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The McLeod phenotype is an X-linked, recessive disorder in which the red blood cells demonstrate acanthocytic morphology and weakened antigenicity in the Kell blood group system. The phenotype is associated with a reduction of in vivo red cell survival, but the permanent hemolytic state is usually compensated by erythropoietic hyperplasia. The McLeod phenotype is accompanied by either a subclinical myopathy and elevated creatine kinase (CK) or X-linked chronic granulomatous disease (CGD). Seven males with the McLeod red-blood-cell phenotype and associated myopathy but not CGD, one male with the McLeod phenotype associated with CGD, and two males known to possess large deletions of the Duchenne muscular dystrophy (DMD) locus were studied. DNA isolated from each patient was screened for the presence or absence of various cloned sequences located in the Xp21 region of the human X chromosome. Two of the seven males who have only the McLeod phenotype and are cousins exhibit deletions for four Xp21 cloned fragments but are not deleted for any portion of either the CGD or the DMD loci. Comparison of the cloned segments absent from these two McLeod cousins with those absent from the two DMD boys and the CGD/McLeod patient leads to the submapping of various cloned DNA segments within the Xp21 region. The results place the locus for the McLeod phenotype within a 500-kb interval distal from the CGD locus toward the DMD locus.

A case of auto-immune hemolytic anemia caused by auto anti-K13 is described. Direct antiglobulin tests using monospecific reagents showed that IgG and the C3 component of complement were present on the patient's red cells. Eluted auto-antibody did not react with Ko or with K:--13 cells. Kell blood group antigenicity of the patient's red cells did not appear to be reduced.

An IgG autoantibody with Kx specificity was found in the blood of a 61-year-old white man. The antibody did not cause hemolysis of his own or transfused Kx-positive red cells. The patient is of common Kell blood type and does not exhibit any clinical or hematologic features of McLeod syndrome.

Microcytic red blood cell states are common clinical problems in both adult and pediatric age groups. The recent widespread availability of electronic blood cell counters for performing routine blood counts has increased the detection of microcytic red blood cells. Physicians must workup both symptomatic and asymptomatic patients with microcytic red blood cells before they can initiate proper therapy and/or counseling. The purpose of this review is threefold: (1) to discuss the causes of microcytic red blood cells in terms of disorders of decreased heme production vs. disorders of decreased globin production, (2) to review the clinical laboratory tests useful in differentiating microcytic red blood cell states, and (3) to present a practical approach for the laboratory workup of microcytic red blood cells.

Acute leukemia with bone or joint symptoms of sufficient magnitude to obscure and delay the correct diagnosis has been reported but is rarely mentioned in the recent literature, particularly in adults. The authors report an adult with rapidly fatal acute leukemia and a clinical course dominated by recurrent osteoarticular symptoms; osteoarticular symptoms preceded the diagnosis of leukemia by 3 months and delayed diagnosis and treatment. The correct diagnosis requires awareness of the osteoarticular manifestations of acute leukemia and examination of blood or bone marrow smear by an experienced observer; a biopsy specimen of bone or joint lesions or examination of cytocentrifuged synovial fluid may aid in diagnosis. The immediate cause of death in our patient was respiratory failure with prominent leukemic interstitial pulmonary infiltrates at autopsy; clinically significant leukemic pulmonary infiltrates have only rarely been reported. The authors review the literature on pulmonary and osteoarticular manifestations caused by acute leukemic infiltrates.

When red cells (RBCs) are treated with papain, one form of the U antigen, which we have named UPS (U papain-sensitive), is almost completely removed or denatured. A second form, UPR (U papain-resistant), remains unaltered on the treated RBCs. Tests on 42 examples of anti-U showed that two contained only anti-UPS, 19 contained only -UPR, and 21 contained separable -UPS and -UPR. In those sera containing both antibodies, anti-UPR was always the stronger of the two. These findings suggest 1) that UPS is located on the Ss sialoglycoprotein (glycophorin B) at a position distal to a papain-sensitive site or that the cleavage point is within the portion of the SGP that comprises UPS, and 2) that UPR is located between the papain-sensitive site and the RBC membrane. The UPS determinant was not denatured by neuraminidase, L-cysteine, trypsin, ficin, or alpha-chymotrypsin, and it was only partially denatured by pronase. The finding that RBCs treated with para-chloromercuribenzoic acid or para-chloromercuriphenyl sulfonic acid did not react with anti-UPR but did continue to react with anti-UPS suggests that the in situ configuration of UPR, but not UPS, is dependent on the presence of one or more disulfide bonds. RBCs of the S-s-U+(weak) phenotype were shown to carry markedly reduced amounts of both UPS and UPR.

Recent immigrants from Southeast Asia were screened for hematologic abnormalities using a multichannel cell counter (Coulter S), peripheral smear, free erythrocyte protoporphyrin (FEP), isoelectric focusing, and a qualitative screen for glucose-6-phosphate dehydrogenase deficiency. Hematologic abnormalities were further defined by hemoglobin electrophoresis, globin electrophoresis, HbA2 levels, and HbF levels. Of the 189 adults studied, 68 (36 percent) were hematologically abnormal, including 28 hemoglobin E (HbE) heterozygotes, six HbE homozygotes, 14 with alpha-thalassemia minor, and 10 with presumptive iron deficiency. Of the 54 people with microcytic (MCV less than 80fl) red blood cells (RBC), 52 had evidence of HbE or thalassemia and two had iron deficiency alone; five had both iron deficiency and a hemoglobinopathy. Homozygosity for HbE results in an asymptomatic condition similar to thalassemia minor with microcytic RBC, large numbers of target cells, normal or slightly reduced hematocrit and greater than 90 percent HbE. People heterozygous for HbE are asymptomatic and have hematologic findings similar to thalassemia minor with slightly reduced or low normal MCV and 25 to 35 percent HbE.

A 3-year-old black male child with X-linked chronic granulomatous disease and red cells of the rare McLeod phenotype is presented. The red cells showed acanthocytosis and did not react with anti-KL. Similarly the leukocytes were nonreactive with anti-Kx. The Xk and Xg linkage could not be investigated since all members of his family were Xg (a+).

Staging laparotomy was performed at the University of Virginia Medical Center on 111 patients with Hodgkin's disease. The operation included multiple liver and lymph node biopsies and, excepting three patients, splenectomy. The histopathology was reviewed and the 111 patients were classified as follows: nodular sclerosis, 74; mixed cellularity, 28; lymphocyte predominance, 7; and undetermined, 2. There were no deaths. Wound, pulmonary or urinary tract complications occurred in 11 patients. One case of postoperative thrombophlebitis occurred and in another case small bowel obstruction developed, and resolved without reoperation. The pathologic stage (PS) following laparotomy was unchanged from the clinical stage (CS) in 64%, reduced in 20%, and advanced in 16%. The therapy, however, was altered in 38% of the patients. Lymphangiography in 103 patients was interpreted as showing lymph node involvement in 38, equivocal involvement in 11, and no involvement in 54. Among the 92 examinations reported as either positive or negative, 77% were confirmed histopathologically, 21% were falsely positive, and 2% were falsely negative. The spleen was positive for Hodgkin's disease in 39% of cases, and in these patients with positive spleens there was no reason to suspect intra-abdominal involvement preoperatively in 21%.

Congenital dysgranulopietic neutropenia (CDN) is a recently proposed entity that describes a small subgroup of children with clinically severe neutropenia. We followed and studied a 3-year-old girl with neutropenia (less than 500/mm3) and recurrent severe infections in whom repeated marrow evaluations revealed large (30-50 microns) multinucleated promyelocytes to polymorphonuclear cells with as many as 4 to 16 nuclei or nuclear lobes, respectively. In addition to the nuclear endoreduplication, ultrastructural and cytochemical evaluation of these cells demonstrated abnormalities in granule genesis and centriole structure. Concomitantly, immunoperoxidase staining indicated that many of the granules were devoid of lactoferrin but not lysozyme. In vitro proliferation studies revealed normal to increased thymidine labeling, normal numbers of colony-forming cells, and normal colony-stimulating activity from blood and marrow mononuclear cells, findings consistent with ineffective myelopoiesis. However, serum folate, B12, and lysozyme levels were normal. The nuclear and cytoplasmic abnormalities in this patient result in an extreme example of CDN, distinct from previously described cases.

An antibody in the serum of a gravida 4, para 3 woman reacted with red cells from two of her children, her husband, and his mother, but with none of more than 2100 reference red cell samples and blood samples from donors. The reactive antigen was inactivated by 2-aminoethylisothiouronium bromide or dithiothreitol-papain treatment. The antigen was immunoprecipitated from paternal red cells with maternal antibody and shown to migrate by sodium dodecylsulfate polyacrylamide gel electropheresis as a single protein of approximately 93,000 daltons. After transfer to nitrocellulose paper by Western blotting, the protein reacted with a rabbit antibody specific for Kell protein. The chemical inactivation and electrophoretic findings were characteristic of Kell group antigens. The reaction with the rabbit antibody establishes that the "new" low incidence antigen was an epitope on Kell group protein and must be coded for by the Kell gene. It has been designated K23.

Rh-negative erythrocytes were found in the blood of an Rh-positive man suffering from myelofibrosis. Nucleated hemopoietic precursors were also circulating in his blood, and these cells had an abnormal chromosome complement from which identifiable chromosome segments had been deleted. Correlation of the serological and cytogenetic findings, combined with previous data, indicates that the Rhesus blood group locus is on the distal portion of the short arm of chromosome No. 1.

Approximately one in 250 people with autoimmunity involving their red cells have IgG autoantibodies with specificity in the Kell blood groups. Red cells of these individuals have an acquired temporary weakening of their Kell antigens. Some of the patients also have allo-anti-K in their serum. This report presents a case in which an IgG autoantibody may define a new high-incidence red cell antigen related to the Kell blood groups. The patient's Kell blood group antigens are depressed, and his serum contains allo-anti-K. It is postulated that reduced red cell Kell antigenicity is caused by enzymatic degradation, possibly of bacterial origin, and that the acquired loss of Kell antigens, the Kell-specific autoimmune state, and the serum all0-anti-K, are all related aspects of one phenomenon.

An 84-year-old woman with intestinal bleeding had marked reduction of red blood cell antigenicity in the Kell system, and a positive direct antiglobulin test caused by auto-anti-Kpb. KX antigen activity of her cell was increased, an observation which supports the belief that KX marks a precursor structure utilized in the normal Kell biosynthetic pathway. It is postulated that reduced Kell antigenicity was an acquired change that resulted from enzymatic degradation, possibly of bacterial origin.

A second example of anti-K19 has been identified in the serum of a black patient immunized by blood transfusions. The antibody was responsible for delayed hemolysis of transfused incompatible red blood cells. The patient's red blood cells are K:--19 but are otherwise of common Kell phenotype. The K19 antigen is closely associated with the Kell blood group although there is, as yet, no pedigree information to confirm that it is produced by the Kell gene. Tests on 10,757 group O blood donors have not revealed any further examples of the K:--19 phenotype.

Female genital tract involvement is a rare manifestation of disseminated coccidioidomycosis; to our knowledge, only ten patients have previously been described in the English literature. We describe a patient who seems to be unique in that she developed female genital tract coccidioidomycosis and coccidioidal peritonitis after chemotherapy for Hodgkin's disease. Coccidioidomycosis of the female genital tract is usually manifest as granulomatous endometritis and/or granulomatous tubo-ovarian disease with peritonitis. The diagnosis of coccidioidomycosis was unsuspected clinically in all 11 reported cases (including our patient); initial diagnosis was made by biopsy or culture in all 11 patients. In eight of the reported cases of female genital tract coccidioidomycosis (including our patient), clinical improvement occurred after treatment with surgery or antifungal chemotherapy; three patients died of disseminated coccidioidomycosis.

Blood group genes are inherited in a straightforward manner and their products are readily detectable. Because of this they are utilized over a wide area of scientific endeavor and provide excellent markers for use in gene mapping of the human chromosomes. Both the Rh and Duffy blood group genes have now been localized to the number 1 chromosome. Studies of a patient whose red cells exhibit mosaicism for the Rh blood group indicate that loss of the end of the short arm of chromosome number 1 is associated with loss of an Rh gene complex. The Rh gene can, therefore, be assigned with some precision to this region of the chromosome.

Five antigenic specificities are associated with the Duffy blood group system. Fya, Fyb, By3 and Fy4 are under the genetic control of a locus near the centromere of chromosome 1. Fy5 is absent from Fy (a-b-) red cells and also from cells that have the Rhnull phenotype. It appears that interaction between Duffy and Rh gene products may be necessary for synthesis of Fy5 antigen. Most Caucasians have a Fya or Fyb gene (or both), inherited by strict Mendelian principles. No evidence has been found to suggest that independently segregating Duffy modifying genes exist. The frequency of Duffy genes varies greatly in different sections of the world population. Aboriginal populations have a high frequency of Fya, Fyb is the most common gene in European Caucasians, and Negroes have a high frequency of an allele named Fy. Anti-Fya is the most common Duffy antibody and is found most frequently in the serum of Caucasians immunized by blood transfusion. The Fya antigen is about 40 times less immunogenic than K antigen of the Kell system. Only about one anti-Fyb serum is found foe every 20 that are anti-Fya. The Fya and Fyb red cell antigen receptors are inactivated by proteolytic enzymes but not by neuraminidase. Sialic acid does not appear to be an essential component of the antigen structure. Duffy antigens appear to be thermolabile membrane proteins and they are not present in a soluble form in plasma or in body secretions.

Benign cartilage-containing mesenchymal tumors of the breast are extremely rare. We describe a patient with chondrolipoma of the breast who presented with a breast mass that was detected by routine mammography. Although the mammographic features of chondrolipoma are not specific, the histologic features are diagnostic and show a well-circumscribed mass composed of benign adipose tissue and lobules of mature cartilage. We also discuss the differential diagnosis of benign mesenchymal tumors of the breast.

A 'new' Lutheran-related antibody, named anti-Lu14, reacts with approximately 2.4% of random bloods. Red cells of the rare Lu:-8 phenotype are Lu:14. The data indicate, with a high probability, that the Lu 14 antigen is a product of an allele of Lu8 and that Lu14 and Lu8 comprise a third pair of alleles at the Lutheran locus. Red cells of the original Sw (a+) propositus are Lu:14. By coincidence, he has inherited two low-incidence genes. This observation may explain the discrepancy in different families concerning a possible relationship between Swa and Lutheran. Pedigree information now suggests that Swa is not a Lutheran gene.

An 18 year old man has red cells of the McLeod phenotype in the Kell system but does not have chronic granulomatous disease. His red cells show acanthocytic morphology and there is evidence of a compensated hemolytic state. Following an accident he was transfused with blood of common Kell type and made anti-K and anti-Km. Leukocytes from the patient are deficient in Kx antigen but the cells appear to have normal function. The mother is a carrier of the variant Xk allele and has a double red-cell populatio of McLeod cells and cells of common Kell type. The family may be informative with respect to linkage between the Xk and Xg loci. One of the mother's 5 brothers and one of her maternal uncles are possible Xk:Xg recombinants.

Extramedullary tumors of hematopoietic tissue can be divided into two categories: those associated with a bone marrow disorder, myelolipomas which have no apparent relation to a bone marrow disorder. The etiology of myelolipoma is unknown and the vast majority are adrenal in location. Extramedullary myelolipomas are usually presacral in location and none of the approximately ten reported cases has been diagnosed before surgery. Although radiographic and ultrasound features of myelolipomas are relatively characteristic, they are not specific and biopsy is required for diagnosis. Microscopic diagnosis requires demonstration of benign lipomatous tissue admixed with cellular hematopoietic tissue resembling normal bone marrow. This study reports a patient with presacral myelolipoma and an unusual finding of urinary retention and azotemia associated with compression of urinary bladder neck by the myelolipoma.

A new antibody, designated anti-K18, reacts with a high frequency red cell antigen that is related to the Kell blood group system. All of more than 2,000 bloods were K:18 but K-0 phenotype red cells are K:-18.

A partially purified blood group-like substance obtained from milk showed I activity with 2 of 21 anti-I sera. With these antisera, certain human ovarian cyst substances considered to be precursors of the A, B, H, Le(a), and Le(b) substances also showed I activity comparable to the milk material. Strong I activity could be produced by one-stage periodate oxidation and Smith degradation of human ovarian cyst A and B substances, or of hog mucin A + H substance, or by mild acid hydrolysis of human saliva or ovarian cyst blood group B substance. The two sera indicate that I specificity appears at intermediate stages in the biosynthesis of the A, B, H, Le(a), and Le(a) substances. Anti-I sera differ strikingly in their specificities, indicating substantial heterogeneity of the I determinants.

The laboratory findings on a blood donor whose blood coagulation time was greatly prolonged are described. The defect was caused by a deficiency of Hageman (contact) factor, the nature of the defect being demonstrated by a simple glass adsorption test using normal serum.