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J M Craig

Publications and source records attributed to J M Craig.

At least 37 records · Page 2Linked to original sources
PubMed1993

Testicular relapse in Philadelphia chromosome positive acute lymphoblastic leukaemia.

A case of Philadelphia-positive (Ph) acute lymphoblastic leukaemia (ALL) in a 40-year-old male is presented. At diagnosis, 80% of bone marrow cells were Ph. Remission with normal blood counts was achieved but the marrow became hypercellular, indicating conversion to chronic granulocytic leukaemia (GCL). The Ph clone persisted with a variable percentage of Ph cells. He developed testicular relapse 38 months from diagnosis. The patient died when engraftment with a matched unrelated bone marrow transplant failed. Molecular investigation of DNA prepared from diagnostic and remission bone marrow and from testicular tissue in relapse revealed the same sized rearranged fragment of the BCR gene using a probe to the major breakpoint cluster region. This case confirms that testicular involvement due to infiltration of the testes by the original Ph leukaemic clone may occur as an unusual complication in Ph ALL. Conversion to chronic-phase GCL, a rare occurrence in Ph ALL, may have contributed to the unusually long survival.

Adult↗
PubMed1993

Prognostic implications of breakpoint and lineage heterogeneity in Philadelphia-positive acute lymphoblastic leukemia: a review.

Philadelphia-positive (Ph) acute lymphoblastic leukemia (ALL) is heterogeneous both in terms of the BCR gene breakpoints (M-bcr and m-bcr) and in the number of cell lineages carrying the Ph chromosome. The impact of these observations on the controversy surrounding Ph ALL and Ph+ chronic granulocytic leukemia (CGL) is unclear. Twenty cases of Ph ALL (four newly investigated and 16 previously published) were classified into nine stem-cell (the Ph in myeloid and lymphoid cells) and 11 lymphoid-restricted cases. Lymphoid cases had a lower leucocyte count (56 x 10(9)/l) than stem-cell cases (151 x 10(9)/l) (p < 0.01). The M-bcr and m-bcr breakpoints (in 14 cases) were found in lymphoid (four cases of each) and stem-cell (five and one cases respectively) cases. Lymphoid cases had significantly shorter event-free survival (median 4 months) than stem-cell cases (median 35 months) (p < 0.01). M-bcr cases were older (mean 41 years) than m-bcr cases (mean 36 years)(p = NS); m-bcr cases had higher leukocyte counts (mean 85 x 10(9)/l) than M-bcr cases (36 x 10(9)/l)(p < 0.01) but breakpoint had no impact on prognosis. Lineage involvement, but not breakpoint, appears to distinguish prognostically important sub-groups of Ph ALL. Paradoxically, lymphoid-restricted cases have a worse prognosis than cases arising in a pluripotent stem-cell.

Adolescent↗
PubMed1991

Ewing's sarcoma t(11;22) in a case of acute nonlymphocytic leukemia.

Chromosome analysis of bone marrow cells from a patient with acute nonlymphocytic leukemia M2 revealed the translocation t(11;22)(q24;q12) usually associated with Ewing's sarcoma. Molecular investigations ruled out the possibility that this was a variant Philadelphia translocation with breakpoints in the major breakpoint cluster region. Although cytogenetic analysis was not available at diagnosis, this abnormality was found both pre- and postallogeneic bone marrow transplant.

Adolescent↗
PubMed1991

Molecular investigation of 19p13 in standard and variant translocations: the E12 probe recognizes the 19p13 breakpoint in cases with t(1;19) and acute leukemia other than pre-B immunophenotype.

The gene E2A has recently been cloned, mapped to 19p13 and shown to be rearranged in cases of pre-B acute lymphoblastic leukemia (ALL) with t(1;19) (q23;p13). Nine cases with a 19p13 breakpoint, four having a phenotype other than pre-B, have been investigated with the E12 probe to the E2A gene. Five cases had t(1;19) (q23;p13) and C-ALL with pre-B phenotype in four out of four cases tested. Two cases had t(1;19) (q21;p13), one with Null cell phenotype, t(4;11), and 'jumping translocations' and the other with acute non-lymphocytic leukemia M5 following bone marrow transplantation for C-ALL. Variant translocations in patients with ALL were t(15;19) (q15;p13) and t(17;19) (q21;p13). Southern blotting with E12 showed rearrangement in the cases with t(1;19) (q23;p13) and t(1;19) (q21;p13), but not in other cases with variant 19p13 breakpoints. Thus rearrangement of the E2A gene is not restricted to cases with pre-B ALL but may also occur in acute leukemias with other immunological phenotypes. Failure to detect rearrangement in 19p13 variants may be due to an E2A breakpoint outside the E12 recognition region. Alternatively, there may be further genes in this location with relevance to leukemogenesis.

Adolescent↗
PubMed1991

Philadelphia positive acute lymphoblastic leukemia in adults: age distribution, BCR breakpoint and prognostic significance.

Clonal karyotype, clinical and blast cell features were established in 113 adults, aged 15-68 (mean 31.2) years with acute lymphoblastic leukemia (ALL). The karyotypes were: Philadelphia positive (Ph+), 23 cases; t(4;11), six cases; other chromosome findings (group II), 84 cases. Ph+ patients were older (mean 39.7 years) at presentation than the group II patients (mean 28.3 years) (p less than 0.0001). Ph+ was less frequent than expected in teenagers (15-20 years) (10.3%) and patients aged 21-50 years (21.8%), and more frequent in patients over 50 years old (43.8%) (p less than 0.01). Follow-up (between 0.5 and 4.5 years) was obtained for 108 patients. Age and karyotype (Ph+ versus group II) were prognostically significant for event-free (EFS) and overall survival (S) (p less than 0.001 in each instance). Ph+ patients fared worse than group II cases in all age groups, but karyotype added prognostic significance to age only when Ph+ and t(4;11) cases were combined (group I) (group I versus group II: EFS, p = 0.054; S, p = 0.043). The Ph breakpoint location M-bcr+ (nine cases) and M-bcr- (14 cases) was irrelevant to age (mean 37.7 and 41.3, respectively) and to prognosis. The findings indicate a fundamental difference between the genetics of ALL in most older and the majority of younger patients which may partly explain the increasingly poor prognosis with age.

Adolescent↗
PubMed1990

First intron and M-bcr breakpoints are restricted to the lymphoid lineage in Philadelphia positive acute lymphoblastic leukemia.

Knowledge of the level of commitment of the target cell in hematological malignancies may have important therapeutic and prognostic implications. Cell lineage involvement was investigated in two cases presenting with acute lymphoblastic leukemia diagnosed on clinical and immunological findings and having the Philadelphia translocation t(9;22)(q34;q11). DNA from cells separated into mononuclear (lymphoid) and granulocytic fractions was hybridized with Philadelphia breakpoint-specific probes. This revealed that the breakpoint giving rise to the Philadelphia chromosome in case 1 was within the major breakpoint cluster region and in case 2 was in the first intron of the BCR gene. Rearrangement was found in the lymphoid but not the granulocyte fraction in each case. It is therefore concluded that the target cell for chromosomal change in these cases was a lymphoid committed progenitor cell, irrespective of breakpoint location.

Adult↗
PubMed1981

Group B beta hemolytic streptococcal sepsis in the newborn.

Group B Beta Hemolytic streptococcal infection among newborn infants has recently grown in importance. The pathological changes in the early onset cases appear to be confined to the lung. In our patients, hyaline membranes with peripheral atelectasis was unusual, although fibrin deposited in areas without accompanying atelectasis may lead to confusion with hyaline membrane disease. The clinical features and pathologic changes caused by GBS had some differences from those due to other organisms giving rise to fatal pneumonia in the newborn. The lungs of GBS-infected babies in our autopsy series were not as heavy, had more alveolar fibrin deposition, but not more hyaline membrane disease than in nonstreptococcal cases. Alveolar inflammation was more marked in nonstreptococcal cases, but the GBS cases had more interstitial inflammation. Massive alveolar bacterial growth was more common in the GBS cases. Chronic thymic involution was less marked in the GBS cases, while acute splenitis was more common. Meningitis was present in four of our nonstreptococcal cases, but in none of the GBS cases. The clinical courses of GBS and nonstreptococcal fatal pneumonias differed. The mothers of infants with GBS infection were less febrile and ahd an increased frequency of prolonged rupture of the membranes, while the infants had a decreased duration of life, compared to those with nonstreptococcal sepsis.

Adult↗
PubMed1971

C1 inhibitor: evidence for decreased hepatic synthesis in hereditary angioneurotic edema.

Although the Cl inhibitor was detected in 5 to 10 percent of normal hepatic parenchymal cells by means of the immunofluorescent technique, none was seen in liver biopsies from two individuals with hereditary angioneurotic edema having low concentrations of Cl inhibitor in the serum. In contrast, the percentages of cells which reacted with fluorescent antiserums to C4 and transferrin were normal. These data suggest that in most subjects with hereditary angioneurotic edema, there is decreased synthesis of the C1 inhibitor but normal synthesis of C4, and that the disease results from this biosynthetic error.

Adult↗