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Biomedical subjects

A Wong

Publications and source records attributed to A Wong.

At least 199 records · Page 11Linked to original sources
PubMed1989

Concomitant 5-fluorouracil infusion, mitomycin C and radical radiation therapy in esophageal squamous cell carcinoma.

This is a retrospective comparison of patients with unresected esophageal squamous cell carcinoma treated by radiation therapy and chemotherapy (21 patients) versus radiation therapy alone (34 patients). Pretreatment characteristics were comparable in both groups. In the combined modality group, treatment was given in split courses with concomitant radiation therapy (20 to 25 Gy in 10 fractions on days 1-12 and days 42-54) and chemotherapy (bolus Mitomycin C on day 1; 96 hr. of continuous 5 Fluorouracil infusion on days 1-4 and days 42-46). There was improvement in local disease control with the combined modality approach. Initial complete response was achieved in 86% of the radiation and chemotherapy group, versus 57% of the radiation alone group. The one-year local relapse-free rate was 67% versus 35%, and 2 year rate was 41% versus 28%. (p less than 0.05). The 1-year and 2-year survival was 64% and 32% respectively, for the radiation and chemotherapy group, versus 28% and 10% respectively for the radiation alone group (p less than 0.05). The majority of patients had disease relapsed, 81% of the combined modality group and 97% of the radiation alone group. However, the pattern of failure was different in the two groups. In the radiation and chemotherapy group, 29% had local failure alone, 53% had distant failure alone, and 18% had both local and distant failure. In the radiation alone group, 33% had local failure alone, 24% had distant failure alone, and 43% had both local and distant failure. Concomitant radiation therapy, 5 Fluorouracil infusion and bolus Mitomycin C is effective treatment for local control in esophageal squamous cell carcinoma, but not for distant hematogenous metastases. This combined modality treatment was well tolerated, with little additional hematological toxicity, esophagitis and stomatitis over radiation therapy alone.

Aged↗
PubMed1989

Release of Vi antigens from Salmonella typhi: implications for virulence and diagnosis.

The release of Vi antigens from three clinical isolates of Salmonella typhi was measured by a Vi-specific monoclonal antibody. Large quantities of Vi antigens were detected in the culture supernates from all three strains using either passive latex agglutination or rocket immunoelectrophoresis. Vi antigens were also detected in broth cultures of S. typhi containing about 10(5) cells/ml using the sandwich enzyme linked immunosorbent assay. The significance of this finding in relationship to the virulence and the diagnosis of S. typhi was discussed.

Antigens, Bacterial↗
PubMed1989

Diagnosis and incidence of cardiac injury in children with blunt thoracic trauma.

Over a 20-month period, we prospectively studied 41 children with blunt thoracic trauma (BTT) to determine the incidence and morbidity of cardiac injury in this population. Four patients died, and the data were incomplete in 10, leaving 27 for analysis. Serial electrocardiograms (ECG) were abnormal in 36% of the patients studied, serial creatine phosphokinase isoenzyme (CK-MB) ratios were elevated in 31%, echocardiogram showed septal dysfunction in 14%, and pyrophosphate scan showed grade 1 uptake in 14%. There was poor correlation among tests, since only four patients had more than one abnormal test. There was no significant difference in Injury Severity Score or Thoracic Abbreviated Injury Scale between patients with and without abnormal investigations. No patient in the study developed arrhythmias or cardiac failure. In 13 trauma-related deaths undergoing autopsy over the same period, including the four with thoracic trauma, none had evidence of cardiac injury. These results indicate a striking lack of consistency in the diagnosis of posttraumatic cardiac injury in children using standard investigations. The absence of adverse cardiac events in surviving patients and the lack of autopsy evidence of cardiac injury in the trauma deaths suggest that the actual incidence and clinical significance of these lesions in children is lower than generally reported. Children with BTT should be followed clinically, and reliance on screening tests should be avoided.

Adolescent↗
PubMed1989

Induction of human interferon gene expression is associated with a nuclear factor that interacts with the NF-kappa B site of the human immunodeficiency virus enhancer.

The relationship between transcription of alpha and beta interferon (IFN-alpha and IFN-beta) genes and the interaction of IFN promoter-binding transcription factors has been examined in monoblastoid U937 cells following priming with recombinant IFN-alpha 2 (rIFN-alpha 2) and Sendai virus induction. Pretreatment of U937 cells with rIFN-alpha 2 prior to Sendai virus infection increased the mRNA levels of IFN-alpha 1, IFN-alpha 2, and IFN-beta as well as the final yield of biologically active IFN. Analysis of nuclear protein-IFN promoter DNA interactions by electrophoretic mobility-shift assays demonstrated increased factor binding to IFN-alpha 1 and IFN-beta regulatory domains, although no new induction-specific complexes were identified. On the basis of competition electrophoretic mobility-shift assay results, factors interacting with the IFN-alpha 1 and IFN-beta promoters appear to be distinct DNA-binding proteins. U937 factor binding was localized to the P2 domain (-64 to -55) of the IFN-beta regulatory element, a sequence motif with 80% homology to the recognition site of transcription factor NF-kappa B. Protein-DNA interactions within the IFN-beta P2 domain were, in fact, specifically competed by either excess homologous P2 fragment or the human immunodeficiency virus enhancer element which contains two duplicated NF-kappa B recognition sites. Hybrid promoter-chloramphenicol acetyltransferase fusion plasmids, containing either the IFN-beta regulatory element or the human immunodeficiency virus enhancer element linked to the simian virus 40 promoter, were analyzed for virus and phorbol ester inducibility in epithelial and lymphoid cells, respectively. In the 293 cell line, both plasmids were constitutively expressed but not virus inducible, while in Jurkat cells, chloramphenicol acetyltransferase activity from these plasmids was induced by tumor-promoting agent treatment. These experiments suggest that induction of IFN gene expression may be controlled in part by transcription regulatory proteins binding to an NF-kappa B-like site within the IFN-beta promoter.

Base Sequence↗
PubMed1989

Manual discrimination and identification of length by the finger-span method.

Experiments were conducted on length resolution for objects held between the thumb and fore-finger. The just noticeable difference in length measured in discrimination experiments is roughly 1 mm for reference lengths of 10 to 20 mm. It increases monotonically with reference length but violates Weber's law. Also, it decreases when the subject is permitted to maintain a constant finger span between trials; however, it tends to increase when the nondominant hand is used. As would be expected from studies of other stimulus dimensions in other sense modalities, resolution is considerably poorer in identification experiments than in discrimination experiments. For stimulus sets that cover a broad range (90 mm), the total information transfer is roughly 2 bits; for those that cover a relatively small range (18 mm), it is roughly 1 bit. The data are analyzed and interpreted using analysis techniques and models that have been used previously in studies of audition (e.g., Durlach & Braida, 1969).

Adult↗
PubMed1988

Interactions of 5-lipoxygenase with membranes: studies on the association of soluble enzyme with membranes and alterations in enzyme activity.

Treatment of rat basophilic leukemia cells (RBL-1) with the calcium ionophore A23187 resulted in activation of 5-lipoxygenase, as indicated by an induction of leukotriene release [Orning, L., Hammarström, S., & Samuelsson, B. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 2017]. The enzyme activation was accompanied by a time-dependent association of 5-lipoxygenase to the particular fraction. When cells were lysed in the presence of 0.05-10 microM CaCl2, the soluble 5-lipoxygenase became associated with the particulate fraction. This was demonstrated by a decrease in immunoreactivities and enzymatic activities in the soluble fraction and a parallel increase in particulate-associated immunoreactivities. The particulate-bound enzyme was not active. Ca2+ induced the membrane association of 5-lipoxygenase when added into the incubation mixtures containing the membrane fraction with either the cytosolic fraction or the purified enzyme. 5-Lipoxygenase also bound to the microsomal-enriched fraction in the presence of Ca2+. Maximal membrane binding was obtained after a 1-min incubation at 4 degrees C. When a fixed amount of isolated membranes (0.2 mg of protein) and increasing cytosolic protein (0.5-4 mg) were used, a linear increase in enzyme binding was observed. The binding became saturated at 3 mg of cytosolic protein/mg of membrane protein. 5-Lipoxygenase binding to the membrane fraction was unaffected by pretreatment of the membranes with trypsin but was inhibited by treating with phospholipase A2, suggesting that phospholipids are involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The effect of nonviral liver damage on the T-lymphocyte helper/suppressor ratio.

In the present investigation an attempt was made to ascertain whether nonviral liver impairment in rats affects the THelper/TSuppressor ratio. Two hepatotoxic agents were used: (i) galactosamine (GA), which causes a drug-induced hepatitis-like damage, and (ii) orotic acid (OA), which induces fatty changes. Since these two substances act as antidotes to one another they were administered to rats either separately or simultaneously. GA caused severe liver damage documented by a 104-, 48-, and 1.6- fold rise in the plasma concentrations of ALT, AST, and ALP and by multiple foci of hepatocyte necrosis. This was followed by a drop in TH/TS ratio from 2.25 observed in the controls to 0.89 in the GA-treated rats. All of these phenomena were prevented by concurrent administration of GA and OA. OA alone did not show an effect on the liver with respect to changes in plasma enzyme concentrations and by light microscopic analysis. However, OA caused a drop in the TH/TS ratio from 2.25 to 1.55. Neither GA nor OA produced a change in TH/TS ratios in in vitro experiments.

Animals↗
PubMed1988

Sequence of the dnaB gene of Salmonella typhimurium.

The dnaB gene of Escherichia coli encodes a helicase that operates at replication forks of the bacterium and certain of its bacteriophages to produce separated strands suitable for subsequent use by primase and DNA polymerase III. Here, we present the sequence of the dnaB gene of Salmonella typhimurium, a functionally interchangeable analog of the E. coli dnaB gene. The DnaB proteins of these two organisms, inferred from the DNA sequences, are identical in length and in 93% of amino acid residues. Extended portions of the DnaB proteins are also similar to two phage-encoded DNA replication proteins: the gene 4 helicase-primase of coliphage T7 and, as reported previously (H. Backhaus and J. B. Petri, Gene 32: 289-303, 1984), the gene 12 protein of Salmonella phage P22. In contrast, little similarity was found between DnaB and either the UvrD repair helicase or transcription termination factor Rho (an RNA-DNA helicase). These results identify S. typhimurium DnaB as a member of the DnaB family of proteins by structural, as well as functional, criteria and provide the basis for the eventual identification, by mutational studies, of residues in DnaB critical for its function.

Amino Acid Sequence↗
PubMed1988

Dominant lethal mutations in the dnaB helicase gene of Salmonella typhimurium.

A class of dominant lethal mutations in the dnaB (replicative helicase) gene of Salmonella typhimurium is described. The mutated genes, when present on multicopy plasmids, interfered with colony formation by Escherichia coli host strains with a functional chromosomal dnaB gene. The lethal phenotype was expressed specifically in supE (glutamine-inserting) host strains and not in Sup+ strains, because the mutant genes, by design, also possessed an amber mutation derived from a glutamine codon. Mutations located at 11 sites by deletion mapping and DNA sequence analysis varied in the temperature dependence and severity of their lethal effects. None of the mutations complemented a dnaB(Ts) host strain at high temperature (42 degrees C). Therefore, these nonfunctional DnaB proteins must engage some component(s) of the DNA replication machinery and inhibit replication. These mutations are predicted to confer limited, specific defects in either the catalytic activity of DnaB or the ability of DnaB to interact with one of its ligands such as DNA, nucleotide, or another replication protein. The variety of mutant sites and detailed phenotypes represented in this group of mutations may indicate the operation of more than one specific mechanism of lethality.

Bacterial Proteins↗
PubMed1988

trans activation of type 1 interferon promoters by simian virus 40 T antigen.

A human transient expression system was used to measure the influence of simian virus 40 T antigen and adenovirus E1a proteins on the activation of alpha interferon subtype 1 (IFN-alpha 1) and IFN-beta promoters linked to the reporter chloramphenicol acetyltransferase gene. Large T-antigen production, amplified by expression plasmid replication in transfected 293 cells, was able to trans activate the IFN-beta promoter 5- to 10-fold, increasing both the constitutive and Sendai virus-induced levels of expression. Surprisingly, the previously quiescent transfected IFN-alpha 1 promoter in T-antigen-expressing cells displayed a level of inducibility similar to IFN-beta. The endogenous IFN-alpha 1 gene was also inducible to a limited extent in cells expressing T antigen. A truncated IFN-beta promoter deleted to position -37 relative to the CAP site was neither inducible nor trans activated by T antigen, suggesting that sequences required for efficient induction were also needed for trans activation. Since 293 cells express adenoviral E1a proteins, experiments were also performed in HeLa cells to assess the relative contribution of T antigen and E1a proteins to IFN trans activation. In HeLa cells, T-antigen coexpression increased the constitutive level of IFN-beta and IFN-alpha 1 promoter activity without augmenting relative inducibility. Coexpression of T antigen and E1a proteins did not have a cooperative effect on type 1 IFN expression.

Adenovirus Early Proteins↗
PubMed1988

A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma.

We determined the therapeutic effect of fluorouracil (5-FU) in combination with folinic acid (FA) in patients with measurable recurrent or metastatic carcinoma of the colon or rectum by comparing it to standard 5-FU therapy in a prospective randomized controlled trial. Patients were randomized to receive either FA, 200 mg/m2/d for five consecutive days, or nothing. All patients received 5-FU, 370 mg/m2/d for five days on the first course, with subsequent dose modifications to maintain equal toxicity in the two arms. One hundred thirty patients were entered on trial and only five were excluded from the analysis because they did not meet the eligibility criteria or they refused therapy after randomization. The two treatment arms were balanced for 11 clinical characteristics. Patients were evaluated for response at the end of every two treatment courses and toxicity after every course of therapy. Median follow-up was 1.45 years. Dose-limiting toxicity was mucositis and diarrhea on this treatment schedule, although neutropenia was apparent. The response rate was 33% (21 of 63 patients) in the 5-FU and FA arm and was 7% (four of 61 patients) in the 5-FU arm (P less than .0005). Time to disease progression was significantly different in the combination arm as compared with the single-agent arm (P = .023). Overall survival was significantly longer for patients treated with 5-FU and FA as compared with those receiving 5-FU alone (P = .05). The median survival was 12.6 months for patients receiving the combination, and 9.6 months for those receiving 5-FU alone. Our results indicate that the combination of 5-FU and FA is effective treatment for patients with metastatic or recurrent carcinoma of the rectum and colon who have not received prior chemotherapy.

Adenocarcinoma↗
PubMed1988

Leukotriene D4 receptor-mediated phosphoinositol hydrolysis and calcium mobilization in rat basophilic leukemic cells.

A basophilic leukemic cell line from rat (RBL-1) was used to characterize leukotriene D4 (LTD4) receptor-mediated biochemical and pharmacological effects. [3H]LTD4 binding to the plasma membrane enriched preparation was stereo-selective, specific and saturable. Sodium ions and guanine nucleotides specifically regulated [3H]LTD4 binding to the membrane receptors. Leukotriene E4 (LTE4) and high affinity specific antagonists bound to the receptor with a rank-order potency equivalent to that for the LTD4 receptors in guinea pig lung. In the [3]myoinositol labeled RBL-1 cells, LTD4 and LTE4 induced a rapid hydrolysis of [3H]phosphoinositides. The biosynthesis of the [3H]inositol-trisphosphate was rapid and was detectable at 15-sec poststimulation. The biosynthesis of [3H]inositol-monophosphate was stereo-selective and specific and was inhibited specifically by receptor antagonists. In fura-2 loaded RBL-1 cells, LTD4 and LTE4 induced a transient intracellular Ca++ mobilization. Agonist-induced Ca++ mobilization was specific and stereo-selective and was inhibited by specific receptor antagonists. The most (greater than 85%) LTD4-induced immediate response of Ca++ mobilization was from intracellular sources, whereas a small amount (less than 15%) was derived from the extracellular milieu. Both components were stimulated by receptor agonists and inhibited by the receptor antagonists, suggesting that they were regulated by the LTD4 membrane receptors. In addition, the results also suggested that a guanine nucleotide binding protein, insensitive to islet activating protein from Bordetella pertussis (not Gi or Go), was involved in the signal transduction mechanisms for LTD4 receptors in RBL-1 cells. These results suggested that the plasma membrane enriched LTD4 receptor was coupled via an islet activating protein insensitive G protein to a phosphoinositide specific phospholipase C. Agonist binding to the receptor could activate phospholipase C and resulted in phosphoinositide hydrolysis. Diacylglycerol and inositol trisphosphate could function as intracellular messengers that trigger or contribute to calcium mobilization in RBL-1 cells.

Animals↗
PubMed1988

Cutaneous fungal flora in twenty horses free of skin or ocular disease.

The fungal flora of the hair and underlying skin from 2 sites was examined qualitatively in 20 horses free of skin or ocular disease. Fungi were isolated from both the hair and the underlying skin of all 20 horses. Twenty-two genera regarded commonly as saprophytes were identified and an additional 2 fungi resembled the perfect state of the cutaneous pathogenic genera Microsporum and Trichophyton. Cladosporium spp, Penicillium spp, and Rhizopus spp were the most frequently isolated saprophytes. In general, similar fungi were isolated from the hair and underlying skin, and differences were not noted in isolates from the saddle and rump regions.

Animals↗
PubMed1987

Evidence for distinct binding sites in the cumene hydroperoxide-dependent metabolism of benzo[a]pyrene catalyzed by cytochrome P-450.

A few constitutive cytochrome P-450 isozymes in male rat liver microsomes catalyzed the metabolism of benzo[a]pyrene (BP) in cumene hydroperoxide (CHP)-dependent reactions, which produced predominantly 3-hydroxyBP and BP quinones. This process varied with the concentration of CHP. At 0.05 mM CHP, 3-hydroxyBP was the major metabolite. An increase in CHP concentration reduced 3-hydroxyBP formation but increased the level of BP quinones. This change in metabolic profile was reversed by preincubation with pyrene. Pyrene selectively inhibited quinone formation and enhanced 3-hydroxyBP formation. Naphthalene, phenanthrene and benz[a]anthracene nonspecifically inhibited total metabolism. BP binding to microsomal protein correlated with quinone formation, suggesting a common precursor reactive intermediate. BP metabolism by female rat liver microsomes also depended on CHP concentration but was much less effective than that in the male. With females, quinones were the major metabolites at all CHP concentrations, and their formation was again modulated by pyrene. These data indicate that two distinct binding sites are responsible for the formation of 3-hydroxyBP and BP quinones.

Animals↗