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K J Jones

Publications and source records attributed to K J Jones.

At least 55 records · Page 3Linked to original sources

Spectral coherence in normal adults: unrestricted principal components analysis; relation of factors to age, gender, and neuropsychologic data.

This paper demonstrates, by means of Principal Components Analysis (PCA), an objective approach to the reduction of large data sets produced by multichannel spectral coherence analyses. Coherence data, gathered from 371 normal healthy adults using Hjorth/Laplacian referencing during waking eyes-open and eyes-closed states, were analyzed by "unrestricted" PCA where neither spatial nor temporal variance was folded into among subject variance. There was substantial data reduction with our 4416 initial coherence variables for each state reduced to just 150 factors containing approximately 80% of the variance reflecting a 30 fold concentration of information content. Varimax rotation of the first 40 factors, encompassing 50% of the total variance for both states, revealed loading patterns primarily bilateral with no hemispheric bias, relationships primarily between distant single electrode pairs, (although a single electrode to multiple electrode pattern was also observed), and involvement of all spectral bands. Elemental left to right and anterior to posterior coherence patterns, often used on an a priori basis for coherence studies, were not evident among the rotated factor loading patterns. On the basis of high loadings upon extra bipolar artifact channels, 32 factors accounting for approximately 40% of the variance were identified as reflecting artifactual coherence relationships. By multiple regression the 48 non-artifactual factor scores successfully predicted subject age. In general, coherence diminished with age, which may partly explain age-related EEG desynchronization in healthy adults. Coherence factors also predicted 6 of 10 neuropsychologic variables. Gender was successfully predicted by discriminant analysis. No global interpretations about coherence and gender or neuropsychologic function were possible, i.e., almost equal numbers of factors increased as decreased in males as females. PCA derived coherence factor scores are useful for subsequent statistical analyses, but their factor loading plots of cortical coupling may require more experience to fully interpret.

Adult↗

The effect of chevron osteotomy with lateral capsular release on the blood supply to the first metatarsal head.

The chevron osteotomy is one of the most widely used distal metatarsal osteotomies for the treatment of hallux valgus in adults. Because the osteotomy interrupts the intraosseous blood supply to the metatarsal head, there has always been a concern that the operation could produce osteonecrosis of the metatarsal head, particularly if the important extraosseous blood supply was also damaged. We used latex injection and a modified Spalteholz technique in cadaveric specimens to demonstrate the effect of the chevron osteotomy, with and without lateral capsular release, on the vascular supply to the first metatarsal head. We found an extensive network of extraosseous vasculature to the metatarsal head both proximal and distal to the site of the osteotomy. Both of these vascular networks were preserved when the osteotomy was done properly. Also, an extensive plantar and plantar lateral network of vessels provided circulation to the head. Potential technical flaws in the performance of the osteotomy included cutting of the first dorsal metatarsal artery by overpenetration of the saw blade and incorrect placement of the proximal arms of the osteotomy inside the joint capsule. These technical errors, alone or in conjunction with extensive capsular stripping, can result in damage to the vessels that supply the metatarsal head.

Aged↗

Androgenic enhancement of motor neuron regeneration.

In conclusion, the available evidence to date suggests that many of the aspects of neuronal functioning affected by gonadal steroids under steady state conditions are also significantly affected by steroids under stress conditions such as axon disconnection. This argues toward a therapeutic usefulness of gonadal steroids in activating and/or accelerating the reparative response of neurons to injury, a concept that will be exciting to test in future clinical studies.

Androgens↗

Axotomy-induced changes in ribosomal RNA levels in female hamster facial motoneurons: differential effects of gender and androgen exposure.

Following facial nerve injury, female hamster facial motoneurons (HFMN) regenerate faster than their male counterparts. Testosterone propionate (TP) markedly accelerates the rate of facial nerve regeneration in males, but has a relatively reduced effect in females. In the present study, we utilized in situ hybridization in conjunction with ribosomal DNA probes to test the hypothesis that in females HFMN axotomy produces a less dramatic cell body response than in males and to examine gender differences in the effects of steroids on peripheral nerve regeneration at the molecular level. The results indicate that in females axotomy alone induced moderate increases in rRNA levels, beginning 2 days postoperatively. These changes were both slower in onset and lower in magnitude than those in the males. TP augmented the effects of axotomy on rRNA levels at the later postoperative times. There were no early, rapid effects of TP, like those observed in males. These molecular data substantiate our previous findings of inherent sex differences in neuronal regeneration and the ability of gonadal steroids to augment the reparative response of peripheral neurons to injury.

Animals↗

Androgenic regulation of tubulin gene expression in axotomized hamster facial motoneurons.

We have previously demonstrated that systemic administration of testosterone increases the rate of axonal regeneration following facial nerve crush in adult male hamsters. In this investigation, the molecular mechanisms by which androgens may enhance axonal regeneration were examined. Specifically, the following question was addressed using Northern blot and in situ hybridization with three cytoskeletal cDNA probes complementary to beta II-, beta III-, and alpha 1-tubulin mRNA: does exogenous testosterone augment axotomy-induced changes in tubulin mRNA expression in hamster facial motoneurons (FMN)? Adult male hamsters were subjected to unilateral facial nerve severance, with the opposite side serving as an internal control. One-half of the animals were subcutaneously implanted with Silastic capsules containing crystalline testosterone propionate and the other half implanted with blank capsules. Postoperative survival times were 2 and 7 d. At 2 d after axotomy alone, no changes in levels of any of the three tubulin mRNAs were observed in the injured FMN. However, by 7 d after axotomy, significant increases in all three tubulin mRNAs were observed. This time course of axotomy-induced changes in tubulin gene expression is consistent with findings in other injured neuronal populations. Administration of testosterone at the time of injury had two major effects on the cytoskeletal response pattern in axotomized FMN. First, testosterone differentially regulated the set of tubulin mRNAs examined, in that beta II-tubulin mRNA levels were selectively altered by the steroid, whereas beta III- or alpha 1-tubulin mRNAs were not.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Testosterone regulation of the regenerative properties of injured rat sciatic motor neurons.

We have previously demonstrated that systemic administration of testosterone differentially regulates the regenerative properties of injured hamster facial motor neurons, which are androgen receptor-containing cranial motor neurons. In this investigation, the hypothesis that testosterone alters the regenerative properties of rat sciatic motor neurons, which are androgen receptor-containing spinal motor neurons, was tested using fast axonal transport of radioactively labeled proteins to assess sciatic nerve regeneration. Adult castrated male rats were subjected to crush axotomy of the sciatic nerve at the level of the gemelli tendons (mid-thigh). One-half of the axotomized animals received subcutaneous implants of testosterone propionate (TP), with the remainder of the animals sham implanted with blank capsules. The outgrowth distances of the leading axons were measured at 5, 6, 7, and 11 days postoperative. Linear regression analysis was accomplished, with the slope of the line representing the regeneration rate and the x-intercept the initial delay of sprout formation. Systemic administration of testosterone resulted in a 13% increase in the rate of regeneration, relative to the control, -TP group. Outgrowth distances were significantly increased in the +TP group only in the later stages of regeneration. However, TP did not shorten the delay in sprout formation in regenerating sciatic motor neurons, but instead produced a small prolongation in the delay time. This pattern of hormonal regulation of the regenerative properties of spinal motoneurons is similar to that previously found in cranial motoneurons. The prolongation of the initial delay may have been a factor in the lack of significant outgrowth distances during the early stages of regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Recovery from facial paralysis following crush injury of the facial nerve in hamsters: differential effects of gender and androgen exposure.

In recent studies, we have shown that administration of androgens to male hamsters enhances functional recovery from facial paralysis induced by facial nerve crush at the level of the stylomastoid foramen. Furthermore, we have established that the mechanism behind this enhancement of regeneration involves an acceleration of the rate of regeneration, without a shortening in the delay of sprout formation. From those studies, several unexpected findings of inherent sex differences emerged. First, intact (nongonadectomized) females have a faster facial nerve regeneration rate than males and, second, testosterone has a less dramatic effect on the rate of regeneration in females compared to males. In the present study, we explored these novel findings of sex differences in the response of motor neurons to injury. Adult intact female hamsters were subjected to right facial nerve crush axotomy at the level of stylomastoid foramen and either implanted with two or four silastic capsules containing 5 alpha-dihydrotestosterone, or sham-implanted for controls. A group of adult intact male hamsters was also subjected to right facial nerve crush axotomy. Animals were observed daily, beginning on Day 1 postoperatively and continuing throughout a 3-week recovery period for signs of functional recovery from facial paralysis. The average day of return of each of four behavioral components (semi-blink, blink reflex, full vibrissae movement, and complete recovery) was calculated for all four experimental groups. The results indicate that intact females recover functional return of movement following crush injury significantly faster than intact males. In contrast to our previous findings in male hamsters, administration of exogenous steroids does not accelerate recovery from facial paralysis in adult female hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

Metabolic changes in axotomized fetal and early postnatal hamster facial motoneurons: an autoradiographic study.

The developing facial neurons of a series of hamsters ranging in age from the 14-day fetus to the 9 day postnatal were axotomized. Postoperative times were graded for each age so that the retrograde response could be observed before any significant amount of cell degeneration or death occurred. The incorporation of tritiated uridine was followed by the autoradiographic procedure. Although grain counts, relative to control values, were significantly reduced only in the axotomized fetus and at 24 hours postoperatively in 4-day postnatal animals, there was also a repression of isotopic incorporation in all the other axotomized animals. These results support data obtained from previous work with the hamsters which indicate that it is not until after the nerve cell nucleolus reaches full cytomorphic maturity (between 15 and 20 days postnatal age in hamster facial neurons) that the axotomized neurons respond with significantly increased incorporation levels of isotope over that of control neurons.

Animals↗

Gonadal steroids as promoting factors in axonal regeneration.

In this article, some of the trophic actions of gonadal steroids on receptor-concentrating neurons within the mammalian brain and spinal cord will be discussed. This will be followed by a summary of our recent data identifying a new role for gonadal steroids as therapeutic agents in neuronal injury and repair.

Animals↗

Testosterone enhancement of the nerve cell body response to injury: evidence using in situ hybridization and ribosomal DNA probes.

In axotomized peripheral motoneurons capable of successful regeneration, one of the earliest morphological indicators of the injury response occurs within the nucleolus. In the initial part of this investigation, we mapped the nucleolar response of injured adult hamster facial motoneurons from a molecular perspective, utilizing in situ hybridization and ribosomal DNA probes complementary to stable rRNA. Recently, we have discovered that the gonadal steroid, testosterone propionate (TP), accelerates recovery from facial paralysis in the hamster by increasing the rate of regeneration of the fastest regrowing axons. In the second part of this study, the hypothesis that TP accomplishes these effects on facial nerve regeneration through an enhancement of the nerve cell body response to injury was tested using in situ hybridization and rDNA probes. Adult intact male hamsters were subjected to right facial nerve axotomies at the stylomastoid foramen. One-half of the axotomized animals received subcutaneous implants of TP, with the remainder sham implanted. In situ hybridization with tritiated rDNA probes was accomplished and levels of hybridizable rRNA assessed both qualitatively and quantitatively. Axotomy alone induced an upregulation in rRNA levels, with peak changes occurring by 24 hr postoperative and continuing through postoperative day 4. These molecular changes in the nucleolar response preceded, by a full day, any morphological signs of the nucleolar reactive pattern previously found in this cell type, and, as such, point to the usefulness of in situ hybridization as a tool to identify the earliest events associated with the axon reaction. A secondary smaller increase in rRNA levels was observed during the later stages of regeneration. TP significantly augmented the ribosomal response to injury, with levels of rRNA increased as early as 6 hr and the magnitude of the response greater than that occurring following axotomy alone. These results provide the first mechanistic step in the identification of the cellular processes underlying gonadal steroid augmentation of neuronal reparative processes. We conclude that TP accelerates the "switch" from a normal to a reparative state and suggest that this priming effect may be causally related to the differential effects of TP on the regenerative properties of this cell type.

Animals↗

Alterations in nuclear envelope invaginations in axotomized fetal and early postnatal hamster facial motoneurons.

In this study, changes in the amount of nuclear envelope invaginations (NEI) were morphometrically assessed after axotomy during late fetal and early postnatal developmental stages in hamster facial motoneurons. These changes were expressed as boundary density or BA (length of nuclear envelope per unit area of nucleus). Axotomy-induced changes in nuclear area and perimeter were also quantitatively determined. At 17 h after axotomy in the fetal operative series, no changes in any of the parameters were seen. At 1 day postoperative (dpo) in newborn, 2 and 4 postnatal day animals, the boundary densities of the total and invaginated portion of the nuclear envelope increased significantly. No corresponding qualitative changes were observed. At 2 dpo in 4 and 7 postnatal day animals, there were significant increases in the boundary densities of both invaginated and total nuclear envelope and a decrease in nuclear area. These changes were not seen at 2 dpo in the 9-day operative series. At 4 dpo in 7 and 9 postnatal day animals, scalloping of the normally smooth nuclear profile, as well as a flattening and elongation in nuclear shape, occurred. These qualitative changes in the 7 and 9 day operated groups were also accompanied by significant changes in all the measured parameters. The boundary density of the invaginated, non-invaginated and total nuclear envelope increased; whereas, nuclear area and perimeter decreased. These results argue against the generally held hypothesis that an increase in nuclear envelope invaginations is indicative of an allied increase in cellular metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ultrastructural changes in the nucleolus of facial motor neurons following axotomy during an early critical period in development.

In this study, the effects of axotomy on the ultrastructure of the nucleolus and associated organelles were examined in fetal, newborn, and early postnatal facial motoneurons of the hamster. Golden hamsters used for this study were the 14-day fetus, newborn (0 days; less than 6 hr) and 2, 4, 7, and 9 days postnatal ages, with 3 animals per group. For prenatal surgeries, pregnant hamsters were anesthetized and the facial nerves severed in the fetuses via electrocautery through the uterine wall and amniotic membrane. For postnatal surgeries, the animals were anesthetized and the right facial nerve exposed and severed at its exit from the stylomastoid foramen. At the appropriate postoperative times, the animals were reanesthetized and perfused-fixed. The facial nuclear groups were dissected and processed for routine electron microscopy. Microbody and coiled body frequencies were determined from the number of neurons containing these structures per number of neurons sampled per animal in each experimental or control group and subjected to statistical analysis. Nucleolar reactive changes that occurred during this developmental sequence fell into two major categories. The first category displayed by most injured cells consisted of an initial compacting of fibrillar material and reduction in vacuolar space. The second category appeared to represent a progression from this first stage of nucleolar reactivity into degenerative changes involving a striking segregation of nucleolar components into five distinct regions. The incidence of microbodies increased as a result of axotomy, whereas the presence of coiled bodies decreased at the later postoperative stages in the older animals. With increasing age and nucleolar maturation, the nucleolar reactive pattern became less pronounced and severe, and neuronal survival predominated. It appears, therefore, that the two categories of nucleolar changes following axotomy during early development correlate with changes observed in nucleoli under conditions of rRNA downregulation. It is hypothesized from these results that a key step in the ability of neurons to survive axotomy and successfully regenerate at these early developmental stages occurs at some point in ribosomal RNA transcription and/or processing. Complementary information at the molecular level concerning changes in nucleolar synthetic activity and ribosome production will be necessary to test this hypothesis.

Animals↗

Differential neuronal expression of c-fos proto-oncogene following peripheral nerve injury or chemically-induced seizure.

Previous work by others has demonstrated that neocortical injury results in the induction of c-fos protooncogene both at and distal to the site of injury. However, secondary effects of focal brain injury, such as spreading depression and seizure activity, also have been shown to induce the expression of c-fos. Thus, it is unclear whether the stimulus inducing c-fos expression after generalized brain trauma is direct neuronal injury or associated, secondary effects of injury. In this study, we tested the hypothesis that a specific axonal disconnection would induce the expression of c-fos proto-oncogene in the injured neurons. The injury paradigm that was used was peripheral axotomy of rodent facial motoneurons. The right facial nerve was severed distal to the stylomastoid foramen, with the left side serving as an internal control. As positive controls, in a separate group of animals, seizures were invoked using bicuculline administered intraperitoneally. At the end of postoperative survival times ranging from 30 min to 24 hr, the animals were sacrificed. For northern blot analysis using a c-fos cDNA probe, total RNA was isolated from the dissected facial nuclear groups in the injury experiments, or whole brain and neocortex in the seizure experiments. For immunocytochemical analysis using a battery of c-fos antibodies, the animals were perfused with paraformaldehyde and processed for routine light microscope immunocytochemistry. In the bicuculline-injected animals, c-fos mRNA was massively induced in whole brain in a manner proportional to the overall level of gross seizure activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Testosterone effects on ribosomal RNA levels in injured peripheral motor neurons: a preliminary report.

We have previously demonstrated that administration of testosterone to hamsters during the early phases of axonal regeneration following facial nerve injury accelerates both the rate of regeneration of the fastest growing population of axons and the return of functional movement. We hypothesized from those studies that testosterone primes the neuronal cell body in such a way as to accelerate the "switch" from a normal to a reparative state. That hypothesis was tested in this study using ribosomal DNA (rDNA) probes in conjunction with in situ hybridization to map the molecular response of the polymerase I system to axotomy, with and without hormone exposure. Adult male hamsters were subjected to right facial nerve severance, with the left side serving as an internal control. Half the animals were administered testosterone propionate via subcutaneous implants. In situ hybridization using a genomic rDNA probe complementary to the 28S rRNA species was accomplished, and levels of rRNA in injured facial neurons assessed both qualitatively and quantitatively. Our initial findings indicate that testosterone markedly upregulates rRNA levels after injury, and support the hypothesis of an acceleration in the metabolic switch to a reparative state. This leads us, in turn, to suggest that this effect of testosterone on the ribosomal system is causally related to the increase in axonal regeneration rate and return of functional movement previously documented in this system.

Animals↗

Ultrastructural and morphometric analysis of neurons in the arcuate nucleus of the female rat hypothalamus following estradiol.

Recent evidence suggests that E2 may act in the ventromedial nucleus of the hypothalamus (VMN) and arcuate nucleus (ARC) through mechanisms partly unique to each area. To examine this hypothesis, we investigated early and discontinuous effects of E2 action on neurons within the ARC from an ultrastructural and morphometric perspective. In contrast to our findings of dramatic, rapid effects of E2 on the structure of VMN neurons, no changes in any of the ultrastructural parameters examined, including the nucleolus, nucleus, nucleoplasm, and the nuclear envelope-RER system, were observed in ARC neurons after either 2 hours of E2 or a discontinuous schedule of 2 h on/7 h off/2 h on of E2. No changes were noted in any of the quantitative parameters examined, including nucleolar, nuclear, and somal area, nuclear shape, and nuclear envelope length after either 2 hours of E2 or a discontinuous schedule of 2 h on/7 h off/2 h on of E2. These morphological results support the hypothesis of differential actions of E2 on various E2-concentrating nuclear groups in the brain.

Animals↗

Modeling age using cognitive, psychosocial and physiological variables: the Boston Normative Aging Study.

A structural equation model is computed for 36 variables from eight domains of data using 100 healthy male subjects whose age varies between 30 and 80 years. Chronological age is required to be an exogenous variable while cognitive function variables are required to be an ultimate endogenous or outcome set. The model suggests that the direct effect of age on cognition is substantially reduced when social, life style, physiological, and brain state variables are allowed to become intervening variables. The study also finds that there is an association between cognitive function and psychosocial measures relating to general psychiatric symptomatology and social support systems.

Adult↗

Testosterone differentially regulates the regenerative properties of injured hamster facial motoneurons.

We have previously demonstrated that systemic administration of testosterone accelerates functional recovery, as measured behaviorally, from facial paralysis induced by facial nerve crush axotomy in gonadectomized adult male hamsters. In this investigation, the hypothesis that testosterone enhances return of motor function by increasing the rate of axonal regeneration following injury was tested using fast axonal transport of radioactively labeled proteins to assess facial nerve regeneration. Adult castrated and intact males, and intact females, were subjected to right facial nerve crush axotomy at the stylomastoid foramen. One-half of the axotomized animals in each group received subcutaneous implants of testosterone, with the remainder of the animals sham implanted. Systemic administration of testosterone resulted in a 26-30% increase in the rate of regeneration of the fastest growing population of axons in the male experimental groups, regardless of whether the animal was castrated or not. This rate increase is similar to that observed in the conditioning lesion paradigm utilized by others. In the females, testosterone had a significant, but less pronounced, effect on the rate of axonal regeneration, which may be due in part to inherent gender-related differences in regenerative properties of facial motoneurons. A surprising finding of this study was that no shortening of the delay of sprout formation by testosterone was observed across the various experimental groups. These data suggest that the mechanism by which gonadal steroids act in the injured nervous system is partly through the differential regulation of the regenerative properties of the injured cell, presumably via hormone receptor-mediated action at the level of the neuronal genome.

Animals↗