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At least 1,027 records · Page 57Linked to original sources

PubMed2006

Behavioral and histological characterization of unilateral cervical spinal cord contusion injury in rats.

Most experimental studies of spinal cord injury (SCI) in rats damage the thoracic cord, with the consequent functional loss being due to interruption of long tracts connecting the caudal spinal cord to the rostral nervous system. Less work has been done evaluating injury to the cervical cord, even though it is the most common level of human SCI. In addition to the long tracts, the cervical spinal cord contains the sensory and motor neurons responsible for upper extremity function. The purpose of this study was to further develop a rat model of cervical spinal cord contusion injury using a modified NYU/MASCIS weight drop device. Mild (6.25 mm) and moderate (12.5 mm) C5 unilateral injuries were produced. Behavioral recovery was examined using a grooming test, a paw preference test, a walkway test (The Catwalk), and a horizontal ladder test. Histological outcome measures included sparing at the lesion epicenter, sparing throughout the extent of the lesion, quantification of myelin loss rostral and caudal to the lesion, and motor neuron counts. Compared to controls, animals receiving SCI exhibited injury severity-specific deficits in forelimb, locomotor, and hindlimb function persisting for 6-weeks post-SCI. Histological analysis revealed ipsilateral containment of the injury, and differentiation between groups on all measures except motor neuron counts. This model has many advantages: (1) minimal animal care requirements post-SCI, (2) within subject controls, (3) functional loss involves primarily the ipsilateral forelimb, and (4) it is a behavioral and histological model for both gray and white matter damage caused by contusive SCI.

Animals↗

PubMed2003

Modulo is a target of Myc selectively required for growth of proliferative cells in Drosophila.

In Drosophila, the homologue of the proto-oncogene Myc is a key regulator of both cell size and cell growth. The identities and roles of dMyc target genes in these processes, however, remain largely unexplored. Here, we investigate the function of the modulo (mod) gene, which encodes a nucleolus localized protein. In gain of function or loss of function experiments, we demonstrate that mod is directly controlled by dMyc. Strikingly, in proliferative imaginal cells, mod loss-of-function impairs both cell growth and cell size, whereas larval endoreplicative tissues grow normally. In contrast to dMyc, over-expressing Mod in wing imaginal discs is not sufficient to induce cell growth. Taken together, our results indicate that mod does not possess the full spectrum of dMyc activities, but is required selectively in proliferative cells to sustain their growth and to maintain their specific size.

Animals↗

PubMed2001

Optimised uncertainty at minimum overall cost to achieve fitness-for-purpose in food analysis.

An optimised uncertainty (OU) methodology is described, that balances the uncertainty of measurements on food against the cost of the measurements and the other expenditure that may arise as a consequence of the possible misclassification of the food. Measurement uncertainty from the sources of primary sampling and chemical analysis is estimated using an existing technique, which is based on the taking of duplicated samples and duplicated analyses. The input information required for the OU method is the actual costs of sampling and analysis, and the expected costs that could arise from either the 'false positive' or 'false negative' classification of batches of food. A loss function is then constructed that calculates the 'expectation of loss' which will arise for a given uncertainty of measurement. This function has a minimum value of cost at an optimal value of uncertainty, which can be estimated numerically. Application of this OU method to a case study on the determination of aflatoxin levels in pistachio nuts has demonstrated this minimum value. Below the optimum value of uncertainty, the costs increased due to higher measurement costs. Above the optimum value, the costs increased due to increasing probability of expenditure on consequences such as unnecessary rejection of the batch, potential litigation or loss of corporate reputation because of undetected contamination. A second stage of the OU method optimises the division of the expenditure on the measurement between that on sampling and that on analysis. The technique is demonstrated as a useful new approach for judging the fitness-for-purpose of chemical measurements in the food industry. Several areas for further development of the technique are identified. By matching the expenditure on the measurement against that caused by the misclassification of the food, the OU method has the potential to reduce overall expenditure whilst ensuring an appropriate reliability of measurement.

Aflatoxins↗

PubMed1993

[Relationship between cerebral circulatory arrest and loss of brain functions--analysis of patients in a state of impending brain death].

To clarify the temporal discrepancies between cerebral circulatory arrest and loss of brain functions in relation to neuroradiological differences of brain damage, we analyzed 100 cases of impending brain death evaluated by neurological findings and continuous, simultaneous neuromonitoring of somatosensory and brainstem auditory evoked potentials (SEP, BAEP), compressed spectral arrays (CSA), and transcranial Doppler sonography (TCD). A) Cases of supratentorial lesions: 1) Loss of brain functions after supratentorial circulatory arrest (TCD) were advanced rostrocaudally -(SEP N20 > CSA) > (BAEP III-V > SEP P13/14). 2) All patients demonstrated supratentorial circulatory arrest (TCD) after both neurological and cerebral (CSA) functions had been lost for more than 6 hours or after loss of neurological, cerebral (CSA), and brainstem (BAEP, SEP) functions. B) Cases of diffuse or infratentorial lesions: Supratentorial circulation persisted in a few cases after loss of all brain functions. C) The interval from supratentorial circulatory arrest to brainstem function loss was longer than that to cerebral function loss. Both intervals were less than 24 hours in almost all cases. In applying ancillary studies to the diagnosis of brain death, consideration should be given to the time lag between cerebral circulatory arrest and loss of brain functions caused by pathophysiological differences in brain damage.

Adolescent↗

PubMed2004

The relationship between standard automated perimetry and GDx VCC measurements.

PURPOSE: To investigate the relationship between retinal light sensitivity measured with standard automated perimetry (SAP) and retardation of the peripapillary retinal nerve fiber layer (RNFL) measured with the GDx VCC (Laser Diagnostic Technologies, Inc., San Diego, CA). METHODS: Forty-seven healthy subjects and 101 patients with glaucoma were examined with SAP and with the commercially available scanning laser polarimeter GDx VCC, with automated individualized compensation of anterior segment birefringence. Individual visual field test points and peripapillary RNFL retardation measurements were grouped into six corresponding sectors. The correlation between perimetry and GDx VCC measurements was determined, and the relationship between RNFL retardation and perimetry, expressed both in the standard decibel scale and in an unlogged scale, was described with linear regression analysis. RESULTS: A statistically significant correlation was found in most sectors between perimetry and GDx VCC measurements in patients with glaucoma, but not in healthy subjects. A linear relationship was found between the unlogged sensitivities and GDx VCC measurements for the superotemporal and inferotemporal sectors. In the decibel scale, this relationship was curvilinear. CONCLUSIONS: GDx VCC measurements of the peripapillary RNFL relate well with functional loss in glaucoma. Based on the observed relationships between function and structure, patients with mild to moderate visual field loss in glaucoma may be better monitored with the GDx VCC and patients who have severe loss, with SAP.

Female↗

PubMed2001

Chronic loss of ovarian function decreases transport of leptin into mouse brain.

Loss of ovarian function, such as occurs with menopause in human beings and ovariectomy in rodents, results in weight gain. Using multiple-time regression analysis, a sensitive technique for quantifying blood-to-brain transport of peptides and polypeptides, we found that mice ovariectomized for at least 5 weeks had markedly reduced entry of the satiety factor leptin into brain. The rate of entry of leptin into brain remained reduced half a year later. The results suggest that the weight gain resulting from loss of ovarian function could be explained by decreased transport of leptin into the brain.

Animals↗

PubMedDate not supplied

Further investigations on the pathophysiology of the compartmental syndrome.

A model compartmental syndrome is described in rabbits in which the intracompartmental pressure may be accurately controlled to investigate the pathophysiologic changes resulting from increased intracompartmental pressure. Oxygenation in the tibialis anterior muscle was measured using a medical mass spectrometer. The Po2 declined with increasing intracompartmental pressure from a control value of 10.8 mmHg to a minumum of 2.8 mmHg at a pressure of 90 mmHg. The functional integrity of the peroneal nerve and compartmental muscle was tested by direct electrical stimulation. Functional deficits were first noted when an intracompartmental pressure of 40 mmHg was exerted for 6 hours. The incidence of functional losses increased with increasing pressures and durations of pressure application. All animals subjected to 100 mmHg for eight or more hours lost both nerve and muscle function. These investigations demonstrate that increased intracompartmental pressure alone, without other associated vascular injury, may produce muscle hypoxia and loss of neuromuscular function. The continuous monitoring of intracompartmental pressures may, therefore, be a useful clinical adjunct in the management of patients at risk for a compartmental syndrome.

Animals↗

PubMed2002

Optimized contaminated land investigation at minimum overall cost to achieve fitness-for-purpose.

A methodology for optimized contaminated land investigation (OCLI) is described that balances the uncertainty of measurements against the cost of taking the measurements and the financial losses that may arise from misclassification of the land. Uncertainty from the sources of both field sampling and chemical analysis is estimated using existing techniques, based on the taking of duplicated samples. The actual costs of sampling and analysis and the expected costs that could arise from either 'false positive' or 'false negative' classification of areas of land were estimated. A loss function was constructed that calculates the expectation of financial loss that will arise for a given uncertainty of measurement. The function shows a clear minimum value of cost at an optimal value of uncertainty. Application of this OCLI technique to two case studies demonstrated this minimum value. Below the optimum value of uncertainty, the costs increased due to higher measurement costs. Above the optimum, the costs increased due to increasing risk of factors such as unnecessary remediation or potential litigation over undetected contamination. Many areas for further development of OCLI are identified, but the technique is demonstrated as a useful new approach to judging fitness-for-purpose of such measurements.

Cost Control↗

PubMed1997

Cellular delivery of neurotrophin-3 promotes corticospinal axonal growth and partial functional recovery after spinal cord injury.

The injured adult mammalian spinal cord shows little spontaneous recovery after injury. In the present study, the contribution of projections in the dorsal half of the spinal cord to functional loss after adult spinal cord injury was examined, together with the effects of transgenic cellular delivery of neurotrophin-3 (NT-3) on morphological and functional disturbances. Adult rats underwent bilateral dorsal column spinal cord lesions that remove the dorsal corticospinal projections or underwent more extensive resections of the entire dorsal spinal cord bilaterally that remove corticospinal, rubrospinal, and cerulospinal projections. Long-lasting functional deficits were observed on a motor grid task requiring detailed integration of sensorimotor skills, but only in animals with dorsal hemisection lesions as opposed to dorsal column lesions. Syngenic primary rat fibroblasts genetically modified to produce NT-3 were then grafted to acute spinal cord dorsal hemisection lesion cavities. Up to 3 months later, significant partial functional recovery occurred in NT-3-grafted animals together with a significant increase in corticospinal axon growth at and distal to the injury site. These findings indicate that (1) several spinal pathways contribute to loss of motor function after spinal cord injury, (2) NT-3 is a neurotrophic factor for the injured corticospinal projection, and (3) functional deficits are partially ameliorated by local cellular delivery of NT-3. Lesions of the corticospinal projection may be necessary, but insufficient in isolation, to cause sensorimotor dysfunction after spinal cord injury in the rat.

Animals↗

PubMed2000

Nanoscale EELS analysis of dielectric function and bandgap properties in gaN and related materials

The low loss region of an EEL spectrum (<50 eV) contains information about excitations of outer shell electrons and thus the electronic structure of a specimen which determines its optical properties. In this work, dedicated electron energy loss spectroscopy (EELS) methods for the experimental acquisition and analysis of spectra are described, which give improved information about the electronic structure near the bandgap region at a spatial resolution in the range of nanometers. For this purpose, we made use of a cold field emission scanning transmission electron microscope (STEM) equipped with a dedicated EELS system. This device provides a subnanometer electron probe and offers an energy resolution of 0.35 eV. Application of suitable deconvolution routines for removal of the zero loss peak extracts information on the bandgap region while the Kramers-Kronig transformation deduces the dielectric properties from the measured energy loss function. These methods have been applied to characterize the optical properties of wide-bandgap materials for the case of III-nitride compounds, which are currently the most promising material for applications on optoelectronic devices working in the blue and ultraviolet spectral range. The obtained results are in excellent agreement with experimental measurements by synchrotron ellipsometry and theoretical studies. The potential of the superior spatial resolution of EELS in a STEM is demonstrated by the analysis of dielectric properties of individual layers of heterostructures and individual defects within wurtzite GaN.

Journal Article↗

PubMed1996

Function changes in spinal muscular atrophy II and III. The DCN/SMA Group.

The course of spinal muscular atrophy (SMA) is not well established except for those patients whose age of onset is before 6 months and who achieve only "sit with support" as their maximum function (Werdnig-Hoffmann disease or SMA I). This study shows that there is another group of SMA patients whose age of onset and maximum function achieved can be used as prognostic guides. Fifty percent of SMA patients who could walk without assistance and whose onset was prior to age 2 years lost the ability to walk independently by age 12. Fifty percent of SMA patients who walked and whose onset was between 2 and 6 years of age lost walking ability by age 44 years. Fifty percent of SMA patients who could walk with assistance as their best function ever achieved lost this ability by age 7 years, unrelated to age of onset; none could walk with assistance after age 14 years. Seventy-five percent of SMA patients who developed the ability to sit independently as their best function were still sitting after age 7 years independent of age of onset; 50% of this group could sit independently after age 14 years. Eighty-five percent of SMA patients who could walk could not negotiate stairs without holding onto a rail. They could raise their hands above the head; however, as they lost walking ability, they lost this function as well. Only one SMA patient whose maximum function was sitting independently could get to the sitting position on his own. Only two of these patients could hold their hands above their heads. All patients with SMA lose function over time. This function loss occurs slowly and is related primarily to maximum function achieved; knowledge of age of onset provides helpful information, especially for predicting the loss of independent walking.

Adolescent↗

PubMed1999

Pathology of the TSH receptor.

Gain of function and loss of function mutations of the TSH receptor have been implicated in the pathogenesis of various thyroid diseases. Gain of function mutations, when somatic, are the first cause of autonomous nodules; when germline, they are responsible for hereditary non-autoimmune toxic thyroid hyperplasia and for some cases of sporadic congenital hyperthyroidism. A subset of mutations modifying the receptor selectivity have recently been found to be involved in the pathogenesis of familial gestational hyperthyroidism. These mutations are of great interest for understanding the mechanism of receptor activation. Loss of function mutations of the TSH receptor are responsible for different phenotypes ranging from asymptomatic resistance to TSH to overt congenital hypothyroidism.

Adenoma↗

PubMed1982

Clawfinger correction: results of extensor-flexor many tailed operation.

The patient with paralytic clawfingers is greatly handicapped. This is especially true for the leprosy patient who needs his hands to earn a living. The inability to 'reach out' with the fingers is the most serious functional loss in an ulnar palsy. This study is a follow up of 155 hands whereby the extensor carpi radialis longus was employed to substitute for this lumbrical-interosseus function. The best results were obtained in hands with full assisted extension. Retropulsion of the metacarpal arch occurred in all hands with total loss of ulnar function.

Fingers↗

PubMed1996

Guidelines for the management of rheumatoid arthritis. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines.

RA is a chronic progressive polyarthritis (with varying systemic features) associated with substantial disability and economic losses. Successful treatment to limit joint damage and functional loss requires early diagnosis and timely initiation of disease-modifying agents. The goal of treatment is to arrest the disease and to achieve remission. Although remission rarely occurs, patients may still benefit from pharmacologic, nonpharmacologic, and if necessary, surgical interventions. Optimal longitudinal treatment requires comprehensive coordinated care and the expertise of a number of providers. Essential components of management include 1) establishment of the diagnosis of RA (versus other forms of polyarthritis), 2) systematic and regular evaluation of disease activity, 3) patient education/rehabilitation interventions, and initial treatment with NSAIDs, 4) use of DMARDs, 5) possible use of local or low-dose oral glucocorticoids, 6) minimization of the impact on the individual's function, 7) assessment of the adequacy of the treatment program, and 8) general health maintenance.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1997

RET in human development and oncogenesis.

Hirschsprung disease and the multiple endocrine neoplasia type 2 syndromes are hereditary disorders related to the abnormal migration, proliferation or survival of neural crest cells and their derivatives. Hirschsprung disease is a frequent disorder of the enteric nervous system, resulting in intestinal obstruction. The multiple endocrine neoplasia type 2 syndromes predispose to cancers of neural crest derivatives. Both diseases are associated with heterozygous mutations in the RET proto-oncogene. RET encodes a transmembrane receptor tyrosine kinase expressed in neural crest lineages and whose ligand, glial-cell-line-derived neurotrophic factor, has been very recently identified. In vitro expression studies demonstrate that while Hirschsprung disease mutations result in loss of function of the mutant RET tyrosine kinase, multiple endocrine neoplasia type 2 mutations lead to its constitutive activation. Thus, the two 'faces' of RET, gain of function and loss of function, each lead to a different syndrome, respectively: multiple endocrine neoplasia type 2, a cancer syndrome, or Hirschsprung disease, a developmental defect.

Animals↗

PubMed2003

[Functional asplenia after severe varicella zoster-infection diagnosis by colour Doppler ultrasound].

Infiltrative, inflammatory or thromboembolic processes in the parenchyma of the spleen can cause a functional loss of the organ. This phenomenon is called functional asplenia and occurs as a complication especially in sickle cell disease, lupus erythematosus and after bone marrow transplantation. We present the case of a patient with Crohn's disease under immunosuppressive therapy who developed a spontaneous covered spleen rupture in the course of a septic shock with DIG due to a Varizella zoster infection. Later on, sonography showed a diminution of the spleen size. No flow signals could be derived by colour doppler measurements from the spleen. Because of the colour doppler findings we suspected a functional asplenia which was then verified by spleen scintigraphy and Howell-Jolly-Bodies in the blood count. Remarkably, the Crohn's disease remains in complete remission since the development of the functional asplenia (for 4 years now). The underlying pathomechanism remains unclear.

Adult↗

PubMed2006

[Principals and clinical applications of optical coherence tomography in glaucoma].

Optical coherence tomography (OCT) supplies morphological information from different retinal layers. In glaucoma, analysis of the nerve fiber layer is gaining more and more significance: Losses in this layer often precede by years functional losses in the visual field and end up in optical nerve head changes. OCT offers a means for imaging and for measurement of the nerve fiber layer besides morphological analysis of ONH as one of the earliest sensitive parameters in modern glaucoma diagnostics. However, because of the lack of extensive comparative data, the priority use of optical coherence morphometry is to be seen mainly in intraindividual follow-up.

Glaucoma↗

PubMed2002

Critical role of photoreceptor apoptosis in functional damage after retinal detachment.

PURPOSE: Although apoptosis is assumed to play a pivotal role in retinal function loss, its mechanism and real influence on retinal function are still unclear. To investigate the relation between retinal function and apoptosis, we studied photoreceptor apoptosis in experimental retinal detachment (RD). METHODS: We induced RD by subretinal injection of sodium hyaluronate in Brown Norway rats. Apoptotic photoreceptors were detected by TdT-dUTP Terminal Nick-End Labeling (TUNEL). To evaluate the function of the detached retina, electroretinograms (ERGs) were taken on day 1, 3 with corneal electrodes and full-field stimulation. RESULTS: Apoptotic DNA fragmentation appeared 12 hours after RD, was most prominent on day 3, and decreased thereafter. The ERGs showed that the amplitudes of dark-adapted a-waves and light adapted 2 Hz b-waves decreased immediately after RD and continued to decrease over time. The administration of Fas/Fc chimera recombinant protein or a caspase inhibitor, Z-VAD.fmk, failed to prevent either photoreceptor apoptosis or retinal functional damage. In contrast, brain derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) significantly impeded both apoptosis and dysfunction. The ERGs recognized the functional changes sensitively, and these ERG changes correlated well to the amount of photoreceptor apoptosis. Immunohistochemical study showed that apoptosis-inducing factor (AIF), a novel caspase-independent apoptotic factor, was relocalized from mitochondria to the nucleus in this process. CONCLUSIONS: The present results showed that apoptosis was a key phenomenon in the retinal dysfunction in RD and that this process was transmitted mainly by mitochondria-dependent pathways rather than Fas/Fas-L or downstream caspase dependent pathways.

Animals↗