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Biomedical subjects

G Dahl

Publications and source records attributed to G Dahl.

At least 19 recordsLinked to original sources
PubMed1995

[Adnexial torsion caused by ovarian hyperstimulation syndrome].

A case of adnexal torsion of an enlarged ovary during early pregnancy after gonadotropin therapy is presented. Adnexal torsion is a rare but serious complication to ovarian hyperstimulation. The diagnosis is difficult, but the combination of ovarian enlargement, abdominal pain, nausea, progressive leukocytosis and anaemia may indicate torsion of the adnex. Prompt diagnosis is important. Simple unwinding of the twisted adnex by a laparoscopic technique has been successful in most cases.

Adnexal Diseases↗
PubMed1995

Use of alternate promoters for tissue-specific expression of the gene coding for connexin32.

The promoter of rat connexin32 (Cx32), the gap junction protein found in liver, was studied in transgenic mice. Cx32 transgenes, containing 2.5-kb of sequence upstream from the promoter, exon I, the entire 6.1-kb intron and the beginning of the coding sequence linked to the gene encoding luciferase (Luc), were found to be expressed in mouse in the same tissue-specific manner as previously reported for Cx32. Another construct lacking the promoter, but retaining 1.8 kb from the 3' end of the intron, was found to be expressed specifically in the nervous system. This result suggested that a second promoter, different from that used in liver, functions in nervous tissue. The use of this promoter in normal rats was corroborated by sequence analysis of reverse-transcribed PCR products obtained from rat nervous tissue RNA. The second promoter drives the synthesis of a second Cx32 mRNA species that is processed to remove a small 345-bp intron that shares its acceptor splice site with the large intron. This finding could have implications for the genetic basis of the X-linked form of Charcot-Marie-Tooth disease (CMT-X) in those patients that do not exhibit mutations in the Cx32-coding region.

Animals↗
PubMed1994

Attempts to define functional domains of gap junction proteins with synthetic peptides.

To map the binding sites involved in channel formation, synthetic peptides representing sequences of connexin 32 were tested for their ability to inhibit cell-cell channel formation. Both large peptides representing most of the two presumed extracellular loops of connexin32 and shorter peptides representing subsets of these larger peptides were found to inhibit cell-cell channel formation. The properties of the peptide inhibition suggested that the binding site is complex, involving several segments of both extracellular loops. One of the peptides (a 12-mer) did not inhibit but instead was found to form channels in membranes. Both in oocyte membranes and in bilayers, the channels formed by the peptide were asymmetrically voltage dependent. Their unit conductances ranged from 20 to 160 pS. These data are discussed in the form of a model in which the connexin sequence represented by the peptide is part of a beta structure providing the lining of the channel pore.

Amino Acid Sequence↗
PubMed1994

Activation of the DNA-binding ability of human heat shock transcription factor 1 may involve the transition from an intramolecular to an intermolecular triple-stranded coiled-coil structure.

Heat stress regulation of human heat shock genes is mediated by human heat shock transcription factor hHSF1, which contains three 4-3 hydrophobic repeats (LZ1 to LZ3). In unstressed human cells (37 degrees C), hHSF1 appears to be in an inactive, monomeric state that may be maintained through intramolecular interactions stabilized by transient interaction with hsp70. Heat stress (39 to 42 degrees C) disrupts these interactions, and hHSF1 homotrimerizes and acquires heat shock element DNA-binding ability. hHSF1 expressed in Xenopus oocytes also assumes a monomeric, non-DNA-binding state and is converted to a trimeric, DNA-binding form upon exposure of the oocytes to heat shock (35 to 37 degrees C in this organism). Because endogenous HSF DNA-binding activity is low and anti-hHSF1 antibody does not recognize Xenopus HSF, we employed this system for mapping regions in hHSF1 that are required for the maintenance of the monomeric state. The results of mutagenesis analyses strongly suggest that the inactive hHSF1 monomer is stabilized by hydrophobic interactions involving all three leucine zippers which may form a triple-stranded coiled coil. Trimerization may enable the DNA-binding function of hHSF1 by facilitating cooperative binding of monomeric DNA-binding domains to the heat shock element motif. This view is supported by observations that several different LexA DNA-binding domain-hHSF1 chimeras bind to a LexA-binding site in a heat-regulated fashion, that single amino acid replacements disrupting the integrity of hydrophobic repeats render these chimeras constitutively trimeric and DNA binding, and that LexA itself binds stably to DNA only as a dimer but not as a monomer in our assays.

Amino Acid Sequence↗
PubMed1992

[Legionnaires' disease--a multifaceted syndrome].

Multiorgan involvement is often seen in Legionella infections. We report two cases, with classical pneumonia complicated by facial paresis and severe kidney affection demanding haemodialysis. One patient had Legionella infection concomitantly with pneumococcal pneumonia. As the diagnosis often is not verified till weeks after onset of illness, it is concluded that the treatment should be started and maintained on clinical suspicion. Isolation of another respiratory pathogen does not exclude the possibility of Legionella infection.

Acute Kidney Injury↗
PubMed1992

Mutational analysis of gap junction formation.

The paired oocyte cell-cell channel assay was used to investigate the mechanisms involved in the process of formation of gap junction channels. Single oocytes, injected with connexin-specific mRNAs, accumulate a pool of precursors from which cell-cell channels can form rapidly upon pairing. Several lines of evidence, including immunohistochemistry and surface labeling, indicate that part of this precursor pool is located in the cell membrane, probably in the form of closed hemichannels. The homophilic binding of hemichannels to each other can be mimicked by synthetic peptides representing the extracellular loop sequences of connexin32. The peptides specifically suppress channel formation. A crucial role is established for the six cysteines in the extracellular domains that are conserved in all vertebrate gap junction proteins. Change of any of these cysteines into serines results in absolute loss of function of the mutant connexin. The effects of thiol-specific reagents on channel formation suggest that docking and/or opening of channels involves disulfide exchange. Several of the variable amino acids in the extracellular loop sequences were found to determine specificity of connexin-connexin interactions.

Amino Acid Sequence↗
PubMed1991

The t(1;22) (p13;q13) is nonrandom and restricted to infants with acute megakaryoblastic leukemia: a Pediatric Oncology Group Study.

We report the nonrandom occurrence and frequency of the t(1;22)(p13;q13) in acute myeloid leukemia (AML) and its close association with the French-American-British M7 subtype of AML in infants (less than 1 year). This chromosomal abnormality occurred in 6 of 252 (2.4%) children and adolescents with AML (6 of 28 infants, 22%; 6 of 18 M7 AML cases overall, 33%; and 6 of 6 M7 cases in infants). Infants with AML of M7 subtype and the t(1;22) often presented with prominent abdominal masses. Two of these infants were not treated and died early. Three of four treated infants entered complete remission with therapy for AML; the remaining infant died of hemorrhage on day 8. Of the three infants who entered remission, only one remains alive and disease free at 5+ months. The other two infants relapsed in the bone marrow at 5 and 2 months from the start of therapy, respectively. We conclude that M7 AML with the t(1;22) usually presents in infants with extensive infiltration of abdominal organs by leukemic cells and may confer a poor prognosis despite intensive AML-directed treatment. Identification of this nonrandom translocation exclusively in infants with acute megakaryoblastic leukemia (AMkL) implies that it may serve as an additional diagnostic marker for this disease and links it to the pathogenesis of AMkL in infants.

Antigens, CD↗
PubMed1991

Cell/cell channel formation involves disulfide exchange.

The oocyte cell/cell-channel assay was used to identify amino acids involved in the process of cell/cell-channel formation. The expression of the rat liver gap-junction protein, connexin 32, in single oocytes, results in the accumulation of a pool of channel precursors. Upon pairing of such oocytes, cell/cell channels form rapidly from this pool. The rate of formation is affected by thiol-specific reagents and the pH. This suggests the involvement of extracellular cysteine residues in the channel formation process. Two connexin-32 mutants were generated by site-directed mutagenesis in which cysteine residues were replaced by serine. Both mutant connexins were unable to form cell/cell channels. Thus, the cysteine residues appear to play an important role in the channel formation process.

Animals↗
PubMed1991

Gating properties of connexin32 cell-cell channels and their mutants expressed in Xenopus oocytes.

Carboxyl-terminal deletion mutants of the gap junction protein connexin32 were tested in the oocyte cell-cell channel assay. Oocytes expressing a mutant lacking 58 carboxyl terminal amino acids were found to exhibit junctional conductances of the same magnitude as oocytes expressing wild-type connexin32. The gating properties of the channels formed by this mutant of connexin32 with respect to transjunctional voltage and cytoplasmic acidification are indistinguishable from those found with wild-type connexin32 channels. This includes a novel pH-dependent voltage gate. In another mutant, two carboxyl terminal serine residues, Ser233 and Ser240, were replaced by Asn residues. This double mutant has properties indistinguishable from wild-type connexin32, suggesting that phosphorylation of either of these serines is not required for channel opening.

Animals↗
PubMed1991

Cell-cell channel formation and lectins.

The oocyte cell-cell channel assay was used to investigate determinants of the rate of channel formation. After injection of connexin-specific mRNA, oocytes accumulate a pool of precursors from which cell-cell channels can form after oocytes are paired. Channel formation was found to be increased if oocytes are pretreated with lectins before pairing. Several lectins differing in their carbohydrate binding affinities can exert this effect. Lectin-specific sugars suppress the effect on cell-cell channel formation only if the sugar is mixed with the lectin before application to the oocyte. If the lectin is first bound to the oocyte and then the sugar is added, no significant inhibition is seen. The promotion of channel formation by lectins is enhanced by adding an incubation period in regular medium after lectin treatment, before pairing of the oocytes. Electron microscopic studies with gold-conjugated lectins show that the lectin receptors are clustered on the free membrane surface and are taken up in endocytotic vesicles. These data suggest that the observed acceleration of cell-cell channel formation by lectins can be attributed to the removal of steric hindrance, which is a consequence of clustering of the bulky glycoprotein lectin receptors as well as of the removal from the surface by endocytosis.

Animals↗
PubMed1989

Acute vincristine neurotoxicity in the presence of hereditary motor and sensory neuropathy type I.

Acute vincristine neurotoxicity leading to a severe motor and sensory neuropathy has been noted in patients with hereditary motor and sensory neuropathy type I (HMSN-I). The case of a 2-year-old boy with acute lymphocytic leukemia and HMSN-I is reported, and additional cases from the literature are reviewed. Severe vincristine neurotoxicity in patients with HMSN-I may be secondary to impairment of both slow and- fast axonal transport. Vincristine should be used with caution in patients with a family history of polyneuropathy.

Charcot-Marie-Tooth Disease↗
PubMed1989

Formation of hybrid cell-cell channels.

The oocyte cell-cell channel assay was used to demonstrate that connexin-43 is a cell-cell channel-forming protein as previously shown for connexin-32. Expression of connexin-32 in one and connexin-43 in the other oocyte of a pair results in the formation of junctional conductances at rates similar to those observed when only one or the other connexin is expressed in both oocytes of a pair. This suggests that hybrid cell-cell channels form in the oocyte system. Hybrid channels also form when a connexin-43 mRNA-injected oocyte is paired with a noninjected oocyte expressing endogenous connexin. The latter hybrids have properties apparently contributed by both types of hemichannels. Pure connexin-43 channels are not voltage gated, whereas pure oocyte channels are voltage dependent; hybrids of these channels rectify.

Animals↗
PubMed1988

Structure of a gap junction gene: rat connexin-32.

A genomic clone for the rat liver gap junction protein (connexin-32) was isolated and characterized by restriction enzyme mapping and sequence analysis. While the complete coding sequence is contained within one uninterrupted block, the 5'-untranslated region of the transcript contains a 6.1 kb intron. Both S1 nuclease protection and primer extension assays indicate multiple transcription start sites. Sequences homologous to cAMP response elements are found near the transcription start sites and within the 3'-end of the intron.

Animals↗
PubMed1987

Expression of functional cell-cell channels from cloned rat liver gap junction complementary DNA.

An oocyte expression system was used to test the relation between a complementary DNA (cDNA) clone encoding the liver gap junction protein and cell-cell channels. Total liver polyadenylated messenger RNA injected into oocytes induced cell-cell channels between paired oocytes. This induction was blocked by simultaneous injection of antisense RNA transcribed from the gap junction cDNA. Messenger RNA selected by hybridization to the cDNA clone and translated in oocyte pairs yielded a higher junctional conductance than unselected liver messenger RNA. Cell-cell channels between oocytes were also formed when the cloned cDNA was expressed under the control of a heat-shock promoter. A concentration-dependent induction of channels was observed in response to injection with in vitro transcribed gap junction messenger RNA. Thus, the liver gap junction cDNA encodes a protein that is essential for the formation of functional cell-cell channels.

Animals↗