To determine the risk of cutaneous neoplasia following photochemotherapy (PUVA), we reviewed patients with psoriasis treated at our unit between 1979 and 1991. Two hundred and forty-five patients were assessed, with a median duration of follow-up of 9.5 years. Fifty-nine per cent were male, and 41% female. The median number of exposures was 59, and the median total dose was 133 J/cm2 for the group as a whole. Non-melanoma skin cancers (NMSC) occurred in six individuals (2.4%). Basal cell carcinoma occurred in all six and one individual also developed four squamous cell carcinomas and Bowen's disease of the penis. No cases of malignant melanoma were recorded. Patients who developed NMSC received a median number of 225 exposures and a median cumulative dose of 654 J/cm2. Compared with a control study population in West Glamorgan, Wales, there was a 1.4 (95% confidence limits (CL) 0.5 and 3.1) times increased risk of NMSC. A statistically significant increased incidence of NMSC was found for patients who had received 100 or more exposures, and 250 or more J/cm2, with risks of 3.7 (95% CL 1.0 and 9.5), and 4.0 (95% CL 1.1 and 10), respectively. A PUVA dose of < 250 J/cm2 or < 100 exposures conferred a minimal increase in risk of NMSC in our study population.

Adult↗

PubMed1996

Specific cleavage of histidine-containing peptides by copper(II).

Copper(II) cleaves with moderate specificity peptides containing Ser-His or Thr-His sequences, at the N-terminal side of the hydroxyaminoacyl residue. The reaction is slow, and is first-order in peptide: CuII complex, with a half-life of several hours at 62 degrees C in sodium bicarbonate buffer, pH 8. Cleavage of other histidine-containing peptides also occurs, at a rate around 10-100-fold less. EDTA completely quenches the cleavage. The reaction is stoichiometric in CuII and is inhibited by amine-containing buffer components; Tris at 19 mM inhibits cleavage by 50%. The reaction has a complex pH-dependence, being very slow below pH 5, and with rates increasing with pH from pH 7 to pH 9.5. Slower degradative side reactions do occur, with destruction of tyrosine residues, particularly in the presence of high concentrations of chloride ion, but the specific cleavage appears to be a hydrolysis, as determined by amino-acid analysis and mass spectrometry of the products. The cleavage is clearly different from the previously described oxidative degradation of proteins catalysed by copper ions. Cleavage of denatured IgG protein occurs with sufficient specificity to reveal distinct bands on SDS-polyacrylamide gel electrophoresis under reducing conditions.

Copper↗

PubMed1996

Specific cleavage of immunoglobulin G by copper ions.

The hinge region of a recombinant-DNA-produced human IgG1 (Campath 1H) is specifically cleavable at a single copper-sensitive peptide bond, yielding a distinct fragment resolved by size-exclusion high-performance liquid chromatography. This novel metal ion-catalysed cleavage at slightly alkaline pH is inhibited by EDTA and its rate is reduced at slightly acidic conditions (pH 5-6) and accelerated by increasing concentrations of cupric ion and higher temperature. Complete cleavage was observed after incubation at pH 8 for 24 h with 1 mM CuCl2. Sequence analysis determined the cleavage site to be the Lys226-Thr227 bond in the hinge-region sequence DKTHT. Cleavage of other IgGs was observed to varying degrees, and specific cleavage of synthetic peptides containing this pentapeptide sequence was also observed.

Alemtuzumab↗

PubMed1996

Long-lasting allergic patch test reactions to nickel sulfate: analysis by nickel quantification and immunocytochemistry.

We previously showed the median duration of positive patch test reactions to nickel sulfate (5% pet.) was 9 days, and defined as long-lasting (LLAPTR) the 14.3% of reactions that persisted for 17 days or longer. The pathomechanisms of LLAPTR are unclear, but may involve either localized antigen persistence or abnormal downregulation of the cellular immune response. In this study, we compared (a) the nickel concentration and (b) the immunocytochemical nature of the local immune reaction, between biopsies from LLAPTR (n = 8) and normally resolving allergic patch test reactions (NRAPTR) (n = 8) to nickel sulfate. The concentration of nickel in LLAPTR (median 0.56 microgram/g, range 0.25-3.87 micrograms/g, mean 0.83 microgram/g, 95% CI 0.35-1.31) and NRAPTR (median 0.58 microgram/g, range 0.2-1.85 micrograms/g, mean 0.88 microgram/g, 95% CI 0.02-1.74) was similar. Activated T lymphocytes, expressing surface IL-2 receptor, HLA DR, DR alpha 1, DP, DQ, and CD2 > CD8 > CD4 antigens, were seen throughout the dermis and occasionally infiltrating the suprabasal layer of the epidermis in all biopsies. CD1 and HLA DR, DR alpha 1, DP, and DQ-expressing Langerhans cells were present throughout the epidermis and occasionally seen in the papillary dermis. HLA DR, DR alpha 1, DP, and DQ antigen expression were also seen on the surface of non-dendritic cells in the epidermis (probably either keratinocytes or T lymphocytes) and vascular endothelial cells in the papillary dermis. There were no significant qualitative or quantitative differences in the immunocytochemical nature of the localized immune reaction between LLAPTR and NRAPTR. These findings suggest that the pathomechanism of LLAPTR to nickel sulfate is unlikely to be explained simply on the basis of nickel concentration or the nature of the localized immune reaction at the patch test site.

Adult↗

PubMed1996

Comparison of outdoor and classroom ozone exposures for school children in Mexico City.

To evaluate methods of reducing exposure of school children in southwest Mexico City to ambient ozone, outdoor ozone levels were compared to indoor levels under three distinct classroom conditions: windows/doors open, air cleaner off; windows/doors closed, air cleaner off; windows/doors closed, air cleaner on. Repeated two-minute average measurements of ozone were made within five minutes of each other inside and outside of six different school classrooms while children were in the room. Outdoor ozone two-minute average levels varied between 64 and 361 ppb; mean outdoor levels were above 160 ppb for each of the three conditions. Adjusting for outdoor relative humidity, for a mean outdoor ozone concentration of 170 ppb, the mean predicted indoor ozone concentrations were 125.3 (+/- 5.7) ppb with windows/doors open; 35.4 (+/- 4.6) ppb with windows/doors closed, air cleaner on. The mean predicted ratios of indoor to outdoor ozone concentrations were 0.71 (+/- 0.03) with windows/doors open; 0.18 (+/- 0.02) ppb with windows/doors closed, air cleaner off; and 0.15 (+/- 0.02) ppb with windows/doors closed, air cleaner on. As outdoor ozone concentrations increased, indoor ozone concentrations increased more rapidly with windows and doors open than with windows and doors closed. Ozone exposure in Mexican schools may be significantly reduced, and can usually be kept below the World Health Organization (WHO) guideline of 80 ppb, by closing windows and doors even when ambient ozone levels reach 300 ppb or more.

Air Pollution↗

PubMed1995

Transcription of interferon-alpha 2 alleles from virus-induced human leucocytes and lymphoblastoid cells of African origin.

It has been previously shown that the genomic DNA of both the lymphoblastoid cell line (Namalwa) and certain human donors (of African origin) contain sequences corresponding to two allelic variants, b and c, of the interferon-alpha 2 gene (IFNA2). Little is known however about the relative expression of these two alleles in heterozygous cells. We have therefore examined the transcription of allelic variants of the human IFNA2 locus by both normal human leucocytes (from a heterozygous donor) and Namalwa cells. Analysis of cDNA clones identified sequences of both allelic variants, IFNA2b and c, indicating active transcription by both cell types. Analysis of tryptic and peptic peptides derived from purified IFN-alpha 2 also demonstrated both IFN-alpha 2b and IFN-alpha 2c proteins. Populations of virus induced heterozygous cells can therefore effectively transcribe and secrete both forms of IFN-alpha 2 simultaneously, with no apparent restrictions on expression of either allele.

Alleles↗

PubMed1995

Meeting infection control standards in the OR.

Quality health care is associated with the absence of negative outcomes in patients. Institutions realize that quality cannot be assured but it can be assessed and methods can be developed to improve patient care. Many heath care institutions, therefore, have begun the conceptual transition from quality assurance model to principles of continuous quality improvement (CQI). This article describes a CQI project that was developed to enhance infection control standards in OR settings. The project involved three phases: development of a survey tool, implementation of an environmental assessment and monitoring model, and transfer of the model to OR staff members. Five months after implementation of the model, the chi-square test revealed there was a significant improvement in compliance (chi 2 = 5.0, P < .03). After 22 months of using the model, compliance to infection control standards remains high and OR staff members have taken ownership of the model by incorporating it into their departmental CQI process.

Hospitals, University↗

PubMed1995

Linear IgA disease (LAD): immunoglobulin deposition in oral and colonic lesions.

Two cases of adult linear IgA disease (LAD) with oral and colonic involvement are presented. Oral findings, for both patients, were of widespread painful ulceration present for two to three months and diagnosis was confirmed by biopsy and direct immunofluorescence. Colonic symptoms preceded oral symptoms in both cases and a number of investigations were undertaken, including routine histological examination, which suggested either lymphocytic colitis or Crohn's disease. Immunofluorescence studies showed linear IgA deposition confined to the distal colon. These cases highlight that large bowel involvement can be a feature of linear IgA disease and for the first time demonstrate IgA deposition at that site.

Aged↗

PubMed1995

Partial N-terminal sequences of larval cuticular proteins from the dipteran Ceratitis capitata.

The partial amino acid sequences ranging in length over 17-30 residues from the N-terminus, have been obtained for nine cuticular proteins of Ceratitis capitata. Sequence similarities indicate that the proteins belong to a family which is related to cuticular proteins isolated from flexible cuticles of Drosophila melanogaster, Manduca sexta, Sarcophaga bullata and Hyalophora cecropia.

Amino Acid Sequence↗

PubMed1995

Major histocompatibility complex class I-restricted cytotoxic T-lymphocyte responses in horses infected with equine herpesvirus 1.

An experimental system that permits sensitive and reproducible detection of equine herpesvirus 1 (EHV-1)-specific cytotoxic T-lymphocyte (CTL) activity in the horse was developed. Peripheral blood mononuclear cells (PBMC) collected from immune horses were restimulated in vitro by culture with live EHV-1. Cytotoxic activity against virus-infected, pokeweed mitogen-stimulated lymphoblast targets was assessed in a 4-h 51Cr release assay. The optimal conditions for in vitro stimulation of equine memory CTLs and for preparation of EHV-1-infected target cells expressing viral antigens were systematically identified by individually testing the effects of variations in responder cell concentration, culture medium composition, serum type, incubation time, antigen form, and exogenous mediator content. By using this optimized system for generation and assay of equine CTLs, the development of EHV-1-specific cytotoxic responses in 12 horses was evaluated after experimental viral infection. CTLs with the capacity for killing EHV-1-infected target cells were detected in equine PBMC as early as 1 week postinfection, reached maximal levels by 2 to 3 weeks, and remained detectable for a year after infection. Equine effector cells mediating lysis of EHV-1-infected targets were predominantly CD8+ T lymphocytes, and the cytotoxicity was specific for virus and restricted by major histocompatibility complex class I molecules. The results define a reliable and convenient experimental system for generation and assay of EHV-1 CTLs which can now be used for more-detailed characterization of the equine CTL response to infection by this herpesvirus pathogen.

Animals↗

PubMed1995

Acute effects of ozone on the pulmonary function of exercising schoolchildren from Mexico City.

The acute effects of ozone (O3) on the change in lung function before and after exercise was assessed in 22 boys and 18 girls from 7 1/2 to 11 yr of age tested up to eight times over a 1 1/2-yr period outdoors (under a tarpaulin) at a school in Mexico City. Ozone and particulates were monitored at an adjacent government station, in the school yard, and under the tarp. Subjects were selected to oversample children with chronic respiratory symptoms, although children with active asthma under regular medication or FEV1 < 80% predicted were excluded. Of the participants, 21 had chronic cough, chronic phlegm, or ever wheeze with colds or apart from colds. Children performed two cycles of treadmill exercise (15 min) and rest (15 min) for a total of 1 h of intermittent exercise. Most subjects attained the target minute ventilation of 35 L/min/m2. Subjects exercised alternately during low ozone hours (8:00-10:00 A.M.) and during peak O3 hours (12:00-2:00 P.M.), to assure a range of exposures. On 85% of exercise days, the maximum daily 1-h average for ambient O3 exceeded the Mexican guideline of 110 parts per billion (ppb). O3 exposure during the hour of exercise was divided into quintiles, and the response was adjusted for repeated measures, subject having a cold, and prior outdoor exercise. Ambient O3 in the fifth quintile (mean = 229 ppb) was associated with a percentage change in FVC (-1.43% +/- 0.70), FEV1 (-2.85% +/- 0.79), FEF25-75% (-6.32 +/- 1.87) and FEV1 (-1.41% +/- 0.46).(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗

PubMed1995

Quantitative variation in sets of triplets and quadruplets: a simulation.

A computer simulation was devised to generate realistic but large samples of twins, triplets, and quadruplets in each of the possible zygosity types. To validate the simulation, I used formulas proposed by Richter and Geisser (1960) to predict the mean value of the sum of squared deviations in each of three types of triplets and five types of quadruplets and to predict the distributions of the sums of squares in pure types (e.g., monozygotic and trizygotic triplets). Use of the formulas to predict distributions in sets of mixed type or to diagnose zygosity requires more advanced mathematical methods, but the simulation readily generates standard populations of all types of sets. If large enough numbers of real triplets or quadruplets ever become available to permit useful comparison with these standards or with the formulas, developmental peculiarities of the higher-order births might be revealed.

Computer Simulation↗

PubMed1994

Did reflexive catalysts drive chemical evolution?

High-energy starting materials and energy sources on the primitive earth would have generated abundant and varied organic molecules of small or medium size. It is questionable, however, whether ordinary chemical evolution could have produced information-carrying polymers. The end point might have been a fixed steady state if some form of autocatalysis had not intervened. Autocatalytic synthesis is possible for small molecules as illustrated by the formose reaction, in which glycolaldehyde condenses with formaldehyde to form sugars, and resulting tetroses may cleave into two molecules of glycolaldehyde. This and other 'reflexive catalysts', some functioning in molecular aggregates, may have energized chemical evolution and carried it to a level at which RNA or an RNA analog could replicate itself.

Adenosine Triphosphate↗

PubMed1994

Helping homeless mentally ill people: what variables mediate and moderate program effects?

This process evaluation study examined what variables moderate and mediate treatment effects on days in stable housing and client satisfaction for homeless mentally ill clients. In general, demographic characteristics did not moderate either outcome variable. Housing contacts, entitlement contacts, mental health contacts, and supportive services were significant mediators of the treatment effect on days in stable housing. Program contacts, mental health contacts, and supportive services were significant mediators of client satisfaction.

Adult↗