Localisation of a gene for central areolar choroidal dystrophy to chromosome 17p.

Central areolar choroidal dystrophy (CACD) is a rare inherited retinal disease which causes progressive profound loss of vision in patients during their 4th decade. We have identified a Northern Irish family with 19 affected individuals in three living generations. We have performed a total genome search and established linkage of CACD in this family to chromosome 17p (multipoint Zmax = 5.65 at D17S938). The genes for phosphatidylinositol transfer protein (PITPN), retinal guanylate cyclase (GUC2D), beta-arrestin 2 (ARRB2), pigment epithelium-derived factor (PEDF) and recoverin (RCV1) map to this region and are candidate genes for retinal disease. Analysis of the coding region of the PITPN gene failed to reveal any mutation in this family.

T-lymphocyte colony formation by lymphocytes from patients with aplastic anaemia.

T-lymphocyte colonies were cultured using lymphocytes from patients with aplastic anaemia and normal donors to assess their respective proliferative activities. Colony numbers from aplastic patient's cells were lower than from normal donors', though this was not significant. When lymphocytes from patients were co-cultured with normal lymphocytes, inhibition of T-colony formation was observed in 8 out of 12 experiments. As the degree of inhibition was greater than if patient cells grew no colonies, then, clearly, normal T-colony formation was inhibited. This ability of patients' lymphocytes to suppress lymphopoiesis might account for the low levels of patient T-colony formation, as well as low in vivo numbers of lymphocytes found in patients with aplastic anaemia. The role of patients' lymphocytes in causing marrow aplasia was investigated. Although the incorporation of patients' lymphocytes in normal granulocyte-macrophage (GM) colony-forming systems inhibited colony growth, in only 1 out of 8 patients was this inhibition significantly greater than that caused by the addition of normal lymphocytes to GM colony systems. Therefore, lymphocytes may not be the primary cause of aplastic anaemia, except for a few rare cases.

Lymphocytes from patients receiving lithium do not inhibit CFU-C growth.

Lymphocyte subset levels and function were examined in 12 patients on lithium therapy and in 11 healthy hospital personnel. Co-culture of allogeneic human bone marrow cells with monocyte-depleted lymphocyte preparations revealed that CFU-C formation was significantly reduced (mean 43% inhibition) in the presence of normal lymphocytes but not with the patients' lymphocytes (less than 5% inhibition). This did not reflect numerical changes in lymphocyte subsets, since these were similar for control and lithium subjects. T colony formation was significantly depressed in the patient group (P less than 0.05), whereas B colony numbers were similar in both groups (P greater than 0.1). The possible role of HLA-incompatibility affecting CFU-C growth was investigated in co-culture experiments, using lymphocytes from HLA-identical twins, one of whom was receiving lithium. In four separate co-culture experiments, the inhibitory effect was shown with lymphocytes from the non-lithium twin but was not demonstrated by the lithium subject. Addition of lithium in vitro to co-cultures of normal marrow and lymphocytes was found to negate the inhibitory phenomenon in a dose-related manner. It is postulated that granulocytosis induced by the administration of lithium may be a manifestation of changes in a lymphocytic control system.

Circulating T-cell subpopulations in lithium-associated granulocytosis.

Granulocytosis is a common feature in patients undergoing lithium therapy. With increasing evidence that T lymphocytes play a role in the control of granulopoiesis, we have investigated the effect of lithium administration on circulating levels of T helper and T suppressor cells, as identified by monoclonal antibodies, to determine whether lithium-induced granulocytosis is mediated through changes in peripheral blood T cell subsets. Lithium carbonate was administered to 10 subjects over a 2 week period. Differential leucocyte counts and T, B, T helper and T suppressor lymphocyte enumerations were performed prior to administration of lithium (Day 1) and on 2 occasions (Day 7 and 14) during ingestion of the drug. Ten healthy control subjects were similarly investigated. Small, but significant elevation (p less than 0.05) in neutrophil counts at 7 and 14 days were observed in subjects taking lithium, serum lithium levels at these times were 0.56 +/- 0.27 and 0.68 +/- 0.17 mmol/l, respectively; lymphocyte and monocyte levels were unaffected. The percentages and absolute numbers of circulating T, B, T helper and T suppressor lymphocytes were not significantly altered (p greater than 0.05) during lithium administration and did not differ significantly (p greater than 0.05) from those recorded for the control group. We were thus unable to demonstrate that short-term lithium administration induced changes in the circulating levels of T helper (OKT4+) or T suppressor (OKT8+) cells.