Biomedical subjects

C C Lee

Publications and source records attributed to C C Lee.

At least 271 records · Page 15Linked to original sources

PubMed1997

Vibrio vulnificus infections: case reports and literature review.

Vibrio vulnificus is an emerging opportunistic pathogen that is responsible for one of the most fulminant food-borne diseases in immunocompromised hosts. The infection should be suspected in patients with underlying liver disorders who present with a prominent skin rash, hypotension and septic parameters especially if they give a history of seafood or shellfish ingestion. Awareness and early recognition of this infection will result in a better outcome for the patient.

Adult↗

PubMed1997

The demography, clinical manifestations and natural history of human immunodeficiency virus (HIV) infection in an older population in Singapore.

In this retrospective study, we report 43 cases (41 males and 2 females) of human immunodeficiency virus (HIV) infection in the Singapore population aged 50 years and above at first presentation. We found an increasing proportion of these older individuals among our HIV-seropositive patients; from 4.8% in 1991 to 16.7% by mid-1996. The mean age at presentation was 59.2 years (range 50 to 75 years). They were mainly heterosexuals (93%) and the majority (79.1%) were previously or currently married. Thirty-six (83.7%) patients had multiple sexual exposures to commercial sex workers. Nearly all had acquired the infection through the sexual route. The majority (76.7%) were symptomatic at presentation. Common clinical presentations were weight loss (72%), respiratory symptoms (60%) and oral candidiasis (56%). More than half (58.1%) of the patients had acquired immunodeficiency virus (AIDS) at the time of first presentation with a low median CD4 count of 17 cells/mm3. Pneumocystis carinii pneumonia and tuberculosis were the common AIDS-defining diseases. Survival in patients presenting with AIDS (median survival 3 months) is poorer compared to younger HIV-seropositive patients (< 50 years; median survival 1 year). No increase in age-related infection or malignancy was seen. Common causes of death were pneumonia and septicaemia. Physicians should consider HIV infection in older patients particularly when he/she presents with unexplained weight loss, respiratory symptoms and oral candidiasis. A history of high-risk sexual behaviour must be sought in all patients, including the elderly.

AIDS-Related Opportunistic Infections↗

PubMed1996

Isolation, mapping, and genomic structure of an X-linked gene for a subunit of human mitochondrial complex I.

We report here the isolation, mapping, and genomic organization of the human NDUFA1 gene, which is a component of NADH:ubiquinone oxidoreductase (complex I). The NDUFA1 cDNA clone and associated genomic cosmid clones were isolated by reciprocal probing of an arrayed human heart cDNA library with a X-chromosome cosmid library and were mapped to Xq24. The NDUFA1 gene, which is highly expressed in human cardiac and skeletal muscle, has an open reading frame of 70 amino acids and shows 80% homology to the bovine MWFE subunit of complex I. By primer extension, the major and minor transcription initiation sites were identified, 99 and 141 nucleotides upstream of the translation initiator ATG, respectively. The NDUFA1 gene is composed of 3 exons and spans about 5.0 kb of genomic DNA. The 5' region of the NDUFA1 gene (approximately 450-bp fragment) lacks conventional TATA and CAAT boxes, but it contains several potential binding sites for transcription factors including SP-1, AP-2, NF1, NRF2-like, APRRE, CRE, MyoD1, CArG, MEF-2, and BRE.

Amino Acid Sequence↗

PubMed1996

Hematologic effects of flt3 ligand in vivo in mice.

We have investigated the effects of in vivo treatment with flt3 ligand (FL) on murine hematopoiesis, including mobilization of progenitors into the peripheral blood (PB). Mice were injected once daily with 10 micrograms recombinant human FL for 15 days. On days 3, 5, 8, 10, 15, and 22, mice were killed and analyzed for the number of leukocytes and colony-forming units (CFU) in bone marrow (BM), spleen, and PB. Splenic and PB cellularity increased with time in FL-treated mice. In the spleen, there was an increase in B cells, myeloid cells, and nucleated erythroid cells; in the PB, there was an increase in lymphocytes, granulocytes, and monocytic cells. The maximal number of CFU in the BM was observed after 3 days of FL treatment, giving 3.7- and 7.3-fold increases in CFU-granulocyte-macrophage (CFU-GM) and CFU-granulocyte, erythrocyte, monocyte, megakaryocyte (CFU-GEMM), respectively, compared with mouse serum albumin (MSA)-treated controls. After 8 days of FL treatment, there was a maximal 123- and 108-fold increase in splenic CFU-GM and CFU-GEMM, respectively. The maximal number CFU-GM and CFU-GEMM were seen in PB on day 10, with 537- and 585-fold increases, respectively. Burst-forming units-erythroid (BFU-E) increased in the same time frame as those of CFU-GM and CFU-GEMM in BM, spleen, and PB, although the magnitude was not as great. Primitive day-13 CFU-spleen (CFU-S) and phenotypically defined stem cells were also mobilized into the PB of FL-treated mice with similar kinetics and magnitude to that of CFU-GM and CFU-GEMM. We conclude from these studies that FL, when administered as a single agent, is a potent mobilizer of hematopoietic progenitors into the PB.

Animals↗

PubMed1996

Stat6 and Jak1 are common elements in platelet-derived growth factor and interleukin-4 signal transduction pathways in NIH 3T3 fibroblasts.

Both platelet-derived growth factor (PDGF) and interleukin-4 (IL-4) play major roles in cell proliferation, differentiation, chemotaxis, and other functional responses. Here, we demonstrate that Stat6, previously shown to be activated by only IL-4 and IL-3, becomes activated after PDGF stimulation of NIH 3T3 fibroblasts. PDGF BB, and to a lesser extent PDGF AA, rapidly induced DNA binding activity from NIH 3T3 cell lysates utilizing the immunoglobulin heavy chain germ line epsilon promoter (Iepsilon) that specifically binds to Stat6 in an electrophoretic mobility shift assay. DNA binding activity could be detected within 5 min and reached maximum levels at approximately 20 min in parental NIH 3T3 cells. An identical mobility shift and time course of PDGF-mediated Iepsilon binding activity was more pronounced in lysates of NIH 3T3 transfectants overexpressing human Stat6 (NIH 3T3-Stat6). The observed radiolabeled Iepsilon mobility shift was competed by unlabeled Iepsilon as well as by the beta-casein gene promoter but not by the interferon-alpha-stimulated response element or the interferon-gamma response region of the guanylate-binding protein gene. A Stat6-specific polyclonal antisera also supershifted the PDGF-induced Iepsilon mobility shift. After PDGF BB treatment, a 100-kDa tyrosine phosphorylated species was detected in anti-Stat6 immunoprecipitates. Cycloheximide had little effect on Stat6 tyrosine phosphorylation. In addition to Stat6, Stat5a, and Stat5b, PDGF BB also induced Jak1 tyrosine phosphorylation suggesting a potential pathway for Stat activation. Strikingly, the concurrent addition of IL-4 enhanced PDGF BB-induced Iepsilon binding activity, Jak1 tyrosine phosphorylation, and [3H]thymidine incorporation. These results provide evidence that Stat6 and Jak1 are common elements in PDGF and IL-4 signaling pathways and suggest that IL-4 could play a role in potentiating certain known PDGF-induced biological responses.

3T3 Cells↗

PubMed1996

Characterization and genomic mapping of genes and pseudogenes of a new human protein tyrosine phosphatase.

Previously described protein tyrosine phosphatases (PTPs) are classified into three types according to their sequence homology and structural features. Here we describe the characterization of genes and pseudogenes of a member of a fourth type of PTP, designated protein tyrosine phosphatase 4A (PTP4A). The 167-amino-acid human PTP4A bears the signature active site of all PTPs, but does not show any other sequence homology to any of the previously described PTPs. Two cDNAs encoding PTP4A that differed in their noncoding regions were isolated. Another cDNA that has a high level of sequence identity with these two cDNAs and a deletion in the coding region was also isolated. Northern analysis using a probe from a common 3'-untranslated region of the cDNAs recognized mRNAs of about 2 and 4 kb. Both species of mRNA were seen in all human adult and fetal tissues tested. Fluorescence in situ hybridization mapping of the corresponding yeast artificial chromosome clones and sequence-tagged site analysis suggested that one of the PTP4A coding genes is located at 1p35 and the other is on chromosome 11. A processed pseudogene for PTP4A was found in the BRCA1 region of 17q21 and shares 96% sequence identity to one of the PTP4A coding cDNAs. Our studies also suggest the existence of another processed pseudogene on chromosome 11.

Adult↗

PubMed1996

Identification of ovarian enhancer-binding factors which bind to ovarian enhancer 1 of the Drosophila genes yp1 and yp2.

It has been reported that three different DNA regions-the fat body enhancer and ovarian enhancers 1 and 2-direct the tissue-specific expression of yp1 and yp2 in Drosophila melanogaster. In the present study, we identified ovarian enhancer 1-specific binding proteins. Electrophoretic mobility shift assay revealed that these proteins are present in the adult ovary, but not in adult testis or fat body. Southwestern blot analysis showed that about 130 kDa and 40 kDa proteins, designated OEF1 and OEF2, respectively, from ovarian nuclear or crude extracts bind specifically to the ovarian enhancer 1. The two proteins were partially purified by streptavidin/agarose-DNA affinity chromatography, and their binding activity was confirmed by electrophoretic mobility shift assay. These ovarian enhancer factors may play an important role in the regulation of transcription of yp1 and yp2 in the ovary.

Animals↗

PubMed1996

Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns.

Semaphorins and collapsins make up a family of conserved genes that encode nerve growth cone guidance signals. We have identified two additional members of the human semaphorin family [human semaphorin A(V) and human semaphorin IV] in chromosome region 3p21.3, where several small cell lung cancer (SCLC) cell lines exhibit homozygous deletions indicative of a tumor suppressor gene. Human semaphorin A(V) has 86% amino acid homology with murine semaphorin A, whereas semaphorin IV is most closely related to murine semaphorin E, with 50% homology. These semaphorin genes are approximately 70 kb apart flanking two GTP-binding protein genes, GNAI-2 and GNAT-1. In contrast, other human semaphorin gene sequences (human semaphorin III and homologues of murine semaphorins B and C) are not located on chromosome 3. Human semaphorin A(V) is translated in vitro into a 90-kDa protein, which accumulates at the endoplasmic reticulum. The human semaphorin A(V) (3.4-kb mRNA) and IV (3.9- and 2.9-kb mRNAs) genes are expressed abundantly but differentially in a variety of human neural and nonneural tissues. Human semaphorin A(V) was expressed in only 1 out of 23 SCLCs and 7 out of 16 non-SCLCs, whereas semaphorin IV was expressed in 19 out of 23 SCLCs and 13 out of 16 non-SCLCs. Mutational analysis in semaphorin A(V) revealed mutations (germ line in one case) in 3 of 40 lung cancers. Our data suggest the need to determine the function of human semaphorins A(V) and IV in nonneural tissues and their role in the pathogenesis of lung cancer.

Amino Acid Sequence↗

PubMed1996

Construction of a 600-kilobase cosmid clone contig and generation of a transcriptional map surrounding the lung cancer tumor suppressor gene (TSG) locus on human chromosome 3p21.3: progress toward the isolation of a lung cancer TSG.

The critical region on human chromosome 3p21.3 harboring a putative lung cancer tumor suppressor gene (TSG) was previously defined by allelotyping and recently refined by overlapping homozygous deletions. We report the construction of a 700-kb (cosmid and one P1 phage) clone contig covering the deletion overlap and its flanks. The minimal set of 23 cosmids comprises 600 kb and is extended by one P1 phage to 700 kb to cover the distal breakpoint of the overlap. The clone contig was extensively characterized by restriction and expression mapping to produce high resolution physical and transcription maps of the cloned region. Potential transcribed fragments were detected by hybridization with PCR-amplified cDNA libraries, direct cDNA selection "zoo" blotting, cDNA screening, and identification of 24 CpG islands. Thus far, 15 new genes represented by partial or full-length cDNAs were isolated, characterized, and precisely positioned on the contig. Two previously cloned genes, namely GNAI-2 and GNAT-1, were also positioned. In addition, the telomeric breakpoint of the NCI H740 deletion and centromeric breakpoint of the overlapping GLC20 deletion were discovered and mapped to define precisely the candidate TSG region. This large cosmid clone contig and high resolution maps will prove crucial in the identification of the lung cancer TSG(s).

Chromosome Mapping↗

PubMed1996

Blood lead levels in Taiwanese adults: distribution and influencing factors.

Five-thousand nine-hundred thirteen Taiwanese adults were selected by multistage sampling methods to investigate environmental lead exposure in Taiwan. The blood specimens were distributed to six laboratories for blood lead levels (BLL) measurement. The mean BLL of the 5913 Taiwanese adults was 8.28 +/- 5.39 microg/dl, with a maximum level of 57.6 microg/dl. The median was 7.0 microg/dl and 90th percentile was 15.0 microg/dl. BLLs were associated with gender, ethnic group, education level, smoking, alcohol consumption, herbal drug consumption, milk consumption, sources of drinking water, level of urbanization, and occupational lead exposure. These results showed that BLLs in Taiwanese adults were stable during the 2-year study. Most of the influencing factors were consistent with other studies, while local risk factors, such as Chinese herbal drug consumption are important ways of preventing the general population from overexposure to lead.

Adolescent↗

PubMed1996

A transcription map in the CATCH22 critical region: identification, mapping, and ordering of four novel transcripts expressed in heart.

The acronym CATCH22 is used to indicate collectively a group of related phenotypes, namely velocardiofacial syndrome (VCFS), DiGeorge anomaly (DGA), and conotruncal anomaly face, which are associated with deletions within 22q11.2 in the great majority of patients. A deletion map has allowed us to delimit a smallest region of deletion overlap, considerably smaller than the commonly deleted region. We have mapped within this region the chromosomal breakpoint of a balanced translocation patient presenting with a DGA/VCFS phenotype, making this region the strongest candidate for the location of the gene(s) responsible for the disease phenotype. We report a systematic gene search in this region and show the presence of at least six distinct transcripts, two of which have been previously described. The region searched was approximately 270 kb; therefore, an average of one transcript every 45 kb was found. We generated eight new ESTs and mapped two ESTs present in public databases. All six transcripts are expressed in heart, an organ involved in 70%-80% of CATCH22 patients. We show that the multimethod approach to search for expressed sequences is effective and indeed necessary for a comprehensive search and provides molecular tools for further characterization of the potential genes identified.

Abnormalities, Multiple↗

PubMed1996

Superoxide production in rat hippocampal neurons: selective imaging with hydroethidine.

Digital-imaging microfluorimetry of the oxidation of hydroethidine (HEt) to ethidium can be used to monitor superoxide (O2-) production selectively within individual rat hippocampal pyramidal neurons in culture and in brain slices. Under assay conditions, oxidation was not accomplished by hydroxyl radical, singlet O2, H2O2, or nitrogen radicals. Neuronal O2- production varied with metabolic activity and age. O2- generation increased after treatment with AMPA, kainic acid, and NMDA, and the mitochondrial uncoupler carbonylcyanide p-(trifluoromethoxy)phenyl hydrazone, but usually not after depolarization (50 mM K+). O2- concentrations were sensitive to scavengers and nitric oxide. HEt oxidation was higher in Ca(2+)-containing versus Ca(2+)-free saline. However, Ca2+ ionophores did not increase oxidation greatly. H2O2 application produced a secondary increase in O2-. The major source of O2- under basal and stimulated conditions appeared to be the mitochondria. Consistent with this, ethidium staining in dendrites was punctate, colocalized with mitochondria, and blocked by CN-.

Animals↗

PubMed1996

Differential expression of D-type G1 cyclins during mouse development and liver regeneration in vivo.

D-type G1 cyclins are the primary cell cycle regulators of G1/S transition in eukaryotic cells, and are differentially expressed in a variety of cell lines in vitro. Little is known, however, about the expression patterns of D-type G1 cyclins in normal mouse in vivo. Thus, in the present study, tissue-specific expressions of cyclin D1 and D3 genes were examined in several tissues derived from adult male mice, and stage-specific expression of cyclin genes was studied in brain, liver, and kidney of developing mice from embryonic day 13 to postnatal day 11. Cell cycle-dependent expression of cyclins was also examined in regenerating livers following partial hepatectomy. Our results indicate that (1) cyclins D1 and D3 are expressed in a tissue-specific manner, with cyclin D1 being highly expressed in kidney and D3 in thymus; (2) cyclin D3 mRNA is abundantly expressed in young proliferating tissues and is gradually reduced during development, whereas cyclin D1 mRNA fluctuates during development; and (3) compensatory regeneration of liver induces cyclin D1 gene expression 12 hr after partial hepatectomy, and cyclin D3 gene expression from 36 to 42 hr (at the time of G1/S transition). In conclusion, this study indicates that cyclin D1 and D3 genes are differentially expressed in vivo in a tissue-specific, developmental stage-dependent, and cell cycle-dependent manner.

Animals↗

PubMed1996

Real-time adaptive motion correction in functional MRI.

Functional magnetic resonance imaging (fMRI) of the brain is often degraded by bulk head motion. Algorithms that address this by retrospective re-registration of images in an fMRI time series are all fundamentally limited by any motion that occurs through-plane. Here, a technique is described that can account for such motion by prospective correction in real time. A navigator echo is used before every image acquisition to detect superior/inferior displacements of the head. The displacement information is then used to adjust the plane of excitation of the ensuing single-shot echo-planar fMRI axial image. These correction updates can be completed in 100 mm with motion sensitivity at least as small as 0.5 mm. The efficacy of this method is documented in phantom and human studies.

Brain↗

PubMed1996

Background exposure of general population to cadmium and lead in Tainan city, Taiwan.

Venous blood samples, 24-h total food duplicate samples, and rice samples were collected from 52 adult non-smoking women in the city of Tainan, southern Taiwan, in 1994, and analyzed for cadmium (Cd) and lead (Pb) by wet-digestion followed by graphite furnace atomic absorption spectrophotometry. Daily dietary intake was 10 micrograms for Cd and 22 micrograms for Pb as geometric means, of which Cd and Pb in rice accounted for 34% and 1.4% of daily Cd and Pb intakes, respectively. The counterpart values for blood were 1.11 ng/ml and 44.5 ng/ml for Cd and Pb, respectively. International comparison with recently published data suggests that the exposure to Cd in Tainan should be among the lowest in the world.

Adult↗

PubMed1996

Vascular dementia of Binswanger's type: clinical, neuroradiological and 99mTc-HMPAO SPET study.

In 24 patients with vascular dementia of Binswanger's type (VDBT) and 14 age-matched neurologically normal volunteers, we investigated the relationship between clinical features, white matter lesions (leuco-araiosis) and cerebral atrophy on computed tomographic (CT) scan, and regional cerebral blood flow. All subjects underwent the Mini-Mental State Examination of Taiwan, version 1 (MMSE-T1), for assessing the severity of cognitive impairment. The patients were subdivided into two groups, one with mild to moderate (group I, MMSE-T1 scores: 11-24, n=11), and the other with severe dementia (group II, MMSE-T1 scores: below 10, n=13). White matter degeneration was evaluated with densitometric methods. Loss of brain parenchyma was estimated with seven linear measurements (Evan's ratio, third ventricle ratio, width of temporal horn tip, anterior-posterior length of temporal horn, anterior-posterior length of Sylvian fissure and width of frontal interhemispheric fissure) by CT scans. Regional cerebral blood flow was determined with technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET). In neuroimaging studies, subcortical leuco-araiosis was localized at the frontal region in group I patients and scattered diffusely in group II patients. 99mTc-HMPAO SPET analysis revealed reduction of regional cerebral blood flow in the frontal lobe in group I patients and widespread reduction of regional cerebral blood flow in group II patients. A correlation between frontal leuco-araiosis and perfusion defect of the frontal pole was demonstrated in group I patients, showing findings typical of subcortical dementia. There was no difference in frontal atrophic measurements between group I patients and controls. Ratios of volumes of lost brain parenchyma and leuco-araiosis were significantly higher in group II patients than in the age-matched controls, corresponding to a diffuse cerebral perfusion defect. These results suggest that patients with VDBT have early frontal lobe involvement with posterior progression. Patients with mild VDBT are more likely to show reduction of frontal cerebral blood flow and leuco-araiosis, while those with severe VDBT are more likely to have diffuse leuco-araiosis, cerebral hypoperfusion and brain atrophy.

Aged↗

PubMed1996

Hypoxic-ischaemic injury of the spinal cord in systemic shock: MRI.

The imaging characteristics of concurrent spinal cord injury in children with hypoxic-ischaemic injury of the brain have not been described. We present the MRI findings of hypoxic-ischaemic injury of the brain and spinal cord following hypovolaemic shock in a 2-year-old girl.

Child, Preschool↗

PubMed1996

Molecular dissection of a cosmid from a gene-rich region in 17q21 and characterization of a candidate gene for alpha-N-acetylglucosaminidase with two cDNA isoforms.

A cosmid mapped to human Chromosome (Chr) 17q21, c140c10, was found to contain a CpG island. We completed the sequence analysis of c140c10 because of two considerations: the cosmid contained an STS from the 17-beta-hydroxysteroid dehydrogenase gene (17-HSD), which was believed to be a neighbor of the breast cancer susceptibility gene, BRCA1; CpG islands are usually associated downstream and/or upstream of human genes. Computer-based exon trapping of the cosmid sequence revealed putative additional exons. With two of those exons used as a probe to screen human placental cDNA libraries, two cDNA isoforms for a novel gene, designated as ufHSD, were isolated. The amino acid sequence of the open reading frames of the cDNA showed no significant homology to any protein in the data base. However, it is possible that our cDNAs are from the gene for alpha-acetylglucosaminidase, which has recently been localized to the same region. Northern analyses show that the major isoform is expressed in all tissues tested, with the highest expression in blood leukocytes and lowest in brain. Finally, our study has shown that the 46.7-kb cosmid c140c10 encompasses loci for five genes and pseudo-genes: PsiPTP4A, ufHSD, 17-HSDI, 17-HSDII, and 22A1.

Acetylglucosaminidase↗