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PubMedDate not supplied

Chlorine-induced damage documented by neurophysiological, neuropsychological, and pulmonary testing.

Chlorine causes acute pulmonary edema and damages airways, thus producing obliterative bronchiolitis. In the case series in this study, its adverse effects were extended to visual and central nervous system impairment. Twenty-two patients exposed briefly to undiluted chlorine at home or work were evaluated with a battery of neurobehavioral and visual tests. Their test scores, expressed as percentage predicted, were compared with those of unexposed subjects. Chlorine-exposed subjects had impaired balance (with eyes open and eyes closed), delayed simple and choice reaction times, impaired color discrimination, impaired visual field performance, decreased hearing, and decreased grip strength. Blink reflex latency was delayed on the right. Cognitive performance (i.e., digit symbol and vocabulary), peg placement, trail making A and B, and verbal recall were significantly below predicted levels. Well-learned memory functions were not impaired. Adverse mood states scores were elevated as were the frequencies of 28 of 35 common symptoms. Forced vital capacities were reduced. The duration of chlorine exposures was from a breath or two to several hours, and exposures were associated with impaired neurophysiologic and neuropsychologic functions. Impairments appeared insidiously, were noted 1 to 48 mo after exposure, and persisted. Such functional losses must be prevented. Additional chlorine-exposed patients should be evaluated for neurological and pulmonary damage.

Adult↗

PubMed2001

Parkin is linked to the ubiquitin pathway.

Autosomal recessive juvenile parkinsonism (AR-JP) is one of the most common forms of familial Parkinson's disease. AR-JP is characterized by selective and massive loss of dopaminergic neurons in the substantia nigra of the midbrain and absence of Lewy bodies, the pathological hallmark of idiopathic Parkinson's disease. Parkin, the causative gene of AR-JP, encodes a 52-kDa protein that is a RING-type ubiquitin (Ub) protein ligase (E3) collaborating with a Ub-conjugating enzyme (E2) belonging to a cognate class of UbcH7 or UbcH8. Analysis of parkin mutations in AP-JP patients reveals that the functional loss of parkin as an E3 enzyme is the molecular basis of AR-JP. Thus it is now clear that AR-JP is due to failure of proteolysis mediated by the Ub-proteasome system and accumulation of as yet unidentified protein(s) causes nigral neuronal death without formation of Lewy bodies. These findings should shed new light on the mechanisms underlying neurodegeneration in sporadic Parkinson's disease as well as AR-JP.

Animals↗

PubMed2005

Mouse axin and axin2/conductin proteins are functionally equivalent in vivo.

Axin is a central component of the canonical Wnt signal transduction machinery, serving as a scaffold for the beta-catenin destruction complex. The related protein Axin2/Conductin, although less extensively studied, is thought to perform similar functions. Loss of Axin causes early embryonic lethality, while Axin2-null mice are viable but have craniofacial defects. Mutations in either gene contribute to cancer in humans. The lack of redundancy between Axin and Axin2 could be due to their different modes of expression: while Axin is expressed ubiquitously, Axin2 is expressed in tissue- and developmental-stage-specific patterns, and its transcription is induced by canonical Wnt signaling. Alternatively, the two proteins might have partially different functions, a hypothesis supported by the observation that they differ in their subcellular localizations in colon epithelial cells. To test the functional equivalence of Axin and Axin2 in vivo, we generated knockin mice in which the Axin gene was replaced with Myc-tagged Axin or Axin2 cDNA. Mice homozygous for the resulting alleles, Axin(Ax) or Axin(Ax2), express no endogenous Axin but express either Myc-Axin or Myc-Axin2 under the control of the Axin locus. Both Axin(Ax/Ax) and Axin(Ax2/Ax2) homozygotes are apparently normal and fertile, demonstrating that the Axin and Axin2 proteins are functionally equivalent.

Alleles↗

PubMedDate not supplied

[Ocular symptoms in pituitary adenomas (author's transl)].

The study of 85 patients suffering from pituitary adenoma, amongst which 56 with a visual failure, allowed to show: 1) The importance of the functional loss a revealing sign of the disease (50% cases). 2) The importance of the ophthalmological examination as a diagnostic argument. The latter, however, needs an extremely methodical examination of the visual fields. The combinated use of the Goldman Perimeter, and the Amsler schemes gave us satisfactory results: 87.5% of patent bitemporal hemianopsiae. It has been useful, in several cases to enhance these methodes by using coloured indexes. All of the patients underwent surgery, with complementary radiotherapy. The functional recovery quality has been shown, in the majority of the cases, to be proportionnal to the operation precocity in relation to the first functional symptoms.

Adenoma↗

PubMed1999

Popliteal artery entrapment syndrome.

Popliteal artery entrapment syndrome (PAES) is a rare cause of exercise-induced leg pain. Entrapment occurs because of an abnormal relationship between the popliteal artery and the surrounding myofascial structures in the popliteal fossa. Arterial insufficiency in the affected limb arises with entrapment of the artery, commonly giving leg symptoms with exertion. The true incidence of PAES in the general population is not known. The aetiology of PAES has an embryological basis related to the development of the popliteal artery and the surrounding musculature. Many different classification schemes have been developed to differentiate the various types of abnormal anatomy that are associated with the syndrome. Repeated popliteal artery compression causes trauma to the arterial wall, leading to premature localised atherosclerosis. The pathology of PAES is believed to be progressive, with arterial thrombosis occurring in some individuals as a natural progression of the disease process. Acute ischaemia can occur if there is an occlusion of the artery or thrombosis within an aneurysm. Clinically, up to 85% of individuals diagnosed with the syndrome are males. The mean age of individuals in a large series was 28 years. The condition can be found bilaterally in 25% of cases. Most individuals present with exercise-induced leg pain, the remainder presenting with acute or chronic ischaemia. The condition can result in significant functional loss for active individuals. Surgery has been advocated to prevent the progression of the disease that is believed to be the natural history of untreated PAES. However, the little research that has been done to determine the prognosis for individuals who have undergone surgery has focused on the patency rate of the arteries after surgery and the presence or absence of complications. Research needs to be done to look at the natural history of untreated PAES and the functional status of athletes after undergoing PAES surgery.

Arterial Occlusive Diseases↗

PubMed1989

Centrosome inheritance in starfish zygotes: selective loss of the maternal centrosome after fertilization.

The mature egg inherits a centrosome from the second meiotic spindle, and the sperm introduces a second centrosome at fertilization. Since only one of these centrosomes survives to be used in development, specific mechanisms must exist to control centrosome inheritance. To investigate how centrosome inheritance is controlled we used starfish eggs as a model system, because they undergo meiosis after fertilization. As a result, the fate of the maternal and paternal centrosomes can be followed by light microscopy and experimentally manipulated in vivo. We show initially that only the paternal centrosome is used in starfish zygote development; the maternal centrosome retained from meiosis II is functionally lost before first mitosis. We then tested a number of possible ways in which the zygote could exert this differential control over the stability of centrosomes initially residing in the same cytoplasm. The results of these experiments can be summarized as follows: (1) Although the microtubule organizing center activity of the maternal centrosome is not degraded after meiosis, the ability of this centrosome to double at successive mitoses is lost. (2) The sperm centrosome is not "masked" from cytoplasmic conditions which could destabilize all centrosomes during or after the meiotic sequence. (3) The functional loss of the maternal centrosome is not due to its cortical location. (4) The loss of this doubling capacity is determined by the egg, not by putative inhibitory factors from the fertilizing sperm. (5) The destabilization of the maternal centrosome is not due to the complete loss of its centrioles. Together, these results demonstrate that all maternal centrosomes are equivalent and that they are intrinsically different from the paternal centrosome. This intrinsic difference, in concert with a change in cytoplasmic conditions after meiosis, determines the selective loss of the maternal centrosome inherited from the meiosis II spindle.

Animals↗

PubMed2004

Some effects of cortical and callosal damage on conscious and unconscious processing of visual information and other sensory inputs.

Although new methods of investigation from the molecular level to cognition are promoting major advances in the study of the functions of the human brain, the analysis of behavioral and psychological deficits following brain damage is still a major tool for the understanding of cerebral organization. The present paper reviews some aspects of work on functional losses and residual abilities following cortical damage that have allowed to distinguish conscious and unconscious levels of visual input processing. Attention is given to the possible contribution of residual conscious vision of color to unconscious form analysis in visual agnosia. The paper also reviews findings on temporary and permanent deficits that occur after selective lesions of a prominent input-output system of the cerebral cortex, the corpus callosum, with the aim of assessing the possibility of establishing a functional callosal topography.

Animals↗

PubMed2003

Oncogenic potential of a dominant negative mutant of interferon regulatory factor 3.

Interferon regulatory factor 3 (IRF3) is activated in response to various environmental stresses including viral infection and DNA-damaging agents. However, the biological function of IRF3 in cell growth is not well understood. We demonstrated that IRF3 markedly inhibited growth and colony formation of cells. IRF3 blocked DNA synthesis and induced apoptosis. Based on this negative control of cell growth by IRF3, we examined whether functional loss of IRF3 may contribute to oncogenic transformation. IRF3 activity was specifically inhibited by expression of its dominant negative mutant. This mutant lacks a portion of the DNA binding domain like IRF3a, an alternative splice form of IRF3 in the cells. This dominant negative inhibition blocked expression of specific IRF3 target genes. Mutant IRF3 efficiently transformed NIH3T3 cells, as demonstrated by anchorage-independent growth in soft agar and tumorigenicity in nude mice. These results imply that IRF3 may function as a tumor suppressor and suggest a possible role for the relative levels of IRF3 and its dominant negative mutant in tumorigenesis.

3T3 Cells↗

PubMed2005

Long-term results of gamma knife surgery for the treatment of craniopharyngioma in 98 consecutive cases.

OBJECT: The authors analyzed the long-term outcomes of gamma knife surgery (GKS) for residual or recurrent craniopharyngiomas after microsurgery and the effects of dose reduction. METHODS: A total of 107 patients with craniopharyngiomas were treated with GKS at Komaki City Hospital during the past 12 years, and 98 patients were followed up for 6 to 148 months (mean 65.5 months). The mean tumor diameter and volume were 18.8 mm and 3.5 ml, respectively. These tumors were treated with a maximal dose of 21.8 Gy and a tumor margin dose of 11.5 Gy by using a mean of 4.5 isocenters. Final overall response rates were as follows: complete response 19.4%, partial response 67.4%, tumor control 79.6%, and tumor progression 20.4%. Reducing the tumor margin dose resulted in decreased therapeutic response and increased tumor progression, although the rate of visual and pituitary function loss also decreased. Among the factors examined, age (for adults) and the nature of the tumor (cystic or mixed) were statistically significant favorable and unfavorable prognostic factors, respectively. The actuarial 5- and 10-year survival rates were 94.1 and 91%, respectively. The progression-free survival rates were 60.8 and 53.8%, respectively. Patient outcomes were reportedly excellent in 45 cases, good in 23, fair in four, and poor in three; 16 patients died. Deterioration both in vision and endocrinological functions were documented as side effects in six patients (6.1%). CONCLUSIONS: Stereotactic GKS is safe and effective, in the long term, as an adjuvant or boost therapy for residual or recurrent craniopharyngiomas after surgical removal and has minimal side effects. New treatment strategies must be devised to manage these tumors.

Adolescent↗

PubMed1997

Consumer and professional ratings of the importance of functional status components.

As the population ages and chronic disease becomes the more dominant form of illness, measures of functional loss and disability assume greater importance in the assessment of both quality of life and the cost-effectiveness of care. The authors studied the responses of consumers and health care professionals regarding the impact on dependency of various levels of disability. Striking differences in perception were noted, raising concerns about the ability of those providing care to assume that the recipients share their values about what is important. This study makes clear the need for more research on functional outcome measurements that incorporate the values of consumers.

Activities of Daily Living↗

PubMed1998

[Eye injuries in childhood].

OBJECTIVE: The purpose of this study was to analyze the epidemiological, damage and preventative aspects of the pediatric ocular injuries treated during the last five years in our hospital. PATIENTS AND METHODS: We have revised all clinical histories of ocular injuries in the Emergency Services of the Asturias Central Hospital from January 1992 to December 1996. Two hundred fifty-seven cases were reviewed and the following parameters were studied: age, sex, kind of injury, causes and places where they originated, hospitalization or no, and functional sequeale. RESULTS: Eighty percent of the cases were male (206 patients). Most, 85.6% (220 cases) did not require hospital attention, while hospitalization was necessary in 14.4% (37 cases). Concerning the latter, 73% (27 cases) were in the hospital less than 7 days, while the other 27% (10 cases) were hospitalized from 8 to 14 days. As for the cause of and the location where the injuries took place, our results were as follows: school-home 33%, playtime-leisure 32%, sports accidents 12%, assaults 10%, traffic accidents 3% and unknown causes 10%. Minor injuries tend to imply the full restitution of sight (a large percentage were revised by their own ophthalmologist). Serious injuries caused the following functional losses: loss of eyeball in 2 cases (traffic accident), monolateral blindness in 2 cases serious amblyopia in 10 cases, and moderate amblyopia in 6 cases. CONCLUSIONS: Males suffer injuries 4 times more frequently than females and these are very infrequent before the age of 3 years. Traffic accident injuries are rare in comparison to in adulthood. Important immediate visual sequale were seen in 7.8% of the cases, although these may also appear later in cases that at first present good function during the acute phase.

Adolescent↗

PubMed1994

Recovery from directional hypokinesia and bradykinesia in unilateral neglect.

Patients with acute right hemisphere (RH) damage and left unilateral neglect may exhibit slowness in both the initiation and execution of goal-directed movements toward the contralesional side (respectively, directional hypokinesia and directional bradykinesia). We retested 13 patients with RH damage, who on initial testing 1 year earlier had shown these impairments on a visually cued sequential movement task. Initiation and execution times were measured separately for leftward and rightward movement sequences, performed in either hemispace and across the body midline. Patients with anterior/subcortical lesions exhibited directional hypokinesia and bradykinesia on initial testing, but no longer showed either after 12 months. It is suggested that the recovery exhibited by these patients was determined conjointly by residual functioning of flexible anterior/subcortical structures involved in response production, in addition to the resolution of transient secondary dysfunction (i.e., diaschisis) of posterior (parietal) areas responsible for attentional orienting and target selection. In contrast, patients with posterior (parietal) lesions continued to exhibit directional hypokinesia after 12 months, probably as a result of permanent damage to a region whose dedicated or specialised functions cannot readily be compensated by other brain areas. These results support the notion that spatial attention and goal-directed movement are subserved by a distributed network involving separate but interconnected brain regions. Distinct functional losses may be predicted, in both the acute and chronic stages postinjury, on the basis of temporary or permanent dysfunction of discrete components of this network.

Adult↗

PubMed2003

Ischemic insult exacerbates acrolein-induced conduction loss and axonal membrane disruption in guinea pig spinal cord white matter.

Cellular destruction following ischemic insult may be due to secondary injury mechanisms, not the oxygen-glucose deprivation itself. We have examined the effect of acrolein, an aldehyde product of lipid peroxidation (LPO) and oxidative stress, on the axons in isolated guinea pig spinal cord white matter following ischemic insult. We have found that acrolein at 50 microM, which is unharmful to spinal cord when applied alone, causes action potential conduction failure and membrane disruption following 1 to 2 h of exposure when applied during the reperfusion period. Ischemic insult also exacerbates the effect of acrolein at 200 microM, which does inflict functional and anatomical damage when applied alone. Unlike metabolic poisoning, acrolein-mediated damage is not a function of axonal size and does not affect the refractoriness in response to dual and multiple stimuli. These results indicate that spinal cord axons, in addition to experiencing elevated free radicals, are more vulnerable to acrolein attack when the level of oxygen and glucose is low. We conclude that free radicals and lipid peroxidation in general, and acrolein in specific, may play a critical role in cellular destruction and functional loss in such injury.

Acrolein↗

PubMed2005

Multiple sclerosis and spasticity.

Spasticity is a common impairment in MS. It can result in significant medical complications and is associated with increased disability. Treatment strategies include skilled rehabilitation strategies, neuromuscular blocks, oral agents, intrathecal management, and surgery. Rehabilitation strategies are central, whereas other strategies are added based on the level of impairment and functional loss. Treatment strategies for spasticity management are far from optimal and are complicated in MS as a result of lesions in the brain and the spinal cord. Pharmaceutical management in MS is complicated by the numerous secondary impairments in MS and its associated polypharmacy.Head-to-head studies of the various agents are rare. The studies that exist are small and do not point to any one strategy over another. Although management is difficult, it is essential for the health, functional status, and well-being of the individual who has MS. Providers must use well-developed clinical skills to arrive at optimal individualized treatment programs and monitor them frequently. For spasticity that is unresponsive, referral to a MS Center with a spasticity program is ideal.

Exercise Therapy↗

PubMed2003

Preventing internal auditory artery vasospasm using topical papaverine: an animal study.

BACKGROUND: Internal auditory artery (IAA) spasm is thought to be one of the causes of postoperative sensory hearing loss after attempted hearing preservation removal of an acoustic neuroma. The use of topical papaverine, a nonspecific vasodilator, to prevent vascular insufficiency to the inner ear and to improve hearing outcomes has been suggested but not proven. MATERIALS AND METHODS: Vasospasm was mechanically induced by compressing the IAA in the control ears of six rabbits after application of topical saline. The subsequent reduction of cochlear blood flow (CBF) was measured using a laser-Doppler (LD) flow-monitoring technique. Functional loss of cochlear activity was verified with distortion product otoacoustic emissions (DPOAE). The contralateral experimental ears were treated with the topical application of papaverine directly to the IAA and cochleovestibular nerve complex. CBF and DPOAE were compared between the control and papaverine treated ears for 3-minute and 5-minute IAA compressions. RESULTS: Every control ear demonstrated some degree of postcompression IAA vasospasm (i.e., reduced CBF) and reduction of DPOAE. Nearly complete recovery of CBF and DPOAE to baseline was observed in all of the papaverine treated ears. CONCLUSIONS: An animal model of IAA vasospasm was described. Mechanically induced vasospasm of the IAA was prevented by the topical application of papaverine. These findings have clinical implications for surgical procedures involving the internal auditory canal/cerebellopontine angle such as acoustic neuroma removal.

Administration, Topical↗

PubMed2001

Loss of tuberin, the tuberous-sclerosis-complex-2 gene product is associated with angiogenesis.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder associated with an alteration of the TSC2 tumor suppressor gene which encodes for the protein product tuberin. The disease is characterized by the development of hamartomas, e.g. cutaneous angiofibromas which consist of vascular cells, interstitial cells, and normal components of the skin. The Eker rat model, an animal model of inherited cancer, has been shown to carry a mutation of TSC2. METHODS: Immunohistochemical analyses of human angiofibromas were performed using antibodies directed against tuberin and angiogenic growth factors. Proliferation of human dermal microvascular endothelial cells (HDMEC) was determined after incubation with the supernatants of TSC2 (+/+) and TSC2 (-/-) rat embryonic fibroblasts (REF) that were derived from the Eker strain. RESULTS: Loss of the expression of tuberin was observed in the interstitial cells of 13 of 39 angiofibromas. The expression of tuberin was retained in the vascular cells. In all analyzed angiofibromas, the angiogenic factors bFGF, PD-ECGF, VEGF and angiogenin were detected in the interstitial cells and/or vascular cells. Expression of PDGF-B and TGF-beta1 was weak. Tissue culture supernatants from TSC2 (-/-) REF stimulated the growth of HDMEC significantly more than supernatants from TSC2 (+/+) REF. CONCLUSION: A functional loss of tuberin may stimulate vascular growth.

Angiofibroma↗

PubMed2002

Domoic acid lesions in nucleus of the solitary tract: time-dependent recovery of hypoxic ventilatory response and peripheral afferent axonal plasticity.

The nucleus of the solitary tract (NTS) plays a pivotal role in the ventilatory response to hypoxia (HVR). However, the effects of excitotoxic lesions and the potential for functional recovery and plasticity remain unknown. Domoic acid (DA) or vehicle were bilaterally injected within the NTS of adult male Sprague Dawley rats. HVR (10% O(2)) and anatomical changes were assessed at 5-90 d after surgery. DA induced dose-dependent HVR attenuations ( approximately 70% at peak effect) that exhibited saturation at concentrations of 0.75-1.0 mm. However, although sodium cyanide-induced ventilatory responses were virtually abolished, DA did not modify baroreceptor gain. Consistent with ventilatory reductions, NTS neurons showed a significant degeneration 3 d after DA injection. In addition, the projection fields and the density of vagal afferent terminals to the NTS, and the motor neurons in the dorsal motor nucleus of the vagus were substantially reduced at 15 d. At 30 d, no functional or neural recovery were apparent. However, at day 60, the reduction in HVR was only approximately 40% of control, and at 90 d, HVR returned to control levels, paralleling regeneration of vagal afferent terminals within the NTS. The regeneration was particularly prominent in the commissural and dorsomedial subnuclei in the absence of cellular recovery. Thus, the integrity of the NTS is critical for HVR, spontaneous HVR recovery occurs after excitotoxic lesions in the NTS, and vagal-glossopharyngeal terminal sprouting in the NTS may underlie the anatomical substrate for such spontaneous functional recovery. The adult brainstem/NTS has self-repairing capabilities and will compensate for functional losses after structural damage by rewiring of its neural circuitry.

Animals↗

PubMed1997

Loss of lung function among sheet metal workers: ten-year study.

One hundred and twenty-two sheet metal workers in New England were examined over a 10-year interval for loss of pulmonary function and the development of asbestosis or asbestos-related pleural fibrosis. Regression models using the generalized estimating equation (GEE) approach were created to investigate the relationship between exposure and pulmonary function after adjusting for smoking status, age, height, and asbestos-related x-ray changes. A history of shipyard work was a significant contributor to the loss of forced vital capacity (FVC). Among smokers, loss in forced expiratory volume at 1 sec (FEV1) also had a significant relationship to prior shipyard work. There was a borderline significant relationship between percentage predicted FEV1 and cumulative years of asbestos exposure in smokers, as well as years-since-initial-exposure in never-smokers. This study supports previous findings of obstructive airway changes in asbestos-exposed workers and identifies shipboard work as an important predictor of loss in pulmonary function even years after shipyard exposure to asbestos has ceased.

Adult↗