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Biomedical subjects

J Lefebvre

Publications and source records attributed to J Lefebvre.

At least 109 records · Page 6Linked to original sources

Specificity of the microimmunofluorescence assay for the serodiagnosis of Chlamydia pneumoniae infections.

Chlamydia pneumoniae infections are mostly confirmed using an indirect microimmunofluorescence test for which potential cross-reactions between antigens from different chlamydial species are not well documented. Using this assay, 928 sera (507 subjects) submitted for Chlamydia pneumoniae serology were tested for specific IgM and IgG to this bacteria using the TW-183 antigen. IgM and IgG reactivities to Chlamydia trachomatis serotypes C, D, E, and L2 and Chlamydia psittaci strain 6BC antigens were also tested. A sample was interpreted as positive only when evenly fluorescent elementary bodies were observed. Twenty-five subjects (4.9%) showed serological evidence of recent Chlamydia pneumoniae infection (IgM positive and (or) IgG seroconversion); 11 of them also showed serological evidence of recent infection with at least one other chlamydial species. Specificity was 50 and 63% for IgM and IgG detection, respectively. These results suggest that mixed or temporally related infections might occur, or, more likely, that some Chlamydia pneumoniae IgM or IgG reactivities might be due to heterotypic antibodies.

Adolescent↗

Normal hemodynamic and coagulation responses to 1-deamino-8-D-arginine vasopressin in a case of lithium-induced nephrogenic diabetes insipidus. Results of treatment by a prostaglandin synthesis inhibitor (indomethacin).

The effect of 1-deamino-8-D-arginine vasopressin (DDAVP) on mean arterial pressure, pulse rate (PR), plasma renin activity (PRA), plasma factor VIIIc and von Willebrand factor were studied in a case of persistent lithium-induced nephrogenic diabetes insipidus (LINDI). 20% decrease in MAP, 22% increase in PR, 100% in PRA, and release of coagulation factors (2- to 3-fold) were noticed after infusion of 0.3 micrograms/kg DDAVP. Urinary prostaglandin (PG) E2 were enhanced. The treatment of this LINDI by PG synthesis inhibitor (PSI) combined with a low osmotic diet (LOD) led to a 51% fall in urine volume, 57% in free water clearance and 75% in sodium clearance. Urinary osmolality rose by 42% but remained low, probably in part because of the LOD. Urinary PGE2 was about one fifth of the initial high value. The results argue for (1) an end-organ resistance to DDAVP confined to the kidneys in LINDI and (2) an effectiveness of indomethacin combined with an LOD.

Adult↗

Prospective trial on captopril-related cough.

OBJECTIVE: Quantify and characterize cough as an adverse reaction secondary to captopril. DESIGN: Cohort analytic study: six-month prospective trial including two-week, placebo, run-in period; five-month, single-blind, active treatment; and two-week, dechallenge period. SETTING: Outpatient clinic. PATIENTS: 199 previously treated or newly diagnosed untreated patients with mild to moderate hypertension. INTERVENTIONS: Captopril 50 mg/d during five months. OUTCOME MEASURES: Self-questionnaires, interviews, dechallenge, and rechallenge periods. Naranjo's algorithm. RESULTS AND CONCLUSIONS: (1) Cumulative incidence of captopril-induced cough over a five-month period was 7.1 percent (95 percent C.I., 6.8-7.4 percent). Incidence of drug withdrawal secondary to severe cough was 1.0 percent; this figure is somewhat similar to first reports about the reaction. (2) Cough was a generally mild to moderate symptom, present day and night in 71.4 percent of patients and resistant to antitussive agents. Cough was not statistically related to sex, age, or smoking habit; however, the female gender and the development of a common cold may be predisposing factors.

Adolescent↗

Estradiol, progesterone and testosterone exposures affect the atrial natriuretic peptide gene expression in vivo in rats.

To clarify the effects of sex hormones on the expression of atrial natriuretic peptide (ANP), ovariectomized and intact female rats were subcutaneously injected with estradiol, progesterone, a mixture of them or olive oil solvent; castrated and untouched male rats were subcutaneously injected with estradiol, testosterone or olive oil, once a day for 7 days. The relative rANP-mRNA contents of rat atrial were measured by molecular hybridization. rANP-cDNA was labeled with 32P as a probe. The results revealed that estradiol and progesterone increased ANP gene expression. Furthermore their effects were associated with administration dose of these hormones and it was shown that they are probably coordinated. The physiological amounts of estradiol and progesterone may maintain suitable levels of rANP-mRNA and androgen may also increase the ANP gene expression in vivo. These experiments suggested that female sex hormone may have a dual purpose in fluid balance.

Animals↗

Cytogenetic and molecular investigations of an abnormal Y chromosome: evidence for a pseudo-dicentric (Yq) isochromosome.

A derivative Y chromosome was found in a 55-year-old man with Lambert-Eaton paraneoplasic pseudomyastheniform disease. Small testicles, azoospermia were noticed and hormonal level values were as in the Klinefelter syndrome. A 45,X/46,XYp+ mosaïcism was described on peripheral blood lymphocytes. Cytogenetic investigations with R-G-C- and Q-banding have been performed. In situ hybridization with the GMGY 10 DNA probe showed two copies of proximal Yp sequences. Southern blot analyses were performed using the Y DNA probes 27a, 47z, 64a7, 50f2 disclosing specific Yp and Yq sequences from the pseudoautosomal boundary to the Yq proximal portion. The der(Y) has been defined as a dicentric isochromosome for the long arm with one active and one apparently suppressed centromere. The breakpoint leading to the der(Y), has been located in the pairing segment of the Y short arm (i.e. Yp11.32). So the der(Y) was interpreted as a psu dic(Y) (qter-->cen-->p11.32 ::p11.32-->qter). There was thus an almost complete duplication of the Y chromosome.

Blotting, Southern↗

[Adenocarcinomatous pleural lesion associated with hypoglycemia].

We report the case of a patient suffering from a glandular pleural lesion. The evolution of the disease was punctuated by periods of hypoglycaemia, which caused a coma. There was no clinically evident explanation for these hypoglycaemic episodes. Investigations revealed adrenal failure, but this adrenal failure was unrelated to the neoplastic process in the patient. This case is a reminder that the cause of hypoglycaemia associated with tumours can really have a paraneoplastic origin and justifies an in depth study to achieve an aetiological diagnosis.

Adenocarcinoma↗

Chlamydia trachomatis cervical infection: prevalence and determinants among women presenting for routine gynecologic examination.

OBJECTIVE: To determine the prevalence of and risk indicators for Chlamydia trachomatis cervical infection among women presenting for a periodic medical examination. DESIGN: Prevalence study. SETTING: Centre local de services communautaires (CLSC) Saint-Louis du Parc, Montreal. PATIENTS: All women presenting for a routine gynecologic examination from May 1985 to July 1986. Of the 773 (99%) who agreed to participate 56 were excluded because of inadequate diagnostic tests (34), antibiotic intake in the preceding 6 weeks (19) or loss to follow-up after the initial visit (3). OUTCOME MEASURES: Culture was the diagnostic standard, but rapid diagnostic tests were also used. From the identified cases logistic regression analysis was used to evaluate the following risk indicators: age, place of residence, use of oral contraceptives, sexual partners and frequency, history of sexually transmitted disease (STD) and abnormalities found on genital examination. MAIN RESULTS: Fifty-one of the women were found to have C. trachomatis infection, for a prevalence rate of 7.1%; 32 (63%) were completely asymptomatic. Three independent indicators were found: age of 25 years or less (odds ratio [OR] 3.2, 95% confidence limits [CL] 1.8 and 5.9), cervical erythema, contact bleeding or mucopurulent exudate (OR 2.5, 95% CL 1.4 and 4.5) and residency in the CLSC area (OR 2.3, 95% CL 1.1 and 5.1). A history of STD or vaginitis had a significant protective effect in women 30 years of age or more (OR 0.2). CONCLUSIONS: Case-finding for chlamydial infection could be an effective public health measure among women 25 years of age or less and among those with signs of cervicitis when they present for a Papanicolaou test.

Adolescent↗

Cyclic AMP stimulation of transferrin secretion by breast cancer cell grown on extracellular matrix or in two-compartment culture chambers.

Extrahepatic synthesis and secretion of transferrin (Tf), the major iron-carrying protein, have been described in normal and tumoral tissues suggesting a potential role for paracrine or autocrine function. In breast tumor cell MCF-7, we have previously shown a Tf secretion stimulated by estradiol which might confer selective growth advantages of these rapidly proliferating cells. The present work refers to possible additional Tf functions related to differentiation of breast tumor cells. We induced MCF-7 cell differentiation by the cyclic AMP derivative, dibutyryl cAMP (dB cAMP) and studied Tf secretion in different culture conditions after labeling with [35S] methionine. Our results demonstrate that dB cAMP stimulates Tf secretion only in culture environment that permits access to the basolateral surface and caters to the polarity requirements of the cell. These results suggest that Tf may also act as a modulator of cellular differentiation in breast cancer cells.

1-Methyl-3-isobutylxanthine↗

Hypothyroidism following combined treatment for hypopharyngeal and laryngeal carcinoma.

The development of hypothyroidism following combined treatment for pharyngeal and laryngeal cancer has received little attention in the literature. We prospectively studied 32 patients over 4 years to determine the incidence of such hypothyroidism and to examine the effect of hemithyroidectomy associated with a combined treatment modality. All patients were men with pharyngeal or laryngeal squamous cell carcinomas and no prior history of thyroid disease. Treatment consisted of radical surgery (30 of 32 patients), followed by postoperative radiotherapy (31 patients). The results of thyroid function tests (free triiodothyronine, free thyroxine, and thyroid-stimulating hormone [TSH]) were all normal preoperatively; tests were repeated every 3 months after treatment. Elevation of TSH values in two successive blood samples was required to make a diagnosis of hypothyroidism. Of 12 patients who underwent hemithyroidectomy as part of total pharyngolaryngectomy and postoperative radiotherapy, 7 became hypothyroid a mean of 6 months after treatment. Twenty patients had similar combined treatment but without thyroid resection. Hypothyroidism developed a mean of 10 months after treatment in only four patients in this group (p less than 0.05). We conclude that hypothyroidism frequently develops following combined treatment for pharyngeal and laryngeal cancer even when thyroid resection has not been performed. Patients should be evaluated postoperatively and carefully monitored by means of serial thyroid function tests.

Carcinoma, Squamous Cell↗

Early hypopituitarism following cavernous sinus thrombosis: total recovery within 1 year.

Hypopituitarism related to cavernous sinus thrombosis is a very rare event which usually occurs at least 1 year after the acute stage. We report a case which distinguished itself from the previously reported cases through (i) its occurrence during the acute stage and (ii) its total recovery within 1 year. Early anterior hypopituitarism is probably more frequent than expected on the basis of reported cases and it may contribute to the high rate of mortality in cavernous sinus thrombosis. This underscores the need to consider hypopituitarism in every patient with cavernous sinus thrombosis.

Adult↗

[Pseudo-hyperkalemia. Apropos of a familial case].

One case of pseudo-hyperkalaemia is reported in a women who suffered of labile hypertension and was previously treated by fluorohydrocortisone because of hyperkalaemia. Clinical examination and ECG were normal. An incubation test performed at different temperatures confirmed the diagnosis. There was no haematological abnormality. Familial screening prompted us to discover 2 affected subjects among four studied, according to autosomal dominant inheritance. This abnormality was due to increased passive membrane permeability to potassium at low temperature out of any hematological syndrome. The diagnostic is important to avoid inappropriate medications.

Aged↗

Insulin-like growth factor 1 receptors (IGF1-R) and IGF1 in human breast tumors.

To appreciate the IGF1 sensitivity of breast tumors we detected IGF1-R with a biochemical assay (RRA). We then localized and quantified IGF1-R on frozen tissue sections by histo-autoradiographic analysis (HAA). In some cases, the IGF1 and IGF1-R mRNA expression were studied by Northern blot analysis. We also studied the IGF1 plasma concentration in primary breast cancers compared to controls. IGF1-R (RRA) were found in 87% (n = 297) of the breast cancers. The mean geometric value was 3.87% (specific binding as percentage of total radioactivity); we found a highly significant correlation between IGF1-R and ER on the one hand (P = 0.0001) and PgR on the other (P = 0.0001) (Spearman test). The presence of IGF1-R was associated with a better prognosis, either on relapse-free survival (actuarial analysis: P = 0.004; Cox analysis: P = 0.005) or overall survival (respectively P = 0.003; P = 0.005). The median duration of follow-up was 30 months. By Cox analysis IGF1-R was a better prognostic factor than ER and PgR. In a series of 77 cases of benign breast disease only 47% (36/77) were positive; the mean geometric level was 1.8%. The HAA IGF1-R quantification in 20 breast carcinomas and 12 cases of benign breast disease confirmed the RRA results and demonstrated that the labeling was localized on the epithelial component. In four breast cancers, we did not detect IGF1 mRNA; IGF1-R probe demonstrated two major mRNAs of 11 and 7 kB. Finally we found that IGF1 plasma level was higher in breast cancer patients than in healthy controls of the same age. These results show that IGF1 is implicated in breast cancer growth and suggest that anti-IGF1 treatment might be useful in human breast cancer: for this reason, we and others carried out a phase II clinical trial with somatostatin.

Autoradiography↗

Bifunctional thrombin inhibitors based on the sequence of hirudin45-65.

The interaction of alpha-thrombin with the hirudin (HV1) fragment N alpha-acetyl desulfo hirudin45-65 (P51) was investigated. Kinetic analysis revealed that P51 inhibits the proteolysis of a tripeptidyl substrate with Ki = 0.72 +/- 0.13 and 0.11 +/- 0.03 microM for bovine and human alpha-thrombins, respectively. The inhibition was partially competitive, affecting substrate binding to the enzyme-inhibitor complex by a factor alpha = 2 (bovine) and alpha = 4 (human) characteristic of hyperbolic inhibitors. P51 also inhibited thrombin-induced fibrin clot formation with IC50 values of 0.94 +/- 0.20 and 0.058 +/- 0.006 microM for bovine and human alpha-thrombins, respectively. The enhanced antithrombin activity for human thrombin could be attributed to species variations in the putative auxiliary "anion" exosite since N alpha-acetyl desulfo hirudin55-65 displayed the same rank order of potency shift in a clotting assay without inhibiting the amidolytic activity of either enzyme. From these observations, a potent thrombin inhibitor was designed having modified residues corresponding to the P1 and P3 recognition sites. N alpha-Acetyl[D-Phe45, Arg47] hirudin45-65 (P53) emerged as a pure competitive inhibitor with a Ki = 2.8 +/- 0.9 nM and IC50 = 4.0 +/- 0.8 nM (human alpha-thrombin) and is designated as a "bifunctional" inhibitor. Its enhanced potency could be explained by a cooperative intramolecular interaction between the COOH-terminal domain of the inhibitor and the auxiliary exosite of thrombin on the one hand, and the modified NH2-terminal residues with the catalytic site on the other.

Amino Acid Sequence↗

Functional beta-adrenergic receptors in breast cancer cells.

Using L-[3H]dihydroalprenolol [( 3H]DHA), a potent beta-adrenergic antagonist, we demonstrated in breast cancer cells the presence of beta-adrenergic receptors with high affinity (Kd 1-9 nM) as shown by Scatchard analyses. Natural and synthetic agonists inhibited the [3H]DHA binding in the following order of potency: L-isoproterenol = L epinephrine much much greater L-norepinephrine, identical to the well-established order of potency for these compounds in producing beta-adrenergic responses. We verified that these compounds actually stimulated cAMP production in breast cancer cells. At the present time, the pathophysiological significance of beta-adrenergic receptors remains unclear. In view of the importance of cAMP in lactose production and in tumor growth mechanisms, it seems to be important to characterize the beta-adrenergic receptors in breast cancer cells in more detail and study their possible involvement in breast tumor growth.

Breast Neoplasms↗

Secretion of transferrin by human breast cancer cells.

Transferrin (Tf), the major iron-binding protein in the plasma of vertebrate species is an essential growth factor for cells in serum-free media and appears to be involved in the regulation of growth and differentiation of human tissues. We report here that human breast cancer cells secrete a factor immunologically similar to Tf. The secretion of Tf by the hormone-responsive cell-line MCF-7 is stimulated by 17 beta-estradiol and reduced by the antiestrogen 4-hydroxy tamoxifen. These data suggest that Tf secreted by breast cancer cells may be an additional autocrine growth factor confering selective advantages to rapidly proliferating breast cancer cells and perhaps permit tumor cell growth in poorly vascularized areas.

Breast Neoplasms↗

Structure of citrus pectins and viscometric study of their solution properties.

Citrus pectins with degrees of methylation between 30 and 72% were carefully characterized in order to determine their charge density and molecular weight distribution, the content in galacturonic acid and in neutral sugars, the degree of methylation and acetylation. Using enzymic degradation it has been found that pectin molecules consist mainly of long homogalacturonan regions with some regions of neutral sugars as side chains attached on rhamnose residues. The viscometric behaviour of the different samples indicates that 0.1 M NaCl, at 25 degrees C, is a good solvent of sodium pectinates. From the evolution of the Huggins parameter, it appears that pectins with 50% of methylated galacturonic groups exhibit a maximum flexibility. A Mark-Houwink exponent of 0.8 has been found in good agreement with theoretical predictions for flexible polymers in a good solvent.

Acetylation↗

Opposite effects of estrogen and catecholestrogen on hormone-sensitive breast cancer cell growth and differentiation.

Catecholestrogens and especially 2-hydroxyestrone (2OH-E1) are estradiol metabolites locally formed in breast cancer cells. The present study demonstrates that the two parent compounds, estradiol (E2) and its metabolite 2OH-E1, exert opposite effects on hormone-sensitive breast cancer cell growth assessed by cell counts and transferrin receptor levels, and also on cell differentiation assessed by secreted proteins such as alpha-lactalbumin and gross cystic disease fluid protein (GCDFP-15). The present findings may highlight estradiol regulation in hormone-sensitive breast cancer cells.

Breast Neoplasms↗