Apolipoprotein(a) induces monocyte chemotactic activity in human vascular endothelial cells

BACKGROUND: Elevated levels of lipoprotein(a) [Lp(a)] are associated with premature atherosclerosis; however, the mechanisms are not known. Recruitment of monocytes to the blood vessel wall is an early event in atherogenesis. METHODS AND RESULTS: This study has found that unoxidized Lp(a) induced human umbilical vein endothelial cells (HUVECs) to secrete monocyte chemotactic activity (MCA), whereas LDL under the same conditions did not. In the absence of HUVECs, Lp(a) had no direct MCA. Endotoxin was shown not to be responsible for the induction of MCA. Actinomycin D and cycloheximide inhibited the HUVEC response to Lp(a), indicating that protein and RNA synthesis were required. The apolipoprotein(a) [apo(a)] portion of Lp(a) was identified as the structural component of Lp(a) responsible for inducing MCA. Lp(a) and apo(a) also stimulated human coronary artery endothelial cells to produce MCA. Granulocyte-monocyte colony-stimulating factor (GM-CSF) antigen was not detected in the Lp(a)-conditioned medium, nor was monocyte chemoattractant protein-1 mRNA induced in HUVECs by Lp(a). CONCLUSIONS: These findings suggest that Lp(a) may be involved in the recruitment of monocytes to the vessel wall and provide a novel mechanism for the participation of Lp(a) in the atherogenic process.     

Frequency and duration of remission after isolated limb perfusion for melanoma

OBJECTIVE: To determine changes of blood pressure and heart rate during apnoea testing for brain death without (A) and with (B) artificial CO2 augmentation. DESIGN: Prospective, consecutive study. SETTING: 12 intensive care units in six towns in Northern Bavaria. PATIENTS AND PARTICIPANTS: A total of 55 apnoea tests were performed on 55 consecutive patients as part of the determination of brain death, 27 without and 28 with CO2 augmentation. INTERVENTIONS: Apnoea tests following oxygenation with 100% O2 either after reduction of ventilatory volume (A) or after insufflation of CO2 during normoventilation (B). In each case, an arterial partial CO2 pressure of at least 8 kPa was documented. RESULTS: All apnoea tests were without serious adverse effects (hypoxia, newly induced cardiac arrhythmia, cardiac asystole). An increased dopamine infusion rate was deemed necessary in only one case of group (A) because of marked systolic hypotension (< 8 kPa). Individual variation of systolic and diastolic blood pressure (BP) did not exceed + 62 to -46% and + 49 to -52% respectively, in group (A) and + 35 to -57% and + 40 to -48% respectively, in group (B). Variation of heart rate (HR) remained within the range + 24 to -31% in group (A) and + 37 to -22% in group (B). CONCLUSIONS: HR varied less than BP. The possibility of a marked relative rise of fall of BP in group (A) was equal; in group (B) there was a lower change of rising BP. The chances for a rise or fall in HR were equal for the two groups. There was a tendency for less variation of cardiovascular parameters in group (B).     

Clinical pharmacology with confidence

The National Institute of Neurological Disorders and Stroke (NINDS) supports research concerning the determinants of normal and pathological development of the nervous system, from the genetic to the environmental. NINDS also funds basic and clinical research concerning the etiology, diagnosis, treatment, consequences, and prevention of the spectrum of neurodevelopmental disorders including neurobehavioral and neurodegenerative disorders (National Advisory Council Neurological Disorders and Stroke, 1989, 1992; Division of Convulsive, Developmental and Neuromuscular Disorders, NINDS, 1993).     

The lipoprotein VirB7 interacts with VirB9 in the membranes of Agrobacterium tumefaciens

VirB9 and VirB7 are essential components of the putative VirB membrane channel required for transfer of the T-complex from Agrobacterium tumefaciens into plants. In this report, we present a biochemical analysis of their interaction and cellular localization. A comparison of relative electrophoretic mobilities under nonreducing and reducing conditions suggested that they form thiol-sensitive complexes with other proteins. Two-dimensional gel electrophoresis identified one complex as a heterodimer of VirB9 and VirB7 covalently linked by a disulfide bond, as well as VirB7 homodimers and monomers. Immunoprecipitation with VirB9-specific antiserum isolated the heterodimeric VirB9-VirB7 complex. Incubation with reducing agent split the complex into its constituent VirB9 and VirB7, which further confirmed linkage via cysteine residues. The interaction between VirB9 and VirB7 also was observed in the yeast two-hybrid system. Membrane attachment of VirB9-VirB7 may be conferred by lipoprotein modification, since labeling with [3H]palmitic acid in A. tumefaciens verified that VirB7 is a lipoprotein associated with VirB9. VirB9 and VirB7 showed equal distribution between inner and outer membranes, in accord with their proposed association with the transmembrane VirB complex.     

Congenital esophageal webs

Modern intracavitary brachytherapy carefully combined with megavoltage external beam radiotherapy is responsible for the high cure rates achieved with radiation treatment of invasive cervical cancers. Pelvic disease recurrence is rare after treatment of patients with tumors < 5 cm in diameter, and even patients with massive tumors 8-10 cm in diameter are cured in 30-50% of cases. Inoperable adenocarcinomas of the endometrium and superficial cancers of the vagina are also effectively treated with intracavitary irradiation. The relative radioresistance of the uterus and vagina, physical advantages resulting from exploitation of the inverse square law, and the radiobiological advantages of low dose rate radiation have combined to make intracavitary irradiation a critical tool in the management of many gynecologic neoplasms.