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Biomedical subjects

P Seguin

Publications and source records attributed to P Seguin.

At least 73 records · Page 4Linked to original sources
PubMed1996

Specificity and affinity of 26 monoclonal antibodies against the CA 125 antigen: first report from the ISOBM TD-1 workshop. International Society for Oncodevelopmental Biology and Medicine.

The specificity of 26 monoclonal antibodies against the CA 125 antigen was investigated in two phases of the ISOBM TD-1 workshop. The binding specificity was studied using CA 125 immunoextracted by specific antibodies immobilized on various solid phases, or on the surface of human cell lines. Immunometric assays using all possible antibody combinations were used to study the topography of antibody binding sites on the antigen. We conclude that the CA 125 antigen carries only two major antigenic domains, which classifies the antibodies as OC125-like (group A) or M11-like (group B). One antibody, OV 197, showed binding specificity related to some of the OC125-like antibodies, but was classified into a separate group C. The OC125-like group of antibodies has four subgroups with different binding specificities. These are A1 = OC 125 and K 95, A2 = K 93, A3 = B43.13, and A4 = ZS 33, B27.1 and CCD 247. Binding of nonlabelled OC 125 or K 95 to CA 125 caused a marked increase in binding of labelled OV 197 to the complex. This conformational change was not observed with any other antibody combinations. Antibody B43.13 could form immunometric assay combinations particularly with antibodies of subgroup A4, indicating that the B43.13 epitope is in the periphery of the binding area of OC125-like antibodies. The M11-like group of antibodies is more homogenous with strong cross-inhibition between most antibodies. Only one antibody, ZR 38, would form an immunoassay combination with other M11-like antibodies and thus represents a distinct subgroup. The main group of M11-like antibodies are M 11, ZR 45, MA602-6, K 91, OV 185, K 101, K 90, K 96, K 97, K 102, CCD 242, 145-9, and 130-22. Antibody OV 197 binds to a domain designated C and is unique, as stated above. Antibody pairs from any two of the three groups may be used in immunometric assays. Three antibodies were not studied by complete cross-inhibition due to low affinity (OV 198 and K 100) or lack of material (MA602-1). OV 198 and K 100 are most likely OC125-like and MA602-1 is M11-like. Antibody affinity was estimated with labelled antigen in solution or with antigen absorbed on microtiter wells. Western blot analysis showed staining both in the stacking gel and corresponding to a molecule of 200 kDa. There was a marked difference between the antibodies in their ability to bind to CA 125 immobilized on a membrane. Strongest binding was observed with the M11-like antibodies, particularly M 11, K 96, K 97, MA602-6, 145-9. Antibodies belonging to the subgroup A4 were the only OC 125-like antibodies which reacted well with CA 125 in Western analysis. Digestion of CA 125 with proteolytic enzymes showed it to be particularly sensitive to trypsin cleavage. However, no low molecular weight fragments with preserved immunoreactivity were found.

Animals↗
PubMed1996

Immunohistochemical characterization of 22 monoclonal antibodies against the CA125 antigen: 2nd report from the ISOBM TD-1 Workshop.

We evaluated the immunohistological (IH) characteristics of 22 different antibodies that were submitted for study in the frame of the TD-1 ISOBM Workshop on monoclonal antibodies against CA125. Information on relative affinities and epitope similarities was obtained from a parallel immunochemical study. Antibodies were tested at concentrations of 10 and 1 micrograms/ml on frozen and paraffin sections. Paraffin sections were stained according to the streptavidin-biotin complex protocol, and frozen sections according to a two-step immunoperoxidase technique. Aminoethylcarbazole served as the chromogen. The tissues were from normal proliferative endometrium (formalin-fixed paraffin-embedded) material and clear-cell adenocarcinoma of the ovary (formalin-fixed paraffin-embedded and frozen material). Sections were scored for staining in epithelial cells, basal, apical and diffuse cytoplasmic and in stromal components. Intensity was graded as 1, 2 or 3 for epithelial cells and as -1, -2 or -3 for stroma. The cumulative scores for each antibody expressed the discriminative properties of specific epithelial staining against background. M11 and M11-like antibodies, as well as OC125 and OC125-like antibodies, in general showed good staining results. Although there was a trend for high-affinity antibodies to show higher scores, there was no clear relationship between affinity and staining result. For nine antibodies (ZR45, MA602-1, K102, K94, K90, OV185, K97, K96, OV198), the reactions in paraffin and frozen sections were of similar intensity. Most of these were of low affinity with one exception: antibody ZR45, a rat monoclonal antibody (MAb) which had a high relative affinity. For eight antibodies (M11, K101, MA602-6, ZS33, B27.1, B43.13, K93, OC125), a loss of specific staining was observed in frozen sections. All but two of these antibodies (MA602-6 and OC125) were of high relative affinity. With four antibodies (K91, ZR38, K95, K100), the reverse situation was observed. One (K100) was of low affinity, two (K95 and K91) of high affinity and the fourth (ZR38) was a rat MAb of high affinity. Mainly due to the increased cytoplasmic staining in carcinoma, the reactivity in paraffin sections was less extensive in normal endometrium compared to ovarian carcinoma for the majority of antibodies, irrespective of their affinity or epitope group. The IH characterization of these antibodies may be of help in selecting antibodies with specific properties for further comparative studies. The reactivity of normal endometrium with all useful antibodies makes it a good candidate for standard external IH tissue control.

Adenocarcinoma, Clear Cell↗
PubMed1996

Microtiter plate immunoenzymometric assay for estrogen receptor.

The estrogen receptor (ER) status of breast cancer is used both as a prognostic factor and as a predictor of response to endocrine therapy. An immunoenzymometric assay for ER was developed on 96-well microtiter plates (EIA96). This technique involves two monoclonal antibodies directed against different epitopes in the B domain of ER. The two-step protocol (16-18 h and 3 h at 4 degrees C) requires 100 microL of cytosol. This assay showed a detection limit of 0.58 pmol/L. Intra- and interassay CVs of clinical specimens were < or = 5% except for the least concentrated sample (6.5 pmol/L, CV = 6.7%). In a comparison study involving cytosols of breast adenocarcinoma tissue biopsies, we compared the EIA96 with the radioligand assay (RLA) and the Abbott ER-EIA, widely used techniques for determining ER concentration in cytosols of breast cancer tumors. The two EIAs showed excellent agreement; however, two samples showed discrepant results by EIA96 and RLA.

Adenocarcinoma↗
PubMed1995

Successful treatment of a brain abscess due to Trichoderma longibrachiatum after surgical resection.

A case of brain abscess due to Trichoderma longibrachiatum in a leukemic patient with prolonged neutropenia is reported. Definitive cure was achieved after neurosurgical resection of the abscess and prolonged antifungal therapy. Trichoderma is a filamentous fungus species, which is only exceptionally pathogenic in humans. This genus and particularly the species Trichoderma longibrachiatum should be added to the growing list of fungi causing infection in immunocompromised patients.

Adolescent↗
PubMed1995

Assessment of urinary pyridinoline excretion with a specific enzyme-linked immunosorbent assay in normal adults and in metabolic bone diseases.

Pyridinoline (Pyr), a specific bone resorption marker, is usually assessed in urine by high-performance liquid chromatography (HPLC) after acid hydrolysis and a prepurification step. Immunoassays have been developed to measure urinary Pyr directly. Here we developed and evaluated an enzyme-linked immunosorbent assay (ELISA), specific for the urinary free Pyr form, in normal adults and in patients with metabolic bone diseases. Urinary Pyr excretion increased significantly with age for men (r = 0.288; p < 0.001) and for women (r = 0.362; p < 0.001). An average 55% increase was noted between premenopausal (n = 41) and early postmenopausal (n = 42) women (mean +/- 1 SD; 22.4 +/- 6.3 nmol Pyr/mmol creatinine and 34.7 +/- 16.8 nmol Pyr/mmol creatinine, respectively; p < 0.001). High Pyr levels were found in patients with hyperthyroidism (n = 29; 126.5 +/- 84.2 nmol Pyr/mmol creatinine), Paget's disease of bone (n = 30; 61.8 +/- 45.8 nmol Pyr/mmol creatinine), and primary hyperparathyroidism (n = 10; 57.4 +/- 23.9 nmol Pyr/mmol creatinine). In patients with Paget's disease, urinary free Pyr excretion was correlated with urinary hydroxyproline, the conventional bone resorption marker (r = 0.87; p < 0.001), and with total alkaline phosphatase, a marker of bone formation (r = 0.55; p < 0.005). Free Pyr measured by ELISA was highly correlated with total Pyr and with total deoxypyridinoline HPLC measurements in postmenopausal women (n = 35; r = 0.94 and 0.91, respectively) and in patients with metabolic bone diseases (n = 22; r = 0.91 and 0.88, respectively; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Cardiac tuberculoma; value of echocardiography and therapeutic management apropos of a case].

The authors report the case of a patient with a large mass in the right ventricle which was a tuberculoma without pulmonary disease. The severity of the right ventricular obstruction required surgical intervention with quadri-antitubercular therapy. Myocardial tuberculomas are very rare and usually reported as post-mortem findings. Only four cases resulting in cure have been previously reported. Current means of investigation such as echocardiography and endomyocardial biopsy allow rapid diagnosis of these tumours and should lead to better medical management with possible surgical intervention and a higher therapeutic success rate.

Adult↗
PubMed1994

Characterization of immunoreactive forms of human osteocalcin generated in vivo and in vitro.

Three monoclonal antibodies recognizing the 5-13, 25-37, and 43-49 sequence of the human osteocalcin were used in competitive and two-site radioimmunoassays (RIA) to characterize specifically various immunoreactive forms of circulating human osteocalcin. The intact molecule accounts for 36% of total in normals (2.6 nM), 46% in patients with osteoporosis (3.1 nM), and 26% in chronic renal failure (6.9 nM). Four fragment were detected in addition to the intact molecule in the serum of healthy adults and patients with metabolic bone disease. N-terminal, mid, and mid C-terminal fragments were present in minute amounts (each accounting for 5-14% of the total circulating osteocalcin immunoreactivity). In contrast, the N-terminal midfragment, probably resulting from the cleavage around amino acids 43-44, represents about 30% (2 nM) of the total osteocalcin immunoreactive level in normals and patients with osteoporosis and up to 50% (13 nM) in patients with chronic renal failure. This large N-terminal midfragment, representing 75-80% of the intact osteocalcin level, is not lower when the plasma assay is performed immediately after sampling (within 20 minutes at 4 degrees C with proteinase inhibitors), indicating that it circulates in vivo. In addition, this fragment was detected in the supernatant of osteoblastic cells, representing about 28% of the intact peptide. Levels of N-terminal midfragment were not changed after treatment of patients with metabolic bone disease (Paget's disease, reflex sympathetic dystrophy, fibrous dysplasia, and osteoporosis) by bisphosphonate, suggesting that it is not released during bone resorption. The osteocalcin level measured with the two-site immunoradiometric assay specific for the intact molecule or with a conventional bovine RIA was rapidly decreased after incubation of serum at room temperature (-20 and -15%, respectively, after 3 h), whereas the total level of intact osteocalcin plus N-terminal midfragment was not changed. Intact osteocalcin loss can be partially avoided by proteinase inhibitors and by incubating serum at 4 degrees C. In conclusion, we characterized multiple immunoreactive forms of osteocalcin that circulate in addition to the intact molecule, none of them being specifically altered in osteoporosis. The N-terminal midfragment circulates in a large amount, probably resulting from cleavage of the intact molecule in the circulation and/or at peripheral sites. These fragments can also be generated in vitro by proteolytic degradation of the intact molecule. To obtain reliable intact osteocalcin values but also reliable levels measured with conventional competitive RIA, careful control of the sampling conditions is warranted.

Adult↗
PubMed1994

[Liposarcoma of the head].

Cephalic localization of liposarcoma is exceptional. We report three cases, in an 87-year-old patient with liposarcoma of the tongue, a 78-year-old patient with multiple recurrent liposarcoma of the orbit and a 42-year-old patient with ethmoido-orbital liposarcoma of metastasis origin. These three cases and a review of the literature were the basis of a summary of the incidence, the anatomic classification and therapeutic options for this type of liposarcomas.

Adult↗
PubMed1994

[Amyloid disease and extreme macroglossia. Apropos of a case].

A case of extreme macroglossia was observed in a patient with amyloid disease and dysglobulinaemia. A medial diamond-shaped glossectomy was required to reduce the size of the tongue. The details of the surgical and anaesthetic procedure are presented. This type of surgery, greatly appreciated by the patient, can only be undertaken after careful preparation. The reported cases are rare and the indication for surgery is difficult due to the unpredictable nature of the local and general clinical course of the disease.

Aged↗
PubMed1992

Measurement of serum osteocalcin with a human-specific two-site immunoradiometric assay.

We developed a sensitive and specific two-site radioimmunoassay (IRMA) for human osteocalcin using human osteocalcin as a standard and two monoclonal antibodies raised against human osteocalcin purified from human cortical bone, a solid-phase anti-25-37 region and a tracer anti-5-13 sequence of the molecule. A wide range of osteocalcin levels (up to 300 ng/ml) can be measured with a sensitivity of 0.4 ng/ml. The intra- and interassay coefficients of variation are less than 4 and 6%, respectively. The recovery of human osteocalcin from serum samples ranges from 96 to 103%. IRMA was linear for serial sample dilutions in a wide range of serum osteocalcin levels, even in patients with chronic renal failure on hemodialysis. Depletion of serum in intact osteocalcin demonstrated that IRMA detects, in addition to the intact peptide, a large N-terminal midregion fragment that represents about 50% of total osteocalcin levels in normals and patients with Paget's disease and up to 75% in patients with chronic renal failure. This large fragment, previously unrecognized because it cannot be distinguished from intact osteocalcin with gel filtration chromatography, is not generated in vitro by incubation of the serum up to 26 h. We measured osteocalcin in the serum of 309 healthy adults (180 men and 129 women, age range 20-95 years), 36 patients with Paget's disease, 12 patients with primary hyperparathyroidism, 70 patients with chronic renal failure on hemodialysis, and 10 patients on corticosteroid therapy, simultaneously with human IRMA and with a conventional radioimmunoassay (RIA) based on bovine reagents. A tight correlation (r = 0.889) was observed between the two assays in the normal population, but the values obtained with IRMA were about threefold higher (mean 23.3 +/- 10.5 versus 7.5 +/- 3.4 ng/ml) than those obtained with RIA. Reported as Z scores, that is, number of standard deviations from the predicted normal mean adjusted for sex and age, these two assays (IRMA and RIA) gave concordant results in patients with Paget's disease (4.05 +/- 6.21 versus 2.41 +/- 2.53), primary hyperparathyroidism (4.14 +/- 7.17 versus 2.13 +/- 2.28), chronic renal failure (25.32 +/- 24.49 versus 6.93 +/- 5.48), and glucocorticoid treatment (-1.48 +/- 0.78 versus -1.11 +/- 0.57). However, IRMA was more discriminant from controls for all these metabolic bone diseases because the absolute values of mean Z scores with IRMA were significantly higher than those obtained with the RIA (p < 0.05-0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

[Skin aplasia of the vertex. Report of a familial form].

The authors report about a familial case of skin aplasia of the vertex cranii, of which they present a form that required emergent surgical repair with a favorable outcome. The investigation allowed tracing two relatives with minor forms expressed as alopecia of the vertex. Skin aplasia of the vertex cranii is an exceptional condition, which consists in the congenital absence of cutaneous, bony and/or dural tissue in the cranium. The various etiopathogenetic, clinical, diagnostic, evolutive and therapeutic aspects are reviewed.

Congenital Abnormalities↗
PubMed1991

[Takayasu's disease and post-traumatic scalp necrosis].

This relates the case of a 19-years old female suffering from Takayasu's disease, who sustained injury with extradural hematoma formation calling for emergent evacuation thereof. The immediate postoperative period in this neurosurgical patient was characterized by extended necrosis of the scalp and underlying bone, due to low blood supply to the head in connection with her disease. The authors review the main characteristics of this rare inflammatory arteriopathy, and point out to the multidisciplinary collaboration which prompted healing of the patient's loss of substance.

Adult↗
PubMed1990

Prediction of relapse and survival in breast cancer patients by pS2 protein status.

Application of systemic adjuvant therapy for primary breast cancer patients requires a more accurate identification of patients at high risk for recurrence. We have quantitatively assessed the cytosolic levels of estrogen-regulated pS2 protein in tumors of 205 breast cancer patients (median follow-up, 47 mo). There were no significant associations between the level of pS2 protein and tumor size, lymph node status, and differentiation grade. Using length of relapse-free survival (RFS) and overall survival (OS) as end points, 11 ng of pS2 protein/mg of cytosol protein were found as the best cutoff level to discriminate between positive (pS2+) and negative (pS2-). Patients with pS2- tumors showed significantly shorter RFS and OS (P less than 0.0001) than patients with pS2+ tumors. Also after adjustment for tumor size, lymph node status, and estrogen receptor (ER) status, pS2 negativity was associated with earlier recurrence and death. Tumors positive for pS2 (55 of 205, 27%) were almost exclusively confined to the subclass of ER+ tumors (53 of 55, 96%). The death rate for patients with pS2+ tumors was one-tenth of the death rate for patients with pS2-/ER- tumors. In the patients with ER+ tumors, the prognostic power of the pS2 status was especially present in patients whose tumors were also positive for the progesterone receptor (5-yr RFS and OS, 85% and 97% for ER+/PgR+/pS2+ tumors compared with 50% and 54% for the patients with ER+/PgR+/pS2- tumors). In patients with axillary lymph node involvement (N+), pS2 status could discriminate strongly between a good and bad prognosis group (5-yr RFS and OS, 65% and 88% for N+/pS2+ compared with 32% and 34% for N+/pS2-). A similar phenomenon was observed in patients without axillary lymph node involvement (5-yr RFS and OS, 89% and 95% for N0/pS2+ compared with 58% and 82% for N0/pS2-). We conclude that the pS2 status of human primary breast tumors is an important variable for the identification of patients at high risk for recurrence and death. Knowledge of the cytosolic pS2 status appeared of particular importance to identify patients at high risk in the ER+/PgR+ subclass of tumors, and in both the N0 and N+ subclasses of patients.

Adult↗