| 2668886 |
Nucleotide sequence of the chitinase B gene of Serratia marcescens QMB1466. |
10.1093/nar/17.13.5395 |
Nucleic Acids Res. |
Nucleotide sequence of the chitinase B gene of Serratia marcescens QMB1466.
Abstract
|
| 2689136 |
Octreotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in conditions associated with excessive peptide secretion |
10.2165/00003495-198938050-00002. |
Drugs |
Octreotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in conditions associated with excessive peptide secretion
Abstract
- Octreotide is an analogue of somatostatin. Like endogenous somatostatin, it exerts a potent inhibitory effect on the release of anterior pituitary growth hormone and thyroid-stimulating hormone, and peptides of the gastroenteropancreatic endocrine system, while overcoming some of the shortcomings of exogenously administered somatostatin, namely a short duration of action, a need for intravenous administration and postinfusion rebound hypersecretion of hormone. Clinical studies have shown that octreotide is effective in the treatment of acromegaly and thyrotrophinomas. In comparative trials octreotide was significantly superior to bromocriptine in patients with acromegaly. Octreotide also appears to provide a significant advantage over existing therapies in the management of the carcinoid syndrome and offers considerable therapeutic potential in reversing carcinoid crises which may be life-threatening. Trials in patients with tumours producing vasoactive intestinal peptide demonstrated that octreotide may be an effective first-line choice for this condition, which has usually metastasised and become refractory to traditional symptomatic therapy. In limited studies in patients with high-output secretory diarrhoea, including cryptosporidium-related diarrhoea associated with AIDS and in patients with small bowel fistulas, octreotide has been shown to be effective in reducing stool/fistula output. However, well-designed clinical trials are still required to confirm its long term usefulness in these disorders. Similarly, although the use of octreotide in other conditions such as neonatal hypoglycaemia caused by nesidioblastosis, reactive pancreatitis, insulin-dependent diabetes mellitus, postprandial hypotension and the dumping syndrome has provided encouraging preliminary results, more studies are needed to clarify the place of octreotide in their treatment. Overall, octreotide appears to be well tolerated with the most frequently reported reactions being pain at the site of injection and gastrointestinal symptoms such as abdominal cramps, nausea, bloating, flatulence, diarrhoea and steatorrhoea. These adverse effects usually abate with time. Additionally, octreotide, like endogenous somatostatin, may also result in cholelithiasis, presumably by altering fat absorption and possibly by decreasing motility of the gallbladder. Thus, octreotide represents a new departure from traditional therapies in the treatment of various pathophysiological states associated with excessive peptide production and secretion. It offers a significant advantage over existing therapies in the medical management of patients with acromegaly, thyrotrophinomas, the carcinoid syndrome, tumours producing vasoactive intestinal peptide and severe secretory diarrhoea in whom conventional management options have either become exhausted or have provided suboptimal symptomatic relief.
|
| 2708366 |
7-Azidoactinomycin D: a novel probe for examining actinomycin D-DNA interactions |
None |
J Biol Chem |
7-Azidoactinomycin D: a novel probe for examining actinomycin D-DNA interactions
Abstract
- The technique of photoaffinity labeling is applied to the actinomycin D system to provide a novel probe for the examination of the interactions of actinomycin D with nucleic acids. The capacity for covalent attachment of actinomycin D will aid greatly in the study of target-site specificities and the correlations of biological effects with biophysical DNA interactions. Through chemical modification of the parent actinomycin D molecule with a photoreactive azido substituent, a functional analog of the parent actinomycin D is generated having equilibrium binding properties identical to those of the parent molecule yet with the capacity to form a covalent attachment to DNA upon photolysis. The results presented here describe the noncovalent interactions of this photoreactive probe to DNA (absence of light) and compares the binding properties observed to those of the parent actinomycin D and 7-aminoactinomycin D analog. These studies demonstrate that the DNA binding properties (i.e. binding affinity, binding site size, and sequence specificity) retained by the 7-azidoactinomycin D, thus providing a suitable probe for examining actinomycin D-DNA interactions.
|
| 2719946 |
Substitution of valine for glycine-558 in the congenital dysthrombin thrombin Quick II alters primary substrate specificity |
10.1021/bi00431a017. |
Biochemistry |
Substitution of valine for glycine-558 in the congenital dysthrombin thrombin Quick II alters primary substrate specificity
Abstract
- Thrombin Quick II is one of two dysfunctional forms of thrombin derived from the previously described congenital dysprothrombin prothrombin Quick. Thrombin Quick II does not clot fibrinogen, hydrolyze p-nitroanilide substrates of thrombin, or bind N2-[5-(dimethylamino)naphthalene-1-sulfonyl]arginine N,N-(3-ethyl-1,5-pentanediyl)amide, a high-affinity competitive inhibitor of thrombin. To determine the structural alteration in thrombin Quick II, the reduced, carboxymethylated protein was hydrolyzed by a lysyl endopeptidase. A peptide not present in a parallel thrombin hydrolysate was identified by reverse-phase chromatography. The peptide was purified by rechromatography and subjected to Edman degradation which showed that Gly-558 of human prothrombin had been replaced by Val. This corresponds to a point mutation of the Gly codon GGC to GUC. This Gly residue, which is highly conserved in the chymotrypsin family of serine proteases, forms part of the substrate binding pocket for bulky aromatic and basic side chains in chymotrypsin and trypsin, respectively. However, in porcine elastase 1, the corresponding residue is threonine. Consistent with the identified structural alteration, thrombin Quick II incorporates [3H]diisopropyl fluorophosphate stoichiometrically and hydrolyzes the elastase substrate succinyl-Ala-Ala-Pro-Leu-p-nitroanilide with a relative kcat/KM of 0.14 when compared to thrombin. This results from a 3-fold increase in KM and a 2.5-fold decrease in kcat for thrombin Quick II when compared to thrombin acting on the same substrate. These results and those of other investigators studying mutant trypsins support the conclusion that the catalytic activity of serine proteases is very sensitive to structural alterations in the primary substrate binding pocket.
|
| 2724139 |
Prophylaxis of cyanobacterial and mushroom cyclic peptide toxins |
None |
J Pharmacol Exp Ther |
Prophylaxis of cyanobacterial and mushroom cyclic peptide toxins
Abstract
- The pathogenicity of virulent cyclic peptide toxins of the cyanobacterium, Microcystis aeruginosa, and the mushroom, Amanita phalloides, was prevented in mice by pretreatment with a variety of chemically unrelated agents including hydrocortisone, shellac, certain diazo and triazine dyes and cyclosporine. A. Despite the diverse nature of the protective agents, a feature commonly associated with protection was the ability to impair hepatic uptake of 51Cr-labeled sheep erythrocytes, a function of hepatic macrophages (Kupffer cells). In addition, several of the protective agents are known to affect other aspects of reticuloendothelial cell function. Therefore it seems likely that the hepatic macrophage is involved in the observed protection, although by what mechanism(s) is unknown. The most remarkable prophylaxis was seen with a single injection of Trypan red, which provided nonimmunologic protection against a lethal dose of a cyanobacterial toxin, cyanoginosin-LR, for periods up to 3 months.
|
| 2724305 |
New cyclic peptides with cytotoxic activity from the ascidian Lissoclinum patella |
10.1021/jm00126a034. |
J Med Chem |
New cyclic peptides with cytotoxic activity from the ascidian Lissoclinum patella
Abstract
- The isolation and structures of a new patellamide (patellamide D) and two new lissoclinamides (lissoclinamides 4 and 5) from the aplousobranch ascidian Lissoclinum patella are described. Structures were determined largely by using two-dimensional NMR techniques and mass spectrometry. These peptides and other members of the patellamide and lissoclinamide families that have been reported previously are found within the obligate algal symbiont of the genus Prochloron. The cytotoxicities of the compounds toward fibroblast and tumor cell lines are reported. One of these compounds, lissoclinamide 4, is markedly more toxic than other members of the family. Structure-activity relationships are discussed.
|
| 2762040 |
Action of cyclosporin A on the tapeworms Hymenolepis microstoma, H. diminuta and Mesocestoides corti in vivo |
10.1017/s0031182000062211. |
Parasitology |
Action of cyclosporin A on the tapeworms Hymenolepis microstoma, H. diminuta and Mesocestoides corti in vivo
Abstract
- The in vivo activity of two cyclosporins, cyclosporin A (CsA) and a non-immunosuppressive derivative of dihydrocylosporin A (DHCsA-d) against three tapeworms, Hymenolepis microstoma, H. diminuta and Mesocestoides corti, has been assessed. CsA reversibly reduced the dry weight of H. microstoma in the mouse, briefly delayed oviposition and had a statistically significant effect on worm numbers recovered. Oral and subcutaneous treatments of both CsA and DHCsA-d were effective in reducing worm weight; juvenile worms were most susceptible but worms of all ages responded to drug by a dramatic reduction in weight from which they recovered. Multiple courses of CsA were no more active than single courses of treatment but dose response suggested that a threshold level of drug was necessary to evoke activity. By contrast, H. diminuta in the rat was completely unaffected by CsA but no explanation for the differences in drug response by these two closely related helminths is forthcoming. Mesocestoides corti responded reversibly to CsA in the mouse by a reduction in asexual proliferation of both liver and peritoneal cavity tetrathyridia. The data presented argue in favour of a range of anti-parasitic activities by cyclosporins but the details of the various putative modes of action remain to be defined.
|
| 2777789 |
Characterization of the promoter region and 3' end of the human insulin receptor gene. |
10.1016/s0021-9258(18)71612-8 |
J. Biol. Chem. |
Characterization of the promoter region and 3' end of the human insulin receptor gene.
Abstract
- The insulin receptor is an essential protein present on the surface of virtually all cells. Little is known about the control of the level of this protein on cellular surfaces, but it has been found that the level of insulin receptor protein correlates roughly with the level of insulin receptor (IR) gene transcripts within cells. Although the protein-encoding region is only about 4000 base pairs (bps), there are multiple species of IR mRNA ranging in size from 5400 to 9400 bps. We have found that the variation in size of these transcripts is due to multiple 3' ends, presumably reflecting alternative polyadenylation, so that the final IR exon ranges in size from 1400 to 5400 bps. The IR gene promoter is like other housekeeping promoters in that it has no TATA or CAAT boxes, is extremely GC-rich, and has multiple transcriptional initiation sites primarily within a 300-bp GC-rich region. Reporter gene analysis using IR promoter-chloramphenicol acetyltransferase (HIRcat) fusion plasmids established regions responsible for promoter activity and verified the localization of the major IR gene transcriptional initiation sites. However, transfection with HIRcat plasmids containing regions from -153 to -1818 resulted in increased utilization of the most 5' IR gene mRNA initiation sites in transfected relative to untransfected cells. Reporter gene analysis also established that a region of the IR promoter and first exon containing all of the transcriptional initiation sites is more active in HepG2 than CV1 cells. Because the steady-state level of expression of the IR gene is much higher in HepG2 than CV1 cells, the
Results of the reporter gene analysis may reflect tissue-specific differences in IR gene transcription. Such tissue-specific transcriptional regulation would be a novel finding in a housekeeping promoter.
|
| 2784905 |
Immunosuppressive activities of cyclosporine metabolites M17 and M21 within a bioassay based on inhibition of interleukin-2 production |
None |
Transplant Proc |
Immunosuppressive activities of cyclosporine metabolites M17 and M21 within a bioassay based on inhibition of interleukin-2 production
Abstract
|
| 2787511 |
An alternative cytoplasmic domain of the integrin beta 3 subunit. |
10.1073/pnas.86.14.5415 |
Proc. Natl. Acad. Sci. U.S.A. |
An alternative cytoplasmic domain of the integrin beta 3 subunit.
Abstract
- A cDNA encoding a new form of the shared beta subunit (beta 3) of the platelet integrin gpIIb/IIIa and the vitronectin receptor was isolated from a placental cDNA library by screening with a beta 3 (gpIIIa) DNA probe. This beta 3 variant differs from the previously reported beta 3 in that the cytoplasmic domain is 8 amino acids shorter and has an alternative, 13-amino acid COOH-terminal peptide. The 3' untranslated region of the cDNA also differs from the previously reported sequence, while the region coding for the transmembrane domain and extracellular domain is identical to it. Reverse transcription combined with polymerase chain reaction was used to show that human placental tissue and two human cell lines contain the variant mRNA. The sequences of the cDNAs for the previously known beta 3 and the variant beta 3 described here suggest that the difference between the cytoplasmic domains of these subunits arises as a result of an alternative mRNA splicing. These cytoplasmic domains may provide alternative means for the beta 3 integrins to interact with cytoskeletal components.
|
| 2790960 |
Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation. |
10.1016/0092-8674(89)90867-2 |
Cell |
Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation.
Abstract
- We have located the distal boundary of the tyrosine kinase domain of the EGF receptor and have identified a distinct sequence in the C' terminus required for EGF-dependent receptor internalization, leading to receptor down-regulation and degradation. Within this receptor domain, an 18 amino acid highly negatively charged region of predicted helical structure is required both for endocytosis via a high-affinity, saturable pathway and for ligand-stimulated increases in cytosolic calcium. In contrast to kinase-inactive, internalization-competent receptors, kinase-active, internalization-defective receptors effectively signaled gene transcription, morphological transformation, and growth. These observations support the hypothesis that mitogenic responses to EGF are mediated by activation of the intrinsic protein tyrosine kinase activity of the membrane-bound receptor, with ligand-induced internalization serving to terminate the signal.
|
| 2806055 |
Characterization of the promoter region of the human insulin receptor gene. |
10.1016/0168-8227(89)90085-5 |
Diabetes Res. Clin. Pract. |
Characterization of the promoter region of the human insulin receptor gene.
Abstract
|
| 2813364 |
On the ion selectivity in Ca-binding proteins: the cyclo(-L-Pro-Gly-)3 peptide as a model |
10.1073/pnas.86.20.7880. |
Proc Natl Acad Sci U S A |
On the ion selectivity in Ca-binding proteins: the cyclo(-L-Pro-Gly-)3 peptide as a model
Abstract
- Calcium plays a crucial role in many cellular processes. Its functions are directly dependent on the high specificity for Ca2+ exhibited by the proteins and ion carriers that bind divalent ions. To elucidate the basis for this specificity we have calculated the relative energies of solvation of calcium and magnesium ions in complexes with cyclo(-L-Pro-Gly-)3, a small synthetic peptide that binds Ca2+ with an affinity comparable to those of the naturally occurring proteins. The results show that the ion selectivity of the peptide resides in the difference in the solvation energies of the competing ions in water. Although the peptide is able to complex Mg2+ better than Ca2+ in the stoichiometries in which cyclo(-L-Pro-Gly-)3 binds divalent ions, it is not always able to provide as much stabilization for Mg2+ as water does. These results also explain why cyclo(-L-Pro-Gly-)3 binds Ca2+ and Mg2+ with different stoichiometries and indicate the source for expected differences in the structures of complexes of the two ions.
|
| 2822163 |
Theoretical conformational analysis of a mu-selective cyclic opioid peptide analog |
10.1002/bip.360260817. |
Biopolymers |
Theoretical conformational analysis of a mu-selective cyclic opioid peptide analog
Abstract
|
| 2822794 |
Effects of cyclic adenosine-3',5'-monophosphate and cyclo(Lys-Pro).HCl neuronotrophic factors in tissue culture |
None |
J Hirnforsch |
Effects of cyclic adenosine-3',5'-monophosphate and cyclo(Lys-Pro).HCl neuronotrophic factors in tissue culture
Abstract
- Explants and cell cultures of embryonic chick ganglia trigeminalia, telencephalon and retina or hippocampus from fetal rats were incubated in maximow chambers in the presence of cyclic AMP and the dipeptide cyclo(Lys-Pro).HCL under various conditions. Maintenance of nerve cells and growth of nerve fibers were observed by morphometrical methods. 1. Cyclo(Lys-Pro).HCL promoted the maintenance of neuroblasts and the growth of nerve fibres in explants of the ganglion trigeminal and retinal cell cultures. The effect depended on the presence of serum in the medium by use of poly-I-lysine substrate. 2. Extern applicated cyclic AMP and the dipeptide SP3-4 = cyclo(Lys-Pro).HCL facilitated neurite growth in PNS cultures. In the presence of the drugs the length of nerve fibers increased for a short term. On CNS explants substance P (SP1-11) and SP3-4 were without effect. Cyclic AMP stimulated the growth of nerve fibers in CNS explants and cell cultures in number and length. 3. Discussed is the effect of SP1-11 and cyclo(Lys-Pro).HCL for competence of nerve fibre regeneration in vitro in relation to increasing cAMP levels, which may then act as an initial second messenger. It is suggested that explants and cell cultures of nervous tissues will be useful as a tool for the further characterisation of factors with neuronotrophic activities.
|
