Biomedical subjects

C Li

Publications and source records attributed to C Li.

At least 469 records · Page 26Linked to original sources

PubMed1999

PAH emission from the industrial boilers.

Polycyclic aromatic hydrocarbons (PAHs) emitted from 25 industrial boilers were investigated. The fuels used for these 25 boilers included 21 heavy oil, two diesel, a co-combustion of heavy oil and natural gas (HO+NG) and a co-combustion of coke oven gas and blast furnace gas (COG+BFG) boilers. PAH samples from the stack flue gas (gas and particle phases) of these 25 boilers were collected by using a PAH stack sampling system. Twenty one individual PAHs were analyzed primarily by a gas chromatography/mass spectrometer (GC/MS). Total-PAH concentration in the flue gas of 83 measured data for these 25 boiler stacks ranged between 29.0 and 4250 microg/m(3) and averaged 488 microg/m(3). The average of PAH-homologue mass (F%) counted for the total-PAH mass was 54.7%, 9.47% and 15.3% for the 2-ring, 3-ring and 4-ring PAHs, respectively. The PAHs in the stack flue gas were dominant in the lower molecular weight PAHs. The emission factors (EFs) of total-PAHs were 13,300, 2920, 2880 and 208 microg/kg-fuel for the heavy oil, diesel, HO+NG and COG+BFG fueled-boiler, respectively. Nap was the most predominant PAH occurring in the stack flue gas. In addition, the EF of 21 individual PAHs in heavy-oil boiler were almost the highest among the four various fueled-boilers except for those of FL and BkF in the diesel boiler. Furthermore, the EF of total-PAHs or BaP for heavy oil were both one order of magnitude higher than that for the diesel-fueled boiler.

Air Pollution↗

PubMed1999

[Effect of aluminium on meiotic maturation of mouse oocyte in vitro].

The effect of aluminium nitrate on the meiotic maturation of mouse oocyte was studied in the culture of mouse oocyte. The results showed that aluminium nitrate could inhibit the extruding of the first polar body and the dose of 30 mg/L and 60 mg/L could affect the viability of mouse oocyte, but little impact on the germinal vesicle breakdown (GVBD) of oocyte. The results indicated that aluminium nitrate might be hazardous to the meiotic maturation of mouse oocyte.

Aluminum Compounds↗

PubMed1999

X-ray crystal structure of aminoimidazole ribonucleotide synthetase (PurM), from the Escherichia coli purine biosynthetic pathway at 2.5 A resolution.

BACKGROUND: The purine biosynthetic pathway in procaryotes enlists eleven enzymes, six of which use ATP. Enzymes 5 and 6 of this pathway, formylglycinamide ribonucleotide (FGAR) amidotransferase (PurL) and aminoimidazole ribonucleotide (AIR) synthetase (PurM) utilize ATP to activate the oxygen of an amide within their substrate toward nucleophilic attack by a nitrogen. AIR synthetase uses the product of PurL, formylglycinamidine ribonucleotide (FGAM) and ATP to make AIR, ADP and P(i). RESULTS: The structure of a hexahistidine-tagged PurM has been solved by multiwavelength anomalous diffraction phasing techniques using protein containing 28 selenomethionines per asymmetric unit. The final model of PurM consists of two crystallographically independent dimers and four sulfates. The overall R factor at 2.5 A resolution is 19.2%, with an R(free) of 26.4%. The active site, identified in part by conserved residues, is proposed to be a long groove generated by the interaction of two monomers. A search of the sequence databases suggests that the ATP-binding sites between PurM and PurL may be structurally conserved. CONCLUSIONS: The first structure of a new class of ATP-binding enzyme, PurM, has been solved and a model for the active site has been proposed. The structure is unprecedented, with an extensive and unusual sheet-mediated intersubunit interaction defining the active-site grooves. Sequence searches suggest that two successive enzymes in the purine biosynthetic pathway, proposed to use similar chemistries, will have similar ATP-binding domains.

Adenosine Triphosphate↗

PubMed1999

Pronounced acute immunosuppression in vivo mediated by HIV Tat challenge.

HIV infection is accompanied by an early immune dysfunction limiting host control of virus and likely contributing to difficulties in achieving a successful vaccine against HIV. We report here that the HIV Tat protein is strongly immunosuppressive, both immediately after immunization of mice with soluble protein (sTat), and in seroconverting humans, and propose that Tat-induced suppression cripples immune surveillance to HIV infection. We show that macrophages are sensitive to sTat stimulation at concentrations 1,000-fold lower (500 pM) than T cells, and this stimulation is accompanied by the immunosuppressive induction of Fas ligand on the macrophage. T cell proliferative defects induced by sTat in vitro can be completely (at lower concentrations of sTat) or partially (at higher concentrations) reversed by antagonists to Fas/Fas ligand interaction. We further report a method to preserve immunogenicity while inactivating Tat immunosuppression through oxidation, which advances the use of oxidized Tat as a component of an anti-HIV vaccine. These observations define additional methods to study the immunosuppressive functions of sTat that now may be rapidly applied to primary isolates from individuals with differing clinical courses. Our findings have immediate relevance for vaccine development, by describing and supporting a strategy that includes inactivated sTat in a multicomponent, anti-HIV vaccine.

AIDS Vaccines↗

PubMed1999

Olfactory dysfunction in multiple sclerosis: relation to longitudinal changes in plaque numbers in central olfactory structures.

Scores on the University of Pennsylvania Smell Identification Test (UPSIT), as well as the numbers of MRI-determined plaques within the inferior frontal and temporal lobes, were obtained on three or four separate occasions in each of five MS patients over an 18- to 20-month period. A close association was observed, longitudinally, between the remission and exacerbation of plaque numbers and UPSIT scores, with more plaques reflecting lower UPSIT scores. These observations further support the hypothesis that olfactory loss in MS is associated with fluctuations in plaque numbers in central olfactory brain regions.

Adult↗

PubMed1999

Heterophilic binding of L1 on unmyelinated sensory axons mediates Schwann cell adhesion and is required for axonal survival.

This study investigated the function of the adhesion molecule L1 in unmyelinated fibers of the peripheral nervous system (PNS) by analysis of L1- deficient mice. We demonstrate that L1 is present on axons and Schwann cells of sensory unmyelinated fibers, but only on Schwann cells of sympathetic unmyelinated fibers. In L1-deficient sensory nerves, Schwann cells formed but failed to retain normal axonal ensheathment. L1-deficient mice had reduced sensory function and loss of unmyelinated axons, while sympathetic unmyelinated axons appeared normal. In nerve transplant studies, loss of axonal-L1, but not Schwann cell-L1, reproduced the L1-deficient phenotype. These data establish that heterophilic axonal-L1 interactions mediate adhesion between unmyelinated sensory axons and Schwann cells, stabilize the polarization of Schwann cell surface membranes, and mediate a trophic effect that assures axonal survival.

Animals↗

PubMed1999

Cyclic strain stress-induced mitogen-activated protein kinase (MAPK) phosphatase 1 expression in vascular smooth muscle cells is regulated by Ras/Rac-MAPK pathways.

Recently, we demonstrated that mechanical stress results in rapid phosphorylation or activation of platelet-derived growth factor receptors in vascular smooth muscle cells (VSMCs) followed by activation of mitogen-activated protein kinases (MAPKs) and AP-1 transcription factors (Hu, Y., Bock, G., Wick, G., and Xu, Q. (1998) FASEB J. 12, 1135-1142). Herein, we provide evidence that VSMC responses to mechanical stress also include induction of MAPK phosphatase-1 (MKP-1), which may serve as a negative regulator of MAPK signaling pathways. When rat VSMCs cultivated on a flexible membrane were subjected to cyclic strain stress (60 cycles/min, 5-30% elongation), induction of MKP-1 proteins and mRNA was observed in time- and strength-dependent manners. Concomitantly, mechanical forces evoked rapid and transient activation of all three members of MAPKs, i.e. extracellular signal-regulated kinases (ERKs), c-Jun NH(2)-terminal protein kinases (JNKs), or stress-activated protein kinases (SAPKs), and p38 MAPKs. Suramin, a growth factor receptor antagonist, completely abolished ERK activation, significantly blocked MKP-1 expression, but not JNK/SAPK and p38 MAPK activation, in response to mechanical stress. Interestingly, VSMC lines stably expressing dominant negative Ras (Ras N17) or Rac (Rac N17) exhibited a marked decrease in MKP-1 expression; the inhibition of ERK kinases (MEK1/2) by PD 98059 or of p38 MAPKs by SB 202190 resulted in a down-regulation of MKP-1 induction. Furthermore, overexpressing MKP-1 in VSMCs led to the dephosphorylation and inactivation of ERKs, JNKs/SAPKs, and p38 MAPKs and inhibition of DNA synthesis. Taken together, our findings demonstrate that mechanical stress induces MKP-1 expression regulated by two signal pathways, including growth factor receptor-Ras-ERK and Rac-JNK/SAPK or p38 MAPK, and that MKP-1 inhibits VSMC proliferation via MAPK inactivation. These results suggest that MKP-1 plays a crucial role in mechanical stress-stimulated signaling leading to VSMC growth and differentiation.

Animals↗

PubMed1999

Leptin receptor activation of SH2 domain containing protein tyrosine phosphatase 2 modulates Ob receptor signal transduction.

Leptin exerts its weight-reducing effects by binding to its receptor and activating signal transduction in hypothalamic neurons and other cell types. To identify the components of the leptin signal transduction pathway, an approach was developed in which bacterially expressed phosphorylated fragments of Ob receptor b (Ob-Rb) were used as affinity agents. Leptin binding to the Ob-Rb form of the leptin receptor leads to tyrosyl phosphorylation of the cytoplasmic domain of its receptor. Two of the three cytoplasmic tyrosines of Ob-Rb, at positions 985 and 1138, are phosphorylated after leptin treatment. Affinity chromatography using a tyrosine-phosphorylated fragment spanning Tyr 985 of Ob-Rb was used to identify proteins that bind to this site. The SH2 domain containing protein tyrosine phosphatase 2 (SHP-2) was isolated from bovine and mouse hypothalamus by using this method. After cotransfection of Ob-Rb, Janus kinase 2 (JAK2), and SHP-2 into 293T cells, leptin results in direct binding of SHP-2 to the phosphorylated Tyr 985. The bound SHP-2 is itself tyrosine phosphorylated after leptin treatment. SHP-2 is not phosphorylated after leptin treatment when a Y-->F 985 receptor mutant is cotransfected. In the absence of SHP-2 phosphorylation, the level of JAK2 phosphorylation was increased. Tyrosyl phosphorylation of the leptin receptor and signal transducer and activater of transcription 3 (STAT3) are not affected by phosphorylation of SHP-2. These data suggest that activation of SHP-2 by the leptin receptor results in a decreased phosphorylation of JAK2 and may act to attenuate leptin signal transduction. The method used in this report can in principle be used to isolate additional components of the leptin, or other, signal transduction pathway.

Amino Acid Sequence↗

PubMed1999

A maternal form of the phosphatase Cdc25A regulates early embryonic cell cycles in Xenopus laevis.

In mammalian cells the Cdc25 family of dual-specificity phosphatases has three distinct isoforms, termed A, B, and C, which are thought to play discrete roles in cell-cycle control. In this paper we report the cloning of Xenopus Cdc25A and demonstrate its developmental regulation and key role in embryonic cell-cycle control. Northern and Western blot analyses show that Cdc25A is absent in oocytes, and synthesis begins within 30 min after fertilization. The protein product is localized in the nucleus in interphase and accumulates continuously until the midblastula transition (MBT), after which it is degraded. Upon injection into newly fertilized eggs, wild-type Cdc25A shortened the cell cycle and accelerated the timing of cleavage, whereas embryos injected with phosphatase-dead Cdc25A displayed a dose-dependent increase in the length of the cell cycle and a slower rate of cleavage. In contrast, injection of the phosphatase-dead Cdc25C isoform had no effect. Western blotting with an antibody specific for phosphorylated tyr15 in Cdc2/Cdk2 revealed a cycle of phosphorylation/dephosphorylation in each cell cycle in control embryos, and in embryos injected with phosphatase-dead Cdc25A there was a twofold increase in the level of p-tyr in Cdc2/Cdk2. Consistent with this, the levels of cyclin B/Cdc2 and cyclin E/Cdk2 histone H1 kinase activity were both reduced by approximately 50% after phosphatase-dead Cdc25A injection. The phosphatase-dead Cdc25A could be recovered in a complex with both Cdks, suggesting that it acts in a dominant-negative fashion. These results indicate that periodic phosphorylation of Cdc2/Cdk2 on tyr15 occurs in each pre-MBT cell cycle, and dephosphorylation of Cdc2/Cdk2 by Cdc25A controls at least in part the length of the cell cycle and the timing of cleavage in pre-MBT embryos. The disappearance of Cdc25A after the MBT may underlie in part the lengthening of the cell cycle at that time.

Amino Acid Sequence↗

PubMed1999

Investigation of the ATP binding site of Escherichia coli aminoimidazole ribonucleotide synthetase using affinity labeling and site-directed mutagenesis.

Aminoimidazole ribonucleotide (AIR) synthetase (PurM) catalyzes the conversion of formylglycinamide ribonucleotide (FGAM) and ATP to AIR, ADP, and P(i), the fifth step in de novo purine biosynthesis. The ATP binding domain of the E. coli enzyme has been investigated using the affinity label [(14)C]-p-fluorosulfonylbenzoyl adenosine (FSBA). This compound results in time-dependent inactivation of the enzyme which is accelerated by the presence of FGAM, and gives a K(i) = 25 microM and a k(inact) = 5.6 x 10(-)(2) min(-)(1). The inactivation is inhibited by ADP and is stoichiometric with respect to AIR synthetase. After trypsin digestion of the labeled enzyme, a single labeled peptide has been isolated, I-X-G-V-V-K, where X is Lys27 modified by FSBA. Site-directed mutants of AIR synthetase were prepared in which this Lys27 was replaced with a Gln, a Leu, and an Arg and the kinetic parameters of the mutant proteins were measured. All three mutants gave k(cat)s similar to the wild-type enzyme and K(m)s for ATP less than that determined for the wild-type enzyme. Efforts to inactivate the chicken liver trifunctional AIR synthetase with FSBA were unsuccessful, despite the presence of a Lys27 equivalent. The role of Lys27 in ATP binding appears to be associated with the methylene linker rather than its epsilon-amino group. The specific labeling of the active site by FSBA has helped to define the active site in the recently determined structure of AIR synthetase [Li, C., Kappock, T. J., Stubbe, J., Weaver, T. M., and Ealick, S. E. (1999) Structure (in press)], and suggests additional flexibility in the ATP binding region.

Adenosine↗

PubMed1999

Interpretation of genetic test results for hereditary nonpolyposis colorectal cancer: implications for clinical predisposition testing.

CONTEXT: Genetic testing for cancer predisposition is evolving from purely research applications to affecting clinical management. OBJECTIVE: To determine how often genetic test results for hereditary nonpolyposis colorectal cancer (HNPCC) can be definitively interpreted and used to guide clinical management. DESIGN: Case-series study conducted in 1996 to 1998 in which a complete sequence analysis of hMSH2 and hMLH1 coding sequence and flanking intronic regions was performed. Mutations were categorized as protein truncating and missense. In the case of missense alterations, additional analyses were performed in an effort to assess pathogenicity. SETTING AND PARTICIPANTS: Families were identified by self-referral or health care provider referral to a cancer genetics program. Participants and kindreds were classified into 1 of 4 categories: (1) Amsterdam criteria for HNPCC, (2) modified Amsterdam criteria for HNPCC, (3) young age at onset, or (4) HNPCC-variant. In addition, each proband was classified according to the Bethesda guidelines for identification of individuals with HNPCC. MAIN OUTCOME MEASURE: Alterations of hMSH2 and hMLH1 genes. RESULTS: Twenty-seven alterations of hMSH2 and hMLH1 were found in 24 of 70 families (34.3%). Of these, deleterious mutations that could be used with confidence in clinical management were identified in 25.7% (18/70) of families. The rates of definitive results for families fulfilling Amsterdam criteria, modified Amsterdam criteria, young age at onset, HNPCC-variant, and Bethesda guidelines were 27 (39.3%), 13 (18.2%), 12 (16.7%), 11 (15.8%), and 21 (30.4%), respectively. The prevalence of missense mutations, genetic heterogeneity of the syndrome, and limited availability of validated functional assays present a challenge in the interpretation of genetic test results of HNPCC families. CONCLUSIONS: The identification of pathogenic mutations in a significant subset of families for whom the results may have marked clinical importance makes genetic testing an important option for HNPCC and HNPCC-like kindreds. However, for the majority of individuals in whom sequence analysis of hMSH2 and hMLH1 does not give a definitive result, intensive follow-up is still warranted.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Increased duration of transgene expression in the lung with plasmid DNA vectors harboring adenovirus E4 open reading frame 3.

For gene therapy to be effective in the treatment of chronic diseases, plasmid DNA (pDNA) vectors that provide persistent expression of therapeutic levels of the transgene product are desirable. Studies in the lung with adenovirus vectors showed that products of the adenovirus E4 region can act both in cis and in trans to increase the duration of expression when transcription of the transgene was under the control of the human cytomegalovirus (CMV) promoter. To determine if these E4-encoded proteins could also effect greater persistence of expression from a nonviral vector, a complex composed of cationic lipid GL-67, a CMV promoter plasmid (pCF1-CAT), and an E4-containing adenovirus vector (Ad2/betagal-4) was instilled into the lungs of BALB/c nu/nu mice. Significant increases in the duration of transgene expression were observed for up to 10 weeks postinstillation compared with expression from mice instilled with control complexes containing an adenovirus vector deleted of most of E4 (Ad2/betagal-2). This effect could also be observed in immunodeficient NIH-rnu rats as well as in immunocompetent BALB/c mice. Studies with CMV promoter mutants indicated that a region proximal to the promoter was necessary for the E4-mediated increase in longevity of expression. In addition to the CMV promoter, a CMV enhancer-human mucin I (MUC-I) hybrid promoter also responded to these E4-encoded proteins with increased persistence of transgene expression, but a human interleukin 8 (IL-8) promoter did not. Ad2/betagal-4 could be replaced by a pDNA vector expressing only the E4 region, indicating that products of the E4 region alone were sufficient in the absence of expression from the rest of the adenovirus genome. Further analysis indicated that the protein encoded by open reading frame 3 (ORF3) alone was sufficient for conferring the increase in persistence of expression. These data indicate that expression of a single protein from the adenovirus genome can significantly improve the duration of transgene expression from pDNA vectors, and increases the feasibility of using nonviral vectors for the treatment of chronic diseases.

Adenoviridae↗

PubMed1999

Correction of enzymatic and lysosomal storage defects in Fabry mice by adenovirus-mediated gene transfer.

Fabry disease is a recessive, X-linked disorder caused by a deficiency of the lysosomal hydrolase alpha-galactosidase A. Deficiency of this enzyme results in progressive deposition of the glycosphingolipid globotriaosylceramide (GL-3) in the vascular lysosomes, with resultant distension of the organelle. The demonstration of a secretory pathway for lysosomal enzymes and their subsequent recapture by distant cells through the mannose 6-phosphate receptor pathway has provided a rationale for somatic gene therapy of lysosomal storage disorders. Toward this end, recombinant adenoviral vectors encoding human alpha-galactosidase A (Ad2/CEHalpha-Gal, Ad2/CMVHIalpha-Gal) were constructed and injected intravenously into Fabry knockout mice. Administration of Ad2/CEHalpha-Gal to the Fabry mice resulted in an elevation of alpha-galactosidase A activity in all tissues, including the liver, lung, kidney, heart, spleen, and muscle, to levels above those observed in normal animals. However, enzymatic expression declined rapidly such that by 12 weeks, only 10% of the activity observed on day 3 remained. Alpha-galactosidase A detected in the plasma of injected animals was in a form that was internalized by Fabry fibroblasts grown in culture. Such internalization occurred via the mannose 6-phosphate receptors. Importantly, concomitant with the increase in enzyme activity was a significant reduction in GL-3 content in all tissues to near normal levels for up to 6 months posttreatment. However, as expression of alpha-galactosidase A declined, low levels of GL-3 reaccumulated in some of the tissues at 6 months. For protracted treatment, we showed that readministration of recombinant adenovirus vectors could be facilitated by transient immunosuppression using a monoclonal antibody against CD40 ligand (MR1). Together, these data demonstrate that the defects in alpha-galactosidase A activity and lysosomal storage of GL-3 in Fabry mice can be corrected by adenovirus-mediated gene transfer. This suggests that gene replacement therapy represents a viable approach for the treatment of Fabry disease and potentially other lysosomal storage disorders.

Adenoviruses, Human↗

PubMed1999

Quality of life in long-term survivors of cervical cancer.

OBJECTIVE: The aim of this study was to evaluate the quality of life within a sample of cervical cancer survivors. STUDY DESIGN: In this study, 46 cervical cancer survivors at clinical stage I or II and one survivor at stage 0, were evaluated. Two control groups were selected from an ongoing cohort study, in which 527 women were postmenopausal and 344 women were postmenopausal with HRT. All controls and cancer survivors completed a self-evaluating questionnaire pertaining to personal conditions, medical surveillance, individual well-being and quality of life. RESULTS: Eighteen cervical cancer survivors were ovaries preserved. A total of 28 survivors, who had an oophorectomy, were compared with the controls. Most of the cancer survivors had a good socio-economic background and an active lifestyle. Forty-two percent were currently under medical surveillance and used medication regularly. The ratio of HRT users was higher in the oophorectomy group (36% in both short- and long-term therapy). With regard to the quality of life, there were no remarkable differences between oophorectomy survivors and controls. Except that the psychological condition in the ovaries preserved group was worse, the rest of the findings concerning the quality of life derived from the ovaries preserved group were rather close to that of the oophorectomy group. CONCLUSION: The quality of life in long-term cervical cancer survivors is generally satisfactory. The positive results may be due to the higher ratio of HRT use, ovarian preservation, good education, working conditions, as well as an active lifestyle.

Adult↗

PubMed1999

Growth cone neuropilin-1 mediates collapsin-1/Sema III facilitation of antero- and retrograde axoplasmic transport.

Collapsin-1/Sema III, a member of the semaphorin family, has been implicated in axonal pathfinding as a repulsive guidance cue. Cellular and molecular mechanisms by which collapsin-1 exerts its action are not fully understood. Collapsin-1 induces growth cone collapse via a pathway which may include neuropilin-1, a cellsurface collapsin-1 binding protein, as well as intracellular CRMP-62 and heterotrimeric G proteins. We previously identified a second action of collapsin-1, the facilitation of antero- and retrograde axoplasmic transport. This response occurs via a mechanism distinct from that causing growth cone collapse. To investigate the possible involvement of neuropilin-1 in the action of collapsin-1 on axoplasmic transport, we produced a soluble neuropilin-1 (sNP-1) lacking the transmembrane and intracellular region. sNP-1 progressively displaced the dose-response curve for collapsin-1 to induce growth cone collapse to higher concentrations. sNP-1 also inhibited collapsin-1-induced augmentation of both antero- and retrograde axoplasmic transport. Furthermore, an anti-neuropilin-1 antibody blocked the collapsin-induced axoplasmic transport. These results together indicate that neuropilin-1 mediates collapsin-1 action on axoplasmic transport. To visualize collapsin-1 binding to endogenous neuropilin-1, we used a truncated collapsin-1-alkaline phosphatase fusion protein (CAP-4). CAP-4 stains the growth cone, neurite, and cell body. However, local application of collapsin-1 to growth cone but to neither neurite nor cell body promotes axoplasmic transport. Thus, growth cone NP-1 mediates the facilitatory action of collapsin-1 on antero- and retrograde axoplasmic transport.

Alkaline Phosphatase↗

PubMed1999

Effects of insulin-like growth factor 1 and testosterone on the proliferation of antlerogenic cells in vitro.

Androgen hormones and growth factors are implicated in pedicle formation and antler transformation in deer. The potential to form a pedicle and an antler is only found in the antlerogenic periosteum (AP) overlying the presumptive antler growth region. Histological studies (Li and Suttie, '94) showed that AP consists of an inner cellular layer and an outer fibrous layer. Pedicle and antler are mainly derived from the cellular layer cells of the AP. Ossification takes place in four stages: intramembranous (IMO), transitional (OPC), pedicle endochondral (pECO) and antler endochondral (aECO). However, the precise mechanism whereby androgen hormones and growth factors control pedicle and antler formation is unknown. The aim of this study was to use cell culture techniques to investigate how testosterone and IGF1 affects the proliferation of antlerogenic cells from the four ossification stages of pedicle/antler in vitro. The results showed that in serum-free medium IGF1 stimulated the proliferation of antlerogenic cells from all four ossification stages in a dose-dependent manner. In contrast, testosterone alone did not show any mitogenic effects on these antlerogenic cells. However, in the presence of IGF1, testosterone increased proliferation of the antlerogenic cells from the IMO and the OPC stages (pedicle tissue), and reduced proliferation of the antlerogenic cells from transformation point (TP) and aECO stages (antler tissue). Therefore, the results from the present in vitro study support the in vivo findings that androgen hormones stimulate pedicle formation but inhibit antler growth. The change in the mitogenic effects of testosterone on antlerogenic cells from positive to negative occurs approximately at the change in ossification type from OPC to pECO. Therefore, these results reinforce the hypothesis that the transformation from a pedicle to an antler takes place at the time when the ossification type changes from OPC to pECO rather than at the time when the pedicle grows to its full species-specific height.

Animals↗

PubMed1999

Links between genetic and environmental factors and prostate cancer risk.

BACKGROUND: Genetic polymorphisms and expression of steroid receptors may explain why some individuals are more at risk of developing prostate cancer. Some risk factors often discussed are androgen stimulation, and vitamin A and D deficiency. Long CAG-repeats in exon 1 of the androgen receptor (AR) gene on the X chromosome seem to have a protective role against androgen overstimulation. Likewise, long vitamin D receptor alleles in the poly-A tract may prevent vitamin D stimulation. METHODS: Blood samples from 59 Swedish patients with sporadic prostate cancers, 59 with hereditary prostate cancer, and 34 Japanese prostate cancer patients were compared with benign controls. Tissue specimens from 37 Swedish and 23 Japanese prostate cancer patients with matching blood samples were investigated by immunohistochemical techniques. RESULTS: The number of CAG-repeats was identical in sporadic and hereditary prostate cancer patients, but the repeats were significantly shorter than in benign controls. Benign Japanese controls were similar to Swedish controls, but Japanese prostate cancers had longer repeats than did controls. Both the vitamin D and A receptor staining was stronger in Japanese than in Swedish prostate cancer specimens. Prostate cancer occurs approximately 5 years later in Japanese compared with Swedish men. CONCLUSIONS: Varying lengths of CAG-repeats of the androgen receptor cannot fully explain racial differences in clinical prostate cancer incidence. A larger content of vitamin A and D receptors may be linked to a delayed onset of clinical prostate cancer in Japanese men.

Asian People↗

PubMed1999

Structure analysis of new homologous compounds Ga2O3(ZnO)m (m = integer) by high-resolution analytical transmission electron microscopy.

The crystal structure of a new homologous compound series, Ga(2)O(3)(ZnO)(m) (m = integer), is determined by high-resolution lattice imaging and high spatial resolution energy-dispersive X-ray spectroscopy (EDS) analysis in a field-emission analytical transmission electron microscope. This work was carried out mainly on the compound with m = 9 (digallium nonazinc dodecaoxide), which belongs to the orthorhombic system and has lattice constants a(o) = 0.33, b(o) = 2.0 and c(o) = 3.4 nm. From the extinction rules three possible space groups are selected and from them a unique space group is assigned as noncentrosymmetric Cmc2(1) (No. 36) on the basis of structural requirements. Ga(2)O(3)(ZnO)(m) is a layered structure consisting of Ga-O and m + 1 Ga/Zn-O layers stacked alternately along the c axis. It is shown that the structure of Ga(2)O(3)(ZnO)(m) differs from that of M(2)O(3)(ZnO)(m) (M = In, Fe; m = integer) reported previously. In Ga(2)O(3)(ZnO)(m) the Ga atoms occupy the tetrahedral sites in the Ga-O layers, whereas the M atoms in the M-O layers occupy the octahedral sites in M(2)O(3)(ZnO)(m) (M = In, Fe).

Journal Article↗