A genome-wide survey of structural variation between human and chimpanzee

Structural changes (deletions, insertions, and inversions) between human and chimpanzee genomes have likely had a significant impact on lineage-specific evolution because of their potential for dramatic and irreversible mutation. The low-quality nature of the current chimpanzee genome assembly precludes the reliable identification of many of these differences. To circumvent this, we applied a method to optimally map chimpanzee fosmid paired-end sequences against the human genome to systematically identify sites of structural variation > or = 12 kb between the two species. Our analysis yielded a total of 651 putative sites of chimpanzee deletion (n = 293), insertions (n = 184), and rearrangements consistent with local inversions between the two genomes (n = 174). We validated a subset (19/23) of insertion and deletions using PCR and Southern blot assays, confirming the accuracy of our method. The events are distributed throughout the genome on all chromosomes but are highly correlated with sites of segmental duplication in human and chimpanzee. These structural variants encompass at least 24 Mb of DNA and overlap with > 245 genes. Seventeen of these genes contain exons missing in the chimpanzee genomic sequence and also show a significant reduction in gene expression in chimpanzee. Compared with the pioneering work of Yunis, Prakash, Dutrillaux, and Lejeune, this analysis expands the number of potential rearrangements between chimpanzees and humans 50-fold. Furthermore, this work prioritizes regions for further finishing in the chimpanzee genome and provides a resource for interrogating functional differences between humans and chimpanzees.     

Three-dimensional ultrasonographic diagnosis and hysteroscopic management of a viable cesarean scar ectopic pregnancy

Implantation of conception material within a cesarean section scar is an extremely rare form of ectopic pregnancy with devastating complications, such as uterine rupture and intractable bleeding. Both 2-D and 3-D transvaginal ultrasonographic devices are used adequately for precise diagnosis, but there is still a lack of consensus concerning management strategies. No therapeutic modality is suggested to be entirely efficacious and safe for preserving uterine integrity. We present here a 29-year-old woman with vaginal bleeding and a gestational sac with a viable embryo of 6 weeks of age that was implanted in a cesarean section scar. Serum beta-hCG levels were 16 792 mIU/mL. Following an unsuccessful treatment course of systemic methotrexate, the patient underwent operative hysteroscopy. Minimally invasive hysteroscopic resection of the ectopic gestational mass without major complication appears to be an alternative therapeutic approach with minimal morbidity and preservation of future fertility.     

Anatomy and clinical significance of the trigeminocerebellar artery

The trigeminocerebellar artery (TCA) is a unique branch of the basilar artery supplying both the trigeminal nerve root and the cerebellar hemisphere. In this study, we describe and demonstrate the microanatomy of the TCA in 45 brainstems and discuss the neurological, neuroradiological and neurosurgical significance. This is the largest series of cadavers in the literature. The close relationship of the TCA to the trigeminal nerve root may have clinical implications including for the etiology of trigeminal neuralgia, thus the neurosurgeon must be aware of the vasculature of the trigeminal nerve root area and the anatomical variations.     

Nephrological factors may cause kidney dysfunction in patients with common variable immunodeficiency

Background/aimCommon variable immunodeficiency (CVID) is a heterogeneous primary deficiency characterized by hypogammaglobulinemia, recurrent infections, an increased risk of autoimmune disease, malignancy, and chronic inflammation. Proteinuria is one of the most important prognostic factors causing progression in kidney disease. Proteinuria causes tubulotoxicity, activates inflammatory markers that cause fibrosis, and consequently nephropathy progression. The data is scant in the literature regarding the inflammation and nephropathy in CVID. Hence, in the present study, we aimed to investigate the relationship between tubular dysfunction, proteinuria, and inflammation in patients with CVID.Materials and methodsThis was a cross-sectional study involving 27 patients with CVID (15 females, 12 males; mean age, 39.88 ± 13.47 years) and 18 control subjects (10 females, 8 males; mean age, 33.83 ± 7.97 years). Patients were evaluated for kidney functions including glomerular filtration rate, fractional excretion of sodium, metabolic acidosis, serum/urine anion gap, 24-h urine proteinuria and, were grouped in terms of proteinuria. Blood samples obtained from the patients with CVID were taken into 2 mL EDTA tube to evaluate peripheral NK cell subgroups according to CD56 and CD16 expression and CD3, CD4, CD 8 expression to determine subtypes T cells. These cells were evaluated by flow cytometry technique.ResultsUrinary density, fractional excretion of sodium, proteinuria, and metabolic acidosis are found to be higher in patients with CVID when compared to healthy controls. In the bivariate correlation analysis, proteinuria was positively correlated with age (r = 0.496, p = < 0.001), CD8+T cells percentage (r = 0.427, p = 0.02). Albumin, CRP, and CD8+T cell percentage were found to be independent variables of proteinuria.ConclusionIncreased chronic ongoing inflammation was found to be associated with proteinuria in patients with CVID. Hence, in routine outpatient clinics, proteinuria should not be overlooked in this group of patients.     

Fukutin mutations in non-Japanese patients with congenital muscular dystrophy: less severe mutations predominate in patients with a non-Walker-Warburg phenotype

Six genes including POMT1, POMT2, POMGNT1, FKRP, Fukutin (FKTN) and LARGE encode proteins involved in the glycosylation of α-dystroglycan (α-DG). Abnormal glycosylation of α-DG is a common finding in Walker-Warburg syndrome (WWS), muscle-eye-brain disease (MEB), Fukuyama congenital muscular dystrophy (FCMD), congenital muscular dystrophy types 1C and 1D and some forms of autosomal recessive limb-girdle muscular dystrophy (LGMD2I, LGMD2K, LGMD2M), and is associated with mutations in the above genes. FCMD, caused by mutations in Fukutin (FKTN), is most frequent in Japan, but an increasing number of FKTN mutations are being reported outside of Japan. We describe four new patients with FKTN mutations and phenotypes ranging from: severe WWS in a Greek-Croatian patient, to congenital muscular dystrophy and cobblestone lissencephaly resembling MEB-FCMD in two Turkish patients, and limb-girdle muscular dystrophy and no mental retardation in a German patient. Four of the five different FKTN mutations have not been previously described.     

The historical evolution of the fornix and its terminology: a review

The historical evolution of the fornix has not been sufficiently reviewed in the literature. In this article, we follow this evolution from the first mention of the fornix in animal dissections of the second century AD, to the legalization of cadaver dissection in the 1300 s, to the introduction of neural staining techniques and the microscope in the seventeenth century, to today. We summarize the focus of fornix studies on memory to reveal its relationship with the hippocampus. We then cover the detection of the fornix and its neural connections noninvasively with the advancement of radiological imaging techniques. Finally, we discuss the prominence of the fornix as a target for deep brain stimulation in Alzheimer’s disease and post-traumatic brain injury memory disorders.

     

Effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on endothelial dysfunction, lipid peroxidation, and hepatocyte morphology in rats with sepsis-induced liver damage

Background

Sepsis remains a difficult problem for clinicians, with its systemic effects and high morbidity and mortality rates. The roles of oxidative stress, endothelial dysfunction, and lipid peroxidation in sepsis-induced organ damage are being investigated.

Objective

The aim of this study was to investigate the effects of selective cyclooxygenase (COX)-2 inhibition on tissue lipid peroxidation, endothelial dysfunction, and hepatic cell morphology in a rat model of sepsis.

Methods

Thirty rats with sepsis induced by cecal ligation and puncture were divided equally into 3 groups: treatment group (rofecoxib 1 mg/kg PO), control group (saline 1 mL PO), and sham group (sham surgery only). All the rats were sacrificed 1 day after sepsis induction. The livers were removed using a median laparotomy for histopathologic and biochemical analysis.

Results

Histomorphologic hepatic damage and lipid peroxidation were significantly reduced in the rofecoxib treatment group compared with the control group (P < 0.05 and P = 0.001, respectively). Endothelial nitric oxide synthase and inducible nitric oxide synthase staining of liver samples was statistically significantly reduced in the treatment group compared with the control group (both, P < 0.001). The hepatic nitric oxide level and malonyldialdehyde activity decreased significantly (P < 0.001 and P = 0.001, respectively) in the rofecoxib group compared with the control group. Hepatic myeloperoxidase activity was similar between the treatment and control groups.

Conclusion

Further investigation of selective COX-2 inhibition as an alternate therapeutic choice for sepsis-induced hepatic damage should be considered.     

Patients with acute on chronic liver failure display "sepsis-like" immune paralysis

BACKGROUND/AIMS: Cellular immune depression is linked to high mortality in sepsis, but has yet to be systematically analysed in liver cirrhosis. The aim of the present study was to directly compare functional immune parameters in patients with acute on chronic liver failure (ACLF), severe sepsis, and non-decompensated cirrhosis. METHODS: Patients with ACLF (n=27) were investigated at admission to a medical ICU. Patients with stable liver cirrhosis (n=24) and severe sepsis (n=31) served as control groups. In all subjects, serum levels of IL-6 and IL-10, ex vivo production of TNF-alpha in a whole blood assay, and monocyte surface HLA-DR expression were determined. RESULTS: In patients with ACLF or sepsis, ex vivo TNF-alpha production and HLA-DR expression were severely decreased compared to subjects with stable cirrhosis (both P<0.001). Contrary, IL-6 levels were highest in septic patients, followed by subjects with ACLF and cirrhotic patients (both P<0.05). Immune dysfunction in ACLF was independent of aetiology of liver cirrhosis and associated with high mortality. CONCLUSIONS: Patients with ACLF and severe sepsis show a similar degree of cellular immune depression. The reduced cellular immune function in subjects with ACLF might contribute to the increased infectious morbidity of these patients and provide a rational basis for prevention strategies.     

Rare variation in partial anomalous venous drainage in 2 cases: diagnosis, assessment methods, and surgical approach

Where pulmonary veins drain and their relationship with an atrial septal defect (ASD) are important. A sinus venosus (high venosum) type of defect is the most common pathology accompanying partial anomalous pulmonary venous connection. Typically, the right superior pulmonary vein and occasionally the middle pulmonary vein drain into the junction of the superior vena cava (SVC) and the right atrium (RA), and a sinus venosus type of ASD usually accompanies these anomalies. In this report, we assess a very rare pathology in which 3 right pulmonary veins (superior, middle, and inferior) drain into the SVC-RA junction with respect to diagnostic methods and in the light of 2 cases involving patients in 2 different age groups.