True hermaphroditism in a child with a chimeric XX/XY chromosome, a double erythrocyte population and an unusual Lewis (a+ b+) phenotype

A 2 years-old Korean girl is seen because of ambiguous external genitalia. Surgical exploration shows the right gonad to be an ovary and the left one to be an ovotestis, thus demonstrating a true hermaphroditism. Cytogenetic studies of peripheral lymphocytes reveal a mixture of 46,XX and 46,XY cells, with a predominant XX cell line. The patient's red cells are composed of two distinct populations differing in three genetically independent blood group systems. The ratios of the two cell lines in various tissues, especially among the cells secreting Lewis antigens, appear to be very different and suggest several hypothesis to explain the highly unusual red cell Lewis phenotype Le (a+ b+). We conclude to a dispermic chimera, however the adopted status of this child prevents any identification of the maternal or paternal contributions. Because of the physical aspect it was decided to remove the ovotestis, to repair the external genitalia and to bring up this child as a female.     

The ultimate and transient effects of a catastrophe which eliminates a fraction of an age group in a population

A catastrophe which eliminates a fraction of an age group in a population is investigated, and the asymptotic reduction in the population is obtained. It is shown that the loss of a youthful group is ultimately more damaging than the loss of an older group. An investigation of the transients following a catastrophe shows that they are reduced to less than 1% of the steady state after a small number of generations.     

Prenatal genotyping for the RhD blood group antigen: considerations in developing an accurate test

Experience performing prenatal genotyping for RHD has shown that consideration must be given to developing a molecular test capable of detecting recombination/gene conversion events involving the RHD and RHCE genes that can lead to erroneous results. Out of 50 prenatal RHD tests performed over the past 5 years, four samples were encountered that gave false-positive results. In only one of the tests, incorrect results were issued to the physician. In the other three instances, the erroneous nature of the test results was revealed through the analysis of multiple regions of the RHD gene and, more importantly, because the mother, and sometimes the father, were tested in parallel with the fetus. In an extension of the observations obtained from the prenatal testing program, a large panel of RhD-negative blood donors were subjected to molecular analysis of the RHD gene. Of 1,183 donors screened, 187 were found to phenotype as RhD negative. Of the 187 donors confirmed RhD negative serologically, 22 (11.8%) were found to retain remnants of the RHD gene that, depending upon the characteristics of the molecular assay performed, could lead to a false-positive result in a genotyping assay. On the basis of the experience presented here, it is recommended that any molecular RHD assay include an analysis of multiple areas of the RHD gene so as to allow for the detection of recombination/gene conversion events between the RHD and RHCE genes. Moreover, it is strongly recommended that the mother (at a minimum) and father be subjected to molecular analysis simultaneously with the fetus to confirm that the known phenotypes of the parent(s) are consistent with their respective genotypes.     

Glycerated hemoglobin, alpha 2A beta 2(82) (EF6) N epsilon-glyceryllysine. A new post-translational modification occurring in erythrocyte bisphosphoglyceromutase deficiency

A new minor Hb fraction initially designated Hbx, has been found in the hemolysate of an erythremic patient that we have previously described with a complete erythrocyte bisphosphoglycerate mutase (EC 5.4.2.4) deficiency. Hbx (3.5% of the total) was detected by isoelectric focusing and exhibited electrophoretic and chromatographic properties similar to those of several variants of the Hb central cavity. By density fractionation of red cells, it was demonstrated that Hbx was an aging hemoglobin as in the case of glycated Hb A1c. Functional studies revealed a low oxygen affinity and almost complete inhibition of the allosteric effect of the organic phosphate effectors. Structural studies demonstrated an absence of tryptic cleavage between the peptides beta T9 and beta T10 suggesting the presence of an adduct on Lys beta 82 or on a neighboring residue. Fast atom bombardment mass spectrometry and a specific enzymatic assay with glyoxylate reductase demonstrated that the beta 82 adduct was a glycerate moiety. It was concluded that Hbx was a glycerylated Hb, alpha 2A beta 2(82) (EF6) N epsilon-glyceryllysine, to our knowledge the first example of glycerylated protein. The mechanism of formation of glyceryl Hb, which was found in the four studied subjects with a bisphosphoglyceromutase deficiency, remains to be determined.     

An increase in the ratio of thromboxane A2 to prostacyclin in association with increased blood pressure in patients on cyclosporine A

The aim of this study was to determine the effect of two years of treatment with cyclosporine A on blood pressure and the rates of secretion into the circulation of the vasoconstrictor thromboxane A2 and the vasodilator prostacyclin. Seven patient suffering from multiple sclerosis took part. Their blood pressures and urinary concentrations of 2,3-dinor-thromboxane A2 (a major urinary metabolite of thromboxane A2) and of 2,3-dinor-6-keto-prostaglandin F1 alpha (the major urinary metabolite of prostacyclin) were determined at the end of two years of treatment with cyclosporine A, and once again three months after cessation of this treatment. No other drugs were given during or after cyclosporine A. Mean arterial blood pressure was 113 +/- 5 mmHg (mean +/- SEM) during the cyclosporine A treatment, but fell to 94 +/- 4 mmHg after the three-month's wash-out period. Urinary excretion of the thromboxane metabolite decreased slightly from 674 +/- 150 pg.mg-1 creatinine during cyclosporine A therapy to 503 +/- 90 pg.mg-1-creatinine after the end of therapy. At the same time the prostacyclin metabolite increased significantly from 82 +/- 17 pg.mg-1 creatinine to 113 +/- 23 pg.mg-1 creatinine (P less than 0.05). The ratio of 2,3-dinor-thromboxane B2 to 2,3-dinor-6-keto-prostaglandin F1 alpha (taken as a measure of vasoconstrictor prostanoid activity) fell significantly from 8.4 +/- 0.8 4.7 +/- 0.6 (P less than 0.005). The shift in prostanoid production observed during cyclosporine A treatment could be one causal factor for the hypertensive and thromboembolic events associated with the use of this drug.     

Heterogeneic expression of blood group A and H isoantigens in bladder tumors: association with nuclear volume

Intratumor heterogeneity is a major problem in immunodiagnosis and treatment of carcinomas. To elucidate the well-known heterogeneity in transitional-cell carcinomas of the ability to express blood group ABO isoantigens, a stereological estimate of the mean nuclear volume in areas expressing blood group antigens was compared to the estimate from areas of identical pathological grade at which antigen expression was deleted. Four microscopic fields were examined from antigen-positive and four from antigen-negative areas in sections from 21 blood group O and 20 blood group A individuals. The sections were stained before examination by an indirect peroxidase method using monoclonal anti-H and anti-A antibodies. The mean nuclear volume increased, as expected, with increasing pathological grade. In blood group O individuals the mean nuclear volume was 241.5 microns 3 in antigen-positive areas and 338.2 microns 3 in antigen-negative areas (2p less than 0.0005) of identical pathological grade. In group A individuals the mean nuclear volume was 217.1 microns 3 in positive areas and 351.1 microns 3 in corresponding negative areas (2p less than 0.0025). The variation in volume parameter was essentially caused by a true variation between tumors (greater than 82%). The results indicate a complex biological mechanism associated with the cellular ability to express blood group antigens.     

Incompatible A antigen expressed in tumors of blood group O individuals: immunochemical, immunohistologic, and enzymatic characterization

Monofucosyl type 1 chain A (type 1 Aa) and difucosyl type 1 chain A (ALeb), but not other types of A antigens, have been detected by application of carrier type-specific monoclonal anti-A antibodies (AH21 and HH3) in colonic tumors of blood group O individuals. An A-transferase activity (UDP-Gal-NAc:H-alpha-GalNAc transferase) was demonstrated in the extract of one of the O tumors expressing A antigen. The incidence of A antigen expression in O tumors was found to be two out of 15 cases, based on TLC immunostaining of glycolipid extracts, and five out of 50 cases, based on immunofluorescent staining of tumors with AH21 and HH3 antibodies.     

An analysis of the blood group composition of a population in Brittany, the Bigoudens

Data are presented on the blood groups of the Bigoudens. Deviations from the expected Hardy-Weinberg distribution are interpreted as the result of a recent mixing of previously separated groups, in addition to the effect of silent alleles and inbreeding. Special reference to the historical evidence of their origin is made.     

AQP3 deficiency in humans and the molecular basis of a novel blood group system,GIL

AQP3 is a water and glycerol channel present on human erythrocytes and in various tissues. By protein and molecular biology analysis, two unrelated probands who developed alloantibodies to the high frequency antigen GIL were found to be AQP3-deficient. The defect is caused by homozygous mutation affecting the 5' donor splice site of intron 5 of the AQP3 gene. This mutation causes the skipping of exon 5 and generates a frameshift and premature stop codon. Functional studies by 90 degrees light scattering using a stopped-flow spectrometer revealed the absence of facilitated glycerol transport across red cell membranes from the probands, but the water and urea transports were normal. Expression studies into COS-7 cells followed by flow cytometry analysis showed that only cells transfected with AQP3 cDNA strongly reacted with anti-GIL antibodies. These findings represent the first reported cases of AQP3 deficiency in humans and provide the molecular basis of a new blood group system, GIL, encoded by the AQP3 protein.     

Estimation of nonpaternity in the Mexican population of Nuevo Leon: A validation study with blood group markers

A method for estimating the general rate of nonpaternity in a population was validated using phenotype data on seven blood groups (A₁A₂BO, MNSs, Rh, Duffy, Lutheran, Kidd, and P) on 396 mother, child, and legal father trios from Nuevo León, Mexico. In all, 32 legal fathers were excluded as the possible father based on genetic exclusions at one or more loci (combined average exclusion probability of 0.694 for specific mother-child phenotype pairs). The maximum likelihood estimate of the general nonpaternity rate in the population was 0.118 ± 0.020. The nonpaternity rates in Nuevo León were also seen to be inversely related with the socioeconomic status of the families, i.e., the highest in the low and the lowest in the high socioeconomic class. We further argue that with the moderately low (69.4%) power of exclusion for these seven blood group systems, the traditional critical values of paternity index (PI ≥ 19) were not good indicators of true paternity, since a considerable fraction (307/364) of nonexcluded legal fathers had a paternity index below 19 based on the seven markers. Implications of these results in the context of genetic-epidemiological studies as well as for detection of true fathers for child-support adjudications are discussed, implying the need to employ a battery of genetic markers (possibly DNA-based tests) that yield a higher power of exclusion. We conclude that even though DNA markers are more informative, the probabilistic approach developed here would still be needed to estimate the true rate of nonpaternity in a population or to evaluate the precision of detecting true fathers. Am J Phys Anthropol 109:281–293, 1999. © 1999 Wiley-Liss, Inc.     

Blood group A glycolipid antigen expression in kidney, ureter, kidney artery, and kidney vein from a blood group A1Le(a-b+) human individual. Evidence for a novel blood group A heptaglycosylceramide based on a type 3 carbohydrate chain

Kidney, ureter, kidney artery, and kidney vein tissue were obtained from a single human transplant specimen. The donors erythrocyte blood group phenotype was A1Le(a-b+). Total non-acid glycolipid fractions were isolated and individual glycolipid components were identified by immunostaining thin layer plates with a panel of monoclonal antibodies and by mass spectrometry of the permethylated and permethylated-reduced total glycolipid fractions. The dominating glycolipids in all tissues were mono- to tetraglycosylceramides. In the kidney, ureter, and artery tissue less than 1% of the glycolipids were of blood group type, having more than 4 sugar residues. In contrast, 14% of the vein glycolipids were of blood group type, and the dominating components were type 1 chain blood group H pentaglycosylceramides and A hexaglycosylceramides. Trace amounts of structurally different blood group A glycolipids (type 1 to 4 core saccharide chains) with up to 10 sugar residues were found in the kidney, ureter, and vein tissues, including evidence for a novel blood group A heptaglycosylceramide based on the type 3 chain in the vein. The only detected A glycolipid antigen in the artery tissue was the blood group A difucosyl type 1 chain heptaglycosylceramide (ALeb) structure. Blood group Lewis and related antigens (Lea, Leb, and ALeb) were expressed in the kidney, ureter, and artery, but were completely lacking in the vein, indicating that the Le gene-coded alpha 1-4-fucosyltransferase was not expressed in this tissue. The X and Y antigens (type 2 chain isomers of the Lea and Leb antigens) were detected only in the kidney tissue.     

Lack of an association between ABO and Rh blood group polymorphisms and stature, body weight, and BMI in a cohort of British women

Analysis of variance shows no significant associations between stature, weight, or body mass index (BMI) and ABO or Rh blood group phenotypes among a sample of mothers in England, Scotland, and Wales whose children were born during March 3-9, 1958. Social factors are significantly associated with stature and weight; the effects of social class of the women's fathers, regions of birth of the women, their ages, whether their education continued beyond age 16 or not, and the total number of births were separated out by regression analysis. The adjusted residual regression of ABO and Rh phenotypes were not significantly related to reported stature, weight, or BMI.     

Diethylnitrosamine-induced increase in gamma-glutamyltranspeptidase in rat liver: its association with thyroid hormone deficiency and its reversal by tri-iodothyronine.

1. The nodular phase of hepatic premalignancy was induced in male Fischer 344 rats by the administration of diethylnitrosamine, 200 mg/kg i.p., followed by promotion utilizing the Solt-Farber promoting regime. 2. Relative to the situation in normal non-treated control rats: the activity of gamma-glutamyltranspeptidase was found to be increased 9.42-fold in homogenate and 7.33-fold in plasma membrane fractions prepared from the livers of saline-injected control rats; and 81.37-fold in homogenates and 91.92-fold in plasma membranes prepared from the livers of diethylnitrosamine-injected rats; plasma levels of total T3 and total T4 were found to be decreased 42.06 and 47.45% in saline-injected control rats and 88.7 and 83.2% in diethylnitrosamine-injected rats, respectively. 3. An early pre-nodular phase of hepatic premalignancy was produced in young immature and mature adult male Fischer 344 rats by the administration of diethylnitrosamine, 75 mg/kg, without subsequent application of the promotion regime. 4. Relative to the situation in control rats: the activity of gamma-glutamyltranspeptidase was found to be increased in liver homogenates prepared from diethylnitrosamine-treated rats, 1.62-fold in young immature rats 1.20-fold in mature adult rats; plasma levels of total T3 were found to be reduced in diethylnitrosamine-treated rats, 28% in young immature rats 9% in mature adult rats. 5. Treatment of diethylnitrosamine-injected young immature male Fischer 344 rats at the prenodular phase of hepatic premalignancy with tri-iodothyronine at 0.005 micrograms/kg s.c. daily for 7 days reversed the diethylnitrosamine-induced increase in liver homogenate gamma-glutamyltranspeptidase activity and the decrease in plasma total T3, restoring these parameters to normal levels.(ABSTRACT TRUNCATED AT 250 WORDS)