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Biomedical subjects

A Larsen

Publications and source records attributed to A Larsen.

At least 19 recordsLinked to original sources

Cloning of the low-affinity murine granulocyte-macrophage colony-stimulating factor receptor and reconstitution of a high-affinity receptor complex.

A cDNA clone (clone 71) that encodes a low-affinity receptor for murine granulocyte-macrophage colony-stimulating factor (GM-CSF) has been isolated by direct expression. This molecule is the homologue of the human GM-CSF receptor alpha subunit, although homology between these molecules is surprisingly low (less than 35% amino acid identity). The cDNA encodes a polypeptide of 387 amino acids, which contains the conserved features of the hematopoietin receptor superfamily. When expressed in COS-7 cells, this clone encodes a protein that binds radiolabeled murine GM-CSF with low affinity. Coexpression of clone 71 with a cDNA corresponding to a low-affinity interleukin 3 (IL-3) receptor (AIC2A) did not alter the affinity of binding of either GM-CSF or IL-3. However, coexpression of clone 71 with the IL-3 receptor-related cDNA AIC2B generated high-affinity binding sites for murine GM-CSF but not murine IL-3. These studies show that clone 71 and AIC2B are capable of forming an alpha beta complex capable of binding murine GM-CSF with high affinity, while AIC2A appears not to be a component of the murine GM-CSF receptor.

Amino Acid Sequence

The human pseudoautosomal GM-CSF receptor alpha subunit gene is autosomal in mouse.

The gene encoding the granulocyte macrophage colony stimulating factor receptor alpha subunit (CSF2RA) has previously been mapped to the pseudoautosomal region of the human sex chromosomes. In contrast, we report that the murine locus, Csf2ra, maps to an autosome in the laboratory mouse. By in situ hybridization and genetic mapping, Csf2ra maps at telomeric band D2 of mouse chromosome 19. This first instance of a pseudoautosomal locus in human being autosomal in mouse, indicates incomplete conservation between the human and mouse X chromosomes and suggests that the genetic content of the pseudoautosomal region may differ between species of eutherian mammals due to chromosomal rearrangements.

Animals

On sensation, perception and thought: a reply to Rönnberg.

A traditional partition of cognitive phenomena into sensation, perception and thought is reintroduced in response to recent arguments (Rönnberg, 1990) for conditions that must be met in order to distinguish between perception and cognition. The suggested division seems grossly compatible with Rönnberg's basic aim and receives support from several different lines of inquiry, including single cell recordings in the brain, neuropsychology, computational studies of vision and experimental psychology.

Cognition

[Surgical treatment of ileus in the radiation-injured intestine].

Between the years 1977 to 1990, ten patients were operated for ileus due to intestinal damage induced by radiotherapy. The patients had received an average radiation dose of 50.2 GY. Average lapse of time between radiotherapy and operation for ileus was 15.5 months. The operation procedures included were five lysis of adhesions, four by-pass operations, three small intestine resections, one large intestine resection, three transversostomies and one ileostomy. Three patients suffered postoperative complications; one got bronchopneumonia, one suffered prolonged paralytic ileus and one suffered anastomotic leakage, sepsis and fistula formation. Five of the patients have died from their malignant illness. For the five remaining patients the observation time varies from six months to 13 years.

Adult

Interleukin 4 alone or in combination with interleukin 1 stimulates 3T3 fibroblasts to produce colony-stimulating factors.

Colony-stimulating activity (CSA) can be produced by fibroblasts when stimulated by interleukin 1 (IL-1). We show that like IL-1, interleukin 4 (IL-4) can stimulate 3T3 fibroblasts to produce CSA. Biological and molecular analyses show that a significant portion of the CSA is colony-stimulating factor 1 (CSF-1) and granulocyte colony-stimulating factor (G-CSF). CSF-1 production in cells stimulated with a combination of both IL-1 and IL-4 was greater than that observed when cells were stimulated with either cytokine alone. However, the data show a synergistic induction of the expression of high levels of G-CSF mRNA and protein in cells incubated in the presence of both IL-1 and IL-4. The concentration of G-CSF in supernatants from cells stimulated with both IL-1 and IL-4 was at least tenfold higher than that measured in supernatants harvested from cells stimulated with either IL-1 or IL-4 alone. Previous investigations have shown that IL-4 had direct effects on hematopoietic progenitor cell growth. The studies described herein indicate that IL-4 is also involved in the regulation of hematopoiesis in an indirect manner, that is, by playing a role in the regulation of hematopoietic growth factor production.

Animals

Alternative forms of the human G-CSF receptor function in growth signal transduction.

Two forms of the human granulocyte colony-stimulating factor (G-CSF) receptor (HuG-CSFR), differing only at the carboxyl terminus, were recently identified by cDNA cloning. In this report we show that transfection and subsequent expression of either cDNA clone in the interleukin-3 (IL-3)-dependent murine cell line BAF/BO3 converts the cells to G-CSF-responsiveness. The transfected cells bound HuG-CSF in a manner indistinguishable from the native receptors. Expression of a mutant form of the HuG-CSFR, with a deletion in the cytoplasmic domain, in BAF/BO3 cells failed to convert the cells to HuG-CSF-responsiveness. In a similar manner, expression of these two HuG-CSFRs in the interleukin-6 (IL-6)-dependent murine hybridoma B9 resulted in the ability of these cells to grow in HuG-CSF [corrected]. These results strongly suggest that sequences in the first 96 amino acids of the cytoplasmic domain of the HuG-CSFR are required for signal transduction in response to ligand binding.

Animals

Expression cloning of a human granulocyte colony-stimulating factor receptor: a structural mosaic of hematopoietin receptor, immunoglobulin, and fibronectin domains.

We report the isolation from a placental library, of two cDNAs that can encode high affinity receptors for granulocyte colony-stimulating factor (G-CSF) when expressed in COS-7 cells. The cDNAs are predicted to encode integral membrane proteins of 759 and 812 amino acids in length. The predicted extracellular and membrane spanning sequences of the two clones are identical, as are the first 96 amino acids of their respective cytoplasmic regions. Different COOH termini of 34 or 87 residues are predicted for the two cDNAs, due apparently to alternate splicing. The receptor with the longer cytoplasmic domain is the closest human homologue of the murine G-CSF receptor recently described by Fukunaga et al. (Fukunaga, R., E. Ishizaka-Ikeda, Y. Seto, and S. Nagata. 1990. Cell. 61:341). A hybridization probe derived from the placental G-CSF receptor cDNA detects a approximately 3-kb transcript in RNAs isolated from placenta and a number of lymphoid and myeloid cells. The extracellular region of the G-CSF receptors is composed of four distinct types of structural domains, previously recognized in other cell surface proteins. In addition to the two domains of the HP receptor family-defining region (Patthy, L. 1990. Cell. 61:13) it incorporates one NH2-terminal Ig-like domain, and three additional repeats of fibronectin type III-like domains. The presence of both an NH2-terminal Ig-like domain and multiple membrane-proximal FN3-like domains suggests that the G-CSF receptor may be derived from an ancestral NCAM-like molecule and that the G-CSF receptor may function in some adhesion or recognition events at the cell surface in addition to the binding of G-CSF.

Amino Acid Sequence

Labetalol in the treatment of epinephrine overdose.

A 31-year-old man being treated for asthma accidently received 3 mg SQ epinephrine. He began retching and vomiting and developed agitation and profuse diaphoresis. He was treated with 5 mg IV labetalol. His symptoms improved significantly, and he required no further treatment. Although he felt a transient increase in his respiratory effort shortly after administration of the drug, he did not develop wheezing or require additional therapy for bronchospasm. The beta-blocking effect of labetalol is greater than the alpha antagonism. The patient exhibited evidence of mild alpha stimulation due to incomplete blockade. This is consistent with previous studies in that labetalol tends to less completely antagonize the alpha effects of a mixed alpha/beta agonist, resulting in a net clinical picture of mild alpha agonism.

Adult

Contact allergy to the fungicide benomyl?

Benomyl is a widely used fungicide. Contact allergy to benomyl has been reported in a few cases. We describe a group of 62 workers, exposed to benomyl. None had contact dermatitis from benomyl. It appears that benomyl at most is a weak sensitizer. We suggest that earlier-reported allergy may represent cross-reactions and/or that the development of contact allergy to benomyl requires previous exposure to other chemically related pesticides.

Adult

Brucellosis: an unusual cause of fever in Kentucky.

Human infection with brucellosis appears to be very uncommon in Kentucky. Only three cases have been reported to the Kentucky Department of Health, Frankfort, in the last 4 years. It is suspected, however, that brucellosis is severely underdiagnosed and under-reported in the United States. A patient recently diagnosed with acute systemic brucellosis reminds us that this illness may still be seen in the Commonwealth.

Acute Disease

Podophyllum derivatives (CPH 82) compared with placebo in the treatment of rheumatoid arthritis.

The efficacy, tolerance, and safety of CPH 82 (semisynthetic lignan glycosides) (Conpharm AB) for patients with rheumatoid arthritis (RA) were assessed in a 12-week double-blind placebo-controlled study. Thirteen patients out of 15 in the CPH 82 group and 10 out of 15 in the placebo group completed the study. No improvement was seen in placebo treated patients. Patients treated with CPH 82 showed a statistically significant improvement in most clinical and immunological variables. Some patients treated with CPH 82 reported gastrointestinal discomfort (diarrhoea and abdominal pain).

Arthritis, Rheumatoid