Animal models of mechanisms of erythrocyte destruction: why aren't the erythrocytes of the newborn rhesus monkey (Macaca mulatta) destroyed by maternal antibodies?
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Biomedical subjects
Publications and source records attributed to W H Stone.
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It was not possible to demonstrate Xga on the erythrocytes of any of 140 rhesus monkeys of both sexes tested with human antiserum rendered specific for Xga by absorption.
The results and agreements of the 1 international BoLA workshop, held in Edinburgh, Scotland in August 1978, are reported. Most of these concern the results from a comparison test of 249 alloantisera to bovine lymphocytes, the antisera being contributed by 9 laboratories. These sera were compared directly in Edinburgh on a panel of lymphocytes from 130 cattle of 21 breeds. In the microlymphocytotoxicity test used 75% of the sera reacted. Sixty eight of these sera were grouped into clusters according to their reaction patterns against the lymphocyte panel. Eleven of these clusters were clearly defined and were given workshop BoLA designations. In addition 22 sera were assigned to subgroups of the agreed clusters. There was no evidence that the method of production of the sera had any effect on their specificity. Although genetic data was not available, the phenotypes of the test panel of lymphocytes are consistent with the clusters detecting antigens controlled by multiple alleles at a single autosomal locus. It was agreed to name the genetic region where this putative locus is located BoLA (bovine lymphocyte antigen).
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Pure RBC aplasia developed in two renal transplant recipients who were receiving long-term azathioprine therapy. With substitution of cyclophosphamide therapy for azathioprine, erythroid hyperplasia and reticulocytosis developed at three weeks in one patient and at three months in the other. Selective erythroid toxic reaction is a potential problem that must be considered when anemia develops in patients receiving long-term azathioprine therapy.
Using cytotoxic serums obtained from multiparous cows or by alloimmunization, we have detected 11 lymphocyte antigens controlled by codominant alleles at a serologically defined locus called BoLA-A (bovine lymphocyte antigens). This locus, along with the lymphocyte defined loci previously reported, establishes the existence of a major histocompatibility system of cattle.
Starch gel electrophoresis of erythrocytes from 1812 Macaca mulatta has unequivocally demonstrated that the 6-phosphogluconate dehydrogenase (6PGD) isozymes are controlled by two autosomal codominant alleles. Limited data on erythrocytes from 89 Macaca speciosa were also consistent with autosomal codominance.
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We present a model of mixed lymphocyte culture (MLC) response which assumes one specificity per locus. It also assumes that an animal A will fail to stimulate animal B if, and only if, the set of specificities possessed by A is a subset of the set of specificities in B. The last assumption implies that non-stimulation is transitive; that is, if A does not stimulate B, and B does not stimulate C, then A will not stimulate C. The inclusion of antigenic sets can be used to partially order the animals in a hierarchy. Partial ordering can detect multiple lymphocyte-defined (LD) loci with relative ease; it indicates the number of antigens present in particular individuals; and it detects exceptions to the rule of transitivity which may expose immune response genes, minor loci, or other mechanisms that affect MLC response. This analytical procedure is most useful when testing half-sib families or hybrids sharing a common parental strain. We have applied this procedure to the MLC in cattle half-sib families and found that the data strongly support the existence of at least four LD loci.
Using the results of all paired one-way mixed lymphocyte culture tests on families of half-sibs, we have established that the lymphocyte-defined system in cattle contains a minimum of two loci. The methodology presented is applicable to studies of the lymphocyte-defined systems of other species.
Cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone were administered for 165, 28-day cycles to 33 patients with metastatic breast cancer. Because of serious infections (fever larger than or equal to 101 degrees F. granulocytes less than 1,000/mm, 3 and hospitalization) and 1 drug death in the first 4 patients, oral calcium leucovorin, 20 to 30 mg/m2 orally, was given 2 days after methotrexate in subsequent treatment cycles. There were 26 cycles without calcium leucovorin and 6 serious infections; 139 cycles with calcium leucovorin and 5 serious infections (p = 0.002). Objective response was seen in 13 of 18 evaluable patients with no previous treatment and in only 2 of 11 patients with previous treatment (p = 0.0065). Equivalent doses were given to all subsets of patients. It is concluded that leucovorin added to the above combination of drugs can preserve antitumor activity while decreasing serious infections and that prior therapy significantly decreases the response rate to this combination.
A microtiter hemagglutination technique was adapted for routine blood typing of rhesus monkeys. The main advantage of the technique is economy of scarce reagents, since they can be used at greater dilutions and in smaller quantities than in the standard tube technique. Furthermore, the technique is sensitive, accurate, and easy to perform.
A new reagent called G-3' has been discovered which detects the product of the G3 allele, regardless of the other G allele in the genotype. With this new reagent we can delineate nine of 10 genotypes of the G blood group system. The explicit detection of G3 revealed an example of the founder principle in that the frequency of this allele between the feral and laboratory-reared monkeys was significantly different.
The erythrocyte antigen (Ecl) of cattle has been isolated using DEAE-cellulose chromatography, Sephadex gel filtration, and isoelectrofocusing. The purified antigen is free from hemoglobin and migrates as a single protein on polyacrylamide gels. It exhibits an absorption maximum at 278 nm and has a molecular weight of about 100 000; its isoelectric point is 4.95. The antigen has a carbohydrate moeity and loses its activity after oxidation with periodate. The evidence suggests that it is not a common isozyme, but is exact identity remains unknown.
A battery of 21 alloimmune blood typing reagents was developed and used for resolving cases of disputed parentage in the rhesus monkey (Macaca mulatta). Using these reagents, the breeding records of a large colony of rhesus monkeys were monitored. Among 1263 complete families typed, 46 (3.6%) disputed parentage cases were discovered by excluding an assigned parent. Of these disputed parentage cases, 76% were resolved and the most probable parents assigned. In addition, the paternity of 63% of the infants born into a man-made troop which included several unrelated adult males was determined. The probability of excluding an incorrectly assigned (randomly chosen) male as a father was calculated as 73% when all 21 reagents are employed.
A 21-year-old patient with metastatic osteosarcoma was receiving methotrexate with leucovorin rescue every 2 weeks. After the second (of four) infusions of methotrexate, a prior solar burn on an area of skin was reactivated in spite of leucovorin rescue. An area of skin treated 5 months previously by radiation was spared the effects of the reactivation phenomenon. No other toxicities appeared. The reactivation of the solar burn is an example of "false photosensitization" and this cutaneous toxicity is not ameliorated by leucovorin. Methotrexate therapy should be delayed until the effects of generalized solar burns have resolved (approximately 1 week).
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This paper describes an allotypic system in cattle called Ec (Erythrocyte cattle). The antigenic determinant is derived from red cells and is detected in lysates by gel precipitation with alloimmune serum. The Ecl specificity is controlled by an autosomal dominant gene and occurs with variable frequencies in different cattle breeds. The Ec system is a very useful genetic marker because the homozygous and heterozygous genotypes show a dosage effect and can be distinguished by the size of the precipitin rings in double diffusion gel precipitation tests.