'Vertition' of integumental organs in mites revisited: a case of fluctuating asymmetry.
Vertition in mites is defined as a meristic variation for a bilateral integumental organ with a separate genetic control for each body side. A prominent hypothesis expressed by Grandjean is the role of vertition in the evolutionary trend towards a reduced number of hair-like organs (mechano- and/or chemo-receptors) known to have occurred in many mite groups. Observations on leg setae in the two-spotted spider mite Tetranychus urticae do not support this hypothesis. Meristic variation for leg setae rather conforms to the notion of fluctuating asymmetry: the difference between the number of leg setae on the right and left sides of the body had a unimodal distribution with a mean of zero. Moreover, lack of heritability for left/right absences of leg setae in an inbred laboratory strain suggests that vertition could be purely environmental. It is therefore argued that meristic variation for hair-like organs in mites is caused by random developmental accidents not corrected by homeostatic mechanisms normally resulting in a perfect bilateral symmetry.


Comparative analysis of the in vivo angiogenic properties of stable prostacyclin analogs: a possible role for peroxisome proliferator-activated receptors.
Until recently, prostacyclin (PGI2) biological activities were thought to be exclusively mediated by cell surface receptors named IP. Recent studies have instead identified a novel pathway of PGI2 signaling, occurring through activation of peroxisome proliferator-activated receptors (PPARs) located in the nucleus. The availability of stable PGI2 analogs with different affinity for IP receptors and PPARs provides the possibility to test the importance and function of this dual pathway in vitro and in vivo. In this study, the in vivo angiogenic properties of different PGI2 analogs and the potential relationship between PPAR-mediated pathways, vascular endothelial growth factor (VEGF), and angiogenesis were investigated. By using the murine corneal model of angiogenesis, we found that PGI2 analogs able to act on nuclear PPARs, such as iloprost and carbaprostacyclin (cPGI), induce angiogenesis in vivo. In contrast, cicaprost, a PGI2 analog that only acts on IP receptors, has no in vivo angiogenic activity. Interestingly, angiogenesis induced by iloprost and cPGI does not differ in extent and morphology from that induced by VEGF and is associated with local increment of VEGF mRNA expression and protein levels. Finally, iloprost-induced angiogenesis is significantly decreased by systemic inhibition of VEGF activity, obtained by gene transfer of a soluble form of the VEGF receptor Flt-1. These data demonstrate that stable PGI2 analogs may have angiogenic properties in vivo, depending on their ability to act on PPARs. The resulting angiogenic process appears to be mediated by VEGF. These findings indicate that important physiological activities in the cardiovascular system, such as angiogenesis and VEGF induction, may be modulated by PGI2 through specific activation of the PPAR signaling pathway in vivo, with potentially important fundamental and clinical implications.


Adjuvant therapy for breast cancer in Kyushu.
There is lack of information on the present status of adjuvant therapy for breast cancer in Kyushu. Therefore, the Kyushu Breast Cancer Study Group (KBC-SG) started registering newly diagnosed breast cancer patients who were to receive adjuvant therapy. During a period from 2001 to 2003, institutions participating in KBC-SG registered new patients who underwent curative surgical treatment for breast cancer to the registration office. One year later, the office sent them inquiries to gather any missing information. A total of 2284 patients were registered from 49 institutions. The mean age was 55, ranging from 30 to 93 years, and 46% had stage I disease. Estrogen and/or progesterone receptor was positive in 71% by immunoperoxidase staining, and HER2 was expressed in 297 (33%) of 906 patients. Twenty percent of the patients underwent adjuvant radiation therapy with or without antineoplastic agents. Overall, 98% received hormonal and/or cytotoxic agents. Anthracycline-containing regimens were given to 628 of 1285 (49%) patients with chemotherapy, while 360 (28%) received oral 5-fluorouracil derivatives with or without oral cyclophosphamide. Anthracycline combination chemotherapy was commonly used as adjuvant therapy, but there were over a quarter of patients only given oral 5-FU derivatives, which might not be recommended by worldwide consensus. Adjuvant radiation therapy was also given to only 20% of the patients in Kyushu, which might be fewer than the report by the Japanese Breast Cancer Society. Based on these data, the KBC-SG will continue cooperative studies to improve the quality of adjuvant treatment for early breast cancer.


[Encephalopathy and Hashimoto thyroiditis].
A generalized epileptic seizure revealed a subactute encephalopathy which was attributed to Hashimoto's thyroiditis. Primary biliary cirrhosis was also discovered. The encephalopathy rapidly followed a favourable course under corticosteroid therapy, which confirms that it was an immune disease.


Multiple urogenital abnormalities in a Persian cat.
A 1.5-year-old female Persian cat was presented for inappetence and azotemia. Ultrasonography and urography revealed multiple abnormalities involving the genitourinary tract, including agenesis of the right kidney and ureter. Gross examination of the abnormal uterus revealed segmental aplasia of right caudal uterine horn causing cranial distension with fluid, a normal left uterine horn, and both normal ovaries. Microscopically, endometrial glands of the right uterine horn were markedly decreased in number. The right uterine horn was hemorrhagic suggesting estrus. This is the first report of this combination of urinary and uterus abnormalities in the veterinary literature.


Spectrum of abdominal and pelvic infections caused by pneumococci in previously healthy adult women.
Eleven cases of pneumococcal infection of abdominal and pelvic origin that occurred in previously healthy adults are described. All cases occurred in women who were admitted to a county hospital in Norway with acute abdominal symptoms such as pain, nausea, vomiting and diarrhea. Explorative laparotomy was performed in eight patients. Three patients had diffuse peritonitis and seven cases were classified as pelvic inflammatory disease; five of these seven patients had pelvic peritonitis. All patients but one were treated with antibiotics, and all survived without long-term sequelae. Although abdominal and genital infections caused by pneumococci are rare, their potential occurrence should not be neglected.


Strategies for increasing adherence to an online smoking cessation intervention for college students.
High rates of Internet use among young adults make online intervention with this population particularly attractive. However, low adherence rates limit the exposure to and the potential effectiveness of these programs. This study identifies strategies for increasing adherence by examining the rates of participation for a 5-week beta (pilot) version and final version of the RealU Web site, an online intervention for college smokers. Three modifications from the beta to the RealU Web site were (a) changing format from a smoking cessation Web site to an online college life magazine, (b) providing proactive peer e-mail support, and (c) adopting a more linear site structure. Participants were recruited via Internet health screening and received US$10 for completing weekly study activities. Enrollment among eligible smokers was higher for the beta compared with the RealU intervention (47/69, 68.1% vs. 517/1618, 32.0%, p<.001), but participants did not differ in terms of age, gender, or past 30-day cigarette or alcohol use. Participation fell sharply during the beta test (53% in week 1 to 26% by week 5) compared with the RealU average of 95% (range 89% to 98%). Participation during each study's final week was much higher in the RealU (93% week 20) compared with the beta (26% week 5, p<.001). After 5 weeks, self-reported 30-day abstinence was higher for RealU intervention participants (16.0%) compared with the beta participants (4.3%, p=.03). The modifications from the beta to RealU Web site described above resulted in high rates of sustained participation over 20 weeks.


Hydatid cysts of the orbit in Xinjiang: a review of 18 cases.
PURPOSE To review the prevalence of orbital hydatid cyst in Xinjiang, China. METHOD. In the records of our hospital and in the issues of Chinese medical journals between 1956 and 1994, we found 18 cases of orbital hydatid cyst, including 10 cases from our hospital, two cases from the ShiHeZi Medical College, three cases from the YiLi local clinical hospital, and three other cases from the HeTian, WuSu and Changji local hospitals. All cases were verified by operation. RESULTS. In our hospital, a review of 3736 cases of hydatid cyst between 1957 and 1992 showed that hydatid cyst of the orbit accounted for 0.3%. Among the 18 cases, 7 were males and 11 females; the age ranged from 3 to 55 years and 15 cases were under 16 years of age (83%).The main symptom of orbital hydatid cyst was proptosis. Before the 1970s, the diagnosis depended on positive serological tests, X-ray examination and a history of infection of other parts of body with Echinococcus granulosus, with final confirmation by operation. In recent years, CT and ultrasonography have made possible a positional and qualitative diagnosis before surgery. With regard to the serological tests, the Intradermal test (ID) was positive in 77% of cases, while Indirect hemagglutination (IHA) and Counter-immuno-electrophoresis (CIEP) were positive in two cases and negative in two cases, respectively. No recurrence was seen when two cases were examined by CT six years after the operation, nor in eight other cases followed by letter for between 8 and 11 years. CONCLUSIONS. Hydatid cyst is an endemic disease in Xinjiang, but orbital hydatid cyst is rarely seen. The diagnosis is relatively easy to make in endemic countries, based on the clinical features, ultrasonography, CT-scan and serology. The main treatment for orbital hydatid cyst is surgery.


Induction of a fatigue-resistant phenotype in rabbit fast muscle by small daily amounts of stimulation.
We have shown that fatigue resistance can be induced in rabbit tibialis anterior (TA) muscles without excessive power loss by continuous stimulation at low frequencies, such as 5 Hz, and that the same result is obtained by delivering a 10-Hz pattern in equal on/off periods. Here we ask whether the same phenotype could be produced with daily amounts of stimulation that would be more appropriate for clinical use. We stimulated rabbit TA muscles for 6 wk, alternating fixed 30-min on periods of stimulation at 10 Hz with off periods of different duration. All patterns transformed fast-glycolytic fibers into fast-oxidative fibers. The muscles had fatigue-resistant properties but retained a higher contractile speed and power production than muscles transformed completely to the slow-oxidative type. We conclude that in the rabbit as little as one 30-min period of stimulation in 24 h can result in a substantial increase in the resistance of the muscle to fatigue.


GENESIS: Phase III trial evaluating BL-8040 + G-CSF to mobilize hematopoietic cells for autologous transplant in myeloma.
Effective hematopoietic cell transplantation relies upon collecting adequate numbers of CD34+ hematopoietic stem cells, typically from peripheral blood. A minimum of ≥2 × 106 CD34+ cells/kg are necessary, while transplants of ≥5-6 × 106 CD34+ cells/kg are associated with improved hematopoietic recovery. Granulocyte colony stimulating factor (G-CSF) remains the gold standard for hematopoietic stem cell mobilization. However, in randomized trials for autologous-hematopoietic cell transplantation in multiple myeloma, approximately 45% of patients remain unable to optimally mobilize with G-CSF alone despite multiple injections and apheresis days. Therefore, reducing mobilization failures remains an unmet need. The study objective is to evaluate the superiority of one dose of BL-8040 plus G-CSF over placebo plus G-CSF to mobilize ≥6.0 × 106 CD34+ cells/kg in up to two apheresis days. ClinicalTrials.gov: NCT03246529.


Reliability of the Closed Kinetic Chain Upper Extremity Stability Test in young adults.
To analyze the reliability indicators of CKCUEST, and to investigate how many sessions are necessary to find a stable score. Reliability study. Biomechanics laboratory. The sample consisted of 36 healthy young adults, of both genders. The subjects performed four CKCUEST with a minimum interval of three days between evaluations. The number of touches in each execution was counted, and then the average values of the number of rings, normalized score and power were calculated. The CKCUEST presented ICC ranging from 0.77 to 0.92 (mean number of touches), 0.80 to 0.94 (normalized score) and 0.91 to 0.98 (power). The Bland-Altman plots showed the presence of systematic error for all measures, as also confirmed by the ANOVA analysis. The scores increased every session for both genders. The boys' scores stabilized in the third session. However, the girls' scores did not stabilize. The CKCUEST presents excellent reliability; however, there is the presence of systematic error between measurements. It is necessary to perform at least three sessions to obtain reliable data for male participants, and the female results were not conclusive.


Growth patterns of monosodium urate monohydrate (gouty and urinary) crystals in gel: An in vitro study.
Monosodium urate monohydrate crystals are deposited in peripheral joints causing gout and elicit an intense localized inflammatory attack whereas in collecting ducts and medullary interstitium as a urinary calculi which causes dysuria, nausea and hematuria. The purpose of present study is to observe possible growth patterns of monosodium urate monohydrate crystals. The crystals were grown in test tubes by single diffusion gel technique and were observed at 7th, 14th, 21st, 28th and 40th day. Needle and spherulite type crystals were observed at 14th day, while arboresque, crystal sheaves, densely branched, dumbbell, mushroom type spherulites, plumose and hexagonal prismatic crystals were observed for the first time. After 40th day complete spherulites were observed with their aggregates. The crystals were characterized by Scanning Electron Microscopy, Energy-Dispersive X-ray and Fourier Transform infra Red spectroscopies. The pattern of MSUM will be helpful to determine the role of different natural products in the modulation, inhibition or promotion of these crystals by affecting the shape, size, transparency, approximate number and total mass of growing crystals. In case of inhibition or modulation it will be helpful for evaluation the prophylactic management whereas the promotion of the crystal will give an idea about the risk factors of gout and kidney stones.


Immunoaffinity isolation of apolipoprotein E-containing lipoproteins.
Discrete apolipoprotein E-containing lipoproteins can be identified when EDTA plasma is fractionated on columns of 4% agarose. The present study has demonstrated, by physical and metabolic criteria, that these apolipoprotein E-containing lipoprotein subclasses may be further isolated by immunoaffinity chromatography. Whole plasma was first bound to an anti-apolipoprotein E immunoadsorbent prior to gel filtration on 4% agarose. After elution from the affinity column and dialysis, the bound fraction was chromatographed on 4% agarose. Discrete subfractions of apolipoprotein E could be demonstrated within elution volumes similar to those observed in the original plasma. When whole plasma was first submitted to gel filtration and the apolipoprotein E-containing lipoproteins of either intermediate- or of high-density lipoprotein (HDL) size were subsequently bound to anti-apolipoprotein E columns, the bound eluted fractions maintained their size and physical properties as shown by electron microscopy and by rechromatography on columns of 4% agarose. The metabolic integrity of apolipoprotein E-containing very-low-density lipoproteins (VLDL) was examined by coinjection into a cynomolgus monkey of 125I-labeled apolipoprotein E-rich and 131I-labeled apolipoprotein E-deficient human VLDL which had been separated by immunoaffinity chromatography. The plasma specific activity time curves of the apolipoprotein B in VLDL, intermediate-density (IDL) and low-density (LDL) lipoproteins demonstrated rates of decay and precursor-product relationships similar to those obtained after injection of whole labeled VLDL, supporting the metabolic integrity of VLDL isolated by immunoaffinity chromatography.


Mutants of Saccharomyces cerevisiae cell division cycle defective in cytokinesis. Biosynthesis of the cell wall and morphology.
The four temperature-sensitive mutants of Saccharomyces cerevisiae in the cell division cycle defective in cytokinesis (cdc, 3, 10, 11 and 12), have been analyzed with respect to the biosynthesis of the cell wall polymers. After 3 hours of incubation at the non-permissive temperature (37 degrees C) these strains stop growing. The synthesis of glucan, mannan and chitin (wall polymers) level off in a similar time, but glucan, mannan and chitin synthases remained active for at least 4 hours. If the mutants are analyzed by transmission and scanning electron microscopy different pictures emerge. Two of the mutants cdc 10 and cdc 12, after 3 hours of incubation at 37 degrees C present apparently normal cytoplasms and cell wall surfaces with multiple elongated buds. The other two mutants, cdc 3 and cdc 11, present a completely disarranged cytoplasmic content and damage at the level of the plasma membrane is evident. These and other observations, suggest that between the execution points of cdc 3 (0.27) and cdc 10 (0.58), essential processes in the assembly of cell membrane occur.


[Appendectomy 1997--open or closed?].
Unlike laparoscopic cholecystectomy, laparoscopic appendectomy (LAE) has not yet become popular. Are there no significant advantages? Or is the poor acceptance of LAE related to its longer learning curve, longer operative times and the need for additional equipment, which lead to some inconvenience when the procedure is done on an emergency basis? LAE may be performed as safely as open appendectomy (OAE) with fewer wound complications. Superior laparoscopic exploration allows an accurate diagnosis and reduces the rate of negative appendectomies. In contrast, postoperative pain, recovery and the cosmetic result are equal to or at best slightly better than in open surgery. Therefore, in the routine patients, there is no need to replace OAE by LAE. In the case of an uncertain diagnosis, the laparoscopic approach is generally superior, allowing thorough abdominal exploration. This has to be considered in each individual case; however, women with lower abdominal pain and suspected appendicitis will certainly benefit from laparoscopy, as well as older patients with an unclear diagnosis. The lower rate of wound infections is beneficial to obese patients and to patients with gangrenous or perforated appendicitis. Furthermore, the decision for one procedure or the other is influenced by the patient's individual preference and cosmetic aspects. The verifiable benefit of the laparoscopic procedure for certain categories of patients and the potential advantages in the individual case suggest that competent handling of laparoscopic technology will be required in future. Therefore, experienced surgeons should take more active interest in instruction and training--even when surgery has to be performed after hours.


Pulmonary Agenesis.
Unilateral opaque lung with ipsilateral mediastinal shift is an uncommon cause of respiratory distress in newborn which can be found on simple radiograph of the chest. Pulmonary agenesis is a rare cause of unilateral opaque lung in the newborn. Nearly 50% cases of pulmonary agenesis are associated with other congenital defects including cardiovascular, skeletal, gastrointestinal or genitourinary systems. We report an infant with agenesis of the right lung associated with other congenital anomalies.


Nonsubtractive spiral phase contrast velocity imaging.
Phase contrast velocity imaging is a standard method for accurate in vivo flow measurement. One drawback, however, is that it lengthens the scan time (or reduces the achievable temporal resolution) because one has to acquire two or more images with different flow sensitivities and subtract their phases to produce the final velocity image. Without this step, non-flow-related phase variations will give rise to an erroneous, spatially varying background velocity. In this paper, we introduce a novel phase contrast velocity imaging technique that requires the acquisition of only a single image. The idea is to estimate the background phase variation from the flow-encoded image itself and then have it removed, leaving only the flow-related phase to generate a corrected flow image. This technique is sensitive to flow in one direction and requires 50% less scan time than conventional phase contrast velocity imaging. Phantom and in vivo results were obtained and compared with those of the conventional method, demonstrating the new method's effectiveness in measuring flow in various vessels of the body. Magn Reson Med 42:704-713, 1999.


Assessment of chronic childhood dysphonia.
Chronic childhood dysphonia is a common condition in the school-age period. Perceived functional disorder is subjective and the alert is usually given by a person not belonging to the child's immediate environment. History-taking often suggests a malformation or acquired lesion. Functional assessment helps measure and diagnose the vocal impairment. Physical and endoscopic assessment in consultation is the key examination: it is only rarely impossible in children and can often found diagnosis. Additional examinations are sometimes necessary.


A new species of <i>Oncopeltus</i> Stål, 1868 (Heteroptera: Lygaeidae) in the nominate subgenus from Ecuador.
Oncopeltus Stål is a lygaeine genus currently comprising 39 species classified in two subgenera (Slater & O'Donnell, 1995). Oncopeltus is distributed in both hemispheres in tropical and temperate areas. Species on this genus are commonly known as milkweed bugs, because of their trophic association with plants in the family Apocynaceae (Scudder & Duffey, 1971). From these plants, the bugs sequester cardenolides making them unpalatable for predators (Duffey & Scudder, 1972). These habits are also accompanied with their brightly reddish coloration, which has been interpreted as aposematism (Duffey & Scudder, 1972, O'Rourke, 1979; Faúndez et al., 2016). As these bugs attack several plants in the subfamily Asclepiadoideae; they have an economic impact on several ornamentally used species, and may sometimes be considered as garden pests (Faúndez & Rocca, 2016; Faúndez et al., 2016). Species of this group are also well known for generating some natural hybrids (O'Rourke, 1979); because of this, their systematic treatment at specific level has been confused, and the identity of several taxa remain unclear. The purpose of this contribution is to describe a new species in this genus from Ecuador.


Eczema and food allergy in an Italian pediatric cohort: no association with TLR-2 and TLR-4 polymorphisms.
Recent studies have indicated that Toll-like receptor polymorphisms or their impaired signalling, specifically TLR-2 and TLR-4, were correlated with a higher risk for allergy. The purpose of this study is to evaluate the associations of TRL-2 and TRL-4 single nucleotide polymorphisms (SNP) and atopic traits in a cohort of 159 Italian allergic children (102 affected by eczema and 57 by IgE-mediated food allergy) and 147 healthy controls recruited in Rome, Italy. DNA was isolated from the peripheral blood and TLR-2 R753Q/TLR-4 D299G polymorphisms were determined by TaqMan MGB probes using Real-Time PCR technique. In the control group, the TLR-2 polymorphism R753Q had a prevalence of 2.5% while the frequency of the TLR-4 D299G was 12%. None of the 159 allergic patients showed the R753Q SNP. By contrast, 7/57 patients with food allergy (12%) and 6/102 subjects with eczema (6%) carried the TLR-4 mutation. In our cohort, no evidence of correlation between TLR-2 or TLR-4 polymorphism and eczema and food allergy incidence and/or severity was found. Further studies are needed to clarify the possible role of TLR-2 and TLR-4 polymorphism in allergic disease, in Italian children.


Survey on ventral hernias: surgeon indications, contraindications, and management of large ventral hernias.
Repair of ventral hernias constitutes one of the most common surgical procedures. Although an abundance of data exists on objective outcome measures, very little information exists on subjective measures of surgeon preference and patient satisfaction in surgical management of ventral hernias. Moreover, there are minimal data on indications for elective repair of ventral hernias. Two questionnaires were sent to a population of general and plastic surgeons active in hernia surgery. The first of these aimed at gathering information from surgeons about their indications and contraindications for repair of ventral hernias. The second survey was aimed at determining surgeons' perception of patient satisfaction with repair of large ventral hernias (greater than 15 cm width). Five hundred sixty-eight surgeons responded to the first survey and 336 responded to the second survey. The most common indications for elective repair of abdominal wall hernias were generalized pain (68.7%) and cosmesis (54.6%), whereas the most common contraindications were morbid obesity (43.3%), American Society of Anesthesiologists Class III or IV (35.4%), and enterocutaneous fistula (33.1%). The majority of surgeons do not routinely repair large abdominal wall hernias in asymptomatic patients, but 31.6 per cent do repair asymptomatic large hernias. Most surgeons reported that the majority of patients had resolution of pain and subjective impression of improved cosmesis after surgery. This study demonstrates uniform indications and contraindications for surgical repair of ventral hernias among surgeons as well as surgeons' perception of improvements in satisfaction of most patients after surgery. Future studies will focus on comparing surgeon and patient satisfaction.


[Effects of oleanolic acid on apoptosis and PTEN expression of Jurkat cells].
This study was aimed to explore the effects of oleanolic acid on PTEN expression and apoptosis of Jurkat cells. The inhibitory rate was measured by Cell Counting Kit-8. The apoptotic nucleus morphous was observed by Hoechst 33258 staining. The apoptosis rate of Jurkat cells were determined by flow cytometry with Annexin V/PI double staining. PTEN mRNA and protein were detected by quantitative real-time PCR and Western blot respectively. The results showed that oleanolic acid inhibited the proliferation of Jurkat cells in time- and dose-dependent manners. The 50% growth inhibition (IC(50)) at 12, 24 and 48 hours were about 85.35 µmol/L, 53.66 µmol/L and 33.18 µmol/L respectively. Flow cytometric assay showed that the apoptotic rates of Jurkat cells treated with oleanolic acid (0, 40, 80 and 160 µmol/L) for 24 hours were 6.72%, 19.8%, 28.72% and 30.12% (p < 0.05). PTEN mRNA and protein expressions were up-regulated in Jurkat cells treated with oleanolic acid of concentration 80 µmol/L and 160 µmol/L for 24 hours. It is concluded that up-regulation of PTEN mRNA and PTEN protein may be involved in oleanolic acid-induced Jurkat cell apoptosis.


[Detection of IgE antibodies to salt-insoluble wheat proteins in sera of patients with atopic dermatitis by ELISA and immunoblotting techniques].
Specific IgE antibodies against salt-insoluble wheat proteins were investigated in sera from 60 patients with atopic dermatitis (AD) positive to wheat specific CAP-RAST. The salt-insoluble wheat protein fraction was prepared from whole protein fraction of wheat flour, which was extracted by PBS containing 6 M urea. IgE antibodies to salt-insoluble proteins were detected in 15 of the sera. IgE-ELISA was applied to these 15 sera, with whole wheat proteins, salt-soluble proteins, and salt-insoluble proteins used as antigens. Wheat specific CAP-RAST values correlated well with the IgE-ELISA titers against salt-soluble proteins (r = 0.918 p < 0.001). On the other hand, IgE-ELISA titers against both the salt-insoluble proteins and the whole wheat proteins correlated least with CAP-RAST values (r = 0.161 and r = 0.113). The inhibition tests indicated that IgE antibodies against salt-insoluble proteins were different from those against salt-soluble ones. Thus, IgE antibodies to salt-insoluble proteins were another antigen target of IgE-mediated allergy manifestation. To determine the molecular weight of antigens reacting with IgE, IgE-immunoblotting was performed. Several polypeptides with molecular weights of 33-45, 84, 90 and 98 KD were detected. However, the antigen patterns of the blots varied depending on the sera used. These findings suggest that salt-insoluble wheat proteins are the major antigens in some wheat-dependent AD, and that IgE detection against salt-insoluble wheat proteins is important for the diagnosis of wheat allergy.


Radon testing in schools in New York State: a 20-year summary.
For nearly 20 years the Department of Health has conducted programs to assist in the measurement and reduction of indoor radon concentrations in 186 schools located primarily in Zone 1 areas of New York State. Although many schools had few or no rooms containing radon above 148 Bq/m(3), some rooms had >740 Bq/m(3) and remediation techniques were utilized to reduce exposure. Short-term radon measurements in the schools showed little correlation to basement and first-floor radon results from single-family homes in the towns.


The dechlorination of pentachlorophenol by zerovalent iron in presence of carboxylic acids.
The dechlorination of pentachlorophenol (PCP) by zerovalent iron (Fe(0)) in presence of low molecular weight carboxylic acids was investigated. The experimental results showed that oxalic acid was advantaged among the selected acids for the dechlorination of PCP. The lower pH value and the higher dosage of Fe(0) were favorable for the enhancement of dechlorination efficiency. With their strong complexing and pH buffering properties, carboxylic acids favored the fresh surface of iron, which benefits to the dechlorination of PCP by Fe(0). Moreover, the oxalate-iron complexes have more reductive activities and then lead to the highest dechlorination efficiency of PCP by Fe(0).


31P NMR study of phosphorus containing metabolites in the uterus of hamster: changes during the estrous cycle and the effect of hormonal manipulation.
Changes in the concentrations of phosphorus containing metabolites were monitored by 31P NMR in the uteri of hamsters during the estrous cycle. Concentrations of phosphocreatine (PCr) and ATP were significantly increased in estrus animals compared to diestrus animals. Concentrations of these metabolites were also increased in immature female hamsters and ovariectomized (OVX) adult hamsters treated with estradiol indicating that estradiol was responsible for this effect. However, the steroid hormones progesterone and testosterone did not increase the concentrations of the phosphorus containing metabolites. Further, immature female hamsters also following treatment with estradiol showed an initial decline in phosphomonoester (PME), PCr, ATP and inorganic phosphate but by 24 h of treatment the concentrations returned to control levels. The NMR study also revealed that the intracellular pH of the hamster uterus was around 7.4 all through the estrous cycle.


[Changes in hemostasis during orthotopic liver transplantation and massive transfusion: a case report].
Changes in hemostasis during orthotopic liver transplantation (OLT) and an intraoperative bleeding complication requiring massive transfusion are discussed. The monitoring of hemostasis included bed-sided thromboelastography, measurement of in vitro platelet function with the thrombostat and routine coagulation tests as well as retrospective analysis of coagulation factors. Changes in hemostasis during OLT were documented as reported previously until reperfusion of the donor organ. Due to an incongruence between the caval veins and massive surgical bleeding, the liver had to be clamped again for reconstruction and perfused with University-of-Wisconsin solution. The second reperfusion was technically uncomplicated. However, the coagulation profile deteriorated dramatically: especially a decrease in platelet function and hyperfibrinolysis led to massive oozing. Successful therapeutical intervention included substitution of packed red blood cells. fresh frozen plasma, platelets. concentrates of hemostatic factors, and aprotinin. The patient was discharged from hospital after 5 weeks with a good liver function and a normal coagulation profile. During OLT, clinically relevant changes in hemostasis can occur suddenly. Therefore. a close perioperative monitoring of primary and secondary coagulation is mandatory.


Afferent innervation of extraocular muscles in the rat studied by retrograde and anterograde horseradish peroxidase transport.
After injection of horseradish peroxidase (HRP) into extraocular muscles of rat perikarya were labeled mainly along the medial edge of the ophthalmic subdivision of the trigeminal ganglion but not in the mesencephalic nucleus of the trigeminal nerve. Injections of HRP into the trigeminal ganglion labeled simple as well as branching and meandering free fiber endings in extraocular muscles. No evidence for muscle spindles was found, but the meandering endings may be considered as candidates for stretch receptors.


Tin ear syndrome: rotational acceleration in pediatric head injuries.
An array of signs pathognomonic of child abuse is described for three young children. The eponym "tin ear syndrome" describes distinct unilateral ear bruising, radiographic evidence of ipisilateral cerebral edema with obliteration of the basilar cisterns, and hemorrhagic retinopathy. Rotational acceleration produced by blunt trauma to the ear is shown to be a necessary and sufficient cause for the production of this syndrome. An approximate value of 4,670 radians/s2 produced by a force of 309 to 347 N (70 to 80 lb) results in shear stress and tearing of the subdural veins, loss of cortical vasomotor tone, cerebral hyperemia, herniation, and death. Past history and environmental circumstances implicated child abuse in every case.


Metastatic spinal intramedullary germinoma with elevated cerebrospinal fluid chorionic gonadotropin: a case report.
We treated a patient whose unusual recurrent germinoma illustrates the diagnostic value of measuring human chorionic gonadotropin beta subunit (HCG-beta) in cerebrospinal fluid (CSF) and serum. A 25-year-old man with a suprasellar germinoma and ventricular dissemination was treated successfully with systemic chemotherapy and cranial irradiation. Six years later he developed progressive numbness and weakness in both upper extremities. Magnetic resonance imaging (MRI) disclosed an intramedullary spinal cord tumor in the cervical region. The CSF concentration of HCG-beta was elevated and exceeded that in serum. After completion of systemic chemotherapy and spinal irradiation, symptoms subsided and the tumor was no longer evident on MRI. Based on the patient's history and the rapid response of the tumor to treatment, the spinal cord tumor was considered a metastatic intramedullary spinal germinoma representing CSF dissemination via the central canal.


Fine-scale genetic population structure of southern pine beetle (Coleoptera: Curculionidae) in Mississippi forests.
The southern pine beetle, Dendroctonus frontalis Zimmerman, is the most destructive insect pest of pine forests in the southeastern United States, Mexico, and Central America. Southern pine beetle aggressively attacks pine trees, and when in epidemic stages, they are capable of killing even the most healthy pine trees in a short period of time. Despite the amount of destruction caused by the southern pine beetle and the amount of monetary loss faced by the timber industry and recreation, the population genetics of this species has been limited to comparisons among distant geographic locations. This study investigates the fine-scale genetic population structure of the southern pine beetle in Mississippi. Very little genetic differentiation was observed among samples. Bayesian assignment testing failed to detect multiple groups within all samples; estimates of genetic differentiation and genetic distance were very low in magnitude; and a Mantel test did not reveal a significant relationship between genetic distance and geographic distance. These results suggest that management of the southern pine beetle needs to consider the potential movements of individuals within and among national forests and should be focused on a large scale, at least as big as continuously forested areas and possibly even multiple forests. These results further suggest that removal of beetle-infested trees is important.


Detection of localized methylmercury contamination by use of the mussel adductor muscle in Minamata Bay and Kagoshima Bay, Japan.
Based on our previous finding that the concentrations of total mercury in mussel adductor muscle approximated those of methylmercury, we compared concentrations of total mercury in the adductor muscle of the mussel Mytilus galloprovincialis, collected from four sites around Minamata City from 1993 to 1995 and four sites in Kagoshima Bay from 1997 to 1998, to assess the level of localized methylmercury contamination. Though the input of mercury from the chemical plant had stopped by around 1970, concentrations of total mercury in the mussel adductor muscle were higher at two sites (26-121 ng/g, n = 135) near the main fallout of wastewater from the chemical plant in Minamata Bay than at the other sites, i.e. two sites 1-5 km from the former sites in Minamata City (6-28 ng/g, n = 52), and all sites in Kagoshima Bay (2-30 ng/g, n = 287). The localized methylmercury contamination around the chemical plant in Minamata Bay was documented also by our sensitive analysis of mercury concentrations in seawater and sediment samples. The survey of concentrations of total mercury in the mussel adductor muscle seems to be useful for monitoring the methylmercury contamination in coastal areas.


Effects of pulsations on carotid sinus control of regional arterial hemodynamics.
Studies were conducted in halothane-anesthetized dogs to evaluate the interaction of mean and pulsatile components of carotid sinus perfusion pressure on the control of regional pressure-flow relations. Pressure and flow were measured simultaneously in the ascending aorta, celiac, mesenteric, renal, and iliac arteries. The carotid sinuses were bilaterally isolated and perfused under controlled conditions. Mean (CSP) and pulsatile components (CSPP) of carotid sinus pressure were varied systemically. Values of mean aortic pressure (AP) at the operating point (AP = CSP) decreased with increasing CSPP (127 +/- 5 at CSPP = 0 to 103 +/- 5 at CSPP = 60). Reflex gains at the operating point also decreased with increasing CSPP (-1.35 +/- 0.16 for CSPP = 0 to -0.92 +/- 0.18 for CSPP = 60). Changes in cardiac output and peripheral resistance nonuniformly contributed to these responses, with the former predominating at low CSPP and the later at high CSPP. Operating-point values of regional resistance generally decreased with increasing CSPP but to different degrees in the various beds. With increasing CSPP amplitude, regional resistance sensitivity at the operating point (i.e., slope) increased in the celiac and decreased in the mesenteric, renal, and iliac vascular beds. Separate changes in mean and pulsatile components of carotid sinus pressure about the normal operating point produce quantitatively similar changes in systemic hemodynamic variables.


Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: a review of the relevant literature.
Soy foods are a traditional staple of Asian diets but because of their purported health benefits they have become popular in recent years among non-Asians, especially postmenopausal women. There are many bioactive soybean components that may contribute to the hypothesized health benefits of soy but most attention has focused on the isoflavones, which have both hormonal and nonhormonal properties. However, despite the possible benefits concerns have been expressed that soy may be contraindicated for some subsets of the population. One concern is that soy may adversely affect thyroid function and interfere with the absorption of synthetic thyroid hormone. Thus, the purpose of this review is to evaluate the relevant literature and provide the clinician guidance for advising their patients about the effects of soy on thyroid function. In total, 14 trials (thyroid function was not the primary health outcome in any trial) were identified in which the effects of soy foods or isoflavones on at least one measure of thyroid function was assessed in presumably healthy subjects; eight involved women only, four involved men, and two both men and women. With only one exception, either no effects or only very modest changes were noted in these trials. Thus, collectively the findings provide little evidence that in euthyroid, iodine-replete individuals, soy foods, or isoflavones adversely affect thyroid function. In contrast, some evidence suggests that soy foods, by inhibiting absorption, may increase the dose of thyroid hormone required by hypothyroid patients. However, hypothyroid adults need not avoid soy foods. In addition, there remains a theoretical concern based on in vitro and animal data that in individuals with compromised thyroid function and/or whose iodine intake is marginal soy foods may increase risk of developing clinical hypothyroidism. Therefore, it is important for soy food consumers to make sure their intake of iodine is adequate.


Social constructivist approaches for brief, episodic, problem-focused family encounters.
Clinicians of many health care disciplines provide health care services to the family unit. Because of the multiple perspectives that individual family members bring to the health care encounter, family-focused primary health care presents special challenges for providers. The need to reconcile multiple individual family member perspectives requires that clinicians develop increasingly more sophisticated, effective, family intervention skills that can be used in busy primary care settings. Social constructivism can provide a means through which clinicians can quickly engage families in creating a consensus on health issues, thus leading to effective, efficient problem solving. This paper reviews the origins and principles of social constructivist thought and describes assessment questions and therapeutic stances that can be used to empower families to become active participants in the process of initiating their own health-related life changes. These approaches are useful for episodic, brief, problem-focused encounters with families in many primary care practice settings.


Increased risk of chronic liver disease in patients with major depressive disorder: A population-based study.
This study investigated the prevalence and incidence of chronic liver disease in patients with major depressive disorder (MDD), and aimed to identify associated factors. Data of 766,427 adult subjects aged ≥18 years were randomly selected from the National Health Research Institute database from the year 2005. The study first searched for subjects with at least one primary diagnosis of MDD in 2005, and then for those with a primary or secondary diagnosis of chronic liver disease were also identified. The differences in the prevalence of chronic liver disease and its associated factors between patients with MDD and the general population in 2005 were then analyzed. We also compared the incidence of chronic liver disease in patients with MDD and in the general population from 2006 to 2010. The prevalence of chronic liver disease in patients with MDD was 2.27 times as high as that of the general population in 2005 (12.4% vs. 5.8%; odds ratio (OR) = 2.27; 95% confidence interval (CI) = 2.07-2.48). The average annual incidence of chronic liver disease in patients with MDD during 2006-2010 was also higher than that of the general population (2.6% vs. 1.7%; risk ratio (RR) = 1.52; 95% CI = 1.37-1.7). Patients with MDD had a significantly higher prevalence and incidence of chronic liver disease than the general population. Among patients with MDD, an older age, the male sex, diabetes, hyperlipidemia and first-generation antipsychotic use were factors associated with chronic liver disease.


Viruses of plant pathogenic fungi.
Mycoviruses are widespread in all major groups of plant pathogenic fungi. They are transmitted intracellularly during cell division, sporogenesis, and cell fusion, but apparently lack an extracellular route for infection. Their natural host ranges are limited to individuals within the same or closely related vegetative compatibility groups. Recent advances, however, allowed the establishment of experimental host ranges for a few mycoviruses. Although the majority of known mycoviruses have dsRNA genomes that are packaged in isometric particles, an increasing number of usually unencapsidated mycoviruses with positive-strand RNA genomes have been reported. We discuss selected mycoviruses that cause debilitating diseases and/or reduce the virulence of their phytopathogenic fungal hosts. Such fungal-virus systems are valuable for the development of novel biocontol strategies and for gaining an insight into the molecular basis of fungal virulence. The availability of viral and host genome sequences and of transformation and transfection protocols for some plant pathogenic fungi will contribute to progress in fungal virology.


The nature of G-bands analyzed by chromosome stretching.
To investigate the nature of G-banding, chromosome stretching was performed on chromosome 6 at the 400-band level of normal human lymphocytes that had been cultivated and harvested using standard techniques. The GTG-banding patterns of five stretched chromosomes 6 were compared microscopically with each other and found to be identical at the 1,400-band level. A high-resolution ideogram at the 1,400-band level was constructed. The banding pattern at this level appeared to be very regular, with all dark bands at the 400-band level splitting into three to six dark subbands. While the dark subbands observed at the 1,400-band level seem to derive solely from the dark bands seen at the 400-band level, light bands visible at the 400-band level do not split into subbands, which is in contrast to the published (ISCN, 1995) ideograms. The splitting process, which was analyzed on the video monitor in more detail, shows that chromosome stretching is due mainly to the appearance of light subbands flanked by dark subbands. To shed more light on this phenomenon, the staining intensity of the dark bands and their subbands was measured while the chromosomes were stretched from the 400- to the 1,400-band level. At first, staining intensity was found to diminish in inverse proportion to the elongation of the chromosome, but then remained relatively unaffected until the dark subbands were gradually split up. After stretching to the 1,400-band level, these dark subbands were followed by newly appearing small light subbands, which were about the same size as the stretched light bands visible at the 400-band level. The results indicate that, in general, the light bands of human chromosomes are the preferentially stretched chromosome regions and that the resolution-dependent characteristic banding pattern of human chromosomes is mainly based on a fixed hierarchy of the stretchability of chromosomes.


Health Policy and Advocacy for New Mexico Medical Students in the Family Medicine Clerkship.
Learners in medical education are often inadequately prepared to address the underlying social determinants of health and disease. The objective of this article is to describe the development, implementation, and evaluation of a Health Policy and Advocacy curriculum incorporated into our family medicine clerkship. We developed a Health Policy and Advocacy course for medical students within our family medicine clerkship. We evaluated the curriculum using a survey of our own design administered to students before and after their clerkship year. We created a mean score for each subscale that measured (1) physician's role, (2) knowledge, and (3) confidence in ability and calculated differences between the pre-survey and the post-survey scores for four medical school classes. We also conducted a focus group to get student input on the new curriculum. Mean scores on the pre- and post-surveys were highest for the subscale regarding attitudes about a physician's role in health policy and advocacy and did not change over time. Scores for self-reported knowledge and confidence in abilities increased significantly from the beginning to the end of the clerkship year. Students were generally positive about the curriculum but had some concerns about finding time for advocacy in their future practices. Training in health care policy and advocacy can be successfully implemented into a medical school curriculum with positive outcomes in students' self-reported knowledge and confidence in their abilities. Work remains on providing advocacy role models for students.


The UIG-1/CDC-42 guanine nucleotide exchange factor acts in parallel to CED-10/Rac1 during axon outgrowth in Caenorhabditis elegans.
During development of the brain, neuronal circuits are formed through the projection of axons and dendrites in response to guidance signals. Rho GTPases (Rac1/RhoA/Cdc42) are major regulators of axo-dendritic outgrowth and guidance due to their role in controlling actin cytoskeletal dynamics, cell adhesion and motility. Functional redundancy of Rho GTPase-regulated pathways in neuronal development can mask the roles of specific GTPases. To examine potential Rho GTPase redundancy, we utilized a recently isolated hypomorphic mutation in a Caenorhabditis elegans Rac1 protein - CED-10(G30E) - which reduces the GTP binding and inhibits axon outgrowth of the PVQ interneurons. Here, we show that the CDC-42-specific guanine nucleotide exchange factor UIG-1 acts in parallel to CED-10/Rac1 to control PVQ axon outgrowth. UIG-1 performs this function in a cell-autonomous manner. Further, we found that transgenic expression of CDC-42 can compensate for aberrant CED-10(G30E)-regulated signalling during PVQ axon outgrowth. Together, our study reveals a previously unappreciated function for CDC-42 in PVQ axon outgrowth in C. elegans.


Use of intrathecally administered morphine in the treatment of postoperative pain after lumbar spinal surgery: a prospective, double-blind, placebo-controlled study.
Improved control of postoperative pain is now known to reduce the incidence of morbidity. Although spinally administered narcotics have found a clear role in chest and abdominal surgery, their role in lumbar spinal surgery is debated. We conducted a prospective, double-blind, randomized, placebo-controlled trial of intrathecally administered morphine sulfate after lumbar spinal surgery in 56 patients. Patients received 0, 0.125, 0.25, or 0.5 mg of intrathecally administered morphine during extradural lumbar spinal operations, and the effects on postoperative analog pain scores, narcotic consumption, complications, and length of hospitalization were assessed. As compared with systemic narcotic administration, intrathecally administered morphine provided superior analgesia in a dose-dependent fashion without an increase in narcotic side effects. Consumption of parenteral narcotics on the first postoperative day and over the total hospitalization period decreased in correlation with increasing doses of intrathecally administered morphine. Mean length of hospitalization was significantly decreased, as compared with the control group, in patients receiving 0.25 or 0.5 mg of intrathecally administered morphine. When proper precautions are observed, intrathecally administered morphine can improve the postoperative care of patients undergoing lumbar spinal surgery.


Levels and sub-cellular distribution of physiologically important metal ions in neuronal cells cultured from chick embryo cerebral cortex.
Mg2+, Ca2+, Mn2+, Zn2+, and Cu content of neurons from chick embryo cortex cultivated in chemically defined serum free growth medium was determined by energy dispersive X-ray fluorescence and atomic absorption spectroscopy. The intracellular volume of cultured neurons was determined to be 2.73 microliters/mg. Intracellular Mn2+, Fe2+, Zn2+, and Cu2+ in the cultivated neurons were 100-200 times the concentrations in the growth medium: Mg2+ and Ca2+ were 0.9 and 1.7 mM respectively, around 20 fold higher than in growth medium. Mg2+, Fe2+, Cu2+ and Zn2+ concentrations in neurons were in the range of ca. 300-600 microM, approximately 2-3 times the values previously reported in glial cells; Ca2+ and Mn2+ content of the neurons were higher by 5 and 10 fold respectively compared to glial cells. In neurons, the subcellular distribution of Fe2+, Cu2+, and Mn2+ follows the rank order: cytosol greater than microsomes greater than mitochondria; for Zn2+ the distribution differs as following: cytosol greater than mitochondria greater than microsomes. Determination of the superoxide dismutase activities in the cultivated neurons indicated that the Mn2+ linked activity predominates whereas, the Cu-Zn dependent enzyme is dominant in glial cells. Enrichment of the culture medium with Mn2+ to 2.5 microM enhanced the Mn-SOD by approximately 33% but the Cu2+-Zn2+ enzyme activity was not modified. The high Mn2+ content, the capacity to accumulate Mn2+, and the predominancy of the Mn-SOD form observed in neurons is in accord with a fundamental functional role for this metal ion in this type of brain cells.


[THE NEED FOR HELP OF FAMILY CAREGIVERS OF PERSONS WITH MENTAL ILLNESS IN A UNIQUE SERVICE FOR FAMILIES AT THE BEER SHEVA MENTAL HEALTH CENTER].
Limited research attention has been given to the needs of family caregivers of persons with mental illness in psychiatric hospitals despite the stressors and difficulties they experience. In light of the recognition of the significance of helping family caregivers, a new model of consultation and support centers for family caregivers, called Meital, has been developed. To examine the needs of family caregivers who receive help in Meital, at the Beer Sheva Mental Health Center. Eighty-five family caregivers participated in the research. They completed a structured questionnaire constructed for this research two weeks after they started receiving services from Meital. The questionnaire included four areas of needs for help. These areas examined the extent of the need for help with respect to each of the items in the instrument. The mean of the extent of need for help of the items in the 'information and knowledge' subscale was the highest. Average to high means of the items of the subscales were found in the subscales relating to 'difficulties stemming from the impact of the situation of the person with mental illness on the function of the family caregiver receiving help,' 'on the function of other family members' and 'difficulties coping with the person with mental illness.' The mean of the items of the subscale 'relationships with professionals and informal systems' was the lowest. An examination of the items within the subscales indicated that items relating to the 'impact of the situation of the person with mental illness on the family caregiver who receives help' were ranked higher than the items relating to the 'impact on the function of other family caregivers.' Items relating to 'relationships with professionals' were ranked higher than items relating to 'relationships with informal systems.' This research emphasizes the importance of implementing the family-centered approach, the basis of the Meital Model, in psychiatric institutions. The focus of this approach is on the need for help of family caregivers beyond the help needed for them to function as a resource of help for the ill person. The findings also illuminate the importance of making information and knowledge accessible for family caregivers.


Diagnostic evaluation of children with daytime incontinence.
This article is one of the standardization documents of the International Children's Continence Society, and discusses how anatomical/iatrogenic and functional/urodynamic causes of daytime incontinence in children of all ages are to be diagnosed, how neurogenic bladder dysfunction or urinary tract infection is excluded as a cause of the wetting, and how further diagnostic evaluation of children with disturbances such as overactive bladder, voiding postponement and dysfunctional voiding is performed. The roles of history taking (including prenatal and perinatal issues and family history), physical examination, diagnostic bladder diaries, noninvasive urodynamic investigations and radiological imaging are delineated but therapy is not within the scope of this document. This document was designed and written by an international panel of authors with a large experience in assessment of children with incontinence. The best evidence was retrieved from the literature and assembled in a standardization document. Assessment of children with daytime symptoms is discussed. A noninvasive approach in these children allows us to select patients who will need a more invasive assessment.


A simplified procedure for the analysis of cholesterol, phospholipids and bile salts in human bile.
Cholesterol, total bile salts and phospholipids have been measured on alcoholic extracts from human bile-rich duodenal contents. Folch extraction before phospholipid assay was found to be unnecessary and, unless fresh samples are used, it is liable to give misleadingly low values. Removal of bile pigment before measuring cholesterol was unnecessary because this estimation was done by gas-liquid chromatography. The methods described provide a simple, reproducible analysis of bile lipids.


Hot spot mutations in Finnish non-small cell lung cancers.
Non-small cell lung cancer (NSCLC) is a common cancer with a poor prognosis. The aim of this study was to screen Finnish NSCLC tumor samples for common cancer-related mutations by targeted next generation sequencing and to determine their concurrences and associations with clinical features. Sequencing libraries were prepared from DNA isolated from formalin-fixed, paraffin-embedded tumor material of 425 patients using the AmpliSeq Colon and Lung panel covering mutational hot spot regions of 22 cancer genes. Sequencing was performed with the Ion Torrent Personal Genome Machine (PGM). Data analysis of the hot spot mutations revealed mutations in 77% of the patients, with 7% having 3 or more mutations reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Two of the most frequently mutated genes were TP53 (46%) and KRAS (25%). KRAS codon 12 mutations were the most recurrently occurring mutations. EGFR mutations were significantly associated with adenocarcinoma, female gender and never/light-smoking history; CTNNB1 mutations with light ex-smokers, PIK3CA and TP53 mutations with squamous cell carcinoma, and KRAS with adenocarcinoma. TP53 mutations were most prevalent in current smokers and ERBB2, ERBB4, PIK3CA, NRAS, NOTCH1, FBWX7, PTEN and STK11 mutations occurred exclusively in a group of ever-smokers, however the association was not statistically significant. No mutation was found that associated with asbestos exposure. Finnish NSCLC patients have a similar mutation profile as other Western patients, however with a higher frequency of BRAF mutations but a lower frequency of STK11 and ERBB2 mutations. Moreover, TP53 mutations occurred frequently with other gene mutations, most commonly with KRAS, MET, EGFR and PIK3CA mutations.


In situ measurement of CO2 and water vapour isotopic compositions at a forest site using mid-infrared laser absorption spectroscopy.
We conducted continuous, high time-resolution measurements of CO2 and water vapour isotopologues ((16)O(12)C(16)O, (16)O(13)C(16)O and (18)O(12)C(16)O for CO2, and H2(18)O for water vapour) in a red pine forest at the foot of Mt. Fuji for 9 days from the end of July 2010 using in situ absorption laser spectroscopy. The δ(18)O values in water vapour were estimated using the δ(2)H-δ(18)O relationship. At a scale of several days, the temporal variations in δ(18)O-CO2 and δ(18)O-H2O are similar. The orders of the daily Keeling plots are almost identical. A possible reason for the similar behaviour of δ(18)O-CO2 and δ(18)O-H2O is considered to be that the air masses with different water vapour isotopic ratios moved into the forest, and changed the atmosphere of the forest. A significant correlation was observed between δ(18)O-CO2 and δ(13)C-CO2 values at nighttime (r(2)≈0.9) due to mixing between soil (and/or leaf) respiration and tropospheric CO2. The ratios of the discrimination coefficients (Δa/Δ) for oxygen (Δa) and carbon (Δ) isotopes during photosynthesis were estimated in the range of 0.7-1.2 from the daytime correlations between δ(18)O-CO2 and δ(13)C-CO2 values.


The influence of warm versus cold climate on the effect of physiotherapy in multiple sclerosis.
To compare the effect of inpatient physiotherapy in a warm versus cold climate in short- and long-term perspectives. Sixty multiple sclerosis (MS) patients with gait problems, without heat intolerance, were included in a randomized cross-over study of 4-week inpatient physiotherapy in warm (Spain) and cold (Norway) climate. The primary outcome, 6-min walk test (6MWT), and secondary physical performance and self-reported measures were scored at screening, baseline, after treatment and at 3 and 6 months of follow-up. Treatment effects were analysed by mixed models. After treatment, the mean walking distance had increased by 70 m in Spain and 49 m in Norway (P = 0.060). Improvement in favour of warm climate was demonstrated at 6 months of follow-up, 43 m (Spain) compared to 20 m (Norway) (P = 0.048). The patients reported less exertion after walking (6MWT) in favour of treatment in Spain at all time points (P < 0.05). No significant differences in change were detected for the other physical performance measures. Most self-reported measures showed more improvement after treatment in Spain, but these improvements were not sustained at follow-up. The results indicate that MS patients without heat intolerance have additional benefits from physiotherapy in a warm climate.


Insect repellants in urban settings.
Why kill bugs when you can just make them go away? Used primarily for biting-insect control, repellants may control household pests as well, once their potential is fully realized. Repellents may provide low-dose, specific and low-toxicity augmentations to conventional pesticides applied around the home and workplace.


Refraction and reflection of diffusion fronts.
Diffusion waves form the basis of several measurement technologies in materials science as well as in biological systems. They are, however, so heavily damped that their observation is a real challenge to the experimentalist. We show that accurate information about the refraction-like and reflection-like behavior of diffusion waves can be obtained by studying diffusion fronts. For this we use hydrogen in a metal as a model system and visualize its 2D migration with an optical indicator. The similarities between classical optics and diffusion, in particular, the applicability of Snell's law to diffusive systems are discussed. Our measurements are in good agreement with numerical simulations.


Nanosized Ultrasound Enhanced-Contrast Agent for in Vivo Tumor Imaging via Intravenous Injection.
To enhance the detection limit of ultrasound (US) imaging, ultrasound enhanced-contrast agents (UECAs) that can go preferentially to the target tissue such as a tumor and amplify the US signal have been developed. However, nanosized UECAs among various UECAs developed are very limited to clearly demonstrate proper ability for selective tumor detection by US imaging upon their intravenous injection. In this study, we prepared CaCO3 nanoparticles that were formed inside a flexible and biocompatible pluronic-based nanocarrier. This nanosized UECA was stable in serum-containing media and generated CO2, more preferentially at low pH; thus, it could be detected by US imaging. After intravenous injection into tumor-bearing mice, this nanosized UECA showed a significant US contrast enhancement at the tumor site in 1 h, in contrast to no change in the liver, followed by a rapid clearance from the body in 24 h. Therefore, the present nanosized UECA could be applied as an effective diagnostic modality for in vivo tumor imaging by ultrasonography.


Studies on the relationship between vitamin D3 status and urinary excretion of calcium in healthy subjects: effects of increased levels of 25-hydroxyvitamin D3.
The metabolic consequences of a rapid increase in vitamin D status in healthy subjects were investigated. Circulating levels of 25-hydroxyvitamin D3 were increased by 224% in 12 healthy men by giving oral vitamin D3 for 7 weeks and by 200% in 15 healthy women by UVB irradiation for 7 weeks. No statistically significant effects on the serum levels of calcium, phosphate, creatinine, urate, albumin, PTH, basal urinary excretion of calcium, fasting urinary excretion of cAMP, or urinary excretion of calcium after calcium load tests were observed with the unpaired t-test. With the paired t-test the small stimulatory effects (about 25%) on basal urinary excretion of calcium became statistically significant in both experiments. The ratio between calcium and creatinine in fasting urine was significantly elevated following UVB irradiation (from 0.11 +/- 0.02 to 0.21 +/- 0.04, p less than 0.025 unpaired t-test, p less than 0.02 paired t-test) but not after oral intake of vitamin D3. The level of 1,25-dihydroxyvitamin D in serum was not affected to a statistically significant degree by oral vitamin D3, whereas there was a slight decrease from 48 +/- 3 to 39 +/- 3 pmol/l following UVB irradiation. It is concluded that an increase in the concentration of 25-hydroxyvitamin D3 up to about 125 nmol/l has small and negligible effects on calcium homeostasis in healthy subjects. This finding is discussed in relation to our previous finding that hypercalciuric renal stone formers have elevated serum levels of 25-hydroxyvitamin D3 as compared with normocalciuric stone formers and healthy subjects.


A Modified Direct-Smear Processing Technique Employing Two-Step Centrifugation/Fixation Is Useful for Detecting High-Grade Urothelial Carcinoma.
To demonstrate the usefulness of a direct-smear processing technique employing two-step centrifugation/fixation processing (TSCFP) in the cytoscreening of high-grade urothelial carcinoma (HGUC). Using the T24 HGUC cell line, we compared the cell yield and the morphological preservation of preparations concurrently processed by direct-smear, SurePath, ThinPrep, and TSCFP techniques. A total of 287 urine cytology cases subjected to TSCFP over a period of 6 years were reviewed and reclassified according to the Paris System for Reporting Urinary Cytology (PSRUC) and correlated with histology results. TSCFP of T24 cells demonstrated good cell yield with a recovery rate of about 70%. Diagnostic features of HGUC, such as a high nuclear/cytoplasmic ratio and irregular/hyperchromatic chromatin, were better discovered in TSCFP smears than in smears prepared with the other methods. Cytological evaluation of 287 voided urine specimens revealed that the rate of unsatisfactory preparations was quite low (0.30%) and the overall sensitivity, specificity, and positive and negative predictive values for urothelial carcinoma were 0.719, 0.923, 0.973, and 0.462, respectively. TSCFP was able to provide adequate preparations for detecting HGUC in urine cytology and could be considered as a promising processing method according to the principal purpose of PSRUC.


[Fatal chest injury from a shotgun slug: homicide, accident or suicide?].
A 78-year-old hunter was found dead beside his raised hide with a gunshot wound to his chest. In the present case, the reconstruction of the shooting event revealed an accident. Disregarding all safety rules, the hunter had placed his superposed rifle-shotgun on the chair and pulled the barrels of the cocked gun towards his body. One of the triggers interlocked with the button of a camping chair's cushion and a shot was fired. Furthermore the morphology of wounds from shotgun slugs is discussed on the basis of the autopsy findngs.


Usefulness of hand-held ultrasound devices in out-of-hospital diagnosis performed by emergency physicians.
To evaluate the usefulness of ultrasonographic examinations as a diagnostic tool for emergency physicians in out-of-hospital settings. Prospective study performed in a French teaching hospital. Eight emergency physicians given ultrasound training for out-of-hospital diagnosis of pleural, peritoneal, or pericardial effusion; deep venous thrombosis; and arterial flow interruption. After clinical examination, a probability of diagnosis ("clinical score") was assigned on visual analog scale from 0 (absent lesion) to 10 (present lesion). Clinical score between 3 and 7 was considered as clinically doubtful. After ultrasound examination, a second probability ("ultrasound score") was similarly determined. Potential usefulness of ultrasound examination was evaluated by calculating the absolute difference between clinical and ultrasound scores. Patients were followed up to determine final diagnosis: present or absent lesion. "Ultrasound usefulness score" (USS) was determined attributing a positive (when ultrasonography increased diagnostic accuracy) or a negative (when ultrasonography decreased diagnostic accuracy) value to the absolute difference between clinical and ultrasound scores. One hundred sixty-nine patients were included and 302 ultrasound examinations performed. Median duration of examination was 6 minutes (5-10 minutes). The suspected lesion was found in 45 cases (17%). Mean USS was +2 (0-4). Ultrasonographic examination improved diagnostic accuracy (ie, positive USS) in 181 (67%) cases, decreased it (ie, negative USS) in 22 (8%) cases, and was not contributive (ie, USS was 0) in 67 (25%) cases. When initial diagnosis was uncertain (n = 115), diagnostic performance reached +4 (3-5) and ultrasonographic examination improved diagnostic accuracy in 103 (90%) cases. Out-of-hospital ultrasonography increased diagnostic accuracy in out-of-hospital settings.


Mycobacterium genavense invasive infection in two children with AIDS: long-term followup.
Mycobacterium genavense is a rare cause of opportunistic infection in immunocompromised hosts. Follow up of two cases of M. genavense invasive infection in children with haemophilia A and AIDS are presented. One patient died 18 months after diagnosis of M. genavense infection of an indirectly related cause, probably of Pneumocystis carinii pneumonia. The second patient still attends our outpatient clinic and the infection is under control. Both presented with abdominal lymphomas and pain and a wasting syndrome. A combination of several drugs against atypical mycobacteria is used for treatment.


Toll-like receptor 4 initiates an innate immune response to lipopolysaccharide in human conjunctival epithelial cells.
Conjunctival epithelial cells serve as a first line of defense against pathogens presented to the innate immune system. The inflammatory response to Gram-negative bacteria is initiated by toll-like receptor 4 (TLR4). This study investigated whether a TLR4 ligand induces production of inflammatory cytokines in human conjunctival epithelial cells (HCECs) through nuclear factor kappa-B (NF-kappaB). HCECs were evaluated for TLR4 expression by reverse transcriptase-polymerase chain reaction, Western blot analysis, and flow cytometric analysis. HCECs were stimulated with various concentrations of lipopolysaccharide (LPS) and the innate immune response was quantified by measuring expression of the inflammatory cytokines IL-6 and IL-8. Functional NF-kappaB activation was examined using a luciferase reporter assay. Expression of TLR4-specific mRNA as well as its corresponding protein was observed in HCECs. Surface and intracellular expression of TLR4 was observed in flow cytometric analysis. Incubation of HCECs with LPS led to secretion of IL-6 and IL-8. Blockade of TLR4- and TNFR-associated factor (TRAF) 6 activity abolished LPS-induced inflammatory response in HCECs and incubation of HCECs with LPS led to activation of the NF-kappaB transcription factor. LPS did not enhance the TLR4 expression at both mRNA and protein levels in HCECs. Our results demonstrate that surface expression of TLR4 in HCECs can elicit a TLR4-mediated innate immune response through TRAF6-NF-kappaB and contribute to an inflammatory environment on the ocular surface.


Application of high hydrostatic pressure for increasing activity and stability of enzymes.
Elevated hydrostatic pressure has been used to increase catalytic activity and thermal stability of alpha-chymotrypsin (CT). For an anilide substrate, characterized by a negative value of the reaction activation volume (DeltaV( not equal)), an increase in pressure at 20 degrees C results in an exponential acceleration of the hydrolysis rate catalyzed by CT reaching a 6.5-fold increase in activity at 4700 atm (4.7 kbar). Due to a strong temperature dependence of DeltaV( not equal), the acceleration effect of high pressure becomes more pronounced at high temperatures. For example, at 50 degrees C, under a pressure of 3.6 kbar, CT shows activity which is more than 30 times higher than the activity at normal conditions (20 degrees C, 1 atm). At pressures of higher than 3.6 kbar, the enzymatic activity is decreased due to a pressure-induced denaturation.Elevated hydrostatic pressure is also efficient for increasing stability of CT against thermal denaturation. For example, at 55 degrees C, CT is almost instantaneously inactivated at atmospheric pressure, whereas under a pressure of 1.8 kbar CT retains its anilide-hydrolyzing activity during several dozen minutes. Additional stabilization can be achieved in the presence of glycerol, which is most effective for protection of CT at an intermediate concentration of 40% (v/v). There has been observed an additivity in stabilization effects of high pressure and glycerol: thermal inactivation of pressure-stabilized CT can be decelerated in a supplementary manner by addition of 40% (v/v) glycerol. The protection effect of glycerol on the catalytic activity and stability of CT becomes especially pronounced when both extreme factors of temperature and pressure reach critical values. For example, at approximately 55 degrees C and 4.7 kbar, enzymatic activity of CT in the presence of 40% (v/v) glycerol is severalfold higher than in aqueous buffer.The results of this study are discussed in terms of the hypotheses which explain the action of external and medium effects on protein structure, such as preferential hydration and osmotic pressure.


A necessary inhumanity?
It is argued that the phrase "Necessary Inhumanity" more accurately describes the alienation required of doctors in some circumstances, than do modern sanitised coinages such as 'clinical detachment.' 'Detachment' and 'objectivity' imply separation, not engagement: creating distance not only from patients, but from the self: the process may well be required, but where it becomes too extreme or prolonged, it can damage everybody, including patients, family members, doctors themselves, and wider society. An awareness of the history of health care in the context of our society might assist self reflection--might help keep initiates in touch with the culture they have been induced to leave and might help them remain humane despite the bruising process of training.


Circulating galectin-1 concentrations in systemic sclerosis: potential contribution to digital vasculopathy.
To determine serum galectin-1 levels and their clinical associations in patients with systemic sclerosis (SSc). Serum galectin-1 levels were examined by enzyme-linked immunosorbent assay in 66 patients with SSc and 24 healthy individuals. No significant differences were observed in serum galectin-1 levels between patients with SSc (9.4 ± 5.6 ng/mL), and healthy individuals (8.9 ± 1.3 ng/mL). Among patients with SSc, no significant differences were seen in serum galectin-1 levels between those with diffuse cutaneous SSc (8.8 ± 5.7 ng/mL; n = 31) and those with limited cutaneous SSc (10.0 ± 5.4 ng/mL; n = 35). Patients with SSc who had increased galectin-1 levels less often had pitting scars/digital ulcers than those with normal galectin-1 levels (17% vs. 49%; P < 0.01). Consistently, galectin-1 levels were significantly lower in SSc patients with pitting scars/digital ulcers than in those without pitting scars/digital ulcers (6.9 ± 4.8 vs. 10.9 ± 5.5 ng/mL; P < 0.01). These results suggest that galectin-1 is a protective factor against the development of digital vasculopathy in SSc. In addition, measurement of serum galectin-1 levels may be useful for risk stratification for the development of digital vasculopathy in the early phase of SSc.


Evaluating the trophic transfer of selenium in aquatic ecosystems using caged fish, X-ray absorption spectroscopy and stable isotope analysis.
This research evaluated the dominant exposure pathways with regard to the bioaccumulation and trophic transfer of selenium (Se) in caged small-bodied fish inhabiting the receiving waters of a uranium-processing mill in northern Saskatchewan, Canada. A 21-day cage study was conducted using wild naïve lake chub (Couesius plumbeus) collected from a reference lake and caged in a reference and an exposure lake downstream of the mill discharge. Caged fish were fed commercially produced Chironomus spp. diets of 1.5 (basal - commercial food) and 5.5 (lab reared in Se-spiked water) μgSe/g (dry weight) at a feeding ration of 10 percent percent body weight/day. Lake chub fed the Se-spiked diet and caged in the reference lake showed increased whole-body Se concentrations compared to chub fed the basal diet after 21 days. Lake chub caged in the exposure lake from both the elevated Se and basal diet groups had significantly greater whole-body Se concentrations compared to the reference lake, and were not significantly different from each other. The use of stable carbon (C), nitrogen (N), and sulphur (S) isotope analyses indicated that alternate benthic food sources native to the exposure lake were likely consumed in conjunction with the controlled diets. Stable isotope analysis of both wild and caged lake chub indicated that the N and S isotopic signatures decreased with increasing Se exposure, which was reflective of the differences in isotopic signatures of the food sources. Dose-dependent substitution of Se for S in methionine as a consequence of dietary Se exposure was illustrated by a decreasing whole-body S isotope signature and an increasing proportion of selenomethionine-like compounds (as measured by synchrotron-based X-ray absorption spectroscopy) with increasing Se exposure. Speciation results from caged lake chub indicated that Se substituted for S in methionine was the dominant Se species found in caged lake chub exposed to dietary sources of Se.


Pathways of heavy metals contamination and associated human health risk in Ajay River basin, India.
The sources of heavy metals and their loads in the Ajay River were investigated based on the seasonal and spatial variations. To identify variation and pathways of heavy metals, seventy-six water samples were estimated for 2 years at nineteen sampling sites. The multifaceted data were applied to evaluate statistical relation between variables and arithmetic calculation of the indices. Fickling plot suggested that the acidic pollutants do not affect the water quality because all samples lie within the neutral pH range. Further, OC showed significant relation with Fe, Mn, Ni and Co. Compositional analysis identified weathering of rocks, mobility of soil and sediment, atmospheric deposition and numerous anthropogenic inputs as major sources of heavy metals. The mean values of heavy metal pollution index (HPI) and pollution index (PI) were found above the critical index and strong loadings respectively due to higher values of Cd, Pb and Fe. Similarly, assessment of human risk revealed that the high load of Cd, Pb and Fe in water body could harm the population. Majority of the samples showed high concentration of heavy metals as compared to regulatory standard and background values, which suggests that the water is highly contaminated through numerous geogenic and anthropogenic sources.


High levels of FVIII and FIX in a pediatric patient with retinal artery occlusion.
A 13-year-old female patient with the diagnosis of retinal artery occlusion was evaluated for thrombophilia. The data revealed high FVIII and FIX levels. The patient had familial clustering. The data indicate that elevated FVIII and FIX could be a risk factor for thrombosis.


Design, synthesis, and biological evaluation of novel quinoline derivatives as HIV-1 Tat-TAR interaction inhibitors.
Thirty-two quinoline derivatives were designed and synthesized as HIV-1 Tat-TAR interaction inhibitors. All the compounds showed high antiviral activities in inhibiting the formation of SIV-induced syncytium in CEM174 cells. Nine of them with low cytotoxicities were evaluated by Tat dependent HIV-1 LTR-driven CAT gene expression colorimetric enzyme assay in human 293T cells, indicating effective inhibitory activities of blocking the Tat-TAR interaction. Molecular modeling experiments indicated that these compounds may inhibit Tat-TAR interaction by binding to Tat protein instead of TAR RNA.


[Dupuytren's contracture. When operate? Conservative preliminary treatment?].
The etiology, symptomatology, clinical findings, course and staging of Dupuytren's contracture are discussed. Surgery is indicated from the second stage onwards; since pain very rarely occurs, it plays no role in establishing the indication for operation. The surgical techniques available are described. Conservative therapy has no influence on the course of the condition, while radiotherapy is inadmissible on account of its side effects. Physical therapy and physiotherapeutic pre-operative measures can improve the results of surgery.


Economic evaluation of early monotherapy versus delayed monotherapy or combination therapy in patients with acute hepatitis C in Germany.
Antiviral treatment of acute hepatitis C virus (HCV) almost doubles the chance of sustained virological response (SVR) compared with that achievable by treating chronic HCV. To conduct a health economic evaluation comparing early and delayed therapies for acute HCV in Germany. One hundred and thirty-three patients with acute HCV were evaluated in two early monotherapy (EMT) studies and 60 in a delayed therapy study. Efficacy was determined by SVR. In the EMT studies, patients were treated with either standard or pegylated interferon for 24 weeks. In the delayed therapy study, patients with persisting infection were treated with interferon monotherapy or combination therapy with ribavirin for a median of 36 weeks. We conducted a cost-effectiveness analysis based on the study results and a linear simulation model based on current treatment recommendations. The SVR rate for the sex-adjusted on-treatment analysis between early and delayed therapies was not significantly different (92.7 vs. 90.9%; P = 0.7). Medication costs accounted for more than 90% in both treatment options. Direct medical costs of early therapy (euro7064/patient) were euro321 lower than those of delayed therapy (P = 0.8). The incremental cost-effectiveness ratio was -178 euro/SVR(%) (confidence interval: -224 to 360 euro/SVR(%)). Average modeled direct medical costs of delayed combination therapy were from euro6745 to euro8299 per patient (from approximately 7% less up to 15% higher than EMT). Spontaneous viral clearance and therapy duration were the most sensitive variables. There was no significant efficacy and cost difference between therapy alternatives in base cases. However, in the majority of scenarios in the sensitivity analyses, EMT was a more cost-effective option in acute HCV therapy.


Asymmetric spermatic cord vessel enhancement and enlargement on contrast-enhanced MDCT as indicators of ipsilateral scrotal pathology.
To determine the association of asymmetric spermatic cord vessel enhancement and enlargement on contrast-enhanced CT with ipsilateral scrotal pathology. This case series included 30 men with contrast-enhanced CT: 10 cases had asymmetric enhancement and enlargement of spermatic cord vessels with confirmed ipsilateral scrotal pathology determined by additional imaging and/or clinical records; 20 negative reference cases had no such findings with normal corresponding scrotal ultrasound. Maximum spermatic vessel diameters and attenuation values were determined bilaterally. Two blinded radiologists independently assessed all exams for interobserver agreement. For cases, maximum spermatic cord vessel diameters were greater ipsilaterally (5.9+/-1.7 mm) than contralaterally (4.0+/-1.1mm), p<0.001. Maximum HU values were greater ipsilaterally (139.5+/-29.5) than contralaterally (70.6+/-17.5), p<0.0003. Maximum spermatic vessel diameters and attenuation values were significantly greater for positive than negative reference cases (p<3.9 x 10(-8) and p<4.9 x 10(-7) respectively). There was substantial interobserver agreement for asymmetric spermatic vessel enlargement (kappa=0.79) and enhancement (kappa=0.73). In 3 cases, the CT findings lead to a scrotal ultrasound that confirmed the diagnosis and altered patient management. MDCT findings of asymmetric spermatic vessel enlargement and enhancement are indicators of ipsilateral scrotal pathology. The detection of such findings may have implications for patient care and should prompt further evaluation of the scrotum in the proper clinical setting.


Pelvic fracture: the last 50 years.
The past 50 years have been a time of rapid progress in the control of mortality and morbidity of pelvic fracture. Early understanding of the anatomic features of the fracture and the potential for major, life-threatening arterial hemorrhage in a small proportion of patients led to multidisciplinary approaches designed to control hemorrhage and temporarily stabilize the fracture. Progress in the diagnosis and management of lower urinary tract injuries has resulted in maintenance of urinary continence and sexual function in a large proportion of patients with pelvic fracture-associated urinary tract injury. Finally, definitive open reduction and fixation of the fracture has led to permanent pelvic stability and pain-free walking in most patients. With successful combination of these approaches, survival and return to a satisfactory level of function is now the rule rather than the exception for patients with severe pelvic fracture.


IL-12 as an adjuvant for cell-mediated immunity.
Recent studies have shown that IL-12 initiates the development of cell-mediated immunity following infection with certain infectious agents. This attribute of IL-12 makes it a potentially effective adjuvant for vaccines. This review summarizes our findings in the Leishmania system, outlining the role of endogenous IL-12 in resistance to L. major and the use of exogenous IL-12 in a vaccine against L. major, and also describes other examples in which IL-12 has been shown to be effective as an adjuvant at inducing protective immunity. The potential use of IL-12 as an adjuvant in therapeutic vaccines is also discussed.


A High-Temperature Order-Disorder Phase Transition Coupled With Conformational Change in the Hybrid Material [C6 H13 NH]2 ⋅ZnBr4.
A new high-temperature, hybrid, phase-transition material, 1-methylpiperidinium tetrabromozincate (1), that shows a reversible transition at 345 K was synthesized. Differential scanning calorimetry and specific heat capacity measurements confirmed this reversible transformation with a large heat hysteresis of 25 K, which describes a typical first-order phase transition in 1. The dielectric constant exhibited a steplike anomaly and showed high and low dielectric states in the high- and room-temperature phases, respectively, and therefore, this hybrid might be considered as a potential switchable dielectric material. The variable-temperature powder X-ray diffraction patterns displayed remarkable shifts between the experimental patterns at the two different phases. Single-crystal X-ray diffraction analyses at various temperatures revealed that the origin of this transformation could be attributed to disordering of the bromine atoms in the anion and the nitrogen atom of the cation. The cation also assumed a conformational change, which was likely induced by the disordered nitrogen atom. The conformational onset of the transformation of the cation from a planar conformer into a relaxed chair also occurred upon decreasing the temperature below transition point; thus, the combined order-disorder and conformational change induced the structural transformation and the change in symmetry.


Molecular basis of the thermostability and thermophilicity of laminarinases: X-ray structure of the hyperthermostable laminarinase from Rhodothermus marinus and molecular dynamics simulations.
Glycosyl hydrolases are enzymes capable of breaking the glycosidic linkage of polysaccharides and have considerable industrial and biotechnological applications. Driven by the later applications, it is frequently desirable that glycosyl hydrolases display stability and activity under extreme environment conditions, such as high temperatures and extreme pHs. Here, we present X-ray structure of the hyperthermophilic laminarinase from Rhodothermus marinus (RmLamR) determined at 1.95 Å resolution and molecular dynamics simulation studies aimed to comprehend the molecular basis for the thermal stability of this class of enzymes. As most thermostable proteins, RmLamR contains a relatively large number of salt bridges, which are not randomly distributed on the structure. On the contrary, they form clusters interconnecting β-sheets of the catalytic domain. Not all salt bridges, however, are beneficial for the protein thermostability: the existence of charge-charge interactions permeating the hydrophobic core of the enzymes actually contributes to destabilize the structure by facilitating water penetration into hydrophobic cavities, as can be seen in the case of mesophilic enzymes. Furthermore, we demonstrate that the mobility of the side-chains is perturbed differently in each class of enzymes. The side-chains of loop residues surrounding the catalytic cleft in the mesophilic laminarinase gain mobility and obstruct the active site at high temperature. By contrast, thermophilic laminarinases preserve their active site flexibility, and the active-site cleft remains accessible for recognition of polysaccharide substrates even at high temperatures. The present results provide structural insights into the role played by salt-bridges and active site flexibility on protein thermal stability and may be relevant for other classes of proteins, particularly glycosyl hydrolases.


Plasmon enhanced spectroscopy.
Surface enhanced spectroscopy encompasses a broad field of linear and nonlinear optical techniques that arose with the discovery of the surface-enhanced Raman scattering (SERS) effect. SERS enabled ultrasensitive and single molecule detection with molecular fingerprint specificity, opening the door for a large variety of chemical sensing applications. Basically, from the beginning it was realized that the necessary condition for SERS to be observed was the presence of a metallic nanostructure, and with this condition, the optical enhancement found a home in the field of plasmonics. Although plasmonic practitioners claim that SERS is "the most spectacular application of plasmonics", perhaps it is more appropriate to say that the spectacular development of plasmonics is due to SERS. Here is a brief recollection from surface enhanced spectroscopy to plasmon enhanced spectroscopy.


Characterization of glucocorticoid receptor in HeLa-S3 cells.
Glucocorticoid receptor of the human cell line HeLa-S3 has been characterized and has been compared to rat and to mouse glucocorticoid receptors. If HeLa cells were lysed in the absence of glucocorticoid, glucocorticoid receptor was isolated in a nonactivated form, which did not bind to DNA-cellulose. If HeLa cells were preincubated with glucocorticoid, glucocorticoid receptor was isolated in an activated, DNA-binding form. HeLa cell glucocorticoid receptor bound [3H]triamcinolone acetonide with a dissociation constant (KD = 1.3 nM at 0 degrees C) that was similar to those of mouse and rat glucocorticoid receptors. Similarly, the relative binding affinities for steroid hormones decreased in the order of triamcinolone acetonide greater than dexamethasone greater than promegestone greater than methyltrienolone greater than aldosterone greater than or equal to moxestrol. Nonactivated and activated receptors were characterized by high-resolution anion-exchange chromatography (FPLC), DNA-cellulose chromatography, and sucrose gradient centrifugation. Human, mouse, and rat nonactivated glucocorticoid receptors had very similar ionic and sedimentation properties. Activated glucocorticoid receptors were eluted at similar salt concentrations from DNA-cellulose columns but at different salt concentrations from the FPLC column. A monoclonal mouse anti-rat liver glucocorticoid receptor antibody [Westphal, H.M., Mugele, K., Beato, M., & Gehring, U. (1984) EMBO J. 3, 1493-1498] did not cross-react with HeLa cell glucocorticoid receptor. Glucocorticoid receptors of HeLa, HTC, and S49.1 cells were affinity labeled with [3H]dexamethasone and with [3H]dexamethasone 21-mesylate. The molecular weights of [3H]dexamethasone 21-mesylate labeled glucocorticoid receptors (MT 96 000 +/- 1000) were undistinguishable by polyacrylamide gel electrophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)


The influence of intraarterial prostaglandin E(1) on vascular hydraulic impedance and infrainguinal graft patency.
To evaluate the influence of intraoperative arterial prostaglandin E(1)(alprostadil) infusion on hydraulic impedance in relation to graft patency. Hydraulic impedance was measured in 115 infrainguinal bypasses by means of the extracorporeal-bypass-flow method (EBF). Fifty-eight femoro-popliteal and 57 femoro-crural polytetrafluoroethylene (PTFE) grafts were included. 10 microg of alprostadil were administered into a temporary bypass and the haemodynamic changes were recorded. The reactions of input (Z(x)) and characteristic (Z(0)) impedances as well as phase relations were derived and related to graft outcome after three years. Significant changes after administration of prostaglandin were observed for overall pressure (74 vs. 84 mmHg, p<0.01), flow rate (194 vs 160 ml/min, p<0.01), input impedance (0.55 vs. 0.75 PRU, p<0.01) and the phase angle of the first harmonic (-18 degrees vs -26 degrees, p<0.01). An increase of at least one degree of the first harmonic phase angle following alprostadil injection in the crural bypass group was associated with a significant better graft prognosis of crural (p<0.01) but not popliteal grafts. Primary and secondary patency rates after three years for crural grafts with an increase of at least one degree were 62% and 63% (n=45) and for non-responders 18% and 0% (n=12, p(prim)<0.01, p(sec)<0.001). All crural bypasses with poor prostaglandin reaction occluded within 9 months (n=12) after the operation. The EBF method allows a combined assessment of peripheral resistance and impedance parameters. The response of the first harmonic phase angle provides important predictive information regarding femoro-crural grafts.


Impairment of mysid (Neomysis integer) swimming ability: an environmentally realistic assessment of the impact of cadmium exposure.
Neomysis integer (Crustacea: Mysidacea), a euryhaline member of the hyperbenthos of the upper reaches of European estuaries, has been identified as a suitable animal for assessing the impacts of chemical pollutants on these estuarine regions. In this study, the effect of a 7 day pre-exposure to environmentally relevant concentrations of cadmium (0.5 and 1.0 microg l(-1)) on the swimming behaviour of N. integer was examined using an annular flume. Cadmium speciation at two salinities (1 and 10 per thousand) that dominate these upper estuarine regions was modelled to ensure mysids were exposed to the same concentration of the toxic free-ion at each salinity. There was no significant difference in the swimming behaviour of mysids exposed to the same free-ion cadmium concentration at the two different salinities. At each salinity, exposure to 0.5 microg Cd2+ (aq) l(-1)resulted in fewer mysids moving forward into the current (normal behaviour) at free stream velocities typical of their natural habitat (e.g. 3-9 cm s(-1)) than non cadmium-exposed mysids. At these low current speeds, cadmium-exposed mysids were either able to maintain position or were swept by the current. The same general responses were recorded for mysids exposed to 1.0 microg Cd2+ (aq) l(-1)except that more mysids showed disrupted swimming ability compared with 0.5 microg Cd2+ (aq) l(-1). At higher current speeds (>12 cm s(-1)), current velocity was the dominant factor affecting mysid swimming behaviour and there was no effect of cadmium on mysids maintaining position. Exposure to cadmium also caused significant disruption of the hyperbenthic behaviour of N. integer and more cadmium-exposed individuals were in the water column than control mysids; this result was more variable at 10 per thousand than 1 per thousand. Results indicate that exposure to cadmium concentrations of 0.5 microg Cd2+(aq) l(-1)would result in displacement of N. integer from its optimum region within the estuarine environment. This conclusion would not be achieved from standard LC(50) tests (e.g. 7 day LC50 = 2.95 microg Cd2+ (aq) l(-1)), highlighting the value of behavioural disruption as a sensitive indicator of environmental chemical contamination.