Numeric terminology of erythrocyte blood group antigens

BACKGROUND: Depression in late life is a significant health problem in the United States. This study examined the relationship between depression and alcohol, cigarette use, family history, and sociodemographic factors in older adult primary care patients. METHODS: As part of a larger clinical trial, 2,732 patients in 24 primary care offices were recruited to complete a self-administered health screening survey. Depression was assessed using Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) criteria for lifetime and current depression. RESULTS: A total of 17.8% of females and 9.4% of males age 60 and over met DSM-III-R criteria for lifetime depression; 10.6% of the females and 5.7% of the males met current depression criteria. Depression was significantly and positively correlated with female gender and family history of mental health problems and negatively correlated with social contact. CONCLUSIONS: Older adults, especially women, should be considered at elevated risk for depression when a family history of mental health problems and self-report of inadequate social connection can be established.     

Disappearance of antibodies to Cromer blood group system antigens during mid pregnancy

We are reporting the case of a 94-year-old male patient with a 10-year history of Parkinson's disease, who was admitted to our hospital with acute obstruction of esophageal passage. Esophageal obstruction was refractory to endoscopic intervention. However, discontinuation of the pre-existing levodopa medication led to its resolution within hours. While dysphagia is commonly encountered in patients with Parkinson's disease, the observed succession of drug discontinuation and resolution of obstruction in this case suggests an as yet rarely described side effect of levodopa. This potential side effect should be included in the differential diagnosis of dysphagia in Parkinson's disease, especially in the case of older patients, who may exhibit an increased rate of intestinal absorption of levodopa.     

Molecular basis for the high-incidence antigens of the Kell blood group system

BACKGROUND: The Kell blood group system is complex, containing at least 21 antigens. Some antigens are organized in five allelic sets; other, mostly high-incidence antigens, may be independently expressed. In this study, the molecular basis of five high-incidence antigens in the Kell system are described. STUDY DESIGN AND METHODS: Genomic DNA sequences from K:-12 (KEL:-12), K:-18 (KEL:-18), K:-19 (KEL:-19), K:-22 (KEL:-22), and TOU-(KEL:-26) persons were sequenced and compared to those from persons with a common Kell phenotype. RESULTS: The various Kell phenotypes are due to point mutations that encode amino acid substitutions. In KEL:-18, two mutations in the same codon were noted. In the various phenotypes, the following KEL mutations were noted: in KEL:-12: A1763G, His548Arg; in KEL:-18: C508T and G509A, Arg130Trp and Arg130Gln; in KEL:-19: G1595A, Arg492Gln; in KEL:-22: C1085T, Ala322Val; and in TOU-:G1337A, Arg406Gln. A son of one of the two people with the TOU-phenotype was heterozygous, and he also had the G1337A mutation. CONCLUSION: The high-incidence antigens of the Kell blood group system are characterized by point mutations leading to amino acid substitutions. The KEL:-18 phenotype could be due to either of two point mutations in the same codon replacing arginine with tryptophan or glutamine. TOU was confirmed as a Kell system antigen, and the inheritance of the mutation was demonstrated.     

Soluble antigens from group B streptococci induce cytokine production in human blood cultures

Group B streptococcal antigens stimulated tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL-6 production in human blood cultures in a concentration- and time-dependent fashion. The minimal concentrations of type-specific polysaccharides, lipoteichoic acid, and group-specific polysaccharide required to produce these effects were, respectively, 0.01, 1, and 10 microg/ml. Cell separation experiments indicated that monocytes were the cell type mainly responsible for cytokine production. Time course studies indicated that TNF-alpha was released before the other cytokines. TNF-alpha, however, did not appear to directly induce IL-1beta, as shown by blockade experiments with anti-TNF-alpha antibodies. IL-6 levels were moderately but significantly decreased by anti-TNF-alpha. These data indicate that several products from group B streptococci are able to directly stimulate human monocytes to release TNF-alpha, IL-1beta, and IL-6. These findings may be clinically relevant, since proinflammatory cytokines can mediate pathophysiologic changes during sepsis.     

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

Three IgM human monoclonal antibodies to Jkb, and one IgM human monoclonal antibody to Jka were produced from the lymphocytes of two immunized donors. Two of the anti-Jkb monoclonal antibodies (MS-7 and MS-9) are of the IgM (kappa) isotype and one (MS-8) is an IgM(lambda). The anti-Jka monoclonal antibody (MS-15) is of the IgM(kappa) 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 micrograms/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.     

Clinical utility of plasma membrane vesicles expressing recombinant glycophorin A-encoded blood group antigens

Siotone granule, a herbal psychotropic formulation was tested for its effectiveness in various models of convulsions in animals. S. granule (100 and 200 mg/kg) offered significant protection against pentylenetetrazol-, maximal electroshock- and strychnine-induced convulsions. In hypoxic stress-induced convulsions only 200 mg/kg was effective. It also reduced percent mortality per se and rendered total protection when given in combination with sub-protective dose of diazepam (0.5 mg/kg) and MK-801 (0.1 mg/kg) against pentylenetetrazol-induced convulsions. The anticonvulsant action of S. granule was blocked by flumazenil (4 mg/kg) suggesting the involvement of GABAergic mechanism.     

Tissue antigens in the saliva of rats. Demonstration of salivary gland specific and nonspecific antigens

Antisera were raised in rabbits against the half-saturated ammonium sulfate soluble fraction of rat saliva. With these antisera, at least four antigens were demonstrated by immunodiffusion in the saliva and in a saline extract of the parotid gland; three of these antigens were also found in a saline extract of the submaxillary gland. Two of the four antigens were salivary gland specific, the other two being shared by the liver,pancreas and testis. The immunofluorescent pattern indicates that these antigens originate from the acinar epithelium of the salivary glands and probably constitute products of secretion and/or cellular turnover.     

Characterization of seven low incidence blood group antigens carried by erythrocyte band 3 protein

Recent studies have demonstrated that band 3 carries antigens of the Diego blood group system and have elucidated the molecular basis of several previously unassigned low incidence and high incidence antigens. Because the available serological data suggested that band 3 may carry additional low incidence blood group antigens, we screened band 3 genomic DNA encoding the membrane domain of band 3 for single-strand conformational polymorphisms. We found that the putative first ectoplasmic loop of band 3 carries blood group antigen ELO, 432 Arg-->Trp; the third putative loop harbors antigens Vga (Van Vugt), 555 Tyr-->His, BOW 561 Pro-->Ser, Wu (Wulfsberg), 565 Gly-->Ala, and Bpa (Bishop), 569 Asn-->Lys; and the putative fourth ectoplasmic loop carries antigens Hga (Hughes), 656 Arg-->Cys, and Moa (Moen), 656 Arg-->His. We studied erythrocytes from carriers of five of these blood group antigens. We found similar levels of reticulocyte mRNA corresponding to the two band 3 gene alleles, normal content and glycosylation of band 3 in the red blood cell membrane, and normal band 3-mediated sulfate influx into red blood cells, suggesting that the mutations do not have major effect on band 3 structure and function. In addition to elucidating the molecular basis of seven low incidence blood group antigens, these results help to create a more accurate structural model of band 3.     

The abundance and organization of polypeptides associated with antigens of the Rh blood group system

Twelve murine monoclonal antibodies, which react with human red cells of common Rh phenotype but give weak or negative reactions with Rh null erythrocytes, were used in quantitative binding assays and competitive binding assays to investigate the abundance and organization of polypeptides involved in the expression of antigens of the Rh blood group system. Antibodies of the R6A-type (R6A, BRIC-69, BRIC-207) and the 2D10-type (MB-2D10, LA18.18, LA23.40) recognize related structures and 100,000-200,000 molecules of each antibody bind maximally to erythrocytes of common Rh phenotype. Antibodies of the BRIC-125 type (BRICs 32, 122, 125, 126, 168, 211) recognize structures that are unrelated to those recognized by R6A-type and 2D10-type antibodies and between 10,000 and 50,000 antibody molecules bind maximally to erythrocytes of the common Rh phenotype. The binding of antibodies of the R6A-type and the 2D10-type, but not of antibodies of the BRIC-125-type could be partially inhibited by human anti-D antibodies (polyclonal and monoclonal) and a murine anti-e-like antibody. These results are consistent with evidence (Moore & Green 1987; Avent et al., 1988b) that the Rh blood group antigens are associated with a complex that comprises two groups of related polypeptides of M(r) 30,000 and M(r) 35,000-100,000, respectively, and suggest that there are 1-2 x 10(5) copies of this complex per erythrocyte. The polypeptide recognized by antibodies of the BRIC-125 type is likely to be associated with this complex.     

Blood group antigens in differentiated thyroid neoplasms

Alteration of cell-surface blood group antigens during malignant transformation is a well-known phenomenon that has not yet been sufficiently investigated in thyroid gland neoplasms. We evaluated 50 normal thyroid glands and 141 differentiated thyroid neoplasms (29 follicular adenomas, 30 follicular carcinomas, 56 papillary carcinomas, and 26 medullary carcinomas) both by the immunoperoxidase technique, using monoclonal antibodies against blood group antigens (A, B, H, Le(a), Le(b), Le(x), and Le(y)) and precursor substances (T, Tn, and sTn), and by affinity to the lectin from Arachis hypogea, to determine the usefulness of these antigens as tumor markers and prognostic factors. Neoplastic tissues showed immunostaining with concordant and nonconcordant expression of ABH antigens. There were statistically significant differences between normal and neoplastic tissues but not among the different neoplasms. Statistically significant differences in Lewis antigen expression were noted between normal and neoplastic tissues and between benign and malignant tumors. Tn and sTn antigen expression showed statistically significant differences between normal and neoplastic tissues. In conclusion, blood group antigens are tumor markers that are expressed more frequently in malignant than in benign neoplasms. The presence of metastases was correlated with enhanced peanut lectin receptors and a loss of A or B antigens.     

Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity

Helicobacter pylori is involved in gastritis, gastric and duodenal ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. Earlier studies already suggested a role for autoimmune phenomena in H. pylori-linked disease. We now report that lipopolysaccharides (LPS) of H. pylori express Lewis y, Lewis x, and H type I blood group structures similar to those commonly occurring in gastric mucosa. Immunization of mice and rabbits with H. pylori cells or purified LPS induced an anti-Lewis x or y or anti-H type I response, yielding antibodies that bound human and murine gastric glandular tissue, granulocytes, adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma cells. Experimental oral infections in mice or natural infection in humans yielded anti-Lewis antibodies also. The beta chain of gastric (H+,K+)-ATPase, the parietal cell proton pump involved in acid secretion, contained Lewis y epitopes; gastric mucin contained Lewis x and y antigenic determinants. Growth in mice of a hybridoma that secretes H. pylori-induced anti-Lewis y monoclonal antibodies resulted in histopathological evidence of gastritis, which indicates a direct pathogenic role for anti-Lewis antibodies. In conclusion, our observations demonstrate that molecular mimicry between H. pylori LPS and the host, based on Lewis antigens, and provide understanding of an autoimmune mechanism for H. pylori-associated type B gastritis.     

Induction of cutaneous lymphocyte-associated antigen expression by group A streptococcal antigens in psoriasis

The cutaneous lymphocyte-associated antigen (CLA) has been proposed as a homing receptor for the selective migration of memory T cells into the skin. To investigate the effect of group A streptococci (GAS) on the migration of T cells in psoriasis, CLA expression was assessed by double-staining for CD3 and the HECA-452 epitope on peripheral blood T cells from 13 patients with psoriasis, 10 patients with other inflammatory skin diseases and 12 normal controls before and after 7 days culture with a GAS sonicate, Candida albicans (control antigen) or medium. In addition, CLA+, and CLA-, CD3+ CD45RO+ subsets were isolated from individuals in each group and V beta 2 expression and proliferation to GAS studied. Mean CLA expression by freshly isolated T cells was almost identical in the three groups. After culture with GAS, T cells from the psoriatic patients and control showed a significant increase in mean percentage CLA+ expression compared to medium (P < 0.002, P < 0.05, respectively). This induction was inhibited by the addition of anti-IL-12 antibody. However, in psoriatic patients, but not in controls, the GAS-induced increase was significantly greater than that of C. albicans (P < 0.002) and was accompanied by a decrease in T cells positive for the peripheral lymph node homing receptor, L-selectin (P < 0.05). The percentage of V beta 2+ T cells was markedly higher in the CLA+ than in the CLA- T-cell subset in psoriatic patients (P < 0.01) and controls; both subsets proliferated to GAS, in each group. These findings suggest a differential modulation of specific tissue homing receptors on T cells by GAS in psoriasis.     

HLA antigens in psoriasis. A family study

HLA antigens were determined in 14 Finnish families with psoriatic members. The pedigrees of all families are presented. The results showed a clear association between HLA B13 and inheritable psoriasis, for all the 14 HLA analysed psoriatic patients in four families had B13. In one family all five psoriatic patients had the haplotype HLA-A10, Bw17; in two other families the association between Bw17 and psoriasis was less obvious. In three families six of the eight children with the haplotype A1, Bw37 had psoriasis. In all these families one parent had psoriasis or psoriatic relatives and the other parent contributed A1, Bw37. It is suggested that Bw37, in association with other genetic factors, indicates a high risk of developing psoriasis. In one family both the father with psoriatic arthritis and the son with post-urethritic Reiter's disease had A2, B27. This haplotype was also possibly associated with psoriatic arthritis in two families.     

Polymorphonuclear neutrophils in saliva and blood: a comparative study of morphology, function and phenotype

Sixteen beagle dogs were injected intradermally with Rickettsia rickettsii. The dogs were divided into four groups (n = 4): 1) infected, non-treated control; 2) infected, treated with doxycycline; 3) infected, treated with doxycycline and an anti-inflammatory dose of corticosteroid; and 4) infected, treated with doxycycline and an immunosuppressive dose of corticosteroid. Thoracic radiographs were made and ocular fluorescein angiography was performed on days 6, 10, 17 post-inoculation. A mild interstitial lung opacity was noted in 4/16 dogs on day 6, 5/16 on day 10 and 3/16 on day 17 post-inoculation. Increased retinal vascular permeability was noted in 8/16 dogs on day 6, 3/16 on day 10 and 1/16 on day 17 post-inoculation. Correlation between the presence of radiographic and retinal lesions was not significant (p = 0.08). Eleven, naturally infected, dogs with thoracic radiographs and a final diagnosis of RMSF were also evaluated. Four of the 11 dogs had an unstructured interstitial pattern. Dogs with acute, experimentally-infected or naturally-occurring RMSF may have subtle pulmonary changes characterized by an unstructured interstitial pattern.     

Linguistics in blood group serology

With a view to terminological uniformity, blood group serologists, immunologists and transfusion physicians should refer only to the "ABo' (zero) in stead of the "ABO' system. They also should use "HLA antibodies' in stead of "anti HLA antibodies'. The new Dutch spelling "resus' in stead of "Rhesus' is incorrect from a historical point of view.     

Preparations of antigens and immunoadsorbents corresponding to the Streptococcus group A cell-wall polysaccharide

The allyl glycosides of a tri-, penta- and hexasaccharide corresponding to the Streptococcus Group A cell-wall polysaccharide were coupled to solid or soluble supports to give immunoaffinity columns and neoglycoproteins, respectively. Cysteamine hydrochloride was added to the allyl glycosides and the resulting cysteamine adducts were used for subsequent coupling to linkers via the amine functionality. The tri- and penta-saccharide cysteamine adducts were coupled directly to the azalactone-derivatized 3M Emphase Biosupport Medium AB 1 to yield two affinity columns. The penta- and hexa- saccharides were coupled to bovine serum albumin or ovalbumin via the conjugate addition of the epsilon-amino groups of lysines on the proteins with the N-acryloylated sugars or the oligosaccharide-squarate adducts, derived in turn from the cysteamine adducts. The efficiency of the above methods is compared.     

Ultrastructural alterations caused by immunological reactions after intracardiac injection of allogeneic antibodies against blood group antigens: an experimental study using the in vitro whole-rat embryo culture

The effects of intracardiac injection of 0.5 microliter allospecific hemolyzing rat-antirat antibodies, directed against the blood group antigens, on the endothelium of the dorsal aortae were studied in 9-14 somite-staged Wistar and RIV:Tax rat embryos, using both transmission electron microscopy (TEM) and immunoelectron microscopy (IEM). In a TEM study it was further investigated if either apoptosis or cell necrosis occurred as a result of the forementioned intracardiac injection. The results were compared to ultrastructural findings of the dorsal aortae in sham- and noninjected rat embryos of the same gestational age. In the control rat embryos, the aortic vascular wall consisted of a single continuous layer of endothelial cells. No clear basal lamina was present in TEM. Furthermore, no immunoreactivity against the endothelium or the intravascular blood cells was noted. Embryos injected with hemolyzing rat-antirat antibodies displayed clefts or pores, and diaphragmatic fenestrations of the endothelial lining of the dorsal aortae after 2 hr. Alterations resembled those induced by vasoactive mediators such as histamine, serotonin, bradykinin, and prostaglandins. The above changes had disappeared 4 and 6 hr after injection with complete restoration of the endothelial lining. Immunogold staining demonstrated Ig depositions along the luminal side of the endothelium, in the vicinity of the intercellular spaces, and in the subendothelial space of the dorsal aortae. Numerous particles were seen located inside intracytoplasmatic vesicles, indicating involvement of transcytoplasmatic transport as well as intracytoplasmatic phagocytosis. Similar depositions were observed in and around intravascular embryonic blood cells. Apoptosis, or programmed cell death, an important component in immunological reactions, occurred in rat embryos injected with hemolyzing rat-antirat antibodies. The excessive amount of apoptosis seen in this study is in accordance with the pathogenetic cell degeneration found in our earlier studies. Cell necrosis was not observed. The results from this study indicate that the endothelium of the dorsal aortae and intravascular blood cells only display a transient reaction following injection with hemolyzing rat-antirat (RAR) antibodies. The temporary reaction is presumably due to the release of vasoactive mediators. The smaller vessels and capillaries are still in an earlier stage of development, displaying fenestration, making them more susceptible for injury after immunological interaction. The results are indicative that the pathogenetic effect of the immunological reaction after intracardiac injection takes place at the level of the microcirculation by "switching on" apoptosis. Programmed cell death is essential in embryogenesis and development. Therefore excessive apoptosis, i.e., inappropriate apoptosis, will eventually induce congenital malformations.