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The multilayered organization of engineered human skin does not influence the formation of sunlight-induced cyclobutane pyrimidine dimers in cellular DNA.

Solar UVB initiates skin cancer mainly by generating highly premutagenic cyclobutane pyrimidine dimers (CPDs) and subsequent mutations in critical growth control genes. It is universally presumed that the upper epidermis in human skin blocks a significant portion of the incident UVB, thereby protecting the cancer-prone basal layer from CPD formation. Using two sensitive techniques for measuring CPD in cellular DNA, we confirmed that the multilayered organization of engineered human skin efficiently shields the basal layer against 254-nm UVC (which is not present in terrestrial sunlight) but, very unexpectedly, provides virtually no protection against environmentally relevant UVB. This underscores the importance of regular sunscreen use, which, in light of our data, may constitute a considerably more important first line of defense against photocarcinogenesis than previously believed.

Biomedical Engineering↗

Elution of filtered granulocytes for transfusion.

Functional and clinical transfusion studies were carried out on granulocytes eluted from nylon filters using ACD Saline solutions and 20% CPD Plasma ACD Saline solutions. Although the average volume of blood and total number of granulocytes filtered were the same, the yield of granulocytes eluted form the filters was 20% greater when 20% CPD plasma was in the eluting solution. Function studies indicated that while the antibacterial capacity of the saline eluted granulocytes was equivalent to that of plasma eluted cells, chemotactic activity was markedly reduced after 24 hours storage in the saline eluted cells. Clinical studies post transfusion also suggest better response from plasma eluted granulocytes.

Blood Bactericidal Activity↗

Relation of smoking to breast cancer by estrogen receptor status.

It has been suggested that smoking is associated with estrogen-negative breast cancer but not with estrogen-positive breast cancer. A population-based case-control study was conducted in Geneva, Switzerland, to determine the relation of passive and active smoking to breast cancer when the referent unexposed category consisted of women unexposed to active and passive smoke. The 242 patients with breast cancer (cases), in whom estrogen receptor (ER) status was determined on biopsy material, were compared with 1,059 women free of breast cancer (controls). Lifetime history of active and passive smoking was recorded year by year, between age 10 and the date of interview. Prevalence rates of ER+ tumors were 74.7% in pre-menopausal women and 74.2% in post-menopausal women. Post-menopausal active smokers had a lower prevalence of ER+ tumors (70.0%, p = ns). Among pre-menopausal women, the age-adjusted ORs of breast cancer with having smoked an average of > or = 20 cigarettes per day (cpd) during lifetime were 2.7 for ER- tumors and 2.6 for ER+ tumors. Among post-menopausal women, corresponding ORs were 5.7 for ER- tumors and 2.4 for ER+ tumors. Smoking was related to both ER- and ER+ breast cancer in pre- and post-menopausal women, but the strength of the association appeared to be greater for ER- tumors among post-menopausal women.

Aged↗

The effect of low-yield cigarette smoking on lung cancer risk.

The effect of low-yield (filter) cigarette (LYC) smoking on lung cancer risk, by two broad histologic groupings (Kreyberg I [KI] and II [KII]), was examined in a large case-control study. Among males, there were 1278 KI patients and 2408 patient controls matched on age, race, hospital, and year of interview and 807 KII patients and 1543 matched patient controls. Among females, there were 513 KI patients and 960 matched patient controls and 499 KII patients and 932 matched patient controls. For the purposes of estimating the reduction in risk due to smoking filter rather than nonfilter cigarettes, odds ratios (OR) for smokers of filter cigarettes only, short-term switchers (i.e., switchers from non-filter to filter cigarettes who had smoked the latter for 1 to 9 years), and long-term switchers (i.e., switchers to filter cigarettes who had smoked filter cigarettes for 10+ years) were calculated relative to smokers of nonfilter cigarettes only (OR = 1.00). Logistic regression was used to obtain estimates adjusted for cigarettes per day (CPD), inhalation, age, and years of schooling. Filter-only smokers of both sexes appeared to have a reduced risk of KI lung cancer (OR = 0.69, 95% confidence interval [CI], 0.37 to 1.27 in males; OR = 0.64, 0.30 to 1.35 in females). Male long-term switchers had a significantly reduced risk (OR = 0.66, 0.49 to 0.90), and female long-term switchers had a nonsignificant reduced risk of KI lung cancer (OR = 0.74, 0.40 to 1.36). The risks of short-term switchers were closer to 1.00 (OR = 0.83, 0.59 to 1.17 in males; OR = 0.99, 0.49 to 2.03 in females). Evidence of a reduction in risk of KII was weaker in males and undetectable in females.

Adenocarcinoma↗

Red cell enzyme activity during blood storage and reactivation of phosphofructokinase.

Activities of 21 red cell enzymes were measured in 15 units of CPD-Al anticoagulated blood before and after 35 days of storage. Paired t-tests revealed that five of the enzyme activities decreased significantly after 35 days of storage (P less than 0.05) while four increased significantly after storage (P less than 0.05). The most striking change was in phosphofructokinase (PFK), which decreased an average of 33% (P less than 0.005). Mean lactate dehydrogenase activity increased to 128% of its zero-day activity (P less than 0.005). Percent red cell survival, determined by reinfusion of a 51Cr-tagged aliquot of stored blood into the autologous donor, was highly correlated with 35-day ATP levels (r = 0.97; P less than 0.001). No significant relationships between two measures of red cell survival and any of the nine significantly altered enzymes were found. Studies of reactivation of PFK in hemolysates using 4 mM concentrations of numerous compounds indicate that the compounds or combinations of compounds used which reactivate PFK significantly all contain at least one high-energy phosphate group. These data suggest that loss of PFK activity during storage may be due to loss of organic phosphates. Whether the changes described have an important role in blood transfusion remains to be determined.

Adenosine Triphosphate↗

Antioxidant metabolism during blood storage and its relationship to posttransfusion red cell survival.

The status of the erythrocyte antioxidant defense system and its relationship to posttransfusion red cell survival were determined in erythrocytes stored for 35 or 42 days in CPD-A1 anticoagulant with a saline-adenine-glucose additive. As storage progressed, there was a significant increase in incubated Heinz body formation (P less than .001) and a significant decrease in reduced glutathione (GSH) stability (P less than .001). Stimulated pentose phosphate shunt activity also declined during storage (P less than .06), while unstimulated shunt activity remained unchanged. The increase in Heinz body formation was associated with decreased GSH stability (r = -.77, P less than .001), which in turn was associated with the decline in stimulated pentose shunt activity (r = .67, P less than .001). The changes in Heinz body formation (r = -.85), GSH stability (r = .83), and stimulated pentose shunt activity (r = .54) were all significantly (P less than .001) related to the decline in adenosine triphosphate (ATP) content of the erythrocyte. Red cell survival 24 hours after transfusion was significantly related to the GSH stability (r = .80, P less than .001) and to the ATP concentration (r = .76, P less than .005) on the day of transfusion. Thus, dysfunction of the erythrocyte antioxidant defense system occurs during blood storage and appears to be related, in part, to ATP depletion. The ability to maintain a normal reduced glutathione concentration during oxidant stress appears to be an important determinant of red cell survival in the peritransfusion period.

Adenosine Triphosphate↗

Cumulative exposure to styrene and visual functions.

BACKGROUND: Results from a 1990-1992 longitudinal study of several reinforced plastics plants showed that for those workers whose styrene exposure had decreased, color vision (CV) improved; while near visual contrast sensitivity (CS) was poorer. METHODS: In 1999, we retested these visual functions in 18 workers with good visual acuity. A cumulative exposure index (CEI), corrected for respirator use, was calculated for each worker. RESULTS: Intra-individual comparison of mandelic acid (MA) showed a significant decrease over time (Friedman; P = 0.015), but current values were not related to CEI. For CV, no significant difference was observed between 1992 and 1999; present results were not related to MA or CEI. The CS profile decreased over time, with significant differences at 3 cpd (Friedman; P < 0.05). CS did not vary with MA levels, but was significantly depressed at the intermediate frequencies among those in the upper CEIH category (Kruskal-Wallis; P < 0.05). CONCLUSIONS: These findings suggest that CS loss increases with long-term cumulative exposure, reflecting chronic damage to the neuro-optic pathways.

Adult↗

Epidemiological and genetic studies of congenital profound deafness in the general population of Sichuan, China.

People with congenital profound deafness (CPD) were surveyed in the general population of Sichuan. The prevalence was 0.082% (104/126, 876) of the general population, male 0.086%, female 0.078%. There was no significant difference in prevalence between urban and rural populations. However the population living in the mountains had a much higher prevalence than people from the foothills and plains (P < 0.05). Amongst the nationalities investigated, there were significant differences in prevalence. Non-Chinese, except for Tibetans, presented a significantly higher prevalence than Han Chinese. There was a significantly higher prevalence among the inbred population (0.82%) than among the non-inbred population (0.72%). An effect of parental age was demonstrated, but no effect of birth order was found. There was a significant seasonal variation in prevalence. Inherited cases could account for 71.2% of all cases, of which 92% were autosomal recessive (AR) and 8% autosomal dominant (AD). Heterogeneity in AR was found with at least 8 different loci. The fitness was 60.26%, the coefficient of selection was 0.3974, mutation rate was estimated to be 2.0 x 10(-4), and no heterozygote advantage was proven.

Adolescent↗

Professional isolation and performance assessment in New Zealand.

INTRODUCTION: Solo and nonurban practice, nonmembership of a professional group, and aging are all associated with underperformance and may be indicators of professional isolation. Although it may lead to underperformance in physicians, there are no clear measures to assess professional isolation. METHODS: By mailed questionnaire, experienced performance assessors were asked to list markers of professional isolation. RESULTS: A set of criteria and descriptors for professional isolation was generated, and included personality; solo practice; poor colleague relationships; outlier practice; MOPS or CPD failure; specialist in only private practice; stress, no relief, complaints, job dissatisfaction; locum, itinerant or part-time practice; cultural barriers; male gender. DISCUSSION: The identification of physicians at risk for professional isolation may enable the prevention of poor performance.

Attitude of Health Personnel↗

Video analysis of chemotactic locomotion of stored human polymorphonuclear leukocytes.

Previous studies of the storage of polymorphonuclear leukocytes (PMNs) have used an empirical approach to define "optimal" conditions. To date, no storage conditions have been described which satisfactorily preserve the chemotactic function of PMNs beyond 24 h. In an effort to define the precise nature of the storage lesion, we studied the chemotactic locomotion of freshly isolated PMNs and PMNs which had been suspended in citrate-phosphate-dextrose-adenine (CPD-A1) plasma and stored in PVC bags, at 20-22 degrees C for 24 h. We used time-lapse video recording and computer image analysis to quantitate the motion of PMNs migrating under agarose. The positions of individual motile cells were traced at 1-min intervals for 5 min. The following parameters were used to quantitate migration: speed (distance/min), persistence of locomotion index (velocity/speed), orientation angle (the angle of the vector describing the next displacement of a cell relative to a direct line toward the chemoattractant), and chemotropic index (cosine of the orientation angle). After 24 h of storage, the following changes were observed: fewer cells migrated, the speed of migrating cells was reduced by 25%, the persistence of locomotion index decreased by 7%, which indicates that migrating cells made slightly more/wider turns, and the chemotropic index was decreased by 30%, which indicates that migrating cells were less accurate in their orientation toward the chemoattractant. Apparently, the storage of PMNs selectively impairs the ability of some cells to orient accurately in a chemotactic gradient and changes the distribution of these locomotor parameters within the population.

Blood Preservation↗

Adults with dyslexia show deficits on spatial frequency doubling and visual attention tasks.

We examine the visual processing of high-functioning adults with developmental dyslexia (mean Performance IQ = 126.5) and current phonological problems. In comparison to an age- and IQ-matched control group, the group with dyslexia showed deficits in two tasks associated with magnocellular/dorsal pathway function. For the 'frequency doubling' stimulus (grating of 0.25 cpd modulated at 25 Hz counterphase flicker), contrast thresholds for detection were raised in the dyslexic group. In conjunction visual search, a display time sufficient for controls to achieve ceiling accuracy at all set sizes (30 ms per item) was inadequate to allow shifts of attention around the display for the group with dyslexia. In contrast, normal performance was found on 'popout' visual search and on a ventral stream acuity task. Correlational analysis revealed a significant relationship between degree of deficit in conjunction search and phonological difficulty. The deficits revealed were specific to functions that rely on magnocellular input. They cannot be attributed to concentration lapses, eye movement problems or slow reaction times in the dyslexic group.

Adult↗

In situ repair of cyclobutane pyrimidine dimers in skin and melanocytic nevi of cutaneous melanoma patients.

The development of cutaneous malignant melanoma (CMM) and its precursor lesions, melanocytic nevi, has been linked to sun exposure. Cyclobutane pyrimidine dimers (CPDs) are the majority of DNA lesions induced by sun exposure. In our study, we investigated if CMM patients have impaired ability to repair CPDs in skin as well as in melanocytic nevi. The repair kinetics were followed up to 3 weeks after exposure to 40 mJ/cm(2) of solar simulating radiation. Altogether 12 CMM patients and 10 healthy controls were included in our study. Buttock skin biopsies were taken at 0 hr, 48 hr and 3 weeks after UV exposure, whereas melanocytic nevi and surrounding skin biopsies were taken only at 0 hr and 3 weeks. The CPD levels were measured by a (32)P-postlabeling method. The results showed that the repair rate of CPDs in neither the skin nor the nevi was significantly different between the CMM patients and the control group. For both groups, the repair rate of TT = C was faster than that for TT = T. The important finding is that about 10% of the initial TT = T damage remained unrepaired after 3 weeks, and was detectable in normal epidermis as well as in nevi of all subjects. We also found that the amount of TT = C and TT = T at 0 hr in nevi was significantly lower than that in surrounding skin (Wilcoxon rank sum test, p < 0.05).

Adult↗

A technique for the induction of labor by the extraovular administration of prostaglandin F2alpha.

Prostaglandin F2alpha (PG F2alpha) was administered to pregnant women at a dosage of 50 microng or 100 microng by extraovular route around the expected time of childbirth in order to induce labor. (1) PG F2alpha 50 microng or 100 microng dissolved in 10 ml of physiological saline solution was infused by extraovular administration through the cervical canal of the uterus with the use of Nelaton catheter No. 9. The catheter was then immediately withdrawn and the patient allowed to return home. (2) Instilation of 10ml of physiological saline solution was carried out for control purposes. (3) Those who reported labor contractions within 24 hours after the infusion were regarded as cases of excellent response, and those who reported labor contractions more than 24 hours after the infusion, or those who showed dilatation and improvement in effacement of the uterine cervical canal though without the occurrence of labor contractions were deemed to be cases of good response. The overall positive response rate (excellent plus good) was 78.9% for primiparae and 85.7% for multiparae in the group receiving 50 microng and 89.5% for primiparae and 100% for multiparae in the group receiving 100 microng. (4) Labor contraction were induced at a rate of almost 100% in those who showed dilatation of the cervical canal of the uterus to the extent of 3 cm or more and effacement to the extent of 50% or more. (5) It is advisable to perform reinfusion of PG F2alpha or instilation of PG F2alpha as a post-treatment in patients with good responses. (6) The infusion of PG F2alpha is effective for the induction of labor in older primiparae, cases of breech presentation and suspected cases of CPD. (7) There were some cases of enhanced response when PG F2alpha was given as posttreatment.

Cervix Uteri↗

Comparison of different drying procedures for scanning electron microscopy using human leukocytes.

Using human leukocytes as test specimens, three different drying procedures for scanning electron microscopy: critical-point drying (CPD), Peldri II, and tetramethylsilane (TMS), were compared. All three procedures produced identical surface morphology preservation. An equal amount of volume shrinkage was observed regardless of the dehydrants and drying techniques employed. Considering the simplicity, convenience, and time saved, air-drying with TMS is by far the best choice for preparing animal cells for scanning electron microscopy.

Desiccation↗

Journal provision and the prevalence of journal clubs: a survey of physiotherapy departments in England and Australia.

BACKGROUND AND PURPOSE: Evidence-based journal clubs can promote evidence-based practice and continuing professional development (CPD). Although studies have evaluated the impact of journal clubs in medical and nursing departments, there is little information concerning journal clubs or journal provision in physiotherapy departments. The present survey was conducted to address this deficit. METHOD: A postal questionnaire, designed to ascertain the type and extent of journal provision, and prevalence and attributes of journal clubs in physiotherapy departments, was distributed to physiotherapy managers in 150 facilities in England and in south-east Australia. Sixty-two per cent of facilities approached in England and 55% of those approached in Australia responded to the survey. RESULTS: The provision of journals in physiotherapy departments was limited, and alternative access to physiotherapy journals was generally poor. Certain facilities were innovative in providing additional journal literature for physiotherapy staff. Physiotherapy journal clubs existed in 42% of responding facilities in England and 18% of those surveyed in Australia. Several facilities provided alternative forms of journal review as part of in-service training. Relatively few journal clubs utilized a 'problem-based' format, which fosters the teaching of critical appraisal skills. Evidence of enthusiasm emerged in some facilities, but in contrast, barriers and a degree of apathy were also revealed in others. CONCLUSIONS: Physiotherapy managers, hospital administrators and academic institutions should jointly agree a strategy to both promote evidence-based journal clubs and to facilitate journal provision within physiotherapy departments.

Australia↗

A novel function of transferrin as a constituent of macromolecular activators of phagocytosis from platelets and their precursors.

Macromolecular activators of phagocytosis from platelets (MAPP:s-MAPP, 1500kDa and 1-MAPP, 300kDa) are glycoproteins released from human platelets and activate leukocyte phagocytosis via the Fc gamma receptors. Their production can be shown in CPD-stored platelets which have lost MAPP releasing activity by incubation with plasma-derived precursos of MAPP (pre-MAPP : pre-s-MAPP, 150kDa and pre-l-MAPP, 300kDa) in the presence of Ca++. Partial amino acid sequence analysis of s-MAPP revealed that it had homogeneity with transferrin (TF). Affinity chromatography using anti TF immunosorbent column showed that all of pre-MAPP and MAPP had immunoreactivity with anti TF antibodies. S-MAPP and 1-MAPP rich preparations from platelet release products lost their activity after treatment with ATP at acidic pH, in which condition iron atoms could be removed from holo-transferrin molecules. In the experiment using polymerized TF and stored platelets, it was shown that platelets incubated with dimer and tetramer TF could produce MAPP function. These results suggest that dimer and tetramer transferrin are precursors of s-MAPP and 1-MAPP, respectively and that iron atoms are necessary for their phagocytosis activating function.

Amino Acid Sequence↗

Production of recombinant salmon calcitonin by amidation of precursor peptide using enzymatic transacylation and photolysis in vitro.

The C terminal amidation is required for full biological activity of salmon calcitonin (sCT). We constructed BL21(DE3)/pGEX-sCT-Ala, an engineering Escherichia coli strain. The soluble fusion protein of GST-sCT-Ala expressed from BL21(DE3)/pGEX-sCT-Ala was purified by affinity chromatography after high density, high expression culture and sonication of bacteria. Following S-sulfonation of the fusion protein, the 33 alanine-extended peptides were released from the fusion protein by cyanogen bromide. The S-sulfonated precursor peptide was transacylated by CPD-Y, o-PNGA as a nucleophile, to produce photosensitive SO(-)(3)-sCT-o-PNGA. After photolysis and folding, the biological activity of sCT was assayed as standard.

Acylation↗

Spatial frequency and right hemisphere: an electrophysiological investigation.

The influence of the spatial frequency of visual stimuli on hemispheric asymmetry has been studied with visual evoked potentials (VEP). Nineteen different sinusoidal gratings (19 SF from 1 to 10 cpd) were presented in an ON-OFF mode to five right-handed subjects. The amplitude of the VEPs and the latency of the first positive component (C1) were analyzed. The results show that in the low range of spatial frequencies, the latency and the amplitude of C1 are similar in both hemispheres. At medium to high spatial frequencies, the VEPs on the right hemisphere (RH) present shorter latencies and larger amplitudes than those on the left hemisphere (LH). These results, discussed in relation to the directional differences in the time of callosal interhemispheric transfer, strengthen the idea that the RH is relatively more sensitive than the LH to the spatial component of the visual stimuli.

Brain↗