Taku Hattori

The effect of furosemide on evoked otoacoustic emissions in guinea pigs

After recording transiently evoked otoacoustic emissions (TEOAEs) to a click stimulus in guinea pigs by using the IL088 which was developed by Bray and Kemp (1987) for easy recording and analysis of TEOAE, the changes after intravenous administration of furosemide (30 mg/kg or 50 mg/kg) were examined. The wave of the TEOAE could be detected from 20 of 24 ears (83%). After the i.v. injection of furosemide (30 mg/kg), TEOAE powers (total echo power and highest peak power in FFT pictures) decreased quickly and showed minimum values after 5-10 min. Then they increased rapidly and recovered normally within 60 min after injection. However, no ears showed TEOAEs during the 5- to 10-min period following the injection of the 50-mg/kg dose of furosemide. They then recovered slowly as compared with the group treated with the lower dose of furosemide (30 mg/kg). These changes are similar to those of the endocochlear potential (EP) after furosemide injection. These data support the notion that the EP can contribute to the mechanism of TEOAE generation.

Soluble ICAM‐1 as a regulator of nasal allergic reaction under natural allergen provocation

Background: Intercellular adhesion molecule‐1 (ICAM‐1) plays a key role in the early stage of the signal cascade leading to cellular extravasation and the development of an inflammatory response. Recently, it has been reported that the soluble form of this adhesion molecule is present in human sera, possibly mediating biological actions.

Cell type-oriented differential modulatory actions of saikosaponin-d on growth responses and DNA fragmentation of lymphocytes triggered by receptor-mediated and receptor-bypassed pathways

We examined the immunoregulatory action of saikosaponin-d (SSd), which was isolated from the root of Bupleurum talcatum L. and had a steroid-like structure, on murine thymocytes, and compared the action with that on spleen cells. Constitutive DNA synthesis or the growth response stimulated with anti-CD3mAb of thymocytes were down-regulated by 3 micrograms/ml SSd, whereas with spleen cells these were up-regulated by the same concentration of SSd. On the other hand, 3 micrograms/ml of SSd greatly up-regulated the growth response and interleukin 2 (IL-2)/interleukin 4 (IL-4) production induced through a receptor-bypassed pathway by calcium ionophore A23187 plus phorbol 12-myristate 13-acetate (PMA) in thymocytes, whereas it only slightly up-regulated them in spleen cells. Moreover, the same concentration of SSd inhibited DNA fragmentation in thymocytes induced by A23187 or PMA. These results suggest a unique cell type-dependent immuno-modulatory action of SSd.

Serum-soluble Fas levels as a marker to distinguish allergic and nonallergic rhinitis

the volunteers who had no sensitization as determined by 7 kinds of RASTs and skin tests. They had no subjective symptoms and no histories of allergic, nasal, or collagen disease. Serum sFas levels in patients with allergic or vasomotor rhinitis were measured by a sandwich ELISA (Medical & Biological Laboratories Co, Nagoya, Japan) and were compared with those in healthy individuals as negative controls and patients with SLE as positive controls. The results were statistically analyzed by the Mann-Whitney U test. RESULTS As shown in Fig 1, the serum sFas levels in patients with allergic rhinitis (0.55 ± 0.35 ng/mL) during the pollen season were less than one third of those in healthy individuals (1.57 ± 0.43 ng/mL). The serum sFas levels in more than 95% of the patients with allergic rhinitis were less than 1 ng/mL. Moreover, serum sFas levels in patients with allergic rhinitis (0.45 ± 0.28 ng/mL) out of season (ie, 1 month after the season) remained significantly lower (P < .0001) than those of healthy individuals. There were no differences in serum sFas levels between patients with vasomotor rhinitis (1.50 ± 0.38 ng/mL) and healthy individuals. The serum sFas levels in all patients with vasomotor rhinitis were greater than 1 ng/mL. As previously reported, levels in patients with SLE (2.55 ± 0.97 ng/mL) were significantly higher (P < .002) than those found in healthy individuals. 3 The magnitude of sFas in patients with SLE and healthy individuals is comparable to the levels reported by Knipping et al,4 although it is more than an order of magnitude lower than the levels reported by Cheng et al. 3 DISCUSSION In this study we demonstrate that the levels of serum sFas in patients with allergic rhinitis were less than 1 ng/mL as opposed to greater than 1 ng/mL in patients with vasomotor rhinitis. These results suggest that the level of serum sFas could be one of the markers used to distinguish allergic rhinitis from nonallergic (vasomotor) rhinitis. The serum sFas level should be a marker to identify allergic subjects rather than active allergic inflammation because serum sFas levels in allergic subjects out of season remained low. Fas is a cell surface molecule that delivers a signal for inducing apoptosis after stimulation with anti-Fas antibody or Fas-ligand. sFas, which is produced by alternative mRNA splicing, antagonizes anti-Fas antibody‐ or Fas ligand‐induced Fas-mediated killing in a dosedependent manner.3,5 Recently, a number of serum sFas

Detection of Herpesvirus DNAs in Perilymph Obtained from Patients with Sensorineural Hearing Loss by Real‐Time Polymerase Chain Reaction

Objectives/Hypothesis: Perilymph and peripheral blood mononuclear cells (PBMCs) from patients with bilateral severe sensorineural hearing loss (SNHL) were evaluated for the presence of DNA from cytomegalovirus (CMV), herpes simplex virus (HSV), and human herpesvirus (HHV)6.

Amount of pollen has an effect on the systemic and local levels of soluble ICAM‐1 in patients with seasonal allergic rhinitis

We investigated whether the amount of antigen has an effect on the systemic and local levels of soluble ICAM‐1 (sICAM‐1) in patients with pollinosis, and assessed its biologic significance. The levels of subjective symptoms and SICAM‐1 in sera and nasal epithelial lining fluids (ELF) from 14 subjects with pollinosis (allergic group) and eight healthy subjects (control group) were measured from pre‐ to postseason in 1993 (total pollen count: 10854/cm2) and 1994 (total pollen count: 415/cm2)), and the results were compared with each other among the four groups. The levels of subjective symptoms and slCAM‐1 in ELF from the allergic group significantly increased during the season in both 1993 and 1994. However, there was a significant difference (P<0.01) between the levels of those in 1993 and those in 1994 during the season. The levels of sICAM‐1 in sera from the allergic group were significantly upregulated during the seasons and postseasons only in 1993, and there was a significant difference (P<0.05) between the levels in 1993 and those in 1994 during the postseason. We conclude that amount of pollen has an influence on the local and systemic levels of sICAM‐1, as well as the scores of subjective symptoms, in patients with seasonal allergic rhinitis.

Blood Flow Measurements in the Ears of Patients Receiving Cochlear Implants

We measured cochlear blood flow in 12 patients who received cochlear implants, using a laser-Doppler probe with an outer diameter of 0.8 mm. The subjects had congenital deafness, idiopathic progressive sensorineural hearing loss, Waardenburgs syndrome, narrow internal auditory canal, or sudden deafness. Putting the probe tip to the site of drilling for cochlear implantation, we measured blood flow before, during, and after the cochlear bony wall was opened. The laser-Doppler output was confirmed even after the tip of the probe was inserted into the perilymphatic space in all cases. Our results revealed that blood flow was maintained in all cochleas, although there was a probability of reduction in blood flow volume. We conclude that laser-Doppler flowmetry is both relatively safe and useful for measuring blood flow in the ears during cochlear implantation procedures.

Blood Flow in the Ears of Patients Receiving Cochlear Implants

We measured cochlear blood flow (CBF) in 55 patients who received cochlear implants, using a laser-Doppler probe placed over the site of drilling in the cochlear bony wall. The subjects included 29 patients with congenital deafness of unknown cause, 8 with idiopathic progressive sensorineural hearing loss, 4 with postmeningitic deafness, 3 with Waardenburgs syndrome, 3 with congenital cytomegalovirus infection, and 8 whose deafness had other causes. There was a wide range of CBF values in patients with congenital deafness of unknown cause. In the patients with idiopathic progressive sensorineural hearing loss, the CBF was significantly lower in patients more than 40 years old. Intracochlear calcification following meningitis appears to be associated with a reduced CBF.

Elevated soluble tumor necrosis factor receptor levels in seasonal allergic rhinitis patients

In this study, we examined the symptom scores and tumor necrosis factor‐alpha (TNF‐α), p55 soluble tumor necrosis factor receptor (sTNFR1), and p75 soluble tumor necrosis factor receptor (sTNFR2) levels in the sera and nasal epithelial lining fluids (ELF) of 20 patients with Japanese cedar pollinosis from the pre‐ to the postseason period, and compared the results with those of 10 nonallergic control subjects. The symptom scores of the allergic subjects were significantly (P<0.01) higher than those of the nonallergic subjects during the early stage and mid‐stage of the season. There were no statistical differences between the allergic and nonallergic subjects in the TNF‐α levels in sera and ELF from the pre‐ to the post‐season. In the allergic subjects, however, the levels of sTNFR1 and sTNFR2 in ELF were significantly elevated during the early stage (P<0.05) and mid‐stage (P<0.01) of the season, whereas those in sera did not change from the pre‐ to the post‐season period. The levels of TNF‐α in ELF were more than 10 times higher than those in sera, whereas the levels of sTNFR1 and sTNFR2 in ELF were less than half of those in sera in the allergic and nonallergic subjects. These results suggest that sTNFR1 and sTNFR2 may play a role in the pathogenesis of nasal allergic reaction.

Evidence of Potential Regulation by Interleukin-4 of the Soluble Intercellular Adhesion Molecule 1 Level in Patients with Seasonal Allergic Rhinitis under Provocation by a Small Amount of Natural Allergen

Interleukin-4 (IL-4) and intercellular adhesion molecule 1 (ICAM-1) are assumed to be involved in the pathogenesis of allergic disease. In this study, we examined the potential link between IL-4 and soluble ICAM-1 (sICAM-1) levels in patients with allergic rhinitis. The levels of sICAM-1 and IL-4 in sera and in nasal epithelial lining fluids (ELF) from 12 patients with Japanese cedar pollinosis were measured preseason through postseason, and the results were compared with those from 7 healthy subjects. In sera from the allergic subjects, the levels of sICAM-1 were upregulated during the early part of the season and downregulated during the middle of the season, with upregulation of the IL-4 levels. Moreover, a negative correlation was found between the serum sICAM-1 levels and serum IL-4 levels during the middle (r = –.80) and late (r = –.73) parts of the season. In ELF from allergic subjects, the levels of sICAM-1 were significantly upregulated during the early and middle parts of the season, and began to be downregulated during the late part of the season, with upregulation of the levels of IL-4. In conclusion, IL-4 possibly acts as a potential suppressor of sICAM-1 in the pathogenesis of seasonal allergic rhinitis, at least under provocation by a small amount of natural allergen.