Age-dependent and lobe-specific spontaneous hyperplasia in the brown Norway rat prostate

PURPOSE: Response of quiescent (Q) and total tumor cells in solid tumors to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in tumor control was also discussed. METHODS AND MATERIALS: C3H/He mice bearing SCC VII tumors received continuous administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-10B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-10B (BPA), the tumors were irradiated with neutrons, or those without 10B-compounds were irradiated with gamma rays. This neutron irradiation was performed using neutrons with three different cadmium (Cd) ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P + Q) tumor cells was determined from tumors that were not pretreated with BrdU. The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). RESULTS: Without 10B-compounds, the MN frequency in Q cells was lower than that in the total cell population. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neutrons compared with gamma rays was larger in Q cells than in total cells, and the RBE values for low-Cd-ratio neutrons tended to be larger than those for high-Cd-ratio neutrons. With 10B-compounds, MN frequency for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons were used. BPA increased the MN frequency for total tumor cells more than BSH. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that in BSH-treated Q cells. This tendency was clearly observed in high-Cd-ratio neutrons. CONCLUSION: From the viewpoint of enhancing the Q-cell sensitivity, tumors should be irradiated with high-Cd-ratio neutrons after BSH administration. However, normal tissue reaction remains to be examined because of its low tumor-to-normal tissue and tumor-to-blood biodistribution ratios.     

Rates of flu-like infection in patients with affective illness

Studies of immunologic profiles of depressed patients are suggestive of chronic viral infection and several investigators have found specific viral protein in some depressed patients. Moreover, several psychotropic drugs have anti-viral activity and can inhibit viral replication. In this preliminary report, we retrospectively examined the rate of reported flu-like episodes before and during psychotropic drug treatment in 236 affectively ill patients: 177 receiving lithium prophylaxis and 59 receiving chronic antidepressant medication. We observed a small but significant reduction in the mean rate of reported flu-like illness during lithium therapy (P < 0.001), with a greater reduction in men vs. women (P < 0.05). We also found a modest reduction in reported flu-like illness during chronic treatment with antidepressants (P = 0.08). Although these observations are preliminary in nature, they complement earlier reports that some psychotropic drugs may have anti-viral activity.     

Structures of competitive inhibitor complexes of protocatechuate 3,4-dioxygenase: multiple exogenous ligand binding orientations within the active site

Protocatechuate 3,4-dioxygenase (3,4-PCD) catalyzes the oxidative ring cleavage of 3,4-dihydroxybenzoate to produce beta-carboxy-cis, cis-muconate. Crystal structures of Pseudomonas putida3,4-PCD [quaternary structure of (alphabetaFe3+)12] complexed with seven competitive inhibitors [3-hydroxyphenylacetate (MHP), 4-hydroxyphenylacetate (PHP), 3-hydroxybenzoate (MHB), 4-hydroxybenzoate (PHB), 3-fluoro-4-hydroxybenzoate (FHB), 3-chloro-4-hydroxybenzoate (CHB), and 3-iodo-4-hydroxybenzoate (IHB)] are reported at 2.0-2.2 A resolution with R-factors of 0. 0.159-0.179. The inhibitors bind in a narrow active site crevasse lined with residues that provide a microenvironment that closely matches the chemical characteristics of the inhibitors. This results in as little as 20% solvent-exposed surface area for the higher-affinity inhibitors (PHB, CHB, and FHB). In uncomplexed 3,4-PCD, the active site Fe3+ is bound at the bottom of the active site crevasse by four endogenous ligands and a solvent molecule (Wat827). The orientations of the endogenous ligands are relatively unperturbed in each inhibitor complex, but the inhibitors themselves bind to or near the iron in a range of positions, all of which perturb the position of Wat827. The three lowest-affinity inhibitors (MHP, PHP, and IHB) yield distorted trigonal bipyramidal iron coordination geometry in which the inhibitor C4-phenolate group displaces the solvent ligand. MHB binds within the active site, but neither its C3-OH group nor the solvent molecule binds to the iron. The C4-phenolate group of the three highest-affinity inhibitors (PHB, CHB, and FHB) coordinates the Fe3+ adjacent to Wat827, resulting in a shift in its position to yield a six-coordinate distorted octahedral geometry. The range of inhibitor orientations may mimic the mechanistically significant stages of substrate binding to 3, 4-PCD. The structure of the final substrate complex is reported in the following paper [Orville, A. M., Lipscomb, J. D., & Ohlendorf, D. H. (1997) Biochemistry 36, 10052-10066].     

Interpretation of the dilated pupil during endoscopic sinus surgery

This article describes the anatomy of the visual pathways and how they should be assessed under anaesthesia. The differential diagnosis of asymmetrical pupils is illustrated with clinical examples and a strategy as to how they should be examined.     

Analysis of the conversion of delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-alpha-aminobutyrate by active-site mutants of Aspergillus nidulans isopenicillin N synthase

In order to study the present situation of music therapy in hospitals of pediatrics and of child and adolescent psychiatry in the FRG, a postal survey at these hospitals was performed. The personnel situation, methods of music therapy and indications for music therapy were examined. The data are analysed according to the kind and the size of hospital; they are compared to results obtained in a survey at out-patient pediatrics and to a similar survey from the year 1990.     

Delayed kinetics of tumor necrosis factor-mediated bystander lysis by peptide-specific CD8+ cytotoxic T lymphocytes

Mouse CD8+ CTL reactive with an H-2Db presented 9-mer peptide of the human papilloma virus 16 (HPV-16) protein E749-57 (RAHYNIVTF) were generated from the splenocytes of wild-type C57BL/6 (B6), B6.perforin-deficient, B6.gld or B6.TNF-deficient mice. In short-term (4 h) assays, CTL from B6, B6.TNF-deficient and B6.gld mice displayed peptide-specific perforin- and/or Fas ligand (FasL)-mediated lysis of E7-transfected mouse RMA lymphoma cells (RMA-E7) or E749-57 peptide-pulsed RMA-S cells, while CD8+ CTL from B6.perforin-deficient mice lysed via FasL exclusively. Rapid and efficient lysis of syngeneic bystander B6 spleen T cell blasts by B6, B6.TNF-deficient or B6.perforin-deficient antigen-activated CTL was mediated apparently exclusively by a FasL/Fas mechanism. By contrast CTL from B6.gld mice did not mediate rapid bystander lysis of B6 blasts. Rather B6.gld CTL delivered delayed bystander lysis after 36-48 h that was mediated by TNF. TNF-mediated bystander lysis of syngeneic blasts appeared to be independent of class I molecules and was mediated at least in part by soluble TNF. By contrast, there was no evidence that soluble FasL-mediated bystander lysis. For the first time, these data indicate that CD8+ CTL may use FasL or TNF in a kinetically and physically distinct fashion to mediate bystander killing.     

Computed tomographic angiographic imaging of abdominal aortic aneurysms: implications for transfemoral endovascular aneurysm management

Guinea pig pancreatic segments were superfused during 10 min with physiological saline solutions containing 10(-6) M acetylcholine (ACh) or histamine (10(-3)-10(-6) M) and the potassium concentration in the effluent [K+]o) was measured by flame photometry. Histamine evoked a transient increase in [K/]o. The removal of calcium from the superfusing solution and addition of 10(-4) M EGTA caused a significant reduction in the histamine-evoked potassium outflow. Replacement of chloride (Cl-) in the physiological salt solution by nitrate (NO3-) caused a significant reduction in the histamine-evoked potassium release. However, when Cl- was replaced by bromide (Br-) the response to histamine was unaffected. Pre-treatment of pancreatic segments with furosemide (10(-4 M) or ouabain (10(-3) M) caused a marked reduction in the histamine-induced potassium release. The results suggest that ionic requirements in histamine-evoked potassium release are the same as those in acetylcholine-evoked potassium efflux.     

Differential diagnosis of dysphagia in children

Dysphagia in children often presents a difficult diagnostic challenge. A systematic approach in each individual can help with diagnosis and treatment. An overview of the differential diagnosis and the diagnostic and treatment options available is provided.