[Location of amino acid substitutions in human hemoglobin. Mass spectrometric rapid analysis of tryptic peptides]. / Lokalizatsiia aminokislotnykh zamen v gemoglobine cheloveka. Mass- spektrometricheskii ékspress-analiz tripticheskikh peptidov.

Point mutations alpha 58 His----Tyr (Hb M Boston), beta 6 Glu--lys (Hb C) and beta 26 Glu----Lys (Hb E) have been identified in abnormal hemoglobins by means of tryptic hydrolysis of their alpha- and beta-chains followed by mass-spectrometry coupled with direct extraction of ions from solution. The abnormal hemoglobin Hb M Boston alpha 58 (E7) His----Tyr has been for the first time found in the blood of a patient from the USSR. This express-method is generally applicable for the identification of point mutation in proteins. The amount of protein necessary for the analysis is 100-1000 pmole. The stability, proteolytic degradation of the identified abnormal Hb's and Hb Bart's were investigated. The molecular pathogenesis of the hemoglobinopathies are discussed from the point of view of the observed properties.

[Hemoglobin M Saskatoon alpha 2 beta 2 63 (E7) His--Tyr. Structural identification, hemichrome formation and proteolytic degradation]. / Gemoglobin M Saskatoon alpha 2 beta 2 63 (E7) His--Tyr. Strukturnaia identifikatsiia, obrazovanie gemikhroma i proteolitichskaia degradatsiia.

During examination of the patient with methemoglobinemia of unclear ethiology abnormal Hb was found in the blood hemolysate. The primary structure determination allowed to identify the variant as Hb M Saskatoon with alpha 2 beta 2 63 (E7) His leads to Tyr substitution, that is the first known case of Hb M Saskatoon bearing in the Soviet Union. From the investigation of some physico-chemical properties it was concluded that not only the distal histidine can play the role of the sixth endogenous ligand at the hemichrome formation. The proteolytic degradation of met Hb M Saskatoon showed, that a shift of the distal residue (E7) to the heme ligand position does not itself lead to a considerable increase of the conformational lability of the protein as in the case of a few hemichrome forms.

[Reproductive compensation in the mothers of patients with homozygous beta-thalassemia]. / Reproduktivnaia kompensatsiia u zhenshchin-materei bol'nykh s gomozigotnoi beta-talassemiei.

The results of examination of fertility of 74 females, residents of Kutcashen and Vartashen districts of Azerbaijan, are presented. The data obtained have shown an increased fertility in females with beta-thalassemia. The value for fertility of the total everborn for mothers with beta-thalassemia is 1.25. These findings indicate that there is some degree of reproductive compensation in families segregating for homozygous beta-thalassemia. The authors conclude that beta-thalassemia gene is maintained in this population at higher values (15,83%), due to the higher fertility of the heterozygous mothers.

[Rare variants of Hb D Punjab, Hb O Arab and polymorphism of human hemoglobins]. / Redkie varianty Hb D Punjab, Hb O Arab i polimorfizm gemoglobina cheloveka.

This report describes the occurrence, study and molecular diagnostics of 40 Hb O Arab beta 121 Glu Lys cases and 4 Hb D punjab beta 121 Glu Gln cases in Bulgaria. Hematological, morphological and clinical data for 12 patients with Hb O arab are listed. Among them we observed 7 simple heterozygotes for Hb O Arab/Hb A, two double heterozygotes-compounds for Hb O/beta+-thalassemia and three compounds for Hb O/beta 0-thalassemia (the latter assumed). Also, general hematological, morphological and clinical data are presented for 4 Hb D Punjab carriers, from which two are simple heterozygotes and two are assumed, as compounds for Hb D/beta 0-thalassemia. The consideration of heterozygosity, homozygosity for both abnormal hemoglobins and of the compound state of Hb O or Hb D/beta-thalassemia or HbS types let us suggest the relative neutrality of the variants and the limitation in their distribution, depending on genetic structure of populations, where they spread. It may be concluded that human hemoglobin is characterized by marked monomorphism. At the same time, the high frequency of HbS, HbE and HbC in some populations can be well explained by contemporary selectionism; the distribution of relatively neutral Hb D Punjab and Hb O Arab with some limitations can follow Kimura's neutralism concept.

[Myocardial function in patients with hereditary hemochromatosis based on echocardiographic data]. / O sostoianii miokarda u bol'nykh nasledstvennym gemokhromatozom po dannym ékhokardiografii.

In order to reveal changes in the myocardium at the preclinical stage of heart failure, 34 patients with hereditary hemochromatosis (HHC) underwent echocardiography in the M-mode. There were 26 men and 8 women aged 24 to 59 years. The control group was made up of 20 healthy persons. The HHC patients over 35 years of age (49.5 years on the average) manifested enlargement of the left ventricular cavity, an increase of the thickness of the interventricular septum and of the posterior heart wall, and reduction of pump function of the left ventricle.

[Köln hemoglobinopathy: 3 patients in one Russian family]. / Gemoglobinopatiia Köln: troe bol'nykh v odnoi russkoi sem'e.

A rare disease with autosomal dominant inheritance was diagnosed in mother, her son and daughter. The condition was due to unstable hemoglobin Köln in 10% quantity. Clinical symptoms manifested most dramatically in a son, moderately in a daughter and slightly in a mother who had undergone splenectomy. All the hemolytic rises were provoked by antipyretics or, in occasional cases, by respiratory viral infections running with hyperthermia. To alleviate the symptoms, the son is scheduled for splenectomy.

[Physical work capacity studied by measured physical loading in patients with hereditary hemochromatosis]. / Issledovanie fizicheskoi rabotosposobnosti v usloviiakh dozirovannoi fizicheskoi nagruzki u bol'nykh naseldstvennym gemokhromatozom.

A significant decrease of work fitness was revealed in 23 patients with verified diagnosis of hereditary hemochromatosis exposed to graded physical exercise. It is assumed that the decrease of exercise tolerance in these patients may be most possibly accounted for by the lowering of myocardial contractility as a result of its injury due to iron overload. It is not excluded, however, that nonspecific dystrophic processes determined by diabetes mellitus, liver damage and coronary atherosclerosis in some cases may develop.

[Modern diagnosis and treatment methods in hereditary hemochromatosis]. / Sovremennaia diagnostika i sposoby lecheniia nasledstvennogo gemokhromatoza.

The authors followed-up 76 patients with hereditary hemochromatosis whose diagnosis was confirmed by morphological signs of liver, pancreatic, pulmonary, gastric, and myocardial changes. The most informative laboratory indices of iron metabolism were defined (transferrin saturation with iron and the level of ferritin in the serum and erythrocytes). HLA typing of probands and their relatives was recommended to specify the hereditary nature of disease.

[Electrophoretic and kinetic properties of the erythrocyte glucose-6-phosphate dehydrogenase of patients with hemolytic anemia related to a deficit in the activity of that enzyme]. / Elektroforeticheskie i kineticheskie svoistva gliukozo-6-fosfatdegidrogenazy éritrotsitov bol'nykh gemoliticheskoi anemiei, sviazannoi s defitsitom aktivnosti étogo fermenta.

Partially purified glucose-6-phosphate dehydrogenase (G6PD) was studied in erythrocytes of patients with hereditary hemolytic anemia. Kinetic and electrophoretic properties of G6PD distinctly varied both in patients--homozygotes and in maternal heterozygotes. All the enzymes studied together with the decreased activity possessed the reduced Km value for NADP and G6P. Anomalous enzymes were shown to differ from normal ones by several patterns (pH-dependency, thermostability, % of the substrate analogues utilization, electrophoretic mobility etc). The mutant variant of G6PD was not described earlier. The anomalies variant was called "Kremenchug" to indicate the place of proband origination.

[Pulmonary arterial hypertension in patients with hereditary hemorrhagic telangiectasia (Osler-Rendu disease)]. / Legochnaia arterial'naia gipertenziia u bol'nykh nasledstvennoi gemorragicheskoi teleangiektaziei (bolezn'iu Randiu-Oslera).

Pulmonary arterial pressure was studied using a noninvasive method in 23 patients with hereditary hemorrhagic telangiectasia (HHT) without clinical and x-ray signs of arterial-venous shunting in the lungs. It was established that pulmonary arterial hypertension was typical of HHT patients. A significant decrease in the volume and frequency of hemorrhages in 12 of 17 HHT patients was combined with a statistically significant decrease in pulmonary arterial pressure as a result of HBO therapy. It was assumed that pulmonary microcirculatory disorders played an important role in HHT pathogenesis and were expressed in metabolic derangement of a number of biologically active substances in the lungs resulting in the development of telangiectasia.

[Pathogenetic mechanisms of the so-called astronauts' anemia]. / Mekhanizmy patogeneza tak nazyvaemoi anemii astronavtov.

The authors analyze the literature data published in the last 20 years on clinical, laboratory, physiological, hematological and biochemical evidence obtained at preflight and postflight examinations of astronauts and experimental animals who spent 5-12 months in space. After space flights the astronauts exhibited a noticeable decrease in red cell mass, in reticulocyte count, hemoglobin and erythropoietin levels (associated with hypochromia and hyposideremia). This condition of erythron in microgravity is termed astronauts' anemia. The authors consider such anemia as an adaptive erythrocytopenic microgravity syndrome with complicated pathogenesis and suggest its model in the form of acquired transitory thalassemia.

[An algorithm for calculating and analyzing the dissociation curves of human blood oxyhemoglobin standardized by 2 and 3 allosteric ligands]. / Algoritm rascheta i analiza krivykh dissotsiatsii oksigemoglobina krovi cheloveka, standartizovannykh po dvum i trem allostericheskim ligandam.

An algorithm of an "OXYHEM" programme intended for standardization of experimentally changed human blood oxyhemoglobin dissociation curves by two (H+, CO2) and three (H+, CO2, 2,3-DPG) allosteric ligands is presented. In the former case all the points of the curve are adjusted to the values of pH--7.4, pCO2--40 mmHg, while in the latter case--to values of pH--7.4, pCO2--40 mmHg and 2,3-DPG concentration 5 mmol per 1 of PBC. Every standardized curve makes it possible to determine P50, Hill's ratio, arteriovenous difference by O2 saturation and content. A comparative analysis of the parameters calculated presents a wide range of data reflecting the state of oxygen transport hemoglobin function in the studied blood.

[Hereditary cyanosis caused by the presence of abnormal hemoglobin M in the blood: its detection, identification and properties]. / Nasledstvennye ysianozy, obuslovlennye prisutstviem v krovi anomal'nykh Hb gruppy M: vyiavlenie, identifikatsiia, svoistva.

A total of 17 cases of anomalous hemoglobin M (Hb M) were detected among subjects of varying nationalities in different regions of the USSR. The methods used for identification of Hb M Saskatoon, Hb M Boston, Hb M Iwate, Hb M Hyde Park have been described, among them--electron paramagnetic resonance. Spectral characteristics, electrophoretic mobility of these Hb in pH gradient, reaction with cyanides, thermal stability, in vitro reduction with methemoglobin reductase, isolated from donor's red blood cells, have been investigated. The functional parameters (log P50 and n) have been determined for hemolysates containing anomalous hemoglobin, as well as for chromatographically pure fractions of anomalous hemoglobins. The importance of the proper diagnosis of hemoglobinosis M has been stressed.

[Indicators of nonspecific immunity in patients with hereditary hemochromatosis]. / Pokazateli nespetsificheskoi zashchity u bo'lnykh nasledstvennym gemokhromatozom.

Parameters of nonspecific defence--complement protein function, circulating immune complex level, neutrophil phagocytic activity, completeness of the phagocytic reaction, C3c level, were evaluated in 162 carriers of hemochromatosis gene (114 homozygotes and 48 heterozygotes with respect to hereditary hemochromatosis) aged from 7 to 64 years. The analysis of the results obtained has permitted a conclusion that the suppression of the complement system function, according to the classic or alternative type, is associated with the disease pathogenesis--hyperferremia, and is caused by the damage of the immunocompetent organs and cells synthesizing individual proteins of the complement, as well as by infectious complications leading to hypocomplementemia with respect to separate components.

[Roentgenologic studies of changes of the osteoarticular system in patients with hereditary hemochromatosis]. / Izmeneniia kostno-sustavnoi sistemy pri nasledstvennom gemokhromatoze po dannym rentgenologicheskogo issledovaniia.

As many as 11 patients suffering from hereditary hemochromatosis were examined on the bones and joints with the aid of X-rays. The given disease entity was marked by very suggestive x-ray sings of changes in the cranium, in the large and small joints, as well as in the long tubular bones, and so forth.

[Dynamics of iron metabolism in patients with homozygotic beta-thalassemia after splenectomy]. / Dinamika metabolizma zheleza u bol'nykh gomozigotnoi beta-talassemiei posle splenéktomii.

Iron metabolism was followed up in patients with homozygotic beta-thalassemia after 6 to 18 months, 2-3 years, and 4 to 12 years after splenectomy. Iron reserves of the body were found gradually increasing with time, this being expressed in very high values of serum and red cell ferritins and serum iron. Noteworthy is also an increase of circulating immune complex levels and appearance of a "free" pool of iron. This necessitates regular check-ups of iron metabolism parameters and timely correction of desferal dose.

[Indicators of iron metabolism in pregnant women and infants]. / Pokazateli metabolizma zheleza u beremennykh zhenshchin i detei rannego vozrasta.

Iron metabolism parameters were studied in pregnant women in time course of trimesters depending on the pregnancy character and in newborns and infants in relation to the antenatal period. The dynamic study of serum and erythrocytic ferritins has confirmed the expediency of iron therapy during pregnancy for prevention of iron deficiency in infants. Differences detected in the rate of using iron reserves by infants of the first year of life depending on the antenatal period character have necessitated an individual approach to preventive iron therapy.

[Transferrin iron-binding capacity in hypersideremia]. / K voprosu ob obshchei zhelezosviazyvaiushchei sposobnosti transferrina pri gipersideremiiakh.

Three methods for evaluation of serum iron-binding capacity have been described: biochemical, immunological based on transferrin assay, and biophysical based on electron-paramagnetic resonance (EPR) spectroscopy of transferrin. Interrelation has been shown between transferrin and general serum iron-binding capacity. Basing on the data presented it is suggested that in secondary hemochromatosis plasma contains an iron pool that is not specifically bound with transferrin, while in primary hemochromatosis such pool was not detected.

[Erythrocytic ferritin in pregnant women and infants in the first year of life]. / Eritrotsitarnyi ferritin u beremennykh zhenshchin i detei rannego vozrasta.

Erythrocytic ferritin levels were followed up in pregnant women with reference to its course, in newborns, and in infants during the first year of life. It is shown that the level of erythrocytic ferritin remains high enough in women with complicated pregnancy attended by a sharp reduction of iron reserves. No clear dependence of erythrocytic ferritin concentration on the character of the antenatal period course was observed in infants. The highest values of erythrocytic ferritin parameters were recorded by the first month and they decreased constantly by the first year of life.

[Relation between circulating immune complexes and serum ferritin in hemosiderosis of different etiologies]. / Vzaimosviaz' mezhdu tsirkuliruiushchimi immunnymi kompleksami i ferritinom syvorotki pri gipersiderozakh razlichnoi étiologii.

Parameters of iron metabolism and humoral immunity were studied in patients with chronic diffuse diseases of the liver (cirrhosis, chronic hepatitis), beta-thalassemia major, dyserythropoiesis, hereditary hemochromatosis. High ferritin content has been recorded in the plasma of these patients, that leads to the formation of antibodies to this protein followed by the production of circulating immune complexes inducing metabolic disorders that aggravate the pathologic process. Plasmapheresis and deferoxamine therapy result in a decrease of ferritin and circulating immune complex content in the plasma, that produces a favourable effect on the patients' condition.