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The abnormalities of lipoprotein metabolism in heterozygous familial hypercholesterolaemia
140
HUMAN GENETICS SOCIETY OF AUSTRALASIA
Pathology (1980), 12, January
inherited syndrome of osseous fragility with sclerae of normal hue. The frequency of presenile hearing loss in patients with 0.1. type 111 and type IV is not known. These observations on the heterogeneity in osteogenesis imperfecta suggest that different patterns of histological, histochemical, ultrastructural and biochemical abnormalities may be found in these different 0.1. types. THE ABNORMALITIES OF LIPOPROTEIN METABOLISM IN HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA
E. D. JANUS,ANNEM. NICOLL,P. R. TURNER, R. WOOTTON & B. LEWIS Department of Chemical Pathology and Metabolic Diseases, St Thomas’ Hospital, London, England Familial hypercholesterolaemia (FH) occurs in an estimated 0.1-0.2% of the population. There is autosomal dominant transmission of the disorder and approximately 50% of affected males have coronary heart disease by age 50. Homozygotes rarely survive beyond their twenties. Studies of lipoprotein metabolism were performed in 14 patients with heterozygous FH and 7 control subjects using injections of autologous I 3 l l labelled very low density lipoprotein (VLDL) and 1251 labelled low density lipoprotein (LDL). In normal subjects VLDL-B peptide synthetic rates varied from 10.3-17.1 mg/kg/24 h (mean 15.1 mg/kg/24 h), LDL-B peptide synthetic rates from 5.2-10.3 mg/kg/24 h (mean 7.7 mg/kg/24 h) and LDL-B peptide fractional catabolic rates (FCR) from 0.245-0.36/d (mean 0.31/d). In heterozygous FH VLDL production was normal in 8 patients with normal triglyceride levels. There was either VLDL overproduction or a catabolic defect in 5 patients with superadded hypertriglyceridaemia. LDL-B peptide synthetic rates range from high normal to markedly increased (8.85-18.0 mg/kg/24h) and LDL-B peptide FCR values were markedly reduced (0.135-1.275/d) thus confirming the known LDL catabolic defect and indicating superadded over-production. In a further study LDL-B peptide production from VLDL-B peptide was estimated in 24 subjects using deconvolution analysis of ‘’’I LDL and 1311 LDL-B peptide activity curves. LDL-B peptide production from VLDL-B peptide and directly measured LDL-B peptide production were essentially equal in 6 normal control subjects and in normocholesterolaemic patients. In 6 patients with FH, LDL-B peptide turnover exceeded LDL-B peptide production from VLDL-B peptide, suggesting direct secretion of up to 50% of the LDL in the patients with this condition. CYTOGENETIC PATTERNS IN ACUTE NON-LYMPHOCYTIC LEUKAEMIA
P. NOLAN,G. SZELAG, J . LYALL,L. GIBSON& 0. M. GARSONCytogenetic Unit, University of Melbourne, Departmenl of Medicine, St Vincent’s Hospital, Fitzroy, Vicioria Chromosome banding studies of the leukaemic cells of patients with acute non-lymphocytic leukaemia (A.N.L.L.) show that both numerical and structural changes occur in 50-60% of patients examined at diagnosis. Identification of chromosomes involved in both types of change indicate that there is a non-random involvement of specific chromosomes. In addition, cytogenetic subgroups can be identified which appear to have prognostic implications. This paper reviews the results of chromosome studies in A.N.L.L.performed in thecytogenetic research unit at St St Vincent’s Hospital, from 1975 to 1978. Using short-term marrow cultures, chromosome studies were carried out on 168 patients at diagnosis; 102 were found to have abnormal karyotypes and 48 showed no chromosome abnormality. No mitoses were obtained from 18 patients. To date trypsin G-banding studies have been satisfactorily performed on 47, of whom 37 had abnormalities. The most common abnormality was trisomy 8. A specifictranslocation between 8 and 21 was identified in 3 patients and a 9;22 translocation in 2 others. All patients with acute erythroleukaemia, and the majority with A.N.L.L. occurring after long-term therapy for other haematological disorders, had abnormal karyotypes with multiple abnormalities. The response of these patients to therapy was poor, whereas those with specific translocations all achieved remission. Ten of 12 patients considered to have a preleukaemic syndrome showed chromosome abnormalities which were most frequently monosomy 7 or partial deletion of the long arms ofchromosome 5,(5q-). Similar findings have been reported in other series, but the frequency of Occurrence appears to show geographical variation. Therefore as cytogenetic patterns seem to have diagnostic, prognostic and aetiological implications in A.N.L.L., chromosome studies should always be performed at diagnosis. A PARTIAL MECHANISM FOR CENTROMERIC SUPPRESSION
Aur DANIELCytogenetrcs Unit, Prince of Wales Hospital, Randwick. New South Wales Of constderable surprise and interest to human cytogeneticists with the advent of chromosome banding, has been the number and diversity of dicentric structural rearrangements. These have been found in sex chromosomal and
HUMAN GENETICS SOCIETY OF AUSTRALASIA
Pathology (1980), 12, January
inherited syndrome of osseous fragility with sclerae of normal hue. The frequency of presenile hearing loss in patients with 0.1. type 111 and type IV is not known. These observations on the heterogeneity in osteogenesis imperfecta suggest that different patterns of histological, histochemical, ultrastructural and biochemical abnormalities may be found in these different 0.1. types. THE ABNORMALITIES OF LIPOPROTEIN METABOLISM IN HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA
E. D. JANUS,ANNEM. NICOLL,P. R. TURNER, R. WOOTTON & B. LEWIS Department of Chemical Pathology and Metabolic Diseases, St Thomas’ Hospital, London, England Familial hypercholesterolaemia (FH) occurs in an estimated 0.1-0.2% of the population. There is autosomal dominant transmission of the disorder and approximately 50% of affected males have coronary heart disease by age 50. Homozygotes rarely survive beyond their twenties. Studies of lipoprotein metabolism were performed in 14 patients with heterozygous FH and 7 control subjects using injections of autologous I 3 l l labelled very low density lipoprotein (VLDL) and 1251 labelled low density lipoprotein (LDL). In normal subjects VLDL-B peptide synthetic rates varied from 10.3-17.1 mg/kg/24 h (mean 15.1 mg/kg/24 h), LDL-B peptide synthetic rates from 5.2-10.3 mg/kg/24 h (mean 7.7 mg/kg/24 h) and LDL-B peptide fractional catabolic rates (FCR) from 0.245-0.36/d (mean 0.31/d). In heterozygous FH VLDL production was normal in 8 patients with normal triglyceride levels. There was either VLDL overproduction or a catabolic defect in 5 patients with superadded hypertriglyceridaemia. LDL-B peptide synthetic rates range from high normal to markedly increased (8.85-18.0 mg/kg/24h) and LDL-B peptide FCR values were markedly reduced (0.135-1.275/d) thus confirming the known LDL catabolic defect and indicating superadded over-production. In a further study LDL-B peptide production from VLDL-B peptide was estimated in 24 subjects using deconvolution analysis of ‘’’I LDL and 1311 LDL-B peptide activity curves. LDL-B peptide production from VLDL-B peptide and directly measured LDL-B peptide production were essentially equal in 6 normal control subjects and in normocholesterolaemic patients. In 6 patients with FH, LDL-B peptide turnover exceeded LDL-B peptide production from VLDL-B peptide, suggesting direct secretion of up to 50% of the LDL in the patients with this condition. CYTOGENETIC PATTERNS IN ACUTE NON-LYMPHOCYTIC LEUKAEMIA
P. NOLAN,G. SZELAG, J . LYALL,L. GIBSON& 0. M. GARSONCytogenetic Unit, University of Melbourne, Departmenl of Medicine, St Vincent’s Hospital, Fitzroy, Vicioria Chromosome banding studies of the leukaemic cells of patients with acute non-lymphocytic leukaemia (A.N.L.L.) show that both numerical and structural changes occur in 50-60% of patients examined at diagnosis. Identification of chromosomes involved in both types of change indicate that there is a non-random involvement of specific chromosomes. In addition, cytogenetic subgroups can be identified which appear to have prognostic implications. This paper reviews the results of chromosome studies in A.N.L.L.performed in thecytogenetic research unit at St St Vincent’s Hospital, from 1975 to 1978. Using short-term marrow cultures, chromosome studies were carried out on 168 patients at diagnosis; 102 were found to have abnormal karyotypes and 48 showed no chromosome abnormality. No mitoses were obtained from 18 patients. To date trypsin G-banding studies have been satisfactorily performed on 47, of whom 37 had abnormalities. The most common abnormality was trisomy 8. A specifictranslocation between 8 and 21 was identified in 3 patients and a 9;22 translocation in 2 others. All patients with acute erythroleukaemia, and the majority with A.N.L.L. occurring after long-term therapy for other haematological disorders, had abnormal karyotypes with multiple abnormalities. The response of these patients to therapy was poor, whereas those with specific translocations all achieved remission. Ten of 12 patients considered to have a preleukaemic syndrome showed chromosome abnormalities which were most frequently monosomy 7 or partial deletion of the long arms ofchromosome 5,(5q-). Similar findings have been reported in other series, but the frequency of Occurrence appears to show geographical variation. Therefore as cytogenetic patterns seem to have diagnostic, prognostic and aetiological implications in A.N.L.L., chromosome studies should always be performed at diagnosis. A PARTIAL MECHANISM FOR CENTROMERIC SUPPRESSION
Aur DANIELCytogenetrcs Unit, Prince of Wales Hospital, Randwick. New South Wales Of constderable surprise and interest to human cytogeneticists with the advent of chromosome banding, has been the number and diversity of dicentric structural rearrangements. These have been found in sex chromosomal and