Current status of solvent/detergent-treated frozen plasma

DNA superhelical tension, an important feature of genomic organization, is known to affect the interactions of intercalating molecules with DNA. However, the effect of torsional tension on nonintercalative DNA-binding chemicals has received less attention. We demonstrate here that the enediyne calicheamicin gamma1I, a strand-breaking agent specific to the minor groove, causes approximately 50% more damage in negatively supercoiled plasmid DNA than in DNA with positive superhelicity. Furthermore, we show that the decrease in damage in positively supercoiled DNA is controlled at the level of thiol activation of the drug. Our results suggest that supercoiling may affect both the activity of nonintercalating genotoxins in vivo and the accessibility of glutathione and other small physiologic molecules to DNA-bound chemicals or reactions occurring in the grooves of DNA.     

Comparison of five PCR methods for detection of Helicobacter pylori DNA in gastric tissues

Five different PCR methods for the detection of Helicobacter pylori were evaluated. The results of this study indicate that of the five PCR methods examined, the ureC (glmM) gene PCR is the most sensitive and specific for the detection of H. pylori in gastric biopsy specimens.     

Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer's disease, and apolipoprotein E-epsilon4/4 genotype

Sleep disruption, nightly restlessness, sundowning, and other circadian disturbances are frequently seen in Alzheimer's disease (AD) patients. Changes in the suprachiasmatic nucleus and pineal gland are thought to be the biological basis for these behavioral disturbances. Melatonin is the main endocrine message for circadian rhythmicity from the pineal. To determine whether melatonin production was affected in AD, melatonin levels were determined in the cerebrospinal fluid (CSF) of 85 patients with AD (mean age, 75 +/- 1.1 yr) and in 82 age-matched controls (mean age, 76 +/- 1.4 yr). Ventricular postmortem CSF was collected from clinically and neuropathologically well defined AD patients and from control subjects without primary neurological or psychiatric disease. In old control subjects (>80 yr of age), CSF melatonin levels were half of those in control subjects of 41-80 yr of age [176 +/- 58 (n = 29) and 330 +/- 66 (n = 53) pg/mL, respectively; P = 0.016]. We did not find a diurnal rhythm in CSF melatonin levels in control subjects. In AD patients the CSF melatonin levels were only one fifth (55 +/- 7 pg/mL) of those in control subjects (273 +/- 47 pg/mL; P = 0.0001). There was no difference in the CSF melatonin levels between the presenile (42 +/- 11 pg/mL; n = 21) and the senile (59 +/- 8 pg/mL; n = 64; P = 0.35) AD patients. The melatonin level in AD patients expressing apolipoprotein E-epsilon3/4 (71 +/- 11 pg/mL) was significantly higher than that in patients expressing apolipoprotein E-epsilon4/4 (32 +/- 8 pg/ml; P = 0.02). In the AD patients no significant correlation was observed between age of onset or duration of AD and CSF melatonin levels. In the present study, a dramatic decrease in the CSF melatonin levels was found in old control subjects and even more so in AD patients. Whether supplementation of melatonin may indeed improve behavioral disturbances in AD patients should be investigated.     

Examination of phosphorylated tau protein as a PHF-precursor at early stage Alzheimer's disease

Hyperphosphorylated tau protein which can be isolated on the basis of insolubility in 1% sarkosyl (A68-tau fraction) is thought to represent a precursor pool for PHF assembly, associated histologically with neuritic pathology, which feeds into a more resistant tangle-associated PHF pool via cross-linking and proteolysis. We examined these predictions at the earliest detectable stages of neurofibrillary pathology. We report that there is no evidence that neuritic pathology represents an early pathologic stage, no evidence of an association between neuritic pathology and phosphorylated tau, no evidence of selective accumulation of phosphorylated tau at early stages of pathology, and no evidence for a precursor/product relationship between phosphorylated tau and PHFs during progression of pathology. We conclude that altered phosphorylation is a secondary process affecting 5% of PHFs and does not explain PHF assembly in Alzheimer's disease.     

Appearance of keratitis in laboratory mice: influence of azathioprine and meticorten

The fibroscopic examination of a case of pemphigus vulgaris is described. The author postulate the fibroscopy as routine examination in the pemphigus with oral lesions.     

Anatomy of the retroperitoneum: observations of the distribution of pathologic fluid collections

Magnetization transfer (MT) imaging with a rapid gradient-echo sequence and pulsed saturation provides an efficient means of acquiring high resolution three-dimensional data in vivo. This paper presents a derivation of the theoretical steady-state signal equation for this sequence based on the two-site coupled Bloch equations. Numerical simulations are used to validate the derived expression and experiments are performed on an agar gel model and normal brain. Experimental agar data indicate that direct saturation of the liquid component can be a major source of signal attenuation whereas MT normally dominates in brain tissue. The signal equation presented here establishes the necessary theory for sequence design and optimization and provides insight into model parameters and experimental results.     

M100907, a selective 5-HT2A receptor antagonist and a potential antipsychotic drug, facilitates N-methyl-D-aspartate-receptor mediated neurotransmission in the rat medial prefrontal cortical neurons in vitro

The technique of intracellular recording was used to examine the effect of M100907 (formerly MDL 100907), a highly selective 5-HT2A receptor antagonist and a potential antipsychotic drug (APD), on N-methyl-D-aspartate (NMDA) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated responses in pyramidal cells of the rat medial prefrontal cortex in in vitro brain slice preparations. Bath administration of M100907, but not its inactive stereoisomer M100009, produced a 350% to 550% increase of NMDA-induced responses in a concentration-dependent manner with an EC50 value of 14 nmol/L, reminiscent of the action of clozapine. M100907 did not alter AMPA responses. Moreover, M100907 significantly increased the amplitude and duration of excitatory postsynaptic potentials and currents evoked by electrical stimulation of the forceps minor. We have generated several lines of evidence indicating that M100907 enhances glutamate receptor-mediated neurotransmission in pyramidal cells of the medial prefrontal cortex by facilitating NMDA-induced release of excitatory amino acids. The robust potentiation of NMDA receptor-mediated neurotransmission may explain, at least partly, the potential antipsychotic action of this compound. Furthermore, if M100907 proves to be an effective APD and if our findings can be extended to other atypical APDs, which are known to possess a relatively high affinity to 5-HT2A receptors, they may account for the purported efficacy of atypical APDs in alleviating some negative symptoms such as cognitive and executive functions.     

Physiological studies of the precedence effect in the inferior colliculus of the kitten

The precedence effect (PE) is a perceptual phenomenon that reflects listeners' ability to suppress echoes in reverberant environments. The PE is not present at birth and appears only several months postnatal. Recent physiological studies have demonstrated correlates of the PE in the central nucleus of the inferior colliculus (ICC) of adult animals. The present study extended the same techniques to search for similar correlates in the ICC of kittens during the first postnatal month. Stimuli consisted of pairs of clicks or noise bursts presented from different locations in free field or with different inter-aural differences in time (ITD) under headphones, with an inter-stimulus-delay (ISD) between their onsets. Results suggest that a physiological correlate of the PE, i.e. suppression of responses to the second source, is present as early as 8 days postnatal, and occurs at similar ISDs to those recorded in adult cats. Suppression in kitten neurons varies with stimulus level, duration, and azimuthal position, in a similar manner to that in adult neurons. The age at which correlates of the PE in the kitten can be found precedes the age at which kittens can localize sound sources effectively, and presumably before the age at which they would demonstrate the PE behaviorally. Thus, the neural mechanisms that might be involved in the first stages of processing PE stimuli may be in place well before the behavioral correlate develops.     

Influences of matrix ductility,interfacial bonding strength,and fiber volume fraction on tensile strength of unidirectional metal matrix composite

A trial to predict the influences of ductility of matrix, interfacial bonding strength, and volume fraction of fiber on the tensile strength of unidirectional metal matrix composites was attempted by means of a Monte Carlo computer simulation method. The main results are summarized as follows. (1) The strength of strongly bonded composites increased with increasing ductility of matrix and then remained nearly constant. (2) When the matrix was ductile, the strength of composite increased with increasing interfacial bonding strength and then remained nearly constant. When the matrix was not ductile, the strength increased but then decreased with interfacial bonding strength. In this case, there was an optimum bonding strength, for which the strength of composite was highest. (3) Concerning the strength of composite as a function of volume fraction of fiber, there arose the case where it is approximately described by the rule of mixtures and also the case where it is not described by this rule, depending on the ductility of matrix, interfacial bonding strength, and scatter of strength of fiber.