Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation

Post-translational modifications play a key role in tau protein aggregation and related neurodegeneration. Because hyperphosphorylation alone does not necessarily cause tau aggregation, other post-translational modifications have been recently explored. Tau acetylation promotes aggregation and inhibits tau’s ability to stabilize microtubules. Recent studies have shown co-localization of acetylated and phosphorylated tau in AD and some 4R tauopathies. We developed a novel monoclonal antibody against acetylated tau at lysine residue 274, which recognizes both 3R and 4R tau, and used immunohistochemistry and immunofluorescence to probe 22 cases, including AD and another eight familial or sporadic tauopathies. Acetylated tau was identified in all tauopathies except argyrophilic grain disease (AGD). AGD is an age-associated, common but atypical 4R tauopathy, not always associated with clinical progression. Pathologically, AGD is characterized by neuropil grains, pre-neurofibrillary tangles, and oligodendroglial coiled bodies, all recognized by phospho-tau antibodies. The lack of acetylated tau in these inclusions suggests that AGD represents a distinctive tauopathy. Our data converge with previous findings to raise the hypothesis that AGD could play a protective role against the spread of AD-related tau pathology. Tau acetylation as a key modification for the propagation tau toxicity deserves further investigation.     

Prevalence,correlates, and comorbidities of four DSM-IV specific phobia subtypes: Results from the Korean Epidemiological Catchment Area study

Although several studies have detected differences in clinical features among specific phobias, there is a shortage of detailed national data on the on the DSM-IV SP subtypes, particularly in the Asian population. To examine the prevalence, demographic and other correlates, and co-morbidities of DSM-IV SP subtypes in a nationwide sample of Korean adults. We recruited 6510 participants aged 18–64 years for this study. Lay interviewers used the Composite International Diagnostic Interview to assess participants. We analyzed socio-demographics, health-related correlates and frequencies of comorbid mental disorders among participants with SP and each subtypes compared to unaffected adults. The prevalence of lifetime DSM-IV SP was 3.8%, and animal phobias were the most prevalent type of SP. Blood–injection–injury phobia was negatively associated with education, whereas situational phobia was positively associated with education. The strongest mental disorder comorbidity was associated with situational phobia; there is a higher probability of comorbid mood (OR=5.73, 95% CI=2.09–15.73), anxiety (OR=7.54, 95% CI=2.34–24.28), and somatoform disorders (OR=7.61, 95% CI=1.64–35.22) with this subtype. Blood–injection–injury phobia was highly associated with alcohol dependence (OR=9.02, 95% CI=3.54–23.02). Specific phobias are heterogeneous with respect to socio-demographic characteristics and comorbidity pattern. Implications of the usefulness of current subtype categories should continue to be investigated.     

Effect of 5% fluoride varnish application on caries among school children in rural Brazil: a randomized controlled trial

Arruda AO, Senthamarai Kannan R, Inglehart MR, Rezende CT, Sohn W. Effect of 5% fluoride varnish application on caries among school children in rural Brazil: a randomized controlled trial. Community Dent Oral Epidemiol 2011. © 2011 John Wiley & Sons A/S Abstract – Objectives: To determine the efficacy of 5% sodium fluoride (NaF) varnish application in reducing caries increments in the permanent dentition of rural Brazilian school children over the course of 12 months. Methods: A double‐blind, randomized, placebo‐controlled trial was conducted with 379 children aged 7–14 years who attended three schools in Brazil between January 2006 and December 2007. During this period, each school was visited four times at 6‐month interval for recruitment, dental examinations, and fluoride varnish applications. Recruited children were randomly assigned to either a treatment (5% NaF varnish, n = 198) or a control group (placebo, n = 181). Trained interviewers collected data on oral health habits and sociodemographic characteristics from the children. Information on the child’s diet was collected through a 7‐day food frequency diary. Caries examinations were conducted using the International Caries Detection and Assessment System (ICDAS). The efficacy of fluoride varnish application on caries prevention was reported as a preventive fraction (PF). Crude caries increments of decayed and filled surfaces (DFS) were compared between fluoride varnish and placebo groups. A generalized linear model (GLM) was constructed to test the differences in DFS increments between the groups after accounting for confounding factors. Results: Of the total sample (N = 379), 210 (55.4%) children had completed 12 months of follow‐up including one or two applications of fluoride varnish or placebo. At the baseline examination, the children in the treatment and control groups presented on average 6.2 and 5.6 DFS, respectively (P < 0.001). After 12 months of follow‐up, the children in the varnish group showed significantly lower DFS increments than did children in the control group (10.8 versus 13.3; P < 0.007), with PF of 40% (95% CI: 34.3–45.7%; P < 0.0001). Conclusions: The results of this study suggest that applications of 5% NaF varnish can be recommended as a public health measure for reducing caries incidence in this high‐caries‐risk population.     

Die Geschichte der Nierentransplantation

The history of kidney transplantation is a history of many unsuccessful efforts and setbacks, but also the history of perseverance, pioneering spirit, and steadfast courage. The first successful transplantation of a dog kidney was done by the Austrian Emerich Ullmann (1861–1937) in 1902. The kidney was connected to the carotid artery of the dog and the ureter ended freely. The organ produced urine for a couple of days before it died. In 1909, there were efforts to transplant human kidneys from deceased patients to monkeys and in the following year the first xenotransplantation in humans was completed. Different kinds of donors were tried: dogs, monkeys, goats and lambs, all without success. In 1939, the first transplantation from a deceased human donor was done by the Russion Yurii Voronoy, the patient survived for only a couple of days, and the organ never worked. In 1953, the first temporarily successful transplantation of a human kidney was performed by Jean Hamburger in Paris. A 16-year-old boy received the kidney of his mother as living donor transplantation. Then in 1954, a milestone was made with the first long-term successful kidney transplantation by Joseph Murray: the transplantation was done between monozygotic twins; the organ survived for 8 years. For his efforts in kidney transplantation, Murray was honored with the Nobel Prize in medicine in 1990. In 1962, the first kidney transplantation between genetically nonrelated patients was done using immunosuppression and in 1963 the first kidney transplantation in Germany was done by Reinhard Nagel and Wilhelm Brosig in Berlin. The aim of this article is to present the history of kidney transplantation from the beginning until today.     

Comparison of 2-Ethyl-Cyanoacrylate and 2-Butyl-Cyanoacrylate for Use on the Calvaria of CD1 Mice

Short-chain cyanoacrylates (SCCA), such as ethyl-2-cyanoacrylate (KrazyGlue, Aron Alpha, Columbus, OH) are commonly used as commercial fast-acting glues. Although once used in clinical medicine as skin adhesives, these products caused tissue toxicity and thus their use in live tissue was discontinued. SCCA were replaced by longer-chain versions (LCCA), such as butyl-cyanoacrylate (Vetbond, 3M, St Paul, Minnesota), which were found to be less toxic than the short-chain formulations. Some researchers prefer to use SCCA due to the belief that they create a stronger bond than do the longer-chain counterparts. In survival surgeries, we compared the bone thickness, bone necrosis, fibrosis, inflammation, and bone regeneration in the calvaria of control (naïve), surgery-only, SCCA-treated, and LCCA-treated mice (n = 20 per group). At 1 and 14 d after surgery, all mice except those treated with SCCA showed statistically similar bone measurements to those of the naive control group. The SCCA group had significantly less bone regeneration than did all other groups. These results suggest that the application of SCCA causes bone damage resulting in the loss of bone regeneration. This finding may assist investigators in choosing a tissue glue for their studies and may support the IACUC in advocating the use of pharmaceutical-grade tissue glues.Abbreviations: LCCA, long-chain cyanoacrylates; SCCA, short-chain cyanoacrylatesCyanoacrylates have been used as tissue adhesives since their synthesis in 1949.⁶ Synthetic cyanoacrylate adhesives belong in the family of liquid monomers formed by alkyl esters of 2-cyanoacrylic acid. The basic formula of the cyanoacrylate adhesive (alkyl-2-cyanoacrylate) has been manipulated to form different cyanoacrylate adhesives with different properties.²⁹ Several 2-cyanoacrylate esters have been synthesized by changing the length of the alkyl chain attached.⁴² The first cyanoacrylates were short-chained, poorly manufactured, and toxic to animals at pharmacologic doses.²⁴ Short-chain cyanoacrylates (SCCA), such as methyl-2-cyanoacrylate and ethyl-2-cyanoacrylate (KrazyGlue [Aron Alpha, Columbus, OH]), continue to be used as fast-acting adhesives.⁵ Although appropriated as tissue glues soon after their discovery, these early SCCA caused tissue toxicity and thus were discontinued in the clinical arena.⁴ Research showed that changing the type of alcohol in the compound to one with a longer molecular chain reduced tissue toxicity. Over time, nontoxic, longer-chain cyanoacrylates (LCCA), such as butyl-cyanoacrylate (Vetbond [3M, St Paul, Minnesota]) and octylcyanoacrylate, were manufactured, leading to their use once again in clinical medicine³³ (Figure 1).Open in a separate windowFigure 1.Trade names for different types of cyanoacrylates.Many researchers contend that SCCA is superior to LCCA in regard to the strength and tenacity of the bond when used to create cranial windows and as an application prior to an overlay of acrylic for cranial implants. However, SCCA is not pharmaceutical-grade, as mandated by the USDA in Policy 3² and the Guide for the Care and Use of Laboratory Animals,²² and therefore can only be used after specific review and approval by an institution''s IACUC. The determination for substitution is generally based on scientific necessity or compound availability.In this study, the effects of applying an SCCA product to mice calvaria were compared with those of an LCCA glue. Specifically, we evaluated bone regeneration, osteocyte numbers, inflammation, and bone remodeling at 2 time points after application. We hypothesized that mice calvaria treated with the SCCA product would show signs of toxicity, compared with skulls treated with the LCCA glue.     

Surgical outcome of synchronous second primary cancer in patients with gastric cancer

PURPOSE: In order to improve the likelihood of curative and safe gastric surgery, this study investigated the clinical features and surgical outcomes of gastric cancer with a synchronous cancer. PATIENTS AND METHODS: The clinicopathological data of 10,090 gastric cancer patients at Samsung Medical Center from September 1994 to December 2006 were retrospectively analyzed. Of them, 90 patients with gastric cancer and a synchronous second primary cancer underwent simultaneous surgery for gastric cancer and second primary cancer. The clinicopathological characteristics of the patients, surgical outcome, and prognosis were examined. RESULTS: The most common synchronous second primary cancer was colorectal cancer (37 patients), followed by hepatocellular carcinoma (13 patients), renal cell carcinoma (11 patients), and pancreatic carcinoma (5 patients). The incidence of a second primary cancer in the gastric cancer patients was higher than the incidence in the general population. Stage I gastric cancer patients had more synchronous cancers than stage II patients (59 vs. 31). Postoperative complications were encountered in 7 patients. Four patients underwent reoperation. Two patients died from hepatic failure and leakage of esophagojejunal anastomosis. The 5-year survival rate of stage I and II gastric cancer was 61% and 39%, respectively. CONCLUSION: Since gastric cancer patients with a synchronous second primary cancer are not rare, the possibility of synchronous cancers in gastric cancer patients should be considered. The prognosis of early stage gastric cancer patients with a synchronous second primary cancer was influenced more by the presence of the second primary cancer than by the gastric cancer itself.     

Multi-disciplinary treatment of a rare pelvic cavity ependymoma

Ependymomas usually develop from neuroectodermal organs. Here, we present an ependymoma arising from the pelvic cavity. A 27-year-old Korean female was admitted to the hospital with a sensation of abdominal fullness. Imaging studies revealed a huge heterogeneous nodular mass in the pelvis and lower abdomen. Laparotomy showed that two large masses with multiple nodules were located between the uterus and rectum and uterus and bladder, respectively. Histologically, the tumor was characterized by compact columnar neoplastic cells divided by fibrovascular septae. The neoplastic cells formed true ependymal rosettes and perivascular pseudorosettes. Immunohistochemical staining showed a strong positive reaction for glial fibrillary acidic protein (GFAP) and vimentin and a partial positive reaction for S100 and EMA. The tumor was thus diagnosed as an ependymoma arising from the pelvic cavity. The patient was treated with a debulking operation and chemotherapy based upon the in vitro chemosensitivity test results. The patient was free of cancer for 4 years following surgery. This is a rare case of extraneural ependymoma for which an in vitro chemosensitivity test was critical in determining the multidisciplinary approach for treatment.