Biomedical subjects

J M Bernstein

Publications and source records attributed to J M Bernstein.

At least 37 records · Page 2Linked to original sources

PubMed1997

Analysis of isolates recovered from multiple sites of the nasopharynx of children colonized by nontypeable Haemophilus influenzae.

To determine whether the nasopharynx of children is colonized by a single or multiple strains of nontypeable Haemophilus influenzae, cultures were obtained from six nasopharyngeal sites in five children. For each child, all isolates yielded identical polymerase chain reaction fingerprints. The results indicate that these children were colonized in the nasopharynx with a single strain of nontypeable Haemophilus influenzae at one time.

Child, Preschool↗

PubMed1997

Urinary tract infections.

Urinary tract infections (UTIs) are still the precipitating cause for 7 million patient visits per year with total costs exceeding one billion dollars. Diagnostic modalities have become more "friendly" for the smaller laboratory with "dip stick" culture tests providing a rapid method of isolation of pathogens. In many cases, empiric therapy is more cost effective than culture in uncomplicated UTIs in women. The etiologic organisms implicated in UTIs have not changed dramatically over the past two decades, with E. coli still accounting for the majority of cases. Antibiotic susceptibility patterns have changed dramatically, with ampicillin losing utility die to the emergence of resistance. Quinolones, which have been exceedingly active against gram-negative enteric pathogens, are no longer universally active and more pathogenic organisms, such as pseudomonas, may be resistant. The emergence of other highly resistant organisms, such as Enterococcus faecium, must be watched for.

Acute Disease↗

PubMed1997

Nasal polyposis: immunohistochemistry and bioelectrical findings (a hypothesis for the development of nasal polyps).

Nasal polyps and turbinates were obtained from individuals undergoing surgery for symptomatic nasal obstruction caused by nonatopic rhinosinusitis or allergic rhinosinusitis. One part of the tissue from each patient was fixed in neutral buffered formalin and prepared for study by histochemical and immunohistochemical methods. Monoclonal antibodies were used to identify macrophages, lymphocytes, and plasma cells. In most cases (12 of 16, 75%) the remainder of the polyp and turbinate samples was treated with protease to achieve disaggregation of the epithelial cells. Those cells were cultured on permeable collagen matrix supports. Transepithelial potential difference and resistance were measured daily. At the time of maximal transepithelial potential difference, the epithelial cells were mounted in modified. Ussing chambers and exposed to a sodium-positive channel blocker (amiloride hydrochloride) and to selected chloride-negative channel agonists (isoproterenol bitartrate and adenosine triphosphate). Middle turbinates and polyps were found to have more macrophages, lymphocytes, plasma cells, HLA-DR-positive cells, and eosinophils than the inferior turbinates. Epithelial cells obtained from polyps exhibited higher transepithelial potential differences and equivalent short-circuit currents than turbinate cell cultures. The responses to amiloride, isoproterenol, and adenosine triphosphate were also greater for polyp than for turbinate cultures. A theory for the pathogenesis of nasal polyps is proposed. Local release of inflammatory mediators could cause sodium absorption and chloride permeability to be higher in polyps than in turbinate epithelia. Increased sodium absorption is consistent with the hypothesis that epithelial fluid absorption contributes to the development of nasal polyps and is a result of the increased recruitment of inflammatory cells, which are present in nasal polyps.

Adenosine Triphosphate↗

PubMed1997

Immunoglobulin G subclass response to major outer membrane proteins of nontypable Haemophilus influenzae in children with acute otitis media.

Children with acute otitis media as the result of nontypable Haemophilus influenzae often develop serum bactericidal and/or opsonic IgG antibodies to this organism during convalescence. Outer membrane proteins appear to be the principal targets for such antibodies. In this study we characterized the IgG subclass responses to major outer membrane proteins of nontypable H. influenzae in otitis-prone children in whom this organism had colonized. Three of the major outer membrane proteins (P2, P5, and P6) were isolated from the homologous nontypable H. influenzae strain recovered from the middle ear at the time of acute infection. Sera were obtained during the acute phase and at 1 and 6 months thereafter. The outer membrane proteins, which were isolated by preparative sodium dodecylsulfate-polyacrylamide gel electrophoresis, were used as test antigens in a quantitative IgG subclass enzyme immunoassay. The results of this analysis indicate that the temporal characteristics and distribution of IgG subclass antibodies were found to differ for each of the outer membrane proteins. Moreover, substantial variation between patients was observed with respect to both temporal characteristics and subclass distribution of the IgG response to the three outer membrane proteins. Significantly, sera from two of three otitis-prone subjects contained detectable levels of IgG antibody to the conserved P6 outer membrane protein at the time of acute infection, with serum from one subject also containing detectable levels of IgG3 antibody to this same protein. Nevertheless, the organism persisted in the middle ears of these patients. The results of this study indicate that otitis-prone children manifest a highly variable IgG subclass response to both conserved (P6) and variable (P2) outer membrane proteins of nontypable H. influenzae. Further study is required to ascertain whether these IgG subclass antibodies are biologically efficacious and whether otitis-prone children possess the immunologic maturity to respond to nontypable H. influenzae outer membrane protein-based vaccines in a predictable manner.

Acute Disease↗

PubMed1997

Middle ear mucin glycoprotein: purification and interaction with nontypable Haemophilus influenzae and Moraxella catarrhalis.

Nontypable Haemophilus influenzae and Moraxella catarrhalis are important pathogens in children and adults. The mechanisms of their adherence to the epithelial cell surface and colonization are not clear. For the pathogen to adhere to the epithelial cell, it must first attach to and penetrate the mucus barrier. Mucin glycoproteins of the mucus layer generally are thought to be involved in bacterial attachment. To understand the precise mechanisms of middle ear mucin-bacterial interactions, we used an overlay binding assay with a highly purified middle ear mucin and outer membrane proteins of both nontypable H. influenzae and M. catarrhalis. Outer membrane proteins P2 and P5 were identified as the major components that medicate the binding between nontypable H. influenzae and human middle ear mucin. Moreover, the 57 kDa protein, CD, of the outer membrane protein of M. catarrhalis was found to be the only protein binding human middle ear mucin. Finally, it appears that a protein-oligosaccharide interaction is responsible for binding because asialo-mucin does not bind to either of the bacteria. Knowledge of the specific bacterial-mucin interaction may provide an understanding of the bacterial-epithelial cell colonization. Conversely, comprehension of this interaction between bacteria and purified mucin may be a strategy to prevent colonization of potential pathogens that cause otitis media and sinusitis in children.

Amino Acids↗

PubMed1997

Sphenoid cranial base defects in siblings presenting with cerebrospinal fluid leak.

Two sisters presented to our medical center with nontraumatic cerebrospinal fluid (CSF) fistulas from left sphenoid sinocranial junction defects. One sister had recurrent meningitis over a 20-year period that prompted a skull base evaluation. Four years later, her younger sister presented with profuse CSF rhinorrhea. Transethmoid sphenoidotomy with sinus obliteration and lumbar-subarachnoid temporary CSF diversion successfully treated one sister, while the other required reoperation and permanent lumbar-peritoneal shunting. In both cases the skull base defect was identically located in the posterolateral left sphenoid sinus. Embryological considerations, evaluation and management are presented.

Case Reports↗

PubMed1996

Role of allergy in eustachian tube blockage and otitis media with effusion: a review.

Recent studies continue to support a role for allergy in the pathogenesis of otitis media with effusion. Although a variety of mechanisms have been proposed to relate these two disease conditions causally, none has been completely validated by experimental or clinical studies. This review suggests that the observed relationship between allergy and otitis media with effusion is caused by mediators of inflammation and cytokines and colony-stimulating factors released by mucosal mast cells and other inflammatory and epithelial cells in the nose and nasopharynx. These mediators produce blockage of the eustachian tube through a number of mechanisms, which may include local injury or vascular- or neural-mediated changes in the eustachian tube opening pressure and in middle ear perfusion. It is likely that the nasal allergic response in patients predisposes to eustachian tube blockage and, if prolonged, causes changes in gas absorption in the middle ear space. This gas exchange primarily involves nitrogen absorption, which may take several days to develop. This persistent underpressure will then lead to middle ear effusion. Irrespective of the theoretical mechanism, the relationship between allergy and otitis media with effusion will remain controversial until well-controlled clinical studies are conducted documenting that in select populations antiallergy therapy is efficacious in preventing or limiting the duration of otitis media with effusion.

Barotrauma↗

PubMed1996

Binding between outer membrane proteins of nontypeable Haemophilus influenzae and human nasopharyngeal mucin.

Bacterial colonization of the epithelial cells precedes infection. Mucins of the epithelial cell secretions modulate bacterial colonization. This study was designed to understand the mechanism of mucin-bacterial interactions and in particular binding between nontypeable Haemophilus influenzae and nasopharyngeal mucin(s). In an overlay assay, binding appears to be mediated by outer membrane proteins P2 and P5 of bacteria and sialic acid-containing oligosaccharides of mucin.

Bacterial Outer Membrane Proteins↗

PubMed1996

Morphologic and motility changes of nasal cilia in primary culture caused by Haemophilus influenzae.

We focused on the pathogenicity of otitis media with effusion (OME) with respect to the susceptibility of the upper respiratory tract mucosa to Haemophilus influenzae. Human nasal polyps in outgrowth culture were used to study H influenzae disturbance of the ciliary beat frequency (CBF) and the morphology of cilia. The CBF of control primary culture was 11.7 +/- 2.7 Hz. The CBF slowed down significantly, to 8.5 +/- 5.7 Hz, after incubation with the filtrate of 10(8) CFU/mL of H influenzae, and to 4.1 +/- 4.1 Hz with a suspension of 10(8) CFU/mL of H influenzae (p<.05). In the morphologic study, we classified the shapes of the cilia into five types: normal cilia, immotile cilia, swollen cilia, clumped cilia, and exfoliated ciliated cells. The abnormal shapes of cilia increased after incubation with the suspension or the filtrate of H influenzae. By scanning electron microscopy, we saw that aggregated bacteria tended to associate with cilia. Thus, the findings suggest that H influenzae disturbs the ciliary clearance of nasal cells and makes them more susceptible to infections.

Adult↗

PubMed1996

Further observations on the role of the MHC genes and certain hearing disorders.

The pathogenetic mechanism of many hearing disorders have not been fully defined. Studies of certain hearing disorders in man have suggested a role for the major histocompatibility complex (MHC)-encoded genes in disease pathogenesis. In a cohort of unrelated patients with Meniere's Disease, otosclerosis and strial presbycusis as well as other types of sensorineural hearing losses, we have identified an extended MHC haplotype common to the majority of these patients, supporting a hypothesis that a gene(s) within the MHC domain may confer susceptibility to these hearing ailments. In addition, a preliminary study of 27 individuals with various hearing maladies, a striking finding is that 44% of the patients express the following extended MHC haplotype in contrast to only 7% of the general population: DQw2-DR3-C4BSf-C4A0-G11:15-Bf:0.4-C2a-HSP70:7.5-TNF a5-B8-Cw7-A1. The expression of this haplotype by subsets of patients with hearing loss is significant in comparison to regional and international controls.

Blotting, Southern↗

PubMed1996

Adenoid lymphocyte responses to outer membrane protein P6 of nontypable Haemophilus influenzae in children with and without otitis media.

The cellular immune responses to nontypable Haemophilus influenzae in adenoids were determined in children by measuring lymphocyte blast transformation and antibody secretion in response to the P6 outer membrane protein. In the lymphocyte transformation assay, stimulation index of adenoid lymphocytes stimulated by P6 in otitis children (2.34 +/- 0.25) was significantly lower than that in non-otitis children (3.91 +/- 0.64, p <0.05). The number of IgM as well as IgA secreting cells after 8 days' culture with P6 were significantly smaller in otitis children (IgM: 7,534 +/- 2,843/10(6) lymphocyte; IgA: 1,573 +/- 620/10(6) lymphocyte) than those in non-otitis children (IgM: 12,994 +/- 2,533, p <0.05; IgA: 2,828 +/- 528, p <0.05). These data suggest that P6 protein is a target for the cellular immune response of the adenoid, and failure of adenoid lymphocytes to recognize it as a specific immunogen may be one of the causes of recurrent otitis media.

Adenoids↗

PubMed1995

Role of allergy in nasal polyposis: a review.

We propose a multivariate theory for the pathogenesis of nasal polyps. Turbulent flow of air in the lateral wall of the nose or viral-bacterial-host interactions produce an inflammatory change in the mucosa of the lateral wall of the nose. Ulceration and prolapse of the submucosa with reepithelialization and new gland formation may then follow. The structural cells of the nasal polyp, including epithelial cells and fibroblasts, have the ability to produce messenger RNA for granulocyte-monocyte colony-stimulating factor and other cytokines. Stimulation of such an effector capability by structural cell-derived cytokines would undoubtedly represent a major amplification pathway of the inflammatory response in nasal polyps. Allergy may be one mechanism for the development of this cascade of events. This microenvironmental structural inflammatory response in the nasal polyp, in turn, can affect the bioelectric integrity of the Na+ and Cl- channels at the luminal surface of the respiratory epithelial cell. The change in the Na+ absorption, which has been demonstrated in our studies, may result in an increased movement of water into the cell and into the interstitial fluid. The resultant edema can lead to growth and enlargement of the nasal polyp. Finally, the rapid recurrence of nasal polyps despite adequate surgery may reflect some intrinsic phenotypic characteristic of nasal epithelial cells in the lateral wall of the nose, which is likely to be under genetic control.

Epithelium↗

PubMed1994

Analysis of respiratory syncytial virus F, G, and SH proteins in cell fusion.

Recombinant expression of the human respiratory syncytial virus (RSV) fusion (F) glycoprotein, receptor-binding glycoprotein (G), and small hydrophobic (SH) protein was performed to determine the role(s) of these proteins in syncytia formation. These studies used a vaccinia virus expressing the bacteriophage (T7) RNA polymerase gene and plasmid vectors containing the RSV genes under the control of a T7 promoter. Within the context of this expression system, expression of any individual RSV gene, or coexpression of F+G genes, did not elicit the formation of syncytia. However, at plasmid input levels which were 10-fold higher than those normally used, coexpression of F+G induced low but detectable levels of cell fusion. In contrast, coexpression of F, G, and SH together elicited extensive cell fusion resembling that of an authentically infected cell monolayer. In addition, coexpression of F and SH elicited significant cell fusion, although to a lesser extent than was observed when G was included. Cell fusion induced by coexpression of F+SH was found to be specific to the RSV proteins, since coexpression of SH with the analogous F proteins from human parainfluenza virus type 3, human parainfluenza virus type 2, Sendai virus, or simian virus type 5 (SV5) did not elicit cell fusion. Finally, coexpression of the SV5 SH protein with the RSV or SV5 glycoproteins also failed to induce syncytia, suggesting type-specific restrictions between the two sets of viral proteins.

Animals↗

PubMed1994

Increased ion transport in cultured nasal polyp epithelial cells.

OBJECTIVE: To measure transepithelial bioelectric properties of cultured human nasal polyp and turbinate epithelial cells to test the hypothesis that nasal polyps have increased rates of ion transport. DESIGN: Cohort study. SETTING: Private referral center. PATIENTS: Individuals undergoing surgery for symptomatic nasal obstruction due to polyps caused by cystic fibrosis, nonatopic rhinosinusitis, or allergic rhinosinusitis. METHODS: Epithelial cells were removed from separated polyp and turbinate samples by protease disaggregation and cultured on permeable collagen matrix supports. Transepithelial potential difference and resistance were measured daily. At the time of maximal transepithelial potential difference, the cultures were mounted in modified Ussing chambers and exposed to a sodium-positive channel blocker (amiloride hydrochloride) and to selected chloride-negative channel agonists (isoproterenol bitartrate, adenosine triphosphate). OUTCOME MEASURES: Maximal transepithelial potential difference, resistance, and equivalent short-circuit current. Bioelectric responses to amiloride, isoproterenol, and adenosine triphosphate. RESULTS: Polyp cultures had higher transepithelial potential difference and equivalent short-circuit current than turbinate cultures. The mediator responses were greater for polyp than for turbinate cultures. CONCLUSIONS: Polyp epithelia have increased Na+ absorption and Cl- permeability relative to turbinate epithelia. These results are consistent with the hypothesis that increased epithelial fluid absorption contributes to the development of nasal polyps.

Absorption↗

PubMed1994

Involvement of the eyebrow fat pad in Graves' orbitopathy.

Involvement of the eyebrow fat pad in Graves' disease has never been reported. We noted that Graves' orbitopathy patients had bulkier eyebrows due to a larger eyebrow fat pad not associated with the preaponeurotic fat. A cadaver model was used to show that the eyebrow fat could be identified with magnetic resonance imaging (MRI) scans. Then, a series of Graves' orbitopathy patients were sent for orbital MRI scans, and the eyebrow fat was measured with maximum lengths and widths. The averages were compared to two groups of patients, one without orbital pathology, and one with orbital pathology causing proptosis but not due to Graves' disease. Graves' patients with early orbitopathy and incipient optic neuropathy or congestive orbits where optic neuropathy had to be ruled out had statistically significant larger eyebrow fat pads than either comparison group. This has clinical significance: The eyebrow fat may need to be debulked during operations such as blepharoplasty. Furthermore, periorbital fat may play a larger role in the disease process than previously thought.

Adipose Tissue↗

PubMed1994

Role of IgE-mediated hypersensitivity in otitis media with effusion: pathophysiologic considerations.

A pathophysiologic model of otitis media with effusion secondary to IgE-mediated hypersensitivity is described. Specific mediators of inflammation are released by mucosal mast cells in the nasal mucosa following the interaction of antigen and specific IgE antibody. These mediators increase vascular permeability, mucosal blood flow, and, most important, mucus production. Furthermore, accessory cell types are recruited by colony-stimulating factors that in turn provide an autocrine-positive feedback for the influx of further inflammatory cells. The eustachian tube is then effectively obstructed by both intrinsic venous engorgement and extrinsic mucus plugs, isolating the middle ear space from the ambient environment. The net result is the increased exchange of nitrogen into the middle ear mucosa from the middle ear cavity. This causes the development of a significant middle ear underpressure that disrupts tight junctions and allows for transudation of fluids into the middle ear space. The prolonged obstruction of the eustachian tube with mucus results in middle ear inflammation, mucosal metaplasia, and increased glandular activities, all of which are hallmarks of chronic otitis media with effusion.

Basophils↗

PubMed1994

Bacterial interference in nasopharyngeal bacterial flora of otitis-prone and non-otitis-prone children.

The quantitative bacteriology of the adenoid was studied in 34 otitis-prone and 25 non-otitis prone children. Viridans streptococci appeared to be the predominant normal flora in children who are non-otitis prone. There was a significant decrease in viridans streptococci in the otitis-prone child compared to the non-otitis-prone child. There was a significant increase in nontypable Haemophilus influenzae (NTHI) in the otitis-prone child. The mechanisms responsible for this alteration of the microecology of bacteria of the nasopharynx may be related, in part, to bacterial interference or to the inappropriate use and over-use of antibiotics. In vitro inhibition of growth of NTHI was demonstrated with selective strains of viridans streptococci. A preliminary analysis of an inhibitory strain and a non-inhibitory strain of viridans streptococci are presented and their biochemical profiles and antibiotic sensitivities were entirely different. A possible mechanism for the inhibition on NTHI by viridans streptococci has been suggested. This mechanism may be related to an alteration of pH in the growth media or the possibility of the utilization of nutrients required for growth of NTHI.

Adenoids↗

PubMed1993

Impaired bacterial killing in early obstructive jaundice.

Sprague-Dawley rats were challenged with intraperitoneal injection of 10(7) Streptococcus pneumoniae 10 days after common duct ligation (BDL) or sham celiotomy (SC). Quantitative bacterial cultures were performed on liver, spleen, lung, kidney, and heart blood samples obtained 4 hours after injection. All 13 (100%) BDL animals had positive heart blood cultures, but only 6 of 12 (50%) SC animals remained bacteremic (p < 0.05). Significantly more viable organisms were recovered from lung, liver, spleen, and kidney of BDL animals compared with SC controls. BDL impaired the host's ability to kill this encapsulated gram-positive organism. Viable bacteria remained in all organs studied, which was associated with continuing bacteremia.

Animals↗