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Biomedical subjects

S Swanson

Publications and source records attributed to S Swanson.

At least 37 records · Page 2Linked to original sources

Correlation between cellular rejection of cardiac allografts and quantitative changes among T-cell subsets identified by V beta epitope expression.

BACKGROUND: Cellular rejection of an allograft is mediated in part by peripheral blood T cells. We tested the hypothesis that quantitative changes in T-cell subsets can be detected in the peripheral blood and that these changes correlate with rejection. METHODS AND RESULTS: T-cell subset analysis was performed by flow cytometry using monoclonal antibodies recognizing six isotypic epitopes of the T-cell receptor beta-chain variable (V) region. These analyses were done at 7-day (mean) time intervals. Fluctuations within a given subset were determined by dividing the number of positive cells observed by the number of positive cells found on the previous analysis. For healthy volunteers observed over a period of 30 days, 119 of 120 subset ratios (99.2%) fell between 0.5 and 2.0. For patients, 57 of 240 subset ratios (23.8%) fell outside of this range (P < .004, chi 2). The occurrence of the abnormal ratios coincided more closely with cellular rejection (mean +/- SD, 7.7 +/- 6.2 days from a positive biopsy; median, 5 days; range, 0 to 28 days) than did the occurrence of normal subset ratios (mean +/- SD, 14.4 +/- 10.9 days from a positive biopsy; median, 11 days; range, 0 to 44 days; P < .005 by Mann-Whitney U test). Regression analysis confirmed a significant (P < .001, R = .91) temporal association between cellular rejection and abnormal subset fluctuations. No correlation was found between abnormal subset ratios and either vascular rejection or use of high-dose prednisone. CONCLUSIONS: T-cell subset measurement may be a method of noninvasive monitoring of cellular rejection after transplantation and may provide insights into the physiology of graft rejection with the potential for the development of more specific immunosuppressive therapy.

Adult↗

Increased frequency of alloantigen-reactive helper T lymphocytes is associated with human cardiac allograft rejection.

Endomyocardial biopsy (EMB) is the standard method of monitoring heart transplant recipients for the development of allograft rejection. To date, noninvasive methods to detect cardiac allograft rejection have lacked adequate sensitivity and specificity for wide clinical application. In this study, limiting dilution analysis (LDA) was used to quantitate the number of donor alloantigen-reactive helper T lymphocytes (HTLs) in the peripheral blood of cardiac transplant recipients. Cadaveric donor splenocytes were cryopreserved, providing a source of donor alloantigenic stimulation for these assays. Peripheral blood mononuclear cells were harvested from cardiac transplant recipients before transplantation and at the time of EMB. LDA of donor-reactive HTLs was conducted simultaneously on all time points to minimize experimental variation, and these data were related to EMB scores. Frequencies of donor-reactive HTLs in pretransplant samples were highly variable, ranging from 1/1381 to < 1/200,000, and correlated poorly with the degree of HLA disparity. During episodes of moderate rejection, donor-specific HTL frequencies increased an average of 6 times their post-transplant baseline frequency. Additionally, 10-fold increases in HTL frequencies were seen preceding EMB-diagnosed rejection in several individuals. These data indicate that episodes of allograft rejection are associated with increases in the number of circulating donor-reactive HTL which are frequently detected before the development of histologically defined rejection. Thus, monitoring HTL frequencies may serve as a non-invasive method for detecting and predicting cardiac allograft rejection. Furthermore, this assay may provide a valuable means of assessing the in vivo efficacy of various immunosuppressive therapies.

Graft Rejection↗

Residual stress in several ceramometal systems.

Residual stress caused by a mismatch of alloy-porcelain thermal contraction can contribute to clinical failure of a ceramometal restoration. This investigation assessed thermal compatibility of three ceramometal alloys and two opaque porcelains. Thermal expansions of the alloys and porcelains were measured by using a straight push-rod dilatometer. Porcelain glass transition temperatures and expansion values were derived from length-versus-temperature curves. Residual stress states in alloy-porcelain pairs were assessed by comparing expansion values of the components at the porcelain glass transition temperatures. Above that temperature the porcelain viscosity is low and stress relief is possible, whereas below the glass transition the porcelain acts as a stress-supporting solid. Expansion values were in general agreement and glass transition temperatures were slightly lower than values previously reported for similar materials. Alloy-porcelain thermal compatibility for the materials tested appeared more dependent on the opaque porcelain than the alloy.

Chemical Phenomena↗

Second generation assays for the detection of antibody to HBsAg using recombinant DNA-derived HBsAg.

A second generation radioimmunoassay (RIA) and enzyme-linked immunoassay (EIA) for the detection and quantitation of the antibody to hepatitis B surface antigen (anti-HBs) was developed which utilizes recombinant DNA-derived HBsAg (rHBsAg) in place of human plasma derived HBsAg. In these sandwich assays, rHBsAg immobilized on a solid phase was used to capture anti-HBs from the specimen and rHBsAg conjugated to horseradish peroxidase or radiolabeled with 125I was used as a detecting reagent. These rHBsAg-based assays were compared to a commercial radioimmunoassay for anti-HBs detection (AUSAB RIA). For a population of 1711 sera and plasma specimens, 99.2% overall agreement was demonstrated between the recombinant RIA and EIA and 98.6% agreement was observed between the recombinant assays and AUSAB-RIA. The recombinant assays demonstrated equivalent sensitivity and detectability to AUSAB RIA. Most discrepant samples were low-level reactive by AUSAB-RIA, generally less than 10 mIU/ml, and likely represent nonspecific reactivity since no other marker for hepatitis B infection was detected in these samples.

Autoimmune Diseases↗

Cytomegalovirus and appendiceal perforation in a patient with acquired immunodeficiency syndrome.

We have reported the case of a patient with AIDS who had appendiceal perforation and periappendiceal abscess. Extensive infection with cytomegalovirus was found in the appendix; no other pathogen could be implicated in the perforation. This case emphasizes the broad spectrum of disease due to cytomegalovirus, particularly in patients with AIDS and other immunodeficiencies.

Acquired Immunodeficiency Syndrome↗

The status of zinc, copper, and metallothionein in cancer patients.

Metallothioneins that bind copper and zinc have an Mr of 6500 daltons, consist of a single polypeptide chain of 61 amino acids, 25-30 percent of whose residues are cysteine, have a metal-binding capacity of between 5 and 7 g atoms/mol, and contain no disulfide bonds or aromatic amino acids. Zincthionein has been postulated to participate in the transport and storage of zinc, which is involved in more than 235 metalloenzymes, including thymidine kinase, RNA polymerase, and ribonuclease, which in turn play crucial roles in the replication and transcription of DNA during cell division. In addition, trace elements including zinc modulate immune response and function. Conversely, zinc deficiency state causes, for example, thymic atrophy and lymphopenia and modifies antibody-mediated responses to both T-cell-dependent and T-cell-independent antigens. The concentrations of copper, zinc, and metallothionein and the copper/zinc ratio are modified in a number of malignancies. For example, the levels of metallothionein in normal and in malignant human livers are 471 and 75 micrograms/g, respectively. In addition, the copper/zinc ratio is significantly increased in human pancreatic cancer from 1.40 to 2.70. Furthermore, studies involving 64Cu in tumor-bearing mice showed that the distribution of 64Cu was altered and that all tumors contained a relatively high level of 64Cu. Moreover, the activity of superoxide dismutase to remove free oxygen radicals is lower in malignant tissues. Finally, the results of clinical studies suggest that the monitoring of the serum copper/zinc ratio may be a valuable tool, not only in determining the extent of malignancies, but also in predicting the efficacy of treatments.

Animals↗

Characterization of metallothionein-like protein in rat brain.

A metallothionein-like protein has been identified recently in the rat brain which resembles in some but not all aspects a hepatic metallothionein. The synthesis of this protein is stimulated following the administration of zinc and copper but not cadmium. The zinc-stimulated protein incorporates 35S cysteine 24-fold higher than the native, unstimulated protein; is blocked by actinomycin D; produces two isoforms by ion exchange chromatography on DEAE Sephadex A 25 columns; and, by high performance liquid chromatography, depicts a similar but not identical profile to zinc-stimulated hepatic metallothionein. Preliminary studies have shown that the metallothionein-like protein isoform I possesses a Mr of 6200 and consists of 60 residues with 12 cysteine and no histidine, arginine, leucine, tyrosine, or phenylalanine. Since the synthesis of this protein is reduced in the brains of zinc-deficient rats, it is postulated that the free pool of zinc may serve as one of the factors that regulates the synthesis of this protein.

Amino Acids↗

DIABEDS: a randomized trial of the effects of physician and/or patient education on diabetes patient outcomes.

To examine the effects of intensive patient and/or physician diabetes education on patient health outcomes, a controlled trial was conducted in which internal medicine residents and their 532 diabetic patients were randomly assigned to: routine care; patient education; physician education; or both patient and physician education. Patient outcome data were analyzed either by analysis of covariance on post intervention values (2-hour post-prandial plasma glucose [PPG]; body weight [BW]; blood pressure [BP]; or analysis of variance conducted on change values (fasting plasma glucose [FPG] and glycosylated hemoglobin [A1Hgb]). After patient education, significant improvements were observed in FPG, A1Hgb, BW, and systolic and diastolic BP. Physician education resulted in significant decreases in FPG, A1Hgb and BW. The combination of patient plus physician education resulted in the greatest improvements in patients' health outcomes including FPG, A1Hgb, PPG, BW and diastolic BP. Adjusted systolic BPs were not significantly different in the two groups. While these physiologic improvements were statistically and probably clinically significant, hyperglycemia and obesity still persisted. Thus, achieving optimal patient outcomes for a chronic disease like diabetes mellitus may require a greater or more effective use of resources than currently estimated.

Clinical Trials as Topic↗

Cytomegalovirus infection initially diagnosed by skin biopsy.

The reported cases of cutaneous involvement by cytomegalovirus (CMV) are mostly limited to descriptions in immunocompromised patients who had other evidence of systemic CMV infection or in patients whose disseminated infection was not diagnosed until autopsy. However, three cases of CMV infection initially diagnosed from antemortem biopsy of skin lesions have been documented in the literature. The authors review in depth one of these three cases and describe two new cases of CMV infection first identified by skin biopsy. The latter two are the first detailed descriptions of this infection in the skin of burned patients. Review of the literature describing cutaneous CMV involvement reveals protean epidermal and dermal manifestations with consistent histologic findings. Recently, however, there has been documentation of histologically occult CMV in patients with disseminated CMV infection. Skin biopsy of cutaneous lesions in immunocompromised patients is important in the diagnosis of systemic CMV infection.

Adult↗

T-immunoblastic lymphoma mimicking B-immunoblastic lymphoma.

A T-cell immunoblastic lymphoma having plasmacytoid features that mimic B-cell immunoblastic lymphoma, is described. The lesion was composed of sheets of pleomorphic plasmacytoid cells that displayed a helper T-cell immunophenotype (Leu-1+, Leu-3+, Leu-4+, Leu-5+, Leu-9-, Leu-2-). Ultrastructural features were consistent with a T-cell lymphoma. Flow cytometric analysis revealed that the cells were DNA triploid and had a high proliferative activity. Although the histology of immunoblastic lymphomas alone may suggest either a T- or B-cell phenotype, immunophenotyping is essential in making this distinction.

Aged↗

Methotrexate interferes with determinations of conjugated bilirubin with the Kodak Ektachem 400.

Immediately after intravenous infusion of a high dose (concentration in serum greater than 1000 mumol/L) of methotrexate, the apparent conjugated bilirubin (Bc) concentrations in serum of two osteosarcoma patients, as measured by the Kodak Ektachem 400 analyzer, were greater than the corresponding total bilirubin concentrations, but decreased as the concentrations of methotrexate in serum decreased. In an interference study we found that methotrexate added to sera containing a wide range of basal Bc concentrations increased the measured Bc concentration in a linear and dose-related fashion. Methotrexate also interfered negatively with measurements of unconjugated bilirubin (Bu). The source of the interference appears to be an overlap in the absorption spectrum of methotrexate with Bc and Bu at 400 nm.

Autoanalysis↗

Gender and oral contraceptive effects on temporary auditory effects of noise.

The first experiment examined thresholds at 4 and 8 kHz and the threshold of octave masking at 4 kHz before and after noise for males, females, and females using oral contraceptives. Females using oral contraceptives evidenced greater threshold shifts at 4 kHz than either of the other two groups. The second experiment examined thresholds and the loudness discrimination index at 4 kHz for males and females before and after noise exposure. Females evidenced greater loudness discrimination index changes both with and without noise exposure than did males. In addition, females responded to the noise with cutaneous vasodilation while males evidenced vasoconstriction.

Adolescent↗

The role of zinc and zinc-binding proteins in regulation of glutamic acid decarboxylase in brain.

At physiological concentrations, zinc stimulates the activity of pyridoxal kinase, enhancing the formation of pyridoxal phosphate, which in turn enhances the activity of glutamic acid decarboxylase. In toxic doses, zinc inhibits glutamic acid decarboxylase directly and may adversely influence the GABA receptor sites. Zinc-binding proteins, which are inducible by zinc, have been identified in brain and regulate the steady state concentration of free Zn2+. Since free Zn2+ is a potent inhibitor of numerous sulfhydryl-containing enzymes, including glutamic acid decarboxylase, we conclude that zinc-binding proteins not only may function as a physiological donors of Zn2+ to zinc apometalloenzymes, but also may play a decisive role in preventing CNS toxicity by preventing the rise of free Zn2+ in the brain.

Adenosine Triphosphate↗

Dissociation between epileptic seizures induced by convulsant drugs and alteration in the concentrations of pyridoxal phosphate in rat brain regions.

Allylglycine increased the concentration of pyridoxal phosphate in cerebral cortex from 1011.4 +/- 25.0 to 1318.0 +/- 66.3 and decreased it in cerebellum from 1289.0 +/- 49 to 1147.7 +/- 119.4 ng/g wet tissue during the preictal period. Mercaptopropionic acid increased the concentration of pyridoxal phosphate in cerebellum from 1525 +/- 91 to 1985.7 +/- 275 ng/g wet tissue. Similar effects were noted in hippocampus and cerebral cortex. Picrotoxin increased the concentration of pyridoxal phosphate in hippocampus from 938.7 +/- 44 to 1043 +/- 118 but decreased it in cerebral cortex from 1124.52 +/- 124 to 979.4 +/- 15 ng/g wet brain. The effects of strychnine were identical to those of allylglycine. Bicuculline reduced the concentration of pyridoxal phosphate in cerebral cortex from 1184 +/- 61 to 1075.14 +/- 78 ng/g wet brain.

3-Mercaptopropionic Acid↗

The presence of zinc-binding proteins in brain.

Zinc is one of the most abundant divalent metal ions in the brain, its concentration being greater than those of copper and manganese. Since free zinc ion is a potent inhibitor of sulfhydryl enzymes, we postulated that zinc in the brain most probably exists bound to macromolecules. As zinc-binding proteins in brain have not been characterized, we attempted to discover the occurrence and properties of these proteins. By using Sephadex G-75 column chromatography calibrated with proteins of known molecular weights, and by other techniques, we detected separate zinc-binding proteins, with apparent estimated molecular weights ranging from 15,000 to 210,000. Unlike the hepatic or renal zinc thioneins, the zinc-binding proteins in brain are not inducible following administration of zinc. Our interpretation of the results is that the major portion of the existing zinc in the brain is bound, and does not exist in free form.

Animals↗