Phenyl Esters Are Potent Inhibitors of Caseinolytic Protease P and Reveal a Stereogenic Switch for Deoligomerization.

Caseinolytic protease P (ClpP) represents a central bacterial degradation machinery that is involved in cell homeostasis and pathogenicity. The functional role of ClpP has been studied by genetic knockouts and through the use of beta-lactones, which remain the only specific inhibitors of ClpP discovered to date. Beta-lactones have served as chemical tools to manipulate ClpP in several organisms; however, their potency, selectivity and stability is limited.

Modelling antibiotic and cytotoxic isoquinoline effects in Staphylococcus aureus, Staphylococcus epidermidis and mammalian cells.

Isoquinolines (IQs) are natural substances with an antibiotic potential we aim to optimize. Specifically, IQ-238 is a synthetic analog of the novel-type N,C-coupled naphthylisoquinoline (NIQ) alkaloid ancisheynine. Recently, we developed and tested other IQs such as IQ-143.

Amythiamicin D and related thiopeptides as inhibitors of the bacterial elongation factor EF-Tu: modification of the amino acid at carbon atom C2 of ring C dramatically influences activity.

Three analogues of amythiamicin D, which differ in the substitution pattern at the methine group adjacent to C2 of the thiazole ring C, were prepared by de novo total synthesis. In amythiamicin D, this carbon atom is (S)-isopropyl substituted. Two of the new analogues carry a hydroxymethyl in place of the isopropyl group, one at an S- (compound 3 a) and the other at an R-configured stereogenic center (3 b).

Mode-of-action studies of the novel bisquaternary bisnaphthalimide MT02 against Staphylococcus aureus.

Screening of various bisquaternary bisnaphthalimides against a variety of human pathogens revealed one compound, designated MT02, with strong inhibitory effects against Gram-positive bacteria. The MICs ranged from 0.31 μg/ml against community-acquired methicillin-resistant Staphylococcus aureus (MRSA) lineage USA300 to 20 μg/ml against Streptococcus pneumoniae.

Pseudolymphomatous cutaneous angiosarcoma: a rare variant of cutaneous angiosarcoma readily mistaken for cutaneous lymphoma.

Cutaneous angiosarcoma is probably the most malignant neoplasm involving the skin. Three clinical variants of cutaneous angiosarcoma are recognized, including angiosarcoma of the scalp and face of elderly patients, angiosarcoma associated with chronic lymphedema, and postirradiation angiosarcoma. Histopathologically, these three variants of angiosarcoma show similar features, which consist of poorly circumscribed, irregularly dilated, and anastomosing vascular channels lined by prominent endothelial cells that dissect through the dermis.

SKY and genetic fingerprinting reveal a cross-contamination of the putative normal colon epithelial cell line NCOL-1.

In vitro studies addressing the primary prevention of colon carcinoma are preferably conducted using normal colonic cells, because these cells are more likely to represent the potential target for prevention in vivo. Established cell lines of normal colonic origin are mostly lacking; however, this is probably due to the difficulties associated with establishment of such cell lines. Cross-contamination with malignant cells is a frequent event, and so any successfully established cell line of normal origin should be scrutinized prior to further investigation.

Metastatic signet ring cell gastric carcinoma presenting as an infrarenal aortic aneurysm.

Metastases to liver, lungs, bone, and adrenal glands are common events in advanced gastric carcinoma. Occasionally, metastases to other parts of the body, such as the prostate gland [1] the gluteal muscle [2], or the cervix [3] are described. However, these are rare events in the natural history of the disease.

Histone-deacetylase inhibitors induce the cathelicidin LL-37 in gastrointestinal cells.

Unlabelled: Histone-deacetylase (HDAC) -inhibitors enhance acetylation of core proteins and this is linked to formation of transcriptionally active chromatin in various cells. In this study, the effect of HDAC inhibitors (butyrate, trichostatin A (TSA)) on the expression of the cathelicidin LL-37 in colon, gastric and hepatocellular cells was investigated.

Methods: LL-37 expression was assessed in colon, gastric and hepatocellular cancer cells after treatment with HDAC-inhibitors.

Butyrate inhibits leukocyte adhesion to endothelial cells via modulation of VCAM-1.

Background: Leukocyte recruitment to areas of inflammation depends on Integrin-VCAM/ICAM interaction. Blocking the vascular cell adhesion molecule (VCAM-1) and the intracellular adhesion molecule (ICAM-1) may have therapeutic benefit for the inflammatory component of bowel disease. Notably, the induction of ICAM and VCAM is mediated by a nuclear factor kappaB (NF-kappaB)-dependent mechanism.

A diagnostic expert system for structured reports, quality assessment, and training of residents in sonography.

Background: The quality of medical reports on diagnostic procedures has a considerable impact on the quality of medical care. Handwritten or otherwise unstructured reports tend to be incomplete, whereas structured questionnaires are of limited flexibility and not considered case-adequate. Thus, medical reports of this kind may promote an incomplete and misleading documentation and, therefore, be problematic with respect to their reliability.

Establishment of a colonic adenoma cell line (GEKI-2): spectral karyotype analysis and functional characterization.

Background And Aims: On the genetic level colonic carcinogenesis is best described by the adenoma-carcinoma sequence, but it may be modulated by exogenous factors, particularly by dietary factors and chemopreventive agents. The protective effects of exogenous factors are thought to be exerted rather in the early stages of the adenoma-carcinoma sequence. Thus, an in vitro model consisting of cells stemming from an colon adenoma would be desirable.

Ultrastructural alterations of primary human liver sinusoidal cells in patients treated for peritonitis.

Acute peritonitis is still associated with a high mortality rate. Bacterial toxins are rapidly cleared from the peritoneal cavity and may induce general sepsis. The hepatic sinusoidal cells are part of the primary defence against these toxins.

Butyrate-enhanced TNFalpha-induced apoptosis is associated with inhibition of NF-kappaB.

Background: Tumor necrosis factor (TNFalpha)-induced apoptosis is limited by concomitant activation of nuclear factor kappa B (NF-kappaB)-dependent anti-apoptotic genes. Butyrate inhibits NF-kappaB activation so that co-treatment with butyrate effectively enhances TNFalpha-induced apoptosis. In this context, the inhibition of NF-kappaB activation and subsequent modulation of (NF-kappaB)-dependent genes was assessed

Materials And Methods: Human colon adenocarcinoma cells (SW620) were incubated with TNFalpha and butyrate.

Assessment of cardiac performance using Tei indices in patients undergoing pulmonary thromboendarterectomy.

Background: This study was designed to evaluate left and right ventricular performance using Tei indices in patients with severe chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy (PTE). The Doppler-derived indices are easily measurable indicators of ventricular function based on nongeometric assessment, which helps overcome some of the difficulties entailed in the geometric assessment of left ventricular (LV) and right ventricular (RV) function in pulmonary hypertension.

Methods: The indices were derived for 24 patients (aged 54+/-14 years) before and after PTE.

Improvement of tricuspid regurgitation after pulmonary thromboendarterectomy.

Background: For patients with chronic thromboembolic pulmonary hypertension who undergo pulmonary thromboendarterectomy (PTE) it has not yet been systematically investigated how operation affects the severity of tricuspid regurgitation (TR). This study sought (1) to evaluate the extent of TR reversibility after operation, (2) to identify potential predictors of the reversibility of TR, and (3) to investigate the influence of geometric and hemodynamic alterations on the extent of TR severity.

Methods: Thirty-nine patients (55+/-12 years) undergoing PTE without tricuspid valve repair were investigated before and 13+/-8 days after operation by Doppler color flow mapping.

Modulation of HMG-N2 binding to chromatin by butyrate-induced acetylation in human colon adenocarcinoma cells.

Butyrate, a short chain fatty acid (SCFA), is generated by anaerobic fermentation of undigested carbohydrates within the colon. Butyrate enhances acetylation of core histones, a process directly linked to the formation of active chromatin and gene expression. However, additional chromatin components also contribute to the formation of transcriptionally active chromatin.

Type I nitric oxide synthase in the human lung is predominantly expressed in capillary endothelial cells.

Nitric oxide (NO) has important functions in the regulation of pulmonary smooth muscle tone. In the human lung, published data on the expression and distribution of neuronal nitric oxide synthase (NOS-I) are contradictory. The aim of this study, therefore, was to determine the predominant cells expressing NOS-I in the human lung.