Frequency of factor V Arg506 Gln in Italians.
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Adult↗
Biomedical subjects
G Merati
Publications and source records attributed to G Merati.
Myocardial metabolism and function in acutely ischemic and hypoxemic isolated rat hearts.
We tested the hypothesis that residual oxygen supply during acute low-flow ischaemia or hypoxemia is a major regulator of myocardial performance, metabolism and recovery. Rat hearts were exposed for 20 min to either ischemia (coronary flow reduced to 10% of baseline), hypoxemia (oxygen content reduced to 10% baseline) or a "mixed" condition (combined ischaemia and hypoxemia). The oxygen supply (coronary flow x oxygen content) was matched in all groups (n = 16 per group). Hypoxemic hearts had the highest performance (systolic and developed pressures, +/- dP/dtmax and oxygen uptake) and content of IMP and AMP. Ischaemic hearts had the highest content of ATP, phosphocreatine, adenine nucleotides and purines. As flow and/or oxygenation were restored, post-ischemic hearts showed better functional and metabolic recovery than post-hypoxemic ones. "Mixed" hearts were more similar to hypoxemic ones during oxygen shortage but to ischemic ones during recovery. We conclude that as oxygenation is critically limiting, coronary flow is relatively more important than oxygen supply in determining myocardial function, metabolism and recovery, most likely secondary to changes in the metabolism of diffusible substances.
Adenine Nucleotides↗
Protein S mRNA in patients with protein S deficiency.
A protein S gene polymorphism, detectable by restriction analysis (BstXI) of amplified exonic sequences (exon 15), was studied in seven Italian families with protein S deficiency. In the 17 individuals heterozygous for the polymorphism the study was extended to platelet mRNA through reverse transcription, amplification and densitometric analysis. mRNA produced by the putative defective protein S genes was absent in three families and reduced to a different extent (as expressed by altered allelic ratios) in four families. The allelic ratios helped to distinguish total protein S deficiency (type I) for free protein S deficiency (type IIa) in families with equivocal phenotypes. This study indicates that the study of platelet mRNA, in association with phenotypic analysis based upon protein S assays in plasma, helps to classify patients with protein S deficiency.
Alleles↗
[Thrombolysis & arrhythmias].
In this study, we assessed one particular aspect of the arrhythmogenic phenomena that occur during reperfusion secondary to thrombolysis, that is the therein involved metabolic mechanisms. The employed experimental model (isolated Langendorff-perfused rat heart) allowed us to distinguish which factor involved during ischemia, low coronary flow or low oxygen tension, is primarily involved during arrhythmogenesis. This was made possible by comparing two settings characterized by the same oxygen supply, but with different coronary flows and PO2 values, i.e., ischemia and hypoxemia. As expected, the contractile dysfunction was higher during reoxygenation at the end of hypoxemia than during reperfusion at the end of ischemia (p < 0.05). However, the incidence of arrhythmias was similar in both cases. Therefore, whereas the contractile dysfunction appears to be more sensitive to coronary flow, the incidence of arrhythmias appears to be more sensitive to the total oxygen supply to the heart. This implies that the mechanisms underlying the development of contractile dysfunction and arrhythmogenesis follow different paths.
Animals↗
A histidine to tyrosine replacement in lysosomal acid lipase causes cholesteryl ester storage disease.
The genetic defect causing cholesteryl ester storage disease (CESD) has been investigated in an 11 year old patient. Lysosomal acid lipase (LAL) activity in cultured skin fibroblasts and peripheral lymphocytes was reduced to approximately 3% and approximately 4% of controls, respectively. The parents had low acid lipase activity in white blood cells. Using the polymerase chain reaction followed by ribonuclease protection assay, we examined the LAL mRNA from the liver of the affected patient to identify small deletion, abnormal splicing or missense mutation. Using this technique we identified a LAL mRNA cytosine to thymidine transition in position 923, predicting a missense substitution of tyrosine for histidine in codon 274. By differential oligonucleotide hybridization on an amplified white blood cell mRNA, the cytosine to thymidine transition was investigated in the family members and in the population. No normal mRNA coding for cytosine in position 923 was detectable in the propositus and mRNA from the phenotypically normal parents coded for both cytosine and thymidine. This can only be accounted for by assuming that the propositus is homozygote for the mutation. The mutation, segregated in the family with levels of acid lipase activity in white blood cells, was not detected in mRNA from 60 normal subjects. These data provide evidence that the cytosine to thymidine transition in position 923 in LAL mRNA causes the clinical expression of CESD in this patient. The predicted substitution of tyrosine for histidine in codon 274 suggests that this amino acid is involved in the structure-function of the lysosomal acid lipase enzyme.
Adolescent↗
Genetics of renal damage in primary hypertension.
Little is known of the genetics of glomerular damage in essential hypertension in humans. The prevalence of end-stage renal disease due to primary hypertension varies from 20% to 30% of all cases of renal failure to as low as 0.002%. This depends not only on differences in diagnostic criteria but also on different racial susceptibility to the disease as well as on different genetic backgrounds in different subsets of individuals of the same race. A review of the literature is provided, together with an example of how a point mutation that causes hypertension in Milan hypertensive rats can provide a model to analyze this issue correctly.
Animals↗
Erythrocyte Na+,K+,Cl- cotransport and kidney function in essential hypertension.
OBJECTIVE: To determine whether essential hypertensive patients with high Na+,K+,Cl- cotransport (COT) display alterations of some indices of kidney tubular reabsorption similar to those observed in Milan hypertensive (MHS) rats, which have high COT in both erythrocytes and kidney tubular cells, and hypertension caused by a primary increase of tubular reabsorption. DESIGN: Two sets of experiments were performed. First, renal function in two subgroups of hypertensive patients (one with 'high' and one with 'normal' COT was compared with that in normotensive controls. Secondly, the natriuretic and diuretic effects of a single oral dose of frusemide (25 mg) were analysed in six high- and in six normal- COT hypertensive patients. RESULTS: Compared with normotensives and with normal-COT hypertensives, high-COT hypertensives had lower fractional uric acid excretion and plasma renin activity with similar glomerular filtration rate and urinary sodium and potassium excretion. COT was negatively correlated with fractional uric acid excretion in the essential hypertensive patients but not in the normotensives. The diuretic natriuretic response to frusemide was much higher in high- than in normal-COT hypertensives. CONCLUSION: These results are consistent with the hypothesis that patients with high COT have abnormal renal handling of sodium similar to that observed in MHS rats.
Adult↗
Antioxidant activity of ubiquinone-3 in human low density lipoprotein.
The ability of ubiquinone-3, a short chain ubiquinone homologue, to prevent Cu2+ induced oxidation of human low density lipoprotein was investigated. The results are as follows: in the presence of ubiquinone-3 the extent of peroxidation, as determined by the formation of thiobarbituric acid reactive substances, was only one third of that found in its absence; the quinone can also prevent the fragmentation of apolipoprotein B-100 and the increase of the net negative surface charge of the particle.
Apolipoprotein B-100↗
Interaction between photosystem I and ferredoxin. Identification by chemical cross-linking of the polypeptide which binds ferredoxin.
Ferredoxin has been effectively cross-linked to photosystem I complex by treatment of purified particles or thylakoids with N-ethyl-3-(3-dimethylaminopropyl)carbodiimide, a zero-length cross-linker which stabilizes protein-protein electrostatic interactions. Analysis of photosystem I polypeptide composition after such a treatment showed a specific decrease of the 20-kDa subunit and the appearance of a new component of about 42 kDa which was recognized by the anti-ferredoxin antibody. Cross-linking of ferredoxin to thylakoids allowed the membrane preparation to photoreduce cytochrome c without requiring exogenous ferredoxin, whereas photosystem I particles purified from treated thylakoids were inactivated in the NADP+ photoreduction activity. From these results, it can be inferred that the polypeptide of 20 kDa is the photosystem I subunit which interacts with ferredoxin during the photosynthetic electron transport.
Carbodiimides↗
[Our experience with intravenous use of "Valium" in anesthesia for electric shock therapy].
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Adult↗
Determination of Lp(a) and APO(a) in an Italian population.
Plasma lipoprotein(a) [Lp(a)] levels were determined in an Italian population subdivided according to age and sex. The distribution of plasma Lp(a) levels was highly skewed, with 75% of the subjects having less than 10 mg/dl. No significant differences were found in the plasma Lp(a) levels of the two age groups, but women had significantly higher levels than men. There was no significant correlation between Lp(a) levels and the other lipid and lipoprotein parameters studied, with the exception of a weak correlation between Lp(a) levels and both total cholesterol and low density lipoprotein-cholesterol in younger women. Apoprotein(a) phenotyping was performed in about one-third of the population; an inverse relationship between the molecular weight of the different isoforms and plasma concentrations of Lp(a) was observed.
Adult↗
Congenital non-spherocytic haemolytic anaemias.
Congenital non-spherocytic haemolytic anaemias are a heterogeneous group of disorders caused by an ineffective normal-type enzyme or, more commonly, by a structurally abnormal and ineffective mutant enzyme. The first part of this paper deals with the laboratory diagnosis of these diseases, which is based on a three-step approach: demonstration of the haemolytic nature of the disease, demonstration that the cause of haemolysis is intracorpuscular and demonstration of the presence of an absolute or relative enzyme deficiency. Moreover, the possible causes of false negative results in standard enzyme assays are briefly commented. The second part focuses on the main clinical, laboratory and biochemical features of the most common enzyme deficiencies of both the Embden-Meyerhof pathway and purine and pyrimidine metabolism, with particular mention of the cases identified in Italy.
5'-Nucleotidase↗