Enzyme studies in GM2 gangliosidiosis,and their application in prenatal diagnosis

Assay of hexosaminidase A and B enzymes in four cases with developmental regression and cherry red spot on fundus examination confirmed that three cases had Tay-Sachs disease, and one case had Sandhoff disease. Prenatal diagnosis was carried out by hexosaminidase enzyme assay in amniotic fluid and cells in one family, and chorionic villus sample in the second family. The fetus was diagnosed to be unaffected in one, and affected in the other family. Assay of hexosaminidase A and B is useful for specific diagnosis of GM₂ gangliosidosis, and for prenatal diagnosis to reduce the burden of these disorders.     

Increased expression of transferrin receptors and iron in amoeboid microglial cells in postnatal rats following an exposure to hypoxia

This study was aimed to ascertain the effects of hypoxia on regulation of iron in the brain of newborn rats. At 3 h and 1 day after hypoxic exposure transferrin receptor expression as detected immunohistochemically with the antibody OX-26, and the iron content as shown by Perls' staining of amoeboid microglial cells was markedly increased. The induced changes, however, were not evident at 10 min and in longer surviving rats killed at 3 and 7 days. It is suggested that the upregulation of transferrin receptor expression coupled with iron uptake by amoeboid microglial cells in the periventricular regions is a protective mechanism to facilitate the sequestration of excess iron that may have been released either from the iron-rich oligodendrocytes, or accumulated due to a disruption of its normal transportation following the hypoxic insult. This would help protect the brain from harmful effects of iron.     

Phase II study of paclitaxel and cisplatin for advanced urothelial cancer

PURPOSE: We examined the role of paclitaxel and cisplatin as first line therapy for metastatic urothelial cancer. MATERIALS AND METHODS: A total of 34 patients were enrolled in this study, and all were eligible for treatment and assessable for response. Patients received 135 mg./m.2 paclitaxel intravenously for 3 hours followed by 70 mg./m.2 cisplatin for 2 hours every 3 weeks to a maximum of 6 cycles. RESULTS: Of the patients 70% experienced a major response to treatment, which was partial/regression in 38% and complete in 32%. Toxicity was manageable with no episodes of grade 4 leukopenia or thrombocytopenia. Nonhematological toxicities included primarily nausea, anorexia and neuropathy, which rarely were severe. CONCLUSIONS: This regimen of paclitaxel and cisplatin is effective, safe and convenient to administer in an outpatient setting for advanced urothelial cancer.     

Recognition and unfolding of human telomeric G-quadruplex by short peptide binding identified from the HRDC domain of BLM helicase

Research in recent decades has revealed that the guanine (G)-quadruplex secondary structure in DNA modulates a variety of cellular events that are mostly related to serious diseases. Systems capable of regulating DNA G-quadruplex structures would therefore be useful for the modulation of various cellular events to produce biological effects. A high specificity for recognition of telomeric G-quadruplex has been observed for BLM helicase. We identified peptides from the HRDC domain of BLM using a molecular docking approach with various available solutions and crystal structures of human telomeres and recently created a peptide library. Herein, we tested one peptide (BLM HRDC peptide) from the library and examined its interaction with human telomeric variant-1 (HTPu-var-1) to understand the basis of G4-protein interactions. Our circular dichroism (CD) data showed that HTPu-var-1 folded into an anti-parallel G-quadruplex, and the CD intensity significantly decreased upon increasing the peptide concentration. There was a significant decrease in hypochromicity due to the formation of G-quadruplex-peptide complex at 295 nm, which indicated the unfolding of structure due to the decrease in stacking interactions. The fluorescence data showed quenching upon titrating the peptide with HTPu-var-1-G4. Electrophoretic mobility shift assay confirmed the unfolding of the G4 structure. Cell viability was significantly reduced in the presence of the BLM peptide, with IC₅₀ values of 10.71 μM and 11.83 μM after 72 and 96 hours, respectively. These results confirmed that the selected peptide has the ability to bind to human telomeric G-quadruplex and unfold it. This is the first report in which a peptide was identified from the HRDC domain of the BLM G4-binding protein for the exploration of the G4-binding motif, which suggests a novel strategy to target G4 using natural key peptide segments.

Schematic representation of (HTPu–var-1-G4) located at the 3′ end, formation of G-quadruplex, model of the G-quadruplex structure, base stacking between G-quadruplex planes, G-quadruplex structure-peptide complex and twisting of G-quadruplex planes upon peptide binding.     

Evaluation of hearing loss in tympanic membrane perforation

To evaluate and analyse the hearing loss in tympanic membrane perforation based on size, site and duration of perforation. The material for this study was comprised of 100 patients of either sex and of age 15?years and above selected randomly. Size of tympanic membrane perforation was assessed under microscope using calibrated wire look. Patients were divided into three groups according to size; group I (0-9?mm(2)), Group II (9-30?mm(2)), Group III (≥?30?mm(2)); according to site into anterior and posterior group; according to involvement of malleus into malleolar and non malleolar and according to duration into Group A (<1?year), Group B (1-5?years), Group C (≥?5?years). Hearing loss was measured in each case with pure tone audiometry. Data was analysed statistically using paired t-test. Hearing loss increased as the perforation size increased [I vs. II (t?-?4.23, p??0.05). Hearing loss was more in malleolar perforation (t?-?5.74, p?相似文献   

Miscarriage risk for asymptomatic women after a normal first-trimester prenatal visit

OBJECTIVE: To estimate the risk of miscarriage among asymptomatic women after a prenatal visit between 6 and 11 weeks of gestation where proof of fetal viability of a singleton was obtained by office ultrasonography at the same visit. METHODS: This was a prospective cohort study performed over 2 years (March 2004-2006) at an antenatal clinic at a large tertiary hospital in Victoria, Australia. Those recruited were 697 asymptomatic women who attended their first antenatal visit between 6 (+2 days) and 11(+6 days) weeks of gestation, where evidence of fetal cardiac activity of a singleton was obtained by office ultrasonography. The main outcome measure was rates of miscarriage, stratified by gestation at presentation. RESULTS: One case was lost to follow-up. The risk of miscarriage among the entire cohort was 11 of 696 (1.6%). The risk fell rapidly with advancing gestation; 9.4% at 6 (completed) weeks of gestation, 4.2% at 7 weeks, 1.5% at 8 weeks, 0.5% at 9 weeks and 0.7% at 10 weeks (chi(2); test for trend P=.001). Most who miscarried received their ultrasound diagnoses many weeks after their visit; five (45%) were diagnosed in the second trimester, and all but one received their ultrasound diagnoses after 10 weeks of gestation. CONCLUSION: For women without symptoms, the risk of miscarriage after attending a first antenatal visit between 6 and 11 weeks is low (1.6% or less), especially if they present at 8 weeks of gestation and beyond. Our data could be used to reassure such women that the probability of progressing to later than 20 weeks of gestation is very good.     

Systematic Investigation of Parameters Affecting the Performance of an Agitated Filter-Dryer

A systematic experimental investigation of contact drying operation was carried out in an agitated Charles Thompson filter-dryer. In this study, the effect of process parameters (wall temperature, impeller speed, fill level) on the drying performance in the filter-dryer is quantified as a function of bed temperature and solvent concentration. In addition, the impact of drying conditions on the particle size distribution was also examined. It was found that in the range of parameters investigated, drying rate increased with wall temperature and reduced bed depth. The effect of impeller speed was variable where favorable drying conditions were strongly dependent on the particle properties. Moreover, decrease in the particle size was evident with an increase in impeller speed and decrease in the bed depth due to increased collision frequency and reduction in the fill volume both leading to particle attrition respectively. Besides, the average wall to solid heat transfer coefficient is also estimated for variable operating conditions. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2198–2213, 2013     

Large mediastinal tumor in a neonate: an anesthetic challenge

Mediastinal tumors pose a grave risk of cardiopulmonary complications during the perioperative course, particularly in neonates and small children. These tumors can cause displacement and compression of vital thoracic structures such as the tracheobronchial tree, the heart, and the great vessels. Catastrophic complications often occur during induction of anesthesia, use of muscle relaxants, positioning, and at the time of extubation. We present our experience of anesthetic management of a neonate with a mediastinal mass who had features of both airway and vascular obstruction.