Promotion of cytoplasmic mislocalization of p27 by Helicobacter pylori in gastric cancer.

The cyclin-dependent kinase (CDK) inhibitor p27 has an important role in cell cycle regulation. Reduced expression of p27 is commonly associated with poor prognosis in many malignancies, including gastric cancer. Cytoplasmic p27 mislocalization may be an additional indicator of high-grade tumors and poor prognosis in cancer. As chronic infection by Helicobacter pylori is the most important risk factor for gastric cancer development, we evaluated the effects of H. pylori on p27 expression and localization in gastric cancer cells. Co-culture of gastric cells with H. pylori induced cytoplasmic p27 expression and reduced nuclear p27 expression in vitro. Cytoplasmic p27 expression was associated with and dependent upon phosphorylation of p27 at T157 and T198: wild-type p27 accumulated in the cytoplasm, but non-phosphorylatable mutants affecting T157 or T198 were nuclear in H. pylori-infected cells. These post-translational p27 changes were secondary to activation of cellular phosphoinositide-3 kinase (PI3K) and AKT signaling pathways, and dependent upon a functional H. pylori cag pathogenicity island. We investigated the clinical significance of cytoplasmic p27 mislocalization in 164 cases of resected gastric cancer in tissue microarrays. In 97 cases (59%), cytoplasmic p27 mislocalization was observed, and this was associated with increased mortality in multivariate analysis. These results show that H. pylori infection induces AKT/PI3K-mediated phosphorylation of p27 at T157 and T198 to cause cytoplasmic p27 mislocalization in gastric cancer, and that p27 mislocalization is an adverse prognostic feature in gastric cancer. This is the first demonstration of the translocation of a specific bacterial virulence factor that post-translationally regulates a host cell CDK inhibitor. This is of particular significance, because p27 has both tumor-suppressive and oncogenic activities, depending upon its subcellular localization. Cytoplasmic mislocalization of p27 induced by H. pylori may be an important mechanistic link between H. pylori infection and gastric carcinogenesis.

Metastatic malignant melanoma presenting as an appendiceal mucocele.

Melanoma metastatic to the appendix is extremely rare. Here we describe a case of a 31-year-old female from Bolivia with a remote history of metastatic malignant melanoma first diagnosed as a cutaneous malignant melanoma ten years prior to this presentation. The patient was being followed for a mucocele which on resection was found to be metastatic melanoma. "Mucocele" is a generic diagnosis that warrants further characterization and treatment.

SV40 associated miRNAs are not detectable in mesotheliomas.

BACKGROUND: Simian virus-40 (SV40) is a DNA tumour virus that was introduced into the human population with contaminated poliovirus vaccine, and its role in mesothelioma is widely debated. PCR based testing has been called into question, as false positives can be because of cross-reactivity with related viruses, or to laboratory contamination. The Institute of Medicine has recommended the development of more sensitive and specific tests to resolve this controversy. METHODS: We have characterized highly sensitive RT-PCR based assays that are specific for SV40-encoded microRNAs (miRNAs), as an alternative to current testing methods. RESULTS: Using this sensitive and specific detection method, we were unable to identify SV40 miRNA expression in human malignant pleural mesothelioma (MM) samples. CONCLUSION: Our work indicates that SV40 miRNAs are not likely to contribute to mesothelioma tumourogenesis, but highlights the value of this approach when compared with the relatively unspecific current testing methods.

Intestinal necrosis due to sodium polystyrene sulfonate (Kayexalate) in sorbitol.

BACKGROUND: Sodium polystyrene sulfonate (SPS, Kayexalate) has been implicated in the development of intestinal necrosis. Sorbitol, added as a cathartic agent, may be primarily responsible. Previous studies have documented bowel necrosis primarily in postoperative, dialysis, and transplant patients. We sought to identify additional clinical characteristics among patients with probable SPS-induced intestinal necrosis. METHODS: Rhode Island Hospital surgical pathology records were reviewed to identify all gastrointestinal specimens reported as containing SPS crystals from December 1998 to June 2007. Patient demographics, medical comorbidities, and hospital courses of histologically verified cases of intestinal necrosis were extracted from the medical records. RESULTS: Twenty-nine patients with reports of SPS crystals were identified. Nine cases were excluded as incidental findings with normal mucosa. Nine patients were excluded as their symptoms began before SPS administration or because an alternate etiology for bowel ischemia was identified. Eleven patients had confirmed intestinal necrosis and a temporal relationship with SPS administration suggestive of SPS-induced necrosis. Only 2 patients were postoperative, and only 4 had end-stage renal disease (ESRD). All patients had documented hyperkalemia, received oral SPS, and developed symptoms of intestinal injury between 3 hours and 11 days after SPS administration. Four patients died. CONCLUSION: Intestinal ischemia is a recognized risk of SPS in sorbitol. Our series highlights that patients may be susceptible even in the absence of ESRD, surgical intervention, or significant comorbidity.

A proteomic analysis reveals the loss of expression of the cell death regulatory gene GRIM-19 in human renal cell carcinomas.

Gene associated with retinoid interferon-induced mortality (GRIM)-19, an inhibitor of transcription factor STAT3, was originally identified as a critical regulatory protein in a genetic screen that was designed to identify the gene products necessary for Interferon (IFN)-beta- and retinoic acid-induced cell death. Over expression of GRIM-19 activates cell death. Conversely, inactivation of its expression promotes cell growth. STAT3 is a transcription factor that regulates gene expression in response to multiple extra cellular growth factors. In contrast to its normal feedback inhibition, a constitutive activation of STAT3 has been documented in several tumors. Although many STAT3-inhibitors are described, their relevance to human cancer is unclear. In an attempt to define the molecular alterations associated with human renal cell carcinoma (RCC) using mass spectrometry, we have discovered that expression of GRIM-19 is lost or severely depressed in a number of primary RCC and in some urinogenital tumors. Using an RCC cell line, we show that down regulation of GRIM-19 promotes tumor growth via an augmentation of STAT3-dependent gene expression. These studies for the first time show a tumor-suppressor like activity of GRIM-19.

Global analysis of the human gastric epithelial transcriptome altered by Helicobacter pylori eradication in vivo.

OBJECTIVE: The transcriptional profile of gastric epithelial cell lines cocultured with Helicobacter pylori and the global gene expression of whole gastric mucosa has been described previously. We aimed to overcome limitations of previous studies by determining the effects of H pylori eradication on the transcriptome of purified human gastric epithelium using each patient as their own control. DESIGN: Laser capture microdissection (LCM) was used to extract mRNA from paraffin-embedded antral epithelium from 10 patients with peptic ulcer disease, before and after H pylori eradication. mRNA was reverse transcribed and applied on to Affymetrix cDNA microarray chips customised for formalin-fixed tissue. Differentially expressed genes were identified and a subset validated by real-time polymerase chain reaction (PCR). RESULTS: A total of 13 817 transcripts decreased and 9680 increased after H pylori eradication. Applying cut-off criteria (p<0.02, fold-change threshold 2.5) reduced the sample to 98 differentially expressed genes. Genes detected included those previously implicated in H pylori pathophysiology such as interleukin 8, chemokine ligand 3, beta defensin and somatostatin, as well as novel genes such as GDDR (TFIZ1), chemokine receptors 7 and 8, and gastrokine. CONCLUSIONS: LCM of archival specimens has enabled the identification of gastric epithelial genes whose expression is considerably altered after H pylori eradication. This study has confirmed the presence of genes previously implicated in the pathogenesis of H pylori, as well as highlighted novel candidates for further investigation.

Cytotoxic phenotype of intra-epithelial lymphocytes in normal and cryptorchid human testicular excurrent ducts.

BACKGROUND: Most testicular and epididymal lymphocytes express T-cell markers, but their cytotoxic potential and activation status have not been reported. In this study, distribution of the cytotoxic cells was compared between normal and cryptorchid testes stratified into two groups: the first with complete absence of germ cells [Sertoli cell-only (SCO)] and the second with arrested spermatogenesis (SCA). METHODS: Immunohistochemistry for the T-lymphocyte marker CD3 and cytotoxic markers CD8, TIA-1 and granzyme B was performed on paraffin-embedded sections. RESULTS: The number of CD8+ and CD3+ intra-epithelial lymphocytes (IELs) increased distally throughout the normal epididymis. TIA-1 immunostaining revealed that a significant proportion of IELs exhibited cytotoxic potential, whereas granzyme B staining disclosed a subpopulation of activated cytotoxic lymphocytes (CTLs). TIA-1/CD8 and granzyme B/CD8 double immunostaining revealed that the vast majority of TIA-1+ and granzyme B+ cells were CD8+. The proportion of activated granzyme B+ lymphocytes increased distally throughout the normal epididymis. The number of TIA-1+ and granzyme B+ intra-epithelial and stromal lymphocytes was significantly increased in the normal as opposed to the SCO cryptorchid epididymis and proximal vas deferens. CONCLUSIONS: These results suggest that exposure of the testicular excurrent ducts to spermatozoa or immature germ cells triggers the activation and recruitment of CTLs. Cytotoxic granule effector mechanisms may contribute to the immunological barrier preventing the immune response to spermatozoa in testicular ducts.

Effect of teenage pregnancy on educational disabilities in kindergarten.

Teenage pregnancies have become a public health issue because of their observed negative effects on perinatal outcomes and long-term morbidity. The association of young maternal age and long-term morbidity is usually confounded, however, by the high prevalence of poverty, low level of education, and single marital status among teenage mothers. The authors assess the independent effect of teenage pregnancy on educational disabilities and educational problems in a total population of children who entered kindergarten in Florida in 1992--1994 and investigate how controlling for potentially confounding factors affects the relation between teenage pregnancies and poor outcome. When no other factors are taken into account, children of teenage mothers have significantly higher odds of placement in certain special education classes and significantly higher occurrence of milder education problems, but when maternal education, marital status, poverty level, and race are controlled, the detrimental effects disappear and even some protective effects are observed. Hence, the increased risk for educational problems and disabilities among children of teenage mothers is attributed not to the effect of young age but to the confounding influences of associated sociodemographic factors. In contrast to teen age, older maternal age has an adverse effect on a child's educational outcome regardless of whether other factors are controlled for or not.

Microscopic analysis and significance of vascular architectural complexity in renal cell carcinoma.

The objective of this study was to evaluate the utility of measuring microvessel fractal dimension (MFD) as a parameter of architectural microvascular complexity in localized renal cell carcinoma (RCC). Forty-nine patients with low-stage clear cell RCC were assessed in a 9-year follow-up retrospective study. Tumor vessels were visualized with the endothelial marker CD34. Tumor microvessel density (MVD) was measured by computerized morphometry. Fractal analysis of the RCC microvascular network was performed and the MFD was computed in each case. Correlation between tumor vascular parameters, histological grade, extent of tumor necrosis and patient survival were tested by uni- and multivariate analyses. A significant correlation was found between tumor grade and decreased survival (P = 0.04). The extent of macroscopic tumor necrosis also significantly correlated with poor prognosis (P = 0.0001). Survival analysis revealed a significantly higher MVD in patients who survived longer than 5 years as compared with those who died before the end of the 5-year follow-up period (MVD = 10.8 +/- 4.7% versus 6.4 +/- 3.7%; P = 0.03). MVD was also inversely associated with the extent of tumor necrosis (P = 0.03). Microvessel fractal dimension was significantly higher in low- as compared with high-grade tumors (1.55 +/- 0.11 versus 1.45 +/- 0.15; P = 0.03). Survival analysis revealed a significantly higher MFD in those who lived >5 years as compared with those who died earlier (1.56 +/- 0.11 versus 1.46 +/- 0.15; P = 0.02). The MFD was inversely associated with the extent of tumor necrosis (P = 0.01). Multivariate analysis revealed that the MFD was the only significant factor to correlate with tumor necrosis, and that tumor necrosis was the only independent predictor of patient survival. These results indicate that the analysis of MFD as a marker of tumor microvascular complexity may provide important prognostic information as well as novel insight into the biology of tumor angiogenesis.

Primary rectal malignant melanoma: report of two cases.

Primary rectal malignant melanoma is an exceptionally rare neoplasm associated with an extremely poor prognosis despite aggressive surgical treatment. We present two female patients with bulky tumors of the lower rectum that were diagnosed as malignant melanoma, above the squamocolumnar junction. Both patients underwent abdominoperineal resection and postoperatively were treated with autologous melanoma cell vaccine. One patient is considered disease free for months after surgery; the second one developed supraclavicular lymph nodes and right lung metastasis after 7 months.

Apoptosis, proliferation, and Fas (APO-1, CD95)/Fas ligand expression in medullary carcinoma of the breast.

Medullary carcinoma (MC) of the breast is a unique subtype of infiltrating ductal carcinoma that is characterized by a prominent lymphoid infiltrate and improved prognosis. Activated granzyme B(+)/CD8(+) cytotoxic T-lymphocytes (CTLs) infiltrating tumour cell nests constitute a major subset within the lymphoid infiltrate. As CTLs destroy target tumour cells by triggering apoptosis, it would be of interest to determine whether the apoptotic rate in MC is increased. This study evaluates the extent of apoptosis in relation to Fas (APO-1, CD95)/Fas ligand (FasL) expression in MC. Fourteen cases of typical MC (TMC) and 15 cases of atypical MC (AMC) classified according to the Ridolfi criteria, as well as 19 cases of poorly differentiated infiltrating ductal carcinoma (PDC) were evaluated. The apoptotic index (AI) was assessed by the TUNEL method on paraffin-embedded tissue. Cell proliferation was evaluated immunohistochemically by PCNA staining. The level of Fas/FasL expression was determined semiquantitatively by immunohistochemistry using a four-grade scoring system. The AI was significantly increased in TMC and AMC as opposed to the PDC subgroup (2.2+/-0.8, 2.1+/-0.8, and 1.3+/-0.6, respectively; p<0.05). A significant proportion (31.8+/-7.9% in TMC and 25.8+/-9.7% in AMC) of the apoptotic tumour cells within tumour nests were in close contact with CD3(+) lymphocytes. Increased apoptosis was not accompanied by increased proliferation of tumour cells. The extent of Fas expression did not differ between the three subgroups. FasL was expressed both by tumour infiltrating lymphocytes in MC and by tumour epithelium in all three subgroups. The observation that the majority of MCs express Fas and are infiltrated by lymphocytes expressing FasL suggests that increased apoptosis in MC is mediated by Fas/FasL. However, our observation that the majority of MCs also express FasL and the fact that tumours co-expressing Fas and FasL did not show increased apoptosis suggest that there may be additional cytotoxic pathways that lead to tumour apoptosis in MC.

The impact of low birth weight, perinatal conditions, and sociodemographic factors on educational outcome in kindergarten.

OBJECTIVE: To assess the relative effects and the impact of perinatal and sociodemographic risk factors on long-term morbidity within a total birth population in Florida. METHODS: School records for 339 171 children entering kindergarten in Florida public schools in the 1992-1993, 1993-1994, or 1994-1995 academic years were matched with Florida birth records from 1985 to 1990. Effects on long-term morbidity were assessed through a multivariate analysis of an educational outcome variable, defined as placement into 9 mutually exclusive categories in kindergarten. Of those categories, 7 were special education (SE) classifications determined by statewide standardized eligibility criteria, 1 was academic problems, and the reference category was regular classroom. Generalized logistic regression was used to simultaneously estimate the odds of placement in SE and academic problems. The impact of all risk factors was assessed via estimated attributable excess/deficit numbers, based on the multivariate analysis. RESULTS: Educational outcome was significantly influenced by both perinatal and sociodemographic factors. Perinatal factors had greater adverse effects on the most severe SE types, with birth weight <1000 g having the greatest effect. Sociodemographic predictors had greater effects on the mild educational disabilities. Because of their greater prevalence, the impact attributable to each of the factors (poverty, male gender, low maternal education, or non-white race) was between 5 and 10 times greater than that of low birth weight and >10 times greater than that of very low birth weight, presence of a congenital anomaly, or prenatal care. CONCLUSIONS: Results are consistent with the hypothesis that adverse perinatal conditions result in severe educational disabilities, whereas less severe outcomes are influenced by sociodemographic factors. Overall, sociodemographic factors have a greater total impact on adverse educational outcomes than perinatal factors.

Cytotoxic phenotype of tumor infiltrating lymphocytes in medullary carcinoma of the breast.

Medullary carcinoma (MC) of the breast is considered to carry a more favorable prognosis than other subtypes of infiltrating ductal carcinoma This is a biological paradox because its clinical behavior contrasts with its anaplastic morphology. MC is characterized by a dense lymphocytic infiltrate. In this study, we determined the cytotoxic potential and activity of tumor infiltrating lymphocytes (TILs) in MC by CD3, CD8, TIA-1, and granzyme B immunostaining on paraffin-embedded sections. Fourteen cases of typical MC (TMC) and 15 cases of atypical MC (AMC) classified according to Ridolfi criteria, and 19 cases of poorly differentiated infiltrating ductal carcinoma (PDC) were studied. TILs were quantified separately into two groups: cells infiltrating tumor nests and cells within stroma The number of CD8+ and TIA-1+ cells infiltrating tumor cell nests were markedly increased in TMC and AMC, as opposed to the PDC subgroup (159.6+/-132.8; 77.4+/-59.3; 9.4+/-10.5 and 171.2+/-152.4; 72.3+/-55.0; 10.8+/-12.7 per high power field, respectively). The number of tumor infiltrating granzyme B+ cells was significantly greater in TMC and AMC, as compared with the PDC subgroup (82.1+/-64.9, 33.9+/-19.7, and 3.1+/-5.1, respectively). Although no significant difference was found between the number of stromal CD3+ and CD8+ lymphocytes among the three subgroups, stromal granzyme B+ cells were significantly elevated in TMC and AMC as compared with the PDC subgroup. Finally, the relative proportion of granzyme B+ as opposed to CD3+ intraepithelial and stromal lymphocytes was greater in TMC and AMC as compared with the PDC subgroup (0.52+/-0.29; 0.47+/-0.31; 0.19+/-0.18 and 0.18+/-0.11; 0.13+/-0.11; 0.06+/-0.05, respectively). The presence of increased numbers of activated cytotoxic lymphocytes in MC of the breast may be a key mechanism active in the host versus tumor response leading to improved prognosis.

Similar and divergent patterns in the regulation of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of MMP-1 gene expression in benign and malignant human thyroid cells.

An imbalance between the activity of matrix metalloproteinases (MMPs) (proteolytic enzymes that degrade protein components of the extracellular matrix) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), may be one of the mechanisms responsible for tumor cell invasion. We have investigated the regulation of MMP-1 and TIMP-1 gene expression in benign and malignant (follicular, anaplastic, and papillary) human thyroid cells. As expected of cells with invasive potential, detectable MMP-1 messenger RNA (mRNA) levels were observed in malignant cells under basal conditions, in contrast to undetectable levels in benign cells. Exposure of these cells, for 1 h, to the active phorbol ester, phorbol 12-myristate 13-acetate (TPA, 100 nmol/L), acting via protein kinase C (PKC), elicited an increase in MMP-1 mRNA, with a peak stimulation after a 3- to 4-h culture period. Epidermal growth factor (EGF, 25 ng/mL), however, acting via protein tyrosine kinase (PTK), stimulated such gene expression in malignant cells but failed to do so in benign cells. TIMP-1 mRNA was not significantly altered by the TPA-PKC, EGF-PTK, or TSH-protein kinase A (PKA) pathways in malignant cells. In benign cells, however, TPA induced a small, though significant, increase in TIMP-1. The MMP-1 stimulation by EGF and lack of TPA-induced rise in TIMP-1 in malignant cells, in sharp contrast to the effects obtained in benign thyrocytes, seems to indicate that the MMP: TIMP balance favors a more extensive extracellular matrix protein breakdown by malignant thyrocytes, as expected of cells exhibiting invasive capacity. TSH (10-500 microU/mL) failed to significantly influence basal MMP-1 or TIMP-1 mRNA levels, but it caused a dose-dependent inhibition in TPA- and EGF-induced MMP-1 mRNA in malignant cells, and TPA-stimulated MMP-1 and TIMP-1 in benign cells. The repressive action of TSH on MMP-1 mRNA was mimicked by forskolin and 8-bromo-cAMP and was abrogated by the PKA inhibitor, H-89, suggesting that the TSH inhibitory action is PKA-mediated. In conclusion, the present study provides novel data on MMP-1 and TIMP-1 gene expression and their modulation by the major signal transduction pathways operating in human thyroid cells. Similar and divergent patterns have emerged in the regulation of such gene expression in benign and malignant human thyrocytes, in many instances in accord with the concept of MMP playing the role of stimulating, and TIMP inhibiting, cell invasion. Although MMP-1 may be just one of the many factors responsible for tumor cell invasion, the present findings demonstrating the possibility, at least in vitro, of repressing MMP gene expression may have important clinical ramifications.

Adaptive hypoxic tolerance in the subterranean mole rat Spalax ehrenbergi: the role of vascular endothelial growth factor.

Spalax ehrenbergi has evolved adaptations that allow it to survive and carry out normal activities in a highly hypoxic environment. A key component of this adaptation is a higher capillary density in some Spalax tissues resulting in a shorter diffusion distance for oxygen. Vascular endothelial growth factor (VEGF) is an angiogenic factor that is critical for angiogenesis during development and in response to tissue ischemia. We demonstrate here that VEGF expression is markedly increased in those Spalax tissues with a higher capillary density relative to the normal laboratory rat Rattus norvegicus. Upregulation of VEGF thus appears to be an additional mechanism by which Spalax has adapted to its hypoxic environment.

Assessment and diagnostic utility of the cytotoxic T-lymphocyte phenotype using the specific markers granzyme-B and TIA-1 in esophageal mucosal biopsies.

Most esophageal intraepithelial lymphocytes (IELs) express T-cell markers. Increased numbers of esophageal IELs have been shown in reflux esophagitis. The cytotoxic potential and activity of esophageal IELs have not as yet been examined. Our objectives were to determine whether esophageal IELs express the recently described cytotoxic T-cell (CTLs) markers, TIA-1 and granzyme-B, and whether the number of CTLs correlates with well-defined endoscopic, clinical, and histological features of esophagitis. In this study, most CD-3+ esophageal IELs exhibit the CD-8+/TIA-1+ T cell with cytotoxic potential phenotype in both histologically normal biopsy specimens and in biopsy specimens with esophagitis. A subpopulation of esophageal IELs that express cytotoxic activity was identified by granzyme-B immunostaining. A significant positive association was found between the number of esophageal IELs seen by light microscopy in biopsy specimens with histological features of reflux (21 IELs/HPF) and Candida esophagitis (31 IELs/HPF) as compared with normal-appearing biopsy specimens (10 IELs/HPF) (P< or =.05). Furthermore, the number of TIA-1 or granzyme-B-positive IELs were significantly increased in biopsy specimens with reflux esophagitis (34 and 15 cells/HPF) and Candida esophagitis (44 and 18 cells/HPF) as compared with normal (11 and 2 cells/HPF) (P< or =.05). Granzyme-B and CD-3-positive IELs were also significantly elevated in biopsy specimens with reflux-associated squamous hyperplasia (P< or =.05). Finally, biopsy specimens of patients with dysphagia and to a lesser extent dyspepsia/heartburn exhibited increased numbers of IELs bearing the cytotoxic phenotype when compared with asymptomatic patients. In conclusion, we provide immunohistochemical evidence that most esophageal IELs exhibit the cytotoxic phenotype and that activated cytotoxic IELs are increased in reflux and Candida esophagitis.

Telomerase activity in patients with transitional cell carcinoma: a preliminary study.

BACKGROUND: Telomerase activity is not detectable in normal cells, and their telomers shorten until the chromosome is unable to replicate. Immortal cells have short but stable chromosomes and increased telomerase activity. Transitional cell carcinoma (TCC) has only a few useful markers of diagnostic or prognostic importance. The objective of this study was to determine whether there was a correlation between telomerase activity and the grade or stage of TCC, and whether the enzyme's activity could serve as a biochemical marker of this tumor. METHODS: The study included 29 patients with TCC. From each patient, samples of urine cells were obtained, and a cup biopsy was taken from an apparently normal area as well as from a part of the bladder tumor resected transurethrally. Control uroepithelial biopsies were taken from normal transitional cell sites from non-TCC patients. Biopsies or cells were subjected to either histologic examination or telomerase activity determination. RESULTS: Twenty-six of 29 (90%) of the tumor biopsies exhibited telomerase activity. Most of the cup biopsies were categorized as metaplastic or dysplastic, and 20 of 29 (69%) of these exhibited telomerase activity. Telomerase activity was found in 17 of 21 (81%) of the urine cells but in only 3 of 14 (21%) of control urine cells. All (10 of 10) of the uroepithelial biopsies taken from non-TCC patients did not show any telomerase activity. CONCLUSIONS: In this study, almost all tumor biopsies exhibited telomerase activity. The high incidence of telomerase activity found in cup biopsies of the malignant field uroepithelial cells from cup biopsies of TCC patients may suggest that telomerase could be activated early in carcinogenesis. A high incidence of telomerase activity was found in voided uroepithelial cells of TCC patients; however, no correlation between this activity and the histologic determination of grading and staging of the tumor was found.

The effect of low-frequency ultrasound on immersed pig lungs.

Acoustic models suggest that high-intensity, low-frequency ultrasound (US) at 21-31 kHz, could cause damage to divers' lungs. The purpose of the study was to investigate lung tissue changes secondary to water-borne low-frequency US produced by commonly used underwater acoustic beacons (pingers). Explanted pig lungs were immersed and exposed to four different modes of low-frequency US pinger transmission. In each trial, 5 pairs of lungs were exposed to sound and 5 pairs served as controls. One central and one peripheral section were taken from each lung and evaluated microscopically for location and extent of damage. When present, microhaemorrhages were primarily found in a patchy alveolar distribution, as well as in the septal and subpleural regions. Only rare focal microhaemorrhages could be found in the Control Group. The results demonstrate a potential hazard to the immersed lungs of large mammals on exposure to prolonged transmission by commercially available underwater pingers. The relevance of these findings to human exposure should be further evaluated.