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Biomedical subjects

K J Jones

Publications and source records attributed to K J Jones.

At least 37 records · Page 2Linked to original sources
PubMed1998

Ribosomal RNA transcriptional activation and processing in hamster facial motoneurons: effects of axotomy with or without exposure to testosterone.

A key step in the ability of neurons to survive injury and successfully regenerate involves ribosomal RNA production. Testosterone propionate (TP), augments facial nerve regeneration in the adult hamster. TP modulates the nucleolar reaction in injured facial motoneurons, such that mature ribosome levels increase more rapidly and in greater magnitude than with injury only. In this study, molecular and electron microscopic stereologic approaches were used to determine the effects of axotomy and steroid treatment on ribosomal transcription and processing in facial motoneurons. Castrated adult male hamsters were subjected to right facial nerve transection at the stylomastoid foramen. Half the animals were subcutaneously implanted with one Silastic TP capsule, with the remainder sham implanted. For the in situ hybridization experiments, postoperative survival times were 0.5, 2, or 6 hours. In situ hybridization with a ribosomal DNA probe specific to the external transcribed spacer region located at the 5' end of the ribosomal gene was accomplished. Transcriptional activation of the rRNA gene occurred rapidly, within 2 hours, after injury only. Unexpectedly, TP treatment did not alter the time course or magnitude of rRNA transcriptional activity. For the electron microscope experiments, the postoperative time of 12 hours was selected. Stereologic analysis of 3 nucleolar subcomponents, fibrillar centers (site of rRNA transcription), nucleolonema (site of rRNA processing), and granular material (site of preribosome storage), was accomplished. TP decreased the nucleolonemal strands and the granular material, relative to injury only. These results suggest that, although rRNA transcription is rapidly activated by axotomy, rRNA processing is temporarily stalled. TP does not affect the early, axotomy-induced transcriptional activation of the ribosomal gene, but may, instead, prevent the subsequent disruption in rRNA processing. An hypothesis for the molecular mechanism by which steroids augment the regenerative capabilities of injured facial motoneurons is presented.

Animals↗
PubMed1998

Differential effects of facial nerve transection on heat shock protein 70 expression in the developing and adult hamster facial nucleus.

In this study, the effects of axotomy on heat shock protein 70 (hsp70) protein levels were analyzed by immunoblotting with a hsp70 antibody that recognized constitutive and inducible forms of the protein. The right facial nerve of postnatal day 4 (neonate) or 100 (adult) hamsters was transected at its exit from the stylomastoid foramen, with the left nerve serving as internal control. Postoperative survival times were 2, 6, 12, and 24 h, with 3 animals per time point. Tissue punches containing individual facial nuclear groups were collected and homogenized. Approximately 10 microg of total protein was loaded onto paired gels and electrophoretically separated. Immunoblots of one gel from each pair were prepared, with the other gel stained in 0.2% Coomassie blue and used for verification of equality of lane loading. The results indicate that hsp70 protein levels increase in the adult, but decrease in the neonate, after axotomy. It is concluded that a stress response to cellular damage is an initial component of the classically described "axon reaction" and that hsp70 plays a role in mediating motoneuron survival after peripheral nerve transection.

Age Factors↗
PubMed1998

Abnormalities of dystrophin, the sarcoglycans, and laminin alpha2 in the muscular dystrophies.

Abnormalities of dystrophin, the sarcoglycans, and laminin alpha2 are responsible for a subset of the muscular dystrophies. In this study we aim to characterise the nature and frequency of abnormalities of these proteins in an Australian population and to formulate an investigative algorithm to aid in approaching the diagnosis of the muscular dystrophies. To reduce ascertainment bias, biopsies with dystrophic (n=131) and non-dystrophic myopathic (n=71) changes were studied with antibodies to dystrophin, alpha, beta, and gamma sarcoglycan, beta dystroglycan, and laminin alpha2, and results were correlated with clinical phenotype. Abnormalities of dystrophin, the sarcoglycans, or laminin alpha2 were present in 61/131 (47%) dystrophic biopsies and in 0/71 myopathic biopsies, suggesting that immunocytochemical study of dystrophin, the sarcoglycans, and laminin alpha2 may, in general, be restricted to patients with dystrophic biopsies. Two patients with mutations identified in gamma sarcoglycan had abnormal dystrophin (by immunocytochemistry and immunoblot), showing that abnormalities of dystrophin may be a secondary phenomenon. Therefore, biopsies should not be excluded from sarcoglycan analysis on the basis of abnormal dystrophin alone. The diagnostic yield was highest in those with severe, rapidly progressive limb-girdle weakness (92%). Laminin alpha2 deficiency was identified in 5/131 (4%) patients; 215 patients presented after infancy, indicating that abnormalities of laminin alpha2 are not limited to the congenital muscular dystrophy phenotype. Overall patterns of immunocytochemistry and immunoblotting provided a guide to mutation analysis and, on the basis of this study, we have formulated a diagnostic algorithm to guide the investigation of patients with muscular dystrophy.

Adolescent↗
PubMed1997

Gonadal steroid regulation of hamster facial nerve regeneration: effects of dihydrotestosterone and estradiol.

We have demonstrated, in a series of experiments, the therapeutic potential of androgens in facial motoneuron regeneration in the adult hamster. Initial work utilized testosterone propionate (TP) as the form of androgen given to adult hamster at the time of facial nerve crush axotomy at its exit from the stylomastoid foramen. TP is capable of being enzymatically converted to estrogen. Thus, the effects of TP on the regenerative properties of facial motoneurons could be due to androgens, estrogens, or both. Recent studies of androgen receptor (AR) mRNA levels suggest that androgens and estrogens work synergistically to regulate AR expression in these motoneurons. In this study, we examined the ability of dihydrotestosterone propionate (DHTP), a nonaromatizable androgen which cannot be converted to estrogen, and estradiol (E2) to alter facial nerve regeneration, using fast axonal transport of radioactively labeled proteins to assess facial nerve regeneration. Adult gonadectomized male hamsters were subjected to right facial nerve crush axotomy, with the left side serving as control, and divided into three groups. One-third of the animals received 1 subcutaneous implant of DHTP, one-third received 1 subcutaneous implant of E2, and the remaining third was sham implanted. Postoperative survival times were 4 and 7 days. As expected, DHTP treatment resulted in an approximately 40% increase in the rate of regeneration, with an associated prolongation in the delay time before sprouting occurred. These effects were slightly greater than previously observed with TP, as might be predicted given the more potent physiological effects observed with DHTP compared to TP. Surprisingly, E2 treatment also resulted in an increase in the rate of regeneration (30%), with minimal effects on the delay time before sprout formation occurred. The results argue for a synergistic role for androgens and estrogens in augmenting peripheral nerve regeneration in the model system used in this study.

Animals↗
PubMed1997

Effects of axotomy and testosterone on androgen receptor mRNA expression in hamster facial motoneurons.

We have previously demonstrated that testosterone propionate (TP) treatment accelerates the rate of regeneration following facial nerve crush axotomy in adult male hamsters. These effects are mediated by androgen receptor (AR) activation and are blocked by pretreatment with the AR antagonist, flutamide. In addition to its beneficial effects on regeneration, TP regulates AR mRNA levels in facial motor neurons (FMN). Gonadectomized (gdx) male hamsters have been shown to have approximately 50% of the AR mRNA levels found in gonadally intact males. Administration of TP to gdx males results in an upregulation in AR mRNA levels after 1 day of treatment. Recent reports in the literature suggest that axotomy also may regulate the expression of AR in motor neurons. In this study, we examined the effects of axotomy and exogenous steroid treatment on the regulation of AR mRNA in hamster FMN. Five days after castration, adult male hamsters were subjected to a right facial nerve axotomy. Half the animals received one 10-mm Silastic capsule filled with 100% crystalline TP, and the remainder were sham implanted. Postoperative survival times were 6 h or 1, 2, 4, 7, or 14 days. In situ hybridization in conjunction with an AR riboprobe and computerized image analysis were used to quantify AR mRNA levels. The contralateral FMN served as internal controls for these experiments, and FMN of gonadally intact males served as additional nonaxotomized controls. As predicted, AR mRNA levels were upregulated in contralateral control FMN after TP treatment. However, this TP-induced upregulation of AR mRNA levels did not occur in the axotomized FMN. These results indicate that axonal injury can disrupt the normal regulatory pattern of AR mRNA expression by exogenous steroids in motoneurons. We conclude that the potentiation of regenerative events by TP does not require augmented synthesis of AR, but, instead, enhanced stabilization of existing receptors.

Animals↗
PubMed1997

A comparison of the postures assumed when using laptop computers and desktop computers.

This study evaluated the postural implications of using a laptop computer. Laptop computer screens and keyboards are joined, and are therefore unable to be adjusted separately in terms of screen height and distance, and keyboard height and distance. The posture required for their use is likely to be constrained, as little adjustment can be made for the anthropometric differences of users. In addition to the postural constraints, the study looked at discomfort levels and performance when using laptops as compared with desktops. Statistical analysis showed significantly greater neck flexion and head tilt with laptop use. The other body angles measured (trunk, shoulder, elbow, wrist, and scapula and neck protraction/retraction) showed no statistical differences. The average discomfort experienced after using the laptop for 20 min, although appearing greater than the discomfort experienced after using the desktop, was not significantly greater. When using the laptop, subjects tended to perform better than when using the desktop, though not significantly so. Possible reasons for the results are discussed and implications of the findings outlined.

Adult↗
PubMed1997

External ophthalmoplegia in neuromuscular disorders: case report and review of the literature.

The extraocular muscles have a number of structural and functional properties that distinguish them from skeletal and cardiac muscle and these differences may be important in the differential involvement of extraocular muscles in various disease states. We present a case of congenital external ophthalmoplegia associated with non progressive generalised weakness. Skeletal muscle biopsy at 4 years of age showed type 1 fibre predominance, variation in fibre size and increased interstitial fibrosis, suggestive of a primary myopathic process. During the investigation of this patient we reviewed the differential diagnosis of neuromuscular disorders with extraocular muscle involvement, and developed an algorithm to assist the clinician in investigation and diagnosis of external ophthalmoplegia. Our patient does not satisfy the diagnostic criteria of any previously described disorders and may thus represent a new syndrome.

Biopsy↗
PubMed1997

Gonadal steroid preservation of central synaptic input to hamster facial motoneurons following peripheral axotomy.

In recent work, we have demonstrated that testosterone propionate accelerates recovery from facial nerve injury in the adult male hamster. Central synaptic stripping following peripheral motor neuron damage is a well-established component of the injury response. Gonadal steroids regulate synaptogenesis in the normal nervous system. In this study, we tested the hypothesis that testosterone propionate administration at the time of facial nerve transection alters the synaptic connectivity of injured facial motoneurons. Adult hamsters were subjected to right facial nerve transection at the level of the stylomastoid foramen. Half the animals received subcutaneous implants of testosterone propionate; the other half were sham implanted. At 5 days postoperative, the animals were killed by intracardiac perfusion-fixation, and the control and axotomized facial nuclear groups from the brainstems of nonhormone- and testosterone propionate-treated animals processed for routine transmission electron microscopy. Quantiative analysis of the synaptic ratio (percent somal membrane covered by synaptic profiles) and the average length of axosomatic synapses was accomplished. The results indicate that axotomy alone resulted in an 81% reduction in the synaptic ratio and a 26% decrease in the average synaptic length of axosomatic synapses. Exposure to testosterone propionate from the time of facial nerve transection resulted in only a 48% reduction in the synaptic ratio and a 16% decrease in the average synaptic length of axosomatic synapses following injury. Thus, testosterone propionate significantly attenuated the amount of synaptic stripping that occurred at 5 days postoperative and the decrease in average length of the remaining synapses as well. It is concluded that gonadal steroids modulate central synaptic plasticity following peripheral nerve injury. The results are discussed in light of our recent findings of steroidal effects on the central astrocyctic response to facial nerve injury as well.

Animals↗
PubMed1997

Alterations in glial fibrillary acidic protein (GFAP) mRNA levels in the hamster facial motor nucleus: effects of axotomy and testosterone.

Testosterone propionate (TP) administered at the time of facial nerve injury in the hamster accelerates the rate of regeneration. In this study, we tested the hypothesis that the mechanism by which TP augments peripheral nerve regeneration involves regulation of glial fibrillary acidic protein (GFAP) mRNA in the facial motor nucleus. Castrated male hamsters were subjected to right facial nerve transection, with half the animals implanted subcutaneously with Silastic capsules containing exogenous TP and the remainder sham implanted. Postoperative survival times were 0.25, 1, 2, 4, 7, and 14 d. Qualitative/quantitative analyses of both film and emulsion autoradiograms were accomplished. Axotomy, with or without TP, resulted in a dramatic increase in GFAP mRNA levels by 1 d post-operative on the axotomized side, relative to controls. GFAP mRNA levels remained elevated throughout all postoperative times in both the nonhormone- and TP-treated animals. Qualitative examination of the film autoradiograms indicated a generalized decrease in the amount of GFAP mRNA in the control and axotomized nuclei of TP-treated animals when compared to the control and axotomized nuclei, respectively, of nonhormone-treated animals. Statistical comparison of the values obtained for both the film and emulsion autoradiograms confirmed this impression. Thus, while the injury-induced increases in GFAP mRNA expression were not blocked by TP, the overall extent of the increase was significantly tempered by steroid treatment. These data suggest that hormonal modulation of the astrocytic response to peripheral nerve injury may be a contributing factor in the ability of steroids to enhance the regenerative capacities of injured motor neurons.

Animals↗
PubMed1997

Gonadal steroid regulation of growth-associated protein GAP-43 mRNA expression in axotomized hamster facial motor neurons.

Treatment with testosterone propionate (TP) after nerve injury is known to accelerate both the rate of axonal regeneration and functional recovery from facial paralysis in the adult male hamster. Peripheral nerve injury is also known to increase the expression of a 43 kilodalton growth-associated protein (GAP-43). In the intact brain, GAP-43 expression is affected by gonadal steroids. We thus postulated that steroidal modulation of GAP-43 gene expression may be a component of the neurotrophic action of TP in regenerating neurons. This issue was examined in hamster facial motor neurons (FMN) which contain androgen receptors and which have been shown to respond to exogenous steroids in a number of previous studies. Castrated adult male hamsters were subjected to right facial nerve transection and treated with either TP via subcutaneous hormone capsule implants, or left untreated (no hormone replacement). At post-injury/treatment times of 0.25, 2, 4, 7, and 14 d, the brain stem regions were harvested, cryostat sections were collected through the facial motor nucleus, and in situ hybridization was done using a 33P-labeled GAP-43 cDNA probe. Quantitative analysis of the autoradiograms by computer assisted grain counting revealed that axotomy produced a dramatic increase in GAP-43 mRNA levels in FMN by 2 d post-axotomy and that this increase remained through 14 d post-injury in both the TP-treated and the untreated group. In the nonhormone-treated group, there was a statistically significant dip in GAP-43 mRNA levels in FMN at 7 d post-operative, relative to 4 d post-operative levels. TP-treatment prevented this transient decline in GAP-43 mRNA levels in axotomized FMN.

Animals↗
PubMed1997

Recent advances in diagnosis of the childhood muscular dystrophies.

Recent advances in molecular genetics research have revolutionised our understanding of the childhood muscular dystrophies. The first breakthrough came in 1987 with the identification of the gene for dystrophin, the protein that is abnormal in X-linked Duchenne muscular dystrophy. Dystrophin is bound to a complex of proteins in the muscle membrane, and primary abnormalities of these proteins have now been identified as the cause of some autosomally inherited forms of muscular dystrophy. A group of transmembrane proteins known as alpha- (adhalin) beta-, gamma- and delta-sarcoglycan are deficient in autosomal recessive limb-girdle muscular dystrophy, and the extracellular matrix protein merosin (alpha2-laminin), is deficient in a subset of patients with congenital muscular dystrophy. Identification of primary deficiencies in these 'dystrophin associated proteins' will result in improved diagnostic accuracy, more accurate genetic counselling and, in some cases, the availability of prenatal diagnosis.

Adolescent↗
PubMed1997

Reversible cerebral hypoperfusion in Lyme encephalopathy.

Lyme encephalopathy (LE) presents with subtle neuropsychiatric symptoms months to years after onset of infection with Borrelia burgdorferi. Brain magnetic resonance images are usually normal. We asked whether quantitative single photon emission computed tomography (SPECT) is a useful method to diagnose LE, to measure the response to antibiotic therapy, and to determine its neuroanatomic basis. In 13 patients with objective evidence of LE, SPECT demonstrated reduced cerebral perfusion (mean perfusion defect index [PDI] = 255), particularly in frontal subcortical and cortical regions. Six months after treatment with 1 month of intravenous ceftriaxone, perfusion significantly improved in all 13 patients (mean PDI = 188). In nine patients with neuropsychiatric symptoms following Lyme disease, but without objective abnormalities (e.g., possible LE), perfusion was similar to that of the treated LE group (mean PDI = 198); six possible LE patients (67%) had already received ceftriaxone prior to our evaluation. Perfusion was significantly lower in patients with LE and possible LE than in 26 normal subjects (mean PDI = 136), but 4 normal subjects (15%) had low perfusion in the LE range. We conclude that LE patients have hypoperfusion of frontal subcortical and cortical structures that is partially reversed after ceftriaxone therapy. However, SPECT cannot be used alone to diagnose LE or determine the presence of active CNS infection.

Adult↗
PubMed1996

Regulation of androgen receptor mRNA expression in hamster facial motoneurons: differential effects of non-aromatizable and aromatizable androgens.

We have previously shown inherent sex differences in the levels of androgen receptor mRNA (AR mRNA) in hamster facial motor neurons (FMN). FMN of intact females contained approximately 50% less AR mRNA than their male counterparts. Gonadectomy in males down-regulated AR mRNA levels in FMN by approximately 50%, whereas no effects of gonadectomy were observed in females. Sex differences in the regulation of AR mRNA levels by exogenous testosterone propionate (TP) were also observed. In those studies, AR mRNA levels were up-regulated after 1 day of treatment with exogenous TP in FMN of gonadectomized (GDX) males and after 7 days in FMN of intact females, with no effects in GDX females. Since TP is aromatizable to estrogen, and given recent findings of transient expression of estrogen receptors (ER) in rodent FMN, the effects of dihydrotestosterone (DHT), a non-aromatizable form of the steroid, on AR mRNA expression in hamster FMN were examined in the present study. If testosterone (TES) were the active hormone regulating AR mRNA levels in FMN, DHT treatment should render a similar regulatory pattern as TP, but if metabolism of TES to estradiol plays a role in AR mRNA regulation, effects of the two treatments should differ. In situ hybridization and computerized image analysis were used to quantify the regulation of AR mRNA by DHT in individual FMN of hamsters of both sexes. Exogenous DHT was administered to intact and gonadectomized (GDX) male and female hamsters by implantation of one 10-mm Silastic capsule for 1, 2 or 7 days. AR mRNA levels were significantly up-regulated in intact females at all time points of DHT exposure, with no effects in GDX groups. These results differ from previous work using TP, in which a modest up-regulation in AR mRNA levels was observed in FMN of intact females only after 7 days. As with TP, DHT exposure gradually down-regulated AR mRNA levels in FMN of intact males. Thus, DHT only regulated AR mRNA levels in intact animals, with endogenous sources of estrogen available, but not in GDX animals, with endogenous estrogens reduced by gonadectomy. Taken together, these results substantiate our previous findings of sex differences in AR mRNA levels/regulation and suggest a synergism between estrogen and androgen in the regulation of AR mRNA levels in peripheral motor neurons.

Animals↗
PubMed1996

Sex differences in androgen receptor mRNA levels and regulation in hamster facial motoneurons.

We have previously shown that testosterone propionate augments hamster facial nerve regeneration to a greater extent in males than females. Further, sex differences in facial nerve regeneration have been observed. From those studies, we hypothesized that sex differences in nerve regeneration could be due to inherent differences in androgen receptor (AR) mRNA content within facial motor neurons (FMN) of male and female hamsters. In the present study, that hypothesis was tested using in situ hybridization, and computerized image analysis to quantify levels and regulation of AR mRNA in individual FMN of hamsters of both sexes. Intact and gonadectomized (gdx) male and female hamsters were used in the initial experiments in the study. In subsequent experiments, exogenous testosterone propionate (TP) was administered to the aforementioned groups of animals by subcutaneous implantation of one 10-mm Silastic capsule for 1, 2 or 7 days. FMN of intact females contained approximately 50% less AR mRNA than their male counterparts. Gonadectomy in males downregulated AR mRNA levels by approximately 50%, whereas no effects of gonadectomy were observed in females. Thus, in all paradigms where TP levels were low relative to the intact males, AR mRNA levels were approximately half of those in the intact male FMN. TP administration induced AR mRNA levels in gdx males within 1 day. Significant effects of TP were not detected in gdx females, and only after 7 days in the intact females. To our knowledge, the results of this study are the first quantitative demonstration of sex differences in steroid receptor mRNA content in a given neuronal population and substantiate the idea that sex differences in the effects of androgens on peripheral nerve regeneration are based on intrinsic sex differences in the levels and regulation of receptor mRNA in motor neurons.

Animals↗
PubMed1996

Arthroscopy in hand surgery.

As arthroscopy of the wrist moves into the second decade, the trend for more indications for both diagnostic and therapeutic procedures will continue. It is only a matter of time before arthroscopic fusions, soft-tissue repairs, and "ectomy" procedures of all kinds become more commonplace. Whereas the advantages of the early therapeutic techniques in preserving soft-tissue structures and shortening recovery are now obvious, we will have to wait and see if the same holds true for more complicated bony and soft-tissue procedures in the next decade.

Arthroscopy↗
PubMed1995

Inhibition of the accelerative effects of testosterone on hamster facial nerve regeneration by the antiandrogen flutamide.

We have previously demonstrated that systemic administration of testosterone propionate (TP) to adult hamsters accelerates the rate of facial nerve regeneration following crush axotomy of the facial nerve at its exit from the stylomastoid foramen. In this study, we utilized flutamide, a potent nonsteroidal antiandrogen, in conjunction with radioisotopic labeling procedures for the assessment of facial nerve regeneration rates to test the hypothesis that TP exerts its accelerative effects on facial nerve regeneration through a receptor-mediated mechanism. Castrated adult male hamsters were subjected to right facial nerve crush axotomies and divided into three groups of axotomized animals: castrate plus one subcutaneous TP implant plus daily injections of flutamide, castrate plus one subcutaneous TP implant plus vehicle injections, and castrate only plus sham implant and vehicle injections. There were two postoperative timepoints: 4 and 7 days. In agreement with previous studies, systemic administration of TP resulted in an approximately 26% increase in the rate of regeneration of the fastest growing population of axons. Exposure to flutamide completely abolished the TP-induced accelerative effects on facial nerve regeneration rate. As a bioassay for the effectiveness of systemic administration of flutamide by subcutaneous injection, seminal vesicle weights were collected from all groups at the end of the postoperative time and compared as a percentage of the seminal vesicle weights of intact (nongonadectomized) male control animals. Castration greatly reduced seminal vesicle weights, whereas exogenous TP restored the seminal vesicle weights to those of the intact male. Flutamide blocked the effects of exogenous TP on seminal vesicle weights and reduced them to castrate levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen Antagonists↗