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Biomedical subjects

J Lee

Publications and source records attributed to J Lee.

At least 271 records · Page 15Linked to original sources

IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1.

We report identification of interleukin (IL)-17E, a novel member of the IL-17 family of cytokines. IL-17E is a ligand for the recently identified protein termed EVI27/IL-17BR, which we term IL-17 receptor homolog 1 (IL-17Rh1) in light of the multiple reported ligand-receptor relationships. Murine EVI27 was identified through its location at a common site of retroviral integration in BXH2 murine myeloid leukemias. IL-17Rh1 shows highest level expression in kidney with moderate expression in multiple other organs, whereas IL-17E mRNA was detected at very low levels in several peripheral tissues. IL-17E induces activation of NF-kappaB and stimulates production of the proinflammatory chemokine IL-8.

Amino Acid Sequence↗

HrpZ(Psph) from the plant pathogen Pseudomonas syringae pv. phaseolicola binds to lipid bilayers and forms an ion-conducting pore in vitro.

The hrp gene clusters of plant pathogenic bacteria control pathogenicity on their host plants and ability to elicit the hypersensitive reaction in resistant plants. Some hrp gene products constitute elements of the type III secretion system, by which effector proteins are exported and delivered into plant cells. Here, we show that the hrpZ gene product from the bean halo-blight pathogen, Pseudomonas syringae pv. phaseolicola (HrpZ(Psph)), is secreted in an hrp-dependent manner in P. syringae pv. phaseolicola and exported by the type III secretion system in the mammalian pathogen Yersinia enterocolitica. HrpZ(Psph) was found to associate stably with liposomes and synthetic bilayer membranes. Under symmetric ionic conditions, addition of 2 nM of purified recombinant HrpZ(Psph) to the cis compartment of planar lipid bilayers provoked an ion current with a large unitary conductivity of 207 pS. HrpZ(Psph)-related proteins from P. syringae pv. tomato or syringae triggered ion currents similar to those stimulated by HrpZ(Psph). The HrpZ(Psph)-mediated ion-conducting pore was permeable for cations but did not mediate fluxes of Cl-. Such pore-forming activity may allow nutrient release and/or delivery of virulence factors during bacterial colonization of host plants.

Animals↗

Study of B Decays to Charmonium States: B-->eta(c)K and B --> chi(c0)K.

In a sample of 9.66x10(6)B&Bmacr; pairs collected with the CLEO detector we make the first observation of B decays to an eta(c) and a kaon. We measure branching fractions B(B+-->eta(c)K+) = (0.69(+0.26)(-0.21)+/-0.08+/-0.20)x10(-3) and B(B degrees -->eta(c)K degrees ) = (1.09(+0.55)(-0.42)+/-0.12+/-0.31)x10(-3), where the first error is statistical, the second is systematic, and the third is from the eta(c) branching fraction uncertainty. From these we extract the eta(c) decay constant in the factorization approximation, f(eta(c)) = 335+/-75 MeV. We also search for B decays to a chi(c0) and a kaon. No evidence for a signal is found and we set 90% C.L. upper limits: B(B+-->chi(c0)K+)<4.8x10(-4) and B(B degrees -->chi(c0)K degrees )<5.0x10(-4).

Journal Article↗

Occupational cancer genetics: infrequent ras oncogenes point mutations in lung cancer samples from chromate workers.

BACKGROUND: Chromium carcinogenicity and mutagenicity are no longer disputed. However, although chromium has various genetic effects that induce cancer, its mechanism of inducing lung cancer in humans is still not fully understood. p53, a tumor suppressor gene, was found to be infrequently mutated in samples of lung cancer in workers with long occupational exposure to chromium, suggesting other cancer-related genes to be targeted in such tumors. METHODS: To assess the contribution of the ras oncogenes in the pathogenesis of chromate-related lung cancer, we studied point mutations at the critical positions of codons 12, 13, and 61 of the Ha-ras and Ki-ras oncogenes in 38 lung cancer samples derived from Japanese patients who worked in the chromate industry for long periods. We used both radioactive isotope and non-radioisotope PCR-SSCP techniques. RESULTS: The results of this study demonstrated that activation of ras genes due to point mutations in chromate-related lung cancer is a rare event. CONCLUSIONS: Ras oncogenes activated by point mutations do not have a major role in the process of tumorigenesis of chromate-related lung cancer.

Adult↗

Aberrant expression of Smad4 results in resistance against the growth-inhibitory effect of transforming growth factor-beta in the SiHa human cervical carcinoma cell line.

Smad proteins activated by TGF-beta form complexes with Smad4. Upon activation, these complexes translocate to the nucleus of the cell, where they induce transcription of genes related to inhibition of cell growth, cell differentiation and apoptosis. We investigated the role of Smads in the TGF-beta-mediated signal-transduction cascade in 4 human cervical cancer cell lines: HeLa, Caski, HT-3 and SiHa. Based on our results, SiHa cells show low mRNA expression of mutated Smad4 (Gly(230)Ala, Ala(488)Val) and of Smads 2, 3, 5 and 6. SiHa cells were likewise defective in TGF-beta signaling, as evidenced by a lack of significant growth inhibition following TGF-beta treatment. In addition, TGF-beta did not induce transcription of the PAI-1 gene or change Smad protein levels. Introduction of Smad3 and/or Smad4 into SiHa cells restored TGF-beta signaling, as determined by activation of the 3TP-lux reporter gene and by prominent apoptotic cell death with PAI-1 induction. Analysis of the downstream targets activated by TGF-beta yielded rapid activation of p38 with subsequent phosphorylation of the transcription factor ATF-2 but unchanged SAPK/JNK activation in the 4 cervical cancer cell lines. Our findings demonstrate that (i) decrease of Smad4 mRNA expression is closely associated with defective TGF-beta response and lack of growth inhibition, (ii) activation of PAI-1 by TGF-beta may be Smad4-dependent and (iii) the Smad and the p38 cascades are triggered by TGF-beta independently of each other in human cervical cancer.

Adenoviridae↗

Characterization of microsatellite markers adjacent to AP-4 on chromosome 16p13.3.

The 1400 kb genomic sequence between the markers D16S406 and D16S423 on chromosome 16p13.3 has been recently sequenced and the interval contains a transcription factor, AP-4, that was identified as a ligand for immunoglobulin-kappa promoter E-box elements,(1)suggesting that AP-4 may be related to immunodeficiency diseases. In addition, chromosome 16p13.3 includes a number of genes including the PKD1 gene,(2,3)the autosomal dominant polycystic kidney disease (ADPKD) gene. ADPKD is characterized by progressive development and enlargement of renal cysts.(4)The size and genomic complexity of the PKD1 gene makes it impractical to detect mutations for prenatal diagnosis. Therefore, pedigree-based linkage analysis remains useful for diagnosis of ADPKD. To increase the number of polymorphic markers in the region around AP-4 gene, we performed database searches of 1400 kb of genomic sequence (from contig NT000677 to NT001573: http://www.ncbi.gov/genome/seq.cgi) across the 16p13.3. A number of dinucleotide or tetranucleotide repeats were found, and 20 microsatellites that contain more than 15 contiguous repeats were chosen for further investigation.

Adult↗

Expression, purification, and characterization of recombinant purine nucleoside phosphorylase from Escherichia coli.

Recombinant purine nucleoside phosphorylase (PNPase) from Escherichia coli was prepared in high yield in order to facilitate its use in coupled assays to measure the kinetics of phosphate-liberating enzymes. The E. coli enzyme was overexpressed in E. coli by inserting the genomic fragment containing the deoD gene downstream of the isopropyl beta-d-thiogalactoside-inducible promotor of pSE380 expression vector. The recombinant protein was purified to approximately 90% homogeneity and with a yield of approximately 9000 units of activity/L of culture, using an efficient one-column procedure. A continuous spectrophotometric assay coupling P(i) release to the phosphorolysis of the nucleoside analogue 7-methylinosine (m(7)Ino) was recently described. Here, we report the steady-state kinetic parameters of the recombinant E. coli PNPase catalyzed reaction with m(7)Ino and P(i) as substrates and compare these parameters with those of a bacterial PNPase commercially available for use in coupled assays. Under the assay conditions described, the recombinant E. coli protein is active at higher pH values and is stable up to a temperature of approximately 55 degrees C and following multiple freeze-thaw cycles. It is activated by high ionic strength but loses some activity following dialysis or concentration under pressure. Finally, a new procedure for the synthesis of m(7)Ino from inosine is described which is safe and cost effective, making the use of this methylated nucleoside in PNPase-coupled P(i) assays more attractive.

Actinomycetales↗

Kojic acid, a potential inhibitor of NF-kappaB activation in transfectant human HaCaT and SCC-13 cells.

The activation of NF-kappaB induced by kojic acid, an inhibitor of tyrosinase for biosynthesis of melanin in melanocytes, was investigated in human transfectant HaCaT and SCC-13 cells. These two keratinocyte cell lines transfected with pNF-kappaB-SEAP-NPT plasmid were used to determine the activation of NF-kappaB. Transfectant cells release the secretory alkaline phosphatase (SEAP) as a transcription reporter in response to the NF-kappaB activity and contain the neomycin phosphotransferase (NPT) gene for the dominant selective marker of geneticin resistance. NF-kappaB activation was measured in the SEAP reporter gene assay using a fluorescence detection method. Kojic acid showed the inhibition of cellular NF-kappaB activity in both human keratinocyte transfectants. It could also downregulate the ultraviolet ray (UVR)-induced activation of NF-kappaB expression in transfectant HaCaT cells. Moreover, the inhibitory activity of kojic acid in transfectant HaCaT cells was found to be more potent than known antioxidants, e.g., vitamin C and N-acetyl-L-cysteine. These results indicate that kojic acid is a potential inhibitor of NF-kappaB activation in human keratinocytes, and suggest the hypothesis that NF-kappaB activation may be involved in kojic acid induced anti-melanogenic effect.

Acetylcysteine↗

Epidural naloxone reduces intestinal hypomotility but not analgesia of epidural morphine.

PURPOSE: Epidural morphine is associated with decreased bowel motility and increased transit time. Low doses of intravenous naloxone reduce morphine-induced pruritus without reversing analgesia, but the effect of epidural naloxone on bowel motility has not been studied. Therefore we evaluated bowel motility and analgesia when naloxone was co-administered with morphine into the epidural space. METHODS: Forty-three patients having combined thoracic epidural and general anesthesia for subtotal gastrectomy were randomly assigned to one of two study groups. All received a bolus dose of 3 mg epidural morphine at the beginning of surgery, followed by a continuous epidural infusion containing 3 mg morphine in 100 ml bupivacaine 0.125% with either no naloxone (control group, n = 18) or a calculated dose of 0.208 microg x kg(-1) x hr(-1) of naloxone (experimental group, n = 25) for 48 hr. We measured the time to the first postoperative passage of flatus and feces to evaluate the restoration of bowel function, and visual analog scales (VAS) for pain during rest and movement. Scores were assessed at 2, 4, 8, 16, 24, 36 and 48 hr postoperatively. RESULTS: The experimental group had a shorter time to the first postoperative passage of flatus (5 1.9 +/- 1 6.6 hr vs 87.0 +/- 19.5 hr, P < 0.001 ) and feces (95.3 +/- 25.0 hr vs 132.9 +/- 29.4 hr, P < 0.001). No differences were found in either resting or active VAS between the two groups. CONCLUSION: Epidural naloxone reduces epidural morphine-induced intestinal hypomotility without reversing its analgesic effects.

Analgesia, Epidural↗

Segmentation by evolution for visualization of the lower extremity of the Visible Man.

Medical image segmentation is the crucial process for three-dimensional (3D) modeling. Many studies have claimed to suggest more accurate ways of segmentation. However, such research seems to have the drawback that it works against the parsimony principle. These methods have to resegment the regions of interest (ROIs) for the already segmented data, without taking advantage of the vast amount of past segmentation results. The present report proposes a "segmentation by evolution" method. It is an advanced segmentation paradigm that incorporates the existing segmentation results. The "segmentation by evolution" paradigm was applied to the color images of the Visible Human data.

Anatomy, Cross-Sectional↗

Hip fracture incidence rates in Singapore 1991-1998.

In this population-based study, we determined the incidence rates of hip fracture among Singapore residents aged 50 years and above. Information was obtained from a centralized database system which captured admissions with the primary diagnosis of a closed hip fracture (ICD-9 codes 820, 820.0, 820.2 and 820.8, n = 12,927) from all health care establishments in the country from 1991 to 1998 inclusive. After removing duplicates, hospital transfers, readmissions and non-acute care admissions, the total number of hip fractures was 9406. Based on the national population census 1990 (n = 464,100) and yearly population estimates, the age-adjusted hip fracture rates for 1991-1998 (per 100,000) were 152 in men and 402 in women. This was 1.5 and over 5 times higher than corresponding rates in the 1960s. From 1991 to 1998, these hip fracture rates tended to increase by 0.7% annually in men and by 1.2% annually in women. Among the three major racial groups, in men, the Chinese had significantly higher age-adjusted hip fracture rates (per 100,000): 168 (95% confidence interval (CI) 158-178) compared with 128 (95% CI 105-152) for Indians and 71 (95% CI 54-88) for Malays. A similar pattern occurred in women: 410 (95% CI 395-425), for Chinese compared with 361 (95% CI 290-432) for Indians and 264 (95% CI 225-303) for Malays. Since the 1960s, the main increases in hip fracture rates have been seen in the Chinese and Malays, with the rates in Indians appearing to decrease. Hip fracture incidence rates in Singapore have risen rapidly over the past 30-40 years, particularly in women, and are now among the highest in Asia. Significant racial differences in hip fracture rates occur within the same community. Time trends in hip fracture rates differed between races.

Age Distribution↗

A unique pattern of mycelial elongation of Blakeslea trispora and its effect on morphological characteristics and beta-carotene synthesis.

The mycelial morphology of Blakeslea trispora was of crucial importance in the production of beta-carotene in submerged cultures of B. trispora. After the spores were inoculated, the time-course variation of mycelial morphology was closely examined under the microscope. With the addition of the non-ionic surfactant (Span 20: Sorbitan monolaurate, E493) to the culture medium, a unique pattern of mycelial elongation was observed: 1) slow formation of germ tubes from spores and 2) appearance of mycelia with very short length, which allowed a well-dispersed growth of B. trispora without significant pellet aggregation. Span 20 appears to act like a paramorphogen. Without Span 20, however, the fungal culture finally formed a big clump of mycelium owing to heavy cross-linking of long mycelia. But the short mycelium maintained in the course of cultivation seemed to be irrelevant to growth inhibition, because the final concentration of dry mycelium was much higher with Span 20 after 3-day cultivation. The 20-fold increase in specific yield of beta-carotene (mg beta-carotene produced per g mycelium) was achieved with this drastic change in the pattern of mycelial elongation. The reason for this result might be more effective mass transfer and/or enhanced sensitivity to environmental oxidative stress in the well-dispersed mycelial cultures of B. trispora.

Carotenoids↗

Unique properties of four lactobacilli in amino acid production and symbiotic mixed culture for lactic acid biosynthesis.

With four Lactobacilli--L. delbrueckii subsp. lactis (ATCC 12315), L. casei (NRRL-B1445), L. delbrueckii (NRRL-B445), and L. heveticus (NRRL-B1937)--the characteristics of cell growth and production of lactate and amino acids were investigated. Especially, the time-course variation in concentration of amino acids (classified into alanine, serine, aspartate, glutamate, aromatic amino acid, and histidine families) was estimated in detail, and the results were systematically compared. It was elucidated that L. delbrueckii (NRRL-B445) and L. helveticus (NRRL-B1937) had quite different characteristics in growth, lactic acid synthesis, and amino acid production. L. helveticus (NRRL-B1937) was superior in the production of amino acids as well as in cell growth, but showed very poor ability in lactic acid production. However, L. delbrueckii (NRRL-B445) showed higher yield of lactic acid despite repressed cell growth, but suffered from severe amino acid deficiency in culture. By modulating the initial concentration of each strain in the mixed culture containing both L. delbrueckii (NRRL-B445) and L. helveticus (NRRL-B1937), the lactic acid production (i.e., the amount of lactic acid produced and lactic acid yield to glucose consumed) was significantly improved, presumably via symbiotic interaction between the two strains.

Amino Acids↗

Association between Helicobacter pylori infection and the risk of gastric cancer in the Korean population: prospective case-controlled study.

BACKGROUND: Gastric cancer is still the most common malignant tumor in Koreans. Although many reports have supported the association of Helicobacter pylori infection and the development of gastric cancer, few studies have been adjusted by variable factors such as age. sex, education, and economic status. Furthermore, most results from areas with a high incidence of gastric cancer, such as China and Korea, have failed to document any relationship between H. pylori infection and gastric cancer. We conducted a prospective case-controlled study, with controls matched for and adjusted by age, sex, education, and economic status, to evaluate the causal relationship between H. pylori infection and gastric cancer in Korean people. METHODS: From March 1997 to October 1998, 136 consecutive patients with gastric cancer, diagnosed by endoscopic histology, and 136 age- and sex-matched control subjects, confirmed to be free of gastric cancer by endoscopy during the same period, were enrolled in the study. The presence of H. pylori infection was determined by enzyme immunoassay (EIA) serology test. RESULTS: Seventy-two of the 136 gastric cancer patients (53%) were positive for H. pylori infection and 54 of the 136 control subjects (40%) were positive for H. pylori infection. The odds ratio (OR), adjusted by variable risk factors, such as age, sex, education, and economic status, for gastric cancer in H. pylori-infected patients was 1.82 (95% confidence internal [CI], 1.10-3.00; P = 0.019). The age- and sex-matched OR by conditional logistic regression was 1.6 (95% CI., 1.01-2.53; P = 0.043). CONCLUSIONS: H. pylori infection may be one of the important risk factors for the development of gastric cancer in Korea, an area of high prevalence of H. pylori infection and a high incidence of gastric cancer.

Adult↗

Sequence variations of hepatitis B virus promoter regions in persistently infected patients.

The HBV in the sera of two chronic active hepatitis patients were analyzed for the promoter sequence heterogeneity. In most cases, the proportion of any particular clone in the total viral populations was less than 50%, showing high mutation rates. In contrast, promoter sequences of HBV from asymptomatic carriers revealed only a few point mutations with no deletions. HBV in chronic patient harbored variants with multiple mutations throughout promoters including 1762 (A-to-T), 1764 (G-to-A) double mutation in C promoter and deletions near CCAAT site in S promoter. Unlike other three promoter regions, C, pre-S1 and S, of HBV which revealed a high level of sequence heterogeneity, the X promoter region (from nt985 to 1430) showed little sequence heterogeneity within a patient. However, the predominant viral clones in two patients were quite different from each other. In addition to mutations in promoter regions, a deletion mutation in the translation start codon was also found in pre-S1 gene. The results in this report indicate that the mutation rates are not the same in all four promoters and that one of the strategies for maintaining persistent infection could be through mutations in viral promoters which then impair the balance of viral gene expressions.

Adult↗

Y chromosome compound haplotypes with the microsatellite markers DXYS265, DXYS266, and DXYS241.

Two newly developed microsatellite markers on Yp11 (DXYS265) and Yq11.21 (DXYS266) and our previously reported marker, on Yp11 (DXYS241), were typed by triplex polymerase chain reaction (PCR) in 102 Japanese, 18 white American, and 17 black American males. The DXYS265 locus revealed three alleles, the DXYS266 locus showed two alleles, while the DXYS241 locus showed five alleles. Nine different compound haplotypes were observed among the males. Of these, two haplotypes were common to all groups, while four were limited to Japanese. Pedigree analysis of 61 Japanese families revealed no mutations of these loci. The triplex PCR developed in this study, as well as the new loci, are useful for tracing paternal lineages in human migration studies and population analysis, in addition to Y chromosome evolutionary studies.

Alleles↗