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M Kearns

Publications and source records attributed to M Kearns.

35 records · Page 2Linked to original sources

Decidual cell-specific surface antigen(s) recognized by monoclonal antibodies: tissue and species distribution.

Decidual cells are direct descendants of endometrial stromal cells and the ultimate progeny of bone marrow-derived precursors. In view of their bone marrow genealogy and demonstrated immunoregulatory role during pregnancy, this study attempted to identify a lineage-specific differentiation marker(s) on murine decidual cells with the hope of tracing their developmental pathway and exploring their familial relationship to other lymphomyeloid cells. Two protein A-binding, IgG2b isotype monoclonal antibodies (secreted by clones 16F12 and 2G4F8) were raised by immunizing virgin CBA mice with syngeneic decidual cells. The presence and the density of the antigenic marker(s) recognized by these antibodies were examined by radioautography on various cell types in single cell suspensions of the decidua, placenta, and lymphomyeloid organs after a sandwich labeling with hybridoma supernatants followed by 125I-protein A. Both antibodies appeared to recognize antigen(s) unique for the decidual cell lineage in mice, humans, and rats. The incidence of antigen-bearing decidual cells increased with gestational age in CBA, C3H, and CD1 mice between days 8 and 14, and in humans between 6 and 10.5 wk; in rats, however, some decline was noted between days 8 and 14. The binding was always higher with 16F12 than with 2G4F8 supernatants. No significant binding of either antibody to trophoblast cells of the placenta or leukocytes within the decidua was noted in any of the above mouse strains or species. Little or no labeling of any cell type was seen on lymphomyeloid cells of the virgin or pregnant CBA mice, but a consistent labeling of a rare blast-type cell in the blood was observed with both antibodies, raising the possibility that this cell may represent the circulating precursor of the decidual cell lineage. It remains to be investigated whether these antibodies are recognizing the same or different differentiation antigen(s) on the decidual cells, and whether a conservation of this antigen(s) during speciation signifies its functional importance.

Animals↗

Cells of the fetomaternal interface: their role in the maintenance of viviparous pregnancy.

An immune system capable of discriminating between self and nonself evolved in nature long before the appearance of the viviparous mode of pregnancy, which brings maternal cells into a direct physical contact with genetically disparate cells of fetal origin. In the hemochorial type of placentation, the former include cells of the maternal immune system. This article briefly reviews the possible mechanisms that may protect the semiallogeneic conceptus in nature, with special reference to the role of the cells at the fetomaternal interface. We also present some new data on the antigenicity of pre- and postimplantation trophoblast cells and the immunobiology of decidual cells. Systemic changes in the maternal immune system appear to represent homeostatic responses to the presence of a semiallogeneic conceptus, unrelated to its protection; mechanisms for this protection must reside locally at the fetomaternal interface. We find that the lack of immunogenicity of the outer (trophoblast) cells of the preimplantation blastocyst can be explained by a transient disappearance of the major histocompatibility (MHC) antigens on their cell surface. However, following implantation and the formation of the placenta, class 1 MHC antigens reappear on certain classes of trophoblast cells, i.e., labyrinthine and spongiotrophoblast cells of the murine placenta. Similarly, cytotrophoblast cells of the early human placenta exhibit the presence of class 1 MHC antigens. An absence of class 2 MHC antigens despite the presence of class 1 antigens cannot entirely explain the lack of trophoblast immunogenicity. A local immunosuppression mediated by trophoblast cells themselves as well as maternal cells of hemopoietic origin in the decidua remain as a strong possibility. Typical decidual cells appear to play a central role in the maintenance of pregnancy because of their numerous functions: nutritive, endocrine, and immunoregulatory. Our studies reveal that they are descendants of bone-marrow-derived precursors, have unique surface markers recognizable with monoclonal antibodies nonreactive with other hemopoietic cell lineages, and have the ability to abrogate mixed lymphocyte reactions in vitro in a genetically unrestricted manner. Further studies directed at the cells of the fetomaternal interface should provide a better insight into the mode of survival of the nature's most commonplace allograft.

Animals↗

Life history of decidual cells: a review.

Decidual cells are a distinctive cell population observed in the mammalian endometrium during pregnancy. Their appearance can also be induced with appropriate stimuli in the hormone-primed pseudopregnant uterus. This review deals with their life history, including the dynamic morphological events during the process of decidualization, cytochemical markers for decidual cell reaction, the surface markers and functions of decidual cells, and, finally, the origin and fate of this cell class. The recent discovery of the bone marrow origin of decidual cell precursors adds a new dimension to decidual cell biology. Future studies of steps in the differentiation of the decidual cell lineage await the identification of unique lineage-specific cell--surface of cytoplasmic marker(s); a precise knowledge of decidual cell functions can only be obtained from a discriminating analysis using purified cell populations.

Animals↗

Bone marrow origin of decidual cell precursors in the pseudopregnant mouse uterus.

Decidual cells are considered to be the endproduct of a hormonally induced transformation of endometrial stromal cells of the uterus. However, the source of these precursors remains unknown. This study of evaluated the possibility of their bone marrow origin by an examination of the H-2 phenotype of decidual cells in pseudopregnant bone marrow chimeras. These chimeras were produced by repopulating lethally irradiated CBA/J female (H-2k) mice with bone marrow from (CBA/J x C57BL/6J) F1 female (H-2kb) mice. Pseudopregnancy was produced with a hormonal regimen followed by an oil-induced decidual stimulus. Chimerism was evaluated radioautographically by an identification of the donor-specific Kb phenotype on cells with an immunolabeling technique with monospecific anti-H-2 serum followed by radioiodinated protein A. The extent of chimerism as indicated by the degree of Kb labeling on decidual cells as well as macrophages contained within the decidual nodules was quantitatively compared with that seen on splenic lymphocytes. Fair to good chimerism, as reflected by labeling for the donor-specific marker (Kb), was seen on splenic lymphocytes and macrophages within the decidual nodules in 6 out of 11 animals. A similar level of chimerism was detected on decidual cells in all but one of these six, in which case this was low. One animal showed low chimerism in the spleen but good chimerism on the decidual cells. The remaining four mice were nonchimeric for all three cell types. These results indicate that decidual cells and macrophages appearing within the decidual nodules of pseudopregnant mice are ultimate descendants of bone marrow cells.

Animals↗

HLA and hyperthyroidism in Ireland.

The distribution of HLA antigens in a group of Irish patients with hyperthyroidism was studied, in an attempt to define whether specific antigens were associated with relapse of the disease following medical therapy. The increase in HLA-B8 and DR3 found by others in this disease was confirmed, but no difference in HLA type was documented in 33 patients who had relapsed compared to 24 who had not relapsed. Forty-six per cent of the relapsed group were DR3 as against 45% of the non-relapsed group.

Female↗

Generalised siderosis from an iris foreign body.

A case is presented of generalised siderosis resulting from a foreign body lodged in the iris. The diagnosis was made 10 years after the initial injury, when the patient presented with another, quite unrelated, eye injury. The metal particle was removed after tests revealed that ocular function was impaired with raised intra ocular pressure, severe field loss and an abnormal electroretinogram (E.R.G.).

Adult↗

Excessive permeability in diabetic maculopathy.

Four cases of diabetic maculopathy with excessive permeability are described. Fluorescence angiography is distinctive, showing profuse early leakage from the entire capillary bed of the posterior pole. Careful studies have failed to reveal any cause for this excessive permeability response at the macula or any constantly associated medical abnormality. The prognosis for visual acuity is poor, and photocoagulation has only rarely been successful in maintaining or improving vision in these patients.

Adult↗

Intra-individual variation of some serum constituents and its relevance to population-based reference ranges.

The advent of high-capacity multi-channel analyzers allows estimation of long-term variability in serum constituents of large numbers of subjects. By frozen storage of specimens with subsequent analysis in a single machine run, long-term analytical variation may be eliminated, thus sharpening the estimates of intra-individual variation. In the present study we used the Vickers M-300 analyzer to obtain the data for such estimates from 37 male volunteers, each bled once a week for 22 weeks. Secimens were analyzed in random order to eliminate any biasing effect of analytical drift during the 4-h machine run. Ten serum constituents were measured. Storage-induced linear trends were small or negligible during the period of specimen collection. Using the ratio of average within-subject variance to the variance among subjects as a guide, serum alkaline phosphatase was found to show the greatest individuality, sodium and potassium the least. Other constitutents showed varying degrees of individuality, but for all these analytes, the usual population-based reference ranges were found to be either insensitive or irrelevant to the study of concentration changes over time within most healthy subjects. Our results generally confirmed those of smaller but comparable earlier studies.

Adult↗

Evaluation of a 20 minute 14C urea breath test for the diagnosis of Helicobacter pylori infection.

The use of 14C-urea breath testing for diagnosis of Helicobacter pylori infection in gastric mucosa has gained widespread acceptance and utilisation. We evaluated a 14C urea breath test (UBT) in 116 patients undergoing endoscopy. Seventy four patients were administered 185 kBq (5 mCi-conventional dose), and 42 patients reduced dose (92.5 IBq, 2.5 mCi) of 14C-urea. All were tested for H. pylori using culture, direct microscopy of gastric biopsies and histological evaluation of paraffin stained sections. Using the mean + three standard deviations as the cut-off value, a sensitivity of 96% and specificity of 100% was found for the conventional dose test. At reduced dose, sensitivity was 100% and specificity 96%. Positive and negative predictive values were 100% and 93% for the conventional dose test, and 96% and 100% for testing at reduced dose. We conclude that the UBT is a simple, non-invasive and useful diagnostic alternative for detection of H. pylori in infected patients. We advocate its use in patients less than 45 years of age without alarm symptoms, and also in cases where the need for endoscopic evaluation is not vital, such as after eradication therapy.

Adult↗