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A survey of 37 cases with basal ganglia calcification (BGC): CT-scan findings of BGC and its relationship to underlying diseases and epilepsy.

Thirty-seven cases that showed bilateral basal ganglia calcification (BGC) were found in 5987 patients. These cases (0.6%) were studied in relation to their CT findings, underlying diseases and epilepsy. CT findings of BGC were divided into "localized" type (33 cases) and "diffuse" type (4 cases). The number of patients with the "localized" type clearly seemed to increase with age. The M:F ratio of the "localized" type was 1:2. The "localized" type was seen in both idiopathic BGC and familial BGC. The "diffuse" type was seen in hypoparathyroidism only. The specific relationship of these two types of BGC to underlying diseases, however, does not fully agree with results so far reported. We experienced a case with familial BGC during this study that appears to be only the 15th so far reported. Partial epilepsy occurred in 75% of epilepsy with BGC, but there seemed to be no direct relationship between BGC and epileptogenicity.

Basal Ganglia Diseases

[Biologic effects of Tween 80 in combination with hyperthermia on human stomach cancer cell line BGC-823].

Cells of human stomach cancer cell line BGC-823 were treated with Tween 80 and hyperthermia 39 degrees C to 43 degrees C for 20 to 100 minutes. Normal human fibroblasts and mitomycin C were used as controls. The results showed Tween 80 greatly reduced the activation energy of BGC-823 cells. Synergistic effect was observed if applied with heat 39 degrees C. With the increase in temperature and time, the inhibitory effect on the cancer cells was gradually intensified. The lethal rate of heat 41 degrees C associated with Tween 80 was 5.2 times as that of heat alone. The inhibitory effect of heat 41 degrees C for 100 minutes combined with Tween 80 was equivalent to 43 degrees C for 100 minutes. In other words, the heat critical Temperature of BGC-823 cells was reduced about 2 degrees C. The measurement of membrane fluidity, SDH activity and the rest also showed heat 41 degrees C produced the highest synergy with Tween 80. The specific and sustained action exceeded that of mitomycin C. The response of the normal cells was mild and reversible. These studies suggest that the synergistic mechanism of Tween 80 and hyperthermia possibly lies on the cell plasma membrane system.

Humans

[Chromosomal localization of transforming oncogene BGC-Ha-ras in gastric cancer cell line].

BGC-Ha-ras, isolated from the human gastric cancer cell line BGC-823 and activated by point mutation, is a transforming oncogene. To study whether this oncogene can still be located in the original position of chromosome 11 of BGC-823 cell line, chromosomal in situ hybridization method was used. The results showed that 31% silver grains were localized on chromosome 11, 83% of which on the 11p15 region, and in addition, 10% grains on distal end of the short arm of the other abnormal chromosome. Such results are significant in further study of the relation between gene localization and carcinogenesis.

Cell Line, Transformed

[The relationship between metastatic phenotype and steady expression of BGC-Ha-ras oncogene from metastasis cell lines in nude mice (abstract)].

NIH/3T3 cells transformed by activated BGC-Ha-ras (6.6 kb) with a point mutation at codon 12 were able to induce tumor in nude mice with lung metastasis. The metastatic phenotype seemed stable in vivo metastasis assay. After two round subculture of the successively induced metastasis foci, two cell lines, GCM-1/3T3 and GCM-2/3T3, were established. In Southern blot analysis it was found that the bands from GCM-1/3T3 and GCM-2/3T3 were the same. Based on Southern analysis and polymerase chain reaction-restriction fragment length polymorphism (PCR-RPLF), it was proved that the activated c-Ha-ras (6.6 kb) existed all along in the genomes of the transformed and metastatic culture cells. Amplification and over-expression of activated c-Ha-ras were shown by DNA and RNA dot blot hybridization in transformed and metastatic culture cells. The metastatic phenotype might be related to the existence and steady expression of the point mutated ras.

Animals

Development of early bovine embryos to the blastocyst stage in serum-free conditioned medium from bovine granulosa cells.

Bovine granulosa cell-conditioned medium (BGC-CM) was prepared in a serum-free medium consisting of TCM 199, 5 micrograms/ml insulin, and 0.5 micrograms/ml aprotinin (TCM 199 IAP). Granulosa cells surrounded with embryos were denuded 24 to 30 h after in vitro fertilization. The proportion of denuded granulosa cell-free embryos that developed to the blastocyst stage in BGC-CM (43/219; 20%) as well as in the co-culture system (43/178; 24%) was significantly greater (P less than 0.001) than in fresh TCM 199 IAP medium (FM: 10/191; 5%), whereas the proportion of embryos that developed to the eight-cell stage was similar (P greater than 0.05) in all three culture systems (95/178; 53% in co-culture, 111/219; 51% in BGC-CM, and 86/191; 45% in FM, respectively). Higher rates of hatching and hatched blastocysts 8.5 days after in vitro fertilization were observed in co-culture (13/44; 29.5%) and in conditioned medium (8/39; 20.5%). On the other hand, no hatching or hatched blastocysts were obtained in the fresh medium (0/7; 0%). Cell numbers per blastocyst in BGC-CM (178.3 cells/blastocyst) were approximately two-fold higher than those in FM (97.1 cells/blastocyst). However, higher cell numbers (249.3 cells/blastocyst) were observed in co-culture with BGC than in BGC-CM. The embryotrophic activity in BGC-CM was stable upon freezing and thawing, lyophilization, and heating at 56 degrees C whereas activity was reduced by dilution in fresh medium, dialysis, pronase digestion, and heating at 80 degrees C. These results suggest that BGC cultured in a serum-free medium can synthesize and secrete an embryotrophic factor(s) that supports blastocyst formation in vitro beyond the 8- to 16-cell stage.

Animals

Calcification of the basal ganglia in Down's syndrome and Alzheimer's disease.

The prevalence and severity of calcification in the basal ganglia (BGC) has been examined histopathologically in 194 patients divided into ten diagnostic categories. The prevalence and severity of BGC was greater (for age) in Down's syndrome and in patients under 75 years of age with Alzheimer's disease. The severity, but not the prevalence, of BGC was greater in Down's syndrome than in patients of similar age with Alzheimer's disease. Both the prevalence and the severity of BGC in patients over 75 years of age with Alzheimer's disease were as expected for age alone. The increased prevalence and severity of BGC in Down's syndrome and in younger patients with Alzheimer's disease appeared not to be related to the presence of dementia or degenerative disease per se, nor was it affected by the presence of cerebral infarction. BGC may result from an age-related disturbance of the structure of arteries within the globus pallidus, which is accelerated (or occurs prematurely) in Down's syndrome and in younger patients with Alzheimer's disease, but probably does not form part of that spectrum of changes that constitutes the pathological basis of Alzheimer's disease.

Adolescent

Clinicopathologic and immunohistochemical characteristics of bronchial gland cell type adenocarcinoma of the lung.

Twenty-three cases of bronchial gland cell (BGC) type lung adenocarcinoma were examined clinicopathologically and immunohistochemically. BGC type adenocarcinoma was defined as adenocarcinoma showing histologic and cytologic differentiation toward the bronchial gland. This type of adenocarcinoma occurred more frequently in younger patients (mean age, 50.5 years) than in patients with other types of adenocarcinoma (mean age, 60.1 years). It had a tendency to arise from relatively large bronchi and show endobronchial growth. However, there was no difference in disease stage based on tumor, nodal involvement, metastases (TNM) factors and outcome between BGC type adenocarcinoma and peripheral type adenocarcinoma. Immunohistochemically, 50%, 68%, and 64% of BGC type adenocarcinomas were positive for carcinoembryonic antigen, surfactant apoprotein, and secretory component, respectively. Peripheral type adenocarcinomas showed similar rates of immunohistochemical stainability of these antigens. The positive reaction of BGC type adenocarcinomas with anti-surfactant apoprotein antibody may indicate maintenance of traces of differentiation toward peripheral airway epithelium. Lactoferrin is characteristically detected in BGC type adenocarcinomas, although the positive rate was not very high.

Adenocarcinoma, Bronchiolo-Alveolar

Benchmarking methods for measuring biosynthetic gene cluster similarity and determination of gene cluster families.

MOTIVATION: Natural products are often produced by a set of biosynthetic enzymes that are encoded by genes clustered together in the producer's genome, referred to as a biosynthetic gene cluster (BGC). The ability to compare and cluster BGCs is essential for several applications, including predicting which bacteria will make a known product and assessing the potential diversity of natural products produced by a set of bacteria. There are multiple methods for comparing and clustering BGCs based on their similarity, but there has been a lack of investigation into how strongly BGC similarity relates to product structural similarity and how these methods perform relative to each other. RESULTS: Using publicly available databases, we developed a benchmark dataset to assess how well different BGC similarity metrics correlate with the structural similarity of their products and how well these methods cluster BGCs. We found that all methods showed moderate correlation between BGC and structural similarity, with correlations improving for more similar BGCs and varying significantly by BGC biosynthetic class. Analysis of outliers revealed some outliers were due to mistakes or omissions in public datasets, while others represented deviation between BGC similarity and product structural similarity. All methods generally performed better on clustering metrics, with BiG-SCAPE performing the best after errors in the public datasets had been corrected. AVAILABILITY AND IMPLEMENTATION: Scripts and data required to reproduce the results are available at https://github.com/aswalker-lab/BGC-clustering-benchmark and processed similarity, clusters, and scaffolds are also available at https://huggingface.co/datasets/allie-walker/BGC-clustering-benchmark. Code is also available at Zenodo: 10.5281/zenodo.17373546.

Multigene Family

The high rate of prevalence of CT-detected basal ganglia calcification in neuropsychiatric (CNS) brucellosis.

Of 65 cases presenting with neuropsychiatric manifestations of brucellosis (CNS-brucellosis), 9(13.8%) had CT-detected basal ganglia calcification (BGC). Of these, 5 had meningitis and 4 had psychiatric manifestations as presenting features. The diagnosis of brucellosis was made by the finding of consistent history and physical findings and the presence of significantly elevated antibody titres and/or positive culture in the blood and/or CSF. In all the cases, BGC was in the form of punctate hyperdense non-enhancing shadows with average density 44.5-58.4 and maximum density 49-64HU. The calcification was unilateral in 3 cases, bilateral and symmetrical in 4 and bilateral but asymmetrical in 2. None of the cases had other predisposing conditions to BGC and in one of the cases did specific anti-brucella treatment effect a detectable change in the BGC. The finding of CT-detected BGC in patients coming from areas endemic for brucellosis should alert physicians to the possibility of underlying brucellar infection.

Adolescent

[Experimental study of composites of bovine bone morphogenetic protein and bio-active glass ceramic implanted into surgically produced periodontal bony defects in dogs].

Bovine bone morphogenetic protein (bBMP) was incorporated with bio-active glass ceramic (BGC). The composite of bBMP-BGC and BGC were implanted into the surgically produced periodontal osseous defects in dogs. Observations at 10, 16, 20, and 24 weeks show that the implants of BMP-BGC have the ability of bone induction and enhance the regeneration of periodontal bony defects in a relatively short time, but the implants of BGC alone only have the ability of bone-conduction, these is no bone-induction ability, and made a more long time in repairing the periodontal bony defects.

Animals

Fine-grained structural classification of biosynthetic gene cluster-encoded products.

MOTIVATION: Biosynthetic gene clusters (BGCs) are responsible the biosynthesis of many natural products, including a multitude of effective therapeutics and their precursors. Advances in genomic data collection as well as computational techniques have made it possible to identify BGCs at scale. However, accurately determining the types of BGC-encoded products from genomic content remains elusive. RESULTS: Here, we introduce BGC annotation tool (BGCat), a machine learning method for fine-grained structural classification of BGC-encoded products, leveraging the NPClassifier natural product nomenclature. Our method leverages a pre-trained protein language model for creating meaningful gene representations and a deep neural network for class label prediction. We show the method outperforms state-of-the-art approaches in coarse-grained product classification and is effective for detailed classification. We implement a clustering-based augmentation strategy for BGC-product relationships, addressing a crucial gap in the available datasets. We then introduce the concept of product class profiles of gene cluster families (GCFs), associating each GCF with a probabilistic distribution of product types and offering a new perspective on GCF functions. Lastly, we use BGCat to provide new product class labels for over 100k BGCs in antiSMASH DB that presently have minimal information about their products. AVAILABILITY AND IMPLEMENTATION: The source code and trained model weights are freely available at https://github.com/HassounLab/BGCat.

Multigene Family

Alveolar ridge augmentation with bioactive glass ceramics: a histological study.

A particulate BGC (bioactive glass ceramics), has been developed as a new bone graft biomaterial for alveolar ridge augmentation and has been evaluated by simulated animal models. Five beagle dogs were used in this investigation. Prior to augmentation the mandibular posterior teeth of the animals were extracted. Three months after the extractions, the porous BGC particles were packed into the subperiosteal tunnels in the ridges with a special syringe. The animals were killed at different time intervals and the specimens were examined by light microscopy, scanning electron microscopy (SEM), and X-ray energy dispersive analysis (EDAX), respectively. The results of this study indicate that the BGC particles are firmly combined with the adjacent hard and soft tissues by the bone bonding interface between the implants and the alveolar bone, and by the ingrowth of bone or fibrous connective tissue into the interspaces and the pores of the particles. The results have demonstrated that particulate BGC with pores is an excellent implant material for alveolar ridge augmentation because of its very good biocompatibility.

Alveolar Process

Significance of basal ganglia calcification on computed tomography in children.

We reviewed 6,428 head computed tomography (CT) scans performed on 4,283 children at our institution over a 3-year period and found basal ganglia calcification (BGC) in 48 (1.1%) of the patients. Their mean age at the time of detection was 5.3 years (range: 0.5-20 years); 16 (33%) patients had cancer, 14 (29%) had tuberous sclerosis or congenital infection and 18 (38%) had other medical conditions. All patients with cancer had been treated with radiation therapy, receiving a mean dose of 4,583 cGy (range: 1,800-5,500 cGy) to the diencephalon, and calcifications first became apparent at a median of 10 months after treatment. Other medical conditions included neonatal asphyxia (3), metabolic disease (3) (Kearns Sayre, MELAS, Krabbe's), congenital anomalies (3), meningitis (2), Fahr's disease (1) and others (6). Neurologic symptoms were common in children of all groups, but could not be correlated to BGC changes. Calcium and phosphorus metabolism was evaluated in 19 patients and was abnormal in 1. We conclude that BGC on CT in childhood occur primarily as an aftermath of the cancer treatment or in children with generalized neurologic dysfunction. Many children with BGC are delayed in their development, but calcifications are not directly related to specific forms of neurologic dysfunction. Rather, ther appear to serve as markers for more extensive brain damage.

Adolescent

[Expression of the surface antigen in human gastric cancer cells and the relation to cell cycles--correlated analysis with flow cytometry].

Expression of tumor-associated antigen in different gastric cancer cell lines and different phases of cell cycle was studied cytochemically. The antigen was recognized by the monoclonal antibody (McAb) PC1 against gastric cancer cells. By using the McAb PC1 as first antibody, the indirect immunofluorescence stain and the peroxidase-anti-peroxidase (PAP) stain were done on the gastric cancer cell lines (MGC 803, SGC 7901 and BGC 823). It was shown that PC1 antigen was mainly expressed on the membrane of these cells and only a certain percentage of the cells gave the positive reaction with different intensities. It was obvious that the expression of PC1 antigen was heterogeneous in nature. The heterogeneity of the PC1 antigen expression in gastric cancer cells might be due to either various subpopulations in the cell lines or different phases of cell cycle. In order to go further into the question, we studied quantitatively the expression of PC1 antigen in gastric cancer cell lines (MGC 803, STC 7901 and BGC 823) and the relationship between the antigen expression and cell cycle by double fluorescence stain and two-dimensional flow cytometry. It was found that expression levels of PC1 antigen in these cell lines were in the following order: MGC 803 greater than SGC 7901 greater than BGC 823. The PC1 antigen predominantly expressed on G1 phase for MGC 803 and G1, G2-M phase for SGC 7901 respectively. And uniform low level of PC1 antigen expression was found for BGC 823 throughout the cell cycle. Therefore, the PC1 antigen expression is dependent on cell cycle in MGC 803 and SGC 7901 cell lines.

Antigens, Neoplasm

Genetic background of neurological disorders with basal ganglia calcification.

BACKGROUND: Bilateral basal ganglia calcifications (BGCs), if severe, are known hallmarks for idiopathic BGC disease (IBGC), but if milder, are often considered radiological findings of unknown significance. In previous studies, only a minority of patients with BGC had monogenic forms of IBGC. METHODS: We studied consecutive patients from a tertiary neurology clinic with bilateral BGCs of variable severity, and their families. We analyzed known IBGC genes, and an extended panel of genes linked to monogenic stroke and metabolic conditions. Clinical, radiological, and genetic data were collected, including vascular risk factors, cerebrovascular events, imaging findings (total calcification score, white matter hyperintensities, ischemic/hemorrhagic lesions), and relevant family history. RESULTS: Twenty-four families with BGCs and neurological symptoms were analyzed. Disease-causing variants were identified in 14 families (58.3%). Eight patients had IBGC (variants in SLC20A2, PDGFB, MYORG), 4 had mitochondrial disease (MT-TL1), and 2 had monogenic vascular conditions (GAL, MAP3K6). Three variants were novel. BGC severity was highest in IBGC cases, while vascular and mitochondrial cases had milder calcifications. White matter hyperintensities were seen in 94.7% of cases and correlated highly with the total calcification score. Clinical vascular events had occurred in 41.7% cases. No monogenic cause was found in 10 patients, although many of these showed clinical or radiological features suggestive of monogenic disease. CONCLUSIONS: Bilateral BGCs can occur in many neurogenetic disorders apart from IBGCs, and a broader genetic search increases the diagnostic yield. Patients with BGCs frequently had clinical cerebrovascular events, which emphasizes the role of cerebrovascular pathology in BGCs.

Humans

Biosynthesis and Glycosylation of Antarlides, the Polyene Macrolides Possessing Androgen Receptor Antagonistic Activity.

Antarlides (ATLs) are tetraene macrolides discovered from Streptomyces spp. They demonstrated excellent antagonist activities toward mutated androgen receptors (ARs) related to the drug resistances in AR-targeted prostate cancer treatment. Herein, a biosynthetic gene cluster (BGC) of type I modular polyketide synthases (PKSs) from S. conglobatus ATCC 31005 was verified to be responsible for the biosynthesis of ATLs in the heterologous host S. lividans SBT5. The atl BGC was also activated in situ in S. conglobatus by equipping a strong promoter for the PKS genes operon. Unexpectedly, a new glycosylated product, ATL D1, was produced in the heterologous expression. ATL D1 was also generated in the S. conglobatus mutant bearing activated atl BGC through the introduction of a GT1 family glycosyltransferase gene mgt from S. lividans. Enzymatic analysis showed that the protein MGT catalyzed the glycosylation of ATL D to yield ATL D1 by attaching a β-d-glucose to the C11-hydroxyl position. Moreover, site-directed mutation of MGT resulted in an iterative glycosylation to yield ATL D2 bearing a disaccharide at the C11-hydroxyl. These results offer a platform for constructing efficient biosynthetic pathway of ATLs, and the O-glycosylation could be applied to improve the pharmaceutical properties of ATLs.

Glycosylation

Multichassis Expression of Cyanobacterial and Other Bacterial Biosynthetic Gene Clusters.

Heterologous expression of biosynthetic gene clusters (BGCs) is a powerful strategy for natural product (NP) discovery, yet achieving consistent expression across microbial hosts remains challenging. Here, we developed cross-phyla vector systems enabling the expression of BGCs from cyanobacteria and other bacterial origins in Gram-negative Escherichia coli, Gram-positive Bacillus subtilis, and two model cyanobacterial strains including unicellular Synechocystis PCC 6803 and filamentous Anabaena sp. PCC 7120. Following validation using constitutive and inducible expression of the enhanced yellow fluorescent protein (eYFP), we applied these vectors to express the shinorine and violacein BGCs in all four hosts. Promoter tuning, substrate feeding, BGC refactoring, and inducible control enhanced NP production and mitigated host toxicity. Notably, we demonstrated that B. subtilis can serve as a chassis for cyanobacterial NP BGC expression. Our results provide versatile expression platforms for probing BGC function and accelerating natural product discovery from diverse cyanobacterial and other bacterial lineages.

Multigene Family