Accurate and efficient detection of pulmonary seed embolization in prostate iodine-125 permanent brachytherapy with a collimated gamma scintillation survey meter

Pulmonary seed embolization is frequently observed in permanent prostate brachytherapy. Postoperative chest radiographic examination does not always detect seed embolization. To overcome this deficiency, a low energy gamma scintillation survey meter was converted to a seed-migration detector by adding a cone-shaped single-hole collimation cap to the window end of the scintillation probe. The response functions of the seed-migration detector to iodine-125 (I-125) for different source-to-detector distances in air and in water were measured. The spatial discrimination power of the survey meter, represented by the full width at half maximum measured in water, is typically improved from more than 7 cm to about 3 cm. Seventy-nine patients with I-125 implantation were scanned with the seed-migration detector at the patients' 30-day postevaluation visit. Fifteen patients showed single-seed embolization to the chest region and four patients displayed two-seed embolization. In other words, 24% of the patients present with embolized seeds. The detection accuracy of each patient was validated by a comprehensive investigation procedure. The comprehensive investigation consists of reviewing the patient's treatment history, orally questioning the patient for possible seed loss via the urethra route outside the hospital, examining all available chest radiographs before and after the seed implantation, and counting the seeds on the postevaluation CT scans. In comparison, examinations relying only on the analysis of postoperative chest radiographs yielded a false-positive detection in four patients and a false-negative detection in two patients. Another advantage of the seed-migration detector is that multiple seed-migration scans can be performed without exposing the patient to any additional radiation, for this device is a passive detector. Our clinical implementation also demonstrated that the seed-migration detector is a convenient and cost-effective method. As a result of this study, we stopped ordering the postoperative chest radiographs in a patient's regular postevaluation visit. Only if the detector shows radioactivity outside a patient's pelvis are a pair of anteroposterior and lateral chest radiographs of the patient ordered to document the location of the embolized seeds.     

Modulation of Whole-Cell Currents in Plasmodium Falciparum-Infected Human Red Blood Cells by Holding Potential and Serum

Recent electrophysiological studies have identified novel ion channel activity in the host plasma membrane of Plasmodium falciparum -infected human red blood cells (RBCs). However, conflicting data have been published with regard to the characteristics of induced channel activity measured in the whole-cell configuration of the patch-clamp technique. In an effort to establish the reasons for these discrepancies, we demonstrate here two factors that have been found to modulate whole-cell recordings in malaria-infected RBCs. Firstly, negative holding potentials reduced inward currents (i.e. at negative potentials), although this result was highly complex. Secondly, the addition of human serum increased outward currents (i.e. at positive potentials) by approximately 4-fold and inward currents by approximately 2-fold. These two effects may help to resolve the conflicting data in the literature, although further investigation is required to understand the underlying mechanisms and their physiological relevance in detail.     

Protection of Chicken Embryos by Viridans Streptococci Against the Lethal Effect of Staphylococcus aureus

Chicken embryos were used to investigate the mechanism by which viridans streptococci inhibit the growth of pathogenic staphylococci. Ten-day-old embryonated eggs were infected allantoically. At a concentration of 1.8 x 10(2) colony-forming units (CFU) of viridans streptococci, the percentage of fatalities was less than 10%. There was 80% fatality with 8 x 10(1) CFU of Staphylococcus aureus strain 502A and 100% when a 100-fold increase in concentration was used. An inoculum size of 10(2) to 10(3) CFU of viridans streptococci was chosen to protect the embryos against the lethal effect of strain 502A when challenged 24 h later. The survival after challenging at 4 days was 93% in protected eggs and 37% in unprotected eggs. Chicken embryos receiving heat-killed viridans and challenged with strain 502A when examined after 4 days did not demonstrate a protective effect. This protection of embryonated eggs could not be transferred by administration of sterile filtrate of allantoic fluid in which protecting strain was grown. The experimental infection of embryonated eggs has demonstrated that prior allantoic infection with viridans streptococci affords significant protection against subsequent challenge with virulent staphylococci.     

Effect of Synthetic Truncated Apolipoprotein C-I Peptide on Plasma Lipoprotein Cholesterol in Nonhuman Primates

The present studies were conducted to determinewhether a synthetic truncated apoC-I peptide thatinhibits CETP activity in baboons would raise plasmaHDL cholesterol levels in nonhuman primates with lowHDL levels. We used 2 cynomolgus monkeys and 3baboons fed a cholesterol- and fat-enriched diet. Incynomolgus monkeys, we injected synthetic truncatedapoC-I inhibitor peptide at a dose of 20mg/kgand, in baboons, at doses of 10, 15, and 20mg/kgat weekly intervals. Blood samples were collected 3times a week and VLDL + LDL and HDL cholesterolconcentrations were measured. In cynomolgus monkeys,administration of the inhibitor peptide caused arapid decrease in VLDL + LDL cholesterolconcentrations (30%–60%) and an increase in HDLcholesterol concentrations (10%–20%). VLDL + LDLcholesterol concentrations returned to baselinelevels in approximately 15days. In baboons,administration of the synthetic inhibitor peptidecaused a decrease in VLDL + LDL cholesterol (20%–60%)and an increase in HDL cholesterol (10%–20%). VLDL+ LDL cholesterol returned to baseline levels byday 21, whereas HDL cholesterol concentrationsremained elevated for up to 26days. ApoA-Iconcentrations increased, whereas apoE andtriglyceride concentrations decreased. Subcutaneousand intravenous administrations of the inhibitorpeptide had similar effects on LDL and HDLcholesterol concentrations. There was no change inbody weight, food consumption, or plasma IgGlevels of any baboon during the study. Thesestudies suggest that the truncated apoC-I peptide canbe used to raise HDL in humans.     

Protein aggregation and deposition: implications for ion channel formation and membrane damage

Protein deposition, aggregation, and formation of amyloids are associated with a wide range of pathologies, including several neurodegenerative diseases. Aggregation and deposition are a result of malfunction in protein folding, assembly, and transport, caused by protein mutation and/or changes in the cell environment. The mechanism of protein deposition and aggregation is triggered when the hydrophobic and positively charged regions of the misfolded proteins are exposed. The cells aim to regulate these misfolded and malfunctioning aggregation-prone proteins by degradation mechanisms, e.g., proteosomes, and/or by storing them in specialized compartments, e.g., Russell bodies and aggresomes. During these processes, however, some aggregation-prone protein intermediates are capable of aggregation and forming beta-sheet based channels in various negatively charged cellular membranes. Adverse cellular conditions, transitional metals, cellular proteins, and genetic mutations play an important role in the formation and function of these non-intrinsic channels. These channels, which can damage membrane function, are pathologic because they can disrupt the metabolic, ionic, and water homeostasis and distort signal transduction. We propose that different conformations of aggregation-prone proteins could alter cell regulation by modifying several ion transport systems and also by forming heterogeneous ion channels. The changes in membrane transport systems are proposed as early steps in impairing neuronal function preceding fibril formation. We conclude that these changes damage the membrane by compromising its integrity and increasing its ion permeability. This mechanism of membrane damage is a general mechanism that may explain other malfunctioning protein processing-related pathologies.     

Axillary lymph node cellular immune response to HER-2/neu peptides in patients with carcinoma of the breast.

HER-2/neu peptides have recently been shown to induce a proliferative response by peripheral CD4(+) T cells in breast cancer patients. To investigate potential differences in the local cellular immune response between breast cancer patients with and without nodal metastases, lymphocytes were isolated from axillary lymph nodes from patients with breast cancer, and proliferative and cytokine responses to HER-2/neu peptides were determined. Freshly isolated lymphocytes from lymph nodes of 7 women undergoing surgery for invasive breast cancer were plated at 20 x 10(5) cells per well in triplicate. Cells were stimulated with HER-2/neu peptides at 50 microg/ml and with control antigens. Incorporation of tritium-labeled thymidine was determined 4 days later. The levels of the cytokines interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and IL-10 were determined at priming and at restimulation with HER-2/neu peptides using a cytokine-specific, double-sandwich, enzyme-linked immunosorbent assay (ELISA). Lymphocytes isolated from the axillary lymph nodes of the patients mounted significant cellular immune response to HER-2/neu peptides, manifested by proliferation and specific cytokine elaboration. Proliferative responses to HER-2/neu peptides were seen in lymphocytes of patients with and without overexpression of HER-2/neu in the primary tumor. In some patients, the proliferative response to HER-2/neu peptides in lymphocytes from lymph nodes with metastases was absent or blunted compared with the response in lymphocytes from lymph nodes without metastases from the same patient (p < 0.05). HER-2/neu peptides induced a predominantly T helper type 1 (Th1) pattern of cytokine response in nodal lymphocytes isolated from breast cancer patients. A Th1-specific cytokine production pattern was maintained at priming and restimulation with HER-2/neu peptides and was amplified with IL-12 costimulation. These results indicate that HER-2/neu peptides can activate T cells in draining lymph nodes from women with invasive breast cancer. This activation is associated with a predominantly Th1 cytokine response, which suggests that conditioning with HER-2/neu peptides may be of value in the development of breast cancer vaccines.     

Bacteriostatic effects of horse sera and serum fractions on Clostridium welchii type A, and the abolition of bacteriostasis by iron salts

Under a variety of conditions of concentration, Eh, and pH, horse anti-Clostridium welchii serum and normal horse serum exerted similar bacteriostatic effects against Cl. welchii Type A. Ferric iron abolished the bacteriostatic effect when added during the first 2 hours of incubation at Eh+60 mV. Ferrous iron abolished the bacteriostatic effect when added after 3 hours. Ferric iron abolished the bacteriostatic effect at—140 mV. A mixture consisting of horse β₂- and γ-globulins together with human transferrin exerted a bacteriostatic effect similar to that of whole serum. This system responded in the same way as whole serum to the addition of iron. A mixture of horse β₂- and γ-globulins exerted an immediate bactericidal effect which could not be prevented by ferric iron.