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Biomedical subjects

J A Leon

Publications and source records attributed to J A Leon.

17 recordsLinked to original sources
PubMed1995

Endoscopy under operating microscope. A new device.

Existing technical conditions make it difficult for a single surgeon to simultaneously observe the endoscope and the observation field of the operating microscope. Video endoscopy is not adapted, because it respects neither the constraints of microsurgery (the surgeon has to stop observing the binoculars of the microscope to watch the video screen) nor the micromanipulations necessary for the specialties using micro endoscopy. A new device is described that closely joins endoscope and microscope. This coupling device allows the surgeon to permanently control and alternate the images according to his choice. The surgeon is able to observe in the binoculars the images transmitted by the endoscope and/or the operating microscope. This device respects the requirements of the microscope and, thanks to its optical capabilities, the endoscopic image is improved. The professions requiring double observation will improve their ability in diagnosis and therapy.

Endoscopes↗
PubMed1994

New approaches for the development and application of monoclonal antibodies for the diagnosis and therapy of human cancer.

Monoclonal antibodies (MAbs) represent potentially important reagents for both the diagnosis and therapy of human cancer. Innovative approaches are resulting in the improved production of MAbs and an enhanced ability to use these molecules therapeutically. Application of genetic engineering to MAb development is also resulting in the production of MAbs displaying enhanced target specificity. Of particular value for cancer therapy will be catalytic, bispecific, anti-idiotypic and human MAbs. By using agents that can augment the expression of tumor-associated antigens on cancer cells, a further increase in the utility of MAbs in cancer therapy will be forthcoming.

Amino Acid Sequence↗
PubMed1993

Wild-type adenovirus type 5 transforming genes function as transdominant suppressors of oncogenesis in mutant adenovirus type 5 transformed rat embryo fibroblast cells.

Transformation of cloned rat embryo fibroblast (CREF) cells with the host-range adenovirus type 5 (Ad5) mutant, H5hr1, results in transformants with a fibroblastic morphology which displays a cold-sensitive transformation phenotype and oncogenic potential in both nude mice and syngeneic rats. In contrast, wild-type (wt) Ad5 transformed CREF cells are epithelioid in morphology, temperature independent for transformation, and nontumorigenic. The present studies were conducted to analyze the contribution of the mutated E1A and E1B regions of H5hr1 in regulating the biological properties of H5hr1-transformed CREF cells. CREF cells were constructed which contain the mutated E1A and E1B transforming regions of H5hr1 and either a wt Ad5 E1A gene, a wt Ad5 E1B gene, or both a wt Ad5 E1A and a wt E1B gene. A wt Ad5 E1A gene was sufficient in reversing the cold-sensitive transformation phenotype. By using a wt Ad5 E1A gene under the transcriptional control of a dexamethasone-inducible mouse mammary tumor virus promoter, a direct suppressive effect of wt Ad5 E1A on colony formation in monolayer culture and agar growth of H5hr1-transformed cells was demonstrated. Expression of a wt Ad5 E1A, a wt Ad5 E1B, or both wt transforming genes in H5hr1-transformed CREF cells also suppressed oncogenicity. The ability or inability to form tumors in animals was found not to correlate with sensitivity to natural killer cell-mediated lysis. These results indicate that both the wt Ad5 E1A and wt Ad5 E1B genes can function as dominant suppressors of the oncogenic process when coexpressed in H5hr1-transformed CREF cells. This effect does not require large quantities of wt Ad5 E1A or E1B transforming proteins, nor is it directly related to the acquisition of a natural killer cell cytolysis-susceptible phenotype.

Adenovirus E1A Proteins↗
PubMed1993

Radioimmunoimaging of human breast carcinoma xenografts in nude mouse model with 111In-labeled new monoclonal antibody EBA-1 and F(ab')2 fragments.

Radioimmunoimaging characteristics of a new monoclonal antibody EBA-1 and its F(ab')2 fragments utilizing nu/nu mice bearing human breast carcinoma xenografts are described. 111In-DTPA conjugates of EBA-1 localized with tumor/blood ratios of 0.99 +/- 0.10 (P < 0.3) and 4.65 +/- 1.60 (P < 0.05), and localization indices of 1.25 and 2.61 at 24 and 72 h, respectively. A tumor/blood ratio as high as 28.86 +/- 6.90 (P < 0.025) was obtained with EBA-1 F(ab')2 radioconjugates at 48 h. These results suggest that EBA-1 and its F(ab')2 might be useful reagents in radioimmunoimaging and radioimmunotherapy.

Animals↗
PubMed1992

Modulation of the antigenic phenotype of human breast carcinoma cells by modifiers of protein kinase C activity and recombinant human interferons.

In the present study we have analyzed the effect of a synthetic protein kinase C (PKC) activator 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol (ADMB) and the natural PKC-activating tumor-promoting agents 12-O-tetradecanoylphorbol 13-acetate (TPA) and mezerein on the antigenic phenotype of T47D human breast carcinoma cells. All three agents increased the surface expression of the tumor-associated antigen BCA 225 and various cellular antigens, including HLA class II antigens, intercellular adhesion molecule 1 (ICAM-1) and c-erbB-2. Expression of the same antigens was also upregulated to various extents in T47D cells by recombinant fibroblast (IFN beta) and immune (IFN gamma) interferon. Shedding of BCA 225 from T47D cells was induced by TPA, mezerein, IFN beta and IFN gamma, whereas ADMB did not display this activity. The ability of ADMB, TPA and mezerein to modulate the antigenic phenotype of T47D cells appears to involve a PKC-mediated pathway, since the PKC inhibitor, H-7, eliminates antigenic modulation. In contrast, the ability of IFN beta and IFN gamma to enhance the synthesis, expression and shedding of BCA 225, as well as to enhance HLA class II antigens, c-erbB-2 and ICAM-1 expression, was either unchanged or modestly reduced by simultaneous exposure to H-7. Analysis of steady-state mRNA levels for HLA class I antigens, HLA class II-DR beta antigen, ICAM-1 and c-erbB-2 indicated that the ability of H-7 to inhibit expression of these antigens in TPA-, mezerein- and ADMB-treated cells was not a consequence of a reduction in the steady-state levels of mRNAs for these antigens. The results of the present investigation indicate that the biochemical pathways mediating enhanced antigenic expression in T47D cells induced by TPA, mezerein and the synthetic PKC activator ADMB are different from those induced by recombinant interferons. Furthermore, up-regulation of antigenic expression in T47D cells can occur by a PKC-dependent or a PKC-independent pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Tumor localization in nude mice bearing human breast carcinoma xenografts using 111In-DTPA conjugates of monoclonal antibodies.

Biodistribution of monoclonal antibody T43 and its F(ab')2 111In-DTPA conjugates were determined in nu/nu mice bearing human breast tumor and rat pituitary tumor xenografts. T43 localized in the target tumor with tumor/blood ratios of 3.9 (P less than 0.01) and 4.5 (P less than 0.05) at 48 and 72 h, respectively. T43 F(ab')2 fragments localized with tumor/blood ratio of 14.2 (P less than 0.1) at 72 h. Tumors as small as 4 mm were detected without computer subtraction technique. These studies suggest that T43 and T43 F(ab')2 might be useful reagents in radioimaging.

Animals↗
PubMed1991

Microendoscopic ocular surgery: a new intraoperative, diagnostic and therapeutic strategy. Part I: Endoscopic equipment/methodology applied to cataract surgery with intraocular lens implantation.

During posterior chamber implantation, endoscopy is the only direct method that allows objective observation of the retroiridal space. We use it to define the parameters of the posterior chamber intraocular lens (isolation, inertia, centering). An oval endoscopic probe is preferred and the multivision system allows observation of the endoscopic images under the operative microscope eyepiece. Beside "blind" posterior chamber implantation, a "controlled" endoscopic posterior implantation can be defined.

Anterior Chamber↗
PubMed1991

Microendoscopic ocular surgery: a new intraoperative, diagnostic and therapeutic strategy. Part II: Preliminary results from the study of glaucomatous eyes.

Endoscopy allows intraoperative examination of the retroiridal space; this procedure has been used during the combined surgery of trabeculectomy, extracapsular extraction, and posterior chamber intraocular lens implantation. Information obtained by preoperative gonioscopic examination of the iridocorneal angle is presented with information obtained by intraoperative endoscopic examination of the iridocorneal and ciliary angles. Our initial endoscopic findings are impressive and include morphological analysis of ciliary processes, variations in their appearance, degree of opening of the iridociliary angle, and study of ciliary capillaries.

Adult↗
PubMed1990

Effects of fluorouracil and fluorouridine on protein synthesis in rabbit retina.

5-Fluorouracil (5-FU) and its active metabolite 5-fluorouridine (FUR) are currently being evaluated for the treatment of proliferative vitreoretinopathy and the control of scarring after glaucoma filtering procedures. To test for retinal toxicity, the authors examined the effect of intravitreal injections of 5-FU and FUR on protein synthesis in rabbit retinal photoreceptors and ganglion cells. In addition, the toxic effect of subconjunctival 5-FU injections, after a trephine filtering procedure, on ganglion cell protein synthesis was examined. Albino rabbit eyes were given either unilateral intravitreal injections of 1 mg of 5-FU, 2.5 mg of 5-FU, or 0.1 mg of FUR, or subconjunctival injections of 3 mg of 5-FU twice daily after a trephine procedure. Quantitative autoradiography was used to study ganglion cells and photoreceptor outer segment renewal, and scintillation counting was used to quantify newly synthesized protein transported axonally from ganglion cell bodies to the superior colliculus (SC). Marked reduction of labeled protein reaching the SC was noted after either intravitreal 0.1 mg of FUR (41% inhibition after a single injection and 53% after two injections) or 2.5 mg of 5-FU (41% after one injection and 26% after two injections). This reduction was still present after 8 days in eyes receiving 0.1 mg of FUR (32%) and 2.5 mg of 5-FU (22%). Quantitative autoradiography of retinal photoreceptors and ganglion cells corroborated these data, demonstrating inhibition of outer segment renewal after one or two injections of either 0.1 mg of FUR or 2.5 mg of 5-FU. This inhibitory effect was statistically significant using the paired t-test for both drugs. No mean inhibition was observed after intravitreal 1 mg of 5-FU injections or after subconjunctival injections of 5-FU.

Animals↗
PubMed1989

Acute macular neuroretinopathy following intravenous sympathomimetics.

Three young women developed acute macular neuroretinopathy with persistent paracentral scotomas following acute hypertension caused by intravenous sympathomimetics. The temporal relationship of the acute onset of symptoms suggests either acute hypertension or a direct retinal effect of sympathomimetics as the cause of the retinal changes.

Acute Disease↗
PubMed1988

Immunocytochemical distribution of a breast carcinoma associated glycoprotein identified by monoclonal antibodies.

A glycoprotein, BCA-225 (Mr 225,000-250,000), has been identified in cells and spent medium of clone 11 T47D breast carcinoma cells by three murine monoclonal antibodies, CU18, CU26, and CU46. The antigen was localized in paraffin sections of 167/178 (94%) Bouin's-fixed human breast carcinoma tissues and few other carcinomas (1/8 lung [squamous], 4/4 uterine cervix) in an intracellular pattern, whereas an apical or glycocalyx distribution was seen in several normal tissues, benign lesions, and malignant tumors. Although the immunocytochemical staining patterns observed with these antibodies have many similarities to those described with other previously reported monoclonal antibodies, notable differences include the lack of reactivity of CU18, CU26, and CU46 with lactating mammary gland and with gastrointestinal malignancies. BCA-225 binds to wheat germ lectin, not to concanavalin A, but monoclonal antibody binding does not appear to involve the carbohydrate component of the molecule. The frequency of the immunocytochemical detection of BCA-225 in breast carcinomas and its restricted distribution in other human tissues suggest considerable clinical potential for this antigen and its corresponding monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed1987

Middle ear prosthesis: significance in magnetic resonance imaging.

The Armstrong model of the Schuknecht gel foam and wire prosthesis was tested in the magnetic field of a 1.5 Tesla magnet. The wire component of the prosthesis was found to be non-magnetic. Patients with this prosthesis can therefore undergo MRI examination safely. Two previous articles from the non radiologic literature concerning the magnetic properties of metallic middle ear prostheses are reviewed.

Aged↗
PubMed1976

Stability of population growth determined by 2 X 2 Leslie matrix with density-dependent elements.

The matrix considered contains four elements, each a function of total number. A special case for which the matrix may be appropriate is when the population may be divided into juveniles and adults, and the survival rates and fecundity are the same for all members of each group. This is true, at least approximatley, for many species of birds. The conditions for stability are determined and are illustrated with a model based on the data collected on the Marley Wood, Oxford, population of the Great tit (Parus major L.). A reformulation of the conditons permits comparison with the conditions for a population with identical survival rates and fecundity for all age groups, i.e., a population without effective age structure. Conditions under which the age structure may be ignored when discussing stability are considered.

Age Factors↗
PubMedDate not supplied

Increased surface expression and shedding of tumor associated antigens by human breast carcinoma cells treated with recombinant human interferons or phorbol ester tumor promoters.

In the present study we have evaluated the effect of recombinant interferons, including leukocyte (IFN-alpha A), fibroblast (IFN-beta) and immune (IFN-gamma), and the tumor promoting agent 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on the expression of tumor associated antigens (TAA) and class II HLA-DR antigens on human breast carcinoma cell lines. The effect of these agents on the shedding of a high molecular weight tumor associated glycoprotein, BCA-225, was also determined. All three interferons and TPA enhanced the expression of the Mr 180,000 carcinoembryonic antigen (CEA) and CEA-related TAA recognized by monoclonal antibody B1.1 in both T47D and MCF-7 human breast carcinoma cell lines. The three types of interferons and TPA differed in their absolute TAA-augmenting ability, even in single-cell subclones derived from MCF-7 cells and previously shown to display a differential susceptibility to IFN-alpha augmentation of B1.1 expression. In general, IFN-gamma was more effective than IFN-alpha, IFN-beta or TPA in augmenting the expression of TAA, CEA and BCA-225, and HLA-DR expression in T47D and MCF-7 cells. Differences were also apparent in the ability of the three interferon preparations and TPA to induce shedding of BCA-225 in T47D and MCF-7 cells and their subclones. As observed with TAA expression, IFN-gamma was the most effective preparation in inducing TAA shedding. IFN-gamma also induced the expression and the shedding of BCA-225 by a subclone of T47D cells, T47D cl 17, which normally displays a reduced expression of BCA-225 and does not spontaneously shed this TAA without exposure to IFN-gamma. Recombinant leukocyte interferon (IFN-alpha A) also enhanced BCA-225 expression on T47D cells grown as xenografts in nude mice in vivo. The results of the present study emphasize the complexity of potential antigenic responses which can be induced in human breast carcinoma cells when they are exposed to biological response modulators, including different types of interferon, and tumor promoting agents, such as TPA. This investigation also indicates that both classes of agents can differentially augment expression and/or shedding of TAA by specific breast carcinoma cell lines as well as subclones derived from the same breast carcinoma cell line.

Antibodies, Monoclonal↗