Angiotensin I-converting enzyme and angiotensinogen gene interaction and prediction of essential hypertension.

To prove whether the interaction between insertion/deletion (I/D) angiotensin I converting enzyme (ACE) and M235T angiotensinogen (AGT) gene polymorphic alleles could contribute to causing essential hypertension, we examined subjects from the Czech Republic (365 Caucasians total; 202 normotensives and 163 hypertensives). Subjects were genotyped for insertion/deletion polymorphism of ACE (I/D ACE, intron 16) and for M235T polymorphism of angiotensinogen gene (AGT, exon 2) by means of the polymerase chain reaction (PCR) method. The case-control approach was used. Fisher's exact test followed by Holmes's test to overcome the problem of multiple comparisons were used for the statistical analysis of data. No association of single gene allelic variants with essential hypertension was found in our population. Having compared only double homozygote combinations, the association of the DDMM genotype with essential hypertension was proven (P = 0.0081). To the contrary, IITT (P = 0.0086) was found more frequently in normotensive subjects. We conclude that the interaction of the I/D ACE and M235T AGT polymorphic alleles can contribute to essential hypertension, despite the absence of single gene associations with the condition.

Angiotensin I-converting enzyme (ACE) polymorphism and ABO blood groups as factors codetermining plasma ACE activity.

The activity of serum angiotensin I-converting enzyme (ACE) was measured in 197 unrelated healthy Caucasian subjects. Plasma ACE activity was correlated with sex, ABO blood groups, and ACE insertion/deletion (I/D) polymorphism. Marked differences in plasma ACE activity levels were observed both among the blood groups and among ACE phenotypes. The corresponding ACE activities were as follows: blood group A, 19.45+/-0.96 (mean+/-SE); O, 20.74+/-1.58; B, 26.17+/-1.40; AB, 24.77+/-1.93 (U/mL: F=4.173; p=0.006983). With ACE genotypes: II, 16.96+/-1.33; ID, 24.25+/-1.05; DD, 27.14+/-1.20 (U/mL; F=6.359; p=0.002165). No difference was observed between men and women. The I/D polymorphism and the ABO system turned out to be two independent (additive) factors influencing plasma ACE activity. Together, they are responsible for 9.56% of the phenotypic variability of ACE. We discuss the role of the ABO system in the known effects of glycosylation of proteins.

Biochemical and immunological studies in calves living over three months with a total artificial heart.

Changes in serum proteins, enzymes and isoenzymes of lactate dehydrogenase (LDH) were compared in long-term surviving calves with a total artificial heart without influencing their central venous pressure (CVP) and calves in which CVP was lowered by antihypertensive drugs administered from day 60 to the end of the experiment. Antihypertensive drugs helped keep CVP within physiological levels for longer and aided liver function as well as evidenced by the different values for the parameters studied in the two groups.

Evaluation study of calves with total artificial heart (TAH) surviving for 218-293 days of pumping.

Evaluation of five longest surviving calves among a total of 54 longterm survivors, at the Brno Research Centre was performed. These calves were treated by administration of antihypertensives and partially by electrical stimulation of the right atrium to reduce central venous pressure (CVP). Treatment for CVP was effective, as compared with two groups of 5 calves each not treated in this way, and it is assumed to be an important factor for prolongation of survival. Mineralization of driving diaphragms was present in all these calves. No preventive measures of this pathologic change were performed in this group. Another complication is hemolysis, which is partly caused by immune mechanisms initiated by administration of alpha-methyl dopa and partly by mechanical destruction due to a heavily mineralized driving diaphragm. The prevention of mineralization is another important problem for future research. Other problems, concerning the survival of TAH recipients are discussed.

The Hp, Gc, Gm, Km and beta 2-glycoprotein I genetic variants in hairy cell leukemia: no apparent association.

No significant differences could be observed when Hp, Gc, Gm, Km and beta 2-glycoprotein I phenotypes of 50 patients with hairy cell leukemia were compared with healthy unrelated adults.

Acute phase protein profiles in hairy-cell leukemia. Study in 50 patients. Effects of splenectomy.

Serum levels of 15 "positive and negative acute-phase proteins" were measured in 50 patients with hairy-cell leukemia (HCL) and in normal controls. The specific analysis of the protein levels was completed with the combined data of total serum protein and zonal electrophoresis. In HCL patients all electrophoretic globulin fractions were significantly increased, while the albumin fraction was decreased. The changes in albumin levels were more apparent in the nonsplenectomized patients, while the total protein was increased in the splenectomized cases as well as in the total HCL series. Compared with the control groups, in the nonsplenectomized patients both the mean relative increments in the level of some positive acute-phase proteins (such as orosomucoid) and the mean relative decrements in the level of some negative acute-phase proteins (such as alpha 2HS-glycoprotein) were 3 times the values found in the splenectomized patients. The occurrence of elevated values of C-reactive protein was significantly higher in the nonsplenectomized patients than in the splenectomized ones. These differences between the acute-phase proteins of the two subgroups of HCL patients were in agreement with erythrocyte sedimentation rate values. This indicates that the acute-phase protein formula is generally more favorable in splenectomized cases than in nonsplenectomized patients, at least during the first two post-splenectomy years.

Specific serum protein levels in women using intrauterine contraceptive device.

The report is concerned with the levels of 17 specific serum proteins in 46 women using plastic nonmedicated intrauterine contraceptive device (IUCD) Dana-Super. Blood samplings were carried out three times: just before the IUCD introduction, 30 and 54 weeks after the insertion of IUCD. The following proteins except haptoglobin were quantitatively determined by radial immunodiffusion: prealbumin, albumin, orosomucoid, alpha 1-antitrypsin, ceruloplasmin, alpha 2HS-glycoprotein, alpha 2-macroglobulin, hemopexin, C3-component, transferrin, beta 2-glycoprotein I, C-reactive protein and immunoglobulins IgG, IgA, IgM and IgD. Moderately increased values were found for alpha 2HS-glycoprotein and beta 2-glycoprotein I in sera taken 30 weeks after the insertion of IUCD. AT the same time the augmentation of alpha 1-antitrypsin was established. This might be evoked by the raised protease activity in biological fluids of genital region. The raise in consequence of IUCD application of transferrin and the decrease of haptoglobin at the first postinsertion examination and the decrease of hemopexin and albumin at the second may be associated with higher menstrual bleeding followed by iron deficiency. All other proteins as well as the acute phase proteins showed only minor if any differences as compared with the corresponding start values. Similarly, there is no evidence of a systemic immunoglobulin response to IUCD use.

PIP: The report is concerned with the levels of 17 specific serum proteins in 46 women using plastic nonmedicated Dana-Super IUDs. Blood samplings were carried out 3 times: just before IUD introduction, and 30 and 54 weeks after the insertion of IUD. The following proteins except haptoglobin were quantitatively determined by radial immunodiffusion: prealbumin, albumin, orosomucoid, alpha1-antitrypsin, ceruloplasmin, alpha2-HS-glycoprotein, alpha2-macroglobulin, hemopexin, C3-component, transferrin, beta2-glycoprotein 1, C-reactive protein and immunoglobulins IgG, IgA, IgM and IgD. Moderately increased values were found for alpha2HS-glycoprotein and beta2-glycoprotein 1 in sera taken 30 weeks after the insertion of IUD. At the same time the augmentation of alpha1-antitrypsin was established. This might be evoked by the raised protease activity in biological fluids of genital region. The raise in consequence of IUD application of transferrin and the decrease of haptoglobin at the 1st postinsertion examination and the decrease of hemopexin and albumin at the 2nd may be associated with higher menstrual bleeding followed by iron deficiency. All other proteins as well as the acute phase proteins showed only minor if any differences as compared with the corresponding start values. Similarly, there is no evidence of a systemic immunoglobulin response to IUD use.

Individual serum proteins and acute phase reactants in monoclonal immunoglobulinopathies. A study in patients with macroglobulinemia.

Thirty-four patients with primary macroglobulinemia (Waldenström) were compared with healthy subjects and myeloma patients previously studied regarding their levels of 17 specific serum proteins. Quantitative changes of individual serum proteins were discussed with the respect to their biologic functions. Moreover linear correlations between the serum proteins studied were examined. Selected hematological data at diagnosis of macroglobulinemia have been also reported. The concentration of IgM monoclonal component (MC) was in 88% of macroglobulinemic sera above 1000 mg/dl. If no hyperproteinemia and IgM excess are concerned 5 proteins were found elevated (orosomucoid, alpha1-antitrypsin, ceruloplasmin, C-reactive protein (CRP), hemopexin) and 7 were decreased (prealbumin, albumin, alpha2HS glycoprotein, transferrin, C3-component, IgA, IgD). Differences in mean levels of 4 proteins (haptoglobin, alpha2 macroglobulin, beta2-glycoprotein I, IgG) did not reach statistical significance. CRO was demonstrable in two-thirds of patients and the CRO levels more than 1 mg/dl were noticed in a half of them. changes of phase proteins in macroglobulinemia were similar to those observed in myeloma and other malignancies. In the present series as previously in myeloma no positive relationship could be demonstrated between the concentration of MC and individual acute phase proteins. The levels of polyclonal IgG and IgA, not IgD were found significantly higher in macroglobulinemia than in myeloma, thus polyclonal formula in macroglobulinemia being more favorable. In contrast to myeloma the IgM MC showed at 5% level no significant negative correlation with polyclonal immunoglobulins (IgG, IgA, IgD) among which positive mutual correlations were noticed.

Individual serum proteins and acute phase reactants in monoclonal immunoglobulinopathies (a study in patients with IgG myeloma).

In 92 patients with multiple myeloma and IgG monoclonal proteinemia concentrations of seventeen different serum proteins were specifically determined. Prealbumin, albumin, alpha, HS-glycoprotein, alpha-macroglobulin, transferrin and immunoglobulins IgA, IgM and IgD were significantly decreased in patients with IgG myeloma. On the contrary the means found for the typical acute phase proteins i.e. haptoglobin, orosomucoid and CRP were significantly elevated. No significant differences were demonstrated for less typical acute phase protients, i.e. alpha1-antitrypsin, ceruloplasmin and C3-component as well as for hemopexin and beta2-glycoprotein I. CRP values were strongly elevated in some sera, however in majority of patients they were within the normal limits. Negative correlation was found between monoclonal IgG and the most of the studied proteins inclusive immunoglobulins IgA, IgM and IgD. No correlation was demonstrated between the monoclonal IgG and the triad of typical acute phase proteins. Positive correlation was found between monoclonal IgG and the total serum protein and further among the proteins negatively correlated with monoclonal IgG as well as among the individual acute phase proteins. Explanation of the correlations reported has been suggested.

Multiple myeloma in two brothers. Immunoglobulin levels among their relatives.

The reports on the occurrence of myeloma in two or more members of the same family are very scanty, and until present, only about twenty observations of the familial occurrence have been reported. In this paper the observation of multiple myeloma in two brothers is described. The clinical diagnosis was confirmed by the bone marrow biopsy which showed an infiltration of abnormal plasma cells. X-ray examination of the skeleton revealed typical osteolytic changes in one patient and diffuse osteoporosis in the other. Moreoever both patients had a massive monoclonal protein fraction in serum and Bence-Jones protein in urine. In one case the monoclonal serum protein was of the IgG-K type and in the other, of the IgA-K type. Thus the antigenic determinants were different in the class specificity. Immunoglobulin studies among healthy relatives of the two brothers demonstrated much higher incidence of the polyclonal increase in one immunoglobulin class than could be expected in the population. Without evidence of monoclonal serum protein, unusally high IgA serum levels, more than 500 mg/100 ml, were observed in seven of seventeen healthy family members. This could be explained on genetic basis in connection with the familial occurrence of myeloma either by an abnormal distribution of plasma cell clones or by their abnormal activity. However, a defective control mechanism in protein synthesis may also be taken into consideration.