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Biomedical subjects

M Boyer

Publications and source records attributed to M Boyer.

At least 73 records · Page 4Linked to original sources
PubMed1992

Localization and identification of actin structures involved in the filamin-actin interaction.

The interface between gizzard filamin and skeletal muscle actin was located on the actin monomer. Conserved sequences 105-120 and 360-372, in the actin subdomain 1 near the myosin binding sites, were involved in this interaction. The corresponding peptides for these sequences were each found to bind filamin and compete in the actin-filamin interaction. When these two peptides were used together in the presence of filamin and filamentous actin, they dissociated sedimentable complexes formed by these two proteins.

Actins↗
PubMed1992

Localization of a myosin subfragment-1 interaction site on the C-terminal part of actin.

The actin-myosin head complex in the rigor state reveals several high-affinity sites on the actin molecule in sequences 18-28 and 40-113. In the presence of Mg(2+)-ATP, participation of the actin N-terminal 1-7 sequence is known to occur. The proximity of the C-terminal region of actin to the A1 light chain of the myosin head [S-1(A1)] (where S-1 is myosin subfragment-1) was described previously. We observed that C-terminal antigenic structures located near Met-305, Met-325 and Met-355 and the C-terminal end (Cys-374) of actin are markedly modified in the presence of S-1(A1), S-1(A2) and scallop S-1 and in the absence of Mg(2+)-ATP. This seems to rule out any important specific involvement of the A1 light chain in the described conformational changes. An S-1-binding site was located in this actin C-terminal region by testing the tryptic CB9 peptide (360-372 sequence) previously implicated in the A1 light chain interaction. This peptide was able to bind well to S-1(A1), S-1(A2) and scallop S-1, but not in the presence of Mg(2+)-pyrophosphate. These results strengthen the hypothesis of a multisite interface between S-1 and actin located in the actin subdomain I.

Actins↗
PubMed1992

Teratogenic Agent Information Centre: fifteen years of counseling and pregnancy follow-up.

The Teratogenic Agent Information Centre was set up 15 years ago in response to a growing demand from a medical profession struggling to cope with the problem of teratogenic risk. Our goal was to provide information on the real nature of the risk and to monitor all at-risk pregnancies so as to obtain data in a field where there are still, unfortunately, many gaps in our knowledge. The results of these 15 years have been most encouraging, in that physicians have been provided with specialized information and the follow-up of gestations had provided considerable clinical data, which has contributed to advancing our understanding in this domain.

Counseling↗
PubMed1992

Unusually diverse T cell response to a repeating tripeptide epitope.

The immune system utilizes a diverse T cell repertoire for the recognition of foreign antigens in the context of self MHC gene products. We have examined the potential diversity of the T cell response directed to a immunodominant repeating tripeptide epitope (EYA)5. This peptide represents one of the two T cell epitopes on the synthetic alpha-helical polypeptide antigen Poly 18, Poly EYK(EYA)5 in H-2d mice and does not require antigen processing prior to presentation to Poly 18-specific T cell hybridomas. The T cell response directed to the repeating tripeptide epitope (EYA)5 is extremely heterogenous even though the epitope has a relatively simple amino acid sequence. We have analyzed the fine specificity of 21 randomly chosen Poly 18-reactive, (EYA)5-specific and H-2d-restricted T cell hybridomas derived from H-2d, H-2bxd, and H-2b----H-2bxd Poly 18-responding mice to determine the number of unique antigen reactivity patterns represented by this T cell population. We used alanine- and/or lysine-substituted (EYA)5 peptides and a panel of haplotype-varied splenocytes and observed a great deal of microheterogeneity in response. We find that 13 of the 21 hybridomas have a distinct fine antigen specificity and T cell receptors. The binding of (EYA)5 to the antigen-binding groove of I-Ad appears to generate a highly diversified T cell response. Therefore, (EYA)5-I-Ad complex allows the activation of unrelated T cell clonotypes with the same overall antigen specificity and MHC restriction, but with distinct microheterogeneity in response and receptor usage.

Alanine↗
PubMed1992

Toxicity of treatment of germ cell tumors.

Great progress has been made in the management of testicular cancer in the past 15 years, with the attainment of the expectation of cure for most patients. In all of the efforts to reduce the toxicity of treatment, one governing principle should be retained: we must not reduce the chance of successful treatment in our attempts to avoid toxicity. Continued progress will only be achieved by the meticulous implementation of carefully structured trials with appropriate follow-up schedules. If future studies are effected in an unstructured and uncontrolled fashion, physicians could become the most common cause of death of patients with testicular cancer.

Antineoplastic Agents↗
PubMed1990

Localization of a new alpha-actinin binding site in the COOH-terminal part of actin sequence.

The interaction of filamentous actin with alpha-actinin, an actin cross-linking protein, is well established. On the other hand, monomeric actin-alpha-actinin interaction has been a subject of controversy. In this report, we have characterized the interaction of monomeric actin, coated on plastic plates under conditions of non-polymerization, with alpha-actinin in presence of magnesium. Using specific polyclonal anti-actin antibodies, with the whole molecule or purified peptides, we have localized two sites of interaction on action molecule: one near Thr-103 and a new one in the twenty last amino acids.

Actinin↗
PubMed1990

Activation-induced cell death in T cell hybridomas is due to apoptosis. Morphologic aspects and DNA fragmentation.

Some T cell hybridomas, upon activation via the TCR, rapidly undergo cell death. In this paper, we demonstrate that this activation-induced cell death (AICD) is accompanied by morphologic changes seen at the electron and light microscopy levels. The most striking changes are an extensive condensation of the chromatin and formation of membrane blebs. In addition to the morphologic changes, a significant portion of genomic DNA is broken at an interval of approximately 200 bp, producing a ladder of oligonucleosome-sized fragments after gel electrophoresis. Taken together, these observations indicate that AICD proceeds via apoptosis, or programmed cell death. This is additionally supported by the observation that AICD-associated phenomena are at least partially inhibited by cycloheximide or actinomycin D. Curiously, AICD and its associated DNA fragmentation are completely inhibited by aurintricarboxylic acid, a known nuclease inhibitor. The possible relationship between AICD in vitro, and the negative selection process (wherein selection may proceed via AICD of developing, autoreactive thymocytes) is discussed.

Aurintricarboxylic Acid↗
PubMed1990

Critical role of an amino acid residue in a T cell determinant is due to its interaction with a neighboring non-critical residue.

Several lines of evidence support the concept of two functionally distinct sites on antigen: the epitope, involved in interaction with the T cell receptor and the agretope, interacting with Ia. We investigated the Ia and T cell receptor interaction sites on the synthetic polypeptide antigen poly-18 [poly-EYK(EYA)5] using T cell hybridoma clones specific for this antigen in the context of I-Ad. Peptides with amino acid sequences related to poly-18 were synthesized. These were used to identify the critical residues in the minimum peptide sequence required for activation. Clone A.1.1 responds to the minimal peptide EYK(EYA)4 but not to (EYA)5. This identifies Lys3 as a critical amino acid for this hybridoma. Surprisingly, the substituted peptide EYAEAA(EYA)3 could activate A.1.1, indicating that an Ala at position 5 instead of a Tyr obviates the critical requirement for Lys3. This demonstrates that the function of critical residues may extend beyond contacting the T cell receptor or Ia, to include a third role: that of interacting with other amino acids of the T cell epitope, thus influencing the antigen's recognition by T cells.

Amino Acid Sequence↗
PubMed1990

Characterization of agretopes and epitopes involved in the presentation of beef insulin to T cells.

Beef insulin-specific I-Ad-restricted T cell hybridomas were derived from the fusion of antigen-primed (BALB/c X B6)F1 T cells with BW5147 thymoma. Specificity analysis revealed that the A-chain loop region is involved in antigen recognition. Hybridoma A20.2.15 is specific for beef insulin and cross-reacted with sheep insulin, but not with pork insulin. Using synthetic peptides we showed that the A-chain loop containing peptide A1-A14 jointed to the B7-B15 peptide by a disulfide bond can activate this hybridoma. Fragments generated by enzyme digest further suggest that the peptide recognized on beef insulin appears to involve A-chain loop residues A5-A12 and B-chain residues B7-B13 that are linked by the A7-B7 disulfide bridge. We found that beef insulin needs to be processed prior to T cell activation. Glutaraldehyde fixation and chloroquine treatment of presenting cells abolished their capacity to present insulin. Beef insulin denatured by pH changes cannot activate, thus suggesting that simple denaturation is not sufficient for presentation by antigen presenting cells. Finally, the agretope on beef insulin is comprised of two functional regions B7-B13 on the B chain and the A-chain loop in the A-chain, while residues A8 and A10 are probably involved in interaction with the T cell receptor.

Amino Acid Sequence↗
PubMed1990

Functional degeneracy of residues in a T cell peptide epitope contributes to its recognition by different T cell hybridomas.

Synthetic antigen Poly EYK(EYA)5 induces T cells of narrowly defined fine specificity as represented by the two I-Ad-restricted T cell hybridomas, A.1.1 and B.1.1. Both these hybridomas recognize the minimum 15-amino-acid peptide sequence EYK(EYA)4. We have characterized the residues involved in the recognition of EYK(EYA)4 peptide by these hybridomas with synthetic peptides and discovered a distinct functional hierarchy for the residues in the sequence. Even with the repeating tripeptide (EYA)5, which is recognized by B.1.1 cells, the residues that are essential cluster near the middle of the sequence but not near the N- or C-terminal region. Different MHC binding and TCR contacting residues were found for each of the hybridomas. The results suggest that different T cells either recognize different parts of the peptide MHC complex or that the peptide binds to MHC in multiple conformations. This was supported by the fact that Poly EYK(EYA)5 is alpha-helical but the peptides used here showed only a slight propensity to adopt this structure and it did not correlate with their functional activity. We also found that (EYA)5 does not compete with EYK(EYA)4 in the stimulation of A.1.1 cells despite its obvious capacity to interact with I-Ad when it stimulates B.1.1 cells. This may be because these peptides have a low affinity for Ia and therefore only appropriate TCR interactions would stabilize the antigen-Ia complex. In conclusion, antigen-MHC-TCR interaction appears to be a dynamic process which allows recognition of different residues of a T cell determinant by different T cells.

Amino Acid Sequence↗
PubMed1990

Lack of late toxicity in patients treated with cisplatin-containing combination chemotherapy for metastatic testicular cancer.

To date, the prevalence and nature of the late toxicity of cisplatin-based combination chemotherapy for advanced testicular cancer has been poorly documented. Thirty men with a median age of 35 years (range, 23 to 63), who had undergone such treatment were assessed with detailed investigation to determine the type and frequency of chronic toxicity. The median follow-up from the time of commencement of chemotherapy was 75 months (range, 48 to 126). The most common late toxic effects were high tone hearing loss in 23 men (77%) and electrophysiological evidence of peripheral nerve damage in 15 (50%). Both the hearing and nerve abnormalities were predominantly asymptomatic. In addition, elevation of serum cholesterol, noted in 20 patients (67%), was significant (P = .014) when compared with a control population. Hyperuricemia was present in nine patients (30%). Only one patient, with other risk factors (smoking, family history), had evidence of ischaemic heart disease while 20% (all with a smoking history) had a diminished single breath diffusing capacity for carbon monoxide (DLCO). Cisplatin-based chemotherapy is relatively free of major long-term side effects and should not be withheld for fear of late toxicity.

Adult↗
PubMed1989

Lung dissolution of uranium tetrafluoride in rats and baboons. Comparison with dissolution by alveolar macrophages in culture and chemical dissolution.

Lung dissolution of industrial uranium tetrafluoride (UF4) was tested in rats and baboons by intratracheal instillation and inhalation, to check the W classification given to UF4 by the International Commission on Radiological Protection. Rats and baboons were given 10 and 160 micrograms of UF4 per animal respectively. Lung clearance, urinary excretion and tissue distribution of uranium were measured in rats, and urinary excretion was measured in baboons. After intratracheal instillation, daily urinary excretion was fast in both species; 4.8 +/- 0.7 X 10(-2) of the initial lung burden (ILB) in rats and 2.9 +/- 0.3 X 10(-2) in baboons. After inhalation of dry UF4 powder, daily urinary excretion was 5.6 +/- 2.2 X 10(-2) of the ILB in rats and the lung clearance half-life was 7.3 d. The amounts of uranium excreted by rats and baboons were compared to the amounts dissolved in vitro by alveolar macrophages from both species, and also to the amount dissolved chemically by a serum simulant. Both rat and baboon macrophages were clearly shown to be involved in the mechanism of uranium dissolution, since on the first day of macrophage culture, they dissolved 20 and 40% respectively of the amounts of UF4 added to the macrophage cultures, again illustrating the fast dissolution of UF4.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗