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Biomedical subjects

K J Jones

Publications and source records attributed to K J Jones.

At least 73 records · Page 4Linked to original sources
PubMed1990

Ultrastructural and morphometric analysis of nucleolar and nuclear changes during the early growth period in hamster facial neurons.

In this study, progressive developmental changes in the nucleus and associated organelles, including the nucleolus, coiled bodies, nuclear envelope, and nucleoplasm, of hamster facial motor neurons were characterized by two parallel analyses: ultrastructural and morphometric. Golden hamsters (Mesocricetus auratus) used for this series were the 14-day fetus, newborn (less than 6 hr), and 1, 2, 3, 4, 5, 7, 9, 11 and 13 days postnatal ages, with 3 animals per group. Following anesthesia and perfusion fixation, facial nuclear groups were dissected and processed for electron microscopy. Electron micrographs and camera lucida tracings of nuclear profiles were collected and analyzed. The ultrastructural analysis revealed progressive changes in the nucleolus from a compact, segregated type to a reticulated form characteristic of actively protein-secreting cells. Nucleolar microbodies and fibrillar centers were seen at all ages; the latter structures appeared to decrease in size and increase with age in the series. The nucleolus-associated chromatin became less condensed, suggesting an increase in the incorporation of rDNA into the nucleolus proper. Coiled bodies, both free and attached to nucleoli, were found in varying frequencies. The nucleoplasm of neurons at the earliest stages contained large numbers of heterochromatin clumps, which decreased concomitantly with an increase in interchromatin granules and fibrils during the later stages. Nuclear envelope invaginations, polarized along one side of the nucleus, increased throughout the developmental period examined. These changes occurred in concert with a 61% increase in nuclear size and a 47% increase in the length of nuclear envelope. The sequence of nuclear changes observed during this early period of normal facial neuronal growth completes the study of a series of distinctly defined cytomorphic events in this cell type, the lability of which can be experimentally tested for their functional roles in neuronal development.

Animals↗
PubMed1990

Testosterone-induced acceleration of recovery from facial paralysis in male hamsters: temporal requirements of hormone exposure.

In this study, the temporal requirements of testosterone propionate (TP) exposure necessary for acceleration of recovery from facial paralysis to occur following facial nerve crush were examined. For each of two series of experiments, adult castrated male hamsters were subjected to crush axotomies of the facial nerve at its exit from the stylomastoid foramen. In the first experimental paradigm, one-half of the animals with facial nerve crush axotomies received subcutaneous TP capsules beginning on postoperative (PO) day 6 and continuing throughout the regeneration period, with the remainder of the animals sham implanted. The results indicate that, without the early exposure to TP, the accelerative effects of the hormone on facial nerve regeneration were abolished. In the second experimental paradigm, one-half of the animals with facial nerve crush axotomies received subcutaneous TP implants immediately after the crush surgeries and until PO day 7, with the remainder of the animals sham implanted. The results indicate that an early, discontinuous dose of TP immediately after crush surgeries was sufficient to produce a partial accelerative effect on the return of facial nerve function. It is hypothesized from these findings that there is a priming effect of TP that is exerted at the level of the neuron, temporally precedes behavioral recovery by a week or more and is critical to subsequent acceleration of recovery from facial paralysis.

Animals↗
PubMed1990

Steroid hormone regulation of ribosomal RNA in rat hypothalamus: early detection using in situ hybridization and precursor-product ribosomal DNA probes.

In the female rat, behavioral and endocrine aspects of reproduction are controlled, in part, by the action of the steroid hormone estradiol on several regions of the brain, including the ventrolateral portion of the ventromedial hypothalamus (VL-VMN) and the arcuate nucleus of the hypothalamus (ARC). Quantitative assessment of the effects of estradiol on the regulation of ribosomal RNA in rat hypothalamus was accomplished in this study by tandem in situ hybridization experiments with 2 ribosomal DNA probes specific to the initial transcript (precursor) or mature, stable (product) rRNA. This novel approach allowed the regulation of RNA processing by steroid hormones to be analyzed in the individual neuron, a particularly important concern in heterogeneous tissue such as the brain. Estradiol was administered subcutaneously to ovariectomized rats for 15 min, 30 min, or 2 hr, or a discontinuous schedule of 2 hr on/7 hr off/2 hr on. Levels of precursor and product rRNA were measured in VL-VMN and ARC neurons using a computerized image-analysis system. Significant increases in the levels of precursor rRNA were observed only in the VL-VMN as early as 30 min after hormone exposure, with a doubling in the amount of precursor rRNA occurring at 2 hr. No changes in product rRNA were observed in either brain region at these early times. These data, in conjunction with our previous findings of increases in product rRNA after longer hormone exposure times, lead us to conclude that rRNA gene transcription is activated in rat hypothalamic neurons within 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Induction of heat shock protein 70 mRNA in adult hamster facial nuclear groups following axotomy of the facial nerve.

In this study, the effects of axotomy on heat shock protein 70 (hsp70) mRNA levels were analyzed by northern blot hybridization with a mouse-inducible hsp70 cDNA probe. The right facial nerve of adult golden hamsters was axotomized external to the skull, with the left nerve serving as sham-operated and internal control. Postoperative survival times were 0.5, 2, 6, 12, and 24 hr, with three to six animals per time point. Total RNA in the axotomized and control facial nuclear groups, dissected from the brain stem, was isolated by guanidinium-thiocyanate extraction and analyzed by northern hybridization and scanning densitometry. For normalization, the blots were rehybridized with a genomic cDNA probe complementary to the 28 S rRNA. At 0.5 hr postoperative, there was a 68% induction of hsp70 mRNA levels as compared to control. This increase peaked at 2 hr postoperative with a 280% induction and declined subsequently to 160% at 6 hr, 33% at 12 hr, and -56% at 24 hr, relative to control levels. As a positive control, hyperthermia-induced hsp70 expression was established in hamster whole brain using northern blot hybridization and the mouse-inducible hsp70 cDNA probe. There was a 126% increase in hsp70 mRNA levels relative to control at 1.5 hr following hyperthermia. By 6.5 hr after the 1.5-hr hyperthermic period, there was a 40% decrease in hsp70 mRNA levels below control. The results provide the first evidence that peripheral axotomy acts as a cell stressor to induce the expression of hsp70 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Testosterone-induced acceleration of recovery from facial paralysis following crush axotomy of the facial nerve in male hamsters.

In this study, the effects of testosterone propionate (TP) on recovery from facial paralysis following crush axotomy of the facial nerve in male hamsters were examined. In the first experiment, TP (5 mg/ml sesame oil; 0.1 ml) was injected subcutaneously and on alternate days in one-half of the animals subjected to crush axotomies of the facial nerve, with the second half receiving vehicle alone. An accelerative effect of TP on recovery from facial paralysis was observed near the end of the first and beginning of the second week after crush axotomy. When the dosage and frequency were doubled in the next experiment, a greater accelerative effect of TP on recovery from facial paralysis was observed. In the last experiment, castrated animals were used in order to eliminate the endogenous source of the hormone and two different modes of hormone administration, TP implants vs TP injections, were compared. The results of that experiment indicate that continuous exposure to the hormone, in the form of subcutaneous implants of 100% crystalline TP, had the most pronounced effect on acceleration of recovery from facial paralysis. In addition, no differences in the responses of the castrated, axotomized animals and the normal, axotomized animals were found. This suggests that the presence of endogenous hormone contributes little to the acceleration of functional recovery observed with TP. Finally, the time course of the accelerative effect of TP suggests that the hormone is acting primarily at the level of the facial neuron, which contains androgen receptors, and perhaps secondarily at the level of the facial muscles, which are also known to contain androgen receptors.

Animals↗
PubMed1988

Steroid hormones and neurotrophism: relationship to nerve injury.

Current data on the neurotrophic effects of steroid hormones suggest that, in brain and spinal cord regions containing receptor systems, steroids act at the level of RNA and protein synthesis to effect metabolic changes associated with nerve-cell survival, elaboration/maintenance of dendritic and axonal processes, synaptogenesis, and neurotransmission. While many of these effects appear to be associated with the neuroanatomical systems involved in the endocrine and behavioral aspects of reproduction, evidence does exist for similar neurotrophic effects outside the reproductive sphere. Both estrogens and androgens appear to exert this stimulatory, growthlike effect on target neurons. The effects of progesterone are not discussed in this review because relatively little information is available regarding the independent effects of progesterone on the brain. We have just completed a study (Jones et al., 1987b) which suggests that progesterone may act independently in the brain to affect protein synthesis. A number of conclusions concerning the mechanism of steroid action in producing trophic effects on neurons can be drawn. First, the time course of hormone action is similar to that found in nonneural target tissue, such as the uterus. Second, steroid hormones act on neurons through receptor-mediated genomic activation. Third, this effect on the genome appears to be at the level of both transcription and translation. Fourth, there is brain-region specificity in the gene products resulting from steroid hormone administration. Finally, short-term exposure to estrogens or androgens generally results in an anabolic response within target neurons. The brain and spinal cord, injured either by disease or by experimentally induced trauma, is responsive in a reparative manner to exogenous and/or endogenous gonadal steroid hormones. The mechanism underlying this therapeutic role of steroids on damaged neurons is not known but has been postulated to involve direct action of steroid hormones or target neurons. It has been hypothesized that two diseases, Alzheimer's and ALS, may be related to steroid hormone/receptor deficiencies. In this regard, Appel (1981) has suggested that putative "neurotrophic hormones" acting at the synapse may be critical in maintaining the neural networks affected in ALS, Alzheimer's disease, and parkinsonism. Extending that hypothesis to include direct action of such putative hormones within the cell body and at the level of the genome, the evidence presented in this discussion would argue that possible candidates could be gonadal steroids.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgens↗
PubMed1988

Quantitative assessment of early and discontinuous estradiol-induced effects on ventromedial hypothalamic and preoptic area proteins in female rat brain.

In this study, changes in individual proteins in the ventromedial hypothalamus (VMN) and the preoptic area (POA) of the female rat brain were quantitatively assessed following either a short treatment (2 h) or a discontinuous schedule of estradiol. Ovariectomized (OVX) rats were implanted with estradiol capsules or sham-implanted for the appropriate paradigm and sacrificed by decapitation. Punches of brain tissue containing the VMN and POA were incubated with 35S-methionine and 35S-cysteine, and the labeled proteins separated by two-dimensional gel electrophoresis. Estradiol-induced changes were quantitatively assessed by computerized optical densitometry and subjected to a normalization procedure between pairs of estradiol-treated and OVX control gels. A number of proteins within the VMN and POA were found to be positively or negatively affected in labeling after either hormone administration paradigm. In both brain regions, the population of proteins affected in labeling after 2 h of estradiol treatment were markedly different from those affected after the discontinuous hormone paradigm. Comparison of the VMN and POA also indicated that the populations of proteins affected in labeling by either hormone treatment paradigm were different, with there being only 3 proteins (from a total of 39) affected in the same direction and 2 affected in the opposite direction by the hormone in both regions. These findings lend support to the hypothesis that administration of estradiol results in a molecular cascade of events within brain regions involved in the control of reproductive behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Differential effects of axotomy on immature and mature hamster facial neurons: a tritiated-uridine autoradiographic study.

In this study, tritiated-uridine incorporation was autoradiographically examined following axotomy of hamster facial motor neurons (HFMN) at the critical development age of 15 days postnatal and in the adult. The postoperative times selected were 0.5, 1, 2, and 4 days. In the 15-day operative series, no changes in incorporation were observed at any of the postoperative times, except at 4 days postoperative, when there was a decrease in tritiated-uridine incorporation in the axotomized neurons relative to the controls. In the adult operative series there were no changes in incorporation at 0.5 or 1 day postoperative, relative to the controls. At 2 days postoperative in the adult, there was a transient increase in tritiated-uridine incorporation that returned to control levels by 4 days postoperative. When axotomized and control cytoplasmic/nuclear grain densities were compared, no changes were found in either operative series. These results of the time course of axotomy-induced changes in RNA synthesis in HFMN corroborate our previous findings of an age-dependent reactive sequence in HFMN and lend support to the hypothesis that the young neurons are synthesizing at peak capacity related to final growth and cannot be stimulated further by axotomy. As discussed, the transient increase in RNA levels in the adult, the lack of any changes in the rate of transfer of RNA from the nucleus to the cytoplasm, and the decrease in RNA levels in the 15-day neurons may be related to the presence of an unusual intranucleolar body within the nucleolus of HFMN that contains ribosomal precursors.

Aging↗
PubMed1987

Quantitative assessment of the synergistic and independent effects of estradiol and progesterone on ventromedial hypothalamic and preoptic-area proteins in female rat brain.

In this study, quantitative assessment of the synergistic and independent effects of estradiol and progesterone on protein synthesis in the ventromedial hypothalamus (VMN) and the preoptic area (POA) was accomplished using in vitro 35S-methionine and 35S-cystein labeling, two-dimensional gel electrophoresis, and computerized densitometry. Ovariectomized (OVX) rats were divided into four groups. Group 1 was implanted with estradiol (E) capsules for 6 hr and injected with progesterone (P; 0.1 ml, 5 mg/ml propylene glycol) at 20 hr. Group 3 was sham-implanted for 6 hr and injected with 0.01 ml P at 20 hr. Group 4 was sham-planted for 6 hr and injected with vehicle alone at 20 hr. All animals were sacrificed at 24 hr. A number of proteins in both VMN and POA were found to be increased or decreased in labeling by E plus P, E alone, and P alone. Two important synergistic effects of the hormones were found. First, the effects of E on labeling of several proteins in both brain regions were countered by P, and conversely, the effects of P on labeling of several proteins in both brain regions were countered by E. Second, E priming increased the number of proteins affected in labeling by P in both brain regions. Comparison of the effects of E and P on proteins in the VMN and POA indicated that the populations of proteins affected in labeling were markedly different. These results begin to clarify the mechanism in which E and P affect neuronal functioning in two regions involved in the control of reproduction and lend support to the hypothesis that gonadal steroids accomplished their action on brain tissue via a mechanism that is partly unique to the brain region.

Animals↗
PubMed1986

Ultrastructural changes in the nucleoplasm of hamster facial neurons during a postnatal maturation period.

Changes in the characteristics of the nucleoplasm were examined in young hamster facial motoneurons of 15 and 20 days postnatal age and in the adult (100 days postnatal age) at both the light and electron microscope levels. In toluidine-blue stained 1-micron thick sections, a progressive increase in basophilic islands within the nucleoplasm occurred during maturation. Ultrastructural changes that were observed during final development included a transition from a homogeneous, 'filled-in' appearing nucleoplasm to a clumped-appearing nucleoplasm. This process principally involved the formation of distinct clusters of interchromatin granules that was associated with a loss of fine fibrils, an increase in clear spaces between intervening fibrillar and granular material, and an increase in small scattered clumps of heterochromatin. These changes in both ribonucleoprotein (RNP)-and DNA-containing nuclear constituents (interchromatin granules and heterochromatin, respectively) occurred during a postnatal maturational period previously demonstrated to involve other alterations in nuclear structures. It is interpreted that these cytomorphic changes in the nucleoplasm reflect an underlying metabolic shift at the transcriptional level during the transition from an actively growing neuron to an adult functioning neuron.

Animals↗
PubMed1986

Differential effects of axotomy on immature and mature hamster facial neurons: a time course study of initial nucleolar and nuclear changes.

The early nuclear and nucleolar responses at 0.5, 1, 2 and 4 days after axotomy were observed in neurons just before and after the completion of nuclear maturation. Axotomy of hamster facial motor neurons at a postnatal age of 15 days did not produce any changes within the nucleus that were significantly different from those of control cells. In addition, no significant changes were evident in the adults at 0.5 and 1 day after axotomy. At postoperative days 2 and 4, however, the adult neurons showed enlargement of the nucleus and nucleolus. Nucleolonemal strands became more rounded and distinct, and the large cluster of granules located centrally in the nucleolus disaggregated. The irregularly distributed clumps of nucleolus-associated chromatin dispersed to form a thin shell about the nucleolar periphery. In adults at postoperative day 4, the nucleoplasmic granules became more homogeneous and less distinctly outlined than normal. The peak of both nucleolar and nuclear responses coincided at 2 days after injury in the adult, i.e. 2 days before the previously documented chromatolytic peak at 4 days after injury. These studies on the ultrastructural level support our previous hypothesis that the 15-day neurons are synthesizing at peak capacity related to their rapid growth phase and cannot be stimulated further by axotomy. The adult neurons, however, do undergo a metabolic reorganization for regenerative synthesis, and the nucleolar and nuclear changes observed are indicative of transcriptive alterations involving the underlying genome.

Animals↗
PubMed1986

Immunological response to stress in agoraphobia and panic attacks.

The authors studied in vitro immune function as measured by lymphocytic proliferative response to mitogen stimulation in 36 patients with agoraphobia and panic attacks who were participating in a double-blind placebo-controlled psychopharmacological study of anxiety disorder. No significant difference in immune status was observed between panic patients and healthy controls.

Adult↗
PubMed1986

In situ hybridization detection of estradiol-induced changes in ribosomal RNA levels in rat brain.

In this study, quantitative assessment of estradiol (E2)-induced changes in levels of ribosomal RNA within brain regions concentrating the hormone was accomplished by in situ hybridization with nick-translated tritiated ribosomal DNA probes and use of a computer-based image analysis system. Ovariectomized rats were either implanted with estradiol capsules for 6 h, 24 h, or 15 days, or sham-implanted under the same time course to serve as controls. The mean number of grains, somal area, and grain density of neurons within three E2-concentrating brain regions, the ventrolateral portion of the ventromedial and the arcuate nuclei of the hypothalamus (VL-VMN and ARC, respectively) and the corticomedial nucleus of the amygdala (AMY) were determined. In the VL-VMN and ARC, levels of rRNA were significantly increased after 6 h of E2 treatment (70% and 30%, respectively) and after 24 h of E2 treatment (60% and 62%, respectively). However, these effects on rRNA levels in VL-VMN and ARC were not observed after prolonged exposure of 15 days to the hormone. Neuronal hypertrophy was present only after 24 h of E2 treatment in the VL-VMN and ARC (32% and 14%, respectively). No changes were found in the AMY. As an additional internal control, measurements were also collected from the dorsomedial portion of the VMN (DM-VMN), a region with few E2-concentrating neurons. No changes in any of the parameters were found in DM-VMN at any time after exposure to the hormone. By extending the in situ hybridization technique to the quantitative level, these findings demonstrate differential estrogenic regulation of a known gene product, rRNA, in rat brain that is temporally and regionally specific.

Animals↗
PubMed1986

Regional specificity in estradiol effects on [3H]uridine incorporation in rat brain.

In this study, the effects of 15 days of estradiol (E2) on tritiated-uridine incorporation were autoradiographically examined, on a cell-by-cell basis, in 4 E2-concentrating regions of the female rat brain. These areas included the ventromedial hypothalamus and medial amygdala nucleus, 2 regions involved in the behavioral components of reproduction, and the medial preoptic area and arcuate nucleus of the hypothalamus, 2 regions involved in the endocrine components of reproduction. Chronic E2 caused a 50% and 52% increase in tritiated-uridine incorporation in the arcuate nucleus and medial preoptic area, but was without effect in the ventromedial hypothalamus and medial amygdala nucleus. Somal area was also increased with E2 in the arcuate nucleus and medial preoptic area (16% and 43%, respectively) but not in the ventromedial hypothalamus and medial amygdala nucleus. The results indicate that the effects of estradiol on levels of newly synthesized RNA vary in a functionally and regionally specific manner within the brain.

Amygdala↗
PubMed1986

Dental anxiety--the development of a measurement model.

A more detailed measurement instrument for dental anxiety has been developed. To investigate the dimensionability of the response, two instruments were administered to 452 persons. The first set of items (33) concerned stimuli which might prove fearsome to patients. Some of these were dental specific, others were not. A second instrument (20 items) elicited the anxiety symptoms experienced. By comparing separate Kaiser-Caffrey Alpha Factor Analyses two factors were identified within each instrument. These were labelled "generalized" phobias and "dental specific" phobias; and "endogenous" and "exogenous" (anticipatory) anxiety symptoms. Four scales were constructed using simple summations of highly loaded variables. The scales are quite reliable. Although correlations among the scales proved to be significant they are all quite low, indicating that the four scales give more or less non-redundant information about the patient. The scale had discriminating validity in differentiating between patients who acknowledge experiencing spontaneous panic/anxiety attacks and those who did not. The data confirm that dental fears are relatively independent of other generalized anticipatory fears. The results cast doubt on previously held assumptions regarding the unidimensionality of anxiety. They are consistent with a new classification of anxiety and phobic disorders presented elsewhere. The implications for research and patient management are discussed.

Anxiety Disorders↗