Functional evidence of decreased tumorigenicity associated with monochromosome transfer of chromosome 14 in esophageal cancer and the mapping of tumor-suppressive regions to 14q32

Despite the abundant evidence of high allelic loss of chromosome arm 14q in human cancers, tumor-suppressor genes mapped to this chromosome have yet to be identified. To narrow the search for candidate genes, we performed monochromosome transfer of chromosome 14 into an esophageal carcinoma cell line, SLMT-1 S1. Statistically significant suppression of the tumorigenic potential of microcell hybrids containing the transferred chromosome 14 provided functional evidence that tumor-suppressive regions of chromosome 14 are essential for esophageal cancer. Tumor segregants emerging in nude mice during the tumorigenicity assay were analyzed by detailed PCR-microsatellite typing to identify critical nonrandomly eliminated regions (CRs). A 680-kb CR mapped to 14q32.13 and an approximately 2.2-Mb CR mapped to 14q32.33 were delineated. Dual-color BAC FISH analysis of microcell hybrids and tumor segregants verified the selective loss of the 14q32.13 region. In contrast, similar transfers of an intact chromosome 11 into SLMT-1 S1 did not significantly suppress tumor formation. These functional complementation studies showing the correlation of tumorigenic potential with critical regions of chromosome 14 validated the importance of the 14q32 region in tumor suppression in esophageal cancer. The present study also paved the path for further identification of novel tumor-suppressor genes that are relevant to the molecular pathogenesis of esophageal cancer.     

Metal-containing initiator systems, 34. Polymerization of vinyl monomers initiated by the binary system cobaltocene/bis(ethyl acetoacetato)copper (II)

The effect of some metallocenes such as ferrocene (Fe(C₅H₅)₂), nickelocene (Ni(C₅H₅)₂), and cobaltocene (Co(C₅H₅)₂), on the vinyl polymerization initiated with bis(ethyl acetoacetato)-copper(II) (Cu(eacac)₂) was investigated. Co(C₅H₅)₂ was found to exert a markedly accelerating effect on the polymerization of methyl methacrylate (MMA) with Cu(eacac)₂. The polymerization of MMA with the system Co(C₅H₅)₂/Cu(eacac)₂ at 50°C was found to be fairly affected by the solvent used. The results of copolymerization of MMA with styrene (St) and the effect of hydroquinone (HQ) on the polymerization of MMA with Co(C₅H₅)₂/Cu(eacac)₂ showed that the polymerization proceeds via a radical mechanism. The polymerization of MMA with Co(C₅H₅)₂/Cu(eacac)₂ was studied kinetically in acetone. The overall activation energy of the polymerization was calculated to be 86,3 kJ/mol (20,6 kcal/mol). This value was somewhat higher than that (17,6 kcal/mol) obtained for the polymerization of MMA with Cu(eacac)₂ alone. The polymerization rate (R_p) is represented by the following equation: R_p = k[Co(C₅H₅)₂]^0,5 [Cu(eacac)₂]^0,2 [MMA]^1,3. The high order in monomer concentration suggests a participation of the monomer in the initiation process of this polymerization. This is supported by the examination of the ESR spectrum of the system Co(C₅H₅)₂/Cu(eacac)₂/MMA/acetone, where reduction of Cu(II) to Cu(I) occurs. To elucidate the initiation mechanism, the spin trapping technique was applied to the system Co(C₅H₅)₂/Cu(eacac)₂/methyl acrylate. From these results, an initiation mechanism for the binary initiator system Co(C₅H₅)₂/Cu(eacac)₂ is proposed and discussed.     

Is a Titanium Implant for Total Knee Arthroplasty Better? A Randomized Controlled Study

BackgroundLighter weight and lower modulus are potential advantages of titanium (Ti) implants over cobalt chrome (CoCr) implants in total knee arthroplasty (TKA). This study was conducted to determine whether Ti implants in TKA resulted in better clinical outcomes and radiologic results.MethodsOne hundred and eight patients (216 knees) with knee arthritis warranting bilateral primary TKA were randomly allocated to undergo Ti rotating-platform TKA in one knee and CoCr rotating-platform TKA in the contralateral knee. The mean follow-up period was 5.3 years (range, 1-7 years). The weight of Ti implants was one-third lighter than that of CoCr implants (133.9 g vs 390.1 g, P < .01). Clinical outcomes were evaluated using clinical scores, patient preferences (lightness, comfort, naturalness, and satisfaction), gait analysis (kinetic and kinematic data), range of motion, and degree of pain. Radiologic results were evaluated based on the radiolucent line (RLL), degree of medial tibial bone loss, and loosening as seen on X-ray.ResultsNo significant differences were observed in clinical scores or patient preference. Regarding implant weight, approximately 70% of patients did not perceive the Ti implant as lighter. No significant differences were observed in gait analysis, range of motion, or degree of pain. The RLL was seen in 9% of the Ti implant group and 19% of the CoCr implant group.ConclusionThe lighter Ti implant did not show any clinical benefit over CoCr implants. The lightness of the Ti implant is not sufficient to matter or be noticeable. However, the Ti implant showed lower rate of RLL than the CoCr implant.Level of Evidencelevel I, randomized controlled trial.     

Higher Undercarboxylated to Total Osteocalcin Ratio Is Associated With Reduced Physical Function and Increased 15-Year Falls-Related Hospitalizations: The Perth Longitudinal Study of Aging Women

Evidence from animal models suggests that undercarboxylated osteocalcin (ucOC) is involved in muscle mass maintenance and strength. In humans, the ucOC to total (t)OC ratio may be related to muscle strength and perhaps physical function and falls risk, but data are limited. We tested the hypothesis that ucOC and ucOC/tOC ratio are associated with muscle function (muscle strength and physical function) in older women and 15-year falls-related hospitalizations. Serum tOC and ucOC were assessed in 1261 older women (mean age 75.2 ± 2.7 years) forming the Perth Longitudinal Study of Aging Women (1998 to 2013). Timed-up-and-go (TUG) and grip strength were assessed at baseline and at 5 years. Falls-related hospitalizations (14.5-year follow-up) were captured by the Hospital Morbidity Data Collection, via the Western Australian Data Linkage System. At baseline, women with higher ucOC/tOC ratio (quartile 4) had slower TUG performance compared with quartile 1 (~0.68 seconds, p < .01). Grip strength and 5-year change of TUG and grip were not different (p > .05) between quartiles. Fear of falling limiting house, outdoor, and combined activities was significantly different across quartiles (p < .05). Higher ucOC/tOC was significantly associated with poorer TUG performance at baseline and 5-year change in performance, increased walking aid use, and fear of falling (all p < .05). Higher ucOC was related to lower grip strength at baseline (p < .05) but not 5-year change in strength. Those with the highest ucOC/tOC had greater falls-related hospitalizations (unadjusted log rank, p = .004) remaining significant after adjusting for key variables (hazard ratio [HR] = 1.31, 95% confidence interval [CI] 1.09–1.57, p = .004). We identified a large proportion of older women with high ucOC/tOC ratio who had reduced physical function, including its long-term decline and increased risk of falls-related hospitalizations. Early identification of women at higher risk can enable prevention and intervention strategies to occur, reducing risk for injurious falls. © 2020 American Society for Bone and Mineral Research (ASBMR)..     

Adjusting for measurement error to assess health effects of variability in biomarkers. Multicenter AIDS Cohort Study.

Longitudinal studies of health effects often relate individuals' biomarker levels to disease progression. Repeated measurements also provide an opportunity to assess within-individual biomarker variability, and it is reasonable to postulate that this measure might provide additional information about a particular outcome variable. Given the existing precedent for application of adjustment methods to account for measurement error in subject-specific average levels of a covariate, this concept motivates the application of such methods to incorporate variability as well. In this paper, we investigate the nature of the relationship between the decline of CD4 cell count induced by infection with human immunodeficiency virus, and CD4 level and variability prior to infection. We first describe the distribution of repeated CD4 measurements prior to infection using a model that accounts both for random average levels and random subject-specific variance components. Based on this model, we define true unobservable random variables that correspond to prior level and stability. We perform a linear regression analysis, using these latent variables as covariates, by means of a full maximum likelihood approach. We compare the resulting parameter estimates with those based on regressions employing sample-based estimates of pre-infection levels and variances, and empirical Bayes estimates of these quantities. Although the final inferences are similar to those based on the unadjusted analysis, we find that the magnitude of association with prior level decreases, while that with prior stability increases. Stratified analyses indicate that smoking status affects the relationship between prior CD4 level and initial CD4 decline. We point out advantages associated with the maximum likelihood approach in this particular application.     

Central neuropathic pain in Parkinson's disease

INTRODUCTION: Central pain is one type of pain that occurs in patients with Parkinson's disease (PD). Because of its low incidence and prevalence, it often goes unnoticed and affected patients do not therefore receive adequate analgesic therapy, which increases their suffering. It is a burning pain with spontaneous onset and periods of exacerbation; pain is poorly localised and usually more intense on the more affected side. Its pathophysiology on patients with PD is not clearly defined. METHODS: We performed a search and systematic selection of all clinical studies published from January 1986 to September 2010 concerning central neuropathic pain in Parkinson's disease. CONCLUSIONS: Treatment with L-Dopa has not been demonstrated to have an analgesic effect on this type of pain. Future studies are required to improve our understanding of this condition, and to develop interventions for preventing and treating it.     

Lichen Striatus Occurring after Allogenic Peripheral Blood Stem Cell Transplantation in an Adult with Aplastic Anemia

Lichens striatus (LS) is an acquired, self-limiting inflammatory dermatosis that follows the lines of Blaschko. The etiology of the eruption is unknown, but several theories have been proposed with focus on environmental factors, viral infection, cutaneous injury, hypersensitivity, and genetic predisposition. We describe a 19-year-old woman who developed a unilateral linear eruption 17 months after allogenic peripheral blood stem cell transplantation. Histopathology revealed features, which were consistent with LS. To the best of our knowledge, our patient is the first case describing the appearance of LS occurring after allogenic stem cell transplantation. We speculate that this condition represents an unusual form of localized, chronic graft-versus-host disease.