Modulation of yeast telomerase activity by Cdc13 and Est1 in vitro.

Telomerase is the enzyme involved in extending telomeric DNA. Control of telomerase activity by modulating its access to chromosome ends is one of the most important fundamental mechanisms. This study established an in vitro yeast telomerase reconstitution system that resembles telomere replication in vivo. In this system, a tailed-duplex DNA formed by telomeric DNA was employed to mimic the structure of telomeres. The core catalytic components of telomerase Est2/Tlc1 RNA were used as the telomeric DNA extension machinery. Using the reconstituted systems, this study found that binding of Cdc13 to telomeric DNA inhibited the access of telomerase to its substrate. The result was further confirmed by a single-molecule approach using the tethered-particle motion (TPM)-based telomerase assay. The findings also showed that the inhibitory effect can be relieved by telomerase-associated protein Est1, consistent with the role of Cdc13 and Est1 in regulating telomere extension in vivo. Significantly, this study found that the DNA binding property of Cdc13 was altered by Est1, providing the first mechanistic evidence of Est1 regulating the access of telomerase to its substrate. Thus, the roles of Cdc13 and Est1 in modulating telomerase activity were clearly defined using the in vitro reconstituted system.

Pif1 regulates telomere length by preferentially removing telomerase from long telomere ends.

Telomerase, a ribonucleoprotein complex, is responsible for maintaining the telomere length at chromosome ends. Using its RNA component as a template, telomerase uses its reverse transcriptase activity to extend the 3'-end single-stranded, repetitive telomeric DNA sequence. Pif1, a 5'-to-3' helicase, has been suggested to regulate telomerase activity. We used single-molecule experiments to directly show that Pif1 helicase regulates telomerase activity by removing telomerase from telomere ends, allowing the cycling of the telomerase for additional extension processes. This telomerase removal efficiency increases at longer ssDNA gaps and at higher Pif1 concentrations. The enhanced telomerase removal efficiency by Pif1 at the longer single-stranded telomeric DNA suggests a way of how Pif1 regulates telomerase activity and maintains telomere length.

Can pillar suturing promote efficacy of adenotonsillectomy for pediatric OSAS? A prospective randomized controlled trial.

OBJECTIVES/HYPOTHESIS: Pediatric obstructive sleep apnea syndrome (OSAS) is a common disorder with serious clinical implications if left untreated. The recommended initial treatment for pediatric patients with obstructive sleep apnea syndrome (OSAS) is adenotonsillectomy. However, recent reports have shown variable surgical results with adenotonsillectomy in the treatment of pediatric OSAS. STUDY DESIGN: Prospective, controlled study. METHODS: From April 2007 to August 2010, 24 participants were assigned alternatively to either adenotonsillectomy with pillar suturing (intervention group) or adenotonsillectomy alone (control group). RESULT: The average improvement in apnea hypopnea index (AHI) was 42.6% in the control group and 79.9% in the intervention group (P=0.037). The success rate was 50% in the control group and 91.6% in the intervention group (P=0.034). Six patients (50%) in the intervention group achieved complete resolution of pediatric OSAS, as defined by an AHI <1/hour, compared to 2 patients (16.7%) in the control group (P=0.097). CONCLUSION: Adenotonsillectomy with pillar suturing showed significant improvement in treating pediatric patients with OSAS compared to adenotonsillectomy alone. The procedure is simple and safe. LEVEL OF EVIDENCE: 4.

Focal stenosis in right upper lobe bronchus in a recurrently wheezing child sequentially studied by multidetector-row spiral computed tomography and scintigraphy.

Lower respiratory tract infections associated with wheezing are not uncommon in infants and young children. Among the wheezing-associated disorders, allergic etiologies are more commonly encountered than anatomic anomalies. We present a 3-year-old girl with a sudden attack of asthmatic symptoms including dyspnea, cyanosis and diffuse wheezing Based on a history of choking, and atelectasis in the right upper lobe detected by chest films, flexible tracheobronchoscopy was arranged and incidentally detected a stenotic orifice in the right upper lobe bronchus. Multidetector-row spiral computed tomography and pulmonary scintigraphy subsequently also disclosed the focal stenosis. She suffered from recurrent wheezing, pneumonia and lung atelectasis during 1 year of follow-up. We emphasize the diagnosis, clinical course and management of focal stenosis in the right upper lobe bronchus.

Proton magnetic resonance spectroscopy of late-life major depressive disorder.

The primary goal of this study was to examine the biochemical abnormalities of late-life major depression by using 3-tesla (3-T) proton magnetic resonance spectroscopy ((1)H-MRS). The antidepressant effects on the biochemical abnormalities were investigated as well. Study participants were 27 elderly patients with major depressive disorders (among which 9 were on antidepressant medication) and 19 comparison elderly subjects. (1)H-MRS spectra were acquired from voxels that were placed in the left frontal white matter, left periventricular white matter, and left basal ganglia. Ratios of N-acetylaspartate (NAA), choline (Cho) and myo-inositol to creatine were calculated. Patients with late-life major depressive disorder had a significantly lower NAA/creatine ratio in the left frontal white matter, and higher Cho/creatine and myo-inositol/creatine ratios in the left basal ganglia when compared with the control subjects. The myo-inositol correlated with global cognitive function among the patients. The biochemical abnormalities in late-life major depressive disorder were found on the left side of the frontal white matter and the basal ganglia. Neuron degeneration in the frontal white matter and second messenger system dysfunction or glial dysfunction in the basal ganglia are suggested to be associated with late-life depression.

Evaluation of residual functional lung volume on Tc-99m DTPA aerosol ventilation and Tc-99m MAA perfusion scintigraphy in primary ciliary dyskinesia (Kartagener syndrome).

Kartagener syndrome is diagnosed as sinusitis, bronchitis (bronchiectasis), and situs inversus by the clinical features. It is a subclass of primary ciliary dyskinesia (PCD) disease. A 12-year-old girl who had frequent upper and lower airway infections since birth, which was confirmed as Kartagener syndrome by HRCT imaging. We present the residual functional lung volume and mucociliary clearance findings seen on Tc-99m DTPA aerosol ventilation and Tc-99m MAA perfusion scintigraphy.

Detection of intracranial hemorrhage: comparison between gradient-echo images and b0 images obtained from diffusion-weighted echo-planar sequences on 3.0T MRI.

In this study, we compared the effectiveness of b0 echo-planar MR images (EPI) imaging with gradient recalled echo (GRE) in detecting acute hemorrhage. Brain images in 69 patients who suffered from acute infarction were reviewed. Nine of them had suffered from acute hemorrhage. Comparing b0EPI and GRE images side-by-side, we found no significant different effectiveness in detecting hemorrhage (P = .522, > or =.05). We concluded that b0EPI imaging could detect hemorrhagic lesions as effectively as GRE can without additional acquisition time.

Distinction between high-grade gliomas and solitary metastases using peritumoral 3-T magnetic resonance spectroscopy, diffusion, and perfusion imagings.

This study compared the effectiveness of relative cerebral blood volume, apparent diffusion coefficient, and spectroscopic imaging in differentiating between primary high-grade gliomas and solitary metastases. A 3.0-T MR unit was used to perform proton MR spectroscopy, diffusion imaging, and conventional MR imaging on 26 patients who had solitary brain tumors (14 high-grade gliomas and 12 metastases). All diagnoses were confirmed by biopsy. Twelve perfusion MR studies (8 high-grade gliomas and 4 metastases) were also performed. The results showed that the choline to creatine ratio and relative cerebral blood volume in the peritumoral regions of high-grade gliomas were significantly higher than they were in the metastases. The apparent diffusion coefficient values in tumoral and peritumoral regions of metastases were significantly higher than they were in the primary gliomas. Although conventional MR imaging characteristics of solitary metastases and primary high-grade gliomas may sometimes be similar, the peritumoral perfusion-weighted and spectroscopic MR imaging enable distinction between the two. Diffusion-weighted imaging techniques were complementary techniques to make a differential diagnosis between the two malignant tumors.

Chordoma mimicking the trigeminal schwannoma: a case report.

Intracranial chordomas are rare tumor arising from the remnants of embryologic notochord. Bony destruction and tumor calcification are their characters. Now we represent an extra-axial tumor with an unusual dumbbell shape in the right Meckel's cave and the appearance mimics the trigeminal schwannomas. However, the histopathological findings reveal a chordoma. Bony destruction in the right petrous bone and clivus provides a hint to make appropriate diagnosis.

A case report of an unusual location of pericruciate meniscal cyst with adjacent bony erosion.

Meniscal cysts are uncommon cystic lesions around the knee, and pericruciate meniscal cysts are the most rare types. Here we present an unusual case of a pericruciate meniscal cyst located laterally to the anterior cruciate ligament (ACL), causing erosion of the adjacent tibial plateau.