Search PubMed⌕ Search

Biomedical subjects

S Adams

Publications and source records attributed to S Adams.

At least 145 records · Page 8Linked to original sources
PubMed1993

Comparison of actual and random-positioning-model distributions of peptide scavenging and T cell-presented sites in antigenic proteins.

In a peptide with a T cell-presented epitope (T site), a folded structure with a hydrophobic surface, 'the scavenger (S) site', may regulate transfer to major histocompatibility complex class II molecules. Three procedures which were proposed to identify T sites selected for amphipathic helical patterns but not T sites. In testing whether S sites lay in or near T sites, we found their linkage was not greater than that generated by a model in which segments of equal length and number to the S and T sites for each protein were distributed at random. This study establishes criteria for evaluation of schemes to predict functional motifs in antigenic proteins.

Amino Acid Sequence↗
PubMed1993

Laparoscopic management of acute small bowel obstruction.

Acute small bowel obstruction is commonly due to band adhesions. In the past it has had an overall mortality rate of up to 11% for elderly patients. In this paper we report three cases of small bowel obstruction, treated by laparoscopic division of the causative bands. All patients recovered rapidly and were discharged within 5 days of surgery.

Acute Disease↗
PubMed1993

A novel technetium-99m labeled monoclonal antibody (174H.64) for staging head and neck cancer by immuno-SPECT.

A novel murine monoclonal antibody (MAb 174H.64) was labeled with 99mTc by a direct method. MAb 174H.64 detects a cytokeratin-associated antigen which is expressed by over 90% of all squamous cell carcinomas. Panendoscopy, sonography and computerized tomography scan were performed in all cases as well as magnetic resonance imaging (in selected patients). Pre-operative immunoscintigraphy was performed in 21 patients with histologically proven primary carcinomas (18 with remaining primary tumors and 3 with lymph node recurrences). Scintigraphic images were obtained 4-6 h after injection of 1.1 GBq of the 99mTc-labeled antibody (2 mg). Late images were acquired 18 to 24 h after injection. Single-Photon-Emission-Computed Tomography (SPECT) of the head and thorax was performed in all patients. The primary tumors were immunoscintigraphically visualized in all 18 patients with remaining primary tumor. Fifteen of 18 loco-regional lymph node metastases were visualized by immunoscintigraphy (the smallest lesions had a diameter of < 1 cm), in one patient lymph node metastases were detected by immunoscan only. Two metastatically involved lymph nodes were identified by histology only (micrometastases). Distant metastases were present in 3 patients, of which two were identified by immunoscintigraphy. Immuno-SPECT according to this method was a sensitive and specific imaging modality for preoperative staging of patients with squamous cell carcinoma of the head and neck and detected lymph node metastases with higher accuracy than conventional clinical and imaging modalities.

Animals↗
PubMed1992

Use of multiple-cause mortality data in epidemiologic analyses: US rate and proportion files developed by the National Institute for Occupational Safety and Health and the National Cancer Institute.

The authors have created US mortality rates (age, sex, race, and calendar-time specific) and proportions, using multiple cause-of-death data, for the years 1960-1989. Multiple cause-of-death data include the usual underlying cause of death from the death certificate as well as contributory causes and other significant conditions. US multiple-cause rates and proportions enable the user to calculate the expected occurrences of disease on the death certificates of a cohort under study. There is an average of 2.66 causes and/or contributory conditions listed on US death certificates, increasing over time from 2.54 in the 1960s to 2.76 in the 1980s. The ratio of multiple-cause listings to underlying cause listings varies by disease, from low ratios for cancers to high ratios for diseases such as diabetes, arthritis, prostate disease, hypertension, pneumoconiosis, and renal disease. Use of these data is illustrated with two cohorts. Multiple-cause analysis (but not underlying cause analysis) revealed twofold significant excesses of renal disease and arthritis among granite cutters. For workers exposed to dioxin, neither multiple-cause nor underlying cause analysis indicated any excess of diabetes, an outcome of a priori interest. Good candidates for multiple-cause analysis are diseases that are of long duration, not necessarily fatal, yet serious enough to be listed on the death certificate.

Cause of Death↗
PubMed1992

Characteristics and development of the murine B-1b (Ly-1 B sister) cell population.

In this paper we have outlined the evidence for two distinct branches of the B-1 cell lineage. The data show that phenotypically B-1a and B-1b cells are essentially identical, distinguished only by the presence or absence of the CD5 antigen. Functionally no differences between the two populations have yet been identified. Both produce anti-PtC antibodies, a specificity not observed in conventional B cells. Both produced high levels of IgM as measured in adoptive transfer experiments. Developmentally, B-1a and B-1b cells are indistinguishable with respect to generation from progenitors present in fetal liver and omentum, feedback regulation of new B-1a and B-1b cells from bone marrow, self-replenishment from Ig+ cells following adoptive transfer, and the generation of clonal populations. The major difference in the two populations is seen in the development of B-1a and B-1b cells from B220- progenitors in the adult bone marrow. Although B220- B-1a progenitors are rare in adult (greater than 6 weeks) bone marrow, the progenitors for B-1b cells persist well into adulthood. Our understanding of B-1b cell ontogeny is at a stage similar to that of B-1a cells five years ago. We have evidence from transfer experiments that strongly suggests the existence of two distinct progenitors for B-1a and B-1b, but we have yet to physically separate these progenitors as Solvansen et al. have done for B-1 and conventional B cells. Furthermore we must determine whether the B-1b cells that develop from fetal liver and bone marrow are functionally and developmentally equivalent to those that develop from adult bone marrow. As with B-1a cells, the role of B-1b cells in the immune system is unclear. Although we have not yet discerned functional differences between B-1a and B-1b, given the recent identification of CD72 (Lyb-2) as the ligand for CD5, it is tempting to speculate that B-1a cells are more involved in B-B cell interactions such as idiotype-anti-idiotype regulation of the early B-cell repertoire and that B-1b cells are more involved in B-T cell interactions. Whatever their function, it is clear that in trying to understand the role of the B-1 lineage it is important to consider both the B-1a and B-1b lineages.

Aging↗
PubMed1992

Differential development of progenitor activity for three B-cell lineages.

Cell-transfer studies presented here distinguish three murine B cell lineages: conventional B cells, which develop late and are continually replenished from progenitors in adult bone marrow; Ly-1 B cells (B-1a), which develop early and maintain their numbers by self-replenishment; and Ly-1B "sister" (B-1b) cells, which share many of the properties of Ly-1 B cells, including self-replenishment and feedback regulation of development but can also readily develop from progenitors in adult bone marrow. The sequential emergence of these lineages, the time at which their progenitors function during ontogeny, and the distinctions among their repertoires and functions suggest that evolution has created a layered immune system in which the immune response potential of each successive lineage is adapted to its particular niche.

Animals↗
PubMed1992

Bispecific monoclonal antibody regulation of Fc gamma RIII-directed tumor cytotoxicity by large granular lymphocytes.

Bispecific monoclonal antibodies (BsMAbs) prepared by somatic cell fusion bind monovalently to their targets and yet are extremely potent enhancers of target cell lysis by relevant effector cells. The mechanisms underlying this efficiency are not known. To investigate this property, we studied the ability of selected antibodies to modulate potentiation of tumor lysis by a bispecific antibody (CL158) which targets Fc gamma RIII-expressing cells, via the 3G8 epitope, to malignant cells expressing CA19-9 antigen. Antibodies directed against the 3G8 and B73.1 epitopes of Fc gamma RIII efficiently inhibited BsMAb-mediated SW948 tumor cell lysis by interleukin-2 (IL-2)-activated lymphocytes (PBLs). Unexpectedly, Leu 19 antibody reversed antibody-dependent but not antibody-independent lysis of 51Cr-labeled SW948 cells by IL-2-activated PBLs in a concentration-dependent fashion. Leu 19 binds to CD56, a neural cell adhesion molecule (N-CAM) isoform expressed by large granular lymphocytes (LGLs). The effects of Leu 19 on bispecific antibody promotion of lysis were due to competition for binding to the 3G8 epitope of Fc gamma RIII and led to inhibition of binding between LGLs and SW948 cells. Leu 19 did not inhibit antibody-dependent lysis by the monospecific, bivalent IgG2a variant of CA19-9 antibody. These studies show that competition assays can be useful in dissecting the relevant mechanisms underlying BsMAb-promoted lysis. Steric constraints between effector cell trigger molecules (i.e., Fc gamma RIII) and CAM such as N-CAM may regulate the function of these molecules. Understanding the roles of diverse CAM in this phenomenon will facilitate efforts to expand and use defined effector cell populations with maximal lytic potential and to identify potentially responsive tumor phenotypes.

Antibodies, Monoclonal↗
PubMed1992

Anti-DNA antibodies form immune deposits at distinct glomerular and vascular sites.

To investigate the capacity of lupus autoAb to produce glomerular immune deposits (ID) and nephritis, 24 murine monoclonal (m) anti-DNA antibodies (Ab), derived from either MRL-lpr/lpr, SNF1 or NZB lupus-prone mice and selected based on properties shared with nephritogenic Ig, were administered i.p. (as hybridomas) and i.v. (as purified Ig) to normal mice; at least four mice/mAb were evaluated. Three general patterns of immune deposit formation (IDF) were observed: extracellular ID within glomeruli (+/- blood vessels, N = 8); intranuclear ID (N = 5); or minimal or no ID (N = 11). The four MRL m anti-DNA Ab that produced significant extracellular ID demonstrated different disease profiles including: (a) mesangial and subendothelial ID with anti-basement membrane staining, associated with proliferative glomerulonephritis, PMN infiltration, and proteinuria; (b) diffuse fine granular mesangial and extraglomerular vascular ID, associated with proliferative glomerulonephritis and proteinuria; (c) dense intramembranous ID and intraluminal ID, associated with capillary wall thickening, mesangial interposition and expansion, aneurysmal dilatation and intraluminal occlusion of glomerular capillary loops, and heavy proteinuria; and (d) mesangial and extraglomerular vascular ID, associated with mild segmental mesangial expansion, without proteinuria. These MRL mAb were derived from four different mice, and they had variable pIs and isotypes. They all cross reacted with multiple autoantigens (autoAg), however, their autoAg binding profiles were distinguishable. Among the SNF1 derived mAb, four produced histologically and clinically indistinguishable disease characterized by diffuse mesangial and capillary wall ID, associated with cellular proliferation/infiltration and proteinuria. Three of the four mAb were derived from the same mouse and were clonally related; they were: IgG2b with SWR allotype, relatively cationic, highly cross reactive with similar Ag binding patterns, idiotypically related and encoded by identical VH and nearly identical VL sequences. We conclude that both the capacity of lupus autoAb to form ID and the location of IDF are dependent on properties unique to individual Ig. The results also indicate that the Ag binding region of the autoAb is influential in this process, and they suggest that multiple Ab-Ag interactions contribute to IDF in individuals with lupus nephritis. Furthermore, these observations raise the possibility that the pathologic and clinical abnormalities resulting from these interactions are influenced by the location of IDF, and that the dominant interaction, in a given individual, may be highly influential in the phenotypic expression of nephritis.

Animals↗
PubMed1992

The serpin-enzyme complex (SEC) receptor mediates the neutrophil chemotactic effect of alpha-1 antitrypsin-elastase complexes and amyloid-beta peptide.

The serpin-enzyme complex (SEC) receptor mediates catabolism of alpha 1-antitrypsin (alpha 1-AT)-elastase complexes and increases in synthesis of alpha 1-AT in cell culture. The SEC receptor recognizes a pentapeptide domain on alpha 1-AT-elastase complexes (alpha 1-AT 370-374), and the same domain in several other serpins, amyloid-beta peptide, substance P, and other tachykinins. Thus, it has also been implicated in the biological properties of these ligands, including the neurotoxic effect of amyloid-beta peptide. In this study, we examined the possibility that the SEC receptor mediates the previously described neutrophil chemotactic activity of alpha 1-AT-elastase complexes, and whether the other ligands for the SEC receptor have neutrophil chemotactic activity. The results show that 125I-peptide 105Y (based on alpha 1-AT 359-374) binds specifically and saturably to human neutrophils, and the characteristics of this binding are almost identical to that of monocytes and hepatoma-derived hepatocytes. Peptide 105Y and amyloid-beta peptide mediate chemotaxis for neutrophils with maximal stimulation at 1-10 nM. Mutant or deleted forms of peptide 105Y, which do not bind to the SEC receptor, have no effect. The neutrophil chemotactic effect of alpha 1-AT-elastase complexes is blocked by antiserum to peptide 105Y and by antiserum to the SEC receptor, but not by control antiserum. Preincubation of neutrophils with peptide 105Y or substance P completely blocks the chemotactic activity of amyloid-beta peptide, but not that of FMLP. These results, therefore, indicate that the SEC receptor can be modulated by homologous desensitization and raise the possibility that pharmacological manipulation of this receptor will modify the local tissue response to inflammation/injury and the neuropathologic reaction of Alzheimer's disease.

Alzheimer Disease↗
PubMed1991

Junctional region sequences of T-cell receptor beta-chain genes expressed by pathogenic anti-DNA autoantibody-inducing helper T cells from lupus mice: possible selection by cationic autoantigens.

We rescued from the spleens of 10 (SWR x NZB)F1 (SNF1) mice with lupus nephritis the T cells that were activated in vivo and cloned 268 T-cell lines and hybridomas. Only 12% of these T-cell clones had the functional ability to preferentially augment the production of pathogenic anti-DNA autoantibodies. Among these, 16 helper T-cell (Th-cell) clones that were mostly CD4+ and had the strongest autoantibody-inducing ability were analyzed for T-cell receptor (TCR) beta-chain gene usage. Seven of the 16 Th-cell clones expressed beta-chain variable region (V beta) V beta 8 (8.2 or 8.3) genes and three expressed V beta 4, whereas two clones each used a V beta 1 or V beta 2 or V beta 14 gene, suggesting some restriction in TCR gene usage. Although heterogeneous, the V-D-J junctional region sequences of TCR beta-chain genes used by these Th-cell clones invariably encoded one or more negatively charged residues (aspartic or glutamic acid) that had been generated in most cases by unspecified nucleotide (N) additions. Representative pathogenic autoantibody-inducing Th-cell clones could rapidly induce the development of lupus nephritis when injected into young prenephritic SNF1 mice. The pathogenic autoantibody-inducing Th cells expressing the anionic residues in their TCR beta-chain junctions (complementarity-determining region CDR3) were probably selected by some cationic autoantigenic peptide presented by the anti-DNA B cells they preferentially helped. These results offer a clue regarding the nature of the primary autoantigen that may drive the pathogenic autoimmune response in lupus.

Amino Acid Sequence↗
PubMed1991

Late potentials and their relation to ventricular function in human immunodeficiency virus infection.

Signal-averaged electrocardiograms were performed in 225 patients with serologic evidence of human immunodeficiency virus infection as part of a prospective longitudinal study of patients with HIV-associated heart disease and 12 seronegative control subjects. The duration of signal-averaged QRS vector, root-mean-square voltage of the terminal 40 ms of the vector magnitude and the duration of the low-amplitude (less than 40 microV) signal were determined during serial visits at 4-month intervals. One or more of these variables was abnormal on initial visit in 59 of patients (26%); QRS duration was greater than 114 ms in 9 patients (4%), root-mean-square voltage less than 20 microV in 55 patients (24%) and low-amplitude signal duration greater than 39 ms in 43 (19%). In contrast, none of the seronegative control subjects had any abnormal variables (p less than 0.03). During follow-up (mean 10 +/- 8 months), 26 patients with initially normal studies developed abnormal variables and 24 with abnormal signal-averaged electrocardiograms reverted to normal. Left ventricular contractility was assessed by echocardiography using the rate-corrected velocity of fiber shortening-end-diastolic wall stress relation. Late potentials were not related to contractile abnormalities. Clinical arrhythmias were rare and did not appear more frequent among patients with late potentials. Thus, late potentials were both common and evanescent in patients infected with human immunodeficiency virus.

Adult↗
PubMed1991

The interaction of caldesmon with the COOH terminus of actin.

Caldesmon interacts with the NH2-terminal region of actin. It is now shown in airfuge centrifugation experiments that modification of the penultimate cysteine residue of actin significantly weakens its binding to caldesmon both in the presence and absence of tropomyosin. Furthermore, as revealed by fluorescence measurements, caldesmon increases the exposure of the COOH-terminal region of actin to the solvent. This effect of caldesmon, like its inhibitory effect on actomyosin ATPase activity, is enhanced in the presence of tropomyosin. Proteolytic removal of the last three COOH-terminal residues of actin, containing the modified cysteine residue, restores the normal binding between caldesmon and actin. These results establish a correlation between the binding of caldesmon to actin and the conformation of the COOH-terminal region of actin and suggest an indirect rather than direct interaction between caldesmon and this part of actin.

Actins↗