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Biomedical subjects

J Noel

Publications and source records attributed to J Noel.

At least 19 recordsLinked to original sources
PubMed2001

Disruption of the GluR2-NSF interaction protects primary hippocampal neurons from ischemic stress.

A specific interaction between the AMPA receptor subunits GluR2 and GluR3 and the fusion protein NSF has recently been identified. Disruption of this interaction by adenoviral-mediated expression of a peptide (pep2m) corresponding to the NSF-binding region of GluR2 results in a dramatic reduction in surface expression of AMPA receptors in primary hippocampal neurons. Here we report that expression of pep2m from a recently developed neuronal-specific adenoviral system gave significant neuroprotection to primary CA1-CA3 hippocampal neurons following stimulation with kainate (KA) and this was accompanied by a reduction in Ca(2+) influx. Protection was also observed following glucose deprivation and exposure to ischemic buffer in the absence of any NMDA receptor antagonists. These results provide strong evidence that AMPA receptors play a direct role in mediating postischemic neurotoxicity.

Animals↗
PubMed2001

Impact of surgical resection of rectovaginal pouch of douglas endometriotic nodules on pelvic pain and some elements of patients' sex life.

STUDY OBJECTIVE: To assess the impact of laparoscopic resection of endometriotic nodules in the rectovaginal pouch of Douglas on women's pain symptoms, analgesic intake, work absenteeism, work difficulties, and some elements of sex life. DESIGN: Observational study (Canadian Task Force classification II-2). SETTING: Gynecology department at a university hospital. PATIENTS: Twenty-six women with rectovaginal pouch of Douglas endometriotic nodules and no evidence of other potential cause of pain at physical examination, laparoscopy, and transvaginal ultrasonography. INTERVENTION: Laparoscopic resection of endometriotic nodules with the CO2 laser until no residual induration was felt in surrounding tissues. MEASUREMENTS AND MAIN RESULTS: Significant statistical differences were found between preoperative and postoperative pain scores, percentages of women absent from work, percentages taking analgesics or nonsteroidal antiinflammatory drugs, and percentages having work difficulties due to pain. A significant difference also was found in frequencies of sexual desire and coitus. CONCLUSION: Endometriotic nodules in the rectovaginal pouch of Douglas may be responsible for major pelvic pain and also for sexual dysfunction (lack of sexual desire, dyspareunia). Laparoscopic resection of the nodules significantly improves these conditions. (J Am Assoc Gynecol Laparosc 8(1):55-60, 2001)

Adult↗
PubMed2001

Evidence of human papilloma virus infection but lack of Epstein-Barr virus in lymphoepithelioma-like carcinoma of uterine cervix: report of two cases and review of the literature.

Lymphoepithelioma-like carcinoma (LELC) of uterine cervix is an uncommon variant of squamous cell carcinoma (SCC). We report here 2 new cases in which DNA sequences from human papilloma virus (HPV) types 16 and 18 were detected by polymerase chain reaction (PCR). To the best of our knowledge, HPV infection has not been previously described in similar cases occuring in European women. Moreover, Epstein-Barr virus (EBV), which is frequently associated with cervical LELC in Asian women, was absent in our 2 cases. These results suggest that HPVs but not EBV can play a role in the pathogenesis of LELC occuring in women originating from Western countries.

Carcinoma, Squamous Cell↗
PubMed2000

Ca2+ depletion and inositol 1,4,5-trisphosphate-evoked activation of Ca2+ entry in single guinea pig hepatocytes.

Store-operated Ca(2+) entry was investigated by monitoring the Ca(2+)-dependent K(+) permeability in voltage-clamped guinea pig hepatocytes. In physiological conditions, intracellular Ca(2+) stores are discharged following agonist stimulation, but depletion of this stores can be achieved using Ca(2+)-Mg(2+)-ATPase inhibitors such as 2,5-di(tert-butyl)-1,4-benzohydroquinone and thapsigargin. The effect of internal Ca(2+) store depletion on Ca(2+) influx was tested in single cells using inositol 1,4,5-trisphosphate (InsP(3)) release from caged InsP(3) after treatment of the cells with 2, 5-di(tert-butyl)-1,4-benzohydroquinone or thapsigargin in Ca(2+)-free solutions. We show that the photolytic release of 1-d-myo-inositol 1,4-bisphosphate 5-phosphorothioate, a stable analog of InsP(3), and Ca(2+) store depletion have additive effects to activate a high level of Ca(2+) entry in single guinea pig hepatocytes. These results suggest that there is a direct functional interaction between InsP(3) receptors and Ca(2+) channels in the plasma membrane, although the nature of these Ca(2+) channels in hepatocytes is unclear.

Animals↗
PubMed2000

K-wire position in tension band wiring of the olecranon - a comparison of two techniques.

Tension band wiring is a recognised standard treatment for olecranon fractures. We studied the effect of K-wire position on backing out of the wire in a group of 80 patients with closed transverse olecranon fractures with a minimum follow-up time of 9 months. The rate of wires backing out as seen on X-ray was three times greater in patients who had K-wires passed down the long axis of the ulna rather than across the anterior cortex as recommended by the AO group. There was a corresponding higher rate of local complications in these patients. 42% of this group had to have the metal removed compared with 11.4% of the transcortical group. We compared the biomechanical properties of both K-wires positions in a human cadaveric model. The maximum pull-out strength for each configuration was recorded in 20 elbow joints. The average maximum pullout strength for the intramedullary wires was 56.3 N (range 27. 7-95.6 N) and 122.7 N for the transcortical wires (range 56.7-201.2). The results of both the clinical study and biomechanical data support the routine use of transcortical placement of K-wires in tension-band wiring of transverse olecranon fractures.

Adolescent↗
PubMed2000

A new form of long-term depression in the perirhinal cortex.

We demonstrate a form of long-term depression (LTD) in the perirhinal cortex that relies on interaction between different glutamate receptors. Group II metabotropic glutamate (mGlu) receptors facilitated group I mGlu receptor-mediated increases in intracellular calcium. This facilitation plus NMDA receptor activation may be necessary for induction of LTD at resting membrane potentials. However, depolarization enhanced NMDA receptor function and removed the requirement of synergy between group I and group II mGlu receptors: under these conditions, activation of only NMDA and group I mGlu receptors was required for LTD. Such glutamate receptor interactions potentially provide new rules for synaptic plasticity. These forms of LTD occur in the perirhinal cortex, where long-term decreases in neuronal responsiveness may mediate recognition memory.

2-Amino-5-phosphonovalerate↗
PubMed2000

Cold weather seasonality of gastroenteritis associated with Norwalk-like viruses.

Norwalk-like viruses (NLVs) are the most common cause of acute nonbacterial gastroenteritis in adults, but little is known about their seasonality. The lack of specific diagnostic tools impeded study of these viruses in the past, and surveys using electron microscopy often grouped NLVs with other unrelated viruses. A search of the scientific literature found eight surveys of gastroenteritis, which were conducted for at least 1 year, that specifically identified NLVs. Unpublished data from laboratories of 4 NLV researchers were also used. These surveys, which were conducted in eight countries, reported sporadic cases and outbreaks of NLV-associated gastroenteritis among all age groups. The monthly occurrence of these cases and outbreaks was plotted, and while transmission occurred year-round in most surveys, a cold weather peak was demonstrated in 11 of the 12 studies. This key epidemiologic feature of the viruses has important implications concerning their mode of transmission and for understanding the etiology of acute gastroenteritis in adults.

Adult↗
PubMed2000

The epidemiology of enteric caliciviruses from humans: a reassessment using new diagnostics.

In the United States, acute gastroenteritis is one of the most commonly noted illnesses on hospital discharge records and death certificates, yet few of these cases have an etiologic diagnosis. The application of new molecular diagnostic methods has shown caliciviruses (previously referred to as the Norwalk family of viruses or small round structured viruses) to be the most common cause of acute gastroenteritis (AGE) outbreaks in the United States, and they may emerge as a common cause of sporadic cases of AGE among both children and adults. Novel molecular methods have permitted outbreak strains to be traced back to their common source and have led to the first identification of virus in implicated vehicles of infection-water, shellfish, and foods contaminated both at their source and by food handlers. The broad application of these methods to routine diagnosis in hospitals and public health laboratories is advancing our appreciation of the full burden of calicivirus-associated diarrhea, and it is opening new avenues for its prevention and control.

Acute Disease↗
PubMed2000

Smooth muscles are frequent components of endometriotic lesions.

Deep infiltrating endometriosis (deeper than 5 mm under the peritoneum) often takes the form of a nodular lesion (or 'adenomyotic nodule') consisting of smooth muscles and fibrosis with active glands and scanty stroma. Thus, among endometriotic lesions, a certain distinction is drawn between musculo-glandular lesions and glandular lesions composed of endometrial-like epithelium surrounded by a cell-producing (cytogenous) stroma. The aim of this study was to detect by immunohistochemistry, with a monoclonal antibody against muscle-specific actin, the presence of smooth muscles in 54 endometriotic lesions originating from four different pelvic locations (peritoneum, ovary, rectovaginal septum and uterosacral ligaments) and to quantify the smooth muscle content. Smooth muscles were frequent components of endometriotic lesions in pelvic locations. In addition, smooth muscles were significantly (P < 0. 001) more abundant in endometriotic lesions than in their respective unaffected sites. This finding supports, at least partially, the occurrence of a metaplastic phenomenon in the pathogenesis of endometriotic lesions. The definition of distinct endometriotic entities based on the difference in the tissue composition of the lesions (endometriotic nodules versus adenomyotic nodules) is inconsistent with the very frequent presence of smooth muscle cells in endometriosis irrespective of its localization.

Actins↗
PubMed1999

Dimerization inhibits the activity of receptor-like protein-tyrosine phosphatase-alpha.

Protein-tyrosine phosphatases (PTPs) are vital for regulating tryosine phosphorylation in many processes, including growth and differentiation. The regulation of receptor-like PTP (RPTP) activity remains poorly understood, but based on the crystal structure of RPTPalpha domain 1 we have proposed that dimerization can negatively regulate activity, through the interaction of an inhibitory 'wedge' on one monomer with the catalytic cleft of domain 1 in the other monomer. Here we show that dimerization inhibits the activity of a full-length RPTP in vivo. We generated stable disulphide-bonded full-length RPTPalpha homodimers by expressing mutants with single cysteines at different positions in the ectodomain juxtamembrane region. Expression of wild-type RPTPalpha and Phe135Cys and Thr141Cys mutants in RPTPalpha-null mouse embryo cells increased dephosphorylation and activity of Tyr 529 in the protein tyrosine kinase c-Src; in contrast, expression of a Pro137Cys mutant did not. Mutation of Pro 210/211 to leucine in the inhibitory wedge of the Pro137Cys mutant restored its ability to activate c-Src, indicating that dimerization may inhibit full-length RPTPalpha activity in a manner stereochemically consistent with RPTPalpha crystal structures. Our results suggest that RPTPalpha activity can in principle be negatively regulated by dimerization in vivo.

Animals↗
PubMed1999

A new member of the endonuclease III family of DNA repair enzymes that removes methylated purines from DNA.

DNA is constantly exposed to endogenous andexogenous alkylating agents that can modify its bases,resulting in mutagenesis in the absence of DNA repair [1,2]. Alkylation damage is removed by the action of DNA glycosylases, which initiate the base excision repair pathway and protect the sequence information of the genome [3-5]. We have identified a new class of methylpurine DNA glycosylase, designated MpgII, that is a member of the endonuclease III family of DNA repair enzymes. We expressed and purified MpgII from Thermotoga maritima and found that the enzyme releases both 7-methylguanine and 3-methyladenine from DNA. We cloned the MpgII genes from T. maritima and from Aquifex aeolicus and found that both genes could restore methylmethanesulfonate (MMS) resistance to Escherichia coli alkA tagA double mutants, which are deficient in the repair of alkylated bases. Analogous genes are found in other Bacteria and Archaea and appear to be the only genes coding for methylpurine DNA glycosylase activity in these organisms. MpgII is the fifth member of the endonuclease III family of DNA repair enzymes, suggesting that the endonuclease III protein scaffold has been modified during evolution to recognize and repair a variety of DNA damage.

Amino Acid Sequence↗
PubMed1999

Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism.

Here, we show that disruption of N-ethylmaleimide-sensitive fusion protein- (NSF-) GluR2 interaction by infusion into cultured hippocampal neurons of a blocking peptide (pep2m) caused a rapid decrease in the frequency but no change in the amplitude of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs). N-methyl-D-aspartate (NMDA) receptor-mediated mEPSCs were not changed. Viral expression of pep2m reduced the surface expression of alpha-amino-3-hydroxy-5-methyl-isoxazolepropionate (AMPA) receptors, whereas NMDA receptor surface expression in the same living cells was unchanged. In permeabilized neurons, the total amount of GluR2 immunoreactivity was unchanged, and a punctate distribution of GluR2 was observed throughout the dendritic tree. These data suggest that the NSF-GluR2 interaction is required for the surface expression of GluR2-containing AMPA receptors and that disruption of the interaction leads to the functional elimination of AMPA receptors at synapses.

Adenoviridae↗
PubMed1999

Pre-Kaposi's sarcoma: an expansion of the spectrum of Kaposi's sarcoma lesions.

We report on a lymphoedematous form of classic Kaposi's sarcoma (KS) in which characteristic purplish lesions were surrounded by atypical oedematous, flesh-coloured papules. Histological examination of these papular lesions revealed a proliferation of grouped, rather thick-walled capillaries with inflammatory infiltrates. Hot-start PCR amplification with KS 330-233 primer sequences demonstrated the presence of human herpesvirus 8 (HHV-8) sequences. In addition, cells isolated from these oedematous papules showed morphological and immunohistochemical features similar to those reported for KS-derived spindle cells. As a whole, these results suggest that these oedematous papular lesions represent pre-KS lesions and may expand the clinico-pathological spectrum of KS. The role of oedema in their induction is discussed.

Aged↗
PubMed1998

NSF binding to GluR2 regulates synaptic transmission.

Here, we show that N-ethylmaleimide-sensitive fusion protein (NSF) interacts directly and selectively with the intracellular C-terminal domain of the GluR2 subunit of AMPA receptors. The interaction requires all three domains of NSF but occurs between residues Lys-844 and Gln-853 of rat GluR2, with Asn-851 playing a critical role. Loading of decapeptides corresponding to the NSF-binding domain of GluR2 into rat hippocampal CA1 pyramidal neurons results in a marked, progressive decrement of AMPA receptor-mediated synaptic transmission. This reduction in synaptic transmission was also observed when an anti-NSF monoclonal antibody (mAb) was loaded into CA1 neurons. These results demonstrate a previously unsuspected direct interaction in the postsynaptic neuron between two major proteins involved in synaptic transmission and suggest a rapid NSF-dependent modulation of AMPA receptor function.

Amino Acid Sequence↗
PubMed1997

Outbreak of viral gastroenteritis due to a contaminated well. International consequences.

CONTEXT: Small round-structured viruses (SRSVs) are known to cause viral gastroenteritis, but until now have not been confirmed in the implicated vehicle in outbreaks. OBJECTIVE: Investigation of a gastroenteritis outbreak. DESIGN: After applying epidemiologic methods to locate the outbreak source, we conducted environmental and laboratory investigations to elucidate the cause. SETTING: Tourists traveling by bus through Alaska and the Yukon Territory of Canada. PARTICIPANTS: Staff of a restaurant at a business complex implicated as the outbreak source, convenience sample of persons on buses that had stopped there, and bus employees. MAIN OUTCOME MEASURES: Odds ratios (ORs) for illness associated with exposures. Water samples from the restaurant and stool specimens from tourists and restaurant staff were examined by nucleic acid amplification using reverse transcription polymerase chain reaction and sequencing of viral amplification products. RESULTS: The itineraries of groups of tourists manifesting vomiting or diarrhea were traced back to a restaurant where buses had stopped 33 to 36 hours previously. Water consumption was associated with illness (OR, 5.3; 95% confidence interval [CI], 2.3-12.6). Eighteen of 26 employees of the business complex were ill; although not the index case, an employee ill shortly before the outbreak lived in a building connected to a septic pit, which was found to contaminate the well supplying the restaurant's water. Genotype 2/P2B SRSV was identified in stool specimens of 2 tourists and 1 restaurant employee. Stools and water samples yielded identical amplification product sequences. CONCLUSIONS: The investigation documented SRSVs in a vehicle epidemiologically linked to a gastroenteritis outbreak. The findings demonstrate the power of molecular detection and identification and underscore the importance of fundamental public health practices such as restaurant inspection, assurance of a safe water supply, and disease surveillance.

Base Sequence↗
PubMed1997

Pre-steady-state study of recombinant sesquiterpene cyclases.

An Escherichia coli expression system was used to generate hexahistidyl-tagged plant sesquiterpene cyclases, which were readily purified by a single affinity chromatographic step. Genes for Hyoscyamus muticus vetispiradiene synthase (HVS), a chimeric 5-epi-aristolochene synthase (CH3), and a chimeric sesquiterpene cyclase possessing multifunctional epi-aristolochene and vetispiradiene activity (CH4) were expressed in bacterial cells, which resulted in the sesquiterpene cyclases accumulating to 50% of the total protein and 35% of the soluble protein. From initial velocity experiments, the Michaelis constant for HVS was 3.5 microM, while CH3 and CH4 exhibited smaller values of 0.7 and 0.4 microM, respectively. Steady-state catalytic constants were from 0.02 to 0.04 s-1. A combination of pre-steady-state rapid quench experiments, isotope trapping experiments, and experiments to measure the burst rate constant as a function of substrate concentration revealed that turnover in all three cyclases is limited by a step after the initial chemical step involving rupture of the carbon-oxygen bond in farnesyl diphosphate (FPP). Rate constants for the limiting step were 10-70-fold smaller than for the initial chemical step. Dissociation constants for the enzyme-substrate complex (20-70 microM) were determined from the pre-steady-state experiments and were significantly larger than the observed Michaelis constants. A mechanism that involves an initial, rapid equilibration of enzyme with substrate to form an enzyme-substrate complex, followed by a slower conversion of FPP to an enzyme-bound hydrocarbon and a subsequent rate-limiting step, is proposed for the three enzymes. Interestingly, the multifunctional chimeric enzyme CH4 exhibited both a tighter binding of FPP and a faster conversion of FPP to products than either of its wild-type parents.

Alkyl and Aryl Transferases↗