• Clinical and Experimental Pediatrics
• /
• v.50 no.10
• /
• pp.1018-1023
• /
• 2007

Hereditary hemorrhagic telagiectasia (HHT), which is characterized by the classic triad of mucocutaneous telangiectases, arteriovenous malformations (AVMs) and inheritance, is an autosomal dominant disorder. The characteristic manifestations of HHT are all due to abnormalities of the vascular structure. This report deals with the case of a 14-year-old girl with typical features of HHT that include recurrent epistaxis, mucocutanous telangiectases, pulmonary and cerebral AVMs and a familial occurrence.

• Environmental Mutagens and Carcinogens
• /
• v.22 no.1
• /
• pp.54-59
• /
• 2002

We have used cDNA microarray hybridization to identify gene regulated in response to gamma-irradiation in U-937 cell. The cDNA-chip was composed entirely of 1,000 human cancer related gene including apoptosis and angiogenesis etc. In gamma-irradiated U-937 cell, highly charged protein, ribosomal protein L32, four and a half LIM domains 3, lipocalin 2 (oncogene 24p3) and interleukin 15, ataxia telangiectasia mutated (includes complementation groups A, C and D) genes showed increased level of its transcription, and cell division cycle 25A, dihydrofolate reductase, topoisomerase (DNA) II beta(180kD), kinase suppressor of ras and strarigin genes showed reduced level of its transcription compared to untreated U-937 cell. The significant change of level of transcription was not found in well-known ionizing radiation(IR)-responsive gene, such as transcription factor TP53 and p53 related gene, except ataxia telangiectasia mutated gene.

• Biomolecules & Therapeutics
• /
• v.31 no.5
• /
• pp.559-565
• /
• 2023

Ataxia-telangiectasia mutated (ATM), a master kinase of the DNA damage response (DDR), phosphorylates a multitude of substrates to activate signaling pathways after DNA double-strand breaks (DSBs). ATM inhibitors have been evaluated as anticancer drugs to potentiate the cytotoxicity of DNA damage-based cancer therapy. ATM is also involved in autophagy, a conserved cellular process that maintains homeostasis by degrading unnecessary proteins and dysfunctional organelles. In this study, we report that ATM inhibitors (KU-55933 and KU-60019) provoked accumulation of autophagosomes and p62 and restrained autolysosome formation. Under autophagy-inducing conditions, the ATM inhibitors caused excessive autophagosome accumulation and cell death. This new function of ATM in autophagy was also observed in numerous cell lines. Repression of ATM expression using an siRNA inhibited autophagic flux at the autolysosome formation step and induced cell death under autophagy-inducing conditions. Taken together, our results suggest that ATM is involved in autolysosome formation and that the use of ATM inhibitors in cancer therapy may be expanded.

• Journal of Oral Medicine and Pain
• /
• v.37 no.3
• /
• pp.135-139
• /
• 2012

Hereditary hemorrhagic telangiectasia is a rare autosomal dorminant disease that features abnormal and fragile vascular dilations of terminal vessels in skin and mucous membranes, as well as arteriovenous malformations of internal organs, particularly lungs, brain, and liver. Often patients have not been diagnosed with HHT for a long time, and undiagnosed HHT patients unnecessarily develop serious complications such as severe life-threatening hemorrhage, stroke or brain abscess. Therefore, early detection and appropriate screening is very important. Early detection of HHT allows the appropriate screening for the presence of silent disease such as AVMs in the lungs, liver, or brain, and preventive treatment in the patient and their affected family members. Dentists should be familiar with HHT because the telangiectases on skin and oral mucosa are often the most dramatic and most easily identified component of HHT. Recently, we experienced a case of HHT. We present the case with a review of the literature.

• Archives of Pharmacal Research
• /
• v.21 no.6
• /
• pp.640-644
• /
• 1998

AT cells exhibit defective cell cycle regulation following DNA damage. Previous studies have shown that induction of p53 and p2i proteins are delayed in response to ionizing rad iation, resulting in the failure of G1/S checkpoint in AT cells. In this study, further investigation of the molecular mechanisms underlying G1/S phase progression in AT cells was conducted. Exponentially growing normal and AT cells were exposed to 2 Gly of ionizing radiation and the expression levels and functional activities of Rb and E2F-1 proteins were determined. We observed overexpression of hyperphosphorylated Rb and E2F-1 proteins in AT cells, which was unaffected post-irradiation. Furthermore, gel shift assays showed that E2F-1-DNA binding was constitutive in AT cells, whereas it was inhibited in control cells following exposure to ionizing radiation. The data suggests that abnormalities in the function of Rb and E2F-1 proteins may also be responsible for the failure of AT cells to arrest in the G1/S checkpoint in response to DNA damage.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.4
• /
• pp.914-921
• /
• 1997

Hereditary hemorrhagic telangiectasia(Osler-Rendu-Weber Syndrome) is characterized by telangiectasia of the skin and mucous membranes and intermittent bleeding from vascular abnormalities. About 20% of patients with this syndrome have pulmonary arteriovenous fistulas. Pulmonary arteriovenous fistula is uncommon malformation which has an abnormal connection between the pulmonary capillary bed, in which venous blood in the pulmonary artery is shunted through the fistula into the pulmonary vein without exposure to alveolar oxygen and result in unoxygenated, desaturated systemic arterial blood, polycythemia, cyanosis and clubbing. Death often results from cerebral abscess and rupture of the malformation with massive hemorrhage. Therapeutic intervention is recommended for all symptomatic patients because of the risk of those serious complications. Treatment options include surgery and transcatheter obliteration with steel coils or detachable balloons. Therapeutic embolization has the advantages that multiple bilateral pulmonary arteriovenous fistulas can be occluded and also that the procedure can be repeated if necessary. Recently we experienced a case of the multiple bilateral pulmonary arteriovenous fistulas associated with telangiectatic change of hepatic artery and multiple angiodysplasia on the gastric mucosa in 41 years old female patient who had mild dyspnea of exertion(NYHA class II). clubbing finger, severe iron deficiency anemia. She was treated with embolization technique using steel coils and iron replacement. After the therapeutic embolization. significant improvement of dyspnea of exertion with disappearance of multiple pulmonary nodule on follow-up simple chest x-ray was noted. During the subsequent six months follow-up period, she had the improvement of symptoms and iron deficiency anemia.

• Journal of Korean Neurosurgical Society
• /
• v.67 no.3
• /
• pp.270-279
• /
• 2024

Prompt medical attention is crucial for congenital intracranial vascular malformations in children and newborns due to potential severe outcomes. Imaging is pivotal for accurate identification, given the diverse risks and treatment strategies. This article aims to enhance the identification and understanding of congenital intracranial vascular abnormalities including arteriovenous malformation, arteriovenous fistula, cavernous malformation, capillary telangiectasia, developmental venous anomaly, and sinus pericranii in pediatric patients.

• Radiation Oncology Journal
• /
• v.31 no.2
• /
• pp.81-87
• /
• 2013

Purpose: To describe chronic rectal mucosal damage after pelvic radiotherapy (RT) for cervical cancer and correlate these findings with clinical symptoms and radiation dose. Materials and Methods: Thirty-two patients who underwent pelvic RT were diagnosed with radiation-induced proctitis based on endoscopy findings. The median follow-up period was 35 months after external beam radiotherapy (EBRT) and intracavitary radiotherapy (ICR). The Vienna Rectoscopy Score (VRS) was used to describe the endoscopic findings and compared to the European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) morbidity score and the dosimetric parameters of RT (the ratio of rectal dose calculated at the rectal point [RP] to the prescribed dose, biologically effective dose [BED] at the RP in the ICR and EBRT plans, ${\alpha}/{\beta}$ = 3). Results: Rectal symptoms were noted in 28 patients (rectal bleeding in 21 patients, bowel habit changes in 6, mucosal stools in 1), and 4 patients had no symptoms. Endoscopic findings included telangiectasia in 18 patients, congested mucosa in 20, ulceration in 5, and stricture in 1. The RP ratio, $BED_{ICR}$, $BED_{ICR+EBRT}$ was significantly associated with the VRS (RP ratio, median 76.5%; $BED_{ICR}$, median 37.1 $Gy_3$; $BED_{ICR+EBRT}$, median 102.5 $Gy_3$; p < 0.001). The VRS was significantly associated with the EORTC/RTOG score (p = 0.038). Conclusion: The most prevalent endoscopic findings of RT-induced proctitis were telangiectasia and congested mucosa. The VRS was significantly associated with the EORTC/RTOG score and RP radiation dose.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.3
• /
• pp.649-653
• /
• 1998

Pulmonary arteriovenous fistula is a congenital vascular malformation in lung resulting from abnormal capillary development and the exact etiology is not well known but it may occur with or without hereditary hemorrhagic telangiectasia. Hereditary hemorrhagic telangiectasia (HHT) or Rendu-osler-Weber disease is an autosomal dominant vascular disorder which associates epistaxis, mucocutaneous and visceral telangicetases, and recurrent hemorrhage with chronic anemia and visceral shuntings. Recently we experienced a case of the pulmonary arteriovenous fistula in a 23 year-old woman with a family history of this disease, which was confirmed by pulmonary angiography.

• BMB Reports
• /
• v.44 no.5
• /
• pp.352-357
• /
• 2011

The effect of human MutY homolog (hMYH) on the activation of checkpoint proteins in response to hydroxyurea (HU) and ultraviolet (UV) treatment was investigated in hMYH-disrupted HEK293 cells. hMYH-disrupted cells decreased the phosphorylation of Chk1 upon HU or UV treatment and increased the phosphorylation of Cdk2 and the amount of Cdc25A, but not Cdc25C. In siMYH-transfected cells, the increased rate of phosphorylated Chk1 upon HU or UV treatment was lower than that in siGFP-transfected cells, meaning that hMYH was involved in the activation mechanism of Chk1 upon DNA damage. The phosphorylation of ataxia telangiectasia and Rad3-related protein (ATR) upon HU or UV treatment was decreased in hMYH-disrupted HEK293 and HaCaT cells. Co-immunoprecipitation experiments showed that hMYH was immunoprecipitated by anti-ATR. These results suggest that hMYH may interact with ATR and function as a mediator of Chk1 phosphorylation in response to DNA damage.