Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genetic Load”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 901 records · Page 50Linked to original sources
PubMed2003

[Sperm antibodies and immunologic intolerance to metals in infertile couples].

OBJECTIVE: Verification of the hypothesis of a relationship between the presence of antibodies against sperm cells and immunological reactivity to some metals in infertile couples by the MELISA test. SETTING: Department of Obstetrics and Gynecology, Medical Faculty, Charles University and Faculty Hospital, Plzen. METHOD: From 23 female patients and 21 men (a total of 44 subjects treated for infertility) with confirmed serum antibodies against sperm cells the authors isolated lymphocytyes from the peripheral blood stream, divided them into individual cultures and investigated them by the MELISA test using different metal compounds. RESULTS: The outcome of the MELISA test are values of the stimulation index (SI) by means of which the authors investigated the reactivity of the organism to the given metal. Special attention was devoted to compounds of organic and inorganic mercury. The SI values were subsequently compared with different data obtained from a detailed anamnestic questionnaire which was focused specially on contact with metals and on allergic reactions. In the investigated group of patients the authors detected a positive immune reactivity to inorganic mercury, Ag, Al, Fe. In some subjects they found a very high positive immune reactivity to inorganic mercury, Ni, Al, Cd and Ti. The control groups were formed by healthy fertile subjects without antibodies against sperm cells and with physiological SI values. CONCLUSION: The authors did not prove a direct relationship between the intensity of the laboratory reactivity to metals and the presence of antibodies against sperm cells which cause deterioration of fertility. An exogenous load of metals could in case of genetic predisposition be only one of the factors which participate in the formation of antibodies against sperm cells. The investigation proved that its is not essential, contrary to the view of many stomatologists, to eliminate metal compounds completely from dental practice.

Adult↗
PubMed2005

Simulation of manual materials handling: biomechanial assessment under different lifting conditions.

Manual material handling (MMH) tasks were evaluated and compared under different lifting conditions. For the theoretical evaluations, a two-dimensional sagittally symmetric human-body model was established to compute the moment and joint load time histories for MMH tasks for a variety of different lift specifications and constraints such as lifting durations, loads, and modes. Nonlinear control techniques and genetic algorithms were utilized in the optimizations to explore optimal lifting patterns. Since the kinetic measures such as joint moments are vital metrics in the assessment of the likelihood of injury, the simulation results obtained may be compared using these metrics for each lift type, so that the superiority of a lifting method or protocol relative to another may be determined.

Algorithms↗
PubMed1985

[Multiple gangrene of the digits in a female patient with liver cirrhosis, diabetes mellitus and cryoglobulinemia].

A case is described with multiple gangrene of the fingers of a female, aged 55, with confirmed cirrhosis of liver and diabetes mellitus. Cryoglobulins were established in the serum. A disturbed immunological balance was present and the family loading with collagenosis raises the problem of genetic moments of the disturbed homeostasis. The existing diabetic microangiopathy, histologically confirmed by biopsy of skin and subcutaneous tissue, brings forward the question of the complex pathogenesis of gangrene. At the end of her stay in the clinic, the patient developed cerebral apoplexy.

Brain Ischemia↗
PubMed1980

Ultrastructural and morphometric investigations into the arterial wall of the genetically hypertensive rat.

A number of injurious agents, including "load-failure" of hemodynamic or metabolic origin, constitute "risk factors"for the wall of a blood vessel. We are here concerned with arterial hypertension, which is a primary risk factor for the production of atherosclerotic change. The SHR (spontaneously hypertensive rat) has been included among the more extensive series of experiments conducted by our research team (STAUBESAND et al.) as a particular model for the investigation of metabolic and hemodynamic "load-failure". The aims of the present contribution are to describe the morphological changes in the diseased vessel wall and to support these findings morphometrically.

Aging↗
PubMed1995

Nucleotide pool imbalances in the livers of patients with urea cycle disorders associated with increased levels of orotic aciduria.

Liver samples obtained at autopsy from patients with ornithine transcarbamylase (OTC) deficiency, a urea cycle disorder that is associated with high levels of orotic acid biosynthesis and excretion were analysed for nucleotide pools. As a control, liver samples from patients with a deficiency of mitochondrial carbamyl phosphate synthetase (CPS-I) which is not associated with increased levels of orotic acidurias were also analysed. The results show that liver tissue from OTC deficiency patients exhibited an increased ratio of uridine nucleotides to adenosine nucleotides, while in CPS-I deficiency patients, no such increase was noted. This study indicates that genetic disorders that are associated with increased loads of orotic acid exhibit abnormally high ratios of uridine to adenosine nucleotides in the liver. This type of imbalance is analogous to that seen in the liver of rats and mice exposed to an orotic acid supplemented or an arginine-deficient diet under liver tumor promoting conditions. It is likely that an imbalance in nucleotide pools may have a significant role in the pathophysiology associated with these disorders.

Adenine Nucleotides↗
PubMed1994

A population-based study of familial Alzheimer disease: linkage to chromosomes 14, 19, and 21.

Linkage of Alzheimer disease (AD) to DNA markers on chromosomes 14, 19, and 21 was studied in 10 families in which the disease was apparently inherited as an autosomal dominant trait. Families were derived from a Dutch population-based epidemiologic study of early-onset AD. Although in all probands the onset of AD was at or before age 65 years, the mean age at onset was after age 65 years in four families (referred to as "LOAD"). Among the six families with early-onset AD (referred to as "EOAD," i.e., mean age of onset of AD of relatives was at or before age 65 years), conclusive linkage to 14q24.3 was found in one family with a very early onset (around 47 years), while linkage to the same region was excluded in two other families. For the LOAD families, predominantly negative lod scores were obtained, and the overall lod score excluded linkage to chromosome 14. The results with markers on chromosome 19 and chromosome 21 were not conclusive for EOAD and LOAD. The findings of our study confirm genetic heterogeneity within familial EOAD.

Aged↗
PubMed1994

Hyperhomocysteinaemia: a newly recognized risk factor for vascular disease.

In the past decade significant progress has been made in understanding of hyperhomocysteinaemia and its association with the proneness to premature development of vascular disease. Pooled data from a large number of studies demonstrate that mild hyperhomocysteinaemia after standardized methionine loading is present in 21% of patients with coronary artery disease, in 24% of patients with cerebrovascular disease, and in 32% of patients with peripheral vascular disease. A relative risk of 13.0 (95% confidence interval 5.9-28.1) of vascular disease at relatively young age can be calculated in subjects with such abnormal response to methionine loading. Pathological homocysteine levels are affected by genetic defects in homocysteine metabolism which have still not been completely clarified and which are more complex than originally supposed. Furthermore, a variety of non-genetic determinants such as deficiency of folate or vitamin B12 has to be taken into account. Mild hyperhomocysteinaemia can be reduced to normal in virtually all cases by simple and safe treatment with vitamin B6, folic acid, and betaine, each of which is involved in methionine metabolism. A clinically beneficial effect of such an intervention, which is currently under investigation, could make large-scale screening mandatory for this risk factor.

Arteriosclerosis↗
PubMed1998

Metabolic basis for hypertriglyceridaemia in familial combined hyperlipidaemia.

Familial combined hyperlipidaemia (FCH) is not a single entity with a clearly defined cause but can occur through an increased fatty acid flux from adipose cells, lipoprotein lipase dysfunction or apolipoprotein CIII abnormalities. A dynamic model of the metabolic processes of FCH has been used to describe how lipolysis of adipose cells may ultimately contribute to the formation of atherosclerotic plaques. Elevated circulating levels of chylomicrons are broken down to produce atherogenic remnants. One of the roles of lipoprotein lipase is in the low density lipoprotein (LDL) receptor-like protein-mediated uptake of lipoprotein remnants in the liver and up to 20% of FCH patients show a genetic abnormality of this enzyme. Vitamin A loading and measurement of chylomicron retinyl palmitate levels has further demonstrated impaired chylomicron remnant metabolism in these patients. Macrophages located in the vascular walls engulf remnants but are unable to metabolize their cholesterol. These cells contribute to atherosclerotic plaques. In terms of atherogenic potential, triglyceride levels are found to be higher and the hypertriglyceridaemia more severe in fed than in fasted patients. A case study of a patient with abetalipoproteinaemia suggests that the hypertriglyceridaemia seen in patients with FCH may be the result of an abnormality in microsomal triglyceride transport protein function. Studies also suggest a direct relationship between the post-prandial triglyceride levels and LDL cholesterol levels in the fasting state of patients with FCH and sporadic hypercholesterolaemia.

Coronary Artery Disease↗
PubMed2001

The role of viral load determination for the management of human immunodeficiency virus, hepatitis B virus and hepatitis C virus infection.

During the last 5 years, considerable scientific and financial efforts have been made in the development of quantitative nucleic acid detection technology. For detection of human immunodeficiency virus (HIV), quantitative culture is time consuming, cumbersome and requires appropriate laboratory safety equipment. Quantitative determination of p24 antigen by enzyme immunoassay is of limited value due to its relatively poor sensitivity. Therefore, quantitative determination of viral load using nucleic acid amplification techniques is the most accurate, prognostic marker for HIV type 1 infection, independently of the CD4+ cell count. Hepatitis B virus (HBV) is not cultivable in vitro. Serological assays allow an accurate diagnosis and follow-up of acute or chronic infection. Quantification of HBV DNA is used for the monitoring of antiviral therapy, determination of infectivity and for resolution of unclear serological profiles, e.g. isolated anti-HBc reactivity, as well as for patients in which HBV mutants are suspected. Hepatitis C virus (HCV) can only be detected by molecular based assays because no cell culture system, which permits a reliable isolation of clinical specimens, is currently available. Furthermore, early diagnosis and follow-up of infection cannot be achieved with antibody serology. The prognostic relevance of quantitative HCV RNA determination is of limited value for the long-term prognosis of chronic hepatitis C. However, viral load may predict the outcome of antiviral therapy. Genetic diversity is another challenge for HCV RNA quantification.

HIV Infections↗
PubMed1994

[A new natriuretic factor acting like loop diuretics. Kinetics in normal and hypertensive rats].

We have recently described that urines from salt-loaded rats contain a potent natriuretic factor acting at the Na-K-Cl cotransport system (CIF: "Cotransport Inhibitory Factor"). Here we investigated the kinetics of the urinary CIF excretion which follows an oral salt-load: (i) in normal rats, relative to that of the atrial natriuretic peptide (ANP) and (ii) in an experimental model of salt-dependent genetic hypertension (Dahl's rats). Thus, Wistar rats were orally loaded with 2% NaCl for 8 days. Urinary CIF excretion was measured by testing the inhibitory potency of urines on bumetanide-sensitive lithium efflux in lithium-loaded human erythrocytes. Plasmatic levels of ANP were measured by radioimmunoassay. Plasma ANP rapidly and transiently increased during the first 24 hs of salt-load, decreasing thereafter down to normal levels in 6-8 days. Conversely, CIF slowly increased after 24 hs up to maximal constant levels after 5 days of salt-loading. Dahl salt-sensitive rats exhibited highly significant increases in urinary CIF excretion with respect to salt-resistant rats. In the basal state (before salt-loading) urinary CIF excretion was 101 +/- 13 vs 17.6 +/- 4.5 units/day in salt-sensitive vs. salt-resistant rats (n = 7 for each group, p < 0.001). This difference was maintained after salt loading (3 380 +/- 990 vs. 456 +/- 159 units/day, p < 0.05 at day 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Heritability of plasma amyloid beta in typical late-onset Alzheimer's disease pedigrees.

Plasma amyloid beta42 peptide (Abeta42) levels are significantly elevated in all genetic forms of early-onset Alzheimer's disease caused by familial Alzheimer's disease mutations or Down's syndrome. Moreover, recent studies have determined that both plasma Abeta42 and Abeta40 levels are significantly elevated in late-onset Alzheimer's disease (LOAD) patients, their cognitively normal first-degree relatives, and members of typical LOAD families when compared to appropriate controls. To determine the magnitude of the genetic component affecting plasma Abeta levels, we estimated the heritability of plasma Abeta42 and Abeta40 in 15 extended, multigenerational LOAD pedigrees, using a variance components method. Heritability estimates as high as 73 and 54% were found for plasma Abeta42 and Abeta40 levels, respectively. Inclusion of the ApoE epsilon4 dosage as a covariate was not found to have a significant effect on the heritability of these traits. These results suggest that genetic determinants other than ApoE account for a very substantial percentage of the phenotypic variance in plasma Abeta levels. The high heritability and the significant elevation of these traits in LOAD pedigrees suggest that at least some of the genetic determinants of plasma Abeta levels may lead to elevated Abeta and LOAD in these families. Thus, we suggest that plasma Abeta levels are quantitative traits that may be excellent surrogate markers for use in linkage analysis to identify loci that are important in typical LOAD.

Adult↗
PubMed1992

Deficit of birthrates in winter and spring months in distinct subgroups of mainly genetically determined schizophrenia.

The birthrates of 507 schizophrenic patients with high familial loading were compared to the general population. The patient group showed a clearcut decrease in births within a defined winter and spring period. In particular, this was obvious if Leonhard's classification of schizophrenia was applied. The hypothesis is proposed that, in some fetuses at high genetic risk for schizophrenia, an exaggerated level of abortions or stillbirths occurs if additional environmental noxious agents are present in a crucial period of brain maturation. Pertinent evidence in support of this is found in literature.

Adult↗
PubMed2004

Biomechanics of back pain.

This paper offers a mechanistic account of back pain which attempts to incorporate all of the most important recent advances in spinal research. Anatomical and pain-provocation studies show that severe and chronic back pain most often originates in the lumbar intervertebral discs, the apophyseal joints, and the sacroiliac joints. Psychosocial factors influence many aspects of back pain behaviour but they are not important determinants of who will experience back pain in the first place. Back pain is closely (but not invariably) associated with structural pathology such as intervertebral disc prolapse and endplate fractures, although age-related biochemical changes such as those revealed by a 'dark disc' on MRI have little clinical relevance. All features of structural pathology (including disc prolapse) can be re-created in cadaveric specimens by severe or repetitive mechanical loading, with a combination of bending and compression being particularly harmful to the spine. Structural disruption alters the mechanical environment of disc cells in a manner that leads to cell-mediated degenerative changes, and animal experiments confirm that surgical disruption of a disc is followed by widespread disc degeneration. Some people are more vulnerable to spinal degeneration than others, largely because of their genetic inheritance. Age-related biochemical changes and loading history can also affect tissue vulnerability. Finally the concept of 'functional pathology' is introduced, according to which, back pain can arise because postural habits generate painful stress concentrations within innervated tissues, even though the stresses are not high enough to cause physical disruption.

Biomechanical Phenomena↗
PubMedDate not supplied

[Genetic and somatic effects of ionizing radiation in humans and animals (comparative aspect)].

Genetic effects of ionizing radiation in the progeny of exposed parents could be conventionally subdivided on three main types. 1. Severe developmental disorders (fetus death, stillbirth, early postnatal mortality, malformation, hereditary disease, sterility). These effects are known to be caused by so called "gross" mutations (genomic, chromosomal, those of essential genes) with dominant harmful effects. Although found in rodents, insects, fishes they have not been found in humans. The proposal is made that the higher reproductive potency of a species the higher its tolerance for defective organisms. Due to strong selection against severe defects at the earliest stage of pregnancy, this genetic effect of radiation is likely to be difficult to detect in people. 2. Increased cancer risk manifested as elevated incidence of spontaneous tumors and increased sensitivity to carcinogenic agents. 3. Decreased fitness (non-carcinogenic negative health effects). These two last types of radiation genetic effects are presumably due to instability and functional inferiority of cell genome in the progeny of irradiated parents. The genetic background of these effects is suggested to be the load of induced minor mutations in regulatory genes (mini-, microsatelite loci) or/and epigenomic rearrangements of DNA in parental germ cells transmitted to progeny. These radiation genetic effects are much more obvious in animals as compared to humans. Apparently, they are difficult to find in humans because of their essential dependence on promotive (life style) factors, which are impossible to control in the offspring of irradiated people. A comparison of somatic (in irradiated organisms) and genetic (in the progeny of irradiated parents) effects of radiation provide evidence on the phenomenological as well as pathogenic similarity.

Animals↗
PubMed2004

Genetic variability of hepatitis C virus NS3 protein in human leukocyte antigen-A2 liver transplant recipients with recurrent hepatitis C.

The association between the severity of chronic hepatitis C and the variability of the hepatitis C virus (HCV) genome remains controversial, but to our knowledge few data are available to date regarding T-cell epitope coding regions in transplant patients. In the current study, we identified 21 human leukocyte antigen (HLA)-A2-positive Spanish patients with chronic hepatitis C, 14 immunosuppressed liver transplant recipients, and 7 immunocompetent controls. Alanine aminotransferase, aspartate aminotransferase, viral load, and rate of fibrosis progression were determined. Genetic distances of HCV isolates and variations in epitopes of the HCV nonstructural 3 protein (NS3-1393 LIFCHSKKK and NS3-1406 KLVALGINAV) were compared between patients with slow or fast progression of fibrosis. Isolates from transplant patients with fast progression were found to be more divergent (P =.03), had a higher mean value of synonymous (dS) variations (P =.02), and some were differentiated in a phylogenetic tree, compared with isolates from patients with slow progression. The HLA-A2-restricted NS3-1406 epitope was found to be more variable (20 of 21 isolates differed from the prototype) compared with the A3-restricted NS3-1392 epitope (19% vs. 1.25% variation). A shift in the viral peptide was not detected in a subset of transplant patients, but was evident in two of three nontransplant patients with follow-up. There was no correlation noted between a particular amino acid variation and fibrosis progression (slow or fast) in either transplant or nontransplant patients. The results of the current study suggest that 1) there may be different HCV-1b strains in our geographic area, 2) immunosuppression appears to have little effect in amino acid variation at the HCV NS3-1406 epitope, and 3) variations over time might be more frequent in nonimmunosuppressed patients.

Adult↗
PubMed1991

Effect of aging and hypertension on myosin biochemistry and gene expression in the rat heart.

The mechanisms by which the aged heart adapts to a superimposed pressure load such as hypertension have not been described. We therefore investigated biochemical and molecular genetic adaptations in the 24-month-old rat heart subjected to renovascular hypertension. Compared with 4-month-old rats, aging was associated with a 68% increase in left ventricular mass without any change in heart weight-to-body weight ratio, a 33% reduction in calcium-activated myosin ATPase activity, and a shift from a V1 to a V3 predominant myosin heavy chain (MHC) isoform distribution. A 46% reduction in alpha-MHC mRNA and a reciprocal increase in beta-MHC mRNA was seen. When hypertension was superimposed, there was a further 75% increase in ventricular mass, a 63% increase in heart weight-to-body weight ratio, and a 19% reduction in myosin ATPase. Myosin isozyme distribution was further shifted to V3, and the ratio of alpha-MHC to beta-MHC mRNA was reduced. In addition, with hypertension a significant (greater than 50%) reduction in the mRNA level of the cardiac sarcoplasmic reticular calcium-activated ATPase was seen. These data demonstrate that the aged myocardium is able to respond to a superimposed pressure load with a molecular genetic and protein synthetic pattern of hypertrophy analogous to that seen in younger animals.

Aging↗
PubMed1998

Haemochromatosis.

Primary, hereditary or genetic haemochromatosis is one of the most common inherited disorders in a Caucasian populations with a disease frequency of 1:300-400 and a carrier frequency of approximately 10%. The basic genetic defect remains unknown, although the haemochromatosis gene has now been cloned and is known to be a member of the MHC non-classical class I family. Many factors--environmental, genetic and non-genetic in nature--influence the degree of iron loading in affected individuals. In particular, pathological and physiological blood loss influence iron stores in haemochromatosis. The iron concentration in the liver is an important determinant of survival because a hepatic iron concentration in excess of 400 mumol/g dry weight is usually associated with cirrhosis. Patients with cirrhosis secondary to haemochromatosis are at risk of hepatocellular carcinoma. The combination of improved awareness of the disease and the appropriate use of genetic testing for the common C282Y mutation should lead to earlier diagnosis and therapy.

Hemochromatosis↗
PubMed2006

Polymorphisms in the phosphate and tensin homolog gene are not associated with late-onset Alzheimer's disease.

The varepsilon4 allele of the APOE locus is the only confirmed risk factor for late-onset Alzheimer's disease (LOAD). The phosphate and tensin homolog (PTEN) gene is both a biological and positional candidate gene for LOAD. Eight polymorphisms spanning this gene were selected from dbSNP and genotyped in pooled DNA samples of both cases and controls. No evidence for association with LOAD was obtained in this study although further investigation revealed low levels of linkage disequlibrium (LD) between the genotyped SNPs. Our results suggest that it is unlikely that genetic variation within the PTEN gene contributes to risk of LOAD.

Aged↗