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At least 811 records · Page 45Linked to original sources
PubMed2006

Vulcanibacillus modesticaldus gen. nov., sp. nov., a strictly anaerobic, nitrate-reducing bacterium from deep-sea hydrothermal vents.

A novel anaerobic, moderately thermophilic, spore-forming bacterium, designated strain BRT, was isolated from deep-sea hydrothermal core samples collected at the Rainbow vent field on the Mid-Atlantic Ridge (36 degrees 14' N 33 degrees 54' W). The cells were found to be rod-shaped, non-motile, Gram-positive and spore-forming. The organism grew in the temperature range 37-60 degrees C, with an optimum at 55 degrees C, and at pH values in the range 6-8.5, with an optimum around pH 7. NaCl concentrations for growth were in the range 10-40 g l(-1), with an optimum at 20-30 g l(-1). Strain BRT grew chemo-organoheterotrophically with carbohydrates, proteinaceous substrates and organic acids with nitrate as electron acceptor. The novel isolate was not able to ferment. The G+C content of the genomic DNA was 34.5 mol%. Phylogenetic analysis of the 16S rRNA gene sequence placed strain BRT in the Bacillaceae within the class 'Bacilli'. On the basis of the phenotypic and phylogenetic data, this isolate should be described as a member of a novel genus, for which the name Vulcanibacillus gen. nov. is proposed. The type species is Vulcanibacillus modesticaldus sp. nov., with the type strain BRT (=DSM 14931T=JCM 12998T).

Atlantic Ocean↗
PubMed2018

Midface toddler excoriation syndrome (MiTES) can be caused by autosomal recessive biallelic mutations in a gene for congenital insensitivity to pain, PRDM12.

BACKGROUND: Midface toddler excoriation syndrome (MiTES) is a condition recently reported in three unrelated children. Habitual scratching from the first year of life inflicted deep, chronic, scarring wounds around the nose and eyes. One child had a mild neurological deficit but there was no other evidence of insensitivity to pain. Bilateral distribution and localization to the midface distinguish MiTES from other causes of self-inflicted skin damage such as trigeminal trophic syndrome. An earlier study of five siblings from a consanguineous Irish family, with lesions corresponding to MiTES plus other sensory deficits, showed homozygous mutations in a gene for hereditary sensory and autonomic neuropathy type VIII (HSAN8), PRDM12. OBJECTIVES: To study further cases of MiTES, including analysis of PRDM12. METHODS: We describe five further children, from four families, with facial lesions typical of MiTES, in whom mutation analysis of PRDM12 was carried out. RESULTS: Homozygous or compound heterozygous pathogenic expansions of the PRDM12 polyalanine tract were found in four of five affected individuals, in three families. CONCLUSIONS: Our finding of autosomal recessive mutations in PRDM12 in four of five patients with MiTES extends the phenotypic spectrum of PRDM12 mutations, which usually cause HSAN8, characterized by mutilating self-inflicted wounds of the extremities, lips and tongue. By contrast, MiTES shows severe midfacial lesions with little if any evidence of generalized pain insensitivity. The condition is probably genetically heterogeneous, and other congenital insensitivity to pain and HSAN genes such as SCN11A may be implicated. This new understanding of the nature of MiTES, which can masquerade as factitious disease, will facilitate appropriate management.

Alleles↗
PubMed1985

Requirements for zygotic gene activity during gastrulation in Drosophila melanogaster.

Mutations at the folded gastrulation (fog) and twisted gastrulation (tsg) loci interfere with early morphogenetic movements in Drosophila melanogaster. fog embryos do not form a normal posterior midgut and although their germbands do elongate, they do not extend dorsally. As a result, when normal embryos have fully extended germbands, the germbands in mutant embryos are folded into the interior on the ventral side of the embryo. tsg embryos have abnormally deep dorsal folds during early gastrulation, associated with the failure of dorsal cells to slip laterally to make way for the expanding germband. Both fog and tsg embryos continue to develop, but form disorganized first instar larvae. fog and tsg are zygotically active genes expressed at least by 10 and 20 min after the onset of gastrulation. Both mutations are viable in homozygous germ cells and the wild-type genes need not be expressed during oogenesis for survival of heterozygous progeny. Elimination of fog+ gene product from maternal germ cells does, however, affect the extent of folding observed during gastrulation in viable heterozygotes. Analysis of fog adult and larval gynandromorphs indicates that normal folded gastrulation gene function is only required at the posterior region of the embryo, most probably in the cells giving rise to the posterior midgut or proctodeum. The relative survival of fog mosaics suggests that embryos with mosaic "lethal foci" also die during embryogenesis, although the typical fog phenotype is only produced when the entire focus is mutant. In contrast to the fog focus, no particular cell must be wild type in tsg mosaics for survival. Wild-type cells on the dorsal side of the embryo, however, are most effective in rescuing the embryo. This indicates that normal tsg gene product may be required only on the dorsal side of the embryo, potentially in the region which gives rise to the amnion serosa.

Animals↗
PubMed2004

Development and distribution of mast cells and neuropeptides in human fetus duodenum.

AIM: To study the developmental regularities and heterogeneity of mast cells (MC) in human fetus duodenum and the distribution and developmental regularities of substance P(SP), calcitonin gene-related peptide (CGRP)-immunoreactive (IR) peptidergic nerves in fetus duodenum, as well as the relationship between MC, SP and CGRP- IR peptidergic nerves. METHODS: Duodena from 21 cases of human fetus and one term infant were stained by hematoxylin-eosin (HE), toluidine blue (TB) and immunohistochemical avidin-biotinylated peroxidase complex (ABC) method. RESULTS: Lobe-shape intestinal villi in duodenum were already developed at the twelfth week. At the 21st wk, muscular mucosa appeared gradually, and four layers were observed in the wall of duodenum. TB staining showed that the granules in the immature MC were pale violet, while the mature MC were strong violet in color by TB staining. Connective tissue MC (CTMC) appeared occasionally in submucosa and muscular layer of duodenum at the 16th wk. While the mucosa MC (MMC) appeared at the 18th wk. At the 22nd wk, both CTMC and MMC were activated, and distributed in the surrounding blood vessels and ganglions. The verge of some MC were unclear, and showed degranular phenomena. At the 14th wk, SP and CGRP-IR nerve fibers and cells appeared in the myenteric and submucous plexuses in small intestine, and the responses were turn strongly. Neurons were light to deep brown, and nerve fibers were present as varicose and liner profiles. On the corresponding site of serial sections, SP and CGRP immunohistochemical reactions were coexisted in one nerve fiber or cell. Some of MC showed SP and CGRP-IR positive staining. CONCLUSION: There are two heterogeneous kinds of MC in duodenum, MMC and CTMC. MC might play an important role in regulating blood circulation and sensation.

Calcitonin Gene-Related Peptide↗
PubMed2003

Clostridium caminithermale sp. nov., a slightly halophilic and moderately thermophilic bacterium isolated from an Atlantic deep-sea hydrothermal chimney.

A strictly anaerobic, slightly halophilic and moderately thermophilic, sporulating rod designated strain DVird3T was isolated from deep-sea hydrothermal vent samples collected at a depth of approximately 800 m on the Atlantic Ocean Ridge. Strain DVird3T possessed a few laterally inserted flagella, had a DNA G + C content of 33.1 mol% and grew optimally at pH 6.6 and at 45 degrees C. Growth was observed at temperatures between 20 and 58 degrees C and at pH values between 5.8 and 8.2. The optimum NaCl concentration for growth was 3% sea salt (30 g l(-1)); no growth was observed in the presence of 15 or 60 g sea salt l(-1). Strain DVird3T is heterotrophic and utilizes some sugars and various single amino acids. Acetate was the main fatty acid detected from carbohydrate fermentation, together with H2 and CO2. Gelatin was used as an energy source. It performed the Stickland reaction. Phylogenetically, strain DVird3T branched with members of cluster XI of the order Clostridiales, with Clostridium halophilum as its closest relative (similarity of 94.6%). On the basis of its phenotypic, genotypic and phylogenetic characteristics, strain DVird3T (= DSM 15212T = CIP 107654T) is proposed as the type strain of a novel species of the genus Clostridium, Clostridium caminithermale sp. nov.

Atlantic Ocean↗
PubMed2004

Anatomy of the pelvic plexus and innervation of the prostate gland.

We have examined the anatomy of the pelvic (inferior hypogastric) plexus in six male cadavers, paying particular attention to gross anatomical landmarks that might aid in locating it and have used immunohistochemistry to study the small branches of the plexus that supply the prostate gland. The pelvic plexus was found two finger breadths lateral to the third anterior sacral foramina, lying deep to a line drawn from third sacral vertebra, the conventional level of the recto-sigmoid junction, and the palpable posterior superior surface of the pubic symphysis. Immunohistochemical staining showed small nerve branches from the pelvic plexus entering the prostate gland and the presence of ganglia within the prostate gland that contained both tyrosine hydroxylase positive and negative neuronal cell bodies. This information may be useful in nerve-sparing surgical procedures and in discussions of the functional implications of perturbations of prostate innervation.

Aged↗
PubMed2004

Frontotemporal dementia with ubiquitinated neuronal inclusions presenting with primary lateral sclerosis and parkinsonism: clinicopathological report of an autopsy case.

We report a case displaying upper motor sign, parkinsonism, and behavioral abnormality, with marked degeneration of the precentral cortex, neostriatum and frontotemporal lobes, as well as ubiquitinated neuronal inclusions. The patient was a 66-year-old male at the time of death. At age 57, he noticed progressive difficulties in speaking and swallowing. At age 60, he was severely anarthric and displayed emotional lability and incontinence. Neurologically, very poor movement of tongue was observed, but without atrophy or fasciculation. Deep tendon reflexes were hyperactive. Grasp reflex and snout reflex were also positive. Needle electromyography revealed no abnormalities. A diagnosis of primary lateral sclerosis and character change was made. At age 62, he developed bradykinesia and rigidity of the neck and all extremities. Treatment with carbidopa-levodopa was initiated, but resulted in minimal improvement. At age 65, he was bed-ridden, and had repeated occurrences of aspiration pneumonia; he died of pneumonia. Neuropathological examination revealed marked atrophy of the frontal and temporal lobes with Betz cells completely absent and moderate atrophy of the neostriatum. The spinal cord and nerve roots appeared normal. Immunohistochemically, ubiquitin-positive but tau-negative intraneuronal inclusions were found in the frontal and temporal cortices, including the precentral cortex and the hippocampal dentate gyrus, and the neostriatum. This case could be included with inclusion-associated disorders such as frontotemporal dementia or amyotrophic lateral sclerosis with dementia, and furthermore, predominant upper motor sign and parkinsonism could represent phenotypes of clinical manifestations with such inclusions.

Cerebral Cortex↗
PubMed1990

Serous surface carcinoma of the peritoneum: a clinicopathologic study of 22 cases.

Serous surface carcinoma (SSC) of the peritoneum is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. In this study of 22 cases of SSC, it was found that the main clinical manifestations of SSC were abdominal pain and enlargement. In most cases, SSC evenly involved the entire mesothelial surface but rarely was predominant in or even limited to the pelvis. It frequently invaded the submesothelium, but deep invasion into abdominal and pelvic organs or local metastasis was rare, and distant metastasis was not seen at presentation. Microscopically, SSC was a high-grade tumor frequently showing high mitotic rate, psammomas bodies, and necrosis. The tumor was usually contiguous with hyperplastic mesothelium on either ovarian surface or other locations. Tumor cells in all cases except one showed cytoplasmic or surface neutral or acidic mucin or both. Tumor cells stained positive for keratin (100% of cases), epithelial membrane antigen (100%), Leu-M1 (45%), B72.3 (85%), vimentin (35%), and carcinoembryonic antigen (25%). Electron microscopic studies of six cases showed epithelial differentiation in each. Seven patients (32%) were alive with no clinical disease at 3 to 31 months, one patient (4%) was alive with extensive local disease at 24 months, 11 patients (50%) died almost exclusively of local recurrence at 1 to 70 months, and three patients (14%) died of operative complications. It is concluded that SSC arises from peritoneal mesothelium but has epithelial phenotype. It can be morphologically differentiated from other conditions with similar laparotomy findings, such as malignant mesothelioma, benign papillary mesothelioma, cystic mesothelioma, and benign or borderline peritoneal serous tumors. The prognosis of SSC is poor, and most patients die of uncontrollable local disease.

Adult↗
PubMed2002

Thioalkalispira microaerophila gen. nov., sp. nov., a novel lithoautotrophic, sulfur-oxidizing bacterium from a soda lake.

An anaerobic enrichment medium (pH 10) with thiosulfate as electron donor and nitrate as electron acceptor was inoculated with sediment from soda lake Fazda (Wadi Natrun, Egypt); a novel strain, ALEN 1(T), was isolated from the subsequent enrichment culture. Cells of strain ALEN 1(T) had a spiral morphology (0.3-0.45 x 1-4 microm), were motile and had a single polar flagellum. Sphaeroplasts were formed by the cells and were rapidly lysed during prolonged aerobic incubation of cultures. Cells of strain ALEN 1(T) contained a membrane-associated yellow pigment. The metabolism of this novel organism was obligately chemolithoautotrophic, and thiosulfate or sulfide were utilized as electron donors. Washed cells of strain ALEN 1(T) oxidized thiosulfate, sulfide, polysulfide and elemental sulfur to sulfate. Best growth was observed when the strain was grown under micro-oxic conditions (1-2% O2 in gas phase), whereas growth was inhibited under fully oxic conditions. Nitrate was reduced to nitrite without growth of the novel organism, but other nitrogen oxides were not utilized as electron acceptors. Strain ALEN 1(T) was alkaliphilic and moderately halophilic. It grew between pH 8 and 10.4 (optimum around pH 10) with a salt concentration of between 0.3 and 1.5 M Na+ (optimum 0-5 M). The maximum growth rate (0.08 h(-1)) of the organism was achieved in a thiosulfate-limited micro-oxic continuous culture (pH 10). Phylogenetic analyses of the 16S rDNA sequences of strain ALEN 1(T) and its closest relatives demonstrated that this strain formed a deep branch within the gamma-Proteobacteria, with no obvious association to any described cluster of species/genera. On the basis of its unique physiological properties and distinct phylogenetic position, it is proposed that strain ALEN 1(T) (= DSM 14786(T) = UNICEM 212(T)) represents a novel genus within the gamma-Proteobacteria, for which the name Thioalkalispira is proposed. It is also proposed that the type species of this novel genus be named Thioalkalispira microaerophila.

Base Sequence↗
PubMed2005

Ancient DNA.

In the past two decades, ancient DNA research has progressed from the retrieval of small fragments of mitochondrial DNA from a few late Holocene specimens, to large-scale studies of ancient populations, phenotypically important nuclear loci, and even whole mitochondrial genome sequences of extinct species. However, the field is still regularly marred by erroneous reports, which underestimate the extent of contamination within laboratories and samples themselves. An improved understanding of these processes and the effects of damage on ancient DNA templates has started to provide a more robust basis for research. Recent methodological advances have included the characterization of Pleistocene mammal populations and discoveries of DNA preserved in ancient sediments. Increasingly, ancient genetic information is providing a unique means to test assumptions used in evolutionary and population genetics studies to reconstruct the past. Initial results have revealed surprisingly complex population histories, and indicate that modern phylogeographic studies may give misleading impressions about even the recent evolutionary past. With the advent and uptake of appropriate methodologies, ancient DNA is now positioned to become a powerful tool in biological research and is also evolving new and unexpected uses, such as in the search for extinct or extant life in the deep biosphere and on other planets.

DNA↗
PubMed2006

Rubellimicrobium thermophilum gen. nov., sp. nov., a red-pigmented, moderately thermophilic bacterium isolated from coloured slime deposits in paper machines.

Six red-pigmented strains of the Alphaproteobacteria with optimal growth between 45 and 54 degrees C were previously isolated from coloured biofilms in two fine-paper machines and one pulp dryer. The strains were found to be resistant to 15 p.p.m. 2,2-dibromo-3-nitrilopropionamide, a common industrial biocide. 16S RNA gene sequence similarity of the isolates was 99.7-100 %. Ribotyping using the restriction enzymes PvuII and EcoRI showed that four of the isolates (C-lvk-R2A-1, C-lvk-R2A-2(T), C-R2A-52d and C-R2A-5d) belong to a single species. 16S rRNA gene-based phylogenetic analysis revealed that, together with Rhodobacter blasticus ATCC 33485(T), the isolates form a deep line of descent (94.7-94.9 % sequence similarity) within the family Rhodobacteraceae loosely affiliated with the Rhodobacter/Paracoccus clade. The isolates were strictly aerobic and oxidase-positive (catalase was weakly positive) and utilized a wide range of substrates including pentoses, hexoses, oligosaccharides and sugar alcohols. The predominant constituents in their cellular fatty acid profiles were C(19 : 0) cyclo omega8c (39-44 %), C(18 : 0) (21-24 %) and C(16 : 0) (21-23 %). Fatty acids present in smaller amounts included C(18 : 1)omega7c, C(10 : 0) 3-OH, C(18 : 1)omega7c 11-methyl, C(20 : 2)omega6,9c and C(17 : 0) cyclo, amongst others. Polar lipids included diphosphatidylglycerol, phosphatidylcholine and an unidentified aminolipid, but not phosphatidylethanolamine. Carotenoid pigments were synthesized but bacteriochlorophyll a was not. The polyamine patterns consisted of the major compounds putrescine, spermidine and sym-homospermidine. The major respiratory lipoquinone was ubiquinone Q-10. The DNA G+C content was 69.4-70.2 mol%. On the basis of the phylogenetic and phenotypic evidence, the biofilm isolates were classified in a new genus, Rubellimicrobium gen. nov.; four of the isolates are assigned to the type species, Rubellimicrobium thermophilum gen. nov., sp. nov. Strain C-lvk-R2A-2(T) (=CCUG 51817(T) = DSM 16684(T) = HAMBI 2421(T)) is the type strain of Rubellimicrobium thermophilum.

DNA, Bacterial↗
PubMed1989

Epithelioid sarcoma or malignant rhabdoid tumor of soft tissue? Epithelioid immunophenotype and rhabdoid karyotype.

Two children and one young adult with extremity sarcomas demonstrating an aggressive clinical behavior are described. Histologically, all three tumors displayed features compatible with a deep-seated epithelioid sarcoma or with a malignant rhabdoid tumor of soft tissue. Immunohistologically, both vimentin and epithelial antigens were demonstrated; however, no desmin was detectable. In all three cases, the DNA profile was diploid. In one case, a trisomy of chromosome 2 was found in the tumor cells, a phenomenon also observed in embryonal rhabdomyosarcomas. It is concluded that, although the immunohistologic findings support the epithelioid character of the tumors, this chromosomal finding suggests a relationship with rhabdomyosarcomas and justifies the designation of rhabdoid.

Adult↗
PubMed2000

Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness.

The human beta(2)-adrenergic receptor gene has multiple single-nucleotide polymorphisms (SNPs), but the relevance of chromosomally phased SNPs (haplotypes) is not known. The phylogeny and the in vitro and in vivo consequences of variations in the 5' upstream and ORF were delineated in a multiethnic reference population and an asthmatic cohort. Thirteen SNPs were found organized into 12 haplotypes out of the theoretically possible 8,192 combinations. Deep divergence in the distribution of some haplotypes was noted in Caucasian, African-American, Asian, and Hispanic-Latino ethnic groups with >20-fold differences among the frequencies of the four major haplotypes. The relevance of the five most common beta(2)-adrenergic receptor haplotype pairs was determined in vivo by assessing the bronchodilator response to beta agonist in asthmatics. Mean responses by haplotype pair varied by >2-fold, and response was significantly related to the haplotype pair (P = 0.007) but not to individual SNPs. Expression vectors representing two of the haplotypes differing at eight of the SNP loci and associated with divergent in vivo responsiveness to agonist were used to transfect HEK293 cells. beta(2)-adrenergic receptor mRNA levels and receptor density in cells transfected with the haplotype associated with the greater physiologic response were approximately 50% greater than those transfected with the lower response haplotype. The results indicate that the unique interactions of multiple SNPs within a haplotype ultimately can affect biologic and therapeutic phenotype and that individual SNPs may have poor predictive power as pharmacogenetic loci.

Base Sequence↗
PubMed1999

Isolation of chloroform-resistant mutants of filamentous phage: localization in models of phage structure.

Interaction of fd or M13 filamentous phage with a chloroform/water interface induces morphological change, contracting the filaments sequentially into shortened rods (I-forms), and then into spheroidal particles (S-forms). To further investigate this phage contraction, 34 and 26 chloroform-resistant isolates of fd and M13, respectively, were selected after chloroform treatment of wild-type phages at pH 8. 2 and 4 degrees C. DNA sequencing of gene VIII of the 34 fd isolates revealed five different mutants: these were D5H, M28L, V31L, I37T, and S50T. All 26 M13 isolates were I37T. These mutants exhibited variable sensitivity to chloroform, but all contracted much more slowly than wild-type phage during treatment at 4 degrees C. They all contracted like wild-type phage at 37 degrees C. Site-directed mutagenesis showed that the indicated single mutations carried the chloroform resistance. In structural models of the phage, the D5H locus is on the outside and the S50T locus is on the inside. The M28L and I37T loci are buried in a mostly hydrophobic region in the middle. Although these four mutants are spread out radially, they are localized in the axial direction into a thin disk in the model. The last mutant locus, V31L, is out of this disk, but this locus is proximal to the M28L and I37T loci and also in contact with the surface via a deep hydrophobic hole or depression. These five mutants, their locations, and their variable affects on contraction suggest that chloroform-induced contraction involves a specific mechanism rather than a generalized solvent-induced denaturation and that the critical structural changes occur in a localized level in the phage. These results add weight to suggestions that the sequential contraction of filaments-->I-forms-->S-forms mimic corresponding steps in phage penetration, and, in the reverse order, for phage assembly.

Bacteriophage M13↗
PubMed2000

Ultrastructural analyses of the Caenorhabditis elegans sqt-1(sc13) left roller mutant.

The sqt-1 gene is 1 of the several loci in Caenorhabditis elegans that primarily affects organismal morphology. Certain mutations in the sqt-1 gene can produce left roller animals, i.e., they rotate around their long axis and move in circular paths. We describe the morphological alterations seen in the cuticle of the left roller sqt-1(sc13). Deep-etched replica analyses showed that the fibrous layer is composed of a unique strand of parallel fibers, instead of the 2 meeting at an angle of 60 degrees as observed in the wild-type strain. In addition, honeycomb elements, fibers organized in a pentagonal fashion above the fibrous layer, completely fill the intermediate layer that is empty spaces in the wild type. These morphological alterations are likely to be involved in generating the helical twist of the sqt-1(sc13) left roller mutant.

Animals↗
PubMed1999

Alteration of sialyl Lewis epitope expression in pterygium.

PURPOSE: Mucin-related antigens are abundantly expressed by the cells of the normal human conjunctiva. The pattern of these antigens in pterygium, and especially the role of Galbeta1-3GlcNAc alpha2,3-sialyltransferase (ST3Gal III), sialyltransferase necessary to build the sialyl-Le(a) (Lewis(a)) antigen, were studied. METHODS: Immunoperoxidase staining was performed on 28 pterygia using different monoclonal antibodies: anti-M1 (against the peptidic core of gastric mucins encoded by MUC 5AC gene), anti-Le(a)(7LE), anti-sialyl Le(a)(NS 19-9), and anti-Le(b)(2-25LE). A serologic Lewis determination was done in 18 patients. ST3Gal III sialyltransferase expression was also studied in 10 healthy conjunctiva and 10 pterygia by reverse transcriptase-polymerase chain reaction (RT-PCR). Glyceraldehyde-3-phosphate-dehydrogenase was used as an endogenous internal control. RESULTS: First, Le(a), sialyl Le(a), and Le(b) immunoreactivities either decreased or were no longer detectable in pterygium goblet cells as opposed to normal conjunctiva. Second, unlike in pterygium, the Lewis immunoreactivity, which is mainly located in the surface epithelial cells in the normal conjunctiva, was occasionally restricted to the epithelial cells of the deep layers. However, M1 mucins did show an identical pattern expression in a normal conjunctiva and pterygium. ST3Gal III expression was significantly lower in pterygium (0.20+/-0.02 AU [arbitrary units]) than in normal conjunctiva (0.95+/-0.12 AU). CONCLUSIONS: ST3Gal III gene is less expressed in pterygium than in normal conjunctiva. This observation could explain the decrease of sialyl Le(a) expression observed in pterygium by immunohistology.

ABO Blood-Group System↗
PubMed2006

Ghrelin and the growth hormone secretagogue receptor constitute a novel autocrine pathway in astrocytoma motility.

Originally thought of as a stomach-derived endocrine peptide acting via its receptors in the central nervous system to stimulate food intake and growth hormone expression, ghrelin and its receptor (growth hormone secretagogue receptor (GHS-R)) are widely expressed in a number of organ systems, including cancer cells. However, the direct functional role of ghrelin and its receptor in tumors of central nervous system origin remains to be defined. Here, we demonstrate that the human astrocytoma cell lines U-118, U-87, CCF-STTG1, and SW1088 express 6-, 11-, 15-, and 29-fold higher levels of GHS-R compared with primary normal human astrocytes. The ligation of GHS-R by ghrelin on these cells resulted in an increase in intracellular calcium mobilization, protein kinase C activation, actin polymerization, matrix metalloproteinase-2 activity, and astrocytoma motility. In addition, ghrelin led to actin polymerization and membrane ruffling on cells, with the specific co-localization of the small GTPase Rac1 with GHS-R on the leading edge of the astrocytoma cells and imparting the tumor cells with a motile phenotype. Disruption of the endogenous ghrelin/GHS-R pathway by RNA interference resulted in diminished motility, matrix metalloproteinase activity, and Rac expression, whereas tumor cells stably overexpressing GHS-R exhibited increased cell motility. The relevance of ghrelin and GHS-R expression was verified in clinically relevant tissues from 20 patients with oligodendrogliomas and grade II-IV astrocytomas. Analysis of a central nervous system tumor tissue microarray revealed that strong GHS-R and ghrelin expression was significantly more common in high grade tumors compared with low grade ones. Together, these findings suggest a novel role for the ghrelin/GHS-R axis in astrocytoma cell migration and invasiveness of cancers of central nervous system origin.

Astrocytoma↗
PubMed2006

Alanine aminotransferase levels and fatty liver in childhood obesity: associations with insulin resistance, adiponectin, and visceral fat.

BACKGROUND: Concurrent with the rise in obesity, nonalcoholic fatty liver disease is recognized as the leading cause of serum aminotransferase elevations in obese youth. Nevertheless, the complete metabolic phenotype associated with abnormalities in biomarkers of liver injury and intrahepatic fat accumulation remains to be established. METHODS: In a multiethnic cohort of 392 obese adolescents, alanine aminotransferase (ALT) levels were related with parameters of insulin sensitivity, glucose, and lipid metabolism as well as adipocytokines and biomarkers of inflammation. A subset of 72 adolescents had determination of abdominal fat partitioning and intrahepatic fat accumulation using magnetic resonance imaging. FINDINGS: Elevated ALT (> 35 U/liter) was found in 14% of adolescents, with a predominance of male gender and white/Hispanic race/ethnicity. After adjusting for potential confounders, rising ALT was associated with reduced insulin sensitivity and glucose tolerance as well as rising free fatty acids and triglycerides. Worsening of glucose and lipid metabolism was already evident as ALT levels rose into the upper half of the normal range (18-35 U/liter). When hepatic fat fraction was assessed using fast magnetic resonance imaging, 32% of subjects had an increased hepatic fat fraction, which was associated with decreased insulin sensitivity and adiponectin, and increased triglycerides, visceral fat, and deep to superficial sc fat ratio. The prevalence of the metabolic syndrome was significantly greater in those with fatty liver. INTERPRETATION: Deterioration in glucose and lipid metabolism is associated even with modest ALT elevations. Hepatic fat accumulation in childhood obesity is strongly associated with the triad of insulin resistance, increased visceral fat, and hypoadiponectinemia. Hence, hepatic steatosis may be a core feature of the metabolic syndrome.

Adiponectin↗