Molecular cytogenetics : an indispensable tool for cancer diagnosis
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Thomas SK Wan, Edmond SK Ma PMID:22537925
Cytogenetic aberrations may escape detection or recognition in traditional karyotyping. The past decade has seen an explosion of methodological advances in molecular cytogenetics technology. These cytogenetics techniques add color to the black and white world of conventional banding. Fluorescence in-situ hybridization (FISH) study has emerged as an indispensable tool for both basic and clinical research, as well as diagnostics, in leukemia and cancers. FISH can be used to identify chromosomal abnormalities through fluorescent labeled DNA probes that target specific DNA sequences. Subsequently, FISH-based tests such as multicolor karyotyping, comparative genomic hybridization (CGH) and array CGH have been used in emerging clinical applications as they enable resolution of complex karyotypic aberrations and whole global scanning of genomic imbalances. More recently, crossspecies array CGH analysis has also been employed in cancer gene identification. The clinical impact of FISH is pivotal, especially in the diagnosis, prognosis and treatment decisions for hematological diseases, all of which facilitate the practice of personalized medicine. This review summarizes the methodology and current utilization of these FISH techniques in unraveling chromosomal changes and highlights how the field is moving away from conventional methods towards molecular cytogenetics approaches. In addition, the potential of the more recently developed FISH tests in contributing information to genetic abnormalities is illustrated.
Host factors in the replication of positive-strand RNA viruses
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Robert YL Wang, Kui Li PMID:22537926
Viruses are obligate, intracellular parasites that depend on host cells for successful propagation. Upon infection of host cells, positivestrand RNA viruses exploit and hijack cellular machinery and reprogram these cells into viral "factories" through various protein-protein, protein- RNA, and protein-lipid interactions. The molecular interplay between host factors and invading viruses is a continuous process throughout the entire viral life cycle and determines virus host range and viral pathogenesis, as well as driving viral evolution. Studies of host factors have contributed insights into their normal cellular functions and helped identify attractive targets for antiviral drug development. With the development of high throughput screening, functional genomics, and proteomics technologies, host factors participating in viral life cycles have been identified rapidly in recent years. In this review, we summarize the recent advances in virus-host cell interactions in positive-strand RNA virus infections and focus on host factors that facilitate viral replication.
Ultrasound microbubble contrast agents for diagnostic and therapeutic applications : current status and future design
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Shih-Tsung Kang, Chih-Kuang Yeh PMID:22537927
Ultrasound contrast agents are highly echogenic microbubbles with many unique properties. Microbubbles can basically improve the sensitivity of conventional ultrasound imaging to the microcirculation. The resonance of microbubbles in response to an incident ultrasound pulse results in nonlinear harmonic emission that serves as the signature of microbubbles in microbubble-specific imaging. Inertial cavitation and destruction of microbubbles can produce a strong mechanical stress enhancing the permeability of the surrounding tissues, and can further increase the extravasation of drugs from the blood into the cytoplasm or interstitium. Stable cavitation by high-frequency ultrasound can also mildly increase tissue permeability without causing any damage even at a high acoustic pressure. Microbubbles can carry drugs, release them upon ultrasound-mediated microbubble destruction, and simultaneously enhance vascular permeability to increase drug deposition in tissues. Various targeting ligands can be conjugated to the surface of microbubbles to attain ligand-directed and site-specific accumulation for targeted imaging. In addition to current developments in microbubble technology, this review introduces our studies of the applications of microbubble-specific imaging, ultrasound-aided drug delivery, and targeted imaging. These applicationsare promising but may require further improvement for clinical use.
Extract of sporoderm-broken germinating spores of ganoderma lucidum activates human polymorphonuclear neutrophils via the P38 mitogen-activated protein kinase pathway
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Pei-Yu Hsu, Jiun-Liang Chern, Hsing-Yu Chen, Sien-Hung Yang PMID:22537928
Background: Ganoderma lucidum (G. lucidum) has been used in traditional Chinese medicine for thousands of years because of its immunomodulatory properties. It is believed that G. lucidum enhances the human immune response by improving the function of human polymorphonuclear neutrophils (PMNs); nevertheless, the actual mechanism by which G. lucidum acts on human PMNs remains unknown. In this study, we investigated the molecular pathways through which G. lucidum activates human PMNs.
Methods: The phagocytic activity of PMNs was evaluated with and without treatment with the extract of sporoderm-broken germinating spores of G. lucidum. The same activity was measured after G. lucidum treatment with or without p38 mitogen-activated protein kinase (p38 MAPK) inhibitor. The activation of p38 MAPK was also evaluated with or without treatment with the extract of sporoderm-broken germinating spores of G. lucidum.
Results: In this study, we found that the extract of G. lucidum enhanced the phagocytic activity of PMNs in a dose-dependent manner, but this response was attenuated by treatment with SB203580, a p38 MAPK inhibitor. The extract of G. lucidum also enhanced activation of p38 MAPK in a dose-dependent manner.
Conclusion: These results clearly show that the extract of G. lucidum can modulate human immunity by activating human PMNs via the p38 MAPK pathway. These results may be of clinical importance to doctors of traditional Chinese medicine.
Background: Hyperbilirubinemia is a common disorder during the neonatal period. Severe neonatal hyperbilirubinemia (NH) carries a potential for permanent neurological impairment. The current study analyzed possible etiologies leading to NH.
Methods: A retrospective cohort of neonates with total serum bilirubin (TSB) ≥ 20 mg/dL was surveyed from 1995 to 2007. Subjects with gestational ages < 34 weeks were excluded, leaving a total of 413 enrolled neonates.
Results: The most common etiology in relation to marked NH was breast milk feeding (38.5%), followed by glucose-6-phospahate dehydrogenase (G6PD) deficiency (24.0%), ABO incompatibility (21.8%), extravascular hemorrhage (6.5%), Rh incompatibility (2.9%), bacterial infection (2.2%), hereditary spherocytosis (1.2%), dehydration (1.2%), diabetic mother (1.0%), polycythemia (0.7%), and gastrointestinal obstruction (0.7%). Other rare etiologies included Down syndrome, Chinese herb intake, asphyxia, galactosemia and congenital hypothyroidism. We did not identify any known cause in 63 neonates (15.3%). Neonates with more than one etiology tended to have higher TSB than subjects without a known etiology (p < 0.05). Anemia was more common in those with G6PD deficiency, blood group incompatibility, hereditary spherocytosis, and gastrointestinal obstruction. Neonates fed breast milk tended to have prolonged NH.
Conclusion: This study depicts the clinical features of marked NH. Breast milk feeding, G6PD deficiency and ABO incompatibility are common etiologies in Taiwan. Prolonged NH is more common in neonates fed breast milk than those who were given formula.
Anthropometric study of the bicipital groove in Indians and its clinical implications
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BV Murlimanju, Latha V Prabhu, Mangala M Pai, M Shreya, KU Prashanth, Chettiar Ganesh Kumar, Chitra Prakash Rao PMID:22537930
Background: Since morphometric data on the upper end of the humerus from Indian anatomical samples are scarce, this study was undertaken with reference to orthopedic surgery. The aim was to determine the length, width and depth of the bicipital groove and to find the incidence of a supratubercular ridge of Meyer in an Indian population.
Methods: The study included 104 unpaired dry humeri (48 right side and 56 left) which belonged to the anatomy laboratory of our institution. The length, width and depth of the bicipital groove were measured with a digital vernier caliper. The data were tabulated as mean ± SD and statistically compared between the right and left sides.
Results: The mean length, width and depth of the bicipital groove were 84.6 ± 10.9 mm, 8.5 ± 2.3 mm and 4.4 ± 1.8 mm, respectively, which corresponded to 27.8% of the total length, 32.2% of the transverse width and 17% of the anteroposterior widh of the humerus, respectively. There was no statistically significant difference in these parameters between the left and right sides (p > 0.05). A supratubercular ridge of Meyer was seen in 24 (23.1%) of the humeri.
Conclusion: The study determined the morphometric parameters of the bicipital groove in an Indian population. We believe that this study will be an important reference for scientific research, and the details are also important for anthropologists and clinical anatomists.
Pierce and push : A simplified method to facilitate laparoscopic myomectomy
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Pei-Ju Wu, Kai-Yun Wu, Chien-Min Han, Hsuan Su, Chin-Jung Wang, Chyi-Long Lee PMID:22537931
Background: The aim of this study was to present our experience with a novel approach called the pierce and push (PP) method which uses a stainless steel centimeter probe instead of a 5 mm claw forceps to enucleate fibroids in a laparoscopic myomectomy (LM).
Methods: A retrospective chart review of 90 women with symptomatic uterine fibroids who underwent an LM was performed. Cases of LM with the PP method were compared with a matched control group of LM with a 5 mm claw forceps. The operative time, tumor separation time, specimen removal time, amount of blood loss, requirement for blood transfusion and length of hospital stay were compared between groups.
Results: The two groups were matched by age, body mass index, previous cesarean delivery, main fibroid size, and number and weight of fibroids. The tumor separation time was significantly shorter in the PP group than the claw forceps group (9.7 ± 3.1 minutes versus 17.1 ± 4.4 minutes, p < 0.001). The length of the operation, hospitalization time, specimen removal time, amount of blood loss, and requirement for blood transfusion were not significantly different between groups.
Conclusion: A stainless steel centimeter probe has an advantage over a 5 mm claw forceps in pushing and pulling fibroids. Our findings indicate that the PP method was much more effective in excision of fibroids than a 5 mm claw grasper in LM.
Background: Eccrine angiomatous hamartoma (EAH) comprises a rare nevoid proliferation of normal eccrine glands and small blood vessels and occasionally other elements in the middle and deep dermis with variable clinical manifestations. Case series have rarely been published except for case reports and literature reviews. The aims of this article were to investigate the clinical and pathologic features of patients with EAH in Taiwan and to compare our results with the results of previous studies.
Methods: A retrospective review of medical records and histopathological findings was performed on patients diagnosed with EAH in a medical center in Taiwan between 1994 and 2010.
Results: Fifteen patients with pathologically diagnosed EAH were collected. The mean age at the time of diagnosis was 38.6 years (range, birth to 67 years). The male to female ratio was 3 to 2. In most cases, EAH arose as a single lesion on a lower extremity. The symptoms and signs most commonly associated with EAH were pain (60%), hypertrichosis (13.3%), itching (13.3%) and hyperhidrosis (6.7%). Additional pathological findings included hemangioma (13.3%), verrucous hemangioma (6.7%), arteriovenous malformation (6.7%), and angiokeratoma (6.7%). None of the patients experienced spontaneous regression of the lesions before excision. Excisions were done in one patient under general anesthesia, and ten patients with local anesthesia. Four patients were kept under observation. Tumor recurrences were noted in two out of the eleven patients whose lesions were excised.
Conclusion: Compared with cases in the literature, we found additional histopathological findings and an increased tumor recurrence risk in our cohort. EAH remains a benign and uncommon hamartomatous condition. Further multi-center, retrospective studies with larger case numbers are needed to better characterize the disease presentation in Asian populations.
Background: Centrally located large hepatocellular carcinoma (HCC) is a difficult issue in surgery. These HCCs can be treated by hemi-/extended or central hepatectomies. The aim of this study was to analyze the results of hemi-/extended and central hepatectomies.
Methods: One hundred and four patients with centrally-located large tumors were retrospectively reviewed. Patients were divided into group 1 (n = 41) with hemi-/extended hepatectomies, and group 2 (n = 63) with central hepatectomies. Characteristics were analyzed between groups and survival rates were calculated.
Results: Parenchyma resection was limited in group 2. The resection margin in 92.6% of group 2 patients was < 1 cm, compared with 78.9% of group 1 patients (p = 0.056). The 1- and 5-year disease-free survival rates were 50% and 38.9% for group 1, and 50% and 15% for group 2 (p = 0.279). The 1-, 5-year overall survival rates were 89.5% and 66.2% for group 1 and 87.5% and 53.1% for group 2 (p = 0.786). Cirrhosis, the preoperative aspartate aminotransferase (AST) level and lower resected liver weight were independent factors impairing survival.
Conclusion: Hemi-/extended and central hepatectomies have comparable complication rates and long-term survival rates for patients with centrally located large HCC. Cirrhosis, the AST level and resected liver weight were independent factors determining long-term survival.