Biomedical subjects

N Meiri

Publications and source records attributed to N Meiri.

At least 19 recordsLinked to original sources

PubMed2001

Modified testicular expression of stress-associated "readthrough" acetylcholinesterase predicts male infertility.

Male infertility is often attributed to stress. However, the protein or proteins that mediate stress-related infertility are not yet known. Overexpression of the "readthrough" variant of acetylcholinesterase (AChE-R) is involved in the cellular stress response in a variety of mammalian tissues. Here, we report testicular overexpression of AChE-R in heads, but not tails, of postmeiotic spermatozoa from mice subjected to a transient psychological stress compared with age-matched control mice. Transgenic mice overexpressing AChE-R displayed reduced sperm counts, decreased seminal gland weight, and impaired sperm motility compared with age-matched nontransgenic controls. AChE-R was prominent in meiotic phase spermatocytes and in tails, but not heads, of testicular spermatozoa from AChE-R transgenic mice. Head-localized AChE-R was characteristic of human sperm from fertile donors. In contrast, sperm head AChE-R staining was conspicuously reduced in samples from human couples for whom the cause of infertility could not be determined, similar to the pattern found in transgenic mice. These findings indicate AChE-R involvement in impaired sperm quality, which suggests that it is a molecular marker for stress-related infertility.

Acetylcholinesterase↗

PubMed2001

[Virtual bronchoscopy].

Flexible bronchoscopy represents a clinically well-established invasive diagnostic tool. Virtual bronchoscopies, calculated from thin-slice CT sections, allow astonishing immitations of reality although principal differences exist between both technologies: the fact that colour representation is artificial and concommitant interventions are impossible limits the clinical use of virtual bronchoscopy. However, its value increases when calculations can be attained within minutes due to technological advancements, and when virtually any chest CT is suitable for further postprocessing. Indications, findings and the clinical role of virtual bronchoscopy are discussed.

Bronchoscopy↗

PubMed2001

CT colonography: data acquisition and patient preparation techniques.

The success of a virtual endoscopy is essentially dependent on the image quality of the corresponding 3-dimensional reconstructions. Before loading image data on a post-processing computer, certain prerequisites concerning the source data must be met. To carry out a CT colonography, the source data must be of good quality. High spatial resolution in all geometrical directions, continuous data acquisition without gaps, and artefact-free images are pivotal factors influencing source data. A generally applicable rule is that the size of the smallest detectable polyp is limited by the nominal slice thickness, emphasizing the ultimate importance of the initially chosen primary slice collimation. Furthermore, calculation of an endoluminal view is impossible without sufficient distension of the bowels. Thorough patient preparation that accommodates the technical circumstances for post-processing is also required for attaining a high sensitivity in polyp detection.

Cathartics↗

PubMed2001

Na(+)-K(+)-ATPase gene expression in the avian eggshell gland: distinct regulation in different cell types.

The avian eggshell gland (ESG) is a tissue specialized in transporting the Ca(2+) required for eggshell formation and represents a unique biological system in which the calcification process takes place in a circadian fashion. With the use of RNA fingerprinting, a set of genes differentially induced at the time of calcification was detected, one of which was identified as the alpha(1)-subunit of Na(+)-K(+)-ATPase. The gene was expressed in a circadian manner in both cell types populating the ESG, but in different temporal patterns, suggesting distinct mechanisms of regulation. Ca(2+) flux and mechanical strain were found to regulate gene expression in the inner glandular epithelium and the pseudostratified epithelium facing the lumen, respectively. Mechanical strain also affected gene expression in cell layers facing the lumen in other parts of the oviduct. Only the alpha(1)-isoform, not the alpha(2)- or alpha(3)-isoform, of Na(+)-K(+)-ATPase was expressed in the ESG. In summary, we demonstrate that the alpha(1)-subunit Na(+)-K(+)-ATPase gene is expressed in different epithelial cell types in the ESG and is regulated by various mechanisms, which may reflect the disparity in the physiological roles of the cells in the process of eggshell formation.

Animals↗

PubMed2000

Colonography using multislice CT.

Computed tomography (CT) represents the preferred imaging modality for imaging the large bowel when virtual endoscopic reconstructions are desired. Using the spiral acquisition technique, it has become possible to scan the entire abdomen within a single breathhold, however, slice thicknesses of 5 mm or more are necessary should the breathhold not last longer than 30-40 s. With the advent of multislice CT, contiguous 1-mm slices can be obtained through the entire abdomen while even shortening the breathhold to 25-30 s. The improved speed and spatial resolution of multislice CT results in remarkably sharp virtual reconstructions allowing detection of polyps with sizes less than 3 mm. The disadvantages must still be considered including a dataset consisting of up to 800 images representing a new challenge for postprocessing hard- and software.

Colon↗

PubMed2000

New insight in eggshell formation.

The matrix proteins that participate in crystalization fulfill important functions during the formation of the calcified tissues and contribute to the biomechanical properties of the mature product. We suggest that osteopontin (OPN) is part of an array of macromolecules synthesized and secreted by the cells adjacent to the mineralization front that self-assemble outside the cell and direct crystal formation. The OPN meets the theoretical requirements for involvement in the mineralization process. The phosphorylated residues of acidic phosphoprotein have been shown to exist in the protein as reactive monoesters that are available for interaction with other ions, among them crystal constituents such as calcium ions. In addition, sulfation of OPN was also found to be associated with mineralization of other tissues. In contrast to the calbindin gene, whose expression is dependent on the calcium flux, the regulation of OPN synthesis is at least in part dependent on the mechanical strain imposed by the resident egg. These results demonstrate the complexity of the regulation of the matrix genes governing eggshell formation.

Animals↗

PubMed2000

Spatial learning induced changes in expression of the ryanodine type II receptor in the rat hippocampus.

Calcium signaling critical to neural functions is mediated through Ca(2+) channels localized on both the plasma membrane and intracellular organelles such as endoplasmic reticulum. Whereas Ca(2+) influx occurs via the voltage- or/and ligand-sensitive Ca(2+) channels, Ca(2+) release from intracellular stores that amplifies further the Ca(2+) signal is thought to be involved in more profound and lasting changes in neurons. The ryanodine receptor, one of the two major intracellular Ca(2+) channels, has been an important target for studying Ca(2+) signaling in brain functions, including learning and memory, due to its characteristic Ca(2+)-induced Ca(2+) release. In this study, we report regional and cellular distributions of the type-2 ryanodine receptor (RyR2) mRNA in the rat brain, and effects of spatial learning on RyR2 gene expression at mRNA and protein levels in the rat hippocampus. Using in situ hybridization, reverse transcription polymerase chain reaction, and ribonuclease protection assays, significant increases in RyR2 mRNA were found in the hippocampus of rats trained in an intensive water maze task. With immunoprecipitation and immunoblotting, protein levels of RyR2 were also demonstrated to be increased in the microsomal fractions prepared from hippocampi of trained rats. These results suggest that RyR2, and hence the RyR2-mediated Ca(2+) signals, may be involved in memory processing after spatial learning. The increases in RyR2 mRNA and protein at 12 and 24 h after training could contribute to more permanent changes such as structural modifications during long-term memory storage. Zhao, W., Meiri, N., Xu, H., Cavallaro, S., Quattrone, A., Zhang, L., Alkon, D. A. Spatial learning induced changes in expression of the ryanodine type II receptor in the rat hippocampus.

Animals↗

PubMed1999

Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats.

Evidence accumulated from clinical and basic research has indirectly implicated the insulin receptor (IR) in brain cognitive functions, including learning and memory (Wickelgren, I. (1998) Science 280, 517-519). The present study investigates correlative changes in IR expression, phosphorylation, and associated signaling molecules in the rat hippocampus following water maze training. Although the distribution of IR protein matched that of IR mRNA in most forebrain regions, a dissociation of the IR mRNA and protein expression patterns was found in the cerebellar cortex. After training, IR mRNA in the CA1 and dentate gyrus of the hippocampus was up-regulated, and there was increased accumulation of IR protein in the hippocampal crude synaptic membrane fraction. In the CA1 pyramidal neurons, changes in the distribution pattern of IR in particular cellular compartments, such as the nucleus and dendritic regions, was observed only in trained animals. Although IR showed a low level of in vivo tyrosine phosphorylation, an insulin-stimulated increase of in vitro Tyr phosphorylation of IR was detected in trained animals, suggesting that learning may induce IR functional changes, such as enhanced receptor sensitivity. Furthermore, a training-induced co-immunoprecipitation of IR with Shc-66 was detected, along with changes in in vivo Tyr phosphorylation of Shc and mitogen-activated protein kinase, as well as accumulation of Shc-66, Shc-52, and Grb-2 in hippocampal synaptic membrane fractions following training. These findings suggest that IR may participate in memory processing through activation of its receptor Tyr kinase activity, and they suggest possible engagement of Shc/Grb-2/Ras/mitogen-activated protein kinase cascades.

3T3 Cells↗

PubMed1999

Kir6.2 oligoantisense administered into the globus pallidus reduces apomorphine-induced turning in 6-OHDA hemiparkinsonian rats.

ATP-sensitive inwardly rectifying potassium channels (KATPs) couple cell metabolism with its membrane potential. The best characterized KATP is the pancreatic KATP which is an heteromultimer of Kir6.2 and SUR1 protein subunits. KATPs are found in a variety of excitable cells, including neurons of the central nervous system. Basal ganglia (BG), especially in the substantia nigra (SN) reticulata and the globus pallidus (GP), have a high density of KATPs. Pharmacological modulation of the KATPs within the BG alters GABAergic activity and produces behavioural changes. However, the relatively high concentrations of drugs used might not have been entirely selective for the KATPs and may have acted at presynaptic nerve terminals as well as on the post-synaptic neurons. As an alternative means of examining the role of KATPs in regulating motor behavior, we used oligoantisense technology to diminish selectively Kir6.2 formation in the GP neurons. We then examined the effect of reduction in Kir6.2 expression on apomorphine-induced turning behavior in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the SN. Two weeks after injection of 6-OHDA, contralateral circling in response to apomorphine (0.25 mg/kg sc) was recorded. Kir6.2 antisense oligodeoxyribonucleotide (ODN) was then administered daily for 6 days into the GP ipsilateral to the 6-OHDA injection. Responses to apomorphine were then tested again and the animals killed to determine the effect of the antisense ODN on Kir6. 2 mRNA. Administration of Kir6.2 antisense ODN significantly attenuated apomorphine-induced contralateral turning and specifically reduced Kir6.2 mRNA in the injected GP. These results are consistent with pharmacological experiments which suggest that KATP channels in the GP are involved in motor responses to apomorphine in 6-OHDA lesioned rats, localizing the effects to the GP neurons, probably through modulation of the GABAergic system.

Animals↗

PubMed1998

Memory and long-term potentiation (LTP) dissociated: normal spatial memory despite CA1 LTP elimination with Kv1.4 antisense.

Long-term potentiation (LTP) in the hippocampal slice preparation has been proposed as an in vitro model for long-term memory. However, correlation of LTP with memory in living animals has been difficult to demonstrate. Furthermore, in the last few years evidence has accumulated that dissociate the two. Because potassium channels might determine the weight of synapses in networks, we studied the role of Kv1.4, a presynaptic A-type voltage-dependent K+ channel, in both memory and LTP. Reverse transcription-PCR and Western blot analysis with specific antibodies showed that antisense oligodeoxyribonucleotide to Kv1.4 microinjected intraventricularly into rat brains obstructed hippocampal Kv1.4 mRNA, "knocking down" the protein in the hippocampus. This antisense knockdown had no effect on rat spatial maze learning, memory, or exploratory behavior, but eliminated both early- and late-phase LTP and reduced paired-pulse facilitation (a presynaptic effect) in CA1 pyramidal neurons without affecting dentate gyrus LTP. This presynaptic Kv1.4 knockdown together with previous postsynaptic Kv1.1 knockdown demonstrates that CA1 LTP is neither necessary nor sufficient for rat spatial memory.

Animals↗

PubMed1998

Hippocampal synaptic plasticity in mice overexpressing an embryonic subunit of the NMDA receptor.

The effects of changing NMDA receptor subunit composition on synaptic plasticity in the hippocampus were analyzed by creating transgenic mice overexpressing NR2D, a predominantly embryonic NMDA receptor subunit. NMDA-evoked currents in the transgenic mice had smaller amplitudes and slower kinetics. The transgenics also displayed age-dependent deficits in synaptic plasticity in area CA1 of the hippocampus. Long-term depression was selectively impaired in juvenile mice when NR2D overexpression was moderate. In mature mice, overexpression of NR2D was associated with a reduction of both NR2B and Ca2+-independent activity of Ca2+- and calmodulin-dependent protein kinase II. These biochemical changes were correlated with a marked impairment of NMDA-dependent long-term potentiation, but spatial behavior was normal in these mice. These results show that the developmental regulation of NMDA receptor subunit composition alters the frequency at which modification of synaptic responses occur after afferent stimulation.

2-Amino-5-phosphonovalerate↗

PubMed1998

Lateral ventricle injection of the protein synthesis inhibitor anisomycin impairs long-term memory in a spatial memory task.

Although protein synthesis inhibition has been shown to affect long-term memory in a wide variety of animal species, cases have been reported in which protein synthesis inhibition failed to affect memory consolidation [S. Wittstock, R. Menzel, Color learning and memory in honey bees are not affected by protein synthesis inhibition, Behav. Neural Biol., 62 (1994) 224-229.]. Most findings argue that the critical time for protein synthesis is during or immediately after training. However, other reports show a second time window, hours after training, where protein synthesis inhibition can cause amnesia [F.M. Freeman, S.P.R. Rose, A.B. Scholey, Two time windows of anisomycin-induced amnesia for passive avoidance training in the day-old chick, Neurobiol. Learn. Mem., 63 (1995) 291-295.][G. Grecksch, H. Matthies, Two sensitive periods for the amnesic effect of anisomycin, Pharmacol. Biochem. Behav., 12 (1980) 663-665.]. In this study, we addressed two questions: (1) Is protein synthesis essential for spatial memory? and (2) At what injection time window(s) will protein synthesis inhibition cause spatial memory amnesia? We report that bilateral intraventricular microinjection of anisomycin (Ani) impairs consolidation of long-term memory, in the hippocampal-dependent Morris water maze spatial memory task. Memory was impaired in a dose-dependent manner without affecting short-term memory. Spatial memory was affected only if Ani was injected 20 min before performing the task and not in any other time window before or after the behavioral test. The inhibition did not affect pre-existing memories or the capability to memorize once the effect of the inhibition diminished.

Animals↗

PubMed1998

Safe and easy power injection of contrast material through a central line.

Power-assisted injection of contrast material into an antecubital vein is commonly used in CT and has been proven superior to manual injection. Power-assisted injection through a central line bares the risk of rupturing the line because manual control over the pressure applied by the power injector is lacking. We present a simple safety device which allows manual control of the pressure by means of an interposed three-way stopcock combined with a small syringe for pressure equalization.

Catheterization, Central Venous↗

PubMed1998

Virtual endoscopy of the small bowel: phantom study and preliminary clinical results.

The purpose of this study was to determine the optimal scanning technique for lesion detection in a small bowel phantom and to evaluate the virtual endoscopy (VE) technique in patients. A small bowel phantom with a fold thickness of 7 mm and length of 115 cm was prepared with nine round lesions (3 x 1 mm, 2 x 2 mm, 2 x 3 mm, 2 x 4 mm). Spiral CT parameters were 7/7/4, 3/5/2, 3/5/1, 1.5/3/1 (slice thickness/table feed/reconstruction interval). VE was done using volume rendering technique with 1 cm distance between images and 120 degrees viewing angle. Two masked readers were asked to determine the number and location of the lesions. Seven patients underwent an abdominal CT during one breathhold after placement of a duodenal tube and filling of the small bowel with methyl cellulose contrast solution. VE images were compared with the axial slices with respect to detectability of pathology. With the 7/7/4 protocol only the 4-mm lesions were visualised with fuzzy contours. The 3/5/2 protocol showed both 4-mm lesions, one 3-mm lesion and one false positive lesion. The 3/5/1 protocol showed both 4-mm and both 3-mm (one uncertain) lesions with improved sharpness, and no false positive lesions. One 2-mm and one 1-mm lesion were additionally seen with the 1.5/3/1 protocol. Path definition was difficult in sharp turns or kinks in the lumen. In all patients, no difference was found between VE and axial slices for bowel pathology; however, axial slices showed 'outside' information that was not included in VE. We conclude that the 3/5/2 protocol may be regarded as an optimal compromise between lesion detection, coverage during one breathhold, and number of reconstructed images in patients; round lesions of 4 mm in diameter can be detected with high certainty.

Adult↗

PubMed1998

Low-dose spiral computed tomography for measuring abdominal fat volume and distribution in a clinical setting.

OBJECTIVES: Computed tomography (CT) has been used to measure body composition, however, a technique with reduced radiation exposure has not yet been introduced. This study tested a low-dose spiral CT technique on a phantom to determine its validity and reproducibility. The method was then applied for volume and distribution measurements in patients. DESIGN: Construction and measurement of a phantom followed by measurement of patients referred to CT for clinical indications. SETTING: Radiology Department, University Hospital. SUBJECTS: Twenty-four post-gastrectomy patients. INTERVENTION: A 22 cm phantom with a known amount of water and fat was scanned using high- and low-dose technique, standard and double table speed during a volumetric scan. The low-dose technique was implemented in the patient group. Total volume, total fat and four defined compartmental fat volumes in the truncal area were measured. RESULTS: The mean fat volume measured using the low-dose CT technique in the phantom was 0.2% above the actual fat content. The coefficient of variation for this method was 5%. By using low-dose, double speed instead of standard-dose technique, radiation exposure to the skin was decreased by more than 90% (equivalent to 4 mGy) of what is used in diagnostic imaging. The patient scans showed that no significant differences in BMI and total measured volume existed between female and male patients, but percent fat and percent subcutaneous fat were significantly larger in women (P = 0.006 and 0.002, respectively), as were percent intraabdominal and mediastinal fat in men (P = 0.002 and 0.003 respectively). CONCLUSIONS: Low-dose spiral CT accurately measures fat volume in vitro, and can be used in vivo for compartmental fat measurements.

Abdomen↗

PubMed1997

Late memory-related genes in the hippocampus revealed by RNA fingerprinting.

Although long-term memory is thought to require a cellular program of gene expression and increased protein synthesis, the identity of proteins critical for associative memory is largely unknown. We used RNA fingerprinting to identify candidate memory-related genes (MRGs), which were up-regulated in the hippocampus of water maze-trained rats, a brain area that is critically involved in spatial learning. Two of the original 10 candidate genes implicated by RNA fingerprinting, the rat homolog of the ryanodine receptor type-2 and glutamate dehydrogenase (EC 1.4.1.3), were further investigated by Northern blot analysis, reverse transcription-PCR, and in situ hybridization and confirmed as MRGs with distinct temporal and regional expression. Successive RNA screening as illustrated here may help to reveal a spectrum of MRGs as they appear in distinct domains of memory storage.

Animals↗

PubMed1997

Reversible antisense inhibition of Shaker-like Kv1.1 potassium channel expression impairs associative memory in mouse and rat.

Long-term memory is thought to be subserved by functional remodeling of neuronal circuits. Changes in the weights of existing synapses in networks might depend on voltage-gated potassium currents. We therefore studied the physiological role of potassium channels in memory, concentrating on the Shaker-like Kv1.1, a late rectifying potassium channel that is highly localized within dendrites of hippocampal CA3 pyramidal and dentate gyrus granular cells. Repeated intracerebroventricular injection of antisense oligodeoxyribonucleotide to Kv1.1 reduces expression of its particular intracellular mRNA target, decreases late rectifying K+ current(s) in dentate granule cells, and impairs memory but not other motor or sensory behaviors, in two different learning paradigms, mouse passive avoidance and rat spatial memory. The latter, hippocampal-dependent memory loss occurred in the absence of long-term potentiation changes recorded both from the dentate gyrus or CA1. The specificity of the reversible antisense targeting of mRNA in adult animal brains may avoid irreversible developmental and genetic background effects that accompany transgenic "knockouts".

Animals↗

PubMed1995

Modulation of protein tyrosine phosphorylation in rat insular cortex after conditioned taste aversion training.

Protein tyrosine phosphorylation is a major signal transduction pathway involved in cellular metabolism, growth, and differentiation. Recent data indicate that tyrosine phosphorylation also plays a role in neuronal plasticity. We are using conditioned taste aversion, a fast and robust associative learning paradigm subserved among other brain areas by the insular cortex, to investigate molecular correlates of learning and memory in the rat cortex. In conditioned taste aversion, rats learn to associate a novel taste (e.g., saccharin) with delayed poisoning (e.g., by LiCl injection). Here we report that after conditioned taste aversion training, there is a rapid and marked increase in tyrosine phosphorylation of a set of proteins in the insular cortex but not in other brain areas. A major protein so modulated, of 180 kDa, is abundant in a membrane fraction and remains modulated for more than an hour after training. Exposure of the rats to the novel taste alone results in only a small modulation of the aforementioned proteins whereas administration of the malaise-inducing agent per se has no effect. To the best of our knowledge, this is the first demonstration of modulation of protein tyrosine phosphorylation in the brain after a behavioral experience.

Animals↗