Human tumour-associated cell adhesion protein MN/CA IX: identification of M75 epitope and of the region mediating cell adhesion

MN/CA IX is a cell surface protein, strongly associated with several types of human carcinomas. It exerts activity of carbonic anhydrase and capacity of binding to cell surface receptors. In the present work, we used affinity purified MN/CA IX protein to demonstrate that the cells adhere to immobilized MN/CA IX and that the monoclonal antibody M75 abrogates cell attachment to MN/CA IX. Using synthetic oligopeptides, we identified M75 epitope and located it in the proteoglycan domain, which contains a sixfold tandem repeat of six amino acids GEEDLP. From phage display library of random heptapeptides we identified and chemically synthesized those which compete for the epitope with M75 and inhibit adhesion of cells to MN/CA IX. These heptapeptides might serve as lead compounds for drug design. © 2000 Cancer Research Campaig

Navigating institutional pressure in state-socialist and democratic regimes: The case of movement brontosaurus

Using the case of Movement Brontosaurus, a Czech organization founded in state socialist times, this article investigates how civic associations and nongovernmental organizations seeking to promote alternatives to the status quo respond to institutional pressures in different political and social contexts. The case shows that under state socialism, Brontosaurus appeared to conform to state mandates and societal expectations. However, its formal structure was decoupled from many activities to obscure its oppositional intent.After the transition to democracy, the organization was only able to maintain its place in society after it aligned its structure and practices with each other and openly expressed its alternative agenda. The findings demonstrate how social change and alternative lifestyle organizations vary their responses to institutional pressure in ways that enable them to realize their values and pursue their missions while accounting for the political and social contexts in which they are embedded

Changes in the Diagnosis of Stroke and Cardiovascular Conditions in Primary Care During First 2 COVID-19 Waves in the Netherlands

BACKGROUND AND OBJECTIVES: Although there is evidence of disruption in acute cerebrovascular and cardiovascular care during the coronavirus disease 2019 (COVID-19) pandemic, its downstream effect in primary care is less clear. We investigated how the pandemic affected utilization of cerebrovascular and cardiovascular care in general practices (GPs) and determined changes in GP-recorded diagnoses of selected cerebrovascular and cardiovascular outcomes. METHODS: From electronic health records of 166,929 primary care patients aged 30 or over within the Rotterdam region, the Netherlands, we extracted the number of consultations related to cerebrovascular and cardiovascular care, and first diagnoses of selected cerebrovascular and cardiovascular risk factors (hypertension, diabetes, lipid disorders), conditions, and events (angina, atrial fibrillation, TIA, myocardial infarction, stroke). We quantified changes in those outcomes during the first COVID-19 wave (March–May 2020) and thereafter (June–December 2020) by comparing them to the same period in 2016–2019. We also estimated the number of potentially missed diagnoses for each outcome. RESULTS: The number of GP consultations related to cerebrovascular and cardiovascular care declined by 38% (0.62, 95% confidence interval 0.56–0.68) during the first wave, as compared to expected counts based on prepandemic levels. Substantial declines in the number of new diagnoses were observed for cerebrovascular events: 37% for TIA (0.63, 0.41–0.96) and 29% for stroke (0.71, 0.59–0.84), while no significant changes were observed for cardiovascular events (myocardial infarction [0.91, 0.74–1.14], angina [0.77, 0.48–1.25]). The counts across individual diagnoses recovered following June 2020, but the number of GP consultations related to cerebrovascular and cardiovascular care remained lower than expected throughout the June to December period (0.93, 0.88–0.98). DISCUSSION: While new diagnoses of acute cardiovascular events remained stable during the COVID-19 pandemic, diagnoses of cerebrovascular events declined substantially compared to prepandemic levels, possibly due to incorrect perception of risk by patients. These findings emphasize the need to improve symptom recognition of cerebrovascular events among the general public and to encourage urgent presentation despite any physical distancing measures

LVV-Hemorphin-7 Lowers Blood Pressure in Spontaneously Hypertensive Rats: Radiotelemetry Study

Summary Cardiovascular effects of LVV-hemorphin-7, a member of the family of fragments from β-chain of human or bovine hemoglobin, were studied in conscious spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats by radiotelemetry. Intraperitoneal injection of hemorphin in a dose of 100 µg/kg significantly decreased blood pressure in SHR, whereas negligible effect was seen in normotensive WKY rats. Blood pressure changes were accompanied by reduction of heart rate. In conclusion, a direct effect of LVV-hemorphin-7 on blood pressure was demonstrated in SHR. These biologically active peptides could be involved in blood pressure regulation especially in hypertensive rats, but the precise mechanism should be elucidated