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Biomedical subjects

J Qian

Publications and source records attributed to J Qian.

At least 199 records · Page 11Linked to original sources

Prostatic intraepithelial neoplasia and well differentiated adenocarcinoma maintain an intact basement membrane.

The status of the basement membrane in prostatic intraepithelial neoplasia (PIN) and adenocarcinoma is unsettled. Previous studies using antibodies directed against Type IV collagen have been hindered by intense staining around the stromal smooth muscle fibers, making interpretation of acinar staining difficult. We employed a monoclonal antibody to heparan sulfate proteoglycan (HSPG) to overcome this problem, recognizing that HSPG is present in the basement membrane of epithelial and endothelial cells, but not stromal smooth muscle cells. In 22 totally-embedded whole mount radical prostatectomies for adenocarcinoma which contained PIN, intense HSPG immunoreactivity was observed in the basement membrane of all normal and hyperplastic acini, 98% of acini with high grade PIN, and 100% of acini of well differentiated (Gleason score 5) adenocarcinoma; vessels served as the internal positive control, with consistent staining throughout each specimen. The extent of HSPG immunoreactivity in cancer decreased with increasing Gleason grade (measured as percent of acini staining, in 10% increments; p = 0.002). These findings indicate that HSPG is a consistent component of the basement membrane of benign, hyperplastic, and early neoplastic prostatic acini, and, unlike other extracellular matrix proteins such as type IV collagen, is not hindered by background staining around stromal smooth muscle cells. High grade PIN and well differentiated adenocarcinoma usually maintain an intact basement membrane, and loss of the basement membrane occurs with histologic dedifferentiation.

Adenocarcinoma↗

The extent and zonal location of prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia: relationship with carcinoma in radical prostatectomy specimens.

High grade prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH) are considered putative precursors of prostatic adenocarcinoma. We determined the extent and zonal distribution of PIN and AAH in totally-embedded radical prostatectomies with prostate cancer, including 195 cases with PIN and 217 with AAH. PIN was identified in 86% of the cases. The mean volume of PIN was 1.32 cc (range, 0-8.12 cc), and was greater for PIN within 2 mm of cancer (mean, 1.0 cc) than for PIN more than 2 mm from cancer (mean, 0.3 cc). PIN was usually multicentric (64.5% of cases) and located in the non-transition zone (63%) or all zones (36%). The volume of PIN was positively correlated with the volume of cancer, patient age, pathologic stage and Gleason score. AAH was identified in 23.0% of the cases, and was more frequent in the transition zone (19.8% of cases) than in the non-transition (peripheral and central) zone (6.0%). The number of foci of AAH in the transition zone was always greater than that in the non-transition zone. AAH was frequently multicentric (46% of cases), especially in the transition zone (47% of transition zone cases) compared with the non-transition zone (23% of non-transition zone cases). The mean volume of AAH was 0.029 cc (range, 0-1.29 cc), and was much higher in the transition zone than in the non-transition zone. AAH was more common in older patients and those with greater prostatic weight, higher prostatic volume, greater percent of nodular hyperplasia, greater volume of cancer, greater percent of Gleason patterns 4 and 5 cancer, higher volume of prostatic intraepithelial neoplasia and higher serum prostate specific antigen concentration. Our results indicate that the extent and zonal distribution of high grade PIN and carcinoma are strongly associated, and that PIN is frequently multicentric; this supports the hypothesis that PIN is a premalignant lesion. AAH and carcinoma show a weak but significant association; if AAH is a premalignant lesion, it probably is associated with a subset of cancers arising in the transition zone.

Aged↗

Atypical adenomatous hyperplasia of the prostate. Relationship with carcinoma in 217 whole-mount radical prostatectomies.

Atypical adenomatous hyperplasia (AAH) of the prostate is a microscopic proliferation of small glands that may be mistaken for adenocarcinoma. The extent and multicentricity of this histopathologic lesion have not been fully defined, and the spatial relationship with carcinoma has not been described in whole-mount surgical specimens. We sought to determine whether the extent and zonal location of AAH is related to prostate cancer by evaluating 217 totally embedded radical prostatectomy specimens with cancer. All but 17 patients had clinically localized cancer, and none had received preoperative therapy. The number of foci and volume of AAH were measured using a grid-counting method; proximity to cancer was recorded as either less than or equal to 2 mm from cancer or greater than 2 mm from cancer. AAH was identified in 23.0% of cases and was more frequent in the transition zone (19.8% of cases) than in the nontransition (peripheral and central) zone (6.0%). It was found within 2 mm of cancer in 34% of cases of AAH, including 30% of cases in the transition zone and 31% cases in the nontrasition zone. The number of foci of AAH in the transition zone was always greater than that in the nontransition zone, regardless of whether it was within 2 mm of cancer or more than 2 mm from cancer. AAH was frequently multicentric (46% of cases), especially in the transition zone (47% of transition zone cases) compared with the nontransition zone (23% of nontransition zone cases). The mean volume of AAH was 0.029 cc (range, 0-1.29 cc) and was much higher in the transition zone than the nontransition zone, regardless of whether it was within 2 mm of cancer or more than 2 mm from cancer. In cases of AAH within 2 mm of cancer, the volume was lower than in cases more than 2 mm from cancer; this was true regardless of zonal location. AAH was more common in older patients and in those with greater prostatic weight, higher prostatic volume, greater percentage of nodular hyperplasia, greater volume of cancer, greater percent of Gleason patterns 4 and 5 cancer, higher volume of prostatic intraepithelial neoplasia, and higher serum prostate-specific antigen level. There was no correlation of number of foci of AAH or volume of AAH with pathologic stage, seminal vesicle invasion, Gleason primary pattern or score, nuclear grade, perineural invasion by tumor, or DNA ploidy. Our results indicate that AAH is usually found iin the transition zone in association with nodular hyperplasia and is often multicentric. The extent and zonal distribution of AAH and carcinoma show a weak but significant association.

Aged↗

Minimal or no cancer in radical prostatectomy specimens. Report of 13 cases of the "vanishing cancer phenomenon".

Early detection efforts identify prostate cancer at lower clinical and pathologic stages, often resulting in smaller volumes of tumor in radical prostatectomy specimens. In some cases, complete sampling of the radical prostatectomy specimen for biopsy-proven adenocarcinoma reveals minimal or no residual cancer. We evaluated the clinical and pathologic findings in 13 such cases in an effort to document this finding, which we refer to as the "vanishing cancer phenomenon." The mean number of prostate slides examined per case was 79 (range, 34-248). Carcinoma was absent in two cases, present in a single focus in eight cases, and present in two foci in three cases. Mean cancer volume in the 10 cases with residual tumor was 0.019 cc (range, 0.003-0.038); the largest single dimension of any tumor focus was 3 mm. All cancers were well differentiated or moderately differentiated in the biopsy and prostatectomy. Our results indicate that in some cases cancer may be extremely difficult or impossible to find in the prostatectomy specimen despite exhaustive sampling. The incidence of this "vanishing cancer phenomenon" is probably increasing because more low-stage cancers are being treated by prostatectomy. The inability to identify cancer in a prostate removed for needle biopsy-proven carcinoma may not indicate technical failure.

Adenocarcinoma↗

Influence of hemodialysis membranes on gene expression and plasma levels of interleukin-1 beta.

Plasma levels of interleukin-1 beta (IL-1 beta) were measured in 10 normal subjects, in 11 nondialyzed end-stage renal failure (ESRD) patients, and in 22 hemodialysis (HD) patients. Of the HD patients, 7 were dialyzed with Cuprophan (CU), 7 with polymethylmethacrylate (PMMA), and 8 with polysulphone (PS) dialyzers. In normal controls, nondialyzed ESRD patients, and HD equipped with CU, PAMM, and PS dialyzers, plasma levels of IL-1 beta were 10.73 +/- 5.24 pg/ml, 9.97 +/- 3.61 pg/ml, 13.17 +/- 4.04 pg/ml, 15.16 +/- 6.16 pg/ml, and 13.96 +/- 5.47 pg/ml, respectively. There were no statistically significant differences among the groups (p > or = 0.05). In contrast, the gene expression of IL-1 beta for peripheral blood mononuclear cells (PBMC) by in situ hybridization showed differences among the groups. The gene for IL-1 beta for PBMC appears in HD equipped with different membranes, but not in cases of nondialyzed uremic patients and normal subjects. With computer imaging analysis, we carried out quantitative analysis of cells in in situ hybridization with an area of positive spots to an area of total cells. In HD with CU, PMMA, and PS, the results were 10.64 +/- 1.07, 3.34 +/- 0.74, and 3.27 +/- 0.64%, respectively. The levels of IL-1 beta gene expression in CU were higher than that in PMMA or PS. There were statistically significant differences (p < or = 0.001) between CU and PMMA or PS and no significant difference between the PMMA and PS (p > or = 0.05). We suggest measuring the gene expression of cytokines for PBMC and which may be better than measuring cytokine levels only for investigating the blood compatibility of dialyzers, which may help in understanding chronic complications of the dialysis procedure.

Adult↗

Prostatic intraepithelial neoplasia is a risk factor for adenocarcinoma: predictive accuracy in needle biopsies.

PURPOSE: High grade prostatic intraepithelial neoplasia is considered the most likely precursor of prostatic adenocarcinoma. However, the natural history and predictive value of prostatic intraepithelial neoplasia for cancer are unknown. MATERIALS AND METHODS: To examine the predictive value of high grade prostatic intraepithelial neoplasia, we conducted a retrospective clinic based comparative study of 100 patients with high grade prostatic intraepithelial neoplasia and 112 without prostatic intraepithelial neoplasia on needle biopsies matched for digital rectal examination findings, patient age and serum prostate specific antigen level. Only patients who had 1 or more followup biopsies were included. RESULTS: Adenocarcinoma was identified in 35% of subsequent biopsies from patients with prostatic intraepithelial neoplasia, compared with 13% of control biopsies. The likelihood of finding cancer increased as the interval from initial biopsy increased. High grade prostatic intraepithelial neoplasia, patient age and serum prostate specific antigen concentration were jointly highly significant predictors of cancer, with prostatic intraepithelial neoplasia providing the highest risk ratio of 14.93 (95% confidence intervals 5.6 to 39.8). No other candidate predictor was significant, including digital rectal examination findings, transrectal ultrasound results, amount of prostatic intraepithelial neoplasia on biopsy and architectural pattern of prostatic intraepithelial neoplasia. CONCLUSIONS: These results indicate that the presence of high grade prostatic intraepithelial neoplasia on needle biopsy is strongly predictive of carcinoma. Prostatic intraepithelial neoplasia should be reported in needle biopsies and biopsy repeated. These finding support the hypothesis that prostatic intraepithelial neoplasia is a precursor of prostate cancer.

Adenocarcinoma↗

The incidence of high grade prostatic intraepithelial neoplasia in needle biopsies.

PURPOSE: High grade prostatic intraepithelial neoplasia is the most likely precursor of invasive prostate cancer. The identification of prostatic intraepithelial neoplasia in needle biopsy specimens warrants repeat biopsy because of its high predictive value for cancer. The incidence of prostatic intraepithelial neoplasia in contemporary needle biopsies is unknown. MATERIALS AND METHODS: To determine the incidence of patients requiring repeat needle biopsy because of abnormal findings in needle aspirations (high grade prostatic intraepithelial neoplasia and microscopic foci suspicious for but not diagnostic of malignancy), we compared the pathological findings in 400 prostatic needle biopsies, including 200 consecutive cases from an academic medical center (Mayo Clinic) and an equal number from a private practice laboratory (Glendale Memorial Hospital and Health Center). RESULTS: The biopsies revealed similar findings from the 2 medical centers: benign prostatic tissue in 41.5 to 50% of the cases, prostatic intraepithelial neoplasia in 16.5 to 9.5%, foci suspicious for but not diagnostic of malignancy in 1.5 to 2.5% and cancer in 40.5 to 38% (Mayo Clinic versus Glendale Memorial, respectively). Clinical information was available from the 200 Mayo Clinic patients who underwent biopsy, and there was no difference in the distribution of findings by digital rectal examination or transrectal ultrasound, although the median serum prostate specific antigen concentration was higher in patients with prostatic intraepithelial neoplasia and cancer than in those with benign biopsies. CONCLUSIONS: High grade prostatic intraepithelial neoplasia is a frequent finding in needle biopsies and is present in up to 16.5% of the cases. There was no apparent difference in the incidence of prostatic intraepithelial neoplasia and cancer between 2 geographically diverse medical centers. Up to 18% of patients are candidates for another biopsy based on needle biopsy findings of prostatic intraepithelial neoplasia or foci suspicious for but not diagnostic of malignancy.

Adult↗

Prospective analysis of multifocality in renal cell carcinoma: influence of histological pattern, grade, number, size, volume and deoxyribonucleic acid ploidy.

In an effort to characterize more fully multifocal renal cell carcinoma, 100 radical nephrectomy specimens with localized renal cell carcinoma were analyzed in a prospective fashion. Analysis of each specimen consisted of preoperative computerized tomography or magnetic resonance imaging, standard pathological examination with frozen section and 3 mm. step sectioning under magnification. Multifocal renal cell carcinoma was found in 16 specimens. Multifocal disease was suspected by preoperative imaging in 7 specimens (44%) and confirmed after standard pathological investigation in 10 (63%). Papillary and mixed histological patterns occurred at a significantly increased rate in specimens with multifocal disease (p = 0.011). Other parameters, such as stage, tumor size and volume, histological grade and deoxyribonucleic acid ploidy were evaluated and did not correlate with the presence or extent of multifocality. The number of secondary tumors per specimen varied from 1 to 50 (median 2) and were of higher grade in 3 (19%) and of lower grade in 2 (12%) when compared with the predominant tumor. In conclusion, information from preoperative and to some degree intraoperative tests (except histological pattern) cannot reliably predict multifocality. The true risk for unknown multifocality in a surgical setting seems to be 6%, which roughly corresponds to the incidence of locally recurrent disease in published large institutional series.

Adult↗

Potential markers of prostate cancer aggressiveness detected by fluorescence in situ hybridization in needle biopsies.

Fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, 11, and 12 was used to evaluate multiple 18-gauge needle biopsy cores from 50 randomly selected radical prostatectomy specimens. FISH analysis detected 26 diploid (52%), 7 tetraploid (14%), and 17 aneuploid tumors (34%). The FISH results were concordant with flow cytometric (FCM) DNA content measurements of the corresponding prostatectomy specimens for 31 tumors. For the 19 FISH/FCM discordant tumors, FISH was more sensitive than FCM for detecting ploidy anomalies. Common numerical chromosome alterations were gains of chromosomes 7 and 8, which were found in 13 (76%) and 10 (59%) aneuploid tumors, respectively. Gain of chromosome 7 was strongly associated with higher Gleason score (> or = 8) (P < 0.0001) and with advanced tumor pathological stages (stages T3 + T4; P < 0.01). Gain of chromosome 8 also correlated with higher Gleason score (P < 0.01). FISH showed intratumoral ploidy heterogeneity in 3 of 41 (7%) studied tumors. Among 17 noncancerous adjacent tissue specimens, chromosome alterations were observed in one, which contained high-grade prostatic intraepithelial neoplasia. Combined FISH and fluorescent leukocyte common antigen staining showed that infiltrating leukocytes do not contribute to the observed gains of chromosomes 7 and 8 in prostate cancer tissue. These results demonstrate that (a) FISH analysis of prostate needle biopsy-sized specimens can be a practical, sensitive method for determination of nuclear ploidy and numerical chromosome alterations; and (b) gains of chromosomes 7 and 8 are common numerical alterations of prostate cancer cells and may be potential markers of tumor behavior and patient prognosis.

Biopsy, Needle↗

Chemically selected subclones of the CEM cell line demonstrate resistance to HIV-1 infection resulting from a selective loss of NF-kappa B DNA binding proteins.

To delineate cellular genes that are required for optimal HIV-1 infection, CEM cells were subjected to treatment with the chemical mutagen ethylmethanesulfonate (EMS) and subclones were selected based on their increased resistance to HIV-1 infection and reduced syncytium formation, despite relatively normal CD4 expression (20,000 to 25,000 receptors/cell). Two subclones with this phenotype demonstrated a diminished capacity of HIV-1 long terminal repeat-chloramphenicol acetyl transferase expression either after treatment with the protein kinase C activator PMA, or through Tat-mediated transactivation. In this study, we show that the cellular levels of the NF-kappa B DNA binding proteins (but not AP1 or SP1) are markedly reduced in these cell mutants both at the mRNA and protein levels, resulting in reduced nuclear localization of p50/p65 after PMA induction or treatment with the lymphokine TNF-alpha. Transient reconstitution with a plasmid expressing p50 resulted in partial recovery of PMA-inducible LTR-chloramphenicol acetyl transferase expression. These data suggest that, at least in the CEM T cell line, a selective reduction in the NF-kappa B DNA binding proteins is sufficient to curtail HIV-1 infection.

Base Sequence↗

Involvement of protein kinase C in the axonal growth-promoting effect on spinal cord neurons by target-derived astrocytes.

Astroglial cells participate in a variety of developmental events during neuronal morphogenesis. We have shown that axonal, but not dendritic, outgrowth of spinal cord neurons can be promoted by a diffusible factor or factors secreted from target region-derived cerebellar astroglia in vitro in comparison with spinal astroglia. In the present study, we examined the involvement of protein kinase C (PKC) in the axon-promoting effect by astroglia. The inhibition of PKC by sphingosine or by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) at high concentration greatly reduced the mean axonal length of spinal neurons cultured in medium conditioned by cerebellar astroglia (SCn-CBg), while activation of PKC by TPA at low concentration, or by retinoic acid, was not additive to the glial effect. The activation of PKC by TPA or retinoic acid promoted axon growth of spinal neurons cultured in medium conditioned by spinal astroglia (SCn-SCg), which otherwise would not be as supportive for axon growth as cerebellar astroglia. Western blotting and PKC activity assays showed that there was a trend for increased PKC activity and protein levels (in particular, PKC beta) in SCn-CBg cultures, which correlated with enhanced axon growth. Inhibition of PKC by sphingosine appeared to decrease protein levels, especially PKC beta, which correlated with suppressed axon outgrowth. In SCn-SCg cultures, phorbol ester activation of PKC increased both activity and protein levels of both PKC alpha and PKC beta. This activation correlated with stimulated axonal outgrowth. These results suggest that the glial signaling that regulates specific axonal outgrowth by target astroglia is mediated in part by the PKC second messenger system.

Animals↗

A differential geometric treatment of protein structure comparison.

The technique of model-building a protein of known sequence but unknown tertiary structure from the structures of homologous proteins is probably so far the most reliable means of mapping from primary to tertiary structure. A key step towards the realization of the aim is to develop ways of aligning three-dimensional structures of homologous proteins, thereby deriving the rules useful for protein modelling. We have developed a generalized differential-geometric representation of protein local conformation for use in a protein comparison program which aligns protein sequences on the basis of their sequence and conformational knowledge. Because the differential-geometric distance measure between local conformations is independent of the coordinate frame and remains chirality information, the comparison program is easily implemented, relatively rational and reasonably fast. The utility of this program for aligning closely and distantly related homologous proteins is demonstrated by multiple alignment of globins, serine proteinases and aspartic proteinase domains. Particularly, the method has reached the rational alignment between the mammalian and microbial serine proteinases as compared with many published alignment programs.

Amino Acid Sequence↗

Simple and robust screening of pooled yeast artificial chromosome libraries by the restriction enzyme digestion of polymerase chain reaction products.

The polymerase chain reaction (PCR)-based method for screening pooled yeast artificial chromosome (YAC) libraries was modified by adding a step for the restriction enzyme digestion of the PCR products. This modification significantly increased the reliability of YAC screening and made it possible to identify YAC clones without a cumbersome verification step by colony hybridization and/or Southern blotting. Using this method, we assigned 39 mouse YAC clones to a mouse genetic map with 13 biallelic, polymorphic expressed sequence tags. This method provides a fast, reliable way to identify YAC clones with PCR-based sequence-tagged sites.

Animals↗

[The frequency-domain analysis of TEOAE in neonates and youths].

Transiently evoked acoustic emissions (TEOAE) is a rapid, noninvasive and objective audiologic method. It has been used in clinic. In order to observe effects of transient stimulus sounds on TEOAE, TEOAE evoked by click and tone-pip (1kHz, 2kHz) was examined in 18 neonates and 18 youths. The observed TEOAE waveforms were used for frequency-domain analysis. The results revealed that there were no significant differences in TEOAE incidence between the neonates and youths, and among the three kinds of stimuli. The incidence of the click evoked acoustic emission in the neonate group (within 4 days post partum) was 91.7%, it was lower than those reported by other authors. The frequency-domain analysis showed that there were no significant differences of bandwidth among the three kinds of stimuli, but the frequency peak was different according to the different stimulus sounds. It was found that there were somewhat dependence of TEOAE characteristic spectrum on stimulus sound frequency, this might be related to the mechanical tuning property of the inner ear and the resonance of the external and the middle ear.

Acoustic Stimulation↗

[Inhibitory effects of fifteen kinds of Chinese herbal drugs, vegetables and chemicals on SOS response].

Effects of 15 kinds of herbal drugs, vegetables and chemicals on lex-dependent sfi-SOS response were determined by micropersistent and/or pulse models induced by 4-Nitroquinoline-N-oxide (4NQO) and Mitomycin C (MMC) in Escherichia coli(E. coli) PQ37 and PQ35, respectively. Results showed the water extract of Rhizoma Polygonati (RP), Fructus Chebulae (FC), Radix Polygoni Multiflori (RPM), Fructus Ligustri Lucidi (FLL), Bulbus Fritillariae Thunbergii (BFT), shell of water chestnut with a pedicle, Chinese chives juice, and solutions of 5-Fluorouracil, Tannic acid and garlicin could inhibit SOS responses with a dose-response relationship and suggested the inhibitory effects took place both inside and outside E. coli cells. Water extract of FC, FLL, BFT, shell of water chestnut with a pedicle, Chinese chives juice and solution of 5-Fluorouracil and Tannic acid could intracellularly inhibit SOS responses induced by MMC in E. coli PQ35, and acetone extract of Grifola Frondosa (GF) could extracellularly inhibit SOS responses in E. coli PQ37 and intracellularly in PQ35 induced by 4NQO or MMC. Water extract of raw hawthorn. Radix Angelicae Duhuricae (RAD), Radix Ophiopogonis (RO), and 5-Fluorodeoxyuridine could extracellularly inhibit SOS responses induced by 4NQO in E coli PQ37. The possible mechanisms of intracellular inhibition and antidamage repair were discussed in the paper.

4-Nitroquinoline-1-oxide↗