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Biomedical subjects

E H Weiss

Publications and source records attributed to E H Weiss.

90 records · Page 5Linked to original sources

Human complement factor H: expression of an additional truncated gene product of 43 kDa in human liver.

The human complement factor H is an important factor in the control of the alternative pathway and also induces the stimulation of B cells and macrophages in vitro. Using a human factor H cDNA clone as probe, two factor H-specific transcripts of 4.4 and 1.8 kb were detected in four human livers. Both mRNAs were found independently of the expression of an acute phase marker SAA, in these livers, indicating that their presence is not linked to an acute phase state. The shorter transcript was cloned in two cDNA plasmids H-19 and H-20, lacking only seven amino acids of the N-terminus of the mature factor H protein. The deduced protein sequence showed that this protein is identical to the N-terminal portion of the large classical factor H of 150 kDa mol. mass. Parallel to the finding that the N-terminal sequence of factor H is expressed by two distinct mRNA species, evidence is presented that the C-terminal sequence is also contained on two different transcripts, the common 4.4-kb mRNA and an additional 1.0-kb mRNA. A novel, short form of human complement factor H of 43 kDa was detected in human sera which represents the translation product of the 1.8-kb factor H-specific mRNA detected in human liver. Five distinct epitopes detected with 6 monoclonal antibodies are present on both the 150-kDa factor H protein and the truncated 43-kDa molecule. We conclude that additional H-specific mRNAs are found in human liver and that at least one of them is translated yielding a truncated form of factor H.

Amino Acid Sequence↗

A synthesis of research on nutrition education at the elementary school level.

This literature review emphasizes the importance of teacher training, teaching strategies, parental involvement, curricular concerns, administrative support, and social/cultural factors on the impact of nutrition education programs at the elementary school level. The characteristics, implementation, and effectiveness of selected elementary nutrition education programs are reviewed, and instructional methods and materials shown effective through research are identified and discussed.

Culture↗

Lack of class I H-2 antigens in cells transformed by radiation leukemia virus is associated with methylation and rearrangement of H-2 DNA.

Transformation of murine thymocytes by radiation leukemia virus is associated with reduced expression of the class I antigens encoded in the major histocompatibility complex (MHC) and increased methylation and altered restriction enzyme patterns of MHC DNA. These changes may play a role in host susceptibility to virus-induced leukemogenesis and accord with the notion that viral genomes play a regulatory function when they integrate adjacent to histocompatibility genes.

Animals↗

Interaction between Kb and Q4 gene sequences generates the Kbm6 mutation.

Genetic interaction as a mechanism for the generation of mutations is suggested by recurrent, multiple nucleotide substitutions that are identical to nucleotide sequences elsewhere in the genome. We have sequenced the mutant K gene from the bm6 mouse, which is one of a series of eight closely related, yet independently occurring mutants known collectively as the "bg series." Two changes from the Kb gene are found, positioned 15 nucleotides apart: an A-to-T change and a T-to-C change in the codons corresponding to amino acids 116 and 121, resulting in Tyr-to-Phe and Cys-to-Arg substitutions, respectively. Hybridization analysis with an oligonucleotide specific for the altered Kbm6 sequence identifies one donor gene, Q4, located in the Qa region of the H-2 complex. The two altered nucleotides that differentiate Kbm6 and Kb are present in Q4 in a region where Kb and Q4 are otherwise identical for 95 nucleotides, delineating the maximum genetic transfer between the two genes. Because the Kbm6 mutation arose in an homozygous mouse these data indicate that the Q4 gene contains the only donor sequence and demonstrates that Q-region gene sequences can interact with the Kb gene to generate variant K molecules.

Animals↗

Duplicated gene pairs and alleles of class I genes in the Qa2 region of the murine major histocompatibility complex: a comparison.

DNA restriction maps of the major histocompatibility complex and hybridization with low copy probes have previously revealed strong homology between the Q6-Q7 and the Q8-Q9 class I gene pairs in the Qa2 region of the C57BL/10 mouse. After DNA sequence analysis of the Q7, Q8 and Q9 genes, we have compared the Q7 gene with its apparent allele, 27.1, from the BALB/c mouse; the 99% homology between Q7 and 27.1 indicates that this is a non-polymorphic gene. Comparison of Q7 with Q9, its homologue in the Q8-Q9 gene pair, revealed greater than 99% homology, thus supporting our proposal that the Qa2 region has evolved by the duplication of gene pairs. Q7 was also found to be homologous (93%) to Q8, the second member of the Q8-Q9 pair. However, the first exon (encoding the leader sequence) as well as the first intron of Q7 and Q8, which are presumably not subject to strong selective pressure, are essentially identical in nucleotide sequence (having only one mismatch), which suggests that greater than 200 bp of DNA may have been exchanged by gene conversion. Furthermore, transcripts of both Q7 and Q8 would have termination codons derived from the exon that normally encodes the transmembrane domain, thus these genes could encode either membrane-bound class I proteins that lack a cytoplasmic protein domain or class I proteins that are secreted.

Alleles↗

Organization, sequence and expression of the HLA-B27 gene: a molecular approach to analyze HLA and disease associations.

Among the numerous autoimmune diseases associated with various HLA alleles, the one with the highest relative risk so far reported has been ankylosing spondylitis with HLA-B27. To examine this relationship more directly, we have cloned the gene encoding the HLA-B27 antigen and determined its complete DNA sequence. Comparison of the HLA-B27 sequence with that of the allelic HLA-B27 shows a high level of homology. Mutations are distributed evenly between exons and introns. Exon 1 and intron 1 are the most divergent ones, and the degree of divergence distinctly declines towards the 3' end. The HLA-B57 gene when transfected into murine L cells is expressed on the cell surface and reacts with a panel of monoclonal antibodies directed against monomorphic and polymorphic determinants associated with HLA-B27 antigen. The isolation of this gene allows for the first time a search for structural features which make the HLA-B27 antigen a high risk genetic factor for a group of rheumatoid disorders, in particular ankylosing spondylitis.

Amino Acid Sequence↗

Evolution and expression of the transplantation antigen gene family.

We have cloned 26 different class I genes that are located in the major histocompatibility complex of the C57BL/10 mouse. Two of the three class I genes found in the H-2 complex encode the H-2Kb and H-2Db antigens; the other 23 class I genes map to the adjacent Tla complex. We have grouped the cosmids containing these genes into three clusters: one cluster links the H-2K and I-A regions, one cluster links the H-2D and Qa-2 regions, and the final cluster maps to the TL region. The class I gene organizations in the Qa-2 and TL regions of the C57BL/10 and BALB/c mice are generally similar, but there are several polymorphic segments. The Qa-2 region of both mice seems to have evolved by the duplication of gene pairs; furthermore, the H-2K region may have been generated by the translocation of a gene pair from the Qa-2 region. We have evidence that several of the genes in the Qa-2 region are expressed.

Animals↗

A nonpolymorphic class I gene in the murine major histocompatibility complex.

DNA sequence analysis of a class I gene (Q10), which maps to the Qa2,3 locus in the C57BL/10 (H-2b haplotype) mouse, reveals that it is almost identical to a cDNA clone (pH16) isolated from a SWR/J (H-2q haplotype) mouse liver cDNA library. Exon 5, in particular, has an unusual structure such that a polypeptide product is unlikely to be anchored in the cell membrane. Our findings suggest that the two sequences are derived from allelic class I genes, which are nonpolymorphic, in contrast to H-2K allelic sequences from the same mice, and they may encode liver-specific polypeptides of unknown function. Our previous studies indicate that the Q10 gene is a potential donor gene for the generation of mutations at the H-2K locus by inter-gene transfer of genetic information. Thus the lack of polymorphism in class I genes at the Q10 locus implies either that they are not recipients for such exchanges or that selective pressure prevents the accumulation of mutations in genes at this locus.

Alleles↗

Murine leukemia virus sequences are encoded in the murine major histocompatibility complex.

The studies reported here localize murine leukemia viral sequences to the TL region of the major histocompatibility complex, H-2. We examined a battery of 38 cosmids, isolated from two large genomic libraries constructed from C57BL/10 spleen DNA, that define 25 class I gene sequences. The viral probes used hybridized with only four cosmids, containing overlapping mouse sequences, that define four class I gene-related sequences in a region of 90 kilobases of DNA. The data show that two distinct viral envelope sequences are contained in the cluster. One of these sequences is situated with its 3' end next to the 3' end of a class I sequence. The other sequence, which does not contain the entire viral envelope, is proximal to the 3' end of a different class I sequence. Hybridization of the viral probes with the H-2 cosmid clones does not appear to be due to homology between viral and H-2 sequences. Rather, the viral sequences detected appear to be linked to or inserted amid class I genes. These findings may be significant in understanding molecular mechanisms involved in the generation of H-2 class I gene diversity.

Animals↗

Isolation and characterization of a human collagen alpha 1(I)-like gene from a cosmid library.

We have isolated a human collagen alpha 1(I)-like gene from a cosmid library. The clone which contains 37kb of human DNA has been shown to contain this gene by DNA sequencing, hybrid arrest and hybrid selection assays and Northern blot hybridizations. The collagen gene sequence extends through most of the cloned DNA and must, therefore, be at least 35kb in length.

Base Sequence↗

A potential donor gene for the bm1 gene conversion event in the C57BL mouse.

The mammalian major histocompatibility complex (MHC; H-2 complex in mouse) is a large multigene complex which encodes cell-surface antigens involved in the cellular immune response to foreign antigens. Class I polypeptides expressed at the H-2K and H-2D loci of numerous mouse strains exhibit an unusually high degree of genetic polymorphism, which is assumed to be related to their function as primary recognition elements in the immune response. We suggested that this H-2 polymorphism may arise by gene conversion-like events between non-allelic class I genes. This is supported by our recent comparison of the DNA sequences of the normal H-2Kb gene sequence, from the C57BL/10 mouse, and a mutant form of this gene called H-2Kbm1: the mutant allele differs from the H-2Kb gene in seven bases out of a region of 13 bases in exon 3 of the class I gene (which encodes alpha 2 (C1) the second highly polymorphic protein domain), suggesting that this region of new sequence had been introduced into the H-2Kb sequence following unequal pairing of two class I genes in the genome of the C57BL mouse. Schulze et al. have obtained similar results. Here we report work identifying a potential donor gene in our library of 26 class I genes cloned from the C57BL/10 mouse.

Animals↗

Organization and evolution of the class I gene family in the major histocompatibility complex of the C57BL/10 mouse.

The major histocompatibility complex (MHC) encodes several classes of protein vital to the regulation of the immune response. We have isolated 26 class I genes that map to this region in the C57BL/10 mouse and linked these into three gene clusters. The number of genes differs from the number found in the BALB/c strain and comparison of the organization of the class I genes in these two strains shows conserved regions and polymorphic regions which probably result from deletions, insertions and translocations within the MHC.

Animals↗

Organization of the AKR Qa region: structure of a divergent class I sequence, Q5k.

We established the organization of the AKR Qa region and determined the sequence of the Q4 and Q5 genes. Restriction mapping and genomic Southern blot analysis revealed that the AKR strain codes for only three H-2K homologous genes in this region. The AKR Q5 gene is not homologous to the Q5 gene of the C57BL strain, but is presumably allelic to the Q5 gene isolated from Balb/c. The organization and structure of the AKR Qa family is virtually identical to the Qa genes of the C3H mouse. The AKR Q5 gene, in contrast to other H-2K homologous Qa region genes, codes for a typical transmembrane region, and upon transfection into BHK cells, a 1.6 kb Q5 transcript is detected.

Amino Acid Sequence↗