Biomedical subjects
Publications and source records attributed to R Berger.
The chromosome localization of a 5.4 kb DNA genomic probe of proto-oncogene c-ets 1 has been analysed in an acute monocytic leukemia with t (1; 11) (q21; q23) translocation. The c-ets probe has been translocated onto the rearranged chromosome 1, suggesting the involvement of the proto-oncogene in leukemias with chromosome rearrangements at band 11 q23.
The importance of banded chromosome analyses in predicting long-term outcome in acute lymphoblastic leukemia (ALL) was evaluated in this follow-up study of 329 patients from the Third International Workshop on Chromosomes in Leukemia. Patients were divided into ten groups according to pretreatment karyotype: no abnormalities, one of the following structural abnormalities [the Philadelphia chromosome, translocations involving 8q24,t(4;11), 14q+, 6q-] or, in the remaining cases, modal number [less than 46, 46, 47 to 50, greater than 50]. Achievement and duration of complete remission (CR) and survival differed among chromosome groups (P less than .0001). Karyotype was an independent prognostic factor for duration of first CR and survival, even when age, initial leukocyte count (WBC), French-American-British (FAB) type, and immunologic phenotype were considered. Among adults, prolonged remission and survival were uncommon in all chromosome groups. Only in the normal karyotype group was median survival even two years. Among children, striking differences in long-term remission and survival were seen depending upon karyotype. Children in the greater than 50 group did best, with 70% remaining in first CR for a median duration in excess of five years. Children in the 47-50, 6q-, and normal karyotype groups also had prolonged survivals. In contrast, certain translocations [t(9;22)(q34;q11), t(4;11)(q21;q14-23), t(8;14)(q24;q32)] identified children who had short survivals, even in the presence of favorable prognostic factors including a low WBC, L1 morphology, and non-T, non-B immunologic phenotype. We conclude that chromosome analysis is required at diagnosis in patients with ALL, and that children with these specific translocations should be managed as having high-risk ALL.
An exceptional case of acute myeloblastic leukemia (M2) with t(8;21) relapsed as an acute monoblastic leukemia (M5). At that time only a minority of metaphases exhibited a t(8;21) and/or abnormality of chromosome No 11 long arm whereas various other chromosomal changes were present. The existence of a relapse of M2 with t(8;21) as M5 is discussed in relation to the commitment of the cells which became leukemic, and to the possibility of a second leukemia.
The combined Measles-Mumps-Rubella vaccines commercially available for use are safe, highly immunogenic, and protective. But the acceptance rate of these vaccines by the public and also by the general practitioners in most part of Europe is not a very high one. One of the reasons for this low acceptance-rate is the fear of side-reactions. In spite of that only exceptional cases of dangerous allergic reactions induced by such vaccines, especially the lay population can be scared by the contraindications mentioned in the "physician circular-patent product information". Therefore it was worthwhile to test a new trivalent vaccine produced exclusively on human tissue without using any avian protein or animal protein extracts or antibiotics. Under double-blind conditions 120 children aged between 15 and 24 months received either the new vaccine or the commercially available M-M-R-II vaccine produced by MSD. Measles and Rubella antibodies were tested by hemagglutination-inhibition tests, Mumps by the immuno-fluorescence technique. No reports of major side-effects were received from the 12 physicians participating in the trial. The seroconversion rates recorded 6 to 8 weeks after vaccination were high (95-100%) and there was no statistically significant difference between the two vaccines with regard to immunogenic potency.
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To isolate DNA segments specific to chromosome band 14q11, which has been implicated in a number of human T-cell malignancies, a genomic DNA library was prepared from a variant cell subline of the human lymphoblastic KE37 cell line. This subline (KE37-R) bears a t(8;14) (q24;q11) translocation, and the breakpoint on the resulting chromosome 8q+ has been located at the 3' end of the third c-myc exon. Three molecular clones were isolated by screening the library with a c-myc exon 3 probe, and one of them (lambda K40) was analyzed in detail. It contains a 15-kb insert consisting of 4.5 kb of sequence from chromosome 8 (e.g., downstream of c-myc exon 3) and sequences from chromosome 14. The origin of these latter sequences was established by hybridizing DNA from chromosomes sorted by flow cytometry to a lambda K40 subclone containing only chromosome 14 presumptive sequences and by Southern blot analysis of rodent X human somatic hybrid cell DNA with the same probe. No cross-hybridization was found between the lambda K40 clone and a cDNA clone for the alpha chain T-cell receptor gene which is also located in 14q11. A preliminary survey of DNAs from human T-cell malignancies with a probe corresponding to chromosome 14 sequences of lambda K40 clone revealed for some of them restriction patterns different from those of the germ line DNA. The fact that the rearrangement observed in a leukemic patient was not found in DNA from lymphocytes obtained during remission excluded any polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS)
The results of a field trial with a novel, live attenuated human diploid cell vaccine (HDCV) against measles, mumps and rubella are described. The study was performed double blind and included 120 children aged 15 to 24 months. 60 children received the new vaccine and a control group of another 60 children were vaccinated with M-M-RR II. The seroconversion rates found 6 to 8 weeks after the vaccination were high without exception (95% to 100%). The multiple chi 2-test revealed no statistically significant difference in immunogenic efficacy between the two vaccines (p greater than 0.05). No reports of side effects were received from the 12 physicians participating in the study. It is pointed out that all components of the new vaccine are highly attenuated and that the vaccine is free of avian protein, animal protein extracts and antibiotics. This excludes all theoretical and practical contraindications due to the corresponding hypersensitivities.
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Two new European Burkitt's lymphoma (BL) cases are reported. Their karyotypic abnormalities were unusual, without involvement of chromosomes #8, #14, #2, or #22. However, in both tumors, a 6q- chromosome was, present. These findings raise questions about the definition of BL and the involvement of various different DNA sequences in the mechanisms of BL genesis.
The c-mos proto-oncogene is the cellular counterpart of the viral oncogene v-mos isolated from Moloney murine sarcoma virus. The c-mos gene locus has previously been assigned to human chromosome 8. By both in situ hybridization and molecular hydridization to sorted chromosome DNA (using a c-mos probe) we have localized the c-mos gene to band 8q11. This regional localization is at variance with the one previously reported at 8q22 and may explain why no rearrangement of c-mos has been found in acute leukaemia with the chromosomal translocation t(8;21)(q22;q22).
An EcoRI restriction fragment length polymorphism (RFLP) was detected in the 3' end of the locus of the c-erb-A proto-oncogene. The frequency of the rarer allele was around 3.0% in a normal population of 107 unrelated individuals. This frequency did not significantly differ in DNA samples from patients with breast tumors or acute leukemias.
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The diagnostic value of the fluorescent immunosorbent test for IgG gliadin antibodies (FIST) has been investigated in comparison with the LIF test--the competence of the gluten subfractions B2 and B3 in releasing lymphokines from peripheral lymphocytes in vitro--in 96 patients with coeliac disease (CD) under various dietary conditions. In untreated children with CD during their first 2 years of life, the FIST showed 100% sensitivity with 95% specificity, whilst the LIF test showed only 70% sensitivity and 73% specificity. Therefore it can be concluded that the FIST as a screening test is superior to the LIF. In older children with a proved recurrence of the mucosal abnormality after reintroduction of a normal diet, only 44% showed increased IgG gliadin antibody titres whereas 70% proved to be positive in the LIF test. Under a controlled gluten challenge all six patients reacted with a distinct increase in gliadin antibody titres whereas the LIF test changed from positive to negative and vice versa without following any clear principle. These results emphasize the inadequacy of the LIF test as a diagnostic method, both in untreated CD and under controlled gluten challenge.
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Cytological and cytogenetic studies on 17 acute myelomonocytic leukemia with bone marrow eosinophilia (M4EO) are reported. Cytological criteria include an unusual high proportion of eosinophilic cells containing abnormal granules. Abnormal karyotypes have been found in 12 patients but chromosome 16 abnormalities were present in only 9. In two of them only one such mitosis was detected whereas in 7 others inv(16)(p13q22) and/or del (16)(q22) clones were present. However in 16 cases normal karyotypes were also present. Other abnormal clones coexisted in three patients, suggesting that chromosome 16 abnormalities are not linked to a primary leukemogenic event. M4EO was found to be associated with a favourable prognosis.