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H-1 MR spectroscopic imaging of white matter signal hyperintensities: Alzheimer disease and ischemic vascular dementia.

PURPOSE: To investigate the association of white matter signal hyperintensities (WMSHs) with changes in hydrogen-1 metabolites. MATERIALS AND METHODS: T2-weighted magnetic resonance (MR) imaging and H-1 MR spectroscopic imaging were performed in 21 elderly control subjects without or with minimal WMSHs, eight elderly subjects with substantial WMSHs, 11 probable Alzheimer disease patients with WMSHs, and eight ischemic vascular dementia (IVD) patients with WMSHs. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and creatine-containing metabolites (Cr) were analyzed. RESULTS: Differences in regional metabolite levels were found within the supraventricular brain of elderly control subjects. In Alzheimer disease patients, extensive WMSHs showed a lower percentage of NAA and a higher percentage of Cho compared with contralateral normal-appearing white matter (NAWM); in IVD patients, extensive and large WMSHs were associated with a higher percentage of Cho and a lower percentage of Cr compared with contralateral NAWM. CONCLUSION: Regional metabolite variation and the presence of WMSHs are important covariants that must be accounted for in analysis of MR spectroscopic data.

Aged↗

Insulin sensitivity and liver insulin receptor structure in ducks from two genera.

Insulin sensitivity and liver insulin receptor structure were studied in 5-wk-old ducks from two genera (Muscovy and Pekin). In the fasting state, both duck types were equally resistant to exogenous insulin compared with chicken. Despite the low potency of duck insulin, the number of insulin receptors was lower in Muscovy duck and similar in Pekin duck and chicken liver membranes. After 125I-insulin cross-linking, the size of the alpha-subunit of the receptors from the three species was 135,000. Wheat germ agglutinin-purified receptors from the three species were contaminated by an active and unusual adenosinetriphosphatase (ATPase) contaminant (highest activity in Muscovy duck). Sequential purification of solubilized receptor from both duck types on lentil and then wheat germ agglutinin lectins led to a fraction of receptors very poor in ATPase activity that exhibited a beta-subunit size (95,000) and tyrosine kinase activity similar to those of ATPase-free chicken insulin receptors. Therefore the ducks from the two genera exhibit an alpha-beta-structure for liver insulin receptors and a clear difference in the number of liver insulin receptors. Their sensitivity to insulin is, however, similarly decreased compared with chicken.

Animals↗

Distribution of haptoglobin subtypes in French Basques.

THE Hl1f, Hp1s and Hp2 gene frequencies were studied in two French population samples: one from the Toulouse area and one from a Basque district. The hp alpha1F and alpha1S polypeptide chains were determined by a simple technique. The observations were in accordance with previous findings in Caucasoid populations. The frequency of the Hp1S gene was slightly higher in the Basque sample than in the group from Toulouse.

France↗

Relationship between Hp1S and Hp2 gene frequencies among human populations.

In this work, we present new data on the Hp1alpha- and Hp2alpha-chains polymorphism in different populations. We confirm the singularity of the geographical distribution of the Hp2 alleles in our samples. The analysis of the results shows that a significant correlation exists in the population between the Hp1S and Hp2 gene frequencies. An additional Hp1alpha-chain variant is described in a Pyrenean sample.

Algeria↗

Study of red blood cell and serum enzymes in five Pyrenean communities and in a Basque population sample.

Until recently, no data on genetic polymorphisms in the populations living on the northern side of the Pyrenees have been available, except for the Basques. Several investigations were done lately on rural communities in various geographic zones in the Pyrenees from the eastern to the western part. In this paper, the results for the following enzyme polymorphisms are reported: acid phosphatases, AK, ADA, PGM1 and PGM2, 6PGD, NADH diaphorase, SOD, MDH, TGP, G6PD, C5 esterase (E2 locus), serum cholinesterase (E1 locus). Significant variation in gene frequencies was observed over the distinct geographic zones for the main polymorphic system. Furthermore, some rare alleles were found: a new G6PD variant (Luz-Saint-Sauveur), the presence of ADA3 and ADA5 alleles in two groups of the Central Pyrenees, a Dia2 gene among Basques and in the Pays de Sault, a high rate of Ea1 allele in the Basque group. The values obtained for the degree of heterozygosity are in agreement with the relative isolation of the different groups studied and confirm the importance of sociocultural factors in the evolution of the genetic background of rural communities in Europe.

Acid Phosphatase↗

Erythrocyte glyoxalase I and esterase D polymorphisms in four French populations.

The genetic polymorphism of two new erythrocyte markers GLO I (EC 4.4.1.5) and esterase D (EC 3.1.1.1) has been investigated in four French populations: Basques and Toulouse groups (southwest area), Lille and Strasbourg (northern and eastern part of the territory). The distribution of GLO I and EsD alleles within these communities has shown some significant differences. Basques samples are characterized by the highest frequency of EsD1 gene (0.911) and the lower rate of GLO1 (0.364). The observed data are compared with other results previously reported in France and in Western European populations.

Electrophoresis, Starch Gel↗

Gc, Tf, Hp subtype and alpha 1-antitrypsin polymorphisms in a Pygmy Bi-Aka sample.

Protein polymorphism is studied in more than 900 serum samples during different investigations conducted in a Bi Aka Pygmy group. The Gc, Tf and alpha 1-antitrypsin subtype polymorphisms were determined after isoelectric focusing while the haptoglobins alpha and alpha 2-peptides were studied on PAGE. A high frequency of the Hp2 gene is noted while Hp1F and Hp1S gene frequencies are similar. According to the Gc1S and Gc2 gene frequencies this group falls within the cluster of the melanoderm populations such as the Sara, Bantu and Peulhs. The two subtypes of TfC1 and TfC2 are present in this sample. TfC3 is absent. The TfD1 variant frequency is one of the highest observed in African groups. The alpha 1-antitrypsin polymorphism corresponds to the presence of the three PiM subtypes. No other variants are observed, neither PiS nor PiZ. For the first time a highly significant association is described between the TfD1 and Gc1A1 (GcAb) genes. Family pedigrees do not permit the ascertainment of the linkage between the two loci.

Black People↗

Human red-cell acid phosphatase (ACP1): a new mutant (ACP1*KUK) detected by isoelectric focusing, kinetics of thermostability and substrate activity.

A new rare mutant of the red-cell acid phosphatase (ACP1) is described using conventional gel electrophoresis and isoelectric focusing migration. According to the electrophoretic patterns obtained, the new mutant ACP1* KUK is different from the ACP* H and ACP1* A' variants already described. The enzyme activities and the thermostability curves definitively confirm the existence of a new variant. The transmission of this mutant was followed through a pedigree of three generations. The family originated from Czechoslovakia. The frequency of the variant is probably less than 0.001.

Acid Phosphatase↗

Human red-cell acid phosphatase (ACP1): kinetic and thermodynamic characterization of the KUK variant.

The Km constant and the sensitivity to inhibitors were determined for the rare variant KUK of red cell acid phosphatase. At the same time, the thermodynamic energies of activation and of inactivation were measured. The kinetic parameters were not very different from those of the usual ACP1 C alloenzymes. However, they differed in their thermodynamic energies: the conformational structure of the ACP1 KUK protein being less stable.

Acid Phosphatase↗

Age-related insulin resistance: a review.

Impaired glucose tolerance occurs with age. This impairment is multifactorial including a decrease in insulin-mediated glucose uptake by peripheral tissues and a delay in insulin-induced suppression of hepatic glucose output. A post-binding defect in insulin action such as a reduced capacity to transcribe more glucose transporter mRNA and/or a reduced translocation of preformed glucose transporters to plasma membrane is incriminated. However, insulin resistance with age is not a constant finding and other mechanism(s) has (have) to be involved in old individuals with impaired glucose tolerance and normal tissue insulin sensitivity.

Aging↗

Polymorphism of the CA-I locus of carbonic anhydrase in baboon.

Polymorphism of erythrocytic carbonic anhydrase was studied by means of the usual technique of starch gel electrophoresis in Papio papio, Papio hamadryas, Papio cynocephalus and Papio anubis. In a sample containing both Papio cynocephalus and Papio anubis, examples of the homozygote CA-Ib/CA-Ib were found. A study of parental transmission established the CA-Ib allelic form.

Alleles↗

Proton magnetic resonance spectroscopy of the medial prefrontal cortex in patients with deficit schizophrenia: preliminary report.

OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) was used to study medial prefrontal metabolic impairments in schizophrenic patients with the deficit syndrome. METHOD: The subjects were 22 schizophrenic patients categorized as deficit (N=5) or nondeficit (N=17) and 21 healthy subjects. (1)H-MRS was performed for the right and the left medial prefrontal cortex. RESULTS: The patients with the deficit syndrome had significantly lower ratios of N-acetylaspartate to creatine plus phosphocreatine than did the healthy subjects or nondeficit patients. CONCLUSIONS: As N-acetylaspartate levels could reflect neuronal density and/or viability, this finding suggests a neuronal loss in the medial prefrontal cortex of deficit patients.

Aspartic Acid↗

Cannabis arteritis revisited--ten new case reports.

The purpose of this paper was to revisit the old concept of cannabis arteritis first described in the 1960s and report 10 new cases. Ten male patients, with a median age of 23.7 years developed subacute distal ischemia of lower or upper limbs, leading to necrosis in the toes and/or fingers and sometimes to distal limb gangrene. Two of the patients also presented with venous thrombosis and three patients were suffering from a recent Raynaud's phenomenon. Biological test results did not show evidence of the classical vascular risk factors for thrombosis. Arteriographic evaluation in all cases revealed distal abnormalities in the arteries of feet, legs, forearms, and hands resembling those of Buerger's disease. A collateral circulation sometimes with opacification of the vasa nervorum was noted. In some cases, arterial proximal atherosclerotic lesions and venous thrombosis were observed. All patients were moderate tobacco smokers and regular cannabis users. Despite treatment with ilomedine and heparin in all cases, five amputations were necessary in four patients. The vasoconstrictor effect of cannabis on the vascular system has been known for a long time. It has been shown that delta-8- and delta-9-tetrahydrocanabinols may induce peripheral vasoconstrictor activity. Cannabis arteritis resembles Buerger's disease, but patients were moderate tobacco smokers and regular cannabis users. These cases show that prolonged use of cannabis could be an additive risk factor for juvenile and young adult arteritis. Cannabis arteritis is a forgotten and severe occlusive vascular disease occurring in young adults. Search for cannabis use may be an important tool for a better knowledge of arteritis in young smokers.

Adolescent↗

1995 STP Young Investigator Award recipient. Increased rate of apoptosis correlates with hepatocellular proliferation in Fischer-344 rats following long-term exposure to a mixture of groundwater contaminants.

Apoptosis was evaluated in the livers of Fischer-344 rats following observations of increased hepatocellular proliferation from exposures, at low parts per million (ppm) levels, to a drinking water mixture of 7 groundwater contaminants during a 6-mo time-course study. The 7 chemicals used are among the most frequently detected contaminants associated with hazardous waste sites: arsenic, benzene, chloroform, chromium, lead, phenol, and trichloroethylene. Significant increases in 5-bromo-2'-deoxyuridine hepatocellular labeling were present in a unique pattern surrounding large hepatic veins (0.5-2.0 mm). This did not appear to be a regenerative response due to cytotoxicity, as assessed by the absence of increased plasma enzyme activity and the absence of hepatocellular lesions. Immunohistochemical staining for apoptosis, using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method showed patterns of labeling in treated animals that directly correlated to areas of increased hepatocyte proliferation. Apoptotic activity was maximum at the 1-mo exposure time point, whereas proliferating hepatocytes reached a maximum rate at the 10-day time point. This may have been triggered as a compensatory response to the increased cell proliferation or as a protective response to remove cells with altered DNA due to chemical mixture exposure. The principal findings of this paper are that (a) apoptosis directly correlated with changes in cell proliferation: (b) observed effects were produced by repeated exposures to a relatively low-level chemical mixture; and (c) the TUNEL method detected apoptotic cells at very early and late stages, potentially increasing the observable time period for apoptosis.

Animals↗