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Biomedical subjects

R Young

Publications and source records attributed to R Young.

At least 145 records · Page 8Linked to original sources
PubMed1994

Differential expression of the cytotoxic and hemolytic activities of the ApxIIA toxin from Actinobacillus pleuropneumoniae.

The ApxIIA protein secreted from Actinobacillus pleuropneumoniae is both hemolytic and cytotoxic. However, when the cloned apxII operon is expressed in Escherichia coli, two forms of the ApxIIA protein can be recovered. Toxin which remains intracellular has hemolytic and cytotoxic activities, while toxin that is secreted is cytotoxic with little or no hemolytic activity. This indicates that the cytotoxicity of ApxIIA is independent of its hemolytic activity.

Actinobacillus pleuropneumoniae↗
PubMed1993

Peripheral blood progenitor cell transplantation in lymphoma and leukemia using a single apheresis.

Myeloablative treatment and peripheral blood progenitor cell (PBPC) transplantation are increasingly used for lymphomas and leukemias. We have sought to optimize conditions for priming, collection, and engraftment of the leukapheresis product. Fifty-four consecutive adult patients were eligible, 31 with high-grade non-Hodgkin's lymphoma of poor prognosis, 12 with Hodgkin's disease in chemosensitive relapse, and 11 with poor prognosis acute lymphoblastic leukemia. Filgrastim was administered after routine chemotherapy with VAPEC-B or HiCCOM to mobilize PBPC. A rapidly increasing white blood cell count was used to predict the time of peak PBPC release and plan leukapheresis. Forty-five patients underwent leukapheresis. A median of 14 L of blood was processed at a single apheresis. A median of 2.4 x 10(8)/kg mononuclear cells (MNCs), 1.04 x 10(6)/kg granulocyte-macrophage colony-forming cells (GM-CFCs), and 10.6 x 10(6)/kg CD34+ cells were obtained. Slightly fewer MNCs were obtained from the heavily pretreated Hodgkin's disease group. There were no other significant differences in the size or composition of the leukapheresis harvest in the three patient groups. Forty patients underwent high-dose therapy and PBPC transplantation. Filgrastim was administered by daily subcutaneous injection until the absolute neutrophil count was > or = 1 x 10(9)/L for 2 consecutive days. Rapid and sustained hematopoietic engraftment occurred in all patients. The median time to achieve a neutrophil count > or = 0.5 x 10(9)/L was 9 days (range, 8 to 16 days); to achieve a platelet count > or = 20 x 10(9)/L was 10 days (range, 6 to 88 days); and to achieve a platelet count > or = 50 x 10(9)/L was 15.5 days (range, 10 to 100 days). Neutrophil recovery was faster than that of a historical control group treated with autologous bone marrow transplantation and filgrastim, but platelet recovery times were halved in the PBPC group. There was no secondary engraftment failure. Requirements for blood and platelet transfusions, antibiotic use, and parenteral nutrition were similar in the three patient groups. The median number of days in the hospital was 13 (range, 10 to 55) in the PBPC patients, compared with 19 (range, 14 to 51) in the historical controls. Leukapheresis yields (MNC, GM-CFC, and CD34+ cell numbers) were not useful for predicting the times to engraftment. We have shown that sufficient PBPC for transplantation can be obtained at a single leukapheresis after mobilization with routine chemotherapy and filgrastim in patients with non-Hodgkin's lymphoma, Hodgkin's disease, and acute lymphoblastic leukemia, even those heavily pretreated.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Synthesis of two bacteriophage lambda S proteins in an in vivo system.

Bacteriophage lambda has two genes which are essential for lysis: R, a gene encoding a 158-amino-acid (aa) transglycosylase that attacks the peptidoglycan, and S, a gene encoding two inner-membrane-associating proteins, designated S105 and S107 for their predicted lengths in aa residues. S105 and S107 are thought to have opposing roles in lysis, with the former acting as the lethal lysis effector and the latter as a lysis inhibitor. Here, we used a T7-polymerase-mediated expression system to show that S105 and S107 are synthesized at a constant ratio of about 2.5:1 throughout the period leading up to lysis, indicating that lysis scheduling does not require a translationally controlled switch from inhibitor (S107) to effector (S105) synthesis. However, evidence is presented that the mRNA sequences immediately 5' to the ribosome-binding site (RBS) of the S gene are required for the rather limited translation, but not the stability, of the S mRNA. No difference could be found in the pattern of ternary complex formation over the two S start codons in in vitro toe-printing assays with the wild-type mRNA and with mRNA deleted of the upstream sequences. Nevertheless, these results may suggest a role for translational control in S gene expression, if not in its temporal regulation or in the partition between S105 and S107 production.

Amino Acid Sequence↗
PubMed1993

Hispanic-white MMPI comparisons: does psychiatric diagnosis make a difference?

Recent research on Blacks or African-Americans in psychiatric settings suggests that Black-White MMPI differences are minimized or eliminated when researchers match or control for key moderator variables, including psychiatric diagnosis. This study attempted to determine whether Hispanic-White MMPI differences are either minimized or eliminated when Hispanics and Whites are matched on three key moderator variables--age, education, and psychiatric diagnosis. Results suggest that even after controlling for these variables, MMPI differences between Hispanics and Whites are evident. Recommendations for culturally sensitive Hispanic MMPI research are presented.

Adult↗
PubMed1993

Cocaine-stimulus generalization to two new designer drugs: methcathinone and 4-methylaminorex.

Rats were trained to discriminate 8 mg/kg cocaine from saline vehicle for the purpose of examining the stimulus properties of two novel and structurally related drugs of abuse recently confiscated on the illicit market: (+/-)methcathinone and cis(+/-)4-methylaminorex. The stimulus properties of these controlled substance analogs were compared with those of their parent compounds (+/-)cathinone and aminorex, respectively. All agents resulted in cocaine-stimulus generalization with the following rank order of potency: aminorex (ED50 value = 0.8 microM/kg) > methcathinone (1.9 microM/kg) > cathinone (3.7 microM/kg) > 4-methylaminorex (5.2 microM/kg) > cocaine (7.6 microM/kg).

Animals↗
PubMed1993

Antagonism of a (+)N-allylnormetazocine stimulus by (-)PPAP and several structurally related analogs.

Employing rats trained to discriminate 5 mg/kg of the benzomorphan opioid (+)N-allylnormetazocine [(+)NANM] from vehicle, tests of stimulus generalization and antagonism were conducted to determine the influence of several potential sigma-receptor ligands. It has been previously suggested that the (+)NANM stimulus may involve concurrent action at sigma- and phencyclidine (PCP) receptors. Although the low-affinity sigma-antagonist rimcazole was without stimulus-attenuating effect, three novel sigma-ligands--(-)PPAP, CNS 3018, and CNS 3093 (ID50 doses = 3.2, 6.7, and 4.5 mg/kg, respectively)--antagonized the (+)NANM stimulus in a dose-related fashion. The nonselective serotonergic agent 1-(3-trifluoromethyl)phenylpiperazine (TFMPP) produced partial generalization in (+)NANM-trained animals whereas buspirone, a 5-hydroxytryptamine1A (5-HT1A) agonist, attenuated (to 27% drug-appropriate responding) the (+)NANM stimulus. Because the prototypic 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) failed to attenuate the (+)NANM stimulus at pharmacologically relevant doses, it seems unlikely that the (+)NANM stimulus involves a 5-HT1A mechanism. TFMPP and buspirone display modest affinity for sigma-receptors and this may account for the present findings with these agents. The present results neither establish a role for sigma involvement in the stimulus properties of (+)NANM nor eliminate a role for PCP receptors. They do, however, demonstrate that sigma-ligands with little to no affinity for PCP receptors are capable of antagonizing the (+)NANM stimulus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Ion mobility spectrometry of hydrazine, monomethylhydrazine, and ammonia in air with 5-nonanone reagent gas.

Hydrazine (HZ) and monomethylhydrazine (MMH) in air were monitored continuously using a hand-held ion mobility spectrometer equipped with membrane inlet, 63Ni ion source, acetone reagent gas, and ambient temperature drift tube. Response characteristics included detection limit, 6 ppb; linear range, 10-600 ppb; saturated response, >2 ppm; and stable response after 15-30 min. Ammonia interfered in hydrazines detection through a product ion with the same drift time as that for MMH and HZ. Acetone reagent gas was replaced with 5-nonanone to alter drift times of product ions and separate ammonia from MMH and HZ. Patterns in mobility spectra, ion identifications from mass spectra, and fragmentation cross-sections from collisional-induced dissociations suggest that drift times are governed by ion-cluster equilibria in the drift region of the mobility spectrometer. Practical aspects including calibration, stability, and reproducibility are reported from the use of a hand-held mobility spectrometer on the space shuttle Atlantis during mission STS-37.

Ammonia↗
PubMed1993

Treatment of cyclic vomiting in childhood with erythromycin.

Cyclic vomiting syndrome is an unusual cause of episodic emesis in children. It manifests as intermittent episodes of severe vomiting, similar in time of onset and duration, with no symptoms during the intervening period. Dehydration necessitating intravenous fluid therapy may occur. Most therapeutic maneuvers have proven unsuccessful. We report the use of erythromycin as a prokinetic agent in the treatment of cyclic vomiting in 20 children (9 boys, 11 girls). Many patients had mild associated abdominal pain with their vomiting. Thirteen patients had previously been given metoclopramide, but none responded. Two patients were mildly developmentally delayed. Twenty patients were given oral erythromycin ethylsuccinate, approximately 20 mg/kg/day, in 2-4 divided doses for 7 days. This dosage was repeated as needed when symptoms reappeared. Thirteen of 20 patients reported total resolution of symptoms when reevaluated at 2 and 6 months. All males responded, 4 of 13 responders were female, and all seven with partial or no response to therapy were female. This uncontrolled trial suggests that erythromycin may be a useful prokinetic agent in the treatment of cyclic vomiting syndrome in childhood. As the study was uncontrolled, placebo effect cannot be excluded. Case-controlled, double-blinded prospective trials should be considered to evaluate the effectiveness of erythromycin in cyclic vomiting syndrome.

Adolescent↗
PubMed1993

Maternal death from severe retroperitoneal fibrosis.

Idiopathic retroperitoneal fibrosis is uncommon in pregnancy. We have described the case of a pregnant patient with a benign retroperitoneal spindle cell tumor involving the distal duodenum, right ureter, and right iliac artery and vein. She was treated with a left ureteral stent and a right percutaneous nephrostomy. Ultimate cause of death was electrolyte imbalance due to bowel obstruction.

Adult↗
PubMed1993

Phi X174 E complements lambda S and R dysfunction for host cell lysis.

Hybrid lambda phages which have the E lysis gene of the bacteriophage phi X174 in cis to defective nonsense and deletion alleles of the normal lambda lysis genes S and R have been constructed and shown to be fully competent for plaque-forming ability, which demonstrates that the single-gene, lysozyme-independent lysis system of phi X174 and related phages can serve the lytic function for large complex phages. These hybrid phages are unable to form plaques on a slyD host. Moreover, plaque morphology indicates that in E-mediated lysis the soluble lambda R endolysin can participate in lysis, indicating that the protein E-mediated lesions are not completely sealed off from the periplasm.

Bacteriophage lambda↗
PubMed1993

Cloning, sequencing and expression of a Pasteurella haemolytica A1 gene encoding a PurK-like protein.

A membrane protein antigen of Pasteurella haemolytica A1 encoded on the recombinant plasmid pYFC13 is isolated and characterized. Nucleotide sequence analysis of the insert DNA in pYFC13 identified the gene mpa1, which codes a protein of approximately 45 kDa without signal sequence. The deduced amino acids from the DNA sequence are homologous to Bacillus subtilis PurK by 29.4%; to Schizosaccharomyces pombe Pur6 by 29.34%, to Saccharomyces cerevisiae Pur6 by 25.867%; and to E. coli PurK by 25.223% identity, respectively. The purK and pur6 from these organisms are responsible for the activity of 5'-phosphoribosyl- 5-amino-4-imidazole carboxylase which is involved in de novo purine biosynthesis. The protein was over-expressed in E. coli by its own promoter. The antigen we designated as Mpa1, could be localized to the cytoplasmic membrane of both P. haemolytica A1 and E. coli TB1 harbored pYFC13. The Mpa1 was antigenic in rabbit and in cattle since both animals produced antibody against this protein.

Amino Acid Sequence↗
PubMed1993

Helicobacter pylori: a cause of chronic abdominal pain in children.

Approximately one in ten children are seen by a health care professional for a complaint of chronic recurrent abdominal pain. In most cases these complaints are non-organic. Organic causes of abdominal pain may include gastroesophageal reflux, peptic ulcer disease, gallbladder, pancreatic or kidney disease. In addition, infection of the gastric antrum with Helicobacter pylori is now included in the differential diagnosis of chronic abdominal pain in children. H. pylori are "S" or "C" shaped, gram negative bacilli with a smooth outer coat and two to four unipolar flagella. There is no known natural reservoir for H. pylori in the environment. The mode of transmission is also unknown. Multiple drug therapy is necessary to maintain long-term eradication of the organism. Until epidemiologic data are determined, universal precautions should be employed in cases of suspected H. pylori infection.

Abdominal Pain↗
PubMed1992

Zacopride and its optical isomers produce stereoselective antagonism of a 2-methylserotonin discriminative stimulus.

The serotonin 5-HT3 receptor antagonist effects of zacopride and its optical isomers were evaluated in rats trained to discriminate 5.0 mg/kg of 2-methylserotonin (2-Me 5-HT) from saline in a 2-lever operant task. Zacopride and its enantiomers potently antagonized the 2-Me 5-HT stimulus; on the basis of 50% inhibition (ID50) of drug lever responding the order of potency is S(-)-zacopride (ID50 = 0.05 micrograms/kg) greater than (+/-)-zacopride (ID50 = 0.60 micrograms/kg) greater than R(+)-zacopride (ID50 = 1.6 micrograms/kg). The stereoselectivity and potency ratio of zacopride's isomers for antagonizing the 2-Me 5-HT stimulus parallels their previously reported results in binding studies. It is concluded that zacopride's isomers produce antagonism of a 2-Me 5-HT stimulus by stereoselective interaction at 5-HT3 receptors and that stereochemical factors are important in evaluating the stimulus properties of 5-HT3 agents.

Animals↗
PubMed1992

Classification of fungal chitin synthases.

Comparison of the chitin synthase genes of Saccharomyces cerevisiae CHS1 and CHS2 with the Candida albicans CHS1 gene (UDP-N-acetyl-D-glucosamine:chitin 4-beta-N-acetylglucosaminyltransferase, EC 2.4.1.16) revealed two small regions of complete amino acid sequence conservation that were used to design PCR primers. Fragments homologous to chitin synthase (approximately 600 base pairs) were amplified from the genomic DNA of 14 fungal species. These fragments were sequenced, and their deduced amino acid sequences were aligned. With the exception of S. cerevisiae CHS1, the sequences fell into three distinct classes, which could represent separate functional groups. Within each class phylogenetic analysis was performed. Although not the major purpose of the investigation, this analysis tends to confirm some relationships consistent with current taxonomic groupings.

Amino Acid Sequence↗
PubMed1992

5-HT3 agonist 2-methylserotonin as a training drug in discrimination studies.

Using a standard two-lever operant procedure, rats were trained to discriminate 5 mg/kg of the 5-HT3 agonist 2-methylserotonin (2-Me 5-HT; ED50 = 2.6 mg/kg) from saline using a VI 15-s schedule of reinforcement. The 2-Me 5-HT stimulus did not generalize to the 5-HT1/5-HT2 agonist 5-methoxy-N,N-dimethyltryptamine, but did generalize to the new 5-HT3 agonist 1-(m-chlorophenyl)biguanide (ED50 = 1.6 mg kg). The 5-HT3 antagonist ICS 205-930 potently antagonized the 2-Me 5-HT stimulus (ID50 = 0.001 mg/kg), whereas its quaternary amine analog, which does not readily penetrate the blood-brain barrier, failed to completely antagonize the 2-Me 5-HT stimulus at a 10,000-fold higher dose. The results of the present investigation show that 2-Me 5-HT serves as a discriminative stimulus in rats when paired with saline and suggest that its stimulus properties are likely mediated via a central 5-HT3 mechanism. As such, this is the first demonstration that a 5-HT3 agonist can be used as a training drug in drug discrimination studies.

Animals↗
PubMed1992

Aminorex produces stimulus effects similar to amphetamine and unlike those of fenfluramine.

A 4-methyl derivative of aminorex has recently appeared on the clandestine market as a designer drug. In the present study, the stimulus effects of aminorex itself were evaluated in rats trained to discriminate either 0.75 mg/kg S(+)-amphetamine or 1.5 mg/kg fenfluramine from saline. The amphetamine stimulus (ED50 = 0.14 mg/kg) generalized to aminorex (ED50 = 0.23 mg/kg), which was found to be slightly less potent than (+)-amphetamine. Fenfluramine stimulus generalization did not occur to aminorex. Thus, the stimulus effects of aminorex are qualitatively similar to those of amphetamine and unlike those of fenfluramine.

Aminorex↗
PubMed1992

Further studies on N-methyl-1(3,4-methylenedioxyphenyl)-2-aminopropane as a discriminative stimulus: antagonism by 5-hydroxytryptamine3 antagonists.

Using a standard two-lever operant paradigm, male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg N-methyl-1(3,4-methylenedioxyphenyl)-2- aminopropane (MDMA) from saline using a variable-interval 15-s schedule of reinforcement for food reward. Tests of stimulus antagonism were conducted to further define the mechanism of action of MDMA as a discriminative stimulus. Low doses of the 5-hydroxytryptamine1A (5-HT1A) antagonist NAN-190, the 5-HT2 antagonist pirenperone, and the dopamine antagonist haloperidol were able to somewhat attenuate the MDMA stimulus; however, none of these agents decreased MDMA-appropriate responding to less than 46%. The 5-HT3 antagonists zacopride and LY 278584 (ID50 = 0.02 micrograms/kg) antagonized the MDMA discriminative stimulus. Zacopride also attenuated the stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in DOM-trained animals but not those of (+)amphetamine in (+)amphetamine-trained animals. Several possible mechanistic interpretations are provided but it is concluded that MDMA produces its stimulus effects via a complex mechanism involving both dopaminergic and serotonergic components.

3,4-Methylenedioxyamphetamine↗