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Biomedical subjects

P Norris

Publications and source records attributed to P Norris.

At least 37 records · Page 2Linked to original sources
PubMed1997

5-Deoxy-5-C-(5-ethoxycarbonyl-1,2,3,- triazol-1-yl)-1,2-O-isopropylidene-alpha-D-xylofuranose.

Two unrelated molecules of the title compound, ethyl 1-(5-deoxy-1,2-O-isopropylidene-alpha-D-xylofuranos-5-C- yl)-1,2,3-triazole-5-carboxylate, C13H19N3O6, that are not linked by hydrogen bonding, comprise the asymmetric unit. There are no unusual bond lengths or angles. The two molecules differ in the degree of rotation around the methylene C atom that joins the triazole ring to the sugar part of the molecule. Molecules of the same conformation form infinite chains joined by hydrogen bonding between a H atom on the hydroxyl group of one molecule and an N atom in the triazole ring of another molecule generated by the 2(1) screw axis. Relevant intermolecular N...O distances are 3.013 (3) and 2.806 (3) A.

Crystallization↗
PubMed1997

Humanized anti-CD4 monoclonal antibody therapy of autoimmune and inflammatory disease.

We have investigated the biological and therapeutic properties of a humanized anti-CD4 MoAb, hIgG1-CD4, in patients with refractory psoriasis and rheumatoid arthritis (RA). hIgG1-CD4 is a modulating, non-depleting MoAb, which induced a first-dose reaction in most patients treated. It provided brief symptomatic relief in both conditions, and psoriasis appeared easier to control with conventional agents after MoAb therapy. At the doses used, hIgG1-CD4 did not synergize therapeutically with the panlymphocyte MoAb CAMPATH-1H (C1H) in patients with RA treated sequentially with both agents. There were no serious adverse effects definitely attributable to therapy. Our results are compared with those of other CD4 MoAb studies, and factors influencing the outcome of therapy are discussed.

Adolescent↗
PubMed1996

Characterization and interconversions of 2-S-ethyl-2-thio-D-mannose diethyl dithioacetal and the facile epimerization of 2-thio-D-mannopyranose derivatives.

3,4,5,6-Tetra-O-benzoyl-D-glucose diethyl dithioacetal (2) reacts with ethanethiol under acidic conditions to afford 3,4,5,6-tetra-O-benzoyl-2-S-ethyl-2-thio-D-mannose (3), the stereochemistry at C-2 of which has been assigned by chemical conversions on its debenzoylated derivative, the crystalline 2-S-ethyl-2-thio-D-mannose diethyl dithioacetal (4). In the presence of mercuric chloride (1.1 molar equiv), 4 is converted into crystalline ethyl 2-S-ethyl-1,2-dithio-alpha-D-mannofuranoside (5). Complete demercaptalation of 4 affords syrup 2-S-ethyl-2-thio-D-mannopyranose (6), which was characterized as its phenylhydrazone 7 and the crystalline alpha-pyranose tetraacetate 9. Extended treatment of 4 with mercuric chloride and aqueous sodium hydrogencarbonate resulted in isolation of 6, along with its crystalline 2-epimer, 2-S-ethyl-2-thio-beta-D-glucopyranose (10). Remercaptalation of 6 affords the manno diethyl dithioacetal 4 as the major product, whereas similar treatment of 10 yields ethyl 2-S-ethyl-1,2-dithio-alpha-D-glucopyranoside (13). The mechanism of conversion of 2 into 3, as well as the unusually facile interconversion of 2-S-ethyl-2-thio-D-mannose (6) and its D-gluco epimer 10, has been investigated.

Acetals↗
PubMed1996

Somatic hypermutation of Ig genes in patients with xeroderma pigmentosum (XP-D).

Antibody diversification by somatic hypermutation occurs by the introduction of nucleotide substitutions in and around the rearranged Ig V gene segments. Several characteristics of the process suggest that the introduction of mutations is linked to Ig gene transcription. Since there is a connection between mutation and repair with indications that both processes might show linkage to transcription, we asked whether defects in a component of the transcription factor TFIIH which lead to an inability to carry out nucleotide excision repair also affect somatic hypermutation. A PCR strategy was devised that required small samples of peripheral blood and enabled us to monitor hypermutation of a single, abundantly used VH gene. However, the results showed that in xeroderma pigmentosum patients (complementation group D), somatic hypermutaton appears to take place unaffected as regard both extent and distribution.

Genes, Immunoglobulin↗
PubMed1995

Ranitidine-induced photosensitivity.

We report the case of a 72-year-old male patient who developed a florid photosensitive eruption while on ranitidine therapy. Ultraviolet A sensitivity was detected by irradiation monochromator testing, suggesting drug-induced photosensitivity. Ranitidine was concluded to be the cause of his photosensitivity since the eruption resolved and the phototest abnormalities returned to normal following cessation of therapy. Similar cases have been reported to the Committee on Safety of Medicines but not published.

Aged↗
PubMed1994

Measurement of mRNA for E-selectin, VCAM-1 and ICAM-1 by reverse transcription and the polymerase chain reaction.

Stimulation of cultured human umbilical vein endothelial cells by cytokines such as interleukin-1 and tumour necrosis factor induces de novo synthesis and expression of the adhesion molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). In general, alterations in cell surface expression of these molecules are known to be related to increased gene transcription and altered levels of mRNA. The extension of these observations to the study of inflammatory processes in different human organs necessitates the development of techniques for the quantification of mRNA in small tissue samples. Here we present a method for the quantification of mRNA for E-selectin, VCAM-1 and ICAM-1 using reverse transcription and the polymerase chain reaction (RT-PCR). For each molecule of interest a mutant RNA was synthesised consisting of the wild-type sequence deleted of 15-20 bases. The mutant and wild-type RNA sequences are recognised by the same primers, and can therefore be amplified competitively in the same tube by RT-PCR. As the mutant and wild-type RNAs compete for the primers, the amount of wild-type RNA can be determined by the size of the dominant product that results after addition of known quantities of mutant RNA. Using this detection and quantification method we have examined the dose dependency and time course of mRNA accumulation following TNF-alpha stimulation of HUVEC. Similar time-courses of E-selectin, ICAM-1 and VCAM-1 mRNA accumulation were observed by competitive RT-PCR as by laser densitometry of Northern blots. Finally we were able to show that the technique could measure changes in levels of mRNA for these three molecules in human skin biopsies taken at different times during the development of a delayed hypersensitivity response to tuberculin purified protein derivative. This technique should be useful for the study of adhesion molecule mRNA in small tissue culture samples and in biopsies.

Base Sequence↗
PubMed1994

Age and sex modulate effects of stress on the immune system: a multivariate analysis.

Multivariate analyses indicate that both age and sex can modulate examination stress effects on immune factors. Stress lowered eosinophil counts in females but raised them in males. Age modulated stress effects on CD4 and CD8 cells, hemoglobin, and erythrocytes. CD4 decreased more in older subjects; CD8 increased in older and decreased in younger subjects; hemoglobin decreased in younger but not older subjects; erythrocytes increased in older and decreased in younger subjects. Initial age and/or sex differences in levels of neutrophils and lymphocytes were not statistically altered by stress. Stress effects not modulated by age or sex increased serum IgA and IgM, CD19, and stimulated phagocytic activity but decreased serum IgG, CD3, basophils, and unstimulated phagocytic activity. The immunological effects of stress are multiple and are influenced by variations in age and sex of the person.

Adult↗
PubMed1993

Oral psoralen photochemotherapy in severe childhood atopic eczema: an update.

Over a 6-year period, oral psoralen photochemotherapy (oral PUVA) has been used to treat 53 children (mean age 11.2 years) with severe atopic eczema unresponsive to other therapy. Twice-weekly treatment resulted in clearance or near-clearance of disease in 39 (74%) after a mean of 9 weeks. Thirty-two (82%) of these 39 children were subsequently able to achieve remission of disease following gradual withdrawal of treatment; the mean duration of treatment to remission was 37 weeks; the mean cumulative UVA dose was 1118J/cm2, and the mean number of treatments was 59. Twenty-two remain in remission a year after discontinuing treatment. Short- and medium-term adverse effects, other than occasional intolerance of treatment, have not been prominent. Despite anxieties about possible long-term hazards, it is our view that oral PUVA is justified in a small proportion of older children with disabling atopic eczema. We believe that it has substantial advantages over other therapeutic options in selected cases, particularly in providing improved growth and an opportunity for sustained remission.

Adolescent↗
PubMed1992

A comparison of alexithymia in American and Japanese dialysis patients.

A comparison of alexithymia in American and Japanese dialysis patients was performed using the Beth Israel Hospital Questionnaire (BIQ) and the MMPI Alexithymia Scale (MMPI-AS) including structured interviews. No significant differences between the USA and Japan were observed in all dialysis patients with both BIQ and MMPI-AS. However, the alexithymia score in US hemodialysis (HD) patients was significantly lower than that in Japanese HD patients, whereas the alexithymia score in American continuous ambulatory peritoneal dialysis (CAPD) patients was significantly higher than that in Japanese CAPD patients. These results may suggest the possibility that the differences in dialysis policy between USA and Japan have secondary effects on alexithymia, which is one of the psychosomatic factors reflecting self-control ability in dialysis patients.

Adult↗
PubMed1991

Synthesis and biochemical studies of dithioate DNA.

Dithioate DNA was synthesized and used for various biochemical studies. Results from these studies indicate that dithioate DNA is a potent inhibitor of HIV Reverse Transcriptase, activates endogenous RNase H in HeLa cell nuclear extracts, and is a useful probe for studying protein-DNA interactions.

Base Sequence↗
PubMed1991

Allergic contact dermatitis to two antioxidants in latex gloves: 4,4'-thiobis(6-tert-butyl-meta-cresol) (Lowinox 44S36) and butylhydroxyanisole. Allergen alternatives for glove-allergic patients.

Allergic contact dermatitis developed on the hands and/or face of two patients after exposure to latex examination gloves. Both patients were patch test negative to the usual rubber allergens, but both had a positive patch test reaction to 4,4'-thiobis(6-tert-butyl-m-cresol) (Lowinox 44S36). Patient 2 was also patch test positive to butylhydroxyanisole. The patients were tested with other gloves, to find gloves that they could safely use. Glove manufacturers were queried to ascertain the occurrence of Lowinox 44S36 and butylhydroxyanisole in different brands of latex and vinyl examination gloves. A list of gloves and their associated allergens was generated and is provided to assist dermatologists in helping patients choose gloves free of specific allergens.

Allergens↗
PubMed1991

The expression of endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in experimental cutaneous inflammation: a comparison of ultraviolet B erythema and delayed hypersensitivity.

Endothelial cell adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are cytokine-regulated cell surface molecules involved in leukocyte adhesion. We have studied two forms of cutaneous inflammation to investigate in vivo the kinetics of adhesion molecule expression in relation to tissue accumulation of leukocytes. Immunohistology was performed on skin biopsies taken from human volunteers at 1, 6, 24, 72 h, and 1 week after two minimal erythema doses (MED) of ultraviolet B (UV-B) or intra-cutaneous tuberculin-purified protein derivative (PPD) (10-100 U). ELAM-1 expression on vascular endothelium and polymorphonuclear leukocyte infiltration were first observed at 6 h and maximal at 24 h after both UV-B and PPD. At 72 h and 1 week, however, endothelial ELAM-1 was more strongly expressed in PPD biopsies. VCAM-1 was minimally expressed in control skin, and was induced above background levels on endothelium, on some perivascular cells, and on stellate-shaped cells in the upper dermis at 24 h after injection of PPD; it was maintained up to 1 week. In contrast, no induction of VCAM-1 was seen following challenge with either 2 or 8 MED UV-B. Following PPD, but not UV-B, there was marked induction of ICAM-1 expression on basal keratinocytes. In these biopsies, the inflammation induced in response to PPD therefore differed from UV-B-induced inflammation in showing prolonged expression of endothelial ELAM-1, induction of VCAM-1 on endothelium and other cells, and induction of keratinocyte ICAM-1. These differences may result from differences in the cytokines released and may in turn be responsible for the differences in the nature of the leukocytic infiltration during the two types of inflammatory response.

Cell Adhesion↗