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Biomedical subjects

M Fotino

Publications and source records attributed to M Fotino.

At least 91 records · Page 5Linked to original sources

The identification of HL-A antigens on fresh and cultured human endothelial cells.

Human endothelial cells were obtained from the umbilical cord veins of 16 newborns by methods previously described and tested for HL-A antigens by a microcytotoxicity method. HL-A antigens were present on all endothelial cell lines tested. When the HL-A phenotypes of fresh endothelial cells and autologous fetal lymphocytes were compared, a concordance of 70% was observed. When the HL-A phenotypes of maternal lymphocytes and fresh endothelial cells were compared, a maternal contribution to the endothelial cell phenotype was evident in 72% of the possible commmon antigens. Some HL-A antigens were deleted from 11 of 16 endothelial cell lines that were re-typed after 2 weeks in tissue culture. The majority (90%) of deleted antigens were from the second HL-A locus. When three lines of endothelials cells were again re-typed after 6 weeks in culture, no further changes in antigenicity were noted. These findings: a) demonstrate that HL-A antigens are present on human endothelium and suggest that endothelial cells are actively involved in establishing the immunogenicity of a graft, and b) demonstrate that the HL-A antigens on human endothelial cells may be modulated by in vitro culture.

Adult↗

Evidence for linkage between HL-A histocompatibility genes and those involved in the synthesis of the second component of complement.

HL-A analysis of a family with C2 deficiency revealed evidence for close linkage between the C2 defect and the histocompatibility HL-A loci. The propositus was homozygous both for C2 deficiency and the HL-A haplotype 10,W18. Among seven children of three double backcross matings, no recombinants were found. The possible significance of such linkage is discussed.

Complement System Proteins↗

Kidney transplantation: Improvement in patient and graft survival.

Patient and graft survival were reviewed in a series of 249 kidney transplants done from 1963 to March 1973. Patient survival was calculated by the life table method for the periods 1963-1970, and 1970-1973, since in 1970 a formal Kidney Center was established and mortality rates changed. Graft survival was analyzed in terms of donor source, HL-A matching and immune responsiveness to HL-A antigens. Three-year predicted mortality for cadaver kidney recipients was 62% between 1963 and 1969 (42 patients) and 8% between 1970 anid 1973 (67 patients). Similar predicted mortality for related living donors was 30% between 1963 and 1969 (52 patients) and 14% between 1970 and 1973 (85 patients). Mortality has continued to decrease and there has been only one death in the last 87 consecutive transplants, including 57 consecutive cadaver transplants. Oneyear predicted kidney survival for the 10-year period is 44% for cadaveric, 60% for non HL-A identical related living and 90% for HL-A identical sibling donors. In the cadaver group, those sharing 2 or more HL-A antigens had the same kidney survival as the non HL-A identical related living donor grafts. Since cadaver graft recipients are on dialysis for a longer period of time, immune responsiveness can be detected by their response to blood transfusions, whereas this determination could not be made in our related living donor group. Non-responsive cadaver kidney recipients had 80% one year kidney survival. We conclude that transplant mortality can be reduced to less than 10% by the Center approach to treatment of renal disease, dialysis does not adversely affect future transplantation, and excellent (80%) kidney survival can be expected in properly selected cadaver graft recipients.

Blood Transfusion↗

Ragweed hay fever: genetic control and linkage to HL-A haplotypes.

Clinical ragweed pollenosis (hay fever) and IgE antibody production specific for antigen E (the major purified protein antigen from ragweed pollen extract) correlated closely with HL-A haplotypes in successive generations of seven families. HL-A associated IgE antibody responsiveness was antigen specific and extended also to IgE antibody production. These data indicate an immune response (Ir) gene specific for antigen E necessary but not sufficient for the development of hay fever. This appears to be the first documentation of an Ir gene in man.

Adolescent↗

Hereditary C2 deficiency: association with skin lesions resembling the discoid lesion of systemic lupus erythematosus.

Two patients with hereditary homozygous C2 deficiency are described. They showed many similar clinical features. Both had discoid-like skin rashes and serologic abnormalities consistent with SLE, but neither had evidence of involvement of any organ other than skin. Although biopsy of these lesions revealed expected changes by light microscopy, typical immunofluorescent findings were not present. The presence of the HL-A haplotype 10, W18 was seen in both families and was associated with the C2 deficiency gene. The 2 patients were mutually nonreactive in MLC tests and both were found to be homozygous for the LD7a type.

Adult↗

Risk factors for choroidal neovascularization in young patients: a case-control study.

A pair-matched, case-control design was used to study exposure to Histoplasma capsulatum and other environmental factors, and to determine various host characteristics including human leukocyte antigen (HLA) typings in 94 young patients with macular choroidal neovascularization (CNV) and in 94 controls with other eye diseases. Patients with two types of retinal patterns were studied: Type I, or those with CNV with one or no chorioretinal atrophic spots in the posterior pole or periphery (n = 51), and Type II, or those with CNV and 2 or more chorioretinal atrophic spots (n = 43). Our purpose was to explore whether these two variants of idiopathic CNV have different and distinguishable epidemiologies which may or may not be related to prior exposure to Histoplasma. We found that histoplasmin skin tests were negative in all but two Type I cases. The combination of the HLA-B7 and HLA-DR2 markers (but not either marker alone) was significantly increased in Type I cases. Among Type II cases, HLA-B7, HLA-DR2, HLA-DQ1, a positive histoplasmin skin test, myopic refractive error, prior residence in a histoplasmosis endemic area, occupations involving exposure to animals, and hypertension were all significantly increased. Histoplasmin skin test responses were positive in 18 Type II cases (45%). In the multivariate analysis, only DR2 and the combined presence of DQ1 and a positive histoplasmin skin test remained predictive of Type II disease. Our findings suggest that histoplasmin sensitivity is associated with some, but not all, cases of Type II disease. However, histoplasmin sensitivity appears to have no relationship to Type I disease. HLA factors may play a role in both disease types, possibly by producing a modified immune response to Histoplasma and/or other unidentified agents.

Adolescent↗

Induction of donor-specific immune modulation and successful renal transplantation with a simplified method of donor-specific blood transfusion.

We developed a new method of donor-specific blood transfusion (DST) for prospective kidney transplant recipients from a living related donor. Forty-four patients were transfused with 100 ml of one-haplotype matched kidney donor's whole blood at 1, 8, and 15 days after its storage. Ten of these patients received azathioprine (1.5 mg/kg per day) in addition to DST. After DST, three patients (6.8%) developed donor-specific lymphocytotoxic antibodies. The incidence of sensitization was not different between azathioprine-treated and untreated patients. Following DST, donor-specific mixed lymphocyte culture (MLC) was significantly suppressed without any accelerated (secondary type) response in early MLC. Subsequently, 24 patients received a kidney transplant from the donor. Graft survival rates were 96% and 90% at 12 and 24 months, respectively. Nine additional patients, seven from a two-haplotype matched sibling and two from a no-haplotype matched sibling also received DST. None of these patients became sensitized following DST, and all have functioning grafts for 6 to 18 months. This study indicates that 100 ml of stored whole blood DST three times at weekly intervals is a practical, less immunizing, and effective approach to enhance graft survival in recipients of a living related donor graft, DST produces donor-specific adaptive responses that might be conductive to successful graft outcome, and this protocol could be used in sibling donor-recipient pairs who do not share a haplotype.

Adult↗