Canine segmental liver autotransplantation: an experimental training and research model.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
A Guerrero
Publications and source records attributed to A Guerrero.
Ligand specificity of pheromone-binding proteins of the processionary moth.
Photoaffinity labeling of proteins extracted from sensory hairs and antennal branches of the processionary moth Thaumetopoea pityocampa with a tritium-labeled diazoacetate analogue of the sex pheromone (Z)-13-hexadecen-11-ynyl acetate revealed a 15-kDa pheromone-binding protein in male moth sensory hairs (SH-15). A different 15-kDa protein in male antennal branches (B-15) was not photolabeled. All extracts except male sensory hairs showed a photolabeled 20-kDa protein; a photolabeled male 30-kDa protein in the branches (B-30) was also observed. The 20-kDa proteins in the sensory hairs (SH-20) and branches (B-20) showed differing affinities for the photoaffinity analogues; moreover, SH-15 exhibits higher affinity for the natural pheromone, (Z)-13-hexadecen-11-ynyl acetate, than for its alcohol metabolite and other analogues in competitive displacement experiments. The affinity shown by the pheromone-binding protein for the metabolic product suggests that the alcohol may be also transported by the binding protein. Interestingly, a shift in labeling from SH-15 to SH-20 was produced in the presence of an excess of the natural pheromone, its alcohol and other analogues. The binding showed little discrimination among structurally similar analogues of the pheromone, while saturated and aromatic molecules showed little affinity for the proteins of either sensory hairs or antennal branches.
Affinity Labels↗
The actin-binding protein, lymphocyte-specific protein 1, is expressed in human leukocytes and human myeloid and lymphoid cell lines.
Lymphocyte-specific protein 1 (LSP1) was originally reported as a lymphocyte-specific actin-binding protein using murine LSP1 probes. Subsequently, we identified LSP1 in polymorphonuclear neutrophils (PMN) and showed that it is the overexpressed 47-kDa protein in neutrophil actin dysfunction with 47- and 89-kDa abnormalities. This suggests that regulation of LSP1 expression in myeloid cells may be a functionally important event. LSP1 expression in human leukocytes, lymphoid cell lines, and myeloid cell lines (PLB985, HL60, and U937), uninduced (U) or induced to granulocytic (GI) or monocytic (MI) differentiation, was analyzed by Northern blot and immunoblot. By immunoblot, LSP1 is strongly expressed in PMN, less expressed in lymphocytes and monocytes (30-40% and 55-65% of the PMN level, respectively). By immunoblot and Northern blot, LSP1 is minimally expressed in U-PLB985 and U-HL60 (< 10% of the PMN level) and is weakly expressed in the B lymphoid cell line Daudi, but is not expressed in the pro-B, pre-B, T lymphoid cell lines tested, U-U937 or MI-U937. LSP1 mRNA and protein are up-regulated in GI-PLB985, GI-HL60, and MI-HL60. In HL60, LSP1 mRNA and protein increase in parallel to a maximum of eightfold the basal level on days 5 to 6 of granulocytic differentiation and four- to fivefold the basal level on day 3 of monocytic differentiation. The results show that LSP1 is expressed in all human leukocytes, and its expression is up-regulated during granulocytic and monocytic differentiation of myeloid cells in vitro. Since its overexpression is implicated in the functional pathogenesis of a novel human neutrophil motile dysfunction and microfilamentous cytoskeletal abnormality (NAD 47/89), finding LSP1 in all human leukocytes suggests that it plays a role in regulating microfilamentous cytoskeleton structure and motile function in all leukocytes. Since the protein is not lymphocyte specific and is an F-actin binding protein, and its isoforms are expressed in stromal and embryonic mesenchymal cells, we propose that the protein's name be changed to leufactin, as an abbreviated form of leukocyte F-actin binding protein.
Actins↗
AM5, a protein-associated polysaccharide, stimulates hematopoiesis and modulates the expression of endogenous hematopoietic growth factors in murine long-term bone marrow cultures.
We have investigated the mechanism behind the hematopoietic stimulation mediated by AM5, a protein-associated polysaccharide that stimulates in vivo the murine hematopoietic system. A dose-dependent increase in hematopoietic progenitors was observed in long-term bone marrow cultures (LTBMCs) treated in vitro with AM5. The stimulatory effect was more marked in colony-forming units-granulocyte-macrophage (CFU-GM) than in CFU-spleen (CFU-S) progenitors and also more significant in the supernatant than in the adherent layer. This stimulatory effect was reversible, and continuous stimulation with high doses of AM5 was conductive to a progressive exhaustion of the culture. The analysis of the CFU-GM stimulating activity present in the supernatant of AM5-treated cultures revealed a dose-dependent induction of granulocyte-macrophage colony-stimulating activity (GM-CSA), in contrast with control cultures in which no CSA was detected. Northern blots of LTBMC-adherent layers obtained after in vitro treatment with AM5 revealed a significant mRNA expression for interleukin 1 alpha (IL-1 alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage CSF (M-CSF) and granulocyte CSF (G-CSF), in contrast with adherent layers from untreated cultures which only expressed, in detectable levels, M-CSF and stem cell factor (SCF). The SCF expression was down-modulated in AM5-treated cultures. Our results strongly suggest that the hematopoietic stimulation induced by AM5 is mediated by the modulated expression of endogenous hematopoietic growth factors.
Animals↗
Intestinal and extraintestinal cryptosporidiosis in AIDS patients.
In a prospective study in AIDS patients with chronic diarrhea, the overall prevalence of intestinal cryptosporidiosis was 15.6% (43/275). The prevalence was higher in homosexual patients (33.3%) than in intravenous drug abusers (10.6%) (p < 0.001). Extraintestinal infection was present in 30% (13/43) of the patients with known intestinal cryptosporidiosis. Eight of the 13 (61.5%) patients with extraintestinal cryptosporidiosis had Cryptosporidium in the bile and 7 of 13 (16.28%) had it in the sputum. Of the seven patients with Cryptosporidium in the sputum, four had respiratory symptoms and an abnormal chest radiograph, although another pulmonary pathogen was isolated simultaneously. Two other patients from whom Cryptosporidium was the sole respiratory pathogen isolated had no respiratory symptoms and normal chest radiographs. The seventh patient had pulmonary symptoms, interstitial infiltrate on chest radiograph and excessive activity on a pulmonary Gallium scan; Cryptosporidium was the only organism detected in induced sputum and bronchoalveolar lavage specimens. The mean CD4+ lymphocyte count in patients with extraintestinal cryptosporidiosis was 55 cells/mm3.
AIDS-Related Opportunistic Infections↗
Quinacrine: sclerosing agent of the utero-tubal junction in women, with anticarcinogenic actions in transplanted tumors in mice.
Quinacrine, an acridine derivative that was in widespread use as an anti-malarial, has been shown to have both sclerosant and anticarcinogenic actions. The sclerosant action of quinacrine has been used to produce occlusion of Fallopian tube in both experimental animals and women, and several clinical studies are reviewed. Both actions of quinacrine are potentiated by steroidal and non-steroidal antiprostaglandins as well as by ionic copper. Combinations of quinacrine with antiprostaglandin drugs, and also with copper, improved the efficacy of quinacrine when used for female sterilization and reduced side effects. A review of the experimental and epidemiological evidence suggests that quinacrine has no carcinogenic effects.
Animals↗
Effects and mode of action of 1,4-naphthoquinones isolated from Calceolaria sessilis on tumoral cells and Trypanosoma parasites.
The naphthoquinones 2-hydroxy-3-(1,1-dimethylallyl)-1,4-naphthoquinone (CS-1), (-)-2,3,3-trimethyl-2-3-dihydronaphtho[2,3-b]furan-4,9-quinone (CS-3), and 2-acetoxy-3-(1,1-dimethylallyl)-1,4-naphthoquinone (CS-5) isolated from Calceolaria sessilis were tested against Trypanosoma cruzi epimastigotes, the TA3 tumor cell line and the methotrexate-resistant subline TA3-MTX-R. Naphthoquinone CS-3 was the most active; the 50% culture growth inhibition (I50) on T. cruzi (Tulahuén and LQ strain and DM28c clone) was at concentrations ranging from 2.1 to 5.2 mumolar. Also CS-3 inhibited TA3 and TA3-MTX-R culture growth with an I50 of 2.1 and 3.8 mumolar, respectively. Naphthoquinone CS-3 inhibited the respiration of the tumor cells by interfering with the electron transport at some point between NADH and ubiquinone. The respiration of T. cruzi was not inhibited by naphthoquinone CS-3. Naphthoquinone CS-3 produced a temporary increase of oxygen consumption in T. cruzi and tumor cells, suggesting the generation and participation of free radicals.
Animals↗
Right-sided endocarditis caused by Staphylococcus aureus in drug abusers.
A prospective, open, and randomized study of right-sided endocarditis caused by Staphylococcus aureus in drug abuse patients is reported. The following parenteral treatments were compared. Group A patients were treated with 2 g of cloxacillin every 4 h and 1.5 mg of gentamicin per kg of body weight every 8 h for 2 weeks. Group B patients were treated with teicoplanin at 10 mg/kg/12 h on the 1st to 3rd days, 6 mg/kg/12 h on the 4th to 7th days, and 7 mg/kg/24 h on the 8th days. Drug abusers with bacteremia caused by S. aureus and suggestive signs of endocarditis were included. Clinical failures were observed in one patient in group A and in four of six patients in group B. Three patients in group B developed breakthrough bacteremia with teicoplanin-susceptible strains on days +6, +14, and +19. Serum teicoplanin levels and serum bactericidal titers showed a decrease in the 2nd week, when dosages received were 7 mg/kg/day. In conclusion, in treatment of right-sided endocarditis caused by S. aureus in drug abusers with teicoplanin, the use of dosages of 7 mg/kg/day is not recommended even if patients have received dosages of 12 mg/kg/day during the 1st week.
Cloxacillin↗
Inhibition of tumoral cell respiration and growth by nordihydroguaiaretic acid.
The effects of nordihydroguaiaretic acid (NDGA), best known as an inhibitor of lipoxygenase activities, on the culture growth, oxygen consumption, ATP level, viability, and redox state of some electron carriers of intact TA3 and 786A ascites tumor cells have been studied. NDGA inhibited the respiration rate of these two tumor cell lines by preventing electron flow through the respiratory chain. Consequently, ATP levels, cell viability and culture growth rates were decreased. NDGA did not noticeably inhibit electron flow through both cytochrome oxidase and ubiquinone-cytochrome b-c1 complex. Also, the presence of NDGA changed to redox state of NAD(P)+ to a more reduced level, and the redox states of ubiquinone, cytochrome b and cytochromes c + c1 changed to a more oxidized level. These observations suggest that the electron transport in the tumor mitochondria was inhibited by NDGA at the NADH-dehydrogenase-ubiquinone level (energy-conserving site 1). As a consequence, mitochondrial ATP synthesis would be interrupted. This event could be related to the cytotoxic effect of NDGA.
Adenosine Triphosphate↗
[Efficacy of intracavitary amphotericin B in the treatment of aspergilloma associated with the acquired immunodeficiency syndrome].
Explore the source record for details and available documents.
AIDS-Related Opportunistic Infections↗
Evidence for a Ca(2+)-gated ryanodine-sensitive Ca2+ release channel in visceral smooth muscle.
Although a role for the ryanodine receptor (RyR) in Ca2+ signaling in smooth muscle has been inferred, direct information on the biochemical and functional properties of the receptor has been largely lacking. Studies were thus carried out to purify and characterize the RyR in stomach smooth muscle cells from the toad Bufo marinus. Intracellular Ca2+ measurements with the Ca(2+)-sensitive fluorescent indicator fura-2 under voltage clamp indicated the presence of a caffeine- and ryanodine-sensitive internal store for Ca2+ in these cells. The (CHAPS)-solubilized, [3H]ryanodine-labeled RyR of toad smooth muscle was partially purified from microsomal membranes by rate density centrifugation as a 30-S protein complex. SDS/PAGE indicated the comigration of a high molecular weight polypeptide with the peak attributed to 30-S RyR, which had a mobility similar to the cardiac RyR and on immunoblots cross-reacted with a monoclonal antibody to the canine cardiac RyR. Following planar lipid bilayer reconstitution of 30-S stomach muscle RyR fractions, single-channel currents (830 pS with 250 mM K+ as the permeant ion) were observed that were activated by Ca2+ and modified by ryanodine. In vesicle-45Ca2+ efflux measurements, the toad channel was activated to a greater extent at 100-1000 microM than 1-10 microM Ca2+. These results suggest that toad stomach muscle contains a ryanodine-sensitive Ca2+ release channel with properties similar but not identical to those of the mammalian skeletal and cardiac Ca(2+)-release channels.
Animals↗
The 47-kD protein increased in neutrophil actin dysfunction with 47- and 89-kD protein abnormalities is lymphocyte-specific protein.
A male child born of related parents suffered recurrent infections because of neutrophil actin dysfunction with increased amounts of a 47-kD protein and decreased amounts of an 89-kD protein (NAD 47/89). The patient and family members were studied to define the nature of the abnormal proteins and to examine their role in the functional defects of neutrophil actin dysfunction (NAD) 47/89 polymorphonuclear neutrophils (PMNs). NAD 47/89 PMNs are defective in motility, microfilamentous cytoskeletal structure, and formyl peptide-induced actin polymerization and express increased amounts of a 47-kD protein and decreased amounts of an 89-kD proteins intermediate abnormality in amount of 47-kD and 89-kD proteins in PMNs from parents and a female sibling suggest the disease is an autosomal recessive disorder. Immunoblots with monoclonal antibody (MoAb1) and polyclonal antibody raised to 47-kD protein showed the 89-kD protein is antigenically distinct from the 47-kD protein and the 89-kD protein is not gelsolin. 125I-actin binding to one-dimensional (1 D) and 2 D gels of PMN proteins from NAD 47/89 proband, family members, and controls showed the 47-kD protein binds actin, is acidic (pl = 4.5 to 4.7), is recognized by the MoAb1, exists on 2-D gels as three distinct actin binding species (MWapp 52 kD, 47-kD, and 44-kD), and is present in control PMNs in lesser amount than in PMNs of NAD 47/89 proband or parents. Immunoaffinity purification of the 47 kD actin binding protein on MoAb1 matrix yielded a multimolecular complex with proteins of MWapp 180 kD, 71 kD, 47 kD and actin. Cloning, sequencing, and expression of a 1.58-kb cDNA selected for MoAb1 reactivity from a HL60 expression library and microsequence of native PMNs, 47-kD actin binding protein showed the overexpressed 47-kD protein is lymphocyte-specific protein 1 (LSP1), which is a known actin binding protein. The results show LSP1 is expressed in PMNs and suggest overexpression of LSP1 is related to the motility and cytoskeletal abnormalities in NAD 47/89 PMNs.
Actins↗
Quinacrine and copper, compounds with anticonceptive and antineoplastic activity.
Changes in the evolution of a malignant transplantable tumor in mice to whom quinacrine, copper and zinc were supplied in drinking water are reported. Male AJ mice were inoculated in the right thigh with 1,000,000 TA3 or TA3 MTXR tumoral cells. Three experiments were designed with different types of tumors and different schedules of quinacrine and cations administered in drinking water. The animals that received quinacrine or quinacrine plus copper in drinking water had significantly smaller tumors, and some groups had a high rate of complete tumor regression (up to 60%). Quinacrine and copper have synergistic antineoplastic activity. Zinc salts do not improve the antitumoral effect of quinacrine. The relevant fact of this experiment lies in the fact that a large number of women using IUDs with copper could occasionally be treated with quinacrine.
Animals↗
Synthesis of trifluoromethyl ketones as inhibitors of antennal esterases of insects.
A variety of long chain aliphatic and aromatic trifluoromethyl ketones I-XIV has been conveniently prepared, many of them for the first time, from the corresponding Grignard or organolithium derivatives. Two of them, (Z)-1,1,1-trifluoro-15-octadecen-13-yn-2-one (XV) and (Z)-1,1,1-trifluoro-16-nonadecen-14-yn-2-one (XVI), structurally-closed analogues of (Z)-13-hexadecen-11-ynyl acetate, the sex pheromone of the processionary moth Thaumetopoea pityocampa, have been stereospecifically synthesized in excellent yield by a convenient new method. The procedure involves lithiation of the corresponding iododerivative XXIX and XXX with one equivalent of tert-BuLi to obviate addition of the reagent to the enyne system. Some of the compounds have already been tested and found to be good inhibitors of antennal esterases in the Egyptian armyworm Spodoptera littoralis and the pheromone action in the processionary moth Thaumetopoea pityocampa. beta-Thiotrifluoromethyl ketones XVII-XX, which are expected to enhance the inhibition activity of the parent ketones due to their higher hydration constants, have also been prepared in good yields.
Animals↗
Caffeine activates a Ca(2+)-permeable, nonselective cation channel in smooth muscle cells.
The effects of caffeine on cytoplasmic [Ca2+] ([Ca2+]i) and plasma membrane currents were studied in single gastric smooth muscle cells dissociated from the toad, Bufo marinus. Experiments were carried out using Fura-2 for measuring [Ca2+]i and tight-seal voltage-clamp techniques for recording membrane currents. When the membrane potential was held at -80 mV, in 15% of the cells studied caffeine increased [Ca2+]i without having any effect on membrane currents. In these cells ryanodine completely abolished any caffeine induced increase in [Ca2+]i. In the other cells caffeine caused both an increase in [Ca2+]i and activation of an 80-pS nonselective cation channel. In this group of cells ryanodine only partially blocked the increase in [Ca2+]i induced by caffeine; moreover, the change in [Ca2+]i that did occur was tightly coupled to the time course and magnitude of the cation current through these channels. In the presence of ryanodine, blockade of the 80-pS channel by GdCl3 or decreasing the driving force for Ca2+ influx through the plasma membrane by holding the membrane potential at +60 mV almost completely blocked the increase in [Ca2+]i induced by caffeine. Thus, the channel activated by caffeine appears to be permeable to Ca2+. Caffeine activated the cation channel even when [Ca2+]i was clamped to below 10 nM when the patch pipette contained 10 mM BAPTA suggesting that caffeine directly activates the channel and that it is not being activated by the increase in Ca2+ that occurs when caffeine is applied to the cell. Corroborating this suggestion were additional results showing that when the membrane was depolarized to activate voltage-gated Ca2+ channels or when Ca2+ was released from carbachol-sensitive internal Ca2+ stores, the 80-pS channel was not activated. Moreover, caffeine was able to activate the channel in the presence of ryanodine at both positive and negative potentials, both conditions preventing release of Ca2+ from stores and the former preventing its influx. In summary, in gastric smooth muscle cells caffeine transiently releases Ca2+ from a ryanodine-sensitive internal store and also increases Ca2+ influx through the plasma membrane by activating an 80-pS cation channel by a mechanism which does not seem to involve an elevation of [Ca2+]i.
Animals↗
Simultaneous measurement of Ca2+ release and influx into smooth muscle cells in response to caffeine. A novel approach for calculating the fraction of current carried by calcium.
Activation of ryanodine receptors on the sarcoplasmic reticulum of single smooth muscle cells from the stomach muscularis of Bufo marinus by caffeine is accompanied by a rise in cytoplasmic [Ca2+] ([Ca2+]i), and the opening of nonselective cationic plasma membrane channels. To understand how each of these pathways contributes to the rise in [Ca2+]i, one needs to separately monitor Ca2+ entry through them. Such information was obtained from simultaneous measurements of ionic currents and [Ca2+]i by the development of a novel and general method to assess the fraction of current induced by an agonist that is carried by Ca2+. Application of this method to the currents induced in these smooth muscle cells by caffeine revealed that approximately 20% of the current passing through the membrane channels activated following caffeine application is carried by Ca2+. Based on this information we found that while Ca2+ entry through these channels rises slowly, release of Ca2+ from stores, while starting at the same time, is much faster and briefer. Detailed quantitative analysis of the Ca2+ release from stores suggests that it most likely decays due to depletion of Ca2+ in those stores. When caffeine was applied twice to a cell with only a brief (30 s) interval in between, the amount of Ca2+ released from stores was markedly diminished following the second caffeine application whereas the current carried in part by Ca2+ entry across the plasma membrane was not significantly affected. These and other studies described in the preceding paper indicate that activation of the nonselective cation plasma membrane channels in response to caffeine was not caused as a consequence of emptying of internal Ca2+ stores. Rather, it is proposed that caffeine activates these membrane channels either by direct interaction or alternatively by a linkage between ryanodine receptors on the sarcoplasmic reticulum and the nonselective cation channels on the surface membrane.
Animals↗
Trifluoromethyl ketones as inhibitors of the processionary moth sex pheromone.
Aliphatic and aromatic trifluoromethyl ketones have been evaluated in the laboratory and in the field as inhibitors of the pheromone response of the processionary moth Thaumetopoea pityocampa males. Among them, two compounds, (Z)-1,1,1-trifluoro-15-octadecen-13-yn-2-one and (Z)-1,1,1-trifluoro-16-nonadecen-14-yn-2-one, are closely related analogs of the natural pheromone (Z)-13-hexadecen-11-ynyl acetate. In the laboratory experiments, carried out by pre-exposure of males to vapors of the chemicals, alpha-naphthyl trifluoromethyl ketone, beta-naphthyl trifluoromethyl ketone, 1,1,1-trifluorotetradecan-2-one and (Z)-16-nonadecen-14-yn-2-one displayed notable blockage of the pheromone detection on EAG. The activity of 1,1,1-trifluorotetradecan-2-one is postulated to be due to the inhibition of the pheromone-degrading esterase. In general, the compounds have shown low specificity for the substrate and exhibited only a modest or null EAG intrinsic activity. In the field, benzyl trifluoromethyl ketone, trifluoroacetophenone, (Z)-1,1,1-trifluoro-15-octadecen-13-yn-2-one, (Z)-1,1,1-trifluoro-16-nonadecen-14-yn-2-one and beta-naphthyl trifluoroacetate showed a remarkable disruptant effect when mixed with the pheromone in 1:0.1, 1:1 and 1:10 ratio. (Z)-16-Nonadecen-14-yn-2-one has been found to be a modest agonist of the natural pheromone, exhibiting an attractant activity threefold lower than the parent molecule.
Animals↗