Vortex fluctuations and interlayer coupling in cuprates.
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Journal Article↗
Biomedical subjects
F Chen
Publications and source records attributed to F Chen.
Antigenic regions of human chromogranin A and their topographic relationships with structural/functional domains.
Chromogranin A is a protein contained in the secretory granules of many neuroendocrine cells. The linear antigenic sites of human chromogranin A were studied by examining the cross-reaction of polyclonal and monoclonal anti-chromogranin A antibodies with native chromogranin A and with synthetic peptides encompassing most of the chromogranin A sequence. Chromogranin A residues 1-20, 47-67, 107-158, 254-297, 331-375, and 395-419 were found to be poorly or not antigenic, while residues 25-46, 163-210, 231-253, 298-314 and 68-106, 222-230, 315-330, 376-394 were found to contain weak and strong antigenic sites, respectively. Residues 68-70 (GAK) and 81-90 (GFEDELSEVL) were strongly recognized by two mouse mAbs (B4E11 and A11, respectively). Since mAb A11 has been previously used for immunohistochemical analysis of chromogranin-A-producing tissues from different species and for in vivo imaging of chromogranin-A-positive endocrine tumors, these results imply that at least part of the 81-90 region is surface-exposed in cryostat tissue sections as well as in vivo. The results may help in selecting new antibodies with improved affinity and immunogenicity for in vivo targeting of chromogranin-A-producing tumors.
Amino Acid Sequence↗
Disruption of DNA-PK in Ku80 mutant xrs-6 and the implications in DNA double-strand break repair.
The Chinese hamster ovary (CHO) mutant cell line xrs-6C is highly sensitive to radiation and is deficient in DNA double-strand break (DSB) repair. The repair defect of xrs-6C is complemented by the human DSB repair gene designated as XRCC5. This gene was recently identified as Ku80, which encodes the human autoantigen protein Ku p80. Ku80 protein forms heterodimer with the Ku70 subunit to form a complex that possesses a DNA end-binding activity. Ku70/Ku80 heterodimer can recruit the catalytic p350 subunit of the DNA-dependent protein kinase. It is demonstrated here that, while the Ku70 mRNA expression is normal in the xrs-6C mutant, Ku70 protein is undetectable. However, introduction of human Ku80 gene into the mutant lead to increased expression of Ku70 protein and restored Ku70 binding to DNA ends, suggesting that mutation of the Ku80 gene affected the formation of Ku70/Ku80 dimers and the stability of the Ku70 protein. We also demonstrated that, although p350 protein expression in the mutants was unaffected, the capacity of p350 to bind to DNA ends was impaired in the mutants. After introduction of the human Ku80 into the mutant, the association of p350 with DNA end was restored, accompanied by recovery in cell survival and DNA double-strand break repair. The results in this report show that mutation of the Ku80 gene disrupts formation of the Ku70/Ku80 dimer and compromises the ability of Ku protein to recruit the DNA-PK p350 subunit to DNA double-strand breaks, causing a dysfunction of DNA DSB repair in the cell.
Animals↗
Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan.
Germline mutation analysis was performed in 469 VHL families from North America, Europe, and Japan. Germline mutations were identified in 300/469 (63%) of the families tested; 137 distinct intragenic germline mutations were detected. Most of the germline VHL mutations (124/137) occurred in 1-2 families; a few occured in four or more families. The common germline VHL mutations were: delPhe76, Asn78Ser, Arg161Stop, Arg167Gln, Arg167Trp, and Leu178Pro. In this large series, it was possible to compare the effects of identical germline mutations in different populations. Germline VHL mutations produced similar cancer phenotypes in Caucasian and Japanese VHL families. Germline VHL mutations were identified that produced three distinct cancer phenotypes: (1) renal carcinoma without pheochromocytoma, (2) renal carcinoma with pheochromocytoma, and (3) pheochromocytoma alone. The catalog of VHL germline mutations with phenotype information should be useful for diagnostic and prognostic studies of VHL and for studies of genotype-phenotype correlations in VHL.
Adrenal Gland Neoplasms↗
Loss of heterozygosity on chromosome arm 3p in nasopharyngeal carcinoma.
We have examined 17 primary undifferentiated nasopharyngeal carcinoma biopsies for allelic loss on 3p, comparing the findings in tumors with those in normal lymphocyte DNA from the same patients. Ten polymorphic microsatellite markers were used between 3p13 and 3p26. Allelic loss was observed in 12 samples (70%). Two loci were most frequently affected: D3S1067 (3p21.1-14.3) in 60% and D3S1217 (3p14.2-14.1) in 58%. One tumor seemed to have a homozygous deletion at 3p26, detected by the D3S1297 marker. Analysis of the clinical data showed that an increased number of aberrations in 3p was correlated with more advanced tumor stages.
Adult↗
Developmental changes in the effects of pH on contraction and Ca2+ current in rabbit heart.
Protons inhibit Ca2+ current and contraction in heart muscle. The present study compares the effects of lowering the pH of the bath solution on single-cell contraction, action potential configuration and Ca2+ currents between neonatal and adult rabbit hearts. We found that a reduction of extracellular pH from 7.3 to 6.3 decreased cell contraction amplitude to 84.3% of control in isolated neonatal myocytes. A comparable change in extracellular pH resulted in a decrease in cell contraction to 56.2% of control in adult cells. Similarly, tension generation in intact neonatal papillary muscles was less sensitive to a decrease in external pH as compared to papillary muscles from adult animals. In addition, acidosis caused a less pronounced inhibition of Ca2+ current in neonatal cells than in adult cells (85 +/- 4% nu 62 +/- 4% of control, pH = 6.3, P < 0.001; 63 +/- 5% nu 32 +/- 5% of control, pH = 5.8, P < 0.001). Thus, the effect of external acidosis on myocardial contractility is commensurate with the effect on trans-sarcolemmal Ca2+ current. The membrane potential at which peak Ca2+ current occurred was not altered by low pH in neonatal cells but was shifted toward positive potentials by 17.7 mV in adult myocytes. Further, low external pH solution reduced Ca2+ current conductance more in adult cells than in neonatal cells. Moreover, action potential configuration in neonatal cells was altered less by acidosis as compared with adult cells. These findings may help explain the greater resistance of neonatal hearts to extracellular acidosis.
Action Potentials↗
Hand and finger skin temperatures in convective and contact cold exposure.
The present study aimed at investigating the spatial variability of skin temperature (Tsk) measured at various points on the hand during convective and cold contact exposure. A group of 8 subjects participated in a study of convective cooling of the hand (60 min) and 20 subjects to contact cooling of the finger pad (5 min). Experiments were carried out in a small climatic chamber into which the hand was inserted. For convective cold exposure, Tsk was measured at seven points on the palmer surface of the fingers of the left hand, one on the palmar surface and one on the dorsal surface of the hand. The air temperature inside the mini-chamber was 0, 4, 10 and 16 degrees C. With the contact cold exposure, the subjects touched at constant pressures an aluminum cube cooled to temperatures of -7, 0 and 7 degrees C in the same mini-chamber. Contact Tsk was measured on the finger pad of the index finger of the left hand. The Tsk of the proximal phalanx of the index finger (on both palm and back sides), and of the middle phalanx of the little finger was also measured. The variation of Tsk between the proximal and the distal phalanx of the index finger was between 1.5 to 10 degrees C during the convective cold exposure to an air temperature of 0 degree C. Considerable gradients persisted between the hand and fingers (from 2 to 17 degrees C at 0 degree C air temperature) and between the phalanges of the finger (from 0.5 to 11.4 degrees C at 0 degree C air temperature). The onset of cold induced vasodilatation (CIVD) on different fingers varied from about 5 to 15 min and it did not always appear in every finger. For contact cold exposure, when Tsk on the contact skin cooled down to nearly 0 degree C, the temperature at the area close to the contact skin could still be 30 degrees C. Some cases of CIVD were observed in the contact skin area, but not on other measuring points of the same finger. These results indicated that local thermal stimuli were the temperature may require five or more measuring points. Our results strongly emphasised a need to consider the large spatial and individual variations in the prediction and modelling of extremity cooling.
Adult↗
The novel UGT1 gene complex links bilirubin, xenobiotics, and therapeutic drug metabolism by encoding UDP-glucuronosyltransferase isozymes with a common carboxyl terminus.
The UDP-glucuronosyltransferase system (transferase) plays an important role in the pharmacokinetics of clearance of endogenous metabolites, therapeutic drugs, and xenobiotics. The human bilirubin and phenol transferases are encoded by the same gene complex which we designate UGT1. The gene arrangement indicates there are 6 exon 1s each with a promoter and each of which can predictably undergo differential splicing to the 4 common exons (2 through 5) to generate possibly 6 different mRNAs. The entire unique amino acid terminus of each isoform is encoded by an exon 1, and the common carboxyl terminus is encoded by the 4 common exons. Evidence supports the existence of other exon 1s upstream of the currently described locus. The 13-bp deletion in exon 2 represents the most common defect, to date, in the Crigler-Najjar, Type I individuals. Different point mutations in the 4 common exons and in exon 1 of UGT1A, however, also account for defective bilirubin transferase activity. The gene arrangement, in conjunction with the toxicity data from the Gunn rat, leads to the prediction that detoxification of bilirubin, xenobiotics, and therapeutic drugs is linked to the UGT1 locus. The Crigler-Najjar syndromes are uncommon, but the Gilbert individuals are commonly represented in 6% of the population. It is expected that, similar to the deleterious mutations in the common region of the UGT1 locus in Crigler-Najjar, Type I individuals, there is a range of moderate to intermediate deleterious mutations in this region of the gene of at least some Gilbert's individuals. Linkages, therefore, at this locus could signal that these individuals are at risk for certain drug toxicities and/or idiosyncratic drug reactions.
Animals↗
Mutations in the VHL tumor suppressor gene and associated lesions in families with von Hippel-Lindau disease from central Europe.
von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome predisposing to retinal, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma and pancreatic tumors. Clinically two types of the disease can be distinguished: VHL type 1 (without pheochromocytoma) and VHL type 2 (with pheochromocytoma). We report VHL germline mutations and trends in phenotypic variation in families from central Europe. We identified 28 mutations in 53/65 (81.5%) families with 18 (64%) mutations being unique to this population. Whereas types and distribution of mutations as well as a strong correlation of missense mutations with the VHL 2 phenotype were similar to those identified in other populations, these families have provided new insights into the molecular basis for variability in the VHL 2 phenotype. Seven different missense mutations in exons 1 and 3 varied in their biological consequences from a minimal VHL 2 phenotype with pheochromocytoma only to a full VHL 2 phenotype with RCC and pancreatic lesion. These findings contribute to a better understanding of the fundamental mechanisms of VHL disease and its phenotypic variability. Further, we have provided rapid VHL screening for the families in central Europe, which has resulted in improved diagnosis and clinical management.
Base Sequence↗
Fatal myocardial ischemia caused by compression of the left coronary system by a large left sinus of Valsalva aneurysm.
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Aged↗
Lobular distribution of human liver phenol and bilirubin uridine 5'-diphosphate glucuronosyltransferase messenger RNAs.
BACKGROUND & AIMS: Heterogeneity in uridine 5'-diphosphate (UDP) glucuronosyltransferase expression across the human hepatic acinus may be important in the manifestation of certain zone-specific chemical hepatotoxicities. Previous immunohistochemical studies suggested that a phenol transferase induced by polycyclic aromatic hydrocarbons may be differentially expressed in centrilobular hepatocytes of rats. The aim of this study was to assess the distribution of the phenol and bilirubin transferases in human liver at the RNA level. METHODS: In situ RNA hybridization was used with two human liver samples and specific probes for the phenol transferase RNA, HLUG P1, and the bilirubin transferase RNAs, HUG-Br1 and HUG-Br2. RESULTS: The highest density signals were observed for the bilirubin transferase RNAs, both appearing to be evenly expressed in hepatocytes across the liver lobule. Slightly higher density of HUG-Br1 message was observed in some centrilobular hepatocytes surrounding larger central vein structures. HLUG P1 RNA was expressed at low levels (approximately fivefold greater than background signal) and was evenly distributed. CONCLUSIONS: The data suggest that a species difference exists in the distribution of the human and rat phenol transferase. No evidence was found for significant zonation in the pattern of expression of either the phenol or bilirubin transferase genes in human liver.
Base Sequence↗
A transcription map of the DiGeorge and velo-cardio-facial syndrome minimal critical region on 22q11.
The majority of patients with DiGeorge syndrome (DGS) and velo-cardio-facial syndrome (VCFS) have a microdeletion of 22q11. Using translocation breakpoints and fluorescence in situ hybridization analysis (FISH), the minimal DiGeorge critical region (MDGCR) has been narrowed to 250 kb in the vicinity of D22S75 (N25). The construction of a detailed transcription map covering the MDGCR is an essential first step toward the identification of genes important to the etiology of DGS/VCFS, two complex disorders. We have identified a minimum of 11 transcription units encoded in the MDGCR using a combination of methods including cDNA selection, RT-PCR, RACE and genomic sequencing. This approach is somewhat unique and may serve as a model for gene identification. Of the 11 transcripts, one is the previously reported DGCR2/IDD/LAN gene, and three revealed a high level of similarity to mammalian genes: a Mus musculus serine/threonine kinase, a rat tricarboxylate transport protein and a bovine clathrin heavy chain. The remaining transcripts do not demonstrate any significant homology to genes of known function. The identification of these transcription units in the MDGCR will facilitate their further characterization and help elucidate their role in the etiology of DGS/VCFS.
Abnormalities, Multiple↗
The morbidity of defunctioning stomata.
BACKGROUND: The choice of a defunctioning stoma in restorative resection of rectal carcinoma is unclear. Traditionally, the loop colostomy has been preferred. METHODS: All patients with either a defunctioning loop ileostomy or colostomy treated by a single surgeon (MS) were studied. The morbidity of stoma construction and closure, as well as problems experienced in the intervening period, were entered on a database. RESULTS: No significant difference in the morbidity of closure was noted when loop ileostomy was compared to loop colostomy. Although a trend favouring loop ileostomy was noted when interval morbidity was examined, this difference was not statistically significant. CONCLUSIONS: Loop colostomy and ileostomy are both effective in defunctioning the distal colon following a restorative resection for rectal carcinoma. There is some morbidity associated with both but when a stoma is constructed, loop ileostomy is preferable. The loop ileostomy is generally easier to manage and is not associated with a greater rate of complications (in its construction and closure) than the loop colostomy.
Adolescent↗
Induction of nitric oxide and nitric oxide synthase mRNA by silica and lipopolysaccharide in PMA-primed THP-1 cells.
Nitric oxide (NO), a nitrogen-free radical, plays an important role in mediating inflammatory reaction and cytotoxicity of tissue. To determine whether NO was involved in silica-induced pulmonary tissue damage, we studied the effects of silica on nitric oxide (NO) production and inducible NO synthase (iNOS) mRNA expression by THP-1 cells, a monocyte-like cell line with properties of the pulmonary alveolar macrophage. Experimental results showed that silica elicited a marked stimulation of nitric oxide production in a time-dependent manner by THP-1 cells in vitro following the priming of these cells with the phorbol ester PMA. Both nitric oxide synthase inhibitor N-monomethyl-L-arginine (NMMA) and xanthine oxidase inhibitor allopurinol can partially suppress silica-induced NO production in PMA-primed THP-1 cells. Northern blot analysis indicated that, after 2 h of silica exposure, PMA-primed THP-1 cells began to express iNOS mRNA, which reached peak expression at 8 h. Endotoxin treatment of these cells produced a similar effect. These results indicated that silica is a potent inducer of NO production in macrophages and its ability to induce tissue damage may partially be attributed to its ability to initiate excessive production of nitric oxide from macrophages.
Allopurinol↗
Genetic diversity in marine algal virus communities as revealed by sequence analysis of DNA polymerase genes.
Algal-virus-specific PCR primers were used to amplify DNA polymerase gene (pol) fragments (683 to 689 bp) from the virus-sized fraction (0.02 to 0.2 microns) concentrated from inshore and offshore water samples collected from the Gulf of Mexico. Algal-virus-like DNA pol genes were detected in five samples collected from the surface and deep chlorophyll maximum. PCR products from an offshore station were cloned, and the genetic diversity of 33 fragments was examined by restriction fragment length polymorphism and sequence analysis. The five different genotypes or operational taxonomic units (OTUs) that were identified on the basis of restriction fragment length polymorphism banding patterns were present in different relative abundances (9 to 34%). One clone from each OTU was sequenced, and phylogenetic analysis showed that all of the OTUs fell within the family Phycodnaviridae. Four of the OTUs fell within a group of viruses (MpV) which infect the photosynthetic picoplankter Micromonas pusilla. The genetic diversity among these genotypes was as large as that previously found for MpV isolates from different oceans. The remaining genotype formed its own clade between viruses which infect M. pusilla and Chrysochromulina brevifilum. These results imply that marine virus communities contain a diverse assemblage of MpV-like viruses, as well as other unknown members of the Phycodnaviridae.
Base Sequence↗
Karyotype instability in Cryptococcus neoformans infection.
The electrophoretic karyotypes of 32 clinical and 3 environmental Cryptococcus neoformans isolates from New York City were studied by contour clamped homogeneous electrophoresis. There was extensive variation among the electrophoretic karyotypes of isolates from different patients. Sequential C. neoformans isolates from patients with chronic or relapsing infection had very similar karyotypes. However, minor differences in electrophoretic karyotypes were detected among sequential isolates from 50% of the patients studied, suggesting the occurrence of chromosomal rearrangements or deletions in vivo. This hypothesis was tested by infecting mice, recovering isolates from mouse organs, and comparing the electrophoretic karyotypes before and after passage. Three clinical and three environmental strains were studied before and after passage in mice. Karyotype differences were detected after mouse passage for one clinical and two environmental strains. Our results indicate (i) extensive karyotype variation among isolates from a small geographic regions, (ii) a high frequency of electrophoretic karyotype differences among sequential isolates from individual patients, and (iii) the occurrence of electrophoretic karyotype changes during experimental infection of mice. The implications of these observations are discussed.
AIDS-Related Opportunistic Infections↗
Retrovirus packaging cells based on 10A1 murine leukemia virus for production of vectors that use multiple receptors for cell entry.
10A1 murine leukemia virus can enter cells by using either of two different cell surface phosphate transport proteins, the gibbon ape leukemia virus receptor Glvr-1 (Pit-1) or the amphotropic retrovirus receptor Ram-1 (Pit-2). Glvr-1 and Ram-1 are widely expressed in different tissues, but the relative amounts of each are highly variable. We have developed retrovirus packaging cell lines based on 10A1 virus to take advantage of this dual receptor utilization to improve gene transfer rates in somatic cells of animals and humans, in which the relative levels of the two receptors are not always known. Optimization of the Env expression vector allowed the generation of packaging lines that produce helper-free vector titers up to 10(7)/ml. By interference analysis, we found that a 10A1 pseudotype retroviral vector can utilize Ram-1 for efficient entry into mouse, rat, and human cells and can utilize Glvr-1 for entry into mouse and human cells but not for entry into rat cells. The 10A1 pseudotype vector efficiently enters mouse cells by using Glvr-1, while entry into human cells is much less efficient. Thus, the 10A1 pseudotype packaging cells may be advantageous compared with the standard amphotropic packaging cells because vectors produced by the cells can use an additional receptor for cell entry. These packaging cells will also be useful to further explore the complicated pattern of receptor usage conferred by the 10A1 viral surface protein.
Animals↗
Genotype-phenotype correlation in von Hippel-Lindau disease: identification of a mutation associated with VHL type 2A.
A family with von Hippel-Lindau disease (VHL) type 2A has been shown to have a T to C missense mutation at nucleotide 547 of the VHL gene. This gives further support for the proposal to associate the 547 T to C mutation with phenotype VHL 2A.
DNA Mutational Analysis↗