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Biomedical subjects

J Pickett

Publications and source records attributed to J Pickett.

At least 19 recordsLinked to original sources
PubMed2001

Causes of death in autism.

The objective of this study was to determine which causes of death are more frequent in persons with autism, and by how much, compared with the general population. Subjects were 13,111 ambulatory Californians with autism, followed between 1983 and 1997. The units of study were person-years, each linked to the subject's age, sex, and cause of death (if any) for the specific year. Observed numbers of cause-specific deaths were compared with numbers expected according to general population mortality rates. Standardized mortality rates (SMRs) were computed for each mental retardation level. Elevated death rates were observed for several causes, including seizures and accidents such as suffocation and drowning; elevated mortality due to respiratory disease was observed among persons with severe mental retardation. Overall, excess mortality was especially marked for persons with severe mental retardation, but life expectancy is reduced even for persons who are fully ambulatory and who have only mild mental retardation.

Adolescent↗
PubMed2001

Current investigations in autism brain tissue research.

Brain tissue research has developed into a high-tech, multifaceted approach to understanding neurological disorders. Directed toward autism spectrum disorders, this investigative approach combines with other disciplines, such as imaging and genetics, to help explain the range and intensity of behaviors that characterize these disorders. This report is intended as an update on current autism brain research efforts and has a dual purpose: first, to disseminate information to the scientific community in the hope of stimulating more thinking about autism research and future collaborations; and second, to let the autism community know what is happening with this precious resource that was donated in the hope of determining the cause of autism and finding effective treatments.

Autistic Disorder↗
PubMed1999

Acute stress persistently enhances estrogen levels in the female rat.

Here we tested whether exposure to either tailshock or swim stress alters ovarian hormone levels, estrogen and progesterone, in females and whether the effects are persistent. Adrenal hormone levels were also measured in males and females. Estradiol levels were elevated in unstressed females during proestrus relative to females in other stages of estrous, and exposure to the stressors enhanced estradiol beyond basal levels. For females stressed during diestrus 2, estradiol levels were elevated immediately after stressor cessation and up to 24 hrs. Exposure to tailshock, but not swim-stress, transiently enhanced progesterone in females stressed during the stage of proestrus and estrus. Glucocorticoid levels were elevated in response to both stressors and were supraelevated in females under both basal and stress conditions relative to males, particularly in blood from females exposed to acute swim stress. These results indicate that exposure to a relatively acute stressful event immediately and persistently enhances serum estradiol and are discussed in the context of reports that exposure to the same stressors immediately and persistently impairs associative learning in the female rat.

Acute Disease↗
PubMed1998

Stages of estrous mediate the stress-induced impairment of associative learning in the female rat.

Exposure to a stressful event facilitates classical eyeblink conditioning in male rats and impairs conditioning in females. The contribution of stages of estrous to the stress-induced impairment of eyeblink conditioning was evaluated. Females in proestrus, estrus and diestrus were either exposed to an acute stressor of intermittent tailshocks or swim stress and compared to unstressed females in the three stages. Females in proestrus, when estrogen levels are high, acquired the conditioned response at a facilitated rate relative to females in other stages. However, exposure to a stressor of either intermittent tailshocks or inescapable swim stress severely impaired acquisition in females during proestrus. These results suggest that the enhancing effect of estrogen on procedural memory formation is disrupted by previous exposure to a stressful event.

Animals↗
PubMed1995

Distribution of growth-associated class I alpha-tubulin and class II beta-tubulin mRNAs in adult rat brain.

A comprehensive survey of class I alpha-tubulin (alpha 1) and class II beta-tubulin (beta II) mRNAs was performed using in situ hybridization in order to determine the extent of continued expression of these immature tubulin isotype mRNAs in the adult rat brain. Qualitatively similar distributions of the two isotype mRNAs were observed, with marked variations in hybridization intensity of both probes apparent across different brain regions. Neurons in a wide variety of structures throughout the brain exhibited intense hybridization signals. While the presence of large numbers of neurons with a moderate hybridization intensity could account for the relatively high level of total binding in some regions such as the cerebellar and dentate granule layers, in most cases higher regional mRNA levels reflected greater hybridization intensity per neuron. Little variability in hybridization intensity was typically seen between individual cells within specific nuclei throughout the brain. The presence of occasional intensely labeled neurons scattered throughout the basal ganglia provided the most striking exception to this pattern. While no qualitative differences between the distributions of alpha 1-tubulin and beta II-tubulin mRNAs were observed, consistent differences in the relative intensity of hybridization for alpha 1-tubulin versus beta II-tubulin mRNA were apparent in a few brain regions. Expression by glia did not appear to contribute significantly to detectable levels of either alpha 1-tubulin or beta II-tubulin mRNA. These findings suggest that continued expression of growth-associated tubulin isotype mRNAs may have functional significance in specific neuronal populations of the adult brain. Partial overlap between the distributions of alpha 1- and beta II-tubulin mRNAs and that of GAP-43 mRNA is discussed, as are potential roles for growth-associated tubulin gene expression in supporting cytoskeletal turnover, reactive axonal growth, and dendritic remodeling in the adult brain.

Animals↗
PubMed1995

Coordinated upregulation of alpha 1- and beta II-tubulin mRNAs during collateral axonal sprouting of central peptidergic neurons.

An in situ hybridization study was performed to determine the relationship between levels of mRNAs for the axonal growth-associated alpha 1-tubulin and beta II-tubulin isotypes and the process of collateral axonal sprouting by identified central nervous system (CNS) neurons. A unilateral hypothalamic knife-cut was used to hemisect the hypothalamoneurohypophysial tract, which results in a robust collateral sprouting response by the uninjured neurons of the contralateral supraoptic nucleus (SON) (Watt and Paden: Exp Neurol 111:9-24, 1991). At 10 and 30-35 days after the lesion, cryosections of the SON were obtained and hybridized with 35S-labeled cDNA probes specific to alpha 1- and beta II-tubulin mRNAs. Quantitative evaluation of the resulting autoradiographs revealed that alpha 1-tubulin mRNA levels were significantly increased by 10 days in SON neurons that were undergoing collateral sprouting compared to controls and that this increase was sustained at 30-35 days post-lesion. Less marked increases in hybridization intensity of the beta II-tubulin probe were also apparent in sprouting neurons at both 10 and 30-35 days after the lesion, but were statistically significant only at 10 days. The measured increases in intensity of hybridization of alpha 1- and beta II-tubulin probes are likely to be conservative estimates of the underlying increase in alpha 1- and beta II-tubulin mRNA levels because sprouting SON neurons undergo significant hypertrophy. High levels of both alpha 1- and beta II-tubulin mRNAs were also seen in surviving axotomized SON neurons ipsilateral to the hypothalamic lesion. We conclude that the pattern of regulation of alpha 1- and beta II-tubulin mRNAs in CNS neurons which are capable of supporting new axonal growth includes three elements: maintenance of significant basal alpha 1- and beta II-tubulin mRNA pools in mature neurons, rapid increases in the pool size of the mRNAs following stimulation of collateral sprouting, and sustained elevation of mRNA levels during the period of axonal sprouting.

Animals↗
PubMed1995

Acoustic-phonetic context considerations for speech recognition testing of hearing-impaired listeners.

OBJECTIVE: To test for differences in the identification of consonants in carrier sentences versus in VCVs extracted from the sentences, as a function of listeners' hearing-loss categories: moderate, severe, profound. To examine whether pauses inserted in the sentences will facilitate identification of the consonants. DESIGN: Voiced stops and fricatives were identified by 11 listeners with moderate hearing losses and by 7 listeners with severe losses (between subjects design) for the conditions of consonants in sentences and in VCVs extracted from the sentences (repeated measures). Nine of these listeners also identified the consonants in the sentences with pauses. Six normal-hearing listeners were tested for the consonants in the extracted VCVs and the sentences. Voiceless stops and fricatives were identified by 4 listeners with profound losses, 18 with severe losses, and 8 with moderate losses (between subjects) for the conditions of extracted VCVs and the sentences (repeated measures). All listeners were selected on the basis of their hearing levels. RESULTS: The listeners with moderate to severe hearing loss identified the voiced stops and fricatives more poorly when the syllables were in the carrier sentences than when extracted. Insertion of the pauses in the sentence did not improve performance significantly. The normal hearing listeners showed no differences in consonant identification between the two conditions, perhaps due to "ceiling effects". The voiceless stops and fricatives were also identified more poorly when in the extracted VCVs than in the carrier sentences by other listeners with moderate to profound hearing loss. CONCLUSIONS: Listeners with moderate or greater hearing loss can show poorer identification of consonants that are embedded midway in carrier sentences than when the acoustically identical consonants are in VCVs extracted from the sentences. The performance reduction for the consonants in sentences is not relieved from insertion of brief artificial pauses in the sentences. Further research is needed determine whether hearing-impaired listeners' identification of consonants in target words of clinical word recognition tests is facilitated when the words are extracted from carrier phrases.

Audiometry, Pure-Tone↗
PubMed1994

Comparison of changes in beta-tubulin and NF gene expression in rat DRG neurons under regeneration-permissive and regeneration-prohibitive conditions.

To examine the question of whether or not prevention of axonal regrowth after injury affects the molecular responses of neurons to axotomy, Northern blotting and in situ hybridization were used to study changes in the mRNA levels of neurofilament (NF) proteins and tubulins in rat dorsal root ganglion (DRG) cells. Adult male rats sustained either a crush lesion of the mid-sciatic nerve (regeneration-permissive condition) or a cut lesion of the sciatic nerve combined with ligation of the proximal nerve stump and removal of a large segment of the distal nerve (regeneration-prohibitive condition). At 14 days post-injury, the relative levels of the low (NF-L) and middle (NF-M) molecular weight NF protein mRNAs, as well as those of beta II- and beta III-tubulin, were examined in the L4 and L5 DRG. The data showed that the levels of NF-L and NF-M mRNAs decreased while beta II- and beta III-tubulin mRNA levels increased in the DRG after either crush axotomy or cut/ligation axotomy of the sciatic nerve, suggesting that the elicitation of these molecular changes by axon disconnection is independent of the ultimate success or failure of the axonal regrowth process. However, cut/ligation axotomy had a more pronounced effect than did crush injury on the mRNA changes. This result suggests that feedback mechanisms from regrowing axons are important in regulating the extent of the cytoskeletal mRNA changes in injured neurons.

Animals↗
PubMed1993

Expression of the class III beta-tubulin gene during axonal regeneration of rat dorsal root ganglion neurons.

The effect of peripheral axotomy on the expression of the class III beta-tubulin gene in adult dorsal root ganglion (DRG) neurons was examined. Of the 5 isotypic classes of beta-tubulin expressed in the mammalian nervous system, only the class III beta-tubulin is neuron specific. While information about the expression of several of the tubulin genes during neuronal development and regeneration has become available recently, very little is known about the expression of beta III-tubulin during axonal regeneration. To explore this issue, we examined axotomy-induced changes in beta III-tubulin mRNA levels in adult rat lumbar dorsal root ganglion (DRG) neurons at different times (1-28 days) after unilateral sciatic nerve crush using northern blotting of total RNA and quantitative in situ hybridization. These studies showed an initial decrease in beta III-tubulin mRNA levels in axotomized DRG neurons as compared to contralateral controls at 1 day after injury followed by robust increases in beta III-tubulin mRNA levels relative to contralateral controls from 1 to 4 weeks after injury. We postulate that beta III-tubulin may play an essential role in axonal growth because of its unique neuron-specific pattern of expression and its substantial increase in neurons that have been stimulated to regrow their axons.

Animals↗
PubMed1989

Dural lacerations and thoracolumbar fractures.

In the pre-CT era, Miller et al. reported the presence of dural lacerations (DL) and herniations of the cauda equina in a group of patients with thoracolumbar fractures that involved separation of the pedicles, as detailed on plain radiographs. Recently, these injuries have been well characterized on CT scan. We retrospectively reviewed our series of thoracolumbar burst fractures to assess the predictive value of CT for the presence of a DL, and the clinical significance of this finding. Twenty-five patients with 27 levels of injury were assessed. Dural lacerations were noted in eight (32%) of the cases. These were significantly associated with posterior element fractures noted on axial CT, and with motor neurologic deficits. There was no correlation between the presence of a DL and the degree of spinal canal compromise. Dural lacerations occur relatively frequently in patients with thoracolumbar fractures that require operative management. Their presence should be of particular concern in those cases with a motor deficit on presentation and a posterior element fracture on axial CT scan.

Adolescent↗
PubMed1988

Effects of routine pupillary dilation on functional daylight vision.

The visual acuity of 100 patients between the ages of 16 and 66 years, seen for routine ophthalmologic examination, was measured before and after dilation. All patients had a predilation visual acuity of 20/40 or better. Postdilation binocular visual acuity using the patients' usual correction was measured first in the office and then outdoors, both with the patient's back to and the patient facing the sun, with and without the aid of postmydriatic sunglasses. Twelve percent experienced disabling photophobia even with the use of postmydriatic sunglasses, with 3% having significant objective visual loss defined as 20/50 or worse. No objective visual loss was found in 30 controls examined outdoors before dilation, without sunglasses. We recommend that patients who have experienced significant photophobia with dilation in the past, or who have never before undergone dilation, make arrangements for transportation after a dilated examination.

Adolescent↗
PubMed1974

Lipid catabolism of relapsing fever borreliae.

Relapsing fever borreliae require lipid compounds for growth in vitro. In this study, the major pathways of lipid catabolism in three species of tick-borne relapsing fever borreliae were investigated. Thin-layer chromatography was used to compare chloroform-methanol extracts of fresh culture media with extracts of exhausted culture media after organisms were removed by centrifugation. The chromatographic data demonstrated that lysolecithin was removed from the culture media during growth of the spirochetes, whereas lecithin, sphingomyelin, triglycerides, and cholesterol esters were not affected by growth of the organisms. Sonic extracts of the organism were tested for the presence of specific enzymes of lipid catabolism. Lysolecithinase, glycerophosphorylcholine diesterase, and acid phosphatase activities were demonstrated. Thus, these organisms can sequentially dissimilate lysolecithin to fatty acids, choline, inorganic phosphate, and glycerol. Assays for phospholipases A, C, and D, alpha-glycerophosphate dehydrogenase, alkaline phosphatase, and lipase were negative.

Acid Phosphatase↗
PubMedDate not supplied

Long-term effects of axotomy on beta-tubulin and NF gene expression in rat DRG neurons.

To compare the long-term recovery of gene expression in dorsal root ganglion (DRG) neurons under conditions of regeneration vs. non-regeneration, Northern blotting and in situ hybridization were used to assess steady-state neurofilament (NF) and beta tubulin mRNA levels 12 weeks following axonal injury. Adult male rats sustained either a crush lesion of the mid-sciatic nerve (regeneration occurs), or a cut lesion of the sciatic nerve combined with ligation of the proximal nerve stump and removal of a large segment of the distal nerve (regeneration does not occur). In the latter case, neuroma formation physically prevented axonal regeneration. Results of Northern blotting of total RNA obtained from the DRG indicated that NF-L and NF-M mRNA levels had largely returned to control levels at 12 weeks following crush axotomy but were still substantially depressed following cut/ligation injury of the sciatic nerve at that time. In situ hybridization studies indicated that both crush and cut/ligation axotomy resulted in significantly lower NF-L mRNA levels in large-sized (> 1000 micron2) DRG neurons at 12 weeks post-axotomy. Discrepancies in the conclusions from Northern blotting and in situ hybridization experiments were also noted in the case of tubulin mRNA changes at long intervals after axotomy. In situ hybridization data derived from the large-sized DRG neurons using a coding region beta-tubulin cDNA (which recognizes both beta II and beta III mRNAs) showed complete recovery of beta-tubulin mRNA levels in surviving large-sized DRG neurons after crush axotomy, but significantly elevated tubulin mRNA levels in surviving large DRG cells at 12 weeks after cut/ligation axotomy. In contrast, Northern blotting results indicated that beta II-tubulin mRNA levels in the crush axotomy condition remained elevated relative to control while they were substantially lower than control in cut/ligation axotomy samples. Results from analysis of beta III-tubulin mRNA changes were not conclusive. The lack of complete correspondence in the results from the two different methods of analysis of mRNA changes (blotting vs. in situ) is likely to be due to selective loss of large-sized DRG neurons in the long-standing cut/ligation injury condition. This would influence results from blotting data, where RNA is derived from the DRG as a whole, more so than in situ hybridization experiments which specifically focus on the surviving large-sized neurons. Overall, data from these experiments indicate that altered patterns of gene expression remain in the DRG for long intervals after axonal injury, whether or not axonal regeneration has been successful.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗