Universal newborn screening: A roadmap for action.

Newborn screening (NBS) prevents morbidity and mortality by screening babies for selected disorders in the first days of life so that early diagnosis and treatment can be initiated. Congenital disorders impact an estimated 8 million or 6% of annual births worldwide, and of the top five that contribute 25% to the global burden of these disorders, three can be identified and managed by NBS. There are determined pockets of activity in Latin America, Sub-Saharan Africa, and the Asia Pacific region, where partnerships among government, non-governmental organizations, academia, the private sector and civil society are developing novel NBS programs that are both saving lives and preventing disability in those who survive.

Structures and fatty acid compositions of neutral glycosphingolipids of human plasma.

Major neutral glycosphingolipids were isolated from human plasma and their structures and fatty acid compositions studied. The four neutral glycosphingolipids of plasma were characterized as Glc beta(1 leads to 1)ceramide, Gal beta(1 leads to 1)- ceramide, Gal beta(1 leads to 4) Glc beta (1 leads to 1)ceramide, Gal alpha(1 leads to 4) Gal beta(1 leads to 4) Glc beta(1 leads to 1)ceramide and GalNAc beta(1 leads to 3) Gal (1 leads to 4) Gal (1 leads to 4) Glc beta(1 leads to 1)-ceramide. The glycosphingolipids contained mostly short chain fatty acids of which most prominent was C16. Erythrocyte glucosylceramide and lactosylceramide exhibited similar fatty acid compositions as their plasma counterparts. Triglycosylceramide and globoside of erythrocytes contained almost exclusively long-chain fatty acids. In lactosylceramide obtained from "p" erythrocytes, an accumulation of long-chain fatty acids was found; this accumulation was not observed, however, in lactosylceramide isolated from "p" plasma. It was concluded that plasma and erythrocyte glycosphingolipids are synthesized at separate sites where short- and long-chain fatty acids, respectively, are available. Plasma and erythrocyte glucosylceramide, and probably a fraction of lactosylceramide, exchange between plasma and erythrocyte pools. The latter conclusion is discussed in the light of the relative roles of carbohydrate and lipid moieties of the glycosphingolipids in maintaining their association with erythrocyte membranes.

Serological and immunochemical characterization of anti-PP1Pk (anti-Tja) antibodies in blood group little p individuals. Blood group A type 4 recognition due to internal binding.

Serum samples from 13 blood group little p individuals were tested by radioimmunoassay for their IgG antibody subclass distribution against the P, P1 and Pk antigens. There was no uniform subclass distribution pattern, although all but one had IgG3 antibodies against all the P system antigens tested. Studies were performed adsorbing anti-Tja serum sequentially to columns with synthetic carbohydrate antigenic determinants within the P system coupled to silica beads (SynsorbsR). The effect on agglutinin and indirect antiglobulin titers was determined after adsorption to SynsorbsR with different P-system antigens (P1, Pk, P). Adsorption to all the three SynsorbsR was needed to eliminate or strongly reduce antibody titers. The effect on IgM, IgG, IgA as well as IgG subclass antibody binding to P, P1 and Pk antigens was also determined by radioimmunoassay and chromatogram binding assay. Anti-PP1Pk antibodies from a little p woman with repeated abortions were shown to bind to glycosphingolipid antigens prepared from one of the aborted placentae using a chromatogram binding assay. This binding was eliminated by serum adsorption to SynsorbsR with P1, Pk and P carbohydrates. Anti-PP1Pk antibodies were also shown to bind to extended structures in the globoseries, i.e. globopentaosylceramide, globohexaosylceramide (globo-H) and globoheptaosylceramide (globo-A). This binding is most probably due to antibodies recognizing internal sequences in the carbohydrate chain. Attempts were made to visualize the binding epitope of the antibodies by computer molecular modelling.

Globo-A--a new receptor specificity for attaching Escherichia coli.

Uropathogenic Escherichia coli strains designated as ONAP, based on their O negative A positive agglutination of human P1 erythrocytes, were shown to prefer the globo-A glycolipid as a receptor structure. The dependence on both the A terminal and the globoseries chain was confirmed by agglutination of human AP1, but not Ap or OP1 erythrocytes and by binding to the globo-A glycolipid on TLC plates. Neither Gal alpha 1----4Gal beta nor the A trisaccharide GalNAc alpha 1----3(Fuc alpha 1----2)Gal beta alone functioned as receptors. The bacteria thus appeared to recognize an epitope resulting from the combination of the terminal and internal structures.

Studies on a form of alpha 2-antiplasmin in plasma which does not interact with the lysine-binding sites in plasminogen.

A method for the specific determination of a form of alpha 2-antiplasmin which does not interact with the lysine-binding sites in plasminogen (NPB-AP) has been elaborated. Basically, the method is an electroimmnoassay utilizing an intermediate gel, which adsorbs the plasminogen-binding form of alpha 2-antiplasmin (PB-AP). The plasma concentration of NPB-AP in healthy individuals was determined as 0.40 mumol/1 +/- 0.14 (SD), constituting 35% +/- 11 (SD) of the total plasma alpha 2-antiplasmin concentration. During extensive plasmapheresis of two pregnant severely D-immunized women the NPB-AP form decreased significantly, while the PB-AP form increased, thus maintaining the total alpha 2-antiplasmin at an almost constant level. The increased biosynthesis rate of alpha 2-antiplasmin during the extensive plasmapheresis is thus accounted for by PB-AP indicating this form to be the one primarily synthesized and that the non-binding form is formed in plasma from PB-AP secondarily.

HLA antigens in allergic contact dermatitis.

The relationship between HLA factors and allergic contact dermatitis was examined in a series of 149 patients with unequivocal positive reactions to one or several allergens on epicutaneous testing. Nine statistically significant associations involving 6 different HLA antigens and 6 different allergens were found. Four allergens (chromium, formalin, balsam of Peru and wool alcohol) were positively associated with the B7 antigen. Furthermore chromium allergy was associated with A3, formalin allergy with A2 (negative association) and A9, nickel allergy with B8 and colophony allergy with B27. The B7 antigen and the combination A3+B7 showed significant regressions on number of allergies. The results fit the hypothesis that some HLA factors (like B7) may predispose for multiple contact allergy and others for allergen specific reactions.

HLA antigens in patients with otosclerosis.

Seventy-four (50 females and 24 males) consecutively sampled patients with otosclerosis were tissue typed for HLA A and B antigens. There was no significant increase in any A or B antigen, but the frequency of B40 was significantly lower (p less than 0.05) in patients than in blood donors. No significant difference in HLA antigen frequencies was found between men and women, or in patients with vs. without a family history of otosclerosis.

Fibronectin and other DIC-related variables in patients with moderately severe infections receiving cryoprecipitate.

Plasma fibronectin (Fn), a glucoprotein of suggested importance in host defence during infections also seems to be involved in blood coagulation and to be consumed during clot formation. Low Fn concentrations have been found in patients with DIC, but also in patients with infections without signs of overt DIC. In a randomized trial of Fn supplementation 28 patients with moderately severe infections, hospitalized in the Department for Infectious Diseases, were scheduled to receive either cryoprecipitate from 30 donors (n = 14) or 250-300 ml of stored plasma (n = 14). To elucidate the relationship between Fn plasma levels, Fn-rich cryoprecipitate infusion, and possible low-grade DIC in these patients, we measured platelet count, prothrombin complex (NT), fibrinogen, F V, F VIIIR:Ag, F VIII:C, F XII, plasminogen (Plg), antiplasmin (AP), antithrombin III (AT), kallikrein-inhibiting activity (KI) and spontaneous proteolytic activity (SPA). Compared to healthy controls, high initial values (p less than .001) were found for fibrinogen, F VIIIR:Ag, F VIII:C and SPA. Most values for platelets, F V, Plg, AP and KI were within the reference range. Low levels (p less than .001) were found for Fn, NT, F XII, AT and for the ratio F VIII:C/F CIIIR:Ag. A significant correlation was found between F XII, Plg and AT. Fn correlated poorly to the other variables. Cryoprecipitate infusion normalized the Fn concentration, but had no influence on other measured variables. Thus, although no patient had clinically overt DIC, and all survived, we observed a distinct pattern indicating activation of the coagulation system. Fn levels were low, but were not specifically related to this activation.

Fibronectin and other DIC-related variables in septic ICU patients receiving cryoprecipitate.

In a controlled study of fibronectin supplementation in sepsis, 11 ICU patients in septic shock were scheduled to receive either cryoprecipitate from 20-40 donors (n = 6) or 250-300 ml of stored plasma (n = 5) (two infusions over 24 h). We wanted to: compare some "conventional" DIC variables in the ICU (platelet count, prothrombin complex = NT, FDP) to additional variables: Fibronectin (Fn), fibrinogen (Fg), F V, FVIII R:Ag, F VIII:C activity, F XII, plasminogen (Plg), antiplasmin (AP), antithrombin (AT), kallikrein inhibiting activity (KI) and spontaneous proteolytic activity (SPA): study the effects of cryoprecipitate or plasma infusion on three variables. Samples were taken before the first infusion, and 24 and 48 h after. At onset, high levels (p less than .001 when compared to blood donors) of Fg, VIIIR:Ag and VIII:C were seen. KI levels were within the normal range. F V was low (p less than .05). Fn, NT, XII, Plg, AP and AT were markedly low (p less than .001). SPA showed great variation. When compared to 28 patients with severe infections, but not in septic shock, the ICU group had higher VIIIR:Ag (p less than .05) and VIII:C (p less than .01), and lower XII, Plg, AP and AT (p less than .001). FDP was elevated in all ICU patients. Five patients were thrombocytopenic, and in these a pattern with low levels of Plg and AT was observed. Fn did not correlate well to the other variables measured. These results indicate a marked activation of coagulation and fibrinolysis in these severely ill patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic genealogical studies of 20 north Swedish families with the rare blood group p.

In the county of Västerbotten in northern Sweden, a large number of individuals with the rare blood group p have been found. The ancestors of all known 31 cases were studied genealogically, and the data showed that about one half of all cases (15 out of 31 in 9 out of 20 families) could be traced to one gene source in the north-eastern part of the county in the middle of the 17th century. In two of the families the parents were first cousins and in three they were second cousins. In the 18th and 17th centuries genealogical connections between the parents were found in another 10 of the families.

Population studies in northern Sweden. X. The MN blood groups.

Frequencies of the MN blood groups were studied in a material of 3,312 conscripts and blood donors from the counties of Norrbotten and Västerbotten in northern Sweden. The individuals were distributed according to place of birth into 23 subpopulations. The frequency of the M gene was significantly higher in Norrbotten county than in Västerbotten county. The overall picture of geographical variation was, however, not explainable in terms of Lappish and Finnish influence. In Västerbotten county a significant departure from the Hardy-Weinberg equilibrium (excess of heterozygotes) was found. The inbreeding coefficient FST was found to be high (5.3 . 10(-3)) and significant (p less than 0.001) in Västerbotten county, but low (1.2 . 10(-3) and statistically not significance in Norrbotten county.

Effects of intensive plasmapheresis on the haemostatic system.

Intensive plasmapheresis was performed on 7 alloimmunized pregnant women. About 60% of the plasma volume was removed each day, Monday to Friday, with pauses over the weekends. This treatment resulted in drops in immunoglobulin levels to about 1/3 of the pre-treatment concentrations, whereas the haemostatic parameters studied remained within normal limits. Thus, generally the treatment (as performed in this study) does not seem to induce changes that predispose for thrombotic or haemorrhagic complications. However, in one of the patients, antithrombin III became progressively depleted over the weeks of treatment. Therefore it is suggested that the patients be screened for their haemostatic profile prior to and after a few weeks of plasmapheresis treatment.

Population studies in northern Sweden. XI. The Duffy blood group polymorphism.

Frequencies of the Duffy blood groups were studied in 222 Swedish Lapps and in a series of 3,151 Swedish conscripts and blood donors from the counties of Norrbotten and V asterbotten in northern Sweden. The conscripts and blood donors were distributed according to place of birth into 23 subpopulations. The frequency of the Fya gene among the Lapps was significantly higher than that in the Norrbotten and V asterbotten populations. The inbreeding coefficient FST for northern Sweden was found to be 2.8 . 10(-3) and significant (p less than 0.05). The Fya gene frequency in V asterbotten county was significantly higher than that in Norrbotten county. The overall picture of geographical variation of the Fya gene was not explainable in terms of Lappish and Finnish influence, it was rather contrary to the expected ethnic influence. The reason for this discrepancy is discussed.

Plasma exchange in two patients with rheumatoid vasculitis.

Plasma exchange was performed in 2 patients with classical rheumatoid arthritis, complicated in one case by necrotic vasculitis, and in the other by mononeuritis multiplex. Immediate improvement in the peripheral circulation was observed in both patients with subsequent healing of necroses and nerve function, respectively. The treatment was combined with low doses of corticosteroids and cytostatic agents. After 2 years, both patients were still receiving intermittent plasma exchanges, performed at 3-4 month intervals. A correlation between immediate circulatory improvement and lowered plasma viscosity by the plasma exchange was indicated.

HLA antigens, blood groups and serum protein groups in patients with intermittent claudication.

HLA (A and B) antigens, blood group systems (AB0, Rh, MNSs P, Kell, Lewis and Duffy) and serum group systems (Hp, Tf, Pi, C3 and C4) were studied in patients with intermittent claudication (IC) and controls. HLA antigen A 28 was significantly more common, and blood group 0 was significantly less common among the patients than among the controls. A comparison between patients with IC and those with abdominal aortic aneurysms showed a significant difference between these two groups concerning the MN blood groups.

Isolation of leukaemia-associated inhibitor (LAI)-producing cells from normal peripheral blood.

LAI, leukaemia-associated inhibitor, has previously been shown to be produced by a subpopulation of null cells in myeloid leukaemia, and has the capacity to suppress the proliferation of normal granulopoietic stem cells, CFU-GM, in vitro. In the present study, low density mononuclear cells from normal peripheral blood were separated into adherent/non-adherent, phagocytic/non-phagocytic, T-lymphocytes/non-T cells, and Fc-receptor positive and negative cells in search for LAI-producing cells in normal blood. Cell fractions enriched for NK-cells were isolated from Percoll gradients and NK-activity and LAI-production were assayed in the different fractions. Anti-Leu-2, anti-Leu-3, and anti-HLA-DR were used to deplete mononuclear cells of cells positive for these monoclonals using a panning technique. It is concluded from these studies that normal LAI-producing cells belong to a non-adherent, non-phagocytic, non-T, non-B, Fc-receptor positive population which does not express NK-activity, and which is Leu-2, Leu-3 and HLA-DR negative. The results imply that LAI may be a novel feedback regulator of the proliferative rate of granulopoietic stem cells and that LAI is produced by a small subpopulation of cells in both blood and bone marrow.