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Biomedical subjects

N Yang

Publications and source records attributed to N Yang.

At least 127 records · Page 7Linked to original sources
PubMed1992

Differential molecular mechanism of the estrogen action that regulates lactoferrin gene in human and mouse.

The 5'-flanking region of the human lactoferrin gene was isolated from a human placental genomic library. This genomic clone contains a 16-kilobase pair (kbp) insert and produces seven fragments when digested with the SacI restriction enzyme. We sequenced one of the fragments that comprises 1294 bp of the 5'-flanking sequence, 79 bp of the first exon, and 690 bp of the first intron. A major transcription start site was mapped by primer extension. The region immediately upstream from the transcription initiation site following the first exon is abundant in G and C nucleotides. In the promoter and 5'-flanking region within a 300-bp stretch (-465 to -165) of the DNA, we found a noncanonical TATA box (ATAAA), CAAT-like sequence (CAAC) and sequences homologous to the consensus SP1 binding site, Pu.1/Sp.1 binding element (PU box), two half-palindromic estrogen response elements (EREs; GGTCA), an imperfect ERE (GGTCAAGGCGATC), and a sequence resembling the chicken ovalbumin upstream promoter transcription factor (COUP-TF) binding site (GTCTCACAGGTCA). The COUP-TF binding site and the imperfect ERE shared five nucleotides (GGTCA). With the exception of the two half-palindromic EREs, the elements with very well matched sequences were also found in the corresponding positions in the mouse lactoferrin gene. The synthetic oligonucleotide, including the 26 bp of COUP/ERE sequence, was cloned before the SV40 promoter in a chloramphenicol acetyltransferase reporter construct. These chimeric plasmids were transiently transfected into human endometrium carcinoma RL95-2 cells to assess hormone responsiveness. We found that the COUP/ERE element acted as an enhancer in response to estrogen stimulation. In vitro DNase I footprinting analysis showed binding of the estrogen receptor on the imperfect ERE. In contrast to the mouse lactoferrin COUP/ERE element, COUP-TF does not interact with this element, as demonstrated by band shift assay and site-directed mutagenesis. Therefore, the molecular mechanisms of the estrogen action that govern the lactoferrin gene expression differ between mouse and human.

Amino Acid Sequence↗
PubMed1992

Isolation and characterization of furanomycin nonproducing Streptomyces threomyceticus mutants.

Stable mutants that are blocked in the production of the polyketide antibiotic furanomycin were generated by treatment of Streptomyces threomyceticus (ATCC 15795) with a combination of N-methyl-N'-nitro-N-nitrosoguanidine (NTG) and ultraviolet light. On the basis of their cosynthetic properties in mixed culture, the mutants were grouped into eleven phenotypic classes. The polarity of the cosynthetic reactions for seven classes of mutants was revealed by filtrate feeding experiments. This allowed them to be arranged in the most probable linear sequence of metabolic blocks. One of the remaining groups of mutants exhibited no cosynthetic behavior and is believed to be blocked in a gene that regulates furanomycin biosynthesis.

Amino Acids↗
PubMed1992

[The kinetic observation of serum ketone body levels in surgical patients receiving MCT or LCT emulsions].

The changes of serum beta-hydroxybutyrate concentrations in patients after receiving medium chain triglycerides (MCT) or long chain triglycerides (LCT) were studied. The patients were divided into two groups: in Group 1, the dose of fat was 0.14 g/kg.h for fat emulsion clearance test: and in Group 2, the dose was 0.06 g/kg.h for total parenteral nutrition (TPN) support. The beta-hydroxybutyrate concentrations were estimated by an enzymatic method using Sigma's beta-hydroxybutyrate kit (Sigma Diagnostics, MO 63178, USA). The normal range of beta-hydroxybutyrate concentration in 30 healthy Chinese subjects was 1.04 +/- 1.42 mg/dl (range 0-3.88 mg/dl). In Group 1, we found that the concentrations of beta-hydroxybutyrate rose steadily after fat emulsion infusion. The concentrations in the medium chain triglyceride group were higher than those in long chain triglyceride group. The elevated concentrations of beta-hydroxybutyrate gradually returned to normal levels when the emulsion infusion was stopped. In Group 2, the concentrations of beta-hydroxybutyrate in the patients were within the normal range.

3-Hydroxybutyric Acid↗
PubMed1992

[Study and preparation of Vi-PHA reagent and its application for detection of Salmonella typhi carriers].

Purified S. typhi Vi antigen is sensitized with equal volume of tannic acid treated formalational sheep erythrocytes (SRBC) at a final concentration of 1 microgram/ml. The Vi-passive hemagglutination assay (Vi-PHA) diagnostic reagent is developed to detect Vi antibodies to S. typhi for the detection of chronic carriers after typhoid fever and the screening S. typhi healthy carriers from food-handlers, which is characterized with high sensitivity, strong specificity and good stability. This Vi-PHA reagent is able to detect 1.16 micrograms/ml of Vi antibodies and doesn't make any cross reaction with healthy sera. For the sera of other diseases, the cross rate is only 0.84%. Using this reagent, 19 positive sera (6.93%) are detected from 274 convalescent sera from typhoid fever, 14 convalescents of which are stool-culture S. typhi positive, that persists a positive rate of 73.68%; 3 positive sera are detected from 106 foodhandlers, one of which is stool-culture S. typhi positive. Therefore, the reagent is simple, convenient, rapid and easy to be applicated in basic unit.

Antibodies, Bacterial↗
PubMed1991

Retinoic acid is a negative regulator of AP-1-responsive genes.

We present evidence that retinoic acid can down-regulate transcriptional activation by the nuclear protooncogene c-jun. All three members of the retinoic acid receptor (RAR) subfamily (RAR alpha, RAR beta, and RAR gamma) can repress transcriptional induction of the human collagenase gene or a heterologous promoter that contains the collagenase promoter AP-1-binding site. In contrast, the retinoid X receptor fails to repress Jun/AP-1 activity, demonstrating a significant difference between the two regulatory systems through which retinoids exert their transcriptional control. Analysis of RAR alpha mutants in transfection studies reveals that the DNA-binding domain is important for the inhibition of Jun/AP-1 activity, even though the RAR does not bind the collagenase AP-1 site. Rather, gel-retardation assays reveal that bacterially expressed full-length RAR alpha inhibits binding of Jun protein to target DNA. These data suggest that the RAR alpha may form a nonproductive complex with c-Jun and provides a simple mechanisms by which retinoic acid may limit cell growth and possibly malignant progression.

Animals↗
PubMed1991

Characterization of DNA binding and retinoic acid binding properties of retinoic acid receptor.

High-level expression of the full-length human retinoic acid receptor (RAR) alpha and the DNA binding domain of the RAR in Escherichia coli was achieved by using a T7 RNA polymerase-directed expression system. After induction, full-length RAR protein was produced at an estimated level of 20% of the total bacterial proteins. Both intact RAR molecules and the DNA binding domain bind to the cognate DNA response element with high specificity in the absence of retinoic acid. However, this binding is enhanced to a great extent upon the addition of eukaryotic cell extracts. The factor responsible for this enhancement is heat-sensitive and forms a complex with RAR that binds to DNA and exhibits a distinct migration pattern in the gel-mobility-shift assay. The interaction site of the factor with RAR is localized in the 70-amino acid DNA binding region of RAR. The hormone binding ability of the RAR alpha protein was assayed by a charcoal absorption assay and the RAR protein was found to bind to retinoic acid with a Kd of 2.1 x 10(-10) M.

Animals↗
PubMed1991

Conversion of the human blood group H antigen to A antigen in vitro.

A-transferase (N-acetylgalactosaminyl transferase) was purified from human group A plasma using Sepharose 4B affinity chromatography. Human anti-A antibodies were purified from human serum by adsorption to an immunosorbent column and heat elution in order to detect the A antigen. Conditions appropriate for the development of the A antigen on O red cells were examined and several buffer systems were found to be equally effective. Expression of the developed A antigen was found to be similar to that on group A red cells, indicating that the system in vitro has similar activity to the system in vivo. The H antigen from human saliva was coupled to Sepharose 4B or adsorbed to a nitrocellulose membrane. The A antigen was able to be developed on these materials by the action of group A-transferase. The procedures enabled the identification in vitro of sugar-transferase activities which can be useful in studies within the A,B,H antigen system or other carbohydrate antigen system.

ABO Blood-Group System↗
PubMed1990

Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor.

We present evidence that the glucocorticoid receptor (GR) and transcription factor Jun/AP-1 can reciprocally repress one another's transcriptional activation by a novel mechanism that is independent of DNA binding. Overexpression of c-Jun prevents the glucocorticoid-induced activation of genes carrying a functional glucocorticoid response element (GRE). Conversely, GR is able to repress AP-1-mediated transcriptional activation. Mutant analysis reveals that the ligand binding and DNA binding domains of GR and the region including the leucine zipper of c-Jun are required for repression. Gel retardation analysis demonstrates that bacterially expressed c-Jun disrupts GR-GRE complexes. These data indicate that members of two distinct classes of transcription factors can oppose one another's activity through a mechanism likely involving protein-protein interactions.

Animals↗
PubMed1989

Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. II. Radical prostatectomy treated patients.

Serum prostate specific antigen was determined (Yang polyclonal radioimmunoassay) in 102 men before hospitalization for radical prostatectomy. Prostate specimens were subjected to detailed histological and morphometric analysis. Levels of prostate specific antigen were significantly different between patients with and without a Gleason score of 7 or greater (p less than 0.001), capsular penetration greater than 1 cm. in linear extent (p less than 0.001), seminal vesicle invasion (p less than 0.001) and pelvic lymph node metastasis (p less than 0.005). Prostate specific antigen was strongly correlated with volume of prostate cancer (r equals 0.70). Bivariate and multivariate analyses indicate that cancer volume is the primary determinant of serum prostate specific antigen levels. Prostate specific antigen was elevated 3.5 ng. per ml. for every cc of cancer, a level at least 10 times that observed for benign prostatic hyperplasia. Prostate specific antigen is useful as a preoperative marker because no patient with lymph node metastasis had serum levels of less than 10 ng. per ml. (4 times the upper limit of normal range). Of the patients with greater than 50 ng. per ml. two-thirds had microscopic lymph node metastasis and 90 per cent had seminal vesicle invasion. Serum prostatic acid phosphatase levels showed a significantly weaker correlation with cancer volume (r equals 0.51) and every other pathological parameter. Of the patients 73 per cent had serum prostatic acid phosphatase levels in the normal range (0 to 2.1 ng. per ml.), including 7 per cent who had pelvic lymph node metastasis. Postoperative prostate specific antigen values were available in 97 of 102 patients, with a mean and maximum followup of 12 and 38 months. No patient with pelvic lymph node metastasis achieved an undetectable prostate specific antigen level without adjunctive therapy (hormonal or radiation). No difference in preoperative or postoperative prostate specific antigen levels, cancer volume, seminal vesicle invasion or incidence of pelvic lymph node metastasis was seen between patients with no capsular penetration and those with minimal capsular penetration (1 cm. or less total linear extent of full thickness penetration), providing the first quantitative evidence that small amounts of capsular penetration may not be of biological or prognostic significance.

Acid Phosphatase↗
PubMed1989

Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. IV. Anti-androgen treated patients.

Serum prostate specific antigen was determined (Yang polyclonal radioimmunoassay) in 45 patients after anti-androgen therapy for stage D2, untreated adenocarcinoma of the prostate. Of the patients 9 per cent had undetectable prostate specific antigen levels and 22 per cent were within the normal range (0.0 to 2.5 ng. per ml.), with a mean interval of 2 years since introduction of therapy. Multiple prostate specific antigen values following anti-androgen therapy were available in 36 of 45 patients. The majority of the patients demonstrated an initial, often dramatic decrease in prostate specific antigen levels during the first 6 months after introduction of therapy. After 6 months 21 of 29 patients (72 per cent) had increasing prostate specific antigen levels. Data suggest that serum prostate specific antigen determination 6 months after introduction of therapy is capable of distinguishing patients with a favorable and persisting response to anti-androgen therapy from those in whom a limited response can be expected.

Adenocarcinoma↗
PubMed1988

Identification of a new class of steroid hormone receptors.

The gonads and adrenal glands produce steroids classified into five major groups which include the oestrogens, progestins, androgens, glucocorticoids and mineralocorticoids. Gonadal steroids control the differentiation and growth of the reproductive system, induce and maintain sexual characteristics and modulate reproductive behaviour. Adrenal steroids also influence differentiation as well as being metabolic regulators. The effects of each steroid depend primarily on its specific receptors, the nature of which could therefore provide a basis for classification of steroid hormone action. The successful cloning, sequencing and expression of the human glucocorticoid (hGR) (ref. 1), oestrogen (hER), progesterone (hPR), and mineralocorticoid (hMR) receptors, complementary DNA, plus homologues from various species, provides the first opportunity to study receptor structure and its influence on gene expression. Sequence comparison and mutational analysis show structural features common to all groups of steroid hormone receptors. The receptors share a highly conserved cysteine-rich region which functions as the DNA-binding domain. This common segment allows the genome to be scanned for related gene products: hMR cDNA for example, was isolated using an hGR hybridization probe. In this study, using the DNA-binding domain of the human oestrogen receptor cDNA as a hybridization probe, we have isolated two cDNA clones encoding polypeptides with structural features suggestive of cryptic steroid hormone receptors which could participate in a new hormone response system.

Amino Acid Sequence↗
PubMed1987

Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate.

To compare the clinical usefulness of the serum markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), we measured them by radioimmunoassay in 2200 serum samples from 699 patients, 378 of whom had prostatic cancer. PSA was elevated in 122 of 127 patients with newly diagnosed, untreated prostatic cancer, including 7 of 12 patients with unsuspected early disease and all of 115 with more advanced disease. The PSA level increased with advancing clinical stage and was proportional to the estimated volume of the tumor. The PAP concentration was elevated in only 57 of the patients with cancer and correlated less closely with tumor volume. PSA was increased in 86 percent and PAP in 14 percent of the patients with benign prostatic hyperplasia. After radical prostatectomy for cancer, PSA routinely fell to undetectable levels, with a half-life of 2.2 days. If initially elevated, PAP fell to normal levels within 24 hours but always remained detectable. In six patients followed postoperatively by means of repeated measurements, PSA--but not PAP--appeared to be useful in detecting residual and early recurrence of tumor and in monitoring responses to radiation therapy. Prostate massage increased the levels of both PSA and PAP approximately 1.5 to 2 times. Needle biopsy and transurethral resection increased both considerably. We conclude that PSA is more sensitive than PAP in the detection of prostatic cancer and will probably be more useful in monitoring responses and recurrence after therapy. However, since both PSA and PAP may be elevated in benign prostatic hyperplasia, neither marker is specific.

Acid Phosphatase↗
PubMed1986

Evaluation of prostate-specific antigen and prostatic acid phosphatase as prostate cancer markers.

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hypertrophy (BPH), and prostatitis. PSA has proved to be diagnostically more sensitive than PAP for the detection of prostate cancer: 95.0 per cent vs 60.0 per cent for 40 newly diagnosed cancer cases, and 97.1 per cent vs 65.7 per cent for 35 relapsed cases. This also holds true for those patients with early-stage disease: 71.4 per cent vs 0 per cent for 7 Stage A1 cases. The specificities of PSA and PAP are comparable, 96.8 per cent vs 98.9 per cent, respectively. PSA is also more sensitive for monitoring therapy, since it usually rises before PAP and always precedes clinical signs of relapse. Although PSA may be elevated more frequently than PAP in some patients with BPH and prostatitis, it is postulated that these patients with elevated serum PSA and normal serum PAP may fall into a high-risk sub-population which may have early prostate cancer or precancerous conditions not easily detectable by current clinical and diagnostic techniques. Our data suggest PSA is a sensitive useful tumor marker for the diagnosis and management of prostate cancer. In addition, PAP, in combination with PSA, may serve as a useful adjunct for differential diagnosis and confirmation of advanced stage prostate cancer.

Acid Phosphatase↗
PubMed1986

Relative reliability of five serially measured markers for prognosis of progression in prostate cancer.

During an 8-year period, 1,065 serum specimens were collected from 79 patients with prostate cancer of stages B2 to D1 (group I) and 51 patients with newly diagnosed stage D2 prostate cancer (group II) to evaluate statistically the relative reliability of elevated tumor-associated markers for progressive disease in prostate cancer. Forty of the group I patients and 21 of the group II patients presented a clinical progression of disease during follow-up. With the use of Gail's modification of Cox's regression model, serial acid phosphatase (AcP), total alkaline phosphatase (TAP), bone alkaline phosphatase (BAP), prostatic acid phosphatase (PAP), and prostate-specific antigen (PA) were analyzed. Results from group I patients revealed that only PA (P = .0002) and PAP (P = .0684) were prognostically important markers for detection of imminent disease progression. However, all markers were prognostically important in group II patients. Comparative studies indicated that PA (P = .0052) and PAP (P = .0359) were the more reliable markers for group I patients, whereas PA (P less than .0001), BAP (P = .0007), and PAP (P = .0206) were the more reliable markers for group II patients. Multivariate analyses revealed that, after adjustment for the effect of PA, no other marker was significantly related to the risk of progression. Elevated PA levels were predictive of increased risk 6 months before disease progression in group I patients only (P less than .0001). Overall, the apparent order of prognostic reliability for disease progression was found to be PA greater than PAP greater than BAP greater than AcP greater than TAP.

Acid Phosphatase↗
PubMed1985

Prognostic importance of prostate-specific antigen for monitoring patients with stages B2 to D1 prostate cancer.

To evaluate the prognostic value of prostate-specific antigen (PA) for detection of tumor growth after definitive therapy, 602 sera from 70 patients with stages B2 to D1 prostate cancer (26 of whom recurred) were analyzed in a blind study. Using Cox's proportional-hazards model, a highly significant association was found between serially measured PA and disease-free survival time (p = 0.0002). A positive predictive value of 100% was found for some markedly elevated PA levels and confirmed recurrence of disease. In fact, this study suggested that once a PA level of 88 ng/ml was reached, there was an average time of less than 2 months before a recurrence was clinically confirmed. Tumor growth in patients who recurred was indicated by a PA elevation before recurrence in 92% (24 of 26) as opposed to 20% (9 of 44) in disease-free patients. Additionally, in these 24 of 26 patients, levels of PA were elevated 12 months (mean lead time) before a confirmed disease recurrence. In patients who were still disease free, serial PA appeared to increase concurrently with putative tumor growth as shown by the initial surgical stage. Generally, the greater the PA level the more advanced was the stage of disease (B2 to D1). These data suggest that PA may be a useful adjuvant marker for monitoring tumor growth in patients with regionally confined prostate cancer.

Antigens, Neoplasm↗
PubMed1985

Ovarian carcinoma: a multivariate analysis of prognostic factors.

Five hundred and fifty six women with invasive epithelial ovarian carcinoma were assessed for postoperative treatment between 1966 and 1976. The records of this group were reviewed retrospectively. Sixteen characteristics of the patient and tumor were analyzed for prognostic significance by univariate and multivariate techniques. Tumor grade, the presence of residual disease, and patient performance status are identified as stage-specific independent prognostic factors. These independent factors define patient subsets with good, intermediate, and poor prognosis within each stage. The results show that more effective treatment strategies are required for patients in poor prognosis subsets. Estimates of tumor grade, extent of residual disease, and performance status should be included in reports of treatment outcome.

Adult↗