SEARCH · PubMed Health

Results for “Loss of function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,279 records · Page 71Linked to original sources

PubMed1991

Abnormalities of chromosome 1 and loss of heterozygosity on 1p in primary hepatomas.

Cytogenetic analysis of eight human hepatoma-derived cell lines and one primary hepatocellular carcinoma biopsy revealed multiple chromosome abnormalities; however, only chromosome 1 was consistently affected by rearrangements. Pseudopolysomy 1 as well as chromosome 1 deletions and/or translocations that resulted in loss of the distal 1p region from at least one copy of chromosome 1 were observed in all but one of the cell lines analysed. Molecular analyses of tumor-derived and normal genomic DNA from six cases of hepatocellular carcinoma and from two of hepatoblastoma, using a panel of chromosome 1p-specific DNA probes indicated allelic loss in the distal 1p region in five of the six hepatocellular carcinomas but not in either hepatoblastoma. These results suggest the location of a gene in the distal 1p region whose functional loss may be involved in hepatocellular carcinogenesis.

Carcinoma, Hepatocellular↗

PubMed1986

[Distribution in the body and functional effects of fluorocarbons used as oxygen carriers].

After the infusion of perfluorochemicals (PFC) given as artificial blood gas carriers a temporary storage of the inert substances in tissues of the organism occurs. The time course of this effect was investigated in longitudinal studies in the rat and compared with changes of different organ functions, expressed as changes in the levels of serum enzymes, in the elimination of indocyanine green and in the duration of pentobarbital sleeping time which are dependent on the excretory and detoxifying functions of the liver. The intensity of the elimination of colloidal carbon was used as a measure of the activity of the reticulo endothelial system. Observation of the time course of these functional tests in comparison with the storage of PFC and changes in organ weight of liver and spleen showed that diminutions in function had a distinctly shorter duration than PFC storage, whereas the longest lasting effects were seen in organ weight increase is regarded as a compensatory effect that is associated without functional loss at the maximum of its appearance.

Animals↗

PubMed2000

Sequential testing in the assessment of clinical skills.

PURPOSE: Educators who use standardized-patient-based (SP-based) tests may save resources by using sequential testing. In this approach, students take a short screening test; only those who fail take a second test. This study investigated whether sequential testing increases efficiency with only a minor decrease of validity. METHOD: In 1994-95, first- through fourth-year (Group 1) and sixth-year (Group 2) medical students at the University of Maastricht took SP-based tests. Each test took two days. In a simulation experiment based on the data from those tests, the authors considered the first day as the screening test and the second day as the second test. They investigated efficiency and validity as a function of the cutoff score of the screening test. They developed and evaluated a new method to determine the optimum cutoff score of the screening test, a method based on minimization of the loss represented by the (weighted) numbers of false positives and negatives in the screening test. RESULTS: The negative predictive value (probability that a student would fail the complete test if he or she had failed the screening test) was low (<60%), while the positive predictive value was high (>96%). Accordingly, stringent pass/fail cutoff scores in the screening test (75% for Group 1 and 80% for Group 2) produced optimum results. Using those cutoff values, only 26% and 11% of 'the students would have had to take the complete test to get a "true" score, while only 0.2% and 0.0% of the students who passed the screening test went on to fail the complete test (false positives). CONCLUSIONS: In a sequential SP-based test, the pass/fail cutoff score of the screening test should be stringent. This can considerably reduce testing time (30% to 40%), while keeping the percentage of false positives at an acceptably low level of less than 0.2%. As an alternative to receiver operator characteristic analysis, minimization of the loss function was found to be an appropriate method to determine the optimum cutoff value of the screening test.

Clinical Competence↗

PubMed1989

Visual field versus visual evoked potentials in maculopathies and optic neuropathies.

Both kinetic and static visual fields and visual evoked potential (VEP) were tested in 52 patients with maculopathies and in 29 patients with axial optic neuropathies. The results of central static quantitative perimetry and pattern reversal VEP were compared. The amplitude and latency of P100 were correlated with the total loss of central visual threshold in maculopathies. While the P100 latency was not correlated with the total loss of the central visual threshold in neuropathies, their latency delay was more obvious than that in maculopathies. We arrived at the conclusion that both VEP and visual field are necessary for assessing function loss and reflecting different pathological mechanisms in macular and optic nerve diseases.

Adolescent↗

PubMed2005

Yeast longevity and aging--the mitochondrial connection.

Studies of the yeast Saccharomyces cerevisiae reveal four processes determining life span: metabolism, stress resistance, chromatin-dependent gene regulation, and genome stability. The retrograde response, which signals mitochondrial dysfunction resulting in changes in nuclear gene expression, extends yeast life span and is induced during normal aging. This response involves extensive metabolic adaptations. The retrograde response links metabolism and genome stability during yeast aging. A reduction in the availability of nutrients also extends yeast life span. This metabolic mechanism operates by pathways distinct from the retrograde response, although it shares with the latter some longevity effectors. Life extension by calorie restriction entails re-modeling of mitochondrial function. The retrograde response appears to compensate for age changes, while calorie restriction may be a preventive mechanism. The maintenance of age asymmetry between the mother and daughter yeast cells also depends on mitochondrial function. Loss of this age asymmetry occurs during normal yeast aging and may be a paradigm for stem cell aging. The importance of mitochondrial integrity in yeast longevity is emphasized by the role of prohibition function in attenuating oxidative damage. Our studies point to the central role of mitochondria in yeast aging. They highlight the importance of the maintenance of mitochondrial membrane potential, which drives the transport of biosynthetic precursors derived from the Krebs cycle. Common threads weave their way through the studies of aging in yeast and in other model organisms. This suggests conserved features of aging across phyla.

Caloric Restriction↗

PubMed2000

Mutation and expression analyses reveal differential subcellular compartmentalization of PTEN in endocrine pancreatic tumors compared to normal islet cells.

The pathogenesis of sporadic endocrine pancreatic tumors (EPTs) is still primarily unknown. Comparative genomic hybridization studies revealed loss of 10q in a significant number (nine of 31) of EPTs. The tumor suppressor gene PTEN lies on 10q23, and so, is a candidate to play some role in EPT pathogenesis. Germline PTEN mutations are found in Cowden and Bannayan-Riley-Ruvalcaba syndromes, whereas somatic mutations and deletions are found in a variety of sporadic cancers. The mutation and expression status of PTEN in EPTs has not yet been examined. Mutation analysis of the entire coding region of PTEN including splice sites was performed in 33 tumors, revealing one tumor with somatic L182F (exon 6). Loss of heterozygosity of the 10q23 region was detected in eight of 15 informative malignant (53%) and in none of seven benign EPTs. PTEN expression was assessed in 24 available EPTs by immunohistochemistry using a monoclonal anti-PTEN antibody. Of these 24, 23 tumors showed strong immunoreactivity for PTEN. Only the EPTs with PTEN mutation lacked PTEN protein expression. Although normal islet cells always exhibited predominantly nuclear PTEN immunostaining, 19 of 23 EPTs had a predominantly cytoplasmic PTEN expression pattern. Exocrine pancreatic tissue was PTEN-negative throughout. PTEN mutation is a rare event in malignant EPTs and PTEN protein is expressed in most (23 of 24) EPTs. Thus, intragenic mutation or another means of physical loss of PTEN is rarely involved in the pathogenesis of EPTs. Instead, either an impaired transport system of PTEN to the nucleus or some other means of differential compartmentalization could account for impaired PTEN function. Loss of heterozygosity of the 10q23 region is a frequent event in malignant EPTs and might suggest several hypotheses: a different tumor suppressor gene in the vicinity of PTEN might be principally involved in EPT formation; alternatively, 10q loss, including PTEN, seems to be associated with malignant transformation, but the first step toward neoplasia might involve altered subcellular localization of PTEN.

Adult↗

PubMed1984

The transfer of the abductor digiti quinti: palliative treatment for paralysis of the superficial thenar muscles.

Described by Huber in 1921, the transfer of the abductor digiti quinti constitutes an elegant solution to paralysis of thumb opposition. Interest in this operation was renewed and defended by Littler and more recently by Manske and McCarroll. The technique is simple and we do not believe that it is necessary to detach the muscle from its proximal insertion, thus preserving the force of the transfer. The advantages are as follows: elective reconstitution of antepulsion of the thumb column, which supposes that the adductors and the flexors are intact. A small operative field with limited routes of approach reducing scarring to a minimum. The cosmetic advantage is evident with reconstitution of the thenar contour. The functional loss is minor and in our opinion the abductor digiti quinti appears to be less inexpendable than the flexor digitorum sublimis or the extensor pollicis. The limitations of the operation are the absence of functional deep thenar muscles and adductors as well as, of course, the absence of a healthy abductor digiti quinti as in associated ulnar palsy. The results in 8 operations lead us to think that, when possible, the transfer of the abductor digiti quinti is a particularly interesting solution to paralysis in women and children, but probably insufficient in manual hard labor workers, at least in those who need strong abduction of their thumb.

Humans↗

PubMed2005

Psychosexual health 5 years after hysterectomy: population-based comparison with endometrial ablation for dysfunctional uterine bleeding.

BACKGROUND: We report a population-based comparison of psychosexual health 5 years after contrasting amounts of surgical treatments for heavy periods [dysfunctional uterine bleeding (DUB)]. Women's fears about sexual function after hysterectomy might not be unfounded. The psychosexual problems may return and/or develop with time. The removal of ovaries at the time of hysterectomy is associated with greater deterioration of self-reported sexual function. Surgical menopause significantly impairs sexual wellbeing. We failed to observe uniform beneficial effects of hormone replacement therapy (HRT) on reported psychosexual health. OBJECTIVE: To compare self-reported bothersome sexual function; loss of interest in sex, difficulty in becoming sexually excited and vaginal dryness 5 years after surgical management of DUB [transcervical endometrial resection/ablation (TCRE) or subtotal and total hysterectomy, with and without prophylactic bilateral oophorectomy (BO)]. DESIGN: Prospective cohort study up to 5 years post-surgery for DUB, TCRE or hysterectomy, with or without BO. SETTING: Over 400 NHS and private hospitals in England, Northern Ireland and Wales. COHORT: Of 11,325 women who responded to the 5-year questionnaire, over 9500 (84%) were valid cases, and over 8900 (94%) did complete the questions relating to psychosexual function. Most were between the ages of 39 and 45 years, married or cohabiting. MAIN OUTCOMES: Self-reported experience of bother, recorded as 'some', 'severe' and 'extreme', to questions on (1) libido loss, (2) difficulty with sexual arousal, and (3) vaginal dryness during the past 4 weeks, 5 years after surgery. RESULTS: Five years after surgery for DUB, the crude and adjusted prevalence of psychosexual problems was higher after hysterectomy than after TCRE. Amongst the women with concurrent BO, the age- and HRT-adjusted odds ratios for extreme psychosexual problems were increased by 80% (libido loss), 82% (difficult sex arousal) and 69% (vaginal dryness) compared with TCRE. CONCLUSIONS: Five years after hysterectomy more women reported having bothersome psychosexual function than did the women who had a less invasive operation. Hormone therapy, although related to surgical method, did not reduce this long-term detrimental effect. The odds were particularly high amongst women with concurrent BO. Women should be advised that they might be at higher risk of psychosexual problems following hysterectomy, compared with a less invasive procedure.

Adult↗

PubMed1996

Bayesian individualization via sampling-based methods.

We consider the situation where we wish to adjust the dosage regimen of a patient based on (in general) sparse concentration measurements taken on-line. A Bayesian decision theory approach is taken which requires the specification of an appropriate prior distribution and loss function. A simple method for obtaining samples from the posterior distribution of the pharmacokinetic parameters of the patient is described. In general, these samples are used to obtain a Monte Carlo estimate of the expected loss which is then minimized with respect to the dosage regimen. Some special cases which yield analytic solutions are described. When the prior distribution is based on a population analysis then a method of accounting for the uncertainty in the population parameters is described. Two simulation studies showing how the methods work in practice are presented.

Algorithms↗

PubMed1998

[Iliaco-ureteral fistula and its treatment with a stent graft].

The iliac artery-ureteral fistula is a rare complication which becomes symptomatic with life-endangering bleeding. A typical feature is its intermittent occlusion, which makes diagnosis very difficult. Without knowledge of the correct diagnosis the rate of morbidity, through functional loss of the kidneys, and of mortality can be extremely high. In the following a case is described in which, after radiotherapy and chemotherapy following sigmoid resection due to carcinoma, urinary congestion of the remaining functional kidney occurred during the course of treatment. Following the placing of an endoureteral stent an iliac-ureteral fistula with massive bleeding developed. It was demonstrated by means of angiography. For the first time, therapy with endoluminal stent grafts was successfully applied.

Adenocarcinoma↗

PubMed1992

Pulmonary function in systemic lupus erythematosus is related to distinct clinical, serologic, and nailfold capillary patterns.

PURPOSE: The purpose of this study was to investigate whether systemic lupus erythematosus (SLE) patients with interstitial lung disease represent a particular subset of patients characterized by the presence of clinical, serologic, and nailfold capillary patterns overlapping scleroderma. PATIENTS AND METHODS: In 57 consecutive patients with SLE, a standardized detailed history was obtained and a physical examination performed, directed at signs and symptoms of connective tissue diseases, in particular scleroderma. Additionally, pulmonary function testing, chest radiography, radionuclide transit studies of the esophagus, nailfold capillary microscopy, and detailed serologic studies directed at the antigenic specificities of antinuclear antibodies were performed. Patients were divided into three groups based on the results of pulmonary function testing, i.e., normal lung function, restriction, or isolated impairment of diffusion. Clinical, serologic, and nailfold capillary microscopic findings were compared among these three groups. RESULTS: Twenty patients had normal lung function, 19 had restrictive lung function loss, and 9 had an isolated impairment of the diffusing capacity (T1,CO). Patients with obstructive lung disease (n = 9) were excluded from analysis. Sclerodermatous changes of the hands were associated with a restrictive lung function pattern. Interstitial changes on chest radiograph were associated with isolated impairment of T1,CO. Nailfold capillary abnormalities correlated with decreased T1,CO and Dm, the component of T1,CO representing the diffusing capacity of the alveolocapillary membrane. Antibodies to U1-RNA were associated with restrictive lung function and decreased T1,CO. CONCLUSION: We conclude that interstitial lung disease is present in a subset of SLE patients characterized by an increased prevalence of scleroderma traits and anti-(U1)RNA antibodies. Microvascular changes may contribute to the development of interstitial lung disease in SLE as well as in scleroderma.

Adult↗

PubMed2005

Role of nucleophosmin in embryonic development and tumorigenesis.

Nucleophosmin (also known as NPM, B23, NO38) is a nucleolar protein directly implicated in cancer pathogenesis, as the NPM1 gene is found mutated and rearranged in a number of haematological disorders. Furthermore, the region of chromosome 5 to which NPM1 maps is deleted in a proportion of de novo human myelodysplastic syndromes (MDS), and loss of chromosome 5 is extremely frequent in therapy-related MDS. NPM is a multifunctional protein, and its role in oncogenesis is controversial as NPM has been attributed with both oncogenic and tumour suppressive functions. To study the function of Npm in vivo, we generated a hypomorphic Npm1 mutant series (Npm1+/- < Npm1(hy/hy) < Npm1-/-) in mouse. Here we report that Npm is essential for embryonic development and the maintenance of genomic stability. Npm1-/- and Npm1(hy/hy) mutants have aberrant organogenesis and die between embryonic day E11.5 and E16.5 owing to severe anaemia resulting from defects in primitive haematopoiesis. We show that Npm1 inactivation leads to unrestricted centrosome duplication and genomic instability. We demonstrate that Npm is haploinsufficient in the control of genetic stability and that Npm1 heterozygosity accelerates oncogenesis both in vitro and in vivo. Notably, Npm1+/- mice develop a haematological syndrome with features of human MDS. Our findings uncover an essential developmental role for Npm and implicate its functional loss in tumorigenesis and MDS pathogenesis.

Animals↗

PubMed2005

AtbHLH29 of Arabidopsis thaliana is a functional ortholog of tomato FER involved in controlling iron acquisition in strategy I plants.

AtbHLH29 of Arabidopsis, encoding a bHLH protein, reveals a high similarity to the tomato FER which is proposed as a transcriptional regulator involved in controlling the iron deficiency responses and the iron uptake in tomato. For identification of its biological functions, AtbHLH29 was introduced into the genome of the tomato FER mutant T3238fer mediated by Agrobacterium tumefaciencs. Transgenic plants were regenerated and the stable integration of AtbHLH29 into their genomes was confirmed by Southern hybridization. Molecular analysis demonstrated that expression of the exogenous AtbHLH29 of Arabidopsis in roots of the FER mutant T3238fer enabled to complement the defect functions of FER. The transgenic plants regained the ability to activate the whole iron deficiency responses and showed normal growth as the wild type under iron-limiting stress. Our transformation data demonstrate that AtbHLH29 is a functional ortholog of the tomato FER and can completely replace FER in controlling the effective iron acquisition in tomato. Except of iron, FER protein was directly or indirectly involved in manganese homeostasis due to that loss functions of FER in T3238fer resulted in strong reduction of Mn content in leaves and the defect function on Mn accumulation in leaves was complemented by expression of AtbHLH29 in the transgenic plants. Identification of the similar biological functions of FER and AtbHLH29, which isolated from two systematically wide-diverged "strategy I" plants, suggests that FER might be a universal gene presented in all strategy I plants in controlling effective iron acquisition system in roots.

Arabidopsis↗

PubMed1976

Functional-morphological correlates of renomedullary interstitial cells.

1. Indomethacin treatment of renomedullary interstitial cells (RIC) causes a marked increase in number and size of their lipid droplets. The anti-hypertensive function is retained. 2. After multiple passages in tissue culture, RIC lose their ability to produce an anti-hypertensive effect in hypertensive animals. Along with this functional loss, lipid droplets and a prominent cisternal system become attenuated or disappear. 3. We conclude that preservation of the lipid granule-cisternal organelle relationship is important in preservation of the anti-hypertensive endocrine function of RIC.

Antihypertensive Agents↗

PubMed2002

Receptor crosstalk. Implications for cardiovascular function, disease and therapy.

There are at least three well-defined signalling cascades engaged directly in the physiological regulation of cardiac circulatory function: the beta1-adrenoceptors that control the cardiac contractile apparatus, the renin-angiotensin-aldosterone system involved in regulating blood pressure and the natriuretic peptides contributing at least to the factors determining circulating volume. Apart from these pathways, other cardiac receptor systems, particularly the alpha1-adrenoceptors, adenosine, endothelin and opioid receptors, whose physiological role may not be immediately evident, are also important with respect to regulating cardiovascular function especially in disease. These and the majority of other cardiovascular receptors identified to date belong to the guanine nucleotide binding (G) protein-coupled receptor families that mediate signalling by coupling primarily to three G proteins, the stimulatory (Gs), inhibitory (Gi) and Gq/11 proteins to stimulate the adenylate cyclases and phospholipases, activating a small but diverse subset of effectors and ion channels. These receptor pathways are engaged in crosstalk utilizing second messengers and protein kinases as checkpoints and hubs for diverting, converging, sieving and directing the G protein-mediated messages resulting in different signalling products. Besides, the heart itself is endowed with the means to harmonize these signalling mechanisms and to fend off potentially fatal consequences of functional loss of the essential signalling pathways via compensatory reserve pathways, or by inducing some adaptive mechanisms to be turned on, if and when required. This receptor crosstalk constitutes the underlying basis for sustaining a coherently functional circulatory entity comprising mechanisms controlling the contractile apparatus, blood pressure and circulating volume, both in normal physiology and in disease.

Adaptation, Physiological↗

PubMed1999

Defining meaningful change in Alzheimer's disease trials: the donepezil experience.

Regulatory guidelines in the US and Europe generally require that a drug specifically indicated for treating Alzheimer's disease (AD) must demonstrate an effect upon the core manifestations of dementia. Progressive cognitive and functional losses are the cardinal features of AD. In the US, current guidelines require that new AD treatments show effectiveness on performance-based measures of cognition and on clinician-rated global assessments. Improvement in function is also emphasized in the European guidelines. The primary instruments that have been used to evaluate changes in cognition and global function in most recent AD trials are the cognitive subscale of the Alzheimer's Disease Assessment Scale and a version of the Clinician's Interview Based Impression of Change, respectively. The results from three pivotal trials investigating the acetylcholinesterase inhibitor, donepezil, are used to demonstrate the way in which these tools are used, how to interpret the data they provide, and to determine their overall value in ascertaining efficacy in clinical practice.

Aged↗

PubMed2005

Molecular basis of mechanical modulation of endothelial cell migration.

Vascular endothelial cells (ECs) play important roles in the regulation of vascular functions. Loss of endothelial integrity can lead to vascular diseases such as stenosis resulting from atherosclerosis. The migration of ECs into wounded area in the vessel wall is required for the restoration of its integrity and functions. EC migration results from a balance of externally applied forces (e.g. shear stress), intracellular forces (e.g., those generated by contractile and cytoskeletal proteins), adhesion force between ECs and extracellular matrix (ECM) proteins, and the force of EC-EC coupling through junction proteins. Shear stress modulates EC migration through the regulation of multiple signaling pathways, gene expression, and the reorganization of cytoskeleton, focal adhesion sites, and cell junctions. Investigations of EC migration under shearing can provide valuable knowledge on vascular remodeling process under physiological and pathological conditions.

Animals↗

PubMed2004

Pretreatment with high-fat enteral nutrition reduces endotoxin and tumor necrosis factor-alpha and preserves gut barrier function early after hemorrhagic shock.

Gram-negative sepsis is a potentially fatal clinical syndrome characterized by a proinflammatory response (tumor necrosis factor-alpha) to bacterial (endo)toxins and gut barrier function loss. Recently, we found that high-fat enteral nutrition protects against late bacterial translocation in a model of hemorrhagic shock in rats. However, the basis for this protection is unknown. We hypothesized that the observed protection is the result of an early inhibition of endotoxin and the subsequent inflammatory response resulting in a preserved gut barrier function. Sprague-Dawley rats were divided into a group that was starved overnight (HS-S), fed with a low-fat enteral diet (HS-LF) or fed wih a high-fat enteral diet (HS-HF), and subsequently subjected to a nonlethal hemorrhagic shock. Ninety minutes after hemorrhage, arterial endotoxin significantly decreased in HS-HF rats (4.0 +/- 0.6 pg/mL) compared with HS-LF rats (10.7 +/- 0.9 pg/mL, P = 0.002) and HS-S rats (15.2 +/- 2.2 pg/mL P = 0.001). Interestingly, arterial tumor necrosis factor-alpha was also decreased in HS-HF rats (17.9 +/- 10.4 pg/mL) compared with HS-LF (83.5 +/- 16.7 pg/mL, P < 0.01) and HS-S rats (180.9 +/- 67.9 pg/mL, P < 0.02). Loss of tight junction structure (ZO-1) observed in ileum and colon of control hemorrhagic shock rats was prevented in HS-HF rats. In parallel, intestinal barrier function was preserved in HS-HF rats, evidenced by a reduced permeability to horseradish peroxidase (P < 0.05), less bacterial invasion, and a 10-fold reduction of bacterial translocation early after hemorrhagic shock. This report describes a new strategy to nutritionally prevent endotoxemia, the subsequent inflammatory response and gut barrier failure following hemorrhagic shock. High-fat enteral nutrition requires further evaluation as an intervention to prevent a potentially fatal systemic inflammatory response in patients at risk for sepsis.

Animal Feed↗