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Biomedical subjects

D E Dunn

Publications and source records attributed to D E Dunn.

32 records · Page 2Linked to original sources
PubMed1989

Quantitative evaluation of scanning electron microscopy-examined ciliary morphological changes in control and noise exposed guinea pig cochleas.

Many investigations of noise-induced hearing loss have demonstrated a poor correlation between hearing threshold and hair cell loss. One reason for this is that more subtle changes in the hair cell, such as detailed morphological changes of stereocilia, have not been evaluated. However, examining such changes increases the problem of distinguishing experimental pathological changes from artefacts. Preparation of the specimen for scanning electron microscopy (SEM) may result in too many artefacts for an adequate quantification of defects due to noise exposure. One problem with some earlier studies seems to be lack of controls and/or statistical analysis for the purpose of eliminating the influence of artefacts and spontaneous degeneration. The aim of this study was to compare unexposed and noise-exposed cochleas examined with SEM in order to determine if subtle changes due to noise could be distinguished from preparation artefacts and from spontaneous deterioration. Ten different types of hair cell changes were found in exposed and control animals. By means of using controls for statistical comparison with noise-exposed animals two cell damage categories--hair cell loss and missing stereocilia--were found to be produced by exposure to noise.

Animals↗
PubMed1988

A T cell clone expresses two T cell receptor alpha genes but uses one alpha beta heterodimer for allorecognition and self MHC-restricted antigen recognition.

All of the T cell receptor alpha- and beta-chain rearrangements present in a dual reactive T cell clone were characterized. This clone exhibits allelic exclusion of its beta-chain genes in that only one of the two alleles is productively rearranged. Unexpectedly, it displays two productive V alpha-gene rearrangements, which are both transcribed into 1.5 kb mRNA. The contribution of each of the two productive alpha genes to the dual recognition was analyzed by gene transfer. To this end, each of the two alpha genes was separately transfected with the single productively rearranged beta gene. Transfer of only one of the two alpha beta combinations restored both allogeneic MHC recognition and self MHC-restricted antigen recognition. Thus, T cell dual recognition results from the cross-reactive recognition of an allo-MHC product by a single antigen-specific and MHC-restricted alpha beta T cell receptor. Furthermore, the presence of two productively rearranged alpha-chain genes in a T cell clone raises questions concerning the level at which allelic exclusion operates in T cells.

Animals↗
PubMed1987

Interleukin 2 and concanavalin A stimulate interferon-gamma production in a murine cytolytic T cell clone by different pathways.

We identified a variant murine cytolytic T lymphocyte (CTL) clone which, in contrast to the parent clone and all other murine T cell populations tested, was found to have acquired spontaneously the ability to produce interferon-gamma (IFN-gamma) in response to recombinant interleukin 2 (rIL-2). IFN-gamma production in response to concanavalin A (Con A), which was characteristic of all T cell populations tested, was preserved in this variant. The IFN produced by the variant in response to either stimulus was active in both a macrophage-activating factor assay and an anti-viral assay. Both activities induced by either stimulus could be blocked by monoclonal anti-IFN-gamma antibodies. Upon Northern blot analysis using an IFN-gamma-specific cDNA probe, the IFN-gamma RNA isolated from variant cells stimulated with Con A or IL-2 were found to migrate equivalently. The unusual pattern of responsiveness in this variant CTL was exploited to compare the mechanisms involved in induction of IFN-gamma production by Con A or IL-2. Striking differences were observed. Unlike IFN-gamma production induced by Con A, IFN-gamma production induced by IL-2 was not accompanied by an elevation of intracellular Ca2+ levels, did not require physiologic extracellular Ca2+ levels, and was not inhibited by the immunosuppressive agent cyclosporin A. Thus, in this variant CTL clone, conditions that have ordinarily been associated in an obligate manner with lymphokine gene expression were found instead to be related to the specific mode of stimulation.

Animals↗
PubMed1986

PMA alone induces proliferation of some murine T cell clones but not others.

The responses of cloned murine T cell lines to the phorbol ester, phorbol myristate acetate (PMA), were investigated. PMA alone was able to stimulate proliferation of some clones but not others. Two Lyt-2+, cloned cytolytic T lymphocyte (CTL) lines proliferated in response to stimulation by PMA alone, but several L3T4+, cloned helper T lymphocyte (HTL) lines did not. In contrast, all clones tested released lymphokines in response to stimulation by the combination of PMA and the calcium ionophore A23187. Moreover, all clones proliferated in response to stimulation by the combination of PMA and A23187. The proliferation of HTL in response to PMA + A23187 could be completely inhibited either by cyclosporine A (CsA) or by PC61.5, a monoclonal antibody directed against the murine IL 2 receptor; however, the proliferation of CTL in response to PMA alone was not affected either by CsA or by PC61.5. These results suggest that of the murine T cell clones tested, HTL proliferate in response to stimulation via an IL 2-dependent, autocrine pathway; in contrast, CTL, in addition to an IL 2-dependent pathway, may possess an additional IL 2-independent pathway of proliferation. CTL that proliferate in response to stimulation by PMA alone may be useful models in the study of T cell proliferation.

Animals↗
PubMed1986

Activation of lymphokine genes during stimulation of cloned T cells.

To study the regulation of lymphokine production by T lymphocytes, we have characterized the activation of lymphokine genes in T cells by measuring the levels of lymphokine mRNA in cloned murine T lymphocytes after stimulation. Lymphokine mRNA was not detected in cells taken after seven days of maintenance culture. Following stimulation of T helper lymphocytes L2 and AD9.1 with concanavalin A, lymphokine mRNA appeared, reached peak levels and disappeared over a 43-h time period. A single stimulation event resulted in the induction of mRNA for interleukin 2 (IL 2), IL 3 and interferon gamma. Maximal mRNA levels were generally found at 6 h in the T helper lymphocytes, but could occur as late as 18 h. The lymphokine genes were expressed coordinately; however, in these cloned cells, IL 2 mRNA levels appeared to be lower than the other two mRNAs. Lymphokine titers in the supernatant fluids paralleled the appearance of mRNA but IL 2 titers began to fall after 12 h probably because of utilization of this lymphokine by the activated cells. In the cytolytic T lymphocyte, L3, qualitatively similar kinetics were found after stimulation by lectin or a clonotypic antibody with peak mRNA levels occurring later (18 h) with the antibody. These studies indicate a single stimulating event activates the lymphokine genes of T cells in a coordinate manner; the appearance of the lymphokines in supernatant fluids represents de novo synthesis of these proteins but the levels of lymphokines measured in supernatant fluids reflects both production and utilization rates, and exposure to IL 2 at the time of stimulation is not essential for the production of other lymphokines.

Animals↗
PubMed1986

Dissection technique for cochleas prepared for scanning electron microscopy.

Scanning electron microscopy (SEM) permits a three-dimensional study of the surface morphology of the organ of Corti that is very useful in evaluating the condition of the apical end of the hair cells and the stereocilia. However, some laboratories have experienced problems with curling of the basilar membrane during critical point drying of cochlear specimens prepared for SEM evaluation using the Murakami or osmium thiocarbohydrazide-procedures. This curling of the basilar membrane can obstruct the view of the reticular lamina and the ciliary ends of the hair cells. We have used a dissection method, referred to as the anchor technique, to overcome basilar membrane curling. This technique removes all the structures above the reticular lamina but leaves the basilar membrane attached to the spiral ligament and the lateral bone to which the spiral ligament is anchored. Individual cochlear turns are dissected in this manner and mounted on the same examination stub for SEM evaluation. Maintenance of the lateral attachment of the basilar membrane requires additional dissection time but eliminates the problem of curling during critical point drying. An additional benefit is that mounting the individual turns on the same examination stub facilitates evaluation and photomicroscopy of the surface morphology. The anchor technique has been used successfully on the guinea pig and should be appropriate for most mammalian cochleas.

Animals↗
PubMed1984

Evidence implicating I region-restricted antigen presentation in alloantigen and nominal antigen recognition by a dual-reactive helper T lymphocyte clone.

A helper T lymphocyte clone, designated A10, was generated from spleen cells of a B10.A mouse and demonstrated reactivity to both the nominal protein antigen hen egg ovalbumin (OVA) presented by I-Ak-bearing antigen-presenting cells (APC) and irradiated I-As-bearing spleen cells in the absence of OVA. A stimulatory signal was delivered to the cloned cells by syngeneic spleen cells that were exposed to OVA and then fixed with paraformaldehyde. However, paraformaldehyde-fixed allogeneic spleen cells that bear the I-As determinant recognized by a monoclonal antibody (mAb) were unable, by themselves, to stimulate the A10 cells. The inability of fixed allogeneic spleen cells to stimulate was rectified by the addition of irradiated I-Ak-positive spleen cells, suggesting that at least in this situation, alloantigen must be presented to the alloreactive A10 cells. Further evidence supporting this proposal for class II-restricted presentation of alloantigen included the observations that 1) irradiated I-Ak-negative spleen cells were unable to present the fixed H-2s spleen cells, 2) the anti-I-As mAb blocked the stimulatory signals delivered by irradiated H-2s spleen cells and by fixed H-2s spleen cells plus irradiated syngeneic spleen cells, 3) some anti-I-Ak mAb preparations were able to inhibit stimulation by OVA and by fixed H-2s spleen cells plus irradiated syngeneic spleen cells, and 4) an anti-L3T4a mAb effectively blocked all three stimulatory signals. These data suggested that alloreactivity can be mediated by an antigen-presentation process similar to that proposed for nominal peptide antigen presentation, and that alloantigen in the form of paraformaldehyde-fixed allogeneic spleen cells is recognized in the context of self-determinants before a stimulatory signal can be delivered.

Animals↗
PubMed1980

Strachan's syndrome 30 years after onset.

While a prisoner-of-war in Malaya from 1942-1945, a 29-year-old man developed a painful sensorimotor neuropathy, bilateral central scotomata and sensorineural deafness. Examination 34 years later, after a long period of adequate nutrition, revealed considerable residual deficit. Nerve conduction studies suggested axonal degeneration with prominent collateral reinnervation. This case of Strachan's syndrome is reported to draw attention to the limited functional recovery and to focus attention on this condition at a time when famine conditions are rife in Southeast Asia.

Aged↗
PubMed1979

Manual and continuous-flow colorimetry of triacylglycerols by a fully enzymic method.

We describe a fully enzymic method for manual and continuous-flow colorimetric assay of triacylglycerols (triglycerides) in serum. Triglycerides are enzymically hydrolyzed in 10 min by lipase and microbial esterase. The resulting free glycerol is measured enzymically by glycerol kinase and glycerol-3-phosphate dehydrogenase. The NADH so formed is oxidized by coupling with a tetrazolium salt/diaphorase system. The test follows Beer's law to 8 g/L, and the final color is stable for at least 1 h for serum, 15 min for aqueous triolein standards. The manual assay requires only 25 microliter of serum and few manipulations. A specific triolein standard was developed for calibrating the manual method. For the continuous-flow method, calibration is made with four concentrations of glycerol standard. The procedure is sensitive, has good precision and accuracy, and gives results that compare well with chemical and enzymic commercial kit methods.

Adult↗
PubMedDate not supplied

Occupational exposure to noise and ototoxic organic solvents.

The objectives of this study were to review the literature on the effects of occupational exposure to organic solvents on the auditory system and to identify work settings in which exposure to these agents and to noise might occur. The criteria for selecting the chemicals were (a) evidence available that indicated that the chemicals may affect the auditory system and enhance noise effects, and (b) the ubiquity of their use. References to ototoxicity were noted for three proven neurotoxicants, i.e., carbon disulfide, toluene, and trichloroethylene, and for two probable human neurotoxicants--styrene and xylene. The percentages of workers (estimated by NIOSH National Occupational Exposure Survey) exposed to these solvents in each economic sector are shown. Work settings are identified where multiple exposures occur to solvents and noise. The need for future research is discussed.

Animals↗
PubMedDate not supplied

Trauma of the ear from infrasound.

Twenty-eight chinchillas received continuous or intermittent infrasound (1, 10, 20 Hz) at 150, 160, or 170 dB SPL; there were 7 controls. Serial sections of the temporal bones were examined using light microscopy. Pathologies noted were tympanic membrane perforation, stapes subluxation, bleeding from the middle ear mucosa and tensor tympani, strial pathology, Reissner's membrane rupture, endolymphatic hydrops, saccular wall rupture, hair cell damage, and blood in the cochlear scalae. Continuous infrasound was more damaging than intermittent. Only continuous infrasound produced saccular pathology and perforations of the tympanic membrane. Of the other pathologies observed, continuous infrasound exposures produced 67% of the hair cell damage, 73% of the bleeding in the cochlear scalae, 83% of the strial pathology, and 78% of the cases of cochlear hydrops. 170-dB infrasound exposures produced the highest percentage of ears with pathologies of the three exposure intensities. As frequency increased the percentage of ears with pathologies decreased.

Animals↗
PubMedDate not supplied

Idiopathic orthostatic hypotension controlled with a monoamine oxidase inhibitor and 9-alpha-fluorohydrocortisone.

A case of orthostatic hypotension with autonomic failure is presented, and the patient's clinical response to the combined regime of a monoamine oxidase inhibitor and 9-alpha-fluorohydrocortisone is discussed. This therapy provided a relatively convenient means of alleviating the patient's symptoms and appears to be of considerable value in the management of orthostatic hypotension. However, close patient supervision is essential when these drugs are used as they cause hypertension in the supine position in subjects with poor baroreceptor function.

Blood Pressure↗