Relativistic bound-state problem in the light-front Yukawa model.
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Journal Article↗
Biomedical subjects
K Wilson
Publications and source records attributed to K Wilson.
Retrieval of p53 protein in paraffin-embedded head and neck tumor tissues.
OBJECTIVES: To improve the detection of p53 protein in formalin-fixed, paraffin-embedded head and neck tumor tissues. DESIGN: Cohort. SETTING: University and Veterans Administration medical centers. PATIENTS OR OTHER PARTICIPANTS: Retrospective samples. INTERVENTION: Surgery for head and neck carcinoma. MAIN OUTCOME MEASURES: Retrieval of p53 antigen. Hypothesis formulated after data collection. RESULTS: An antigen retrieval method facilitated the unmasking of previously inaccessible p53 antigenic determinants in formalin-fixed, paraffin-embedded tissues. This approach has made possible a much more reliable and sensitive immunohistochemical detection of p53 antigen. The procedure is simple, requiring only microwave heating of tissue sections to 100 degrees C in the presence of a zinc sulfate solution. CONCLUSIONS: Antigen retrieval method in formalin-fixed, paraffin-embedded tissue demonstrated a significant increase in p53 immunostaining.
Genes, p53↗
Analysis of the frequency of inheritance of transposed Ds elements in Arabidopsis after activation by a CaMV 35S promoter fusion to the Ac transposase gene.
The Ac/Ds transposon system of maize shows low activity in Arabidopsis. However, fusion of the CaMV 35S promoter to the transposase gene (35S::TPase) increases the abundance of the single Ac mRNA encoded by Ac and increases the frequency of Ds excision. In the experiments reported here it is examined whether this high excision frequency is associated with efficient re-insertion of the transposon. This was measured by using a Ds that carried a hygromycin resistance gene (HPT) and was inserted within a streptomycin resistance gene (SPT). Excision of Ds therefore gives rise to streptomycin resistance, while hygromycin resistance is associated with the presence of a transposed Ds or with retention of the element at its original location. Self-fertilisation of most individuals heterozygous for Ds and 35S::TPase produced many streptomycin-resistant (strep(r)) progeny, but in many of these families a small proportion of strep(r) seedlings were also resistant to hygromycin (hyg(r)). Nevertheless, 70% of families tested did give rise to at least one strep(r), hyg(r) seedling, and over 90% of these individuals carried a transposed Ds. In contrast, the Ac promoter fusion to the transposase gene (Ac::TPase) produced fewer strep(r)hyg(r) progeny, and only 53% of these carried a transposed Ds. However, a higher proportion of the strep(r) seedlings were also hyg(r) than after activation by 35S::TPase. We also examined the genotype of strep(r), hyg(r) seedlings and demonstrated that after activation by 35S::TPase many of these were homozygous for the transposed Ds, while this did not occur after activation by Ac::TPase. From these and other data we conclude that excisions driven by 35S::TPase usually occur prior to floral development, and that although a low proportion of strep(r) progeny plants inherit a transposed Ds, those that do can be efficiently selected with an antibiotic resistance gene contained within the element. Our data have important implications for transposon tagging strategies in transgenic plants and these are discussed.
Arabidopsis↗
Fluorescence properties of subtilisins and related proteinases (subtilases): relation to X-ray models.
The fluorescence properties of six subtilases with known X-ray structure were determined using the same experimental conditions and instrumentation. The steady state and nanosecond lifetime measurements were performed on purified samples of phenylmethanesulphonyl-inhibited proteinases in the presence of 20 mM CaCl2 which stabilizes the molecules. The tryptophan emission quantum yield strongly depends on the local environment and varies from 0.02 to 0.10. The efficiency of tyrosine-to-tryptophan energy transfer also varies (0%-70%) in the different enzymes; the most efficient transfer was observed for thermitase. Experiments with nanosecond excitation indicated that the tryptophan fluorescence of subtilases decays with two exponential components. The X-ray models of the six proteinases were analysed in the region of the tryptophyl residues and were used to explain the observed properties.
Endopeptidases↗
The diagnosis of brain death with Tc-99m HMPAO.
Evaluation of blood flow to the brain using various radiopharmaceuticals can be used to confirm brain death. Agents available for this purpose include Tc-99m HMPAO, Tc-99m pertechnetate, Tc-99m glucoheptonate, and Tc-99m DTPA. The authors evaluated the use of Tc-99m HMPAO in 17 patients suspected of brain death using flow images and static images at several time intervals: immediately, between 30 and 60 minutes, and at 2 hours. These studies were compared to several studies performed with Tc-99m glucoheptonate and Tc-99m DTPA. The results of the Tc-99m HMPAO brain death studies correlated well with the patients' clinical conditions. Static images 1 to 2 hours after the injection of 5 to 30 mCi of Tc-99m HMPAO were satisfactory for an accurate interpretation; however, an immediate answer could as easily be supplied using flow images alone. Tc-99m HMPAO was found to be more easily interpreted and less dependent on imaging technique than Tc-99m glucoheptonate and Tc-99m DTPA, and it is the agent of choice for the evaluation of brain death.
Adolescent↗
Serum profiles of insulin-like growth factors and their binding proteins in adults with growth hormone receptor deficiency treated with insulin-like growth factor I.
Six adult patients with growth hormone receptor deficiency (GHRD) (2 men, 4 women) with an identical defect in the growth hormone receptor (GHR) gene, were treated with recombinant human insulin-like growth factor I (IGF-I), 40 micrograms/kg s.c. twice daily, for 7 days. Serum concentrations of IGF peptide and IGF binding protein-3 (IGFBP-3) were measured by specific radioimmunoassays; serum IGFBPs were also measured by Western ligand blotting. The size distribution of both IGF-I and IGF-II was measured in serum following size-exclusion fast-performance liquid chromatography. IGF-I treatment resulted in a normalization of serum IGF-I levels on days 1-7 of treatment and a decrease in serum IGF-II levels. The fall in IGF-II levels and the simultaneous rise in IGF-I levels, however, resulted in an unchanged total serum IGF level. The low IGFBP-3 values did not significantly change during treatment, whereas there was a slight increase in IGFBP-2 levels. Preliminary analysis of size-fractionated sera suggested an increase in IGF-I levels in the 40 and 150 kDa regions at the expense of IGF-II levels. The results suggest that despite the failure of IGF-I treatment to increase IGFBPs significantly, serum IGFBP concentrations were sufficient to maintain normal levels of IGF-I.
Adult↗
Hormonal and metabolic effects and pharmacokinetics of recombinant insulin-like growth factor-I in growth hormone receptor deficiency/Laron syndrome.
Profound growth failure despite elevated GH levels in GH receptor deficiency (GHRD) results from reduced insulin-like growth factor-I (IGF-I) synthesis. Recent reports of improved growth velocity in children with GHRD during IGF-I therapy indicate growth-promoting potential in humans. We evaluated the pharmacokinetics and metabolic/hormonal effects of recombinant human IGF-I (40 micrograms/kg every 12 h) given sc for 7 days to six adults with GHRD. Hypoglycemia (< 2.5 mmol/L) did not occur, and mean 2 h postprandial insulin levels were reduced. Urinary calcium increased 2-fold (P < 0.01), and serum calcium was unchanged. The mean integrated 24-h GH level was suppressed (6.5 +/- 2.1 to 1 +/- 0.2 micrograms/L), as were the number of peaks, area under the curve, and clonidine-stimulated GH release (all P < 0.05). The mean pretreatment IGF-I level (36 +/- 2 micrograms/L) was 19% of the Ecuadorian control value (190 +/- 15 micrograms/L), it achieved a peak (253 +/- 11 micrograms/L) between 2-6 h after IGF-I injection, and at 12 h it was 137 +/- 8 micrograms/L. There were no significant changes in the half-life (8.2 +/- 1.5 to 9.7 +/- 1.9 h) or metabolic clearance (0.35 +/- 0.1 to 0.24 +/- 0.05 mL/kg.min) between days 1 and 7; however, distribution volume increased (183 +/- 10 to 266 +/- 36 mL/kg; P < 0.03). Baseline IGF-II levels were 47% of the control value and decreased during IGF-I therapy (273 +/- 10 to 178 +/- 9 micrograms/L; P < 0.01), correlating inversely with IGF-I levels (r = -0.3; P < 0.001). Although IGF-binding protein-3 (IGFBP-3) levels were not significantly influenced, baseline IGFBP-2 levels (153% of the control) increased 45% (P < 0.01). We conclude that IGF-I (40 micrograms/kg every 12 h) given sc to adults with GHRD is safe; achieves normal levels of IGF-I; reduces insulin, IGF-II, and GH levels; and increases IGFBP-2 concentrations and urinary excretion of calcium.
Adult↗
Dexamethasone induced ultrastructural changes in cultured human trabecular meshwork cells.
Glucocorticoid-induced ocular hypertension has been demonstrated in both animals and humans. It is possible that glucocorticoid-induced changes in trabecular meshwork (TM) cells are responsible for this hypertension. In order to elaborate further the effect of glucocorticoids on the trabecular meshwork, the ultrastructural consequences of dexamethasone (DEX) treatment were examined in three different human TM cell lines. Confluent TM cells were treated with 0.1 microM of DEX for 14 days, and then processed for light, epifluorescent microscopy or transmission electron microscopy (TEM). The effect of DEX treatment on TM cell and nuclear size was quantified using computer assisted morphometrics. Morphometric analysis showed a significant increase in both TM cell and nuclear size after 14 days of DEX treatment. Epifluorescent microscopy of rhodamine-phalloidin stained, control TM cells showed the normal arrangement of stress fibers. In contrast, DEX-treated TM cells showed unusual geodesic dome-like cross-linked actin networks. Control TM cells had the normal complement and arrangement of organelles as well as electron dense inclusions and large vacuoles. DEX-treated TM cells showed stacked arrangements of smooth and rough endoplasmic reticulum, proliferation of the Golgi apparatus, pleomorphic nuclei and increased amounts of extracellular matrix material. The DEX-induced alterations observed in the present study may be an indication of the processes that are occurring in the in vivo disease process.
Actins↗
The future of the long-term care leader. ACHCA Young Leaders Forum, February 1993.
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Forecasting↗
Non-woven, disposable theatre gowns for 'high-risk' surgery.
The ability to resist fluid penetration was measured in body fabric and forearm seams of standard and reinforced non-woven disposable theatre gowns. Six standard use, non-woven gowns showed water strike-through in the body area at pressures ranging between 12.1 +/- 0.8 cmH2O and 23.2 +/- 2.2 cmH2O (means +/- 95% confidence interval). Two products resisted fluid penetration of the forearm seam at pressures similar to that of the fabric alone (16.8 +/- 1.0 cmH2O and 18.6 +/- 0.9 cmH2O respectively) but other standard gowns leaked at significantly lower pressures (range 4.6-6.9 cmH2O). (P < 0.05, Mann-Whitney U test). Six of seven high-protection gowns proved fluid resistant at a pressure in excess of 50 cm in the reinforced body zone but four reinforced gowns leaked at stitched arm seams at a pressure of less than 10 cmH2O despite an inner impermeable layer of fabric covering the forearm. Three gowns with heat or adhesive sealed reinforced arm seams resisted fluid penetration up to a pressure of 50 cmH2O. Standard gowns and some reinforced gowns do not offer full protection against forearm contamination through stitched seams. A gown with sealed seams and impermeable fabric should be chosen for high-risk cases.
Disposable Equipment↗
Crystallization and preliminary X-ray analysis of a fungal endoglucanase I.
An endoglucanase I (EG1) from a fungal source (Humicola insolens) has been crystallized in a number of forms suitable for X-ray diffraction analysis. Four crystal forms have been grown from various precipitants using vapour phase diffusion methods in hanging drops. Three of these crystal forms diffract to beyond 2.5 A resolution. Two forms, obtained from ammonium sulphate at pH 5.4, or 8.0, grow as tetragonal bipyramids in space group P4(1)22 or P4(3)22, with approximate cell dimensions a = b = 102 A, c = 282 A. The other crystal forms were grown from polyethylene glycol 8000 at pH 8.0. One grows as monoclinic plates, space group P2(1), with cell dimensions a = 66.9 A, b = 75.2 A, c = 86.9 A and beta = 102.9 degrees and the other as long hexagonal rods in space group P6(1)22 or P6(5)22, with cell dimensions a = b = 119 A, c = 83 A.
Cellulose 1,4-beta-Cellobiosidase↗
Crystallization and preliminary crystallographic studies of glucosamine-6-phosphate deaminase from Escherichia coli K12.
Hexameric glucosamine-6-phosphate deaminase from Escherichia coli has been crystallized isomorphously with both phosphate and ammonium sulphate as precipitants, over a wide pH range (6.0 to 9.0). The crystals belong to space group R32 and the cell parameters in the hexagonal setting are a = b = 125.9 A and c = 223.2 A. A complete native data set was collected to 2.1 A resolution. Self-rotation function studies suggest that the hexamers sit on the 3-fold axis and have point group symmetry 32, with a non-crystallographic dyad relating two monomers linked by an interchain disulfide bridge. A possible packing for the unit cell is proposed.
Aldose-Ketose Isomerases↗
Molecular cloning and immunological characterization of porcine kidney ferredoxin.
Porcine renodoxon is a kidney mitochondrial iron-sulfur protein (ISP) that functions to transfer electron to cytochromes P450 of the vitamin D pathway. A full-length cDNA clone to porcine renodoxin was isolated in the current investigation and used to study the protein's primary structure and immunological properties. The cysteine ligands for the iron-sulfur center, and the surface protein-binding and phosphorylation sites occupied identical positions in both porcine renodoxin and bovine adrenodoxin. Furthermore, porcine renodoxin was functionally indistinguishable from bovine adrenodoxin and the mature forms of both proteins had the same encoded length and shared approximately 91% sequence similarity. A synthetic peptide to the surface protein-binding region was used to demonstrate the antigenicity of the domain in both the porcine and the bovine ISPs. However, porcine renodoxin displayed only limited immunological identity to other regions of bovine adrenodoxin as measured by competitive enzyme-linked immunosorbent assay. Part of this immunological distinction was attributed to the COOH-terminal processing of porcine renodoxin, an action which negated expression of a COOH-terminal antigenic site that is present in bovine adrenodoxin. Other antigenic differences were linked to charged-residue substitutions that were located in predicted surface domains. The highest frequency of surface-residue substitutions in ferredoxin proteins was predicted for porcine renodoxin, which could provide a basis for understanding why the pig protein appears more antigenically divergent than other ferredoxins.
Adrenodoxin↗
Cloning of the gene encoding Leishmania donovani S-adenosylhomocysteine hydrolase, a potential target for antiparasitic chemotherapy.
A full-length gene encoding the S-adenosylhomocysteine hydrolase (AdoHcyase) enzyme has been isolated from a genomic library of Leishmania donovani DNA in lambda GEM-11 by cross-hybridization to the full-length human AdoHcyase cDNA. The nucleotide sequence of the SalI fragment contained a single open reading frame that encoded a polypeptide of 438 amino acids (47,712 Da). After maximum gap alignment, the predicted amino acid sequence of the leishmanial AdoHcyase was 70-73% identical to AdoHCyases from higher eukaryotes. In addition, a data base search revealed that the primary structure of all AdoHcyase proteins was highly homologous to that of a protein encoded by a mRNA from Drosophila melanogaster that maps near the r element function of the Abd-b homeotic gene. In Northern blots, the SalI fragment hybridized to a 3.0-kb transcript that presumably encodes the parasite enzyme. Southern blot analysis of genomic DNA revealed that the AdoHcyase gene did not exist as a tandemly repeated array within the L. donovani genome. Moreover, monoclonal antibodies generated against human AdoHcyase recognized a leishmanial protein on immunoblots. Finally, the growth of L. donovani promastigotes could be arrested by micromolar concentrations of 3-deazaaristeromycin (C3Ari) and 9-(trans-2',trans-3'-dihydroxycyclopentanyl)adenine, 2 known inhibitors of mammalian AdoHcyase. C3Ari also induced a substantial expansion of the intracellular pools of both AdoHcy and S-adenosylmethionine (AdoMet), as well as a significant diminution of the AdoMet/AdoHcy ratio. Thus, AdoHcyase may have therapeutic potential for the selective treatment of diseases of parasitic origin.
Adenosine↗
Purification of glutathione reductase from muscle of the adult parasitic nematode Ascaris suum.
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Animals↗
Stable amplification of a linear extrachromosomal DNA in mycophenolic acid-resistant Leishmania donovani.
Pulsed field gel electrophoretic analysis of chromosomes of MPA100 cells, a strain of Leishmania donovani that possesses an approx. 15-fold amplified IMP dehydrogenase (IMPDH) gene copy number, revealed a new 280-kb extrachromosomal DNA, IMPDH-280, that was not present in wild type parental cells. Southern blots of these pulsed field gels revealed that the vast majority of the amplified impdh genes were localized on IMPDH-280. In addition to the 700-kb wild type chromosome, the impdh probe also recognized a 740-kb chromosome in the MPA100 genome. The pulse time-dependent relative mobility of IMPDH-280 in pulsed field gels, the failure of limited gamma-irradiation to generate a new discrete DNA fragment, and the susceptibility of IMPDH-280 to lambda-exonuclease digestion, demonstrated that IMPDH-280 was a linear molecule. IMPDH-280 was also recognized by a telomere probe but not by fragments derived from amplified DNAs found in other drug-resistant Leishmania. IMPDH-280 and the drug resistance phenotype remained stable when MPA100 cells were propagated in the absence of drug for 2 years. The appearance of IMPDH-280 in MPA100 cells represents one of the first examples of an amplification of a linear extrachromosomal DNA element mediating drug resistance in Leishmania and the first instance of a linear DNA amplification that is stable in the absence of selective pressure.
Animals↗
Systemic infusion versus bolus chemotherapy with 5-fluorouracil in measurable metastatic colorectal cancer.
From January 31, 1986 to January 31, 1989, 184 eligible patients were enrolled in a randomized study of either infusional or bolus 5-fluorouracil (5-FU) for the treatment of metastatic measurable colorectal cancer. Infusion was administered at an escalated dose schedule starting at 350 mg/m2 per day for 2 weeks with a 2-week rest period on a monthly basis, while bolus 5-FU was started at 400-450 mg/m2 for 5 days every 28 days. In these chemotherapy-naive patients with good performance status, the infusion arm produced a response in 11 of 88 patients versus 6 of 82 in the bolus arm (p = 0.384). Progression free survival was significantly longer (p = 0.0139) in the infusion group (3.8 versus 2.3 months), but no significant difference in survival was observed (p = 0.207). As expected, the toxicities of the regimens were different in character, but each had approximately a 20% incidence of significant toxicities. Neither of these methods of administering fluorouracil results in an exceptional response rate, nor does the infusion have an impact on survival as compared to the bolus route. If this type of complicated infusional approach is to continue, especially with increasing dosage (which could be accomplished on our schedule), randomized studies with survival as an endpoint must remain the gold standard.
Adult↗
Modified adriamycin-vincristine-dexamethasone (m-VAD) in primary refractory and relapsed plasma cell myeloma: an NCI (Canada) pilot study. The National Cancer Institute of Canada Clinical Trials Group.
The purpose of this single arm phase II study was to test a modified version of the three drug combination vincristine, adriamycin and dexamethasone (m-VAD), in which intravenous vincristine (0.4 mg/d) and adriamycin (9 mg/m2 per day) infusions are administered for only 2 h on days 1-4 of each 28 d cycle, in patients with refractory multiple myeloma. In addition, only two 4 d courses of dexamethasone 40 mg/d was given during each cycle. The entry criteria for 44 patients included plasma cell myeloma and a measurable monoclonal peak, either refractory to initial treatment with melphalan and prednisone, or resistant to melphalan and prednisone after initially responding (resistant relapsed disease, 27 patients). Patients treated previously with chemotherapy other than melphalan and prednisone were excluded. There were no complete responses. Of the 41 evaluable patients who completed at least one course of therapy 11 had a partial response (27%, 95% C.I. 14-40%). The response rates were 19% for primary refractory disease patients, and 32% for those with resistant relapsed disease. The median duration of response was 4 months. The median survival for all 44 patients was 7.6 months (5.5 months for primary refractory patients, and 10 months for relapsed resistant disease patients). Episodes of documented bacterial infection occurred in 12 patients, and 10 patients had minor viral infection. The dexamethasone dose was reduced in 12 patients. The median neutrophil nadir was 1.2 x 10(9)/l, and median platelet nadir was 147 x 10(9)/l. Five deaths were judged as treatment related and occurred during marrow cytopenia. The results of this modified form of VAD are inferior to that reported previously for 4 d continuous infusions of vincristine and doxorubicin. This could be related to either patient selection factors, or to a reduction of the efficacy of the drug combination produced by either the shortened intravenous infusions and/or omission of one 4 d course of dexamethasone.
Aged↗