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Results for “Loss of function”

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PubMed1994

Getting around: a simple office workup to assess patient function.

Normal age-related changes in the musculoskeletal, neurologic, and cardiopulmonary systems result in some decline in function for the older patient. The risk of functional loss is heightened when disease and/or a sedentary lifestyle accompany the normal age-related changes. Primary care physicians are in a key position to identify older adults who are at risk to lose function. Two indicators of loss of mobility are lower extremity weakness and balance deficits, and these can be assessed in a simple office work-up. Referral to a physical therapist who specializes in movement analysis may be indicated when an older adult shows signs of functional decline.

Aged↗

PubMed2002

Use of mammalian inner ear antigens for the diagnosis of autoimmune sudden loss of vestibular function.

It has been postulated that bilateral sensorineural hearing loss (SNHL) may be the result of an ongoing autoimmune process against the inner ear and a pattern of progressive bilateral SNHL linked to an autoimmune inner ear disorder has been reported. Various attempts have been made to develop an assay to confirm the diagnosis of autoimmune inner ear disease. In this study we used a Western blot assay to determine the presence of IgG antibodies directed against a PO antigen (30 kDa) of the guinea pig in the sera of patients affected by sudden loss of vestibular function (SLVF). Ten patients affected by vestibular neuritis were enrolled: eight with unilateral vestibular loss and two with sequential bilateral impairment. We also tested nine patients with sudden unilateral hearing loss, five with benign paroxysmal positional vertigo and six normal subjects. In the present study only one patient, a woman affected by bilateral vestibular impairment, had IgG antibodies against the PO protein. Our results indicate either that the antigen PO is not a valid marker for autoimmune unilateral SLVF or that our patients did not have an immunological basis for their disease. However, we can suggest that bilateral impairment of vestibular function and bilateral progressive SNHL are more likely to be immune-mediated disorders and that PO could be a valid marker for these diseases. As bilateral vestibular neuritis is an uncommon disease, a multicentre study is required to confirm our suggestions.

Adult↗

PubMed2000

p53 mutations and loss of p53 function confer multidrug resistance in neuroblastoma.

BACKGROUND: Neuroblastomas often acquire sustained drug resistance during therapy. Sensitivities to carboplatin, etoposide, or melphalan were determined for 18 neuroblastoma cell lines; eight were sensitive and ten were resistant. As p53 mutations are rare in neuroblastomas studied at diagnosis, we determined if acquired p53 mutations and loss of function conferred multidrug resistance. RESULTS: Loss of p53 function (p53-LOF), defined as a failure to induce p21 and/or MDM2 in response to melphalan, was seen in 1/8 drug-sensitive and 6/10 drug-resistant cell lines. In four cell lines p53-LOF was associated with mutations in the DNA binding region of p53, while three cell lines with LOF and four cell lines with functional p53 had no evidence of p53 muta-tions. Nonfunctional and mutated p53 was detected in one resistant cell line, while a sensitive cell line derived from the same patient prior to treatment had functional and wild type (wt) p53. We transfected HPV 16 E6 (which mediates degradation of p53, causing LOF) into two drug-sensitive neuroblastoma cell lines with functional p53. LC(90) values of HPV 16 E6 transfected cell lines were 3-7-fold (melphalan), 8-109-fold (carboplatin), and 2-158-fold (etoposide) greater than that of LXSN-transfected controls. CONCLUSIONS: These data suggest that some neuroblastomas acquire p53 mutations during therapy, which is associated with a loss of p53 function, and can confer high-level multidrug resistance.

Chromosome Deletion↗

PubMed1998

The fate of duplicated genes: loss or new function?

Gene duplication events are important sources of novel gene functions. However, more often than not, a duplicate gene may lose its function and become a pseudogene. What is the relative frequency of these two scenarios: functional divergence versus gene loss? Given that most non-neutral mutations are deleterious, gene loss should be far more frequent than divergence. However, a recent empirical study suggests that about 50% of all gene duplications will lead to functional divergence. The study infers the frequency of functional divergence from the size distribution of gene families produced by two successive genome duplications early in vertebrate evolution. Reasons for this unexpectedly high frequency of functional divergence are discussed.

Animals↗

PubMed1993

Foveal ganglion cell loss is size dependent in experimental glaucoma.

PURPOSE: The purpose of this study was to study the pattern of foveal ganglion cell loss in experimental glaucoma. METHODS: Retinal ganglion cell size and number in the foveal region of seven monkey eyes with experimental glaucoma was determined and compared to normal monkey eyes. Serial sections of macular retina were studied in two regions: the plateau of peak density of ganglion cells (800-1100 microns from the fovea), and within 500 microns of the foveal center. RESULTS: In normal eyes, cell densities were 37,900 +/- 2700 in the foveal plateau and 17,200 +/- 1800 cells/mm2 in the foveal center. There was selective loss of larger ganglion cells in glaucoma eyes. The degree of foveal ganglion cell loss was significantly correlated to the degree of nerve fiber loss in the temporal optic nerve of the same eye. CONCLUSIONS: Detection of early, central visual function loss in glaucoma could be enhanced by testing functions subserved by larger retinal ganglion cells.

Animals↗

PubMed2005

Studying the consequences of immediate loss of gene function in the intestine: APC.

The use of mouse models to study neoplasia is proving particularly powerful in dissecting the mechanisms underlying disease initiation and progression. However, the majority of these models have been somewhat limited in studying the very early effects of loss of gene function, as tumour initiation relies upon either constitutive loss of gene function or spontaneous somatic loss of function. We have therefore adopted a strategy of using an inducible Cre-lox-based system to analyse the effects of loss of gene function, the use of which is reviewed here for the intestinal tumour suppressor APC (adenomatous polyposis coli). Using this approach, we have conditionally and synchronously inactivated APC in virtually all the epithelial cells of the adult murine small intestine. After 5 days following induction of Cre-mediated recombination, mice show grossly altered crypt/villus architecture. Deficiency in APC perturbs migration, alters the normal programme of differentiation and results in increased proliferation and apoptosis. Microarray analysis reveals the transcriptome to be significantly altered; reflecting both gross phenotypic changes and changes in transcriptional activation. These findings demonstrate that APC is indeed the critical determinant of cell fate in the intestinal epithelium, explaining its role as the cellular 'gatekeeper' in preventing neoplasia.

Adenomatous Polyposis Coli↗

PubMed1994

A role for cholesterol as a structural effector of the nicotinic acetylcholine receptor.

The effects of cholesterol on the protein structure and on the ionic channel activity of purified acetylcholine receptor (AcChR) reconstituted into lipid vesicles have been studied, respectively, by Fourier-transform infrared spectroscopy and by rapid kinetics of cation influx. Reconstitution of the AcChR in asolectin phospholipid vesicles in the absence of either cholesterol or the nonpolar lipids present in crude asolectin extracts results in a considerable loss of the ability of the AcChR to support cation channel function. This functional loss is accompanied by spectral changes in the conformationally-sensitive amide I band of the protein infrared spectrum which are indicative of alteration in the protein secondary structure. Quantitative estimation of such alteration by band-fitting analysis reveals a marked decrease in ordered protein structures such as the alpha-helix and beta-pleated sheet, concomitant with an increase in less ordered structures appearing at 1644 cm-1 in the infrared spectrum. Furthermore, the addition of increasing amounts of cholesterol to the reconstituted bilayer produces a progressive, complete recovery both in the control of cation channel function and in the infrared spectrum. This restoration of AcChR structure and function by cholesterol, however, does not occur when the AcChR is reconstituted in vesicles made from purified egg phosphatidylcholine, thus suggesting that the presence in the reconstituted bilayer of phospholipids other than phosphatidylcholine may be required for cholesterol to exert its modulatory effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Amides↗

PubMed1995

An assessment of the association between functional edentulism, obesity, and NIDDM.

OBJECTIVE: To assess the association between a measure of extensive tooth loss (functional edentulism) and obesity with non-insulin-dependent diabetes mellitus (NIDDM) in a racially heterogeneous sample. RESEARCH DESIGN AND METHODS: A cross-sectional survey (370 subjects) was performed by reviewing the medical and dental records of dependently or independently living individuals who were treated as inpatients and/or outpatients at a Department of Veterans Affairs facility. Frequencies and descriptive measures were derived; univariate and multiple logistic regression analyses were conducted to test for associations, confounding, effect modification, and interaction using functional edentulism and obesity as the independent variables and NIDDM as the dependent measure. RESULTS: Functionally edentulous individuals were at significantly greater risk for NIDDM (estimated odds ratio [OR] = 4.06), than the obese (OR = 3.29). These relationships were not confounded by age or race in this sample. Obesity did confound functional edentulism in the multivariable model, suggesting that they act independently on the outcome variable (NIDDM). CONCLUSIONS: Dentist-assessed functional edentulism and physician-diagnosed obesity were significantly associated with NIDDM in this sample of predominantly older men. This finding ought to be considered by primary care providers in formulating dietary strategies in order to facilitate the realization of their therapeutic goals.

Adult↗

PubMed1996

Functional outcome measures to assess interventions for spasticity.

PURPOSE: Clinicians use functional loss as a criterion to treat spasticity, but the connection between function and severity of spasticity is not well established for monitoring spasticity treatment effect. Studies were reviewed which have implemented outcome measures to assess functional changes relative to changes in spasticity. Criteria for review included the reliability and internal validity of the functional measures used and the strengths/weaknesses of the study designs that likely affected the external validity of the measures for this application. Guidelines are provided for the use and development of functional outcome measures in futures studies of spasticity treatment based on this review. DATA IDENTIFICATION: An English-language literature search using MEDLINE and bibliographies of published articles and textbooks was conducted. RESULTS: Very few functional measures demonstrated changes concurrent to a reduction in spasticity. There were multiple potential confounding factors in study protocols, reporting of results, and data analysis that might account for the limited number of measures shown to be valid for this application. Selected standardized ordinal functional outcome scales (the PECS and PEDI) and specific functional tasks were identified as measures that show promise for assessing changes concurrent with altered spasticity level. CONCLUSION: Based on a review of previous studies, functional measures involving posture, positioning, balance, and certain mobility skills have potential, with further test development, to provide needed information regarding the impact of spasticity on functional outcome.

Disability Evaluation↗

PubMedDate not supplied

Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer.

In childhood malignancies such as retinoblastoma and Wilms tumour, of which both familial and sporadic forms exist, recessive mutations of presumed differentiation genes have been implicated in tumorigenesis. A proportion of cases appear with microscopically visible chromosome deletions which indicate the regions where the genes concerned are located. Mutation or loss of one allele causes a cancer predisposition. For tumour development functional loss of the remaining normal allele is also required. In cancers with both familial and sporadic forms, molecular-genetic studies have shown that deletion is often one of the mutational events. Although familial and sporadic forms have never been distinguished in lung cancer, deletions of the short arm of chromosome 3 have been described for small cell lung cancer (SCLC), but their general occurrence in SCLC has been disputed. Using a molecular-genetic approach, we here present evidence for a consistent deletion at the chromosomal region 3p21, not only in SCLC, but in all major types of lung cancer.

Alleles↗

PubMed2002

Loss of heterozygosity as a predictor to map tumor suppressor genes in cancer: molecular basis of its occurrence.

High frequency of chromosomal deletions elicited as losses of heterozygosity is a hallmark of genomic instability in cancer. Functional losses of tumor suppressor genes caused by loss of heterozygosity at defined regions during clonal selection for growth advantage define the minimally lost regions as their likely locations on chromosomes. Loss of heterozygosity is elicited at the molecular or cytogenetic level as a deletion, a gene conversion, single or double homologous and nonhomologous mitotic recombinations, a translocation, chromosome breakage and loss, chromosomal fusion or telomeric end-to-end fusions, or whole chromosome loss with or without accompanying duplication of the retained chromosome. Because of the high level of specificity, loss of heterozygosity has recently become invaluable as a marker for diagnosis and prognosis of cancer. The molecular defects for the occurrence of loss of heterozygosity are derived from disabled caretaker genes, which protect the integrity of DNA, or chromosome segregator genes, which mediate faithful chromosome disjunction.

Chromosome Mapping↗

PubMed1997

Electrical responses of gastric smooth muscles in streptozotocin-induced diabetic rats.

Electrical responses of gastric smooth muscles produced by transmural nerve stimulation, acetylcholine, norepinephrine, or K-free solution were investigated in streptozotocin-induced diabetic rats, using intracellular microelectrode techniques. In muscles from diabetic rats, 1) the resting membrane potential remained unchanged, 2) slow waves disappeared or were markedly reduced in amplitude, 3) the excitatory junction potential was absent, and in most cases only an inhibitory junction potential of reduced amplitude was elicited, 4) the amplitude of the hyperpolarization generated after superfusion with K-free solution was reduced, 5) the sensitivity of the acetylcholine-induced membrane depolarization was increased, and 6) the norepinephrine-induced hyperpolarization was reduced because of functional loss of alpha- and beta-adrenoceptors. Thus diabetes mellitus caused functional impairment of neuromuscular transmission, reduced the maximum activity of the electrogenic pump, increased the sensitivity of muscarinic receptors, reduced the sensitivity of adrenoceptors, and reduced the myogenic activity in gastric smooth muscles. These alterations in the properties of smooth muscle may be involved in the diabetes-induced gastroparesis.

Acetylcholine↗

PubMed2004

Impact of demographic and impairment-related variables on disability associated with plantar fasciitis.

BACKGROUND: Plantar fasciitis is a common foot disorder that impacts many functional activities. Research that quantifies the impact that plantar fasciitis has on function is lacking. In addition, little is known about which variables are associated with disability in patients with plantar fasciitis. The first purpose of this study was to determine if age, gender, body mass index, pain intensity, chronicity of symptoms, or ankle dorsiflexion range of motion was associated with disability in patients with plantar fasciitis. The second purpose was to describe the impact that plantar fasciitis has on functional status in the context of five functional domains: household activities of daily living, usual work and hobbies, nonweightbearing activities, walking-related activities, and running-related activities. METHODS: Fifty consecutive patients diagnosed with unilateral plantar fasciitis were recruited. Demographic and impairment data were collected and all patients completed the Lower Extremity Functional Scale (LEFS), a validated self-report measure of disability. Multiple regression analysis was used to describe the association between the variables and disability. Graphs depicting five domains of function derived from the LEFS were generated to describe the extent of disability. RESULTS: Body mass index (BMI) was the only variable that was significantly associated with disability (F = 9.87, p =.003). Measures of pain intensity, ankle dorsiflexion, age, gender, chronicity, and time spent weightbearing were not related to disability. Plantar fasciitis showed distinct patterns of disability depending on the functional domain that was assessed. CONCLUSIONS: With the exception of BMI, impairment and demographic variables do not predict the extent of functional loss in patients with plantar fasciitis. The most likely domains of function to be at least moderately affected in patients with plantar fasciitis are running-related activities and usual work or hobbies.

Adult↗

PubMed2001

[Therapy of pituitary diseases. What can be achieved with medication and hormones?].

Pharmacotherapy is available only for pituitary adenomas producing growth hormone and prolactin (acromegaly, hyperprolactinemia). While dopamine agonists and somatostatin analogues are usually administered to acromegaly patients only after unsuccessful surgery, dopamine agonists are the treatment of choice in patients with prolactinomas. Replacement treatment in patients with insufficiency of the anterior lobe of the hypophysis is oriented to the extent of the deficits. Theoretically, replacement treatment can be applied for any functional loss. Of essential importance is the replacement of lost adrenal cortical function by the regular administration of physiological doses of hydrocortisone, and of lost thyroid function by the administration of L-thyroxine. In high-stress situations, for example, due to severe illness, the hydrocortisone dose must be increased significantly, and if necessary given parenterally. Gonadal function is replaced either with gonadal steroid hormones or gonadotropin or GnRH in patients wishing to have children. In adults, replacement of growth hormone is also indicated to decrease cardiovascular risk. This, however is very expensive and requires s.c. injections.

Acromegaly↗

PubMedDate not supplied

[Non-functioning renal graft: indications for transplant excision].

Of 107 renal transplants, 25 patients who were restarted on dialysis due to graft failure were studied. Of these, 20 underwent renal transplant nephrectomy. Graft failure was due to a progressive functional loss in 18 (16.8%) and 4 other grafts were non-functioning from the outset. Of these 22 cases, 17 (77.2%) underwent transplant removal. Three (15%) viable grafts were removed, 2 due to urologic complications and 1 due to hemorrhage following percutaneous renal biopsy. A non-functioning renal graft was left in situ in 5 patients. Rejection was the most frequent cause of transplant nephrectomy (45%), followed by arterial thrombosis (25%) and infection (15%). Eighty-five percent of these procedures were performed before one year post-transplantation, usually 1-4 weeks after diagnosis. Only 3 (13.6%) of the 22 non-functioning grafts removed were viable for more than 12 months after transplantation. The surgical technique was subcapsular in 60% and classical in the remaining cases. This was the surgical approach in all emergency cases. Except for one postoperative death directly related with surgery, complications were observed in 10% of the cases. These did not present as being especially uncommonly severe. The estimated 10-year posttransplantation survival rates for patients and grafts were 87.4% and 62.9%, respectively. The clinical evidence for transplant nephrectomy correlated well with the histologic evidence from the surgical specimens relative to the diagnosis of acute rejection and vascular thrombosis, despite its clinical under-utilization, and were discordant for urinary fistula, chronic rejection and sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2005

Psychophysical investigation of ganglion cell loss in early glaucoma.

PURPOSE: To evaluate ganglion cell loss in early glaucoma using a variety of psychophysical tests and to identify optimal perimetric technique(s) for detection of early glaucomatous visual function loss. METHODS: Five perimetric tests, short wavelength automated perimetry (SWAP), temporal modulation perimetry (TMP), frequency doubling technology perimetry (FDT), detection acuity perimetry (DAP), and resolution acuity perimetry (RAP) were compared in their ability to discriminate between normal individuals and patients with early glaucoma or glaucoma suspects. Comparisons were also made by their ability to produce repeatable defects. The tests examined different visual functions that are likely to be mediated by different retinal ganglion cell subpopulations, thereby permitting examination of hypotheses of ganglion cell death in early glaucoma. RESULTS: All visual field tests demonstrated high performance in separating glaucoma patients from normal individuals. SWAP, TMP, FDT, and DAP provided the greatest discrimination between normal individuals and high- and low-risk glaucoma suspects. However, SWAP, TMP, and FDT obtained better consistency across the various analysis approaches (global indices and pointwise) than DAP and RAP. Of all the test types, FDT exhibited the highest proportion of repeatable abnormal test locations, with poor confirmation rates achieved by DAP and RAP. CONCLUSION: The performance of SWAP, FDT, and TMP suggests that these test types may all be suitable for detection of early loss of visual function in glaucoma. Ganglion cell subpopulations with lower levels of redundancy and/or those with larger cell sizes offer the most parsimonious explanation for earliest ganglion cell losses occurring in glaucoma.

Cell Death↗

PubMed2005

Pupil campimetry in patients with visual field loss.

Pupil campimetry is an objective test of the visual field. In pupil campimetry, the pupil light response elicited by focal light stimuli at different locations within the visual field is measured. Pupil campimetry was performed in patients with visual field loss because of different pathologies. The match between reduced pupil response and visual field loss was assessed. The pupil field of 23 patients was recorded by infrared video-pupillography with light stimuli generated on a computer screen. A visual field was obtained on the same day with the Tuebingen Automated Perimeter. Both fields were compared by subjective judgement. Six of nine patients with large, two of five patients with incomplete, and three of six patients with minor field loss showed matching defects in their pupil and their visual fields. In functional loss of visual field sensitivity, no pupil field defect was seen (three patients). In most patients, the loss of visual field sensitivity could be revealed objectively by pupil campimetry.

Adolescent↗

PubMedDate not supplied

Protein exudation induced by manipulation of the intestines and mesentery during laparotomy in rat. A study of the mechanism of 'third space' loss.

BACKGROUND-MATERIALS: Much extracellular fluid administration is required during major surgery because of the functional loss of extracellular fluid. In the present study we investigated the effect of manipulation of the intestines and mesentery in a rat laparotomy model. METHODS-RESULTS-CONCLUSIONS: The results showed that manipulation significantly increased the amount of protein exudated into the peritoneal space and induced a marked histopathological inflammatory response including polymorphonuclear leukocyte infiltration and mast cell degradation. These findings suggest that the inflammatory response induced by manipulation may, at least in part, explain the underlying mechanism of 'third space' loss during abdominal intestinal surgery.

Animals↗