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Biomedical subjects

M Weil

Publications and source records attributed to M Weil.

At least 91 records · Page 5Linked to original sources

Schistosoma mansoni antigens recognized in Biomphalaria glabrata hemolymph by monoclonal antibodies.

In order to identify and characterize Schistosoma mansoni antigens in Biomphalaria glabrata, we examined 19 murine monoclonal antibodies (Mabs) for specific binding to schistosome larvae. None of the murine Mabs induced by infection or by immunization with a crude cercarial antigen (CCA) served this purpose. Two Mabs out of 9 (KCSme22-3 and KCSme22-4) induced by soluble egg antigens reacted with CCA but not with normal snail (NSN) extract. We selected these 2 for studies on detection and characterization of schistosomal antigens in snails. When employed in an ELISA, they differentially detected schistosomal antigens in extracts and cell-free hemolymph (plasma) of infected snails. The selected Mabs bind to cercarial surface as demonstrated by the indirect fluorescent antibody technique (IFAT) with paraformaldehyde-fixed cercariae. The epitopes corresponding to the selected Mabs are periodate sensitive, suggesting the glycoprotein nature of the antigens recognized. Immunoblotting analysis employing the selected Mab revealed 1 antigen in CCA (Mr = 205 kDa) and 3 antigens in snail plasma (Mr = 220 kDa, 180 kDa, and 135 kDa). Schistosomal antigens were first detectable in the snails' plasma 2 weeks after snail infection, and their quantity increased afterwards.

Animals↗

Identification of snails infected with schistosomes by ELISA employing monoclonal antibodies: Schistosoma mansoni in laboratory snails (Biomphalaria glabrata) and in field snails (Biomphalaria pfeifferi) from Kenya.

An enzyme-linked immunosorbent assay (ELISA) employing monoclonal antibodies was used for detecting Schistosoma mansoni antigens in hemolymph of laboratory snails (Biomphalaria glabrata) in Kenya. Infected laboratory snails shedding cercariae were differentially identified by ELISA from uninfected snails with 100% sensitivity and specificity. Prepatent infections were detected by ELISA from 2 weeks after exposure to miracidia. Thus, ELISA revealed infection 3 weeks before maximal patency was reached (5-6 weeks post-exposure). Infected field snails (B. pfeifferi) shedding cercariae were differentially identified by ELISA, with 100% sensitivity and specificity, from uninfected field snails and from snails naturally infected with other trematodes (echinostomes and strigeids). Prepatent infections with S. mansoni were readily identified by ELISA in field snails. A case is demonstrated where infection rate, as determined by shedding test alone, was 9.8%, whereas the combined figure of prepatent and patent infection rates was 22.9%

Animals↗

[Initial chemotherapy with conservative treatment in locally advanced cancers of breast (stages IIIa-IIIb). Apropos of 98 cases].

Ninety-eight patients with locally advanced cancer of the breast (stages IIIa-IIIb) observed between March 1981 and March 1986 were included in a study associating initial (neoadjuvant) intensive chemotherapy with or without hormone therapy, in all cases followed by external irradiation and then by maintenance radiotherapy and chemotherapy. A greater than 50% regression in the volume of the tumour was observed in 91% of patients after the initial chemotherapy, a result which was improved by hormone therapy with a complete clinical remission in 100% of cases after external and interstitial irradiation. The incidence of local recurrence was 11%. The 3 and 5 year survival rates without recurrence were 63% and 56% respectively and the global survival rate was 78% and 65% respectively. The degree of tumoral regression after the initial chemotherapy appeared to be the major prognostic factor.

Adult↗

Interim report of phase II study of new nitrosourea S 10036 in disseminated malignant melanoma.

Thirty-three patients with disseminated malignant melanoma were entered in a phase II study of the new nitrosourea S 10036 using a 100-mg/m2 weekly induction schedule for 3-4 consecutive weeks. Patients who responded to this treatment were followed with a maintenance therapy every 3 weeks. Toxic effects were mainly hematological and consisted of delayed thrombocytopenia and leukopenia. Among 30 patients who could be evaluated, eight partial responses were observed (response rate, 26.67%); among seven patients with cerebral metastasis, two partial responses were observed. This multicentric study is currently being continued to confirm this interim report.

Antineoplastic Agents↗

Results of a conservative treatment combining induction (neoadjuvant) and consolidation chemotherapy, hormonotherapy, and external and interstitial irradiation in 98 patients with locally advanced breast cancer (IIIA-IIIB).

Ninety-eight patients with locally advanced breast cancer (Stage IIIA-IIIB) were entered into a pilot study combining intensive induction (neoadjuvant) chemotherapy (VTMFAP) with or without hormonochemotherapy, external and interstitial radiotherapy, and consolidation chemotherapy with or without hormonochemotherapy. Tumor regression over 50% was observed in 91% patients after chemotherapy, and complete clinical remission occurred in 100% patients after irradiation. The rate of local relapse is 13%. The 3-year disease-free survival is 62% and 3-year global survival is 77%. Initial chemotherapeutic tumor regression greater than 75% is the main predictive factor for disease-free survival.

Antineoplastic Combined Chemotherapy Protocols↗

Neuropsychological and behavioral abnormalities in an adolescent with frontal lobe seizures.

A 13-year-old girl had a reversible frontal syndrome secondary to partial complex seizures. She developed sudden and dramatic behavioral changes including sexual disinhibition, loss of concern for personal hygiene, physical and verbal aggression, and pressured and tangential speech. Although the basic neurologic examination was normal, neuropsychological testing revealed selective impairment on tasks sensitive to frontal dysfunction with relatively normal performance on other tests. This case demonstrates that a frontal syndrome can be caused by partial complex seizures and that behavior comparable to that observed in adults with frontal dysfunction may occur in young adolescents.

Adolescent↗

[LAK cells and immunotherapy of cancer].

Cancer immunotherapy still appears very unsatisfactory in humans. However, it has been shown recently that Interleukin 2 (IL2) could be used to generate, in vitro as well as in vivo, a new anti-tumoral activity directed against fresh tumor cells, allogenic as well as autologous, both of leukemic and solid tumor origin. This activity is not connected with the NK activity, but with a lymphocyte sub-population termed 'Lymphokine Activated Killer (LAK) Cells'. The exact nature of these LAK cell precursors is still a matter of controversy: 'nul' lymphocyte, T or NK markers bearing lymphocytes, or different precursors according to the system of activation that has been used. However, after being activation, these LAK cells always express T cell-markers. The activation has a very short lifespan, explaining the need for a prolonged contact of the cells with IL2, and therefore the necessity to continue injecting the lymphokine in vivo. The clinical results that have been reported so far are still very preliminary. The most common treatment protocol consists of 5 days of IL2 injections followed by 5 days of leukapheresis and in vitro activation of the collected cells, and then auto-transfusion of the activated cells and IL2 during the next 5 days. The clinical toxicity encountered is impressive in terms of frequency as well as severity. Clinical activity seems to be relatively weak. Nevertheless, the concept still appears to be very promising.

Humans↗

Phase I clinical study of the new amino acid-linked nitrosourea, S 10036, administered on a weekly schedule.

Diethyl-1-[3-(2-chloroethyl)-3-nitrosoureido]ethylphosphonate (S 10036) is a new nitrosourea that has been evaluated in a clinical trial because of its activity in the National Cancer Institute panel screen and its rational chemical approach. A Phase I study was conducted in 22 evaluable patients with advanced cancers. The drug was given as a slow i.v. infusion over a period of 60 min on days 1, 8, 15, and 22 followed by a 4-week rest period. The dose levels ranged from 25 to 200 mg/m2/week for 4 consecutive weeks using a modified Fibonacci scheme. Thrombocytopenia was the only acute dose-limiting toxicity and started at a dose of 100 mg/m2/week and above. Hematological toxicity was delayed, cumulative, and dose related. Nausea and vomiting were moderate to severe and dose related. Three responses (one complete and two partials) have been noted. Phase II studies of S 10036 are planned at a dose of 100 mg/m2/week for 4 consecutive weeks ("induction therapy") for patients without prior therapy and 100 mg/m2/week for 3 consecutive weeks for those with prior chemotherapy or radiotherapy. Because of the cumulative toxicity, the recommended dose for the second cycle of S 10036 chemotherapy ("maintenance therapy") is 100 mg/m2/week every 3 weeks.

Adult↗

Soluble circulating Fc gamma receptors in human serum. A new ELISA assay for specific and quantitative detection.

We have developed a simple, rapid, and sensitive enzyme-linked immunoadsorbent assay (ELISA) to measure soluble cell-free human Fc gamma receptor (Fc gamma R) in serum. This assay is based on the use of two monoclonal antibodies directed against different epitopes expressed on the same low avidity human Fc gamma R (CD16), which is present on polymorphonuclear leukocytes, macrophages and NK cells. This sandwich ELISA, which can measure 2 nM concentration of Fc gamma R, has enabled us to demonstrate the presence and to measure the level of soluble cell-free human Fc gamma R (CfH-Fc gamma R) in normal human serum.

Antibodies, Monoclonal↗

[Human recombinant leukocyte interferon alpha-2-A in 22 cases of metastatic malignant melanoma].

Twenty-two patients with metastatic malignant melanoma received either 36 X 10(6) U (15 patients) or 18 X 10(6) U (7 patients) of human recombinant interferon alpha-2-A daily for 3 months by the intramuscular route, with progressive increase of dosage. This was followed in responders by a maintenance treatment consisting of 3 intramuscular injections per week in the same doses as those received at the end of the induction treatment. Out of 18 patients assessable for effectiveness, 1 had complete remission (7 months +) and 3 had partial response (52,61 and 82 days respectively), an overall improvement rate of 22%. The main side-effects observed were: pseudoinfluenza syndrome (100%), fatigue (100%), somnolence (95%), anorexia (90%) and haematological disorders. Dosage reduction was necessary in 13 of the 15 patients receiving 36 MU. This study shows that human recombinant interferon alpha-2-A has antitumoral activity in metastatic malignant melanoma. Other studies, notably with therapeutic combinations, are needed to determine the optimal dosage regimen of the drug and to increase its effectiveness.

Adolescent↗

The efficiency of various laboratory methods for the diagnosis of adenovirus conjunctivitis.

Virological and serological data from 242 patients with conjunctivitis or keratoconjunctivitis, infected with adenovirus type 8, and of 109 patients infected with other adenovirus types were compared by means of an electronic data processing system. About 55% of the patients in both groups showed a diagnostic antibody rise in genus-specific (antihexon) complement-fixation. This rate is significantly lower than that obtained with genus-specific ELISA IgG or IgA, or with neutralization tests against the homologous virus, or with hemagglutination-inhibition in case of adenovirus 8 infection. All these tests showed titer rises in 72 to 85% of the patients; differences were not significant. Virus isolation from conjunctival swabs, taken up to 9 days after onset of disease, was successful in 80 to 90%, thereafter in 30%. The time-course of the various antibody titers showed that genus-specific (antihexon) antibodies mostly rise 9 to 12 days after onset, whereas type-specific neutralizing or hemagglutination-inhibiting antibodies rise 10 to 14 days after onset.

Adenoviridae Infections↗

Adjuvant chemotherapy in ocular malignant melanoma. Study of 20 cases.

The frequency of hematogenously propagated hepatic metastases occurring from ocular melanoma led us to treat 20 patients with adjuvant chemotherapy, 19 patients starting chemotherapy during the month following enucleation and 1 patient, a year after enucleation. With a median follow-up of 6 years, 17 patients (80%) are disease-free. Three patients developed hepatic metastases at 24, 24 and 30 months, respectively. The results suggest that adjuvant chemotherapy is effective in preventing metastases from ocular melanoma.

Actuarial Analysis↗