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Biomedical subjects

J M Williams

Publications and source records attributed to J M Williams.

At least 37 records · Page 2Linked to original sources
PubMed2002

Early alterations in the collagen meshwork and lesions in the ankles are associated with spontaneous osteoarthritis in guinea-pigs.

OBJECTIVE: The purpose of this study was to evaluate matrix changes in knee cartilage prior to development of surface disruptions and to examine the ankle for evidence of osteoarthritis (OA)-like lesions. DESIGN: Guinea-pig ankles and knees were examined histologically or viewed with polarization microscopy to reveal changes in orientation of the collagen fibers. RESULTS: The medial femoral condyles were virtually free of histologic changes at 3 months of age. Changes were present by 6 months. Medial tibial plateau histologic changes were seen at 3 months which became more pronounced with age. Alterations in the collagen meshwork corresponding to areas of proteoglycan (PG) loss were noted in animals with an intact articular surface as early as 3 months. Histologic changes were noted in the ankles as early as 3 months of age which included surface disruptions, cell loss and loss of PG staining. Only knee joint composite histology scores were significantly elevated at 3 months while both knee and ankle scores were significantly elevated at 6 months. Knee and ankle joint scores were not different from each other at 6 months. CONCLUSIONS: Alterations in the orientation of the collagen network of the cartilage correlated with Safranin-O loss suggesting that alterations in collagen:PG interactions play a role in the early phases of the OA process and precede frank histologic changes in the articular surface. The results in this study report for the first time OA-like lesions occurring spontaneously in articular cartilage of the ankle in the guinea-pig.

Aging↗
PubMed2001

Postnatal regulation of limb proprioception by muscle-derived neurotrophin-3.

To investigate the effects of neurotrophin-3 (NT-3) on postnatal proprioceptive neurons and their targets, transgenic mice were generated that use the myosin light chain 1 (mlc) promoter to overexpress NT-3 in skeletal muscle. Ribonuclease protection assays revealed that NT-3 overexpression in hindlimb skeletal muscle began at embryonic day 14 (E14) and continued throughout adulthood. Overexpression of NT-3 during late embryogenesis resulted in increased numbers of large sensory and small fusimotor axons. Within a week of birth, mlc/NT-3 mice retract their limbs to the torso when lifted by the tail. Footprint analysis revealed that mlc/NT-3 mice had significant abnormalities in their gait compared with wild-types. Beam walking and rotorod analysis confirmed the poor limb control by mlc/NT-3 mice. These locomotive deficits progressively worsened with age and were likely related to the formation of morphologically abnormal muscle spindles. The most common spindle anomaly was the presence of excessive intrafusal bag fibers within individual muscle spindles. To assess the role of NT-3 in recovery from nerve injury, sciatic nerve crushes were performed in young adult mice. Two days after injury, mlc/NT-3 mice displayed significantly improved sciatic functional indexes and a significant increase in muscle spindles that remained associated with axons. The latter finding suggests that excess NT-3 in muscle may retard the degeneration of proprioceptive axons after nerve crush. Long-term survival after nerve injury in mlc/NT-3 mice did not induce further changes in spindle number or morphology. These findings demonstrate that, in addition to promoting embryonic proprioceptive neuron survival, postnatal overexpression of NT-3 in muscle leads to abnormal spindle formation and deficits in locomotive control. However, our results also show that NT-3 may be therapeutic for proprioceptive axons immediately after nerve injury by delaying axon degeneration.

Animals↗
PubMed2001

Pharmacological comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HT3A/3B receptors.

The present study determined the detailed pharmacological profile of heterologously expressed human (h) homomeric 5-HT3A receptors in direct comparison to heteromeric h5-HT3A/3B receptors. The very minor differences in their respective pharmacological profiles indicates that the 5-HT3B receptor subunit alters, predominantly, the biophysical rather than the pharmacological properties of the 5-HT3 receptor.

Free Radical Scavengers↗
PubMed2001

Generation of a selective 5-HT3B subunit-recognising polyclonal antibody; identification of immunoreactive cells in rat hippocampus.

The present study generated a polyclonal antibody (AP86/3) that recognises a peptide sequence of the h5-HT(3B) receptor subunit. Western blot analysis of homogenates prepared from cell lines expressing either homomeric (h5-HT(3A)) or heteromeric (h5-HT(3A/3B)) receptors, as well as immunocytochemical studies with the same cell lines, indicated that AP86/3 recognised, selectively, the 5-HT(3B) subunit. Immunohistochemical labelling was also apparent in cells in the rat hippocampus that displayed the distribution and morphology of interneurones.

Animals↗
PubMed2001

The effect of being a victim or witness of family violence on the retrieval of autobiographical memories.

OBJECTIVE: This study was designed to determine whether greater reliance on general memory retrieval in children was related to depression, and whether family violence affected the specificity of children's memory retrieval. METHOD: We compared children who had experienced some form of family violence with children who had never experienced any form of family violence, based on their responses to questions concerning child-parent and interparental disagreements. RESULTS: As expected, there was a positive correlation between the extent of "generic-categoric" memory retrieval and depression level. There was no evidence, however, that autobiographical memory was affected by family violence. CONCLUSIONS: This study is the first to report significant associations between depression and autobiographical memory style in children. The results suggest that the effect of family violence on children's memory retrieval may be mediated by depression.

Adolescent↗
PubMed2001

Prevention of heterotopic ossification after spinal cord injury with indomethacin.

STUDY DESIGN: A randomized, prospective, double-blind, placebo-controlled clinical trial. OBJECTIVES: To determine the effect of indomethacin on the prevention of heterotopic ossification (HO) following spinal cord injury (SCI). SETTING: County Hospital, Miami, Florida, USA. METHODS: Sixteen patients were treated with slow-release indomethacin 75 mg daily and 17 patients received placebo for a period of 3 weeks. Prevention was started 21+/-14 days after SCI. In both groups of patients there was similar age of the patients as well as the level of SCI and ASIA impairment scale. Two methods were used to diagnose HO, bone scintigraphy and radiographic examination. Bone scintigraphy with technetium labeled methylene-diphosphonate was used for diagnosis of early stage, while radiography was used for diagnosis of late stage of HO development. RESULTS: A significantly lower incidence of early HO was found in the indomethacin group (25%) than in the placebo group (65%; P<0.001). Similarly there was a significant reduction of late HO in the indomethacin group (12.5%) as compared to the placebo group (41%; P<0.001). CONCLUSION: Our data suggest that indomethacin used during the first 2 months after SCI is effective in prevention of HO in a significant number of patients.

Adult↗
PubMed2001

Children's understanding of the physical, cognitive and social consequences of impairments.

The present study explored typically developing children's (n = 77) understanding of physical, cognitive and social competencies of children with impairments. Children in each of four age groups (4-5 years, 6-7 years, 9-10 years and 11-12 years) were interviewed to explore their ideas about the abilities of children with physical impairments (minor: missing thumb; major: wheel-chair bound), sensory impairments (vision and hearing), learning disabilities (non-specific and Down's syndrome) and emotional/behavioural difficulties (attention deficit hyperactivity disorder and lack of social skills). Significant age differences were found in children's judgements of the capabilities of children with impairments. Furthermore, children's understanding of the consequences of impairments varied as a function of disability type. Findings are discussed in relation to previous research on children's disability concepts and implications for inclusive education practices.

Activities of Daily Living↗
PubMed2001

A single injection of fibronectin fragments into rabbit knee joints enhances catabolism in the articular cartilage followed by reparative responses but also induces systemic effects in the non-injected knee joints.

OBJECTIVE: To investigate effects on cartilage metabolism and degeneration of injection of fibronectin fragments (Fn-fs) into rabbit knee joints. DESIGN: The knees of adolescent New Zealand white rabbits were intraarticularly injected with rabbit Fn-fs. Cartilage sections from both injected and non-injected joints were treated with Safranin-O, with antibodies to the VDIPEN and NITEGE neoepitopes of degraded aggrecan and to matrix metalloproteinase-3 (MMP-3). Proteoglycan (PG) content of cartilage was measured by a dimethylmethylene blue assay of papain digests. PG synthesis rates were measured by(35)S-sodium sulfate incorporation into explanted cartilage. RESULTS: In the injected joint cartilage, the Fn-fs bound cells in the upper superficial zone maximally between 6 and 24 h. By day 2, MMP-3 protein was enhanced and cartilage PG content and PG synthesis rates were reduced 40% and 70%, respectively. MMP-3 epitope and VDIPEN and NITEGE neoepitopes were also enhanced. The PG content then increased to supernormal levels from days 14 to 35 and then declined to normal levels by day 70, as did PG synthesis rates. In the non-injected joint cartilage, Fn-fs were not detected. Although MMP-3 expression was enhanced between days 2 and 21 as well as VDIPEN neoepitope, the PG content was never reduced but rather enhanced to supernormal levels from days 21 to 35. This was associated with enhanced PG synthesis by day 7, which decreased to control levels by day 70. CONCLUSIONS: In this cartilage degeneration model, loss of cartilage PG is followed by supernormal anabolic responses that facilitate PG restoration. Further, the damage causes a systemic effect of enhanced PG synthesis and content in the non-injected joint cartilage.

Alkaline Phosphatase↗
PubMed2001

Emergency medical care in rural America.

The delivery of high-quality emergency care in a rural setting requires a conceptual framework quite different from that required in urban and suburban environments, given that available resources are limited in the rural setting. The intermittent and episodic nature of seriously ill and injured patients who present to rural emergency departments makes it difficult to plan, staff, and equip in order to provide emergency medical care at the same level seen at higher volume urban or suburban institutions. The objective of this article is to describe the distinctive nature and widely unrecognized features of emergency medicine in rural and remote areas, with a focus on clinical, workforce, and economic issues. We present recommendations for a shift in thinking and a call to action on behalf of all emergency medicine professionals that are based on a realistic assessment of the current status of emergency medicine and that are needed to develop and sustain high-quality emergency medical care in rural America.

Emergency Medical Services↗
PubMed2001

Hospital preparedness for weapons of mass destruction incidents: an initial assessment.

STUDY OBJECTIVE: We performed an assessment of hospital preparedness for weapons of mass destruction (WMD) incidents in Federal Emergency Management Agency (FEMA) Region III. METHODS: Interviews of hospital personnel were completed in 30 hospitals. Data collected included level of preparedness, mass decontamination capabilities, training of hospital staff, and facility security capabilities. RESULTS: No respondents believed their sites were fully prepared to handle a biologic incident, 73% (22/30) believed they were not prepared to manage a chemical weapons incident, and 73% believed they were unprepared to handle a nuclear event. If a WMD incident were to occur, 73% of respondents stated a single-room decontamination process would be set up. Four (13%) hospitals (all rural) reported no decontamination plans. WMD preparedness had been incorporated into hospital disaster plans by 27% (8/30) of facilities. Eighty-seven percent (26/30) believed their emergency department could manage 10 to 50 casualties at once. Only 1 facility had stockpiled any medications for WMD treatment. All facilities had established networks of communication. No hospital had preprepared media statements specific to WMD. Nearly one fourth (7/30) stated that their hospital staff had some training in WMD event management. All reported need for WMD-specific training but identified obstacles to achieving this. Seventy-seven percent (23/30) of hospitals had a facility security plan in place, and half were able to perform a hospital-wide lock down. Ninety-six percent (29/30) reported no awareness regarding the threat of a secondary device. CONCLUSION: Hospitals in this sample do not appear to be prepared to handle WMD events, especially in areas such as mass decontamination, mass medical response, awareness among health care professionals, health communications, and facility security. Further research is warranted, including a detailed assessment of WMD preparedness using a statistically valid sample representative of hospital emergency personnel at the national level.

Biological Warfare↗
PubMed2001

Significant fetal-maternal hemorrhage after termination of pregnancy: implications for development of fetal cell microchimerism.

OBJECTIVE: Recent reports that an association exists between fetal cell microchimerism and autoimmune disease has increased interest in the postpartum persistence of fetal cells. The purpose of this study was to determine, by means of quantitative polymerase chain reaction amplification, whether a significant fetalmaternal hemorrhage occurs after elective termination of pregnancy. STUDY DESIGN: Blood samples were obtained from 23 women who underwent termination of pregnancy immediately before venipuncture; these samples were subjected to analysis by quantitative polymerase chain reaction amplification with the use of Y-chromosome primers. There were 21 male and 2 female fetuses. Results were equilibrated to 16 mL and analyzed by a weighted linear regression analysis to evaluate the correlation between detected fetal nucleated cell equivalents and gestational weeks. RESULTS: Among the 21 known male fetuses, the median number of detected fetal nucleated cell equivalents was 1552 (range, 50-37,618). The female fetuses had no fetal nucleated cell equivalents detected. A positive dependence of male fetal nucleated cell equivalents on gestational age was shown (P <.001). CONCLUSION: Analysis by quantitative polymerase chain reaction amplification demonstrated a large fetal-maternal transfusion after elective abortion. Consideration of the biologic consequences of pregnancy and the potential for future development of fetal cell microchimerism must now extend to a larger population of women.

Abortion, Induced↗
PubMed2001

Overexpression of neurotrophin-3 in skeletal muscle alters normal and injury-induced limb control.

Transgenic overexpression of neurotrophin-3 (NT-3) in mice increases the number of surviving proprioceptive sensory components, including primary sensory neurons, gamma motoneurons and muscle spindles. The numbers of surviving alpha motoneurons are not affected by NT-3 overexpression (Wright et al., Neuron 19: 503-517, 1997). We have assessed the consequences NT-3-stimulated increase in the proprioceptive sensory system by measuring locomotive abilities of mice that overexpress NT-3 in all skeletal muscles (myo/NT-3 mice). In adulthood, one myo/NT-3 transgenic line continues to express NT-3 at high levels in muscle and maintains a hypertrophied proprioceptive system (high-OE myo/NT-3 mice). Compared to wildtypes, high-OE myo/NT-3 mice have nine times the amount of NT-3 protein in the medial gastrocnemius at six weeks of age. Although appearing normal during ordinary activity, high-OE myo/NT-3 mice display a distinct clasping phenotype when lifted by the tail. High-OE myo/NT-3 mice show severe locomotor deficits when performing beam walking and rotorod testing. These mice also demonstrate aberrant foot positioning during normal walking. However, following sciatic nerve crush, overexpression of NT-3 prevents further abnormalities in paw positioning, suggesting NT-3 may attenuate sensorimotor deficits that occur in response to sciatic nerve injury. Our results suggest that increases in proprioceptive sensory neurons, spindles and gamma motoneurons, along with continued postnatal NT-3 overexpression in muscle significantly disrupt normal locomotor control. Importantly, however, NT-3 may lessen initial deficits and thus improve functional recovery after peripheral nerve injury, suggesting these mice may serve as a good model to study NT-3's role in neuroprotection of proprioceptive afferents.

Animals↗
PubMed2001

Butyrate alters the expression and activity of cell cycle components in anaplastic thyroid carcinoma cells.

Anaplastic thyroid carcinoma (ATC) is the most malignant and aggressive form of thyroid cancer. Most patients die within months of diagnosis, primarily due to the absence of effective chemotherapeutic strategies. Identifying alternative therapies is necessary to increase long-term survival. Butyrate elicits a number of responses from cancer cells both in vitro and in vivo including growth repression, cell cycle arrest, differentiation, and apoptosis. Even though many types of cancer cells have been studied, little is known of the response of ATC cells to this drug. In this study, we report that butyrate induces differential cell cycle arrest (arrest in G1 and G2/M phases) in an ATC cell line that correlates with changes in the expression, phosphorylation, and activity of key components of the cell cycle machinery. Exposure to butyrate increases the expression of the cyclin-dependent kinase inhibitors, p21/Cip1 and p27/Kip1, decreases the expression of cyclin A and cyclin B, inhibits the phosphorylation of the retinoblastoma protein (pRb), and decreases the activity of cdk1 and cdk2-associated kinases. These results suggest that butyrate may be useful in the clinical treatment of ATC.

Butyrates↗
PubMed2001

Histone deacetylase inhibitors promote apoptosis and differential cell cycle arrest in anaplastic thyroid cancer cells.

Little information exists concerning the response of anaplastic thyroid carcinoma (ATC) cells to histone deacetylase inhibitors (HDAIs). In this study, the cellular response to the histone deacetylase inhibitors, sodium butyrate and trichostatin A, was analyzed in cell lines derived from primary anaplastic thyroid carcinomas. HDAIs repress the growth (proliferation) of ATC cell lines, independent of p53 status, through the induction of apoptosis and differential cell cycle arrest (arrested in G1 and G2/M). Apoptosis increases in response to drug treatment and is associated with the appearance of the cleaved form of the caspase substrate, poly-(ADP-ribose) polymerase (PARP). Cell cycle arrest is associated with the reduced expression of cyclins A and B, the increased expression of the cyclin-dependent kinase inhibitors, p21(Cip1/WAF1) and p27Kip1, the reduced phosphorylation of the retinoblastoma protein (pRb), and a reduction in cdk2 and cdk1-associated kinase activities. In ATC cells overexpressing cyclin E, drug treatment failed to replicate these events. These results suggest that growth inhibition of ATC cells by HDAIs is due to the promotion of apoptosis through the activation of the caspase cascade and the induction of cell cycle arrest via a reduction in cdk2- and cdk1-associated kinase activities.

Apoptosis↗
PubMed2001

The acute management of head injury.

The management of traumatic brain injury has undergone extensive revision as the results of large collaborative outcome studies have cast doubt on many traditional 'common sense' practices. The primary goal of identifying and treating intracranial hypertension has given way to a focus on secondary brain ischemia, in which cerebral perfusion pressure and oxygen delivery have gained new importance. With the exception of impending herniation, the routine use of hyperventilation and high-dose barbiturates is no longer recommended. Hypertonic saline, given as intermittent boluses, has joined mannitol as an effective means of reducing cerebral edema. Preliminary results from a large multi-center study have cast doubt on the benefit of the broad application of hypothermia in improving outcome in traumatic brain injury.

Journal Article↗
PubMed2001

Resolution of dysphagia following cricopharyngeal myectomy in six young dogs.

Six young dogs were presented with a history of dysphagia and nasal regurgitation since birth. Following cranial nerve examination and assessment of swallowing with fluoroscopy, a diagnosis of cricopharyngeal achalasia was made in each case. In four dogs, concomitant aspiration pneumonia was present. Sectioning and removal of part of the cricopharyngeal muscle resulted in immediate and continued resolution of all signs of dysphagia and nasal regurgitation over follow-up periods of two to eight years. Postoperative complications were not seen in any case. In five of the six dogs, the cricopharyngeal muscle was approached laterally, a technique not previously described.

Animals↗