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Biomedical subjects

M S Leffell

Publications and source records attributed to M S Leffell.

At least 37 records · Page 2Linked to original sources
PubMed1995

Evaluation of HLA antibodies with the PRA-STAT test. An ELISA test using soluble HLA class I molecules.

HLA-specific antibody, present before or after transplantation, may adversely effect graft outcome. Antibody testing by cytotoxicity (CYT) is laborious, requires viable lymphocytes, does not differentiate non-HLA cytotoxic antibody, and cannot be used readily on specimens from patients being treated with cytotoxic antibodies. We have evaluated PRA-STAT, an antibody screening kit that uses an ELISA test with soluble HLA class I molecules as targets. We performed 219 tests on a variety of serum specimens, 128 of which were also tested by CYT. There was a highly significant correlation (r = 0.78, P < 0.001) between PRA-STAT (PS) and CYT for the detection of IgG antibodies. Of 66 sera reactive in both assays, 18% had identical specificities defined in both, 27% were more reactive in PS than in CYT, 8% were more reactive in CYT, and 47% had different specificities in the 2 assays, with overlap in slightly more than half the cases. Of 13 sera reactive only in PS, 2 were from non-transfused, nontransplanted males with no evidence of lymphocyte-reactive antibody by antiglobulin tests. PS uses an IgG-specific conjugate, therefore IgM class I-specific antibodies cannot be identified--however, their presence does affect test outcome. This, as well as the panel composition and interlot reproducibility, are areas we believe need to be addressed. The PRA-STAT system is rapid, does not require viable cells or complement, and can be automated in part. Resolution of the problems identified here and availability of an IgM-specific conjugate should make this test system a valuable tool in histocompatibility testing.

Antibodies↗
PubMed1994

The distribution of HLA antigens and phenotypes among donors and patients in the UNOS registry.

We have analyzed HLA data from the UNOS registry on 20,230 patients on the renal waiting list in 1991 and 18,708 donors from 1988-1992. Significant differences were found in the distribution of HLA antigens for comparisons of the total donor pool and the various racial groups of patients as well as for inter- and intraracial comparisons of donors and patients. Within a racial group, the frequencies of blanks and of broad antigens were usually higher in patients while those of splits were usually higher in donors. Comparisons between the total donor pool and the various racial groups of patients showed that the likelihood of mismatch was greater for African-Americans and Hispanics than for Caucasians but that the chance of mismatch is high for all groups and the average number of antigens mismatched will not vary greatly among the different races. Heterogeneity, as measured by the percentage of the population with different phenotypes, was higher in African-Americans (97.2-99.7%) and Hispanics (97.7-99.4%) than in Caucasians (83.3-86.5%) because of multiple occurrences of a few phenotypes, most containing A1, B8 and DR3, in Caucasians. However, the most common phenotypes of Caucasian donors differed from those of Caucasian patients. All phenotypes were rare (0.007-0.61%) and, with the exception of a small group of Caucasian patients, the likelihood of achieving a good match is low, regardless of race. These data explain the observations that, with the exception of the phenotypically identical match, HLA matching does not influence organ distribution significantly.

HLA Antigens↗
PubMed1992

In vitro effects of interleukin-2 and gamma globulin on immune dysfunction in a patient with severe mucocutaneous herpes simplex virus infection.

A previously healthy woman developed severe, recurrent mucocutaneous herpes simplex virus (HSV) infection at 21 years of age. Immunologic assessment over the past 2 years has revealed persistent T-cell and natural killer cell dysfunction despite normal numbers of these cells as measured by flow cytometry. We studied the effect of recombinant interleukin 2 (rIL-2) and gamma globulin on the patient's mononuclear cells in 18-hour 51Cr release assays using HSV-infected and uninfected target cells. Both gamma globulin and rIL-2 significantly enhanced target cell lysis of HSV-infected target cells (P less than .001), but did not increase lysis of uninfected target cells. Addition of the patient's serum had no effect on HSV-infected target cell lysis despite a high HSV IgG titer, indicating a possible specific abnormality in production of antibody-dependent cellular cytotoxicity antibody.

Adult↗
PubMed1992

Chronic T-lymphocyte activation in chronic renal failure: a study of hemodialysis, CAPD and pre-dialysis patients.

In this study we measured indices of T-lymphocyte activation in normal volunteers, chronic hemodialysis patients, CAPD patients and chronic renal failure patients not yet on dialysis. Serum IL-2 levels were elevated in patients compared to controls. Soluble IL-2 receptors were elevated in all three patient groups and were highest in CAPD patients. Clearance of IL-2 and soluble interleukin receptors was negligible in dialysis and renal failure patients. Hemodialysis patients had a significantly lower percentage of CD3-positive cells than all other groups. Hemodialysis with a variety of membrane/bath combinations did not significantly affect any of the parameters measured. This study provides some support for the hypothesis that chronic T-cell activation is present in renal failure.

Adult↗
PubMed1991

Lymphocyte levels in subjects with and without amalgam restorations.

The claim that mercury from dental amalgam produces "reduced immunocompetence" was examined by measuring the levels of the three major populations of lymphocytes on 37 subjects--21 with amalgam restorations and 16 without. The results of this study show no indication that amalgam restorations affect the human immune system nor do they support the "reduced immunocompetence" claim.

Adult↗
PubMed1990

Tumor necrosis factor, interleukin-1 and beta 2-microglobulin levels in chronic hemodialysis patients.

We measured tumor necrosis factor (TNF alpha), interleukin-1 (IL1-B), and beta-2 microglobulin (B2M) levels in 10 chronic hemodialysis patients before and during dialysis with six different dialysate/dialyzer combinations. The mean pre-dialysis serum level of B2M was 23.4 +/- 11.1 mg/L (nl less than 3 mg/L). There was no significant effect of hemodialysis with any dialysate/dialyzer combination on intradialytic serum B2M levels. Five patients had detectable pre-dialysis serum levels of TNF alpha (greater than 40 pg/ml) at least once and 2 had detectable levels prior to all dialyses. Six patients had detectable pre-dialysis serum levels of IL1-B (greater than 20 pg/ml) at least once, and 2 had detectable levels prior to all dialyses. Serum TNF alpha, IL1-B and B2M levels were not significantly correlated with one another. Our data do not support the hypothesis that blood-membrane interactions significantly affect circulating levels of TNF alpha, IL1-B or B2M. Chronic high level elevations of plasma IL1-B and TNF alpha are not uniformly observed in hemodialysis patients, arguing against a role for these substances as systemic uremic toxins.

Acetates↗
PubMed1990

Evaluation of immunocompetency in juvenile laryngeal papillomatosis.

The morbidity from juvenile laryngeal papillomatosis (JLP), a disease process characterized by recurrent growth of multiple epithelial papillomas, has greatly improved with the advent of immunomodulating agents used in combination with the surgical approach of CO2 laser vaporization. In prospectively evaluating the immunologic status of four pediatric patients with this disorder, one patient repeatedly demonstrated IgG2 subclass deficiency. One of two children found to have subnormal functional natural killer (NK) activity received thrice weekly intramuscular administration of 3,000,000 units/m2 body surface area of human leukocyte (alpha) interferon (IFN). Natural killer function normalized, but therapy was discontinued after 4 months; however, no clinical benefits from IFN administration were observed. Further in vitro evaluation of NK function and lymphokine production is needed, in order eventually to offer more effective immunomodulating agents to such patients. A brief review of the literature concerning JLP is also presented.

Child, Preschool↗
PubMed1989

Type I diabetes in an adolescent with common variable immunodeficiency.

A male adolescent with common variable immunodeficiency developed type I diabetes approximately 1 year after the initiation of immunoglobulin therapy. Immunologic evaluation revealed decreased numbers of T cells and an intrinsic B cell defect in immunoglobulin production. Lymphocytes from the patient failed to generate normal suppressor activity. There were no insulin or islet cell antibodies present in the patient's serum or in the commercial immunoglobulin preparations he received. The patient's HLA phenotype included HLA-DR3 and 4, placing him genetically at high risk for type I diabetes.

Adolescent↗
PubMed1989

Use of transfer factor in a pediatric AIDS patient with disseminated Mycobacterium avium intracellulare.

An 8-year-old male with AIDS and disseminated Mycobacterium avium intracellulare infection was treated with transfer factor (TF) prepared from maternal lymphocytes. Subsequent lymphocyte stimulation studies and repeat cultures failed to demonstrate improvement during treatment. His overall clinical status remained unchanged. No adverse effects of TF were noted.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Transmission of human immunodeficiency virus (HIV) by transplantation: clinical aspects and time course analysis of viral antigenemia and antibody production.

The human immunodeficiency virus (HIV) was transmitted to a patient who received a cadaveric renal transplant from a donor who had received massive blood component replacement. A negative HIV antibody test was obtained on serum drawn immediately after transfusion. After transplantation, pretransfusion sera and sera obtained several hours after transfusion tested positive for HIV antibody, suggesting that transfusions had transiently diluted the patient's serum and resulted in a false-negative HIV antibody test. Immediately after transplantation, the recipient showed a transient increase in HIV antigen levels followed by a more sustained increase representing de-novo antigen synthesis. Antibodies to HIV were detected 51 days after transplant. The recipient has shown no signs or symptoms of HIV infection after 1 year. In potential cadaveric organ donors, HIV antibody testing should be performed on pretransfusion sera or on sera obtained several hours after massive transfusion of blood products.

Adult↗
PubMed1987

Chromosome abnormalities in Peyronie's disease.

Peyronie's disease is a localized and progressive fibrosis of unknown etiology that affects the tunica albuginea of the penis. We examined cytogenetically cell cultures derived from plaque, adjacent tunica, dermis and lymphocytes in patients with Peyronie's disease, and compared the results to cell cultures established from the tunica albuginea of control patients. Chromosomal abnormalities were detected in 9 plaque-derived cell cultures from 7 of 12 Peyronie's disease patients (58 per cent). Cells cultured from adjacent tunica, dermis and lymphocytes from the same patients were karyotypically normal, as were cultures derived from control (chordee and penile scar) patients. Chromosomal aberrations consisted of 5 numerical changes and 4 structural rearrangements, and included chromosomal additions (trisomy 7 and trisomy 8), deletions (45X,-Y), reciprocal translocations and inversions or markers. In 2 instances cultures derived from plaque tissue contained 2 independent chromosomal abnormalities. The apparently random chromosomal changes associated with Peyronie's disease suggests that karyotypic instability may be a common feature of cells within the plaque. It presently is unclear whether this finding represents multiple pathways for the development of Peyronie's disease or secondary consequences of Peyronie's disease.

Aged↗
PubMed1985

An analysis of T lymphocyte subpopulations in patients with Alzheimer's disease.

The relative proportions of regulatory T lymphocyte subpopulations and T lymphocyte proliferative responses to the mitogen phytohemagglutinin (PHA) were studied in 30 patients with clinically apparent Alzheimer's disease (mean age = 71.5). Comparisons were made with 30 age-matched, nondemented healthy controls (mean age = 68.8) and with 20 younger, normal adult controls (mean age = 27.5). The relative percentages of total peripheral T lymphocytes, T helper/inducer lymphocytes (Th), and T suppressor/cytotoxic lymphocytes (Ts) were similar between the Alzheimer patient group and the age-matched controls. However, when the two older groups were compared with the young adult controls, a significant decrease was seen in the percentage of Ts cells, with a concomitant increase in the ratio of Th:Ts. Lymphocyte proliferative responses to PHA were similar in the Alzheimer patients and their age-matched controls; however, when compared with the young adult controls, a significant decrease in responsiveness for both older groups was observed. These results confirm decreases in certain immune indices with aging, but suggest that there are no changes in T lymphocyte subsets or in lymphocyte proliferation, which are unique to Alzheimer's disease.

Adult↗
PubMed1984

Familial third-fourth pharyngeal pouch syndrome with apparent autosomal dominant transmission.

A family is presented in which both siblings and their father had evidence of third-fourth pharyngeal pouch syndrome (DiGeorge syndrome). All three individuals had hypocalcemia and unusual facies. Both infants had truncus arteriosus. One infant had evidence of impaired cell-mediated immunity; the father had a relatively decreased number of T-lymphocytes. The syndrome is uncommon, most cases being isolated, and familial presentations are even rarer. Two recent reports described several affected individuals who also had partial deletions of chromosome 22. Chromosome banding studies in our family were normal. Thus our family demonstrates an autosomal dominant pattern of inheritance, although it cannot be proved that this is a single gene defect. We propose that inasmuch as the presentation of the syndrome is quite varied, thorough family investigation including high-resolution cytogenetic analysis is necessary. Familial cases may be more common and require genetic counseling.

Chromosome Aberrations↗
PubMed1982

Radioimmunoassay versus counterimmune electrophoresis for measurement of serum prostatic acid phosphatase.

Radioimmunoassay (RIA) kits obtained from commercial sources were evaluated and compared with a standard counterimmunoelectrophoretic (CIE) assay for the measurement of prostatic acid phosphatase (PAP) in serum. None of the radioimmunoassays was found to be more sensitive than the CIE assay in detecting elevated serum PAP. Both immunoassays were somewhat more effective clinically in measuring prostatic specific acid phosphatase than an enzyme colorimetric assay. The results obtained by CIE agreed with the results obtained by RIA in 96 per cent of the tests. The number of positive results in patients with confirmed prostate adenocarcinoma increased with disease progression. The low number of positive tests in localized adenocarcinoma (Stages A and B) suggests that neither the CIE nor any RIA procedure is useful for screening unselected populations for adenocarcinoma of the prostate.

Acid Phosphatase↗
PubMed1982

Mechanisms of calcification in Peyronie's disease.

Scanning and transmission electron micrographs demonstrate a calcification process in the penile plaques of patients with Peyronie's disease. Osteoid formation originates from vascular lumina via osteoblast-like cells, which align the calcified plaque. These cells are surrounded gradually by calcified connective tissue. Collagen fibers demonstrate calcification and decreased periodicity.

Calcinosis↗
PubMed1982

Cell culture of Peyronie's disease plaque and normal penile tissue.

Cell cultures derived from Peyronie's disease plaque and normal penile tissue were characterized morphologically and examined by immunofluorescence for actin cable formation, and their growth properties were compared. Relative to normal penile cell cultures which grew as contact inhibited, poorly refractile fibroblast-like cells, plaque derived cell cultures consisted of round and spindle shaped cells that were more refractile and exhibited random crisscross growth patterns. Scanning electron microscopy of plaque derived cell cultures revealed changes in cell surface topography characterized by the appearance of surface membrane blebs amd microvilli. Transmission electron microscopy demonstrated cells containing organized cytoplasmic microfilament bundles and nuclear indentations which resembled myofibroblasts. Such alterations were less extensive or absent in normal penile cell cultures. The amount and extent of actin cable formation was increased in plaque derived compared to normal penile cell cultures. Plaque derived cells also exhibited differences in growth properties and grew to higher saturation densities than their normal counterparts. These results demonstrate that cells derived from Peyronie's disease plaque can be grown in vitro and that these cells are morphologically altered and have an enhanced proliferative capacity. The availability of these cell cultures will permit studies directed at understanding the etiology and pathogenesis of Peyronie's disease.

Actins↗