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S D Lawler

Publications and source records attributed to S D Lawler.

At least 19 recordsLinked to original sources
PubMed1991

A prospective genetic study of complete and partial hydatidiform moles.

Two hundred two hydatidiform moles were classified by pathologic features and ploidy into partial or complete moles. Further classification was made by using genetic polymorphism, the diagnosis being refined by deoxyribonucleic acid technology. Among 51 partial hydatidiform moles, 44 triploids, two tetraploids, and one diploid were identified. Informative triploid partial hydatidiform moles had one maternal and two paternal sets of chromosomes, the likely origin being dispermy. Among 149 complete hydatidiform moles, one was haploid, one was triploid, and 105 were shown to be diploid or androgenetic; 39 of these were proved homozygous, indicating duplication of the male genome, whereas heterozygous origin by dispermy was likely in 13. The locus-specific minisatellite deoxyribonucleic acid probes were particularly useful for the identification of heterozygous complete hydatidiform moles. None of the patients with partial hydatidiform moles had development of a gestational trophoblastic tumor. No difference was detected in the frequency of requirement for chemotherapy between patients with homozygous or heterozygous complete hydatidiform moles.

Blotting, Southern↗
PubMed1990

Serial cytogenetic studies showing persistence of original clone in Hodgkin's disease.

A case of Hodgkin's disease is described in which cytogenetic studies were performed at intervals for 5 years. Clonally related chromosomally rearranged cells persisted during that time, with emergence of more complex karyotypes in the terminal phase of the disease. The chromosome findings are discussed in relation to the limited data available on banded karyotypes in Hodgkin's disease.

Bone Marrow Cells↗
PubMed1990

Cytogenetic studies of leukemic recurrence in recipients of bone marrow allografts.

Cytogenetic studies were made in 20 leukemic patients who relapsed after treatment by allogeneic bone marrow transplantation (BMT). Seven of the eight patients in whom no chromosomal abnormalities were detected in leukemic cells before BMT developed clonal abnormalities after BMT, and in two of these patients two independent clones were observed. Most patients in whom clones were detected before BMT showed evidence of clonal evolution after BMT. Nonclonal abnormalities were also observed in clonal cells. These additional abnormalities, both clonal and nonclonal, were attributed to the effects of total body irradiation received by the patient before BMT. There was no evidence of recurrence of leukemia in donor cells among these patients. We concluded that the cells found in leukemic recurrence were derived from the original leukemic clone.

Adolescent↗
PubMed1990

Gestational trophoblastic tumours following initial diagnosis of partial hydatidiform mole.

11 patients registered with an initial diagnosis of partial hydatidiform mole (PHM) subsequently required chemotherapy for a gestational trophoblastic tumour. In a retrospective review by histopathological examination and measurement of DNA ploidy, the diagnosis was confirmed as PHM in 5 cases and revised to complete hydatidiform mole in 4; in 2 cases there was no evidence of a molar pregnancy. 4 of the patients with PHM had no other known pregnancy before the gestational trophoblastic tumour and in 2 of these patients the tumour was diagnosed histologically as choriocarcinoma. Not all patients in whom PHM was diagnosed at referring hospitals proved to have the condition. Although the risk of a patient with PHM requiring chemotherapy for gestational trophoblastic tumour is of the order of 1 in 200, compared with 1 in 12 after a complete mole, there is no justification for excluding a patient from follow-up after the evacuation of a PHM.

Adult↗
PubMed1989

Cytogenetic studies of 21 patients with acute lymphoblastic leukemia in relapse.

Karyotypes of 21 patients, originally entered into the Third International Workshop on Chromosomes in Leukemia (3IWCL), were investigated in first, second and/or subsequent relapses. Karyotypes at diagnosis were related to the relapses in the following ways: normal to normal (N-N) (five cases); abnormal to normal (A-N) (two cases); abnormal to abnormal with no change (A-A) (five cases); abnormal to abnormal with clonal evolution (A-A+) (eight cases); and normal to abnormal (N-A) (one case). The A-A group comprised two each of t(4;11) and t(9;22) cases and one pseudodiploid case; included in this group were the only two patients who did not receive intensive treatment. Both A-N cases had been pseudodiploid at diagnosis. Clonal evolution A-A+ occurred in patients who had had 47-49 chromosomes or pseudodiploidy at diagnosis and was mainly due to the addition of structural change. The additional abnormalities were different in each case. The only de novo appearance of a clone (N-A) was in host cells in relapse following bone marrow transplantation. Clonal evolution occurred in patients who had been intensively treated and who relapsed late; the median time from diagnosis to relapse studied for the A-A group was 6 months and for the A-A+ group was 24 months. Survival following relapse was shorter for patients who had had a clonal abnormality at any time (median 10 months) than for those with no abnormality at diagnosis or in relapse (median 26 months).

Adolescent↗
PubMed1989

Frequency of heterozygous complete hydatidiform moles, estimated by locus-specific minisatellite and Y chromosome-specific probes.

Restriction fragment length polymorphisms identified with three locus-specific minisatellite probes and banding patterns with Y chromosome-specific probes have been examined in 39 cases of complete hydatidiform mole (CHM) and the parents. All 39 cases were shown to be androgenetic. Of the 39 cases, 8 were identified as heterozygous CHM using the minisatellite probes. Estimates for the total number of heterozygous CHM in the series ranged from 23%-29%, higher than previously reported. Of the eight identified heterozygous CHM, six had Y chromosome-specific sequences whereas two were female; this is not significantly different from the 2:1 ratio expected. The low frequency of 46,XX heterozygous CHM in the literature may reflect difficulties in distinguishing them from 46,XX homozygous CHM. Examination of RFLPs with a small panel of locus-specific minisatellite probes provides a powerful method of classifying hydatidiform mole, enabling the rare heterozygous 46,XX CHM to be accurately identified.

DNA Probes↗
PubMed1989

Chromosomes and other prognostic factors in acute lymphoblastic leukaemia: a long-term follow-up.

Cytogenetic, clinical and laboratory features at diagnosis were examined in a group of 80 children with acute lymphoblastic leukaemia (ALL) who had been followed up for a minimum of 5 1/2 years. The 17 (21%) with high hyperdiploidy tended to have low leucocyte counts and common ALL, but their favourable outcome (75% event-free survival) was independent of these factors. No patient with hypodiploidy survives while the pseudodiploid and normal groups have an intermediate prognosis. Cytogenetic analysis showed examples of patients with the well-recognized translocations and a number with apparently unique ones. Among the latter were some long-term survivors. We conclude that cytogenetic analysis identifies a good risk group of patients who remain well on long-term follow-up, but that the presence of a translocation does not necessarily imply a poor outcome.

Child↗
PubMed1989

Simultaneous application of immunolabelling and in situ hybridization to detect the origin of B and T lymphocytes in a case of acute lymphocytic leukaemia after bone marrow transplantation.

Previous cytogenetic studies, using selective mitogens, on a patient with B cell acute lymphocytic leukaemia during the 6 years of remission after bone marrow transplantation from an HLA-identical sister indicated persistence of recipient B lymphocytes in the peripheral blood. Such studies are necessarily limited to dividing cells at metaphase, which represent only a small proportion of the total cell population. We have now combined the techniques of immunolabelling and in situ hybridization on the patient's peripheral blood lymphocytes in order to define accurately their individual lineage and gender. A clear difference in the proportion of the persisting recipient lymphocytes was found between B and T lymphocyte lineages.

Adolescent↗
PubMed1988

Genetically homozygous choriocarcinoma following pregnancy with hydatidiform mole.

Genetic studies have been made in two cases of primary choriocarcinoma from patients in whom the antecedent pregnancy was a hydatidiform mole. Restriction fragment length polymorphisms of the DNA from the tumour, the patient and her partner were examined and in both cases the tumours were shown to be androgenetic in origin, having only paternal polymorphisms. While one tumour was shown to be heterozygous, two different paternal alleles being demonstrated with some probes, the other tumour was shown to be homozygous for all informative polymorphisms examined. Thus choriocarcinoma can follow complete hydatidiform mole which may be either heterozygous or homozygous.

Adult↗
PubMed1987

The human chorionic gonadotrophin alpha subunit gene in gestational trophoblastic disease. 1. Restriction fragment length polymorphisms in hydatidiform moles.

The distribution of EcoR1 and HindIII restriction fragment length polymorphisms in the region of the gene coding for the alpha subunit of human chorionic gonadotrophin have been examined in 71 normal controls, six families, and 65 cases of hydatidiform mole, all of European origin. In control samples the genotypes generated by the presence or absence of the restriction sites, fitted a Hardy Weinberg distribution while in family studies the two polymorphisms showed Mendelian inheritance. The distribution of the genotypes in hydatidiform moles differed from that in control samples. However, the frequency of the alternative alleles R+, R- and H+, H- was not significantly different in the two populations and differences in the distribution of genotypes could be explained in terms of the unique origin of hydatidiform moles. The frequency of the rare homozygous genotype R-R-,H+H+, which has previously been suggested to be associated with the development of choriocarcinoma, was similar in those complete moles which resolved spontaneously (35 per cent) and those which progressed to trophoblastic tumours (27 per cent). No association was found between the genotype of the hydatidiform mole and the subsequent clinical outcome of the patient. Thus the pattern of restriction fragment length polymorphisms associated with the human chorionic gonadotrophin alpha subunit gene would not appear to be an appropriate marker of clinical outcome in patients with hydatidiform moles.

Female↗
PubMed1985

Long-term effects of chemotherapy on lymphocyte chromosomes from patients treated for gestational trophoblastic tumours.

A cytogenetic follow-up study of patients treated with chemotherapy for gestational trophoblastic tumours was undertaken. In some cases, high levels of chromosome damage were found to persist in lymphocytes for several years after completion of therapy. These results are compared with those found in similar studies of non-malignant and other malignant diseases. The relevance of these findings to the risk of subsequent chemotherapy-induced malignancy is discussed.

Adult↗
PubMed1985

Lymphocytotoxic antibodies in leukemic patients treated with bone marrow transplantation.

Lymphocytotoxic antibodies were studied sequentially in a series of 42 patients with leukemia who received a bone marrow graft. Of these patients, 38% had cytotoxic antibodies before bone marrow transplantation (BMT). After BMT the antibody status changed with time, but 62% of the patients had antibodies at some time after BMT. During the first 10 weeks after BMT, 40% of the patients had antibodies. Thereafter the frequency rose to 50% and remained at that level beyond one year after BMT. In successful grafts the gamma globulins are of donor origin six months after BMT; thus donor B cells are capable of forming lymphocytotoxic antibodies even when the immune system is suppressed by cyclosporine. The antibodies had recognizable HLA specificity in about half the cases before and after BMT. When donor and patient were HLA-identical, HLA specificity did not correspond to donor/recipient antigens. In two cases in which the donor was matched for only one haplotype, antibodies formed by recipient cells, active against donor HLA antigens, were found.

Antilymphocyte Serum↗
PubMed1979

Bone marrow chromosomes in acute lymphoblastic leukaemia: a long-term study.

The bone marrow chromosomes of 25 children with acute lymphoblastic leukaemia (ALL) were examined at diagnosis before treatment, during remission, and in 12 cases, also during relapse. Follow-up was for at least six years. At diagnosis, 17 patients had a major population of chromosomally abnormal cells and of these 11 had identifiable clones. The commonest abnormality was hyperdiploidy. Eight patients had predominantly normal cells, but four of these had a minor abnormal clone. In remission, some samples were completely normal but, when pooled, remission samples had a minor population of chromosomally aberrant cells which were rarely clonal. The incidence of structural abnormalities was the same in patients who ultimately relapsed and those who remained in first remission at the end of the study, but the presence of hyperdiploid cells and/or clones in remission was more frequently associated with subsequent relapse. Relapse patterns were of two kinds: in three patients there was a return of the chromosomal abnormalities seen at diagnosis; in six others, chromosomal features in relapse were distinct from those at diagnosis. It is suggested that relapse associated with distinct chromosomal features may represent malignant transformation of a previously unaffected cell line. While chromosomal abnormalities seen prior to treatment can be related to the leukaemic event alone, abnormalities seen in remission and in relapse may result partly from drug and X-ray treatment. The relative importance of treatment and other factors to chromosomal change in ALL is discussed.

Bone Marrow↗
PubMed1979

The Ph1 chromosome in childhood leukaemia.

Ph1 positive leukaemia was diagnosed in eight of 123 (6.5%) consecutive new cases of childhood leukaemia. Four patients presented as typical chronic granulocytic leukaemia (CGL) and four as acute leukaemia, two of the four children with CGL have since developed blast crisis. Morphological and immunological characterization of the blasts in these six acute cases was suggestive of a lymphoid crisis in three, a mixed crisis in two, and a myeloid crisis in one. Remission was achieved in five of the six patients but lasted more than a year in only two; in one of these two patients the blasts at the time of crisis lacked the Ph1 chromosome and in the other, who presented in myeloid crisis, remission ended in a lymphoid crisis. Cytogenetic studies showed unusual translocations in two of the eight children. Serial examination showed that three children the proportion of Ph1 positive cells in the marrow was reduced to less than 6% at the time of remission from acute leukaemia. We conclude that Ph1 positive leukaemia in childhood presents frequently as acute leukaemia and may even mimic 'good risk' acute lymphoblastic leukaemia. The response to treatment cannot be predicted by morphological or immunological characterization of blast cells. Storage of bone marrow for possible autologous transplantation should be considered in children who achieve remission.

Adolescent↗