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Biomedical subjects

W G Sanger

Publications and source records attributed to W G Sanger.

At least 73 records · Page 4Linked to original sources
PubMed1989

Mapping of the human complement factor I gene to 4q25.

A detailed genetic and physical map of human complement factor I (IF) using somatic cell hybrids, in situ hybridization, and genetic linkage is reported. The gene has been localized to band 4q25. The order GC-INP10-ADH3-EGF-IF-IL2-MNS is proposed for genes on 4q on the basis of genetic and physical mapping techniques. A BclI polymorphism found with the IF probe demonstrated a maternal origin for a de novo deletion of chromosome 4 that was used in physically mapping the gene. The genetic and physical distances around band 4q24 suggest that 1 cM is approximately 1.2 million bp of DNA. This work provides a useful addition to the map of 4q.

Chromosome Mapping↗
PubMed1989

Maternal serum and amniotic fluid alpha-fetoprotein testing: our approach to screening, diagnosis and counseling.

Maternal serum and amniotic fluid alpha-fetoprotein testing has increased significantly in our laboratory and throughout the state since 1985. The results of this test are reported in a novel fashion as multiples of the median. The calculation and reporting of the test results are highly dependent upon gestational age, maternal weight, race and presence or absence of maternal diabetes. When properly interpreted alpha-fetoprotein determinations are a good screening test for early detection of neural tube defects and Trisomy 21 (Down Syndrome). Our approach to screening, diagnosis and counseling is discussed.

Adult↗
PubMed1989

Desmoplastic fibroma arising in fibrous dysplasia. Chromosomal analysis and review of the literature.

A desmoplastic fibroma of bone arose in the fibula of a 17-year-old boy with fibrous dysplasia. This may be the second case of this rare histopathologic association reported in the literature. Benign bone tumors have not previously been subjected to cytogenetic analysis. Analysis of this case revealed a primary abnormal clone trisomic for both chromosomes 3 and 5 and two subclones, one trisomic for chromosome 3 and one trisomic for chromosome 5. This case may also present the first description of nonrandom karyotypic abnormalities in a benign neoplasm of bone.

Adolescent↗
PubMed1989

Chromosomal abnormalities in Hodgkin's disease.

Numerous neoplastic states have associated or causal cytogenetic abnormalities. In some cancers, specific chromosomal abnormalities appear to correlate with the clinical characteristics and prognosis. Cytogenetic analysis of Hodgkin's disease is thought to be technically difficult and only a small number of cases with evaluable results have been reported. We have attempted cytogenetic studies of lymph nodes from 37 patients with Hodgkin's disease. In 29 of the 37 patients (78%), successful chromosomal analysis was accomplished. Chromosomal abnormalities were found in 13 patients (45%); five of these patients had been previously treated with chemotherapy. Numerical changes were found in all patients, most commonly involving chromosomes 5, 9, 15, 18, 22, X, and marker chromosomes. Seven patients also had structural abnormalities. The breakpoints 4q32-34, 6q24, 12q13, 12q23-24, and 13p11-13 were each seen in at least two patients. All but two patients had an admixture of normal cells. Three patients had two or more clones, and one had subclones. No statistically significant correlations between chromosomal abnormalities and clinical characteristics were demonstrated, although the number of patients in each subgroup was small. We conclude that chromosomal studies of Hodgkin's disease are likely to be successful. Additional studies are needed to correlate the karyotypical abnormalities in Hodgkin's disease with clinical and biological characteristics.

Adolescent↗
PubMed1988

Association of DNA content and proliferative activity with clinical outcome in patients with diffuse mixed cell and large cell non-Hodgkin's lymphoma.

Formalin-fixed and paraffin-embedded lymph node biopsy specimens from 52 untreated patients with newly diagnosed diffuse large cell (n = 48) or mixed cell (n = 4) non-Hodgkin's lymphoma (NHL) were analyzed for DNA content and proliferative activity (PA) by flow cytometry. The results obtained by flow cytometry were compared with the results of cytogenetic studies performed on 28 of the specimens. The median age of the patients was 65 years (range, 15-84 years) and the male to female ratio was 3 to 2. All patients were uniformly staged and uniformly treated with cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine, and prednisone. The flow cytometric results were compared statistically by univariate analysis with the rate and duration of complete remission and survival. Tumors with low PA (greater than or equal to 80% of cells in G0/G1 phase) were found in 65% of the patients; 74% of those with low PA versus only 44% of those with high PA achieved an initial complete remission (P less than 0.02). DNA aneuploidy was detected in tumors of 56% of the patients and was associated with a significantly longer duration of complete remission (P less than 0.01). Both low PA and aneuploidy independently predicted longer survival. The predicted 2-year actuarial survival for patients with tumors with low PA was 68% versus 10% for those with high PA (P less than 0.01). Similarly, the 2-year survival of patients with aneuploid tumors was 60% versus 36% for those with diploid tumors (P less than 0.01). The combination of PA and DNA content categorized the patients into four groups with decreasing 2-year survivals: low PA/aneuploid (n = 20), 77%; low PA/diploid (n = 14), 57%; high PA/aneuploid (n = 9), 32%; high PA/diploid (n = 9), 0%. The flow cytometric results correlated well with those of the cytogenetic studies. We conclude that low PA and DNA aneuploidy, both separately and in combination, predict a favorable clinical outcome for patients with diffuse mixed cell and large cell NHL.

Adolescent↗
PubMed1988

Correlation of secondary cytogenetic abnormalities with histologic appearance in non-Hodgkin's lymphomas bearing t(14;18)(q32;q21).

Successful cytogenetic studies were performed on 69 biopsies from 64 patients with non-Hodgkin's lymphoma bearing a t(14;18)(q32;q21) translocation. This translocation appears to be a primary abnormality associated with the development of certain B-cell non-Hodgkin's lymphomas. We correlated the occurrence of secondary abnormalities, in addition to the t(14;18)(q32;q21), with histologic subtype to test the hypothesis that secondary abnormalities correlate with more aggressive histologic appearance. A large number of secondary abnormalities were identified, the most frequent being additional copies of chromosomes 7 (30%), 12 (22%), 18 (22%), 20 (16%), or 21 (14%), deletion of a portion of the long arm of chromosome 6 (17%), and either an additional chromosome 17 or an isochromosome for the long arm of chromosome 17 (13%). An extra chromosome 7 was highly associated with a diffuse histologic pattern; it was present in 52% of patients with a diffuse pattern and in only 15% of those with a follicular pattern (P = .002). A weaker association with a diffuse growth pattern was found for the addition of chromosome 17 or an i(17q); it was found in 24% of patients with a diffuse pattern and only 5% of those with a follicular pattern (P = .05). No other significant correlations between secondary chromosome abnormalities and histologic subtype were identified. Although the explanation for this association is not clear, it appears that patients with B-cell non-Hodgkin's lymphomas bearing the t(14;18)(q32;q21) translocation which also have an additional chromosome 7 are likely to exhibit a diffuse growth pattern.

B-Lymphocytes↗
PubMed1988

Preferential in-vitro growth and expansion of leukemic T lymphoblasts.

An in-vitro culture system was used to selectively grow malignant cells from the bone marrow of a patient with acute T-lymphoblastic leukemia. Molecular analysis of DNA extracted from the bone marrow cells before culture showed the presence of both rearranged and germ line patterns for the T-cell beta receptor (CTB) gene, and chromosomal analysis revealed the presence of a major and a minor abnormal clone. The cells were cultured in RPMI medium supplemented with 20% fetal calf serum, 2% lymphocyte conditioned medium, L-glutamine and antibiotics. The presence of malignant cells in the cultured population was confirmed by morphologic, molecular probing and cytogenetic analysis. After four weeks in culture, DNA extracted from the cultured cells showed only the rearranged pattern for the CTB gene. Chromosomal analysis of the same cultured sample revealed only the presence of the initially predominant abnormal clone. Shortly thereafter, analysis of fresh uncultured bone marrow cells from the patient in relapse revealed that the same chromosomally abnormal clone also predominated in vivo. Thus, our results demonstrate the selective nature of this culture system and its ability to amplify leukemic T-lymphoblasts. This culture system is also useful for detecting occult malignant cells in histologically normal bone marrow.

Adult↗
PubMed1988

Acute leukemia expressing the normal human hematopoietic stem cell membrane glycoprotein CD34 (MY10).

Thirty-one cases of acute leukemia with blast cells greater than or equal to 70% positive for the hematopoietic stem cell Ag, CD34 (MY10, HPCA-1), were identified from the University of Nebraska Medical Center and The Johns Hopkins Oncology Center over an 18-month period. Fourteen of the cases were classified as early B-lineage ALL, 3 cases were other ALL subtypes, and 14 of the cases were ANLL. Five of the 17 cases of ALL expressed one or more myeloid-associated surface Ags, 3 ANLL cases expressed CD10 (CALLA, J5), and T-lymphoid Ags were present in 12 of 31 cases (1 T-cell ALL, 3 of 16 B-lineage ALL cases, and 8 of 14 ANLL cases). Eleven of 12 CD34+ ALL cases studied had abnormal karyotypes; only 7 of 12 CD34+ ANLL cases studied had abnormal karyotypes, and 3 of these were CD10+ ANLL. Six cases were Ph1 positive, including the one mature B cell ALL, 4 early B-lineage ALL, and 1 CD10+ ANLL case. Good and poor prognosis subgroups of high frequency of expression of CD34 leukemias could be identified, generally, as would have been predicted by previously defined criteria. Thus, of the 10 Ph1-negative early B-lineage ALL patients, 9 achieved CR (90%). At the other extreme, the CR rate of CD10- ANLL was 4 of 11 (36%). The leukemias characterized by greater than or equal to 70% of cells positive for CD34 form a relatively undifferentiated subset of the leukemias which may show features associated with more than one lineage, and if CD10- and myeloid morphology, may respond poorly to therapy.

Antigens, CD34↗
PubMed1988

Failure of karyotypic instability to predict clinical progression in patients with dysmyelopoietic syndromes.

Twenty-five patients with leukemia and dysmyelopoietic syndrome underwent serial cytogenetic analysis during the course of their disease. All 21 patients with leukemia had improvement or disappearance of karyotypic abnormalities with effective treatment of their leukemia, and karyotypic progression was observed only in instances of recurrent or progressive leukemia. All four patients with dysmyelopoietic syndrome exhibited karyotypic instability, which was independent of therapeutic interventions or disease progression. The data presented suggest that karyotypic instability in the dysmyelopoietic syndromes may be more common than currently accepted.

Adolescent↗
PubMed1987

Initial and subsequent cytogenetic studies in malignant lymphoma.

Two or more cytogenetic studies of lymph node biopsy specimens from 12 patients with non-Hodgkin's malignant lymphoma were performed. Each of the 12 patients had at least one clonal structural chromosome abnormality in their initial biopsy specimen. A comparison of the chromosome abnormalities in the initial lymph node biopsy specimens with those in subsequent biopsy specimens was made. Structural and numerical chromosome changes were not always accompanied by a change in the histologic type of the lymphoma. Similarly, a change in histologic type was not always associated with the appearance of new structural or numerical abnormalities. Serial cytogenetic studies from additional patients will further our understanding relevant to which chromosome changes are associated with lymphomagenesis and which are secondary or more of an evolutionary nature.

Adult↗
PubMed1987

Cat-eye syndrome with different marker chromosomes in a mother and daughter.

Except for atypical eye findings in the daughter, a mother and daughter with bisatellited marker chromosomes had abnormalities consistent with cat-eye syndrome. The mother's marker chromosome (mar number 1) is derived from one 22 and another acrocentric, possibly also a 22; the daughter's marker (mar number 2) may be an iso-dicentric, inv-dup (22) derivative of mar number 1. The mother has a tertiary trisomy translocation chromosome composed of at least one and perhaps two copies of 22pter----q11.2, whereas the daughter clearly has a secondary trisomy 22pter----q11.2 isochromosome, confirming this region as a cause of cat-eye syndrome. Results of hybridization using a unique sequence probe localized to 22q11 are consistent with the interpretation that both ends of both marker chromosomes are derived from 22.

Abnormalities, Multiple↗
PubMed1987

Chromosomal abnormalities in indolent lymphoma.

Cytogenetic studies were performed on lymph node biopsies from 60 patients with indolent (low grade) non-Hodgkin's lymphoma. Thirty-two of the 39 successfully cultured biopsies had abnormal clones. The 32 abnormal clones represented the following histologies: seven small lymphocytic lymphoma (SL), eight follicular small cleaved cell lymphoma (FSC), 14 follicular mixed, small cleaved, and large cell lymphoma (FM), and three composite lymphomas. One of the composite lymphomas had FSC/DSC (diffuse small cleaved cell) and the other two FM/DM (diffuse mixed, small cleaved and large cell). Twenty-seven of the 32 biopsies were immunologically typed, and all were B cell. The clones all exhibited more structural than numerical abnormalities, and there was no difference in the modal chromosome number of the abnormal clones found in each histology. Biopsies with no normal cells were more frequently found in the SL histology (71%) than in the two follicular lymphoma groups (54%-55%). A translocation of the 14q32 segment was the most common abnormality found in all three histologies. In the follicular lymphomas a t(14;18)(q32;q21) was seen in 52% (13 of 25) of these patients, this translocation was not observed in the SL patients. Overall 84% (21 of 25) of the follicular lymphoma patients had abnormalities of 14q32 and/or 18q21. Other specific abnormalities included anomalies of chromosome #3 in FM, an abnormal 10q in FSC and FM lymphoma, and a high incidence of +18 and chromosome #1 abnormalities in patients with t(14;18). The presence of specific chromosome abnormalities in the indolent lymphoma patients suggests a relationship between certain karyotypic features and histology.

Adult↗
PubMed1987

Missing Y chromosomes in lymph nodes from patients with non-Hodgkin's lymphoma.

Five of 86 male patients with non-Hodgkin's lymphoma had chromosomally abnormal clones in their lymph nodes, which involved a missing Y chromosome. The loss of the Y chromosome was confined to the malignant cells when normal cells were present. The patients ranged in age from 41 to 85 years. All five patients had B-cell lymphomas with the histologic subtype diffuse large cell in two patients and immunoblastic, follicular large cell and follicular mixed in a single patient each. The t(14; 18)(q32;q21) chromosome abnormality accompanied the missing Y chromosome in four of the five patients. It appears that Y chromosome loss is one of the secondary abnormalities associated with non-Hodgkin's lymphoma.

Adult↗
PubMed1987

Intermediate lymphocytic lymphoma: immunophenotypic and cytogenetic findings.

A detailed immunohistologic and cytogenetic analysis of 12 cases of intermediate lymphocytic lymphoma was performed. The characteristic immunophenotype of intermediate lymphocytic lymphoma was: surface IgM and IgD+, BA1+, B1+, BA2-, B2-, B4+, Leu 14+, Leu 1+, HLA-DR+, and common acute lymphocytic leukemia associated (CALLA) antigen negative. Clonal chromosome abnormalities were identified in ten cases, with structural or numerical abnormalities of chromosomes 11 or 12 in nine cases. Five cases had structural abnormalities involving the long arm of chromosome 11; three of these had translocations with chromosome 14 at band q32. Three cases had trisomy 12, and one case had a translocation involving the long arm of chromosome 12. The tenth case had a translocation involving the long arms of chromosomes 7 and 9. These characteristic immunophenotypic and cytogenetic findings suggest a close lineage relationship between intermediate lymphocytic lymphoma and small lymphocytic (well differentiated) lymphoma/chronic lymphocytic leukemia. Their differing clinical, cytologic, and architectural features suggest, however, that intermediate lymphocytic lymphoma should be considered a separate category of lymphocytic lymphoma in the International Working Formulation.

Biopsy↗
PubMed1986

Familial lethal sleep apnea.

Three of six siblings presented with sleep apnea between 18 and 26 months of age. Twin females and a male had normal growth and development without antecedent neurologic or apparent metabolic disorder. The females presented at 25 and 27 months respectively with irregular respiration and episodes of apnea. Twin A succumbed to an apneic episode while sleeping. Central sleep apnea was diagnosed in twin B at the Stanford Sleep Clinic. She died following an apneic episode three months after evaluation. The male presented at 18 months with fatal sleep apnea. A fourth child was evaluated for sleep apnea at 7 weeks of age with several hospitalizations before her death at 31 months. She and remaining family members were extensively studied for inherited neurologic disorders including subacute necrotizing encephalomyopathy (SANE, Leigh disease). This family with lethal sleep apnea presents an association with SANE with minimal neurologic signs and symptoms and neuropathologic involvement. Lesions were confined to the respiratory centers of the lower brain stem, making sleep apnea explicable. This child and family members tested positive or borderline for inhibitor substance thiamine triphosphate (TTP). All testing for TTP inhibitor substance was performed in Professor Jack R. Cooper's laboratory, Department of Pharmacology, Yale University School of Medicine, New Haven, Conn. These cases present an interesting and instructive lesson emphasizing the need for extensive evaluation of children with unsuspected sleep apnea with early demise.

Adult↗
PubMed1986

Cytogenetic abnormalities in noncutaneous peripheral T-cell lymphoma.

Cytogenetic studies were performed on lymph nodes from eight patients with noncutaneous peripheral T-cell lymphoma. At least one chromosomally abnormal clone was identified in each patient. Chromosomes having structural abnormalities in two or more patients included chromosome #1 (four), chromosome #2 (three), chromosome #4 (two), chromosome #8 (two), chromosome #14 (two), and chromosome #17 (two). The abnormal clones from seven patients had structural abnormalities involving either chromosomes #1 or #2, and the eighth patient had an abnormal clone that was trisomic for chromosome #1. We did not observe structural rearrangements in chromosome #14 at bands q11 or q12 in any of our cases, in contrast to previous suggestions that this chromosomal region may play a critical role in the development of T-cell lymphomas. Our findings suggest that other nonrandom chromosome abnormalities are common and may be important in the development of noncutaneous peripheral T-cell lymphomas.

Adult↗