A spectrum of novel NPHS1 and NPHS2 gene mutations in pediatric nephrotic syndrome patients from Pakistan

Background

Mutations in the NPHS1 and NPHS2 genes are among the main causes of early-onset and familial steroid resistant nephrotic syndrome respectively. This study was carried out to assess the frequencies of mutations in these two genes in a cohort of Pakistani pediatric NS patients.

Methods

Mutation analysis was carried out by direct sequencing of the NPHS1 and NPHS2 genes in 145 nephrotic syndrome (NS) patients. This cohort included 36 samples of congenital or infantile onset NS cases and 39 samples of familial cases obtained from 30 families.

Results

A total of 7 homozygous (6 novel) mutations were found in the NPHS1 gene and 4 homozygous mutations in the NPHS2 gene. All mutations in the NPHS1 gene were found in the early onset cases. Of these, one patient has a family history of NS. Homozygous p.R229Q mutation in the NPHS2 gene was found in two children with childhood-onset NS.

Conclusions

Our results show a low prevalence of disease causing mutations in the NPHS1 (22% early onset, 5.5% overall) and NPHS2 (3.3% early onset and 3.4% overall) genes in the Pakistani NS children as compared to the European populations. In contrast to the high frequency of the NPHS2 gene mutations reported for familial SRNS in Europe, no mutation was found in the familial Pakistani cases. To our knowledge, this is the first comprehensive screening of the NPHS1 and NPHS2 gene mutations in sporadic and familial NS cases from South Asia.     

Diagnostic and therapeutic dilemma associated with atypical glandular cells on liquid‐based cervical cytology

K. Chummun, M. Fitzpatrick, P. Lenehan, P. Boylan, E. Mooney and G. Flannelly
Diagnostic and therapeutic dilemma associated with atypical glandular cells on liquid‐based cervical cytology Background: In 2008, the management of women in Ireland with atypical glandular cells changed to immediate referral to colposcopy. The optimal management of these women is unclear. A balance between the detection of occult disease and overtreatment is required. Methods: Our study aim was to document the experience of this policy at the National Maternity Hospital, Dublin. Information from the computerized data management system was analysed with the statistical package SPSS. Results: In 2009, 156 women attended colposcopy following a single atypical glandular cell diagnosis on liquid‐based cytology. The mean age was 41 years. Thirty (19.2%) women had abnormal vaginal bleeding, 31 (19.9%) were smokers and 34 (21.8%) had received previous treatment. The colposcopy was satisfactory in 125 (80.1%) and unsatisfactory in 31 (19.9%). Cervical histology was available for 146 (93.6%) women: 57 excisional procedures and 89 diagnostic biopsies. Abnormal histology was detected in 46 women (31.5%). Four women (2.7%) had invasive cancer, five (3.4%) had adenocarcinoma in situ, 21 (14.4%) had cervical intraepithelial neoplasia (CIN) grade 2 or 3 and 16 (11.0%) had CIN1. No abnormality was detected in 100 women (68.5%), including 35 (61.4%) of those who had undergone excisional procedures. The colposcopic impression in this group was unsatisfactory in 10 women (28.6%), glandular abnormalities in six (17.1%), high‐ and low‐grade changes in 12 (34.2%) and six (17.1%) women, respectively, and normal in one (2.9%). The findings were essentially negative in the remaining 10 women: overall, 30 (19.2%) of the 156 women referred to colposcopy had at least CIN2. Conclusion: This study confirmed significant levels of high‐grade disease in women referred to colposcopy with atypical glandular cells on cytology. Concerns about undetected endocervical disease resulted in high levels of negative excisional biopsies. Alternative strategies, including endometrial sampling, human papillomavirus testing and discussion at clinicopathological meeting, should be considered.     

Ultrasonography assessment of hepatobiliary abnormalities in 3359 subjects with Opisthorchis viverrini infection in endemic areas of Thailand

A cross sectional study on hepatobiliary abnormalities in opisthorchiasis was performed in 8936 males and females aged from 20 to 60 years from 90 villages of Khon Kaen province, Northeast Thailand. All were stool-examined for Opisthorchis viverrini infection by standard quantitative formalin/ethyl acetate concentration technique. Of these, 3359 participants with stool egg positive underwent ultrasonography of the upper abdomen. The hepatobiliary abnormalities detected by ultrasound are described here. This study found a significantly higher frequency of advanced periductal fibrosis in persons with chronic opisthorchiasis (23.6%), particularly in males. Risks of the fibrosis included intensity of infection, and age younger than 30 years. Height of left lobe of the liver, cross-section of the gallbladder dimensions post fatty meal, sludge, and, interestingly, intrahepatic duct stones were significantly associated with the advanced periductal fibrosis. Eleven suspected cholangiocarcinoma (CCA) cases were observed. This study emphasizes the current status of high O. viverrini infection rate and the existence of hepatobiliary abnormalities including suspected CCA in opisthorchiasis endemic areas of Thailand.     

Prevalence and predictors of bridging of coronary arteries in a large Indonesian population, as detected by 64-slice computed tomography scan

Background

Multislice computed tomography (MSCT) can be used to detect myocardial bridging (MB) of coronary arteries. However, most published studies included small cohorts and did not collect data about predictors. We investigated prevalence and predictors of MB in an Indonesian population.

Methods

All patients who had MSCT at Cinere Hospital, Jakarta, Indonesia between 2006 and 2009 were included in a prospective registry. MB was defined when at least half of the coronary artery was imbedded within the myocardium with a normal epicardial course of the proximal and distal portion.

Results

Of the 934 patients (mean age 53 years, 37.8 % female), MB could be observed in 152 patients (16.3 %). Patients with MB were younger compared with those without MB. Coronary risk factors were not different between the two groups. Coronary calcifications and moderate to severe coronary stenoses were less prevalent in patients with MB, also after adjusting for differences in age. At the time of diagnosis, only a few patients with MB were treated with beta-blockers (35 %) or calcium channel blockers (13 %).

Conclusions

Prevalence of myocardial bridging as detected by MSCT is relatively high. Patients with MB were younger and had a lower prevalence of coronary sclerosis. MB could be the cause of their unexplained symptoms. Follow-up studies are necessary to assess the symptoms of these patients, their response to treatment and the incidence of (coronary) events. MSCT can be used to identify patients for potential new treatment strategies.     

SCANNING ELECTRON MICROSCOPY OBSERVATIONS OF DEFORMITIES IN SMALL PENNATE DIATOMS EXPOSED TO HIGH CADMIUM CONCENTRATIONS1

Different types of malformations are likely to affect the morphology of diatoms when exposed to particularly unstable environmental conditions, the most easily identifiable being distortion of the whole frustule. In the present study, we investigated, by means of SEM, valve abnormalities induced by high cadmium contamination (100 μg · L^?1) in small pennate diatoms. Changes in the shape of Amphora pediculus (Kütz.) Grunow and anomalous sculpturing of the cell wall of many species, such as Encyonema minutum (Hilse) D. G. Mann, Mayamaea agrestris (Hust.) Lange‐Bert., Gomphonema parvulum (Kütz.) Kütz., or Eolimna minima (Grunow) Lange‐Bert., were observed, which were not, or almost not, noticeable in the LM. With consideration to current knowledge of diatom morphogenesis, metal uptake by the cell would induce, directly or indirectly, damage to many cytoplasmic components (e.g., microtubules, cytoskeleton, Golgi‐derived vesicles) involved in the precisely organized silica deposition. This study confirms that many species, whatever their size, are likely to exhibit morphological abnormalities under cadmium stress, and that this indicator may be valuable for the biomonitoring of metal contamination, even if SEM observations are not necessary for routine studies.     

Agnathia and associated malformations in a male rhesus monkey

BACKGROUND: Agnathia is a rare malformation characterized by the absence of the mandible. METHODS: A male rhesus monkey with malformations was found dead and studied by internal examination, radiographs and histopathology. RESULTS: A case of a rare first branchial arch anomaly with agenesis of the mandible and tongue is presented. The animal also had visceral deformities. However, ears were normal in shape and only slightly low in position. The craniofacial malformations may reflect incomplete separation of the first branchial arch into its maxillary and mandibular processes. CONCLUSIONS: The association between the craniofacial and other corporal anomalies is unclear.     

Chromosome number variation in three mouse embryonic stem cell lines during culture

Although mouse embryonic stem cell lines (mESCs) have been established since 1981, systematic studies about chromosomal changes during culture are lacking. In this study, we report the results of a cytogenetic analysis performed on three mESC lines (named UPV02, UPV06 and UPV08) cultured for a period of 3 months. At time intervals, the variation of the chromosome number together with the expression of markers of the undifferentiated status, i.e., OCT-4, SSEA-1, FOM-1 and alkaline phosphatase activity, were determined. The three mESC lines showed a progressive loss of euploid metaphases during the 3 months period of culture. Chromosome abnormalities were accumulated at the latest passages analysed. Metacentric chromosomes were the most frequent chromosome abnormality observed throughout the period of culture. Interestingly, in coincidence with, or few passages after, the drop of euploidy, the alkaline phosphatase activity was partially or totally lost, whereas the OCT-4, SSEA-1 and FOM-1 stem markers were always positive throughout the period of culture. Our results remark the necessity to perform the karyotype analysis during culture in order to develop new culture conditions to maintain the correct chromosome complement in long-term culture of mESC lines.     

Congenital asplenia and group B streptococcus sepsis in the adult: case report and review of the literature

Asplenia is associated with an increased incidence of fatal and life-threatening sepsis caused by encapsulated pathogens. Isolated congenital asplenia is a very rare condition, with only 33 cases reported in the literature. The authors report another case of this condition complicated by overwhelming Group B streptococcus sepsis secondary to paronychia that was managed successfully.     

Role of the conserved oligomeric Golgi (COG) complex in protein glycosylation

The Golgi apparatus is a central hub for both protein and lipid trafficking/sorting and is also a major site for glycosylation in the cell. This organelle employs a cohort of peripheral membrane proteins and protein complexes to keep its structural and functional organization. The conserved oligomeric Golgi (COG) complex is an evolutionary conserved peripheral membrane protein complex that is proposed to act as a retrograde vesicle tethering factor in intra-Golgi trafficking. The COG protein complex consists of eight subunits, distributed in two lobes, Lobe A (Cog1-4) and Lobe B (Cog5-8). Malfunctions in the COG complex have a significant impact on processes such as protein sorting, glycosylation, and Golgi integrity. A deletion of Lobe A COG subunits in yeasts causes severe growth defects while mutations in COG1, COG7, and COG8 in humans cause novel types of congenital disorders of glycosylation. These pathologies involve a change in structural Golgi phenotype and function. Recent results indicate that down-regulation of COG function results in the resident Golgi glycosyltransferases/glycosidases to be mislocalized or degraded.