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9 result(s) for "MERAM, ANDREW T."
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Cystathione β-Synthase Is Increased in Thyroid Malignancies
Cystathione β-synthase (CBS) catalyzes the conversion of homocysteine and cysteine to hydrogen sulfide (H S) and cystathione, via the trans-sulfuration pathway. CBS protein expression levels are increased in several different human malignancies, with increased protein expression correlating with parameters such as tumor stage, anaplasia, metastases, and chemotherapy resistance. This study employed tissue microarrays to examine CBS expression in benign thyroid tissue, thyroid oncocytomas, thyroid follicular adenomas, and in follicular, papillary, anaplastic, and medullary thyroid carcinomas. CBS expression was increased in all thyroid carcinomas types compared to benign thyroid tissue, but not in thyroid follicular adenomas or oncocytomas. A similar pattern was observed for nicotinamide phosphoribosyltransferase (NAMPT) tissue microarray analysis comparing thyroid adenomas and follicular carcinomas. For the first time, we showed that an H S-syntheszing enzyme plays a role in thyroid malignancies. Additionally, our data suggest that CBS and NAMPT immunohistochemistry may be useful in differentiating follicular adenomas from follicular carcinomas.
Nicotinamide Phosphoribosyl Transferase Is Increased in Osteosarcomas and Chondrosarcomas Compared to Benign Bone and Cartilage
Primary bone neoplasms include osteosarcomas (OS), chondrosarcomas (CS), and giant cell tumors (GCT). Nicotinamide phosphoribosyl transferase (NAMPT) catalyzes the rate-limiting step of nicotinamide adenine dinucleotide synthesis and is increased in multiple tumor types. In malignancies, NAMPT expression often correlates positively with tumor grade, chemotherapy resistance, and metastatic potential. Tissue microarray was used to examine NAMPT expression in benign bone and cartilage, GCTs, OS, and different CS grades. For the first time, we showed that NAMPT expression was increased in GCTs and OS compared to benign bone, and in CS compared to benign cartilage. Its expression also increased with higher CS grade. Our data indicate that NAMPT plays a role in bone sarcomas and GCTs, and its higher expression may contribute to increased tumor aggressiveness.
Lingual Alveolar Soft Part Sarcoma in a 78-Year-Old Woman: A Case Report and Comprehensive Review of the Literature from 1952 to 2022
Background Alveolar soft part sarcoma (ASPS) is a rare translocation-related soft tissue sarcoma, occurring mainly in the limbs and trunk in young adults and adolescents. ASPS is rarely seen in the head and neck and one fourth of those cases described are tongue primary. Given its nonspecific symptoms, clinical findings, and rarity in this location, lingual ASPS (L-ASPS) has been reported to be commonly misdiagnosed as various benign tumors, leading to adverse outcomes. Methods We report a case of L-ASPS occurring in the oldest (78 years) female patient published to date and comprehensively review the literature from 1952 to 2022. Results She presented with a slow-growing (2-year duration) tongue mass, measuring 3.5 cm on palpation. Intraoperative frozen section could not render the definitive diagnosis. The pathological findings of the tumor were characteristic of ASPS with eosinophilic polygonal cells in an organoid/nested pattern, rich sinusoidal capillaries, and TFE3 immunoreactivity, except for the strong diffuse aberrant cytoplasmic CD68 immunoexpression and absence of intracytoplasmic crystalline inclusions on PAS with diastase. After TFE3 gene rearrangement had been identified with fluorescent in-situ hybridization, reflex testing confirmed a rearrangement of TFE3 gene with the known fusion partner ASPSCR1 . Conclusions ASPS should be included in the differential diagnoses in cases of any slow-growing lingual masses (especially vascular ones) with non-specific clinical pictures, regardless of the patient’s age.
Hydrogen Sulfide Is Increased in Oral Squamous Cell Carcinoma Compared to Adjacent Benign Oral Mucosae
Hydrogen sulfide (H S) and the enzymes that synthesize it, cystathionine-b-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate, are increased in different human malignancies. Due to its short half-life, H S concentrations have not been directly measured in a human malignancy. Here we directly measured in vivo H S levels within oral squamous cell carcinoma (OSCC). Punch biopsies of OSCC and benign mucosae from 15 patients were analyzed by HPLC, western blotting, and tissue microarray analyses. H S concentrations were significantly higher in OSCC compared to adjacent benign oral mucosae. Western blot and tissue microarray studies revealed significantly increased cystathionine-b-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate, phopho-Stat3, mitoNEET, hTERT, and MAPK protein levels in OSCC. H S concentrations and the enzymes that synthesize it are significantly increased in OSCC. Here, for the first time H S concentrations within a living human malignancy were measured and compared to adjacent counterpart benign tissue.
Panfacial and Naso‐Orbito‐Ethmoid (NOE) Fractures
The facial skeleton receives support and stability from a series of transverse and vertical facial buttresses. Facial buttresses represent areas of thick bone that support the surrounding thinner facial bones, sustain masticatory forces, and protect vital structures. Restoration of facial width, height, and projection is achieved by reducing and reconstructing the facial buttresses. The patient is prepped and draped to allow for visualization of all involved structures and normal adjacent anatomy. Naso‐orbital‐ethmoidal (NOE) fractures are reduced and fixated by reconstructing the nasomaxillary vertical facial buttresses and the superior and middle transverse facial buttresses. Complications are specific to the bones and structures involved as panfacial and NOE‐type fractures involve numerous facial regions. Important anatomical landmarks include knowledge of the correct horizontal and vertical buttresses of the craniomaxillofacial skeleton. In cases involving mandible fractures, physiotherapy is utilized to prevent and/or address postoperative trismus and ankylosis of the condyles.
Development and validation of a structured survey questionnaire on knowledge, attitude, preventive practice, and treatment-seeking behaviour regarding dengue among the resident population of Sabah, Malaysia: an exploratory factor analysis
Background Several studies have reported a significant association of knowledge, attitude and preventive practice (KAP) regarding dengue infection among community’s resident in endemic areas. In this study we aimed to assess and develop a reliable and valid KAP survey on the subject of dengue that is suitable for the resident population of Sabah, Malaysia. Methods A community-based cross-sectional study was conducted from October 2019 to February 2020 involving 468 respondents. Information on the socio-demographic characteristics of the participants (six items), their KAP (44, 15 and 18 items on knowledge, attitude and practice, respectively) and treatment-seeking behaviour (five items) towards dengue was collected using a structured questionnaire. Data analysis was performed using SPSS and R software in the R Studio environment. The knowledge section was analysed by two-parameter logistic item response theory (2-PL IRT) using ltm package. The construct validity and reliability of items for sections on attitude, practice and treatment-seeking behaviour were analysed using psy package. Results For the knowledge section, only 70.5% (31/44) of items were within or close to the parameter acceptable range of −3 to + 3 of difficulty. In terms of discrimination, 65.9% (29/44) of items were within or close to the acceptable range of 0.35 to 2.5, and 24 items (54.5%) failed to fit the 2-PL IRT model (P < 0.05) after assessing by goodness-of-fit analysis. Only eight items were reliable and retained in the attitude section with a Kaiser–Meyer–Olkin (KMO) test value of > 0.7, while based on the communalities, 11 items in the attitude section were excluded due to very low h2, factor loading values and low correlation with the total (< 0.5). The practice section was found suitable for factor analysis because the KMO value was > 0.7. The communalities of the practice section showed that seven items had low h2 values (< 0.3), which were therefore excluded from further analysis, and only 11 items were retained. Conclusions The KAP items retained in the final version of the survey were reliable and valid to be use as a questionnaire reference when conducting future similar studies among the population of Sabah.
Hydrogen Sulfide and Hydrogen Sulfide-Synthesizing Enzymes Are Altered in a Case of Oral Adenoid Cystic Carcinoma
Adenoid cystic carcinomas (ACC) constitute 1% of all head and neck malignancies and are very rare in the oral cavity. With < 60 oral ACCs described, their pathobiology is incompletely understood. Here, we report a case of oral cavity ACC in a 54-year-old woman. Since recent studies have demonstrated that several human tumors overexpress the hydrogen sulfide (H 2 S)-synthesizing enzymes cystathionine-β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), and also show dysregulated H 2 S levels, we examined these biomarkers in the oral ACC and compared the results to those of adjacent benign oral epithelium. Western blotting was used to compare the protein expression of CBS, CSE, 3-MST, nicotinamide phosphoribosyl transferase, and mitoNEET in ACC and adjacent benign oral mucosae. High-performance liquid chromatography was used to quantify the differences in tissue H 2 S concentrations between the two biopsy types. We found that all the proteins examined here were increased in the ACC compared to adjacent benign oral mucosae. Interestingly, H 2 S concentrations were decreased approximately 30% in ACC compared to benign mucosae. Thus, in one example of this rare tumor type, the enzymes that synthesize H 2 S are increased, while tissue H 2 S levels are lower than those found in adjacent benign oral mucosae. Although limited to a single rare tumor type, to our knowledge this is the second time H 2 S concentrations have been directly quantified inside a human tumor. Last, our results may indicate that alterations in H 2 S synthesis and metabolism may be important in the pathobiology of ACC.
Hydrogen Sulfide-Synthesizing Enzymes Are Altered in a Case of Oral Cavity Mucoepidermoid Carcinoma
Mucoepidermoid carcinoma (MEC) is the most common malignant epithelial neoplasm of the salivary glands. MECs of the mouth floor are rare, with only a few cases reported. Here we report a MEC of the mouth floor in a 55-year-old woman. Since several studies have shown that hydrogen sulfide (H 2 S)-synthesizing enzymes are often increased in malignant tumors compared to benign counterpart tissues, we used western blotting to compare the protein levels of cystathionine-β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) in a mouth floor MEC to adjacent benign oral mucosae. We also used high-performance liquid chromatography to quantify possible differences in tissue sulfur fraction concentrations between the two biopsy types. Last, we used western blotting to examine nicotinamide phosphoribosyl transferase (Nampt), mitoNEET, and phospho-ser727-Stat3 levels in the biopsies. We found that all the proteins and phospho-ser727-Stat3 are increased in the MEC compared to benign mucosae. Interestingly, free H 2 S levels, acid-labile, and the sulfane sulfur factions were essentially the same between the MEC and benign tissue. Although limited to a single and unusual tumor type, to our knowledge this is only the third time H 2 S concentrations were directly quantified inside a human tumor. Last, our results replicate those of two previous studies where the H 2 S-synthesizing enzymes are increased in a malignant tumor, while free H 2 S is either not increased or only slightly increased, suggesting that malignant tumors rapidly metabolize H 2 S as part of tumor maintenance and growth.