Does prostate cancer start at puberty?
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Age Factors↗
Biomedical subjects
H Yu
Publications and source records attributed to H Yu.
Prostate specific antigen--a new constituent of breast cyst fluid.
We demonstrate for the first time that prostate specific antigen (PSA) is a component of breast cyst fluid. At the cutoff level of 0.01 or 0.03 micrograms/L of PSA, 64% or 43% of cyst fluids are positive for PSA, respectively. PSA in cyst fluid, as characterized by high performance liquid chromatography, exists in almost equal concentrations as free PSA, with a molecular weight of 33 KDa, and as PSA bound to alpha 1-antichymotrypsin, with a molecular weight of 100 KDa. PSA presence was also characterized in cyst fluid by Western blot analysis. These data suggest that PSA is a frequent component of breast cyst fluid. More studies are needed to establish the role of this serine protease in normal breast, gross breast cystic disease, and breast cancer.
Adult↗
Prostate specific antigen in breast cancer, benign breast disease and normal breast tissue.
Prostate specific antigen (PSA) is a tumor marker used widely for the diagnosis and monitoring of prostatic adenocarcinoma. Recently, we provided evidence that PSA may also be produced by breast tumors. In this report we examined quantitatively the PSA levels in 199 breast tumors, 48 tissues with benign breast disease (BBD, 34 fibroadenomas), and 36 normal breast tissues. Significant amounts of PSA (> or = 0.030 ng of PSA per mg of total protein) were found in 28% of breast tumors, 65% of BBD tissues, and 33% of normal breast tissues. PSA positivity in breast tumors was highest in stage I disease (34%) and decreased with disease stage (24% in stage II and 18% in stage III-IV). Using polymerase chain reaction amplification we have shown PSA mRNA presence in patients with PSA protein-positive tissues (benign and malignant) but not in patients with PSA protein-negative tissues. Our data suggest that PSA is expressed frequently by normal breast tissue, by tissue of benign breast diseases, and by breast cancer tissue. Highest expression is seen in benign breast disease and lowest expression in advanced stage cancerous tissue. As PSA production is mediated by steroid hormones and their receptors, we propose that PSA may be a new marker of steroid hormone action in the normal or diseased female breast. The role of this enzyme in the development of breast diseases including breast cancer is currently unknown.
Adolescent↗
Transfection alters ion transport in MDCK cells.
In the course of an investigation into the effect of Tamm-Horsfall protein (THP) on ion transport, we performed stable transfection of THP into MDCK cells using the SV40 or the cytomegalovirus (CMV) promoter. As controls, we transfected MDCK cells with an "empty" plasmid containing SV40 or CMV promoter but without THP cDNA. In another set of controls, we subjected cells to transfection procedures without DNA (mock transfection). K influx was not altered in cells subjected to mock transfection procedures without DNA, but both ouabain sensitive (OS) and ouabain resistant (OR) components of K influx were diminished in cells transfected with THP cDNA using either SV40 or CMV promoter. However, K influx was also reduced in cells transfected with a control plasmid containing either the SV40 promoter alone, or the CMV promoter alone, without the THP cDNA. Thus, the transport alterations were caused by transfection and not by THP. The reduction in ouabain-sensitive K influx was accompanied by a proportional reduction in the abundance of Na-K pump units as assessed by [3H] ouabain binding. [3H] bumetanide binding, a measure of the number of functioning NaK2Cl cotransporter sites, was reduced pari passu with the reduction in bumetanide-sensitive K influx. These results highlight the possibility that alterations in properties of transfected cells may not be solely due to the presence of transfected protein, but the result of some process associated with transfection itself. Without appropriate controls to evaluate this possibility, results of transfection studies are subject to potentially faulty and misleading interpretation.
Cell Line↗
Antiphospholipid antibodies and fetal death.
OBJECTIVE: To determine the type of recurrent pregnancy loss associated with antiphospholipid antibodies. METHODS: This was a retrospective analysis of women who had two or more pregnancy losses and who were tested for antiphospholipid antibodies. The specific type of pregnancy losses were determined in patients with and without antiphospholipid antibodies. RESULTS: In our highly selected referral population, 76 of 366 women (21%) tested positive for lupus anticoagulant or anticardiolipin antibodies of 20 or more immunoglobulin-G phospholipid antibody units. Pregnancy loss occurred in 280 of 333 (84%) prior pregnancies in women with and 1240 of 1479 (84%) without antiphospholipid antibodies. However, 50% of pregnancy losses in women with antiphospholipid antibodies were fetal deaths, compared with less than 15% in women who were antiphospholipid antibody-negative. More than 80% of women with antiphospholipid antibodies had at least one fetal death, compared with less than 25% of women without (P < .001). The specificity of fetal death for the presence of antiphospholipid antibodies in patients with recurrent pregnancy loss was 76%. In contrast, two or more early first-trimester losses without fetal death had a specificity of only 6% for antiphospholipid antibodies. CONCLUSION: Fetal death is more characteristic of the type of loss experienced by patients with recurrent pregnancy loss than early first-trimester pregnancy loss in women with antiphospholipid antibodies.
Abortion, Habitual↗
Use of the USDT flow immunosensor for quantitation of benzoylecgonine in urine.
The flow immunosensor works on a principle somewhat distinct from other immunoassay systems in that it performs a displacement immunoassay. Antibody-coated matrices are saturated with fluorescently labeled benzoylecgonine (BE), which is released and measured in the presence of BE-containing urine and measured downstream from the matrix. The same antibody matrix can be used for many samples. A flow immunosensor instrument, built by US Drug Testing, Inc., has recently received "Premarket Notification' (510(K)) from the Food and Drug Administration (FDA) to screen urine for the presence of the cocaine metabolite BE. The performance of the flow immunosensor for screening BE in urine was validated by comparison with results of a blind study using the Syva EMIT, the Abbott TDx and gas chromatography-mass spectroscopy (GC-MS). Potentially interfering drugs were also spiked into urine and evaluated using the flow immunosensor. While the FDA approval is for determining whether the BE concentration is above or below the 300 micrograms/l cutoff recommended by the National Institute of Drug Abuse, we have also shown that the flow immunosensor can be adapted to produce quantitative determinations of the amount of BE in the urine samples. The reliability of the quantitation was confirmed by testing 100 urine samples containing unknown amounts of BE using the flow immunosensor. GC-MS and the Abbott TDx system. Comparison of quantitative data obtained using the immunosensor and GC-MS showed a 97% correlation, compared with a much lower value for data from the TDx and GC-MS.
Antibody Specificity↗
Prostate-specific antigen in amniotic fluid of normal and abnormal pregnancies.
OBJECTIVE: To examine if prostate-specific antigen (PSA) is present in amniotic fluid or maternal serum during pregnancy and if its presence is associated with fetal abnormalities. METHODS: Samples tested included amniotic fluids from 853 pregnant women for whom amniocentesis was performed; 312 nonpregnant women who donated blood; 259 pregnant women who donated blood at various gestational ages. Amniotic fluid or serum PSA was measured with an ultrasensitive time-resolved immunofluorometric procedure. 372 pregnancies were studied for the presence of genotypic or phenotypic fetal abnormalities. RESULTS: PSA was present in most amniotic fluids; the median PSA concentration increased from gestational week 11 to 22 and stabilized thereafter until delivery. The most prominent PSA concentration change occurred during gestational weeks 13-14. Pregnant women had significantly higher serum PSA concentrations than nonpregnant women; the pattern of serum PSA concentration change during pregnancy was similar to that of amniotic fluid; however, serum PSA concentrations were lower by a factor of 20-40. No association existed between amniotic fluid PSA and maternal age, gender of fetus, or length of abstinence of mother from sexual intercourse. After gestational week 15, fetuses with trisomy 21 or 18, anencephaly, or renal disorders were associated with low amniotic fluid PSA levels. CONCLUSION: Our data suggest that PSA may play a role in fetal development, especially at gestational ages between 13-20 weeks. The diagnostic usefulness of PSA in identifying fetal abnormalities remains to be determined.
Amniocentesis↗
Re: The clinical usefulness of prostate specific antigen: update 1994.
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Breast Neoplasms↗
Nuclear versus perinuclear and cytoplasmic calcium in osteoclasts.
We measured fluorescence from the calcium indicator Fluo-3 in multinucleated osteoclasts. In the initial state, each nucleus is surrounded by a ring of bright fluorescence. Following activation of purinergic receptors by 100 microM ATP there is a pulse of cellular fluorescence increase, and nuclear fluorescence intensity becomes greater than that of the cytoplasm. This is followed by a period during which the fluorescence of the cell decreases below that of the initial state. During the pulsed increase following purinergic receptor activation, the perinuclear fluorescence intensity does not increase as much as that in the nuclear centers and, following this pulse, the perinuclear fluorescence intensity decreases more than that in the nuclear centers, relative to the initial state. Measurements in which Mn2+ was introduced into the cell show that the number of Fluo-3 molecules per unit horizontal area in the nuclear centers is slightly greater than that in the perinuclear regions, and more than twice that in the surrounding cytoplasm. These results show that there is a much higher free calcium concentration in the perinuclear regions than in the nuclear centers in the initial state, with a release of free calcium from the perinuclear regions following activation of the purinergic receptors. These data also provide evidence that the free calcium concentration in the nuclear centers is lower than in the cytoplasm in the initial state.
Aniline Compounds↗
Analysis of intestinal perfusion data for highly permeable drugs using a numerical aqueous resistance--nonlinear regression method.
PURPOSE: To develop, validate and apply a method for analyzing the intestinal perfusion data of highly permeable compounds using the Numerical Aqueous Resistance (NAR) theory and nonlinear regression (NAR-NLR) and to compare the results with the well-established Modified Boundary Layer (MBL) Analysis. METHODS: The NAR-NLR method was validated and the results were compared to the MBL analysis results using previously reported cephradine jejunal perfusion data. Using the Single Pass Intestinal Perfusion (SPIP) method, the concentration dependence of intestinal permeability was investigated for formycin B, proline, and thymidine, three compounds reported to be absorbed by carrier-mediated transport processes. The MBL and NAR-NLR analyses were then applied to the three sets of SPIP data. RESULTS: The results demonstrate that the intrinsic MBL transport parameters were highly variable and, in one case, the analyses failed to give a statistically significant Michaelis constant. The MBL mean dimensionless wall permeabilities (P*w) were greater than the NAR-NLR P*w and were also highly variable. In all cases, the NAR-NLR variability was significantly lower than the MBL variability. The extreme variability in the MBL-calculated P*w is due to the sensitivity of P*w when the fraction of unabsorbed drug (Cm/Co) is low or, alternatively, when P*w approached the aqueous permeability, P*aq. CONCLUSIONS: The NAR-NLR method facilitates the analysis of intestinal perfusion data for highly permeable compounds such as those absorbed by carrier-mediated processes at concentrations below their Km. The method also allows for the use of a wider range of flow conditions than the MBL analysis resulting in more reliable and less variable estimates of intestinal transport parameters as well as intestinal wall permeabilities.
Animals↗
Associations between insulin-like growth factors and their binding proteins and other prognostic indicators in breast cancer.
Recent studies have suggested that insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) may be implicated in the development and progression of breast cancer. Prostate-specific antigen (PSA), a serine protease, may play a role in the regulation of IGFs' function through cleavage of IGFBP-3, resulting in release of active IGFs from IGFBP-3. As IGFs, IGFBPs and PSA are all present in breast cancer, possible associations among these proteins were speculated. In this study, we have measured PSA, IGF-I, IGF-II, IGFBP-1 and IGFBP-3 in tumour tissue cytosols from 200 women with primary breast cancer, and have examined relationships between IGFs or IGFBPs and PSA along with other markers, including p53 protein, steroid hormone receptors (oestrogen and progesterone), cathepsin-D, epidermal growth factor receptor, Her-2/neu protein, S-phase fraction and DNA ploidy. Correlations or associations between PSA and IGF-I, IGF-II, IGFBP-1 or IGFBP-3 were not observed. IGF-II was positively correlated with both IGFBP-3 and IGFBP-1. IGF-I was not associated with either of the two binding proteins, nor with IGF-II. Both IGF-II and IGFBP-3 were inversely associated with the oestrogen receptor, and IGFBP-3 was also positively associated with S-phase fraction. Our finding of IGF-II and IGFBP-3 in association with unfavourable prognostic indicators of breast cancer suggests that IGFs may be involved in the progression of breast cancer.
Biomarkers, Tumor↗
Creatine kinase BB isoenzyme levels in tumour cytosols and survival of breast cancer patients.
Creatinine kinase BB (CK-BB) is elevated in many tumours including those of the breast. We have recently described a new, highly sensitive and specific method for measuring CK-BB, based on monoclonal antibodies and time-resolved fluorometry. Using this method, we quantitated CK-BB in 172 breast tumour cytosols and examined the associations between CK-BB and other clinicopathological variables and patient survival. High CK-BB levels were seen more frequently in tumours from patients who were younger (age < 50 years), patients who qualified for chemotherapy and patients with oestrogen receptor-positive tumours. No association was seen between CK-BB and tumour stage, grade, size, histological type or the progesterone receptor. In univariate analysis, the risk of relapse or death was higher in the group with tumours containing high CK-BB levels but the difference did not reach statistical significance. In multivariate analysis, the risk of death was statistically significantly higher in the high-CK-BB group. Analysis of subsets of patients revealed that patients with oestrogen receptor-negative cancer have higher risk of death if their tumours contain high levels of CK-BB. Our data suggest that, in general, CK-BB is associated with more aggressive tumours but its value as a prognostic indicator is limited. CK-BB content of breast tumours may be more useful as an aid in selecting therapy directed at inhibiting this enzyme activity and thus depriving tumour cells of their energy source.
Adult↗
Altered age-dependent modulation of tissue renin messenger RNA levels in the spontaneously hypertensive rat.
OBJECTIVE: To evaluate the possible role of tissue renin overproduction in the pathogenesis and time course of hypertension development in the spontaneously hypertensive rat (SHR) of the Okamoto strain by measuring tissue renin gene expression at different stages of hypertension development. DESIGN: Measurements of kidney, adrenal gland and brain stem renin messenger RNA (mRNA) levels were performed in SHR aged 4, 12, 20 and 36 weeks and in age-matched normotensive Wistar-Kyoto (WKY) rats. METHODS: A fully quantitative, competitive reverse transcriptase polymerase chain reaction method was used to measure tissue renin mRNA levels. Plasma renin concentrations were measured by radioimmunoassay. RESULTS: Compared with age-matched WKY rats, renin mRNA levels in the adrenal gland of SHR were significantly higher at ages 4, 12 and 36 weeks. Brain stem renin mRNA levels were significantly higher in SHR than in WKY rats at ages 4, 12 and 20 weeks. In contrast, renal renin mRNA levels were consistently lower in SHR at all ages, as were plasma renin concentrations. CONCLUSIONS: The present study indicates an important role for renin gene expression both in adrenal and in brain stem tissues in the pathogenesis of hypertension in SHR. Adrenal and brain renin-angiotensin systems may interact with each other synergistically in the development and maintenance of hypertension in SHR. Suppressed renal renin gene expression could then be an indirect consequence of the amplified renin-angiotensin system in the adrenal gland and in the brain or a baroreceptor-mediated consequence of its hypertension.
Adrenal Glands↗
Molecules in intense laser fields: Enhanced ionization in a one-dimensional model of H2.
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Journal Article↗
Reduction of Saccharomyces cell adhesion by liquid mechanical vibration.
The effect of liquid mechanical vibration on the adhesion of Saccharomyces cerevisiae cells to the internal glass surface of a pipette was studied using a 25 Hz vibration source. The maximum vibration amplitude was 1.06 mm (peak to peak) along the pipette direction. Relative movements between the pipette and yeast suspension in it were produced by vibration and reduced the cell adhesion. The reduction in adhesion was affected by both vibration amplitude and suspension pH. Analysis showed that in routine cell counts, cell adhesion to the pipette wall was a significant error source. The construction of a vibration device for routine cell count work appears feasible.
Cell Adhesion↗
Hypericin-induced phototoxicity in cultured fibroblasts and swine erythrocytes.
Hypericin is a naturally occurring photosensitizer, whose presence in plants has been responsible for cutaneous phototoxicity in grazing animals. The photosensitizing properties of this agent have recently been exploited in models for anti-tumor and anti-viral activity. The cytotoxicity of hypericin and light was assessed in 3T3 mouse fibroblasts using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide)] assay and the lactate dehydrogenase (LDH) leakage assay. Membrane damage was assessed in swine erythrocytes using hemolysis, potassium (K+) leakage and formation of lipid hydroperoxides. Concentration- and light-dependent decreases in fibroblast viability were seen starting at hypericin concentrations of 1.25 microM and light power flux levels of 24 J/cm2 using a visible light source and at 0.417 microM hypericin and a similar light dose using a solar simulator. No LDH leakage was observed at hypericin concentrations up to 30 microM and visible light up to 144 J/cm2. Light-and/or concentration-dependent increases in hemolysis, K+ leakage and formation of lipid hydroperoxides in red blood cell (RBC) membranes were observed, but at concentrations and light doses much greater than those required to induce cytotoxicity in fibroblasts. Lipid peroxidation and hemolysis occurred at 15 microM hypericin and 24 J/cm2 (visible light source). Potassium ion leakage occurred at concentrations and light levels as low as 5 microM and 12 J/cm2 or 15 microM and 4.8 J/cm2 (visible light source) but was still a less sensitive indicator than fibroblast cytotoxicity. Evidence for both type I and type II reactions was shown in RBC membranes by TLC analysis of cholesterol products. In the absence of light, hypericin appears to be relatively nontoxic in the models tested.
3T3 Cells↗
Oral cavity absorption of (R)-8-hydroxy-2-(di-n-propylamino)tetralin and (S)-8-acetyl-2-(di-n-propylamino)tetralin in the rat.
The present communication reports on the efficacy of (R)-8-OH-DPAT ((R)-8-hydroxy-2-(di-n-propylamino)tetralin) and (S)-LY-41 ((S)-8-acetyl-2-(di-n-propylamino)tetralin) in displaying the 5-HT1A syndrome and decreasing body temperature after administration of the compound subcutaneously into the gastric ventricle or into the oral cavity in the rat. The dose range eliciting a clear-cut HT1A syndrome and hypothermia after oral cavity administration was 1/10-1/30 that of the gastric ventricle dose range, but 10-30 times higher than the dose range used for subcutaneous administration of both (R)-8-OH-DPAT and (S)-LY-41. Determination of the concentrations of (R)-8-OH-DPAT in plasma and brain tissue confirmed a higher bioavailability after oral cavity than after gastric ventricle administration; plasma and brain tissue concentrations of the drug were found to be approximately 3 times those after 10 mumol/kg-1 orally than after 100 mumol/kg-1 gastroventrically at 15-60 min after administration of (R)-8-OH-DPAT. These findings suggest that the oral cavity may be an important site for drug delivery of 8-OH-DPAT, LY-41 and other compounds with a low gastrointestinal bioavailability.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Immunomagnetic-electrochemiluminescent detection of Escherichia coli O157 and Salmonella typhimurium in foods and environmental water samples.
Hemorrhagic Escherichia coli O157:H7 strains and other virulent enteric pathogens can pose a serious health threat in tainted meats, poultry, and even drinking water. Traditional culture-based methods for assay of enteric pathogens in foods and water sources are relatively slow, and results can be ambiguous. Immunomagnetic separation (IMS) and detection methods have been investigated and appear promising for rapid bacterial assay of foods and environmental samples. In this work, a commercial sensor which combines IMS with electrochemiluminescence (ECL) detection is evaluated for detection of E. coli O157 and Salmonella typhimurium in foods and fomites. Results indicate that detection limits are in the range of 100 to 1,000 bacteria per ml in pristine buffer for E. coli O157 and S. typhimurium, respectively, or 1,000 to 2,000 bacteria per ml in food samples (depending on the sample) and that total processing and assay time is rapid (< 1 h) even in food samples. An immunologic "hook" or high-antigen-concentration prozone effect was observed above 10(4) and 10(5) bacteria per ml for E. coli O157 and S. typhimurium, respectively. IMS was accomplished in milk, juices, serum, supernatant fluids from ground beef, finely minced chicken, and fish suspensions as well as several freshwater sources and followed by ECL assay. Some samples, especially fish, gave unexpectedly high background ECL. Conversely, low ECL intensity was observed in nonfat and 2% fat milk samples, which appeared to be related to binding or entrapment of the antibody-coated magnetic beads by particulates in the milk, as revealed by microscopy. Results of this evaluation suggest the feasibility of immunomagnetic-ECL methodology for rapid, sensitive, and facile preliminary screening of various foods and fomites for the presence of virulent enteric pathogens.
Animals↗