NMR Microscopy of Single Neurons Using Spin Echo and Line Narrowed 2DFT Imaging

NMR microimages of single neural cells were acquired at 500 MHz using a conventional spin echo pulse sequence and a line-narrowing sequence that eliminates susceptibility effects. The data show that any contribution to the measured T₂ relaxation rate arising from diffusion in local field inhomogeneities using spin echo sequences at high fields and high spatial resolution is relatively small. We conclude that the measured T₂ difference between the nucleus and cytoplasm in these cells represents primarily a true T₂ relaxation effect arising from the interactions of water with macromolecules in the two compartments and does not result from microsusceptibility differences. These observations have implications regarding water compartmentation in single cells and the interpretation of the MR characteristics of tissues in vivo.     

Effects of cholinergic modulation on serum insulin-like growth factor4 and its binding proteins in normal and diabetic subjects*

OBJECTIVE We wished to study alterations In serum Insulin-like growth factor-I (IGF-I) and its binding proteins in subjects with insulin dependent diabetes mellitus (IDDM) and possible relations with metabolic and GH secretory status, before and after cholinergic modulation. In addition, we have Investigated whether cholinergic modulation exerts any effects on IGF-I secretion, Independently of any actions on GH secretory status. DESIGN All subjects received OH releasing hormone (GHRH) 1-44; 80 μg i.v.) alone and 60 minutes following 120mg of pyridostigmine orally or 200 mg of plrenzepine orally. The three tests were carried out In random order at least one week apart. Blood was sampled at 15-mInute Intervals over 120 minutes. PATIENTS Twelve male subjects with IDDM and no clinical evidence of complications were selected on the basis of HbA₁ levels to provide a wide range of metabolic control. SIX normal male subjects were also studied. MEASUREMENTS Serum IGF-I, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were measured at regular intervals throughout the study. Fasting plasma glucose and HbA₁ were measured before each study to provide measures of metabolic control. RESULTS Serum IGF-I and IGFBP-3 levels were significantly lower while serum IGFBP-I levels were significantly higher In the diabetic subjects. Plrenzepine had no effect on serum IGF-I, IGFBP-1 or IGFBP-3 In diabetic subjects but caused a significant Increase In serum IGF-I and IGFBP-3 levels in normal subjects. Pyridostigmine had no effect on IGF-I, IGFBP-1 or IGFBP-3 In either diabetic or normal subjects. IGFBP-1 levels were significantly correlated with fasting plasma glucose but no correlation was demonstrated between measures of diabetic control and serum IGF-I or IGFBP-3 levels In diabetic subjects, nor was there any correlation between OH responses to GHRH alone or after plrenzepine or pyridostigmine pretreatment and serum levels of IGF-I, IGFBP-1 or IGFBP-3. CONCLUSION These data confirm that subjects with IDDM have reduced serum IGF-I and IGFBP-3 and Increased IGFBP-1 levels, the latter being directly related to the fasting plasma glucose concentrations. The absence of any relation between changes In the IGF-I system and altered GH neuroregulation after cholinergic modulation suggests that changes In IGF-I are not the sole contributors to the altered GH neuroregulation which occurs In IDDM. We have also shown an acute stimulatory effect of pirenzepine on serum IGF-I and IGFBP-3 In normal subjects which Is not present in IDDM although the underlying mechanism Is unknown.     

Iotrolan in urography: efficacy and tolerance in comparison with iohexol and iopamidol

Iotrolan was compared with iohexol and iopamidol for efficacy and general tolerance in excretory urography in three controlled, randomized, inte-individual, double-blind studies. Two hundred and eighty-four patients received fixed doses of 100 ml, 120 ml or 150 ml iotrolan 280 or iohexol 300/iopamidol 300 by rapid or bolus injection. Contrast quality in films taken 3–40 min after injection was rated by experienced radiologists both on an overall basis and with regard to distinct anatomical regions (parenchyma, pelvicalyceal system, ureter, bladder). In all studies, contrast quality was assessed as better in the iotrolan group. In two studies (dosages 100 and 120 ml), significant differences in contrast quality were found in lavour of iotrolan (P < 0.05), and in the third study (dosage 150 ml) there was a trend towards better contrast quality in the iotrolan group (P = 0.06). General tolerance of iotrolan was good with only minor side effects (iotrolan 6.3%, iohexol/iopamidol 9.9%), but the difference was not significant. No severe adverse reactions were observed with iotrolan. In comparison with non-ionic monomers, iotrolan shows very good efficacy and general tolerance for excretory urography.     

Ultrasound for diagnosis of apophyseal injuries

Avulsion injuries of the apophysis is a problem in young athletes. A correct diagnosis is necessary for establishing the appropriate treatment and the rehabilitation program. However, it is often difficult to distinguish between a simple muscle strain and an avulsion fracture. The X-ray examination is helpful only when an ossification center of the apophysis exists. Ultrasonography is considered the suitable diagnostic tool for these cases. From June 1988 to June 1993, 243 young athletes were seen with an anamnestic and clinically suspected apophyseal injury of the lower extremity. In all cases X-ray examination and ultrasound examination were performed. In 80 cases the diagnosis was confirmed by X-ray examination and in 97 by ultrasonography. Four criteria were defined for the sonographic examination: (a) a hypoechogenic zone, (b) increased distance to the apophysis, (c) dislocation of the apophysis, and (d) mobility of the apophysis on dynamic examination. These criteria are correlated to (a) edema, (b) lysis, (c) avulsion, and (d) unstable avulsion of the apophysis. Ultrasonography is a proven technique for the detection of apophyseal injuries. In comparison to X-ray examination, it has the advantages of no radiation exposure, early detection even without ossification center, and dynamic examination.     

Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists

The antagonist pharmacology of glutamate neurotoxicity was quantitatively examined in murine cortical cell cultures. Addition of 1-3 mM DL-2-amino-5-phosphonovalerate (APV), or its active isomer D-APV, acutely to the exposure solution selectively blocked the neuroexcitation and neuronal cell selectively blocked the neuroexcitation and neuronal cell loss produced by N-methyl-D-aspartate (NMDA), with relatively little effect on that produced by either kainate or quisqualate. As expected, this selective NMDA receptor blockade only partially reduced the neuroexcitation or acute neuronal swelling produced by the broad-spectrum agonist glutamate; surprisingly, however, this blockade was sufficient to reduce glutamate-induced neuronal cell loss markedly. Lower concentrations of APV or D-APV had much less protective effect, suggesting that the blockade of a large number of NMDA receptors was required to acutely antagonize glutamate neurotoxicity. This requirement may be caused by the amplification of small amounts of acute glutamate-induced injury by subsequent release of endogenous NMDA agonists from injured neurons, as the "late" addition of 10-1000 microM APV or D-APV (after termination of glutamate exposure) also reduced resultant neuronal damage. If APV or D-APV were present both during and after glutamate exposure, a summation dose-protection relationship was obtained, showing substantial protective efficacy at low micromolar antagonist concentrations. Screening of several other excitatory amino acid antagonists confirmed that the ability to antagonize glutamate neurotoxicity might correlate with ability to block NMDA-induced neuroexcitation: The reported NMDA antagonists ketamine and DL-2-amino-7-phosphono-heptanoate, as well as the broad-spectrum antagonist kynurenate, were all found to attenuate glutamate neurotoxicity substantially; whereas gamma-D-glutamylaminomethyl sulfonate and L-glutamate diethyl ester, compounds reported to block predominantly quisqualate or kainate receptors, did not affect glutamate neurotoxicity. The present study suggests that glutamate neurotoxicity may be predominantly mediated by the activation of the NMDA subclass of glutamate receptors--occurring both directly, during exposure to exogenous compound, and indirectly, due to the subsequent release of endogenous NMDA agonists. Given other studies linking NMDA receptors to channels with unusually high calcium permeability, this suggestion is consistent with previous data showing that glutamate neurotoxicity depends heavily on extracellular calcium.     

Contribution of neo-electroencephalography in adult functional and psychiatric disorders]

Two comparative studies of the basic activity at rest, with closed eyes taken in conventional EEG and analysed in Neo-EEG are carried out in adults showing functional or psychiatric disorders. The first open study involves 18 subjects suffering from a affection called "neurodystony" and 24 depressed subjects. The second study made in double-blind compares the results of the conventional EEG with the Neo-EEG in 19 depressed patients, 28 alcoholic patients and 26 psychotic patients. The Neo-EEG discloses abnormalities in about 60% of the cases when the conventional EEG is normal. The conventional EEG as well as the Neo-EEG diagnose a greater number of low voltage in alcoholic subjects and clear abnormalities in psychotic subjects. Low voltage is never detected in psychotic patients. In depressives, the Neo-EEG shows about 65% of abnormalities of which an asymmetry of the basic frequency in the center of the two hemispheres when they are analysed separately. That asymmetry develops in parallel with the clinical state. The asymmetry is also found in psychotic patients. In nervous or neurodystonic subjects, the Neo-EEG only discloses 25% of abnormalities. The Neo-EEG appears as an easy method, able to detect dysfunctions which cannot be disclosed with the conventional EEG and useful to follow their developments. Moreover, the result of this technique brings to the fore abnormalities not detected with the conventional EEG: this eventually leads to prescribe other therapies than those initially considered.     

Role of Escherichia coli K capsular antigens during complement activation, C3 fixation, and opsonization.

Escherichia coli strains with K capsular polysaccharides are relatively resistant to phagocytosis by polymorphonuclear leukocytes, in contrast to E. coli strains without K antigens. This inhibition of phagocytosis is related to an impaired recognition of the K+ strains by the phagocytes due to ineffective opsonization. All five strains without K antigens were readily phagocytized after opsonization in 5% normal serum, compared with no uptake of the K+ strains. Evidence is presented that the decreased opsonization of the K+ strains in normal serum is caused by a low rate of complement activation of the strains, with subsequent absence of C3b fixation or C3d fixation or both to the cell wall of the bacteria. After removal of the K+ antigens by heating of a K+ E. coli strain, the strain was able to activate complement, to bind C3b or C3d or both, and to become opsonized. Complement was then activated via the classical and alternative pathways, which was comparable to the complement consumption by K- E. coli.     

Inhibitability and enhanceability of basophil histamine release in asthmatic and normal subjects

Circulating human basophils contain histamine, a potent mediator of inflammation. Previous in vitro studies have shown that histamine 'releasability' in asthmatic subjects differs from normal subjects but have not evaluated possible differences in the immunopharmacological control of the release of this mediator which might account for these differences. The purpose of the present study was to examine the immunopharmacologic control of basophil histamine release in 14 asthmatics and 10 normal subjects who were characterized by pulmonary function tests, allergic status (skin tests and serum IgE levels) and nonspecific airways reactivity to methacholine and histamine. Basophils were stimulated with anti-IgE, and the inhibitory effects of the H2 agonist, dimaprit, and dibutyryl cyclic AMP (dbcAMP), as well as the enhancing properties of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and indomethacin on the modulation of histamine release, were investigated. Although no statistically significant differences were seen in the percent histamine release triggered by anti-IgE in these two groups, enhancement of histamine release by 5-HPETE was more consistent in the asthmatic subjects (10 of 10) than in control subjects (6 of 8). The percent increase in histamine release produced by 5-HPETE in asthmatic subjects averaged 3.9 +/- 1.3% using 0.03 micrograms anti-IgE/ml and 4.8 +/- 3.2% using 0.1 microgram anti-IgE/ml (p less than 0.002, Wilcoxon's signed rank test), and averaged 3.0 +/- 4.3 and 3.1 +/- 5.3%, respectively, in control subjects (p greater than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)