Obstetric morbidity and the diagnostic dilemma in pregnancy in rudimentary horn: retrospective analysis

Background  

Pregnancy in rudimentary horn of uterus, a form of ectopic gestation, is associated with significant rates of morbidity and mortality. Despite the recent advances in the ultrasonography, diagnosis of cornual pregnancy still remains elusive; with confirmatory diagnosis usually made during laparotomy. The aim of the present study is to analyze the obstetric implications and the diagnostic dilemma of rudimentary horn pregnancy.     

A method for single-cell sorting and expansion of genetically modified human embryonic stem cells

Genetic modification of human embryonic stem (hES) cells is essential for studies of gene function and differentiation. The expression of transgenes may direct tissue-specific differentiation and aid in the identification of various differentiated cell types. Stable genomic integration of transgenes is optimal because hES cell differentiation can span several days to weeks and include numerous cell divisions, and establishing homogeneous modified cell lines will facilitate research studies. Herein we provide a method for producing and expanding hES cell lines from single cells that have been isolated by fluorescence-activated cell sorting (FACS) following genetic modification by lentivirus vectors. Using this method, we have established enhanced green fluorescent protein (eGFP)-expressing hES cell lines that are pluripotent, contain a diploid chromosomal content, and stably express eGFP following more than 2 months of routine culture and in vivo differentiation.     

Evidence of increased cell proliferation in the hippocampus in children with Ammon's horn sclerosis

Previous studies of Ammon's horn sclerosis (AHS) suggest that AHS is both the result of and the cause of seizures, and support the idea that seizures cause alterations in cell numbers and location. To test the hypothesis that epilepsy induces neurogenesis/gliogenesis, hippocampal cell proliferation was assessed in AHS. Twelve and four resected hippocampi in patients with AHS and with tumor-related epilepsy (TRE), respectively, and 11 autopsy controls were immunostained for Ki-67. Total number of Ki-67-positive cells (KiPC) in each hippocampal area was counted. Selected cases were further studied with double immunohistochemical labeling. KiPC were observed in all three groups. Total numbers of KiPC were significantly higher in AHS cases than in controls, but were not significantly different between TRE cases and controls. Significant differences were observed in the dentate gyrus, the cornu ammonis (CA)-4 region, and the fissura hippocampi between the AHS and control groups. In double immunolabeling, nestin was positive in some KiPC. The existence of neurogenesis/gliogenesis was shown in the hippocampi of pediatric patients with AHS. Increased numbers of progenitor cells in the hippocampi with AHS appear not to be due to seizures per se, but to be more associated with the specific cause of epilepsy.     

Role of granulosa cell mitogen-activated protein kinase 3/1 in gonadotropin-mediated meiotic resumption from diplotene arrest of mammalian oocytes

In mammals, preovulatory oocytes are encircled by several layers of granulosa cells (GCs) in follicular microenvironment. These follicular oocytes are arrested at diplotene arrest due to high level of cyclic nucleotides from encircling GCs. Pituitary gonadotropin acts at the level of encircling GCs and increases adenosine 3′,5′-cyclic monophosphate (cAMP) and guanosine 3′,5′-cyclic monophosphate (cGMP) and activates mitogen-activated protein kinase 3/1 (MAPK3/1) signaling pathway. The MAPK3/1 disrupts the gap junctions between encircling GCs and oocyte. The disruption of gap junctions interrupts the transfer of cyclic nucleotides to the oocyte that results a drop in intraoocyte cAMP level. A transient decrease in oocyte cAMP level triggers maturation promoting factor (MPF) destabilization. The destabilized MPF finally triggers meiotic resumption from diplotene arrest in follicular oocyte. Thus, MAPK3/1 from GCs origin plays important role in gonadotropin-mediated meiotic resumption from diplotene arrest in follicular oocyte of mammals.     

Physical activity and quality of life in head and neck cancer survivors

Purpose To examine the prevalence of exercise in head and neck cancer survivors and determine preliminary associations with quality of life (QoL), fatigue, and depression.Materials and methods Fifty-nine of 65 (91%) eligible head and neck cancer survivors recruited from an academic oncology clinic completed a self-administered survey including the modified Godin Leisure-Time Exercise Questionnaire and Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N), which includes physical, social, emotional and functional well-being (FWB) as well as additional concerns, and the FACT-General (FACT-G). Medical variables were obtained by medical record review.Results The majority of participants were men (83%) and were Caucasian (92%), with mean age of 58±12.8. Cancer sites were primarily the oral cavity (24%), oropharynx (37%), or larynx (25%), with 20% being stage I, 7% stage II, 19% stage III, and 54% stage IV disease. Chemotherapy and/or radiation were ongoing in 14% of the participants. Half of the participants (51%) were diagnosed <6 months ago. Only three (5%) participants reported any vigorous exercise minutes (M=7.3±35.4), and only seven (12%) participants reported any moderate exercise minutes (M=19.5±70.6). Light exercise was reported by 26 (44%) (M=83.4±147.1). Only five (8.5%) participants were meeting current public health exercise guidelines. Partial correlations adjusting for age, medical comorbidity, and alcohol use showed that the total exercise minutes (i.e., light + moderate + vigorous) was positively associated with FWB (r=0.30, p=0.027), FACT-G (r=0.25, p=0.071), and FACT-H&N (r=0.26, p=0.064), was negatively associated with fatigue (r=−0.27, p=0.051), and had no association with depression (r=0.10, p=0.500).Conclusions Few head and neck cancer survivors are participating in any moderate or vigorous exercise, and over half are completely sedentary. Meaningful and potentially beneficial associations between total exercise minutes, QoL, and fatigue were demonstrated. An exercise intervention may have utility in this understudied cancer survivor group. Further research is warranted.     

Increased post‐induction intensification improves outcome in children and adolescents with a markedly elevated white blood cell count (≥200 × 109/l) with T cell acute lymphoblastic leukaemia but not B cell disease: a report from the Children's Oncology Group

Children and adolescents presenting with a markedly elevated white blood cell (ME WBC) count (WBC ≥200 × 10⁹/l) comprise a unique subset of high‐risk patients with acute lymphoblastic leukaemia (ALL). We evaluated the outcomes of the 251 patients (12% of the study population) with ME WBC treated on the Children's Cancer Group‐1961 protocol. Patients were evaluated for early response to treatment by bone marrow morphology; those with a rapid early response were randomized to treatment regimens testing longer and stronger post‐induction therapy. We found that ME WBC patients have a poorer outcome compared to those patients presenting with a WBC <200 × 10⁹/l (5‐year event‐free survival 62% vs. 73%, P = 0·0005). Longer duration of therapy worsened outcome for T cell ME WBC with a trend to poorer outcome in B‐ALL ME WBC patients. Augmented therapy benefits T cell ME WBC patients, similar to the entire study cohort, however, there appeared to be no impact on survival for B‐ALL ME WBC patients. ME WBC was not a prognostic factor for T cell patients. In patients with high risk features, B lineage disease in association with ME WBC has a negative impact on survival.     

Plasmodium falciparum cysteine protease falcipain-2 cleaves erythrocyte membrane skeletal proteins at late stages of parasite development

Plasmodium falciparum-derived cysteine protease falcipain-2 cleaves host erythrocyte hemoglobin at acidic pH and specific components of the membrane skeleton at neutral pH. Analysis of stage-specific expression of these 2 proteolytic activities of falcipain-2 shows that hemoglobin-hydrolyzing activity is maximum in early trophozoites and declines rapidly at late stages, whereas the membrane skeletal protein hydrolyzing activity is markedly increased at the late trophozoite and schizont stages. Among the erythrocyte membrane skeletal proteins, ankyrin and protein 4.1 are cleaved by native and recombinant falcipain-2 near their C-termini. To identify the precise peptide sequence at the hydrolysis site of protein 4.1, we used a recombinant construct of protein 4.1 as substrate followed by MALDI-MS analysis of the cleaved product. We show that falcipain-2-mediated cleavage of protein 4.1 occurs immediately after lysine 437, which lies within a region of the spectrin-actin-binding domain critical for erythrocyte membrane stability. A 16-mer peptide containing the cleavage site completely inhibited the enzyme activity and blocked falcipain-2-induced fragmentation of erythrocyte ghosts. Based on these results, we propose that falcipain-2 cleaves hemoglobin in the acidic food vacuole at the early trophozoite stage, whereas it cleaves specific components of the red cell skeleton at the late trophozoite and schizont stages. It is the proteolysis of skeletal proteins that causes membrane instability, which, in turn, facilitates parasite release in vivo.