The effects of transurethral resection and cystoprostatectomy on dissemination of epithelial cells in the circulation of patients with bladder cancer

This study was undertaken to evaluate the risk of haematogenous dissemination of epithelial cells induced by endoscopic resection and/or cystoprostatectomy for transitional cell carcinoma of the bladder. Thirty-three patients were studied. Thirty-one had different stages and grades of bladder cancer and two patients had benign bladder conditions. Twenty-five cancer patients required transurethral resection of their bladder tumour. Of those, 20 had superficial disease (pTaG1–G2: n = 19; pT1G2: n = 1) and five had muscle invasive tumours (pT2G3: n = 2; pT3aG3: n = 1; pT4G3: n = 2). Five patients underwent radical cystoprostatectomy for muscle invasive cancers (pT2G3: n = 3; pT3bG3: n = 1; pT4G3: n = 1) and one man received chemotherapy for metastatic disease. Venous blood (10 ml) was obtained from the antecubital fossa in each patient, before and 1–2 h after completion of surgery, and prior to treatment in the metastatic patient. An indirect immunocytochemical technique was used to detect circulating epithelial cells after centrifugation on Ficoll gradient and fixation of mononuclear cells on slides, using a monoclonal antibody directed against three cytokeratins: CK8, CK18 and CK19. Circulating epithelial cells were detected only in the patient with metastatic disease. None of the other patients had evidence of epithelial circulating cells before or after surgery. The results suggest that irrespective of disease stage and grade, neither endoscopic nor open bladder surgery leads to detectable dissemination of urothelial cells in the peripheral circulation. These procedures are therefore unlikely to increase the risk of progression and metastasis in transitional cell carcinoma of the bladder. © 1999 Cancer Research Campaig

Family members' experience with in-hospital health care after severe traumatic brain injury : a national multicentre study.

Background Family member’s experience and satisfaction of health care in the acute care and in-patient rehabilitation are important indicators of the quality of health care services provided to patients with severe traumatic brain injury (TBI). The objective was to assess family members’ experience of the health care provided in-hospital to patients with severe TBI, to relate experiences to family member and patient demographics, patients’ function and rehabilitation pathways. Methods Prospective national multicentre study of 122 family members of patients with severe TBI. The family experience of care questionnaire in severe traumatic brain injury (FECQ-TBI) was applied. Independent sample t-tests or analysis of variance (ANOVA) were used to compare the means between 2 or more groups. Paired samples t-tests were used to investigate differences between experience in the acute and rehabilitation phases. Results Best family members` experience were found regarding information during the acute phase, poorest scores were related to discharge. A significantly better care experience was reported in the acute phase compared with the rehabilitation phase (p < 0.05). Worst family members` experience was related to information about consequences of the injury. Patient’s dependency level (p < 0.05) and transferral to non-specialized rehabilitation were related to a worse family members` experience (p < 0.01). Conclusions This study underscores the need of better information to family members of patients with severe TBI in the rehabilitation as well as the discharge phase. The results may be important to improve the services provided to family members and individuals with severe TBI

High sensitive troponin T and heart fatty acid binding protein: Novel biomarker in heart failure with normal ejection fraction?: A cross-sectional study

Background: High sensitive troponin T (hsTnT) and heart fatty acid binding protein (hFABP) are both markers of myocardial injury and predict adverse outcome in patients with systolic heart failure (SHF). We tested whether hsTnT and hFABP plasma levels are elevated in patients with heart failure with normal ejection fraction (HFnEF). Methods: We analyzed hsTnT, hFABP and N-terminal brain natriuretic peptide in 130 patients comprising 49 HFnEF patients, 51 patients with asymptomatic left ventricular diastolic dysfunction (LVDD), and 30 controls with normal diastolic function. Patients were classified to have HFnEF when the diagnostic criteria as recommended by the European Society of Cardiology were met. Results: Levels of hs TnT and hFABP were significantly higher in patients with asymptomatic LVDD and HFnEF (both p < 0.001) compared to controls. The hsTnT levels were 5.6 [0.0-9.8] pg/ml in LVDD vs. 8.5 [3.9-17.5] pg/ml in HFnEF vs. < 0.03 [< 0.03-6.4] pg/ml in controls; hFABP levels were 3029 [2533-3761] pg/ml in LVDD vs. 3669 [2918-4839] pg/ml in HFnEF vs. 2361 [1860-3081] pg/ml in controls. Furthermore, hsTnT and hFABP levels were higher in subjects with HFnEF compared to LVDD (p = 0.015 and p = 0.022). Conclusion: In HFnEF patients, hsTnT and hFABP are elevated independent of coronary artery disease, suggesting that ongoing myocardial damage plays a critical role in the pathophysiology. A combination of biomarkers and echocardiographic parameters might improve diagnostic accuracy and risk stratification of patients with HFnEF

Detection of large molecular weight cytokeratin 8 as carrier protein of CA19–9 in non-small-cell lung cancer cell lines

It has been reported that cytokeratin 8 (CK8) is expressed in all non-small-cell lung cancers (NSCLC). We hypothesized that antigenic changes of CK8 may occur in some NSCLC cell lines. To prove this, Western immunoblot analysis using anti-human CK8 monoclonal antibodies as well as immunohistological staining of CK8 were performed in NSCLC cell lines. As a result, CK8 which had a higher molecular weight than recombinant CK8 was demonstrated in two of eight NSCLC cell lines. In addition, this CK8 contained antigenic epitopes of CA19–9. This CK8 with higher molecular weight, may have played a role in the process of invasion or metastasis of NSCLC. © 1999 Cancer Research Campaig

A Model of Ischemia-Induced Neuroblast Activation in the Adult Subventricular Zone

We have developed a rat brain organotypic culture model, in which tissue slices contain cortex-subventricular zone-striatum regions, to model neuroblast activity in response to in vitro ischemia. Neuroblast activation has been described in terms of two main parameters, proliferation and migration from the subventricular zone into the injured cortex. We observed distinct phases of neuroblast activation as is known to occur after in vivo ischemia. Thus, immediately after oxygen/glucose deprivation (6–24 hours), neuroblasts reduce their proliferative and migratory activity, whereas, at longer time points after the insult (2 to 5 days), they start to proliferate and migrate into the damaged cortex. Antagonism of ionotropic receptors for extracellular ATP during and after the insult unmasks an early activation of neuroblasts in the subventricular zone, which responded with a rapid and intense migration of neuroblasts into the damaged cortex (within 24 hours). The process is further enhanced by elevating the production of the chemoattractant SDf-1α and may also be boosted by blocking the activation of microglia. This organotypic model which we have developed is an excellent in vitro system to study neurogenesis after ischemia and other neurodegenerative diseases. Its application has revealed a SOS response to oxygen/glucose deprivation, which is inhibited by unfavorable conditions due to the ischemic environment. Finally, experimental quantifications have allowed us to elaborate a mathematical model to describe neuroblast activation and to develop a computer simulation which should have promising applications for the screening of drug candidates for novel therapies of ischemia-related pathologies

Conserved and variable correlated mutations in the plant MADS protein network

<p>Abstract</p> <p>Background</p> <p>Plant MADS domain proteins are involved in a variety of developmental processes for which their ability to form various interactions is a key requisite. However, not much is known about the structure of these proteins or their complexes, whereas such knowledge would be valuable for a better understanding of their function. Here, we analyze those proteins and the complexes they form using a correlated mutation approach in combination with available structural, bioinformatics and experimental data.</p> <p>Results</p> <p>Correlated mutations are affected by several types of noise, which is difficult to disentangle from the real signal. In our analysis of the MADS domain proteins, we apply for the first time a correlated mutation analysis to a family of interacting proteins. This provides a unique way to investigate the amount of signal that is present in correlated mutations because it allows direct comparison of mutations in various family members and assessing their conservation. We show that correlated mutations in general are conserved within the various family members, and if not, the variability at the respective positions is less in the proteins in which the correlated mutation does not occur. Also, intermolecular correlated mutation signals for interacting pairs of proteins display clear overlap with other bioinformatics data, which is not the case for non-interacting protein pairs, an observation which validates the intermolecular correlated mutations. Having validated the correlated mutation results, we apply them to infer the structural organization of the MADS domain proteins.</p> <p>Conclusion</p> <p>Our analysis enables understanding of the structural organization of the MADS domain proteins, including support for predicted helices based on correlated mutation patterns, and evidence for a specific interaction site in those proteins.</p

Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner

HIV's ability to establish long-lived latent infection is mainly due to transcriptional silencing in resting memory T lymphocytes and other non dividing cells including monocytes. Despite an undetectable viral load in patients treated with potent antiretrovirals, current therapy is unable to purge the virus from these latent reservoirs. In order to broaden the inhibitory range and effectiveness of current antiretrovirals, the potential of bryostatin was investigated as an HIV inhibitor and latent activator. Bryostatin revealed antiviral activity against R5- and X4-tropic viruses in receptor independent and partly via transient decrease in CD4/CXCR4 expression. Further, bryostatin at low nanomolar concentrations robustly reactivated latent viral infection in monocytic and lymphocytic cells via activation of Protein Kinase C (PKC) -α and -δ, because PKC inhibitors rottlerin and GF109203X abrogated the bryostatin effect. Bryostatin specifically modulated novel PKC (nPKC) involving stress induced AMP Kinase (AMPK) inasmuch as an inhibitor of AMPK, compound C partially ablated the viral reactivation effect. Above all, bryostatin was non-toxic in vitro and was unable to provoke T-cell activation. The dual role of bryostatin on HIV life cycle may be a beneficial adjunct to the treatment of HIV especially by purging latent virus from different cellular reservoirs such as brain and lymphoid organs

Genetic Dissection of Strain Dependent Paraquat-induced Neurodegeneration in the Substantia Nigra Pars Compacta

The etiology of the vast majority of Parkinson's disease (PD) cases is unknown. It is generally accepted that there is an interaction between exposures to environmental agents with underlying genetic sensitivity. Recent epidemiological studies have shown that people living in agricultural communities have an increased risk of PD. Within these communities, paraquat (PQ) is one of the most utilized herbicides. PQ acts as a direct redox cycling agent to induce formation of free radicals and when administered to mice induces the cardinal symptoms of parkinsonism, including loss of TH+-positive dopaminergic (DA) neurons in the ventral midbrain's substantia nigra pars compacta (SNpc). Here we show that PQ-induced SNpc neuron loss is highly dependent on genetic background: C57BL/6J mice rapidly lose ∼50% of their SNpc DA neurons, whereas inbred Swiss-Webster (SWR/J) mice do not show any significant loss. We intercrossed these two strains to map quantitative trait loci (QTLs) that underlie PQ-induced SNpc neuron loss. Using genome-wide linkage analysis we detected two significant QTLs. The first is located on chromosome 5 (Chr 5) centered near D5Mit338, whereas the second is on Chr 14 centered near D14Mit206. These two QTLs map to different loci than a previously identified QTL (Mptp1) that controls a significant portion of strain sensitivity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), suggesting that the mechanism of action of these two parkinsonian neurotoxins are different