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Recent suggestions of a correlation between the extent of acquired deletions of the long arm of chromosome 5 [del(5q)] in association with myelodysplastic syndromes and acute non-lymphoblastic leukemia, and the morphological features, prompted us to review 34 patients with these conditions and del(5q). We found no correlation between the morphological diagnosis with which the patient presented and the extent of the deletion of 5q. All cases showed involvement of band 5q31, in common with most previously reported series. The consistent involvement of 5q31 is in keeping with the concept that a single gene at band 5q31 may be involved in the pathogenesis of these myeloid clonal expansions and that the deletion of genes in the long arm of chromosome 5, known to be involved in hemopoietic growth regulation, is unlikely to be the principal determinant of the hematological disorder.

The last decade has been very exciting for cancer cytogeneticists. At the start of the decade, the role of cytogenetics in clinical medicine was still unclear. Many felt that such investigations were largely of academic interest. Today, cytogenetic investigations are considered essential in many cancers, where they contribute in diagnosis, staging, choice of therapeutic protocol, and monitoring of the effects of therapy. The number of primary chromosome changes in human cancer exceeds 100, and while the majority of these changes are associated with haematological malignancies, the contribution from the solid tumours is now growing rapidly. Closer ties between scientists and physicians involved in laboratory and clinical medicine have resulted in the emergence of many well-defined cytogenetic-clinicopathological entities. With the advances in molecular biology that characterized the 1980s came the disappearance of all scepticism about the critical role played by chromosome change in oncogenesis. To date, we have learned more about the details of cancer biology in chronic myeloid leukaemia and the lymphoid malignancies through the molecular dissection of primary chromosome changes than through any other approach. Further studies will, no doubt, lead us to an understanding of the molecular basis of many of the primary and secondary chromosome changes that are non-randomly acquired in human cancer.

An analysis of the results of a compulsory proficiency testing programme in immunohaematology is presented. Error rates have been calculated for the determination of ABO and Rh(D) groups, the direct antiglobulin test and antibody detection according to defined criteria. The introduction of proficiency testing has been associated with alterations in error rates for some determinations. An educational programme introduced for laboratories with poor performance has proved effective in improving their results in the proficiency testing programme.

An Indian (Asian) patient with compound heterozygosity for Hb Riyadh and beta 0-thalassemia is described. Hb Riyadh forms about 95% of the hemoglobin present. The clinico-pathological picture is identical to that of simple beta-thalassemia trait confirming the harmless nature of the substitution beta 120(GH3) Lys leads to Asn.

An absolute lymphocyte count is included in the routine results provided by most automated blood cell counters, providing a prompt indication of peripheral blood lymphocytosis. Transient lymphocytosis is seen in many acutely ill patients, including those with multiple injuries. We have observed a significantly higher death rate among trauma patients with lymphocytosis at presentation; patients with lymphocytosis, on subsequent assessment of injury, proved to have higher Injury Severity Scores than those without lymphocytosis. Investigation of lymphocyte subsets in nine patients with lymphocytosis showed an increase in T cells, reversal of the CD4:CD8 ratio, and, in seven patients, an increase in "natural killer" cells. The presence of lymphocytosis and its early detection as part of a routine blood count may supply a readily available means of identifying a high-risk trauma patient.

Using electron microscopy radioautography, the deposition of intravenously administered iron in the duodenal epithelium was studied in normal mice, iron-overloaded and iron-deficient mice, and in mice with X-linked anemia (gene symbol sla) 4 and 24 hours after injection of 59Fe. The resolution of radioautography with 59Fe was determined with a line source and the distance from the hot line within which half of the grains fell (HD value) was 1650 A. In normal, iron-overloaded, and sla mice, radioiron was localized in the undifferentiated crypt cells at 4 hours and in the absorptive cells of the luminal half of the villi, at 24 hours. At both times, the vast majority of the grains was seen over the areas rich in free ribosomes and rough endoplasmic reticulum. In iron-deficient mice, grains were not found at either time. The amount of iron incorporated in the crypt cells was related to the size of the body iron stores. It is postulated that the amount of iron incorporated in the crypt cells is the result of interaction between uptake and return to the blood of the circulating iron. Once the crypt cells have differentiated into absorptive cells, the uptake and recirculation of iron from and to the blood would cease, leaving an amount of "message" iron which determines the absorptive cell's subsequent capacity for iron transfer to the plasma. In sla mice, in spite of tissue iron deficiency, the amount of iron deposited was similar to that of normal mice and markedly increased after treatment of the anemia. The accumulation of iron in the crypt cells may result from the decreased return to the blood of the incorporated circulating iron, due to the postulated deficient iron carrier mechanism in sla, or may be a consequence of increased avidity of the absorptive cells for circulating iron. In either event, the result would be that the absorptive cell receives an inappropriate message with resulting inappropriate absorption of iron.

Since April 1975 the proficiency of laboratories in Ontario that perform immunohematology tests has been assessed. While the majority of test samples have required only ABO and Rh(D) typing, others have posed problems. The error rate in uncomplicated ABO typing was 1.3/1,000 in 17,479 tests and that in straightforward Rh(D) grouping, 6.6/1,000 in 17,757 tests. False-negative (36/1,000) and false-positive (1.4/1,000) direct antiglobulin tests occurred. Errors in detection of strong alloantibodies (e.g., anti-D) were 19.7, 10.2 and 5.1/1,000 in three test samples. A2B or A2 cells with anti-A1 in serum were sent out in two surveys; error rates in ABO interpretation were 189 and 52/1,000, respectively. Laboratories also experienced difficulty in interpreting the Rh(D) type of cells with positive antiglobulin tests. These surveys have had several effects: (1) laboratories with poor performance have been identified, (2) patterns of practice have been influenced, (3) areas of ignorance have been identified, and (4) a stimulus has been provided for continuing education in immunohematology.

Using a panel of monoclonal antibodies, cells from lymph node biopsies have been examined in three patients with small cell carcinoma presenting with cervical lymphadenopathy. Two patients had small (oat) cell carcinoma of the lung; in the third patient, a primary tumor was not found. Two lymph node biopsies showed typical small (oat) cell carcinoma, and one was an intermediate cell variant; in the last, lung biopsy showed small (oat) cell carcinoma. Electron microscopy demonstrated desmosomes in all three tumors. In each case, lymph node cell suspensions were examined by indirect immunofluorescence with the use of a panel of monoclonal antibodies to antigens usually associated with lymphoid or myeloid cells. In two of the three cases malignant cells were positive with the lymphoid marker BA-2; in two cases malignant cells were positive with OK1a1, a marker for the Ia-like antigen (HLA-DR); and in one case malignant cells were positive with My-1. Caution is needed in the interpretation of cell surface marker studies in the differential diagnosis of small round cell tumors.

We have observed previously that the rate of cortisol catabolism by lymphocytes (CCL) was indicative of the vulnerability of these cells to cortisol. We attempted to ascertain whether cortisol-sensitive lymphocytes (e.g. thymocytes) metabolize cortisol at a different rate from cortisol-resistant cells and whether lymphocytes in which cortisol catabolism is inhibited become cortisol sensitive. The work was facilitated by the observation that an ethanol extract plasma from patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) had the capacity to inhibit CCL. The capacity of thymocytes to metabolize cortisol was found to be 11 times lower than that of peripheral lymphocytes. Inhibition of CCL with an ethanol extract of plasma from AIDS/ARC patients made the cells vulnerable to cortisol, causing them to die at a rate seven times greater than that of control samples. It is suggested that these findings may have important implications with regard to the nature of lymphocyte depletion in AIDS/ARC patients or in people at risk of developing the syndrome.

A second example of chronic myeloid leukemia showing translocation of material from the long arm of chromosome #22 to the long arm of chromosome #21, ( 21q +:22q-), is reported. The patient presented with the typical clinico-pathologic features of the disease.

A patient with chronic myeloid leukemia is described in whom a novel complex translocation was found among chromosomes #4, #9, and #22, resulting in a "masked" Philadelphia chromosome. The breakpoint in chromosome #4 (band q21) is in the same region as the breakpoint seen in the t(4;11), which is associated with some forms of acute leukemia.

A proficiency testing program in immunohematology, involving over 240 laboratories, was used to assess the detection of anti-D in six concentrations ranging from 11 to 8,500 ng/mL. Using the indirect antiglobulin test, more than 98% of laboratories reporting detected anti-D at all concentrations. Enzyme and albumin antiglobulin methods as routinely practiced did not clearly increase sensitivity, and the direct agglutination methods used were much less sensitive than indirect antiglobulin methods. If proficiency testing truly reflects performance in practice in Ontario, Canada, the sensitivity of manual indirect antiglobulin methods in routine use for the detection of anti-D appears to meet reasonable expectations of these technics.

Fifty-six patients with unexplained lymphocytosis were investigated with a panel of antibodies to lymphocyte surface antigens. In 23 the distribution of cell surface markers suggested reactive lymphocytosis. The remaining 33 patients showed a distribution of cell surface markers that indicated or suggested a diagnosis of B-cell lymphoproliferative disease. Two illustrative case reports show how such studies performed early in the investigation of unexplained lymphocytosis may permit earlier diagnosis of the underlying mechanism.

A case of idiopathic acquired sideroblastic anaemia transforming to acute myelofibrosis is reported. The appearance of atypical megakaryocytic proliferation in idiopathic acquired sideroblastic anaemia may presage the development of an acute myelofibrotic phase of this usually chronic disease.

A patient with acute nonlymphoblastic leukemia (FAB M4), showing a near tetraploid chromosome complement on his marrow cells, was treated with low dose cytosine arabinoside and achieved remission. During remission the near tetraploid marrow chromosome complement disappeared and reappeared upon relapse of leukemia. These findings are interpreted as evidence against differentiation induction in the leukemic cell line as a mechanism for remission of the disease in this patient.

A compulsory programme of proficiency testing in immunohaematology has been conducted for the last 4 years. The collection, processing and analysis of testing data reported by participating laboratories depends on a computer-based system, which allows the generation of reports for participants and working documents essential to the functioning of a committee which supervises the operation of the programme. The options open to the committee in coping with laboratories with poor performance are summarized.

A comparative study of proficiency testing models in immunohaematology has been carried out between the United Kingdom National External Quality Assessment Scheme and the Laboratory Proficiency Testing Program of the Ontario Medical Association, using material supplied by both programmes to laboratories in the United Kingdom and Ontario. The results suggest that the general standard of performance in immunohaematology practice is similar in the two jurisdictions and that, where clear differences are seen, these reflect differences in technique or in educational emphasis.

An adult with long-standing neutropenia had the functional granulocyte abnormalities typical of the lazy leucocyte syndrome. Scanning electron microscopy of the patient's neutrophils showed alteration in the surface configuration of the cell with coarsening of the normal fine ruffles and the appearance of knob-like projections. Similar functional and anatomical changes were induced in normal neutrophils by treatment with vinblastine. The lazy leucocyte syndrome may be a consequence of altered membrane microfilamentous protein structure or function, and undue rigidity of the affected neutrophils may explain the clinicopathological features of the disease.

While using the natural killer (NK) cell-associated HNK-1 antibody in a panel of hematopoietic cell markers, the authors found that metastatic tumor cells in the bone marrow of a patient with disseminated prostatic carcinoma stained strongly with this antibody using an indirect immunofluorescence technique. More than 50% of cells from the patient's prostate also reacted with HNK-1. Subsequent study of frozen sections of prostate tissue from patients with benign prostatic hypertrophy (BPH) showed that HNK-1 reacted with prostatic epithelium and the contents of the glandular lumina. Two other markers associated with NK cells (OKM1 and OKT3) were not detected on nonneoplastic or neoplastic prostatic epithelial cells using a two-color immunofluorescence technique. Recent reports have shown that the HNK-1 antibody also detects an antigen on cells of neuroectodermal origin. The authors have concluded that HNK-1 also reacts with prognostic epithelium in patients with BPH and may be useful as another marker for metastatic carcinoma of the prostate.

Cell structure abnormalties are found in acute leukaemia and preleukaemic states. Studies on bone marrow cells and peripheral leucocytes of 4 patients with idiopathic acquired sideroblastic anaemia showed patterns in cell culture similar to those reported in acute leukaemia: 2 of these patients later developed leukaemia. Other patients with idiopathic, secondary or congenital sideroblastosis showed no such cell culture abnormalities, and none developed leukaemia. Studies such as this suggest that cell culture methods detect altered cellular function preceding overt leukaemia and that these abnormal findings may be helpful in the evaluation of patient groups with an increased incidence of leukaemia.

Untreated patients with acute granulocytic leukemia showed impairment of microbicidal activity and,, in one, this was associated with myeloperoxidase deficiency and staphylococcal infection. In chronic granulocytic leukemia, there was no significant impairment of microbial killing. However, reduction in the capacity to reduce nitro-blue tetrazolium indicated some disturbance of neutrophil function in this disorder.

A circulating anticoagulant inhibiting antihaemophilic globulin (A.H.G.) is described in an otherwise healthy 70-year-old woman, and the therapeutic response to steroids is discussed. The nature and pathogenesis of the anticoagulant remain obscure, but its properties and behaviour do not support an autoimmune aetiology.

An assessment of the Coulter model S automatic blood counter has been carried out. The standard deviations for the haemoglobin concentration, haematocrit, red cell count, and white cell count are, respectively, +/- 0.15 g/100 ml, +/- 0.45%, +/- 0.04 m/c mm, and +/- 0.47 thous/c mm. These results are clearly more accurate than careful manual estimates, performed for comparison on the same samples. Details of the comparisons are presented. A comparison is also made with routine daily estimations.;Carryover' from one sample to the next was found to be about 2%, and tests in the ranges likely to be found in practice showed good linearity for the haemoglobin estimation, haematocrit, red cell count, and white cell count. A brief account of instrument failures is given.The performance of the Coulter model S compares well with that of other automated equipment for which detailed evaluations are available.