Impact of Hepatitis B and Hepatitis C Virus Infections in a Hematology-Oncology Unit at a Children's Hospital in Nicaragua, 1997 to 1999

The risk of acquiring both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in patients with hematological-oncological disorders has been documented. However, the impact and risk factors for such infections from different geographical areas vary, and the use of both immunological and molecular assays to determine HCV infections has been our approach. Children from a hematology-oncology unit (HOU) in Nicaragua were studied for both HBV and HCV serological markers; studies for the latter used both immunological (anti-HCV) and molecular (HCV RNA) assays. The children from the HOU included patients with leukemia, lymphoma, other neoplasias, and anemia and a smaller group with other hematological diseases. As a control group, children from other units at the same hospital were enrolled, as well as health care workers attending both patient populations. Pertinent clinical and personal data for each child at the HOU were obtained for statistical analysis. Of the 625 children from the HOU enrolled in this study 53.3% were infected with HCV and 29.4% had a prior or present HBV infection. In the child patient control group 3.2% had HBV markers and all were negative for HCV. The group of children with leukemia had the highest infection rate for both HBV and HCV. However, the determination of anti-HCV was found to have an overall low sensitivity in children from HOU, and a retest consisting of a molecular assay to determine HCV RNA was performed to better establish the total number of HCV-infected subjects in this group. The highest independent risk factor for infection was hospitalization. The very high prevalence rates for both HBV and HCV infection in this patient group indicate an urgent need to implement better control of known risk factors and to consider the use of both immunological and molecular assays for HCV diagnostic purposes.     

Systems Medicine: from molecular features and models to the clinic in COPD

Background and hypothesis

Chronic Obstructive Pulmonary Disease (COPD) patients are characterized by heterogeneous clinical manifestations and patterns of disease progression. Two major factors that can be used to identify COPD subtypes are muscle dysfunction/wasting and co-morbidity patterns. We hypothesized that COPD heterogeneity is in part the result of complex interactions between several genes and pathways. We explored the possibility of using a Systems Medicine approach to identify such pathways, as well as to generate predictive computational models that may be used in clinic practice.

Objective and method

Our overarching goal is to generate clinically applicable predictive models that characterize COPD heterogeneity through a Systems Medicine approach. To this end we have developed a general framework, consisting of three steps/objectives: (1) feature identification, (2) model generation and statistical validation, and (3) application and validation of the predictive models in the clinical scenario. We used muscle dysfunction and co-morbidity as test cases for this framework.

Results

In the study of muscle wasting we identified relevant features (genes) by a network analysis and generated predictive models that integrate mechanistic and probabilistic models. This allowed us to characterize muscle wasting as a general de-regulation of pathway interactions. In the co-morbidity analysis we identified relevant features (genes/pathways) by the integration of gene-disease and disease-disease associations. We further present a detailed characterization of co-morbidities in COPD patients that was implemented into a predictive model. In both use cases we were able to achieve predictive modeling but we also identified several key challenges, the most pressing being the validation and implementation into actual clinical practice.

Conclusions

The results confirm the potential of the Systems Medicine approach to study complex diseases and generate clinically relevant predictive models. Our study also highlights important obstacles and bottlenecks for such approaches (e.g. data availability and normalization of frameworks among others) and suggests specific proposals to overcome them.

     

AGE‐modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

Biomechanical strain imposed by age‐related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end‐product (AGE)‐dependent non‐enzymatic crosslinking of its major components, collagen IV and laminin. We used this model to demonstrate that antibody targeted blockade of CTLD2, the second of eight C‐type lectin‐like domains in Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) that can recognize glycosylated collagens, reversed actinomyosin‐based contractility [myosin‐light chain‐2 (MLC2) phosphorylation], loss of cell polarity, loss of cell–cell junctions, luminal infiltration and basal invasion induced by AGE‐modified basal lamina matrix in PEC acini. Our in vitro results were concordant with luminal occlusion of acini in the prostate glands of adult Endo180^{ΔEx2–6/ΔEx2–6} mice, with constitutively exposed CTLD2 and decreased survival of men with early (non‐invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE‐dependent modification of the basal lamina induces invasive behaviour in non‐transformed PECs via a molecular mechanism linked to cancer progression. This study provides a rationale for targeting CTLD2 in Endo180 in prostate cancer and other pathologies in which increased basal lamina thickness and tissue stiffness are driving factors. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Gorgan (Turkmen in Iran) HLA genetics: transplantation,pharmacogenomics and anthropology

HLA class I and II alleles have been studied in a population from Gorgan (North East Iranian city bordering Turkmenistan). This population is composed of mainly Turkmen who speak Oghuz Turkish language. Comparison of Gorgan people HLA profile has been carried out with about 7984 HLA chromosomes from other worldwide populations; extended haplotypes and three dimension genetic distances have been calculated by using neighbor-joining and correspondence relatedness analyses. Most frequent extended HLA haplotypes show a Siberian/Mediterranean admixture and closest populations are Chuvashians (North Caspian Sea, Russia) and other geographically close populations like Siberian Mansi, Buryats and other Iranians. New extended HLA haplotypes have been found, such as: A*31:01-B*35:01-DRB1*15:01-DQB1*03:01, A*01:01-B*35:01-DRB1*03:01-DQB1*02:01. Relationships of Turkmen with Kurgan (Gorgan) archaeological mounds, Scythians and Sarmatians are discussed. This study is also useful for a future transplantation Gorgan waiting list, Gorgan HLA and disease epidemiology and HLA pharmacogenomics.     

Clasificación de cesáreas por Grupos de Robson en dos periodos comparativos en el Hospital de Manacor

Objective

To identify groups of women with changes in cesarean rates in two different periods.

Subjects and methods

Deliveries in the Manacor Hospital in 2000-2001 and 2005-2006, were analyzed through a retrospective review of clinical records and were grouped using Robsońs classification.

Results

The cesarean rate increased from 14 to 18.6% with a statistically significant increase among women with a single cephalic pregnancy at term who underwent labor induction or elective cesarean section. These two groups were the major contributors to the cesarean rate at our hospital.

Conclusion

A trend towards an increase in the rates of cesarean section was found during the study period. Robson's Classification allowed us to identify the groups of women contributing to this increase.     

Cyclin D1 expression and histopathologic features in vestibular schwannomas.

OBJECTIVE: To evaluate cyclin D1 expression in vestibular schwannoma and its relationship with histologic, clinical, and radiologic features. PATIENTS: Twenty-one patients with histologically confirmed vestibular schwannoma. INTERVENTION: Immunohistochemistry analysis was performed with anticyclin D1. Histopathologic features studied included Antoni pattern and nuclear and stromal degenerative changes. Clinical charts, audiometric data, and magnetic resonance imaging characteristics were reviewed. MAIN OUTCOME MEASURES: Cyclin D1 expression and its association with histologic, clinical, and radiologic findings. RESULTS: Cyclin D1 expression was found in 52% of cases. Cyclin D1 expression was more frequent in right-sided tumors (p = 0.02) and in tumors with nuclear degenerative changes (p < 0.0001). Patients with negative cyclin D1 expression had longer duration of deafness (p = 0.02) and higher 2,000-Hz hearing thresholds (p = 0.04) than cyclin D1+ patients. CONCLUSION: Cyclin D1 expression, present in nearly half of the cases, may play a role in the development of these tumors. Further studies are needed to fully understand the contributions of histopathologic and immunohistochemical factors to vestibular schwannoma biological activity.     

Velopharyngeal insufficiency as the initial manifestation of a Myotonic Dystrophy type 1: A case report

Velopharyngeal insufficiency (VPI) is a disorder affecting nasal resonance during speech. The most common cause of VPI is a cleft palate. However, VPI can occur as a consequence of a neuromuscular or neurologic disorder without a palatal malformation. Myotonic Dystrophy type 1 is a hereditary muscular disorder. In these cases, the abnormality is located on the 19q13.3 region, including a myotonic dystrophy protein kinase CTG repeat. This disease has several clinical manifestation features depending of the number of CTG repeats. The myotonic dystrophy can affect several muscle groups. VPI associated with the involvement of the velopharyngeal muscles, has been reported as the main clinical feature in some cases. The purpose of this paper is to present a case of VPI as the main clinical manifestation in a patient with a Myotonic Dystrophy type 1.     

Salmonella-specific monoclonal antibodies against recombinant Salmonella typhi 36-kilodalton porin.

Mouse monoclonal antibodies were raised against recombinant Salmonella typhi 36-kDa porin monomer. Specificities of 16 monoclonal antibodies were analyzed as reactivity patterns in dot immunobinding and Western blot (immunoblot) assays using isolated outer membrane proteins of gram-negative bacteria and cloned purified S. typhi porin monomers and trimers. Four monoclonal antibodies were specific for Salmonella spp.     

Profilin-mediated food-induced allergic reactions are associated with oral epithelial remodeling

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