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Biomedical subjects

M Robinson

Publications and source records attributed to M Robinson.

At least 145 records · Page 8Linked to original sources
PubMed1997

Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi-centre double-blind study.

INTRODUCTION: Relapse of erosive oesophagitis occurs in almost all patients if treatment is stopped after initial healing. AIM: To assess the potential of different therapeutic regimens of omeprazole to prevent relapse of erosive reflux oesophagitis after initial healing with omeprazole. PATIENTS AND METHODS: Patients whose active erosive reflux oesophagitis (grade > or = 2) had healed (grade 0 or 1) after 4-8 weeks of open-label omeprazole 40 mg daily (phase I) were eligible to join a multi-centre, 6-month double-blind, placebo-controlled maintenance study (phase II), which included endoscopy, symptom assessments, serum gastrin measurements, and gastric fundic biopsies. During phase I, endoscopy was performed at weeks 0, 4, and 8. At the end of phase I, 429 of 472 patients (91%) were healed, and there were significant reductions in heartburn, dysphagia and acid regurgitation. Of the 429 patients who healed, 406 joined phase II and were randomized to one of three groups: 20 mg omeprazole daily (n = 138), 20 mg omeprazole for 3 consecutive days each week (n = 137), or placebo (n = 131). During phase II, endoscopy was performed at months 1, 3, and 6 or at symptomatic relapse. RESULTS: The percentages of patients still in endoscopic remission at 6 months were 11% for placebo, 34% for omeprazole 3-days-a-week, and 70% for omeprazole daily. Both omeprazole regimens were superior to placebo in preventing recurrence of symptoms (P < 0.001); however, omeprazole 20 mg daily was superior to omeprazole 20 mg 3-days-a-week (P < 0.001). Compared to baseline, omeprazole therapy resulted in no significant differences among treatment groups in the distribution of gastric endocrine cells. CONCLUSIONS: These results show that after healing of erosive oesophagitis with 4-8 weeks of omeprazole, relapse of oesophagitis and recurrence of reflux symptoms can be prevented in 70% of patients with a maintenance regimen of 20 mg daily, but that intermittent dosing comprising 3 consecutive days each week significantly compromises efficacy.

Anti-Ulcer Agents↗
PubMed1997

Non-specific binding of IgG1 to Heligmosomoides polygyrus: adult worm homogenate superantigen is a target for immunoglobulin-induced inhibition.

Previous evidence had indicated that selected antigens contained in H. polygyrus adult worm homogenate (AWH) could bind non-specifically to mouse IgG1. To determine whether H. polygyrus superantigen was one of these binding molecules, an inhibition assay was carried out using monoclonal antibodies (MoAb) to block the in vitro superantigen response. The results indicated that non-specific IgG1 binding could inhibit the cellular response to the superantigen. This assumption was tested using affinity chromatography to extract those antigens which bound non-specifically to mouse IgG1. Both the protein fraction which bound to the column and the unfractionated AWH demonstrated superantigen activity, as described previously. In contrast, the unbound fraction contained no superantigen activity. None of the tested fractions exhibited non-specific mitogen activity. These results indicate that the superantigen produced by H. polygyrus binds to host IgG1 of any specificity and this binding can inhibit further host recognition of this molecule. Additionally, it was demonstrated that an apparently similar superantigen is also contained in L4 homogenate, and is strongly represented in the excretory/secretory (E/S) proteins produced by both adult and L4 parasitic stages. Therefore, it is probable that H. polygyrus superantigen influences the host during both the L4 and adult stages of the life-cycle.

Animals↗
PubMed1997

Using partner hospitals in collaborative benchmarking..

In May 1994 the Physiotherapy Department at John Hunter Hospital received a Commonwealth Best Practice in the Health Sector grant to design a critical pathway for the treatment of stroke. The implementation of the pathway at John Hunter Hospital and the introduction of the methodology to secondary sites (The Alfred Healthcare Group, Melbourne, and Royal Hobart & Repatriation General Hospitals, Hobart) resulted in the development of a Benchmarking Consortium. This paper will discuss the importance of benchmarking in understanding clinical processes, and the methodology employed to ensure that meaningful benchmarks were achieved.

Ancillary Services, Hospital↗
PubMed1997

Cytoplasmic tails of beta 1, beta 2, and beta 7 integrins differentially regulate LFA-1 function in K562 cells.

The beta 2 integrin lymphocyte function-associated antigen 1 (LFA-1) mediates activation-dependent adhesion of lymphocytes. To investigate whether lymphocyte-specific elements are essential for LFA-1 function, we expressed LFA-1 in the erythroleukemic cell line K562, which expresses only the integrin very late antigen 5. We observed that LFA-1-expressing K562 cannot bind to intercellular adhesion molecule 1-coated surfaces when stimulated by phorbol 12-myristate 13-acetate (PMA), whereas the LFA-1-activating antibody KIM185 markedly enhanced adhesion. Because the endogenously expressed beta 1 integrin very late antigen 5 is readily activated by PMA, we investigated the role of the cytoplasmic domain of distinct beta subunits in regulating LFA-1 function. Transfection of chimeric LFA-1 receptors in K562 cells reveals that replacement of the beta 2 cytoplasmic tail with the beta 1 but not the beta 7 cytoplasmic tail completely restores PMA responsiveness of LFA-1, whereas a beta 2 cytoplasmic deletion mutant of LFA-1 is constitutively active. Both deletion of the beta 2 cytoplasmic tail or replacement by the beta 1 cytoplasmic tail alters the localization of LFA-1 into clusters, thereby regulating LFA-1 activation and LFA-1-mediated adhesion to intercellular adhesion molecule 1. These data demonstrate that distinct signaling routes activate beta 1 and beta 2 integrins through the beta-chain and hint at the involvement of lymphocyte-specific signal transduction elements in beta 2 and beta 7 integrin activation that are absent in the nonlymphocytic cell line K562.

Amino Acid Sequence↗
PubMed1997

Chromosome 3p14 homozygous deletions and sequence analysis of FRA3B.

Loss of heterozygosity (LOH) involving 3p occurs in many carcinomas but is complicated by the identification of four distinct homozygous deletion regions. One putative target, 3p14.2, contains the common fragile site, FRA3B, a hereditary renal carcinoma-associated 3;8 translocation and the candidate tumor suppressor gene, FHIT. Using a approximately 300 kb comsid/lambda contig, we identified homozygous deletions in cervix, breast, lung and colorectal carcinoma cell lines. The smallest deletion (CC19) was shown not to involve FHIT coding exons and no DNA sequence alterations were present in the transcript. We also detected discontinuous deletions as well as deletions in non-tumor DNAs, suggesting that FHIT is not a selective target. Further, we demonstrate that some reported FHIT aberrations represent normal splicing variation. DNA sequence analysis of 110 kb demonstrated that the region is high in A-T content, LINEs and MER repeats, whereas Alu elements are reduced. We note an intriguing similarity in repeat sequence composition between FRA3B and a 152 kb segment from the Fragile-X region. We also identified similarity between a FRA3B segment and a small polydispersed circular DNA. In contrast to the selective loss of a tumor suppressor gene, we propose an alternative hypothesis, that some putative targets including FRA3B may undergo loss as a consequence of genomic instability. This instability is not due to DNA mismatch repair deficiency, but may correlate in part with p53 inactivation.

Acid Anhydride Hydrolases↗
PubMed1997

Evolution of isochores in rodents.

The most deviant isochore pattern within mammals was found in rat and mouse; most other mammals possess a different kind of isochore organization called the "general pattern." However, isochore patterns remain largely unknown in rodents other than mouse and rat. To investigate the taxonomic distribution of isochore patterns in rodents, we sequenced the nuclear gene LCAT (lecithin:cholesterol acyltransferase) from 17 rodents species (bringing the total of LCAT sequences in rodent to 19) and compared their GC contents at third codon positions and in introns. We also analyzed an extensive sequence database from rodents other than rat and mouse. All murid LCAT sequences are much poorer in GC than all nonrodent LCAT sequences, and the hamster sequence database shows exactly the same isochore pattern as rat and mouse. Thus, all murids share the same special isochore pattern--GC homogenization. LCAT sequences are GC-poor in hystricomorphs too, but the guinea pig sequence database indicates that large changes in GC content occur without an overall modification of the isochore pattern. This novel mode of isochore evolution is called GC reordering. LCAT sequences also show that the evolution of isochores in sciurids and glirids is nonconservative in comparison with that in nonrodents. Thus, at least two novel patterns of isochore evolution were found. No rodent investigated to date shared the general mammalian pattern.

Animals↗
PubMed1997

Hair cycle stage of the mouse vibrissa follicle determines subsequent fiber growth and follicle behavior in vitro.

The establishment of culture models representative of all aspects of in vivo hair follicle behavior is an important goal for theoretic and analytic studies. Rodent vibrissa follicles have regular, predictable, and relatively short growth cycles. In this investigation, we took advantage of these properties; we classified mouse vibrissa follicles according to different phases in the hair cycle and then compared fiber growth and morphologic changes in culture. Follicles isolated in the early phase of the growth cycle produced fine growing fibers with an average growth that exceeded 3 mm over 15 d. Even when hair growth had slowed or halted subsequently, histology showed that these follicles retained an anagen-like morphology. By contrast, follicles isolated toward the end of the growing cycle produced thicker fibers for much shorter periods, after which growth ceased and the fibers lifted up from the base of the follicle. Internally, these specimens resembled their telogen counterparts in situ. Follicles isolated in mid-growth demonstrated intermediate fiber growth characteristics. In organ culture, mouse vibrissa follicles therefore closely reflect their in vivo origin in growth characteristics and cycle timing. These data provide new opportunities for studying hair growth cycle mechanisms in vitro, but present a caveat for quantitative studies because there may be a greater growth cycle-related variation than has previously been assumed.

Animals↗
PubMed1997

Protein interactions in the herpes simplex virus type 1 VP16-induced complex: VP16 peptide inhibition and mutational analysis of host cell factor requirements.

The herpes simplex virus VP16 protein functions as a potent transcriptional activator and targets DNA sites with the consensus TAATGARAT present in all the viral immediate-early gene promoters. To do so, VP16 directs assembly of a multiprotein complex involving two cellular proteins, host cell factor (HCF) and the Oct-1 DNA-binding transcription factor. To investigate the importance of specific protein-protein interactions to formation of this VP16-induced complex (VIC), we used oligopeptides to prevent VIC assembly. Linear and cyclic peptides corresponding to a region of VP16 previously implicated in complex formation were potent inhibitors of VIC assembly. To further characterize the protein interactions involved, we cloned a human cDNA encoding the minimal VP16 interaction domain of HCF, containing amino acids 1 to 380 [HCF (1-380)]. The REHAYS-based peptides active in preventing VIC assembly were found to specifically block binding of VP16 to HCF (1-380), without affecting VP16-Oct-1 binding. The inhibitory activity of these VP16 peptides was strictly sequence specific for the EHAY residues. Site-directed mutagenesis of the HCF (1-380) domain revealed residues E102 and K105 to be critical determinants in support of VIC formation. Alteration of a single residue in HCF, K105, was shown to virtually abolish complex assembly. Interestingly however, none of the HCF mutants that were impaired in their ability to support complex formation exhibited defects in direct VP16 binding, supporting loss of function at a higher order in complex assembly.

Amino Acid Sequence↗
PubMed1997

Short chain fatty acid rectal irrigation for left-sided ulcerative colitis: a randomised, placebo controlled trial.

BACKGROUND: Short chain fatty acid (SCFA) deficiency is associated with colitis in animals and humans, and the mucosal metabolism of these compounds is decreased in ulcerative colitis. AIMS: To assess the efficacy of topical SCFA treatment in ulcerative colitis. PATIENTS AND METHODS: 103 patients with distal ulcerative colitis were entered into a six week, double-blind, placebo controlled trial of rectal SCFA twice daily; patients who were unchanged on placebo were offered SCFA in an open-label extension trial. RESULTS: Of the 91 patients completing the trial, more patients in the SCFA treated than in the placebo treated group improved (33% v 20%, p = 0.14, NS). Those on SCFA also had larger, but statistically non-significant, reductions in every component of their clinical and histological activity scores. In patients with a relatively short current episode of colitis (< 6 months, n = 42), more responded to SCFA than to placebo (48% v 18%, p = 0.03). These patients also had larger, but statistically non-significant, decreases in their clinical activity index (p = 0.08 v placebo). Every patient who improved used at least five of six of the prescribed rectal SCFA irrigations, whereas only 37% who did not improve were as compliant. In the open-label extension trial, 65% improved on SCFA; these patients also had significant reductions (p < 0.02) in their clinical and histological activity scores. CONCLUSIONS: Although SCFA enemas were not of therapeutic value in this controlled trial, the results suggest efficacy in subsets of patients with distal ulcerative colitis including those with short active episodes. Prolonged contact with rectal mucosa seems to be necessary for therapeutic benefit.

Acute Disease↗
PubMed1997

Effect of increasing doses of hypertonic saline on mucociliary clearance in patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis are known to have decreased mucociliary clearance. It has previously been shown that inhalation of a 7.0% solution of hypertonic saline significantly improved mucociliary clearance in a group of adult patients with cystic fibrosis. The aim of this study was to measure the response to increasing concentrations of inhaled hypertonic saline. METHODS: Ten patients (seven men) of mean (SE) age 22 (4) years and mean forced expiratory volume in one second (FEV1) 52.0 (6.7)% predicted completed the study. Mucociliary clearance was measured using a radioaerosol technique for 90 minutes after the interventions which comprised 0.9% NaCl + voluntary cough (control), 3.0% NaCl, 7.0% NaCl, and 12% NaCl. RESULTS: There was a significant increase in the amount of activity cleared from the right lung with all concentrations of hypertonic saline (HS) compared with control. The amount cleared at 90 minutes on the control day was 12.7% (95% confidence interval (CI) 9.8 to 17.2) compared with 19.7% (95% CI 13.6 to 29.5) for 3% HS, 23.8% (95% CI 15.9 to 36.7) for 7% HS and 26.0% (95% CI 19.8 to 35.9) for 12% HS. The improvement in mucociliary clearance was not solely due to coughing as the number of coughs recorded on the control day exceeded that recorded on any other day. The hypertonic saline did not induce a clinically significant change in FEV1. CONCLUSIONS: Within the range of concentrations examined in this study, the effect of hypertonic saline appears to be dose dependent. Inhalation of hypertonic saline remains a potentially useful treatment for patients with cystic fibrosis.

Administration, Inhalation↗
PubMed1997

Margin of safety for discharge after apnea in preterm infants.

OBJECTIVE: Most neonatologists include an apnea-free period in the criteria for the discharge of preterm infants. However, the length of time one should wait after the cessation of apnea before sending an infant home without a monitor is debated. We undertook this study in an attempt to define a minimal and safe observation period between the time of the last apnea episode and discharge. METHODS: We reasoned that in infants with idiopathic apnea of prematurity, the intervals between days on which apnea occurs gradually increase until some point at which clinically significant apnea ceases. Therefore, knowledge about the intervals between days on which apnea occurred just before the last apnea would provide a reasonable estimate of the minimal safe observation interval between the last apnea and discharge. We reviewed the charts of 266 infants born in 1993 and 1994 at </=32 weeks' gestational age or weighing </=1500 g at birth from two institutions to determine the intervals between the day on which the last apnea occurred and the previous two days on which apnea occurred. One hundred seventy-five infants were excluded because they never experienced apnea, or data about the last apnea was missing, or they were on xanthines during the period encompassing the last 3 apnea days, or they weighed <1500 g or were <34 weeks' postmenstrual age at the time of the last apnea. Of the 91 remaining infants, gestational age at birth, birth weight, 1- and 5-minute Apgar scores, and discharge weight were not different between the two institutions. For each infant we determined the longest of the intervals between the 2 days on which apnea occurred previous to the day of the last apnea (MAXINT for maximum interval). The infants were then ordered by MAXINT and, starting at the longest MAXINT, the medical records of each infant were carefully examined for other conditions known to be associated with apnea (eg, recovering from anesthesia, sepsis, chronic lung disease, and so forth). The minimal safe observation period was then defined as the longest MAXINT in which there was at least 1 infant with no other explanation for the apnea other than prematurity. RESULTS: The median duration of the intervals between the 2 days on which apnea occurred previous to the day on which the last apnea occurred were 3. 0 and 2.0 days and the median duration of the MAXINT was 4.0 days. On careful examination of the charts, it was determined that each of 13 infants with a MAXINT preceding the day on which the last apnea occurred of greater than 8 days had some other condition that might result in apnea, including residual lung disease, sepsis, surgery, and so forth. In contrast, among the group of infants with a MAXINT of </=8 days, at least 1 infant at each MAXINT (eg, 1 to 8) had significant apnea with no other explanation other than prematurity. CONCLUSIONS: We conclude that otherwise healthy preterm infants continue to have apneas separated by as many as 8 days before the last apnea before discharge. Conversely, infants with longer apnea intervals often have identifiable risk factors other than apnea of prematurity.

Apnea↗
PubMed1997

Lansoprazole heals erosive reflux esophagitis resistant to histamine H2-receptor antagonist therapy.

PURPOSE: We conducted a randomized, double-blind, multicenter clinical trial to determine whether lansoprazole was superior to continued therapy with histamine H2-receptor antagonist therapy in healing erosive reflux esophagitis. METHODS: Investigators from nine medical centers enrolled 159 patients with endoscopically documented esophageal erosions and/or ulcers that had failed to heal with 12 or more wk of at least standard dosages of histamine H2-receptor antagonist therapy. Patients received ranitidine 150 mg b.i.d. for 8 wk or lansoprazole 30 mg for 4 wk followed by either lansoprazole 30 mg or lansoprazole 60 mg for another 4 wk of treatment. Patients underwent endoscopy at screening and at weeks 2, 4, and 8. RESULTS: At 2, 4, and 8 wk of therapy, healing rates were significantly higher in the lansoprazole group compared with the ranitidine group (p < 0.001). By 8 wk, 84% of the lansoprazole group were healed as opposed to only 32% of the ranitidine group. Lansoprazole was superior to ranitidine in providing relief of upper abdominal burning and daytime heartburn (p < 0.001) and reducing the need for antacids (p < 0.001). Lansoprazole patients had less interference with sleep and less day time drowsiness than ranitidine patients (p = 0.05). The percentages of patients with adverse events were similar in both groups. Fasting serum gastrin levels at weeks 4 and 8 were significantly higher in the lansoprazole group compared with the ranitidine group. CONCLUSION: Eight weeks of lansoprazole therapy is safe, superior to continued ranitidine therapy, and effective in healing more than 80% of patients with erosive reflux esophagitis previously resistant to histamine H2-receptor antagonist therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Optimizing therapy for inflammatory bowel disease.

This review focuses on current developments in the major categories of therapy used in the management of inflammatory bowel disease (IBD). Conventional corticosteroids, although a mainstay of the acute treatment of IBD for many years, have many drawbacks, including a variety of side effects--particularly with chronic use. Budesonide appears to be relatively safe and at least moderately effective in inducing remission in active distal ulcerative colitis (UC) and Crohn's disease. Aminosalicylates, both oral and topical, have proven useful in managing mild-to-moderate active UC and mild active Crohn's disease, as well as in maintaining remission. Data from recent trials suggest that higher doses of mesalamine are generally more efficacious than lower doses. In addition, a combination of oral and rectal formulations may succeed when one route, alone, is not successful. The immunomodulatory agents azathioprine, 6-mercaptopurine, and methotrexate have been shown to be effective in the treatment of IBD and are now widely accepted as valuable parts of the therapeutic armamentarium. Cyclosporine, although effective, is associated with many toxicities, and patients must be monitored closely in centers experienced with this agent. Clinical trials of IL-10, IL-11, and anti-TNFalpha have also shown promise. Antibiotics have been used empirically for many years in the treatment of IBD. Larger clinical trials are warranted to explore the potential efficacy of antibiotic therapy. This has been accomplished with metronidazole in Crohn's disease, and other antibiotic trials are underway at this time. The investigational agents acemannan, heparin, and transdermal nicotine have also shown variable degrees of promise as possible therapies for IBD. Despite the variety of agents available for the treatment of IBD, none is ideal or universally accepted. Ongoing research into the well-established therapeutic agents, as well as novel drugs with more precise targets, may contribute to the design of a more nearly optimal regimen for IBD in the not-too-distant future.

Adrenal Cortex Hormones↗
PubMed1996

Sensitivity and selectivity in protein similarity searches: a comparison of Smith-Waterman in hardware to BLAST and FASTA.

To predict the functions of a possible protein product of any new or uncharacterized DNA sequence, it is important first to detect all significant similarities between the encoded amino acid sequence and any accumulated protein sequence data. We have implemented a set of queries and database sequences and proceeded to test and compare various similarity search methods and their parameterizations. We demonstrate here that the Smith-Waterman (S-W) dynamic programming method and the optimized version of FASTA are significantly better able to distinguish true similarities from statistical noise than is the popular database search tool BLAST. Also, a simple "log-length normalization" of S-W scores based on the query and target sequence lengths greatly increased the selectivity of the S-W searches, exceeding the default normalization method of FASTA. An implementation of the modified S-W algorithm in hardware (the Fast Data Finder) is able to match the accuracy of software versions while greatly speeding up its execution. We present here the selectivity and sensitivity data from these tests as well as results for various scoring matrices. We present data that will help users to choose threshold score values for evaluation of database search results. We also illustrate the impact of using simple-sequence masking tools such as SEG or XNU.

Computers↗
PubMed1996

The Clementine bistatic radar experiment.

During the Clementine 1 mission, a bistatic radar experiment measured the magnitude and polarization of the radar echo versus bistatic angle, beta, for selected lunar areas. Observations of the lunar south pole yield a same-sense polarization enhancement around beta = 0. Analysis shows that the observed enhancement is localized to the permanently shadowed regions of the lunar south pole. Radar observations of periodically solar-illuminated lunar surfaces, including the north pole, yielded no such enhancement. A probable explanation for these differences is the presence of low-loss volume scatterers, such as water ice, in the permanently shadowed region at the south pole.

Extraterrestrial Environment↗
PubMed1996

ETO and AML1 phosphoproteins are expressed in CD34+ hematopoietic progenitors: implications for t(8;21) leukemogenesis and monitoring residual disease.

To study acute myelogenous leukemia 1 (AML1) transcription factor, ETO protein, and t(8;21) AML chimeric AML1/ ETO protein in normal hematopoiesis and in leukemia, we raised rabbit antisera to a bacterially expressed polypeptide containing amino acid residues 1 to 220 of ETO and to synthetic peptides extending from residues 528 to 548 of ETO and 32 to 50 of AML1. The latter was selected to have little chance of cross-reactivity with other members of the PEBP2 alpha family. With affinity-purified reagents, we observed immunofluorescent staining for both AML1 and ETO in the nucleus of HEL, K562, and Kasumi-1 leukemic cell lines, the last from a t(8;21) AML. Biochemical analysis confirmed specificity of the antibodies and the nuclear localization of the antigens, the latter being exclusive for AML1 and primary for ETO. Immunoprecipitations of metabolically labeled 32P-proteins from Kasumi-1 cells show that AML1 and ETO are phosphorylated on serine and threonine. Investigations with normal bone marrow reveal AML1 and ETO are coexpressed in megakaryocytes and that each is expressed in a portion of the approximately 10-microns-diameter cells residing there. Using a CD34+ enriched population mobilized to peripheral blood, we found AML1 and, unexpectedly, ETO present in these cells. Because of this, we conclude that the expression of ETO in hematopoietic cells is not by itself leukemogenic. Also, because ETO would not be exclusively expressed as part of chimeric AML1/ETO in leukemic patients, its presence cannot be used to monitor t(8;21) AML residual disease.

Acute Disease↗