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Biomedical subjects

K J Jones

Publications and source records attributed to K J Jones.

At least 19 recordsLinked to original sources
PubMed2000

Kinetics of facial motoneuron loss following facial nerve transection in severe combined immunodeficient mice.

We have recently shown that cells of the acquired immune system are crucial components of motoneuron survival after injury (Serpe et al. [1999] J. Neurosci. 19:RC7). The goal of the present study was to determine the kinetics of facial motoneuron (FMN) loss in wild-type, scid, and reconstituted scid mice after a right facial nerve axotomy at the stylomastoid foramen. Scid mice showed a significant decrease in FMN survival at all weekly postoperative (wpo) times. One, two, four, and ten wpo, ipsilateral FMN survival in scid mice was 90% +/- 1.8%, 84% +/- 1.3%, 52% +/- 3.7%, and 45% +/- 2.5%, respectively, of the contralateral, unoperated side. In contrast, FMN loss after axotomy in wild-type and reconstituted scid mice was not observed until 4 wpo (86% +/- 2.5% and 83% +/- 3.5%, respectively) relative to the contralateral, unoperated side. However, the levels of FMN in both wild-type and reconstituted scid mice were significantly higher than those in the nonreconstituted scid at 4 wpo. By 10 wpo, FMN survival in both wild-type and reconstituted scid mice had continued to decline significantly (60% +/- 2.1% and 58% +/- 3.1%, respectively) relative to the contralateral, unoperated side but were still significantly higher than that of the nonreconstituted scid at 10 wpo. Several important controls were also added to this study. Because the scid mutation is present in all cells (although it specifically results in a loss of V(D)J recombination mechanisms, we wanted to rule out the actual DNA mutation as causal in FMN loss). To accomplish this, we used the recombinase-activating gene-2 knockout (RAG-2 KO) mouse model, in which the RAG-2 has been disrupted and prevents maturation of T and B cells. As with the scid model, there was a significant loss of FMN at 4 wpo in the RAG-2 KO that could be reversed with whole splenocyte reconstitution. We also compared FMN numbers in nonaxotomized facial nuclei from both scid and RAG-2 KO mice relative to wild-type controls. No differences in normal numbers of FMN were found in either the mutation or the gene knockout model. The ability of T and B lymphocytes to rescue FMN from cell death after peripheral nerve injury supports the hypothesis that cells of the acquired immune system produce neurotrophic factors or neurocytokines to support neuronal survival until target reconnection occurs.

Animals↗
PubMed2000

Neuroregeneration and voiding behavior patterns after pudendal nerve crush in female rats.

Since the pudendal nerve innervates the external urethral sphincter, pudendal nerve injury and resultant neuroregeneration should affect voiding behavior. In this study, neuroregenerative activity of pudendal nerve was correlated to the changes in urinary behavior in female rats. Eighteen female rats underwent bilateral pudendal nerve crush, and 17 to 21 age-matched rats were used as unoperated controls. Urinary volume and frequency were recorded 6 and 13 days post-operatively (dpo). Initiation of pudendal nerve regeneration was indicated by an upregulation of beta(II) tubulin mRNA in the dorsolateral motoneurons (DLM), as measured at 7 and 14 dpo by in situ hybridization with radio-labeled beta(II) tubulin cDNA. At 6 dpo, mean volume voided by the crush group was significantly decreased compared to the control group during the light cycle (P < 0.05). At 7 dpo, the DLM mRNA level was significantly increased in the nerve crush group compared to the control group (P < 0.05). At 13 dpo, there were no differences in volume or frequency between the two groups, suggesting a return to normal voiding behavior. At 14 dpo, there was no significant difference in DLM mRNA levels between crush and control groups. Initiation of nerve regeneration occurs before normalization of voiding behavior after pudendal nerve crush. This data suggest that treatments to accelerate nerve regeneration would improve functional recovery of neurologically based incontinence.

Animals↗
PubMed2000

Androgen receptor mRNA regulation in adult male and female hamster facial motoneurons: effects of axotomy and exogenous androgens.

Testosterone propionate (TP) administration at the time of facial nerve injury in the adult hamster augments the regenerative properties of the injured facial motoneurons (FMN), with the androgen receptor (AR) playing a key role in mediating the actions of TP on facial nerve regeneration. The purpose of the present study was to determine the effects of axotomy on AR mRNA expression in FMN. This was accomplished using in situ hybridization in conjunction with a (35)S-labeled AR riboprobe. Gonadally intact adult male and gonadectomized (gdx) adult female hamsters were subjected to a right facial nerve axotomy, with the left side serving as internal, unoperated control. Half the animals were subcutaneously implanted with a 10-mm TP Silastic capsule, and the other half were sham-implanted. An additional group of nonaxotomized, gonadally intact males was also included. Postaxotomy survival times were 1, 4, and 7 days. At 1 postoperative day 1, there were no effects of axotomy on AR mRNA levels. By postoperative days 4 and 7, axotomy caused a significant decrease in AR mRNA levels in FMN of gonadally intact males, relative to either the contralateral control FMN of the same animals or FMN from the group of gonadally intact males that were not subjected to facial nerve axotomy. There were no significant differences between AR mRNA levels in contralateral control FMN and FMN from the gonadally intact group of nonaxotomized males. TP administration at the time of axotomy had no effect on AR mRNA levels in either the axotomized or contrala(teral control FMN of gonadally intact males, relative to the nonaxotomized, gonadally intact male group. Corroborating our previous work, AR mRNA levels were reduced in the contralateral control FMN of gdx females, relative to the nonaxotomized, gonadally intact male group, with axotomy having no additional effects. The data are discussed in a mechanistic framework suggesting how TP acts to augment facial nerve regeneration.

Animals↗
PubMed2000

A randomized trial of cerclage versus no cerclage among patients with ultrasonographically detected second-trimester preterm dilatation of the internal os.

OBJECTIVE: The aim of this study was to compare perinatal outcomes of patients with second-trimester ultrasonographic evidence of preterm dilatation of the internal os treated with cerclage versus those of patients not treated with cerclage. STUDY DESIGN: From May 1998 through June 1999 patients with ultrasonographic evidence of preterm dilatation of the internal os between 16 and 24 weeks' gestation were randomly assigned to receive a McDonald cerclage or no cerclage. Before random assignment all patients underwent amniocentesis and urogenital cultures and then received 48 hours of therapy with indomethacin and antibiotics. After treatment each patient was followed up as an outpatient with bed rest and weekly ultrasonographic evaluation. RESULTS: Of the 61 patients 31 were randomly assigned to cerclage and 30 were randomly assigned to no cerclage. There were no differences between groups with respect to maternal demographic characteristics, risk factors for preterm birth, cervical measurements, rescue procedures, readmission, chorioamnionitis, and abruptio placentae. The mean gestational age at delivery (33.5 +/- 6.3 weeks) and the perinatal death rate (12. 9%) in the cerclage group were similar to the mean gestational age at delivery (34.7 +/- 4.7 weeks; P =.4) and the perinatal death rate (10.0%; P =.9) in the no-cerclage group. CONCLUSION: Treatment with McDonald cerclage of preterm dilatation of the cervix detected ultrasonographically during the second trimester did not improve perinatal outcomes.

Cervix Uteri↗
PubMed1999

Androgenic regulation of the central glia response following nerve damage.

Current research on the effects of gonadal steroids on the brain and spinal cord indicates that these agents have profound trophic effects on many aspects of neuronal functioning, including cell survival, growth and metabolism, elaboration of processes, synaptogenesis, and neurotransmission (Jones et al., 1985; Luine, 1985; Nordeen et al., 1985; Matsumoto et al., 1988a,b; Gould et al., 1990). Since many of the aspects of normal neuronal functioning altered by gonadal steroids are affected by injury to the nervous system, we initiated a series of experiments designed to exploit the trophic capabilities of steroids as therapeutic agents in neuronal injury and repair (Kujawa et al., 1989, 1991; Kujawa and Jones, 1990). Three steroid-sensitive model systems were used for these studies: the hamster facial motoneuron, the rat sciatic motoneuron, and the hamster rubrospinal motoneuron. The results of our initial series of experiments suggest that androgens, and possibly estrogens, act either directly or indirectly on the injured motoneuron and enhance elements of the neuronal reparative response that are critical to successful recovery of function. Recently, we discovered that gonadal steroids may also modulate the central glia response to nerve damage. In this review, a summary of our data identifying a therapeutic role for androgens in enhancing the reparative response of motoneurons to injury is presented. This is followed by a discussion of the effects of androgens on the glial response to injury.

Androgens↗
PubMed1999

Differential regulation of cytoskeletal gene expression in hamster facial motoneurons: effects of axotomy and testosterone treatment.

We have previously demonstrated that systemic administration of testosterone increases the rate of axonal regeneration following facial nerve crush in adult male hamsters. In the present study, the molecular mechanisms by which androgens could enhance axonal regeneration were examined at a cellular level. Specifically, the following question was addressed using quantitative in situ hybridization with cDNA probes complementary to betaII, and alpha1 tubulin mRNAs: Does exogenous testosterone augment axotomy-induced changes in tubulin mRNA expression in hamster facial motoneurons (FMN)? Castrated adult male hamsters were subjected to right facial nerve severance, with the left side serving as internal control. One-half of the animals received testosterone replacement in the form of subcutaneously implanted silastic capsules containing crystalline testosterone propionate, and the other half were implanted with blank capsules immediately following the axotomy. Postoperative survival times from 2-14 days were examined. Axotomy alone resulted in a significant increase in the levels of both betaII and alpha1 tubulin mRNAs in facial motor neurons between 2-14 days after injury. Administration of testosterone selectively augmented the axotomy-induced increases in betaII-tubulin, but not alpha1 tubulin, mRNA, levels at 7 and 14 days post axotomy. These results demonstrating an effect of testosterone in altering the neuronal cytoskeletal response to axotomy suggest that testosterone may enhance the regenerative properties of motor neurons via molecular mechanisms that involve selective alterations of the neuronal cytoskeleton.

Animals↗
PubMed1999

Estrogen receptor expression in the facial nucleus of adult hamsters: does axotomy recapitulate development?

Testosterone propionate (TP) augments hamster facial motoneuron regeneration following axonal injury by an androgen-mediated mechanism. Although many of the trophic properties of TP are androgenic, TP can be metabolized to estradiol (E). We have recently shown that E administered in supraphysiological doses can also enhance facial nerve regeneration. The mechanism by which E alters nerve regeneration is unknown. The recent discovery of transient estrogen receptor (ER) expression in the developing rat facial motor nucleus (FMN), coupled with the concept that regeneration may recapitulate development, has led to the hypothesis that facial nerve injury may transiently induce expression of ER in the adult hamster FMN or one of its chief afferents, the principal nucleus of the trigeminal nerve (Nu5). In the present study, this hypothesis was tested using steroid hormone autoradiographic procedures. The right facial nerve was injured in castrated or castrated plus TP adult hamsters. A gonadally intact, nonaxtomized group of hamsters was also included to examine constitutive expression of ER in the FMN or Nu5. The paraventricular nucleus of the hypothalamus (PVN; positive control), FMN, and Nu5, were qualitatively and quantitatively examined for the presence of ER. As expected, ER were present in the PVN-positive control in all groups. ER were neither present nor induced with facial nerve injury or TP administration in either the FMN or Nu5. Alternate mechanisms by which E enhancement of facial nerve regeneration without ER might be explained are discussed.

Animals↗
PubMed1999

Exacerbation of facial motoneuron loss after facial nerve transection in severe combined immunodeficient (scid) mice.

The immune system functions to protect an organism against microbial infections and may be involved in the reparative response to nerve injury. The goal of this study was to determine whether the immune system plays a role in regulating motoneuron survival after a peripheral nerve injury. After a right facial nerve axotomy, facial motoneuron (FMN) survival in C.B-17 (+/+) wild-type mice was found to be 87 +/- 3.0% of the unaxotomized left side control. In contrast, facial nerve axotomy in C.B-17 (-/-) severe combined immunodeficient (scid) mice, lacking functional T and B lymphocytes, resulted in an average FMN survival of 55 +/- 3.5% relative to the unaxotomized left side control. This represented an approximately 40% decrease in FMN survival compared with wild-type controls. The reconstitution of scid mice with wild-type splenocytes containing T and B lymphocytes restored FMN survival in these mice to the level of the wild-type controls. These results suggest that immune cells associated with acquired immunity play a role in regulating motoneuron survival after a peripheral nerve injury.

Animals↗
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↗