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Biomedical subjects

R Green

Publications and source records attributed to R Green.

At least 271 records · Page 15Linked to original sources
PubMed1991

Comparing serum ferritin values from different population surveys.

This report compares serum ferritin data collected in recently conducted Health and Nutrition Examination Surveys by age, sex, and ethnic group. Serum ferritin assays and selected confounding variables are examined to explore the basis of the difference in serum ferritin values obtained from the different surveys.

Confounding Factors, Epidemiologic↗
PubMed1990

Mutational analysis of conserved nucleotides in a self-splicing group I intron.

We have constructed all single base substitutions in almost all of the highly conserved residues of the Tetrahymena self-splicing intron. Mutation of highly conserved residues almost invariably leads to loss of enzymatic activity. In many cases, activity could be regained by making additional mutations that restored predicted base-pairings; these second site suppressors in general confirm the secondary structure derived from phylogenetic data. At several positions, our suppression data can be most readily explained by assuming non-Watson-Crick base-pairings. In addition to the requirements imposed by the secondary structure, the sequence of the intron is constrained by "negative interactions", the exclusion of particular nucleotide sequences that would form undesirable secondary structures. A comparison of genetic and phylogenetic data suggests sites that may be involved in tertiary structural interactions.

Animals↗
PubMed1990

Expression of transcobalamin II receptors by human leukemia K562 and HL-60 cells.

Plasma membrane receptors for the serum cobalamin-binding protein transcobalamin II (TCII) were identified on human leukemia K562 and HL-60 cells using immunoaffinity-purified human TCII labeled with [57Co]cyanocobalamin. The Bmax values for TCII receptors on proliferating K562 and HL-60 cells were 4,500 and 2,700 per cell, respectively. Corresponding dissociation constants (kd) were 8.0 x 10(-11) mol/L and 9.0 x 10(-11) mol/L. Rabbit TCII also bound to K562 and HL-60 cells but with slightly reduced affinities. Calcium was required for the binding of transcobalamin II to K562 cells. Brief treatment of these cells with trypsin resulted in almost total loss of surface binding activity. After removal of trypsin, surface receptors for TCII slowly reappeared, reaching pretrypsin treatment densities only after 24 hours. Reappearance of receptors was blocked by cycloheximide. TCII receptor densities on K562 and HL-60 cells correlated inversely with the concentration of cobalamin in the culture medium. This suggests that intracellular stores of cobalamin may affect the expression of transcobalamin receptors. Nonproliferating stationary-phase K562 cells had low TCII receptor densities (less than 1,200 receptors/cell). However, the density of TCII receptors increased substantially when cells were subcultured in fresh medium. Up-regulation of receptor expression coincided with increased 3H-thymidine incorporation, which preceded the resumption of cellular proliferation as measured by cell density. In the presence of cytosine arabinoside, which induces erythroid differentiation, K562 cells down-regulated expression of TCII receptors. When HL-60 cells were subcultured in fresh medium containing dimethysulfoxide to induce granulocytic differentiation, the up-regulation of TCII receptors was suppressed. This event occurred well before a diminution of 3H-thymidine incorporation and cessation of proliferation. Thus, changes in the regulation of expression of TCII receptors correlate with both the proliferative and differentiation status of cells.

Cell Division↗
PubMed1990

In vitro genetic analysis of the Tetrahymena self-splicing intron.

The availability of methods for the amplification of nucleic acid sequences allows the genetic analysis in vitro of the structural and functional properties of many nucleic acids. We have now developed an in vitro selection and amplification system, and used it to analyse the self-splicing Tetrahymena ribozyme. A much wider range of selective conditions can be used in vitro than is possible with standard in vivo methods, and many more variants can be handled in vitro than in vivo. This method can be used to isolate the wild-type ribozyme, and structural variants that are as active as the wild type, from a pool of over 250,000 variants in only three cycles of selection and amplification.

Animals↗
PubMed1990

Glutathionylcobalamin as an intermediate in the formation of cobalamin coenzymes.

To evaluate the possible role of glutathionylcobalamin (GS-Cbl) in the intracellular metabolism of cobalamin, the following reactions were analyzed using extracts of rabbit spleen: (i) decyanation of cyanocobalamin; (ii) utilization of GS-Cbl by cobalamin reductase; (iii) participation of GS-Cbl in methionine biosynthesis; and (iv) conversion of GS-Cbl to adenosylcobalamin. Decyanation of cyanocobalamin required reduced glutathione which appeared to form a complex with the cobalamin. This complex decomposed during the extraction steps to sulfitocobalamin which was identified by high-performance liquid chromatography. Cobalamin reductase in spleen extract was more active with GS-Cbl than with aquocobalamin or cyanocobalamin as substrates (specific activities: 10.4, 2.8 and 0.93 nmol/mg/min, respectively). Methionine synthase utilized GS-Cbl as cofactor more efficiently than aquocobalamin or cyanocobalamin based on initial rates of enzyme activity. This suggests that GS-Cbl is a more direct precursor of the coenzyme required for methionine synthase. Formation of adenosylcobalaminm from GS-Cb1 was four times greater than from aquocobalamin alone. Based on these results, we propose that GS-Cbl or a closely related thiol-cobalamin adduct is a proximal precursor in cobalamin coenzyme biosynthesis.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1990

Human error on the flight deck.

Despite terrorist bombs and structural failures, human error on the flight deck continues to account for the majority of aircraft accidents. The Royal Air Force (RAF) Institute of Aviation Medicine (IAM) has investigated the psychology of such error since the early 1970s, and to this end has used two principal techniques. The first has involved assisting in the official inquiries into both RAF and civil flying accidents, and the second has involved setting up a reporting system that permits any commercial pilot to report his own everyday errors, in complete confidence, to the RAF IAM. The latter system possesses the clear benefit of gathering error data untainted by considerations of culpability, and sometimes permits system rectification before the occurrence of accidents. This paper examines selected examples of errors associated with the design of equipment and with the social psychology of crews, and suggests that some consideration of the psychology of organizations may be necessary to ensure that the problems of human error are given the degree of consideration they require.

Accidents, Aviation↗
PubMed1990

Transcobalamin II deficiency presenting with methylmalonic aciduria and homocystinuria and abnormal absorption of cobalamin.

An infant with deficiency of transcobalamin II (TCII) presented with virtually complete failure to thrive and life-threatening pancytopenia. Methylmalonic acid and homocystine were found in the urine. The concentration of B12 in the serum was 26 pg/ml. Fibroblasts derived from the patient failed to take up labeled cobalamin in the absence of a source of TCII. Uptake was normal in the presence of TCII. Treatment with parenteral cobalamin reversed the clinical and hematological manifestations of the disease but she developed glossitis when the interval between injections was lengthened. Intestinal absorption of 57Co-cobalamin was less than 1% and remained abnormal when highly purified human intrinsic factor was given along with the labeled B12. Absorption improved when the labeled B12 was given together with rabbit TCII. The data suggest that TCII as well as intrinsic factor is required for transport of cobalamin from the intestine to the blood.

Failure to Thrive↗
PubMed1990

The optional E. coli prr locus encodes a latent form of phage T4-induced anticodon nuclease.

The optional Escherichia coli prr locus restricts phage T4 mutants lacking polynucleotide kinase or RNA ligase. Underlying this restriction is the specific manifestation of the T4-induced anticodon nuclease, an enzyme which triggers the cleavage-ligation of the host tRNALys. We report here the molecular cloning, nucleotide sequence and mutational analysis of prr-associated DNA. The results indicate that prr encodes a latent form of anticodon nuclease consisting of a core enzyme and cognate masking agents. They suggest that the T4-encoded factors of anticodon nuclease counteract the prr-encoded masking agents, thus activating the latent enzyme. The encoding of a tRNA cleavage-ligation pathway by two separate genetic systems which cohabitate E. coli may provide a clue to the evolution of RNA splicing mechanisms mediated by proteins.

Amino Acid Sequence↗
PubMed1990

Phase I and pharmacology study of intravesical mitoxantrone for recurrent superficial bladder tumors.

A phase 1 study of intravesical mitoxantrone was done in patients with superficial bladder tumors recurrent after previous intravesical therapy. Mitoxantrone (5 to 10.5 mg.) was instilled in the bladder via catheter and was left in situ for 2 hours. Each patient received 6 treatments at 1-week intervals. Pharmacology studies were conducted in a subset of consenting patients. Dysuria, urinary frequency and hematuria were dose-limiting at 10 to 10.5 mg., the dose recommended for our phase 2 studies. One patient treated with 7.5 mg. mitoxantrone had bladder contracture after severe bladder injury caused by the drug. The interval free of recurrence increased in 5 of 8 patients treated with 10 to 10.5 mg. mitoxantrone and in 6 of 19 treated at lower dose levels. One patient who had residual evaluable tumor in the bladder at treatment experienced a complete remission for 16 months. Only 1 of 18 patients who underwent pharmacology studies had any mitoxantrone detectable in the blood after intravesical administration. This patient had severe irritative symptoms at treatment. No systemic toxicity was noted in any patient. Of the mitoxantrone instilled into the bladder 33 to 100% (mean 75%) was recovered in the specimen voided at the end of treatment. In summary, intravesical mitoxantrone is reasonably well tolerated and should be studied further at a dose of 10 mg. per week for 6 weeks. Caution should be exercised, since bladder contracture was seen in 1 patient. Systemic absorption and toxicity are negligible.

Administration, Intravesical↗
PubMed1990

A model preclinical, clinical, and graduate educational curriculum in emergency medicine for medical students and rotating residents.

The Society for Academic Emergency Medicine model curriculum for medical students and rotating residents was developed over a two-year period. The document was created as a complementary work to the undergraduate Core Content to provide appropriate emphasis, structure, and suggestions on the teaching of emergency medicine core curriculum topics at all levels. Consensus on the curriculum contents was reached from a national sample of emergency medicine educators. An educational matrix format was used to enhance flexibility based on the educational level of the learner and the instructional strengths of the teacher, and allowing for incorporation of a problem-based learning format. An outline of document contents and representative samples from each section are included; the entire document is available from SAEM.

Curriculum↗
PubMed1990

The effect of loop diuretics on fluid reabsorption from the rat proximal convoluted tubule.

The effects of the 'loop diuretics' bumetanide, furosemide and piretanide on fluid reabsorption from the rat proximal convoluted tubule have been tested to assess whether a Na(+)-Cl- cotransport mechanism can support fluid reabsorption from this nephron segment. Proximal convoluted tubules were perfused in vivo at 25 nl min-1 with chloride Ringer solutions containing [3H]inulin. Fluid reabsorptive rate (Jv) was 2.05 +/- 0.07 nl mm-1 min-1 (n = 115) from control chloride Ringer. Bumetanide at 10(-6) and 10(-5) M reduced Jv by about 40%. Bumetanide at 10(-7) M, furosemide (10(-4) and 10(-5) M) and piretanide (10(-4) and 10(-5) M) had no effect on Jv. At 10(-3) M, furosemide and piretanide reduced Jv by about 45%. The results show that luminal application of loop diuretics lowers fluid reabsorption from the proximal convoluted tubule and the order of potency for inhibiting reabsorption is bumetanide greater than furosemide identical to piretanide. The specificity of the loop diuretics at their effective concentrations needs to be confirmed, however, before attribution of a role for Na(+)-Cl- co-transport in the support of proximal tubule fluid reabsorption.

Absorption↗
PubMed1990

Effect of vasoactive intestinal peptide, bombesin and substance P on fluid secretion by isolated rat pancreatic ducts.

1. We have used micropuncture techniques to study the regulation of fluid secretion by interlobular ducts isolated from the pancreas of copper-deficient rats. 2. Ducts isolated from different strains of Wistar rats exhibited quantitative differences in basal fluid secretion; however, secretion rates measured in the presence of secretin were similar. 3. Vasoactive intestinal peptide had no effect on fluid transport. 4. Bombesin stimulated fluid secretion, and this effect was abolished by removal of extracellular bicarbonate. 5. Substance P inhibited basal secretion, and that stimulated by bombesin and secretin. These inhibitory effects were partially reversed by spantide. 6. Substance P also inhibited fluid secretion stimulated by dibutyryl cyclic AMP and forskolin. This places the site of inhibition mediated by substance P at a point in the secretory mechanism distal to the generation of cyclic AMP. 7. We conclude that rat pancreatic duct cells possess receptors for bombesin and substance P, in addition to 'secretin-preferring' receptors. Since VIP had no effect on fluid transport, it is unlikely that 'VIP-preferring' receptors are present on rat duct cells.

Animals↗