, on rare occasion, ovulation cycles occur spontaneously. Anatomical studies demonstrate that reproductive recovery is dependent on the outgrowth of GnRH axons to the host median eminence. Some but not all of the GnRH neurons within the grafts contribute to this innervation. GnRH axons exit into the host along well-defined pathways, recapitulating in part the paths taken by normal axons. How the graft and host are integrated to produce the panoply of reproductive responses is the subject of current study.

Animals↗
PubMed1990

Intramedullary locking nails for femoral shaft fractures in elderly patients.

Fractures of the femoral shaft are generally considered to affect young patients, but we have reviewed 24 cases in patients over 60 years who have been treated by locked nailing, usually by closed methods. Most were women with low-velocity injuries, but despite this, 14 fractures were significantly comminuted. The complication rate was 54% with a peri-operative mortality of 17%. Most complications were the general ones of operating on elderly patients. Specific complications included: fractures below an abnormal hip, proximal fracture related to the nail and poor purchase in the distal femur. In all survivors, the femoral shaft fractures united satisfactorily, and the fixation allowed early mobilisation. The locking nail appears to be an effective method of managing femoral shaft fractures in the elderly patient.

Aged↗
PubMed1989

Identification of gonadotropin releasing hormone (GnRH) neurons projecting to the median eminence from third ventricular preoptic area grafts in hypogonadal mice.

Functional gonadotropin releasing hormone (GnRH) neurosecretory activity can be restored in genetically hypogonadal (hpg) adult mice with grafts of GnRH-containing fetal or neonatal septal-preoptic area (S/POA) tissue. Neurons implanted into the third ventricle of the host brain survive and send out axons which innervate one of the normal targets of these neurons, the median eminence (ME). Fibers terminate near primary portal vessels where GnRH is available for release into the vasculature, and this axonal outgrowth is essential for the stimulation of gonadotropin secretion, gonadal and accessory sex structure growth, gametogenesis, and fertility. Although it is known that GnRH axons reach their target, it is not known if all such neurons in a graft contribute to the projection. Taking advantage of the fact that axons in the ME, the sole host target, are outside the blood-brain barrier (BBB), long-term grafted animals were injected intraperitoneally with a retrograde tracer, Fluorogold (FG). Normal male mice were injected for comparison. Animals were sacrificed 5 days after injection and brain sections in the area of the graft were stained immunocytochemically for GnRH. In the normal male mice, two-thirds of the GnRH neurons were double-labeled with FG. In grafted individuals which showed increased gonadal growth, the percentage of labeled cells ranged from 17 to 75%. The results indicate that despite tissue injury, ectopic location, and a vastly reduced population, transplanted fetal GnRH neurons recapitulate a pattern seen in normal intact mice where some but not all neurons were capable of capturing a peripherally delivered tracer.

Animals↗
PubMed1989

Estradiol-concentrating cells in the brains of hypogonadal female mice and in their intraventricular preoptic area implants.

Estradiol-concentrating cells were evaluated in the brains of hypogonadal female mice and in their intraventricular preoptic area brain grafts using autoradiography for [3H]estradiol. Normal distribution of estradiol-concentrating cells was observed in the brains of the hypogonadal mice with dense collections of these cells in the lateral septum; the medial preoptic area; the medial anterior hypothalamus; the ventromedial, arcuate, and periventricular nuclei of the hypothalamus; and the medial and cortical nuclei of the amygdala. In addition, estradiol-concentrating cells were present in all the transplants, with the estimated number of such cells in the transplants ranging from 390 to 2600. There was no correlation between numbers of estradiol-concentrating cells within the transplants and degree of reproductive recovery in the hypogonadal mice. Gonadotropin-releasing hormone (GnRH) immunocytochemistry of alternate sections revealed GnRH-immunoreactive material within the grafts and immunoreactive fibers exiting the grafts and entering the hosts' median eminence. No specific relationship between GnRH cells and estradiol-concentrating cells was evident within the grafts, nor was there any indication of identity of estrogen-concentrating cells with GnRH cells.

Animals↗
PubMed1989

Influence of induced hypotension and spinal distraction on feline spinal somatosensory evoked potentials.

Spinal cord injury may occur during surgical correction of spinal deformity, which is performed frequently under hypotensive anaesthesia. We have investigated the interaction between pharmacologically induced hypotension and distraction on feline spinal cord function. Twelve anaesthetized cats were subjected to hypotension (mean arterial pressure (MAP) 60 mm Hg) using a mixture of sodium nitroprusside and trimetaphan (1:5). No significant changes were observed in somatosensory evoked potentials recorded at T11. In six cats distraction was applied at L2-3 in 2.5-mm increments up to 1 cm, while MAP was maintained at 100 mm Hg (normotensive group). The remaining cats were subjected to the same distraction procedure at an MAP of 60 mm Hg (hypotensive group). In the hypotensive group, a reduction in amplitude of evoked response occurred at significantly less distraction than in the normotensive group. These data indicate that the feline spinal cord is more sensitive to spinal distraction under hypotensive conditions.

Animals↗
PubMed1989

The geometry of the muscles of the lumbar spine determined by magnetic resonance imaging.

Magnetic Resonance Imaging (MRI) is a new multiplanar imaging technique that clearly demonstrates soft tissue anatomy. The lumbar spines of 26 males have been scanned. From the transverse scans, the position and cross-sectional areas of the muscles of the lumbar region were recorded. Regression analysis was performed to relate these values to trunk measurements and body weight. Sagittal scans were used to measure the angles to the vertical of the lumbar discs and of the skin overlying the spinous processes. The position of each lumbar disc relative to two skin points was measured. These parameters can then be used in biochemical calculations of low-back forces.

Adolescent↗
PubMed1989

Effects of gonadectomy and treatment with gonadal steroids and luteinizing hormone secretion in hypogonadal male and female mice with preoptic area implants.

The ability of male and female hypogonadal (hpg) mice with preoptic area (POA) grafts to show negative feedback was studied. GnRH neurons within POA grafts send axons into the median eminence of the hpg host (HPG/POA), resulting in increased gonadotropin production and gonadal development in the mice that are genetically unable to produce GnRH. The present studies evaluated whether negative feedback, an aspect of normal reproductive function, is present in male and female HPG/POA mice. In normal male mice plasma LH was increased 1 or 5 months after castration and returned to baseline after testosterone propionate treatment. In contrast, no alterations in plasma LH were measured in similarly treated HPG/POA males. HPG/POA female mice were ovariectomized 6 weeks or 3 or 6 months after graft surgery and received sc 17 beta-estradiol (E2) implants 3 months later. Normal mice were studied when 6 weeks old and 8 months old (age-matched to HPG/POA mice ovariectomized 3 months after graft surgery). Further, to determine whether the mice were capable of positive feedback, 1 week after receiving E2 implants, mice in the 6-week and 3-month postgraft surgery groups were challenged with sequential administration of estradiol benzoate and progesterone. The significant increase in plasma LH after ovariectomy or decrease after E2 implant in normal female mice was not present in most HPG/POA female mice. Just 2 of the 24 HPG/POA females studied had increased plasma LH after gonadectomy, and in only 1 of these was plasma LH suppressed by E2 treatment. The ability of an individual HPG/POA mouse to show positive feedback did not predict the ability to show negative feedback, nor did the ability to show negative feedback predict positive feedback capability. Among the mice that failed to respond to ovariectomy with increased LH release were some that had elevated LH in response to steroid challenge or had spontaneously ovulated. On the other hand, neither mouse that had increased LH release after ovariectomy had shown positive feedback to a steroid challenge. Immunocytochemical evaluation revealed GnRH cells within the grafts and GnRH fiber innervation of the host's median eminence, but there was no correlation between numbers of GnRH cells or extent of innervation with the ability to show either negative or positive feedback, nor was the presence of vasoactive intestinal peptide cells within the grafts of predictive value. The failure of negative feedback in most of the HPG/POA mice tested may be due to the failure to establish as yet unidentified but essential afferents to the grafted GnRH cells and/or their axonal processes.

Animals↗
PubMed1988

Quantitative analysis of synaptic input to gonadotropin-releasing hormone neurons in normal mice and hpg mice with preoptic area grafts.

Mutant hypogonadal (hpg) mice with a truncated gene for the precursor to gonadotropin-releasing hormone (GnRH) show certain aspects of recovery of reproductive function after receiving grafts of normal preoptic area into the third ventricle. We have previously shown that GnRH neurons from within the grafts can innervate the appropriate neural-hemal target in the host. To determine if in turn these exogenously derived neurons receive a synaptic input comparable to the GnRH neurons in the normal animal we have now carried out a quantitative ultrastructural analysis to compare the synaptic input to GnRH neurons in the normal preoptic area and in the grafts. In almost all cases GnRH cells or dendrites in normal brains and within the grafts received a synaptic input. In normal animals, input to GnRH dendritic profiles was significantly greater (P less than 0.001) than to the somatic plasma membrane and this trend was also observed within the grafts though the difference was not statistically significant. In addition, no statistically significant difference was found between the input to GnRH structures within the grafts and in normal preoptic area. However, a substantial variability in input among grafted animals was evident which was not observed in normal animals. The sources of variability within the grafts are discussed and we suggest that the deficiencies and differences that exist in regulation of gonadotropin secretion among grafted hpg animals may be reflected in aberrant synaptic input.

Animals↗
PubMed1988

Diabetes in Western Australian children: descriptive epidemiology.

The prevalence and incidence of diabetes mellitus in the age group zero to 14 years in Western Australia were determined from a survey by means of Schools Health Services. Additional information from the State's computer-linked hospital records system, the State's only children's hospital, diabetic clinics and physicians enabled virtually complete ascertainment of cases of childhood diabetes. Only 60% of school-age diabetic children were known to school nurses before the survey, but the nurses were able to identify two-thirds of the remainder during the survey. Among non-Aboriginal children, the prevalence of diabetes in the age group zero to 14 years was 0.59 per 1000 children and the incidence was 12.3 per 100,000 children per year. These rates are somewhat lower than those that have been reported from the United Kingdom and North America, and substantially lower than the rates that were reported from Scandinavia. All but one of the diabetic children who were identified required insulin and were assumed to be insulin-dependent. An excess of boys was found. None of 8715 Aboriginal or part-Aboriginal children had insulin-dependent diabetes mellitus, which indicates that this racial group has a low prevalence of this condition. In case--control studies, which used questionnaires for parents, no significant trends were found in relation to the history of immunizations or of specific viral illnesses except for a past history of varicella which was less frequent in diabetic children. A past history of established breast-feeding (of more than one week) was less frequent in diabetic children, as was the ingestion of vitamin C supplements before the onset of diabetes. Some evidence for a seasonality of onset was obtained. The diabetic children were absent from school for more days and had more admissions to hospital than did non-diabetic children. The majority of diabetic children were prescribed insulin twice a day or more often (84%); performed home blood-glucose monitoring (74%); and attended hospital diabetic clinics (91%).

Adolescent↗
PubMed1988

Thymocyte maturity in male and female hypogonadal mice and the effect of preoptic area brain grafts.

Hypogonadal mice with a genetic deficiency of gonadotropin-releasing hormone (GnRH) have low levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and gonadal steroids. In this study we found differences from normal mice in many aspects of thymic development. Thymus weights and cellularity were higher in hypogonadal than in normal male mice but lower in hypogonadal than in normal females. Although all normal mice had higher proportions of mature, single staining thymocytes (CD8+ or CD4+) than seen in hypogonadal mice, there was a sex difference in the basis for this shift. Significantly more double-staining (CD8+, CD4+) thymocytes were seen in hypogonadal males than in normal males while both groups had similar single-staining populations. However, in females, both single-staining CD8+ and CD4+ thymocytes were more numerous in normal than in hypogonadal females while numbers of double-staining cells were similar in the two groups. These studies indicate that a mature thymocyte profile may be arrived at through differential effects of reproductive hormones in males and females. When brain grafts containing GnRH cells were used to correct reproductive deficits in hypogonadal mice, there were higher splenocyte counts in males with grafts, a similar trend in females, and a lower ratio of single staining CD4+ to CD8+ thymocytes in all females with grafts vs. all females without, regardless of whether or not the grafts corrected the reproductive hormone status of the recipients, indicating an effect of the graft surgery on the immune system.

Animals↗
PubMed1988

Effect of neonatal androgenization on positive feedback in female mice.

Exposure of female mice to androgens within 5 days of birth impairs fertility. Such treatment in rats results in a post-pubertal acyclic state of persistent vaginal cornification and in an inability, when ovariectomized, to show normal positive feedback on luteinizing hormone (LH) release in response to steroid challenge. In the present study, we explored whether neonatally androgenized mice demonstrate positive feedback. Female mice were administered 100 micrograms of testosterone propionate (TP) on either Day 1 (TP1) or Day 5 (TP5) after birth, or vehicle on Day 1 (SO1). Androgen-treated mice had a statistically significant advance in onset of vaginal opening as compared with vehicle-treated mice. All mice that received TP entered constant vaginal estrus, whereas those given vehicle showed variable cytology. All mice were ovariectomized at 7 wk of age and received Silastic capsules containing a priming dose of 17 beta-estradiol. When all mice were challenged 1 wk later with sequential administration of estradiol benzoate and progesterone, a significant increase in plasma LH level was present only in the vehicle-treated mice. We conclude that neonatal androgenization defeminizes the neuroendocrine mechanisms controlling gonadotropin release.

Aging↗
PubMed1988

Transplanted gonadotropin-releasing hormone neurons promote pulsatile luteinizing hormone secretion in congenitally hypogonadal (hpg) male mice.

Congenitally hypogonadal (hpg) male mice are unable to synthesize biologically active gonadotropin-releasing hormone (GnRH). Implantation of normal fetal preoptic area tissue containing GnRH neurons into the third ventricle of adult hpg males significantly elevates pituitary levels of luteinizing hormone (LH) and corrects their hypogonadism. In all responding animals, immunoreactive GnRH neurons within the transplant innervate the median eminence of the host. To assess whether gonadal recovery in hpg hosts results from pulsatile secretion of GnRH from grafted neurons, we compared the pattern of variation in plasma LH levels in 19 hpg graft recipients with testicular growth to that of 10 normal adult mice. All animals were castrated prior to receiving an indwelling catheter in the jugular vein. Sequential blood samples were collected (t = 10 min) and assayed for LH. Pulsatile LH secretion was seen in 11 of 19 hpg hosts and in all control mice. While there was great variability between individual animals, measures of baseline LH, LH pulse amplitude and duration, interpulse interval, and LH pulse frequency revealed no difference between hpg graft recipients and normal castrates in their LH pulse pattern. Immunocytochemical analysis of the brain in hpg hosts suggested no correlation between any parameter of pulse activity and individual differences in GnRH cell number or GnRH fiber outgrowth into the median eminence. Sources of variation in LH secretion among graft recipients, and between hpg hosts and normal mice, are discussed. We suggest that transplanted GnRH neurons are capable of integration into a GnRH 'pulse generator' which can support a near-normal pattern of pulsatile LH secretion, leading to testicular growth and steroid production.

Animals↗