Genetic aspects of vitamin D-deficient rickets: genetic markers of blood]

Polymorphism of the AB0 blood groups, haptoglobin Hp, vitamin-D-binding protein (Gc), transferrin (Tf), alpha 1-antitrypsin (alpha 1-AT) and serum alkaline phosphatase (Pp) was studied in a group of children suffering from rickets (VDDR) and in a adequate control group of healthy individuals of the same sex-age composition. Considerable differences were revealed between the VDDR patients and healthy individuals in frequencies of the PIM1 and PIM2 factors on the alpha 1-AT system, r and p of the AB0 system as well as the Hp. Increase in a portion of one of the homozygotes for the Hp and for the alpha 1-AT system took place at the expense of other homozygote proportion (the latter being decreased). Heterozygotes frequencies remained intact in both compared groups. Atypical combination of phenotypes and gene frequencies was observed in a group of patients in the alpha 1-AT and AB0 systems as compared with usual distribution in European population. Higher frequencies of rare alleles of the loci under study were observed in the VDDR patients, which is partially reflected in increase in heterozygosity level in total within a cogort of patients analysed. Combination of the Hp 1-1 (Hp)--A(AB0)--M2M2 (alpha 1-AT) factors should be considered as unfavourable in rickets prognosis.     

Clinico-immunological characteristics of dysentery in persons with different blood groups]

The authors studied the frequency of distribution of the ABO system blood groups in 392 adults and 322 children suffering from acute dysentery. X2 criterion and double-factor dispersion analysis were used for statistical analysis. Deficiency of persons with B III and AB IV blood group. Phagocytosis indices were decreased in them with the elevated neutrophil damage index.     

Distribution of the ABO blood groups and the HP,TF, GC,PI and C3 serum proteins in Yakuts

In Yakut populations examined, polymorphisms of immunological and serum protein markers, including AB0 and Rhesus blood groups, HP, TF, GC, PI and C3, were revealed. Gene frequencies for the systems studied fell into the following ranges: AB0 system: r, 0.514 to 0.663; p, 0.136 to 0.306; q, 0.110 to 0.337; haptoglobin HP*1: 0.214 to 0.431; transferrin TF*C: 0.700 to 1.0; group specific component GC*1: 0.821 to 0.978; PI*M1 proteinase inhibitor (or alpha 1-antitrypsin) PIM1: 0.860 to 0.946; and third component of the complement C3*F: 0.031 to 0.143.     

Significance of persons with different blood groups in the influenza type A epidemic process

To study the susceptibility of persons with different blood groups to influenza A, the presence of infection in a group of young children placed under constant observation for 6 years (1974-1980) and in a group of donors observed during 1979-1980 was studied in different epidemic situations. The susceptibility of the persons under observation to type A influenza viruses was shown to depend both on the blood group of the subjects and on the properties of circulating viruses. Persons with group B (III) blood were more susceptible to the virus at the period when new antigenic variants and serotypes appeared, persons with group O (I) blood were more susceptible to influenza infection at the period of the circulation of virulent strains, while persons with group A (II) blood were more susceptible at the period when less virulent strains circulated. The susceptibility of persons with different blood groups was found to change as changes in the properties of the strains occurred in the process of their circulation.     

Levels of alpha 1-antitrypsin and alpha 2-macroglobulin in blood serum and its antitryptic capacity

Immunochemical analysis in combination with gel filtration and isoelectric focusing made it possible to state that in blood serum of healthy people 81.3 +/- 0.5% of administered trypsin is bound with alpha 1-antitrypsin and 18.7 +/- 0.6%--with alpha 2-macroglobulin. The latter is functionally heterogeneous, only 40% of it is bound with trypsin and in the formed complex the antigenic properties of trypsin and alpha 2-macroglobulin are lost. A great number of blood serum alpha 1-antitrypsin cannot fix trypsin. The content of such alpha 1-antitrypsin rises sharply with pathology available. In the immunochemical estimation of the organism inhibitory potential relative to proteolytic enzymes not only the amount of the inhibitor but also its functional activity should be taken into account. The data of immunochemical research of the blood serum isoelectrophoregrams show that the most considerable changes under conditions of pathology occur in alpha 2-macroglobulin.     

A study of diabetes in relation to blood groups and cholesterol levels

Summary Four hundred and sixteen patients suffering from diabetes were studied for AB0 Rhesus blood groups, to find out whether there is any association between blood group and diabetes. Though the relative incidence was found to be higher in blood group 0 and B, the difference was not statistically significant. This study confirms the earlier findings of high cholesterol levels in diabetes, particularly in patients with blood groups A and AB, and the overall mean cholesterol level as 253 mg/100 ml. This study also shows that diabetes with a cholesterol level of more than 300 mg/100 ml is a coronary risk factor.

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Zusammenfassung 416 Patienten mit Diabetes wurden nach AB0 und Rh untersucht, um Assoziationen zwischen Blutgruppe und Diabetes zu finden. Es fand sich ein leichtes, nicht signifikantes Überwiegen von 0 und B. Ein besonders hoher Serum-Cholesteral-Spiegel fand sich beim Diabetes insbesondere bei Patienten der Gruppen A und AB. Die Studie zeigt auch, daß ein Cholesteral-Spiegel von mehr als 300 mg% ein Risikofaktor für Coronarerkrankungen ist.

     

Interaction between haptoglobin subtypes and AB0 blood groups in a Bengalee population

Blood samples from 621 individuals of a Caste Hindu Population from West Bengal (India) were investigated in an attempt to find out an association between the AB0 blood groups and Haptoglobin (HP) subtypes. AB0 blood grouping was done on the basis of the agglutination test with standard anti-sera. Haptoglobin subtyping only for the HP*1 allele was done by Polyacrylamide Gel Electrophoresis (PAGE). A significant association was found with a significantly lower HP*1S allele frequency in blood group 0 versus other AB0 blood groups. A comparatively higher allele frequency of HP*1S was found in this population sample. An inverse relationship between HP*1S and HP*2 has been revealed in each blood group. It appears that the major portion of HP*1 alleles in the A, B, and AB blood groups belongs to the HP*1S allele compared to that of the 0 blood group.     

State of the nonspecific humoral factors of the body's natural resistance in patients with suppurative and septic infections having various ABO system blood groups]

The results of surveying 140 patients with severe purulent and septic infections of staphylococcal etiology, when compared with the distribution of the blood groups (as classified according to the ABO system) in 180 healthy donors, revealed that generalized purulent infections occurred most frequently in patients with blood groups A (II) and AB (IV), and more seldom in patients with blood groups O (I) and B (III). The average content of lysozyme, complement and normal antibodies to E. coli, as well as the average level of general bactericidal activity in the blood sera of the patients were considerably lower than in the blood sera of healthy donors; at the same time content of lysozyme, complement and normal antibodies in the blood sera of patients having different groups of blood did not reflect the degree of their predisposition or resistance to staphylococcal infections. The general bactericidal activity of the blood serum was found to correlate with the degree of predisposition or resistance to purulent septic infections of staphylococcal etiology to a greater extent than other characteristics.     

AB0 blood groups,inv serum groups,and serum proteins in leprosy patients from West Bengal (India)

Summary The associations between ABO blood groups and prevalence as well as type and severity of the leprosy infection were examined in 1034 Indians from West Bengal (leprosy patients and normal controls). There are no associations in the present series; combined analysis of 41 series from the literature (ours included) gives a slightly, but significantly higher frequency of groups A and AB as compared to B and 0 in leprosy patients. Groups A, B, and AB are also somewhat more frequent in lepromatous as compared with nonlepromatous leprosy.A lower level of ₂-globulins in the serum of leprosy patients of groups A and AB as compared with patients of groups B and 0, which had been described earlier in 683 leprosy patients from Thailand, was confirmed in the present series.In the Thai series of patients, a significant association between the AB0 blood groups and the Inv serum groups was observed: Persons having blood group A and AB as well as the Inv (1) type were significantly more frequent than expected. This association, however, was not confirmed in the Indian material.

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Zusammenfassung Die Beziehungen zwischen AB0-Blutgruppen sowie Häufigkeit, Typ und Verlauf der Lepraerkrankung wurden an 1034 Indern aus West-Bengalen (Lepra-Patienten und normalen Kontrollen) untersucht. In dieser Serie fanden sich keine Beziehungen. Eine kombinierte Analyse von 41 Serien aus der Literatur (unsere eingeschlossen) gibt eine gering, aber signifikant erhöhte Häufigkeit der Gruppen A und AB im Vergleich zu B und 0 bei Lepra-Patienten. Die Gruppen A, B und AB sind im Gesamtmaterial ebenfalls etwas häufiger bei lepromatöser im Vergleich zu nichtlepromatöser Lepra.Bei 683 Lepra-Patienten aus Thailand hatten wir zuvor eine Verminderung der ₂-globuline bei Gruppen A und AB im Vergleich zu B und 0 beschrieben. Dieser Befund wurde an dem indischen Material bestätigt.Bei den thailändischen Patienten fanden sich auch Hinweise für eine Beziehung zwischen AB0- und Serum Inv-Gruppen: Personen, die sowohl A oder AB als auch den Typ Inv (1) aufwiesen, waren signifikant häufiger als erwartet. Dieser Befund konnte jedoch in dem indischen Material nicht bestätigt werden.

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This study was supported by the Deutsche Forschungsgemeinschaft.     

Comparison of the inhibition of thrombin by three plasma protease inhibitors.

Human alpha-thrombin is inhibited by the circulating protease inhibitors alpha1-antitrypsin, antithrombin III, and alpha2-macroglobulin. Kinetic analyses of the inhibitor thrombin interactions were carried out utilizing either fibrinogen or the synthetic substrate Bz-Phe-Val-Arg-p-nitroanilide as substrates to determine residual thrombin activity. These studies demonstrated that the inhibition of thrombin by alpha1-antitrypsin, antithrombin III, and alpha2-macroglobulin followed second-order kinetics. The rate constants for the inhibition of thrombin by alpha1-antitrypsin, antithrombin III, and alpha2-macroglobulin are 6.51 +/- 0.38 x 10(3), 3.36 +/- 0.34 x 10(5), and 2.93 +/- 0.02 x 10(4) M-1 min-1, respectively. Comparison of the second-order rate constants and the normal plasma levels of the three inhibitors demonstrates that, under the in vitro conditions utilized, antithrombin III is five times and alpha2-macroglobulin is one-third as effective as alpha1-antitrypsin in the inhibition of thrombin.     

The association of ovarian cancer with various genetic markers

The distribution of blood groups AB0, Rh, P1, MN and Haptoglobins among ovarian cancer patients was studied. Significant associations between ovarian cancer and B(III) and MN blood groups as well as the 2-1 variant of haptoglobin were revealed. These data should be kept in mind when forming the high risk groups among population, in relation to ovarian cancer.     

Factor XIII of blood coagulation decreases the susceptibility of collagen precursors to proteolysis.

Factor XIII, the transglutaminase of blood coagulation, was found to reduce the susceptibility of collagen precursors synthesized by skin fibroblasts in vitro to proteolytic activity. Several hypotheses for the mechanism of action of FXIII are proposed. One of them is the self-association of collagen precursors as well as their association with other proteins present in the serum or synthesized by fibroblasts to form a high molecular weight complex. This complex contains, among others, collagen I and partially processed precursors (alpha 1, alpha 2, pN-alpha 1, and pN-alpha 2 chains), collagen III and its precursors (alpha 1 and pN-alpha 1 chains), fibronectin and FXIII. This study indicates that FXIII modifies the structural organisation of the synthesized products of fibroblasts and may partially protect them against proteolytic degradation.     

Distribution of AB0 and RH blood group alleles in different populations of southern Punjab, Pakistan.

The analysis of a sample of 1632 individuals from patients of the Nishtar Teaching Hospital, Multan, suggests that different ethnic groups (Araeen, Mughals, Syed, Jat, Rajputs, Baloch and Pathan) are not significantly different from another with regard to the distribution of RH blood group alleles (RH*d around 0.30). The distributions of the AB0 blood group alleles suggest that different ethnic groups are not significantly different from the average alele frequencies (AB0*A = 0.23, AB0*B = 0.33, AB0*0 = 0.47) except for the Pathan ethnic group (AB0*A = 0.35, AB0*B = 0.47, AB0*0 = 0.27). The populations of different geographic areas are not significantly different from the average allele frequencies, except for the southern district of Rahim Yar Khan (AB0*A = 0.12) and the northern district of Sahiwal (AB0*A = 0.19). The populations of Sahiwal (RH*d = 0.35) and Muzaffargarh (RH*d = 0.36) yield significantly different allele frequencies at the RH locus. The interpopulation differences can be explained by the geographic distance. There is a significant difference in the frequencies of the AB0 alleles between rural and urban populations, suggesting that rural populations maintain their isolation from urban populations. Rural and urban populations are not significantly different from one another concerning the allele frequencies at the RH locus.     

The identification of epitopic sites in human alpha 1-proteinase inhibitor.

Human alpha 1-proteinase inhibitor (alpha 1-PI) yielded nine fragments on cleavage with CNBr. The amino acid sequences of these fragments were determined. Three of these CNBr-cleavage fragments, namely fragment I (residues 64-220), fragment II (residues 243-351) and fragment III (residues 1-63), were found to bind rabbit polyclonal antibodies against chemically oxidized alpha 1-PI and mouse polyclonal antibodies against native alpha 1-PI by the Bio-Dot method (enzyme-linked immunosorbent assay on nitrocellulose). These fragments, I, II and III, inhibited by 60%, 25% and 5% respectively the binding between alpha 1-PI and the rabbit antibodies. Fragments I, II and III were subjected to proteolytic digestion, and 15, ten and five peptides were obtained from these fragments respectively. Only four of these peptides showed binding to the mouse antibodies against native alpha 1-PI. These were residues 40-63, 79-86, 176-206 and 299-323. A panel of monoclonal antibodies was prepared by conventional hybridoma technology, with chemically oxidized alpha 1-PI as the antigen. The ability of the monoclonal antibodies to bind native alpha 1-PI and CNBr-cleavage fragments I-III was determined. The monoclonal antibodies fell into three categories. Most (over 90%) belonged to group I, which was capable of binding alpha 1-PI and only fragment I. Antibodies in groups II and III bound alpha 1-PI and either fragment II or fragment III respectively. The ability of the peptides derived from proteolytic digestion of fragments I, II and III to bind three monoclonal antibodies representing each of the three groups was determined. Among all the peptides tested, only one (residues 176-206) derived from fragment I showed binding to the antibodies from group I, one (residues 299-323) derived from fragment II showed binding to the antibodies from group II, and one (residues 40-63) from fragment III showed binding to the antibodies from group III. Each of these three peptides also inhibited the binding between alpha 1-PI and the corresponding monoclonal antibodies. From these data we concluded that at least four epitopic regions (residues 40-63, 79-86, 176-206 and 299-323) were present in alpha 1-PI. Specific monoclonal antibodies to three of these sites were obtained.     

AB0 blood groups and smallpox in a rural population of West Bengal and Bihar (India)

The problem was reexamined whether there is a relationship between the AB0 blood groups and incidence, severity and outcome of smallpox. In persons suffering from smallpox, and living in rural areas of West Bengal and Bihar, India, severity and outcome of the disease were registered, and the AB0 blood groups were determined. Healthy siblings were used as controls for incidence. Four series were available:

1. 1.
   200 suffering patients and 200 controls examined during summer 1965 in the Burdwan district. West Bengal.     
   
   

Effect of the ABO blood group phenotype on the Staphylococcus aureus bacterial carrier state

326 employees of 4 medical institutions (1 regional hospital, 2 city hospitals and a maternity clinic) were examined for the presence of S. aureus carriership. Examinations were made every 3 months for 3 recent years. The results of these examinations were compared with the distribution of the blood groups in the AB0 system among the carriers. Constant and malignant carrier state was detected mainly in persons with blood group A.     

Expression of PiM-and PiZ-mutated forms of the human alpha 1-antitrypsin gene in transfected monkey COS1 cells

The PiZ mutation of the gene coding for alpha 1-antitrypsin results in a serum deficiency of this protein leading to early onset emphysema and liver disease. The PiZ gene has a Z-specific point mutation in exon V together with a point mutation in exon III which is also present in some normal (PiM) individuals. There has thus far been no system to study the effects of PiZ point mutations in tissue culture. We constructed plasmids containing alpha 1-antitrypsin cDNA synthetically altered at either exon III or exon V mutation sites and linked to simian virus 40 promoter sequences. Such constructs with the exon V mutation were transfected into monkey COS1 cells followed by analysis of expression of alpha 1-antitrypsin gene products. COS1 cells normally synthesize virtually no alpha 1-antitrypsin mRNA or protein. alpha 1-Antitrypsin mRNA is transcribed at high levels in cells transfected with either M or Z plasmids. Immunologic staining of COS1 cells within 48 h of transfection localizes alpha 1-antitrypsin protein to specific regions of the cytoplasm. This extranuclear localization is also observed with human HepG2 hepatoma cells, which synthesize alpha 1-antitrypsin at high levels, and with human SK-Hep1 hepatoma cells transfected with an M plasmid. The cloned synthetically altered alpha 1-antitrypsin genes provide a system for dissecting contributions of distinct point mutations to the pathological effects of the PiZ protein.     

The immunohistochemical detection in the human placenta of proteins related to the blood coagulation system]

Distribution in mature human placenta of plasminogen, pregnancy-associated inhibitors of proteases (pregnancy-associated protein A (PAPP-A) and alpha 2--pregnancy-associated glycoprotein, and also of not associated with pregnancy alpha 2-macroglobulin and alpha 1-antitrypsin was examined. Primary monospecific antibodies and secondary antibodies labeled with colloid gold were used. Plasminogen was detected in the fetal and maternal blood, and also on the surface of some placental villi (as thin positively stained rims). Pregnancy-associated protease inhibitors were detected in the syncytium of the villi of all histological types and also in the fetal and maternal blood. Staining for alpha 2-macroglobulin was most intensive. This antigen was detected in the maternal and fetal blood and on the surface of the villi. alpha 2-antitrypsin was detected in the fetal and maternal blood. It has been shown that both free plasminogen and its inhibitors are retained on the surface of the placental villi.     

Blood groups of the ABO system of chronic carriers of typhoid bacteria and typhoid patients in Uzbekistan]

Blood groups of the ABO system were studied in 186 chronic carriers of typhoid bacilli and in 392 patients with typhoid fever from various districts of the Uzbek SSR. In comparison with control (healthy persons), carriers displayed a higher percentage of persons with A (II) blood group (50.88 and 42.64 against 37.51 and 32.13 in control) and a lesser percentage of persons with the O (I) blood group (21.05 and 22.48 against 32.93 and 32.07 in control). These data demonstrated that predisposition of persons with the A (II) blood group to chronic typhoid carrier state was characteristic of the Asian part of the country. In comparison with control, there were significantly less persons with the O (I) blood group and more with the AB (IV) blood group. Possible correlative mechanisms between the blood group and the typhoid infection and the development of chronic typhoid carrier state is discussed.     

Association of ABO and Rh(D) blood groups with filariasis

ABO and Rh blood groups in 344 filarial patients and 320 controls matched with respect to age, community and residence are reported. An excess of B and a deficiency of AB was observed among the filarial patients. The relative risks for the B and AB were 1.53 and 0.36, respectively. Only males showed clearly significant risks. The Rh(D) blood groups revealed no association with filariasis.