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Biomedical subjects

A Szymanowicz

Publications and source records attributed to A Szymanowicz.

12 recordsLinked to original sources

Hemoglobin Roanne [alpha 94(G1) Asp-->Glu]: a variant of the alpha 1 beta 2 interface with an unexpected high oxygen affinity.

In hemoglobin (Hb) Roanne, the aspartate residue alpha 94(G1) is replaced by a glutamic acid. This residue plays a key role in the structural changes affecting the alpha 1 beta 2 contact area during the deoxy- to oxy-state transition in the hemoglobin molecule. Aspartate alpha 94(G1) is involved in several contacts both in the deoxy- and oxy-structures. The most important of those is a hydrogen bond with asparagine beta 102 (G4), stabilizing the oxygenated structure. Alteration of this contact usually leads to a decrease in oxygen affinity. Hb Roanne is the first example in which an increased oxygen affinity was found as a result of a structural modification at this position. Functional data suggested that the mechanisms responsible for this altered property are a destabilisation of the T-structure and a modification of the allosteric equilibrium.

Aged↗

Increased renal excretion of 3 hydroxyproline in patients with active glomerular nephropathies and with polycystic renal disease.

The renal excretion of 3 hydroxyproline (3 HYP) and 4 hydroxyproline (4 HYP) was investigated in control subjects and in patients with various renal diseases. In normal adult subjects urinary 3 HYP was 12.5 +/- 3.5 (SD) mumoles/24 hr, 4 HYP was 226 +/- 62 mumoles/24 hr and the percentage ratio 3 HYP/4 HYP 5.4 +/- 0.5. This ratio was reduced during growth because of a relative excess of 4 HYP. In patients with acute glomerular disease (n = 12) 3 HYP was increased to 17.1 +/- 5.8 mumoles/24 hr (P less than 0.01), and the ratio 3 HYP/4 HYP was 7.3 +/- 0.7% (P less than 0.01). Such an increase in 3 HYP was not observed in patients with chronic glomerulonephritis (n = 24) where 3 HYP was 9.6 +/- 5.0 mumoles/24 hr and 3 HYP/4 HYP 5.7 +/- 1.6% or with diabetic glomerulopathy (n = 6). In patients with chronic interstitial nephritis (n = 8) the 3 HYP/4 HYP ratio was decreased except in patients with polycystic renal disease (PKD) where it was increased (P less than 0.001). The daily urinary content of 3 HYP and 4 HYP was slightly altered by renal insufficiency. Urinary 3 HYP did not change significantly in patients with GN with the nephrotic syndrome whatever the histological lesion. These results indicate that urinary 3 HYP: 1) is increased when glomerulonephritis is clinically acute or subacute; 2) is increased in PKD whatever the level of renal insufficiency.

Acute Kidney Injury↗

Polymorphism of urinary 4-hydroxyproline-containing polypeptides.

Using molecular sieve chromatography on Bio-Gel P-2 and then on Bio-Gel P-30, hydroxyproline-containing urinary polypeptides (molecular weight greater than 1500 daltons) were separated into eight fractions. The three main fractions were separated further on phosphocellulose giving seven, nineteen and twelve peaks, respectively, each containing 4-hydroxyproline. Hypotheses about the origin of certain polypeptides are proposed, which take into account the sequence of type I collagen. Among these 38 polypeptides only one shows a quantitative variation in Paget's bone disease and was thus purified. It consists of equal amounts of glycine, proline and 4-hydroxyproline. This particular polypeptide may originate from the N-terminal propeptide of type I collagen.

Amino Acids↗

Urinary 3-hydroxyproline in renal disease.

The renal excretion of 3-hydroxyproline (3-HYP), an isomer of 4-hydroxyproline (4-HYP) found 6-10 times more in basement membrane collagen than in interstitial collagen, was investigated in control subjects and in 58 adult patients with various kidney diseases. With the exception of polykystic renal disease, all the nephropathies were investigated by renal biopsy. In normal adult subjects urinary 3-HYP was 12.5 +/- 3.5 (SD) mumol/24 h, 4-HYP 226 +/- 62 mumol/24 h and the percentage ratio 3-HYP/4-HYP 5.5 +/- 0.5. This ratio was twice as little during growth because of a relative excess of 4-HYP. In patients with acute glomerular disease (acute and subacute glomerulonephritis, lupus nephritis...) (n = 13) 3-HYP was 17.1 +/- 5.8 mumol/24 h (p less than 0.01 when compared with the normal) and 4-HYP 234 +/- 77 mumol/24 h. The ratio between the two values was 7.3 +/- 0.7 (p less than 0.001). Such an increase in 3-HYP was not observed in patients with chronic glomerulonephritis (n = 24) where 3-HYP was 9.6 +/- 5.7 mumol/24 h and 3-HYP/4-HYP 6.0 +/- 1.6, neither in patients with diabetic glomerulonephritis (n = 6). In chronic interstitial nephritis (n = 8) the 3-HYP/4-HYP ratio was decreased with the exception of polykystic renal diseases (PKD), where it was increased (p less than 0.001). The daily urinary contents of 3-HYP and 4-HYP were slightly altered by renal insufficiency. In glomerulonephritis with nephrotic syndrome whatever the histological lesions, urinary 3-HYP did not change significantly. These preliminary results indicate that urinary 3-HYP (1) is increased when glomerulonephritis is clinically acute or subacute; (2) is increased in PKD suggesting a possible inborn error of collagen metabolism.

Adolescent↗

Fractionation and structure of several hydroxyproline-containing urinary peptides, with special reference to some 3-hydroxyproline-containing peptides.

After a preliminary separation of the hydroxyproline-containing peptides on Biogel P 2, the largest peptides are fractionated on phosphocellulose and the smallest ones on QAE-Sephadex. The fractions obtained from QAE-Sephadex are subfractionated on a column of Dowex 50-M-82. The total number of hydroxyproline-containing peptides from human urine is not less than 78. Sixteen di, tri and pentapeptides have been purified, their N-terminal amino acids and amino acid compositions determined and a structure is proposed. 3 of these peptides contain 3-hydroxyproline and one of these 3 peptides probably originates from basement membrane collagen.

Chromatography, Ion Exchange↗

A column chromatography fractionation of the hydroxyproline-containing urinary peptides with continuous automatic detection.

Dialyzable and non-dialyzable urinary hydroxyproline-containing peptides are chromatographed respectively on QAE-Sephadex and on phosphocellulose. They are detected and quantitated by continuous hydrolysis in 3.3 N NaOH followed by oxidation by chloramine T and colorimetry with p-dimethylamino-benzaldehyde. The patterns of dialyzable urinary hypropeptides do not show significant qualitative differences between normal subjects and patients suffering from Paget's bone disease or cancer metastases of bone. The patterns of non-dialyzable urinary hypropeptides, show more variability in the case of normal subjects and differ more largely in the case of Paget's disease of bone.

Autoanalysis↗

[Biomarkers for toxicity and metabolic abnormalities of the main severe poisonings. Clinical and toxicologic symptoms. Conservative determination].

The members of the joint group "Toxicology and Clinical Biology" of the French Society of Clinical Biology (SFBC), the French Society of Analytical Toxicology (SFTA), and the Society of Clinical Toxicology (STC), suggest guidelines to meet the requirements of clinical biologists who are not specialized in toxicology. Based on good laboratory practice they propose a number of guidelines. Three synthetic tables have been established. They are not only toxicity biomarkers and metabolic disorders associated with the main severe intoxications, but also clinical signs that are observed during these intoxications, finally biological sampling as a precautionary measure. The table also takes into account approximately fifty xenobiotics: main clinical signs emergency, identification or quantification of the suspected product, useful biological markers, therapeutic, quantitations necessary to take into consideration patient care, and poison antidotes, are described. Recommendations regarding medical and forensic techniques are also proposed by the group. It is also necessary to collect and store biological samples when the individual patients are in charge. These samples will be analyzed or not depending on the individual case history.

Biomarkers↗

[A proposal of ready-made interpretative comments applicable to serum protein electrophoresis].

Zone electrophoresis for separation and quantification of serum proteins is useful in numerous pathological situations to make clinical diagnostics, to follow the evolution of a disease or to evaluate the efficiency of a treatment. The biologist must apply professional recommendations according to the official nomenclature of biological analysis. He must attach a comment to each result in order to help the physician to perform the best interpretation of the results. To answer those needs, a work of standardization of these comments has been realized by a group of biologists. They are members of the national college of biologists (CNBH). All the commentaries are assembled in a thesaurus which could be a base of ready-made comments, favouring the interpretation of serum protein electrophoresis results.

Biology↗