We determined whether whole body tilt would shift the axis of optokinetic nystagmus (OKN) and optokineticafter nystagmus (OKAN) induced by full-field rotation at 35°/sec. Fifteen normal people were positioned upright or tilted 30°, 60° or 90° to both sides. Stripes of 5° were projected on a 10-foot dome around the subject's yaw axis. Each trial lasted 45sec. The lights were then extinguished, and the subject remained in darkness for 30sec. while after-nystagmus (OKAN) was recorded. Horizontal and vertical eye movements were recorded by video-oculography at 60Hz. Eye position and velocity data were stored on optic disk cartridge by use of the data acquisition system.
A. OKAN: For the subject in the upright position, the OKN velocity vector was aligned with both gravity and the subject's yaw axis with two minor exceptions. When the subject was tilted, a vertical OKN component (VOKN) appeared in a majority of subjects. For all 15 subjects, the mean angle of the OKN velocity vector regravity (Vectorg) was 22.6±7.2° at 30° tilted position. The Vectorg were 48.5±10.3° at 60° tilted position, and 76.4±12.6° at 90° tilted position. This represented shifts of the OKN velocity vector from the body axis of 7.4°, 11.5° and 13.6°, respectively. The horizontal OKN (HOKN) gain remained unchanged in different positions.
B. OKAN: The duration of HOKAN and initial slow phase velocity (SPV) of HOKAN decreased as the body position increased from upright to 30°, 60° and 90° tilted position, respectively. The incidence and initial SPV of VOKAN and Re-Body did not change as the body position increased from upright to 30°, 60° and 90° tilted position, respectively. Thus, VOKN was observed during HOKN as subjects were tilted and tended to vector to gravity, but VOKAN was not always observed during horizontal OKAN when subjects were tilted.

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Because of its many advantages, free jejunal transfer has gained wide acceptance for pharyngoesophageal reconstruction after ablative surgery. Because the jejunum is well vascularized, it facilitates good wound healing, and has a low incidence of anastomotic insufficiency, fistula formation and stricture. However, voice rehabilitation in this group of patients can be difficult. Therefore, we performed primary tracheojejunal shunt operations for voice restoration with jejunum siphons using Nozaki's method (type 3).
In this procedure, after dividing a section of the jejunum into two segments, the reconstructed neopharyngoesophagus is anastomosed in a side-to-end fashion to the fabricated shunt using the other segment of the jejunum, as an “elephant nose shunt” so called because of its appearance. Voice restoration can be achieved in patients who undergo laryngopharyngoesophagectomy through these reconstructive procedures.
We performed this surgery for nine hypopharyngeal cancer patients after total pharyngo-laryngo-esophagectomy. Following placement of the shunt, no special care was required. Only one patient developed a severe aspiration. No leakage was seen and the swallowing function was preserved in all patients. Four of nine patients could speak well following these procedures. A vibratory source is created in the neoesophagus, above the elephant shunt. During speech production, narrowing of the inside and vibration of the jejunal mucosa can be observed using a laryngeal fiber scope. In order to study the acoustical characteristics of shunt speech, voice analysis was performed in patients with restored phonatory function using Computerized Speech Lab Model 4300 (KAY). Irregularities of pitch periods in the voice sample were measured using Jita (the pitch period) and Jitt (relative evaluation of the pitch) for the very short term (cycle-to-cycle), and PPQ (pitch period pertubation quotient) for the short term (cycle to-cycle with a smoothing factor of 5 periods). Irregularities of the peak-to-peak amplitude were measured using ShdB (evaluation in dB of the peak-to-peak amplitude) and Shim (relative evaluation of the peak-to-peak amplitude) for the very short term (cycle-to-cycle), and APQ (amplitude perturbation quotient) for the short term (cycle-to-cycle with a smoothing factor of 11 periods). The pertubation parameters of shunt speech are larger than normal ones not only in terms of the period but also in terms of the amplitude. These results are similar to those of laryngeal polyps, recurrent nerve palsy and esophageal speech.
Recovery of phonation using Nozaki's type 3 method with the elephant nose shunt appears promising for pharyngo-laryngo-esophagectomized patients.

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Nasal allergy is the most common type I allergic disease. During allergic reaction, chemical mediators may be released from residual cell, and thus, attract additional inflammatory cells. One mediator implicated in this response is bradykinin (BK), a potent proinflammatory nonapeptide. This study was designed to investigate the effects of BK on nasal mucosa, and to determine the role of angiotensin-converting enzyme (ACE) in BK-induced nasal responses.
BK nasal provocation (100μg) was studied in 7 normal volunteers and 7 patients with perennial allergic rhinitis. After provoking of BK response, nasal secretions and saline lavage fluids were collected for analysis of total protein (a protein secretion marker), albumin (a vascular permeability marker), and lysozyme (a serous cell marker). In addition, after administering of Captopril 50mg, a specific ACE inhibitor, the same protocol was performed.
In both groups, BK induced plasma exudation and serous gland secretion. Premedication with captopril did not alter BK-induced responses in normal individuals. In allergic patients, captopril enhanced BK-induced vascular permeability, but not glandular secretion. These results indicate that allergic subjects have nasal hyperresponsiveness to BK, and that ACE predominantly modulates the vascular permeability of allergic nasal mucosa. It seems likely that BK may contribute to the expression of nasal allergic symptoms, and that inhibition of ACE may lead to increased nasal responsiveness.

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To determine the systemic immune response to alpha-streptococci (Str. sanguis, Str. salivarius and Str. mitis) and β-streptococcus (Str. pyogenes T12) in patients with tonsil-related pustulosis palmaris et plantaris (PPP), we measured serum antibody levels to whole cell body antigens of Streptococcus (Str.) sanguis, Str. salivarius, Str. mitis or Str. pyogenes by enzyme-linked immunosorbent assay (ELISA). The serum IgG antibody levels to α-streptococci, Str. sanguis and Str. salivarius were significantly higher in patients with PPP (n=44) than in patients with recurrent tonsillitis (RT: n=25) and in healthy adults (n=17). Serum antibody IgG level to Str. pyogenes was not different among the 3 groups. The IgA antibody levels against any Streptococcus strain were not different among the 3 groups. The IgM antibody levels to Str. pyogenes were significantly higher in patients with RT than in patients with PPP.
In western blot analysis, the serum IgG antibodies against 25-27 kDa protein from whole cell body of Str. sanguis, Str. salivarius and Str. mitis were found more frequently in patients with PPP than in healty adults. However, the western blot profile in Str. pyogenes was not different between PPP and healthy adults. No significant difference was seen in the western blot profile of IgM or IgM antibodies to any streptococcal whole cell bodies. These data suggest that systemic hyper immune response to α-streptococci may be present in patients with tonsil-related PPP and the 25-27 kDa protein of the organism may be the target for this immunologic abnomality.

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Since glutathione is considered to be an important mediator of cancer cell resistance to cisplatin-based chemotherapy, we investigated glutathione in head and neck cancer by both laboratory and clinical investigations. Materials and Methods: Intracellular glutathione concentration was measured in 7 different cell lines that originated from head and neck cancer and was correlated to their IC₅₀ to cisplatin. Expression of γ-glutamyl cysteine (γ-GCS) mRNA was assessed by in situ hybridization and γ-glutamyl transpeptidase (GGT) expression was assessed with immnunohistochemistry of 56 biopsy specimens from 51 clinical cases. Both these enzymes are important for maintainance of intracellular glutathione concentration.
Results: Intracellular glutathione concentration was strongly correlated with cisplatin IC₅₀ (R²=0.814, P=0.0012), suggesting that glutathione plays a major role in cisplatin resistance in head and neck cancer. High γ-GCS expression was observed in 27 out of 47 specimens (57%), but the response rate to chemotherapy (63%) in the high expression group was not significantly different to the low expression group (P=0.20). High GGT expression was observed in 32 out of 53 specimens (60%), but the response rate in the high GGT group was not significantly different to that of the GGT group.
Conclusion: Although intracellular glutathione plays an important role in resistance to cisplatin in head and cancer cell lines, we failed to prove that two enzymes that contribute to the maintainance of intracellular glutathione concentration are predictive factors for the response to cisplatin-based chemotherapy. Since clinical cases are further complicated by interactions of the immune-system, involvement of a variety of genes related to oncogenesis, and accompanying drugs such as 5FU, it is very difficult to determine a single factor to predict the response to cisplatin. More precise analysis is necessary to determine how head and neck cancer resists cisplatin.

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Purpose: To estimate the influence of EGFR, p53, and angiogenesis to the survival of laryngeal cancer patients. Patients: Ninety-seven laryngeal cancer patients who received initial treatment at Gifu University Hospital from 1986 to 1996. Patients were classified as follows: T2, 51; T3, 35; T4, 13. Method: Using monoclonal antibodies against EGFR, p53, and factor VIII, respectively, immunohistochemical staining was performed on surgically obtained biopsy specimens. Univariate and multivariate regression analyses in accordance with Cox proportional hazards model were performed to adjust for the possible confounding effects and interactions of each factor. Three different end points, i. e. any death, cancer-related death, and cancer relapse (either local recurrence or distant metastasis), were used to evaluate overall survival, cause-specific survival, and relapse-free survival, respectively. Result: In univariate analysis, sex (P=0.0052), age (P=0.0038), T stage (P=0.0096) and N stage (P=0.0261) were significantly correlated with overall survival; sex (P=0.0076), T stage (P=0.0167) and factor VIII expression (P=0.0443) were related to cause-specific survival; T stage (P=0.0005) and EGFR expression (P=0.0103) were related to relapse-free survival. In multivariate analysis, supraglottis (P=0.0296) and factor VIII expression (P=0.0345) were significantly correlated with overall survival; supraglottis (P=0.0333), T stage (P=0.0179) and factor VIII expression (P=0.0134) were significantly correlated with cause-specific survival; T stage (P=0.0166), chemotherapy (P=0.0087) and EGFR expression (P=0.0016) were significantly correlated with relapse-free survival. Conclusion: The present study confirmed that multivariate analysis in accordance with the Cox proportional hazards model revealed that angiogenesis was an independent predictor of overall survival and cause-specific survival, and that EGFR expression was an independent predictor of relapse-free survival in patients with T2, T3 or T4 laryngeal cancer.

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To clarify the cytokine profile of tonsils, cytokine mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). The mRNA of interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-8, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were expressed on the whole tonsillar tissue of all 5 subjects with recurrent tonsillitis, obstructive sleep apnea syndrome caused by tonsillar hypertrophy or tonsillar focal infection. These cytokine mRNAs were detected in tonsillar mononuclear cells freshly isolated from all or 14 of 15 subjects. The CD4, CD8 and CD19-positive cells were purified using immunomagnetic beads. The CD4-positive cells expressed mRNA of IL-1β, IL-2, IL-4, IL-8, IFN-γ and TNF-α. The CD8-positivie cells expressed mRNA of IFN-γ and TNF-α. The CD19-positive cells expressed mRNA of IL-1β, IL-6, IL-8 and TNF-α. Quantitative measurement of PCR products in tonsillar mononuclear cells revealed that the IL-8 mRNA was expressed at a higher level than any other cytokine. A comparison among tonsillar diseases mentioned above revealed that the IL-1β and TNF-α mRNA were expressed at significantly higher levels in tonsillar mononuclear cells from patients with recurrent tonsillitis than in patients with obstructive sleep apnea syndrome caused by tonsillar hypertrophy. These data indicate that tonsils are active immunologic organs containing a wide variety of cytokines.

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Using two-color flow cytometry, we measured intracellular expression of interleukin-1 alpha (IL-1α), IL-2, IL-4, IL-6, IL-8, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in tonsillar mononuclear cells freshly isolated and stimulated by phorbol myristate acetate (PMA) and ionomycin. In freshly isolated tonsillar mononuclear cells, IL-1α was produced in 0.39% of CD3 cells, 0.48% of CD4 cells, 0.66% of CD19 and 11.2% of CD14 cells; TNF-α was found in 5.4% of CD14 cells. After 8-hour culture without any mitogens, IL-4, IL-8, TNF-α and IL-1α were detected in 2.1%, 0.8%, 0.55%, and 0.42% of tonsillar mononuclear cells, respectively. Flow cytometric detection of intracellular cytokines in tonsillar mononuclear cells stimulated with PMA and ionomycin revealed that CD3 cells produced IL-1α, IL-2, IL-4, IL-8, IFN-γ and TNF-α, and CD19 cells produced IL-1α, IL-6, IL-8 and TFN-α. In CD3 cells, the number of cells producing IL-2 and TNF-α were significantly higher than those expressing other cytokines; and the number of cells producing IFN-γ and IL-8 were significantly higher than those expressing IL-4 and IL-1α. In CD19 cells, the number of cells producing IL-6 and TNF-α were significantly higher than those of IL-8 and IL-1α; and the number of cells producing IL-8 was significantly higher than that of IL-1α. There was no difference in the number of CD3 and CD19 cells producing any cytokine between the adult recurrent tonsillitis group and adult obstructive sleep apnea syndrome group. However, the number of CD3 cells producing IL-2 or TNF-α and CD19 cells producing IL-1α, IL-6 or TNF-α were significantly lower in children than that of adults (p<0.05). These findings indicate that the cytokine production in tonsillar mononuclear cells is heterogenous according to the subset and activation, and that flow cytometric analysis of intracellular cytokines is a useful means to investigate the pathophysiological role of cytokines in the tonsils.

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Initiation of gait in relation to aging in normal adults and patients with equilibrium disorders were examined by a large force platform to analyze trace of the center of foot pressure while walking with eyes open.
Sixty normal adults and fifty-one patients with equilibrium disorders underwent examinations.
Normal adult subjects were divided into three groups by depending on the age; the young age group (20-39 years), the middle age group (40-64 years), and the aged group (over 65 years). The patients consisted of peripheral vestibular disorders and central equilibrium disorders. Analyzed items were step length (mm), step width (mm), cadence (steps/min), walking speed (m/min), step length/body height (step length ratio), step width/step length, and LG/LS.
The aged group showed characteristic gait pattern: marked shortness of step length, broadness of step width, slight decrease in cadence, slowness of walking speed and increased body sway during walking. Instable body sway was expressed by step width/step length and LG/LS. No statistically significant difference was obtained between the normal young and the normal middle age groups.
The patients with central equilibrium disorders showed shortness of step length in comparison with contemporary normal generations. Both patients with peripheral and central disorders revealed remarkable lower walking speed. In the patients with central disorders the walking was characterized with increase of body sway during their walking.

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