Characterisation of erythrocyte shapes and sizes by NMR diffusion-diffraction of water: correlations with electron micrographs

Irradiation of the mammalian foetus produces a broad spectrum of congenital abnormalities, growth retardations, developmental delays, and functional deficits, depending upon the dose and the specific gestational phase of irradiation. The developing brain is particularly susceptible to production of deleterious effects, with decreased brain size, behavioural alterations, and mental retardation having been documented. Supplementing the limited human data, rodent models have been extensively used to investigate the specific processes by which relatively low doses, with correspondingly minor cellular damage to the developing neocortex, can produce dramatic postnatal consequences in brain structure and function. The effects of a variety of physical (dose, linear energy transfer, dose rate, fractionation) and biological (species, strain, gestational age, time course post-irradiation) parameters have been examined in an attempt to provide much needed information on such critical aspects as dose response, threshold doses for effect, and extrapolation to human risk estimates. Various acute cellular responses (e.g. appearance of pyknotic cells and macrophages) observed in the developing neocortex 0-24 h after in utero irradiation can be associated with postnatal effects. Moreover, it is possible to correlate thinning of specific layers of the cerebral cortex with specific behavioural aberrations, allowing prediction of brain structural changes from functional alterations, and vice versa. Thus, it is possible to speculate as to the mechanisms and targets for extremely sensitive, radiation-induced cellular damage in the developing foetal brain, that will interfere with the orderly and precisely programmed development of the mammalian brain, leading finally to postnatal expression as delays in growth and development, perturbations in behaviour, and alterations in brain structure.     

Diagnosis and management of traumatic aorto-right ventricular fistulas

BACKGROUND: Traumatic aorto-right ventricular (Ao-RV) fistulas are rare lesions that result in congestive heart failure if left untreated. Early diagnosis and prompt surgical intervention are required to avoid the natural outcome of cardiac decompensation. METHODS: All cases of traumatic Ao-RV fistula described in the English literature since 1958 were reviewed. The clinical presentation, methods of diagnosis, and treatment strategies were assessed to determine the pathophysiology, natural history, and outcome of surgical intervention. RESULTS: Forty cases of traumatic Ao-RV fistulas were described in the English literature. There were 39 men and 1 woman, with a mean age of 28.3 years (range, 15 to 50 years). Twenty-two (55%) patients had isolated Ao-RV fistulas. Fourteen (35%) had Ao-RV fistulas with aortic insufficiency. Definitive surgical repair was performed in 38 patients. The associated aortic valve injuries were managed with repair techniques or replacement with prosthetic devices. The surgical outcomes in all patients were satisfactory. CONCLUSIONS: The pathophysiology and natural history of Ao-RV fistulas involves the development of congestive heart failure. Traumatic aortic insufficiency frequently is associated with this disorder. Early diagnosis and prompt treatment are necessary to avoid the natural outcome of cardiac decompensation. Definitive repair should be performed with the aid of cardiopulmonary bypass during the same hospitalization.     

Sublabial, transseptal, transsphenoidal approach to the pituitary region guided by the ACUSTAR I system

Myocardial infarction occurring in young people with angiographically normal coronary arteries is well described but the pathophysiology of this condition remains unknown. Coronary artery spasm in association with thrombus formation and minimal atheromatous disease or spontaneous coronary artery dissection are possible causes. Two young men presented with severe chest pain after acute alcohol intoxication and each sustained an extensive anterior myocardial infarction. Investigations including intravascular ultrasound showed no evidence of atherosclerotic coronary artery disease. Coronary artery spasm associated with acute alcohol intoxication as well as prothrombotic state and endothelial damage related to cigarette smoking may be mechanisms leading to acute myocardial infarction in these cases. Acute myocardial infarction occurs in young persons with normal coronary arteries and the diagnosis should be considered in young patients presenting with severe chest pain, particularly those abusing cocaine or alcohol, so that reperfusion therapy can be initiated promptly.     

Histomorphometric, physical, and mechanical effects of spaceflight and insulin-like growth factor-I on rat long bones

Pituitary adenylate cyclase activating peptide and vasoactive intestinal peptide belong to the same neuropeptide family. Both peptides are present in nerve fibers in the gastric wall and are thought to be involved in the regulation of inflammatory processes. Experimental ulcers were induced in the rat gastric mucosa by local application of acetic acid. During the healing process we examined the PACAP and VIP innervation by means of immunohistochemistry and in situ hybridization. The ulcer area was examined from day 1 to day 15 after ulcer induction. There was a marked depletion of PACAP in nerve fibers at the ulcer margin from day 1 and onwards. On day 10 and day 15, PACAP-immunoreactive nerve fibers could again be visualized at the ulcer margin. In contrast, VIP immunoreactive nerve fibers were present at the ulcer margin at all time points studied. From day 10 following ulcer induction PACAP- and VIP- immunoreactive nerve fibers were increased in frequency in the smooth muscle beneath the ulcer. An upregulation of VIP and PACAP mRNA was also demonstrated in the myenteric ganglia adjacent to ulcer. The present results indicate that neuronal PACAP and VIP react differently to the inflammation at the ulcer margin but similarly in the smooth muscle during the ulcer healing.     

125I-Tyr1]biphalin binding to opioid receptors of rat brain and NG108-15 cell membranes

Mono iodinated analogues of biphalin [(Tyr-D-Ala-Gly-Phe-NH-)2], both nonradioactive [I-Tyr1]biphalin and radioactive [125I-Tyr1]biphalin have been synthesized. The radioligand binding profiles of these compounds for two types of tissues, rat brain membranes, and NG108-15 cell membranes were identical to the parent biphalin. This is additional evidence for the hypothesis that biphalin behaves like a monomeric ligand and that only one intact tyrosine is necessary for high biological activity. The second tyrosine could be used for successful radioiodination which may greatly simplify biochemical and pharmacological studies of biphalin. The results of receptor binding studies show that the binding of both biphalin and [I-Tyr1]biphalin to the delta and mu opioid receptors are not independent. [125I-Tyr1]Biphalin binds to delta receptors as shown in NG108-15 cell membranes. Nevertheless, [125I]biphalin binding to delta receptors in rat brain membranes was hardly evident and mu receptor binding predominated or at least was much more readily detectable in this preparation.     

Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins

OBJECTIVE: The study aimed to assess the frequency, indications, and outcome of additional ocular procedures after initial treatment of vitrectomy (VIT) or tap-biopsy (TAP) for patients with endophthalmitis after cataract extraction. DESIGN: The study design was an analysis of observational data collected as part of a multicenter, randomized clinical trial. PARTICIPANTS: Of the 420 patients enrolled in the Endophthalmitis Vitrectomy Study, the 148 who had additional procedures were compared with the 272 who did not. MAIN OUTCOME MEASURES: The types, indications, and number of additional ocular procedures were assessed. A masked examiner measured visual acuity 9 to 12 months after study entry. RESULTS: Within 1 week of study entry, 8% of VIT eyes and 13% of TAP eyes underwent additional procedures, 14% for complications of the initial procedure and 86% for worsening ocular inflammation or infection. Cultures were obtained in 33 of the 38 eyes operated on for worsening inflammation or infection and were positive in 42%. Cultures obtained from the early additional procedures were positive more frequently in eyes with an initial TAP (71%) than in eyes with an initial VIT (13%). Both virulence of initial microbiologic organism isolated and poor presenting vision were risk factors for requirement of reoperation. In all cases in which a single organism was cultured at the initial procedure, when the reculture was positive, it was the same organism. Late additional procedures (after 7 days) were required in 27% of patients. Visual outcome was much worse for eyes that had an additional procedure compared to eyes that did not, and this was especially the case for eyes that had an early additional procedure. Only 15% of eyes that had an early additional procedure achieved 20/40 visual acuity as compared to 57% of eyes that did not. CONCLUSION: Need for an additional procedure was a marker of more severe disease, and patients who underwent additional procedures achieved poorer visual acuity at final follow-up.     

Role of gap junctions in lung neoplasia

Reduced gap junctional intercellular communication (GJIC) has been noted in many types of neoplastic cells and may contribute to the neoplastic phenotype. This study assessed GJIC (by fluorescent dye-coupling) and gap junction protein (connexin) expression in mouse and human lung carcinoma cell lines and investigated whether reduced GJIC was involved in their neoplastic phenotype. Dye-coupling and connexin43 (Cx43) expression were much lower in most of the carcinoma lines (16 of 22) compared to nontransformed lung epithelial cells. Other connexins were not detected. A poorly communicating mouse lung carcinoma cell line (E9) was transfected with Cx43 or transduced with Cx32 and several stable clones were isolated that had 2- to 4-fold increased dye coupling. When evaluated for growth in vitro, the population doubling times were increased and the saturation densities were decreased in the clones. When assessed for tumorigenicity, the parental E9 cells formed tumors with a 100% incidence (6/6 mice), whereas the clones varied in tumorigenic response (0-88% incidence). The best communicating clone (E9-2) was not tumorigenic. The highly communicating Cx32 clone, E9/32-9, gave a tumor incidence of 88%. These results suggest that restoration of GJIC by forced connexin expression can reduce the growth and tumorigenicity of lung carcinoma cells in a connexin-specific manner.     

The hypocholesterolemic and antiatherogenic effects of Cholazol H, a chemically functionalized insoluble fiber with bile acid sequestrant properties in hamsters

Cholazol H (Alpha-Beta Technology, Worcester, MA), a chemically functionalized, insoluble dietary fiber with bile acid sequestrant properties, was studied in 30 male F1 B Golden Syrian hamsters for its effect on plasma lipid concentrations and early atherogenesis in experiment 1. In experiment 2, 30 male Golden Syrian hamsters were studied for the effects on plasma lipids and fecal excretion of bile acids. In experiment 1, three groups of 10 hamsters each were fed a chow-based hypercholesterolemic diet supplemented with 5% coconut oil and 0.1% cholesterol for 6 weeks. After 6 weeks, hamsters were continued on the diet with either 0% drug (hypercholesterolemic diet [HCD]), 0.5% cholestyramine (CSTY), or 0.5% Cholazol H for 8 weeks. Fasting plasma lipids were measured at weeks 6, 10, and 14, and early atherosclerosis (fatty streak formation) was measured at week 14. Relative to HCD, CSTY and Cholazol H significantly lowered plasma total cholesterol (TC) (-37%, P < .03, and -30%, P < .04, respectively) and plasma very-low and low-density lipoprotein-cholesterol (nonHDL-C) (-45%, P < .02, and -36%, P < .03, respectively) with no significant effects on plasma HDL-C or triglycerides (TG). Despite similar reductions in nonHDL-C, only Cholazol H significantly prevented early atherosclerosis (-38%, P < .02) relative to HCD. In experiment 2, three groups of 10 hamsters each were fed a chow-based hypercholesterolemic diet supplemented with 10% coconut oil and 0.05% cholesterol and either 0% drug HCD, 0.5% CSTY, or 0.5% Cholazol H for 4 weeks. Fasting plasma lipids were measured at weeks 2 and 4, and fecal bile acids were measured at week 4. Both Cholazol H and CSTY were equally effective in significantly lowering plasma TC (-16%, P < .003, and -13%, P < .01, respectively) and nonHDL-C (-22%, P < .004, and -18%, P < .02, respectively), with no significant effect on HDL-C and TG relative to HCD. Cholazol H and CSTY produced a significantly greater concentration of fecal total bile acids (39%, P < .001, and 28%, P < .002, respectively) relative to HCD. Also, there was a 48% (P < .002) and 65% (P < .001) greater fecal concentration of cholic acid (CA) for Cholazol H-treated hamsters compared with HCD- and CSTY-treated hamsters, respectively. Cholazol H also significantly increased fecal concentration of deoxycholic acid (DCA; 56%, P < .02) compared with HCD. In summary, Cholazol H is as effective as CSTY for prevention of diet-induced hypercholesterolemia and early atherosclerosis in hamsters.