A protein interaction map for cell polarity development.

Many genes required for cell polarity development in budding yeast have been identified and arranged into a functional hierarchy. Core elements of the hierarchy are widely conserved, underlying cell polarity development in diverse eukaryotes. To enumerate more fully the protein-protein interactions that mediate cell polarity development, and to uncover novel mechanisms that coordinate the numerous events involved, we carried out a large-scale two-hybrid experiment. 68 Gal4 DNA binding domain fusions of yeast proteins associated with the actin cytoskeleton, septins, the secretory apparatus, and Rho-type GTPases were used to screen an array of yeast transformants that express approximately 90% of the predicted Saccharomyces cerevisiae open reading frames as Gal4 activation domain fusions. 191 protein-protein interactions were detected, of which 128 had not been described previously. 44 interactions implicated 20 previously uncharacterized proteins in cell polarity development. Further insights into possible roles of 13 of these proteins were revealed by their multiple two-hybrid interactions and by subcellular localization. Included in the interaction network were associations of Cdc42 and Rho1 pathways with proteins involved in exocytosis, septin organization, actin assembly, microtubule organization, autophagy, cytokinesis, and cell wall synthesis. Other interactions suggested direct connections between Rho1- and Cdc42-regulated pathways; the secretory apparatus and regulators of polarity establishment; actin assembly and the morphogenesis checkpoint; and the exocytic and endocytic machinery. In total, a network of interactions that provide an integrated response of signaling proteins, the cytoskeleton, and organelles to the spatial cues that direct polarity development was revealed.

The role of allopurinol and deferoxamine in preventing pressure ulcers in pigs.

Ischemia and reperfusion may be important in the pathogenesis of pressure ulcers. On the basis of this hypothesis, the effects of intermittent pressure and the anti-free radical agents allopurinol and deferoxamine were studied in a pig model in which a pressure of 150 mmHg was applied intermittently to the scapulae. Cutaneous blood flow, transcutaneous oxygen tension, skin and muscle damage, and muscle levels of adenosine triphosphate were quantified. A control group of pigs (n = 6) was untreated, the allopurinol group (n = 6) received oral allopurinol beginning 2 days before the experiment, and the deferoxamine group (n = 6) received an intramuscular injection of deferoxamine 2 hours before the experiment. Pressure (150 mmHg) was applied to the scapulae for 210 minutes, and it was relieved for 30 minutes. This 4-hour cycle was repeated continuously for 48 hours, and it resulted in pressure injuries in all animals. Allopurinol and deferoxamine improved cutaneous blood flow and tissue oxygenation, but only deferoxamine could significantly reduce cutaneous and skeletal muscle necrosis (p < 0.001). This study suggests a future role for anti-free radical agents in the reduction of pressure-induced injury.

[The dedicated amateur]. / Den hängivne amatören: installationsföreläsning vid tillträdandet av professuren i idéhistoria vid Umeå universitet den 9 oktober 1993.

This is the text of an inauguration lecture at Umeå Universitiy (a chair of the history of science and ideas). The lecture is based on a study of magazines like Populär Teknik (Popular Technology), popular science literature, handbooks for mechanical and electrical experimentation, mail-order catalogs etc. from 1920-50, and its theme is that amateurs and hobbyists interested in popular science, technology and "do-it-yourself" have played an important role in modern society. Here we find a world exclusively occupied by boys and men, where it is made a virtue of playing with technological toys, and where mechanical and electrical tinkering becomes a significant part of the construction of masculinity. But the activities of amateurs and hoppyists can also be seen as an important way of self-education where the boy may get in touch with the scientific and technological frontier of the time, and there are many examples (e.g. in early history of radio or personal computers) where amateurs invented and developed new technology. The spirit of amateurs and hobbyists can even contain elements of a modern civic ideal: don't become dependent upon professional experts, don't trust authorities or big business that want to control technology, trust yourself and your knowledge. In short: do it yourself.

Tissue plasminogen activator (t-PA) and placental plasminogen activator inhibitor (PAI-2) in gingival fluid from 8-9-year-old children.

High concentrations of tissue plasminogen activator (t-PA) and placental type plasminogen activator inhibitor (PAI-2) have previously been found in gingival crevicular fluid (GCF) of adults. In the present study, the levels were examined in 16 children aged 8-9 yr. Sampling of GCF was performed with small disks of Millipore-filter. t-PA and PAI-2 were analyzed with enzyme-linked immunosorbent assays with low method errors. The mean concentration of t-PA was slightly higher than in adults, while the mean PAI-2-concentration was slightly lower. An intraindividual study comparing healthy and inflamed sites in the children showed slightly higher concentrations in GCF from inflamed sites. No change was observed in the balance between t-PA and PAI-2.

Clinical evaluation of preventive and class-I composite resin restorations.

This study was initiated in 1986 in response to increased interest in restorative procedures favoring preservation of tooth substance and in the search for alternatives to dental amalgams. Eighty-seven preventive resin restorations in permanent molars and 35 occlusal composite resin restorations in primary molars (limited size) and 13 in premolars were followed up for 2 years. They were placed by a large number of operators, mainly dental students under supervision, and rated by five calibrated instructors in accordance with an internationally accepted system for the evaluation of the clinical performance of dental materials. One composite resin (Occlusin) was used. A survival model was used to calculate the cumulative theoretical number of successful treatments of children who had dropped out. For none of the 6 clinical variables was the success rate lower than 91%, and only 3 of 26 failures were of a nature requiring remake or correction. The failures occurred, with a few exceptions, during the 1st year of observation. The two types of restoration have thus proved to be efficient treatments fulfilling all reasonable requirements in modern operative dentistry.

Sweets and other sugary products tend to be the primary etiologic factors in dental caries.

The aim of this study was to analyze the relationships between caries incidence and each of seven caries-related factors in a group of 15- to 18-yr-olds as well as in single and combined subgroups representing favorable or less favorable fractions of six of the factors. Sixty-nine 18-yr-olds were interviewed about consumption of sweets and other sugar-containing products during the past 3 yr and examined for oral hygiene, salivary counts of mutants streptococci and lactobacilli, salivary flow rate and oral sugar clearance time at the ages of 15 and 18. Simple linear correlations and a stepwise multiple regression analysis were used to compare ranks and explanatory values. The highest correlations were obtained for intake of sweets and intake of other sugary products, with r values increasing from 0.25 and 0.16, respectively, in the total material to 0.70 and 0.67 in less favorable fractions of oral hygiene, salivary flow rate and other sugary products in the former case, sweets in the latter. The stepwise multiple regression analysis revealed that sweets and other sugary products contributed 12 percentage points to the total explanatory value, which was as low as 19%.

Variation of posterior approximal caries incidence with consumption of sweets with regard to other caries-related factors in 15-18-year-olds.

The aim of this study was to analyze the relationships between caries incidence and a number of caries-related factors in 15-18-yr-olds, in order to estimate the explanatory value of consumption of sweets under different conditions. Sixty-nine 18-yr-olds were interviewed about consumption of sweets and other sugar-containing products during the past 3 yr. Data on oral hygiene, salivary counts of mutans streptococci and lactobacilli, salivary flow rate and oral sugar clearance time were collected when the individuals were 15 and 18 yr old. Caries incidence for the 3-yr period was expressed as a percentage of the number of caries-free approximal surfaces of premolars and molars at the age of 15. Simple linear correlations between caries incidence and the different variables showed that lactobacilli count ranked first (r = 0.26), sweets second (r = 0.25), and mutans streptococci count third (r = 0.24). The r value for caries incidence and consumption of sweets increased in subgroups with combinations of poor oral hygiene, a high intake of other sugary products and a low salivary flow rate (r = 0.67-0.70). In conclusion, consumption of sweets should still be considered an important caries-related factor and particularly harmful when oral hygiene is poor and consumption of other sugary products is high.

Immunotherapy with cat- and dog-dander extracts. V. Effects of 3 years of treatment.

The effect of a 3-year course of cat or dog immunotherapy (IT) was evaluated in 32 patients with a history of asthma on exposure to cat or dog. Twenty-one subjects (14 children and seven adults) received cat IT and 11 subjects (six children and five adults) received dog IT. Bronchial challenges with allergen and histamine were performed once a year. Specific IgE, IgG1, and IgG4 were measured, and skin prick tests were done in connection with the challenges. Allergen sensitivity decreased significantly in both treated groups (p less than 0.001 and p less than 0.05 in the cat-allergen and dog-allergen treated groups, respectively). Bronchial hyperreactivity measured by the provocative concentration of histamine causing a 20% decrease in peak expiratory flow in the cat-allergen treated patients (p less than 0.001) but not in the dog-allergen treated patients. Skin sensitivity decreased in both groups (p less than 0.01 and p less than 0.05), whereas specific IgE increased initially but dropped to the pretreatment level during the second year. Specific IgG1 and IgG4 increased during the first and second year in the cat-allergen treated group (p less than 0.01 and p less than 0.001), whereas only IgG4 increased in the dog-allergen treated group (p less than 0.01). Five cat-allergen treated children and one of the adults who completed 3 years of therapy had mild systemic reactions. We conclude that cat IT ameliorated bronchial allergen sensitivity and bronchial hyperreactivity and resulted in an adequate antibody response. Dog IT was less efficacious but led to attenuation of bronchial allergen sensitivity.

Caries and consumption of sweets in 15- and 18-year-olds interviewed with visualization.

The aim of this study was first to investigate the relationship at group level between approximal caries, restorations in posterior regions and consumption of sweets during the past 3 yr in 15-yr-old schoolchildren selected for different caries experience. An interview method was used with the sweets on display. Secondly, the aim was to reinterview the subjects as 18-yr-olds using the same method in order to study the correlation between caries incidence and consumption of sweets during the past 3 yr. Seventy-five individuals from three groups, 30 with 0, 25 with 4-6, and 20 with 12-15 approximal DFS, were selected for the first interview. Sixty-nine of them were reinterviewed 3 yr later. Caries incidence during the 3-yr period was expressed as a percentage of the number of caries-free approximal surfaces of premolars and molars at the age of 15. The results showed no statistically significant differences in mean number of intakes of sweets per day (2.2, 2.2, and 2.8) between the original DFS groups. The correlation coefficient between caries incidence and number of intakes of sweets in the second part of the study was 0.25 (P less than 0.05). After correction for the modifying effect of oral hygiene, the coefficient was 0.51 (P less than 0.01) in the less favorable fraction and 0.11 (P greater than 0.05) in the favorable fraction.

Per capita consumption of sugar-containing products and dental caries in Sweden from 1960 to 1985.

The aim of the present report was to analyze sugar consumption in relation to dental caries in Sweden from 1960 to 1985. Sugar consumption is based on official statistics from the National Swedish Agricultural Board and is expressed in grams per person and day. Over this quarter-century total sugar consumption decreased approximately 5%, from 116 to 110 g/person/day. A shift occurred from direct consumption to indirect (sugar used by the food industry), the former decreasing from 76 to 50 and the latter rising from 40 to 60 g/person/day. Available epidemiologic data on dental caries in children from the National Swedish Board of Health and Welfare indicate that the frequency of caries decreased dramatically from 1960 to 1985, though comparable data were difficult to obtain for the whole 25-yr period. The conclusion from this study is that these changes in caries prevalence in Sweden cannot be attributed to a corresponding decrease in the per capita consumption of sugar and sugar-containing products. On the contrary, the intake of some products traditionally related to dental caries, such as candy and soft drinks, increased during 1960-1985.

Immunotherapy with cat- and dog-dander extracts. IV. Effects of 2 years of treatment.

Thirty-five patients (20 children and 15 adults) with animal-dander asthma completed 2 years of immunotherapy with partly purified and standardized cat- or dog-danger extracts. The first year of the study was performed double-blind with a placebo-treated control group. These 15 patients were transferred to active treatment for a second year. All patients were followed by use of the skin prick test (SPT), allergen and histamine bronchial challenges, and tests for allergen-specific IgE, IgG1, and IgG4 levels. In the group treated with active extracts for 2 years (group A), the previously reported decrease in bronchial responsiveness to cat extract (p less than 0.001) and histamine (p less than 0.01) was even more pronounced after the second year. After 1 year of active treatment in the original placebo group (group B), a significant decrease in the bronchial responsiveness to cat extract was noted (p less than 0.001). The responsiveness to histamine was decreased only in the patients treated with cat-dander extracts (p less than 0.05). A significant decrease in the SPT (p less than 0.001) and an increase in the allergen-specific IgE (p less than 0.001) and IgG4 (p less than 0.001) was also noted in patients (group B) treated with cat-dander extracts. The side effects in the two groups (A and B) were negligible, except for some systemic side effects, especially among the children during the initial phase of immunotherapy. The symptoms were mild and responded promptly to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambient nitrogen dioxide concentrations increase bronchial responsiveness in subjects with mild asthma.

Twenty subjects with mild asthma were exposed at rest in a body plethysmograph, to NO2 at 0, 260, 510 and 1,000 micrograms.m3, for 30 min on four separate days. Bronchial responsiveness (histamine inhalation test) was measured after each exposure session. Airway resistance (Raw), thoracic gas volume (TGV) and specific airway resistance (sRaw) were measured before, during and after exposure, and the breathing pattern was monitored during the whole session. Bronchial responsiveness increased significantly after 30 min exposure to 510 micrograms.m3 NO2 (p less than 0.01). There were also tendencies to an increased bronchial responsiveness after exposure to 260 and 1,000 micron.m3 NO2, but these changes were not statistically significant. Effects on airway resistance and breathing pattern were not demonstrated by exposure to 0-1,000 micrograms.m3 NO2. We conclude that short-term NO2 exposure at about 500 micrograms.m3 slightly affects human bronchial responsiveness in subjects with mild asthma.

Specific airway conductance and airway conductance-lung volume curves in normal and asthmatic subjects.

Airway conductance (Gaw) depends on lung volume (TGV). An approximate correction for this volume dependence can be obtained by calculating specific airway conductance (sGaw = Gaw-TGV). In this study, Gaw-TGV curves were compared with sGaw in 30 healthy and 20 asthmatic subjects who were studied by body plethysmography. Gaw, TGV and sGaw were measured five times at three to five different lung volumes. sGaw was dependent on TGV, the regression having a negative slope (-0.24 and -0.27 kPa-1.s-1.l-1, in the group without and with asthma, respectively). A change in TGV by 1 l caused a 9 and 11% decrease in sGaw, respectively. Bronchial obstruction induced by histamine inhalation in the asthmatic subjects increased the dependence on TGV by sGaw, now with a positive slope. Thus, a change in TGV by 1 l caused a 20-100% increase in sGaw, depending on the degree of airway obstruction. The Gaw-TGV curve was approximately linear around the resting lung volume. The coefficient of variation in determining the slope of the Gaw-TGV curve was as high as 110 and 153% in health and asthmatic subjects, respectively. It is concluded that sGaw, although rapidly determined, has a systematic error in its correction of lung volume dependence, which the Gaw-TGV curve does not. The Gaw-TGV curve therefore has advantages in research work, but since its construction is time consuming it is hardly suitable in clinical practice.

Immunotherapy with cat- and dog-dander extracts. II. In vivo and in vitro immunologic effects observed in a 1-year double-blind placebo study.

The effects of immunotherapy on the skin prick test, allergen-specific IgE, and IgG in 39 patients (19 adults and 20 children), treated with partially purified cat- or dog-dander extracts or placebo for 1 year, were studied by use of a double-blind protocol. IgG levels were measured by three different assays: IgG RAST, IgG4 RAST, and Staph A IgG1, 2, and 4. The skin prick test reaction decreased continuously in the allergen-treated patients, the decrease being the first sign of an immunologic effect of the therapy. Allergen-specific IgE levels increased during the first 9 months in both children and adults. The RAST activity during the last 3 months continued to rise for the children, whereas it declined for the adults. IgG levels measured by all three methods demonstrated an increase in the allergen-treated patients and no increase in the placebo-treated patients. The children developed higher values on IgG RAST and IgG4 RAST than the adults. IgG RAST correlated negatively with IgE levels in the cat allergen-treated group. No correlation between skin prick test results, IgE levels, and IgG levels was found, nor was there any correlation between these parameters and the patients' own subjective evaluation or the allergen bronchial challenge test. In summary, the expected change in skin prick test reaction and allergen-specific IgE and IgG levels was found. The children tended to be more immunologically active than the adults.

Immunotherapy with cat- and dog-dander extracts. III. Allergen-specific immunoglobulin responses in a 1-year double-blind placebo study.

An investigation was made of the specific antibody response to individual antigens in 40 patients taking part in a double-blind placebo study of immunotherapy with cat- or dog-dander extracts. Antigen-specific IgE levels were measured by means of CRIE, and the results were expressed as scores. The patients demonstrated IgE specificities toward 1 to 5 antigens. Cat-dander antigens Nos. 4 (cat Ag 1) and 7, and dog antigens Nos. 6 and 13, produced the highest scores, but high IgE binding was also found for dog albumin. After 1 year of treatment, the IgE responses of the two treatment groups (allergen and placebo) were statistically indistinguishable from those before the start of treatment. There was a tendency toward a reduction in score for two of the dander antigens (cat Ag 1 and dog Ag No. 13), and no new IgE specificities appeared. Antigen-specific IgG levels were measured by means of CIE with patient serum incorporated in an intermediate gel, and the results were expressed as plus/minus precipitins. Only two patients had precipitating antibodies before the start of treatment (one against cat albumin and one against cat Ag 1). During the course of treatment, the production of antigen-specific IgGs was observed in 18/22 allergen- and 1/18 placebo-treated patients. For the cat allergen-treated group, the specificities were directed against cat antigens Nos. 2, 3 (cat albumin), 4 (cat Ag 1), and 7, and for the dog allergen-treated group, against dog antigens Nos. 2 (dog albumin), 13, and 20.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunotherapy with partially purified and standardized animal dander extracts. I. Clinical results from a double-blind study on patients with animal dander asthma.

Forty-one patients (21 adults and 20 children) with cat dander-or dog dander-induced asthma were selected for immunotherapy with standardized and partially purified cat- or dog-dander extracts by use of a double-blind protocol. Based on sex, age, clinical history, results of bronchial challenge, and crossed radioimmunoelectrophoresis studies, the patients were stratified in matched pairs, and the treatment alternatives were distributed randomly among the pairs. Twenty-two patients treated with allergen (15 with cat allergen and seven with dog allergen) and 17 patients receiving placebo therapy completed the first year of treatment. In the cat allergen-treated group, the bronchial sensitivity toward cat and histamine decreased (p less than 0.001 and p less than 0.05, respectively). Measured by bronchial challenge, the cat allergen-treated patients could tolerate 11 times more allergen at the end than at the start of the study, and they also demonstrated a tendency toward less pronounced symptoms after exposure to cat and dog allergens. No significant changes were observed in the dog allergen treated- or placebo-treated groups. The adverse effects in general were negligible except for some systemic side effects during rush hyposensitization, especially among the children, but these were mild and responded promptly to treatment.

HDL2 and HDL3 lipid levels in coronary artery disease.

The concentrations of cholesterol (C) and phospholipid (PL) levels in the high density lipoprotein (HDL) fraction and the HDL2 and HDL3 subfractions were determined in 74 men with incapacitating angina pectoris and coronary artery disease (CAD) verified by angiography. An equal number of randomly sampled healthy men matched for age, occupation and place of living constituted the control group. The HDL2 and HDL3 fractions were separated by a combination of ultracentrifugation and precipitation. The levels of HDL-C and HDL-PL were reduced in the CAD patients. The reduction of HDL lipids was attributed to both the HDL2 and HDL3 fractions. Proportionally there was a greater reduction of C and PL in HDL2 than in HDL3. The decrease of HDL2-C and HDL3-PL were significant also after allowance for the influences of obesity and triglyceride level. The reductions of HDL2 and HDL3 were significant as well in smoking as in nonsmoking CAD patients and both in patients with and without beta-adrenoceptor blocking drugs.