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L B Rall

Publications and source records attributed to L B Rall.

At least 19 recordsLinked to original sources
PubMed1991

Insulin-like growth factor I and II gene expression in Balb/C mouse liver during postnatal development.

We studied the developmental shift from IGF-II to IGF-I mRNA synthesis in Balb/C mouse liver. IGF-I mRNA levels were low at birth, increased with age to peak at weaning, and IGF-I gene expression again increased during puberty. IGF-II expression was high during early postnatal development, but became nondetectable at weaning. Thus in early life there is a reciprocal relationship of rising IGF-I and falling IGF-II mRNA. Northern analysis revealed four IGF-I mRNA transcripts ranging from 1.1-7.0 kb, with the 1.1 kb being the most prominent. Five IGF-II transcripts ranging from 1.7-4.0 kb were found, with the 4.0 kb being the most prominent. The pattern of Serum IGF-I and IGF-II values paralleled liver IGF-I and IGF-II mRNA levels.

Aging↗
PubMed1989

Localization of epidermal growth factor precursor in tooth and lung during embryonic mouse development.

The murine epidermal growth factor (EGF) precursor is a 1217 amino acid protein which contains mature EGF (amino acid residues 977-1029) as well as eight EGF-like repeats. Although the highest levels of EGF are found in the adult male mouse submandibular gland, the results of in situ hybridization studies and mRNA analyses suggest that EGF precursor mRNA is synthesized in several adult mouse tissues including the lung and the incisor. To determine if EGF precursor gene expression is intrinsic to the developmental program for either embryonic tooth or lung organogenesis, sense and antisense oligodeoxyribonucleotide probes corresponding to amino acids 1070-1081 of the precursor were used to localize cellular sites of synthesis of EGF precursor mRNA by in situ hybridization. Antibodies directed against amino acid residues 348-691 of the precursor were used in immunodetection techniques to identify either EGF precursor protein or processed derivatives. In contrast to earlier reports indicating that embryonic mouse tissues do not synthesize EGF precursor mRNA, we found that EGF precursor mRNA is present in clusters of ectoderm-, mesoderm-, and ectomesenchyme-derived cells associated with embryonic teeth and lung organs. Moreover, epitopes common to the EGF precursor were immunolocalized in both the epithelial and mesenchymal tissues of embryonic mouse tooth and lung organs. These results suggest that the EGF precursor and/or motifs contained within the precursor molecule, including mature EGF, may play an instructive or permissive role in epithelial-mesenchymal interactions pursuant to organogenesis.

Aging↗
PubMed1986

Human epidermal growth factor precursor: cDNA sequence, expression in vitro and gene organization.

Complementary DNA clones encoding the human kidney epidermal growth factor (EGF) precursor have been isolated and sequenced. They predict the sequence of a 1,207 amino acid protein which contains EGF flanked by polypeptide segments of 970 and 184 residues at its NH2- and COOH-termini, respectively. The structural organization of the human EGF precursor is similar to that previously described for the mouse protein and there is 66% identity between the two sequences. Transfection of COS-7 cells with the human EGF precursor cDNA linked to the SV40 early promoter indicate that it can be synthesized as a membrane protein with its NH2-terminus external to the cell surface. The human EGF precursor gene is approximately 110 kilobase pairs and has 24 exons. Its exon-intron organization revealed that various domains of the EGF precursor are encoded by individual exons. Moreover, 15 of the 24 exons encode protein segments that are homologous to sequences in other proteins. Exon duplication and shuffling appear to have played an important role in determining the present structure of this protein.

Amino Acid Sequence↗
PubMed1986

Sequences of liver cDNAs encoding two different mouse insulin-like growth factor I precursors.

Complementary DNAs encoding mouse liver insulin-like growth factor I (IGF-I) have been isolated and sequenced. Alternative RNA splicing results in the synthesis of two types of mouse IGF-I precursor that differ in the size and sequence of the COOH-terminal peptide. The sequences of the signal peptides, IGF-I moieties and the first 16 amino acids of the COOH-terminal peptides or E-domains of the two precursors are identical. The sequence difference results from the presence in preproIGF-IB mRNA of a 52 base insertion which introduces a 17 amino acid segment into the COOH-terminal peptide of preproIGF-IB and also causes a shift in the reading frame of the mRNA. As a consequence of this insertion, the COOH-terminal 19 and 25 amino acids of mouse preproIGF-IA and -IB, respectively, are different. The sequences of mouse and human preproIGF-IA are highly conserved and possess 94% identity. In contrast, the sequences of mouse and human preproIGF-IB are quite different in the region of the COOH-terminal peptide. A comparison of the sequences of mouse and human preproIGF-IB mRNA indicates that they are generated by different molecular mechanisms.

Amino Acid Sequence↗
PubMed1986

Sequence of a placental cDNA encoding the mouse insulin-like growth factor II precursor.

cDNAs encoding the mouse insulin-like growth factor II (IGF-II) precursor have been isolated from a placental library and sequenced. Mouse prepro-IGF-II is predicted to be 180 amino acids and has 84% and 97% identity with human and rat IGF-II precursors, respectively. There are two prepro-IGF-II transcripts in mouse placenta; the major transcript is 3850 bases and the minor one is 4800 bases. Prepro-IGF-II mRNA cannot be detected in adult mouse liver, but it is readily detected in adult human liver, indicating that there are differences in the regulation of expression of the IGF-II gene in the liver of adult mice and human beings.

Animals↗
PubMed1986

The gene for human transforming growth factor alpha is on the short arm of chromosome 2.

Transforming growth factor alpha is a polypeptide growth factor that participates in the reversible transformation of cells in vitro and is secreted by many transformed cell lines. It also shares sequence and functional homologies with epidermal growth factor. Working with a cloned cDNA probe (lambda hTGF1-10) and derivatives, we have mapped this gene (TGFA) to 2p13 with the use of somatic cell hybrids and in situ hybridization. This is the same region involved in the 2;8 translocations of Burkitt lymphoma. Such a rearrangement could orient c-myc (8q24) adjacent to TGFA, resulting in activation of one or both of these genes.

Animals↗
PubMed1986

Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas.

The insulin-like growth factors I and II (IGF-I and -II) are proteins which stimulate cell proliferation and are important in normal human growth and development. They are coded for by separate genes and bind to specific cell surface receptors, eliciting a mitogenic response. IGFs are secreted by several cell lines derived from adult tumors. We have examined a number of human adult tumors for IGF messenger RNA (mRNA) expression and found IGF-II mRNA levels were consistently elevated in two types, colon carcinoma and liposarcoma. Adult colonic mucosa contains low levels of IGF-I and -II mRNA while several colon tumors, particularly of rectal and rectosigmoid origin, contained significantly elevated levels of IGF-II message. Over 90% of liposarcomas examined contained greatly elevated levels of IGF-II mRNA while control tissue (adipose) contained very low or undetectable IGF mRNA levels. Many of these tumors also contained elevated IGF-I mRNA levels. Northern analysis of these RNAs revealed differences in the abundance and sizes of IGF transcripts compared to other normal and malignant tissues known to express IGF.

Carcinoma↗
PubMed1985

The human apolipoprotein AII gene: structural organization and sites of expression.

The complete nucleotide sequence of the human apolipoprotein All gene together with 911 bases of 5' flanking sequence and 687 bases of 3' flanking sequence have been determined. The mRNA coding region is interrupted by three introns of 169, 293 and 395bp. The Intro-exon structure of the apo All gene is similar to that of the apo AI, apo CIII and apo E genes: three introns separate 4 coding sequences specifying the 5' untranslated region, pre-peptide, a short N-terminal domain and a C-terminal domain composed of a variable number of lipid-binding amphipathic helices. Intron II carries a 33bp dG-dT repetitive element adjacent to the 3' splice junction which has the potential to adopt the Z-DNA conformation. The 5' and 3' terminuses of the mRNA have been identified by primer extension and S1 nuclease mapping. A number of short direct repeats are found in the 5' flanking region and an inverted repeat occurs between the CAAT and TATA boxes. Downstream of the the gene is an Alu family repeat containing a polymorphic MspI site, the deletion of which is associated with increased circulating levels of apoAII. ApoAII gene expression was demonstrated in adult human liver and HepG2 cells but not in human small intestine. Of ten Rhesus monkey tissues examined apo All mRNA was detected only in liver.

Amino Acid Sequence↗
PubMed1985

Human alpha 2-macroglobulin gene is located on chromosome 12.

A cDNA clone encoding amino acids 809-1451 of the protease inhibitor alpha 2-macroglobulin has been isolated from an adult human liver cDNA library. This cDNA was used to examine DNA samples prepared from a panel of human-mouse somatic cell hybrids with different numbers and combinations of human chromosomes for the presence of the human alpha 2-macroglobulin gene. The cosegregation of this gene and chromosome 12 in the cell hybrid panel indicated that the alpha 2-macroglobulin structural gene (designated A2M) is on human chromosome 12.

Amino Acid Sequence↗
PubMed1985

Isolation of the human insulin-like growth factor genes: insulin-like growth factor II and insulin genes are contiguous.

Overlapping recombinant clones that encompass the insulin-like growth factor (IGF) I and II genes have been isolated from a human genomic DNA library. Each gene is present once per haploid genome; the IGF-I gene spans greater than 35 kilobase pairs (kbp) and the IGF-II gene is at least 15 kbp. The exon-intron organization of these genes is similar, each having four exons, which is one more than the related insulin gene. Comparison of the restriction endonuclease cleavage maps of the IGF-II and insulin genes, including their flanking regions and hybridization with an IGF-II cDNA probe, revealed that they are adjacent to one another. The IGF-II and insulin genes have the same polarity and are separated by 12.6 kbp of intergenic DNA that includes a dispersed middle repetitive Alu sequence. The order of the genes is 5'-insulin-IGF-II-3'.

Base Sequence↗
PubMed1983

Synthesis of hepatitis B surface antigen in mammalian cells: expression of the entire gene and the coding region.

We have constructed two simian virus 40 early replacement recombinants that have the coding sequences for hepatitis B virus surface antigen (HBsAg). One construction, LSV-HBsAg, has the coding region for HBsAg but not the portion encoding the putative pre-surface antigen leader. Transformed monkey kidney cells (COS) infected with this recombinant express large quantities of the characteristic partially glycosylated HBsAg molecule, which are assembled into 22-nm particles that appear similar to those produced by human liver cells infected with hepatitis B virus. This result indicates that the pre-surface antigen sequences are not required for the synthesis of HBsAg or its assembly into particulate structures. The second recombinant, LSV-HBpresAg, has the entire surface antigen gene, including the putative promoter and pre-surface antigen region. COS cells infected with this recombinant plasmid produce 40- to 50-fold less HBsAg than those infected with the LSV-HBsAg recombinant plasmid. RNA mapping studies suggest that the transcription of the HBsAg gene is initiated at more than one site, or alternatively, that RNA splicing of transcripts occurs in the pre-surface antigen region.

Animals↗
PubMed1983

Transcription of hepatitis B virus by RNA polymerase II.

We employed an in vitro cell-free transcription system to locate RNA polymerase II promoters on the hepatitis B virus genome. The strongest promoter precedes the surface antigen (HBsAg) gene, which is comprised of a long (500 base pairs) presurface region as well as the mature HBsAg coding sequence. The origin of this transcript was localized by using truncated templates and S1 endonuclease mapping. The activity of the promoter was confirmed in transfection experiments in which the complete HBsAg gene was introduced into monkey kidney cells via a simian virus 40 expression vector. A second RNA polymerase II promoter preceding the HBcAg gene was also active in the cell-free system. The presence of multiple promoters in the hepatitis B virus genome suggests that the relative levels of viral-specific proteins detected in liver and serum may reflect differential or regulated promoter efficiency.

Base Sequence↗
PubMed1983

Hepatitis B virus encodes an RNA polymerase III transcript.

We demonstrated that cloned hepatitis B virus (HBV) DNA directs the synthesis of a 700-base RNA (HBV 700) by RNA polymerase III in a cell-free transcription system. HBV 700 is the only transcript known to originate from the viral short strand and has been mapped to the region between roughly 1,635 and 954 base pairs on the viral map, between the surface and core antigen coding sequences but overlapping and opposing the putative DNA polymerase and B protein genes. The in vitro initiation sites for the HBV 700 and core antigen RNAs are only 50 bases apart, suggesting that these two genes may be coordinately regulated. Moreover, both of these initiation sites appear to lie within the approximately 300-base double-stranded region (the nick region) between the 5' end of the HBV short strand and the nick in the viral long strand. We found two unusual sequence elements in the nick region that are conserved between the human and woodchuck viruses.

DNA, Viral↗
PubMed1982

Hepatitis B viral DNA in liver and serum of asymptomatic carriers.

Cloned DNA probes were used to test for hepatitis B virus (HBV) DNA in the liver and serum of 14 asymptomatic hepatitis B surface antigen (HBsAg) carriers and two former carriers. The results were compared with serological markers of HBV infection and liver histopathology. Three groups of carriers were distinguished. In group I, HBV DNA was present in both liver and serum. Hepatitis B e antigen (HBeAg), a marker of viral replication, was uniformly positive in serum. In one individual in this group, viral DNA was also integrated into liver genomic DNA. In group II, lower levels of nonintegrated HBV DNA were detected in the liver, but no HBV DNA was found in the serum. HBeAg was negative and with one exception there were antibodies to HBeAg. Integrated viral DNA was present in each case. In group III, there was no detectable nonintegrated viral DNA in serum or liver, but one individual had integrated sequences. All carriers lacked antibodies to HBsAg and had antibodies to hepatitis B core antigen and demonstrated nonspecific histological abnormalities in the liver. These findings indicate significant quantitative and qualitative differences among asymptomatic HBsAg carriers and suggest that their infectivity may be highly variable.

Adolescent↗
PubMed1980

Integration of hepatitis B virus sequences and their expression in a human hepatoma cell.

Hepatitis derived from hepatitis B virus (HBV) infection is endemic throughout the world, but it is particularly prevalent in Asia and Africa. In these areas, demographic studies show a strong coincidence between HBV infection (assayed by HBV antigenic markers) and the incidence of primary liver cancer. On these grounds, a causal link between HBV infection and primary hepatocellular cancer has been proposed. Recently, a human hepatoma cell line (PLC/PRF/5; Alexander cells) has been shown to produce hepatitis B surface antigen (HBsAg). We show here that the Alexander cell line contains at least six (four complete and two partial) hepatitis B viral genomes integrated into high molecular weight host DNA. An analysis using specific probes to fragments of the HBV genome suggests that integration of the virus in most cases occurs at the nicked cohesive end region of the virus. Expression of viral sequences using Northern blots demonstrates the presence of RNA transcripts specific for the surface antigen sequences of HBV DNA and the absence of detectable transcripts corresponding to the hepatitis B core antigen.

Carcinoma, Hepatocellular↗