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Biomedical subjects

H M Lederman

Publications and source records attributed to H M Lederman.

At least 55 records · Page 3Linked to original sources

Haemophilus influenzae type b immunization in infants on peritoneal dialysis. Pediatric Peritoneal Dialysis Study Consortium.

As part of a multi-center collaborative study, we measured antibody levels to Haemophilus influenzae type b (Hib) in ten chronic peritoneal dialysis (CPD) patients, aged 39 months or less, who were immunized while on CPD. Nine of the ten developed protective antibody levels to Hib. Four patients had serial measurements of antibody and all maintained protective levels, although the levels did decrease in two patients. Thus most, but not all, infants immunized with Hib vaccine while on CPD develop protective antibody levels. The factors responsible for vaccine failure are not clear. Whether patients maintain protective antibody over time needs to be determined.

Antibodies, Bacterial↗

Pneumococcal polysaccharide vaccine in children with chronic renal disease: a prospective study of antibody response and duration.

We studied the antibody response to pneumococcal serotypes 3 and 14 after pneumococcal polysaccharide vaccine was administered to 41 children with renal disease. One month after vaccination, 76% and 61% of patients achieved at least a twofold titer rise to serotypes 3 and 14, respectively; this finding was comparable to historic control values. One year after vaccination, the majority of patients retained protective antibody levels. Achieving a titer > or = 1.0 microgram/ml IgG at 1 month was highly predictive of retaining a protective antibody level > or = 0.15 microgram/ml at 1 year.

Adolescent↗

Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of the literature.

The true incidence of sarcoidosis in common variable immunodeficiency (CVID) is unknown. We report here 8 cases of sarcoidosis among 80 patients with CVID followed in our clinics, along with 22 well-documented cases reported in the literature. Sarcoidosis, therefore, represents an important entity to consider among patients with CVID who exhibit clinical, radiographic, laboratory, and biopsy findings compatible with sarcoidosis. Conversely, the diagnosis of CVID should be considered in patients with sarcoidosis who do not exhibit the characteristic hypergammaglobulinemia and who have a history of recurrent infections. Although many features of sarcoidosis are similar in patients with CVID to those in patients with sarcoidosis alone, there are many important differences. Patients with CVID in whom sarcoidosis develops present with hypogammaglobulinemia rather than hypergammaglobulinemia and have a higher prevalence of recurrent infections, thrombocytopenia, and splenic involvement. Steroids, in most cases, appeared helpful in reducing adenopathy and splenomegaly, improving uveitis, lowering serum alkaline phosphatase, and reversing hematologic abnormalities. The underlying pathophysiology responsible for the association of these 2 disorders in the same patient remains obscure. However, as more patients are identified, it may be possible to gain a better understanding of the immunologic defect responsible for the dual presentation of these 2 relatively uncommon diseases.

Adult↗

Hematologic consequences of Borna disease virus infection of rat bone marrow and thymus stromal cells.

Borna disease virus (BDV) was previously believed to have a strict tropism for the nervous system. BDV has recently been identified by a reverse transcription-polymerization chain reaction-enzyme immunosorbent assay (RT-PCR-EIA) in bone marrow cells and peripheral blood mononuclear cells (PBMC) in BDV-infected Lewis rats. We now report the identification of BDV RNA and infectious virus in thymus cells from rats infected either as neonates (PTI-NB) or as adults (4 weeks of age). Based on in vitro studies, we determined that the BDV-infected cells in bone marrow and thymus tissue are fibroblastic stromal cells. Bone marrow stromal cells are nonhematopoietic, fixed-tissue elements that support hematopoiesis, and, thus, it was not surprising that BDV infection altered the recovery from granulocytopenia and leukocytopenia after myelosuppressive treatment. Notably, unlike other immunotropic and neurotropic viruses, BDV does not appear to infect cells of myeloid or lymphoid lineages. We also report the association between BDV in the thymus with the lack, or loss, of encephalitis in neonatally inoculated rats or adult-inoculated rats during the chronic stage of disease.

Alkaline Phosphatase↗

IgG subclass levels in pediatric patients on chronic peritoneal dialysis.

Patients maintained on chronic peritoneal dialysis (CPD) have been reported to have a variety of abnormalities of humoral immunity, including hypogammaglobulinemia, altered response to vaccination, and selective absence of IgG2. We measured serum immunoglobulin and IgG subclass levels in 22 pediatric CPD patients followed at our institution; 8 patients had low total IgG; 4 of these had low levels of IgG2 and 3 also had low IgG1, but IgG2 levels were detected in all patients. Thus, many pediatric CPD patients may have low IgG, and some may have low IgG1 and IgG2 as a reflection of low total IgG. However, we did not demonstrate a selective absence of IgG2 in these patients.

Adolescent↗

Cytokine production by peripheral blood mononuclear cells from pediatric chronic peritoneal dialysis patients.

Previous reports have documented impaired cytokine production by peritoneal macrophages in chronic peritoneal dialysis (CPD) patients. To determine if this observed defect was a reflection of systemic mononuclear cell dysfunction, the function of peripheral blood mononuclear cells obtained from pediatric patients on CPD was assessed after stimulation with lipopolysaccharide (LPS). Levels of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) mRNA and protein were measured before and after stimulation with LPS. There was no significant difference in the response of mononuclear cells from CPD patients and normal controls in terms of increase in TNF-alpha mRNA [median stimulation index (SI) = 6.6 vs. 3.7, P = 0.35] or IL-1 beta mRNA (median SI = 6.2 vs. 6.5, P = 1.0). There was also no significant difference between the median increase in TNF-alpha protein secretion (median 372 pg/ml vs. 373 pg/ml, P = 0.60). These results suggest that systemic mononuclear cell function may be intact in CPD patients, and therefore this does not account for the dysfunction of peritoneal macrophages that has been previously reported.

Adolescent↗

Immunodeficiency and elevated CD4 T lymphocyte counts in two patients coinfected with human immunodeficiency virus and human lymphotropic virus type I.

We describe two patients who were coinfected with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus (HTLV) type I. They had clinical evidence of immunodeficiency (anergy, oral candidiasis, and disseminated herpes zoster) despite having elevated CD4 T lymphocyte counts (range, 2,450-5,292/mm3). We conclude that CD4 lymphocyte counts may not be reliable markers of immunologic competence in patients coinfected with HIV and HTLV-I.

Adult↗

Temporomandibular joint and mandibular growth alterations in patients with juvenile rheumatoid arthritis.

OBJECTIVE: To determine the frequency and type of lesions of the temporomandibular joints (TMJ) as well as orthodontic alterations present in patients with juvenile rheumatoid arthritis (JRA). METHODS: Twenty-six patients had their TMJ evaluated clinically and by high resolution computer tomography. The patients were also submitted to orthodontic evaluation. Children with isolated malocclusion were used as a control group. RESULTS: Computer tomography detected TMJ alterations in 13 (50%) patients with JRA. Bilateral mild lesions were the most frequent. TMJ alterations were especially observed in young patients with JRA with the systemic and polyarticular type of onset. Worse functional class and corticosteroid therapy were also related to TMJ involvement. We observed orthodontic alterations in 18 patients with JRA (69%): midline deviation, convex facial profile. Class II molar relation, crowded lower anterior teeth, anterior open bite, and reduction in the maximum opening of the mouth. Severe TMJ lesions were correlated to cephalometric alterations, suggesting decreased mandibular growth.

Adolescent↗

Neisseria sicca peritonitis in a patient maintained on chronic peritoneal dialysis.

Neisseria sicca, previously classified as a "nonpathogenic" organism, has now been recognized as a cause of many infections, including endocarditis and meningitis. However, it has not been reported as a cause of peritonitis. We present a case of documented N. sicca peritonitis immediately following an episode of Staphylococcus aureus peritonitis in a pediatric chronic peritoneal dialysis (CPD) patient. N. sicca should be considered as a possible pathogen in CPD-associated peritonitis.

Anti-Bacterial Agents↗

Effects of hypoxia on interleukin-2 mRNA expression by T lymphocytes.

OBJECTIVE: To investigate the effects of hypoxia on T-lymphocyte expression of IL-2 messenger RNA (mRNA), after cell activation with phorbol ester and ionomycin. DESIGN: Prospective, controlled, cellular trial. SETTING: University research laboratory. SUBJECTS: EL4.6.1 cells, a murine T-cell lymphoma line. INTERVENTIONS: Tissue culture media was deoxygenated and flushed continuously with 100% helium to maintain a PO2 of 30 to 40 torr (< 40 torr [< 5.3 kPa]), or flushed with 10% oxygen/90% helium to maintain a PO2 of 45 to 55 torr (> 45 torr [> 6.0 kPa]). The pH was maintained between 7.3 and 7.6. The media was inoculated with EL4 cells. Aliquots of cells were obtained at intervals and divided into two groups: an immediate group, stimulated immediately, and an overnight group that was returned to normal incubator conditions of 5% CO2/humidified room air for 18 hrs before stimulation. MEASUREMENTS AND MAIN RESULTS: Gas tension, pH, cell count, and viability were determined for each aliquot. Cells were stimulated with phorbol myristate acetate and ionomycin for 4 hrs, at which time levels of interleukin-2 (IL-2) messenger RNA (mRNA) and gamma actin mRNA were measured by solution hybridization and enzyme immunoassay. The results were expressed as IL-2 mRNA/gamma actin mRNA ratio, normalised to baseline room air values. Cell viability and housekeeping functions (gamma actin mRNA expression) were unaffected by hypoxia. Cells exposed to a PO2 of < 40 torr (< 5.3 kPa) demonstrated a dramatic reduction in IL-2 mRNA expression with increasing duration of hypoxia. These effects persisted after an 18-hr recovery period. There was no effect on IL-2 mRNA expression when cells were exposed to a PO2 of > 45 torr (> 6.0 kPa). CONCLUSIONS: The regulation of IL-2 transcription in the T lymphocyte appears to be exquisitely sensitive to changes in oxygen tension. Exposure to a PO2 of < 40 torr (< 5.3 kPa) causes prolonged impairment of IL-2 mRNA expression. IL-2 is an important growth factor for T and NK cells, and plays a pivotal role in the regulation of the host's immune response. The long-lasting effects of brief hypoxic exposure may, in part, explain the critically ill patient's predisposition to infectious complications.

Animals↗

Hypogammaglobulinemia and fatal sepsis in an infant maintained on peritoneal dialysis.

Chronic peritoneal dialysis (CPD) is a common form of renal replacement therapy in children. Recent studies suggest that immunological abnormalities, in particular hypogammaglobulinemia, may develop in children and infants on peritoneal dialysis. We report an infant maintained on CPD who died of gram-negative sepsis. At post-mortem examination, he was noted to have severe panhypogammaglobulinemia.

Agammaglobulinemia↗

Characterization of a glial cell line persistently infected with borna disease virus (BDV): influence of neurotrophic factors on BDV protein and RNA expression.

Borna disease virus (BDV) infects cells of the nervous system in a wide range of species. Previous work suggests that there are differences in BDV replication in neuronal cells and glial cells. Many neurons are lysed by the immunopathologic response to BDV; lysis of dentate gyrus neurons in the absence of encephalitis is seen in rats inoculated with BDV as neonates. In contrast, persistently BDV-infected astrocytes increase over the course of BDV infection. Therefore, we compared BDV replication in neuronal (SK-N-SH and SK-N-SHEP) and astrocytic (C6) cell lines. While SK-N-SH cells produced more infectious virions per cell, the C6 cells contained more BDV proteins and RNA. BDV sequences in the supernatants of both cell types were identified, despite low titers of infectious virus, suggesting the release of incomplete virions into the medium. C6 cells secreted a factor or factors into the medium that enhanced the production of BDV proteins and RNA in other cell lines. In addition, nerve growth factor treatment produced the same enhancement. Thus, BDV replication in certain neural cells in vitro may be linked to the production of cell-specific factors which affect viral replication.

Animals↗

Anti-tetanus toxoid antibodies in intravenous gamma globulin: an alternative to tetanus immune globulin.

The levels of anti-tetanus toxoid IgG antibodies were measured in 29 lots of intravenous gamma globulin (IVIG). The antibody levels varied from 4 to 90 IU/mL (geometric mean, 18.6; 90% confidence interval, 9.7-35.7). The variation from manufacturer to manufacturer accounted for most of the observed differences among lots; there was relatively little variability among multiple lots from a single manufacturer. IVIG may be an acceptable alternative to horse or human tetanus immune globulin.

Antibodies, Bacterial↗