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Biomedical subjects

S Martin

Publications and source records attributed to S Martin.

At least 415 records · Page 23Linked to original sources
PubMed1993

Serum intercellular adhesion molecule-1 in childhood malignancy.

Levels of soluble intercellular adhesion molecule-1 (ICAM-1) were measured in serum samples taken at diagnosis from pediatric patients with Hodgkin's disease (n = 69), acute lymphoblastic leukemia (n = 28), Wilms' tumor (n = 20), osteosarcoma (n = 17), rhabdomyosarcoma (n = 18), or Ewing's sarcoma (n = 15). Median levels of serum ICAM-1 were significantly higher in acute lymphoblastic leukemia and Hodgkin's disease than in controls and other malignancies. Levels were positively correlated with disease stage for patients with Hodgkin's disease, Ewing's sarcoma or Wilms' tumor, and with the frequency of relapse in Hodgkin's disease (P = .016). Serum levels were normal in all of 76 patients tested in remission. It remains to be determined whether increased serum ICAM-1 levels simply reflect a greater tumor burden or whether this molecule contributes directly to the progression of childhood malignancies.

Adolescent↗
PubMed1993

Structural complexity of antigenic determinants for class I MHC-restricted, hapten-specific T cells. Two qualitatively differing types of H-2Kb-restricted TNP epitopes.

The understanding of chemically induced allergic or autoimmune disorders requires a detailed structural analysis of the antigenic determinants produced by chemical modification of cells. Using H-2Kb-restricted, TNP-specific cytotoxic mouse T cells and synthetic, Kb-associating TNP-peptides, we define at least two types of functionally distinguishable TNP epitopes. The first one contains TNP in position 4 of different Kb-binding octapeptides and is detected by the majority of in vitro-induced TNP/Kb-specific CTL. This immunodominant structure could be imitated by oligo-glycine based "designer peptides," containing only the Kb "anchor-residues" and TNP-Lys in position 4. A second, qualitatively different determinant is created by TNP-Lys in position 7. T cells of such specificity are rare and recognize TNP only in context of unique peptide sequences. In this case, designer peptides revealed a complex antigenic determinant comprised of TNP-7 and unmodified amino acids in positions 3 and 4. Chances to form a particular determinant of this type by chemical modification are small and, thus, each clone will detect only few epitopes per cell. In contrast, the dominant TNP-4 epitope on differing peptides results in highly repetitive determinants. TCR specific for the rare TNP-7 structure were found to simultaneously contact TNP in position 7 and unmodified amino acids in positions 3 and 4. However, they may also react individually with either the peptide or the hapten part of these complex determinants. This implies a potentially important role of such structures in the induction of autoimmunities: resting T cells, bearing low affinity receptors to self peptides may be activated by peptide/hapten complexes and allow recall responses to the isolated peptide epitope of the unmodified self peptide.

Amino Acid Sequence↗
PubMed1993

[Successful prevention of rhinovirus infections with chimeric ICAM-1 immunoglobulin in vitro].

The intercellular adhesion molecule 1 (ICAM-1) is used as cellular receptor by 90% of human rhinoviruses (HRV). Recently, a recombinant, soluble ICAM-1 (sICAM-1) has been shown to be effective in prevention of the cytopathic effect of rhinovirus infection in vitro. Aim of this study was the production of molecules with multivalent binding sites. Different chimeric proteins were constructed by fusion of two or five extracellular domains of ICAM-1 with the constant regions of IgA1, IgM and IgG1 by polymerase chain reactions (PCR). IgA- and IgG-immunoadhesion molecules were expressed in eucaryotic cells as dimers, IgM-immunoadhesion molecules as decamers. Immunoadhesion molecules were compared to sICAM-1 for their ability to neutralize HRV: The chimeric protein of five N-terminal domains of ICAM-1 and the constant regions of IgA1 was 150 times more potent than sICAM-1 in neutralizing HRV. The first and the second N-terminal of ICAM-1 fused to IgA1 or IgM were five times more active, however, fused to IgG1 four times less active than sICAM-1. Sedimentation analyses of [H3]-leucin labled HRV after preincubation with the different immunoadhesion molecules showed a dose-dependent induction of a conformational change of the viral capsid proteins. The order of efficiency of the chimeric proteins was consistent to the neutralizing experiments. Our results showed that HRV neutralizing can be dramatically increased by multimerization of ICAM-1. The chimeric molecule between IgA1 and ICAM-1 seems to be a potential candidate for clinical testing to prevent and treat HRV-infections.

Cell Adhesion Molecules↗
PubMed1993

Identification and preliminary characterization of a protein motif related to the zinc finger.

We have identified a protein motif, related to the zinc finger, which defines a newly discovered family of proteins. The motif was found in the sequence of the human RING1 gene, which is proximal to the major histocompatibility complex region on chromosome six. We propose naming this motif the "RING finger" and it is found in 27 proteins, all of which have putative DNA binding functions. We have synthesized a peptide corresponding to the RING1 motif and examined a number of properties, including metal and DNA binding. We provide evidence to support the suggestion that the RING finger motif is the DNA binding domain of this newly defined family of proteins.

Amino Acid Sequence↗
PubMed1993

HLA mismatching and cytomegalovirus infection as risk factors for transplant failure in cyclosporin-treated renal allograft recipients.

In a study of the effects on renal allograft survival of HLA mismatching, mismatching for cytomegalovirus (CMV) antibody status, and post-transplant CMV infection, 148 cyclosporin-treated renal transplant recipients were given kidneys optimally matched for HLA-A, -B, and -DR antigens but not matched for CMV antibody status. Mismatching for HLA-B and -DR antigens was associated with a greater number of rejection episodes and a lower graft survival, but mismatching for CMV antibody status and posttransplant primary or recurrent CMV infection exerted no effect on graft survival. The role of matching of renal transplant recipients and donors for CMV antibody status in preference to HLA matching (proposed as a means of reducing the mortality associated with primary CMV infection) is discussed.

Antibodies, Viral↗
PubMed1993

Intracellular processing of hapten-modified protein for MHC class I presentation: cytoplasmic delivery by pH-sensitive liposomes.

Phagocytic or endocytic uptake of pH-sensitive liposomes has been shown to result in the release of entrapped material into the cytosol. This system can therefore be applied to the targeted delivery of protein antigens into the MHC class I presentation pathway of antigen-processing cells. We have used trinitrophenyl (TNP)-modified chicken ovalbumin encapsulated in liposomes to examine the intracellular processing of haptenated proteins and the presentation of TNP-modified peptides to MHC class I-restricted hapten-specific CTL. Here, we demonstrate for the first time that hapten-modified proteins can undergo intracellular processing by macrophages, that similar peptides are produced in the form of unmodified or haptenated derivatives, and that TNP-peptides are transported to the cell surface and presented to class I-restricted CTL via the ER/Golgi pathway. This system can now be used to study T-cell responses to naturally processed hapten-conjugated peptides in vitro and in vivo.

Animals↗
PubMed1993

Purified MHC class I molecules present hapten-conjugated peptides to TNP/H-2Kb-specific T cell hybridomas.

Several trinitrophenyl (TNP)-specific mouse cytotoxic T cell (CTL) clones recognize TNP-conjugated peptides in association with class I MHC Kb-molecules. Here we show that CD8+ T cell hybridomas derived from these CTL exhibit the same pattern of antigen-specificity as their parent CTL-clones. These T cell hybridomas reacted with TNBS- or TNP-peptide modified syngeneic target cells, and also with affinity purified, immobilized Kb-molecules preloaded with TNP-peptides. These findings demonstrate most directly that MHC-associated, haptenated peptides create functional antigenic epitopes for TNP-specific CTL. Furthermore, using purified Kb-molecules and a panel of Kb-binding TNP-conjugated peptides, we demonstrated that the epitope density is a critical factor in triggering these T cell hybridomas. Chemical modification of immobilized Kb-layers resulted in poor antigenicity, implying low epitope density and therefore arguing against covalent MHC-haptenization as a major source of T cell antigenic determinants.

Animals↗
PubMed1993

The association between a positive T and B cell flow cytometry crossmatch and renal transplant failure.

Between January 1989 and June 1991 329 consecutive cadaveric renal transplants were carried out at this centre and, of those, 36 (10.9%) have failed. In order to assess whether the use of flow cytometry crossmatching (FCXM) would have predicted these failures, we carried out a retrospective T and B cell FCXM study comparing the failure group with a control group of 30 recipients carefully selected from patients transplanted during the same period. The number of first and second transplants in the control and failure groups was 25,5 and 23,8 respectively with six of the controls and three of the failures having panel reactive lymphocytotoxic antibodies > 50%. Stored donor material was available for 31 of the 36 failures. Two colour FCXM was performed using R-phycoerythrin-conjugated antihuman CD3 and antihuman CD19 to identify T and B cells respectively. For each recipient, three pretransplant and one post-transplant sera were tested against lymphocytes from the recipient's kidney donor. A fluorescein isothiocyanate conjugated F(ab')2 rabbit antihuman IgG was used to detect recipient IgG alloantibodies bound to donor T and/or B cells. There were no T or B cell FCXM positive (+) results in the control group whereas 11 of the 31 (35%) failures overall and nine of the 23 (39%) who failed within three months were T and B cell FCXM+ pretransplant (p = 0.0002). Seven of the nine FCXM+ results in the early failure group were with historic sera and two with historic and current sera.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1993

Anti-inflammatory activity of the essential oil of Bupleurum fruticescens.

The essential oil of Bupleurum fruticescens was investigated qualitatively and quantitatively by GC and GC-MS analyses. The anti-inflammatory activity of the whole essential oil and its major components was also investigated in the rat hindpaw edema model induced by carrageenin or by PGE1. The anti-inflammatory activity shown by the essential oil can be attributed to the two major components, alpha-pinene and beta-caryophyllene. In order to know the role of the adrenal glands in the anti-inflammatory activity exerted by the two major components of the essential oil, they were studied against the carrageenin-induced hindpaw edema in adrenolectomized rats. It is concluded that alpha-pinene needs the integrity of the adrenal glands to exert its anti-inflammatory activity, as opposed to beta-caryophyllene which was also active in adrenolectomized animals.

Animals↗
PubMed1993

Acoustic reflectometry for airway measurements in man: implementation and validation.

A practical implementation of acoustic reflectometry for determining airway areas in routine clinical use is described. Advances over previous systems include portability, free breathing during measurements, no need to equilibrate with helium/oxygen, and real-time display of airway areas. Validation of the reflectometer with an airway model gave accuracies and reproducibilities (coefficient of variation (CV)) in the range 5-10%. With human volunteers, the within-run CV was typically 10%, and the day-to-day CV was 20%. The effect of breathing pattern on airway areas is demonstrated. In ten normal volunteers, acoustic and magnetic resonance imaging (MRI) methods of assessing pharyngeal and glottal areas were compared. The results (mean +/- SD) for the oropharynx were 1.0 +/- 0.3 cm2 acoustically and 0.9 +/- 0.5 cm2 by MRI (p = 0.77). The corresponding figures for glottal areas were 1.3 +/- 0.3 cm2 and 1.1 +/- 0.4 cm2 (p = 0.09).

Humans↗
PubMed1993

The proportion of herpes simplex virus-specific cytotoxic T lymphocytes (Tc) that recognize glycoprotein C varies between individual mice and is dependent on the form of immunization.

In mice the immune response to HSV-1 includes a brisk Tc response that is intimately associated with the control of infection. This report evaluated the Tc response to gC, one of the envelope glycoproteins of HSV-1. This protein was recognized as a target antigen for Tc from HSV-1 immune mice only if they expressed the H-2Kb MHC allele. However, even within these "responder" strains of mice the proportion of gC specific Tc was highly variable. The failure of HSV-induced Tc to recognize gC in the context of other class 1 MHC haplotypes (H-2d and H-2k) was demonstrable at the clonal level and could not be attributed to peculiarities of the recombinant constructs. Surprisingly, despite the inability of H-2k-restricted, HSV-1-induced Tc to recognize gC, when a vaccinia gC virus construct was used to immunize H-2k strains of mice it showed a variable ability to induce memory Tc populations capable of lysing HSV-1-infected autologous cells. Of added importance was the correlation of this induced Tc response with optimum protection against subsequent challenge with HSV-1. This demonstrated that despite the presence of suitable epitopes, the context of the immunogen would also influence its ability to induce Tc. Consequently, the potential repertoire of available HSV-1-specific Tc specificities is larger than indicated by studying animals immunized with HSV.

Animals↗
PubMed1993

Sister chromatid fusion initiates amplification of the dihydrofolate reductase gene in Chinese hamster cells.

We have utilized a dihydrofolate reductase (DHFR) probe in combination with selected probes from other positions along the 2q chromosome arm in a two-color fluorescence in situ hybridization analysis of early DHFR gene amplification events in CHO cells. These studies show clearly that the most frequent initiating event is the formation of a giant inverted duplication, resulting from chromosome breakage and terminal fusion or a reverse unequal sister chromatid exchange. The dicentric chromosomes thus formed initiate bridge/breakage/fusion cycles that appear to mediate subsequent amplification steps to higher copy number.

Animals↗