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Biomedical subjects

R A Moscicki

Publications and source records attributed to R A Moscicki.

At least 19 recordsLinked to original sources
PubMed1996

Repeat administration of an adenovirus vector encoding cystic fibrosis transmembrane conductance regulator to the nasal epithelium of patients with cystic fibrosis.

Cystic fibrosis (CF) is a common autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator gene. Recombinant adenoviruses have shown promise as vectors for transfer of CF transmembrane conductance regulator cDNA to airway epithelia and correction of the Cl- transport defect. However, because adenovirus-mediated gene transfer is transient, use of adenovirus as a vector for treatment of CF would require repeated administration. Therefore, we evaluated repeat administration of an adenovirus vector to the nasal epithelium of patients with CF with five escalating doses of up to 10(10) infectious units. There were no detectable adverse affects. All subjects were initially seropositive but developed additional humoral immune responses. The vector partially corrected the defect in airway epithelial Cl- transport in some subjects, although there was variability between subjects and there was less correction with subsequent administration, perhaps because the immune response limited gene transfer. Future work must focus on vectors with increased efficiency and with the ability to evade host defenses.

Adenoviridae↗
PubMed1995

Serum antibodies to heat shock protein 70 in sensorineural hearing loss.

OBJECTIVE: To identify the 68-kd target of antibody in serum samples from patients with idiopathic, progressive, bilateral sensorineural hearing loss. DESIGN: To purify target protein from renal extracts using gel filtration, ion-exchange chromatography, and polyacrylamide gel electrophoresis and to transfer to nitrocellulose membranes. The purified protein was digested with trypsin, and peptide fragments were separated by high-pressure liquid chromatography. RESULTS: One fraction obtained by high-performance liquid chromatography contained a peptide of 2776 molecular weight. The sequence of a stretch of 22 amino acids within this peptide was identical to that of amino acids 424 through 445 of heat shock protein 70 (HSP70). On Western blotting, monoclonal antibody directed against HSP70 (but capable of recognizing both constitutive HSP70 [HSC70] and stress-inducible HSP70) reacted with the purified 68-kd protein. We compared the reactivity of serum samples from six patients with idiopathic, progressive, bilateral sensorineural hearing loss, as well as monoclonal antibody to HSC70, and monoclonal antibody to HSP70 with renal extract. The pattern obtained suggested that patient antibodies are preferentially directed at HSP70. CONCLUSION: The target of antibody in serum samples from patients with idiopathic, progressive, bilateral sensorineural hearing loss is HSP70.

Amino Acid Sequence↗
PubMed1995

Serum antibodies against heat shock protein 70 in Menière's disease.

Menière's syndrome of fluctuating sensorineural hearing loss, episodic vertigo, and tinnitus is the clinical presentation resulting from several different pathologic processes. The present study was designed to probe for immunologic factors in Menière's disease. It has previously been shown that the presence of circulating antibodies against a 68-kD protein detected by Western blot immunoassay of serum from patients with idiopathic, progressive, bilateral sensorineural hearing loss (IPB SNHL) is highly correlated with both activity of disease and corticosteroid responsiveness of the hearing loss. The authors recently have identified the 68-kD protein as heat shock protein 70 (HSP70). This study presents a retrospective review of results of Western blot assays in 30 patients meeting strict AAO-HNS diagnostic criteria for Menière's disease. Overall, 47% of patients had anti-HSP70 antibodies. When broken down by clinical pattern, anti-HSP70 antibodies were present in 58.8% of bilateral Menière's disease, 37.5% of contralateral delayed endolymphatic hydrops, and 33.3% of unilateral Menière's disease with IPB SNHL in the second affected ear. Detection of antibodies to HSP may serve to identify a subset of patients with Menière's disease in whom immunologic factors have a pathogenic role.

Adult↗
PubMed1994

Immune-mediated inner ear disorders.

Immune-mediated inner ear disease is characterized by sensorineural hearing loss which is most often rapidly progressive and bilateral, may be accompanied by vestibular symptoms, and for which no cause can otherwise be identified. The problem may occur alone or in combination with other systemic autoimmune disorders. Recognition of this entity is important as a substantial number of such patients experience improvement in hearing following treatment with corticosteroids with or without other immunosuppressive agents. Immune response to inner ear antigens can be helpful in establishing the diagnosis. The lymphocyte transformation assay has been used in identifying such responses but is limited by sensitivity and inhibited by immunosuppression. Western blot identification of serum antibodies to a 68-kD antigen of the inner ear appears to be a promising means of identifying patients with immune-mediated inner ear disease. The antibody is present in the majority of patients with clinical features consistent with the disorder; it correlates with disease activity and is predictive of response to treatment. Nevertheless, response to corticosteroid therapy remains the most convincing evidence of the disease.

Antibody Formation↗
PubMed1992

T cell heterogeneity in patients with common variable immunodeficiency as assessed by abnormalities of T cell subpopulations and T cell receptor gene analysis.

T lymphocyte regulation of immunoglobulin production may be abnormal in some patients with common variable immunodeficiency (CVI). Phenotypic analysis of peripheral blood T lymphocytes from nine patients with CVI was conducted to examine whether an abnormal distribution could be detected in a functionally distinct T lymphocyte subpopulation. The percentage of CD8+ lymphocytes proved to be increased in some patients and decreased in others. In comparison with normal controls, many patients with CVI had reduced percentages of lymphocytes expressing both CD4 and CD45RA, a phenotype associate with naive CD4+ cells. There was no significant difference in CD4+ populations bearing CD29 or leucocyte adhesion molecule-1 (LAM-1) antigens. The pattern of gene rearrangement of the T cell antigen receptor (TCR) was studied using peripheral blood lymphocytes from these patients with CVI. Genomic DNA from freshly isolated lymphocytes as well as from selectively propagated CD4+ or CD8+ populations were examined using Southern blot analysis and a probe for the beta chain of the TCR. A polyclonal pattern of TCR gene rearrangement, without the appearance of dominant non-germline bands, was demonstrated in all patient samples. These data suggest that the T lymphocytes in patients with CVI have a polyclonal pattern of TCR rearrangement despite an abnormal distribution of T cell subpopulations in some patients.

Adult↗
PubMed1992

Bovine temporal bones as a source of inner ear antigen.

Modern immunologic techniques of immunostaining, immunoblotting, and creation of monoclonal antibodies are gaining wide application in studies of development, function, and pathology of the ear. These techniques require a source of inner ear tissue for production of antigen extract. Human tissue is not readily available, and other mammalian species common in auditory research are small in size. Bovine temporal bones are readily available, and the membranous portions of the inner ear are abundant and easily accessible. Herein we report our technique for acquisition and dissection of bovine temporal bones and preparation and preservation of inner ear antigen.

Animals↗
PubMed1990

Anaphylaxis during induction of general anesthesia: subsequent evaluation and management.

Twenty-seven patients were referred for evaluation of anaphylaxis after induction of general anesthesia (GA) in which thiobarbiturates, muscle relaxants, or antibiotics were administered intravenously. Skin testing by the prick and intracutaneous methods was performed with dilutions of the thiobarbiturates and muscle relaxants; beta-lactam reagents were used in patients who had also received these drugs. No skin test reactivity was noted in 16 normal subjects. Skin tests were positive in 13 patients (thiobarbiturates in five, muscle relaxants in six, and antibiotics in two patients). Two patients were dermatographic and yielded indeterminate skin test results. Eleven of the 27 patients subsequently had GA; all patients received a premedication regimen of prednisone and diphenhydramine. Of three patients with negative skin tests, one experienced an arrhythmia, but no other signs attributable to anaphylaxis were noted. One patient with dermatographism had GA without a reaction. Positive skin tests implicated an agent that was avoided in seven patients; one of these patients experienced delayed urticaria/angioedema after the completion of GA. Thus, no patients developed anaphylaxis during subsequent GA for which agents producing positive skin tests were avoided, and a premedication regimen was used.

Adolescent↗
PubMed1990

Monoclonal antibodies to rat Kupffer cells. Anti-KCA-1 distinguishes Kupffer cells from other macrophages.

Two monoclonal antibodies, anti-KCA-1 and anti-KCA-2, directed against rat Kupffer cells (hepatic sinusoidal macrophages) were developed. Immunohistologic studies of the liver and analysis of isolated hepatic cells by immunofluorescence and flow cytometry showed that the reactivity of these antibodies was restricted to macrophages. Both KCA-1+ and KCA-2+ cells were located predominantly in the periportal region; in contrast, Ia+ sinusoidal cells were located primarily in the centrilobular region. Macrophagelike cells within the portal tracts expressed KCA-2 but not KCA-1. These findings indicate the presence of heterogeneity within the macrophage population of the liver. Anti-KCA-1 reactivity appeared to be almost entirely restricted to Kupffer cells; only a few macrophages in the thymus and a small number of cells in the bone marrow expressed KCA-1. In contrast, KCA-2 was more widely distributed; splenic, lymph node, and intestinal macrophages were intensely stained with anti-KCA-2. These studies indicate that KCA-1 is a marker of Kupffer cells.

Animals↗
PubMed1989

Lymphedema, lymphocytic myocarditis, and sarcoidlike granulomatosis. Manifestations of Whipple's disease.

A patient with Whipple's disease presented with a long prodromal period characterized by granulomatous lymphadenitis and progressive lymphedema of the extremities. No gastrointestinal tract symptoms were present and a small bowel biopsy sample was normal. His clinical condition deteriorated with the onset of lymphocytic myocarditis. At autopsy, intestinal involvement with macrophages that stained positively with periodic acid-Schiff was limited primarily to the submucosa. Diffuse fibrous effacement of lymph nodes with afferent lymphangiectasia seemed to be the mechanism of diffuse lymphedema, protein-losing enteropathy, and hypoproteinemia. Whipple's disease, therefore, should be considered in the differential diagnosis of patients presenting with granulomatous disease, lymphocytic myocarditis, or unusual lymphedema.

Adult↗
PubMed1984

Immunopathology of pityriasis lichenoides acuta.

Eleven biopsy specimens (five papules and six dusky or crusted lesions) from four patients with pityriasis lichenoides et varioliformis acuta ( PLEVA ) were studied by direct immunofluorescence and immunoperoxidase technics. Slight vascular deposits of IgM and C3 were present in most lesions. Slight perivascular deposits of fibrin were observed in early lesions; more extensive perivascular and interstitial deposits of fibrin were detected in advanced lesions. Most of the infiltrating cells were T lymphocytes; cells with cytotoxic/suppressor phenotype (T8-positive) were generally more numerous than cells with helper/inducer phenotype (Leu-3a-positive, T4-positive). A marked increase in epidermal T8-positive cells over epidermal Leu-3a/T4-positive cells was found in late lesions. Moreover, a reduction of the ratio of circulating T4-positive to T8-positive cells was observed in most cases. The number of epidermal T6-positive (Langerhans/indeterminate) cells was decreased in the lower as compared with the upper stratum spinosum. About 5% of perivascular infiltrating cells were T6-positive. These results suggest that cell-mediated immune mechanisms are probably important in the pathogenesis of PLEVA .

Adult↗
PubMed1984

Lymphocyte activation antigens. I. A monoclonal antibody, anti-Act I, defines a new late lymphocyte activation antigen.

Lymphocyte activation entails a sequence of events identified by analyzing the time course of expression of various distinctive cell surface molecules on lymphocytes that appear early (before initiation of DNA synthesis), parallel with DNA synthesis and cellular proliferation, or late (after peak proliferation). In this study we present identification of a novel late lymphocyte activation antigen, Act I, utilizing a murine monoclonal antibody. Anti-Act I was identified in a fusion of NS1 with BALB/c spleen cells immunized with a human tetanus toxoid-reactive T lymphoblast line. Flow cytometry analysis shows that Act I antigen is present in markedly greater amounts on activated T and B lymphocytes than on resting, small peripheral blood lymphocytes. Act I expression by these lymphocytes is promoted by PHA, tetanus toxoid, or alloantigens and lags behind maximal thymidine incorporation by 1 to 2 days. Thymocytes can be triggered to express Act I antigen during maturation induced by PHA/T cell growth factor stimulation. In vitro, anti-Act I does not affect antigen- or lectin-stimulated T cell proliferation, T cell-mediated lymphocytotoxicity, or T cell growth factor-induced proliferation of T lymphoblasts. By immunoperoxidase analysis, Act I antigen is restricted to lymphoid tissue, staining many lymphocytes in the paracortex, germinal centers, and mantle zones of lymph nodes, tonsil, and spleen. By immunoprecipitation, the Act I antigen is a single band of 63,000 m.w. on reduced or nonreduced SDS gels. The distribution, size, time course, and functional correlates indicate that Act I is different from other known T cell activation markers detected with anti-Tac, OKT9, B3/25, OKT10, 4F2, CBL1, and anti-Ia-like antibodies. Although the function of Act I is still undetermined, it may serve as a useful marker of a late stage of activation in vitro and in vivo.

Animals↗
PubMed1983

T-cell subsets in human lymphocytes maintained in IL-2 medium after PHA or mixed lymphocyte reaction activation.

The culture of human T lymphocytes in interleukin-2 (IL-2) containing growth factor medium results in a significant shift in the T-lymphocytes subsets isolated from such cultures at weekly intervals. If normal peripheral blood mononuclear cells are stimulated with phytohemagglutinin (PHA) or in a mixed lymphocyte reaction (MLR), the resulting T lymphoblasts can be propagated in growth factor medium. Staining of the cultured cells with monoclonal antibodies was evaluated by indirect immunofluorescence on a laser-activated flow cytometer (Ortho Spectrum III). The antibodies used were: OKT3 (mature T lymphocytes), OKT4 (helper/inducer T lymphocytes), OKT8 (cytotoxic/suppressor T lymphocytes, OKT10 (immature and "activated" lymphocytes), OKT11a (cells which rosette with sheep erythrocytes), and OKIa-I (HLA-DR constant region). Both PHA and MLR activation resulted in initial preservation of the OKT4+ subset predominance over OKT8+ T lymphocytes noted on normal circulating blood lymphocytes. However, during culture in T-cell growth factor medium, there was a progressive increase in the percentage of OKT8+ cells, and a concomitant decrease in OKT4+ lymphoblasts. The increase in OKT8+ cells in the MLR-stimulated cultures was paralleled by an increase in specific cell-mediated cytotoxicity against the stimulating lymphocyte population. In addition to the shift in T-lymphocyte subset, there was virtual 100% staining with OKT3 and OKT11a, indicating the T-cell nature of the proliferating cells. OKT10 which was present on a small subset of fresh blood lymphocytes appeared rapidly in stimulated cultures, and was retained on virtually all lymphoblasts of either OKT4+ or OKT8+ subset. OKIa-1 cells increased slowly in PHA-stimulated cultures. HLA-DR+ T cells were detected earlier in MLR cultures. The activation of T lymphocytes results in a significant increase in the number of molecules of OKT11a bound per cell, in concert with the increased avidity of T lymphoblasts for sheep erythrocytes. The significant change in the phenotype and function of lymphoblasts isolated from long-term cultures demonstrates the importance of monitoring cultures, and the potential hazards in equating a cultured cell population with a freshly isolated one.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1983

Modulation of surface antigens of a human monocyte cell line, U937, during incubation with T lymphocyte-conditioned medium: detection of T4 antigen and its presence on normal blood monocytes.

The human monocyte line, U937, derived from an individual with histiocytic lymphoma, undergoes morphological and functional changes when incubated with medium conditioned by lectin-stimulated cloned human T lymphocytes. Using monoclonal antibodies and flow cytometry, we therefore analyzed alterations in surface components that might accompany these morphological changes, in comparison with components present on normal blood monocytes. The U937 cells possess three surface antigens in common with blood monocytes, detected with OKM1, 4F2, and anti-monocyte.2 (the last monocyte specific). DR antigen was not detectable on U937 cells with three anti-DR framework antibodies but was detected on blood monocytes. Unexpectedly, OKT4, a monoclonal antibody to T4 antigen previously believed to be restricted to helper T lymphocytes, also reacted with U937 cells. Six monoclonal antibodies to other epitopes on T4 also reacted with U937 cells. None of these could be inhibited by blocking of Fc receptors. T4 with its various epitopes were also expressed on normal human blood monocytes. Other lymphocyte surface markers (T3, T8, T6) and fibronectin were not detectable on U937 cells or monocytes. An individual, whose lymphocytes lacked the epitope detected with OKT4 but had epitopes detected with OKT4 A, B, C, and D, had monocytes with identical reactivity, evidence that the T4 on monocytes and lymphocytes are products of the same structural gene. Stimulation of U937 cells for 24 hours with supernatants from Con A-stimulated T lymphocyte clones caused an increase in expression of OKM1 and Fc receptor activity and a decrease in expression of T4, consistent with a more mature phenotype of blood monocytes. Although the function of the T4 molecule is unknown, it is notable that it is displayed by two cells of distinct lineage which interact in the response to soluble antigens.

Animals↗
PubMed1982

Reduction of the fraction of circulating helper-inducer T cells identified by monoclonal antibodies in psoriatic patients treated with long-term psoralen/ultraviolet-A radiation (PUVA).

Ultraviolet radiation has been found to alter the distribution and function of human lymphocytes. To determine whether photochemotherapy (PUVA) alters circulating levels of T cell subset marker-bearing lymphocytes, cells from 9 patients with psoriasis undergoing PUVA therapy for several years (mean 4.6 +/- 1.4 yr), 17 patients with active untreated psoriasis, and 20 healthy volunteers were reacted with monoclonal antibodies to T cell surface markers, including OKT3 (all peripheral blood T cells), OKT4 (helper/inducer T cells), OKT6 (common thymocytes), and OKT8 (suppressor/cytotoxic T cells), and analyzed by flow cytometry. There were no differences in the distribution of T cell subsets between healthy volunteers and patients with active psoriasis. In contrast, the percentages of lymphocytes reacting with OKT3 and OKT4 were lower (by 16% and 12% percent respectively, p less than 0.0025) in the PUVA-treated patients compared to healthy volunteers or patients with active psoriasis that had not received PUVA therapy. There was no difference in the percentage of OKT8 and OKT6 bearing cells. Squamous cell carcinoma of the skin subsequently developed in 2 of 3 PUVA-treated patients with the lowest percentages of T4-bearing cells. These findings indicate that long-term PUVA therapy is associated with a reduction in circulating helper/inducer T cells. This reduction may have a role in the altered immune function reported in PUVA-treated patients.

Antibodies, Monoclonal↗