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Biomedical subjects

D C Linch

Publications and source records attributed to D C Linch.

At least 271 records · Page 15Linked to original sources
PubMed1982

Phenotypic analysis of fetal blood leucocytes: potential for prenatal diagnosis of immunodeficiency disorders.

Recent technological advances allow the detection and quantitation of subsets of leucocytes using monoclonal antibodies. We have taken advantage of this to study the ontogeny of fetal blood leucocytes, using very small blood samples obtained at fetoscopy. By 14 weeks gestation T cells represent 35 per cent or more of fetal leucocytes and the distribution of the helper/inducer and suppressor/cytotoxic subsets is similar to that of adults. B lymphocytes before 16 1/2 weeks are low (4-20 per cent), but rise to a mean of 28 per cent in 17-26 week fetuses. Granulocytic cells, many of which are phenotypically immature, represent 18-34 per cent of total leucocytes. The methodology employed is very reliable and offers the opportunity for the prenatal diagnosis of some immunodeficiency disorders, since using the same reagents we have diagnosed children with severe combined immunodeficiency shortly after birth.

Antibodies, Monoclonal↗
PubMed1982

Red cell membrane protein anomalies in congenital dyserythropoietic anaemia, type II (HEMP AS).

In all of six cases of congenital dyserythropoietic anaemia, type II (HEMPAS), gel electrophoresis in the presence of SDS revealed abnormally rapid migration of the preponderant integral membrane protein, band 3. After proteolysis of intact cells, the remaining part of the band 3, comprising the intramembrane segment and the cytoplasmic domain, migrated electrophoretically as a single band, identical in mobility to that from normal cells treated in the same manner. The anomaly thus resides in the extracellular domain of the protein, which is the glycosylated part of the chain. Peptide digests of the band 3 showed no evidence of a missing protein segment in the abnormal cells and the amino acid composition of the peptides derived from proteolysis of the extracellular protein of intact cells was also normal. We infer that the anomaly is one of glycosylation. The major glycoproteins, detected by carbohydrate-specific (PAS) stain appear normal in SDS gels. However, when the more sensitive procedure of reacting after electrophoresis with radioiodinated lentil lectin is employed, some additional minor protein components are revealed. In particular one species of apparent subunit molecular weight about 150 000 appeared in all cases of HEMPAS examined and in no normals. This component is not accessible to proteolysis by chymotrypsin or Streptomyces griseus protease, and may be associated with the inner membrane patches, characteristic of the HEMPAS condition. Overall cell shape and microviscosity of the membrane bilayer, as measured by fluorescence polarization of a lipid-soluble fluorophore, were substantially normal in HEMPAS cells.

Adolescent↗
PubMed1982

A chronic myeloproliferative disorder associated with monosomy 7 in the bone marrow cells; normal karyotype in acute transformation.

A chronic myeloproliferative disorder associated with monosomy 7 of the bone marrow cells is described in a male infant. After nearly 4 years, during which time no drug therapy was given, the disease transformed to a 'blast crisis' and at this stage the karyotypes of the marrow and unstimulated blood cells were shown to be normal. It is proposed that the development of the myeloproliferative disorder associated with monosomy 7 is a multistage process and the acquisition of the chromosomal abnormality is a secondary event.

Bone Marrow↗
PubMed1982

The morphology and cytochemistry of human T-cell subpopulations defined by monoclonal antibodies and Fc receptors.

Leu 2a+ (suppressor/cytotoxic) and Leu 3a+ (helper/inducer) T-cell subsets of normal peripheral blood lymphocytes, purified by fluorescence-activated cell sorting, respectively showed 50 +/- 22% (range 31-92%) and 82 +/- 9% (range 69-93%) dot non-specific esterase (NSE) and 48 +/- 20% (range 31-91%) and 79 +/- 10% (range 64-92%) dot acid-phosphatase (APase) staining. Mature T cells defined by monoclonal antibody (UCHT1) displayed 81% and 79% dot NSE and APase positivity, while E-rosetting cells not staining with UCHT1 showed only 15% and 10% dot-positivity and were generally larger cells with more abundant cytoplasm. Examination of Fc-rosetting cells within the different T-cell subsets showed that dot positivity was not directly related to microFc receptor (microFcR) expression; particularly among Leu 2a+ lymphocytes, many microFcR+ cells lacked dot staining. It is concluded that dot staining for hydrolytic enzymes is a marker of true T-cells (as defined by monoclonal antibodies), although a minority of such cells (approximately 20%) lack this staining pattern. Although Leu 3a+ cells display a higher percentage of dot positivity than do Leu 2a+ cells, the difference is not clinically useful, and the two cell populations are not readily distinguishable on morphological grounds. The previously reported association between dot staining and microFc receptor expression is shown to be an indirect one, attributable to the fact that most T-cells, defined by monoclonal antisera, possess microFcR whereas most E+ UCHT1- cells lack microFcR.

Acid Phosphatase↗
PubMed1982

A megakaryocytic thrombocytopenia associated with the excess of Leu 2a+ suppressor cells.

8 patients with acute myeloid leukaemia (AML), either at presentation or in remission, had normal T-cell subsets as defined by Fc receptors and monoclonal antisera. In contrast, a persistant excess of T lymphocytes staining with Leu 2a (defining suppressor cells) was noted in a case of AML in which persistant amegakaryocytic thrombocytopenia occurred after other haemopoietic lines had recovered from ablative chemotherapy. It is suggested that the 2a+ cells were involved in the suppression of megakaryocytopoiesis, and the phenotype of the lymphoid cells is compared and contrasted with previously described cases of other cytopenias associated with an excess of suppressor cells.

Adult↗
PubMed1982

Bone marrow processing and cryopreservation.

Three different closed procedures for concentrating bone marrow progenitor cells prior to cryopreservation have been compared. These were by a manual double centrifugation method, a Hemonetics 30 cell separator and an Aminco Celltrifuge. The best results were achieved using the paediatric pheresis set on the Hemonetics model 30. Marrow was frozen in 120 ml aliquots in a programmed freezer with rapid cooling of the freezing chamber during the phase change from the liquid to the solid state. After freeze-thawing the average nucleated cell recovery was approximately 50% and the progenitor cell recovery 80%.

Bone Marrow Cells↗
PubMed1982

T cell and monocyte requirements for erythropoiesis.

Progenitor cell fractions from normal human marrow have been prepared by a method that enables low numbers of cells to be cultured and results in very little T cell or monocyte contamination. The enrichment of 14- and 21-day BFU-E was similar to that for CFU-GM and the readdition of sheep red blood rosette-forming cells had no effect on BFU-E growth. The significance of the discrepancy in cellular requirements for the growth of blood and bone marrow BFU-E is discussed.

Animals↗
PubMed1982

Cytopenia and T cell proliferation.

A group of patients with neutropenia or erythroid aplasia associated with T cell proliferation were evaluated to assess the phenotype(s) and functions of T cells observed in these conditions. These patients have near normal numbers of helper/inducer cells but an excess of cells belonging to the suppressor/cytotoxic subset. The characteristic phenotype of these cells is E+, OKT3+, OKT1+1-, OKT8+, Fc gamma R+, and they frequently bear HLA-DR antigen. These cells respond poorly to T cell mitogens and will suppress the response of normal peripheral blood mononuclear cells to mitogens. They fail to suppress PWM-induced immunoglobulin synthesis. Although the natural killer activity in these patients is sometimes low, this subset of T cells possesses cytotoxic capability demonstrable in assays for antibody-dependent cell-mediated cytotoxicity. The evidence for a direct effect of the T cells on BFUE and CFUGM is poor.

Agranulocytosis↗
PubMed1982

Studies of circulating hemopoietic progenitor cells in human fetal blood.

High levels of committed erythroid and granulocytic/monocytic progenitor cells have been demonstrated in fresh blood obtained at fetoscopy. The fetal progenitor cells were more sensitive to appropriate stimuli (erythropoietin and colony-stimulating factor) than adult progenitor cells grown under the same conditions, and this was shown to be due to intrinsic differences in the progenitor cells at the different developmental stages.

Adult↗