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Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 235 records · Page 13Linked to original sources
PubMed1995

Learning by internal medicine residents: differences and similarities of perceptions by residents and faculty.

OBJECTIVE: To learn about what enhances or hinders learning in postgraduate medical education. DESIGN AND PARTICIPANTS: Through the use of critical incident interviews, 20 internal medicine residents and 20 attending physicians/faculty were asked to describe specific situations where resident learning had occurred and where it had not occurred. SETTING: A large teaching hospital in the Midwest. MEASUREMENTS AND MAIN RESULTS: Factors positively associated with learning were mentioned frequently (faculty involvement, interaction, and reflection in discussion), and others only rarely (knowing outcomes of effort, resident reading) by both the faculty and the residents. Others were mentioned more often by the residents (feeling relaxed) or by the faculty (technical rationality). CONCLUSIONS: Residents and attendings do not always agree as to what facilitates resident learning. Recognizing actions that residents believe facilitate learning may help faculty more effectively promote resident learning. Because of the similarities of resident training across the country, the results from this study can be applied to other programs.

Data Interpretation, Statistical↗
PubMed1995

Design of ruthenium-cytochrome c derivatives to measure electron transfer to cytochrome c peroxidase.

A new technique has been introduced to measure interprotein electron transfer which involves photoexcitation of a tris(bipyridine)ruthenium (Ru) complex covalently attached to one of the proteins. Four different strategies have been developed to specifically attach Ru to protein lysine amino groups, histidine imidazole groups, and cysteine sulhydryl groups. These strategies have been used to prepare more than 20 different singly-labeled Ru-cytochrome c derivatives. The new ruthenium photoexcitation technique has been used to study the mechanism for electron transfer between cytochrome c and cytochrome c peroxidase. Laser excitation of a complex between Ru-cytochrome c and cytochrome c peroxidase compound I results in formation of Ru(II*) which is a strong reducing agent, and rapidly transfers an electron to heme c Fe(III) to form Fe(II). The heme c Fe(II) then rapidly transfers an electron to the Trp-191 radical cation in CMPI. The rate constant for this reaction is 6 x 10(4) s-1 for a horse Ru-cytochrome c derivative labeled at lysine 27, and greater than 10(6) s-1 for yeast Ru-cytochrome c derivatives. A second laser flash results in electron transfer from heme c to the oxyferryl heme in cytochrome c peroxidase compound II with a rate constant of 350 s-1. The ruthenium photoreduction technique has been used to study the interaction domain between the two proteins, the pathway for electron transfer to the radical cation and the oxyferryl heme, and the specific residues in the heme crevice which control the electron transfer properties of the Trp-191 radical cation and the oxyferryl heme.

Animals↗
PubMed1995

Antennal lobe projection patterns of olfactory receptor neurons involved in sex pheromone detection in Spodoptera littoralis (Lepidoptera: Noctuidae).

Pheromone-specific receptor neurons in male and female cotton leafworms, Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae) were typed physiologically and traced into the antennal lobe using cobalt lysine as a marker. In male S. littoralis, the macroglomerular complex (MGC), which is responsible for the initial integration of information concerning sex pheromone components, contains three glomerular compartments as revealed in a morphological study. No such specialized structure was seen in the female. In the male, olfactory receptor neurons that responded selectively to stimulation with the major sex pheromone component, (Z)9, (E)11-tetradecadienyl acetate (Z9E11-14:OAc), had arborizations that were restricted to a large glomerulus of the MGC (designated a), situated near the antennal nerve entrance into the antennal lobe. Neurons that were stimulated by (Z)9,(E)12-tetradecadienyl acetate (Z9E12-14:OAc), a second pheromone component, had arborizations in a lateral, smaller glomerulus of the MGC (designated c), while receptor neurons specifically tuned to a behavioural antagonist, (Z)-9-tetradecenol (Z9-14:OH), projected to a medial glomerulus of the MGC (b). In the female, receptor neurons tuned to the major pheromone component projected to a glomerulus situated at the entrance of the antennal nerve. This glomerulus did, however, not have the size or the structure of the male MGC. A second neuron housed in the same sensillum projected its axon to an ordinary glomerulus situated medially in the antennal lobe.

Animals↗
PubMed1995

Functional capacities of clonal antibodies to Haemophilus influenzae type b polysaccharide.

Haemophilus influenzae type b (Hib) is an important pathogen for young children, and children can be protected with antibodies (Abs) to Hib polysaccharide (PS) capsule, a linear polymer of ribosyl ribitol phosphate. The structure of anti-Hib-PS Abs has been well characterized at the molecular level; about two-thirds of anti-Hib-PS Abs use a V kappa gene named A2, and the remaining anti-Hib-PS Abs use one of many other VL genes. In order to understand the structural basis for the variability in the function of these Abs, we prepared 18 clonally pure Abs from adults and studied their affinity, avidity, bactericidal potency in vitro, and ability to reduce bacteremia in newborn rats. Affinities and avidities were determined as the inverse of the concentrations of short (3 repeating units) and long (20 repeating units) ligands which could bind 50% of anti-Hib-PS Ab in solution, respectively. No significant correlations between the protection of newborn rats and affinity (r = 0.02) or avidity (r = 0.16) were observed. The amount of Ab required to kill 50% of bacteria in vitro decreased with avidity (r = -0.32), as expected. However, Abs with high affinity were unexpectedly found to have less bactericidal activity (r = 0.38). This suggests that avidity may be a better predictor of Ab function than affinity. Affinity and avidity results were negatively correlated (r = 0.76, P = 0.0022), and Abs that had A2 V kappa gene products had higher avidity (P < 0.05) and lower affinity (P = 0.06) than Abs that had other VL genes. A possible explanation of these observations is that the epitope for Abs with the A2 gene is within the Hib-PS chain itself, whereas the epitope for Abs with a non-A2 gene is the terminus of Hib-PS.

Animals↗
PubMed1995

Induction of ornithine-urea cycle enzymes and nitrogen metabolism and excretion in rainbow trout (Oncorhynchus mykiss) during early life stages

The ornithine&shy;urea cycle (OUC) is present in elasmobranch fish and many terrestrial vertebrates. Recently, a functional OUC has been reported in a few teleost species, suggesting that all teleost fish have the genes for the OUC, but expression is relatively rare. We investigated the possibility that the OUC is expressed during early development in trout as a mechanism for detoxifying ammonia produced from the catabolism of yolk protein. We followed ammonia and urea excretion rates, tissue ammonia and urea levels and OUC enzyme activities in rainbow trout up to 93 days after fertilization. Both ammonia and urea tissue concentrations increased several-fold in the first 40 days after fertilization (embryo stage), peaking at 1.7 mmol N l-1 and 2.5 mmol N l-1, respectively. Ammonia excretion could be detected in 4-day-old embryos, but urea excretion was not initiated until after hatching (day 45). Urea excretion in larval fish (days 42&shy;93) increased several-fold and by day 93 was 14 % of total nitrogen excretion, as found in adult trout. Glutamine synthetase (GSase) and arginase activities were detected in 'whole animal' homogenates just after hatching and the levels of activity increased markedly to day 93. Carbamoyl phosphate synthetase (CPSase) and ornithine transcarbamylase (OTCase) were first detected in 40-day-old embryos; activities peaked between days 53 and 71 and then subsequently decreased. Adult liver enzyme activity for GSase was several-fold lower than in whole larval trout and OTCase and CPSase III (glutamine- and N-acetylglutamate-dependent CPSase catalysing the first step of the OUC) activities were essentially absent in adult liver. We conclude that embryonic and larval trout are primarily ammoniotelic. Urea is synthesized immediately after fertilization, but is not excreted until after the embryo is hatched. The results provide evidence for the presence of the OUC in larval rainbow trout, since four of the OUC enzymes are induced just after hatching and the levels of activity are relatively high compared with those in adult liver tissue. Furthermore, we suggest that all teleosts have retained the OUC genes, which are expressed only during certain stages of development (embryogenesis), and in a few rare species expression is maintained throughout the life cycle to cope with unusual environmental conditions (e.g. alkaline water, air exposure).

Journal Article↗
PubMed1995

Identification of tissue-infiltrating lymphocytes expressing PEN5, a mucin-like glycoprotein selectively expressed on natural killer cells.

PEN5 is a carbohydrate epitope selectively expressed on peripheral blood natural killer cells. We have used a monoclonal antibody reactive with PEN5 to survey the expression of PEN5+ large granule lymphocytes in a variety of human tissues. PEN5+ cells are scattered throughout lymphoid (eg, lymph node, tonsil, thymus, spleen, and intestine) and nonlymphoid (eg, liver, esophagus, lung, and uterus) organs. Due to their relatively abundant cytoplasm, these cells are somewhat larger than resting tissue lymphocytes. The majority of splenic (87 +/- 13%, n = 5) and hepatic (92 +/- 6%, n = 5) PEN5+ lymphocytes coexpress TIA-1, a cytotoxic granule protein found in natural killer cells. In some tissues (eg, tonsil and Peyer's patch), however, relatively few PEN5+ lymphocytes coexpress TIA-1, possibly reflecting different stages of activation or differentiation. Our results indicate that PEN5 may be a useful marker of tissue-infiltrating natural killer cells and reveal these cells to be surprisingly abundant in lymphoid tissues.

Amino Sugars↗
PubMed1995

Mutagenesis.

Choosing the right mutagen means selecting the right combination of mutagen efficiency and mutagen specificity. For mutagen efficiency, nothing beats EMS. It is extremely potent, it is easy to use, and its mutational specificity is well documented. If mutations other than G/C-->A/T transitions are desired, mutagens other than EMS must be used. Based on initial observations, ENU appears to be as efficient as EMS. Work with other organisms predicts that ENU will yield a wider variety of transitions and transversions than EMS. If this proves to be true, ENU will become an important mutagen for routine genetic analysis. For investigators wanting large multigene deletions, gamma irradiation, UV irradiation, formaldehyde, and DEO are the mutagens of choice. Gamma irradiation yields the highest frequency of events by far, but may also yield more complex rearrangements. Based on limited information, UV irradiation, formaldehyde, and DEO appear to be effective deletion mutagens. Of the three, UV appears to be the most efficient. For investigators wanting small intragenic deletions, TMP appears most effective. TMP is not very potent, but a large proportion of TMP-induced unc-22 mutations are small deletions. Hopefully this will be true of all genes. For investigators wanting other types of genome rearrangements (e.g., translocations, crossover suppressors), gamma irradiation (or possibly X irradiation) is effective. For transposon insertions, mut-2 (especially strain TR679) provides the highest possible frequency of events. Because mut-2 activates several families of transposons, it yields insertions in genes that are poor targets for Tc1. Manipulating a strain with such high frequencies of spontaneous mutations, however, can be problematical (see above). For Tc1-specific events, mut-6 (strain RW7097) is the best choice. It provides frequencies comparable to those of Bergerac, but its Tc1 copy number is much lower. A reasonable strategy for spontaneous mutagenesis is to use TR679 only if mutants are not obtained in strains with lower levels of activity (e.g., MT3126 or RW7097).

Animals↗
PubMed1995

Cutaneous metastases from squamous cell carcinoma of the vulva. A case report and review of the literature.

Cancer of the vulva, the fourth most common malignancy of the female genital tract, accounts for approximately 4% of all gynecologic malignancies. Only one prior case of a cutaneous metastasis from a vulvar cancer has been previously reported and involved a FIGO Stage III (T2N1M0) lesion. We report a patient with Stage II (T2N0M0) vulvar carcinoma who developed cutaneous metastases. This case demonstrates the ability of vulvar carcinoma to disseminate hematogenously, despite complete surgical resection with negative skin margins, and negative lymph nodes. In addition, this case emphasizes the importance of careful and close follow-up of all patients with vulvar carcinoma.

Carcinoma, Squamous Cell↗
PubMed1994

Intron-exon organization and chromosomal localization of the human TIA-1 gene.

TIA-1 is a 40-kDa cytotoxic granule-associated RNA-binding protein (p40-TIA-1), the expression of which is restricted to cytolytic lymphocytes. The major granule-associated species is a 15-kDa protein (p15-TIA-1) that seems to be derived from the carboxyl terminus of p40-TIA-1. Although some evidence suggests that p15-TIA-1 is derived from p40-TIA-1 by proteolytic processing, it is also possible that each isoform is derived from discrete mRNA initiated from alternative promoters within the TIA-1 gene. To learn more about the relationship between p15-TIA-1 and p40-TIA-1, we have determined the complete intron-exon organization of the TIA-1 gene. The gene consists of 13 exons separated by 12 intervening sequences and spans greater than 46 kb of DNA located on chromosome 2, band p13. The transcription start site of the mRNA transcript encoding p40-TIA-1 was identified by primer extension and S1 mapping analysis. The putative promoter region preceding this transcription start site stimulated the expression of a reporter gene in transfected Jurkat and YT cells. Attempts to identify a second promoter capable of initiating an mRNA encoding p15-TIA-1 were unsuccessful, supporting the possibility that p15-TIA-1 can be derived from p40-TIA-1 proteolytically. Granule-associated serine proteases that have been implicated in cytolytic lymphocyte killing (granzyme A and granzyme B) were unable to cleave TIA-1, suggesting that processing may occur before TIA-1 enters the cytotoxic granule.

Amino Acid Sequence↗
PubMed1994

Mutagenesis of the hairpin ribozyme.

Extensive in vitro mutagenesis studies have been performed on the hairpin ribozyme and substrate in an effort to refine the overall secondary structure of the molecule and provide further insight into what elements are essential for activity. A secondary structure consisting of four helices and five loop regions remains the basic model as originally proposed. Two helices, helix 1 and 2, form between the substrate and ribozyme while helices 3 and 4 are within the ribozyme itself. Our results suggest that helices 3 and 4 are smaller than previously proposed, consisting of four base pairs and three base pairs respectively. Helix 4 can be extended without loss of activity and loop 3 at the closed end of the hairpin model can be varied in sequence with retention of activity. There is an unpaired nucleotide between helices 2 and 3 consisting of a single A base, suggesting the opportunity for flexibility within the tertiary structure at this point. Comparisons are made between the new data and previously published mutagenesis and phylogenetic data. Substrate targeting rules require base pairing between helices 1 and 2 with cleavage (*) occurring in a preferred 5'(g/c/u)n*guc3' sequence of the substrate.

Base Composition↗
PubMed1994

Activation-induced proteolysis of cytoplasmic domain of zeta in T cell receptors and Fc receptors.

The CD3-T cell receptor (TCR) complex on T cells and the Fc gamma receptor type III (Fc gamma RIII)-zeta-gamma complex on natural killer cells are functionally analogous activation receptors that associate with a family of disulfide-linked dimers composed of the related subunits zeta and gamma. Immunochemical analysis of receptor complexes separated on two-dimensional diagonal gels allowed the identification of a previously uncharacterized zeta-p14 heterodimer. zeta-p14 is a component of both CD3-TCR and Fc gamma RIII-zeta-gamma. Peptide mapping analysis shows that p14 is structurally related to zeta, suggesting that it is either: (i) derived from zeta proteolytically or (ii) the product of an alternatively spliced mRNA. The observation that COS cells transformed with a cDNA encoding zeta express zeta-p14 supports the former possibility. The expression of CD3-TCR complexes including zeta-p14 increases following activation with phorbol 12-myristate 13-acetate or concanavalin A, suggesting that proteolysis of zeta may contribute to receptor modulation or desensitization.

Cells, Cultured↗
PubMed1994

Evidence for involvement of beta-glucan-binding cell surface lectins in human natural killer cell function.

We have studied the effects of yeast cell wall derivatives (zymosan and particulate beta-glucan), on the cytolytic effector function of human natural killer cells. Both zymosan and particulate beta-glucan were found to inhibit the NK-cell-mediated killing of K562, Molt-4, U937, and HL60 tumor cells. Zymosan also inhibited the IL-2-dependent proliferation of NK cells, suggesting that some component of the yeast cell wall delivers a down-modulatory signal affecting multiple NK cell functions. NK cell surface molecules capable of binding both zymosan and Sepharose-immobilized pustulan (linear 1,6-beta-D-glucan, a carbohydrate component of zymosan and particulate beta-glucan) were identified in detergent lysates prepared from surface iodinated NK cells. Our results suggest that NK cells express cell surface beta-glucan-binding lectins that may contribute to NK-cell-mediated natural cytotoxicity.

Cell Wall↗
PubMed1994

Altered endothelin-1 induced contraction and second messenger generation in bovine retinal microvascular pericytes cultured in high glucose medium.

The effect of simulated hyperglycaemia on bovine retinal pericytes was studied following culture of these cells for 10 days under normal (5 mmol/l) and elevated (25 mmol/l) glucose conditions in the absence of endothelial cells. Pericytes cultured under high ambient glucose exhibited both a delayed and reduced contractile response following stimulation with endothelin-1. Stimulation with 10(-7) mol/l endothelin-1 for 30 s caused significant contraction in cells grown in both 5 mmol/l and 25 mmol/l glucose. The former also contracted significantly with 10(-8) mol/l endothelin-1. Further, at all concentrations tested, statistical comparison of the time course of contraction showed a significant difference (p < 0.02) in the reduction of planimetric surface area between the two cell groups. Since neither binding of endothelin-1 nor the number of receptors for this peptide were significantly different (p > 0.1) between bovine retinal pericytes grown for 10 days under normo- or hyperglycaemic conditions, it became apparent that the altered contractility in bovine retinal pericytes following culture in high glucose must be due to post-binding intracellular disturbance(s). Indeed, both basal and 15 s post-stimulation with 10(-8) mol/l endothelin-1, levels of inositol trisphosphate were significantly reduced (p < 0.05 and p < 0.02, respectively) in pericytes cultured for 10 days in 25 mmol/l glucose. These results show that endothelial-independent alterations in contractility of pericytes occur when they are grown in conditions which simulate hyperglycaemia. The results also suggest that the observed attenuation in response to endothelin-1 stimulation evident in pericytes grown under simulated hyperglycaemic conditions is not due to alterations in peptide binding.

Animals↗
PubMed1994

The Tc5 family of transposable elements in Caenorhabditis elegans.

We have identified Tc5, a new family of transposable genetic elements in the nematode Caenorhabditis elegans. All wild-type varieties of C. elegans that we examined contain 4-6 copies of Tc5 per haploid genome, but we did not observe transposition or excision of Tc5 in these strains. Tc5 is active, however, in the mut-2 mutant strain TR679. Of 60 spontaneous unc-22 mutations isolated from strain TR679, three were caused by insertion of Tc5. All three Tc5-induced mutations are unstable; revertants results from precise or nearly precise excision of Tc5. Individual Tc5 elements are similar to each other in size and structure. The 3.2-kb element is bounded by inverted terminal repeats of nearly 500 bp. Eight of the ten terminal nucleotides of Tc5 are identical to the corresponding nucleotides of Tc4. Further, both elements recognize the same target site for insertion (CTNAG) and both cause duplication of the central TNA trinucleotide upon insertion. Other than these similarities to Tc4, Tc5 is unrelated to the three other transposon families (Tc1, Tc3 and Tc4) that transpose and excise at high frequency in mut-2 mutant strains. Mechanisms are discussed by which four apparently unrelated transposon families are all affected by the same mut-2 mutation.

Animals↗