PubMed Health⌕ Search

Biomedical subjects

V Lindgren

Publications and source records attributed to V Lindgren.

At least 37 records · Page 2Linked to original sources
PubMed1991

Diagnosis of Angelman syndrome in infants.

The diagnosis of Angelman syndrome (AS) has seldom been made in infants because the previously described characteristic manifestations usually are not apparent until after age 2 years. We describe 4 AS patients, one of whom has oculocutaneous albinism, who were less than 2 years old when first evaluated. All 4 have deletions of the region q11.2-q13 of chromosome 15. In the 3 cases in which parents were available for study the deleted chromosome 15 was maternally derived, as determined by cytological markers. All of the patients presented with severe to profound global developmental delay and postnatal-onset microcephaly; they had seizures, hypotonia, hyperreflexia, and hyperkinesis. All were hypopigmented as compared to their relatives. Each had eye abnormalities; all had choroidal pigment hypoplasia. None were initially described as having an abnormal appearance. We believe that AS is far more common than previously thought and present these 4 children to emphasize the manifestations that may be helpful in making the diagnosis in the young patient. We also emphasize the hypopigmentation that patients with AS frequently have, including what we think is the first reported case of albinism and AS.

Chromosome Deletion↗
PubMed1990

Novel isodicentric chromosome 18 in an abnormal infant with a mosaic karyotype [46,XY/46,XY,-18,+dic(18)(q12.2]).

A previously unreported isodicentric chromosome 18 was discovered in an abnormal infant boy whose mosaic karyotype was 46,XY/46,XY,-18,+idic(18)(q12.2). His constellation of congenital anomalies was typical of the 18q-syndrome. The clinical and cytogenetic characteristics of this patient are reported, and the literature concerning isochromosomes of 18 is reviewed.

Chromosome Aberrations↗
PubMed1990

Genetic mapping of the structural gene for phospholipase C of Pseudomonas aeruginosa PAO.

An insertion mutation constructed by gene replacement methods was used to map the gene corresponding to the hemolytic phospholipase C (plcS gene) in Pseudomonas aeruginosa PAO1 by R68.45-mediated conjugation. plcS mapped approximately at 67 min on the 75-min chromosomal map (B. W. Holloway, K. O'Hoy, and H. Matsumoto, p. 213-221, in S. J. O'Brien, ed., Genetic Maps 1987, vol. 4, 1987), between the markers pur-67 and pru-375 and considerably distal to the regulatory genes plcA and plcB, which are located at approximately 12 min.

Chromosome Mapping↗
PubMed1990

Regional assignments of the zinc finger Y-linked gene (ZFY) and related sequences on human and mouse chromosomes.

Recent chromosome walking experiments have identified a candidate gene (ZFY) for the testis-determining factor on the human Y chromosome (Page et al., 1987). We report here the regional assignments of the ZFY gene and related sequences in the human and the mouse. By in situ hybridization, we assigned ZFX and ZFY to human chromosome bands Xp21 and Yp11.3, respectively. Although the mouse harbors two Zfy genes, only one site at band A1 of its Y chromosome was significantly labeled. The mouse Zfx gene and the Zfa gene on chromosome 10 were assigned to bands XD and 10B5, respectively. These assignments of the ZFX gene in human and mouse add another marker to the conserved syntenic group for evaluating the evolutionary relationship of the human and mouse X chromosomes.

Animals↗
PubMed1989

Specific chromosomal abnormalities characterize fibrosarcomas of bovine papillomavirus type 1 transgenic mice.

In the BPV1.69 line of transgenic mice, the bovine papillomavirus type 1 genome elicits both benign dermal fibroblastic proliferation (fibromatoses) and malignant fibrosarcomas. Because these lesions arise only with time, nonviral factors appear to be involved. We have karyotyped several primary tumors as well as a series of low-passage cell lines derived both from fibromatoses and from fibrosarcomas. The fibrosarcomas, but not the preneoplastic fibromatoses, show consistent abnormalities of one or both of two chromosomes, chromosome 8 (trisomy or duplication) and chromosome 14 (monosomy or translocation). The chromosomal abnormalities are not a direct consequence of the viral integration, which we have mapped to chromosome 15 by in situ hybridization. These results suggest that transgenic mice can be used to study the role(s) of cytogenetic changes in tumorigenesis and may direct the search for genes involved in tumor progression.

Animals↗
PubMed1989

Tumorigenic latency and separable stages during fibrosarcoma development in transgenic mice carrying papillomavirus genomes.

Transgenic mice have been established carrying the genomes of bovine papillomavirus type 1 (BPV-1), and human papillomaviruses types 5 and 18. Transcriptional dormancy is characteristic of all three viral genomes in transgenic mouse lines maintained for 2-4 years. Only BPV-1, which induces both dermal and epidermal pathology in its natural host, has been found to elicit abnormalities when carried in transgenic mice. The BPV-1 genome acts in these mice as a tissue specific oncogene, in that it elaborates the development of skin fibrosarcomas. Three abnormal stages are evident: two distinct and successive stages of a proliferative hyperplasia (a mild and an aggressive fibromatoses), and the solid tumors (fibrosarcomas). Analysis of tissue biopsies and of derivative cell cultures from each pathology confirms that this pathway is composed of separate stages. Notably, progression from hyperplasia to neoplasia is accompanied by specific cytogenetic changes, which appear necessary in addition to the actions of the BPV oncogenes. The reproducibility of the tumorigenic pathway induced by the BPV genome is providing inroads into the molecular genetic and biochemical mechanisms of tumor development.

Animals↗
PubMed1988

Chromosomal localization of human Na+, K+-ATPase alpha- and beta-subunit genes.

Na+, K+-ATPase is a heterodimeric enzyme responsible for the active maintenance of sodium and potassium gradients across the plasma membrane. Recently, cDNAs for several tissue-specific isoforms of the larger catalytic alpha-subunit and the smaller beta-subunit have been cloned. We have hybridized rat brain and human kidney cDNA probes, as well as human genomic isoform-specific DNA fragments, to Southern filters containing panels of rodent X human somatic cell hybrid lines. The results obtained have allowed us to assign the loci for the ubiquitously expressed alpha-chain (ATP1A1) to human chromosome 1, region 1p21----cen, and for the alpha 2 isoform that predominates in neural and muscle tissues (ATP1A2) to chromosome 1, region cen----q32. A common PstI RFLP was detected with the ATP1A2 probe. The alpha 3 gene, which is expressed primarily in neural tissues (ATP1A3), was assigned to human chromosome 19. A fourth alpha gene of unknown function (alpha D) that was isolated by molecular cloning (ATP1AL1) was mapped to chromosome 13. Although evidence to date had suggested a single gene for the beta-subunit, we found hybridizing restriction fragments derived from two different human chromosomes. On the basis of knowledge of conserved linkage groups on human and murine chromosomes, we propose that the coding gene ATP 1B is located on the long arm of human chromosome 1 and that the sequence on human chromosome 4 (ATP 1BL1) is either a related gene or a pseudogene.

Animals↗
PubMed1987

Characterization of a Pseudomonas aeruginosa transposon insertion mutant with defective release of exoenzymes.

A Pseudomonas aeruginosa transposon insertion mutant with defective release of several exoenzymes has been characterized. The Tn5-751 insertion mutation was located in the previously described xcp-1 locus at 0 min on the chromosomal map and caused several exoenzymes to remain in cell-bound form. At least one of the exoenzymes, elastase, was accumulated in the periplasmic space. The periplasmic elastase had the same Mr as the extracellular enzyme produced by the wild-type strain. The virulence of the mutant was comparable to that of wild-type strains in experimental burn infection in mice. The presence of an easily selectable antibiotic resistance marker in the xcp-1 locus offers the possibility of cloning the gene(s) involved in exoprotein secretion.

ADP Ribose Transferases↗
PubMed1987

Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines.

We cloned and analyzed the integrated human papillomavirus type 16 (HPV-16) genomes that are present in the human cervical carcinoma cell lines SiHa and CaSki. The single HPV-16 genome in the SiHa line was cloned as a 10-kilobase (kb) HindIII fragment. Integration of the HPV-16 genome occurred at bases 3132 and 3384 with disruption of the E2 and E4 open reading frames (ORFs). An additional 52-base-pair deletion of HPV-16 sequences fused the E2 and E4 ORFs. the 5' portion of the disrupted E2 ORF terminated immediately in the contiguous human right-flanking sequences. Heteroduplex analysis of this cloned integrated viral genome with the prototype HPV-16 DNA revealed no other deletions, insertions, or rearrangements. DNA sequence analysis of the E1 ORF, however, revealed the presence of an additional guanine at nucleotide 1138, resulting in the fusion of the E1a and E1b ORFs into a single E1 ORF. Sequence analysis of the human flanking sequences revealed one-half of an Alu sequence at the left junction and a sequence highly homologous to the human O repeat in the right-flanking region. Analysis of the three most abundant BamHI clones from the CaSki line showed that these consisted of full-length, 7.9-kb HPV-16 DNA; a 6.5-kb genome resulting from a 1.4-kb deletion of the long control region; and a 10.5-kb clone generated by a 2.6-kb tandem repeat of the 3' early region. These HPV-16 genomes were arranged in the host chromosomes as head-to-tail, tandemly repeated arrays. Transcription analysis revealed expression of the HPV-16 genome in each of these two cervical carcinoma cell lines, albeit at significantly different levels. Preliminary mapping of the viral RNA with subgenomic strand-specific probes indicated that viral transcription appeared to be derived primarily from the E6 and E7 ORFs.

Amino Acid Sequence↗
PubMed1985

The pattern and clinical significance of karyotypic abnormalities in patients with idiopathic and postpolycythemic myelofibrosis.

Six of eight (75%) patients with postpolycythemic myelofibrosis (PPMF) and 11 of 20 (55%) patients with idiopathic myelofibrosis (MF), seen at the University of Chicago, had abnormal karyotypes in cells of bone marrow origin. The specific chromosomal findings and their clinical significance in these patients were analyzed. A review of the literature added the findings from abnormal karyotype studies in 10 patients with PPMF and 36 patients with MF to this series. The demonstration of an increased frequency of cytogenetic abnormalities after cytotoxic therapy in polycythemia vera (PV) implies that such therapy may have a role in the development of chromosomal changes seen in treated PV and PPMF. The cytogenetic abnormalities in MF appear to be unrelated to therapy except possibly for an association with partial or complete losses of chromosome 5 or 7. Trisomy 8 is the only finding that is more common in MF than in PPMF. Other abnormalities were more common in PPMF, particularly 20q-, loss of 7 or 7q-, and trisomy 9, and to a lesser extent trisomy 1q and 5q-. Cytogenetic abnormalities do not show a pattern that can be used to distinguish between PPMF and MF, nor are they useful in the prognosis of MF or in initial studies in PPMF. PPMF does appear to have a higher tendency toward leukemic transformation than does MF, and an evolution in karyotype appears to have serious prognostic implications in PPMF in regard to this transition.

Adult↗
PubMed1985

Human genes involved in cholesterol metabolism: chromosomal mapping of the loci for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase with cDNA probes.

Cellular cholesterol metabolism is regulated primarily through the coordinate expression of two proteins, the low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34). We have used cDNA probes for the human genes encoding these proteins to determine the precise chromosomal location of the two loci. By in situ hybridization we have regionally mapped the LDL receptor gene, LDLR, to the short arm of chromosome 19 in bands p13.1-p13.3. This result concurs with and extends a previous study in which LDLR was mapped to chromosome 19 by screening somatic cell hybrids with a species-specific monoclonal antibody. We have assigned the HMG-CoA reductase gene, HMGCR, to chromosome 5 by Southern blotting of DNA from a somatic cell hybrid panel and to bands 5q13.3-q14 by in situ hybridizations of the cDNA probe to human metaphase cells with normal and rearranged chromosomes.

Cholesterol↗
PubMed1985

Human U1 small nuclear RNA pseudogenes do not map to the site of the U1 genes in 1p36 but are clustered in 1q12-q22.

Human U1 small nuclear RNA is encoded by approximately 30 gene copies. All of the U1 genes share several kilobases of essentially perfect flanking homology both upstream and downstream from the U1 coding region, but remarkably, for many U1 genes excellent flanking homology extends at least 24 kilobases upstream and 20 kilobases downstream. Class I U1 RNA pseudogenes are abundant in the human genome. These pseudogenes contain a complete but imperfect U1 coding region and possess extensive flanking homology to the true U1 genes. We mapped four class I pseudogenes by in situ hybridization to the long arm of chromosome 1, bands q12-q22, a region distinct from the site on the distal short arm of chromosome 1 to which the U1 genes have been previously mapped (Lund et al., Mol. Cell. Biol. 3:2211-2220, 1983; Naylor et al., Somat. Cell Mol. Genet. 10:307-313, 1984). We confirmed our in situ hybridization results by genomic blotting experiments with somatic cell hybrid lines with translocation products of human chromosome 1. These experiments provide further evidence that class I U1 pseudogenes and the true U1 genes are not interspersed. The results, along with those published elsewhere (Bernstein et al., Mol. Cell. Biol. 5:2159-2171, 1985), suggest that gene amplification may be responsible for the sequence homogeneity of the human U1 gene family.

Animals↗
PubMed1985

Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome.

We are reporting a male patient who suffered from chronic granulomatous disease associated with cytochrome b-245 deficiency and McLeod red cell phenotype, Duchenne muscular dystrophy, and retinitis pigmentosa. On cytogenetic analysis, he seemed to have a very subtle interstitial deletion of part of band Xp21. Since it was impossible to know whether this material was truly deleted or inserted elsewhere in the genome, somatic cell and molecular studies were carried out. In somatic cell hybrids, the deleted X chromosome was isolated on a Chinese hamster background. Southern blot analysis with 20 single-copy probes, that had been mapped to the X short arm, led to the discovery of one (probe 754) that is missing from this patient's X chromosome and also from his total DNA. This proves that he, indeed, has a deletion rather than a balanced insertion. The results provide cytological mapping information for the X-linked phenotypes present in this patient. Furthermore, probe 754 recognizes a restriction fragment length polymorphism of high frequency that makes it the most powerful probe currently available for linkage studies with X-linked muscular dystrophy.

Animals↗
PubMed1984

Human ornithine transcarbamylase locus mapped to band Xp21.1 near the Duchenne muscular dystrophy locus.

The gene for the mitochondrial enzyme ornithine transcarbamylase was mapped to the short arm of the X chromosome by in situ hybridization experiments, with DNA complementary to the human ornithine transcarbamylase gene used as a probe. A series of cell lines with X chromosome abnormalities was used to localize the gene to band Xp21.1. Because the gene maps near the Duchenne muscular dystrophy locus, the ornithine transcarbamylase probe may be useful in carrier detection and prenatal diagnosis of Duchenne muscular dystrophy as well as of ornithine transcarbamylase deficiency.

Animals↗
PubMed1984

Comparative analysis of mouse-human hybrids with rearranged chromosomes 1 by in situ hybridization and Southern blotting: high-resolution mapping of NRAS, NGFB, and AMY on human chromosome 1.

The human protooncogene NRAS and the genes for the beta-subunit of nerve growth factor (NGFB) and for amylase (AMY) have previously been assigned to the proximal short arm of chromosome 1, but their precise positions have not been unequivocally established. By in situ hybridization of DNA probes for the three genes, we have ascertained the location of complementary sequences in mouse-human somatic cell hybrids that contained translocations of chromosome 1. The results agreed with the presence or absence of the human sequences as determined by Southern blotting of hybrid cell DNA. The in situ data confirmed that the genes were present on the cytologically recognized rearranged chromosome. Compared to the autoradiographic silver grain distribution on normal human chromosome 1, our in situ results obtained with the translocation chromosomes allowed much greater precision of mapping. Both NRAS and NGFB map to band 1p22, and AMY was confirmed in band 1p21.

Amylases↗
PubMed1983

Chromosome replication in normal and transformed human lymphocytes.

We analyzed the late-replication patterns of human B-lymphocyte chromosomes before and after transformation by Epstein-Barr virus. There were no statistically significant differences between normal cells and transformed cells derived from the same male individual; therefore, the order of termination of chromosome replication was unchanged by transformation. We also examined the replication patterns of T lymphocytes from the same donor and found no differences between normal B and T cells.

B-Lymphocytes↗
PubMed1983

Cellular aspects of DNA repair.

DNA repair reactions are under cellular control. In bacteria, the reactions removing 0(6)-methylguanine and 3-methyladenine are inducible. It is not clear whether similar inducibility occurs in human lymphoblastoid cells. Nonetheless, the ability to manufacture the 0(6)-methylguanine acceptor protein does seem to be controlled by some chromosomal mechanism which is superimposed on the structural gene. This control system may affect reactions other than the removal of 0(6)-methylguanine. Insofar as this is so, transformed human lymphoblastoid cells have a system reminiscent of that found in bacteria.

Animals↗