Biomedical subjects

H Wiener

Publications and source records attributed to H Wiener.

At least 19 recordsLinked to original sources

PubMed2005

Association studies of transforming growth factor-beta 1 and Alzheimer's disease.

Substantial laboratory evidence suggests Transforming Growth Factor-beta1 (TGFB1) is linked to Alzheimer's Disease (AD) pathology. The purpose of the study was to estimate the genetic association of TGFB1 with AD while controlling for apolipoprotein E4 allele (APOE4) status, the only well-established genetic risk factor for AD. Two study populations were genotyped for the TGFB1-509 and +869 single nucleotide polymorphisms (SNPs) that have been associated with TGFB1 levels. Constituting these populations were 203 families from the NIMH AD Genetic Initiative with at least two affected siblings and a normal sibling, and a population of 126 African-American (AA) AD cases versus 93 age matched controls. Results from family-based analyses showed a significant association between the TGFB1 -509 SNP and AD for the entire set of 203 families (P = 0.007), and a subset of these families without a homozygous APOE4 family member (P = 0.026). Results from family-based analyses on the TGFB1 +869 SNP were not significant in the 203 families. While associations for the main effects of the TGFB1 +869 and -509 SNP with AD in the AA case-control study were also not significant, results did indicate that TGFB1 may function as an effect modifier of APOE4 risk. Specifically, the odds of AD associated with having at least one APOE4 allele increased in an additive fashion with one or two copies of the higher producer allele when stratified by TGFB1 -509 genotype and by TGFB1 +869 genotype. Results support a role for TGFB1 in AD pathogenesis.

Aged↗

PubMed2004

Cytopathology in Austria.

Cervical cancer screening developed rapidly during the 1970s. Today, approximately 1.5 million smears are taken annually, so 50% of the target population are screened every year, 30% are cytologically underserved (24% never had a smears, 6% only once). This figure correlates with the fact that there are still 30% deaths from cervical cancer compared with 1960. Since 1998 a voluntary quality assurance programme was introduced by the Austrian Society of Cytology, based on comparison of results reported from participating laboratories.

Adult↗

PubMed2001

Detection of upper urinary tract transitional cell carcinoma with ImmunoCyt: a preliminary report.

OBJECTIVES: To assess the clinical performance of ImmunoCyt in the detection of upper urinary tract transitional cell carcinoma (UT-TCC). This newly developed immunocytochemical test detects three cellular markers specific for TCC. METHODS: Thirty-seven patients with symptoms and/or findings on imaging suggestive of UT tumors were prospectively evaluated. All patients underwent a standard cytologic evaluation and ImmunoCyt testing of voided urine, as well as imaging studies. Urine samples were also obtained from the UT of 32 patients by ureteral catheterization and tested by cytologic analysis and ImmunoCyt. RESULTS: Sixteen patients had UT-TCC as documented by the final histologic evaluation. The sensitivity of testing the voided urine from 37 patients was 50% for cytologic analysis, 75% for ImmunoCyt, and 87% for both methods combined. The cytologic evaluation detected no G1, 1 (17%) of 6 G2, and 7 (100%) of 7 G3 tumors. ImmunoCyt detected 1 (33%) of 3 G1, 6 (100%) of 6 G2, and 5 (71%) of 7 G3 tumors. The sensitivity in the 32 urine samples obtained from the UT was 82% for cytologic analysis, 91% for ImmunoCyt, and 100% for both methods combined. Cytologic analysis detected all G2 and G3 (100% sensitivity) and no G1 tumors. ImmunoCyt detected 2 (100% sensitivity) of 2 G1, 4 (100%) of 4 G2, and 4 (80%) of 5 G3 tumors. The test specificity, calculated in 21 patients free of TCC, was 100% for cytologic analysis in voided and ureteral urine specimens and 95% and 100% for ImmunoCyt in voided and ureteral urine samples, respectively. CONCLUSIONS: The results of this preliminary study show that ImmunoCyt complements cytologic analysis in detecting UT-TCC, mainly because of its high sensitivity to low-grade TCC. The combination of cytologic testing and ImmunoCyt gives 100% sensitivity in detecting UT-TCC in UT urine samples.

Adult↗

PubMed2001

Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels.

During ischemic stroke, neurons at risk are exposed to pathologically high levels of intracellular calcium (Ca++), initiating a fatal biochemical cascade. To protect these neurons, we have developed openers of large-conductance, Ca++-activated (maxi-K or BK) potassium channels, thereby augmenting an endogenous mechanism for regulating Ca++ entry and membrane potential. The novel fluoro-oxindoles BMS-204352 and racemic compound 1 are potent, effective and uniquely Ca++-sensitive openers of maxi-K channels. In rat models of permanent large-vessel stroke, BMS-204352 provided significant levels of cortical neuroprotection when administered two hours after the onset of occlusion, but had no effects on blood pressure or cerebral blood flow. This novel approach may restrict Ca++ entry in neurons at risk while having minimal side effects.

Animals↗

PubMed2000

Cervical cancer screening in Austria.

Austria's target population of women aged 20 years and over consists of 3 million people. There is mainly opportunistic screening, except in one county with a target population of 120000, in which organised screening has been practiced for several years. There are approximately 1.5 million smears annually, exclusively taken by gynaecologists. The recommended screening interval is 1 year. The slides are screened by MTs with a maximum workload of 12000 smears annually in 65 laboratories, mainly headed by pathologists. As shown by Vutuc and colleagues (Wien Klin Wochenschr 1999, 111, 354-359) the opportunistic screening system covers 60% of the Austrian target population leaving an unsatisfactorily high rate of underserved, mainly postmenopausal, women. Nevertheless, the cervical cancer mortality rate could have been decreased to one third during the past 40 years.

Adult↗

PubMed2000

Malignant cell detection by fluorescence in situ hybridization (FISH) in effusions from patients with carcinoma.

Cytological diagnosis of malignant cells in effusions is hampered by difficulties in the differentiation from reactive mesothelial cells. Because interphase cytogenetics by fluorescence in situ hybridization (FISH) might complement cytological evaluation, we determined the power of tumor cell detection using FISH and cytology in 201 effusions from patients with advanced cancer. Furthermore, 9 primary breast tumors were FISH-karyotyped, and chromosomal aberrations were compared with those of corresponding metastatic effusion cells. By using centromeric probes representing chromosomes 7, 8, 11, 12, 17, and 18, a rate of malignancy-associated aneusomy combined for the 6 chromosomes was detected in an overall of 44.8% of effusion specimens (range, 31.8% to 39.3% for the individual chromosome), comparable to cytology (43.3%). The combination of just 2 FISH probes (namely, representing chromosome pairs 8/11 and 8/17) was almost equally efficient in the identification of aneusomy. Approximately one fourth of the cytologically negative effusions were FISH positive and vice versa. From the initially FISH-negative effusions, 18.9% could be subsequently classified positive with dual-color FISH by visualization of intranuclear chromosomal complexity in rare aneuploid cells. Thus, "overall FISH analysis," including dual-color evaluation, identified tumor cells in significantly more effusions (55.2%, P = .001) than conventional cytology, implying greater sensitivity. Finally, our finding that numerical aberration patterns in primary breast tumors and corresponding metastatic effusions are comparable indicates that FISH examination of primary tumors will indicate the centromeric probe(s) best suited for an efficient search for metastasis in the individual case.

Adenocarcinoma↗

PubMed1999

Fluorescence in situ hybridization in cervical smears: detection of numerical aberrations of chromosomes 7, 3, and X and relationship to HPV infection.

BACKGROUND: Human papillomavirus (HPV) is known to play a pivotal role in cervical carcinogenesis. Chromosomal aberrations are known to be related to different biological behaviors of malignant lesions. We analyzed whether numerical chromosomal aberrations, related to more aggressive tumor types, are found not only in high-grade squamous intraepithelial lesions (HSIL) but also in low-grade SIL (LSIL) of the cervix and evaluated their relationship to HPV infection. METHODS: Eighty women (19 to 74 years of age) were included in this study and grouped according to the Bethesda System: within normal limits (WNL), LSIL, and HSIL. By FISH, chromosomes 7 and X, and in part chromosome 3, were analyzed for numerical aberrations. Using the hybrid capture system HPV detection was performed. RESULTS: All 20 patients with cervical smear WNL had regular diploid chromosomal pattern and were negative for HPV. Thirteen of the 29 (41.2%) patients with LSIL showed trisomy 7, in association with trisomy X in 4 cases (12.9%). Single trisomy X was detected in 4 cases (12.9%). In 3 of 15 (20%) cases analyzed for chromosome 3 trisomy was observed. Trisomy 3 was associated with trisomy 7 and X or with trisomy 7 alone. The hybrid capture test was performed in 16 patients of this group. Two patients were positive for HPV probe A, 9 for probe B, and 2 for A and B, and 3 patients were negative. Twenty-three of the 29 patients (79.3%) with HSIL showed trisomy 7. Twelve of the 29 patients (41.3%) had an additional trisomy X. Single trisomy X was seen in only 2 cases (6. 9%). Twenty-two patients with HSIL were tested also for chromosome 3. Nine of the 22 patients (40.9%) showed trisomy 3, associated with trisomy 7 or with trisomy 7 and X. In 25 of the 29 patients HPV detection by the hybrid capture system was performed. HPV probe B was positive in 15 cases (60%). One patient was positive for both probes, A and B. Nine (36%) of the patients with HSIL were negative for both HPV probes. No positivity was observed for HPV probe A alone. CONCLUSION: Our data confirm the pivotal role of HPV in cervical carcinogenesis as it seems to cause changes in the chromosomal pattern of premalignant lesions. Additionally, trisomy 7 may be considered an early event in cervical carcinogenesis, persisting and increasing with progression of the lesion. The roles of trisomy 3 and X need further evaluation.

Adult↗

PubMed1999

Immunocyt: a new tool for detecting transitional cell cancer of the urinary tract.

PURPOSE: The limitations of cytology and the invasiveness of cystoscopy for detecting bladder cancer generate increasing interest in noninvasive, urine bound diagnostic tools. We assessed the diagnostic value of the newly developed immunocytochemical test, Immunocyt, which detects cellular markers specific for transitional cell cancer in the voided urine of patients with bladder cancer. MATERIALS AND METHODS: Participating in our prospective study were 264 consecutive patients with a mean age of 65.9 years, including 114 in whom symptoms were suggestive of bladder cancer and 150 who were being followed after complete transurethral resection of superficial transitional cell carcinoma. Voided urine specimens were evaluated by standard cytology and the Immunocyt test, which traces the monoclonal antibodies M344, LDQ10 and 19A211 against transitional cell carcinoma in exfoliated urothelial cells. In all cases cystoscopy was subsequently performed and any suspicious lesion was evaluated by biopsy. RESULTS: Histologically proved transitional cell carcinoma was found in 79 patients. Immunocyt with cytology had 89.9% sensitivity overall (84, 88 and 96.5% in grades 1 to 3 disease, respectively). A total of 34 (43%), 3 (3.8%) and 34 (43%) cases were positive on Immunocyt only, cytology only and both evaluations, respectively. In 8 cases (10.1%) both tests were negative. Overall Immunocyt only was 86.1% sensitive (84, 84 and 89.6% in grades 1 to 3 disease, respectively) and 79.4% specific. Overall cytology only was 46.8% sensitive (4, 52 and 79.3% in grades 1 to 3 disease, respectively) and 98.2% specific. CONCLUSIONS: Immunocyt is a noninvasive, highly sensitive test for detecting transitional cell carcinoma of all grades and stages. When combined with conventional urinary cytology, it may replace cystoscopy in select patients, especially in followup protocols of low grade transitional cell carcinoma.

Adult↗

PubMed1999

Multifocality of transitional cell carcinoma results from genetic instability of entire transitional epithelium.

OBJECTIVES: Multifocality of transitional cell carcinoma (TCC) has been attributed to seeding of exfoliated tumor cells or to a general sensitivity of the entire urothelium to carcinogenic stimuli. By contrast, TCC has been shown to evolve as a consequence of genetic defects and chromosomal instability. We analyzed chromosomal patterns, total DNA content, and p53 and Ki67 expression in malignant and normal transitional cells to evaluate their relationship to the development of multifocal TCC. METHODS: Included in the study were 47 patients, 16 women and 31 men, with a mean age of 70.04 years (range 37 to 83). Of 47 patients, 45 had TCC of the urinary bladder and 7 of those had synchronous ureteral involvement. Two patients had ureteral TCC and a history of TCC of the bladder. Using fluorescence in situ hybridization, numerical aberrations of chromosomes 7, 9, and 17 were detected in imprint specimens of histologically verified tumor and "normal" urothelium and were compared with static ploidy and p53 and Ki67 expression. RESULTS: Chromosome 7 was altered in 93.6%, chromosome 9 in 63.8% (including monosomy), and chromosome 17 in 87.2% of the 47 analyzed tumor and normal imprints. Differences between tumor and normal epithelium were observed in aberrational frequencies (number of cells showing chromosomal aberrations calculated on 200 cells counted, given in percentages). DNA content was aneuploid in all tumor specimens, but diploid in 20 (42.5%) of 47 normal specimens, according to lower aberration frequencies in these patients. p53 detection was positive in 82.9% of the tumor specimens and 76.6% of the normal specimens. Ki67 was positive in 87.2% of the tumor imprints and in 72.3% of the normal specimens. CONCLUSIONS: These data suggest a general genetic instability as a reason for multifocality in the entire transitional epithelium.

Adult↗

PubMed1999

Associations of MHC genes with levels of caries-inducing organisms and caries severity in African-American women.

The aim of this investigation was to evaluate the relationship between MHC alleles at the HLA-DRB1, DQB1 and TNFa microsatellite loci and levels of oral bacteria that play a role in the etiology of dental caries, and the DMFS index in 186 AA primparous women. The average age of the cohort was 20.8+/-3.7 years. The median DMFS index was 9 (range 0-68). High levels of S. mutans were positively associated with DRB1*3 and DRB1*4 presence (p < or = 0.005). DRB1*8 was positively associated with higher levels of S. mutans as a percentage of total Streptococci (p = 0.04). DRB1*1 was positively associated with high levels L. casei (p = 0.04). DQB1 alleles were not observed associated with oral bacterial levels. TNFa allele 103 was negatively associated (p = 0.04), and TNFa 117 was positively associated (p = 0.007), with high levels of L. acidophilus. No significant associations were observed between any DRB1, DQB1 or TNFa allele and the DMFS index. These results support an hypothesis of an association between host HLA class II and TNFa genetic profile and colonization of S. mutans, L. casei, and L. acidophilus thought to be pathogens involved in the etiology of dental caries.

Adolescent↗

PubMed1998

High incidence of nephrogenic adenoma of the bladder after renal transplantation.

BACKGROUND: Tumors of the bladder termed nephrogenic adenomas in kidney allograft recipients are believed to develop as urothelial metaplastic proliferations in response to mechanical trauma, chemical noxae, irradiation, and bacterial or viral pathogens. We report on the incidence of nephrogenic adenoma of the bladder in patients who received renal transplants during a period of 7 years and 3 months at the University Hospital of Vienna. METHODS: Diagnosis was obtained by cystoscopy and histological analysis. Nephrogenic adenoma was treated by transurethral electroresection and administration of antibiotics in case of urinary tract infections. Follow-up consisted of cytological controls of urine and bladder irrigation fluid as well as of cystoscopy every 3 months. RESULTS: In 7 of 1328 renal allograft recipients, nephrogenic adenoma could be detected after 7 to 60 months following renal transplantation. In five patients, recurrence was detected 9 to 23 months after diagnosis of the initial lesion. No evidence of malignant degeneration was observed in any patient. Nephrogenic adenoma was not related to immunosuppressive therapy, cytomegalovirus disease, or gancyclovir therapy. CONCLUSIONS: We suggest that after successful transurethral electroresection of nephrogenic adenomas, cytological controls are adequate every 3 months. Only in renal transplant patients with recurrence of voiding disturbances, macrohematuria, or urinary tract infection are cystoscopy and biopsy indicated in the routine follow-up regimen.

Adenoma↗

PubMed1998

N-acetylneuraminic acids (nana): a potential key in renal calculogenesis.

N-Acetylneuraminic acids (NANA) promote binding of calcium ions to macromolecules and cells, increase the intrinsic viscosity of glycoproteins and facilitate gel formation in water. Since these properties are crucial in urinary calculogenesis, we evaluated NANA levels in urine and serum as well as their expression in kidney tissues. Using a modified thiobarbituric acid assay, the evaluation of free and bound NANA in 24-h urine samples revealed a ratio of 1.87 in 33 non-stone-formers but a reversed ratio of 0.84 in 41 recurrent calcium oxalate stone-formers. Time kinetics revealed a gradual rise in NANA expression until 48 h of culture and a significantly higher release into supernatants of papillary renal epithelial cells (REC) when compared with cortical REC. To examine NANA distribution in kidney tissues, paraffin-embedded biopsies from five normal and six stone-forming kidneys were labeled with the biotinylated NANA-specific lectins Maackia amurensis (MAA) and Sambucus nigra (SNA). Immunohistochemistry revealed intense luminal MAA reactivity of distal tubular REC and collecting ducts in 96.7% and 91.5% of normal and stone-forming kidneys respectively. By contrast, there was a marked difference between normal and stone-forming kidneys for SNA reactivity (17.7% vs 95%) at the same locations. Finally, the glycocalyx of recurrent stone-formers showed altered sialylglycoside linkages [alpha(2,6) instead of alpha(2,3)] that may indicate an altered REC function. Given the calcium-binding potential of NANA, their increased local concentration within the glycocalyx layer in the distal nephron may either initiate stone formation or facilitate attachment of microcrystals to REC.

Adult↗

PubMed1998

Does topical instillation therapy influence chromosomal aberrations in superficial bladder cancer?

PURPOSE: Patients with a high risk for superficial bladder cancer are treated by topical immuno-or chemotherapy after transurethral resection to reduce the chance of recurrence and/or progression. The aim of this study was to analyse if cytogenetical abnormalities, which are known to be constantly related to bladder cancer, are modified or eliminated by topical immuno- or chemotherapy. MATERIALS AND METHODS: Using fluorescence in situ hybridization (FISH), the influence of topical instillation therapy with Bacillus Calmette-Gúerin (BCG) and Mitomycin C (MMC) on numerical aberrations of chromosomes 7, 9 and 17 was investigated in 25 patients with transitional cell cancer (TCC) of the bladder. Data were compared with histological and clinical outcome. Fifteen TCC patients with similar histological criteria without instillation therapy served as controls. Median follow-up was 30 +/- 2 months. RESULTS: After BCG treatment 10 of 15 patients (66.6%) developed recurrent and 2/15 (13.3%) progressive disease. Three of 15 patients (20.0%) had no evidence of disease. Numerical aberrations did not change in 8 of the 15 BCG patients (53.3%) and changed to a more aggressive pattern in 40.0% (6/15). Five of 10 MMC treated patients (50.0%) developed a recurrent tumor, 2/10 (20.0%) progressed and 3/10 (30.0%) had no evidence of disease. Four of 10 (40.0%) of these patients showed stable and 5/10 (50.0%) progressive chromosomal patterns. Only one patient in each group with primary chromosomal alterations changed to a regular diploid chromosomal pattern after therapy according to a complete clinical remission. CONCLUSION: Even though topical immuno- and chemotherapy may be useful to delay recurrence and progression, chromosomal patterns remain basically unstable.

Administration, Intravesical↗

PubMed1998

Nephrogenic adenoma in renal transplant recipients: a truly benign lesion?

OBJECTIVES: Nephrogenic adenoma is a benign metaplastic lesion of the urinary bladder, reported to occur as a response to inflammation, trauma, intravesical therapies, and after renal transplantation. The aim of this study was to evaluate on the basis of chromosomal analysis whether nephrogenic adenoma really is benign. METHODS: Twelve renal transplant recipients with histologically verified nephrogenic adenoma were analyzed for numerical aberrations of chromosomes 7, 9, and 17. Results were related to total DNA content, p53 and Ki-67 positivity, and clinical outcome. Ten patients with superficial bladder cancer and 10 healthy renal transplant recipients formed the control groups. RESULTS: All 12 patients with nephrogenic adenoma had monosomy 9 in a mean of 24.3% (range 20% to 30%) of the evaluated cells; 3 patients had an additional trisomy 7 in a mean of 8% (range 6% to 10%) of the counted cells. Chromosome 1 7 was disomic in all patients. DNA histograms were diploid in 11 of the 12 patients and aneuploid in 1 patient. No p53 and Ki-67 positivity was present in this group. All patients with superficial bladder cancer had monosomy 9 in a mean of 79.8% (range 75% to 85%) of the counted cells. Two patients were found to have an additional trisomy 7 in 50% and 65% of the cells, respectively. The latter had an aneuploid histogram; the others had haploid/diploid histograms. p53 was negative in all specimens. Ki-67 positivity was present in 70% of these patients. All healthy transplant recipients had disomic chromosomal patterns according to diploid DNA histograms and negative immunocytochemical results. CONCLUSIONS: Even if in a lower percentage of cells, aberrations of chromosome 7 and 9 were detected in nephrogenic adenoma. It therefore cannot be excluded that nephrogenic adenomas in immunosuppressed renal transplant recipients may develop into malignant lesions.

Adolescent↗

PubMed1998

Phenotypic and functional characterization of mast cells derived from renal tumor tissues.

Mast cells (MCs) originate from multipotent hematopoietic progenitor cells. However, MCs in various organs are heterogenous in terms of mediator or receptor expression and response to diverse stimuli. We characterized the phenotype and functional properties of human renal mast cells (HRMCs). Tissue was obtained from 17 patients suffering from renal tumors (transitional cell carcinoma, n = 4; renal cell carcinoma, n = 13). HRMCs were isolated by collagenase digestion. Double staining with toluidine blue and immunofluorescence using monoclonal antibodies (mAbs) revealed expression of stem cell factor (SCF)-receptor (c-kit/CD117), CD9, CD29, CD33, CD43, CD44, CD54, and CD63 on HRMCs. In contrast, HRMCs were not recognized by mAbs to CD2, CD3, CD4, CD11b, CD14, CD15, CD16, CDw17, CD19, or CD23. HRMCs were also negative for CD116 (granulocyte-macrophage colony-stimulating factor [GM-CSF] receptor alpha), CD123 (interleukin [IL]-3Ralpha), CD121a (IL-1R type I), CD122 (IL-2Rbeta), and CD127 (IL-7R) and were also found to lack C5aR (CD88). Ligand-induced activation of HRMCs through immunoglobulin (Ig)E-R or SCF-R (c-kit) resulted in histamine secretion (control: <10%; alphaIgE, 1 microg/mL: 50.12 +/-5.18%; rhSCF, 100 ng/mL: 29.24 +/- 22.39), whereas recombinant C5a, erythropoietin (EPO), IL-1 through 10, and GM-CSF exerted no effects. As determined by in situ staining, HRMCs contained tryptase, but only low or undetectable amounts of chymase. Electron microscopy confirmed the presence of MCs in renal tissues and revealed a scroll-rich granule population in HRMCs. Together, HRMCs are tryptase+, C5aR- mast cells exhibiting phenotypic and functional properties similar to those of lung MCs.

Adult↗

PubMed1997

Fluorescence in situ hybridization identifies more aggressive types of primarily noninvasive (stage pTa) bladder cancer.

PURPOSE: We evaluated the genetic changes in cytological specimens of bladder cancer by fluorescence in situ hybridization, and related them to stage and grade of the tumor, ploidy, p53 and Ki-67 expression, and clinical outcome to determine a simple method to identify tumors with a poorer prognosis. MATERIALS AND METHODS: Using fluorescence in situ hybridization the numerical aberrations of chromosomes 7, 9 and 17 in barbotages and imprints of 50 patients with transitional cell cancer of the bladder were determined. Of the patients 29 had a primary stage pTa tumor, while 21 with stage pT1 or greater disease formed the control group. Data were compared to ploidy status, and Ki-67 and p53 immunoreactivity. RESULTS: Repeated monosomy 9 and haploid or diploid status on static ploidy determination were found in patients with primary stage pTa tumors without recurrence. Immunoreactivity of p53 was negative in all of these patients, while there was a low percentage of positive staining for Ki-67. Patients with recurrent and progressive disease had a high incidence of trisomy 7 and 17, aneuploid status and high positivity for both immunological markers. For chromosomes 7 and 17, and ploidy status bivariate analysis showed a significant difference. CONCLUSIONS: The evaluation of chromosomal aberrations in barbotage and imprint specimens clearly establishes a relationship between chromosomal defects and aggressiveness of the tumor. The majority of nonaggressive stage pTa transitional cell carcinomas can be distinguished from potentially lethal cases by fluorescence in situ hybridization at a diagnostic point when the grading is not yet prognostic.

Adult↗

PubMed1997

Conventional bladder wash cytology performed by four experts versus quantitative image analysis.

Bladder wash cytology provides superior results for the detection of bladder malignancies than does voided urine analysis. Image analysis systems have been developed for quantification of cytologic features. In this study, routine bladder wash cytology is compared with an automated image analysis system (QUANTICYT). We studied a random set of 100 bladder wash samples from a population of 1614 patients in follow-up after bladder cancer. Four experienced pathologists interpreted the same 100 Papanicolaou-stained slides. Cytologic and image analysis results were compared for prediction of a cystoscopic lesion, histologic abnormalities, and tumor recurrence. After application of receiver operating characteristic curves, prediction of a cystoscopic lesion by cytology and image analysis was comparable. Both the image analysis system and the cytologic examination detected all of the high-grade lesions. Image analysis was superior to cytologic analysis for the prediction of tumor recurrence after normal findings at cystoscopic examination.

Cell Nucleus↗

PubMed1996

Regulation of Ca2+-activated K+ channel from rabbit distal colon epithelium by phosphorylation and dephosphorylation.

The Ca2+-activated maxi K+ channel is predominant in the basolateral membrane of the surface cells in the distal colon. It may play a role in the regulation of the aldosterone-stimulated Na+ reabsorption from the intestinal lumen. Previous measurements of these basolateral K+ channels in planar lipid bilayers and in plasma membrane vesicles have shown a very high sensitivity to Ca2+ with a K0.5 ranging from 20 nm to 300 nm, whereas other studies have a much lower sensitivity to Ca2+. To investigate whether this difference could be due to modulation by second messenger systems, the effect of phosphorylation and dephosphorylation was examined. After addition of phosphatase, the K+ channels lost their high sensitivity to Ca2+, yet they could still be activated by high concentrations of Ca2+ (10 micron). Furthermore, the high sensitivity to Ca2+ could be restored after phosphorylation catalyzed by a cAMP dependent protein kinase. There was no effect of addition of protein kinase C. In agreement with the involvement of enzymatic processes, lag periods of 30-120 sec for dephosphorylation and of 10-280 sec for phosphorylation were observed. The phosphorylation state of the channel did not influence the single channel conductance. The results demonstrate that the high sensitivity to Ca2+ of the maxi K+ channel from rabbit distal colon is a property of the phosphorylated form of the channel protein, and that the difference in Ca2+ sensitivity between the dephosphorylated and phosphorylated forms of the channel protein is more than one order of magnitude. The variety in Ca2+ sensitivities for maxi K+ channels from tissue to tissue and from different studies on the same tissue could be due to modification by second messenger systems.

Animals↗