Biomedical subjects

D R Trune

Publications and source records attributed to D R Trune.

At least 37 records · Page 2Linked to original sources

PubMed1997

Inner ear DNA receptors in MRL/lpr autoimmune mice: potential 30 and 70 kDa link between autoimmune disease and hearing loss.

Inner ear function and systemic autoimmune disease were evaluated in the MRL/lpr mouse to determine their relationship with alterations in cell surface DNA receptors of 28-30 and 68-70 kDa size. Auditory brainstem response thresholds in the autoimmune disease mice were significantly elevated as early as 2 months of age when compared to MRL/++ controls. Hearing thresholds continued to rise with progression of the disease, manifested as increasing spleen weights, antinuclear (anti-DNA) antibodies, and serum immune complexes. Cochlear membranous labyrinth cells in the autoimmune mice bound less DNA, suggesting the DNA receptors were abnormally occupied by circulating antibodies. Western blots of a murine T-cell line probed with autoimmune mouse sera demonstrated reactivity to 28-30 and 68-70 kDa proteins after disease onset. It is hypothesized that cell surface DNA binding molecules could be masked or down-regulated by circulating antibodies in autoimmune disease. This interference with DNA receptor activity may be occurring within the inner ear and underlie the cochlear dysfunction seen in autoimmune sensorineural hearing loss.

Analysis of Variance↗

PubMed1996

Auditory function in the C3H/HeJ and C3H/HeSnJ mouse strains.

The C3H inbred mouse strain arose in 1920 and includes several substrains, such as the C3H/HeJ and C3H/HeSnJ variants. However, use of these C3H mice in hearing research has been limited because their auditory function has not been described. Therefore, the purpose of this study was to characterize auditory function in two C3H representative substrains. C3H/HeJ and C3H/HeSnJ mice were obtained from Jackson Laboratories for auditory brainstem response (ABR) testing at ages from 2 to 30 months. Animals were tested with tone bursts at frequencies of 4,8,16,24, and 32 kHz. These early responses were evaluated for age-related threshold shifts as an index of peripheral auditory function. Both strains show normal sensitivity up to 14 months of age. Thresholds for both strains were slightly elevated at most frequencies at 18 months. C3H/HeSnJ mice tested at 30 months demonstrated little hearing function due to extensive sensorineural degeneration. Thus, these C3H strains maintain excellent cochlear function past 1 year of age.

Animals↗

PubMed1996

Decreased auditory function in the C3H/lpr autoimmune disease mouse.

To better understand autoimmune-related inner ear disease, cochlear structure and function were evaluated in the C3H/lpr autoimmune strain mouse, a model for systemic lupus erythematosus. C3H/lpr mice were examined at ages from 2 to 12 months along with age-matched C3H/HeJ controls. Autoimmune disease onset occurred at 3-4 months of age as serum immune complexes, antinuclear antibodies, and spleen weights were significantly elevated. Auditory brainstem response (ABR) audiometry showed normal auditory thresholds in C3H/lpr mice at 4 months of age, but elevated thresholds by 6 months, particularly in the high frequencies. Examination of the cochleas revealed no apparent loss of hair cells or spiral ganglion neurons, even in those mice with 50 dB SPL threshold shifts. However, changes were observed in the stria vascularis, including edematous spaces, enlarged capillaries, and thickened vessel linings. These findings imply that cochlear dysfunction in the autoimmune disease mice is the result of stria vascularis pathology.

Analysis of Variance↗

PubMed1995

Computerized digital photography in auditory research: a comparison of publication-quality digital printers with traditional darkroom methods.

Digital photography is the rapidly developing field of computer processing of images generated either directly from a digital camera or from scanned conventional film. Subsequent photographs output from digital color printers are publication-quality and superior to conventional darkroom prints because of greater image control (exposure, contrast, color correction). Because final print quality is the most critical factor in the research application of digital photography, we evaluated the photographic output of several continuous-tone digital printers. Digital images from selected microscopic sections of the middle and inner ear were generated by scanning black and white film and Ektachrome color transparencies and sent to commercial representatives for printing. Photographs from some printers were as good or better than traditional darkroom prints of the same film when evaluated for resolution, image quality, and costs. It is our hope that the hearing research field will benefit enormously by adoption of chemical-free digital photography because of its quality, convenience, speed, and low cost.

Animals↗

PubMed1994

Tumor angiogenesis, the p53 antigen, and cervical metastasis in squamous carcinoma of the tongue.

A more accurate method of detecting nodal disease in squamous cell carcinoma of the tongue is needed so that treatment of the neck with its associated morbidity can safely be reserved for patients who actually have metastatic disease. Tumor angiogenesis and the expression of the p53 antigen--which have each been shown to be predictive of metastasis in breast and colon cancer, respectively--are examined for their ability to predict neck metastasis in tongue cancer. Fifty-seven patients with T1 and T2 squamous cell carcinoma of the oral tongue, whose neck disease was examined by dissection or by 2-year follow-up, were studied. Twenty-eight patients (49%) were node positive and 29 patients (51%) were node negative. The primary tumors were immunohistochemically stained for the p53 antigen and for factor VIII, which allowed the blood vessels within the tumor to be quantitated. The mean vessel counts per x200 high-power field were 59.8 and 61.5 for node-positive and node-negative patients, respectively (p = 0.8). Node-positive patients showed overexpression of p53 43% of the time, vs. 61% for node-negative patients (p = 0.17). Multivariate analysis confirmed that no difference in tumor angiogenesis or the expression of the p53 antigen was found between tumors that had metastasized and those that had not. Therefore neither tumor angiogenesis nor the p53 tumor marker is clinically useful in determining lymph node metastasis in these patients.

Carcinoma, Squamous Cell↗

PubMed1993

Inner ear basic fibroblast growth factor in CBA/J, C3H/HeJ, and autoimmune Palmerston north mice.

Basic fibroblast growth factor (bFGF) has a mitogenic effect on fibroblasts and osteoblasts for matrix proliferation and on endothelial cells for neovascularization. Because otic capsule osteogenesis in autoimmune disease subjects often involves abnormal matrix and vascular changes, bFGF may serve as a potential mediator for such bone disorders. To investigate this relationship, bFGF was evaluated in the Palmerston North autoimmune strain mouse, which develops otic capsule sclerotic lesions during the progression of its systemic disease. Inner ears from PN mice, along with control CBA/J and C3H/HeJ mice, were immunohistochemically stained with antibodies against bFGF to identify its presence and possible role in otic capsule disease. Although cells reactive for bFGF were observed along the lining of the otic capsule in all three strains, a significantly higher frequency was observed in the PN mice. Other sites of staining included connective tissue around the tensor tympani muscle and the geniculate ganglion. This identification of bFGF in the otic capsule raises the possibility that it may play some role in normal bone maintenance, as well as abnormal bone or connective tissue remodeling in autoimmune disease.

Animals↗

PubMed1993

Pathology of labial salivary gland cellular aggregates in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune inflammatory disease in which lymphocytic infiltration of the lacrimal and salivary glands is the hallmark of disease diagnosis. The present study was conducted to identify developmental features of labial salivary gland histopathology to permit earlier diagnosis of SS patients with borderline biopsies. Control subjects were chosen on the basis of clinical presentation consistent with SS, but whose biopsies did not meet current focus score criteria. Intraglandular connective tissue and diffuse cellular infiltration were significantly greater in SS patients than in controls. Glands in both groups had small cellular aggregates (10 to 50 cells/100 microns2), but those in SS patients were more numerous, larger, and contained more lymphocytes, plasma cells, and active fibroblasts. The large inflammatory foci characteristic of SS appeared to be formed by the enlargement and merging of these aggregates. This suggested aggregate formation was the earliest stage of pathology. Therefore, a comprehensive analysis of these cellular aggregates in borderline or negative biopsies could identify at-risk patients and lead to earlier diagnosis and intervention in the disease.

Biopsy↗

PubMed1993

Morphometric analysis of human retinal pigment epithelium: correlation with age and location.

Flat bleached preparations of retinal pigment epithelial (RPE) cells from foveal, temporal posterior pole, and temporal equatorial fundus locations of 20 normal human eyes from donors age ranked from 13 to 96 years were analyzed for density, and 10 were analyzed for area, hexagonality and polymegathism. These factors were related to fundus locations and age. Foveal RPE cells were significantly more dense and more hexagonal in eyes from younger donors. Loss of hexagonality in the fovea, but not elsewhere, was correlated with increasing age. As the eye ages, foveal RPE cells selectively lose unique morphologic characteristics and resemble nonfoveal cells. These morphologic changes resemble other pathologic features of age-related degeneration in their proclivity for the fovea and posterior pole.

Adolescent↗

PubMed1992

Cochlear IgG in the C3H/lpr autoimmune strain mouse.

The inner ear of the C3H/lpr autoimmune strain mouse was evaluated to identify potential mechanisms by which systemic autoimmune disease interferes with auditory function. The inner ears were immunohistochemically stained for IgG at ages before (2 months) and after (6-10 months) autoimmune disease onset and compared to age-matched nonautoimmune C3H/HeJ controls. Immunoreactivity for IgG was not seen in the 2 month C3H/lpr autoimmune mice or in either age group of the C3H/HeJ controls. On the other hand, all older C3H/lpr mice showed reaction product in the vessels of the cochlea, particularly the stria vascularis and bony capsule. Less frequent sites of staining were the geniculate ganglion, marrow cavities of the bony capsule, tensor tympani muscle, and on one occasion, a hair cell of the organ of Corti. These findings indicate that IgG is widespread within the cochlea and its vessels during systemic autoimmune disease and not directed against any specific sensorineural structure. This suggests a generalized or indirect mechanism whereby such systemic disease affects the inner ear.

Animals↗

PubMed1992

Stria vascularis ultrastructural pathology in the C3H/lpr autoimmune strain mouse: a potential mechanism for immune-related hearing loss.

The stria vascularis in the C3H/lpr autoimmune strain mouse was ultrastructurally examined in order to better understand the potential mechanisms by which systemic autoimmune disease affects the ear. The inner ear from C3H/lpr mice before disease onset and C3H/HeJ controls showed no apparent pathology. However, the stria vascularis from older C3H/lpr mice after systemic autoimmune disease onset showed considerable intercellular edema around the stria capillaries and thickening of the capillary basement membrane, compared to controls. These observations suggest that perivascular abnormalities, which are the hallmark of systemic autoimmune diseases, may underlie the stria dysfunction and hearing loss seen in autoimmune diseases in humans.

Animals↗

PubMed1992

Lacrimal and salivary gland inflammation in the C3H/Ipr autoimmune strain mouse: a potential mode for Sjögren's syndrome.

Sjögren's syndrome is an autoimmune inflammatory disease that affects the lacrimal and salivary glands. To identify a potential animal model for study of Sjögren's syndrome, an evaluation was made of lacrimal and salivary glands in the C3H/Ipr autoimmune strain mouse at ages before (2 months) and after (5 months) systemic autoimmune disease onset at 3 to 4 months. Quantitative and qualitative analyses of C3H/Ipr lacrimal and salivary (parotid, submandibular, and sublingual) gland histopathology were performed using age-matched C3H/HeJ nonautoimmune mice to control for inflammation of nonautoimmune origin. No lacrimal or salivary gland inflammation was seen in either of the strains at 2 months of age and measures of systemic autoimmune disease were negative. At 5 months of age, the nonautoimmune C3H/HeJ controls showed a slight increase in lacrimal gland inflammation, but this was not significantly different from the 2 month old controls. A significant increase in lacrimal gland inflammation was found in the 5 month old C3H/Ipr autoimmune mice in a histologic pattern similar to that of Sjögren's syndrome in human beings. Furthermore, the degree of inflammation was positively correlated with serum immune complexes and spleen weight. Sporadic inflammation of the submandibular gland was seen in both autoimmune and control mice, but this was neither statistically significant nor correlated with measures of autoimmunity. No significant inflammation was seen in the parotid or sublingual glands.

Animals↗

PubMed1992

Immunohistochemical analysis of otic capsule osteogenesis in the Palmerston North autoimmune mouse.

Autoimmunity and the immune complex disease associated with it have been hypothesized to be the cause of several idiopathic diseases of the inner ear--including the new bone formation associated with otic capsule osteogenesis and otosclerosis. The Palmerston North (PN) autoimmune mouse strain, which exhibits both spontaneous systemic autoimmune disease and otic capsule bone formation, has been proposed as a model relating these two disease processes. To investigate the potential role of immunopathologic processes in PN otic capsule lesion formation, inner ears from PN mice were immunostained for the presence of IgG and complement (C3), two immunologic markers involved in the development of the vascular and perivascular changes associated with immune complex deposition. Both systemic autoimmune disease and otic capsule bony lesions were confirmed in all animals. However, immunohistochemical analyses did not establish a direct relationship between the two conditions as complement was absent in all lesions and IgG stained positive in only one instance. These results suggest that immune complex deposition is not directly involved in the otic capsule lesions of the PN mouse, and alternate mechanisms relating autoimmune disease and otic capsule osteogenesis must be explored.

Animals↗

PubMed1990

Histochemistry of otic capsule sclerotic lesions in Palmerston North autoimmune strain mice.

Otic capsule osteogenesis is a common finding in temporal bones from autoimmune disease individuals. However, the underlying cellular mechanisms are poorly understood. Therefore, to better understand this relationship of autoimmune disease and otic capsule pathology, inner ear sclerotic lesions of the Palmerston North autoimmune disease mouse were histochemically stained to identify their content and potential osteogenic processes. Lesions stained positive for calcium, amyloid, fibrinoid, and glycoproteins (PAS), but negative for collagen, calcium oxalate, reticular fibers and glycosaminoglycans (Alcian Blue). Amyloid and fibrinoid deposition are associated with other immune disease, which suggests these local processes may provide a protein substructure that calcifies in lesion progression. Similar cellular mechanisms may underlie certain types or phases of human autoimmune otic capsule disease.

Amyloid↗

PubMed1990

Otic capsule bony lesions in the Palmerston North autoimmune mouse.

Otosclerosis is an otic capsule disorder of unknown etiology. While autoimmunity has been proposed as part of the etiopathogenesis of otosclerosis, no spontaneous autoimmune disease animal model has been identified. In the Palmerston North mouse, a model for systemic lupus erythematosus, sclerotic lesions consistently develop within the modiolus that are correlated with systemic autoimmune disease symptoms. No lesions were seen in 2-month-old mice, which is before autoimmune disease onset at 4 months. Lesions were first seen in mice at 6 to 8 months of age and increased in size and frequency thereafter. By 20 months, all ears examined had the otic capsule lesions, which were primarily perivascular in location and composed of both noncellular and cellular elements. The noncellular material was globular to fibrillar in arrangement and stained positively for calcium. The associated cells appeared to be metabolically active fibroblasts. It is proposed that the Palmerston North mouse may serve as a model to further investigate the role of autoimmunity in otosclerosis and other forms of otic capsule osteogenesis.

Animals↗

PubMed1990

The effect of prolonged aspirin therapy on experimental balloon-catheter arterial wall injury.

Indications for aspirin following percutaneous transluminal angioplasty are not well defined. Although aspirin's early antithrombotic effect is believed to be beneficial, the long-term influence of aspirin on myointimal proliferative response following balloon-catheter angioplasty is still being investigated. This study quantitates arterial wall thickening, including intimal hyperplasia, at 4 months following balloon-catheter aortic injury in New Zealand white rabbits (n = 12), comparing aspirin treatment (30 mg/kg) with controls. Aspirin was administered daily for 1 month prior and 4 months following aortic injury. Myointimal proliferation was noted in both groups. The mean area of the intima and media as well as the maximum thickness of the intima were similar (p greater than .05) in both the aspirin treatment and control groups. Cellular hyperplasia was evaluated by media smooth muscle cell counts using an ocular reticle. There was a trend toward higher cell counts with aspirin treatment, although there was no significant difference between the two groups. Prolonged aspirin therapy did not alter the degree of myointimal hyperplasia at 4 months postinjury in our model.

Animals↗

PubMed1989

Variables affecting the auditory brainstem response: audiogram, age, gender and head size.

Correlations between the ABR (auditory brainstem response) and the variables of hearing loss, gender, head size and age were determined in simple and multiple regression analyses in 334 ears. The stepwise multiple regression analyses for waves I, III and V of the ABR was used to determine the relative importance of the variables. Regression equations were calculated for the latency of each wave. Wave I latency for all subjects is best predicted by hearing threshold at 8 kHz, gender and age, in that order. Wave III latency depends upon hearing threshold at 4 kHz, age and gender. The latency of wave V is best predicted by gender, age and head diameter with threshold at 4 kHz being of minor importance. The I-V interval depends upon head diameter and threshold at 8 and 4 kHz with age of minor importance. Hearing loss at 8 kHz would shorten the I-V interval, while a loss at 4 kHz would be expected to lengthen the interval. Correlations of these variables with the amplitude of I, III and V are also described. Latency and amplitude are correlated with different subject variables suggesting differences in their generation.

Acoustic Stimulation↗

PubMed1989

Low cost device for removing human and small primate temporal bone plugs.

Previously, only the expensive oscillating saw and Schuknecht temporal trephine were available for removing human temporal bone plugs and no trephines were made for smaller research primates. An inexpensive hole saw has been modified for removing such plugs with an electric drill. This device is less expensive, easier to use, causes less potential impact damage to the plug, and the size of the hole saw can be varied for the size of the skull.

Animals↗

PubMed1989

Autoimmune disease and cochlear pathology in the C3H/lpr strain mouse.

The C3H/lpr autoimmune strain mouse is a model for spontaneous systemic lupus erythematosus. Inner ear structure and function were examined during systemic autoimmune disease progression to identify correlated auditory system pathology. Onset of the systemic disease occurred at 2-3 months of age and was characterized by elevated serum immune complexes, cryoglobulins, and antinuclear antibodies. Coincident with the onset of autoimmune disease was degeneration of the stria vascularis. Early edema of the stria occurred in the apex and progressed basalward with duration of the disease. By 10 months of age, stria vascularis area was smaller and auditory brainstem response thresholds were elevated. No degeneration of hair cells was seen at any age, suggesting that the stria vascularis may be the primary anatomic site of autoimmune auditory damage in this mouse model.

Age Factors↗