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At least 19 recordsLinked to original sources
PubMed1989

Couture v. Couture.

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Advance Directives↗
PubMed1999

A new approach to the synthesis of efaroxan.

Efaroxan was synthetised by cyclisation of the tertiary alcohol 2 which was prepared by the ring opening of the gem-disubstituted epoxide 3 with ortho-metallated fluorobenzene.

Adrenergic alpha-Antagonists↗
PubMed1995

High-level expression of recombinant porcine LH receptor in baculovirus-infected insect cells or caterpillars.

Porcine LH receptor ectodomain was overexpressed in insect cells and lepidopteran larvae using the recombinant baculovirus expression system. A low multiplicity of infection yielded the largest active production, of approximately 10(7) receptors/cell or 3 micrograms active receptor/mg total protein in infected cells. The truncated ectodomain solubilized with Triton X-100 bound its ligand with a high affinity which was comparable with that of the native membrane receptor. Increasing the multiplicity of infection resulted in an optimum protein production of 0.6 mg receptor/mg total protein in infected cells. This receptor was largely inactive, probably trapped within aggregation pools. Active receptor could be recovered by dilution of the samples. No secretion of recombinant receptor was ever observed whatever the conditions of infection. Expression of the recombinant receptor in insect larvae was also tested. This low-cost system failed both to increase the amount of active receptor and to induce secretion into the haemolymph. Two methods remain for producing sizeable amounts of active receptor with this baculovirus/insect cell system. One relies on immunoaffinity purification of the active protein and requires large-scale production, and the other is based on the purification of overexpressed inactive receptor followed by renaturation.

Amino Acid Sequence↗
PubMed2003

Histopathology of bronchiolar disorders.

Bronchiolar pathologic lesions result from the interplay between inflammatory and mesenchymal cells following injury to bronchioles. Offending agents include viruses, bacteria, fungi, cigarette smoke, toxic inhalants, inorganic dusts, allergens, and systemic or localized autoimmune or inflammatory processes. Bronchiolar pathologic lesions also arise in the context of allograft transplantation and pathology of the large airways and in the setting of an idiopathic disorder. Given the great variety of sources of injury and diversity of clinical, radiological, and functional patterns that result, it is no surprise that most morphological abnormalities of the bronchioles are not specific. They thus represent a diagnostic challenge to the surgical pathologist, and the necessity of a multidisciplinary (clinical/radiological/pathologic) approach cannot be overemphasized. After a survey of the normal histology of bronchioles, we present a pragmatic classification that reflects the spectrum of bronchiolar pathology, illustrating the intimate interdependence of clinical, radiological, and pathologic findings in assessing the significance of bronchiolar lesions. This classification is intended to be applicable to surgical pathology material that can be correlated with clinical disease syndromes. It includes asthma-associated bronchiolar changes, chronic bronchitis/emphysema-associated bronchiolar changes, cellular bronchiolitis, respiratory bronchiolitis, bronchiolitis obliterans with intraluminal polyps/ BOOP, constrictive bronchiolitis, mineral dust small airway disease, peribronchiolar fibrosis and bronchiolar metaplasia, and bronchiolocentric nodules.

Journal Article↗
PubMed1989

A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors.

We conducted a randomized, double-blind, placebo-controlled trial of postoperative therapy with tamoxifen (10 mg twice a day) in 2644 patients with breast cancer, histologically negative axillary nodes, and estrogen-receptor-positive (greater than or equal to 10 fmol) tumors. No survival advantage was observed during four years of follow-up (92 percent for placebo vs. 93 percent for tamoxifen; P = 0.3). There was a significant prolongation of disease-free survival among women treated with tamoxifen, as compared with those receiving placebo (83 percent vs. 77 percent; P less than 0.00001). This advantage was observed in both the patients less than or equal to 49 years old (P = 0.0005) and those greater than or equal to 50 (P = 0.0008), particularly in the former, among whom the rate of treatment failure was reduced by 44 percent. Multivariate analysis indicated that all subgroups of patients benefited. Tamoxifen significantly reduced the rate of treatment failure at local and distant sites, tumors in the opposite breast, and the incidence of tumor recurrence after lumpectomy and breast irradiation. The benefit was attained with a low incidence of clinically appreciable toxic effects. The magnitude of the improvement obtained does not preclude the need for future trials in which patients given tamoxifen could serve as the control group in an evaluation of potentially better therapies. Tamoxifen treatment is justified in patients who meet the eligibility criteria of the present study and who refuse to participate in those trials. Since patients with tumors too small for conventional analysis of estrogen-receptor and progesterone-receptor concentrations were not eligible for this study, no information is available to indicate that such patients should receive tamoxifen.

Adult↗
PubMed1989

Systemic therapy in patients with node-negative breast cancer. A commentary based on two National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials.

OBJECTIVE: To determine whether in the previous National Surgical Adjuvant Breast and Bowel Project (NSABP) studies of node-negative breast cancer there were either cohorts of patients with a prognosis favorable enough to preclude using systemic therapy or subsets of patients who failed to benefit from the treatments. DESIGN: Randomized clinical trials with stratification after surgery. SETTING: NSABP trials at institutions in the United States and Canada. PATIENTS: Data were collected on 731 eligible patients (Protocol B-13) with estrogen-receptor-negative tumors who randomly received either no therapy after surgery or sequential methotrexate and fluorouracil (M----F) followed by leucovorin. Data were also collected on 2834 patients (Protocol B-14) with estrogen-receptor-positive tumors who randomly received either placebo or tamoxifen treatment. The percentage of patients surviving disease-free was determined through 4 years of follow-up using life-table estimates. INTERVENTIONS: Protocol B-13 patients received 12 courses of M----F given intravenously on days 1 and 8 every 4 weeks. Leucovorin therapy was begun 24 hours after M----F administration. Protocol B-14 patients received 5-year treatment with either tamoxifen (10 mg twice daily by mouth) or placebo. RESULTS: When the outcome of untreated patients in either trial was related to the stratification variables, women were found to have a disease-free survival of less than 80% through 4 years of follow-up. This percentage is apt to decrease because the probability of treatment failure increases with time. In both trials, all subsets of women benefited from M----F or tamoxifen therapy. CONCLUSIONS: The disease-free survival of all cohorts of node-negative patients with estrogen-receptor-negative or estrogen-receptor-positive tumors was poor enough to justify systemic treatment. The benefits of the therapies used are insufficient to eliminate the need for assessing putatively better regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Reconstitution of a high-affinity functional lutropin receptor by coexpression of its extracellular and membrane domains.

The glycoprotein hormone receptors differ from other G protein-coupled receptors by their large extracellular domain which mediates ligand binding. Cooperation between the G-protein coupled membrane domain, the extracellular domain and the hormone in establishing high-affinity binding and efficient transduction is likely to exist. Expression plasmids encoding the full-length porcine LH-hCG receptor (1-696), its extracellular (1-297) and membrane domain (298-696), as well as the alpha and beta subunits of hCG were constructed. We report that coexpression in COS cells of the two LH-hCG receptor domains restores cell surface high-affinity hormone binding and hormone dependent adenylyl cyclase activation, suggesting sufficient interactions between the two receptor domains to reconstitute a complete functional molecule. Moreover, the two hormone subunits and the two receptor domains are able to associate within coexpressing COS cells into an active complex.

Adenylyl Cyclases↗
PubMed1993

Suppression of fertility in male mice by immunization against LH receptor.

We have investigated the potential contraceptive effects of immunization against the luteinizing hormone (LH) receptor in male mice at the prepubertal stage. Two N-terminal fragments of the porcine LH receptor encoding amino acids 1-297 and 1-370 were produced in large quantities through the Baculovirus insect cell system. We have immunized three-week-old mice from two Balb/c stocks of differing fecundity with Sf9 insect cells producing the short (1-297) or long (1-370) recombinant LH receptor. A booster injection was performed at six weeks using purified antigens. Ten days later, the immunized male mice were mated over a period of two weeks with adult untreated females. After weaning of the first litters, the same partners were mated once again under the same conditions. There was no decrease in the antiserum titers against the antigens over a two-month period. The circulating testosterone decreased as the anti-LH receptor antibodies increased. The fertility of the treated male mice was reduced up to 75%, depending on the mouse stock, the antigen used and the time separating immunization and mating. The impaired fertility was mostly due to male sterilization (up to 60% of sterile mates). The delay between mating and birth was enhanced by the treatment, reflecting delayed fertility and/or delayed male behaviour acquisition.

Animals↗
PubMed1995

The porcine follitropin receptor: cDNA cloning, functional expression and chromosomal localization of the gene.

The porcine follitropin receptor-encoding cDNA (pFSHR) was cloned using reverse transcription-polymerase chain reaction (RT-PCR). Total RNA from porcine granulosa cells was used as template. Two overlapping cDNA fragments encoding, respectively, aa 1 to 290 and aa 191 to 694 of the pFSHR were obtained. Taken together, the two fragments represented the whole coding sequence, assuming a comparable length for the FSHR from the porcine, rat and human species. Functionality of the cloned receptor was assessed by expression experiments; COS cells transfected with the pFSHR cDNA exhibited high-affinity specific binding for [125I]hFSH and FSH-dependent cAMP production. The primary sequence of the porcine FSHR N-terminal hormone-binding domain showed high percentages of identity with the sequences from ovine, human, and rat origins. A truncated form of the pFSHR cDNA, lacking aa 75 to 124 in the N-terminal domain, was also cloned and sequenced. A PCR-derived cDNA fragment of 1.45 kb was used as gene-specific hybridisation probe to map the pFSHR-encoding gene by radioactive in situ hybridization. This gene was found co-localized (as in human) with the porcine lutropin hormone receptor (pLHR)-encoding gene on the q2.2-q2.3 region of pig chromosome 3.

Amino Acid Sequence↗
PubMed1997

Effect of angiotensin II on a spinal nociceptive reflex in the rat: receptor and mechanism of action.

The effect on thermonociceptive threshold of intrathecally (i.t.) administered angiotensin II (Ang II) was assessed in the rat tail-flick test. Rats were pretreated, 15 min earlier, with i.t. naloxone (opiate antagonist), losartan (Ang II selective antagonist at AT1 receptor) or [Sar1, Leu8] Ang II (non selective Ang II receptor antagonist) to define the mechanism of action and the nature of the receptor subtype. Ang II (0.65-6.5 nmol) induced antinociceptive effects that peaked at 1 min post-injection and returned to baseline after 5-10 min. Naloxone (10 microg) completely inhibited the response to 6.5 nmol Ang II. Losartan (65 pmol) and [Sar1, Leu8] Ang II (6.5 nmol) blocked the antinociception induced by Ang II but were inactive against [MePhe7]neurokinin B. Furthermore, losartan failed to affect the hyperalgesic responses induced by substance P (6.5 nmol) or [beta-Ala8]neurokinin A (6.5 nmol). This study provides the first functional evidence that Ang II inhibits the transmission of thermal nociceptive information through an endogenous opioid mechanism and the activation of an AT1 receptor in the rat spinal cord.

Angiotensin II↗
PubMed2002

[Distal radial-ulnar arthrosis and radial-carpal arthrosis: evaluation on a population from the end of the 15th century to the beginning of the 18th century].

The authors report on a study on the wrists from a medieval population (end of the 15th-century, beginning of the 18th century). The distal radio-ulnar arthrosis and the radio-carpal arthrosis were assessed after a macroscopic examination of the wrist bones. Statistical treatment of the data led to correlations with age, sex and bilateral nature of injuries. The distal radio-ulnar arthrosis has statistic correlation with age (P < 0.05). There is no relationship between sex and bilateral nature of injuries. For the radio-carpal arthrosis, injuries are often present for elderly woman (P < 0.01) and young man (P < 0.05). The bilateral nature of arthrosis increases with age (P < 0.05). The wrists which are damaged by the distal radio-ulnar arthrosis are often associated with radio-carpal injuries (P < 0.05). The absence of any obvious osseous traumatic aetiology suggests a bilateral ligamentous distension for women and elderly men. A traumatic ligament rupture can be incriminated for young men maybe related to repeated microtraumatic activities.

Adolescent↗
PubMed2004

Induction of infertility in adult male bonnet monkeys by immunization with phage-expressed peptides of the extracellular domain of FSH receptor.

Active immunization of proven fertile adult male bonnet monkeys (Macaca radiata) with phage-expressed follicle-stimulating hormone receptor (FSHR)-specific peptides from the extracellular domain resulted in a progressive drop in sperm count with all animals becoming azoospermic by day 100. However, serum testosterone concentrations were unaltered during the entire course of study and animals exhibited normal mating behaviour. Breeding studies with proven fertile female monkeys revealed that all the immunized males were infertile. Following interruption of immunization on day 225, sperm counts returned to normal with restoration of fertility. These results indicate that infertility can be induced in adult male monkeys by interfering with the action of FSH using specific peptides of the extracellular domain of FSHR as antigens, without the risk of producing cross-reacting antibodies to the other glycoprotein hormones.

Animals↗