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Biomedical subjects

M F Hansen

Publications and source records attributed to M F Hansen.

At least 55 records · Page 3Linked to original sources
PubMed1990

Structural alterations at the putative retinoblastoma locus in some human leukemias and preleukemia.

Homozygous loss of alleles of the retinoblastoma susceptibility locus (RB1) has been implicated in the onset of many different solid tumors. Heterozygous deletions of chromosome 13q14, the region containing the RB1 locus, have been observed by us in several subvariants of leukemia and preleukemia. We examined four cases of leukemia and one case of preleukemia for homozygous inactivation of the RB1 locus; in at least one case, evidence supports the concept that homozygous loss of both alleles of RB1 was an important step during leukemogenesis.

Adolescent↗
PubMed1989

Loss of genetic information in cancer.

The determination and comparison of genotypic combinations at genomic loci in normal and tumour tissues from patients with various types of cancer have defined the chromosomal locations of loci at which recessive mutations play a role in disease. The predisposing nature of some of these mutant alleles is exemplified in studies of retinoblastoma and osteogenic sarcoma. These two clinically associated diseases share a pathogenetically causal predisposition that maps to chromosome position 13q14. A similar mechanism at 11p15.5 is involved in the development of the embryonal variant of rhabdomyo-sarcoma, Wilms' tumour and hepatoblastoma. Finally, genomic alteration of chromosome 10 is apparent in glioblastomas and mixed tumours of glioblastoma/astrocytoma grade III but not in homogenous astrocytoma grades II or III, suggesting the definition of a locus involved in tumour progression and, perhaps, an approach to molecular genetic staging of tumours.

Blotting, Southern↗
PubMed1989

Molecular detection of chromosomal translocations that disrupt the putative retinoblastoma susceptibility locus.

A candidate DNA sequence with many of the properties predicted for the retinoblastoma susceptibility (RB1) locus has been cloned (S. H. Friend, R. Bernards, S. Rogelj, R. A. Weinberg, J. M. Rapaport, D. M. Albert, and T. P. Dryja, Nature [London] 323:643-645, 1986). The large size of this gene (ca. 200 kilobases [kb]) and its multiple dispersed exons (Wiggs et al., N. Engl. J. Med. 318:151-157, 1988) complicate molecular screening strategies important in prenatal and presymptomatic diagnosis and in carrier detection. Here we used field inversion gel electrophoresis (FIGE) to construct a restriction map of approximately 1,000 kb of DNA surrounding the RB1 locus and to detect the translocation breakpoints in three retinoblastoma patients. DNA probes from either the 5' or 3' end of the gene were used to detect a 250-kb EagI restriction fragment in DNA from unaffected individuals. Both probes identified an additional hybridizing fragment in the DNA from each patient, permitting the breakpoints in all three to be mapped within the cloned RB1 gene. Analysis of the breakpoint in one translocation cell line allowed the RB1 gene to be oriented with its 5' end toward the centromere. The 5' end of the gene also appeared to be associated with a clustering of sites for several infrequently cleaving restriction enzymes, indicating the presence of an HpaII tiny fragment island. The detection and mapping of the translocation breakpoints of all three retinoblastoma patients to within the putative RB1 gene substantiated the authenticity of this candidate sequence and demonstrated the utility of FIGE in detecting chromosomal rearrangements affecting this locus.

Base Sequence↗
PubMed1988

Tumor suppressors: recessive mutations that lead to cancer.

Several lines of evidence point to the involvement of recessive mutations in the predisposition to, and hence initiation of, cancer in vivo. Analyses of the genetic behavior of transformed cells suggest that at least one way to explain these events is to invoke loci which suppress the tumorous phenotype and which are inactivated by mutation. These suppressors are the subject of much speculation, but whether or not they are ultimately determined to be the regulators of differentiation antigens, growth factors, or proto-oncogenes, it is certain that the investigation of such loci will allow yet another glimpse at the inner mysteries of organismal development.

Animals↗
PubMed1987

Mothers' problem-solving skill and use of help with infant-related issues: the role of importance and need for action.

Examination was made of the relationship of mothers' appraisal of the importance of and need for action around infant-related issues to maternal experience (parity and time since birth), use of help, and perceived problem-solving competence. Sixty-two mothers (38 primiparae and 24 multiparae) kept for 90 days post-birth a daily log of issues, rated for importance and for need for action, and of help used. Mothers also reported perceived problem-solving competence on an 11-item scale. Findings indicated tentativeness in ratings of importance and action. Ratings of importance were associated with action ratings, except for temperament issues. Action ratings for baby care and illness issues decreased significantly with time. Otherwise, maternal experience had no effect on ratings. More of the variance in perceived competence than use of help was explained by action and importance ratings.

Adaptation, Psychological↗
PubMed1986

Pseudoaneurysms complicating pancreatitis: detection by CT.

Complications of pancreatitis such as pseudocyst formation and abscess are well known to radiologists. Secondary formation of pseudoaneurysms has not been emphasized in the radiologic literature. The great morbidity and mortality associated with pseudoaneurysms emphasize the importance of early detection. Three patients are described whose angiographically proved pseudoaneurysms were demonstrated on contrast material-enhanced abdominal CT scans obtained for evaluation of pancreatitis. A homogeneously enhancing structure within or adjacent to a pancreatic pseudocyst or contiguous with a vascular structure should be considered highly suspicious for an associated pseudoaneurysm.

Aneurysm↗
PubMed1985

Genetic origin of mutations predisposing to retinoblastoma.

Retinoblastoma is one of several human tumors to which predisposition can be inherited. Molecular genetic analysis of several nonheritable cases has led to the hypothesis that this tumor develops after the occurrence of specific mitotic events involving human chromosome 13. These events reveal initial predisposing recessive mutations. Evidence is presented that similar chromosomal events occur in tumors from heritable cases. The chromosome 13 found in the tumors was the one carrying the predisposing germline mutation and not the homolog containing the wild-type allele at the Rb-1 locus. These results suggest a new approach for identifying recessive mutant genes that lead to cancer and a conceptual basis for accurate prenatal predictions of cancer predisposition.

Alleles↗
PubMed1985

Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition.

Survivors of the heritable form of retinoblastoma subsequently develop second primary osteosarcomas at substantially greater frequency than either the general population or survivors of nonheritable retinoblastoma. Here we present molecular genetic evidence that the development of these two disparate tumor types involves specific somatic loss of constitutional heterozygosity for the region of human chromosome 13 that includes the RB1 locus. Similar events occur during the genesis of nonheritable osteosarcoma but not in several other embryonal tumors or sarcomas. These findings suggest that a conceptual approach toward defining the number of genes whose recessive mutant forms predispose to cancer is the molecular genetic analysis of clinically associated tumor types. They also suggest that the molecular basis of mixed cancer families may be the differential expression of a single pleiotropic recessive mutation by tissue specific mitotic segregation abnormalities.

Alleles↗