We have determined the nucleotide sequence of a segment of chromosome III contained in the right part of the lambda PM3270 clone, for a total of 8824 bp. This sequence contains an unusual long open reading frame, YCR601, of 6501 bp that encodes for a protein of 2167 amino acids that show no homology with other known proteins. YCR601 was disrupted by internal deletion and insertion of LEU2 gene and is a non-essential gene, however, it is transcribed during vegetative growth yielding a polyadenylated mRNA of approximately 7 kb.

Amino Acid Sequence↗

PubMedDate not supplied

Osmotic stress mimics effects of vasopressin on learned behaviour.

It has been suggested that arginine vasopressin (AVP) is involved in the retention of learned responses, in addition to its classical physiological functions of water retention and modulation of blood pressure. AVP administered subcutaneously (s.c.), intraventricularly or intracerebrally can prolong extinction of active avoidance behaviour and can enhance retention in inhibitory (passive) avoidance. These effects have been interpreted as a direct action of AVP on the central nervous system to facilitate memory consolidation. AVP also has facilitatory effects on cognitive function in humans, and marked deficits in AVP function have been associated with certain types of psychopathology. Alternative hypotheses for the behavioural actions of AVP have involved motivational constructs such as arousal, and our recent work has focused on the role of arousal resulting from the activation of peripheral visceral signals in the behavioural effects of peripherally administered AVP. The development of a specific antagonist for AVP, 1-deaminopenicillamine-2-O-methyl tyrosine arginine vasopressin (dPTyr(Me)AVP), which can reverse the behavioural effects of exogenously administered AVP, has provided a powerful tool for examining the role of AVP in the behavioural responses produced by physiological challenges known to release vasopressin. However, the relationship between the behavioural effects of exogenously administered AVP and the behavioural function of endogenously released AVP has not been evaluated. We report here that a potent peripheral osmotic stimulus, the intraperitoneal (i.p.) injection of hypertonic saline, at doses known to release AVP both centrally and peripherally, will produce behavioural effects similar to those of exogenously administered AVP. Furthermore, the prolongation of active avoidance induced by this osmotic stimulus is reversed by pretreatment with dPTyr(Me)AVP, suggesting that endogenously released AVP may also produce behavioural effects.

Animals↗

PubMedDate not supplied

Oxytocin induces morphological plasticity in the adult hypothalamo-neurohypophysial system.

The hypothalamo-neurohypophysial system offers a unique example in the adult mammalian central nervous system (CNS) of a functional and structural plasticity related to a physiological state. During lactation, oxytocin neurones evolve a synchronized electrical activation which permits pulsatile hormone release at milk ejection. At the same time, in the supraoptic (SON) and paraventricular nuclei, glial coverage of neurones diminishes, so that large portions of their surface membrane become directly juxtaposed; synaptic remodelling also associates pairs of neurones through the formation of common presynaptic terminals. These structural changes, reversible after weaning, affect exclusively oxytocinergic neurones and could facilitate their synchronized electrical activity. As several observations suggest that oxytocin itself is released centrally, we have examined the effect of prolonged intracerebroventricular infusions of oxytocin on the structure of the SON of non-lactating animals. We report here that the peptide indeed engenders the structural reorganization characteristic of the oxytocin system when it is physiologically activated. Similar infusion of vasopressin has no effect. Our observations thus demonstrate that a central neuropeptide can induce anatomical changes in the adult CNS, and suggest that oxytocin can regulate its own release by contributing to the dramatic restructuring of the nuclei containing the neurones responsible for its secretion.

Animals↗

PubMedDate not supplied

Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Rizatriptan 030 Study Group.

Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P = 0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours (P < or = 0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg (P = 0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain-free response (P = 0.032), reduction in functional disability (P = 0.015), and relief of nausea at 2 hours (P = 0.010). Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg (33%, P = 0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.

Administration, Oral↗

PubMedDate not supplied

Use of noninvasive monitoring in hemorrhagic shock.

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Adult↗

PubMedDate not supplied

MRI of esthesioneuroblastoma.

OBJECTIVE: Esthesioneuroblastomas are uncommon tumors originating in the olfactory epithelium of the superior nasal cavity. Accurate staging appropriately guides therapy and predicts survival. The MR appearance and pattern of contrast enhancement in these tumors have not been well described. The goals of this article were to analyze the MRI characteristics of esthesioneuroblastoma, including extent of tumor, differentiation from obstructive sinus disease, MR signal, and pattern of contrast enhancement. MATERIALS AND METHODS: The MR examinations of six patients with proven advanced esthesioneuroblastoma were reviewed. Standard SE T1- and T2-weighted axial images were obtained [550-600/15-25 and 2,000-2,760/80-90 (TR/TE), respectively], followed by postcontrast axial and coronal T1-weighted sequences in all patients. RESULTS: Five of the six tumors were centered in the superior nasal cavity and one was centered in the lateral ethmoid air cells. Five tumors extended intracranially. Postobstructive sinus disease was always encountered. As compared to gray matter, the signal on T1-weighted images was either hypo- or isointense. On T2-weighted images, the signal varied from iso- to hyperintensity. Contrast enhancement was intense and of variable uniformity. CONCLUSION: Magnetic resonance signal characteristics helped to distinguish obstructive sinus disease from tumor. The MR signal characteristics and pattern of contrast enhancement were nonspecific for esthesioneuroblastoma. Enhanced images, particularly in the coronal plane, were very helpful in identifying intracranial extension.

Adult↗

PubMedDate not supplied

A novel opioid mechanism seems to modulate phagocytosis in Tetrahymena.

We have previously reported that a beta-endorphin-like substance inhibits phagocytosis in Tetrahymena perhaps by a mu-like opioid receptor. We now report a further characterization of the elements involved in the signal transduction mechanism of this opioid. Affinity chromatography followed by immunoblots of both intracellular extracts and extracellular medium reveal the presence of two main proteins of 64 and 75 kDa. These molecular weights are much higher than that of any known opioid peptide or precursor protein and suggest that we may be dealing with either a novel opioid or with proteins that by chance cross-react with anti-beta-endorphin antibody. Nevertheless, when the biological activity of these proteins was tested it was found that they had an effect similar to that of mammalian beta-endorphin, namely inhibition of phagocytosis by a naloxone-reversible mechanism. We have probed a size-selected Tetrahymena library with a pro-opiomelanocortin probe and have obtained several positive clones; the sequencing of their inserts should establish whether we are dealing with a bona fide member of the opioid family. Another aspect we have been studying is the G-proteins which appear to be involved in the modulation of phagocytosis. We have found, by means of Western blotting (using an antibody against the conserved GTP-binding region of the alpha-subunit), two bands of 51 and 59 kDa; no alpha-subunit of 59 kDa had been reported previously and may represent a novel G-protein. In spite of these differences, the opioid signal transduction mechanism appears to remarkably resemble that present in more complex organisms.

Animals↗

PubMedDate not supplied

Spontaneous late carotid-cutaneous fistula following radical neck dissection: a case report.

The authors present an unusual case of a spontaneous carotid-cutaneous fistula occurring as a late complication 4 years after radical neck dissection and postoperative radiation therapy for tonsillar squamous cell carcinoma in a 50-year-old patient. The etiologic factors predisposing patients to carotid artery rupture following radical neck dissection and a surgical option for carotid artery reconstruction instead of ligation are discussed.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

c-myc, c-erb-B2, nm23 and p53 expression in human endometriosis.

We studied the expression of oncogenes and tumor-suppressor genes in human endometriosis in a retrospective pilot study. Sixteen patients with histologically verified pelvic endometriosis at the university-based tertiary care referral center were studied. Immunohistochemical determination of c-myc, c-erb-B2, nm23 and p53 expression in archival, paraffin-embedded pathological samples were used from patients operated upon for pelvic endometriosis. c-myc was expressed in 8/15 cases (53.3%). nm23 was expressed in 7/16 cases (43.7%). c-erb-B2 and p53 reactivity was undetectable in the samples studied. The c-myc oncogene and nm23 are overexpressed in many cases of endometriosis, and may play a still undefined role in its pathogenesis. Immuno-histochemistry is a useful tool for the study of oncogenic activation in this disease.

Biopsy↗

PubMedDate not supplied

Glutathione S-transferase (GSTM1 and GSTT1)-dependent risk for colorectal cancer.

BACKGROUND: The deleted GSTT1 and GSTM1 genotypes (null genotypes) resulting in loss of transferase activity are found in 10-20% and 50-60% of the population, respectively. PATIENTS AND METHODS: The GSTT1- and GSTM1-dependent risk for sporadic colorectal cancer (CRC) was studied in 247 incident CRC cases and 296 hospital-based controls. RESULTS: The GSTT1-null genotype was found to be 1.5 times more prevalent in CRC patients (17.4%) compared with controls (11.1%) (crude OR 1.6; p = 0.03). The GSTM1-null genotype was found to be equally prevalent in cases and controls (53%). Multivariate analysis showed a significant 1.7-fold risk for CRC associated with the GSTT1-null genotypes (p = 0.04) and this increased to 2.9 for smokers (p = 0.02). CONCLUSION: This study provides evidence of gene-environment interaction and illustrates the importance of further research into the role of genetic susceptibility for CRC.

Aged↗

PubMedDate not supplied

[Impregnation and liberation of nicotine with hydrogen copolymer discs].

Reticulated copolymers with products N-vinyl-2 pyrrolidone (NVP), hydroxy-2 ethyl (HEMA) and methyl methacrylate (MMA) were realized in disc form. Nicotine was used as active principle. On these discs the following study was carried out: permeation, percentage of liquid absorbed, texture, as well as nicotine release kinetics. A 2-variable (NVP and HEMA/MMA), 5-level experimental plan has enabled the outlining of the significant differences on the action of these parameters. The release kinetics show particularly that these discs behave as forms of prolonged released and that the released quantities are sufficient to envisage the use of these reticulated copolymers within the framework of a transdermal system.

Administration, Cutaneous↗

PubMedDate not supplied

[Application of the Weibull function to the study of in vivo/in vitro correlation].

After transformation of concentration-time curves by integration, the Weibull function is calculated, producing an equation for a derived function representing the plasma (or salivary) kinetics. This model can be employed in the analysis of in vivo/in vitro correlations, since cumulated dissolution percentages can be directly expressed as Weibull functions. A method was developed for prediction of salivary kinetics from in vitro dissolution data and the in vivo kinetics of a solution of the drug. This method was applied to results obtained for slow release formulations of acetaminophen and theophylline administered by the oral route.

Humans↗

PubMedDate not supplied

[Comparative study of five sustained-release theophylline preparations].

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Child↗

PubMedDate not supplied

[Diffusion of theophylline in alveolar lavage fluid].

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Bronchoalveolar Lavage Fluid↗