PubMed Health⌕ Search

Biomedical subjects

N C Cheng

Publications and source records attributed to N C Cheng.

At least 19 recordsLinked to original sources
PubMed2004

Protein binding and antimicrobial activity of ceftriaxone: comparative assessments by gradient plate technique and time-kill study.

In conjunction with initial bactericidal rate measurements, this study evaluated the impact of protein binding on the antimicrobial activity of ceftriaxone employing the gradient plate technique. Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 were employed as test organisms. At various albumin concentrations (0 to < or = 16% w/v), the effects of albumin binding were estimated by the shift in concentration-responses (via initial bactericidal rate) and the distance of inhibition zone (DIZ) on gradient agar plates. Supplementation with 4% albumin reduced the antimicrobial activity of ceftriaxone against E. coli as suggested by the similar 1.5-fold shift in both initial bactericidal rate and DIZ when compared to those with no albumin. As with S. aureus, the inclusion of albumin increased the initial bactericidal rate but the DIZ assessments showed a reduction in antimicrobial activity. The reason for the difference observed on the initial bactericidal effect between the two species is unknown. However, the similar patterns of change in the DIZ data at increasing albumin concentrations from 0 to 4% for both organisms suggest consistency and reproducibility of the gradient plate technique. This technique appears to be an attractive alternative for the assessment of the effect of protein binding on antibiotics.

Albumins↗
PubMed2001

Clinical characteristics of Group G streptococcal bacteremia in Taiwan.

The results of this retrospective study showed that Group G streptococcal bacteremia was an acute febrile disease with low mortality. Most patients were > 60 y old but there was a strong association between age < 60 y and malignancy. Cases clustered in summer and the most common port of entry was the skin.

Acute Disease↗
PubMed2000

Mice with a targeted disruption of the Fanconi anemia homolog Fanca.

Fanconi anemia (FA) is a hereditary chromosomal instability syndrome with cancer predisposition. Bone marrow failure resulting in pancytopenia is the main cause of death of FA patients. Diagnosis of FA is based on their cellular hypersensitivity to DNA crosslinking agents and chromosome breakages. Somatic complementation experiments suggest the involvement of at least eight genes in FA. The gene for complementation group A (FANCA) is defective in the majority of FA patients. We show here that mice deficient of FANCA: are viable and have no detectable developmental abnormalities. The hematological parameters showed a slightly decreased platelet count and a slightly increased erythrocyte mean cell volume in mice at young age, but this did not progress to anemia. Consistent with the clinical phenotype of FA patients, both male and female mice showed hypogonadism and impaired fertility. Furthermore, embryonic fibroblasts of the knock-out mice exhibited spontaneous chromosomal instability and were hyper-responsive to the clastogenic effect of the crosslinker mitomycin C.

Animals↗
PubMed2000

Cloning and characterization of murine fanconi anemia group A gene: Fanca protein is expressed in lymphoid tissues, testis, and ovary.

Fanconi anemia (FA) is an autosomal recessive disorder in humans characterized by bone marrow failure, cancer predisposition, and cellular hypersensitivity to cross-linking agents such as mitomycin C and diepoxybutane. FA genes display a caretaker function essential for maintenance of genomic integrity. We have cloned the murine homolog of FANCA, the gene mutated in the major FA complementation group (FA-A). The full-length mouse Fanca cDNA consists of 4503 bp and encodes a protein with a predicted molecular weight of 161 kDa. The deduced Fanca mouse protein shares 81% amino acid sequence similarity and 66% identity with the human protein. The nuclear localization signal and partial leucine zipper consensus motifs found in the human FANCA protein were also present in the murine homolog. In spite of the species difference, the murine Fanca cDNA was capable of correcting the cross-linker sensitive phenotype of human FA-A cells, suggesting functional conservation. Based on Northern as well as Western blots, Fanca was mainly expressed in lymphoid tissues, testis, and ovary. This expression pattern correlates with some of the clinical symptoms observed in FA patients. The availability of the murine Fanca cDNA now allows the gene to be studied in experimental mouse models.

Amino Acid Sequence↗
PubMed1998

Unusual pulmonary manifestations of disseminated Penicillium marneffei infection in three AIDS patients.

Penicillium marneffei is a rare fungal pathogen which can cause human infections in people predominantly living in South-east Asia and the southern portion of China. We report three cases of systemic P. marneffei infection in patients infected with HIV who lived in or had travelled to endemic areas. The clinical manifestation includes high fever, chills, weight loss, general malaise, chronic cough, haemoptysis, multiple skin lesions, abnormal liver function, etc. Chest X-ray showed single or multiple cavitary lesions with smooth or irregular thin wall. P. marneffei is cultured from blood, sputum, skin biopsy, sono-guide aspiration and bronchoscopic biopsy. After antifungal therapy with intravenous amphotericin B or oral fluconazole, skin lesions resolved completely within 2 weeks and cavitary lesions in the lungs changed to chronic fibrotic and interstitial processes after several months to a few years later. Our two cases had been treated as either pulmonary tuberculosis or suspected malignancy. A definite diagnosis and early treatment are important because this fungal infection is a marker of AIDS in South-east Asia.

AIDS-Related Opportunistic Infections↗
PubMed1996

Lack of class I HLA expression in neuroblastoma is associated with high N-myc expression and hypomethylation due to loss of the MEMO-1 locus.

Class I HLA expression is low in neuroblastoma tumours and cell lines. We have recently mapped a modifier of methylation for HLA-C (MEMO-1) to chromosomal bands 1p35-36.1, a region deleted in many neuroblastomas. Hypomethylation of HLA-C is strongly correlated with allelic loss of the MEMO-1 locus. Here, we show that loss of MEMO-1 is associated with hypomethylation of both the 5' and 3' regions of class I HLA loci. We next investigated the relationship between methylation and expression of class I HLA in 28 cell lines of neuroectodermal tumours. Cell lines with hypermethylated HLA-C and HLA-A loci have relatively high expression, while most cell lines with hypomethylated loci have no or a reduced expression. It was reported earlier that high expression of c- or N-myc can suppress class I HLA expression. Remarkably, also N-myc amplification in neuroblastomas is associated with allelic loss of 1p35-36. Therefore, we have analysed the relationships between allelic loss of the MEMO-1 locus, class I HLA methylation and expression, and N-myc amplification and expression. This study shows a tight inter-relationship between these phenomena. Our data suggest a model in which hypomethylation of class I HLA due to loss of the MEMO-1 locus and high N-myc expression could collaborate in the down-regulation of class I HLA expression.

Cell Fusion↗
PubMed1996

No mutations found by RET mutation scanning in sporadic and hereditary neuroblastoma.

Neuroblastoma occasionally occurs in diseases associated with abnormal neurocrest differentiation, e.g. Hirschsprung disease. Expression studies in developing mice suggest that the proto-oncogene RET plays a role in neurocrest differentiation. In humans expression of RET is limited to certain tumor types, including neuroblastoma, that derive from migrating neural crest cells. Mutations of RET are found associated with Hirschsprung disease. These data prompted us to investigate expression of RET and to search for gene mutations in neuroblastoma. Out of 16 neuroblastoma cell lines analyzed, 9 show clear expression of RET in a Northern blot analysis. In a single strandt conformation polymorphism (SSCP) analysis of all exons, no mutations were detected other than neutral polymorphisms. In a patient with neuroblastoma, from a family in which different neurocrestopathies, including neuroblastoma and Hirschsprung disease, had occurred, we also failed to detect RET mutations. Possibly, expression of RET in neuroblastoma merely reflects the differentiation status of the tumor cells. The absence of mutations suggests that RET does not play a crucial role in the tumorigenesis of neuroblastoma.

Drosophila Proteins↗
PubMed1996

Expression cloning of a cDNA for the major Fanconi anaemia gene, FAA.

Fanconi anaemia (FA) is an autosomal recessive disorder characterized by a diversity of clinical symptoms including skeletal abnormalities, progressive bone marrow failure and a marked predisposition to cancer. FA cells exhibit chromosomal instability and hyper-responsiveness to the clastogenic and cytotoxic effects of bifunctional alkylating (cross-linking) agents, such as diepoxybutane (DEB) and mitomycin C (MMC). Five complementation groups (A-E) have been distinguished on the basis of somatic cell hybridization experiments, with group FA-A accounting for over 65% of the cases analysed. A cDNA for the group C gene (FAC) was reported and localized to chromosome 9q22.3 (ref.8). Genetic map positions were recently reported for two more FA genes, FAA (16q24.3) and FAD (3p22-26). Here we report the isolation of a cDNA representing the FAA gene, following an expression cloning method similar to the one used to clone the FAC gene. The 5.5-kb cDNA has an open reading frame of 4,368 nucleotides. In contrast to the 63-kD cytosolic protein encoded by the FAC gene, the predicted FAA protein (M(r) 162, 752) contains two overlapping bipartite nuclear localization signals and a partial leucine zipper consensus, which are suggestive of a nuclear localization.

Amino Acid Sequence↗
PubMed1996

A human modifier of methylation for class I HLA genes (MEMO-1) maps to chromosomal bands 1p35-36.1.

Class I HLA genes are expressed in almost all tissues, but expression is low or undetectable in many neuroblastomas. We analysed class I HLA methylation in normal tissues and in 28 neuroectodermal tumour cell lines. HLA-C is hypermethylated in normal adult tissues and 13 cell lines, while 15 cell lines show the hypomethylated phenotype. Hypomethylation of HLA-C strongly correlates with hemizygous deletion of a 9 cM interval on 1p35-36.1, suggesting that this region encodes a modifier of methylation for HLA-C. To test whether hypomethylation of class I HLA genes results from loss of a modifier gene, we fused a hypomethylating neuroblastoma cell line with a hypermethylating cell line. Methylation of class I HLA genes was induced in the hybrids. Furthermore, methylation of HLA-C, -E and -A genes, which are encoded in a 1.4 Mb region on 6p21, is correlated in most cell lines. Our results suggest that 1p35-36.1 encodes a modifier of methylation for class I HLA genes, that is deleted in many neuroblastomas.

Alleles↗
PubMed1995

Identification of two distinct chromosome 12-derived amplification units in neuroblastoma cell line NGP.

The neuroblastoma cell line NGP contains two homogeneously staining regions (hsr). One of these hsrs contains MYCN sequences. Reverse painting experiments demonstrated that the second HSR consisted of two chromosome 12-derived amplification units, located at 12q14-15 and 12q24. Southern blot and fluorescence in situ hybridization (FISH) analysis showed amplification of genes located at 12q14-15: SAS, MDM2, and CDK4, GLI, CHOP, CDK2, and A2MR were found not to be amplified. FISH further demonstrated amplification of RSN, a gene located at 12q24. The finding of two distinct chromosome 12 amplification units in a neuroblastoma cell line NGP is reminiscent of recent findings in well-differentiated liposarcoma (WDLPS) and other sarcomas. The second amplification unit on chromosome 12 in NGP is located more distal (12q24) than the one observed in WDLPS (12q21). The mechanism and biologic significance of this amplification process in neuroblastoma and WDLPS remain to be elucidated.

Chromosomes, Human, Pair 12↗
PubMed1995

Deletion mapping in neuroblastoma cell lines suggests two distinct tumor suppressor genes in the 1p35-36 region, only one of which is associated with N-myc amplification.

Neuroblastoma is characterized by deletions of the short arm of chromosome 1 (1p) and amplification of the N-myc oncogene. We have made somatic cell hybrids of two human neuroblastoma cell lines, one with and one without N-myc expression and amplification. The expression of the amplified N-myc gene is completely switched off in the hybrids. This suggests that N-myc expression results from loss of a repressor function. As N-myc amplification is associated with loss of heterozygosity (LOH) of 1p36, we analysed 1p deletions in 16 neuroblastoma cell lines. The seven cell lines without N-myc amplification have no deletions or relatively small deletions, with an SRO on 1p36.23-33. This suggests that a tumor suppressor gene maps in this region. All nine cell lines with N-myc amplification have larger deletions, with an SRO from 1p35-36.1 to the telomere. This suggests that a second tumor suppressor gene which is associated with N-myc amplification maps more proximally. Fine mapping of 1p36 deletions in the two cell lines of the fusion experiment suggests that the distal locus is not a repressor of N-myc expression, but the more proximal locus could be a candidate for this function.

Blotting, Northern↗
PubMed1995

Molecular cytogenetic analysis of 1;17 translocations in neuroblastoma.

Loss of chromosome 1 short arm material, resulting from terminal deletions or unbalanced translocations, is a frequent finding in advanced neuroblastoma. In translocations, often relatively small portions of a second chromosome are translocated to the chromosome 1 short arm. The chromosomal origin of this translocated material could often not be identified using banding analysis only. Recent studies, applying fluorescent in situ hybridisation, showed that in the majority of these translocations, chromosome 17 is involved. In this study, the nonrandom occurrence of unbalanced 1;17 translocations is further supported by their presence in 3/7 neuroblastoma cell lines. Analysis of the 1p breakpoints extends our earlier observation of breakpoint heterogeneity. A similar scattering of 17q breakpoints was observed. The 1p and 17q breakpoints of the constitutional 1;17 translocation did not coincide with any of the 1;17 translocation breakpoints found in neuroblastoma cell lines. Cell lines, not containing 1;17 translocations, contained other chromosome 17 rearrangements. As a result, extra copies of 17q are found in all cell lines, suggesting a role for genes on 17q in neuroblastoma development. The possible significance of 1;17 translocations in neuroblastoma is discussed.

Chromosome Mapping↗
PubMed1995

Successful treatment of subcutaneous mycoses with fluconazole: a report of two cases.

Lymphocutaneous sporotrichosis and chromoblastomycosis are subcutaneous mycoses caused by traumatic implantation of the fungus into the skin. Medical treatments for chromoblastomycosis has been disappointing, while lymphocutaneous sporotrichosis usually responds well to iodides. Here we present a case of chromomycosis and a case of lymphocutaneous sporotrichosis. Both patients were treated successfully with fluconazole.

Adult↗
PubMed1994

1;17 translocations and other chromosome 17 rearrangements in human primary neuroblastoma tumors and cell lines.

We report on the finding of a t(1;17) in two primary neuroblastomas. Subsequent fluorescence in situ hybridization (FISH) analysis revealed the presence of 1;17 translocations in four out of nine neuroblastoma cell lines. The chromosome 1 short arm breakpoints were determined using region-specific probes. FISH screening also demonstrated or confirmed the presence of 11;17 translocations in three cell lines and other chromosome 17 rearrangements in those cell lines that did not carry a t(1;17) or t(11;17). Our data extend previous cytogenetic findings and suggest that, in addition to the known involvement of chromosome 1, one or more genes on chromosome 17 also play a role in neuroblastoma development.

Adrenal Gland Neoplasms↗
PubMed1993

Activation of the mas oncogene involves coupling to human alphoid sequences.

We have shown previously that mouse NIH3T3 cells transfected with DNA from a human ovarian carcinoma were rendered tumourigenic by an activated mas oncogene in four independent transfection experiments. In all cases the 5'-noncoding region was rearranged in comparison to the original ovarian tumour DNA. We now report that in all four transfectants the newly acquired sequences consist of human centromeric alpha satellite repeat DNA. In at least three transfectants the alphoid DNA originates from the centromere of chromosome three. Analysis of the sequences of the recombination site in one transfectant revealed that a homologous sequence of five base pairs (CAGCA) is present in both parental strands, and might thus have contributed to the recombinational event. To establish a conclusive role for alphoid DNA in the activation of mas, we performed a co-transfection experiment in NIH3T3 cells with cloned alphoid DNA and the mas coding sequence. We show that the transfectants expressing a transformed phenotype contain amplified mas linked to alphoid DNA. NIH3T3 cells transfected with plasmids that contained alphoid sequences cloned directly upstream of the mas coding sequence, and injected into nude mice, gave rise to tumours with amplified mas sequences (7/7). In six of these tumours the alphoid sequences were amplified as well. Our data suggest a novel mechanism of oncogene activation: recombination with normal alphoid repeat DNA resulting in amplification of the oncogene.

3T3 Cells↗
PubMed1992

Cloning and characterization of the Drosophila homolog of the xeroderma pigmentosum complementation-group B correcting gene, ERCC3.

Previously the human nucleotide excision repair gene ERCC3 was shown to be responsible for a rare combination of the autosomal recessive DNA repair disorders xeroderma pigmentosum (complementation group B) and Cockayne's syndrome (complementation group C). The human and mouse ERCC3 proteins contain several sequence motifs suggesting that it is a nucleic acid or chromatin binding helicase. To study the significance of these domains and the overall evolutionary conservation of the gene, the homolog from Drosophila melanogaster was isolated by low stringency hybridizations using two flanking probes of the human ERCC3 cDNA. The flanking probe strategy selects for long stretches of nucleotide sequence homology, and avoids isolation of small regions with fortuitous homology. In situ hybridization localized the gene onto chromosome III 67E3/4, a region devoid of known D.melanogaster mutagen sensitive mutants. Northern blot analysis showed that the gene is continuously expressed in all stages of fly development. A slight increase (2-3 times) of ERCC3Dm transcript was observed in the later stages. Two almost full length cDNAs were isolated, which have different 5' untranslated regions (UTR). The SD4 cDNA harbours only one long open reading frame (ORF) coding for ERCC3Dm. Another clone (SD2), however, has the potential to encode two proteins: a 170 amino acids polypeptide starting at the optimal first ATG has no detectable homology with any other proteins currently in the data bases, and another ORF beginning at the suboptimal second startcodon which is identical to that of SD4. Comparison of the encoded ERCC3Dm protein with the homologous proteins of mouse and man shows a strong amino acid conservation (71% identity), especially in the postulated DNA binding region and seven 'helicase' domains. The ERCC3Dm sequence is fully consistent with the presumed functions and the high conservation of these regions strengthens their functional significance. Microinjection and DNA transfection of ERCC3Dm into human xeroderma pigmentosum (c.g. B) fibroblasts and group 3 rodent mutants did not yield detectable correction. One of the possibilities to explain these negative findings is that the D.melanogaster protein may be unable to function in a mammalian repair context.

Amino Acid Sequence↗