Mitochondrial kinase signalling pathways in myocardial protection from ischaemia/reperfusion-induced necrosis.
Multiple cardioprotective signal pathways that are activated by ischaemic preconditioning (IPC) and those by IPC mimetics converge on mitochondria. Recent studies have shown that pools of Akt, protein kinase C-ε, extracellular-regulated kinases, glycogen synthase kinase-3beta (GSK-3beta), and hexokinases (HK) I and II, are localized in mitochondria in addition to their pools in the cytosol. Accumulating evidence indicates that such 'mitochondrial protein kinases' receive signals from cytosolic molecules and enhance tolerance of myocytes to injury. Proteomic analyses suggest that these kinases form complexes with each other and with subunit proteins of the mitochondrial permeability transition pore (mPTP). Functional relationships between the protein kinases in mitochondria have not been fully clarified, but GSK-3beta and HKs appear to be at the end of the signal pathways and directly responsible for inhibition of opening of the mPTP and, thus, for myocyte protection from necrosis. In this review, recent findings supporting roles of mitochondrial protein kinases in protection from myocardial necrosis after ischaemia/reperfusion are summarized and discussed.


Blindness resulting from orbital cellulitis following rhinoplasty.
Ophthalmic complications occurring after non-ophthalmic surgery are rare. We present a case of orbital cellulitis in a 24-year-old woman, who had undergone augmentation rhinoplasty in combination with breast augmentation. Symptoms included pain, swelling, erythema and eventual loss of vision in the left eye. Intravenous administration of antibiotics did not halt the rapid progression of this infection. On the sixth postoperative day, the patient underwent left-orbital evisceration to prevent the spread of infection to other organ systems. Despite aggressive therapy, the sequela was permanent, unilateral blindness. Orbital cellulitis in aesthetic surgery is extremely rare. In patients undergoing rhinoplasties that may be prolonged due to other concomitant cosmetic procedures, aseptic preoperative preparation and careful monitoring for signs of orbital infection are recommended.


The neural crest is contiguous with the cardiac conduction system in the mouse embryo: a role in induction?
In this study we present data on the spatial relationship between neural crest-derived cells (NCC) and the specialized cardiac conduction system (CCS) in the developing murine heart. Using Wnt1-Cre/R26R conditional reporter mice that express beta-galactosidase from ROSA26 upon Cre-mediated recombination, two populations of NCC are seen: one migrates through the arterial pole and contributes to the bundle branches, whereas the second population enters by way of the venous pole and provides cells to the sinoatrial and atrioventricular node areas. The CCS/ lacZ construct is found in the myocardium of the early embryonic heart and afterward only persists in the definitive CCS and is acknowledged as a reporter for the developing conduction system. The contiguous expression of both reporters is suggestive for a potential role of cardiac NCC in the induction of the final differentiation of the CCS.


The effects of the flow pattern on organic oxidation and nitrification in aerated submerged biofilters.
Previous research has shown that a submerged biofilter is effective in removing organic matter and total organic nitrogen. Upflow and downflow biofilters were set up to investigate the different oxidative efficiencies on organic matter and ammonia nitrogen of different biofilter positions and to compare the biological activities of the upflow and downflow patterns. A comparison of the operational characteristics of the two types of biofilters is discussed. The main COD removal zone is 0-20 cm in the upflow biofilter, but in the downflow biofilter it occurs in the submerged zone. The nitrification process is dependent on the HRT and the residual COD. In the downflow biofilter, the efficiency of the nitrification increases with the HRT. The growth of nitrifying bacteria has a tendency to take place in higher zones in the downflow biofilter, especially for a longer HRT. Batch tests measured the biological activity of heterotrophs and nitrifying autotrophs with decomposition rates. In the upflow biofilter, the nitrification rates increased while the COD oxidative rates decreased with the height of the biofilter, so the effect of the HRT on the activity of the nitrifying autotrophs is significant. However, in the down biofilter, the activity of the nitrifying autotrophs was similar at different heights in the same HRT runs with the maximum nitrifying autotrophs activity being at an HRT of 6 hours.


The conservative treatment of pediatric mandibular fracture with prefabricated surgical splint: a case report.
The use of rigid fixation in children is controversial and may cause growth retardation along cranial suture lines. Intermaxillary fixation for mandibular fractures should be used cautiously as bony ankylosis in the temporomandibular joint (TMJ) and trismus may develop. The high osteogenic potential of the pediatric mandible allows non-surgical management to be successful in younger patients with conservative approaches. In this case, successful conservative treatment of mandibular fracture of a 3-year-old patient is presented.


Alpha-tocopherol decreases interleukin-1 beta release from activated human monocytes by inhibition of 5-lipoxygenase.
Cardiovascular disease is the leading cause of morbidity and mortality in westernized populations. Low levels of alpha-tocopherol (AT) are associated with increased incidence of atherosclerosis and increased intakes appear to be protective. Recently, we showed that supplementation with AT resulted in significant decreases in monocyte superoxide anion release, lipid oxidation, interleukin-1 beta (IL-1 beta) release, and adhesion to endothelium. The reduction in superoxide and lipid oxidation by AT seemed to be mediated by inhibition of protein kinase C. The aim of this study was to investigate the mechanism(s) by which AT inhibits IL-1 beta release. Potential mechanisms examined included its effect as an antioxidant and its inhibitory effects on protein kinase C and the cyclooxygenase-lipoxygenase pathways. Although AT decreased superoxide release from activated monocytes, superoxide dismutase and catalase had no effect on IL-1 beta release. Also, a similar antioxidant, beta-tocopherol, had no effect on IL-1 beta release. The protein kinase C inhibitor, bisindolylmaleimide, did not inhibit IL-1 beta release from activated monocytes, in spite of AT decreasing protein kinase C activity. Leukotriene B4, a major product of 5-lipoxygenase, has been shown to augment IL-1beta release. In the presence of AT, a significant reduction in leukotriene B4 and IL-1 beta levels was observed, which was reversed by the addition of leukotriene B4. Similar observations were seen with specific inhibitors of 5-lipoxygenase. The product of cyclooxygenase, prostaglandin E2, has been shown to inhibit IL-1 beta activity in some systems. However, AT had no significant effect on prostaglandin E2 levels in activated monocytes. In the presence of indomethacin, a cyclooxygenase inhibitor, AT inhibited IL-1 beta activity. Also, AT had no effect on IL-1 beta mRNA levels or stability, suggesting a posttranscriptional effect. Thus, in activated human monocytes, AT exerts a novel biological effect of inhibiting the release of the proinflammatory cytokine, IL-1 beta, via inhibition of the 5-lipoxygenase pathway.


Predictors of benefit from an atopic dermatitis education programme.
Multidisciplinary, age-related, structured, group educational programmes for children with atopic dermatitis (AD) and their parents have shown positive long-term outcomes with respect to quality of life and coping behaviour of the participants. We aimed to identify predictors of favourable long-term outcome of an education measure for parents of children with AD aged 3 months to 7 years in the framework of The German Atopic Dermatitis Intervention Study (GADIS). In an exploratory approach, the data of 274 child-parent pairs were analysed with respect to the influence of various somatic and psychological variables as possible predictors of treatment success. Changes in parents' QoL, SCORAD (Scoring Atopic Dermatitis), topical corticosteroid use and parents' knowledge about AD between baseline and 12-months' follow-up were chosen as measures of long-term treatment success (outcome). Psychological rather than somatic parameters were identified as predictors of treatment success. Parents who had negative treatment experiences in the past and possessed only poor coping abilities with regard to scratch control benefitted the most from the training programme. The outcome of the education measure was independent of parents' schooling, vocational level and income. Parents of children with AD who lack adequate coping abilities should be particularly encouraged to take part in such an education programme.


A multicenter, open-label, long-term study of three-year infliximab administration in Japanese patients with ankylosing spondylitis.
To investigate the efficacy, safety, and pharmacokinetics of infliximab (IFX) in Japanese patients with active ankylosing spondylitis (AS). In this multicenter open-label study, IFX was infused at 5 mg/kg to 33 Japanese patients with active AS using or intolerable to non-steroidal anti-inflammatory drugs (NSAIDs) at Weeks 0, 2, and 6, and then every six weeks for approximately three years (mean: 149.5 weeks). Assessment in Ankylosing Spondylitis (ASAS) 20 response at Week 24 (primary endpoint) was 97.0% (32/33) and was thereafter maintained at approximately 90% over the three-year study period. Improvements in range of motion, physical function, inflammatory parameters, and quality of life (QOL) were all maintained throughout the three-year study period. A serum IFX level of ≥5 μg/mL was maintained with six-week infusion intervals, and only two patients (6.1%) developed antibodies to IFX. Specific adverse events in AS patients were not observed. These findings suggest that a 5 mg/kg administration of IFX at six-week intervals to Japanese patients with active AS is safe, effective and provides long-term therapeutic benefits.


Identification by peptide analysis of the spectrin-binding protein in human erythrocytes.
One-dimensional and two-dimensional peptide-mapping techniques are used to identify the protein which gives rise to the 72,000 dalton alpha-chymotryptic fragment previously shown to be the membrane attachment site for spectrin. Peptide maps of the 72,000 dalton fragment are very different from maps of Bands 1, 2, 2.9, 3, 3.1, 4.1, and 4.2 and very similar to maps of the apparently closely homologous polypeptides, Bands 2.1, 2.2, 2.3, and 2.6. Limited proteolysis of erythrocyte membranes is shown to generate Band 3', another polypeptide which has been associated with spectrin-binding activity. Peptide maps of Band 3' are very similar to maps of Band 2.1, suggesting that Band 3' is also a proteolytic fragment of Band 2.1. It is concluded that Band 2.1 and possibly some or all of the other, related polypeptides which electrophorese in the 2 region is (are) the spectrin-binding protein(s) of the human erythrocyte.


Clearance in vulvar lichen sclerosus: a realistic treatment endpoint or a chimera?
According to the current guidelines, the aim of vulvar lichen sclerosus (VLS) treatment was to improve symptoms and signs, not to cure. To assess (i) the rate of patients with VLS who achieved complete clearance of symptoms or objective features, or both, with a 12-week pharmacological treatment and (ii) the predictive value of therapeutic response to the demographic and clinical features. We retrospectively included patients with VLS who had undergone any topical treatment for 12 weeks; demographics, history, VLS-related symptoms and objective features recorded at baseline and on completion of treatment were collected and elaborated. The primary study endpoint was to assess the rate of patients achieving complete clearance of global subjective score (GSS), or in global objective score (GOS), and in both scores. One hundred and ninety-six patients were included; 24 (12.2%) were asymptomatic at baseline, and nine (4.6%) dropped out. After treatment, 78 patients (47.3%) achieved GSS = 0, 40 (21.4%) achieved GOS = 0, and 23 (13.9%) achieved complete clearance of both symptoms and signs. Lower symptom scores at baseline and shorter disease duration were associated with the achievement of symptom clearance at the end of the treatment. Earlier disease onset, diagnosis and beginning of study treatment as well as lower baseline GOS were significantly associated with complete recovery of VLS signs and clearance of both symptoms and signs. A relevant part of patients who undergo a 12-week topical treatment is not completely cured of VLS. It may be hypothesized that these patients, in spite of a significant improvement, may still have substantial residual disease and, as a result, its effect on their quality of life.


[Effect of exercise on rats with renal injury].
Effect of exercise on rats with renal injury was studied. Nephritis was induced in rats by injection of anti-GBM antibody followed by ligation of a branch of the left renal artery after nephrectomy of the right kidney. Moderate daily treadmill exercise was forced on these experimental rats for ten weeks. Sedentary nephritic rats that received the same treatment described above served as controls. The sedentary nephritic rats suffered progressively increasing proteinuria during the time course of the experiment, whereas the nephritic rats with daily treadmill exercise experienced less proteinuria. Mild proteinuria was induced by daily treadmill exercise forced on non-nephritic rats that had received only nephrectomy of the right kidney, but no NTS injection. Light microscopy and immunofluorescence microscopy revealed severe glomerular injury in the sedentary nephritic rats, however, less glomerular injury was seen in nephritic rats with treadmill exercise. Serum cholesterol level was higher in the sedentary rats than in the rats with daily treadmill exercise. The results suggest that daily exercise by nephritic rats will not aggravate renal injury.


Chiral recognition by CD-sensitive dimeric zinc porphyrin host. 2. Structural studies of host-guest complexes with chiral alcohol and monoamine conjugates.
A structural study of complexes formed between a dimeric zinc porphyrin tweezer (host) and chiral monoalcohols and monoamines derivatized by a bidentate carrier molecule (guest) confirmed that their CD couplets arise from the preferred porphyrin helicity of 1:1 host-guest complexes. NMR experiments and molecular modeling of selected tweezer complexes revealed that the preferred conformation is the one in which the L (larger) group protrudes from the porphyrin sandwich; this preferred helicity of the complex determines the CD of the complexes. It was found that the porphyrin ring-current induced (1)H chemical shifts and molecular modeling studies of the complex lead to the assignments of relative steric size of the L (large)/M (medium) substituents attached to the stereogenic center. The assignments, in turn, are correlated with the sign of the CD exciton couplet that establishes the absolute configuration at the stereogenic center. Variable-temperature NMR experiments proved that the observed increase in CD amplitude at lower temperatures derives from conformational changes in the preferred offset geometry between two porphyrin rings.


The influence of menu labeling on calories selected or consumed: a systematic review and meta-analysis.
Recent menu labeling initiatives in North America involve posting the calorie content of standard menu items, sometimes with other nutrients of public health concern, with or without contextual information (such as the recommended daily caloric intake for an average adult) or interpretive information (such as traffic light symbols). It is not clear whether this is an effective method to convey nutrition information to consumers wanting to make more-informed food choices. Of particular concern are those consumers who may be limited in their food and health literacy skills to make informed food choices to meet their dietary needs or goals. The purpose of this systematic review was to determine whether the provision of menu-based nutrition information affects the selection and consumption of calories in restaurants and other foodservice establishments. A secondary objective was to determine whether the format of the nutrition information (informative vs contextual or interpretive) influences calorie selection or consumption. Several bibliographic databases were searched for experimental or quasiexperimental studies that tested the effect of providing nutrition information in a restaurant or other foodservice setting on calories selected or consumed. Studies that recruited generally healthy, noninstitutionalized adolescents or adults were included. When two or more studies reported similar outcomes and sufficient data were available, meta-analysis was performed. Menu labeling with calories alone did not have the intended effect of decreasing calories selected or consumed (-31 kcal [P=0.35] and -13 kcal [P=0.61], respectively). The addition of contextual or interpretive nutrition information on menus appeared to assist consumers in the selection and consumption of fewer calories (-67 kcal [P=0.008] and -81 kcal [P=0.007], respectively). Sex influenced the effect of menu labeling on selection and consumption of calories, with women using the information to select and consume fewer calories. The findings of this review support the inclusion of contextual or interpretive nutrition information with calories on restaurant menus to help consumers select and consume fewer calories when eating outside the home. Further exploration is needed to determine the optimal approach for providing this menu-based nutrition information, particularly for those consumers who may be limited in their food and health literacy skills.


[Analysis of CLCN1 gene mutations in a family affected with myotonia congenita].
To detect potential mutations of chloride channel l (CLCN1) gene in a family affected with myotonia congenita. Clinical data of the proband and her parents and brother was collected. The coding regions of the CLCN1 gene were subjected to PCR and Sanger sequencing. Two missense mutations (c.937G>A and c.1205C>T), which were respectively located within exons 8 and 11 of the CLCN1 gene, were identified in the proband. The mother and father of the proband were found to harbor the c.937G>A and c.1205C>T mutation, respectively, whilst neither mutation was found in her brother. The novel missense CLCN1 mutations probably underlie the disease in this family. These have enriched the spectrum of CLCN1 mutations and may facilitate further research on this disorder.


The history of dental hygiene in South Korea.
This historical narrative highlights the origin and development of the dental hygiene profession in South Korea. The legacy of early American missionaries to Korea includes profound and long-lasting contributions in medicine, education and theology. Many of Korea's top universities today have their roots in the missionary schools of the late nineteenth century, including Yonsei University, home of the first dental hygiene program in Korea. From Yonsei in Seoul, the dental hygiene profession spread throughout the country, includingtheAmerican missionary-based program in Kwangju in 1977. Contributions included clinical and didactic education, as well as professional leadership and development. American dental missionaries developed the profession of dental hygiene in Korea, and provided guidance to Korean dentists and hygienists for its growth and expansion.


Resynchronizing estrus and ovulation after not-pregnant diagnosis and various ovarian states including cysts.
We compared outcomes of 2 protocols used to resynchronize estrus and ovulation in dairy females after a not-pregnant diagnosis. Nulliparous heifers and lactating cows in which artificial insemination (AI) occurred 41 +/- 1 d earlier were presented every 2 to 3 wk for pregnancy diagnosis by using ultrasonography. Ovaries were scanned, follicles were mapped and sized, presence of corpus luteum was noted, and GnRH was injected (d 0). Females were assigned randomly to receive PGF(2alpha) 7 d later (d 7) and then either received estradiol cypionate (ECP) 24 h after PGF(2alpha) (d 8; Heatsynch; n = 230) or a second GnRH injection 48 h after PGF(2alpha) (d 9; Ovsynch; n = 224). Those detected in estrus since their not-pregnant diagnosis were inseminated, whereas the remainder received a timed AI (TAI) between 65 and 74 h after PGF(2alpha). Ovarian scans and blood collected before injections for progesterone analysis were used to classify 4 ovarian status groups: anestrus, follicular cysts, luteal cysts, and cycling, plus an unknown group of females in which no blood sampling or ovarian scans were made. Few females (5.1%) were inseminated between not-pregnant diagnosis and d 8. On d 10, more ECP- than GnRH-treated females were inseminated after detected estrus (24 vs. 6%). Overall, more Ovsynch than Heatsynch females received a TAI (82 vs. 62%). Conception rates tended to be greater for females inseminated after estrus (37%) than after TAI (29%), particularly for those treated with Heatsynch (41 vs. 27%) than with Ovsynch (33 vs. 31%). Those inseminated after estrus conceived 31 +/- 8 d sooner than those receiving the TAI. Conception rates for females having elevated progesterone 7 d after the not-pregnant diagnosis were greater than those having low progesterone in Heatsynch (42%; n = 133 vs. 25%; n = 55) and Ovsynch protocols (33%; n = 142 vs. 15%; n = 45), respectively. Conception rates were greater in nulliparous heifers than in lactating cows (43 vs. 28%) regardless of protocol used. Although overall pregnancy outcomes after a not-pregnant diagnosis were similar in response to either the Ovsynch and Heatsynch protocols, inseminations performed after detected estrus before the scheduled TAI reduced days to eventual conception and tended to increase conception rates, particularly after Heatsynch.


[Bone and Stem Cells. The mechanism of osteogenic differentiation from mesenchymal stem cell].
Osteoblasts and osteocytes originate from pluripotent mesenchymal stem cells. Mesenchymal stem cells commit to osteogenic lineage and differentiate into mature osteoblasts and osteocytes through osteoprogenitor cells and preosteoblasts in response to multiple stimuli. The osteoblast commitment, differentiation, and functions are governed by several transcription factors. Among these transcription factors, runt-related transcription factor 2 (Runx2) is a crucial factor in osteoblast differentiation and controls bone formation. Differentiation toward these osteogenic lineage is controlled by a multitude of cytokines including WNTs, bone morphogenetic protein (BMP) , transforming growth factor-β (TGF-β) , hedgehog, parathyroid hormone (PTH) /parathyroid hormone related protein (PTHrP) , insulin-like growth factor-1 (IGF-1) , fibroblast growth factor (FGF) , and Notch. Although regulation of Runx2 activity is a point of convergence of many of the signal transduction routes, there is also a high degree of cross-talk between these pathways. Thus, the combined action of the signal transduction pathways induced by some cytokines determines the commitment and differentiation of mesenchymal stem cells toward the osteogenic lineage.


Immune responses of pigs after experimental infection with a European strain of Porcine reproductive and respiratory syndrome virus.
The purpose of this experiment was to study the immune response of pigs during an experimental infection with a European strain of Porcine reproductive and respiratory syndrome virus (PRRSV). Five pigs were challenged intranasally with PRRSV strain VP21 and another five were kept as controls. Clinical course and humoral and cell-mediated responses were monitored for 70 days post-infection (p.i.). Infected pigs developed mild signs at 24 h p.i. Viraemia was detectable by nested RT-PCR until day 14 p.i. Earliest seroconversions (ELISA) were seen by day 7 p.i. (three of five animals) and, by day 14, all inoculated pigs had seroconverted (ELISA and immunoperoxidase monolayer assay). Virus-neutralizing antibodies were undetectable until day 56 p.i. and, by day 70 p.i., two inoculated pigs still were negative. Flow-cytometry assays using peripheral blood mononuclear cells (PBMC) showed an upshift in CD8(+) cells (day 7 p.i.) and a downshift of CD21(+) cells (days 7 and 28 p.i.). Regarding cell-mediated responses, development of PRRSV-specific gamma interferon-secreting cells (IFN-gamma-SC) and interleukin 4-secreting cells (IL4-SC) in PBMC was examined by ELISPOT assay. IFN-gamma-SC were not detected significantly until day 14 p.i., whereas, for IL4-SC, no differences between groups were seen. Concurrently with the onset of viraemia and the development of clinical signs, serum haptoglobin levels and interleukin 10 (IL10) in PRRSV-stimulated PBMC-culture supernatants increased significantly. These differences disappeared later on. For IL2, IL4, IL8 or transforming growth factor beta, no differences were seen among groups. These results are compatible with a model in which the immune response does not fully control the outcome of the infection.


Fluid-phase immunoradiometric assay for the detection of qualitative abnormalities of factor VIII/von Willebrand factor in variants of von Willebrand's disease.
Antigenic reactivity of F.VIII/WF in variants of von Willebrand's disease (vWd) was studied with both fluid-phase and solid-phase immunoradiometric assays. Two different (rabbit and goat) 125I-labeled specific antibodies against purified F.VIII/WF were used in both their divalent (IgG) and their monovalent (Fab fragment) forms. Dose-response curves obtained by reacting a constant amount of antibody with serial dilutions of plasmas from normal or homozygous vWd demonstrated the specificity of the test. The accuracy was significantly higher with 125I-Fab fragments of goat anti-F.VIII/WF antiserum that intact goat IgG or rabbit IgG or Fab fragments. The significant decrease of the slope of the dose-response curves obtained with plasma from variants of vWd has been interpreted as due to the presence of abnormal F.VIII/WF molecules with decreased antigenic reactivity. A similar anomaly was found in cryosupernatant prepared from normal plasma, paralleling similarities demonstrated between variants of vWd and cryosupernatant. Results of experiments performed by reacting constant plasma dilutions from control or variants of confirmed the decreased antigenic reactivity of variant F.VIII/WF.


Identification of G alpha s messenger ribonucleic acid splice variants in human granulosa cells.
Granulosa cells are essential for follicular development and corpus luteum formation and their functions are regulated by gonadotrophins through G protein-coupled receptors. The dominant second messenger pathway involves the stimulation of cyclic AMP formation by G alpha s-linked receptors. In this paper we have investigated the expression of G alpha s mRNA splice variants in relation to expression of G alpha s protein isoforms in granulosa cells obtained from patients undergoing in vitro fertilization. We have carried out ribonuclease protection assays using cRNA riboprobes which are capable of detecting all G alpha s mRNA isoforms as well as quantifying total amounts of G alpha s mRNA. Granulosa cells express the message for G alpha s-Large and G alpha s-Small and the presence of two distinct protein products was confirmed by immunoblotting using the antibody RM/1. Moreover, the data show that a significant fraction of G alpha s-Large and G alpha s-Small mRNAs contain an extra CAG codon. This should generate proteins with an extra serine residue, resulting in G alpha s variants with the consensus sequence of a protein kinase C phosphorylation site. These results highlight the possible interaction between different signalling pathways in the control of cAMP production and the need to investigate the relationship between G alpha s variants and different adenylyl cyclase isozymes in patients with normal and abnormal ovarian function.


Identification of genes involved in metabolism and signalling of abscisic acid and gibberellins during Epimedium pseudowushanense B.L.Guo seed morphophysiological dormancy.
Key genes involved in metabolism and signalling of abscisic acid and gibberellins during Epimedium pseudowushanense B.L.Guo seed morphophysiological dormancy release were identified using phytochemistry, transcriptomics, and bioinformatic methods. The molecular mechanism of seed morphophysiological dormancy of Epimedium pseudowushanense B.L.Guo. remains largely unknown. The endogenous abscisic acid (ABA) and gibberellin (GA) content of E. pseudowushanense seeds at three developmental stages were quantitatively determined. The results showed the levels of ABA in E. pseudowushanense seeds decreased during seed embryo growth and development, while levels of GA3 increased during seed embryo growth, and levels of GA4 increased during seed dormancy release and seed sprouting. A high-throughput sequencing method was used to determine the E. pseudowushanense seed transcriptome. The transcriptome data were assembled as 178,613 unigenes and the numbers of differentially expressed unigenes between the seed development stages were compared. Computer analysis of reference pathways revealed that 12 candidate genes were likely to be involved in metabolism and signalling of ABA and GAs. The expression patterns of these genes were revealed by real-time quantitative PCR. Phylogenetic relationships among the deduced E. pseudowushanense proteins and their homologous proteins in other plant species were analysed. The results indicated that EpNCED1, EpNCED2, EpCYP707A1, and EpCYP707A2 are likely to be involved in ABA biosynthesis and catabolism. EpSnRK2 is likely implicated in ABA signalling during seed dormancy. EpGA3ox is likely to be involved in GA biosynthesis. EpDELLA1 and EpDELLA2 are likely implicated in GA signalling. This study is the first to provide the E. pseudowushanense seed transcriptome and the key genes involved in metabolism and signalling of ABA and GAs, and it is valuable for studies on the mechanism of seed morphophysiological dormancy.


Victor Horsley (1857-1916) and the temperance movement.
For nearly all of his life Victor Horsley campaigned against the evils of alcohol. This led him into direct conflict with politicians, brewers, publicans and the army. His views are of interest today when the subject of excessive consumption of alcohol is the subject of great public concern.


Latency to CNS oxygen toxicity in rats as a function of PCO(2) and PO(2).
Central nervous system (CNS) oxygen toxicity can occur as convulsions and loss of consciousness, without any premonitory symptoms. We have made a quantitative study of the effect of inspired carbon dioxide on sensitivity to oxygen toxicity in the rat. Rats were exposed to four oxygen pressures (PO(2); 456, 507, 608 and 709 kPa) and an inspired partial pressure of carbon dioxide (PCO(2)) in the range 0-12 kPa until the appearance of the electroencephalograph first electrical discharge (FED) that precedes the clinical convulsions. Exposures were conducted at a thermoneutral temperature of 27 degrees C. Latency to the FED decreased linearly with the increase in PCO(2) at all four PO(2) values studied. This decrease, which is probably related to the cerebral vasodilatory effect of carbon dioxide, reached a minimal value that remained constant on further elevation of PCO(2). The slopes (absolute value) and intercepts of latency to the FED as a function of carbon dioxide decreased with the increase in PO(2). This log-linear relationship made possible the derivation of equations that describe latency to the FED as a function of both PO(2) and PCO(2) in the PCO(2) - dependent range: Latency (min) = e((5.19-0.0040)(P)(O(2)))-e((2.77-0.0034)(P)(O(2))) x PCO(2) (kPa), and in the PCO(2)-independent range: Latency(min) = e((2.44-0. 0009)(P)(O(2))). A PCO(2) as low as 1 kPa significantly reduced the latency to the FED. It is suggested that in closed-circuit oxygen diving, any accumulation of carbon dioxide should be avoided in order to minimize the risk of CNS oxygen toxicity.


Malignant transformation of a solitary fibrous tumor of the liver and intractable hypoglycemia.
Sarcomas of the liver are rare. We report a case of intractable hypoglycemia secondary to a solitary fibrous tumor that underwent malignant transformation into a fibrosarcoma. A 70-year-old man presented with a hepatic mass and tumor-associated hypoglycemia which was resistant to medical management. Blood tests were remarkable only for elevated serum insulin-like growth factor (IGF)-2. The hypoglycemia resolved following resection of a solitary fibrous tumor surrounded by a high-grade fibrosarcoma. Real time reverse transcriptase polymerase chain reaction (RT-PCR) measured elevated levels of IGF2 mRNA in both the solitary fibrous tumor and the fibrosarcoma. Immunoblotting demonstrated a series of bands in the size range of pro-IGF2. Unfortunately, disseminated metastases developed 1 year later, concurrent with a recurrence of hypoglycemia, marked again by elevation of serum IGF2. Solitary fibrous tumors of the liver have a real risk of malignant transformation. The severity of the tumor-associated hypoglycemia may parallel the tumor burden and activity. The syndrome is the systemic effect of IGF2 secreted by the tumor. Surgery can treat the hypoglycemia syndrome and the underlying malignancy.


[Determination of trace organochlorine pesticides in soil using isotope dilution-high resolution gas chromatography].
A method for the determination of trace organochlorine pesticides (OCPs) in soil using isotope dilution and high resolution gas chromatography-high resolution mass spectrometry (ID-HRGC-HRMS) was developed. The sample was extracted by accelerated solvent extractor (ASE) and cleaned-up by a Florisil solid phase extraction (SPE) cartridge. The analytes were separated by HRGC on a DB-5MS column (30 mx 0.25 mm x 0.25 microm) and determined by HRMS. The identifications of OCPs were based on the retention time of 13C-labelled standard and the abundance ratio of the two exact mass-to-charge ratios. The quantitative analysis was performed using the ratios of the integrated areas of the 13C-labelled standards. This method has the recoveries ranging from 77.3% to 114.5% and the relative standard deviations (RSD) less than 10.81% (n=5). The limits of detection (LODs) of this method for all OCPs were lower than 0.04 pg/g. The results indicated that the method is rapid, selective and sensitive for precise determination requirements of organochlorine pesticides at trace level in soil.


In vitro assays for the anaphase-promoting complex/cyclosome (APC/C) in Xenopus egg extracts.
The anaphase-promoting complex/cyclosome (APC/C), a large (20S) multisubunit E3 ligase, has an essential role to ubiquitylate numerous substrates at specific times during mitosis and G1 phase as well as in meiosis. The deregulation of the APC/C causes cell death or genomic instability, which is a hallmark of cancers. Although 13 years have passed since its discovery, the molecular mechanisms of the APC/C-dependent ubiquitylation and proteolysis are still poorly understood. The development of in vitro systems enables the identification of new substrates and investigation of the molecular mechanisms by which the APC/C recognizes its substrates. This chapter describes in vitro assays reconstituted in Xenopus egg extracts.


Breastfeeding's protection against illness-induced anorexia is mediated partially by docosahexaenoic acid.
To test whether breastfeeding's protection against anorectic responses to infection is mediated by n-3 fatty acids' attenuation of interleukin (IL)-1beta and tumor necrosis factor (TNF)alpha. Experimental and observational studies. A hospital-based study was conducted. Five groups of infants were followed; three in the experimental and two in the observational study. Breast-fed- (BF-1), DHA-supplemented formula- (SFF-1), and non-DHA-supplemented formula-fed (FF-1) infants were studied before and after immunization against diphtheria, tetanus, pertussis and haemophilus influenzae type b. Pre- and post-immunization energy intakes (EI) and serum IL-1beta and TNFalpha were measured. The two other groups, breast-fed (BF-2) and formula-fed (FF-2) infants with pneumonia were followed throughout hospitalization. EI, IL-1beta and TNFalpha were measured at admission and discharge. Baseline erythrocyte fatty acid contents were determined. Both cytokines increased following immunization in all feeding groups. Post-immunization reductions in EI of SFF-1 infants (-11.8+/-5%, CI(95)=-23.3, 1.4%, P=0.07) were intermediate to those observed in BF-1 (-5.2+/-4.2%, CI(95)=-15.2, 5.9%, P=0.27) and FF-1 infants (-18+/-4.4%, CI(95)=-29%, -5.4%, P=0.02). In the observational study, TNFalpha (17.2+/-8.3 vs 3.4+/-3.0 ng/l, P=0.001) and decreases in EI (-31+/-43 vs -15+/-31%, CI(95)=-34%, 0.001%, P=0.056) were greater in FF-2 than in BF-2 infants at admission. Breastfeeding duration was associated positively with docosahexaenoic acid (DHA) erythrocyte contents, and negatively with admission TNFalpha. Decreases in EIs were associated with IL-1beta and TNFalpha concentrations. Reductions in EI following immunologic or infectious stimuli were associated with increases in IL-1beta and TNFalpha. Those reductions were attenuated by breastfeeding, and mediated in part by tissue DHA.


[Relative factors of expectant management of ectopic pregnancy].
To analyze select patients of ectopic pregnancy for expectant management. Retrospective analyses were conducted for the relative factors of 180 cases of ectopic pregnancy with expectant management at Department of Family Planning of our hospital from August 2004 to January 2012. Their general clinical data, clinical manifestations and laboratory tests were collected. The cases requiring neither surgery nor drug therapy belonged to the cure group while the rest fell into the failure group. A total of 140 patients were successfully managed with a cure rate of 75.27%. There was no significant difference between two groups in size of mass on ultrasonography (P > 0.05). The cases with gestational sac of mass on ultrasonography had statistical difference between two groups (P < 0.05). Statistical difference existed between two groups (P < 0.01) in initial blood beta-human chorionic gonadotropin (β-hCG), initial bloodβ-hCG and D3-5/D0 (ratio of bloodβ-hCG at day 3 - 5 and initial) were the variables for predicting the likelihood of successful expectant management under the ROC curve. The Youden Index was the largest at an initial bloodβ-hCG of 634 IU/L or D3-5/D0 of 0.711. At blood β-hCG ≤ 634 IU/L or D3-5/D0 < 0.711, expectant management may be offered. And mass with gestational sac on ultrasonography is a relative factor of expectant management.


Dynameomics: mass annotation of protein dynamics and unfolding in water by high-throughput atomistic molecular dynamics simulations.
The goal of Dynameomics is to perform atomistic molecular dynamics (MD) simulations of representative proteins from all known folds in explicit water in their native state and along their thermal unfolding pathways. Here we present 188-fold representatives and their native state simulations and analyses. These 188 targets represent 67% of all the structures in the Protein Data Bank. The behavior of several specific targets is highlighted to illustrate general properties in the full dataset and to demonstrate the role of MD in understanding protein function and stability. As an example of what can be learned from mining the Dynameomics database, we identified a protein fold with heightened localized dynamics. In one member of this fold family, the motion affects the exposure of its phosphorylation site and acts as an entropy sink to offset another portion of the protein that is relatively immobile in order to present a consistent interface for protein docking. In another member of this family, a polymorphism in the highly mobile region leads to a host of disease phenotypes. We have constructed a web site to provide access to a novel hybrid relational/multidimensional database (described in the succeeding two papers) to view and interrogate simulations of the top 30 targets: http://www.dynameomics.org. The Dynameomics database, currently the largest collection of protein simulations and protein structures in the world, should also be useful for determining the rules governing protein folding and kinetic stability, which should aid in deciphering genomic information and for protein engineering and design.


Dynamic rearrangements of transvacuolar strands in BY-2 cells imply a role of myosin in remodeling the plant actin cytoskeleton.
Plant cells typically contain a large central vacuole that confines the cytoplasm and organelles to the periphery of the cell and the vicinity of the nucleus. These two domains are often connected by transvacuolar strands (TVS), thin tubular structures that traverse the vacuole. The TVS are thought to act as important transport routes for the distribution of organelles and metabolites, and also to play a role in the positioning of the nucleus. Most TVS depend on internal actin filaments for their existence, and rearrangements of TVS can therefore indicate modifications in the actin cytoskeleton. In this study we describe time-lapse observations of tobacco BY-2 suspension-cultured cells that document the dynamic behavior of TVS. The TVS formed, branched, and collapsed, and their attachment points in the nuclear or cortical cytoplasm, as well as on other TVS, moved around. These dynamic rearrangements were inhibited within 5 min by the myosin inhibitor 2,3-butanedione monoxime (BDM). In particular, the movements of TVS attachment points and the variations in TVS length were significantly reduced in the presence of the drug. Similarly, movements of the nucleus were reduced by two thirds in BDM-treated cells. The number of TVS, together with the number of attachment and branch points, also dropped during BDM treatment. All effects of BDM on TVS dynamics were reversible upon removal of the drug. These results suggest a role for myosin motors in the rearrangement of TVS, which is likely to occur through their interaction with actin filaments.


Total mandibular alveolar osteotomy: an alternate choice to other surgical procedures.
Patients whose facial esthetics are not severely compromised but who need surgical intervention for the correction of a dentoskeletal problem can be treated by repositioning of the whole mandibular alveolar segment in the direction needed to allow for such correction. The challenge to achieve efficient and relatively stable results with the use of combined orthodontic and surgical methods has been met by the use of various surgical techniques. The lower total alveolar osteotomy is another viable surgical technique that could be considered when treatment is being planned in an orthognathic surgical case. Its indications, contraindications, advantages, and disadvantages are described, and cases are reported to exemplify problems that can be corrected with this approach.


Francis Bacon and the Art-Nature Distinction.
Commentators generally expound Bacon's position on the art-nature relationship in terms of how much it retained or departed from traditional conceptions. This paper argues that an appreciation of the Baconian meaning of the terms "art" and "nature" requires a close examination of his wider cosmogonical speculations. Bacon's cosmogonical account moves from a state of unbridled chaos to the relatively stable system for which the term "nature" is normally used. The fundamental principle lying at the heart of Baconian cosmogony is an enriched and appetitive matter: eternal, unchanging, and the plenipotentiary source of all things. Successive limitations of matter's absolute power produced a lazy and habitual nature, which Bacon labelled "nature free." To shift nature from this otiose condition, the Baconian operator recapitulates the original binding of matter. Bacon designated the systematic procedures of binding nature the science of magic. Magic is Bacon's human counterpart to the original cosmogonical process that gave rise to the current system of nature. In Bacon's cosmogony, all possible worlds unfold out of matter: the function of art is to shake out nature's hidden folds. Hence, the distinction between naturalia and artificialia maps on to the distinction between actual and potential. Nature free is without purpose, but art - nature bound - knowingly brings into being an alternative nature designed for human utility.


Marfan's syndrome with aortic valve endocarditis.
Marfans syndrome is an Autosomal dominant disorder of the connective tissues resulting in abnormalities of the musculoskeletal system, cardiovascular system and eyes. It has a prevalence of 1 in 100,000 population1 and occurs in all ethnic groups. It may be familial or due to new mutation (30%), in the fibrillin gene on arm of chromosome 15. It is estimated that one person in every 3000-5000 has Marfans syndrome may have cardiovascular abnormalities and may be complicated by infective endocartditis. About 90% of Marfan patients will develop cardiac complications2. The patient under discussion has musculoskeletal (Tall stature, reduced upper-lower segment ratio, arm-span to height ratio > 1.05, high arched palate) and Cardiovascular features (Severe aortic regurgitation complicated with infective endocarditis).


RBCs labeled at two biotin densities permit simultaneous and repeated measurements of circulating RBC volume.
The extend potential applications of a nonradioactive method for measuring circulating RBC volume, we tested the hypothesis that RBC volume could be determined independently using two populations of RBCs labeled with low-density biotin (LDB1) and high-density biotin (HDB). In 10 healthy adults, autologous RBCs were labeled with HDB, LDB, or 51Cr. The labeled RBCs were mixed and transfused. RBC volume was measured in postinfusion peripheral venous blood by quantitating dilution of each population of labeled RBCs. RBC volume measured using either LDB or HDB cells agreed well with RBC volume measured using 51Cr. For the regression of RBC volume by LDB versus RBC volume by 51Cr, correlation = 0.994 and slope = 0.933. For HDB versus 51Cr, correlation = 0.982 and slope = 0.953. RBC volume measured a second time in four subjects with HDB agreed well; mean CV for the differences between HDB and 51Cr were less than 5 percent. Using RBCs labeled with two different densities of biotin, RBC volume can be accurately measured simultaneously and repeatedly in the same subject without radiation exposure.


Right ventricular diastolic function in dialysis patients could be affected by vascular access.
Tricuspid annular plane excursion (TAPSE) measurement in echocardiography is a measure of heart diastolic distensibility: a low TAPSE indicates reduced ventricular distensibility leading to diastolic dysfunction. It is a good prognostic index for cardiac mortality risk in congestive heart failure patients, adding significant prognostic information to the NYHA clinical classification. Our study was designed to evaluate the effect of a single hemodialysis (HD) session on diastolic function and TAPSE, focusing on the effects of vascular access typology. Twenty chronically uremic patients (age 51 ± 10 years, dialytic age 24 ± 8 months), without overt heart disease, underwent conventional two-dimensional and Doppler echocardiography immediately before starting and 15 min after ending a mid-week HD session. Ten patients had distal radiocephalic arterovenous fistula (AVF), and 10 had permanent central venous catheters (CVC). The amount of fluid removed by HD was 2,706 ± 1,047 g/session. HD led to a reduction in TAPSE, left ventricle end-diastole volume, left ventricle end-systole volume, right ventricle end-diastole diameter, peak early transmitral flow velocity, and the ratio of early to late Doppler velocities of diastolic mitral flow. AVF patients showed greater right ventricle diameters versus CVC patients, while TAPSE appeared higher in the latter. Only the AVF patient group showed TAPSE values <15 mm. Our data confirm the effects of terminal uremia on right ventricle function (chamber dilation, impaired diastolic function), showing that these abnormalities are more frequent in AVF patients as opposed to CVC patients. It is reasonable to explain these clinical features as the effect of preload increase operated by AVF.


Participation of GABA in the sensitivity control of the OFF-response in the turtle ERG.
The intensity-response--V/log I, function of the d-wave in the turtle ERG was investigated before and after blockade of the GABAergic transmission by 0.4 mmol/l picrotoxin (PT) under conditions of two adapting background illuminations--0.01 and 10 lx. After PT the d-wave V/log I curves showed a shift to the left along the intensity axis under both adapting conditions, revealing an increase in the gain and the contrast sensitivity of the retinal elements involved in the d-wave generation. These changes were similar to the changes in the b-wave V/log I function described under similar conditions. The relative increase of the b- and d- wave amplitude had approximately equal values at both background levels at higher stimulus intensities. In the range of low stimulus intensity, however, at background illumination of 0.01 lx the relative increase of the d-wave was considerably greater than that of the b-wave. The experimental data obtained were best fitted by the Naka-Rushton equation. The participation of the GABAergic neurons on the d-wave sensitivity control is discussed.


Effects of dietary sucrose option on the diabetic syndrome of the eSS rat.
The eSS rat is a model of human spontaneous non-insulin-dependent diabetes. Male eSS rats were divided at the age of 4 months into two groups (eSSA and eSSB), both receiving the usual commercial balanced diet with sucrose also made available to eSSA. Sucrose intake did not imply a higher caloric diet, and no differences were found between groups in body weight and plasma triglyceride levels from 6 to 12 months of age. Sucrose option resulted in lower protein, lipid and carbohydrate intakes in eSSA animals. Plasma glucose values were higher in eSSA at different times of the tolerance curve. Likewise, eSSA kidneys showed significantly higher capsular and glomerular diameters and there was a discrete PAS-positive thickening of their basement membrane. We conclude that prolonged ad libitum sucrose intake, without weight gain, causes a moderate metabolic impairment and renal lesions in the eSS diabetic rat.


Electrically detected interferometry of Majorana fermions in a topological insulator.
Majorana fermions are zero-energy quasiparticles that may exist in superconducting vortices and interfaces, but their detection is problematic since they have no charge. This is an obstacle to the realization of topological quantum computation, which relies on Majorana fermions to store qubits in a way which is insensitive to decoherence. We show how a pair of neutral Majorana fermions can be converted reversibly into a charged Dirac fermion. These two types of fermions are predicted to exist on the metallic surface of a topological insulator (such as Bi2Se3). Our Dirac-Majorana fermion converter enables electrical detection of a qubit by an interferometric measurement.


Physicochemical and catalytic properties of acylase I from aspergillus melleus immobilized on amino- and carbonyl-grafted stöber silica.
Acylase I from Aspergillus melleus was immobilized on supports consisting of unmodified and modified silica. Modification was performed using 3-aminopropyltriethoxysilane (APTES) and glutaraldehyde (GA). The effectiveness of immobilization was investigated using the standard Bradford method in addition to a number of physicochemical techniques, including spectroscopic methods (FTIR, 29 Si and 13 C CP MAS NMR), porous structure and elemental analysis, and zeta potential measurement. A determination of catalytic activity was made based on the deacetylation reaction of N-acetyl-l-methionine. Furthermore, the effect of pH and temperature on the catalytic activity of the free and immobilized enzyme, as well as the reusability of the silica-bound aminoacylase, were determined. The immobilized systems demonstrated a high degree of catalytic activity. The best catalytic parameters were those of aminoacylase immobilized on silica modified with APTES (apparent activity 3937 U/g, relative activity 61.6%). © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:767-777, 2018.


Adipocytes as a source of increased circulating levels of nicotinamide phosphoribosyltransferase/visfatin in active acromegaly.
Nicotinamide phosphoribosyltransferase (NAMPT)/visfatin is a widely expressed protein with various effects on glucose and lipid metabolism, cell survival, and inflammation. We hypothesized that NAMPT was related to metabolic disturbances in active acromegaly. Body composition, glucose metabolism, and NAMPT levels were measured in 47 patients with active, untreated acromegaly and 24 age-, sex-, and body mass index-matched controls. The in vitro effects of GH/IGF-I on NAMPT expression in human sc adipocytes (SCA), visceral adipocytes, osteoblasts, and hepatocytes were studied. The effects of overnight incubation with the highly specific NAMPT inhibitor FK866 on the GH-stimulated monocyte chemotactic protein-1 and IL-6 expression in mature SCA were evaluated. NAMPT was increased in active acromegaly (P = 0.004) and correlated negatively with limb (arms + legs) fat percentage (% fat, r = -0.32; P = 0.032). After adjusting for age, gender, leptin, and GH, the circulating NAMPT correlated negatively with limb and total body fat percentage (% fat limbs, r = -0.43, P = 0.006; % fat total body, r = -0.36, P = 0.022) and correlated positively with limb and total body lean percentage (% lean limbs, r = 0.31, P = 0.047; % lean total body, r = 0.33, P = 0.034). No correlation between NAMPT and glucose metabolic parameters was found. In vitro studies revealed that GH increased NAMPT expression in adipocytes. The inhibition of NAMPT enzymatic activity attenuated GH-induced monocyte chemotactic protein-1 expression in SCA. NAMPT is increased in active acromegaly and may be an inflammatory mediator that causes monocyte infiltration in adipose tissue.


Structure and function of the repressor of bacteriophage lambda. II. Isolation and characterization of a lambda mutant which produces repressor having higher affinity for operators.
By mutagenizing a lambda cIts (lambda cI857) lysogen, a lambda mutant has been isolated with a wild-type phenotype. This mutant phage lysogenizes with low efficiency and produces a low burst. Though the initial rates of repressor synthesis in Escherichia coli after infection with wild-type and mutant lambda are the same, the maximum level of repressor that is synthesized in the latter case is only about 30% of that synthesized in the former. Virulent lambda plates on the lysogen of mutant lambda with slightly less efficiency producing very tiny plaques. Operator-binding studies made in vitro with purified mutant and wild-type repressors show that the binding curve of the former repressor is a rectangular hyperbola while that of the latter is sigmoid. The half-lives of the complexes of mutant and wild-type repressors with right operator are 133 and 27 min, respectively. All these results suggest that the mutant repressor possibly has a higher affinity for the operators. This mutant has been named lambda cIha (ha = high affinity).


Prenatal diagnosis of the RSH/Smith-Lemli-Opitz syndrome.
The RSH/Smith-Lemli-Opitz syndrome (RSH/SLOS) is a relatively common, autosomal recessive malformation syndrome comprising distinctive facial, limb and genital anomalies, and mental retardation. Most patients with a clinical diagnosis of RSH/SLOS have a defect of cholesterol biosynthesis at the level of 3beta-hydroxysteroid-delta7-reductase, resulting in a decreased level of cholesterol and an increased level of 7-dehydrocholesterol (7DHC) in body fluids and tissues. We report on our experience with the prenatal diagnosis of RSH/SLOS by quantitative sterol chromatography in amniotic fluid (AF) and chorionic villus (CV). Of 76 AF and nine CV samples analyzed for various indications, 20 were diagnostic of RSH/SLOS based on an increased level of 7DHC in the fluid or tissue. Of 39 fetuses at a 25% risk for RSH/SLOS, 10(25.6%) were affected. Twenty-nine pregnancies not known to be at risk for RSH/SLOS were studied because of either a fetal abnormality characteristic of RSH/SLOS detected by ultrasound, a low maternal serum uE3 level (MSuE3), or both. None of the pregnancies tested, because of a low MSuE3 but lacking a sonographic abnormality characteristic of RSH/SLOS, was affected. However, three of four pregnancies with a low MSuE3 and an RSH/SLOS-type fetal abnormality were positive. RSH/ SLOS was diagnosed in two additional pregnancies on which MSuE3 data were not available but in which fetal anomalies were identified. Of these five RSH/SLOS fetuses identified in pregnancies not otherwise at risk for RSH/SLOS, the presenting sonographic anomaly was either polydactyly, ambiguous genitalia, or both. Evaluation of the biochemical parameters and clinical severity of RSH/SLOS showed that there was an inverse correlation between clinical severity and both the level of AF 7DHC and the level of MSuE3. Based on these earlier and more extensive studies, we conclude that accurate prenatal diagnosis of RSH/ SLOS is possible by sterol analysis of AF and, most likely, CV specimens as well. Furthermore, our findings suggest that MSuE3 levels in combination with sonography may provide useful diagnostic and prognostic information in the absence of a family history of RSH/SLOS.


Concurrent summer influenza and pertussis outbreaks in a nursing home in Sydney, Australia.
To report on the investigation of a summer outbreak of acute respiratory illness among residents of a Sydney nursing home. An epidemiologic and microbiological investigation of the resident cohort at the time of the outbreak and medical record review 5 months later. A nursing home located in Sydney, Australia, during February to July 1999. The cohort of residents present in the nursing home at the time of the outbreak. Public health interventions included recommendations regarding hygiene, cohorting of residents and staff, closure to further admissions, and prompt reporting of illness; and virologic and serologic studies of residents. Of the 69 residents (mean age, 85.1 years), 35 fulfilled the case definition of acute respiratory illness. Influenza A infection was confirmed in 19 residents, and phylogenetic analysis of the resulting isolate, designated H3N2 A/Sydney/203/99, showed that it differed from strains isolated in eastern Australia during the same period. Serologic evidence of Bordetella infection was also found in 10 residents; however, stratified epidemiologic analysis pointed to influenza A as the cause of illness. The investigation revealed an unusual summer outbreak of influenza A concurrent with subclinical pertussis infection. Surveillance of acute respiratory illness in nursing homes throughout the year, rather than solely during epidemic periods, in combination with appropriate public health laboratory support, would allow initiation of a timely public health response to outbreaks of acute respiratory illness in this setting.


Sport in the trenches: the new deal for masculinity in France.
During the First World War, the life of a soldier was not just reduced to the trenches. In daily military life behind the lines, soldiers had recreational activities, some of which were seen as a test of virility, such as visiting brothels, and also, as we want to show in this paper, sport practices. For most of the French citizen-soldiers, who were working class and mainly from the countryside, the contact with allied soldiers has to be understood as a significant step in the social construction of gender. Educated in gymnastics, shooting and military exercises, French infantrymen (Poilus) and civilians saw allied sports and soldier-sportsmen as models of a modern masculinity. In a descriptive study of the development of football in the French army, our article tries to demonstrate firstly, that football learnt in the army by workers and the French rural society extended the influence of sport and its part in the construction of masculinity in France. Secondly, we show that the official recognition of sport in 1917 by the French army led to the definition of a modern French masculinity and to the recognition of the sportsmen-soldier as the model of hegemonic masculinity.


Behavioural and pharmacological characterisation of the elevated "zero-maze" as an animal model of anxiety.
The elevated "zero-maze" is a modification of the elevated plus-maze model of anxiety in rats which incorporates both traditional and novel ethological measures in the analysis of drug effects. The novel design comprises an elevated annular platform with two opposite enclosed quadrants and two open, removing any ambiguity in interpretation of time spent on the central square of the traditional design and allowing uninterrupted exploration. Using this model, the reference benzodiazepine anxiolytics, diazepam (0.125-0.5 mg/kg) and chlordiazepoxide (0.5-2.0 mg/kg) significantly increased the percentage of time spent in the open quadrants (% TO) and the frequency of head dips over the edge of the platform (HDIPS), and reduced the frequency of stretched attend postures (SAP) from the closed to open quadrants. In contrast, the anxiogenic drug m-chlorophenyl-piperazine (mCPP; 0.25-1.0 mg/kg) induced the opposite effects, decreasing %TO and HDIPS, and increasing SAP. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.001-0.1 mg/kg) had no effects on either %TO or HDIPS, but did decrease SAP at 0.01 mg/kg although not at higher or lower doses. Similarly, the 5-HT3 receptor antagonist, ondansetron (0.0001-1.0 mg/kg) decreased SAP and increased %TO at 0.01 mg/kg, but not at other doses. The present data suggest that a combination of the novel "zero-maze" design and a detailed ethological analysis provides a sensitive model for the detection of anxiolytic/anxiogenic drug action.


Peroxisome proliferator-activated receptor gamma polymorphism and periodontitis in pregnant Japanese women.
Recent studies suggest an association between maternal periodontitis and preterm birth, although the association remains controversial. It was suggested that mechanisms such as a genetic predisposition for a hyperinflammatory response cause periodontitis and preterm births. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor and ligand-dependent transcription factor. PPARgamma inhibits the transcriptional activity of the genes that produce proinflammatory mediators and repress periodontitis. Recently, a common polymorphism, proline(PRO)-to-alanine(ALA) mutation at codon12 in exonB (Pro12Ala: rs 1801282) PPARgamma, was reported to reduce the ability to transactivate responsive promoters. In this study, we tested whether the PPARgammaPro12Ala polymorphism was associated with maternal periodontitis and/or preterm birth. Genomic DNA was isolated from the venous blood of pregnant Japanese women (term birth: n = 72; preterm birth: n = 58). The PPARgammaPro12Ala genotype was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Within 5 days after labor, clinical periodontal parameters were evaluated, and periodontopathic bacteria from the subgingival plaque were detected by species-specific PCR. The mean clinical attachment level (P = 0.012), mean probing depth (P = 0.031), mean gingival index (P = 0.037), and percentages of sites with bleeding on probing (P = 0.041) in women with the PPARgammaPro12Ala genotype were significantly higher than in women with the PPARgammaPro12Pro genotype. However, there was no association between preterm birth and periodontitis. We suggest that the PPARgammaPro12Ala polymorphism may represent a genetic susceptibility factor for the clinical measurements of periodontitis in a limited number of pregnant Japanese women, but it probably cannot influence the relationship between periodontitis and preterm birth.


Differential responses to anxiogenic challenge studies in patients with major depressive disorder and panic disorder.
Anxiogenic challenge studies (intravenous lactate infusion and oral fenfluramine challenge) were conducted in 17 patients with panic disorder (PD), 12 patients with major depressive disorder and a history of panic attacks (MDD-PD), 27 patients with major depression and no history of panic (MDD), and 12 normal controls. PD and MDD-PD patients revealed significantly greater anxiogenic responses to lactate infusion and fenfluramine administration than either MDD patients or controls. PD patients revealed the most robust anxiogenic responses to both challenges as well as associated significant prolactin and cortisol responses to fenfluramine. The findings suggest that the predisposition to panic attacks as seen in PD and MDD-PD patients may represent a distinct neurobiological diathesis which may coexist with a major depressive diathesis in some patients. The delineation of subgroups within the more heterogenous groups of patients with MDD and/or PD will lead to greater precision in the development of clinical treatment strategies. Thus, MDD-PD patients (better called panic-depressives) may have a more severe illness than patients with MDD alone which must be accounted for in the course of pharmacotherapy and psychotherapy.


New insights on neuronal alterations in jimpy mutant brain.
In spite of abundant data on oligodendrocyte abnormalities in dysmyelinated jimpy brain, little is known about the axonal damage and the expression of neuronal genes. Recent findings indicate that Nogo-A, oligodendrocyte-myelin glycoprotein (OMgp), and myelin-associated glycoprotein (MAG) inhibit axonal growth by binding a common receptor, the Nogo-A receptor (NgR)-p75 complex. In order to evaluate neuronal modifications in the absence of myelin and in the presence of abnormal oligodendrocytes at different developmental stages, the expression of these inhibitory proteins and their receptors was investigated in jimpy mutant brain. Despite the decrease in oligodendrocyte number at P15 and P25 in jimpy, Nogo-A and OMgp mRNA levels are not significantly different compared with control, suggesting an overexpression of neuronal Nogo-A and OMgp in mutant. Double immunolabeling for Nogo-A and neurofilaments shows strong axonal staining of Nogo-A in jimpy and its down-regulation in oligodendrocytes. The current data raise questions about functions of Nogo-A other than neurite growth inhibition in the CNS. No significant changes in NgR mRNA levels were observed in jimpy, where the increase in p75 level can be correlated with the cell death of oligodendrocytes. In the paranodal region, the cell adhesion molecule neurofascin glial isoform NFN155 mRNA level is reduced by 40% whereas neuronal form NFN186 is up-regulated. These results may explain the failure of paranodal region organization, even with normal level of CASPR (paranodin) mRNA detected in jimpy brain.


Cytofluorescence localization of adriamycin in the nervous system. I. Distribution of the drug in the central nervous system of normal adult mice after intravenous injection.
By a fluorescence-microscopic technique the distribution of the antineoplastic glycoside, adriamycin (doxorubicin), was studied in the CNS of normal adult mice after i.v. injection. Doses comparable to those used in patients for the treatment of malignant diseases were used. The drug did not have access to areas of the brain within the blood-brain barrier but, except for the subcommissural organ, it was consistently localized in the nuclei of neurons and/or glial cells of the circumventricular organs (postremal area, subfornical organ, median eminence, neurohypophysis) as well as in cells of the choroid plexus and lamina cribrosa of the optic nerve. The nuclear fluorescence was accompanied by a less intense extracellular fluorescence when the survival time was shorter than 1 min after the injection. The fluorescence emitted by adriamycin was seen as early as 15 s after injection and showed its highest intensity at 1 and 15 min later. After 24 h fluorescence was no longer observed except for the ependymal zone of the median eminence. Our study thus shows that adriamycin passes from the blood into the nervous parenchyma in those areas of the brain located outside the blood-brain barrier. This finding raises the question whether in such regions there are any neurotoxicologic effects produced by the drug which have not yet been detected.


Performance of ceramic ultrafiltration membranes and fouling behavior of a dye-polysaccharide binary system.
Ultrafiltration membrane processes have become an established technology in the treatment and reuse of secondary effluents. Nevertheless, membrane fouling arises as a major obstacle in the efficient operation of these systems. In the current study, the performance of tubular ultrafiltration ceramic membranes was evaluated according to the roles exerted by membrane pore size, transmembrane pressure and feed concentration on a binary foulant system simulating textile wastewater. For that purpose, carboxymethyl cellulose sodium salt (CMC) and an azo dye were used as colloidal and organic foulants, respectively. Results showed that a larger pore size enabled more solutes to get adsorbed into the pores, producing a sharp permeate flux decline attributed to the rapid pore blockage. Besides, an increase in CMC concentration enhanced severe fouling in the case of the tighter membrane. Concerning separation efficiency, organic matter was almost completely removed with removal efficiency above 98.5%. Regarding the dye, 93% of rejection was achieved. Comparable removal efficiencies were attributed to the dynamic membrane formed by the cake layer, which governed process performance in terms of rejection and selectivity. As a result, none of the evaluated parameters showed significant influence on separation efficiency, supporting the significant role of cake layer on filtration process.


Antimutagenic and antigenotoxic potential of grape juice concentrate in blood and liver of rats exposed to cadmium.
The aim of this study was to evaluate the antimutagenic and antigenotoxic potential of grape juice concentrate in rodent organs exposed to cadmium chloride intoxication. A total of 15 Wistar rats were distributed into three groups (n = 5), as follows: control group (CTRL; nontreated group), cadmium group (Cd), and cadmium-grape juice group (Cd + GJ). Exposed animals received intraperitoneal injection of cadmium chloride (1.2 mg/kg body weight) diluted in water and, after 15 days, Cd + GJ group received grape juice concentrate for 15 days, by gavage (0.8 mL, 1.18 mg of polyphenols kg(-1) day(-1)). Grape juice concentrate was able to decrease genotoxic effects induced by cadmium in peripheral blood and liver cells as depicted by single cell gel (comet) and micronucleus assays. A decrease for anti-8-hydroxy-20-deoxyguanosine (8OHdG) expression in hepatocytes of animals exposed to cadmium and treated with grape juice concentrate was also detected. Higher CuZn-SOD activity was observed in liver cells of the Cd + GJ group. No remarkable differences were seen regarding Mn-SOD activity among groups. Taken together, our results demonstrate that grape juice concentrate was able to exert antimutagenic and antigenotoxic activities in blood and liver cells of rats exposed to cadmium.


Juvenile diabetes mellitus after forty years.
Seventy-three patients with juvenile diabetes mellitus for a mean duration of 42.9 years were retrospectively studied on a multidisciplinary basis. Only three of this group of patients were socially disabled as a result of their long-standing illness. Of all the complications, insulin-induced hypoglycemia was most common. Although diabetic retinopathy was clinically evident in about 75 per cent of patients, only 50 per cent of these seventy-three patients had a significant visual impairment. Nephropathy was apparent in 59 per cent of patients, and neuropathy was demonstrable in half of them. Significant peripheral vascular system impairment was present in 40 per cent and major cardiac complication in 20 percent.


Upregulation of annexin A1 expression by butyrate in human melanoma cells induces invasion by inhibiting E-cadherin expression.
Epithelial to mesenchymal transition (EMT) is a critical step in the metastasis of epithelial cancer cells. Butyrate, which is produced from dietary fiber by colonic bacterial fermentation, has been reported to influence EMT. However, some studies have reported that butyrate promotes EMT, while others have reported an inhibitory effect. To clarify these controversial results, it is necessary to elucidate the mechanism by which butyrate can influence EMT. In this study, we examined the potential role of annexin A1 (ANXA1), which was previously reported to promote EMT in breast cancer cells, as a mediator of EMT regulation by butyrate. We found that ANXA1 mRNA and protein were expressed in highly invasive melanoma cell lines (A2058 and A375), but not in SK-MEL-5 cells, which are less invasive. We also showed that butyrate induced ANXA1 mRNA and protein expression and promoted EMT-related cell invasion in SK-MEL-5 cells. Downregulation of ANXA1 expression using specific small interfering RNAs in butyrate-treated SK-MEL-5 cells resulted in increased expression of the epithelial marker E-cadherin and decreased cell invasion. Moreover, overexpressing ANXA1 decreased the expression of the E-cadherin. Collectively, these results indicate that butyrate induces the expression of ANXA1 in human melanoma cells, which then promotes invasion through activating the EMT signaling pathway.


Magic-echo phase-encoding solid imaging with improved time resolution.
The magic-echo phase-encoding solid imaging (MEPSI) sequence is based on the magic-echo pulse sequence for the refocusing of the dipolar interaction and on pure phase-encoding for spatial resolution in all dimensions. MEPSI has many advantages; however, as a consequence of pure phase-encoding, it is very time-consuming. In the following, two strategies are proposed to decrease the time necessary for the acquisition of an image by a factor of 2 per dimension.


The response of plasma arginine vasopressin to 14 h water deprivation in the elderly.
The response of plasma arginine vasopressin (AVP) to 14 h water deprivation was investigated in 30 healthy elderly individuals ranging in age from 63 to 87 years, with a mean age of 76.5 years. The mean AVP concentrations, both at normal hydration and after the water deprivation test, were significantly lower than those in the young. Moreover, the post-test mean value of Uosm/Posm in the elderly increased up to 1.55 +/- 0.52, which is lower than that in the young in whom the value was greater than 2. These results suggest that the aged are prone to incomplete diabetes insipidus. This pathological state might predispose to electrolyte imbalance in the elderly.


Increased beta-adrenergic sensitivity correlates with visceral hypersensitivity in patients with constipation-predominant irritable bowel syndrome.
Autonomic imbalance has been proposed to be a pathophysiological factor for irritable bowel syndrome (IBS). The aim of this study was to assess beta-adrenergic abnormalities in IBS and to evaluate their relationship to visceral hypersensitivity and other symptoms of IBS patients. Sixteen IBS patients and 16 control subjects were recruited into this study. Participants were asked to complete a questionnaire regarding bowel symptoms, and in order to study beta-adrenergic sensitivity, isoproterenol stimulation tests were performed and visceral hypersensitivity was evaluated by barostat test. Results showed that beta-adrenergic activity and rectal sensitivity were more pronounced in IBS patients than in normal control patients (P < 0.01). Although both IBS subgroups also exhibited more pronounced beta-adrenergic sensitivity than did the controls (P < 0.05), a significant correlation between beta-adrenergic activity and maximally tolerable pressures on the barostat test was found only in IBS-C patients (P = 0.03, R = 0.855). In addition, patients with "hard or lumpy" stools exhibited a higher degree of beta-adrenergic activity (P = 0.00). We conclude that increased beta-adrenergic activity significantly correlated with visceral hypersensitivity in constipation-predominant IBS and symptoms of hard or lumpy stools in IBS patients.


Rapid purification of enzymes of fatty acid biosynthesis from rat adipose tissue.
Acetyl CoA carboxylase, ATP-citrate lyase and fatty acid synthetase were purified to homogeneity by a simple procedure. The purification method consists of polymerization of acetyl CoA carboxylase with citrate followed by avidin-Sepharose affinity chromatography. ATP-citrate lyase and fatty acid synthetase were isolated as by-products of acetyl CoA carboxylase purification and are separated from each other by chromatography on DE-52. ATP-citrate lyase was further purified by CoA-agarose affinity chromatography and fatty acid synthetase was purified on Bio-Gel A-1.5m. Purified ATP-citrate lyase, acetyl CoA carboxylase and fatty acid synthetase had specific activities of 9.9, 2.8 and 1.8 U/mg respectively with an over all recovery of 30, 25 and 50% respectively. Using these purified enzymes, we found that ATP-citrate lyase and acetyl CoA carboxylase were phosphorylated in vitro by both cAMP-dependent protein kinase and ATP-citrate lyase kinase whereas fatty acid synthetase was not phosphorylated by these protein kinases.


Triple Aim Is Triply Tough: Can You Focus on Three Things at Once?
The I3 POP Collaborative sought to improve health of patients attending North Carolina, South Carolina, and Virginia primary care teaching practices using the triple aim framework of better quality, appropriate utilization, and enhanced patient experience. We examined change in triple aim measures over 3 years, and identified correlates of improvement. Twenty-nine teaching practices representing 23 residency programs participated. The Institute for Health Care Improvement Breakthrough Series Collaborative model was tailored to focus on at least one triple aim goal and programs submitted data annually on all collaborative measures. Outcome measures included quality (chronic illness, prevention); utilization (hospitalization, emergency department visits, referrals) and patient experience (access, continuity). Participant interviews explored supports and barriers to improvement. Six of 29 practices (21%) were unable to extract measures from their electronic health records (EHR). All of the remaining 23 practices reported improvement in at least one measure, with 11 seeing at least 10% improvement; seven (24%) improved measures in all three triple aim areas, with two experiencing at least 10% improvement. Practices with a greater number of patient visits were more likely to show improved measures (odds ratio [OR] 10.8, 95% confidence interval [CI]: .68-172.2, P=0.03). Practice interviews revealed that engaged leadership and systems supports were more common in higher performing practices. Simultaneous attainment of improvement in all three triple aim goals by teaching practices is difficult. I3 POP practices that were able to pull and report data improved on at least one measure. Future work needs to focus on cultivating leadership and systems supporting large scale improvement.


[Effect of cadmium sulphate on the metabolism of carbohydrates in organism of rats of different ages].
The influence of cadmium sulfate on concentration of glucose, lactate, piruvate, alpha-ketoglutarate, malate, oxaloacetate in blood of 3-, 6- and 18-month-old poisoned rats was established the results of our researches. It was found, that poisoning of rats by cadmium sulfate causes the rise of concentration of glucose, metabolites of citric acid cycle and glycolysis in blood of animals of all age groups explored. The research results prove that in blood of 3-month-old poisoned rats the level of glycolysis and citric acid cycle activation is considerably higher in comparison with that of 6- and 18-month-old animals. As a result, a comparison of age-specific dynamics of changes of carbohydrate metabolism indices in the blood of rats, poisoned by cadmium showed that the organism of 3-month-old rats is more sensitive to toxic influence of cadmium.


DNAJC3 mutation in Thai familial type 2 diabetes mellitus.
Type 2 diabetes mellitus (T2D) is a heterogeneous disease, with certain cases presenting an autosomal dominant type. The rare coding variants of disease‑causing genes in T2D remain mostly unclear. The present study aimed to identify the disease‑causing gene conducting whole exome sequencing in a Thai T2D family with an autosomal dominant transmission of T2D with no evidence of mutations in known maturity‑onset diabetes of the young (MODY) genes. Candidate variants were selected according to certain criteria of mutation prediction programs, followed by segregation analysis with diabetes in the family. The results demonstrated that, of the 68,817 variants obtained, 122 were considered as candidate variants subsequent to the filtering processes. Genotyping of these variants revealed that DnaJ homolog subfamily C member 3 (DNAJC3) p.H238N segregated with diabetes in the family. This mutation was also identified in another proband from the autosomal dominant T2D family without mutation in known MODY genes and was segregated with diabetes. This variant was also identified in 14/1,000 older‑onset T2D patients [minor allele frequency (MAF)=0.007], 2/500 non‑diabetic controls (MAF=0.002) and 3 prediabetic individuals who were previously classified as non‑diabetic controls. In silico mutagenesis and protein modeling of p.H238N revealed changes of the polar contacts across the tetratricopeptide repeat (TPR) motif and TPR subdomains, which may affect the protein tertiary structure. Furthermore, the expression of DNAJC3 H238N protein was 0.68±0.08 fold (P<0.05) lower when compared with that of the wild‑type, possibly due to protein instability. Thus, DNAJC3 p.H238N is likely to be a variant causing diabetes.


Effect of ileal infusion of lipid on jejunal motor patterns after a nutrient and nonnutrient meal.
To investigate how ileal lipid delays small bowel transit, pressure activity was recorded at multiple sites in the human small intestine during ileal infusion of either lipid or saline. Initial studies showed that ileal lipid reduced the contraction rate in the jejunum but not in the duodenum or ileum. The effect of ileal lipid was further investigated by recording pressures at seven sites in the jejunum after ingestion of either a nutrient or a nonnutrient meal. The nutrient meal induced an irregular motility pattern; ileal lipid significantly reduced the contraction rate, the percentage of contractions involved in propagated events, the mean length of propagation, and the propagation index. The nonnutrient meal induced a pattern containing discrete clusters of contractions. Ileal lipid significantly reduced the occurrence of contraction clusters and the mean length of propagation. Thus, although the delay in small bowel transit observed during ileal infusion of lipid can be explained by reductions in the rate and the degree of propagation of jejunal contractions, the mechanism varies according to the type of meal.


Quality of life in Parkinson's disease patients: validation of the Short-Form Eight-item Parkinson's Disease Questionnaire (PDQ-8) in Taiwan.
This study sought to evaluate the Chinese version of the eight-item Parkinson's Disease Questionnaire (PDQ-8), through standard psychometric techniques. A cross-sectional study was conducted on 100 Parkinson's disease patients attending a Movement Disorders Unit. Neurologists' assessments were based on Hoehn and Yahr, Schwab and England and Unified Parkinson's Disease Rating Scales. Patients' self-evaluations included the Taiwanese Depression Questionnaire, the 39-item Parkinson's Disease Questionnaire (PDQ-39) and PDQ-8, pain, and Pittsburgh Sleep Quality Index. Analyses for internal consistency, inter-rater reliability, and construct validity were performed. There was no evidence of floor or ceiling effects. The alpha coefficient was 0.81. Correlation of social support and bodily discomfort with the PDQ-8 was modest (0.46 and 0.36, respectively). PDQ-8 convergent validity with the PDQ-39 was very high (r = 0.96), and known-groups validity proved satisfactory. The results of this study suggest the PDQ-8 is a valid and reliable disease-specific health-related quality-of-life instrument for Parkinson's disease in Taiwan when used independently of the PDQ-39.


Essential sulfhydryl groups in diamine oxidase from Euphorbia characias latex.
Diamine oxidase from Euphorbia characias latex contains two sulfhydryl groups per mole of dimeric enzyme. The sulfhydryl groups are unreactive in the native enzyme but can be readily titrated by 4,4'-dithiodipyridine after protein denaturation, or anaerobically in the presence of the amine substrate. In the presence of both substrates (diamine and oxygen) they react sluggishly. The sulfhydryl groups show different reactivity toward various reagents, but in every case their modification inhibits catalytic activity. The insensitivity of the native enzyme to specific reagents suggests that the sulfhydryl groups are positioned in the interior of the protein and shielded from the solvent. Their reactivity in the presence of the amine substrate could be attributed to a conformational change occurring upon substrate binding or after substrate oxidation.


Economic botany collections: A source of material evidence for exploring historical changes in Chinese medicinal materials.
Many Chinese medicinal materials (CMMs) have changed over centuries of use, particularly in terms of their botanical identity and processing methods. In some cases, these changes have important implications for safety and efficacy in modern clinical practice. As most previous research has focused on clarifying the evolution of CMMs by analyzing traditional Chinese materia medica ("bencao") literature, assessments of historical collections are needed to validate these conclusions with material evidence. Historical collections of Chinese medicines reveal the market materials in circulation at a given moment in time, and represent an underexploited resource for analyzing the evolution of Chinese herbal medicines. This study compares specimens from a rare collection of CMMs from the 1920s with contemporary market materials; by highlighting examples of changes in botanical identity and processing that remain relevant for safe clinical practice in the modern era, this work aims to stimulate further research into previously unexplored historical collections of Chinese medicines. 620 specimens of CMMs that were collected from Chinese pharmacies in the Malay peninsula in the 1920s were examined macroscopically and compared with current pharmacopoeia specifications and authentic contemporary samples. These historical specimens, which are stored in the UK in the Economic Botany Collections (EBC) of Royal Botanic Gardens Kew, were morphologically examined, photographed, and compared to authentic CMMs stored at the Bank of China (Hong Kong) Chinese Medicines Center at Hong Kong Baptist University, as well as authentic herbarium-vouchered specimens from the Leon Collection (LC) at the Kew EBC. Case studies were selected to illustrate examples of historical changes in botanical identity, used plant parts, and processing methods. This investigation confirmed that confusion due to shared common names and regional variations in the botanical identity of certain CMMs has been a persistent issue over time. Additionally, historical changes in processing methods and the plant parts used were observed for some CMMs. In some cases, these changes have direct implications for the safe clinical practice of Chinese medicine. This preliminary assessment illustrated the significant potential of collections for clarifying historical changes in CMMs. More research is needed to investigate pre-modern collections of CMMs, including a more comprehensive assessment of the holdings in the Kew EBC and other European collections that have not yet been explored from the perspective of Chinese medicine.


Lung cell reactions in guinea pigs after inhalation of asbestos (amosite).
To study the long-term effect of inhaled asbestos, guinea-pigs were exposed to airborne amosite at a concentration of 49 mg/m3, 2 h/day for 3 or 6 weeks and examined up to 2 years after exposure. Macrophages in lung lavage fluid (LLF) were increased at 16, 24 and 93 weeks and lymphocytes at 24 weeks. Examination of lung wall cells (LWC) 2 years after exposure compared to cells obtained by LLF showed higher proportions of LWC lymphocytes and neutrophils. Percoll gradient centrifugation of these cells showed a higher proportion of high density macrophages in LLF from the amosite-exposed animal and an increased number of low density lymphocytes in the LW. Cathepsin D was increased in LLF at 8 and 24 weeks and in alveolar macrophages 24 weeks and 2 years after exposure. Fibroblast cultures exposed to LLF did not show any statistical significant changes in their collagen synthesis. Histology 93 weeks after exposure showed macrophage and mediastinal lymph node accumulation of asbestos, as well as collagen in alveolar walls. Granulomas were found in the vicinity of blood vessels and in connection with the bronchioles. The data suggest that amosite at low doses ultimately causes fibrosis with a reaction pattern different from that seen in silicosis. The inflammation and fibrosis seems to develop only within the interstitium.


[The trend sport snowblading and its risks].
The study analysed the results of an examination of 3557 skiing, snowboarding and snowblading injuries treated at the Department of Trauma Surgery at the Klinikum Garmisch-Partenkirchen in winter seasons 99/00 through 02/03. In this study group, a total of 70 injuries occurred while snowblading. These injuries are compared to the remaining injuries resulting from skiing, carving or snowboarding accidents. This study intends to contribute to the tracking and recording of injuries occurring during snowblading, a sport that is popular but not yet well-addressed in medical literature. The results show that snowblading injuries are similar to those of skiing, but different from those attributable to snowboarding, particularly with regard to the affected parts of the body and injury patterns. Acrobatic jumps increase significantly the risk of fractures of the lower extremities. However, ruptures of ligaments, especially of the ACL, are seen more rarely in snowblading than in carving or conventional skiing. Distorsions, on the other hand, are observed significantly more often among snowbladers when compared with carvers and snowboarders. Release bindings for snowblades could reduce the risk of injuries.


Development of a measure of resident satisfaction with the nursing home.
A satisfaction instrument specifically designed for use with nursing home residents, the Satisfaction with the Nursing Home Instrument (SNHI), was developed and tested with a sample of 110 nursing home residents from three proprietary facilities in Minnesota. As hypothesized, significant relationships were found between SNHI scores and measures of affect (negatively associated with depression and positively associated with morale), providing support for the construct validity of the scale. The lack of a significant relationship between SNHI scores and both age and mental status confirmed the predicted divergent validity of the instrument. The alpha coefficient for the 29-item scale was 0.81.


[Accelerated laboratory diagnosis of bacterial pneumonia].
The effectiveness of countercurrent immunoelectrophoresis (CIE) used for the accelerated differential diagnosis of pneumococcal, staphylococcal, mycoplasmal and Legionella infections in cases of pneumonia has been shown. The presence of correlation between the results obtained in the bacterial study of sputa and bronchial washings and in CIE has been revealed, which gives grounds for recommending CIE for the accelerated diagnosis of pneumococcal pneumonia on the basis of the analysis of sputa, bronchial washings and blood sera obtained from patients. In Legionella infection the passive hemagglutination test with antigenic diagnostica has proved to be more effective for accelerated diagnosis than CIE.


Purification and partial characterization of paralytic shellfish poison-binding protein from Acanthocardia tuberculatum.
A paralytic shellfish poison-binding protein (PSPBP) was purified 16.6-fold from the foot of the Moroccan cockles Acanthocardia tuberculatum. Using affinity chromatography, 2.5mg of PSPBP showing homogeneity on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was obtained from 93 mg of crude extract. The purified PSPBP exhibits a specific activity of about 2.78 mU/mg proteins and has estimated molecular weight of 181 kDa. Observation of a single band equivalent to 88 kDa on SDS-PAGE under reducing conditions suggested it to be a homodimer. The optimal temperature and pH for the purified PSPBP were respectively 30 degrees C and 7.0.


Endodontic management of a mandibular second premolar with four roots and four root canals with the aid of spiral computed tomography: a case report.
Aberrations in the root canal anatomy are a commonly occurring phenomenon. A thorough knowledge of the basic root canal anatomy and its variations is necessary for successful completion of the endodontic treatment. Mandibular second premolars usually have a single root and a single root canal. The incidence of three separate roots itself in this tooth is quite rare, and the presence of four separate roots and four distinct root canals has never been reported in literature so far. The use of spiral computed tomography scan in this rare case greatly contributed towards making a confirmatory diagnosis and successful nonsurgical endodontic management thereafter.


Regioselective covalent modification of hemoglobin in search of antisickling agents.
Although the molecular defect in sickle hemoglobin that produces sickle cell disease has been known for decades, there is still no effective drug treatment that acts on hemoglobin itself. In this work, a series of diversely substituted isothiocyanates (R-NCS) were examined for their regioselective reaction with hemoglobin in an attempt to alter the solubility properties of sickle hemoglobin. Electrospray mass spectrometry, molecular modeling, X-ray crystallography, and conventional protein chemistry were used to study this regioselectivity and the resulting increase in solubility of the modified hemoglobin. Depending on the attached R-group, the isothiocyanates were found to react either with the Cysbeta93 or the N-terminal amine of the alpha-chain. One of the most effective compounds in the series, 2-(N,N-dimethylamino)ethyl isothiocyanate, selectively reacts with the thiol of Cysbeta93 which, in conjunction with the cationic group, was seen to perturb the local hemoglobin structure. This modified HbS shows an approximately 30% increase in solubility for the fully deoxygenated state, along with a significant increase in oxygen affinity. This compound and a related analogue appear to readily traverse the erythrocyte membrane. A discussion of the relation of these structural changes to inhibition of gelation is presented. The dual activities of increasing HbS oxygen affinity and directly inhibiting deoxy HbS polymerization, in conjunction with facile membrane traversal, suggest that these cationic isothiocyanates show substantial promise as lead compounds for development of therapeutic agents for sickle cell disease.


The changing clinical presentation of recurrent primary biliary cirrhosis after liver transplantation.
Recurrent disease after liver transplant is a significant problem. Recurrent primary biliary cirrhosis (RPBC) is a histologic diagnosis. Clinical data is unreliable in predicting or diagnosing recurrence. RPBC appears to have a changing clinical presentation in recent years. The diagnosis of RPBC after liver transplantation was made histologically. Data were obtained from our prospectively maintained liver-transplant database and evaluated statistically. Between 1985 and 1999, 1,835 liver transplants were performed, 169 for PBC. One hundred fifty-six patients were evaluated (one patient received retransplantation, and 13 were excluded). Seventeen (10.9%) experienced recurrence. Median posttransplantation follow-up time was 72.1 months. Median time to recurrence was 49.6 months. Median follow-up time after recurrence was 11.5 months. Neither acute rejection episodes (P=0.34) nor OKT3 use (P=0.36) before diagnosis of recurrence was significant. The combination of cyclosporine, azathioprine, and prednisolone demonstrated recurrence in 6 of 71 (8.4%). Six of 49 (12.2%) patients treated with cyclosporine with or without mycophenolate mofetil and prednisolone experienced recurrence. Six of 36 (16.7%) patients treated with tacrolimus and prednisolone with or without mycophenolate mofetil experienced recurrence. Patients treated with cyclosporine had numerically fewer recurrences than those treated with tacrolimus (P=0.11). Patients with RPBC demonstrated prolonged survival. Clinical factors did not aid in predicting RPBC. The clinical course of RPBC appears to be different than in the earlier years of liver transplantation. Immunosuppression may play a role. The use and type of antimetabolite drugs had no affect on recurrence. RPBC demonstrated a different clinical course with tacrolimus treatment (shorter time to recurrence) and increased incidence when compared with cyclosporine treatment. Controlled randomized studies are necessary to determine differences between tacrolimus and cyclosporine treatment, if any.