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Biomedical subjects

C D Balaban

Publications and source records attributed to C D Balaban.

At least 37 records · Page 2Linked to original sources

Postnatal development of eustachian tube cartilage. A study of normal and cleft palate cases.

Infants with cleft palate (CP) display eustachian tube (ET) dysfunction. This study compared the postnatal development of the volume of ET cartilage in 34 normal cases and 10 CP cases using a personal computer. In cases with age under 1 month old, the total volume of ET cartilage was 61.94+/-20.89 mm(3) (mean+/-S.D.) in 16 normal control cases and 50.07+/-24.69 mm(3) in nine CP cases (t-test, not significantly different from normal). The ratio of lateral lamina (LL) to medial lamina (ML) volume (LL/ML) was reduced significantly (t-test, P<0.001) from 0.23+/-0.07 in 16 normal control cases to 0.09+/-0.05 in nine CP cases under 1 month old. In 34 normal ET cases whose ages were under 20 years, statistically significant positive correlations were found between the total volume of ET cartilage (y1) and age (x), volume of LL (y2) and age, and volume of ML (y3) and age (P<0.01, r=0.731, 0.614, 0.719). The regression lines were y1=20.37x+95.57, y2=2.02x+15.60, and y3=18. 35x+79.97. With the result obtained from this study, it is assumed that immaturity of the ET cartilage in infants, especially that of LL of the ET cartilage in CP infants, may be a significant risk factor for developing otitis media with effusion.

Adolescent↗

Zonal organization of flocculo-vestibular connections in rats.

Anatomical and electrophysiological evidence has contributed to the hypothesis that microzones in the mammalian flocculus are organized to reflect control of eye movements in the planes of semicircular canals. Adult male Long-Evans rats received iontophoretic injections of FluoroGold and/or tetramethylrhodamine dextran amine (10,000 molecular weight, "FluoroRuby") into the vestibular nuclei. The distribution of retrogradely labeled Purkinje cells revealed that efferent projections from the dorsal surface of the flocculus and the ventral paraflocculus to the superior vestibular nucleus, rostral medial vestibular nucleus, ventral lateral vestibular nucleus, and caudal aspect of the vestibular nuclear complex (caudal medial vestibular nucleus, inferior vestibular nucleus and nucleus prepositus hypoglossi) tended to correspond to previously identified climbing fiber zones [Ruigrok et al. (1992) J. comp. Neurol. 316, 129-150] in a manner consistent with other mammals. However, vestibular nucleus projections from the ventral surface of the flocculus did not appear to respect climbing fiber zonal boundaries. Rather, climbing fiber zones each contained interdigitated groups of Purkinje cells that project to different vestibular nuclear regions. It is suggested that this pattern of flocculus efferent organization is a specialization for controlling the activity of primary and accessory extraocular muscle pairs to confine vestibulo-ocular reflexes within semicircular canal planes when the "center of regard" is located at different eccentricities.

Animals↗

Cellular distribution of mucosa-associated lymphoid tissue with otitis media in children.

This study examined mucosa-associated lymphoid tissue (MALT) in the eustachian tube (ET), middle ear (ME), and mastoid antrum (MA) in 163 celloidin-embedded temporal bones from children with or without otitis media. Otitis media was defined by the presence of histopathologically identified inflammatory cell infiltration in the mucosa or cavity of the ME. We found MALT in the ET in 30 cases (46.2%), in the ME in 19 cases (29.2%), and in the MA in 4 cases (6.2%) out of 65 cases of otitis media, and in the ET in 7 (7.1%), in the ME in 0, and in the MA in 0 out of 98 specimens without otitis media. No MALT appeared in any children under the age of 1 month. Immunohistochemical methods were used to investigate MALT in 12 horizontally cut temporal bones with OM. The follicular area contained OPD4-positive (helper-inducer T) cells and a few CD8-positive (cytotoxic and suppressor T) cells, whereas the parafollicular area contained OPD4-positive and CD8-positive T cells. CD57-positive (natural killer) cells were confined to the germinal center. CD30-positive (activated T and B) cells were observed throughout the follicles. A few CD15-positive (granulocyte, monocyte) cells were found in the follicles. Histopathologic and immunohistochemical findings were indistinguishable for MALT in the ET, ME, and MA. Our results suggest that MALT may be a mechanism for producing a rapid and massive local immune reaction to repeated bacterial infections via the ET.

Antigens, CD↗

Protein kinase C inhibition blocks the early appearance of vestibular compensation.

This study tests the hypothesis that activation of protein kinase C (PKC) is a critical step for early recovery from spontaneous nystagmus after unilateral ablation of the vestibular periphery. Halothane-NO(2)-O(2)-anesthetized Long-Evans rats received a 5-microl intracerebroventricular bolus of vehicle (distilled water, six rats), PKC inhibitor [Iso-H-7 (10 mM, four rats; 50 mM, five rats) or bisindolemaleimide I (Bis-I, 10 microM six rats)], PKG and PKA inhibitor (A-3, 1 mM, six rats), or the serine-threonine protein kinase inhibitor H-7 (1 mM, five rats; 10 mM, five rats). Surgical unilateral labyrinthectomy (UL) was completed within 15 min. Sham control groups showed no nystagmus. Bis-I and Iso-H-7 significantly retarded the disappearance of spontaneous nystagmus quick phases for 8 h after UL (p<0.05). The effects of Iso-H-7 were dose-dependent: more nystagmus quick phases (p<0.05) were present in the 50 mM than the 10 mM group at 7 and 8 h post-UL. The rats given A-3 showed a delayed retardation of nystagmus loss, which differed significantly (p<0.05) from controls at 4-8 h after labyrinthectomy. The number of nystagmus quick phases was significantly greater than controls (p<0. 05) in the 10 mM H-7 group at 4, 5, 6 and 48 h post-UL, but only at 6 and 24 h post-UL in the 1 mM H-7 group. Thus, PKC activation is an important early requirement for vestibular compensation during the acute post-labyrinthectomy period, while cyclic-nucleotide dependent kinases may be important in a later time frame.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Time course of burn to repeated applications of capsaicin.

Human subjects rated the burn of 100 ppm capsaicin applied to the tongue via filter paper and replaced every minute. Capsaicin was presented at a constant concentration for 10 min, followed by 10 min of blank stimuli; this sequence was then repeated once. Both sensitization and desensitization were seen. A dynamic model composed of a level detector and change detector predicted the results and also previous data. Thus, the model provides a parsimonious description of responses to constant and intermittent capsaicin stimulation.

Adult↗

Organization of the coeruleo-vestibular pathway in rats, rabbits, and monkeys.

Inputs from locus coeruleus (LC) appear to be important for altering sensorimotor responses in situations requiring increase vigilance or alertness. This study documents the organization of coeruleo-vestibular pathways in rats, rabbits and monkeys. A lateral descending noradrenergic bundle (LDB) projects from LC to the superior vestibular nucleus (SVN) and rostral lateral vestibular nucleus (LVN). A medial descending noradrenergic bundle (MDB) projects from LC to LVN, the medial vestibular nucleus (MVN), group y and rostral nucleus prepositus hypoglossi (rNPH). There is a characteristic, specific pattern of innervation of vestibular nuclear regions across the three species. A quantitative analysis revealed four distinct innervation density levels (minimal, low, intermediate and high) across the vestibular nuclei. The densest plexuses of noradrenergic fibers were observed in the SVN and LVN. Less dense innervation was observed in the MVN, and minimal innervation was observed in the inferior vestibular nucleus (IVN). In monkeys and rabbits, rostral MVN contained a higher innervation density than the rat MVN. In monkeys, the rNPH also contained a dense plexus of fibers. Selective destruction of terminal LC projections (distal axons and terminals) by the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) resulted in a dramatic reduction of immunoreactive fibers within the vestibular nuclear complex of rats, suggesting that the source of these immunoreactive fibers is LC. Retrograde tracer injections into the vestibular nuclei resulted in labeled cells in the ipsilateral, caudal LC and adjacent nucleus subcoeruleus. It is hypothesized that the regional differences in noradrenergic innervation are a substrate for differentially altering vestibulo-ocular and vestibulo-spinal responses during changes in alertness or vigilance.

Animals↗

Effects of ethacrynic acid on intraocular pressure of anesthetized rats.

Ethacrynic acid (ECA) lowers intraocular pressure (i.o.p.) by an effect usually ascribed to increased drainage of aqueous humor by the trabecular meshwork. Here, we describe the effects of a continuous 2-hr intracameral infusion of balanced salt solution (BSS), with or without 2 mM ECA (sodium salt), on IOP of pentobarbital anesthetized rats. The infusion was divided into a constant (0.05 microliter/min) and a periodic (0.25 microliter/min) component that cycled 4 min on then 4 min off. This permitted the calculation of dynamic changes in resistive (trabecular and uveoslceral drainage) and nonresistive (aqueous synthesis, episcleral venous pressure) components of IOP by fitting a second-order transfer function to the responses. ECA markedly blunted the BSS-induced rise in IOP (P < 0.01). The rise in resistive mechanisms (ocular impedance) was transiently blunted by ECA (P < 0.05) during the third and fourth 8-min cycles, and nonresistive mechanisms were reduced by ECA from cycles 3-10 (P < 0.05). Then, at the end of the infusion, the control and ECA dynamic values were similar (P < 0.05), although IOP of ECA-treated rats was still slightly reduced (P < 0.05). The most likely explanation is a summation of small changes in both resistive and nonresistive components of IOP dynamics. Systemic blood pressure was unchanged within either group. The well-known effects of ECA on the trabecular meshwork, alone, are insufficient to explain the dynamic changes in IOP observed in this model.

Anesthesia↗

Histopathological changes of the eustachian tube cartilage and the tensor veli palatini muscle with aging.

OBJECTIVES: The eustachian tube (ET) and the tensor veli palatini muscle (TVPM) are thought to play an important role in ventilatory function. Calcification of the ET cartilage and the replacement of TVPM by fat tissue are often observed histologically in elderly patients. To our knowledge, however, there are no quantitative studies of these pathological findings in relation to age. STUDY DESIGN: The calcification of the ET cartilage and the atrophy of the TVPM in 36 normal human temporal bones obtained from 36 individuals with ages ranging from 2 days to 88 years were investigated. METHODS: The number of calcified chondrocytes in the midportion of the ET cartilage was quantified as the average number of cells per square millimeter. Atrophy of the TVPM was evaluated at the midportion of the site where the TVPM is attached to the tip of lateral lamina of ET cartilage. A grade of 0, 1, 2, 3, or 4 was assessed for each section, which indicated approximately 0% to 5%, 5% to 30%, 30% to 70%, 70% to 95%, or 95% to 100% of the TVPM replacement by fat tissue, respectively. RESULTS: A statistically significant correlation was found between the number of the calcified cells and aging (P < .001). A statistically significant correlation was also found between the degree of the atrophy of TVPM and aging (P < .001). CONCLUSIONS: The calcification of the ET cartilage and the atrophy of the TVPM are closely associated with aging. Therefore, it is suggested that these two findings may be a predisposing factor for ET dysfunction in elderly adults.

Adolescent↗

Vestibular autonomic regulation (including motion sickness and the mechanism of vomiting).

Autonomic manifestations of vestibular dysfunction and motion sickness are well established in the clinical literature. Recent studies of 'vestibular autonomic regulation' have focused predominantly on autonomic responses to stimulation of the vestibular sense organs in the inner ear. These studies have shown that autonomic responses to vestibular stimulation are regionally selective and have defined a 'vestibulosympathetic reflex' in animal experiments. Outside the realm of experimental preparations, however, the importance of vestibular inputs in autonomic regulation is unclear because controls for secondary factors, such as affective/emotional responses and cardiovascular responses elicited by muscle contraction and regional blood pooling, have been inadequate. Anatomic and physiologic evidence of an extensive convergence of vestibular and autonomic information in the brainstem suggests though that there may be an integrated representation of gravitoinertial acceleration from vestibular, somatic, and visceral receptors for somatic and visceral motor control. In the case of vestibular dysfunction or motion sickness, the unpleasant visceral manifestations (e.g. epigastric discomfort, nausea or vomiting) may contribute to conditioned situational avoidance and the development of agoraphobia.

Agoraphobia↗

Aqueous humor dynamics in anesthetized rats infused with intracameral apraclonidine.

We studied the acute effects of the ocular hypotensive drug, apraclonidine (AP), on intraocular pressure (IOP) and aqueous humor dynamics of anesthetized rats during infusion-induced ocular hypertension. Two infusions were made into the anterior chamber of the eye: one was constant at a rate of 0.05 microl/min, the other was cyclic, at a rate of 0.25 microl/min, with the pump on for 4 min, then off for 4 min. Data were processed by complex demodulation and analysis of a second-order transfer function. This permitted separate calculations of resistive components (Ao), i.e., trabecular meshwork and uveoscleral outflows, and residual pressure (RP) estimating nonresistive components, i.e., aqueous synthesis and episcleral venous pressure. A balanced salt solution (BSS) and AP (0. 0005%) were tested. AP markedly delayed the within-group rise in IOP: 20 min for BSS vs. 60 min for AP (p < 0.001). IOP of AP rats was less than control for 100 min (p < 0.05). The infusions raised Ao in both groups (p < 0.05). AP initially had a transient inhibitory effect (p < 0.05). Infusions raised RP in both groups. AP had a strong inhibitory effect for the first 8 cycles (p < 0.05). These data document that the acute effects of AP in this in vivo rat model of ocular hypertension were to delay increases in IOP, mainly by reducing nonresistive components of aqueous humor dynamics. Transient inhibition of resistive mechanisms also occurred.

Adrenergic alpha-Agonists↗

Inflammatory response to chronic otitis media in DiGeorge syndrome: a case study using immunohistochemistry on archival temporal bone sections.

Immunohistochemical analyses were conducted on archival celloidin-embedded human temporal bone sections from an 8-month-old boy with chronic otitis media and DiGeorge syndrome. We employed antigen retrieval methods with saturated sodium hydroxide-methanol solution, microwave incubation, and proteolytic treatment to demonstrate the distribution of T-lymphocytes, B-lymphocytes, macrophages, and intercellular adhesion molecule 1 (ICAM-1) expression in the middle ear. B-lymphocytes and macrophages were observed predominantly within the middle ear mucosa. T-lymphocytes were rare. Further, ICAM-1 was expressed in the vascular endothelium of the lamina propria, as well as infiltrating mononuclear cells. This suggests that the expression of ICAM-1 can be induced in the middle ear with otitis media, even if T-lymphocytes are depressed in a cell-mediated immunodeficiency disorder such as DiGeorge syndrome.

Antibodies, Monoclonal↗

Timolol effects on aqueous humor dynamics in eyes of anesthetized rats.

Anterior chambers of the eyes of male rats were cannulated under pentobarbital anesthesia for intracameral infusions of balanced salt solution (BSS) and intraocular pressure (IOP) recording. Blood pressure was recorded from a femoral artery. IOP was recorded during a 2-h intracameral infusion composed of a constant component (0.05 microl/min) and a periodic component (0.25 microl/min), cycling at 4 min on and then 4 min off. After a 20-min baseline period, 1 drop of timolol (0.5%) or BSS was applied to the cornea and repeated 1 h later. Intracameral infusions of BSS and 0.05% timolol were also compared. Topical timolol slightly delayed the BSS-induced IOP rise (p <.05). Complex demodulation and the estimated gain parameter of a second-order transfer function fit to the periodic responses revealed that topical timolol also reduced (p <.05) passive outflow resistance. Intracameral timolol markedly delayed the BSS-induced rise in IOP. Initially, timolol decreased both outflow impedance and nonresistive components (p <.05) of IOP, but these effects dissipated by 2 h when IOPs were similar. In all experiments, within-group blood pressure was unchanged. Topical and intracameral timolol have different effects on IOP. The data support the opinion that, in vivo, timolol acts at beta-receptors that control both outflow impedance and nonresistive mechanisms, probably vascular, to lower IOP.

Administration, Topical↗

A role of climbing fibers in regulation of flocculonodular lobe protein kinase C expression during vestibular compensation.

The behavioral recovery from unilateral labyrinthectomy (UL) in rats is accompanied by asymmetric expression of Protein kinase C (PKC) in parasagittal regions of the flocculonodular lobe within 6 h after UL, which resolves to the control, symmetric pattern within 24 h. These changes consist of a regionally selective increase in the number of PKC-immunopositive Purkinje cells contralateral to the lesion. This study tested the hypotheses (1) that climbing fiber innervation inhibits PKC expression and (2) that climbing fibers are essential for the observed changes in PKC expression within 6 h after UL. The patterns of flocculonodular lobe Purkinje cell PKCdelta expression were analyzed 6 h post-operatively in both UL and sham-operated that had been treated previously with 3-acetylpyridine to destroy the inferior olive. These data were compared with previous results from rats with an intact olive. The results suggest that at least two signals regulate the zonal distribution of Purkinje cell PKCdelta expression in the flocculonodular lobe during the early period of compensation from UL. Climbing fiber activation appears to reduce PKC expression, while extraolivary mechanisms appear to up-regulate PKC expression. It is suggested that the climbing fiber signals may act as a molecular 'filter' or 'automatic gain control' which adjusts the contributions of these kinases to synaptic plasticity within the context of the background activity of climbing fibers.

Animals↗

Molecules, motion, and man.

The application of cell and molecular biology techniques to vestibular research is resulting in rapid changes in our understanding of the fundamental mechanisms of vestibular function. The clinical problems encountered in space travel together with the acute and chronic vestibular dysfunction affecting many of the patients otolaryngologists care for have driven this research at a rapid pace. A review of these methods and highlights of the major advances are discussed.

Animals↗

Transient changes in flocculonodular lobe protein kinase C expression during vestibular compensation.

Protein kinase C (PKC) is a family of intracellular signal transduction enzymes, comprising isoforms that vary in sensitivity to calcium, arachidonic acid, and diacylglycerol. PKC isoforms alpha, gamma, and delta are expressed by cerebellar Purkinje cells and neurons in the cerebellar nuclei and vestibular nuclei of the Long-Evans rat. In control rats, these PKCs are distributed symmetrically in the flocculonodular-lobe Purkinje cells. Behavioral recovery from vestibular dysfunction produced by unilateral labyrinthectomy (UL) is accompanied by asymmetric expression of PKC isoforms in these regions within 6 hr after UL. These expression changes were localized within parasagittal regions of the flocculus and nodulus. The distribution of PKCalpha, -gamma, and -delta were identical, suggesting that they are coregulated in cerebellar Purkinje cells during this early compensatory period. The pattern of Purkinje cell PKC expression returned to the control, symmetric distribution within 24 hr after UL. It is hypothesized that these regional changes in Purkinje cell PKC expression are an early intracellular signal contributing to vestibular compensation. In particular, regulation of PKC expression may contribute to changes in the efficacy of cerebellar synaptic plasticity during the acute post-UL period.

Animals↗

Mechanisms for vasopressin effects on intraocular pressure in anesthetized rats.

Continuous intracameral infusions of a balanced salt solution (0.175 microliter min-1) have been reported to raise intraocular pressure (IOP) in anesthetized rats. Palm et al. (1995) previously reported that this effect was attenuated significantly by inclusion of arginine-vasopressin (AVP, 10 ng 0.175 microliter-1) in the infusate. This study used experimental and computer simulation methods to investigate factors underlying these changes in IOP. First, constant intracameral infusions of artificial cerebrospinal fluid (aCSF) at different fixed rates (0.049-0.35 microliter min-1) were used to estimate the outflow resistance. Secondly, IOP responses were measured during an 2 hr intracameral infusion of either aCSF or AVP that was the sum of a small constant component (0.05 microliter min-1) and a larger periodic component (0.25 microliter min-1, cycling for 4 min on, then 4 min off); the mean infusion rate was 0.175 microliter min-1. As shown previously for 0.175 microliter min-1 constant infusions, the periodic aCSF infusion induced a significant rise in IOP that was attenuated by AVP administration. Complex demodulation analysis and the estimated gain parameter of a second order transfer function fit to the periodic responses indicated that outflow resistance increased significantly during the infusions in both aCSF and AVP groups, but that the indices of resistance did not differ significantly between aCSF and AVP infused eyes. This finding implies that changes in outflow resistance do not explain the difference in IOP responses to intracameral aCSF and AVP. The two responses differed significantly, though, in damping factors, such that the aCSF responses were considerably more underdamped than the AVP responses. It is hypothesized that aCSF-induced increase in IOP reflects both (1) a small component reflecting increased outflow resistance and (2) a larger non-resistive component. Since the non-resistive component is insensitive to pretreatment with acetazolamide, it is suggested that the aCSF-induced elevation in IOP reflects primarily vascular perfusion changes that are reduced by local vasoconstrictor actions of AVP. The latter mechanism likely maintains vascular perfusion of the globe when intraocular hypertension develops.

Animals↗

Connections of the caudal ventrolateral medullary reticular formation in the cat brainstem.

A region of the caudal ventrolateral medullary reticular formation (CVLM) participates in baroreceptor, vestibulosympathetic, and somatosympathetic reflexes; the adjacent retroambigual area is involved in generating respiratory-related activity and is essential for control of the upper airway during vocalization. However, little is known about the connections of the CVLM in the cat. In order to determine the locations of terminations of CVLM neurons, the anterograde tracers Phaseolus vulgaris leucoagglutinin and tetramethylrhodamine dextran amine were injected into this region. These injections produced a dense concentration of labeled axons throughout the lateral medullary reticular formation (lateral tegmental field), including the retrofacial nucleus and nucleus ambiguus, regions of the rostral ventrolateral medulla, the lateral and ventrolateral aspects of the hypoglossal nucleus, nucleus intercalatus, and the facial nucleus. A smaller number of labeled axons were located in the medial, lateral, and commissural subnuclei of nucleus tractus solitarius, the A5 region of the pontine reticular formation, the ventral and medial portions of the spinal and motor trigeminal nuclei, locus coeruleus, and the parabrachial nucleus. We confirmed the projection from the CVLM to both the rostral ventrolateral medulla and lateral tegmental field using retrograde tracing. Injections of biotinylated dextran amine or Fluorogold into these regions resulted in retrogradely labeled cell bodies in the CVLM. However, the neurons projecting to the lateral tegmental field were located mainly dorsal to those projecting to the rostral ventrolateral medulla, suggesting that these neurons form two groups, possibly with different inputs. Injections of retrograde tracers into the lateral tegmental field and rostral ventrolateral medulla also produced labeled cell bodies in other regions, including the medial and inferior vestibular nuclei and nucleus solitarius. These data are consistent with the view that the CVLM of the cat is a multifunctional area that regulates blood pressure, produces vocalization, affects the shape of the oral cavity, and elicits contraction of particular facial muscles.

Animals↗