Tolerance induction by liver grafting and FK 506 treatment in nonhuman primates.
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Biomedical subjects
Publications and source records attributed to T Tono.
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Sensorineural hearing loss (SNHL) has been documented in patients with otitis media. Despite a number of clinical and pathologic works dealing with this common problem, animal studies searching for possible relationships between the middle ear inflammation and cochlear function remain insufficient. Bacterial inoculation and ototoxins and inflammatory products in the middle ear cavity cause SNHL in rodents. Human serum albumin placed in the middle ear cavity in chinchillas also produces SNHL, owing to the effects of nonspecific inflammation in the middle ear cavity. Most of the middle ear inflammatory mediators enter the inner ear through the round window route, and alteration of the permeability of the round window membrane plays an important role in causing cochlear dysfunction. Although an immunologic response in the middle ear plays an important role in otitis media, the immunologic response in the inner ear as it relates to middle ear inflammatory mediators requires further study.
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This study provides evidence of antibodies playing an important role in hamster-to-rat cardiac xenograft rejection and discusses the use of 15-deoxyspergualin (DSG) to suppress this first-set rejection, as well as hyperacute rejection induced by sensitization. The effect of recipient splenectomy (Spx) as an adjuvant to DSG to control first set xenograft rejection was also examined. When hyperimmune serum was taken from control recipients at rejection time and injected i.v. into new recipients of cardiac xenografts, hyperacute graft rejection resulted. Survival depended on the amount of serum injected and ranged from 14.7 +/- 2.5 min with 3 ml of serum to 233.3 +/- 61.1 min with 0.5 ml. Experiments on first-set xenograft rejection revealed that a dose of 2.5 mg/kg/day DSG could prolong xenograft survival from 3.4 +/- 0.5 days in untreated controls to 9.5 +/- 2.6 days (P less than 0.01). A dose of 5 mg/kg/day DSG, though it increased graft survival to 16.4 +/- 5.9 days, proved to be toxic to the recipients. Spx alone prolonged xenograft survival to 5.2 +/- 0.4 days, and, when combined with 2.5 mg/kg/day DSG administration, prolonged graft survival to 22.1 +/- 5.5 days (P less than 0.01 vs. DSG alone). The appearance of cytotoxic antibodies was delayed, and titers decreased from 1:256 in untreated controls to 1:16-1:64 both in the group that underwent Spx only and in the group that received 2.5 mg/kg/day DSG. Combined treatment suppressed antibody response for more than two weeks. Experiments on hyperacute rejection induced by sensitization revealed that 1 ml of hamster whole blood transfused into prospective heart recipients 1 week before grafting resulted in graft loss in 18.2 +/- 6.1 min. Pretransplant transfusion and concomitant daily administration of 5 mg/kg/day DSG until one day after grafting not only prevented hyperacute rejection but prolonged graft survival to 7.0 +/- 0.7 days. This survival was significantly longer than with DSG alone (4.2 +/- 0.8 days, P less than 0.01). We concluded that the marked suppression of antibody formation by DSG plays a major role in preventing first-set xenograft rejection and hyperacute rejection induced by sensitization.
Encapsulated nerve endings were found in both the subepidermal connective tissue and the lamina propria of a human tympanic membrane. The structure of the corpuscles was round or oval and contained a number of axon terminals with mitochondria and Schwann cell processes. Amorphous materials were present in the intercellular space. These features appear to be advantageous in transmitting mechanical forces on the capsule to the axon terminals and are comparable to the function of a mechanoreceptor. Resultant changes in the shape and stiffness of the tympanic membrane as the result of its dislocation indicate similar changes in the pressure on the corpuscle. The arrangement of the sensory corpuscles suggests that they may play a role in detecting pressure changes in the middle ear cavity.
A new conception of the pathogenesis of cholesteatoma is proposed based on clinical results of anterior tympanotomy, a procedure developed in order to prevent recurrence of cholesteatoma following retraction pocket formation after canal-up operation. In the cholesteatomatous ear, there is always a long, thick bony septum between the epitympanum and the supratubal recess. This septum is called the anterior attic bony plate, forming the tympanic diaphragm together with the tensor tympani mucosal fold. In anterior tympanotomy, this bony plate is removed finishing intact canal wall mastoidectomy, making a new ventilating route to the eustachian tube. With this technique, the rate of recurrence was reduced from 17 to 5%. Based on these results it is proposed that the real pathogenesis of cholesteatoma is not tubal dysfunction, but the osseous tympanic diaphragm.
The condition of the mastoidectomy cavity following intact canal wall tympanoplasty (ICWT) is always of great interest to the otosurgeon. We evaluated the status of postoperative aeration in a stable ear following ICWT for various types of chronic otitis media using high-resolution computed tomography (CT). The mastoidectomy cavity in all the cases of simple suppurative otitis is totally aerated and that in over 60% of the cases of adhesive otitis, attic type cholesteatoma and adhesive type cholesteatoma is obliterated by a soft tissue density mass. The size of aerated spaces in the postoperative middle ear cavity not only depends on the type of chronic otitis media but also tends to correlate with the degree of mastoid pneumatization in the opposite ear. CT is useful for the postoperative assessment of middle ear aeration.
A new technique of laryngoplasty using the function of the suprahyoid muscles (hyoid transposition laryngoplasty) was reported. Total laryngectomy is carried out as usual and the tracheal stump is anastomosed directly to the hypopharynx. The hyoid bone is cut medially, then transpositioned and sutured to the posterolateral margins of the tracheal stump. With this procedure, the new glottis is pressed strongly to the tongue base during swallowing and aspiration is avoided. Postoperative swallowing and speech in the cases operated on with this method were satisfactory, and even nasal respiration was possible in some cases.
Morphological changes in nasal blood vessels induced by alpha- and beta-adrenergic and cholinergic agonists were studied under a scanning electron microscope after removal of extracellular connective tissue and the basal lamina. Arterioles were constricted and dilatated following topical application of alpha-adrenergic and cholinergic agonists. Distinctive morphological changes were observed on their smooth muscle cells. Smooth muscle cells of constricted arterioles had a rugged surface with numerous fine invaginations. However, in dilatated arterioles the cells had a smooth surface and intercellular spaces were clearly revealed. No remarkable changes were produced in smooth muscle cells by the beta-adrenergic agonist. It is concluded that nasal arterioles are sensitive to alpha-adrenergic and cholinergic stimulation but not to beta-adrenergic stimulation.
Arteriovenous anastomosis (AVA) in nasal respiratory mucosa of humans and guinea pigs were studied with scanning electron microscopy (SEM) after removal of extracellular connective tissues by tryptic digestion and HCl hydrolysis. The shape of AVA in humans is different from that in guinea pigs. In guinea pigs, it is simple with no specific structure observed on the vessels. In humans, it is characterized by a spherical swelling at the intermediate segment. The Tunica media of the spherical body is formed by the aggregation of spindle-shaped cells and receives a rich nerve supply. These findings suggest powerful contractility of human AVA compared with guinea pigs. Arteriovenous anastomosis in human nasal respiratory mucosa may strongly influence arterial blood flow into the cavernosus sinusoid and determine the characteristic microcirculatory pattern in human nasal mucosa.
The stria vascularis and the spiral prominence in the lateral cochlear wall were observed with scanning electron microscopy (SEM) after dissolving out the epithelial layer and the basement membrane by tryptic digestion and HCl hydrolysis. The external sulcus cells have regularly arranged pegs and a fine basal interdigitation on the cell surface. The strial vessel and the spiral prominence vessel could be visualized well and the characteristic surface view of their periendothelial cells presented. The former has cytoplasmic processes with a fine branching appearance similar to red coral and the latter has bulged popcorn like processes. Their functional significance is discussed.
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PURPOSE: A high jugular bulb (JB) is thought to affect structures of the inner ear and possibly cause symptoms there, but clear histological findings of an anatomical relationship between a high JB and the inner ear have not yet been described. MATERIALS AND METHODS: We surveyed horizontal sections of 1,591 temporal bones from the collection of the Otopathology Laboratory at the University of Minnesota in Minneapolis, Minnesota, defining a high JB as a JB extending above the inferior margin of the basal cochlear turn. RESULTS: In 65 specimens (16%), we found a high JB with its vascular wall obviously thinner than that of a low JB. Bony resorption was occasionally observed around high JBs. Sixteen specimens showed a bony deshiscence between the JB and the endolymphatic sac. Clinical charts showed no obvious symptoms associated with a high JB. CONCLUSIONS: Our findings suggest that the JB may have potential to expand upward postnatally. Although our study confirmed occasional bony dehiscence between the JB and the endolymphatic sac, JBs with this involvement may have only a minor effect on function in the inner ear.
A mitochondrial mutation at nucleotide 1555 has been reported to be susceptible to aminoglycoside antibiotics as well as one of the causes of nonsyndromic sensorineural hearing loss. We herewith report 2 cases bearing the 1555 A-->G mitochondrial mutation who had hearing loss after short-term exposure to the new aminoglycoside antibiotic, isepamicin sulfate. Even when using aminoglycoside antibiotics with milder side effects, careful attention should be paid in applying them to patients with particular genetic backgrounds.
Recent genetic studies have shown that hereditary susceptibility to aminoglycoside antibiotics is caused by the 1555 A-->G mitochondrial mutation. We found the 1555 mutation in 4 out of 68 postlingual deaf patients who were candidates for cochlear implantation. All 4 patients developed bilateral profound hearing loss following administration of aminoglycosides. The pedigree of the family shows exclusively maternal transmission of hearing impairment in each case. On comparison with neuro-otological findings from aminoglycoside-induced deaf patients without the 1555 mutation, four distinct characteristics were noted: (1) a progressive nature of hearing loss; (2) better residual pure-tone thresholds; (3) lower thresholds for electrical promontory stimulation, and (4) well-preserved vestibular function. Although other factors such as differing dosages and/or administration routes may also be involved, profound hearing loss associated with the 1555 mutation may be due to a different pathogenic mechanism, i.e., strial dysfunction rather than a direct insult to the hair cells.
Two-staged intact canal wall tympanoplasty is a common operation for treatment of middle ear cholesteatoma. MRI provides better tissue differentiation of the middle ear and/or mastoid, which often become occupied with soft density tissue after the first operation. If MRI was able to detect the presence of a recurrent or residual cholesteatoma with sufficient sensitivity and specificity, this may facilitate a decrease in the number of second-look procedures. This study compared MRI findings to surgical findings at second-look surgery and calculated the correlation rates between the two sets of findings. Thirty ears having undergone intact canal wall tympanoplasty for cholesteatoma at the initial operation were examined by MRI prior to the second look. Otoscopic findings of the tympanic membrane were nonsuspect in all cases. The true positive rate was 11/30 (37%) and the true negative rate was 10/30 (33%), leading to a radiosurgical correlation of 70%, whereas the false positive rate was 6/30 (20%) and the false negative rate was 3/30 (10%). This indicates that 30% of the MRI findings were incorrect. Therefore, at the present time, MRI does not appear as a likely replacement for second-look surgery in cases of intact canal wall tympanoplasty.