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Short-term plasticity of Bergmann glial cell extrasynaptic currents during parallel fiber stimulation in rat cerebellum.

Bergmann glial cells (BGC) enclose the synapses of Purkinje neurons (PN) and interneurons in the molecular layer of the cerebellar cortex. During synaptic transmission, glutamate evokes inward currents in the glia by activation of Ca2+-permeable aminohydroxymethylisoxazole propionic acid receptors (AMPAR) and electrogenic transporters. We describe the plasticity of BGC currents during paired-pulse and repetitive stimulation of parallel fibers in cerebellar slices. Paired-pulse facilitation (PPF) of BGC AMPAR currents was 4-fold, twice that of PN PPF. Experiments with a low-affinity AMPAR antagonist showed an increase in extrasynaptic glutamate concentration during the second pulse of the pair. PPF of glial transporter currents was 1.8-fold, similar to synaptic PPF. Tetanic stimulation revealed that facilitation of BGC AMPAR currents is not sustained during high-frequency stimulation, and substantial depression is observed after a few pulses. Consequently, Ca2+ influx through glial AMPARs would initially be facilitated but subsequently depressed, generating a transient Ca2+ influx in response to a sustained tetanus. This pattern of plasticity may be important in enabling Bergmann glial cell processes to detect and support synapses with high-frequency input. Finally, a new current was observed in BGC during repetitive stimulation. It was blocked by NBQX and intracellular GDP-beta-S, increased by glutamate uptake inhibition, had PPF similar to synaptic PPF, and was unaffected by an inhibitor of fast glial AMPAR currents. The evidence suggests that activation of neuronal AMPARs causes the release of a paracrine messenger to activate a G-protein coupled receptor in the BGC.

Animals↗

Basal ganglia calcification and psychotic symptoms in the very old.

BACKGROUND: Basal ganglia calcification (BGC) is associated with psychotic symptoms in young and middle-aged patient samples. METHODS: We studied the cross-sectional relationship between psychotic symptoms and BGC in a population sample of non-demented 85-year-olds, of whom 86 were mentally healthy, 11 had hallucinations or delusions, 21 had mood disorders and 20 had anxiety disorders. BGC was measured using computerized tomography (CT). Mental disorders were diagnosed using DSM-III-R criteria and psychotic symptoms were evaluated using information from psychiatric examinations, key-informant interviews and review medical records. RESULTS: BGC on CT was observed in 19% of mentally healthy and 64% of non-demented individuals with hallucinations or delusions [Odds Ratio (OR) 7.7, 95% Confidence Intervals (CI) 2.9-29.7, p=0.003]. There were no associations between BGC and mood or anxiety disorders. CONCLUSIONS: BGC is strongly associated with psychotic symptoms in very old age, possibly due to a disturbance in the basal ganglia dopaminergic system.

Affective Disorders, Psychotic↗

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↗

Fibroblast growth factor stimulates the gene expression and production of tissue inhibitor of metalloproteinase-1 in bovine granulosa cells.

The hormonal control of tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression and production by growth factors, gonadotrophins, and serum factors in cultured bovine granulosa cells (BGC) were investigated. Confluent cultures of BGC were exposed to various factors in a defined medium and levels of TIMP-1 in the conditioned medium were determined by enzyme immunoassay. Basic fibroblast growth factor (bFGF) and acidic fibroblast growth factor (aFGF) showed potent stimulation of cell proliferation and TIMP-1 production by BGC, while insulin stimulated growth but not TIMP-1 production. Basic FGF stimulated TIMP-1 production and BGC cell proliferation in a dose-dependent manner. A time course of TIMP-1 production showed substantially increased levels between 18 and 24 h in both control and bFGF-stimulated BGC cultures with bFGF-stimulated cultures having markedly higher TIMP-1 production at all time points. Consistent with the TIMP-1 production data, bFGF and aFGF increased the expression of TIMP-1 mRNA as determined by northern blot analysis, while insulin, inhibited TIMP-1 mRNA levels. These results indicate that FGF-induced TIMP-1 production by BGC may support bovine embryo development in vitro.

Animals↗

Blood glucose dependence of visual flicker threshold.

BACKGROUND: Published research indicated that fluctuations in blood glucose concentration (BGC) change the biochemical balance of the retina and may alter the sensitivity of retinal cells. Low-contrast flicker was used in this research to measure the changes in sensitivity of the retina accompanying shifts in BGC. METHODS: In five subjects without diabetes and four subjects with diabetes, simultaneous measurements of flicker thresholds, using a two-alternative, forced choice psychometric test, and BGC, were made every 15 to 30 minutes for several hours, while BGC was allowed to fluctuate spontaneously. RESULTS: Flicker thresholds were found to rise and fall, generally tracking BGC in each subject. First-day flicker threshold measurements were used to "calibrate" the method for each subject, and subsequent days' measurements were used to infer blood glucose. The resulting inferred blood glucose values correlated with BGC measured from blood samples in the range of 70 mg/dL to 500 mg/dL with a maximum error of +/-33% in 97% of the measurements. CONCLUSIONS: The feasibility of using flicker sensitivity for monitoring blood glucose levels noninvasively is discussed. Improvements in the testing method can potentially reach +/-18% error margin with 1-minute measurements, according to computer simulations. Devices using a visual test would be inexpensive to manufacture and would need no disposable supplies. Planned research will assess the long-term stability of flicker threshold measurements and will determine the applicability of the technique in diabetic retinopathy, in hypoglycemia and in the presence of fatigue and inattention.

Blood Glucose↗

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↗

Basal-granulated cells in human Brunner's glands.

Basal-granulated cells (BGC) in the human duodenal bulb were observed by light and electron microscopy, and both the cell types and their population densities in the duodenal crypts and in the Brunner's glands were compared. The number of the BGC in the Brunner's glands was much smaller than in the crypts. On the basis of their ultrastructural features, nine types of BGC, i.e. an EC cell, N cell, D cell, D1 cell, S cell, I cell, G cell, L cell and P cell were identified in the human duodenal bulb. In the duodenal crypts, as is generally recognized, EC cells were most numerous, making up 40% of the total BGC. N cells and D cells were around 10% of the total, and S cells, I cells and L cells were less than 10%, respectively. By contrast, in Brunner's glands, D cells and small granule-containing cells such as S cells, I cells and D1 cells were predominant, accounting for about 80% of the total BGC. EC cells and N cells were about 10% or less, respectively. These results indicate that the Brunner's glands are definitely different from the ordinary intestinal mucosa in regard to their BGC population, and are considered to have endocrine functions mainly performed by D1 cells, S cells and I cells.

Adult↗

Assessment of the relationship between glucose and A1c using kinetic modeling.

Treatment goals for diabetic patients are directed towards lowering A1c values by controlling blood glucose concentrations (BGC), making it important to understand the relationship between the two parameters. Because findings from clinical trials about the relationship between BGC and A1c values show a profound variability around the obtained regression lines, they are difficult to apply to individual patients. Therefore, a model was developed and applied based on the kinetics of HbA1c formation and removal. It takes the instability of A1c and loss of hemoglobin into consideration. Data from clinical studies and hypothetical scenarios were used to test the model and to describe the relationship between A1c and BGC. A close agreement between experimental and calculated data was obtained in steady-state and non-steady-state conditions. Aside the erythrocyte life span, the chemical instability of A1c appears to affect A1c levels markedly and their changes due to therapy. A threefold increase in BGC over 30 days prior to A1c measurement can cause an increase in A1c value of about 120% as compared with 4% when it occurs 4 months prior to A1c measurement. Profound daily fluctuations in BGC result in minor changes in A1c. In conclusion, A1c provides information about a patient's glycemia, mainly over the past 2 months, and may not reflect well daily blood glucose fluctuations. This model might be suitable to identify individual differences in glycation rates.

Algorithms↗

Contralateral groin recurrence in patients with stage I Bartholin's gland squamous cell carcinoma and negative ipsilateral nodes: report on two cases and implications for lymphadenectomy.

BACKGROUND: Modalities of inguinal lymphadenectomy in patients with early stage Bartholin's gland squamous cell carcinoma (BGC) remain discussed. The aim of this paper is to report 2 patients with stage 1 BGC and negative ipsilateral groin nodes who developed a contralateral groin recurrence. CASES: Two patients treated for BGC and undergoing an ipsilateral groin nodes dissection (with absence of nodal involvement) presented contralateral groin recurrence. These recurrences were observed 14 and 3 months after the initial treatment in the first and second case. In the first case, the nodal recurrence was associated with a local vaginal recurrence. CONCLUSIONS: These 2 cases suggest that << cross >> groin nodal involvement can occur, even in patients with early stage BGC. Bilateral groin dissection should be performed in patients with BGC.

Adult↗

Tissue inhibitor of metalloproteinases (TIMP-1) produced by granulosa and oviduct cells enhances in vitro development of bovine embryo.

Embryogenesis-stimulating activity (ESA) was found in serum-free conditioned media (CM) of bovine cumulus/granulosa cells (BGC) and bovine oviductal epithelial cells (BOEC). The CM of BGC (BGC-CM) contained two molecular species of ESA, one with a low molecular weight (M(r) 30,000) and another with a high molecular weight (M(r) 80,000); but only the activity with low molecular weight was detected in CM of BOEC by gel-permeation chromatography. The smaller ESA (embryogenin-1) in BGC-CM was purified to homogeneity, as a common activity in both CM by a combination of gel-permeation chromatography, ion-exchange chromatography, and reverse-phase HPLC. Embryogenin-1 has a molecular weight of 31,100 (reduced) and has been identified as a bovine tissue inhibitor of metalloproteinase-1 by NH2-terminal amino acid sequence analysis. Western blot analysis, anti-proteinase activities against metalloproteinases, and the nucleotide sequence of cDNA isolated from a lambda gt11 cDNA library of the bovine ovary by a polyclonal antibody against embryogenin-1. These data suggest that the tissue inhibitor of metalloproteinase-1 produced by BGC and BOEC is a major ESA for in vitro development of bovine embryos.

Amino Acid Sequence↗

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↗

[Apoptosis of human gastric cancer cells induced by bcl-2 antisense oligodeoxynucleotides].

OBJECTIVE: To study the regulation of bcl-2 gene expression and induction of apoptosis by bcl-2 antisense oligodeoxynucleotides (AS-ODN) on human gastric cancer cell line BGC-823 in vitro. METHODS: Two bcl-2 AS-ODNs were synthesized, one covering the initiation sequence of translation of bcl-2 mRNA (AS-ODN1) and the other covering the protein coding region (AS-ODN2). BGC-823 cells in logarithmic phase of growth were cultured in the presence of free or liposome (DOTAP)-encapsulated AS-ODN. Cell growth was assessed by MTT method. The expression of bcl-2 at mRNA and protein levels was examined by RT-PCR and flow cytometry, respectively. Electron microscopy and flow cytometry were used to demonstrate apoptotic changes in AS-ODN-treated cells. RESULTS: Both AS-ODNs inhibited proliferation of BGC-823 cells. The inhibitory activity of AS-ODN2 was stronger than that of AS-ODN1. AS-ODNs encapsulated in liposome led to more marked inhibition of cell growth than free AS-ODNs. Both AS-ODNs reduced bcl-2 expression of BGC-823 cells at mRNA and protein levels. Apoptosis of BGC-823 cells were demonstrated by the appearance of apoptotic bodies, chromatin condensation and pre-G1 peak on flow cytometric analysis. CONCLUSION: Antisense oligodeoxynucleotide of bcl-2 decreases bcl-2 gene expression and induces apoptosis of human gastric cancer cells in vitro.

Apoptosis↗

[Mechanism of retinoic acid receptor alpha-mediated growth inhibition of gastric cancer cells by all-trans retinoic acid].

OBJECTIVE: To study the mechanism of retinoic acid receptor alpha(RAR alpha) in mediating growth inhibition of gastric cancer cells by all-trans retinoic acid(ATRA). METHODS: Expression of RAR alpha was detected by Northern blot. After anti-sense RAR alpha or sense RAR alpha had been transfected into gastric cancer cell lines BGC-823 and MKN-45 respectively, the inhibitory effect of ATRA on cell growth in stable clones was analyzed using MTT assay and colony forming assay in soft agar. The transcriptional activation of retinoic acid response element (RARE) was measured by CAT assay. RESULTS: ATRA could induce expression of RAR alpha in BGC-823 cells, but not in MKN-45 cells. In stable clones, ATRA could inhibit growth of MKN-45 cells transfected with RAR alpha gene, but could not inhibit that of BGC-823 cells transfected with antisense RAR alpha. Transient transfection and CAT assay showed higher beta-RAR response element (beta RARE) transcriptional activation induced by ATRA in MKN-45 cells transfected with RAR alpha compared to parental MKN-45 cells, while lower beta RARE transcriptional activation was seen in BGC cells transfected with antisense RAR alpha gene compared to parental BGC-823 cells. CONCLUSION: Sufficient level of RAR alpha is required for growth inhibition of gastric cancer cells by ATRA.

Antineoplastic Agents↗

[Biocompatibility studies on bioactive glass ceramics and polylactic acid combined with cultured bone marrow stromal cells in vitro].

OBJECTIVE: To study the biocompatibility on bioactive glass ceramics (BGC) and polylactic acid (PLA) combined with cultured bone marrow stromal cells (BMSCs) in bone tissue engineering. METHODS: BMSCs were cultured combined with BGC and PLA in vitro, and the morphological characters, cell proliferation, protein content, and alkaline phosphatase activity were detected. RESULTS: BMSCs could be attached to and extended on both BGC and PLA, and normally grown, proliferated, had active function. BGC could promote cell proliferation. CONCLUSION: The results show that both BGC and PLA have good biocompatibility with BMSCs, they can be used as biomaterials for cell transplantation in tissue engineering.

Animals↗

Correlative microscopy of cerebellar Bergmann glial cells.

Double fluorescent labelling of rat cerebellar cortex using antibody to glial fibrillary acidic protein (GFAP) and Alexa fluor conjugates for secondary detection for confocal laser scanning microscope (CLSM), field emission scanning electron microscopy (FESEM) of Rhesus monkey cerebellar cortex, ultrathin sectioning and freeze-etching replica method for transmission electron microscopy of mouse cerebellar cortex have been examined in an attempt to obtain a new and more accurate view of three-dimensional image of Bergmann glial cells (BGC) and their topographic relations in the molecular layer. Intense immunopositive GFAP green staining was observed in the BGC and glial limiting layer. Secondary antibody conjugated with Alexa fluor 488 and Alexa fluor 668-1B4 stained in red capillary endothelial cells and microglial cells. BGC morphology revealed the existence of several cell types or subpopulations of BGC. Bergmann glial fibers, in palisade arrangement, branch and rebranch forming a complex glial network in the molecular layer. Field emission SEM and freeze-fracture SEM method show the SE-I image of high mass dense Bergmann glial cytoplasm ensheathing like a veil the Purkinje cell (PC) soma and dendritric arborization. Bergmann glial fibers appeared completely surrounding individual parallel fibers or parallel fiber bundles, terminal climbing fiber collaterals, basket and stellate cells and capillaries. Freeze-etching direct replicas showed the typical orthogonal arrangement of intramembrane particles, corresponding to the large repertoire of BGC receptors. The study reveals three-dimensional Bergmann glial cells heterogeneity and the complex network formed by Bergmann glial cells in the molecular layer.

Animals↗

[Translocation of orphan receptor TR3 from nuclei to mitochondria induced by staurosporine].

BACKGROUND & OBJECTIVE: Staurosporine (STS), a non- specific protein kinase inhibitor, can extensively induce cell apoptosis. Orphan receptor TR3, an immediate-early response gene, belongs to the steroid/thyroid receptor superfamily. After stimulated by apoptosis-inducing agents, TR3 is expressed rapidly and translocates from nuclei to mitochondria,which finally induces cell apoptosis. This study was to investigate the mechanism by which STS induces apoptosis of gastric cancer cell line BGC-823,and its correlation with translocation of TR3 in BGC-823 cells. METHODS: Fluorescent microscopy was used to observe apoptotic morphology of BGC-823 cells after treated with STS for 3 and 24 h and stained by DAPI, and determine cell apoptotic rate. Laser scan confocal microscopy and Western blot were performed to investigate translocation of orphan receptor TR3 and the release of cytochrome c. Flow cytometry and confocal microscopy were used to examine mitochondrial membrane potential. RESULTS: After treated for 3 h,and 24 h,apoptosis rates of BGC-823 cells in STS-treatment groups were higher than those of cells in control groups (15.7% vs. 4.0%, and 39.4% vs. 4.7%). After BGC-823 cells exposed to STS for 3 h,TR3 translocated from nuclei to mitochondria, mitochondrial membrane potential was decreased, and cytochrome c released from mitochondria to the cytoplasm. CONCLUSION: TR3, in response to STS, translocates from nuclei to cytoplasm, where it targets to mitochondria to induce cytochrome c release, finally results in apoptosis of gastric cancer cells.

Active Transport, Cell Nucleus↗

[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↗