T. Wilkinson

A new hybrid haemoglobin: haemoglobin Strumica/Beograd occurring in an individual with four haemoglobins.

Summary An investigation of the cord blood from full term twin infants revealed an additional haemoglobin F component due to an abnormal alpha chain. The father of the twins, whose blood picture was normal, was shown to have normal alpha and beta polypeptide chains together with variant alpha and beta polypeptide chains. Electrophoresis showed that he had four major haemoglobin components. Separation of the haemoglobin fractions by column chromatography, globin preparation, chain separation, tryptic and chymotryptic digestion and peptide map preparation led to the identification of haemoglobin A, haemoglobin Strumica (α2112 His ← Argβ2), haemoglobin D Beograd (α2β2121 Glu ← Val) and a hybrid haemoglobin Strumica D/Beograd (α2112 His ← Arg β2121 Glu ← Val)

Identification of β Vartant Hemoglobins by DNA Restriction Endonuclease Mapping

An alternative method for identifying β variant hemoglobins is described. Computer analysis of restriction sites was used to predict which β variants could be detected by DNA mapping. 61 of 217 variants were shown to have changes in restriction fragment patterns which were useful markers for the abnormal hemoglobin. A further 25 could be identified by polyacrylamide electrophoresis. Implications of DNA analysis in diagnosis of variant hemoglobins are discussed.

A New Hemoglobin with High Oxygen Affinity-Hemoglobin Bunbury: α2β2 [94 (Fg1) Asp→ Asn]

Hemoglobin Bunbury was detected in an Italian woman from Bunbury, Western Australia, following detection of an abnormal hemoglobin by electrophoresis. The variant form accounted for 38% of the total hemoglobin and migrated on cellulose acetate electrophoresis between HbS and HbA. Structural analysis demonstrated a new substitution in the β chain, β94 Asp→ Asn. Hemoglobin Bunbury is stable to both heat and isopropanol denaturation. This variant shows an increase in oxygen affinity and a reduced Bohr effect. Heterozygosity for Hb Bunbury produces no clinical symptoms or compensatory erythrocytes is.

A New Unstable and Low Oxygen Affinity Hemoglobin Variant: HB Stanmore [B111 (G13)VAL→ALA]

Hb Stanmore is a new hemoglobin variant with the amino acid substitution beta 111(G13)Val----Ala. It is unstable and has a low oxygen affinity. The propositus (of Italian nationality) is a double-heterozygote for Hb Stanmore and beta(0)-thalassemia.

HB Geelong [β139(H17)ASN→ASP]

Hb Geelong [β139(H17)Asn → Asp] was detected in a German woman of Polish-Russian descent. It is an unstable variant which appears to increase the severity of a (β+ -thalassemic phenotype in the propositus. The electrophoretic properties of Hb A and Hb Geelong are similar on cellulose acetate in both acidic and alkaline conditions. The electrophoretic mobility and the amino acid analysis of βx T-14 indicated the substitution Asn → Asp at β139. The sequence of βXT-14 was confirmed by dansyl-Edman degradation. The slight increase observed in the P50 of whole blood is not intrinsic to the β139 substitution, but is thought to result from an increased 2,3-diphosphoglycerate level in response to anemia. No family studies were possible to investigate the mode of inheritance of either β+ -thalassemia or Hb Geelong in the propositus. Synthetic globin chain ratios suggest that impaired synthesis of the variant globin chain is partially responsible for the low level of Hb Geelong in peripheral blood.

Hemoglobin Summer Hill β52(D3) Asp→his a New Variant from Sydney, Australia

Hemoglobin Summer Hill was found in a Lebanese woman living in Sydney, New South Wales, Australia. Its structure was shown to be β52(D3) Asp→His. It is a stable hemoglobin which has no significant change in oxygen affinity or heme-cooperativity.

The colony forming cell in acute leukaemia in adults

The colony forming cell (CFC) has the ability to form granulocytic colonies in nutrient agar. In human bone marrow CFC monitors a pre-blast cell granulocytic progenitor. CFC numbers have been assayed in 157 marrow aspirates from 65 adult patients with acute leukaemia. Sixty-one patients were studied in relapse, 18 in remission and 14 in both remission and relapse. All but 5 patients with acute leukaemia had very low or absent bone marrow CFC on presentation. To date, prognosis appears independent of CFC numbers on presentation. Bone marrow colony forming ability was normal in the 18 patients studied during remission. Serial CFC studies in 14 patients with remission indicated that a rise in marrow CFC heralded remission, and during remission CFC numbers were normal. The CFC rise was accompanied by a return of the neutrophil count to normal. In contrast, CFC numbers decreased to zero or very low levels with relapse. In vitro assessment of CFC proliferative status in acute leukaemia suggests that in or with impending remission there is an increased number of CFC in cycle and only small numbers in cycle in relapse. The few colonies that arise from leukaemic marrow are composed of the same cell types as normal marrow colonies. Does this mean leukaemic cells differentiate normally in culture? We suspect such colonies represent differentiation of normal myeloid precursors whose growth from leukaemic marrow is inhibited by leukaemic blast cells or there is ‘dilution’ of normal precursors by the latter.

Thalassaemia in Australia

The composition of the Australian population has altered considerably in the last 30 years, largely as the result of the Federal Government’s immigration policy. The injection of a significant thalassaemic gene pool has implications both at the present time and for the future. Data concerning the ethnic groups in Australia and an analysis of the available figures will be presented and an attempt made to assess the size of the thalassaemia problem. Factors which influence this assessment are mentioned and possible steps to remedy the inadequacy of available data will be discussed. The latter will introduce population screening, diagnostic facilities, genetic counselling and ante natal diagnosis, as they are available and practised in Australia at the present time. The heterogeneity of both β and α thalassaemia will be emphasized and a detailed analysis of all cases of thalassaemia major and haemoglobin H disease should be aimed for, both in relation to genetic counselling and ante natal diagnosis.

Meningeal involvement in acute leukaemia: A review of 4 adults and 2 adolescent cases

With the advent of new drug regimens in the treatment of patients with acute leukaemia and the consequently increased length of survival, it is to be expected there will be an increase in the incidence of meningeal leukaemia. The authors reviewed in some detail the features of meningeal leukaemia. Of the 134 cases of acute leukaemia in adults diagnosed between the years 1965-1970, there were 6 patients exhibiting meningeal involvement during some stage of their illness. Usually the principal presenting symptom was headache and other manifestations included vomiting, tinnitus, nominal aphasia and hyperacusis. The onset of symptoms bore no constant relationship to the state of haematological remission or relapse confirming the findings of other investigators. The CSF findings were considered and the importance of correct diagnosis was stressed, as these troublesome symptoms are invariably relieved by the administration of intrathecal methotrexate. It was found that meningeal involvement is not an indication of the terminal phase of the illness.

A review of acute leukaemia cases at Royal Prince Alfred Hospital

During the years 1965-1970 (inclusive) 159 patients were diagnosed as acute leukaemia. After excluding children and atypical cases, 135 adults with acute leukaemia remained and these were reviewed, being analysed according to age and sex distribution, leukaemic classification, survival after diagnosis, remission rate and its relation to forms of therapy. An initial remission was obtained in 27% and when the patients were divided into lymphoblastic and non-lymphoblastic categories the initial remission rates were 79% and 21% respectively. The median survival for the series was 2 mth. and the duration of life after diagnosis was 10 wk. or less in 50% of patients. Arising from experience in the management of these cases, the authors discussed decisions to withdraw anti-leukaemic agents, factors associated with remission rates, the significance of marrow lymphocytosis, long survivors and the quality of life in these patients.