Biomedical subjects
Publications and source records attributed to J Xu.
Pharmacognostic studies on the shape, microscopic structure and morphology of Fructus Glychrrhizae (Glycyrriza pallidifora)--an adulterant of Fructus Xanthii (Xanthium sibiricum) were carried out and compared with that of Frucus Xanthii to provide a basis for their identification.
Using two-time general rotation-constitution design, the math-mdele has been founded about Angelica sinensis prodution efficiency and quantity of nitrogen, phosphorus and potassium to use by doing experiments in many different spots and production demonstration for testing and verifying. Accordin to the modle, computer is used to simulate the better, through which people can get fresh Chinese angelica over 500 Kg per mu and also net income over 500 yuan per mu. It shows that this is the best combination. 95% density riliability for this plan is 6860-7600 plants, pure nitrogen 18.75-22.2 Kg, P2O5 9.1-11.1 Kg and K2O 4.46-5.37 Kg One mu. Proportion for nitrogen, phosphorus, potassium is 1:0.49:0.24.
The alkaloids of rhizoma of Menispermum dauricum DC growing in Xianning have been subjected to isolation and identification. The results showed that its two major constituents, which are only next of dauricine in content, are dauricinoline and daurinoline, instead of the commonly found daurisoline in the same plant materials from North China.
Absorption spectra of YAlO3: (Nd3+, Lu3+) single crystals for the three crystallographic axes were investigated at room temperature. The absorption band intensities distinctly revealed the anisotropy of YAlO3: (Nd3+, Lu3+). The Judd-Ofelt theory was modified and applied to the treatment of the anisotropic absorption spectra. The absorption cross sections and the electric dipole oscillator strengths of various bands were calculated for three crystallographic axes of YAlO3: (Nd3+, Lu3+) crystals. Three sets of phenomenological parameters omegat(alpha) were determined. The validity of the modified Judd-Ofelt approach is discussed in detail. Moreover, we explained the anisotropy of the optical absorption of YAlO3: (Nd3+, Lu3+).
The optical properties of two thermotropic liquid crystalline copolyesters were characterized by spectroscopic ellipsometry and UV-visible spectroscopy. The differences in the refractive index variation and chromatic dispersion have been revealed and discussed in terms of differences in the vibrating transition of excited electrons and the molecular structures of the polymers.
In clinical studies, both hydroxyurea and butyrate increase fetal hemoglobin expression and ameliorate the symptoms of sickle cell anemia. However, comparative studies of the effects of hydroxyurea and butyrate on the expression of the individual fetal hemoglobin genes, A gamma and G gamma, have not been performed. The present study reports the effects of hydroxyurea and butyrate on steady-state A gamma and G gamma mRNA levels in K562 cells. Because the high degree of homology between the A gamma and G gamma cDNA sequences precludes the use of large cDNA probes for detection of individual fetal hemoglobin gene products, we investigated the specificity of two 20-base oligonucleotide probes synthesized from the region of greatest sequence diversity between these genes. Hybridization experiments demonstrated that the A gamma oligonucleotide probe was specific for A gamma DNA and RNA sequences and the G gamma oligonucleotide probe was specific for G gamma DNA and RNA sequences. These oligonucleotide probes detected both A gamma and G gamma mRNAs in K562 cells. In K562 cells treated with 2 mM sodium butyrate for 168 hours, the G gamma mRNA level increased 3.6-fold, whereas the A gamma mRNA level was not significantly different from untreated cells. Similar results were obtained when K562 cells were treated with 80 microM hydroxyurea. The G gamma mRNA level increased 2.3-fold at 168 hours, whereas the A gamma mRNA level did not change. The above results demonstrate that both butyrate and hydroxyurea selectively increase G gamma expression. Selective regulation of individual fetal hemoglobin genes is also seen in human development, where approximately 70% of the total fetal hemoglobin in the fetus is G gamma. Therefore, understanding the mechanisms by which butyrate and hydroxyurea differentially regulate fetal hemoglobin gene expression may provide insights into the developmental regulation of hemoglobin expression as well as the mechanisms of action of pharmacological agents currently being used to treat sickle cell disease.
Monitoring the frequency of the Philadelphia (Ph) chromosome in chronic myelogenous leukemia (CML) is important in determining the effectiveness of treatment for patients during therapy. This can be done with high resolution by subjecting short-term bone marrow cultures (48 h) to 24 h of mitotic arrest before harvest and detecting Ph-positive (Ph+) metaphases by fluorescence in situ hybridization (FISH) in a procedure termed hypermetaphase FISH or HMF. Here, we compared procedures for detecting Ph+ interphase cells (interphase FISH or I-FISH) in peripheral blood polymorphonucleocytes (PMNs) with HMF results on the bone marrow of the same 26 CML patients in different stages of remission. The probes for I-FISH in these experiments were relatively large (200-300 kb) and sufficiently resolved in PMNs so that 97.5% of the cells were scorable. The correlation between the frequencies of Ph+ cells from the two different cell sources was excellent (r = 0.983, P < 0.0001); however, there was a consistently higher level of Ph+ cells observed in the cycling marrow cells than in the peripheral blood PMNs. This was discussed in terms of current theories of apoptosis in CML cells. The large number of PMNs analyzable by I-FISH (approximately 500/patient in this study) provided sufficiently narrow 99% confidence intervals to suggest the procedure as an effective and efficient method for monitoring the frequency of Ph+ cells in CML patients undergoing therapy. However, for detection and quantification of minimal residual disease, HMF is preferable to I-FISH because of the much lower frequency of false-positive readings with the former procedure.
Head and neck cancer, like lung cancer, is considered a paradigm of an environmentally induced disease. Genetically determined variation in DNA repair capacity is thought to contribute to susceptibility to tobacco-related cancers. In this molecular epidemiology study, we investigated the association between DNA mismatch-repair (MMR) gene expression and the risk of head and neck cancer. Using our newly developed multiplex reverse transcription-PCR assay, we simultaneously evaluated the relative expression levels of five MMR genes (hMSH2, hMLH1, hPMS1, hPMS2, and hGTBP/hMSH6) in the peripheral blood lymphocytes of 78 patients (mean age = 59.6 +/- 12.4 years) with newly diagnosed head and neck cancer and 86 healthy controls (mean age = 58.2 +/- 12.9 years). The relative MMR gene expression was not correlated with disease stage or tumor site in the cases or with smoking and alcohol use in the controls. The expression levels increased with age in both cases and controls, but the mean expression of hMLH1, hPMS1, and hGTBP/hMSH6 was significantly lower in the cases than in the controls (P < 0.05). Using the median expression level in controls as the cutoff value, significantly increased odds ratios (ORs) were associated only with low expression of hMLH1 (OR = 4.4; 95% confidence interval = 2.1-9.1) and hGTBP/hMSH6 (OR = 2.1; 95% confidence interval = 1.1-4.1) after adjustment for age, sex, ethnicity, smoking status, and alcohol use. The results suggest that low hMLH1 and hGTBP/hMSH6 expression is associated with an increased risk of head and neck cancer. Additional studies with a larger number of subjects are warranted to confirm these findings.
We have previously observed that ciliary neurotrophic factor (CNTF) can prevent the degeneration of androgen-sensitive perineal motoneurons and their target muscles, the bulbocavernosus and levator ani (BC/LA), in perinatal female rats. Response to CNTF is dependent on the expression of the alpha component of the CNTF receptor (CNTFRalpha). In the present study, we examined the developmental profile and androgen regulation of CNTFRalpha gene expression in BC/LA muscle, thigh muscle, and lumbosacral spinal cord. CNTFRalpha mRNA was abundantly expressed in the BC/LA and thigh around the time of birth; expression declined progressively after birth and remained low into adulthood. In contrast, CNTFRalpha message remained high in the lumbosacral spinal cord throughout development. Androgen regulation of CNTFRalpha expression was examined in prenatal animals by administering the androgen receptor blocker hydroxyflutamide from embryonic days E18 through E21. Four days of androgen deprivation caused a significant up-regulation of CNTFRalpha mRNA in the BC/LA, thigh, and spinal cord of male fetuses. After castration in adulthood, CNTFRalpha expression in the BC/LA transiently increased, then decreased below control levels. Expression of CNTFRalpha in thigh muscles and the lumbosacral spinal cord was not affected by adult castration. Thus, the perineal muscles and motoneurons are potential sites of direct CNTF action, and expression of the CNTFRalpha gene is modulated by androgen, especially in the androgen-sensitive perineal muscles. Transient up-regulation of CNTFRalpha following castration or androgen receptor blockade may represent a protective response designed to counteract the muscle atrophy normally induced by androgen withdrawal.
Lung cancer is the most frequent cause of cancer deaths in the United States. A strong correlation exists between mutations in the gene encoding the p53 tumor suppressor protein and lung malignancies. Our goal is to prepare a transgenic mouse model with disrupted p53 function in the epithelial cells of the peripheral lung. To achieve this goal, a "dominant negative" mutant form of p53 was expressed from the human surfactant protein C (SPC) promoter. The dominant negative p53 expressed from the SPC promoter will antagonize wild-type p53 functions in alveolar type II pneumocytes and some bronchiolar cells of the transgenic animals and thereby promote development of carcinoma of the lung. This animal model should prove useful to the study of lung carcinogenesis and to the identification of agents that contribute to neoplastic conversion in the lung.
We report on a 16-week-old male fetus with partial trisomy 16 and partial monosomy 22 resulting from 3:3 adjacent-2 segregation of a maternal balanced complex chromosome translocation involving chromosomes 5, 16, and 22. The karyotype of the 29-year-old phenotypically normal mother was 46,XX,t(5;16;22)(q31.3;q12.1;q11.2). The karyotype of the fetus was 46,XY,der (5)t(5;16;22)(q31.3;q12.1;q11.2),+der(16) t(5;16;22)mat,-22. The fetus had multiple congenital anomalies, including bilateral cleft lip and palate.
Pin1 is an essential and conserved mitotic peptidyl-prolyl isomerase (PPIase) that is distinct from members of two other families of conventional PPIases, cyclophilins and FKBPs (FK-506 binding proteins). In response to their phosphorylation during mitosis, Pin1 binds and regulates members of a highly conserved set of proteins that overlaps with antigens recognized by the mitosis-specific monoclonal antibody MPM-2. Pin1 is here shown to be a phosphorylation-dependent PPIase that specifically recognizes the phosphoserine-proline or phosphothreonine-proline bonds present in mitotic phosphoproteins. Both Pin1 and MPM-2 selected similar phosphorylated serine-proline-containing peptides, providing the basis for the specific interaction between Pin1 and MPM-2 antigens. Pin1 preferentially isomerized proline residues preceded by phosphorylated serine or threonine with up to 1300-fold selectivity compared with unphosphorylated peptides. Pin1 may thus regulate mitotic progression by catalyzing sequence-specific and phosphorylation-dependent proline isomerization.
Methylation of the C5 position of cytosine in CG dinucleotides represents an important element in the control of gene expression in eukaryotic cells. This major groove modification of DNA causes changes in DNA conformation that are recognized by DNA-binding proteins and DNA-damaging chemicals. We have observed that CG methylation affects the DNA damage produced by the enediyne esperamicin A1 and its analog lacking the intercalating anthranilate, esperamicin C. Fragments of the human phosphoglycerate kinase gene (PGK1) and the plasmid pUC19 were methylated with SssI methylase and subjected to damage by esperamicins A1 and C. Damage produced by esperamicin A1 was enhanced 1.5-2-fold near a single CG sequence at position -101 in PGK1 and in a region containing several methylated CG dinucleotides between positions -120 and -131. Esperamicin C-induced damage was enhanced to a similar degree in PGK1 but only at the site that contained multiple CG dinucleotides. There was enhancement of damage for both drugs in the pUC19 fragment at several sites near CG sequences. Analysis of the chemistry of esperamicin-induced DNA damage suggests that cytosine methylation does not affect the identity of drug-abstracted hydrogen atoms. The damage chemistry was also used to identify the DNA binding orientation of the esperamicins. The anthranilate of esperamicin A1 is predicted to intercalate in a CT step four base pairs in a 3'-direction to the CG sequence at -101 in PGK1 and in a CG dinucleotide at the site containing multiple CGs (positions -120 to -131). These observations are consistent with other studies that indicate a long range effect of cytosine methylation on DNA conformation.
The proliferation, migration, survival, and differentiation of oligodendrocyte progenitor cells, precursors to myelin-forming oligodendrocytes in the CNS, are controlled by a number of polypeptide growth factors in vitro. The requirement and roles for individual factors in vivo, however, are primarily unknown. We have used a cell transplantation approach to examine the role of fibroblast growth factor (FGF) in oligodendrocyte development in vivo. A dominant-negative version of the FGF receptor-1 transgene was introduced into oligodendrocyte progenitors in vitro, generating cells that were nonresponsive to FGF but responsive to other mitogens. When transplanted into the brains of neonatal rats, mutant cells were unable to migrate and remained within the ventricles. These results suggest a role for FGF signaling in establishing a motile phenotype for oligodendrocyte progenitor cell migration in vivo and illustrate the utility of a somatic cell mutagenesis approach for the study of gene function during CNS development in vivo.
Cerebral cortical maps in adult primates reorganize within minutes-hours after peripheral injuries, but subcortical versus intracortical contributions to this rapid reorganization remain controversial. The present results show that injury of nerves to the hands of adult monkeys triggers rapid (minutes-hours) changes in maps of the hand in the brainstem main cuneate nucleus. These findings suggest that peripheral injury causes an initial concurrent reorganization of brainstem and cortical substrates and that early sensory changes emerge from reorganization involving multiple central levels.
Analyses involving data from many locations throughout the world have now been conducted to assess the association between air pollution and mortality. To date, six independent analyses of mortality data for Philadelphia, Pennsylvania, have been reported. In this new analysis of Philadelphia data for 1974-1988, Poisson regression models were developed to estimate the increased risk of daily mortality associated with air pollution while controlling for longer-term time trends and season and for weather. Model development was based on prior understanding of the effects of these factors on mortality and on consideration of model fit. The authors found moderate correlations of daily concentrations of total suspended particles (TSP), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO), and only slight correlations of ozone (O3) with other pollutants. When included individually in the model, the means of current and previous days' levels of TSP, SO2, and O3 had statistically significant effects on total mortality; pollutant increases of an interquartile range (34.5 micrograms/m3, 12.9 ppb, and 20.2 ppb, respectively) were associated with increases in mortality of around 1% for TSP and SO2, and of around 2% for O3. The effects of TSP and SO2 were diminished when both pollutants were simultaneously included in the model, whether pairwise or in the full multi-pollutant model. These analyses confirm the association between TSP and mortality found in previous studies in Philadelphia and show that the association is robust to consideration of other pollutants in the model.
In a recent study of 91 families having at least three first degree relatives with prostate cancer, we reported the localization of a major susceptibility locus for prostate cancer (HPC1) to chromosome 1 [band q24; J. R. Smith et al., Science (Washington DC), 274: 1371-1373, 1996]. There was significant evidence for locus heterogeneity, with an estimate of 34% of the families being linked to this locus. In this report, we investigate the importance of age at diagnosis of prostate cancer and number of affected individuals within a family as variables in the linkage analysis of an expanded set of markers on 1q24. Under two different models for the prostate cancer locus, we find that the evidence for linkage to HPC1 is provided primarily by large (five or more members affected) families with an early average age at diagnosis. Specifically, for 40 North American families with an average age at diagnosis <65 years, the multipoint lod score is 3.96, whereas for 39 families with an older average age at diagnosis, this value is -0.84. Assuming heterogeneity, the proportion of families linked is 66% for the 14 families with the earliest average ages at diagnoses, but it decreases to 7% for the families with the latest ages at diagnoses. A similar age effect is observed in 12 Swedish pedigrees analyzed. To test the hypotheses generated by these analyses, we examined an additional group of 13 newly identified prostate cancer families. Overall, these families provided additional evidence for linkage to this region (nonparametric linkage Z = 1.91; P = 0.04 at marker D1S1660), contributed primarily by the families in this group with early age at diagnosis [nonparametric linkage Z = 2.50 (P = 0.01) at D1S422]. These results are consistent with the existence of a locus in this region that predisposes men to develop early-onset prostate cancer.
CONTEXT: Approximately 9% of prostate cancer cases have been estimated to result from inheritance of mutated prostate cancer susceptibility genes. Few data exist as to whether there are clinical differences between prostate cancers that are inherited and those that occur in the general population. OBJECTIVE: To investigate phenotypic characteristics of families potentially linked to the hereditary prostate cancer 1 (HPC1) locus on chromosome 1q24-25. DESIGN: Retrospective case study in which clinical data were extracted from medical and pathological records. FAMILIES: A total of 74 North American families with hereditary prostate cancer. Prostate cancer cases from the National Cancer Data Base were used as a reference population for comparison. MAIN OUTCOME MEASURES: The families were divided into 2 groups: either potentially linked (33 families with 133 men with prostate cancer), and thus likely to be carrying an altered HPC1 gene, or potentially unlinked (41 families with 172 men with prostate cancer), on the basis of haplotype analysis in the region of HPC1. The age at diagnosis of prostate cancer, serum prostate-specific antigen levels, digital rectal examination status, stage, grade, primary treatment of prostate cancers, and occurrence of other cancers were compared between the groups. RESULTS: The mean age at diagnosis of prostate cancer for men in potentially linked families was significantly lower than for men in potentially unlinked families (63.7 vs 65.9 years, respectively, P=.01; mean age at diagnosis in the reference population was 71.6 years). Higher-grade cancers (grade 3) were more common in potentially linked families, and advanced-stage disease was found in 41% of the case patients in potentially linked families compared with 31% in both the potentially unlinked families and the reference groups (P=.03 for the latter comparison). In the other clinical parameters, we found no significant differences between the groups. A modest excess of breast cancer and colon cancer was found in potentially linked families in comparison with potentially unlinked families, but this difference was not statistically significant. CONCLUSIONS: Families that provide evidence for segregation of an altered HPC1 gene are characterized by multiple cases of prostate cancer that, in most respects, are indistinguishable from nonhereditary cases. However, 3 characteristics were observed: younger age at diagnosis, higher-grade tumors, and more advanced-stage disease. Our study shows that a significant fraction of hereditary prostate cancers are diagnosed in advanced stages, emphasizing the clinical importance of early detection in men potentially carrying prostate cancer susceptibility genes. These findings support the current recommendations to screen men with a positive family history of prostate cancer beginning at age 40 years.