[Sigmoid diverticulitis revealing a situs inversus at an advanced age].
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Abdominal Pain↗
Biomedical subjects
Q T Nguyen
Publications and source records attributed to Q T Nguyen.
Response of the adult prostate to prepubertal and postpubertal obstruction of the vas deferens in the rat.
OBJECTIVES: To determine whether obstruction of the vas deferens alters several general measures of prostate development during puberty and during prostate maintenance in the adult rat. Previous reports have suggested the possibility that vasectomy results in alterations of prostate function in experimental animals and humans. METHODS: Adult rats and 10-day-old rats were subjected to bilateral sham operations or bilateral vasectomy, and the prostates were extirpated either 14 or 60 days later. The total prostate weight and dorsolateral and ventral lobe total protein per milligram tissue, DNA per milligram tissue, and DNA per milligram protein were determined. Dorsolateral and ventral prostate lobe sections from each group were also stained with hematoxylin-eosin and subjected to histologic examination. RESULTS: The histologic features of the adult rat prostate were not qualitatively altered by vasectomy whether it occurred before puberty or in adult animals with mature prostates. Furthermore, vasectomy did not significantly alter the prostate weight or the protein or DNA content of either the dorsolateral or ventral lobes of the prostate compared with the sham-operated animals of either age. CONCLUSIONS: Vas deferens obstruction does not significantly alter the parameters associated with the development or maintenance of the adult rat prostate measured in this study.
Animals↗
Long-term effects of nonselective endothelin A and B receptor antagonism in postinfarction rat: importance of timing.
BACKGROUND: Some controversy exists as to the effects of endothelin (ET) receptor antagonism on long-term post-myocardial infarction (MI) evolution, particularly as it relates to the timing of the intervention after MI (<24 hours versus 10 days). METHODS AND RESULTS: Sham rats and rats surviving an acute MI for >20 hours (n=301) were assigned to treatment with saline or the nonselective ET(A) and ET(B) receptor antagonist LU 420627 (LU) started <24 hours (early) or 10 days (late) after MI and continued for 100 days. Long-term LU treatment led to increased mortality of rats with large MI, regardless of the timing of initiation of therapy. Early initiation of LU reduced survival from 61% to 16% (P<0.001 versus untreated), and later initiation reduced survival to 36% (P=0.012 versus untreated and P<0.001 versus early initiation). Early initiation of LU led to scar thinning, further left ventricular (LV) dilatation, LV dysfunction, and an excessive rise in right ventricular systolic pressure. Later initiation of LU did not modify scar formation but resulted in LV dilatation and dysfunction compared with the untreated group. Cardiac fibrosis tended to increase in the LU-treated MI groups. LU in the sham group reduced cardiac endothelial constitutive nitric oxide synthase but did not modify the changes that occurred with a large MI. CONCLUSIONS: The use of the nonselective ET(A) and ET(B) receptor antagonist LU results in reduced survival, ventricular dilatation, and dysfunction whether started early or late after MI. Early initiation of LU resulted in scar expansion and a particularly unfavorable outcome.
Animals↗
Myocardial contractile responsiveness to endothelin-1 in the post-infarction rat model of heart failure: effects of chronic quinapril.
Cardiac endothelin-1 (ET-1) levels and ET receptor expression are increased in congestive heart failure (CHF). In order to determine whether this results in increased responsiveness of ET-A or ET-B receptors to ET-1, we evaluated the contractile effects of ET-1 in isolated papillary muscles isolated from hearts of control rats and from rats 4 weeks post myocardial infarction (MI) having received no therapy or chronic quinapril therapy. The ET-1 dose-response was biphasic in normal muscles. The use of the selective ET-A receptor antagonist BQ123 and the selective ET-B receptor antagonist BQ788 revealed that the initial decrease in tension was the result of ET-B receptor stimulation. Blockade of nitric oxide (NO) production with L-NAME abolished the initial decrease in tension. MI resulted in CHF that was partially reversed by quinapril. In MI, the positive inotropic effects of ET-1 were enhanced due to the loss of the initial ET-B receptor mediated decrease in tension, as well as an increase in the positive inotropic effects of ET-A receptors. This was associated with an increase in ET-A and ET-B receptor mRNA and a decrease in cardiac ecNOS protein. Four weeks of therapy with quinapril attenuated the positive inotropic effects of ET-1 and prevented the increase in ET-A receptor mRNA. Although quinapril did not restore the effects of ET-B receptor stimulation or prevent the increase in ET-B mRNA, it did restore cardiac ecNOS protein expression. Thus, the inotropic response to ET-1 is biphasic due to an overall positive inotropic effect of ET-A receptor stimulation and an ET-B receptor mediated decrease in contractility at low ET-1 concentrations which appears to be mediated by cardiac ecNOS (NO). In post-MI CHF, responsiveness to ET-A receptors increases and the ET-B mediated negative inotropic response is lost despite an increase in both receptor subtypes. Quinapril therapy attenuates these effects and normalises cardiac ecNOS protein.
Angiotensin-Converting Enzyme Inhibitors↗
Construction of a two-photon microscope for video-rate Ca(2+) imaging.
We describe the construction of a video-rate two-photon laser scanning microscope, compare its performance to a similar confocal microscope, and illustrate its use for imaging local Ca(2+) transients from cortical neurons in brain slices. Key features include the use of a Ti-sapphire femtosecond laser allowing continuous tuning over a wide (700-1000 nm) wavelength range, a resonant scanning mirror to permit frame acquisition at 30 Hz, and efficient wide-field fluorescence detection. Two-photon imaging provides compelling advantages over confocal microscopy in terms of improved imaging depth and reduced phototoxicity and photobleaching, but the high cost of commercial instruments has limited their widespread adoption. By constructing one's own system the expense is greatly reduced without sacrifice of performance, and the microscope can be more readily tailored to specific applications.
Animals↗
Nerve terminals form but fail to mature when postsynaptic differentiation is blocked: in vivo analysis using mammalian nerve-muscle chimeras.
To better understand the role of the postsynaptic cell in the differentiation of presynaptic terminals, we transplanted muscles that lacked postsynaptic differentiation from mutant mice into normal adult immunocompatible hosts and attached the host nerve to the grafts. Host motor axons innervated wild-type grafted muscle fibers and established normal appearing chimeric neuromuscular junctions. By repeated in vivo imaging, we found that these synapses were stably maintained. Results were different when nerves entered transplanted muscles derived from mice lacking muscle-specific receptor tyrosine kinase (MuSK) or rapsyn, muscle-specific components required for postsynaptic differentiation. Initial steps in presynaptic differentiation (e.g., formation of rudimentary arbors and vesicle clustering at terminals) occurred when wild-type neurites contacted MuSK- or rapsyn deficient muscle fibers, either in vivo or in vitro. However, wild-type terminals contacting MuSK or rapsyn mutant muscle fibers were unable to mature, even when the chimeras were maintained for up to 7 months. Moreover, in contrast to the stability of wild-type synapses, wild-type nerve terminals in mutant muscles underwent continuous remodeling. These results suggest that postsynaptic cells supply two types of signals to motor axons: ones that initiate presynaptic differentiation and others that stabilize the immature contacts so that they can mature. Normal postsynaptic differentiation appears to be dispensable for initial stages of presynaptic differentiation but required for presynaptic maturation.
Animals↗
Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP.
We generated transgenic mice in which red, green, yellow, or cyan fluorescent proteins (together termed XFPs) were selectively expressed in neurons. All four XFPs labeled neurons in their entirety, including axons, nerve terminals, dendrites, and dendritic spines. Remarkably, each of 25 independently generated transgenic lines expressed XFP in a unique pattern, even though all incorporated identical regulatory elements (from the thyl gene). For example, all retinal ganglion cells or many cortical neurons were XFP positive in some lines, whereas only a few ganglion cells or only layer 5 cortical pyramids were labeled in others. In some lines, intense labeling of small neuronal subsets provided a Golgi-like vital stain. In double transgenic mice expressing two different XFPs, it was possible to differentially label 3 neuronal subsets in a single animal.
Animals↗
LU135252, an endothelin(A) receptor antagonist did not prevent pulmonary vascular remodelling or lung fibrosis in a rat model of myocardial infarction.
The early intervention with endothelin(A) (ET(A)) receptor antagonists following coronary artery ligation has been shown to reduce the development of pulmonary hypertension, despite a lack of improvement in left ventricular function. The present study examined the contribution of pulmonary vascular remodelling and the progression of lung fibrosis in the development of pulmonary hypertension and the subsequent role of endothelin-1 in these processes in a rat model of myocardial infarction (MI). The administration of 60 mg kg(-1) per day of the specific ET(A) receptor antagonist LU135253 ((+)-(S)-2-(4, 6-dimethoxy-pyrimidin-2-yloxy)-3-methoxy-3,3-diphenyl-propionic acid) 24 h following coronary artery ligation, failed to improve left ventricular contractile indices, but reduced the extent of pulmonary hypertension, as reflected by the significant decrease in right ventricular systolic pressure. The medial wall thickness of small pulmonary arteries (50 - 200 microm) was significantly increased 4 weeks following MI, albeit LU135253 treatment did not ameliorate this pattern of vascular remodelling. The steady-state mRNA levels of collagen, fibronectin, transforming growth factor-beta(1), and -beta(3) were significantly increased in the lungs of MI rats. The treatment with LU135252 did not alter this pattern of gene expression. Thus, these data demonstrate pulmonary vascular remodelling and the increased expression of extracellular matrix proteins represent underlying mechanisms implicated in the development of pulmonary hypertension in the MI rat. Despite the amelioration of the pulmonary hypertensive state, ET(A) receptor blockade was insufficient to reverse pulmonary vascular remodelling, or the development of lung fibrosis in the MI rat.
Animals↗
The carboxyl methyltransferase modifying G proteins is a metalloenzyme.
The prenylated protein carboxyl methyltransferase (PPMT) catalyzes the posttranslational methylation of isoprenylated C-terminal cysteine residues found in many signaling proteins such as the small monomeric G proteins and the gamma subunits of heterotrimeric G proteins. Here we report that both membrane-bound PPMT from rat kidney and the recombinant bacterially expressed form of the enzyme required divalent cations for catalytic activity. Unlike EDTA and EGTA, the metal chelator 1,10-phenanthroline strongly inhibited the PPMT activity of kidney intracellular membranes in a dose- and time-dependent manner. 1,10-Phenanthroline was found to inhibit the methylation of the prenylcysteine analog N-acetyl-S-all-trans-geranylgeranyl-l-cysteine, a synthetic substrate for PPMT, with an IC(50) of 2.2 mM. Gel electrophoretic analysis demonstrated that 1,10-phenanthroline almost totally abolished the labeling of methylated proteins in kidney intracellular membranes. Immunoblotting analysis showed that one of the two major peaks of (3)H-methylated proteins in intracellular membranes comigrated with the small G proteins Ras, Cdc42, RhoA, and Rab1. In addition, the methylation of immunoprecipitated Ras and RhoA from kidney intracellular membranes was strongly inhibited when 1,10-phenanthroline was present. Treatment of kidney intracellular membranes with 1,10-phenanthroline increased the proteolytic degradation of PPMT by exogenous trypsin, compared to untreated membranes. We conclude from these data that metal ions are essential for the activity and the stabilization of PPMT. The finding that PPMT is a metalloenzyme may provide new insights into the functions played by this methyltransferase in signal transduction processes.
Animals↗
Alternatively spliced isoforms of nerve- and muscle-derived agrin: their roles at the neuromuscular junction.
Agrin induces synaptic differentiation at the skeletal neuromuscular junction (NMJ); both pre- and postsynaptic differentiation are drastically impaired in its absence. Multiple alternatively spliced forms of agrin that differ in binding characteristics and bioactivity are synthesized by nerve and muscle cells. We used surgical chimeras, isoform-specific mutant mice, and nerve-muscle cocultures to determine the origins and nature of the agrin required for synaptogenesis. We show that agrin containing Z exons (Z+) is a critical nerve-derived inducer of postsynaptic differentiation, whereas neural isoforms containing a heparin binding site (Y+) and all muscle-derived isoforms are dispensable for major steps in synaptogenesis. Our results also suggest that the requirement of agrin for presynaptic differentiation is mediated indirectly by its ability to promote postsynaptic production or localization of appropriate retrograde signals.
Agrin↗
Immunnohistological assessment of intestinal eosinophil activation in patients with eosinophilic gastroenteritis and inflammatory bowel disease.
OBJECTIVE: To assess the activation grade of intestinal eosinophils in patients with eosinophilic gastroenteritis (EOG), ulcerative colitis (UC), Crohn's disease (CD), and controls by immunohistochemistry. METHODS: Cecal biopsies were collected from healthy controls and from patients with EOG, CD, UC, and other noninflammatory GI diseases. Immunohistochemistry was performed in sequential sections stained with monoclonal antibodies directed against eosinophil cationic protein (ECP) or eosinophil protein X (EPX) stored in eosinophil granules (EG1) and that secreted by activated eosinophils (EG2). The ratio of EG1 to EG2-positive eosinophils expressed as percentage of lamina propria cells was calculated. ECP and EPX were measured in serum and feces. RESULTS: The percentage of EG1 and EG2-positive lamina propria cells was elevated in EOG and slightly, but not significantly, in UC. The ratio of EG1 to EG2-positive cells was decreased in CD, UC, and other patients as compared to healthy controls. Particularly low EG1 to EG2 ratios were found in EOG. Correspondingly, fecal and serum levels of ECP and EPX, respectively, were highest in patients with EOG. The EG1 to EG2 ratio was negatively correlated with fecal ECP and EPX levels. At sites of actively inflamed mucosa, the EG1 to EG2 ratio was lower than in noninflamed tissue. CONCLUSIONS: Our data strongly suggest that the EG1 to EG2 ratio may be a marker of tissue eosinophil activation. Low ratios (<1) indicate eosinophil activation, whereas ratios > or =1 are found in healthy controls. Furthermore, we show that EOG is characterized by a pronounced intestinal eosinophil accumulation and activation, whereas in CD and UC, eosinophils seem to be activated but their number is not or only slightly elevated compared to controls.
Adult↗
Novel human erythrovirus associated with transient aplastic anemia.
Erythrovirus (formerly parvovirus) B19 causes a wide range of diseases in humans, including anemia due to aplastic crisis. Diagnosis of B19 infection relies on serology and the detection of viral DNA by PCR. These techniques are usually thought to detect all erythrovirus field isolates, since the B19 genome is known to undergo few genetic variations. We have detected an erythrovirus (V9) markedly different from B19 in the serum and bone marrow of a child with transient aplastic anemia. The B19 PCR assay yielded a product that hybridized only very weakly to the B19-specific probe and whose sequence diverged more from those of 24 B19 viruses (11 to 14%) than the divergence found within the B19 group (</=6.65%). Restriction enzyme analysis of the V9 genome revealed that this genetic divergence extended beyond the amplified region. Interestingly, serological tests failed to demonstrate a response characteristic of acute B19 infection. V9 could be a new erythrovirus, and new diagnostic tests are needed for its detection.
Amino Acid Sequence↗
Endothelin A receptor blockade causes adverse left ventricular remodeling but improves pulmonary artery pressure after infarction in the rat.
BACKGROUND: Endothelin A (ETA) receptor antagonists have been shown to improve ventricular remodeling and survival in rats when started 10 days after infarction. Whether starting them earlier would have a more or less beneficial effect is uncertain. METHODS AND RESULTS: Rats surviving an acute myocardial infarction (MI) for 24 hours (n=403) were assigned to saline or the ETA receptor antagonist LU 127043 or its active enantiomer LU 135252 for 4 weeks. Chronic LU treatment had no effect on survival, with 46% of LU rats and 47% of saline-treated rats with large MI surviving to the end of the study. LU treatment led to scar thinning, further left ventricular (LV) dilatation, an increase in LV end-diastolic pressure, and an increase in wet lung weight (P<0.05). Despite this detrimental effect on LV function, LU led to a significant decrease in RV systolic (50+/-2 to 44+/-2 mm Hg, P<0.05 vs saline) and right atrial pressures. LU treatment also prevented the increase in pulmonary ET-1 found in saline-treated rats with large MI but did not modify the increase in cardiac ET-1 in hearts with large MI. CONCLUSIONS: The early use of the ETA receptor antagonists LU 127043 or its active enantiomer LU 135252 after infarction in the rat leads to impaired scar healing and LV dilatation and dysfunction. This is accompanied by a decrease in RV systolic and right atrial pressures and a decrease in pulmonary but not cardiac ET-1 levels. It would thus appear that the early use of ETA receptor antagonists after infarction may be detrimental.
Animals↗
Detection of an erythrovirus sequence distinct from B19 in a child with acute anaemia.
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Acute Disease↗
mRNAs coding for neurotransmitter receptors and voltage-gated sodium channels in the adult rabbit visual cortex after monocular deafferentiation.
It has been postulated that, in the adult visual cortex, visual inputs modulate levels of mRNAs coding for neurotransmitter receptors in an activity-dependent manner. To investigate this possibility, we performed a monocular enucleation in adult rabbits and, 15 days later, collected their left and right visual cortices. Levels of mRNAs coding for voltage-activated sodium channels, and for receptors for kainate/alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), N-methyl-D-aspartate (NMDA), gamma-aminobutyric acid (GABA), and glycine were semiquantitatively estimated in the visual cortices ipsilateral and contralateral to the lesion by the Xenopus oocyte/voltage-clamp expression system. This technique also allowed us to study some of the pharmacological and physiological properties of the channels and receptors expressed in the oocytes. In cells injected with mRNA from left or right cortices of monocularly enucleated and control animals, the amplitudes of currents elicited by kainate or AMPA, which reflect the abundance of mRNAs coding for kainate and AMPA receptors, were similar. There was no difference in the sensitivity to kainate and in the voltage dependence of the kainate response. Responses mediated by NMDA, GABA, and glycine were unaffected by monocular enucleation. Sodium channel peak currents, activation, steady-state inactivation, and sensitivity to tetrodotoxin also remained unchanged after the enucleation. Our data show that mRNAs for major neurotransmitter receptors and ion channels in the adult rabbit visual cortex are not obviously modified by monocular deafferentiation. Thus, our results do not support the idea of a widespread dynamic modulation of mRNAs coding for receptors and ion channels by visual activity in the rabbit visual system.
Afferent Pathways↗
Hyperinnervation of neuromuscular junctions caused by GDNF overexpression in muscle.
Overexpression of glial cell line-derived neurotrophic factor (GDNF) by muscle greatly increased the number of motor axons innervating neuromuscular junctions in neonatal mice. The extent of hyperinnervation correlated with the amount of GDNF expressed in four transgenic lines. Overexpression of GDNF by glia and overexpression of neurotrophin-3 and neurotrophin-4 in muscle did not cause hyperinnervation. Thus, increased amounts of GDNF in postsynaptic target cells can regulate the number of innervating axons.
Animals↗
Hepatitis C virus genotypes implicated in mixed cryoglobulinemia.
Recent reports suggest that hepatitis C virus (HCV) might be a causative agent of mixed cryoglobulinemia. To determine whether the HCV genotype is a factor implicated in the onset of cryoglobulinemia, genotyping by direct sequencing of polymerase chain reaction products of the 5' non coding region was carried out among 45 HCV-infected patients. Genotypes 1 and 2 were found more prevalent in symptomatic cryoglobulinemia patients. Due to the presence of genotypes 4 and 5 found in this panel of French patients (9.3%), HCV genotyping based on sequence determination is recommended.
Case-Control Studies↗
Large-scale analysis of hepatitis C virus serological typing assay: effectiveness and limits.
The HCV (hepatitis C virus) Serotyping 1-6 Assay (Murex Laboratories) was evaluated on 303 French HCV-infected patients. Serological typing results were compared to the genotypes obtained from sequence analyses of the 5' noncoding regions of the virus genome from 46 HCV-infected patients, and assay specificity was found to be high (97.6%). The serological typing assay, run in 257 consecutive HCV-infected patients, yielded an assay sensitivity lower (70.6%) than that previously reported. This finding was attributed mainly to nonreactive sera from human immunodeficiency virus (HIV)-positive patients (P < 0.001) and perhaps reflected cryoglobulin positivity in others. No anti-type 6 reactivity was detected, and the overall serological type distribution values for types 1 to 5 were 67.3, 7.9, 16.4, 6.6, and 0.9%, respectively. A higher prevalence of type 4 was noted among HIV-infected patients (P < 0.001). In addition, serotype 2 was significantly more frequent in cryoglobulinemia positive than in cryoglobulinemia-negative patients (P < 0.05). Although an initial high level (7%) of mixed serological typing reactivities was found, after predilution of serum only two mixed infections could be confirmed (0.9%). It is suggested, therefore, that mixed reactivities have to be interpreted carefully and retested with prediluted serum, particularly when the optical density of the reactivity is > 2.5 or remains > 0.4 after competition with all type-specific peptides. The high specificity and relatively good sensitivity even in immunocompromised patients obtained with this assay indicate that it can be used routinely. Because response to treatment is linked to HCV type, this assay could be used to identify HCV serotype to guide therapeutic decisions.
Case-Control Studies↗