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Biomedical subjects

J M Bernstein

Publications and source records attributed to J M Bernstein.

At least 19 recordsLinked to original sources
PubMed1992

Recurrent otitis media with non-typable Haemophilus influenzae: the role of serum bactericidal antibody.

The effect of serum bactericidal antibody on colonization with non-typable Haemophilus influenzae (NTHI) was studied in 26 children. Serum bactericidal antibody did not prevent colonization with NTHI in the nasopharynx. Antibody was present in 53% before, 91% during and 100% after documented colonization of the nasopharynx with NTHI. In addition, 5 children with recurrent otitis media with effusion (OME) due to NTHI were observed for bactericidal serum antibody during a 4-year period. Bactericidal antibody against the causative NTHI strain was not detected in the acute sera of any patient during each episode, but was observed in the convalescent sera of all of the patients. The bactericidal antibody in the convalescent serum did not appear to be protective against colonization and recurrence of disease by a different heterologous strain of NTHI. However, bactericidal antibody was augmented in some cases by a heterologous infection with NTHI. We confirmed the emergence of new strains of NTHI with DNA fingerprinting and outer membrane protein (OMP) analysis. The data suggest that the immune response to NTHI in OME is usually strain-specific, and furthermore, the results demonstrate that strain-specific bactericidal antibody does not prevent colonization in the nasopharynx with the homologous or heterologous bacterial strains. In general, bactericidal antibody is not cross-protective against heterologous strains of NTHI causing a second or third episode of otitis media with NTHI.

Antibodies, Bacterial↗
PubMed1992

Distribution characteristics of immunoglobulin-secreting cells in adenoids. Relationship to age and disease.

Forty-four adenoids and 52 palatine tonsils from 71 children and adolescents (age 3-21 years) undergoing surgery because of adenoidal hypertrophy or recurrent tonsillitis were examined for the presence of immunoglobulin-secreting cells (ISC) employing an enzyme-linked immunospot assay (ELISPOT). ISC constituted less than 2% of the mononuclear cell population. Adenoids contained IgG, IgA, and IgM ISC in significantly lower numbers than palatine tonsils. The predominant isotype of the ISC was IgG, in adenoids accounting for 62% of the ISC and in palatine tonsils for 73%. The relative numbers for IgA and IgM ISC were similar. A significant correlation existed between autologous adenoids and palatine tonsils for the numbers of IgA and IgM ISC, but not for the numbers of IgG cells. These observations suggest that, adenoid and palatine tonsils display similar immunoglobulin distribution patterns within a single individual. However, individuals with hypertrophied adenoids exhibited a numeric decrease in IgG ISC with increasing age (P less than 0.01). Both lymphoid tissues may be involved in mucosal immune defense.

Adenoids↗
PubMed1992

Active respiratory syncytial virus purified by ion-exchange chromatography: characterization of binding and elution requirements.

Two viruses, respiratory syncytial virus (RSV) and vesicular stomatitis virus (VSV) were used to evaluate viral purification by an affinity resin column (Matrex Cellufine Sulfate (MCS); Amicon Division, WR Grace & Co.). Viable RSV was purified significantly from crude cell lysate by a single pass through a column containing the anionic MCS resin. Most cell protein and albumin eluted from the MCS resin with phosphate buffered saline (PBS) but RSV eluted at high ionic strength, i.e., greater than or equal to 0.6 M NaCl. Further purification was possible by sucrose step gradient centrifugation. The RSV prepared by column purification or by column plus sucrose gradient separation was both intact and infective. RSV and pure samples of VSV were used to optimize ionic strength and salts for elution from the MCS column: 0.8 M NaCl removed most of the viral protein. The capacity of the MCS gel for RSV or VSV was found to be about 0.6-0.8 mg viral protein per ml of hydrated resin. Detergent-solubilized viral membrane proteins bound to the MCS resin in 0.145 M NaCl and eluted with higher salt concentrations. Thus, this resin also may be a useful aid for relatively gentle purification of these proteins.

Centrifugation, Density Gradient↗
PubMed1992

Role of Epstein-Barr virus and interleukin 6 in the development of lymphomas of human origin in SCID mice engrafted with human tonsillar mononuclear cells.

Mice with severe combined immunodeficiency were inoculated intraperitoneally with 50 x 10(6) human tonsillar mononuclear cells (hu-TMCs) from Epstein-Barr virus (EBV) antibody seropositive or seronegative human subjects. Between 5 and 11 weeks later, 29.4% (10/34) of mice injected with hu-TMCs from EBV seropositive donors, but none of 34 animals receiving hu-TMCs from EBV seronegative donors, developed intraabdominal and/or intrathoracic tumours (P, 0.002). By means of in situ hybridization using alpha satellite DNA from human chromosome 17, all tumours produced after cell transfer from EBV seropositive donors were identified to be of human origin. Histologically the tumours resembled large cell lymphomas; the EBV genome was detected by in situ hybridization and EBV nuclear antigen by immunofluorescence in these tumours. The tumours were poly- or oligoclonal, and stained for human IgG and IgM, and less frequently IgA and IgD. Serum levels of human immunoglobulin in animals developing human tumours were significantly higher than in reconstituted mice without tumours and the sera exhibited polyoligo- or monoclonality in immunoelectrophoresis. Human interleukin 6 was detected in the serum of six of 10 animals with human lymphomas, but not in any animals without human lymphoma.

Adolescent↗
PubMed1992

Mucosal immunology of the upper respiratory tract.

The palatine tonsils and nasopharyngeal adenoids represent the predominant immunocompetent tissue of the upper respiratory tract. Its major function is as a first line of defense against viral, bacterial, and food antigens that enter the upper aerodigestive system. Another major function of the tonsils and adenoids is to supply the local mucosal immune system of the upper respiratory tract with dimeric IgA-producing B cells. Secretory IgA has particular hydrophilic properties and is capable of preventing adsorption and penetration of bacteria and/or viruses into the upper respiratory tract mucosa. In addition, the role of the indigenous flora of the upper respiratory tract, particularly the viridans streptococci has been emphasized as providing a valuable source of bacterial interference to the colonization of potential pathogens.

Adenoids↗
PubMed1992

Immunologic response of adenoidal lymphocytes to respiratory syncytial virus.

Adenoidal lymphocytes obtained from 43 subjects with serum antibodies to respiratory syncytial virus (RSV) were established in culture in vitro and analyzed for immunoglobulin (Ig) and RSV-specific antibody synthesis. Spontaneous synthesis of Ig was consistently observed in culture supernatants. The ratios of IgA to IgG and IgM to IgG in adenoidal lymphocyte culture supernatant were higher than in serum. In cell cultures stimulated with RSV or pokeweed mitogen, RSV antibody activity was detected in 25 of 43 (58.1%) for IgG, 5 of 43 (11.6%) for IgA, and 4 of 43 (9.3%) for IgM. Also, RSV-specific IgG was detected in some supernatants from unstimulated cultures. In seven cases the cultures of autologous tonsillar lymphocytes were also investigated. Autologous organs exhibited similar polyclonal Ig production and RSV-specific antibody synthesis. These observations demonstrate that both adenoids and palatine tonsils are continuously engaged in synthesis of local antibodies to viral pathogens available to the nasopharynx and respiratory mucosa.

Adenoids↗
PubMed1992

Otitis media.

Explore the source record for details and available documents.

Humans↗
PubMed1992

A comparison of netilmicin and tobramycin therapy in patients with renal impairment.

We evaluated the toxicity and efficacy of netilmicin and tobramycin in 89 older adults with serious bacterial infections and pre-existing renal impairment in a prospective, blinded, randomized trial. Complete resolution or improvement of infection occurred at 34/36 (94%) evaluable sites in netilmicin-treated patients and at 26/31 (84%) evaluable sites in tobramycin-treated patients. 10/44 (23%) netilmicin- and 7/45 (16%) tobramycin-treated patients experienced nephrotoxicity during treatment. The mean serum creatinine level improved significantly at the end of therapy compared to pre-treatment in those patients who did not experience nephrotoxicity in both treatment groups. 5/19 (26%) netilmicin-treated patients and 2/18 (11%) tobramycin-treated patients assessable for ototoxicity experienced decrements in auditory thresholds. Ototoxic netilmicin-treated patients had higher serum netilmicin levels than did non-ototoxic patients. Patients who experienced ototoxicity were not more likely to have experienced nephrotoxicity. The rates of toxicity were not statistically different and were similar to those seen in studies of patients with normal pre-treatment renal function.

Aged↗
PubMed1992

The role of IgE-mediated hypersensitivity in the development of otitis media with effusion.

The potential mechanisms of IgE-mediated hypersensitivity in OME have been reviewed. Two important questions were addressed at the beginning of this manuscript: (1) is OME an allergic disease, or (2) is OME a complication of an allergic disease in another part of the respiratory system? In regard to the first question, recurrent OME is associated with allergic rhinitis in about one-third of the studied population. However, of the patients who do have allergic rhinitis, in the great majority of children the middle ear mucosa is not the target organ. Rather, there appears to be increasing evidence that with both nasal provocation and natural antigen provocation in children during a normal allergen season, eustachian tube function is altered by nasal allergy. Whether this is truly physiologic or an artificial phenomenon cannot be determined at this time, as it is not absolutely clear whether the nine-step eustachian tube function test currently performed is really a measure of eustachian tube dysfunction, despite its forming the basis of all studies published so far, although one must conclude from current data that allergic rhinitis can produce eustachian tube dysfunction; there have been no cases in these studies in which allergic rhinitis produced otitis media. However, eustachian tube dysfunction is one of the major precursors in the development of OME. We believe that the anatomic part of the upper respiratory tract involved in the IgE-mediated hypersensitivity is most likely the mucosa of the nasopharyngeal portion of the eustachian tube. Inasmuch as total nasal obstruction, at least in adults, does not produce eustachian tube dysfunction in the great majority of cases, it is proposed that eustachian tube dysfunction that follows nasal provocation and occurs during the normal allergy season does so as a result of the transport of mediators of inflammation from inflammatory cells in the nasal mucosa via the nasal mucociliary system to the nasopharyngeal orifice of the eustachian tube. The role of food allergy is still problematic, but this author suggests that there is some supportive evidence that food immune complexes, particularly with dairy products, may play a role, especially in the otitis-prone child under the age of 2 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Allergens↗
PubMed1991

Distribution and engraftment patterns of human tonsillar mononuclear cells and immunoglobulin-secreting cells in mice with severe combined immunodeficiency: role of the Epstein-Barr virus.

Tonsils seem to be the ideal source of lymphocytes seeding to the mucosa of the respiratory tract. The distribution and engraftment of human lymphocytes injected into mice with severe combined immunodeficiency (SCID) are not well understood. C.B-17 SCID mice were injected intraperitoneally with human tonsillar mononuclear cells (hu-TMC). The hu-TMC-SCID mouse chimeras were subsequently tested for the appearance and distribution of human lymphocytes tagged with H33342 and immunoglobulin-secreting cells in various systemic and mucosal immunocompetent tissues. This was done by fluorescence microscopy of tissue sections for cells supravitally stained before transfer and by an enzyme-linked immunospot assay using cells isolated from murine organs. Most importantly, engraftment of hu-TMC proved to be dependent on the presence of anti-Epstein-Barr virus (EBV) antibody in the donor. hu-TMC engrafted, in decreasing numbers, in the following systemic organs: peritoneal cavity, liver, spleen and bone marrow. Among mucosal tissues tested, hu-TMC were seen in lungs, but not in the intestines. The engraftment of hu-TMC in the lung was more extensive than that in the spleen. These studies demonstrate that hu-TMC engraft in a variety of murine tissues. The striking preference of hu-TMC for the lungs when compared to intestines suggests selective engraftment among distinct mucosal tissues. The hu-TMC-SCID mouse chimera promises to be a unique animal model to study human-mucosa-associated lymphoid cells and EBV-related lymphomagenesis and B cell tumor progression.

Adult↗
PubMed1991

Nasopharyngeal flora in the first three years of life in normal and otitis-prone children.

Nasopharyngeal carriage of the three major middle ear pathogens (Streptococcus pneumoniae, nontypeable Hemophilus influenzae, and Moraxella catarrhalis) was evaluated prospectively in a group of 110 children followed up for the first 3 years of life. The findings suggested that nasopharyngeal carriage of middle ear pathogens increases significantly during respiratory illness among the general population of young children; however, otitis-prone children demonstrated a tendency to carry nontypeable H influenzae at an unusually high rate even during health. This propensity to carry nontypeable H influenzae might explain why nontypeable H influenzae is a major cause of recurrent or chronic otitis media.

Child, Preschool↗
PubMed1991

Nasopharyngeal colonization by nontypeable Hemophilus influenzae in children: the effect of serum bactericidal antibody.

The effect of serum bactericidal antibody on colonization with NTHI was studied in 26 children. Serum bactericidal antibody did not prevent colonization with NTHI in the nasopharynx. Antibody was detected in 53% before, 91% during, and 100% after documented colonization. The log titer of antibody was significantly higher during (1.18 +/- 0.56), p less than 0.002; and after (1.31 +/- 0.29), p greater than 0.001 compared to before colonization (0.49 +/- 0.51). The roles of secretory IgA and normal nasopharyngeal flora in inhibiting pathogenic bacteria are discussed.

Antibodies, Bacterial↗
PubMed1991

The role of autonomic nervous system and inflammatory mediators in nasal hyperreactivity: a review.

The last decade has seen a marked increase in the number of otolaryngologists-head and neck surgeons who have been trained to perform rhinologic surgery. This includes both rhinoseptoplasty and endoscopic sinus surgery. A better understanding of the pathophysiology of rhinitis and sinusitis has also kept pace with this rapid expansion of surgical intervention. For example, significant advances have taken place in our knowledge of the local immune system in the nose, particularly in regard to mucosal and submucosal mast cells and the development of protective antibodies in the nasal mucosa against viral and bacterial infections. We have far more understanding of the complex innervation of the blood vessels and glands in the nasal mucosa and their receptors, and, most recently, a tremendous increase of scientific data has accumulated on the effect of neuropeptides on the nasal mucous membrane. It is imperative that rhinologic surgeons have an understanding and appreciation of the complex patterns of sensory and autonomic innervation of the nose to better evaluate the medical, allergic, and surgical treatment of acute and chronic rhinitis and sinusitis. This discussion will focus on recent advances in our understanding of the biochemical substances that are released by both the autonomic nervous system and the sensory nervous system in the nasal mucosa. The effect of these mediators on both vascular smooth muscle and the seromucinous glands of the nose will be considered. Finally, the dynamic interaction between the inflammatory mediators released by sensory nerves so-called tachykinins-- and the immune system and mast cell degranulation will be considered.

Autonomic Nervous System↗
PubMed1991

Immunologic reactivity in the middle ear in otitis media with effusion.

This article reviews the immunologic reactivity in the middle ear in both the human disease and in animal models of otitis media. It differentiates the role of immune complexes in otitis media in the animal model and in the human form of middle ear inflammation. The effect of immunization of the gut on the mucosal immune system in the middle ear is briefly explored, and the source of lymphocytes that make their way into the middle ear mucosa from other parts of the mucosal immune system and systemic immune system are briefly discussed. Finally, work from the author's laboratory on the immune response of children with recurrent otitis media due to nontypable Haemophilus influenzae is summarized.

Antigen-Antibody Complex↗
PubMed1990

Choice of antibiotics, pharmacokinetics, and dose adjustments in acute and chronic renal failure.

A multitude of antimicrobial agents have become available over the past two decades. Appropriate use of these drugs demands not only an understanding of the antimicrobial spectrum of the agent but of the necessary dose adjustments because of renal or hepatic impairment. The use of computer-assisted pharmacokinetic modeling for dosing potentially toxic drugs such as aminoglycosides and vancomycin should be utilized whenever possible.

Acute Kidney Injury↗
PubMed1990

Macrophage (monocyte)-derived mucous secretagougue (MMS) is released into the fluid of the middle ear of patients with otitis media with effusion.

Macrophage (monocyte)-derived secretagogue (MMS) is a low molecular weight peptide released by activated macrophages. This substance can enhance incorporation of carbohydrates into protein and result in the production of glycoproteins. It is believed that increased glycoproteins lead to the increased tenaciousness of mucoid effusions. Sixteen of 28 middle ear effusions demonstrated significant amounts of MMS. It is suggested that MMS is produced by activated macrophages in MEE and may lead to the development of glycoprotein by secretory epithelial cells. This substance may lead to the development of the mucoid effusion in otitis media with effusion in children.

Adolescent↗
PubMed1990

Human adenoidal organ culture: a model to study nontypable Haemophilus influenzae (NTHI) and other bacterial interactions with nasopharyngeal mucosa--implications in otitis media.

Nontypable Haemophilus influenzae (NTHI) has become the predominant cause of both acute suppurative otitis media and chronic otitis media with effusion. It has now been well-demonstrated that both outer membrane proteins and restriction fragment analysis of the bacterial genomes of concomitant nasopharyngeal and middle ear effusion isolates of NTHI are identical. It is therefore of critical importance to understand the mechanisms whereby bacteria that are present in normal healthy children in small numbers become the predominant organism in the nasopharynx in otitis media. The studies presented here suggest that nontypable Haemophilus influenzae can effectively decrease ciliary function as measured by stroboscopic illumination of ciliary beat frequency on human adenoidal organ culture. This organism also produces significant histopathologic and ultrastructural damage to the epithelial cells and cilia of adenoid organ culture, demonstrated by both light microscopy and scanning electron microscopy. The data suggest the following hypothesis: nontypable Haemophilus influenzae can destroy mucociliary function and allow increased bacterial replication in the mucus overlying the nasopharyngeal mucosa. The mucociliary system of the eustachian tube may also be involved in a similar manner, thus allowing bacteria to enter the middle ear space via the eustachian tube.

Adenoids↗