The relationship between interleukin-13 and angiogenin in patients with bladder cancer.

Participation of anti-inflammatory interleukin-13 (IL-13) in the process of carcinogenesis was well studied. Angiogenesis plays a key role in the process of tumour growth and metastasis. Higher expression of angiogenin (ANG) have been proven in many types of cancers. The aim of the study was to more fully understand the significance of plasma IL-13 as an immunomodulator and ANG as a stimulator of the angiogenesis process in patients with bladder cancer (BC) and to investigate the relationship between parameters. These parameters were examined in the group of BC patients and in subgroups of BC depending on clinical stage: non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC), histopathologic malignancy low grade (LG), high grade (HG) and in primary and recurrent BC. The level of IL-13 and ANG in the plasma of BC patients and controls were measured by enzyme-linked immunosorbent assay. All calculations were done using the STATISTICA 13.3 (TIBCO software Inc.). Plasma levels of IL-13 and ANG were significantly higher in BC patients and in all patient subgroups examined than in the controls (p < 0.001). A negative significant correlation was found between ANG and IL-13 levels in BC-patients. Based on the receiver operating characteristic curves (ROC), IL-13 had good diagnostic value in BC. The presented results may suggest a relationship between angiogenesis and inflammation in the pathogenesis of bladder cancer and the development of this disease. With the increase of IL-13 level in BC-patients plasma, the ANG level decreased.

Uroplakin IIIa Is a Marker in Bladder Cancer but Seems Not to Reflect Chemical Carcinogenesis.

BACKGROUND: Uroplakins are glycoproteins investigated as potential markers of urothelial carcinoma. However, their role in chemical carcinogenesis is uncertain. In this study the diagnostic value of plasma and urine uroplakin IIIa (UPIIIa) levels in bladder cancer (BC) was investigated, particularly in the aspect of environmental exposure to chemical carcinogens, measured by DNA damage and detoxification ability in the BC smoking group. The correlation between uroplakin, 8-OHdG, and GSTπ was investigated. MATERIAL AND METHODS: This study included 61 BC patients and 33 healthy controls. UPIIIa, 8-OHdG, and GSTπ levels were estimated by the immunoenzymatic method (ELISA). RESULTS: UPIIIa levels were elevated in BC patients in plasma (p≤0.001) and in urine (p≤0.001), as were 8-OHdG and GSTπ levels in urine. Moreover, the 8-OHdG level was higher in invasive or high grade tumors. A positive correlation between UPIIIa/GSTπ and 8-OHdG/GSTπ was observed, but no UPIIIa/8-OHdG correlation was noted. CONCLUSION: The study showed the diagnostic value of urine and plasma UPIIIa in BC (good sensitivity, specificity, and predictive value). The lack of UPIIIa correlation with 8-OHdG and smoking suggests that UPIIIa does not reflect the environmental exposure. The increased levels of 8-OHdG and GSTπ in the invasive tumor stage indicate their value in BC monitoring.

Preliminary Evaluation of the Diagnostic Usefulness of Uroplakin 2 with an Assessment of the Antioxidant Potential of Patients with Bladder Cancer.

BACKGROUND: Urothelial carcinoma is the most common type of bladder cancer (BC). It makes up more than 90% of all bladder cancers. Uroplakins are tissue-specific, glycoproteins, playing a role in the construction and function of urothelium. The emergence of uroplakins in the urine and/or plasma may be of potential importance in the early detection of BC. In our study, the diagnostic value of plasma and urine uroplakin 2 (UP2) concentration in bladder cancer was investigated, with an assessment of the antioxidant potential of BC patients. The correlation between UP2, total antioxidant capacity (TAC), and concentration of glutathione (GSH) was also examined. MATERIALS AND METHODS: This study included 61 BC patients and 33 healthy controls. UP2 concentration was estimated by the immunoenzymatic method (ELISA). TAC and GSH were determined in spectrophotometrically methods. RESULTS: UP2 concentration in BC patients was significantly higher (p≤0.001) both in plasma and in urine compared to the control groups (C). TAC concentration in urine (p≤0.001) and GSH concentration in plasma (p=0.047) were significantly lower in BC group compared to the C group. The high specificity and sensitivity for UPK2 in plasma (76%, 80%, respectively) and urine (88%, 84%, respectively) were observed. Positive correlations were observed between concentration of UP2 in plasma and TAC concentration in urine and between UP2 concentration in plasma and GSH concentration in the same material. CONCLUSION: The study showed the early diagnostic value of urine and plasma UP2 in BC. There was a decrease in UP2 concentration in the urine of patients with the development of BC. The decrease of antioxidant systems (TAC, GSH) indicates their relationship with the BC process. Based on the obtained results, it is justified to continue the study in a larger group of patients with BC.

Is the Genetic Background of Co-Stimulatory CD28/CTLA-4 Pathway the Risk Factor for Prostate Cancer?

The impairment of immunological surveillance caused by aberrant T cell activation can lead to an inadequate anti-tumor response. Therefore, deregulation in co-stimulatory pathway might be associated with cancer susceptibility. Here we undertook a prospective study to investigate whether genetic variations in gene encoding molecule CD28 and CTLA-4 playing pivotal role in regulating adoptive immune response can influence susceptibility to prostate cancer. Single nucleotide polymorphisms (SNPs) in CTLA-4 and CD28 genes were genotyped in 301 prostate cancer (PCa) patients and 301 controls. The distributions of the genotypes and haplotypes in the CTLA-4/CD28 SNPs were similar in both studied groups. However, the overrepresentation of carriers of CTLA-4c.49A>G[A] allele and carriers of CTLA-4g.319C>T[T] allele in PCa as compared to controls was observed (p = 0.082 and p = 0.13, respectively). The risk of disease was higher (OR 1.78) for carriers of both susceptibility alleles as compared to carriers of protective genotypes (p = 0.03). The CTLA-4c.49A>G and CTLA-4g.319C>T SNPs might be considered as low risk susceptibility locus for PCa.

CTLA-4 and CD28 genes' polymorphisms and renal cell carcinoma susceptibility in the Polish population--a prospective study.

Polymorphisms in co-stimulatory genes are associated with susceptibility to several malignances such as breast cancer, cervical cancer and chronic lymphocytic leukemia, but have been scarcely investigated in renal cell cancer (RCC). A total of 310 RCC patients and 518 controls were genotyped for single-nucleotide polymorphisms (SNPs) in the CTLA-4 and CD28 genes: CTLA-4c.49A>G (rs231775), CTLA-4g.319C>T (rs5742909), CTLA-4g.*6230G>A (CT60; rs3087243), CTLA-4g.*10223G>T (Jo31; rs11571302), CD28c.17+3T>C (rs3116496) and CD28c.-1042G>A (rs3181098). The distribution of the alleles, genotypes and haplotypes in the CTLA-4 and CD28 genes were similar in the RCC patients and in the controls. However, among the patients with a clear cell RCC (CCRCC), the G allele carriers of CT60 and Jo31 SNPs were overrepresented, and the overrepresentation became significant for the carriers of CT60[G] allele in CCRCC patients with necrosis in the primary tumor (P = 0.046). The CTLA-4c.49A>G[A]/CTLA-4g.319C>T[C]/CT60[A]/Jo31[T]/CD28c.17+3T>C[T]/ CD28c.1042G>A[G] haplotype was associated with an approximately threefold increased risk of primary tumor necrosis in CCRCC patients (P corrected = 0.0000007) and with the advanced stage of disease (IV) (P corrected = 0.001). When stratified by gender, CD28c.-1042G>A[GG] genotype was more frequent in the female CCRCC patients compared with healthy women (P = 0.042). Polymorphisms in the CTLA-4 and CD28 genes, in particular considered together as haplotypes, were associated with increased risk of CCRCC, especially with necrosis and with the advanced stage of disease. The CD28c.-1042G>A SNP modulates the risk of CCRCC in women. These findings indicate that the associations of the CTLA-4 and CD28 polymorphisms with the risk of renal cancer are worth further study in a larger group of patients.

Evaluation of the influence of systemic neoadjuvant chemotherapy on the survival of patients treated for invasive bladder cancer.

OBJECTIVE: To assess the influence of neoadjuvant systemic chemotherapy using a modified methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) scheme in patients with invasive bladder cancer. PATIENTS AND METHODS: Two groups of patients were reviewed retrospectively; group 1 included 51 who received chemotherapy before cystectomy and group 2 included 62 who were treated only with surgery. The mean (range) duration of follow-up was 3.2 (0.25-10.25) years. The patients in group 1 were divided into two subgroups: those with tumour confined to the bladder (T1, T2 and T3a) and the remaining patients with tumour beyond the bladder (T3b, T4a,b). The chemotherapy was administered as routine MVAC, except vinblastine and methotrexate were given at 15 and 22 days during the cycle. A mean of three cycles were administered. RESULTS: The 5-year survival rate in group 1 and 2 was 66% and 58%, respectively (P > 0.3); after 8 years of follow-up the survival rates were 58% and 33%, respectively, and significantly different (P < 0.01). CONCLUSION: Systemic chemotherapy using the modified MVAC scheme in patients subsequently undergoing radical cystectomy improved the survival rate after 8 years of follow-up.

Treatment of high-risk superficial bladder cancer with maintenance bacille Calmette-Guérin therapy: preliminary results.

OBJECTIVE: To evaluate, in a prospective study, the effects and results of maintenance therapy with bacille Calmette-Guérin (BCG) in treating patients with high-risk superficial bladder cancer. PATIENTS AND METHODS: In all, 155 patients were enrolled in a randomized study of transurethral resection alone (53) or combined with intravesical BCG (102) as a treatment for superficial bladder cancer. BCG was administered for six consecutive weeks followed by three weekly instillations in months 3, 6, 12, 18, 24, 30 and 36 after resection. Recurrence, progression, prognostic factors and side-effects were assessed and analysed. RESULTS: After a median (range) follow-up of 23 (6-42) months, 83 of the 102 patients treated with BCG (81%) were disease-free, compared with 24 of the 53 treated with resection alone (45%). There was also a significant difference in tumour progression and time to progression between the trial arms. The disease progressed in eight patients (8%) treated with BCG and in 12 (23%) of those treated by resection alone. Independent risk factors for progression were DNA ploidy status and stage. Only the completion of treatment was predictive of outcome (risk of recurrence) for patients treated with BCG. CONCLUSION: Maintenance BCG therapy was better than resection alone in reducing the incidence of recurrence and progression in patients with high-risk superficial bladder cancer.

Genetically determined sparteine oxidation and sulfadimidine acetylation polymorphism in patients with non-occupational urinary bladder cancer.

The results of our study revealed a predominance of the percentage of extensive metabolizers (EM) of sparteine (94.8%) among 58 patients with non-occupational urinary bladder cancer in comparison with the percentage of extensive metabolizers (91.2%) in healthy persons; the difference being not statistically significant. However, among ultrarapid (EM) oxidators with the metabolic ratio (MR) < 0.5 the difference in the MR frequency distribution between 15 patients with bladder cancer (25.9%) and 18 healthy persons (11.25%) was statistically significant. Therefore, our studies provide some evidence of a possible relationship between the EM sparteine oxidation phenotype and the susceptibility to non-occupational bladder cancer. Not statistically significant slight prevalence of the percentage of slow acetylators (SA) (53.1%) among 32 urinary bladder cancer patients in comparison with the percentage of SA (49%) among 45 healthy persons may confirm the conclusion that a slow acetylator phenotype is not associated with the increased risk of the development of non-occupational urinary bladder cancer.

[Evaluation of kidney parenchyma infection during renal lithiasis]. / Ocena zakazen miazszu nerki w przebiegu kamicy nerkowej.

In 39 patients with renal lithiasis bacteriological investigation of middle stream urine, renal pelvis, renal calculi and kidney parenchyma were performed. In nine of patients presence of bacteria in kidney parenchyma was observed. Infection of kidney parenchyma in six cases was accompanied by bacteriuria in samples from middle stream urine and from renal pelvis. In every case of kidney parenchyma infection, presence of bacteria in renal calculi was observed. In 30 patients with sterile renal parenchyma, bacteriuria was found in 17 cases from middle stream urine and from renal pelvis. In these cases kidney calculi were also infected. It was found that in case of kidney parenchyma infection renal calculi were also infected, but urine from middle stream and renal pelvis can be sterile.

Genetically determined sparteine oxidation polymorphism in a Polish population.

The genetic oxidation polymorphism was determined in 160 healthy Polish volunteers from the south-west of Poland (Wroclaw region), using sparteine as a model drug. The results of a Polish population study revealed a bimodal distribution of the sparteine metabolic ratio and showed the existence of two oxidation phenotypes designated as extensive and poor metabolizers. The frequency of poor metabolizers in our study (8.8%) compares well with most results of poor oxidation metabolizers in Caucasian populations.

Tubulo-papillary adenoma (so-called nephrogenic adenoma) arising in the renal pelvis. Report of a case with a critical consideration of histogenesis and terminology.

This is the first detailed clinical and histopathologic report of a tubulo-papillary adenoma (so-called nephrogenic adenoma) arising in the renal pelvis of a 35-year-old woman. The tumor showed a polypoid exophytic growth and consisted of closely packed tubular formations lined by cuboidal to low columnar cells with an admixture of delicate papillary structures. Its benign nature was indicated by the lack of cellular atypias, the extremely low proliferative activity and the absence of invasiveness. We favor the metaplastic theory of origin rather than an embryologic (dysontogenetic) derivation from mesonephric remnants as the underlying histogenetic principle. The descriptive term "tubulo-papillary adenoma" seems more appropriate than the designation "nephrogenic adenoma". True tumors of this type should clearly be distinguished from metaplastic tubular, papillary or tubulo-papillary cuboidal hyperplasias of the urothelium (so-called nephrogenic metaplasia) which are considered preneoplastic and assumed to be immediate precursors of adenomas of the lower urinary tract.

Laryngeal electromyographic activity in adductor and abductor spasmodic dysphonia.

Vocal symptoms in spasmodic dysphonia (SD) range from strain-strangle phonation and glottal-stop phonatory breaks of adductor SD to breathy phonation and aspirate phonatory breaks of abductor SD. Many SD subjects show both symptom types. Heterogeneity in vocal symptoms contributes to controversy surrounding the etiology(s) of SD. Acoustic/perceptual analyses of vocal symptoms are inconclusive in resolving this controversy. This investigation moves the search for distinguishing features of adductor and abductor SD to the level of neuromuscular control and analysis of intrinsic laryngeal muscle (adductor and abductor) activity. Subjects rated perceptually as primarily adductor or abductor SD sustained production of vegetative gestures and isolated speech sounds (/i/ and /s/). Qualitative and quantitative analyses of electromyographic signals recorded from thyroarytenoid (TA) failed to differentiate SD subjects by symptom type. Analysis of TA and posterior cricoarytenoid (PCA) activity in one abductor SD revealed high levels in both muscles during production of the voiced vowel. Data suggest that a possible explanation for symptom heterogeneity in SD is the relation between disrupted neuromotor input to laryngeal muscles and reflexive or conscious compensations constrained by laryngeal biomechanics.

Preparation time and response complexity effects on stutterers' and nonstutterers' acoustic LRT.

Nonstutterers', mild stutterers', and severe stutterers' acoustic laryngeal reaction times (LRTs) were recorded for isolated vowels and nonpropositional VCV responses in different stimulus conditions governing response preparation. In all stimulus-response conditions severe stutterers produced the longest LRTs, followed in turn by mild stutterers and nonstutterers. The three groups significantly differed from one another in most conditions, but the magnitude of difference between mild and severe stutterers was notably greater than the difference between mild stutterers and nonstutterers. LRT changes as a function of stimulus condition showed that, in general, nonstutterers were best able to use a preparation-facilitating stimulus condition to reduce LRT, and severe stutterers least able to do so. LRT changes as a function of response complexity showed that only nonstutterers produced statistically significant within-group differences. Patterns of LRT change as a combined function of group, stimulus condition, and response type suggest a complex relationship between stutterer severity, preparation time, and type of response complexity. Results illustrate aspects of Goldberg's (1985) model of preparation processes, and support hypotheses that stutterer subgroups show differential preparation deficits along with high motor initiation variability.

Systems architecture for quantification of dynamic myoelectric and kinematic activity of the human vocal tract.

This paper describes a systems architecture useful for scientific investigations that require the acquisition and analysis of multiple, time-synchronous signals in large volume. The architecture has recently been developed by this group to enhance our capability to research and quantify central nervous system function in the production of normal and pathologic speech. The architecture utilizes modern advances in desktop microcomputers and has been designed so that vocal motor control laboratories (or similar settings) with modest funding can more fully participate in comprehensive investigations of speech production. Research experiments organized with this architecture may involve many more subjects and measures than previously possible without significant increases in time and personnel resources. This paper will demonstrate the technique and practicality of this architecture as it is being used to successfully guide research to map hierarchic central nervous system regions of involvement in two speech disorders: spasmodic dysphonia and stuttering. The architecture has broad usefulness to many areas of otolaryngology and health science.

[Immunohistochemical demonstration of L- and M2-pyruvate kinase in primary renal cell carcinomas and their metastases]. / Immunhistochemische Darstellung der L- und M2-Pyruvatkinase in primären Nierenzellkarzinomen und deren Metastasen.

Seventeen renal cell carcinomas (RCC) were classified histologically and investigated for their expression of L- and M2-pyruvate kinase (PK) immunohistochemically. Using monoclonal antibodies we were able to demonstrate L-PK within 15 RCC and two metastases (in thyroid gland and bone) after fixation with aceton and paraffin embedding. In normal renal tissue the enzyme was localized within proximal tubules selectively. No enzyme reaction of L-PK could be demonstrated in renal oncocytoma, thyroid carcinoma, and in carcinomas of renal pelvis and lung. In contrast to this the M2-PK was detectable in all tumors and metastases investigated in this study. The results presented in this paper are able to show that (1) RCC derive from the proximal renal tubules, but not the renal oncocytoma, (2) the detection of L-PK may be helpful for identification of metastases of RCC even if they are undifferentiated and (3) there is an enzyme shift from L-PK to M2-PK within tumor cells of RCC resulting in alteration of glucose utilization from energy supply to syntheses of substrates essential for tumor cells.

[Evaluation of arterial occlusive disease]. / Die Begutachtung arterieller Durchblutungsstörungen

In giving an opinion on arterial circulation disorders, an arterial occlusion is predominant. As a rule, the diagnosis based on anamnestic data, clinical examinations and some functional tests causes no difficulties. An angiography simplifies the evaluation, but it should be carried out only to distinguish a generalized vasculopathy from a local one. The arterial occlusion is a chronic and progressive disease with coronary vessels being mainly involved. The muscular force of the patient is reduced, local infections and traumatisms menace him thus reducing his working capacity. Anticoagulants must often be given continuously, the vascular systems of the heart and the brain may be impaired. It is extremely difficult to elucidate causal relationships, especially in case of injuries suffered during military service. It is the general opinion nowadays that cold-injuries entail a limited angiitis but no generalized vasculopathy.

The activity of certain enzymes in the liver of mice, selected for weight gain.

Examining the weight gains of mice in selected and nonselected lines maintained on a low (10%) and high (20%) protein diet, and of their "crossbreds", it was ascertained that the highest values occurred in selected lines maintained on a high protein level and the lowest in "crossbreds".Analysing the enzyme activity - aldolase, aminotransferase AspAT and AlAT - in the liver of these animals, it was observed that selected mice maintained on either of the protein levels demonstrated usually values significantly lower than for the nonselected ones.