Further Observations on the Blood Factors RhA, RhB, RhC and RhD

The findings in 18 cases of individuals with Rh_o-positive blood who had antibodies in their serum resembling anti-Rh_o in specificity are briefly summarized. One interesting finding is the relatively high frequency of such individuals among Negroes, especially with the blood type Rh^d_o and Rh^abd_o. The significance of these findings is discussed.     

The Rho Variant-Du

A simplified test for the D^u factor employing a reagent containing 25 per cent serum albumin, the "stick" technic to introduce cells and forceful cen-trifugation has been given an extensive trial in a routine blood bank operation. A routine preliminary test with anti-D gave 5,051 negative reactions among 26,753 bloods tested. The D^u tube test was then performed on the former with an anti-CDE reagent in parallel with the indirect antiglobulin test done with anti-D. All bloods positive by one or both tests were tested further for D antigens by an anti-D elution technic; they were also tested for Rh-Hr factors.
Among the 126 bloods positive by elution for the D^ufactor, 122 and 126 were positive respectively by the antiglobulin and the D^u tube tests. The two tests were in agreement on all eight of the type ccD^uee bloods found in the study. The D^utube test, as done with anti-CDE, gave no false negative reactions. It is, thus, concluded that bloods which are negative with this test will be type ccddee and can be labeled "Rh negative tested for D^u. Serological factors which might account for sensitivity of the D^u tube test's being the equal of the antiglobulin test are considered, as are the probabilities of the existence of D variants so weak that they could not be detected by either test.     

Erythrocyte Li+/Na+ and Na+/H+ exchange, cardiac anatomy and function in insulin-dependent diabetics

It has been proposed that an increased activity of cell membrane Na+/H+ exchange, mirrored by increased erythrocyte Li+/Na+ exchange, may facilitate cell hypertrophy and hyperplasia. Patients with insulin-dependent diabetes mellitus may develop a specific cardiomyopathy with systolic and diastolic abnormalities and increased thickness of the left ventricle. Therefore, we have investigated the relationships between erythrocyte Li+/Na+ and Na+/H+ exchange and echocardiographic parameters in 31 male insulin-dependent diabetics (aged 17-68), in good metabolic control. Three had untreated mild hypertension. In all patients the urinary albumin excretion rate was less than 200 micrograms min-1. Ten patients had a Li+/Na+ countertransport higher than 0.37 mmol l-1 cell h-1, the upper normal limit for our laboratory (0.49 +/- 0.10, mean +/- SD). In comparison with the patients with normal countertransport, they had increased interventricular septum thickness and relative wall thickness (h/r). End diastolic volume and cardiac index were reduced while blood pressure and urinary albumin excretion rate were similar. In the whole study group, interventricular septum thickness was significantly correlated to Li+/Na+ exchange (r = 0.61, P less than 0.001) and Na+/H+ exchange (r = 0.35, P less than 0.05), independently of the effect of age and blood pressure. Posterior wall thickness was correlated to Li+/Na+ exchange (r = 0.38, P less than 0.05) and h/r to Li+/Na+ exchange (r = 0.41, P less than 0.05) and to Na+/H+ exchange (r = 0.44, P less than 0.05). Li+/Na+ exchange was negatively correlated to cardiac index (r = -0.37, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

IgG anti-Jka/Jkb antibodies are unlikely to fix complement

Antibodies in the Kidd blood group system show a great deal of serological variability, are notoriously elusive and hence evoke difficulties in detection. However, they have been regularly reported as causing severe immediate or delayed haemolytic transfusion reactions and this clinical potential has been largely attributed to their complement binding ability.
In initial investigations on 43 anti-Jk^a/Jk^b sera with a range of titres of IgG antibody only a few seemed to fix complement, though following repeated tests on 20 of these sera a further five were shown to bind complement, making a total of 12 (27.9%) showing evidence of complement binding. Twenty-three sera were unavailable for re-testing. Subsequent tests revealed that only those sera which showed direct agglutination or were positive with an anti-IgM reagent in an indirect antiglobulin test (IAT) fixed complement. Evaluations on the IgG fractions of six selected potent anti-Jk^a sera failed to reveal any complement-fixing ability although all the original sera bound complement avidly and contained variable amounts of IgM antibody, some at very low subagglutinating levels.
These findings challenge past perceptions and give cause for reflection on the changing methodologies and strategies which could unduly compromise the detection of these potentially clinically damaging antibodies.     

The Expected "Bombay" Groups OhA1 and OhA2

An American family of English extraction is reported in which two Oh ("Bombay") members have transmitted A ₂ genes to their children thus demonstrating that the expression of the gene A ₂, like that of the gene B , can be suppressed in this phenotype. Another American family, of French extraction, shows with a high degree of probability that the expression of the gene A ₁ can be similarly suppressed.     

Human monoclonal antibodies to human blood group antigens Kidd Jka and Jkb

Summary. Three IgM human monoclonal antibodies to Jk^b, and one IgM human monoclonal antibody to Jk^a were produced from the lymphocytes of two immunized donors. Two of the anti-Jk^b monoclonal antibodies (MS-7 and MS-9) are of the IgM(κ) isotype and one (MS-8) is an IgM(λ). The anti-Jk^a monoclonal antibody (MS-15) is of the IgM(κ) isotype. They are all specific for their respective antigens, and give positive agglutinations in saline by the immediate spin technique, even against Jk(a + b +) cells. The heterohybridomas have been shown to be suitable for bulk culture and produce levels of antibody that reach 18 μg/ml in the spent culture supernatant. They offer considerable advantages over currently available reagents in terms of stability, simplicity and speed of use, and will provide a reliable and unlimited supply of what are at the moment rare and unsatisfactory antibodies.     

An Anti‐Diegob (Dib) Antibody Occurring during Pregnancy

A case is reported in which fetal erythrocytes were sensitized by IgG maternal anti‐Di^b, which indicates that Di^b incompatibility must be considered in cases of erythroblastosis fetalis caused by a high‐frequency erythrocyte antigen, especially in persons of Mongoloid or American Indian extraction.     

Another Example of Anti-Jsa

Anti-Js^a resulting from transfusions is reported. The antibody was not detectable six months later. Repeated antibody screening is advised in patients treated by frequent transfusions.     

The Rh Antigen EW

A second white family carrying E^w is reported, the antigen being traced through three generations.     

Another Example of Anti-Jsa

The fourth example of anti-Js^a probably stimulated by blood transfusion is described. Thirty-four of 244 Negroid bloods were Js(a+). All 103 Caucasians and three Indian blood samples were Js(a–).     

The Rho Variant — Du

In a survey of 18,365 bloods for the incidence of the D^u factor, in a population comprised approximately of 72 per cent Caucasoids, 15 per cent Negroids, 10 per cent Mexicans and 3 per cent Orientals, 78 D^u bloods were found of which seven were type ccD^uee. Of the latter, five came from Negroids and two from Caucasoids; the frequency among the two populations approximates respectively one in 6,000 and one in 500. In the general population of this region it is one in 2,500.
The degree of reactivity of the type ccD^uee found in this study was that of the "low grade" variety. However, from the remaining 71 "low grade" D^u bloods, substantially weaker examples were found among type CcD^uee and ccD^uEe. The indirect antiglobulin and ficinized cell method readily detected type ccD^uee; however, among the weaker variants, the antiglobulin method gave the more consistent results.
It is concluded, therefore, that type ccD^uee does occur in this area with a frequency that is considered significant and that its detection rests on the antiglobulin or other equally sensitive methods.     

Local and systemic effects of Na+/K+ ATPase inhibition

The positive inotropic and electrophysiological effects of cardiac glycosides on cardiac muscle are mediated through inhibition of Na⁺/K⁺ ATPase by binding to a specific extracytoplasmic site of the a-subunit of this enzyme. The inhibition of Na⁺/K⁺ ATPase affects ionic flux and produces direct local effects on cardiac contractility, electrical excitability and conduction, but also profound systemic effects mainly as a result of haemodynamic changes. These effects are responsible for beneficial therapeutic as well as toxic effects.
Inhibition of Na⁺/K⁺ ATPase results in potentiation of K⁺ loss from cells and Na⁺ entry into cells, so consequently affects action potential generation and propagation. This also underlines the potentiation of certain effects of cardiac glycosides by hypokalemia and hypomagnesaemia, and the effects of changes in calcium homeostasis on the cardiac glycoside pharmacodynamics. Furthermore, inhibition of Na⁺/Ca⁺⁺ exchange enhances Ca⁺⁺ mobilization and promotes contractility. These effects (locally and systemically) differ greatly, depending on the haemodynamic status and myocardial oxygen supply.
Cardiac glycosides have less affinity for Na⁺/K⁺ ATPases at other sites (e.g. skeletal muscle), but some extracardiac effects (vascular effects, effects on colour vision, CNS and autonomic effects, renal effects) may be related to Na⁺/K⁺ ATPase inhibition.     

Rapid detection of anti-Lub with recombinant Lub protein and the particle gel immunoassay

BACKGROUND: Until now, it was not possible to identify antibodies to red blood cells (RBCs) except with pretyped RBCs. Here, a novel method with particles coated with recombinant Lu^b protein for detection of anti-Lu^b is described.
STUDY DESIGN AND METHODS: Prokaryotic recombinant Lu^b proteins were generated and coupled onto superparamagnetic particles coated with streptavidin. The coated particles were tested in the presence of different serum and plasma samples (13 anti-Lu^b, 6 anti-Lu^a, 20 other antibodies, and 35 serum samples from blood donors) with the particle gel immunoassay (ID-PaGIA).
RESULTS: Lu^b-coated particles reacted with all 13 samples containing anti-Lu^b, but not with any samples lacking anti-Lu^b. In addition, the anti-Lu^b titers were higher with Lu^b-coated particles than with Lu(a–b+) RBCs in almost all cases.
CONCLUSION: Recombinant blood group proteins may be able to dispense with the need for RBCs for identification of certain RBC alloantibodies.     

Erythrocyte Na+-H+ exchanger and Na+-Li+ countertransport activity in primary aldosteronism

Abstract. Several authors have described increased Na-H exchanger activity in essential hypertension but no data are available in secondary forms of hypertension such as primary aldosteronism. We measured Na-H exchanger kinetics together with Na-Li countertransport V _max in the erythrocytes of eight patients with primary aldosteronism and in 15 normotensive control subjects. Plasma aldosterone, plasma renin and plasma potassium were also evaluated. Na-H exchanger V _max appear to be increased in patients with primary aldosteronism and Hill's n , an index of co-operativity amongst intracellular proton binding sites, was significantly lower in patients than in controls. No statistically significant differences were found between affinity for intracellular protons (K50%) and for Na-Li countertransport V _max between the two groups studied. We were unable to find any correlations between Na-H exchanger V _max and Na-Li countertransport V _max in the two groups considered as a whole. From the present data Na-H exchanger overactivity would not appear to be a specific feature of essential hypertension but seems to be characteristic in patients with primary aldosteronism.     

Six Additional Examples of Anti-Ata

Six additional examples of anti-At^a are reported. Four of the antibodies studied prior to the publication of the original anti-Ata (Mrs. August.) were known to be identical to each other but the antibody had never been assigned a name. Besides the propositi, three additional At(a—) people have been found among the siblings. The propositi in these six families as well as that of the original report are Negroes indicating the At(a—) phenotype to be a predominantly Negro characteristic. The characteristics of the sera indicate the antibodies are IgG but there is no clinical evidence that they caused hemolytic disease of the newborn. Many additional antigens of high frequency have been excluded from being the same as At^a. Further information excluding the possible allelic relationship of At^a to known factors of low frequency has been obtained.     

A Further Example of Anti-Kpa

A further example of anti-Kp^a accompanied by anti-Kell is presented. The two antibodies were easily separated and when absorbed and eluted behaved as expected.     

The Third Example of Anti-hrS

A third example of anti-hr^S, first described by Shapiro in 1960, was detected in the serum of a Bantu woman whose newborn infant suffered from mild hemolytic disease of the newborn.