Recombinant human granulocyte colony-stimulating factor in preterm neonates with sepsis and relative neutropenia: a randomized, single-blind, non-placebo-controlled trial

We performed a prospective, randomized, single-blind, non-placebo-controlled trial on preterm (<37 weeks) neonates (birth weight <2000g) with sepsis and absolute neutrophil counts (ANC) <5000?cells?mm(-3) to study the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on all-cause-neonatal mortality and hematological parameters (total leucocyte (TLC, ANC, absolute monocyte and absolute platelet counts). The rhG-CSF group (n?=?20) received 10?μg/kg/day of intravenous infusion of rhG-CSF once daily for 5 days along with conventional therapy, and the control group (n?=?20) received conventional therapy alone. Hematological parameters on Days 0, 1, 3, 5, 7 and 14 of study entry and all-cause mortality rates at discharge were recorded. Baseline characteristics between the rhG-CSF and control group including mean birth weight (1395?±?289 vs. 1500?±?231g), mean gestational age (31.5?±?2.68 vs. 32.6?±?2.23 weeks), initial neonatal complaints and maternal characteristics were comparable. Mortality rates were significantly less among the rhG-CSF group (3/20 (15%) vs. 7/20 (35%), p?5000?cells?mm(-3) faster in the rhG-CSF group, with 80% babies having ANC >5000?cells?mm(-3) by Day 7 of study entry compared with 35% in the control group (p?相似文献   

Perinatal Tuberculosis associated Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis [HLH] is a reactive disorder characterized by generalised non-malignant histiocytic proliferation with prominent hemophagocytosis. It may be either primary [familial (FLH)] or secondary [infection or malignancy associated]. Organisms incriminated for infection associated hemophagocytic syndrome (IAHS) include viruses, bacteria, spirochetes, fungi and parasites. Reports of IAHS associated with tuberculosis in neonates are rare. The authors report a case of perinatal tuberculosis presenting as hemophagocytic lymphohistiocytosis.     

Roundabout is required in the visceral mesoderm for proper microvillus length in the hindgut epithelium

Introduction: In this study we examined Roundabout signaling in the Drosophila embryonic hindgut. Results: Slit and its receptors Roundabout (Robo) and Roundabout 2 (Robo2) localize to discrete regions in the hindgut epithelium and surrounding visceral mesoderm. Loss of robo, robo2 or slit did not disrupt overall hindgut patterning. However, slit and robo mutants showed a decrease in microvillus length on the boundary cells of the hindgut epithelium. Rescue and overexpression analysis revealed that robo is specifically required in the visceral mesoderm for correct microvillus length in the underlying hindgut epithelium. Expression of robo in the visceral mesoderm of robo mutant embryos restored normal microvillus length, while overexpression of robo resulted in an increase in microvillus length. Microvillus length was also increased in robo2 mutants suggesting that robo2 may antagonize robo function in the hindgut. Conclusion: Together, these results establish a novel, dose‐dependent role for Robo in regulating microvilli growth and provide in vivo evidence for the role of the visceral mesoderm in controlling morphological changes in the underlying intestinal epithelium. Developmental Dynamics 241:759–769, 2012. © 2012 Wiley Periodicals, Inc     

A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin

Human exposure to capsaicin, the most abundant pungent chili pepper component, is ubiquitous. Evaluation of capsaicin's carcinogenic potential has produced variable results in in vitro and in vivo genotoxicity and carcinogenicity assays. The capsaicin tested in older studies was often from pepper plant extracts and included other capsaicinoids and diverse impurities. Recent studies utilizing high-purity capsaicin and standardized protocols provide evidence that the genotoxic and carcinogenic potential of capsaicin is quite low and that the purity of capsaicin is important. Several small epidemiological studies suggest a link between capsaicin consumption and stomach or gall bladder cancer, but contamination of capsaicin-containing foods with known carcinogens renders their interpretation problematic. The postulated ability of capsaicin metabolites to damage DNA and promote carcinogenesis remains unsupported. Anticancer activities of capsaicin have been widely reported, as it inhibits the activity of carcinogens and induces apoptosis in numerous cancer cell lines in vitro and explanted into rodents. Diverse mechanisms have been postulated for capsaicin's anticancer properties. One hypothesis is that inhibition of cytochrome P450 enzymes-particularly CYP2E1-retards carcinogen activation but is contradicted by the low potency of capsaicin for CYP inhibition. The potential for dietary capsaicin to act as a chemopreventative is now widely postulated.     

Engulfment adapter PTB domain containing 1 interacts with and affects processing of the amyloid-β precursor protein

Previous studies identified engulfment adapter phosphotyrosine binding (PTB) domain containing 1 (GULP1) as an NPXY-motif interactor of low-density lipoprotein receptor-related protein 1 (LRP1) and suggested a potential relevance in Alzheimer's disease (AD). Since AD associated proteins amyloid-β A4 precursor protein (APP) and LRP1 were shown to interact with the PTB domain of Fe65 and several other adapters via their intracellular NPXY-motifs, we examined a possible interaction of GULP1 PTB domain with the YENPTY-motif of APP. Here we demonstrate that GULP1 is present in human hippocampal and neocortical neurons. Confocal live cell imaging revealed that coexpressed and endogenous GULP1 colocalizes with APP in the Golgi and endoplasmic reticulum. Analysis of the interacting domains by co-immunoprecipitation of point and deletion mutants revealed that the interaction depends on the PTB domain of GULP1 and the YENPTY-motif of APP. Coexpression of GULP1 affected APP cell surface localization and suppressed generation of Aβ40/42 and sAPPα. Taken together, these data identify GULP1 as a novel neuronal APP interacting protein that alters trafficking and processing of APP.     

Apo lipoprotein A1 gene polymorphisms predict cardio-metabolic risk in South Asian immigrants

Objectives: Coronary artery disease (CAD) is a leading cause of death globally with increasing burden in South Asians in the US. Specific genetic variants that influence CAD have not been fully assessed in South Asian Immigrants. The goal is to identify Apo lipoprotein A1 (APOA1) gene polymorphisms and their association with CAD risk factors, metabolic syndrome and dysfunctional HDL (Dys-HDL). Methods: A community-based study on South Asians aged 35-65 years without CAD was conducted. APOA1 gene sequencing was performed and genotypes compared with cardiovascular findings. Results: The prevalence of metabolic syndrome and dysfunctional-HDL was 29.7% and 26%, respectively. Six novel APOA1 gene single nucleotide peptides (SNPs) were analyzed. Three of the six SNPs (G2, G3, and G5) were found to be associated with metabolic syndrome; G2 (T655C) (p=0.044), G3 (T756C) (p=0.037) and G5 (T1001C) (p=0.037). APOA1 gene SNP G1 (T319C) was highly correlated with low HDL levels (p=0.001). In our study, both associations of APOA1 SNPs with metabolic syndrome and low HDL remained after age-adjustment. Conclusion: Discovery of novel gene polymorphisms will help to understand further the causes of excess CAD risk in South Asians so that preventative strategies targeted to high-risk group can be developed.     

Efficient differentiation of human embryonic and induced pluripotent stem cells into functional astrocytes

Human high-grade gliomas (hHGG) remain a therapeutic challenge in neuro-oncology despite current multimodality treatments. We recently demonstrated that murine embryonic stem cell (mESC)-derived astrocytes conditionally expressing proapoptotic genes can successfully be used to induce apoptosis and tumor shrinkage of hHGG tumor in vitro and in an in vivo mouse model. The first step in the translation of these results to the clinical settings, however, requires availability of human embryonic stem cells (hESC)- and/or induced pluripotent cell (hiPSC)-derived astrocytes engineered to express proapoptotic genes. The potential for directed differentiation of hESCs and hiPSCs to functional postmitotic astrocytes is not fully characterized. In this study, we show that once specified to neuro-epithelial lineage, hiPSC could be differentiated to astrocytes with a similar efficiency as hESC. However, our analyses of 2?hESC and 2 hiPSC cell lines showed some variability in differentiation potential into astrocytic lineages. Both the hESC- and hiPSC-derived astrocytes appeared to follow the functional properties of mESC-derived astrocytes, namely, migration and tropism for hHGG. This work provides evidence that hESC- and hiPSC-derived cells are able to generate functionally active astrocytes. These results demonstrate the feasibility of using iPSC-derived astrocytes, a new potential source for therapeutic use for brain tumors and other neurological diseases.     

Cytodiagnosis of histoplasmosis: Case reports from two patients with variable clinical presentation

Histoplasmosis has emerged as an important opportunistic fungal infection in immunocompromised patients. Histoplasma is a dimorphic fungus that primarily involves lung and the environmental reservoir is soil. Although several cases of histoplasmosis have been reported in India but cytological diagnosis was made in a few cases. We are presenting two cases of histoplasmosis diagnosed on fine‐needle aspiration cytology. In the first case, pulmonary histoplasmosis was diagnosed on transbronchial needle aspiration of lung in a 41‐year‐old immunocompetent male, while second case was of disseminated histoplasmosis in 40‐year‐old immunocompromised female diagnosed on cytology of cervical lymph node. FNAC is a simple, safe, and rapid technique to establish the initial diagnosis, thus promoting early treatment and favorable outcome especially in the immunocompromised patients. Diagn. Cytopathol. 2011; © 2011 Wiley Periodicals, Inc.     

Rosai-Dorfman disease: A case report with extranodal thyroid involvement

Rosai-Dorfman Disease (RDD) or Sinus Histiocytosis with Massive Lymphadenopathy (SHML) is a rare disorder typically manifesting as enlarged lymph nodes with or without systemic involvement. These cases are often clinically misdiagnosed as lymphoma. Recognising this entity to distinguish it from lymphoma and other causes of histiocytosis is important because of different treatment modalities for these disorders. Extranodal involvement is also common, often with a particular predilection for the head and neck region. We report a rare case of Rosai-Dorfman Disease with both nodal and extranodal involvement in a 33-year-old woman. The patient had bilateral cervical lymphadenopathy and diffuse thyroid enlargement. Thyroid gland involvement in RDD diagnosed on fine needle aspiration cytology (FNAC) has rarely been reported in literature. FNAC is a useful and reliable tool for the diagnosis of RDD and the biopsy can be avoided in these patients, thus reducing inconvenience to patients.