Posterior Displacement of Meniscal Ramp Lesion Is Observed on Flexed Knee Magnetic Resonance Imaging of Anterior Cruciate Ligament-Deficient Knees.

PURPOSE: To confirm whether posterior displacement of the detached meniscocapsular structure in ramp lesions could be observed on magnetic resonance imaging (MRI) in the flexed knee position and to clarify whether this displacement on MRI is related to greater anterior knee laxity. METHODS: This retrospective comparative trial study included 50 patients with anterior cruciate ligament injuries in whom attendant ramp lesions were observed on preoperative MRI. All patients underwent 3-T MRI at 120° of knee flexion preoperatively. The gap distance of the ramp lesion on sagittal slices was measured, and a distance greater than 1 mm was classified as gap positive. Additionally, joint effusion in the posteromedial recess was quantitatively evaluated by measuring the surface area of joint fluid. Prior to surgery, the side-to-side difference in anterior tibial translation (ATT) on stress radiographs at 20° of knee flexion was measured to evaluate anterior knee laxity. During anterior cruciate ligament reconstruction, the length of the ramp lesion was measured by a scale from the posteromedial portal. RESULTS: Of the 50 knees, 29 had ramp lesion gaps greater than 1 mm on MRI at knee flexion. The gap-positive group had a significantly greater side-to-side difference in ATT (9.6 ± 3.6 mm vs 5.0 ± 2.7 mm, P < .001) and significantly larger ramp lesion length (15.7 ± 4.9 mm vs 11.7 ± 3.9 mm, P = .002) than the gap-negative group. The gap-positive group also had a significantly greater amount of joint effusion than the gap-negative group (P < .001). CONCLUSIONS: Posterior displacement of the detached meniscocapsular structure in ramp lesions can be observed on MRI at knee flexion and is related to greater anterior knee laxity, lesion size, and joint effusion. LEVEL OF EVIDENCE: Level III, retrospective comparative trial.

Modifiable Lifestyle Factors and Cognitive Function in Older People: A Cross-Sectional Observational Study.

Background: The development of evidence-based interventions for delaying or preventing cognitive impairment is an important challenge. Most previous studies using self-report questionnaires face problems with reliability and consistency due to recall bias or misclassification among older people. Therefore, objective measurement of lifestyle components is needed to confirm the relationships between lifestyle factors and cognitive function. Aims: The current study examined the relationship between lifestyle factors collected with wearable sensors and cognitive function among community-dwelling older people using machine learning. Methods: In total, 855 participants (mean age: 73.8 years) wore a wristband sensor for 7.8 days on average every 3 months. Various lifestyle parameters were measured, including walking steps, conversation time, total sleep time (TST), sleep efficiency, time awake after sleep onset, awakening count, napping time, and heart rate. Random forest (RF) regression analysis was used to examine the relationships between total daily sensing data and Mini-Mental State Examination (MMSE) scores. Confounding factor analysis was conducted with models that were adjusted and unadjusted for demographic and vascular risk factors, and selected variables were assessed as risk and protective factors using partial dependence plots (PDPs). Results: Lifestyle data were collected for 31.3 ± 7.1 days per year using wristband sensors. RF regression analysis adjusted for age, gender, and education levels selected four variables, including number of walking steps, conversation time, TST, and heart rate. Moreover, walking steps, conversation time, and heart rate remained after RF regression analysis adjusted for demographic and vascular risk factors. Number of walking steps, conversation time, and heart rate were categorized as protective factors, whereas TST was categorized as a risk factor for cognitive function. Although PDPs of number of walking steps and heart rate revealed continuously increased MMSE scores, those of conversation time and TST and revealed that the tendency in the graph was reversed at the boundary of a particular threshold (321.1 min for conversation time, 434.1 min for TST). Conclusions: Lifestyle factors, such as physical activity, sleep, and social activity appear to be associated with cognitive function among older people. Physical activity and appropriate durations of sleep and conversation are important for cognitive function.

Magnetic Resonance Imaging Diagnosis of Medial Meniscal Ramp Lesions in Patients With Anterior Cruciate Ligament Injuries.

PURPOSE: To prospectively evaluate the sensitivity and specificity of magnetic resonance imaging (MRI) for diagnosing ramp lesions, to compare them between 1.5- and 3-T MRI, and to evaluate whether bone contusion of the posterior lip of the medial tibial plateau was associated with ramp lesions. METHODS: For 155 knees that underwent primary ACL reconstruction, we prospectively examined for ramp lesions and medial meniscal body tears on MRI. MRI diagnosis of ramp lesions required high signal irregularity of the capsular margin or separation in the meniscocapsular junction of the medial meniscus posterior horn on sagittal images. Bone contusion of the posterior lip of the medial tibial plateau was verified in 105 knees with MRI performed within 6 weeks after injury. All ramp lesions were identified by transcondylar observation during surgery. The sensitivity and specificity of MRI for ramp lesions and body tears were measured. Furthermore, we evaluated whether bone contusion of the medial tibial plateau was associated with ramp lesions. The χ-square test was used for statistical analysis. RESULTS: During surgery, ramp lesions were observed in 46 knees and medial meniscal body tears were seen in 35 knees. The sensitivity of MRI for ramp lesions was 71.7% and specificity was 90.5%. The sensitivity for ramp lesions was significantly lower than that for meniscal body tears (94.3%) (P = .01). The sensitivity of 3-T MRI (83.3%) was superior to that of 1.5-T MRI (67.6%), but not significantly different. The incidence of bone contusions was not significantly different among ramp lesions (38.5%), body tears (40.0%), or no tears (30.5%). CONCLUSIONS: The sensitivity of MRI for diagnosing ramp lesions was significantly lower than that for medial meniscal body tears. Bone contusion of the posterior lip of the medial tibial plateau on MRI was not associated with ramp lesions. LEVEL OF EVIDENCE: Level III, comparative trial.

Histopathologic investigations of the unphonated human child vocal fold mucosa.

OBJECTIVES: Vocal fold stellate cells (VFSCs) in the maculae flavae (MFe) located at both ends of the vocal fold mucosa are inferred to be involved in the metabolism of extracellular matrices. MFe are also considered to be an important structure in the growth and development of the human vocal fold mucosa. Tension caused by phonation (vocal fold vibration) is hypothesized to stimulate VFSCs to accelerate production of extracellular matrices. Human child vocal fold mucosae unphonated since birth were investigated histologically. STUDY DESIGN: Histologic analysis of human child vocal fold mucosa. METHODS: Vocal fold mucosae, which have remained unphonated since birth, of two children (7 and 12 years old) with cerebral palsy were investigated by light and electron microscopy and compared with normal subjects. RESULTS: Vocal fold mucosae and MFe were hypoplastic and rudimentary and did not have a vocal ligament, Reinke's space, or the layered structure. The lamina propria appeared as a uniform structure. Some VFSCs in the MFe showed degeneration and not many vesicles were present at the periphery of the cytoplasm. The VFSCs synthesized fewer extracellular matrices, such as fibrous protein and glycosaminoglycan. The VFSCs appeared to have decreased activity. CONCLUSION: Vocal fold vibration (phonation) after birth is an important factor in the growth and development of the human vocal fold mucosa.

Electrical stimulation prevents apoptosis in denervated skeletal muscle.

The purpose of this study was to investigate the hypothesis that electrical stimulation regulates the levels of gene expression related to apoptosis in denervated muscle and prevents muscle atrophy after denervation.Nineteen rats were used in this study. To denervate soleus muscle, sciatic nerve was resected under aseptic condition. Electrical stimulation with 4 mA rectangular pulses of 0.5 ms duration at 2 Hz lasting for 1 hour was delivered to lower limb including the soleus muscle using two surface electrodes. After the stimulation periods of 4 weeks, the levels of gene expression related to apoptosis were evaluated. Electrical stimulation increased valosin-containing protein (VCP) expression and decreased cleaved caspase-12 expression in denervated muscles. These results indicated that electrical stimulation to denervated muscle suppresses ER-specific apoptosis by enhancing VCP expression. We proposed that electrical stimulation would be a potential treatment for preventing atrophy of denervated skeletal muscles.

Carbachol injection into the pontine reticular formation depresses laryngeal muscle activities and airway reflexes in decerebrate cats.

To understand the role of cholinoceptive, medial pontine reticular formation (mPRF) neurons in the control of upper airway, pharyngolaryngeal reflexes, we measured activities of intrinsic laryngeal muscles (posterior cricoarytenoid, PCA; thyroarytenoid, TA), diaphragm (DIA), genioglossus (GG) and a neck muscle (trapezius) in unanesthetized, decerebrated, spontaneously breathing cats with and without mPRF carbachol injections. The ethimoidal nerve was electrically stimulated to evoke sneezing, and the superior laryngeal nerve to evoke the laryngeal reflex, swallowing, and coughing. Carbachol reduced the amplitudes of the spontaneous electromyographic activities in the neck, TA, PCA, GG, and DIA to 7%, 30%, 54%, 45% and 71% of control, respectively, reduced the respiratory rate to 53% without changes in expiratory CO(2) concentration; the magnitude of the laryngeal reflex in the TA muscle to 56%; increased its latency by 13%; and reduced the probability of stimulus-induced sneezing, swallowing, and coughing to less than 40%. These changes lasted more than 1h. These data demonstrate that important upper airway reflexes are suppressed by increasing cholinergic neurotransmission in the mPRF. Because acetylcholine release in the mPRF changes in accordance with sleep-wake cycles, the present findings are relevant to the control of upper airway reflexes during various vigilance states.

Expression and distribution of hyaluronic acid and CD44 in unphonated human vocal fold mucosa.

OBJECTIVES: The tension caused by phonation (vocal fold vibration) is hypothesized to stimulate vocal fold stellate cells (VFSCs) in the maculae flavae (MFe) to accelerate production of extracellular matrices. The distribution of hyaluronic acid (HA) and expression of CD44 (a cell surface receptor for HA) were examined in human vocal fold mucosae (VFMe) that had remained unphonated since birth. METHODS: Five specimens of VFMe (3 adults, 2 children) that had remained unphonated since birth were investigated with Alcian blue staining, hyaluronidase digestion, and immunohistochemistry for CD44. RESULTS: The VFMe containing MFe were hypoplastic and rudimentary. The VFMe did not have a vocal ligament, Reinke's space, or a layered structure, and the lamina propria appeared as a uniform structure. In the children, HA was distributed in the VFMe containing MFe. In the adults, HA had decreased in the VFMe containing MFe. In both groups, the VFSCs in the MFe and the fibroblasts in the lamina propria expressed little CD44. CONCLUSIONS: This study supports the hypothesis that the tensions caused by vocal fold vibration stimulate the VFSCs in the MFe to accelerate production of extracellular matrices and form the layered structure. Phonation after birth is one of the important factors in the growth and development of the human VFMe.

Evaluation of a deep brain stimulation electrode for laryngeal pacing.

OBJECTIVES: The purpose of the present study was to evaluate the suitability of a deep brain stimulation electrode for laryngeal pacing. Of interest was whether the smaller and more closely spaced channels could provide sufficient channel redundancy, controlled current distribution, and discrete activation of the posterior cricoarytenoid (PCA) muscle. METHODS: A study was conducted in dogs under differing states of PCA muscle innervation representing complete denervation to complete synkinetic reinnervation. In 3 animals, stimulated glottal opening was assessed in the innervated state and after chemical denervation by pancuronium bromide. In 3 additional dogs, the left side of the larynx was surgically denervated and compared to the innervated, right side to study an anatomic model of clinical paralysis. RESULTS: The thresholds were lower and the maximum level of abduction was greater for the innervated state. The stimulated glottal opening equaled that of a spontaneously breathing animal. Abductory responses were obtained across all channels in the array, demonstrating its anatomic and physiological compatibility for this application. In the denervated state, responses were only 20% of that of the innervated state with a pulse duration of 0.5 ms. The response could be enhanced to 40% and 60% by increasing the pulse duration to 1 and 2 ms. CONCLUSIONS: A deep brain stimulation electrode could effectively reanimate the PCA muscle to a normal level in a case of synkinetic reinnervation and to as much as 60% of the normal level in a case of complete denervation.

Histopathologic investigations of the unphonated human vocal fold mucosa.

CONCLUSION: Vocal fold vibration (phonation) after birth is one of the important factors in the growth and development of the human vocal fold mucosa. OBJECTIVES: Stellate cells in the maculae flavae located at both ends of the vocal fold mucosa are inferred to be involved in the metabolism of extracellular matrices. Maculae flavae are also considered to be an important structure in the growth and development of the human vocal fold mucosa. Tension caused by phonation (vocal fold vibration) is hypothesized to stimulate stellate cells to accelerate production of extracellular matrices. Vocal fold mucosae unphonated since birth were investigated histologically. SUBJECTS AND METHODS: Vocal fold mucosae, which were unphonated since birth, of three younger adults (17, 24, 28 years old) were investigated by light and electron microscopy. RESULTS: Vocal fold mucosae were hypoplastic and rudimentary and did not have a vocal ligament, Reinke's space or a layered structure. The lamina propria appeared as a uniform structure. Some stellate cells in the maculae flavae showed degeneration. Not many vesicles were present at the periphery of the cytoplasm. The stellate cells synthesized fewer extracellular matrices, such as fibrous protein and glycosaminoglycan. Cytoplasmic processes of the stellate cells were short and shrinking. The stellate cells appeared to have decreased activity.

Inducible nitric oxide synthase expression in various laryngeal lesions in relation to carcinogenesis, angiogenesis, and patients' prognosis.

CONCLUSIONS: The inducible nitric oxide synthase (iNOS) expression leading to vascular endothelial growth factor (VEGF) overexpression may be useful as a factor for predicting recurrence after initial treatment and prognosis in laryngeal squamous cell carcinoma (SCC). OBJECTIVE: We analyzed expression of iNOS, p53, and VEGF in various laryngeal lesions. MATERIALS AND METHODS: The study samples consisted of 63 SCC, 20 dysplasia, 7 polyp, and 5 normal epithelium of the larynx. The expression of iNOS, p53, and VEGF was identified by immunohistological methods. RESULTS: No positive immunostaining for iNOS, p53, and VEGF was observed in normal epithelium and polyps. In contrast, with the progression from mild/moderate dysplasia to severe dysplasia to carcinoma, their expression levels increased. In dysplasia, there was a significant positive correlation among expression of iNOS, p53, and VEGF. In SCC, iNOS expression correlated with VEGF overexpression and microvessel density, but not with p53 overexpression. In SCC, the expression of iNOS and VEGF significantly increased in patients who developed local recurrence and/or metastases after initial treatments. Kaplan-Meier analysis showed that disease-free survival was significantly shorter in patients with iNOS or VEGF expression. Multivariate analysis showed expression of iNOS and VEGF as independent indicators for poor disease-free survival.

Overexpression of small ubiquitin-related modifier-1 and sumoylated Mdm2 in oral squamous cell carcinoma: possible involvement in tumor proliferation and prognosis.

The purpose of this research was to identify a molecular clue to tumor proliferation in oral squamous cell carcinoma (SCC) and to test the value as a predictive marker for prognosis. In cDNA array analysis, small ubiquitin-related modifier-1 (SUMO-1) was expressed at much higher levels in oral SCC tissue and oral SCC cell lines than normal oral epithelium. The result was confirmed by RT-PCR analysis and Western blot analysis. Transfection of the anti-SUMO-1 antisense oligonucleotide to oral SCC cells significantly reduced proliferation of the cells. Immunoprecipitation and Western blot analyses revealed that the oncoprotein Mdm2 was present predominantly as a form of SUMO-1 congestion (sumoylation) rather than as a non-sumoylated form in both oral SCC tissues and cell lines. Immunohistological analysis revealed that patients who showed coexpression of SUMO-1 and Mdm2 experienced more frequently local recurrence after initial treatments. Multivariate analysis confirmed that the dual-high expression of SUMO-1 and Mdm2 was an independent factor for local failure. These result suggested that overexpression of Mdm2 caused by overexpression of SUMO-1 may be involved in tumor aggressiveness even in patients with early stage oral SCC. SUMO-1 may be useful as a novel target for therapy in oral SCC as well as a clinical indicator for tumor recurrence together with Mdm2.

[Therapeutic effects and prognostic factors in tonsillectomy patients with IgA nephropathy].

INTRODUCTION: Because upper respiratory tract infections, particularly tonsillitis, often precede IgA nephropathy (IgAN), IgAN is now recognized as a tonsil-related disease, and reports have shown that tonsillectomy is effective in preventing disease progression in IgAN patients. IgA may thus play an important role in IgAN pathogenesis and development. B cell activation factor belonging to the TNF family (BAFF) is expressed by monocytes, macrophages, and dendritic cells, and may be the mechanism by which macrophages and dendritic cells directly regulate human B-cell activation. BAFF acts as a potent B-cell growth factor and costimulator of immunoglobulin production, including IgA. We studied therapeutic effects and serum BAFF levels as prognostic factors. PATIENTS AND METHODS: Subjects were 41 patients undergoing tonsillectomy and followed up for at least 1 year. Serum samples were obtained from 38 with IgAN and 29 with recurrent tonsillitis as a properative control groups. The remission group consisted of patients with normal renal function without hematuria and proteinuria. Serum BAFF levels were measured by ELISA kits at our laboratory. RESULTS: Overall remission was 39.0%. The disappearance of hematuria increased for long-term follow-up groups, but proteinuria was unchanged. Serum BAFF levels among the two groups did not differ significantly. Among IgAN patients, higher BAFF levels were associated with higher serum IgA/C3 levels. The correlation was weak (p =0.026, r = 0.407). Using 3.2 ng / ml as a cut off point, we compared cumulative improvement in those with high pretreatment BAFF levels to those with low pretreatment levels. Those with high pretreatment BAFF levels had inferior cumulative improvement in hematuria. CONCLUSION: Tonsillectomy was effective in improving hematuria. BAFF appears to be a key factor in tonsillectomy among [gAN patients.

Fos expression in the brainstem nuclei evoked by nasal air-jet stimulation in rats.

BACKGROUND: Noxious stimulation of the nasal mucosa may induce protective reflexes in the upper airway in rats. Previously, we have reported that nasal air-jet stimulation increases the activities of the laryngeal muscles in decerebrate cats; however, the neuronal mechanism of this phenomenon still is not clarified. METHODS: After the application of nasal air-jet stimulation for 2 hours, we investigated the distribution of Fos-positive cells (FPCs) throughout the medulla compared with sham-operated rats using Fos immunoreactivity. RESULTS: FPCs in the spinal trigeminal nucleus, the parvocellular reticular nucleus, and the nucleus of the solitary tract were more frequent than the sham-operated rats. CONCLUSION: These results suggest that the afferents induced by air-jet stimulation were conveyed to these FPCs and that some of these cells might participate in the augmentation of laryngeal muscle activities during nasal air-jet stimulation.

[Analysis of risk factors for deficits in the quality of life in allergic rhinitis patients].

To assess the possible negative aspects in the quality of life (QOL) of patients with allergic rhinitis based on the factors such as the symptoms and examination of the nasal cavity, we examined QOL deficits using the Japanese Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ No1). Thirteen hundred seventy eight allergic rhinitis patients who visited clinics or hospitals between April and July 2003 were assessed for clinical symptoms, had the examination of their nasal cavity graded and answered QOL questionnaires. Gender, period of the disease, antigen, clinical symptoms and the results of the nasal cavity examination were evaluated and analyzed to reveal risk factors associated with negative QOL factors. These negative QOL factors tended to be more severe in women than in men, and more severe in pollen allergy than in house dust mite allergy. There was no association of the period of the disease with negative QOL factors. It was revealed that nasal discharge was the strongest risk factor for problems in usual daily activities, outdoor activities and social functioning in six QOL domains, and nasal congestion was the major factor associated with sleep problems, general physical problems and emotional function. Nasal congestion was also the strongest risk factor in the total score of the QOL questionnaire and the overall face scale of the patients. In the nasal cavity examination, the amount of aqueous secretion was the strongest risk factor for all items associated with negative QOL factors. According to the risk factors we identified, we can treat allergic rhinitis patients taking their QOL into consideration.

Loss of p21 expression is associated with p53 mutations and increased cell proliferation and p27 expression is associated with apoptosis in maxillary sinus squamous cell carcinoma.

CONCLUSIONS: Loss of p21 expression dependent on the p53 mutation may be associated with higher tumor cell proliferation, and low p27 expression may be associated with decreased spontaneous apoptosis, resulting in poorer prognosis in patients with maxillary sinus squamous cell carcinoma (SCC). OBJECTIVE: We have previously reported that p53 mutations and decreased spontaneous apoptosis were associated with poor prognosis in maxillary sinus SCC. However, whether p21 and p27 expression and cell proliferation correlate with either p53 status, spontaneous apoptosis or prognosis in maxillary sinus SCC has not been evaluated. MATERIAL AND METHODS: Seventy patients with maxillary sinus SCC were analyzed. Tumor biopsy specimens were examined for p21 and p27 expression using an immunohistological method. The percentage of proliferating cells labeled by anti-Ki-67 mAb was expressed as the Ki-67 index (KI). RESULTS: Loss of p21 expression correlated with p53 mutations (p=0.0072). The KIs in patients without p21 expression and with p53 mutations were significantly higher than those in patients with p21 expression (p=0.0119) and those without p53 mutations (p=0.0048). Patients with p27 expression showed a significantly higher apoptotic index than those without (p=0.0012). Kaplan-Meier analysis showed that p21 expression was closely associated with prolonged disease-free survival in the group with a normal p53 status (p=0.0472). Multivariate analysis identified high KI as an independent prognostic marker (p=0.047).

Cochlear implantation in an adult patient with auditory neuropathy.

We present a case report of effective cochlear implantation for an adult patient with auditory neuropathy. A 34-year-old man developed bilateral hearing loss at approximately 10 years of age. His speech discrimination score was very severe despite only moderate sensorineural hearing loss. Absence of auditory brainstem responses (ABR) and preservation of distortion product otoacoustic emissions (DPOAE) were confirmed by our audiological examinations. After cochlear implantation, good responses for electrically evoked compound action potential (EAP) and electrically evoked ABR (EABR) were observed. Postoperatively, his audiological performance was significantly improved. We conclude that cochlear implantation can be a valid option for patients with auditory neuropathy.

Expression of CXCR4 and its down-regulation by IFN-gamma in head and neck squamous cell carcinoma.

PURPOSE: The functional expression of CXCR4, which plays roles in cell migration and proliferation in response to its unique ligand stromal cell-derived factor-1 (SDF-1), has been reported in variety of carcinomas. However, CXCR4 expression and its functional role in head and neck squamous cell carcinomas (HNSCC) remain unclear. In this study, we investigated CXCR4 expression and analyzed its functions in HNSCC cell lines. We also attempted to regulate CXCR4 expression using cytokines, such as interleukin-1beta, tumor necrosis factor-alpha, and IFN-gamma. Finally, we investigated correlation between CXCR4 expression and clinical features in patients with HNSCC. EXPERIMENTAL DESIGN: Six HNSCC cell lines were used in this study. Reverse transcription-PCR and flow cytometry analysis were shown for CXCR4 expressions with or without stimulations of cytokines. SDF-1-mediated cell migration was assayed in Matrigel-coated chemotaxis chamber. The SDF-1-mediated cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The SDF-1-mediated signaling pathways were analyzed by Western blot analysis. Biopsy specimens from 56 patients with HNSCC were used for immunohistologic analysis. RESULTS: The significant CXCR4 expression was found in HSQ-89, IMC-3, and Nakamura cells. The SDF-1-mediated cell migration and proliferation were observed in CXCR4-positive cells. SDF-1 also promoted rapid phosphorylation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways in CXCR4-positive cells. The SDF-1-mediated cell migration and proliferation of CXCR4-positive cells were inhibited by neutralization of CXCR4. Among three cytokines tested, IFN-gamma significantly reduced CXCR4 expression and SDF-1-induced cell migration and proliferation of CXCR4-positive cells. Immunohistologic analysis revealed that patients with advanced neck status and patients who developed distant metastases showed significantly higher CXCR4 expression, and the cause-specific survival of patients with CXCR4-expression was significantly shorter. Furthermore, multivariate analysis confirmed that CXCR4 positive was the independent factor for cause-specific death. CONCLUSION: Our results may provide an insight into future therapeutic agent that inhibits tumor metastasis and progression via down-regulating CXCR4 expression in patients with HNSCC.

Effects of injecting GABAergic agents into the medullary reticular formation upon swallowing induced by the superior laryngeal nerve stimulation in decerebrate cats.

The purpose of this study was to elucidate the role of the GABAergic system in the medullary reticular formation (MRF) in the control of swallowing. In acutely decerebrated cats (n = 12), swallowing was induced by electrical stimulation (0.3-6 V at 10-20 Hz for 10-20 s every minute) applied to the superior laryngeal nerve (SLN). The stimulus intensity was adjusted so that swallowing was induced two or four times during the period of the stimulation. Bicuculline, a GABA(A) receptor antagonist, was then injected (0.10-0.15 microl, 5 mM) into the MRF through a stereotaxically placed glass micropipette. In a total of 62 injections, 19 injections (30.6%) increased the frequency of SLN-induced swallowing when it was injected into the lateral part of the MRF corresponding to the nucleus reticularis parvocellularis (NRPv). In eight of the effective injections (42.1%) which increased the frequency of SLN-induced swallowing, SLN stimulation also induced coughing. With two injections, stimulation of the SLN-induced coughing but not facilitation of swallowing. On the other hand, an injection of 0.10-0.15 microl of 5 mM muscimol, a GABA(A) receptor agonist, into the NRPv decreased the frequency of SLN-induced swallowing. These results suggest that the NRPv neurons which are responsible for evoking swallowing are under the tonic inhibitory control of the GABAergic system.

Intestinal gamma delta T cells develop in mice lacking thymus, all lymph nodes, Peyer's patches, and isolated lymphoid follicles.

Through analysis of athymic (nu/nu) mice carrying a transgenic gene encoding GFP instead of RAG-2 product, it has recently been reported that, in the absence of thymopoiesis, mesenteric lymph nodes and Peyer's patches (PP) but not gut cryptopatches are pivotal birthplace of mature T cells such as the thymus-independent intestinal intraepithelial T cells (IEL). To explore and evaluate this important issue, we generated nu/nu mice lacking all lymph nodes (LN) and PP by administration of lymphotoxin-beta receptor-Ig and TNF receptor 55-Ig fusion proteins into the timed pregnant nu/+ mice that had been mated with male nu/nu mice (nu/nu LNP- mice). We also generated nu/nu aly/aly (aly, alymphoplasia) double-mutant mice that inherently lacked all LN, PP, and isolated lymphoid follicles. Although gammadelta-IEL were slightly smaller in number than those in nu/nu mice, substantial colonization of gammadelta-IEL was found to take place in the intestinal epithelia of nu/nu LNP- and nu/nu aly/aly mice. Notably, the population size of a major CD8alphaalpha+ gammadelta-IEL subset was maintained, the use of TCR-gamma-chain variable gene segments by these gammadelta-IEL was unaltered, and the development of cryptopatches remained intact in these nu/nu LNP- and nu/nu aly/aly mice. These findings indicate that all LN, including mesenteric LN, PP, and isolated lymphoid follicles, are not an absolute requirement for the development of gammadelta-IEL in athymic nu/nu mice.

Functional electrical stimulation of laryngeal adductor muscle restores mobility of vocal fold and improves voice sounds in cats with unilateral laryngeal paralysis.

Functional electrical stimulation (FES) has been proposed as a potential treatment for restoring motor functions of denervated motor systems. We investigated whether FES of paralyzed laryngeal adductor muscles could restore adduction to the vocal folds. In addition, we studied the effect of stimulated vocal fold adduction on the intensity and overall quality of voice production. We recorded movement of the vocal fold, electromyographic activity of muscles recruited for vocalization, and sound production in unanesthetized decerebrate cats during FES of the paralyzed thyroarytenoid (TA) muscle. FES of the paralyzed TA muscle induced adduction of the vocal fold. Appropriate stimulus parameters for induction was 1.5-3.0 mA intensity pulses delivered at a frequency of 30-50 pulses per second (pps). FES of the paralyzed TA muscle prolonged phonation time and increased intensity of voice sounds during vocalization induced by electrical stimulation (0.2 ms, 20-50 microA, 50 pps) of the periaqueductal gray (PAG). The quality of voice sounds evaluated by sound spectrography was shown to improve during vocalization with FES. We conclude that FES of the paralyzed laryngeal adductor muscle was effective in restoring adduction of the vocal fold and improving voice sounds impaired by unilateral laryngeal paralysis.