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Biomedical subjects

E C Mariman

Publications and source records attributed to E C Mariman.

70 records · Page 4Linked to original sources
PubMed1993

Gene for hereditary neuropathy with liability to pressure palsies (HNPP) maps to chromosome 17 at or close to the locus for HMSN type 1.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder with an increased susceptibility of peripheral nerves to mechanical lesions resulting in transient nerve palsies. Many carriers remain asymptomatic but can be traced by electrophysiological examination, thereby demonstrating that HNPP is a generalised polyneuropathy. By using highly polymorphic markers linkage analysis was performed in a large family with HNPP. This resulted in a maximum lod score of 4.20 at theta = 0.10 with D17S520. Three-point linkage suggests that the gene for HNPP is located on chromosome 17 in the region between D17S250 (q11.2-q12) and D17S520 (p12), a region that has recently been shown to encompass a locus for another hereditary neuropathy, hereditary motor and sensory neuropathy type 1 (HMSN type 1). This raises the possibility that HNPP and this form of HMSN type 1 are allelic. In keeping with this speculation is our recent finding that D17S122, another marker from the HMSN type 1 region, displays apparent loss of heterozygosity in this family.

Chromosome Mapping↗
PubMed1993

Analysis of a second family with hereditary non-chromaffin paragangliomas locates the underlying gene at the proximal region of chromosome 11q.

The gene for autosomal, dominantly inherited, non-chromaffin paragangliomas has previously been mapped at 11q23-qter by linkage analysis of a single family. In the present study, we have used genetic markers from 11q for the analysis of two distantly related pedigrees with the same disorder. Linkage analysis and haplotyping indicate that the gene underlying the disorder in the present family is located on chromosome 11q proximal to the tyrosinase gene locus (11q14-q21). Closely linked markers are the human homologue of the murine INT2 protooncogene and the anonymous DNA marker D11S527. A maximum lod score of 5.4 (theta = 0.0) has been obtained for linkage between the disorder and the chromosomal region defined by these markers. The human INT2 gene can be regarded as a candidate for the disorder on the basis of its expression pattern during embryogenesis in the mouse. However, haplotype analysis indicates that this gene is probably not the predisposing genetic factor in the present family.

Chromosome Mapping↗
PubMed1993

The insulin-like growth factor type-2 receptor gene is imprinted in the mouse but not in humans.

In mouse, four genes have been found to undergo genomic imprinting resulting in differential expression of maternally and paternally inherited alleles. To determine whether the cognate genes are also subject to imprinting in humans, we have studied allele-specific expression patterns of insulin-like growth factor 2, IGF2-receptor and H19 in human fetal and adult tissues. In keeping with previous findings in mice, our results indicate that in human fetal tissues the paternal H19 alleles is inactive. IGF2 is monoallelically expressed in various tissues but surprisingly not in adult human liver. The human IGF2R gene, another classic example of imprinting in mice, was found to be expressed from both alleles. We provide the first direct evidence for differential imprinting in the human and murine genome.

Adult↗
PubMed1993

Rubinstein-Taybi syndrome caused by submicroscopic deletions within 16p13.3.

The Rubinstein-Taybi syndrome (RTS) is a well-defined complex of congenital malformations characterized by facial abnormalities, broad thumbs and big toes, and mental retardation. The breakpoint of two distinct reciprocal translocations occurring in patients with a clinical diagnosis of RTS was located to the same interval on chromosome 16, between the cosmids N2 and RT1, in band 16p13.3. By using two-color fluorescence in situ hybridization, the signal from RT1 was found to be missing from one chromosome 16 in 6 of 24 patients with RTS. The parents of five of these patients did not show a deletion of RT1, indicating a de novo rearrangement. RTS is caused by submicroscopic interstitial deletions within 16p13.3 in approximately 25% of the patients. The detection of microdeletions will allow the objective conformation of the clinical diagnosis in new patients and provides an excellent tool for the isolation of the gene causally related to the syndrome.

Chromosome Deletion↗
PubMed1993

Deletion at chromosome 16p13.3 as a cause of Rubinstein-Taybi syndrome: clinical aspects.

In the accompanying paper, a chromosomal localization of the Rubinstein-Taybi syndrome by cytogenetic investigations with fluorescence in situ hybridization techniques at chromosome 16p13.3 is described. We investigated 19 of these patients and their parents (a) to ascertain the parental origin of the chromosome with the deletion in families where such a deletion was detected, (b) to disclose whether uniparental disomy plays a role in etiology, and (c) to compare clinical features in patients with a deletion to those in individuals in whom deletions were not detectable. Molecular studies showed a copy of chromosome 16 from each parent in all 19 patients. Uniparental disomy was also excluded for five other chromosome arms known to be imprinted in mice. None of the probes used for determining the origin of the deleted chromosome proved to be informative. The clinical features were essentially the same in patients with and without visible deletion, with a possible exception for the incidence of microcephaly, angulation of thumbs and halluces, and partial duplication of the halluces. A small deletion at 16p13.3 may be found in some patients with Rubinstein-Taybi syndrome. Cytogenetically undetectable deletions, point mutations, mosaicism, heterogeneity, or phenocopy by a nongenetic cause are the most probable explanations for the absence of cytogenetic or molecular abnormalities in other patients with Rubinstein-Taybi syndrome.

Adolescent↗
PubMed1992

Sex ratios of affected and transmitting members of multiple case families with neural tube defects.

In order to study the genetic aspects of the relation between neural tube defects and sex, we selected families with at least two closely related affected members. The sex ratios of both affected and normal transmitting persons were determined in these multiple case families. Our results indicate that there is a relation between the position of the lesion in the spine and sex. Furthermore, the affected persons in one family show significant concordance for sex as shown by the analysis of families with just two affected members. To our surprise, the group of normal transmitters appears to consist of significantly more females than males. This is in contrast to similar families with non-syndromic cleft lip +/- palate, where males predominate both among affected persons and normal transmitters. Finally, affected females most often inherited the predisposition to a neural tube defect from their mother. The possible role of inherited factors is discussed.

Female↗
PubMed1987

Structure and expression of the human creatine kinase B gene.

Various cDNAs for creatine kinase type B (CK-B) were isolated from human cDNA libraries using a 26-oligonucleotide guess-mer probe. One of the cDNAs appeared to be almost full-length and contained an open reading frame coding for the 381 amino acid residues of the human CK-B polypeptide. The nucleotide sequences of the translated region as well as the primary protein structure show a high degree of homology with known CK-B and CK-M sequences of other vertebrates. The level of CK-B RNA as a measure of CK-B gene activity was determined in various human tissues and cultured cells. Our results confirm that CK-B is expressed in a tissue-specific manner and give support to the previously proposed relation between CK-B gene activity and cell proliferation. Screening of genomic DNA with various cDNA regions as probes revealed that there is only one CK-B gene per haploid genome. Gene cloning and sequencing indicated that CK-B is coded for by a relatively small gene of 3.2 kb in size, which is partially overlapped by an HTF island (A. P. Bird (1986) Nature (London) 321, 557-558) with an extremely high G + C content at its 5' end.

Amino Acid Sequence↗
PubMed1986

The AIDS combat: a survey.

The Acquired Immune Deficiency Syndrome is one of the most challenging problems of medical sciences in the last decade, because it is a completely new disease, which appears to be inevitably fatal. Although much effort has been put in the development of therapeutic and prophylactic methods ever since the recognition of this new disease, efficient methods are still lacking, causing the number of victims to rise continuously. In this article I review the progress that has been made in the development of various prophylactic and therapeutic approaches by which science is trying to defeat AIDS. It includes anti-viral drug therapy, reconstitution of the immune system, vaccine development and a few alternative approaches to AIDS therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1984

A model for the excision of introns 1 and 2 from adenoviral major late pre-messenger RNAs.

Total steady-state RNA was extracted from nuclei of HeLa cells late after infection with adenovirus serotype 2. Most of the nuclear RNA is transcribed from the major late transcription unit (16.2 to 100.0 map units). To study the cleavage reactions involved in the splicing of leaders 1 and 2, we have used the S1 nuclease mapping technique with restriction fragments located in the region of intron 1 as DNA probes. The S1 mapping data showed that in total nuclear RNA, RNA species accumulate from which the 5' part of intron 1 has been excised, but which still contain the 3' part of the intron. This indicates that intron 1 can be removed in a stepwise fashion following the 5' to 3' direction. We have compared the nucleotide sequences from the ends of the putative processing intermediates. The internal cleavage sites do not resemble the consensus 5' or 3' splice site sequences. However, they show considerable homology to the sequence 5' A-T-G-A-T-G-G-C-A-T 3', which may act as a signal for internal cleavage. The intermediates are present in both the poly(A)+ and poly(A)- RNA fractions, although with different relative intensities. Primer extension experiments have been performed in which a primer, located with its left end in leader 2, is extended into intron 1. The results show that there may be a cleavage site as short as 35 nucleotides before the 3' splice site. Cleavage at the 3' splice site seems to be rapidly followed by ligation of leader 1 to leader 2. A model for RNA splicing based on these findings and data from the literature is presented.

Adenoviruses, Human↗
PubMed1983

Alternative splicing pathways exist in the formation of adenoviral late messenger RNAs.

Total rapidly labeled RNA was extracted from nuclei of HeLa cells late after infection with adenovirus type 2. Most of this nuclear RNA is transcribed from the major late transcription unit (16.2 to 100.0 map units (m.u.)). To study the cleavage reactions that are involved in RNA splicing, we used the S1 nuclease mapping technique with HindIII B (16.8 to 31.5 m.u.) and XhoI F (15.5 to 22.4 m.u.) restriction fragments as DNA probes. The S1 mapping data showed that both intron 1 (16.3 to 19.1 m.u.) and intron 2 (19.4 to 26.2 m.u.) can be excised in more than one step. Kinetic labeling and pulse--chase experiments demonstrated that certain cleavage sites in the RNA are used within three minutes after the start of transcription, while other cleavages occur only after a significant time-lag. The use of 5.6-dichloro-1-beta-D-ribofuranosylbenzimidazole enabled us to label the nuclear RNA exclusively from the 5' end. Such an approach showed that the first cleavages are introduced in the nascent RNA before the RNA polymerase has passed more than 2000 nucleotides beyond the cleavage site. The chronology of the appearance of processing intermediates that results from cleavage of the RNA indicates that preferentially intron 1 is removed before intron 2. This is an agreement with the finding that leader 1 is ligated to leader 2 before ligation of leader 2 to leader 3 takes place. However, we have found that alternative splicing pathways exist in the excision of introns 1 and 2, demonstrating that cleavage in intron 2 may occur before intron 1 is attacked by the splicing enzymes.

Adenoviruses, Human↗
PubMed1981

Adenoviral heterogeneous nuclear RNA is associated with host cell proteins.

In this study irradiation of intact cells with 244-nm ultraviolet light was used to cross-link hnRNA to proteins that are closely associated with it. In this way proteins interacting specifically with hnRNA could be identified excluding the possibility of non-specific binding of proteins to the RNA during cell fractionation. In uninfected HeLa cells two polypeptides of 41500 and 43000 molecular weight can be cross-linked very efficiently to hnRNA. Other proteins, with molecular weights of 36000 and 37000, were covalently linked less effectively. Irradiation of adenovirus-infected cells results in the cross-linking of the same polypeptides to hnRNA. It was found, however, that hnRNA from adenovirus-infected cells contains both viral and host transcripts. Both classes of transcripts are quantitatively associated with the nuclear matrix and can be cross-linked by irradiation with equal efficiency. To determine whether both adenoviral and cellular transcripts are associated with the same proteins, the cross-linked adenoviral hnRNA-protein complexes were isolated by preparative hybridization to adenoviral DNA immobilized on Sepharose. The results show that the purified cross-linked adenoviral hnRNA-protein complexes also contain the host 41500-Mr and 43000-Mr proteins as major components. This suggests that in the infected cell adenoviral-specific hnRNA is associated with host proteins and that the structural organization of viral hnRNA-protein complexes in infected cells probably is similar to the organization of host hnRNA in uninfected cells.

Adenoviridae↗
PubMed1980

Tryptophan replacement in the C-terminal octapeptide of CCK-PZ. Syntheses of six peptide analogues bearing tryptophan congeners.

Six sulphated octapeptide amide analogues, representing the C-terminal sequence of pancreozymin have been prepared in addition to the natural sequence. The tryptophyl residue which is essential for biological activity was replaced in this series by structurally, closely related analogues each of which resemble the properties of the original moiety to varying extents. The syntheses were so conducted that the C-terminal tetrapeptide amides (modified tetragastrins) could be secured. The results of the measurement of one of the biological parameters are indicated. The activity was determined to elucidate which of the physicochemical properties of the tryptophyl residue is most essential for exertion of biological activity in the described test.

Amino Acid Sequence↗