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D F Gordon

Publications and source records attributed to D F Gordon.

At least 73 records · Page 4Linked to original sources
PubMed1988

Organization and nucleotide sequence of the mouse alpha-subunit gene of the pituitary glycoprotein hormones.

We have isolated and determined the nucleotide sequence of the mouse alpha-subunit gene of the pituitary glycoprotein hormones. No detectable rearrangements were observed from the cloned gene when compared with total genomic DNA. The gene is approximately 13.5 kb in size and consists of 4 exons and 3 introns. The 5' untranslated region is encoded by exon 1 and 14 bp of exon 2. A large first intron of about 10 kb interrupts the 5' untranslated region. The coding region is present in exons 2, 3, and 4, while the 3' untranslated region is contained entirely within exon 4. A number of mouse B1 and B2 repeats are present in the 5'-flanking region, the first and third introns, as well as in the 3'-flanking region. In contrast to the mouse beta-subunit gene of thyrotropin, primer extension analysis revealed that the alpha-subunit gene has a single transcriptional start site and that the primary transcript does not exhibit alternative exon splicing. The transcriptional start site is identical in both mouse pituitaries and in TtT97 thyrotropic tumors and is responsive to thyroidal status. The 5'-flanking region contains a sequence that is homologous to a single copy of the duplicated 18-bp cyclic AMP-responsive element of the human alpha-subunit gene. Sequences homologous to putative thyroid-responsive and estrogen responsive elements are present in the 5'-flanking region and may be important in the multihormonal regulation of the alpha-subunit gene in throtrophs and gonadotrophs, respectively.

Animals↗
PubMed1988

Multiple human progesterone receptor messenger ribonucleic acids and their autoregulation by progestin agonists and antagonists in breast cancer cells.

We have used AB-52, a monoclonal antibody which recognizes both the A (94,000 daltons) and B (120,000 daltons) proteins of human progesterone receptors (hPR), and hPR-50, a PR complementary DNA probe isolated from a T47D-pcD library, to study the structure and hormonal regulation of the hPR mRNAs and proteins in human breast cancer cells. RNA blot hybridization analysis of poly(A+) RNA shows that T47DCO, an estrogen resistant human breast tumor cell line in which PR are constitutively expressed, contain at least six PR mRNAs ranging in size from 2.5 to 11.4 kilobases. All six are mature cytoplasmic messages that are also present in normal human endometrium and in PR-positive MCF-7 breast cancer cells, but not in PR-negative cells. Using hPR-50 RNA synthesized in vitro as a 1.3 kilobase standard, we calculate that MCF-7 cells contain approximately 16 message molecules per cell which are increased to approximately 45 by estradiol treatment; T47DCO cells contain approximately 90 message molecules per cell constitutively expressed. Treatment of T47DCO cells with progesterone leads to down-regulation of immunoreactive A- and B-receptors in the first 8-12 h, followed by their replenishment during the next 48 h. In parallel, hPR message levels initially decrease and then return to pretreatment levels. The synthetic progestin R5020 chronically down-regulates A- and B-receptors; the proteins are profoundly suppressed for at least 48 h, while PR mRNAs fall to less than 15% of control. However, with both hormones, parallel changes in protein and message levels are observed, suggesting that progestational agonists autoregulate the levels of their own receptors by inhibiting transcription of the PR gene. Antagonists appear to have different effects. With the antiprogestin RU 486 there is discordance between hPR protein and message levels which may be due to an ineffective inhibitory interaction between the antagonist-occupied receptors and PR genes, thereby disrupting the negative feedback loop.

Breast Neoplasms↗
PubMed1987

Expression of the beta-subunit gene of murine thyrotropin results in multiple messenger ribonucleic acid species which are generated by alternative exon splicing.

The current studies reveal that expression of the mouse TSH beta-subunit gene in the pituitary gland and TtT97 murine thyrotropic tumor results in multiple mRNAs which arise by alternative splicing. This was deduced by 1) sequencing the extended products of TSH beta mRNA primed with an oligonucleotide complementary to the protein coding region and 2) demonstrating primer extension of oligonucleotides complementary to the optional exon junctions. These results, when correlated with the sequence of the TSH beta gene, revealed a structure comprising five exons and four introns. Exon 1, which is common to all of the mRNAs, and optional exons 2 and 3 code only for 5'-untranslated (UT) sequences, whereas exons 4 (includes one nucleotide of 5'-UT) and 5 encode the protein coding and 3'-UT regions. Multiple splicing events generate mRNAs with 5'-UT regions of 28, 69, 75, and 116 nucleotides which include exon 1, exons 1 and 3, exons 1 and 2, and exons 1, 2, and 3, respectively. In contrast, in the hypothyroid rat pituitary messages possessing optional exons were not detected, and thus the TSH beta mRNA with a 5'-UT region of 28 nucleotides predominated. We identified an additional transcriptional start site located 40 nucleotides upstream in both the mouse and rat TSH beta gene. Optional exon splicing was not detectable in transcripts initiated from the upstream start site of the murine gene. In the hypothyroid state, transcripts initiated at the upstream site were considerably less abundant than those initiated at the downstream site. Transcription from both start sites was inhibited by thyroid hormone in both mice and rats.

Animals↗
PubMed1986

Analysis of the organization and nucleotide sequence of the chromosomal gene for the beta-subunit of rat thyrotropin.

The gene for the beta-subunit of rat thyrotropin has been isolated from a library of rat DNA fragments cloned in bacteriophage lambda. The complete nucleotide sequence of the gene has been determined including a portion of 5'- and 3'-flanking regions. The rat TSH-beta gene contains approximately 4879 nucleotides which ultimately lead to the production of a mRNA of about 554 nucleotides, exclusive of the 3' poly(A) tract. The first exon which represents only 5' untranslated sequences of the mRNA, is separated from the second exon by a very large, 3.9-kbp intervening sequence. The second and third exons are separated by a small, 377-bp intervening sequence. Southern blot analysis of total genomic DNA demonstrated that the rat genome contains sequences similar to the cloned gene, suggesting that no rearrangements occurred during the cloning process.

Animals↗
PubMed1984

Isolation and complete nucleotide sequence of the gene for bovine parathyroid hormone.

The structure of the bovine parathyroid hormone (PTH) gene has been analyzed by Southern blot hybridization of genomic DNA and by nucleotide sequence analysis of a cloned PTH gene. In the Southern analysis, several restriction enzymes produced single fragments that hybridized to PTH cDNA suggesting that there is a single bovine PTH gene. The restriction map of the cloned gene is the same as that determined by Southern blot analysis of bovine DNA. The sequence of 3154 bp of the cloned gene has been determined including 510 bp and 139 bp in the 5' and 3' flanking regions, respectively. The gene contains two introns which separate three exons that code primarily for: (i) the 5' untranslated region, (ii) the pre-sequence of preProPTH, and (iii) PTH and the 3' untranslated region. The gene contains 68% A + T and unusually long stretches of 100- to 150-bp sequences containing alternating A and T nucleotides in the 5' flanking region and intron A. The 5' flanking region contains two TATA sequences, both of which appear to be functional as determined by S1 nuclease mapping. Compared to the rat and human genes, the locations of the introns are identical but the sizes differ. Comparable human and bovine sequences in the flanking regions and introns are about 80% homologous.

Animals↗
PubMed1983

Nucleotide sequence of the bovine growth hormone chromosomal gene.

A library of cloned bovine DNA fragments was constructed and screened for growth hormone sequences. The growth hormone gene was isolated from this library and its nucleotide sequence determined. The likely transcription initiation site was located using the S1 nuclease protection procedure. The bovine growth hormone gene contains approximately 1793 nucleotides and consists of five exons separated by four intervening sequences. The sequence TATAAA is found in the 5' flanking region and probably is involved in facilitating transcription initiation. Comparison of the bovine growth hormone gene to the known sequence of the rat and human genes reveals that the coding regions of the three genes are highly conserved. In general the intervening sequences are much less similar than the coding regions. Interestingly, all three growth hormone genes share a conserved (but nonidentical) 40 base pair region within the 5' flanking region. This conserved region may be an important sequence involved in the hormonal regulation of growth hormone gene transcription. Analysis of GH sequences present in total bovine DNA suggests that the bovine genome contains a gene similar to the cloned gene as well as a different, but related, gene. The functional significance of the two genes remains to be explored. Analysis of nuclear species of growth hormone mRNA has demonstrated the presence of RNAs of 2100, 1400 and 1000 nucleotides containing growth hormone sequences. These likely correspond to a polyadenylated primary transcript, a processing intermediate and mature growth hormone mRNA, respectively.

Amino Acid Sequence↗
PubMed1983

Intravenous balloon pumping for acute right ventricular failure.

A patient with acute right ventricular failure and severe hemodynamic instability following coronary artery revascularization was treated with intra-aortic and intravenous balloon pumping. The intravenous balloon was timed to inflate during diastole and deflate during systole as did the intra-aortic balloon; in fact, the two were connected to the same system through a Y-connector. The intravenous balloon acted as an artificial atrium, which allowed approximately 20% improvement in the cardiac output when this intravenous balloon was functioning. Hemodynamic stability was achieved with this system. Intravenous balloon pumping should be considered for patients with unstable hemodynamics secondary to acute right ventricular failure.

Aged↗
PubMed1982

Surgery for evolving myocardial infarction.

One hundred fifty-six patients underwent emergency coronary revascularization during the early phases of evolving myocardial infarction (MI). There were six hospital deaths (3.8%) and two later deaths (1.3%). Thrombectomy of the MI artery was achieved in 79% of the patients, and 17% of the patients showed no observable lesion in the MI vessel on restudy. Graft patency was 99%. Late follow-up to 62 months disclosed 17 patients with residual limitations. Analysis of the data established criteria for recognizing patients with early MI who would benefit from surgical therapy. The criteria are derived by comparing preoperative and postoperative ventricular anatomy, creatine phosphokinase levels, and hemodynamics.

Clinical Enzyme Tests↗
PubMed1982

Coronary artery spasm following coronary artery revascularization.

Coronary artery spasm is a well-documented phenomenon in patients undergoing medial treatment. We describe coronary artery spasm occurring in the immediate postoperative period following coronary artery bypass operation. The spasm occurred in a vessel that was not operated on and that had no apparent lesion. The diagnosis of spasm was made by coronary angiography immediately after operation. Complications associated with this spasm are discussed. Emphasis is placed on early postoperative angiography for patients whose condition is inexplicably unstable after operation.

Amyl Nitrite↗
PubMed1981

Introduction by molecular cloning of artifactual inverted sequences at the 5' terminus of the sense strand of bovine parathyroid hormone cDNA.

To study the structure and function of the gene for parathyroid hormone, we obtained recombinant plasmids containing bovine parathyroid hormone cDNA. The nucleotide sequence at the 5' terminus (relative to the sense strand) of the cDNA insert in a recombinant plasmid, pPTHi4, was different from that previously reported for the bovine parathyroid hormone cDNA insert of another recombinant plasmid, pPTHm1 [Kronenberg, H. M., McDevitt, B. F., Majzoub, J. A., Nathans, J., Sharp, P. A., Potts, J. T., Jr. & Rich, A. (1979) Proc. Natl. Acad. Sci. USA 76, 4981-4985]. The first 50 nucleotides of the pPTHm1 insert were an inverted complement of nucleotides 2-51 of the pPTHi4 insert. the cDNA insert of another plasmid, pPTHi8, contained a sequence identical to nucleotides 2-51 of the pPTHi4 insert but also contained an additional 42 bases at the 5' terminus. The first 41 bases of the pPTHi8 insert were an inverted repeat of an internal sequence of the pPTHi4 insert corresponding to nucleotides 184-224. Restriction endonuclease analysis of pPTHi8 indicated that the internal sequence corresponding to this region was retained. The nucleotide sequence of a restriction fragment hybridized to parathyroid hormone mRNA and extended toward the 5' terminus of the mRNA with reverse transcriptase confirmed that the sequence at the 5' terminus of the pPTHi4 insert was an accurate copy of the parathyroid hormone mRNA sequence. These data suggest that two types of sequence rearrangements may occur at the 5' terminus, as occurred in pPTHm1, and (ii) an inverted repeat of an internal sequence, as occurred in pPTHi8.

Animals↗
PubMed1981

Surgical therapy for evolving myocardial infarction: Results in 138 patients.

One hundred thirty-eight selected patients underwent emergency coronary artery revascularization as the treatment for early evolving myocardial infarction. Low early and late (3.6 and 2.9%) mortality and morbidity up to 54 months, with favorable post surgical hemodynamic improvement demonstrates the operability with beneficial results in selected patients with early evolving myocardial infarction.

Adult↗
PubMed1980

Synthesis, restriction analysis, and molecular cloning of near full length DNA complementary to bovine parathyroid hormone mRNA.

DNA complementary (cDNA) to a partially purified preparation of bovine parathyroid hormone mRNA was synthesized using avian myeloblastosis viral reverse transcriptase. The PTH cDNA contained about 750 bases and was greater than 95% sensitive to digestion by S1 nuclease. Analysis of the mRNA preparation by excess RNA hybridization to the PTH cDNA revealed one rapidly hybridizing component consisting of 50% of the PTH cDNA. Sequential incubation of the PTH mRNA with reverse transcriptase and E. coli DNA polymerase I produced near full length double-stranded PTH cDNA. Of the 22 restriction endonucleases tested, double-stranded PTH cDNA could be cleaved with Alu I, Mbo II, Sau 3A, Sst I, and Taq I. The restriction fragments corresponding to the 5' terminus of the sense strand were identified for the last three enzymes by comparing the size of fragments obtained from PTH cDNA before and after cleavage of the hairpin loop connecting the two strands by S1 nuclease. The restriction map of the cDNA was used to detect clones of bacteria containing recombinant plasmids with near full length PTH cDNA inserts.

Animals↗
PubMed1980

Clinical trial with a percutaneously inserted intra-aortic balloon pump: a wider spectrum of patient application.

The intra-aortic balloon pump has been proven to be an effective form of therapy in a variety of situations involving actual or potential ventricular power failure. An experience with 12 newly-designed percutaneous PERCOR-TM intra-aortic balloon pumps is discussed. Emphasis is made on the ease of insertion and removal, and on the fact that a trained surgical team in an operating room setting is not necessary. Effectiveness of the balloon in comparison to the traditional intra-aortic balloon pump is also discussed.

Adult↗
PubMed1979

Anoxic hypothermic cardioplegia compared to intermittent anoxic fibrillatory cardiac arrest. Clinical and metabolic experience with 1080 patients.

Appropriately applied, hypothermic cardioplegia allows an excellent surgical setting that can significantly reduce the myocardial ischemic injury resulting from anoxia. One thousand eighty adult and pediatric patients underwent a variety of corrective cardial surgical procedures utilizing cold potassium cardioplegic solution injected into the coronary arteries via the aortic root. Myocardial septal temperature was maintained at 18--20 degrees during arrested time. This group of patients was compared to a group of 220 patients that underwent intermittent normothermic ischemic arrest to perform cardiac surgical procedures. Significant reduction in morbidity, mortality, perioperative myocardial infarction was noted in favor of the cardioplegic group. Metabolic coronary sinus blood analysis in the group undergoing surgery with cardioplegia revealed favorable changes in myocardial lactate and oxygen extraction.

Adult↗