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Biomedical subjects

M Sakagami

Publications and source records attributed to M Sakagami.

At least 19 recordsLinked to original sources
PubMed2001

Enhanced pulmonary absorption following aerosol administration of mucoadhesive powder microspheres.

Mucoadhesive, hydroxypropylcellulose (HPC) microspheres were prepared for powder inhalation and their feasibility for enhancing pulmonary drug absorption was investigated. Respirable-sized microspheres, incorporating crystalline or amorphous fluorescein (used as a model drug), were prepared by spray-drying aqueous or ethanol HPC systems, respectively. These were prepared from a variety of HPC grades (SL, L, M and H types) in different fluorescein-HPC ratios (1:1-1:10). The microspheres were administered to tracheally-intubated guinea pigs as powder aerosols and their fluorescein pharmacokinetics studied, and compared to those for pure crystalline fluorescein ('control'). All microspheres were prepared and aerosolized within a MMAD range of 1.3-2.6 microm (GSD< or =2.1). Fluorescein's dissolution was increased in the amorphous form by 6.5-fold when compared to the crystalline material (83.9-87.2 vs. 13.5 microg/ml, respectively). Poor dissolution for the 'control' crystalline fluorescein appeared to be rate-determined, which showed bi-phasic absorption profiles (T(max)=60 min), simultaneously competing with mucociliary clearance out of the lower airways. While the crystalline/HPC microspheres prolonged absorption, the amorphous fluorescein/HPC microspheres showed rapid absorption with T(max)=0 min (immediately after the administration had terminated). This was explained by enhanced fluorescein dissolution and was consistently observed irrespective of the fluorescein-HPC ratio or HPC grade. However, the microspheres with the least viscous HPC-SL and the lowest fluorescein-HPC ratio (1:1) failed to enhance bioavailability, presumably because the mucociliary clearance was undisturbed. In contrast, the microspheres with the highly viscous HPC-H with ratios > or = 1:4 successfully enhanced absorption, achieving 88.0% bioavailability by virtue of HPC increasing the dissolution and retarding the mucociliary clearance.

Absorption↗
PubMed2001

A code for behavioral inhibition on the basis of color, but not motion, in ventrolateral prefrontal cortex of macaque monkey.

To examine the neural mechanism for behavioral inhibition, we recorded single-cell activity in macaque ventrolateral prefrontal cortex, which is known to receive visual information directly from the inferotemporal cortex. In response to a moving random pattern of colored dots, monkeys had to make a go or no-go response. In the color condition, green indicated go, whereas red indicated no-go, regardless of the motion direction; in the motion condition, upward indicated go, whereas downward indicated no-go, regardless of the color. Approximately one-half of the visual cells were go/no-go differential. A majority of these cells (64/73) showed differential activity only in the color condition; they responded nondifferentially in the motion condition, although the same set of stimuli was used. We classified these cells as "go type" (n = 41) and "no-go type" (n = 23) depending on the color for which they showed a stronger response. Interestingly, in both types of cells, the differential effects were observed only for the no-go-indicating color. Compared with the nondifferential responses in the motion condition, go-type cells in the color condition showed weaker responses to the no-go-indicating color, whereas their responses to the go-indicating color were similar; in contrast, no-go type cells showed stronger responses to the no-go-indicating color, whereas their responses to the go-indicating color were similar. Both types of cells did not show any activity change during the actual execution of the go or no-go response. These results suggest that neurons in ventrolateral prefrontal cortex contribute to stimulus-response association in complex task situations by inhibiting behavioral responses on the basis of visual information from the ventral stream.

Animals↗
PubMed2001

Change in gene expression in facial nerve nuclei and the effect of superoxide dismutase in a rat model of ischemic facial paralysis.

Peripheral nerve injury induces changes in gene expressions of a variety of neuroactive substances in cell somata, which may have roles in the adaptive response to the injury, neuronal survival, growth and regeneration. In this study, we designed a rat model of ischemic peripheral facial paralysis with a selective embolization technique, and observed mRNA expression of calcitonin gene-related peptide (CGRP), c-jun, and growth associated protein (GAP)-43 in facial nerve nuclei using in situ hybridization histochemistry. The rats were demonstrated to have a transient facial paralysis consistently, and thus this method was regarded as a model of minor peripheral nerve injury. The mRNA of CGRP, c-jun and GAP-43 showed a distinct pattern of induction and time course of increase after the ischemic nerve injury. The results suggest that the small injury to the peripheral nerve was able to induce changes in mRNA expression in the cell body of motoneurons. We also investigated the protective effect of superoxide dismutase (SOD), which is a free radical-scavenging enzyme involved in cellular antioxidant defenses. The SOD treatment clearly alleviated the behavioral impairment and decreased the CGRP mRNA expression at 3rd day after injury. These data suggest that a free radical generated by the ischemia may be partially responsible for ischemic nerve damage and the change in gene expression in motoneurons.

Animals↗
PubMed2001

Younger patients have a higher rate of recovery of taste function after middle ear surgery.

BACKGROUND: Although the chorda tympani nerve (CTN) is frequently damaged during tympanoplasty, little attention has been given to the patients' symptoms and taste function. OBJECTIVE: To investigate patients' symptoms and the functional recovery of taste after surgery using electrogustometry (EGM). DESIGN: Prospective study. PATIENTS: Analysis of 163 ears of 156 patients who underwent middle ear surgery from April 1997 through December 1999. There were 18 ears with noninflammatory diseases, 80 with chronic otitis media, and 65 with cholesteatoma. The patients' taste functions were examined 2 days before surgery and 2 weeks and 6 months after surgery. MAIN OUTCOME MEASURES: The taste disturbance before and after middle ear surgery and the relationship between age and the recovery rate of CTN function. RESULTS: Two weeks after surgery, the mean EGM threshold was elevated in all groups regardless of preservation or section of the CTN. Numbness in the tongue and taste disturbance were more frequently found in patients with preservation of CTN than in those with section of the CTN (P =.008 and P =.001, respectively). In patients with preservation of the CTN, 6 months after surgery, the recovery rate of EGM threshold was 83% in those aged 20 years or younger (P =.008 compared with the 2 older groups), 53% in the those aged 21 to 40 years, and 44% in those aged 41 to 60 years. CONCLUSION: Age is an important factor for recovery of taste function after middle ear surgery, which is useful information when explaining complications to patients.

Adolescent↗
PubMed2001

Tympanoplasty with and without mastoidectomy for non-cholesteatomatous chronic otitis media.

OBJECTIVES: Cases of non-cholesteatomatous chronic otits media (COM) were reviewed to determine whether mastoidectomy is helpful when combined with tympanoplasty for these conditions. STUDY DESIGN: A retrospective analysis of 251 ears with non-cholesteatomatous COM operated on by one surgeon (Y.M.) in an 11-year period was conducted. METHODS: Patients in group A (n = 147) were treated by tympanoplasty with mastoidectomy. Patients in group B (n = 104) were operated on without mastoidectomy. RESULTS: Graft success rates were 90.5% in group A and 93.3% in group B. There was no statistically significant difference. Graft success rates of discharging ears were 90.0% in group A and 85.7% in group B. Graft success rates of dry ears were 90.7% in group A and 94.4% in group B. There was no statistically significant difference between discharging ears and dry ears. The rates of the postoperative air-bone gap within 20dB were 81.6% in group A and 90.4% in group B, without a statistically significant difference. CONCLUSIONS: Mastoidectomy is not helpful in tympanoplasty for non-cholesteatomatous COM, even if the ear is discharging.

Bone Conduction↗
PubMed2001

Expression of osteopontin by exudate macrophages in inflammatory tissues of the middle ear: a possible association with development of tympanosclerosis.

Tympanosclerosis is a condition leading to a calcification process in the middle ear, and often develops after chronic inflammation of the middle ear. Since osteopontin (OPN) has been shown to participate in the pathological calcification, we here investigated whether OPN is involved in the process of calcification in tympanosclerosis. The tympanic membrane and middle ear mucosa, obtained from patients of tympanosclerosis and chronic otitis media, were histologically classified depending on the calcification degree. In hyalinized tissues with macroscopic calcification and fibrous tissues with microscopic calcification, OPN was immunohistochemically found in the calcification sites. In inflammatory tissues with microscopic calcification, OPN was also found in the calcifying foci, and many OPN mRNA-expressing cells, determined by in situ hybridization, located around their foci. Moreover, immunohistochemical double staining of OPN and CD68 showed that the OPN-expressing cells were CD68-positive, indicating these cells were macrophages. In inflammatory tissues without calcification, immunohistochemistry of CD68 and in situ hybridization of OPN mRNA revealed that most OPN mRNA-expressing cells were CD68-positive. The expression of OPN mRNA in inflammatory tissues was also shown by reverse transcriptase polymerase chain reaction. These results suggest that OPN secreted by exudate macrophages might be an important regulator in the calcification of tympanosclerosis.

Adolescent↗
PubMed2001

Non-Hodgkin's malignant lymphoma of the sinonasal tract--treatment outcome for 53 patients according to REAL classification.

OBJECTIVE: Although the Working Formulation is commonly used to classify NHL in Japan, it has been recognized as imperfect for primary extranodal lymphoma, especially for patients with sinonasal disease because of their histological characteristics. The present study investigated the clinical characteristics and the prognosis of sinonasal lymphomas according to REAL classification. METHODS: Fifty-three patients with non-Hodgkin's malignant lymphoma (NHL) of the sinonasal tract were treated between 1981 and 1997. The age at clinical presentation was from 10 to 84 years (mean, 52.4 years). According to the Ann Arbor system, there were 30 patients with Stage IE, 13 with Stage IIE, 4 with Stage IIIE, and 6 with Stage IVE lymphomas. Twenty-two patients (41.5%) had B symptoms. The primary sites were the nasal cavity (67.8%), maxillary sinus (20.8%), ethmoidal sinus (9.4%), and frontal sinus (1.9%). The survival data was calculated by Kaplan-Meier method. Statistical analysis was performed with a generalized Wilcoxon method. RESULTS: All of the lymphomas showed a diffuse growth pattern. Based on the origin of the tumor cells, the authors classified NHL of the sinonasal tract into five groups with the REAL classification of Japan: diffuse large B-cell lymphoma (22.6%), peripheral T-cell lymphomas (15.1%), angiocentric lymphoma (35.9%), other lymphomas and unclassified types. Of 53 patients, 39 (73.6%) received chemotherapy and radiotherapy, eight patients received chemotherapy alone, and four patients received radiotherapy alone. The cumulative 5-year survival rates were 28.5% for all of the types, 55.0% for diffuse large B-cell lymphoma, 33.3% for peripheral T-cell lymphoma, and 19.7% for angiocentric lymphoma. Results suggest that conventional combined treatment (CHOP chemotherapy+radiotherapy) is ineffective for NHL of the sinonasal tract, and especially so for NHL in the nasal cavity, NHL with tumor cells with positive T-cell markers, NHL further than Stage IIE and NHL with B symptoms. CONCLUSION: (1) In light of this ineffectiveness, new therapies must be developed to improve patient outcome instead of the conventional combined treatment; (2) REAL classification is clear and useful for sinonasal lymphomas in Japan.

Adolescent↗
PubMed2001

A case of early-onset benign occipital seizure susceptibility syndrome: decreased cerebral blood flow in the occipital region detected by interictal single photon emission computed tomography, corresponding to the epileptogenic focus.

Early-onset benign childhood occipital seizure susceptibility syndrome (EBOSS) recently described by Panayiotopoulos, is an early-onset variant of benign childhood epilepsy with occipital paroxysms. EBOSS is characterized by partial seizures that are predominantly manifested at night and associated with deviation of the eyes, vomiting and impairment of consciousness, but without ictal visual symptoms or postictal headache. The clinical features of our case were consistent with those of EBOSS, and we therefore diagnosed the patient as having a typical form of EBOSS. Neuroimaging by CT, MRI and MR angiography did not reveal a focal lesion. Interictal single photon emission computed tomography (SPECT) revealed decreased cerebral blood flow in the right occipital region corresponding to the epileptogenic focus shown on EEG. It remains unclear whether our finding on SPECT reflects secondary hypoperfusion due to minor morphological abnormality or immediate functional hypoperfusion. No reference to SPECT in a case of EBOSS has appeared in the literature to date. This report provides a better understanding of benign childhood epileptic syndromes with occipital spikes.

Cerebrovascular Circulation↗
PubMed2001

Evaluation of carboxymethylpullulan as a novel carrier for targeting immune tissues.

PURPOSE: To demonstrate the potential of carboxymethylpullulan (CMPul) as a carrier for targeting immune tissues, and to find whether immune tissues could be set as the target of an immunosuppressant to treat autoimmune diseases. METHODS: The biodistribution of CMPul was investigated to evaluate its potency as a carrier for targeting immune tissues. Furthermore, an immunosuppressant-CMPul conjugate was prepared and its suppressive effect on rat adjuvant arthritis was examined. RESULTS: The disappearance rate of 3H-labeled CMPul from the blood circulation was much slower than that of 3H-labeled pullulan (Pul) after intravenous injection to normal rats. The concentration of 3H-labeled CMPul in the spleen and lymph nodes was much higher than that of 3H-labeled Pul at 24 hours after the injection, whereas the concentration of 3H-labeled CMPul in the liver was significantly lower than that of 3H-labeled Pul. A similar targeting property of 3H-labeled CMPul for these immune tissues was observed in arthritic rats. A conjugate composed of a novel immunosuppressant PA-48153C and CMPul showed a suppressive effect on rat adjuvant arthritis judging from a reduction of the arthritic index and spleen weight and an increase of body weight. CONCLUSIONS: CMPul is expected to be a promising carrier for targeting immune tissues with an immunosuppressant to enable treatment of autoimmune diseases.

Animals↗
PubMed2001

Supercharged gastric tube pull-up procedure for total esophageal reconstruction.

Total esophageal reconstruction using a gastric tube is complicated because it sometimes causes postoperative complications such as anastomotic leakage, stenosis, or fistula formation resulting from insufficient blood flow at the distal end. To overcome this problem, during the past 5 years the authors performed seven additional microvascular anastomoses using the short gastric vessels of the gastric tube. No postoperative complications occurred except partial tracheal necrosis in 1 patient. Postoperative radiographic examination showed no reflux or stasis in all patients, and no evidence of necrosis at the anastomotic site of the pulled-up gastric tube was observed by postoperative endoscopy. This technique reduces risk and may contribute to the successful reconstruction of the digestive tract after total esophagectomy.

Aged↗
PubMed2001

Argon plasma surgery for the inferior turbinate of patients with perennial nasal allergy.

OBJECTIVES: Argon plasma coagulation (APC) is a new electrosurgical modality. The advantages of APC are coagulating of the target tissue without contact and the creation of uniformly deep devitalized and coagulated zones. The objectives of the present study were to determine the clinical effects of APC for the inferior turbinate of patients with nasal allergy and to clarify the histological changes in the mucosa after APC. STUDY DESIGN: In a prospective study, 95 patients with perennial nasal allergy were treated with APC. Nasal symptoms and intranasal findings were evaluated preoperatively and 1, 3, and 6 months, and 1 year after the APC. Mucosal specimens from the turbinates were examined under light and electron microscopy. RESULTS: Nasal stuffiness was improved in 77 of 79 (97.5%) patients after 1 month, in 50 of 51 (98.0%) patients after 3 months, in 20 of 23 (87.0%) patients after 6 months, and in 9 of 12 (75.0%) patients at 1 year after the APC. Rhinorrhea was improved in 46 of 75 (61.3%) patients after 1 month, in 40 of 51 (78.4%) patients after 3 months, in 16 of 21 (76.2%) patients after 6 months, and in 6 of 10 (60.0%) patients at 1 year after the APC. The sneezing was improved in 32 of 54 (59.3%) patients after 1 month, in 21 of 35 (60.0%) patients after 3 months, in 10 of 14 (71.4%) patients after 6 months, and in 6 of 8 (75.0%) patients at 1 year after the APC. In the intranasal findings, congestion of the inferior turbinate improved in 75 of 76 (98.7%) patients after 1 month, in 49 of 52 (94.2%) patients after 3 months, in 20 of 23 (87.0%) patients after 6 months, and in 7 of 11 (63.6%) patients at 1 year after the APC. The nasal discharge was reduced in 40 of 75 (53.3%) patients after 1 month, in 32 of 52 (61.5%) patients after 3 months, in 15 of 22 (68.2%) patients after 6 months, and in 5 of 11 (45.5%) patients at 1 year after the APC. No patients needed nasal packing after the APC. CONCLUSIONS: This is the first report on the clinical effects of turbinate surgery for nasal allergy using APC. APC was useful fer turbinate surgery of nasal allergy, especially for nasal stuffiness and congestion of the turbinate.

Adolescent↗
PubMed2001

Responses to task-irrelevant visual features by primate prefrontal neurons.

The primate brain is equipped with prefrontal circuits for interpreting visual information, but how these circuits deal with competing stimulus-response (S-R) associations remains unknown. Here we show different types of responses to task-irrelevant visual features in three functionally dissociated groups of primate prefrontal neurons. Two Japanese macaques participated in a go/no-go task in which they had to discriminate either the color or the motion direction of a visual target to make a correct manual response. Prior to the experiment, the monkeys had been trained extensively so that they acquired fixed associations between visual features and required responses (e.g., "green = go"; "downward motion = no-go"). In this design, the monkey was confronted with a visual target from which it had to extract relevant information (e.g., color in the color-discrimination condition) while ignoring irrelevant information (e.g., motion direction in the color-discrimination condition). We recorded from 436 task-related prefrontal neurons while the monkey performed the multidimensional go/no-go task: 139 (32%) neurons showed go/no-go discrimination based on color as well as motion direction ("integration cells"); 192 neurons (44%) showed go/no-go discrimination only based on color ("color-feature cells"); and 105 neurons (24%) showed go/no-go discrimination only based on motion direction ("motion-feature cells"). Overall, however, 162 neurons (37%) were influenced by irrelevant information: 53 neurons (38%) among integration cells, 71 neurons (37%) among color-feature cells, and 38 neurons (36%) among motion-feature cells. Across all types of neurons, the response to an irrelevant feature was positively correlated with the response to the same feature when it was relevant, indicating that the influence from irrelevant information is a residual from S-R associations that are relevant in a different context. Temporal and anatomical differences among integration, color-feature and motion-feature cells suggested a sequential mode of information processing in prefrontal cortex, with integration cells situated toward the output of the decision-making process. In these cells, the response to irrelevant information appears as a congruency effect, with better go/no-go discrimination when both the relevant and irrelevant feature are associated with the same response than when they are associated with different responses. This congruency effect could be the result of the combined input from color- and motion-feature cells. Thus these data suggest that irrelevant features lead to partial activation of neurons even toward the output of the decision-making process in primate prefrontal cortex.

Animals↗
PubMed2001

[Audiological and equilibrium study of perilymphatic fistulas].

We clinically analyzed 15 cases of perilymphatic fistulas--11 caused by barotraumas and 4 idiopathic--identified by surgery between March 1995 and March 1999 at the Hyogo College of Medicine and affiliated hospitals. Subjects were 11 men and 4 women (aged 14 to 79 years (mean: 46.7 years)). All showed hearing loss in audiography and 12 cases reported tinnitus--stream-like in 5 and poping in 4. Dysequilibrium was seen in 9 cases. Perilymph leakage was detected intraoperatively from the oval window in 9, from the round window in 4, and from both windows in 1, while another had leakage from the fissura ante fenestram. After surgery, hearing level improved by over 10 dB in 9 of the 11 cases operated on within 14 days after onset. Hearing did not improve in 3 of 4 operated on later. Vertigo disappeared after surgery. Dizziness tended to persist in those having canal paresis or paralytic nystagmus before surgery. We suggest that patients with progressive hearing loss should be operated on as soon as possible and that patients with dysequilibrium or without response to conservative treatment undergo surgery within 14 days of onset.

Adolescent↗
PubMed2000

Nerve growth factor applied onto the olfactory epithelium alleviates degenerative changes of the olfactory receptor neurons following axotomy.

The olfactory neuroepithelium of the mammalian nervous system manifests continuous neurogenesis throughout life. Recent studies suggest that neurotrophic factors and their receptors may play a role in the regulation of development and regeneration in the olfactory system. However, there have been very few in vivo studies investigating the effect of exogenous neurotrophic factors in the olfactory system. In the present study, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were administered into the rat olfactory mucosa for 5 days just after the transection of the olfactory nerve. We then examined the effect of exogenous neurotrophic factors on the degenerative changes in axotomized olfactory receptor neurons (ORNs). Further, we examined the location of their receptors, Trk A and Trk B. We found that both mature and immature ORNs expressed more intense signals for olfactory marker protein and beta-tubulin mRNAs, respectively, when NGF was applied to the axotomized olfactory neuroepithelium for 5 days, compared to the ORNs of saline-treated controls. BDNF at a 10 microg total dose did not show this effect. The effect of NGF applied onto the olfactory epithelium is consistent with the immunohistochemical finding that Trk A was present in the dendrites and axon bundles in normal and axotomized ORNs. These results suggest that NGF may protect the degenerative changes in mature and immature ORNs following axotomy through the binding to the Trk A receptor located on the surface of the olfactory epithelium.

Animals↗
PubMed2000

Role of osteopontin in the rodent inner ear as revealed by in situ hybridization.

Osteopontin (OPN) is considered to be a non-collagenous bone matrix protein that is involved in the ossification process. However, OPN has recently been observed in ectopic sites such as the kidney and nervous tissue. In the present study, the expression of OPN mRNA was examined in the rat and mouse inner ear by nonradioisotopic in situ hybridization. Signals of OPN mRNA were observed in the marginal cells of the stria vascularis, spiral ganglion cells, vestibular sensory hair cells, and vestibular dark cells. OPN protein was detected only in the otoconia by immunohistochemistry. The presence of OPN mRNA in the cochlea and vestibular dark cells may indicate that OPN is involved in the regulation of ions in the inner ear fluid. Findings in the saccule and utricle suggest that OPN is one of the protein components of the rodent otoconia and that the vestibular sensory hair cells are involved in the production of otoconia.

Animals↗
PubMed2000

Postoperative results for cholesteatoma in children.

OBJECTIVES: to review the postoperative results for cholesteatoma in children. MATERIALS: 32 ears with acquired cholesteatoma in children operated on by a single surgeon between 1987 and 1995 and followed up more than 2 years. The mean follow-up period was 5.4 years. RESULTS: a one-stage operation was performed in seven ears (21.9%) and preplanned stage operation in 25 ears (78.1%). In the first operation, closed tympanoplasty was performed in 31 ears (96.9%) and open tymapanoplasty in one ear (3.1%). During the second stage operation, residual cholesteatoma was found in 16 ears (64.0%). Recurrent cholesteatoma was detected in 19.4% of ears treated with closed tympanoplasty. The mean postoperative air conduction hearing level was within 20 dB in 12.5%, 30 dB in 40.6% and 40 dB in 78.1%. The hearing results of type III tympanoplasty was better than those of type IV tympanoplasty. CONCLUSIONS: preplanned stage tympanoplasty is safer because of the high risk of recurrent and residual cholesteatoma. Surgical methods should be selected flexibly in individual cases depending upon cavity size, eustachian tube function and hearing level. Cholesteatoma in children should be operated on while stapes is present.

Adolescent↗
PubMed2000

Bilateral same day surgery for bilateral perforated chronic otitis media.

OBJECTIVE: Bilateral same day surgery has been performed rarely because of the risk of postoperative sensorineural hearing loss following conventional myringoplasty or tympanoplasty (CMT). Simple underlay myringoplasty (SUM) through the ear canal has been developed by Yuasa R, Saijo S, Tomioka Y, et al. Office closure of eardrum perforation with fibrin glue (in Japanese), Otolaryngol Head Neck Surg (Tokyo) 1989;61:1117-1122, which has little risk of sensorineural hearing loss. We tried bilateral same day surgery using this technique and evaluated its outcome. METHODS: Of 86 cases with bilateral perforated chronic otitis media that we treated between 1995-1997, 25 cases underwent bilateral same day surgery. Bilateral SUMs was performed on seven patients, SUM and CMT on 16 patients, and bilateral CMTs on two patients. RESULTS: Closure of perforation was successful in 18 patients (72%) on both sides and in seven patients (28%) on one side. Postoperative air-bone gap of less than 20 dB was achieved in 15 cases (60%) on both sides and in 23 cases (92%) on one side. CONCLUSION: Bilateral same day surgery for bilateral perforated chronic otitis media is possible if the operative indications are considered.

Adolescent↗