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In situ epithelial cell invasion in organ culture.
Organ cultures were established from 2-mm punch biopsies of human skin and maintained for 12 days in either serum-free, growth-factor-free basal medium or in medium supplemented with a number of epithelial cell growth factors including epidermal growth factor, insulin, hydrocortisone and pituitary extract. Normal histological architecture was preserved in growth-factor-free basal medium. However, in the presence of exogenous growth factors, the epidermis was thickened and hypertrophied. There was focal loss of the usual maturation progression, accompanied by abnormal keratinization patterns. In some areas, basement membrane disruption occurred and epithelial cells penetrated into the dermis in these areas. Isolated squamous epithelial cells and nests of cells could be clearly seen within the dermal stroma. In additional studies, an enzyme-linked immunosorbent assay was used to assess fibronectin and laminin production. Increased levels of both matrix components were seen in the culture fluids from tissues maintained under conditions which promote invasion. Taken together these findings indicate that growth-factor-stimulated normal squamous epithelial cells have the capacity to carry out functions that lead to concomitant synthesis and break-down of the underlying basement membrane and to invasion of mesenchymal tissue. This organ culture system may help to elucidate mechanisms of in situ invasion by squamous epithelial cells.
Adult↗
Human monocyte cytotoxicity to tumor cells. I. Antibody-dependent cytotoxicity.
Recent investigations examining mononuclear cell antibody-dependent cell-mediated cytotoxicity against tumor cell lines suggest that K lymphocytes and not monocytes are active in this cytotoxic reaction. We have found, however, that in an allogeneic assay system, human monocyte monolayers as well as lymphocytes mediate substantial lysis of 51Cr-labeled antibody-coated CEM lymphoblast tumor cells. This cytotoxicity is temperature-dependent and rapid, with most 51Cr release occurring in the first 4 hr of co-incubation. Interaction between target cell-bound antibody and the monocyte Fc receptor is necessary as demonstrated by the marked fall in antibody-dependent cell-mediated cytotoxicity (ADCC) produced by staphylococcal protein A, high concentrations of nonspecific immunoglobulin, and dilution of the target cell antiserum. Morphologic and functional characteristics of the monocyte-monolayer preparations establish their relative purity (greater than 95%) and indicate that monocytes and not contaminating lymphocytes are responsible for tumor cell lysis. Furthermore, preincubation of monocyte and lymphocyte preparations with latex particles or low concentrations of immunoglobulin distinguished monocyte from lymphocyte ADCC. Thus, normal human monocytes have the capacity to carry out antibody-dependent cytotoxicity against nucleated malignant target cells.
Antibody-Dependent Cell Cytotoxicity↗
Lysenkoism and the population control movement.
The case of Lysenkoism in the Soviet Union helps us understand how people's wrong beliefs can be influenced by what the information they receive from outside, especially when there is a large volume of media coverage and there is no contrary information to be heard. The population control movement in contemporary United States has many parallels to the Lysenko episode.
Genetics, Population↗
[Quality of life and dementia].
OBJECTIVE: To review the relationship between quality of life (QOL) and dementia. Development. QOL is a factor which takes into account all the different aspects of life which make a person feel that life is worth living, such as: 1. Physical health. 2. Functional status. 3. Psychological and cognitive sphere, and 4. Social health. There are two types of instruments for evaluating these aspects: firstly general ones which measure the QOL independently of illness, and secondly those which are specific to the illness concerned. In dementia, QOL covers the same traditional areas: cognitive competence, capacity to carry out everyday activities, social conduct and the balance between positive and negative emotions. However, evaluation of QOL in dementia has its own specific difficulties, since it is often impossible to determine such a fundamental factor as the subjective well-being of the patient, in which case the opinion of the person looking after the patient is essential. According to Lawton's approximation, as well as the subjective aspect of perceived psychic welfare and quality of life, the QOL in dementia is composed of external social and objective dimensions such as behaviorally competence and the quality of the patient's environment. In a review done in 1995 it was found that most of the instruments designed to measure the QOL have not been sufficiently validated for Alzheimer's disease. CONCLUSIONS: QOL in dementia has specific features including external aspects such as the opinion of the carer and the quality of the patient's environment in addition to the subjective aspects. It is necessary to develop and validate specific instruments for QOL in dementia.
Aged↗
Tissue-specific replicating capacity of a chimeric poliovirus that carries the internal ribosome entry site of hepatitis C virus in a new mouse model transgenic for the human poliovirus receptor.
Nucleotides (nt) 108 to 742 of an infectious cDNA clone of poliovirus (PV) Mahoney strain, including the corresponding region of the internal ribosome entry site (IRES), was replaced by nt 28 to 710 of hepatitis C virus (HCV) cDNA corresponding to the whole HCV IRES. A chimeric PV (2A-369) was generated by transfecting mammalian cells with an RNA transcribed in vitro from the cDNA. To examine replicating capacity of virus 2A-369 in the brain and liver of a mouse model for poliomyelitis, a new mouse model (MPVRTg25-61) that is transgenic for human PV receptor (hPVR; CD155) was generated in order to obtain a higher expression level of hPVR in the liver than those of hPVRTg mouse lines generated by us so far. The transgene used was constructed by combining a putative regulatory region of the mouse PVR homolog and the whole structural region of the hPVR gene. Virus 2A-369 replicated well in the liver of MPVRTg25-61 but not in the brain, whereas control Mahoney virus replicated well both in the liver and in the brain. The data suggest that the HCV IRES works more efficiently in the liver than in the brain and that PV IRES works well both in the liver and in the brain. The results support the notion that tissue-specific activity of IRES may be reflected in tissue tropism of a virus whose specific translation initiation is driven by IRES, that is, an IRES-dependent virus tropism.
Animals↗
Phosphorus retention in subsurface constructed wetlands: investigations focused on calcareous materials and their chemical reactions.
Phosphorus removal from wastewater has been of growing interest for some decades to avoid eutrophication in surface water. In subsurface constructed wetlands precipitation and adsorption are the main mechanisms responsible for P uptake. Two media (calcite and recycled crushed concrete (RCC)) were examined in batch and continuous systems. Batch experiments show attractive sorption capacities, however experiments carried out in open reactors pointed out some limitation in retention capacities and effluent quality. RCC is sensitive to a strong dissolution leading to a quick phosphorus precipitation but induces high conductivity and pH values in the treated water. Calcite efficiency depends on the carbonate equilibrium of the solution. Microscopic observations of the calcite surface show crystal growth of phosphorus precipitate. Crystallisation seems to be the main P uptake once a material's surface is covered.
Adsorption↗
Selective induction of allostimulatory capacity after 5-azaC treatment of EBV carrying but not EBV negative Burkitt lymphoma cell lines.
Epstein-Barr virus (EBV) negative and EBV carrying Burkitt lymphoma (BL) lines that remain phenotypically similar to the in vivo tumor cells (operationally defined group I BLs) express high levels of CD10 and CD77, and lack immunoblastic markers such as CD23 and CD39, and the cell adhesion molecules CD11a, CD18, CD54 and CD58. This cell phenotype is associated with poor stimulatory capacity in allogeneic mixed lymphocytes cultures (MLC) [Avila-Carino et al. Int. J. Cancer 40, 691-697 (1987)] EBV carrying BL lines tend to drift spontaneously towards an immunoblastic phenotype in parallel with up-regulation of six EBV-encoded nuclear antigens (EBNA-2 to -6) and two membrane proteins (LMP-1 and -2). These viral antigens are characteristically expressed in all EBV transformed lymphoblastoid cell lines (LCLs) of normal B cell origin and can be induced in group I BL lines by treatment with the DNA demethylating agent 5-azacytidine (5-azaC) [Masucci et al. J. Virol. 65, 1558-1567 (1989)]. We have now studied the effect of 5-azaC on the induction of allogenic T cell proliferation by three EBV negative (Ramos, BL28 and BL41) and four EBV carrying BL lines (Rael, Eli, Chep and Mutu) which stably express a group I phenotype. Pre-treatment with 4-15 microM 5-azaC had no effect on the EBV negative cells but increased the stimulatory capacity of all four EBV carrying lines. LMP-1 was the only viral antigen regularly induced suggesting that its expression may be required for the increase of allostimulation. This was corroborated by the observation that LMP-1 transfection increased 35-70-fold the stimulatory capacity of Rael cells. The cell adhesion molecule CD54 was the only cellular marker selectively up-regulated in all cell lines with increased stimulatory capacity.
Antigens, CD↗
A randomized trial of a decisional aid for mental capacity assessments.
The objective of this study was to evaluate the clinical utility of a decisional aid for mental capacity assessments which was developed using a group judgment methodology. This was carried out by a randomized, controlled trial. The subjects comprised 64 University of Toronto psychiatry residents in postgraduate years 1 through 4. Residents were randomized to carry out mental capacity assessments on simulated cases with, or without, the use of the decisional aid. The main outcome measure was the extent of agreement between the mental capacity determinations of residents and those of experts. There was no difference between the intervention and control groups with respect to the overall mean level of agreement with experts (0.87 vs 0.86, p = 0.88; 95% confidence interval for the difference between the study groups, -0.07 to +0.08). A logistic regression analysis, which adjusted for imbalances between the groups, also revealed no difference between the groups in their agreement with experts. The mean time per competency assessment was significantly longer in the intervention group (19.1 vs 10.8 min; p < 0.001). It was concluded that the decisional aid did not improve the ability of the psychiatry residents to make mental capacity assessments on simulated cases. Despite relatively limited formal training, the psychiatry residents had a high level of agreement with experts.
Adult↗
Physical fatigue in high and very high frequency manual materials handling: perceived exertion and physiological indicators.
This paper presents the results of a preliminary laboratory study undertaken to determine the perceived exertion and physiological responses of highly trained and experienced workers to high (up to 16 repetitions/min) and very high frequency (above 16 repetitions/min) manual lifting, lowering, and carrying/turning tasks. The results indicate that workers engaged in such highly repetitive and physically demanding tasks may operate at psychophysical workloads that may clearly be considered physically fatiguing and unacceptable according to the current physiological design criteria. In this study subjects performing lifting and lowering tasks, on the average, operated at 57% and 52% of their uphill treadmill aerobic capacity, respectively. For carrying and turning tasks, the average metabolic energy expenditure rate corresponded to 43% of subjects' aerobic capacity. The overall heart rates of the study subjects were 155 beats per minute (bpm) for lifting, 144 bpm for lowering, and 142 bpm for carrying and turning. These physiological responses, when compared with recommended physiological design criteria, are excessively high. The ratings of perceived exertion (RPE) for the shoulder, back, and whole body were highest for lifting (range, 10.20-15.50) and least for carrying and turning (range, 10.30-13.40; carrying and turning activities also included RPE of arms). Generally workers perceived the associated physical exertions as acceptable.
Adult↗
[Penetrating capacity of bull spermatozoa in vitro].
Studies were carried out on the penetrating capacity of bull spermatozoa in an estrous secretion, a modification of Kremer's method being employed by the authors. The new method seemed to be more readily applicable in the practice. It was found that the penetrating capacity was highest following thawing of semen at 39 degrees C, the pH value of the secretion being 6.8-6.9. The adding of the cytochrome C enzyme to the spermatozoa at the rate of 1 mg/cm3 of such semen increased the penetrating capacity by 22 per cent. When the thawed semen was allowed to stay for fifteen minutes the penetrating capacity of spermatozoa in the estrous++ secretion dropped by 33 per cent.
Animals↗
Further refinement of the description of the ligand-binding characteristics for the galactoside-binding mistletoe lectin, a plant agglutinin with immunomodulatory potency.
The galactoside-binding lectin from mistletoe (Viscum album L.) is a biological response modifier, eliciting e.g. enhanced secretion of cytokines. This immunological activity warrants the further analysis of its ligand-binding properties with special attention paid to blood group epitopes. To avoid the microheterogeneity and complexity of naturally occurring glycoproteins, chemically strictly defined neoglycoconjugates and a panel of synthetic oligosaccharides were employed in solid-phase assays for direct binding and assessment of the relative inhibitory capacity. Since label incorporation into the lectin, although performed under protective conditions, or surface immobilization by adsorption to plastic may affect its affinity characteristics, the extent of neoglycoconjugate binding in the absence of any interfering substance and in the presence of oligosaccharides was determined comparatively with labeled and with immobilized lectin. In principle, these two factors could be excluded to markedly alter binding features. In addition to lactose, the blood group determinants H and B were strongly reactive. A fucose residue can thus especially be accommodated to the binding site when linked to the non-reducing unit. N-Acetyllactosamine was nearly as potent as an inhibitor as lactose. Lec and the A determinant were notably inferior to the other ABH blood group epitopes. Le(a) and Le(x) and their sialylated derivatives displayed only very weak binding capacity. Among the two natural isomers of sialyllactose, the alpha 2,6-form displayed a higher level of inhibitory capacity than the alpha 2,3-derivative. Isomeric variants of the Thomsen-Friedenreich antigen, too, reduced lectin binding to the lactose-carrying polymer. Their capacities were surpassed by those of the H and the B determinants and a related form of the latter, the P1 epitope. An overlap of specificity with the immunomodulatory human galectin-3 is thus measurable for H/B-like structures. The documented differential reactivity of the mistletoe lectin to blood group oligosaccharides may have a bearing on the responsiveness of blood group-positive cell populations.
Adjuvants, Immunologic↗
Antioxidant capacity in severely burned patients.
Total antioxidant capacity (TAC) was measured after severe burns (non-electric with one exception) in two groups of patients: group A, 24 subjects (19 men and five women) 20-67 years old and group B, eight subjects (six men and two women) 20-54 years old, admitted to the Major Burns Unit of hospital general Vall d'Hebron over a period of nine months. Albumin, uric acid and antioxidant capacity analyses were carried out within 24 hours after injury in both groups, and additionally at 1, 7, 15 and 21 days in group B. Total antioxidant capacity was measured by inhibition of blue-green colour of the ABTS+ cation (600 nm) and compared with reference values obtained in healthy, sex and age-matched volunteers (n = 50). Results showed statistically increased mean antioxidant capacity values at 24 hours (Group A: 1.36 +/- 0.22 mmol/L; Group B: 1.66 +/- 0.39) as compared with reference values (range, 1.0 to 1.44 mmol/L), representing 42% of patients in group A and 50% in group B (overall mean 46%), with no correlation with severity of the burn. The longitudinal study (Group B) showed no correlation between total antioxidant capacity values and time (r = -0.171; ns). A statistically significant correlation was found between albumin and time (r = 0.438; p < 0.05), indicating a clear tendency toward normalisation of plasma albumin values during healing. There was no correlation among total antioxidant capacity, percentage of burned surface and clinical evolution, suggesting a poor sensitivity of the method for the study of this pathology.
Adult↗
The influence of poly(ethylene oxide) and illumination on the copper electrodeposition process onto n-Si(100).
In this study, we examined the influence of illumination and the presence of poly(ethylene oxide) (PEO) as an additive for the copper electrodeposition process onto n-Si(100). The study was carried out by means of cyclic voltammetry (CV) and the potential steps method, from which the corresponding nucleation and growth mechanism (NGM) were determined. Likewise, a morphologic analysis of the deposits obtained at different potential values by means of atomic force microscopy (AFM) was carried out. In a first stage, Mott-Schottky measurements so as to characterize the energetics of the semiconductor/electrolyte interface were made. Also, parallel capacity measurements were carried out in order to determine the surface state density of the substrate. It was found that when PEO concentration is increased, the number of these surface states decreases. The CV results indicated that the presence of PEO inhibits the photoelectrochemical reaction of oxide formation on the surface of the semiconductor. This allows a decrease in the overpotential associated with the electrodeposition process. The analysis of the j/t transients shows that the NGM corresponds to progressive three-dimensional (3D) diffusional controlled (PN3D(Diff)), which was confirmed by the AFM technique. Neither illumination nor the presence of PEO changes the mechanisms. Their influence is in that they diminish the size of the nuclei and the speed with which these are formed, which produces a more homogeneous electrodeposit.
Journal Article↗
Sustainability of health care: a framework for analysis.
This paper introduces a conceptual framework which can be used to study the sustainability of health services in developing countries. A health service is considered sustainable when operated by an organizational system with the long-term ability to mobilize and allocate sufficient resources for activities that meet individual or public health needs. The framework includes three clusters: (1) contextual factors, which outline the task and general environment of the services; (2) an activity profile, which describes the services delivered and the activities carried out to deliver them; and (3) organizational capacity, which shows the carrying ability (capability) of the organization in broad terms. In this framework, health care provision is seen as an open system model where five main factors determine how inputs are converted to outputs, linking them through feedback loops. These factors are aims, technology, structure, culture and process. The framework has proven useful in analyzing factors critical to sustainability, and in describing structures and processes both in basic public services and in private not-for-profit services. It should also be tested on more complex systems, such as national health care.
Delivery of Health Care↗
Nerve repair: correlation of restitution of functional sensibility with specific cognitive capacities.
To test the hypothesis that cognitive capacity is correlated with the outcome of functional sensibility after nerve repair, 19 patients were evaluated 2 to 5 years after median or ulnar nerve repair at the distal forearm level. The sensory evaluation included tests for functional sensibility as well as assessments addressing perception thresholds for touch/pressure and vibration. Psychometric tests for cognitive capacity were also carried out. Multiple regression analysis, correcting for the effect of age and the ability to perceive touch/vibration, was used to investigate the relationship between functional sensibility and cognitive capacity, and to determine which of the tested central nervous factors had the greatest influence on the outcome of recovery of functional sensibility. On a ranking list of such factors verbal learning and visuo-spatial logic capacity were the most important ones, indicating significant correlations with functional sensibility. It is concluded that cognitive capacity factors may play an important role for the functional outcome following nerve repair and that variations in such factors may help to explain the variability in the outcome of nerve repair.
Adolescent↗
Lymphocytes stimulated by allogeneic B cell lines cleave the third component of complement and fix C3 fragments. Their nonspecific lytic capacity is elevated against complement receptor type 2-carrying targets.
Human blood lymphocytes stimulated in mixed cultures by allogeneic B cell lines were shown to cleave C3 molecules. The B cell lines were derived from Burkitt lymphoma patients: 1) established from their EBV-negative lymphoma, 2) the EBV-positive sublines converted in vitro, and 3) lymphoblastoid cell lines (LCL) i.e., B lymphocytes transformed in vitro by EBV. These cell lines differed considerably in their capacity to stimulate allogeneic lymphocytes. The split products of C3 were detected in the supernatants and on the surface of the activated lymphocytes at levels which correlated with the strength of stimulation. Lymphocytes cultured with LCL had the highest levels of thymidine incorporation blast transformation, C3 cleavage, and C3 fragment fixation. Lymphocytes exposed to the EBV-negative Burkitt lymphomas were stimulated weakly and their C3-activating capacity was low. Irrespective of the efficiency of lymphocyte stimulation induced in the cultures, 60 to 70% of the blasts were found to fix C3 fragments. The majority of the lymphocytes which fixed C3 fragments were T blasts that carried the CD3 marker and expressed IL-2R (CD25). CD4 and CD8 cells were represented with equal frequency in the C3-fragment fixing and C3-fragment negative populations. Pre-exposure of the MLC-activated lymphocytes to human serum increased their cytotoxic capacity toward CR type 2-carrying targets. The enhanced lysis was abrogated by F(ab)2 rabbit anti-human C3d or rabbit anti-CR type 2 antibodies. The results suggest that the C3 fragments fixed on the lymphocytes bind to CR on the targets and elevate the avidity of binding between the two interacting cells. This was also indicated by an increase in the frequency of lymphocyte-target conjugates.
Antigens, Differentiation, B-Lymphocyte↗
Heat capacity and electron spin echo evidence for low frequency vibrational modes and lattice disorder in L-alanine at cryogenic temperatures.
With the view of understanding the low frequency (40-50 cm(-1)) motional processes in L-alanine around 4 K, we have carried out heat capacity (CP) and electron spin echo (ESE) measurements on L-alanine and L-alanine-d7. The obtained CP data show the so-called boson peak (seen as a maximum in CP/T3 versus T plots) in the low temperature region (1.8-20 K). The phase memory time, T(M), and spin lattice relaxation time, T1, of the spin probe, the so-called first stable alanine radical (SAR1), *CHCH3COOH, have been measured between 4 and 105 K. The obtained relaxation rate 1/T1 shows an anomalous increase which coincides with the emergence of a boson peak in the low temperature region (4-20 K). Together, the ESE and the CP data confirm the existence of a thermally activated dynamic orientational disorder in the lattices of both compounds below 20 K. The results help explain the discrepancy between the CP data from powders and single crystals of alanine, as well as the proanomalous relaxation mechanisms for SAR1 in these lattices, and they also provide a mechanism for the spin-lattice relaxation process for SAR1 at cryogenic temperatures.
Alanine↗