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D C Chan

Publications and source records attributed to D C Chan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Preliminary experience with a new stable isotope breath test for chylomicron remnant metabolism: a study in central obesity.

We aimed to investigate the metabolism of chylomicron remnants in the postabsorptive state employing a new stable isotope breath test in centrally obese men without overt hyperlipidaemia. Groups of 12 centrally obese and 12 non-obese men of similar age and with similar plasma cholesterol and triacylglycerol (triglyceride) levels were studied. The catabolism of chylomicron remnants was measured using an intravenous injection of a remnant-like emulsion containing cholesteryl [(13)C]oleate. Isotopic enrichment of (13)CO(2) in breath was determined using isotope-ratio mass spectrometry, and a multi-compartmental model (SAAM II program) was used to estimate the fractional catabolic rate (FCR) of the chylomicron remnant-like particles. The plasma concentrations of low-density lipoprotein (LDL)-cholesterol, non-high-density lipoprotein (HDL)-cholesterol and insulin were significantly higher (P<0.05) in the obese than the control subjects. The obese subjects had significantly lower HDL-cholesterol (P<0.05) and, in particular, a decreased FCR of the remnant-like particles compared with lean subjects (0.061+/-0.014 and 0.201+/-0.048 pools/h respectively; P=0.016). In the obese group, the FCR of remnant-like particles was inversely associated with the waist/hip ratio, and with plasma triacylglycerol, cholesterol, LDL-cholesterol and non-HDL-cholesterol levels. In multiple regression analysis, the waist/hip ratio was the best predictor of the FCR of the emulsion. In conclusion, this new test suggests that postabsorptive chylomicron remnant catabolism is impaired in centrally obese subjects without overt hyperlipidaemia. This defect may be due to the degree of adiposity.

Adult↗
PubMed2001

Curing potential of dual-polymerizable resin cements in simulated clinical situations.

STATEMENT OF PROBLEM: Little is known about the ability of dual-polymerizable resin cements to polymerize when they are used in various clinical scenarios. PURPOSE: This study was conducted to determine whether any of 6 commercially available dual-polymerizable resin cements should be classified as an "all-purpose" resin cement. MATERIAL AND METHODS: . Chemical conversion values (C=C converted to C-C, or the extent of the curing reaction) of 6 commercially available dual-polymerizable resin cements were determined with infrared spectroscopy in 5 clinically relevant scenarios. Scenarios included: using each cement in a dual-polymerizable mode (mixing of 2 pastes); light polymerizing curing through Mylar sheets (dual-Mylar), which served as the control; light polymerizing through 3-mm porcelain (dual-3 mm); and no exposure to light (dual-no light). The single-component light-polymerizable product was also tested as follows: exposed directly through Mylar (light-Mylar) or exposed through 3 mm of porcelain (light-3 mm). Results. For each product, dual-Mylar treatment yielded the highest conversion value of all treatments (control for each product). For all products, dual-3 mm conversion was at least 97% of control and equivalent to control, with the exception of Lute-It!. Dual-no light conversion was less than control treatment but at least 86% of control for all products except for Variolink II (62% of control). For all products in dual-no light mode, except Choice and Variolink II, conversion was at least equal to the light-Mylar values. Only 1 product (Variolink II) did not demonstrate increased conversion values for dual-Mylar compared with light-Mylar treatments. For most other products (Calibra, Insure, and Lute-It!), conversion values for light-3 mm were significantly less than for light-Mylar. Conversion values for Nexus, Choice, and Variolink II were equivalent between light-Mylar and light-3 mm treatments. CONCLUSION: The choice of a dual-polymerizable cement should be based on its intended use because not all products polymerize adequately in every clinical situation. Although no cement met the stated criteria for an "all-purpose" cement, those tested did produce a range of product-specific results.

Analysis of Variance↗
PubMed2001

Curing potential of dual-polymerizable resin cements in simulated clinical situations.

STATEMENT OF PROBLEM: Little is known about the ability of dual-polymerizable resin cements to polymerize when they are used in various clinical scenarios. Purpose. This study was conducted to determine whether any of 6 commercially available dual-polymerizable resin cements should be classified as an "all-purpose" resin cement. MATERIAL AND METHODS: Chemical conversion values (C=C converted to C-C, or the extent of the curing reaction) of 6 commercially available dual-polymerizable resin cements were determined with infrared spectroscopy in 5 clinically relevant scenarios. Scenarios included: using each cement in a dual-polymerizable mode (mixing of 2 pastes); light polymerizing curing through Mylar sheets (dual-Mylar), which served as the control; light polymerizing through 3-mm porcelain (dual-3 mm); and no exposure to light (dual-no light). The single-component light-polymerizable product was also tested as follows: exposed directly through Mylar (light-Mylar) or exposed through 3 mm of porcelain (light-3 mm). RESULTS: For each product, dual-Mylar treatment yielded the highest conversion value of all treatments (control for each product). For all products, dual-3 mm conversion was at least 97% of control and equivalent to control, with the exception of Lute-It!. Dual-no light conversion was less than control treatment but at least 86% of control for all products except for Variolink II (62% of control). For all products in dual-no light mode, except Choice and Variolink II, conversion was at least equal to the light-Mylar values. Only 1 product (Variolink II) did not demonstrate increased conversion values for dual-Mylar compared with light-Mylar treatments. For most other products (Calibra, Insure, and Lute-It!), conversion values for light-3 mm were significantly less than for light-Mylar. Conversion values for Nexus, Choice, and Variolink II were equivalent between light-Mylar and light-3 mm treatments. CONCLUSION: The choice of a dual-polymerizable cement should be based on its intended use because not all products polymerize adequately in every clinical situation. Although no cement met the stated criteria for an "all-purpose" cement, those tested did produce a range of product-specific results.

Analysis of Variance↗
PubMed2001

Metabolism-resistant bradykinin antagonists: development and applications.

Bradykinin plays many roles in normal and pathological physiology, but rapid enzymatic degradation made elucidation of its functions extremely difficult. Development of effective degradation-resistant antagonists made it possible to delineate these roles and to open the way for development of new drugs to control pathology due to excess production of bradykinin. Presently available peptide bradykinin antagonists are extremely potent, are completely resistant to enzymatic degradation, and are orally available. Non-peptide bradykinin antagonists have also been discovered. Development of bradykinin antagonists as drugs for cancer, inflammation and trauma is anticipated.

Animals↗
PubMed2001

Expression of Her-2/neu in human lung cancer cell lines by immunohistochemistry and fluorescence in situ hybridization and its relationship to in vitro cytotoxicity by trastuzumab and chemotherapeutic agents.

Overexpression of the Her-2/neu oncogene and receptor protein was reported in approximately 20% of breast cancers and was associated with a poor prognosis. Her-2/neu expression was a predictor for response to trastuzumab, a monoclonal antibody that recognizes the Her-2/neu cell surface receptor. Data regarding the expression of Her-2/neu in lung cancer are far more limited, and there is little information regarding the influence of Her-2/neu expression and response to trastuzumab alone or in combination with chemotherapeutic agents. In this report we evaluated Her-2/neu gene expression by fluorescence in situ hybridization (FISH) and the cell surface expression of the Her-2/neu receptor by immunohistochemistry using the HercepTest and by FACS analysis in 31 lung cancer cell lines with 5 breast cancer cell lines as controls. By FACS, we found Her-2/neu overexpression (mean fluorescence intensity >8) in 2 of the 22 non-small cell lung cancer (NSCLC) cell lines (9%), none of 11 small cell lung cancer (SCLC) cell lines, and 4 of 5 breast cancer cell lines. A positive HercepTest (2+ or 3+) was found in 6 of 19 NSCLC cell lines (26%, 2+; 5%, 3+), 1 of 3 SCLC cell lines (33%), and 4 of 5 breast cancer cell lines (80%). One of 6 NSCLC cell lines examined (17%) had gene amplification with >32 copies of Her-2/neu/cell and had homogeneous staining regions. One NSCLC cell line had a maximum of 14 copies of Her-2/neu/cell, and 3 had modest increases in Her-2/neu gene copy number without gene amplification (maximum 5-8 copies/cell). None of the SCLC cell lines had more than a maximum of 4 copies/cell, whereas the 2 breast cancer cell lines had maximum Her-2/neu copy numbers of 80 and 5, respectively. Aneusomy rather than true amplification was the major cause of increased Her-2/neu expression in most of the NSCLC cell lines. There was a strong correlation when the results of fluorescence-activated cell sorter, HercepTest results, and FISH were compared in pairs. Furthermore, Trastuzumab produced a G(1) cell cycle arrest and growth inhibition only in cell lines expressing Her-2/neu. The IC(50) for growth inhibition was correlated with cell surface Her-2/neu expression. The combination of trastuzumab and chemotherapeutic agents produced more than additive growth inhibition in cell lines expressing Her-2/neu, but the level of additivity was not related to the amount of Her-2/neu expression. These data indicate that trastuzumab alone and in combination with chemotherapeutic agents should be tested in NSCLC patients and that Her-2/neu should be assessed by both immunohistochemistry and FISH methods in these studies to determine which test is the best predictor of outcome.

Antibodies, Monoclonal↗
PubMed2000

Hydroxyapatite and their use as coatings in dental implants: a review.

At present, no standard manufacturing guideline exists for depositing hydroxyapatite (HA) on implant surfaces. Although animal and in vitro studies have reported on the benefits of using HA-coated implants as well as the risks of dissolution, these short-term studies did not demonstrate that the dissolution of the HA coating leads to a loss of implants. In addition, many in vivo and clinical studies did not include the chemical and structural characterization of the coatings, and thus comparisons between studies are difficult. In the clinics, the recommendation is that HA-coated screw implants be used for the anterior maxilla and posterior mandible where the bone depth exceeds 10 mm and when the cortical layer is thinner and spongiosia is less dense. In the posterior maxilla or when the cortical layer is very thin with low density, the use of HA-coated cylindrical implants is recommended. However, there are concerns for using HA-coated implants. The clinician needs to take into consideration the enhanced bacterial susceptibility of HA coatings compared with titanium implants. In addition, the clinician needs to consider the possible failure of HA coatings as a result of coating-substrate interfacial fracture. Finally, besides the surgical skills, it is also important that the clinical investigators be well versed with the materials characterization needed for HA-coated implants, the problems associated with the current HA coatings, and the indications for use. In addition, the correlation between well characterized coatings and their effect on bone formation rate and long-term implant success, coating-implant interfacial strength, and alternative superior coating process need to be investigated further.

Animals↗
PubMed1999

Synergistic effects of new chemopreventive agents and conventional cytotoxic agents against human lung cancer cell lines.

Non-small cell lung cancer (NSCLC) cells have constitutively high expression of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX) 2. These NSCLC cells also have increased prostaglandin expression (PGE2). Many lung cancers also express 12-lipoxygenase RNA and 12-lipoxygenase protein and biosynthesize 12(S)-hydroxyeicosatetraenoic acid, which correlates with their metastatic potential. Several studies have demonstrated that COX-1 and COX-2 inhibitors could inhibit the in vitro growth of human lung cancer cell lines. In this report, we evaluated the growth-inhibitory effects of sulindac sulfide, a COX-1 and COX-2 inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor on human lung cancer cell lines. We compared these effects with those of 13-cis-retinoic acid, a chemoprevention agent, and with the cytotoxic chemotherapeutic agents paclitaxel and cisplatin, alone or in combination. Our goal was to develop new chemoprevention and treatment strategies. Each of the six agents tested inhibited the in vitro growth of three NSCLC and three SCLC cell lines at the highest concentration. Paclitaxel was the most potent agent (IC50 = 0.003-0.150 microM); sulindac sulfide, NDGA, and 13-cis-retinoic acid had intermediate potency (IC50 = 4-80 microM), and cisplatin and exisulind were the least potent (IC50 = 150-500 microM). Combination studies showed synergistic interactions for sulindac sulfide, exisulind, and NDGA with paclitaxel, cisplatin, and 13-cis-retinoic acid, regardless of drug-resistance phenotype. At high concentrations, the combination of 13-cis-retinoic acid and each of the five other drugs resulted in a strong synergistic effect. These studies provide a rationale for chemoprevention (exisulind +/- retinoic acid +/- NDGA) and therapeutic (exisulind +/- paclitaxel +/- cisplatin) studies in patients at risk for, or with, lung cancer.

Antineoplastic Agents↗
PubMed1999

Radiopacity of tantalum oxide nanoparticle filled resins.

OBJECTIVES: Radiopacity of composite resins allows radiographic distinction of existing restorations and recurrent caries. Current composites must be supplemented with heavy metal-containing glasses or minerals to achieve a desired radiopacity. The purpose of this study was to evaluate the radiopacity of Tantalum oxide (Ta2O5) filled resins at varying percentage loadings. METHODS: Methacrylate functionalized Ta2O5 nanoparticles (< 50 nm) in methanol-dissolved or powder forms were mixed into either glycerol dimethacrylate (GDMA) or a bisGMA, TEGDMA, bisEMA mixture (GTE). Specimens were made in a split brass mold (2 x 2 x 15 mm) and compared with an aluminum stepwedge (99.5% pure Al) and a dentin slice of the same thickness. Kodak Ultraspeed periapical X-ray film on a lead plate at a target distance of 45 cm was exposed at 70 kVp and 10 mA, for 0.5 s and processed automatically. Optical density was measured (n = 3) with an RMI Processor Control Densitometer. Radiopacity was calculated as percent relative linear attenuation coefficient (Alpha). ANOVA and Student-Newman-Keuls comparisons were used to determine significance at the 95% confidence level. RESULTS: Radiopacity increased significantly with Ta2O5 loading (p = 0.001). Ta2O5 nanoparticle filled resins enter the optimal range of diagnostic detectability (alpha = 150-250) at 50 wt.% and approach equivalence with enamel at approximately 70 wt.%. SIGNIFICANCE: The introduction of tantalum oxide nanoparticle filler has potential as a miscible component of a resin composite to provide radiopacity for microfiller-type restorative materials and to circumvent the need for hydrolysis-prone glass reinforcing fillers.

Analysis of Variance↗
PubMed1999

Bradykinin antagonists: present progress and future prospects.

Bradykinin (BK) antagonist peptides have been powerful tools for delineating roles of kinins in both normal and pathological physiology and offer promise of drug development for a variety of inflammatory conditions and cancers. At the present time, potent peptide antagonists are available that are either specific for BK B1 or B2 receptors, or are effective on both receptor classes. Non-peptide BK B2 antagonists are now being announced and are under investigation in several companies. The best peptide B1-B2 peptide antagonist is stable against all kininases, is orally available, and has a very long lifetime in vivo. Certain dimers of this antagonist, as well as several smaller molecules, are active against several cancers, both in vitro and in vivo.

Amino Acid Sequence↗
PubMed1999

Novel approach to measure composite conversion kinetics during exposure with stepped or continuous light-curing.

PURPOSE: The objective of this research was to evaluate a novel approach to monitor the polymerization reaction during a light-curing exposure by using infrared (IR) spectroscopy. MATERIALS AND METHODS: An IR spectrometer was equipped to use an attenuated total reflectance (ATR) element as an IR-active substrate. The uncured composite (Herculite XRV, Shade A2, Kerr, Orange, California) was placed against the crystal, and the IR spectrum was continuously obtained during various exposure scenarios. The degree of conversion and the maximum rate of reaction were monitored at 0 mm (top surface), 1 mm, 2 mm, and 3 mm beneath the surface. The exposure conditions included continuous 40-second or 60-second exposures at 100% intensity (800 mW/cm2) or a stepped output of 10 seconds at 17% maximal output (133 mW/cm2) followed by full output for the remainder of the 40-second or 60-second exposure (Elipar Highlight, ESPE, Norristown Pennsylvania). The results were analyzed using MANOVA with appropriate post hoc tests (p < or = .05). RESULTS: For 40-second exposures, the peak conversion rates were significantly reduced (p < .05) when using the stepped exposure mode compared to the continuous exposure: 40-second top surface: stepped = 5.5%/s +/- 0.4, continuous = 10.5%/s +/- 1.0; 1 mm step = 3.6%/s +/- 0.4, continuous mode = 4.8%/s +/- 0.2. The same trend was noted when using the 60-second exposure. Equivalent conversion values (p > .05) beneath the surface between stepped and continuous exposure modes at similar depths 60 seconds after light initiation were only attained at 3 mm 4 for the 40-second exposure. However, using the 60-second exposure, equivalent conversion values between step and continuous exposure modes at similar depths were obtained. Even with a reduced conversion rate at the surface using the stepped cure mode, polymerization shrinkage forces were sufficient to debond the specimens from the test crystal after only 20 seconds into the exposure. This result indicated that stress development in the curing composite was non-uniform, and stress values developed at the surface of the restoration were the greatest. CLINICAL SIGNIFICANCE: Stepped intensity curing for the ESPE Highlight unit was shown to produce significantly lower conversion rates at the surface and at 1-mm depths, but longer exposure times were still required to provide conversion values equivalent to continuous exposure.

Analysis of Variance↗
PubMed1998

Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target.

Synthetic C peptides, corresponding to the C helix of the HIV type 1 (HIV-1) gp41 envelope protein, are potent inhibitors of HIV-1 membrane fusion. One such peptide is in clinical trials. The crystal structure of the gp41 core, in its proposed fusion-active conformation, is a trimer of helical hairpins in which three C helices pack against a central coiled coil. Each C helix shows especially prominent contacts with one of three symmetry-related, hydrophobic cavities on the surface of the coiled coil. We show that the inhibitory activity of the C peptide C34 depends on its ability to bind to this coiled-coil cavity. Moreover, examining a series of C34 peptide variants with modified cavity-binding residues, we find a linear relationship between the logarithm of the inhibitory potency and the stability of the corresponding helical-hairpin complexes. Our results provide strong evidence that this coiled-coil cavity is a good drug target and clarify the mechanism of C peptide inhibition. They also suggest simple, quantitative assays for the identification and evaluation of analogous inhibitors of HIV-1 entry.

Amino Acid Sequence↗
PubMed1998

Crystal structure of the simian immunodeficiency virus (SIV) gp41 core: conserved helical interactions underlie the broad inhibitory activity of gp41 peptides.

The gp41 subunit of the envelope protein complex from human and simian immunodeficiency viruses (HIV and SIV) mediates membrane fusion during viral entry. The crystal structure of the HIV-1 gp41 ectodomain core in its proposed fusion-active state is a six-helix bundle. Here we have reconstituted the core of the SIV gp41 ectodomain with two synthetic peptides called SIV N36 and SIV C34, which form a highly helical trimer of heterodimers. The 2.2 A resolution crystal structure of this SIV N36/C34 complex is very similar to the analogous structure in HIV-1 gp41. In both structures, three N36 helices form a central trimeric coiled coil. Three C34 helices pack in an antiparallel orientation into highly conserved, hydrophobic grooves along the surface of this coiled coil. The conserved nature of the N36-C34 interface suggests that the HIV-1 and SIV peptides are functionally interchangeable. Indeed, a heterotypic complex between HIV-1 N36 and SIV C34 peptides is highly helical and stable. Moreover, as with HIV-1 C34, the SIV C34 peptide is a potent inhibitor of HIV-1 infection. These results identify conserved packing interactions between the N and C helices of gp41 and have implications for the development of C peptide analogs with broad inhibitory activity.

Amino Acid Sequence↗
PubMed1998

Short-term efficacy and tolerability of combination therapy with lovastatin and acipimox in Chinese patients with type 2 diabetes mellitus and mixed dyslipidemia.

In type 2 diabetes, it is not uncommon to find an elevated serum triglyceride and/or reduced high-density lipoprotein (HDL) cholesterol levels; elevated total cholesterol levels often occur as well. To evaluate the short-term efficacy and tolerability of combination therapy with lovastatin and acipimox in Chinese patients with type 2 diabetes who have mixed dyslipidemia, an open-label 6-month trial was conducted. All patients had type 2 diabetes (n = 33) with total cholesterol > or = 6.2 mmol/L and fasting triglyceride > or = 2.8 mmol/L, which had been confirmed twice and persisted for at least 12 weeks after introduction of diet control. After a 4-week run-in period, they were given lovastatin 40 mg daily at night for 12 weeks. Acipimox 250 mg three times a day was then added for a further 12 weeks. After 12 weeks of treatment with lovastatin alone, improvement was observed in total cholesterol (21% reduction), triglyceride (32% reduction), low-density lipoprotein (LDL) cholesterol (5.5% reduction), HDL cholesterol (11.6% elevation), apolipoprotein A-I (4.6% elevation), and apolipoprotein B (20.5% reduction). The addition of acipimox to lovastatin for an additional 12 weeks further reduced serum total cholesterol, triglyceride, LDL cholesterol, and apolipoprotein B, but this additional decrease was not statistically significant. However, HDL cholesterol and apolipoprotein A-I levels were significantly increased by the addition of acipimox (a 14.2% and 9.0% elevation, respectively). Serum creatine phosphokinase increased slightly after 12 weeks of lovastatin but decreased to a concentration similar to baseline after 12 weeks of combination treatment. No patients reported muscle pain or weakness or other side effects. Combination treatment with lovastatin and acipimox appears to be a safe and effective therapy in patients with type 2 diabetes and mixed dyslipidemia, and has particular benefit in elevating serum HDL cholesterol and apolipoprotein A-I levels.

Adult↗
PubMed1998

Anti-growth factor therapy for lung cancer.

Lung cancers are the leading cause of cancer death in developed countries. In the USA, lung cancer accounts for 29% of all cancer deaths. The cure rate for lung cancer is low (14%) because the cancer spreads early and because chemotherapy cannot cure metastatic disease. In small cell lung cancer (SCLC) two-thirds of patients present with metastatic disease in a distant organ (stage IV). In non-small cell lung cancers (adenocarcinoma, squamous carcinoma, large cell carcinoma) one-third present with metastatic disease. Initial chemotherapy produces high response rates in both SCLC (85%-90% response rate) and NSCLC (50% response rate) but response duration is short and drug resistance develops rapidly. Growth factors play an important role in the pathogenesis and the progression of lung cancers. Knowledge of the role of these growth factors, their receptors and their signal pathways has produced new therapeutic targets. Compounds developed toward these targets have completed preclinical testing and are now in clinical trials. Some of these compounds are active in both drug sensitive and drug resistant lung cancers. They also produce synergistic growth inhibition when combined with cytotoxic chemotherapeutic agents. Thus, these compounds may provide a new way to overcome drug resistance in lung cancer.

Journal Article↗
PubMed1998

The effect of sprue design on the marginal accuracy of titanium castings.

The purpose of this study was to measure the effects of sprue number and position on cast titanium crown margins. Twenty-four complete veneer crown wax patterns were fabricated on a stainless steel die with a 30 degrees bevel finish line. Twelve wax patterns were sprued with one 8-gauge wax sprue and the remaining 12-gauge double sprued. All patterns were invested with a phosphate bonded investment. Castings were made with a titanium casting machine following the manufacturer's instructions and using commercially pure titanium (> 99.5%) ingots. The castings were than carefully cleansed and the margins were examined with indirect impression technique. Data were analysed with an ANOVA and the Student's t-test with confidence level at 95%. The results revealed that the marginal discrepancy for the double sprueing group (32.1 +/- 12.8 microm) has significantly less discrepancy (P < 0.001) than the single sprueing group (49.8 +/- 16.4 microm). There was no statistically significant differences in marginal discrepancy between locations within the sprueing techniques (P > 0.05). An improvement in the degree of casting accuracy of titanium crown was indicated by the double sprue design used in this investigation.

Analysis of Variance↗
PubMed1998

Reconstructing hominid Y evolution: X-homologous block, created by X-Y transposition, was disrupted by Yp inversion through LINE-LINE recombination.

The human X and Y chromosomes share many blocks of similar DNA sequence. We conducted mapping and nucleotide sequencing studies of extensive, multi-megabase homologies between Yp and Xq21, which do not recombine during male meiosis. We confirmed and built upon previous evidence that a Yp inversion had occurred during evolution: a single contiguous segment of Xq21 is homologous to two non-contiguous segments of Yp. We precisely defined and sequenced the inversion breakpoints, obtaining evidence that the inversion was mediated by recombination between LINE-1 elements in otherwise non-homologous regions. This inversion appears to have followed a single transposition of an approximately 4 Mb segment from the X to the Y chromosome. These events jointly account for the present arrangement of Yp-Xq21 homologous sequences. Based on Southern blotting studies of primates and of humans drawn from diverse populations, we conclude that both the X-Y transposition and the subsequent, LINE-mediated Yp inversion occurred after the divergence of hominid and chimp lineages but before the radiation of extant human populations. This evolutionary scenario is consistent with our finding of 99.3 +/- 0.2% nucleotide identity between the X and Y chromosomes within the transposed region, which suggests that the transposition occurred approximately 3-4 million years ago, near the time of emergence of Homo . Comparative sequencing of the entire human X and Y chromosomes may reveal a succession of transpositions, inversions and other rearrangements underlying the complex pattern of sequence similarities between the present-day sex chromosomes. With the possible exception of cubitus valgus, phenotypic features of Turner syndrome are absent in individuals monosomic for Yp-Xq21 homologous sequences, suggesting that most of the critical 'Turner genes' are found elsewhere on the X and Y chromosomes.

Base Sequence↗
PubMed1998

Effects of recombinant neutral endopeptidase (EC 3.4.24.11) on the growth of lung cancer cell lines in vitro and in vivo.

Many lung cancers are stimulated by an autocrine/paracrine system of neuroendocrine peptide hormones. Attempts to block this autocrine growth pathway by interactions with specific ligand-receptor binding using monoclonal antibodies and peptide-specific antagonists have been largely unsuccessful because of the heterogeneity of hormone production and receptor expression. In the normal lung, neutral endopeptidase (NEP; CD10, CALLA, enkephalinase, and EC 3.4.24.11) plays a physiological role in degrading biologically active peptides, including all peptides implicated in autocrine growth stimulation of lung cancer. Cigarette smoke decreases the activity of NEP, indicating that the lack of NEP contributes to the dysregulation of the peptide autocrine system. The cloning of the human NEP gene allowed for production of sufficient quantities of recombinant NEP (rNEP) to evaluate its role in inhibiting the growth of lung cancer cells. In this study, we evaluated the ability of rNEP to inactivate the peptides involved in lung cancer signal transduction and to inhibit the growth of lung cancer cells as well as normal lung cells in vitro and in vivo in athymic nude mice. We showed that the growth inhibition of lung cancer cells by rNEP was related to the dose and schedule. Continuous exposure to high doses was required for growth inhibition. These studies confirm the importance of NEP in this autocrine pathway.

Animals↗