PubMed Health⌕ Search

Biomedical subjects

A Inokuchi

Publications and source records attributed to A Inokuchi.

At least 19 recordsLinked to original sources
PubMed1999

The human multidrug resistance protein 2 gene: functional characterization of the 5'-flanking region and expression in hepatic cells.

The human multidrug resistance protein 2 (MRP2), also termed as the canalicular multispecific organic anion transporter (cMOAT), is a member of the adenosine triphosphate-binding cassette transporter superfamily. In the liver, MRP2 mediates the multispecific efflux of various types of organic anions, including glucuronate, sulfate, and glutathione conjugates, across the canalicular hepatocyte membrane to the bile. To investigate how the MRP2 gene is expressed in liver cells, the 5'-flanking region of the human MRP2 gene was isolated from a human placental genomic library. Sequence analysis of the MRP2 promoter showed a number of consensus binding sites for both ubiquitous and liver-enriched transcription factors. Transfection of human hepatic HepG2 cells with a series of 5'-deleted promoter luciferase constructs identified a putative silencer element localized in the -1,659/-491 region and a liver-specific positive regulatory element localized in the -491/-258 region. This latter region contained the liver-abundant transcription factor CCAAT-enhancer binding protein beta (C/EBPbeta). The transcriptional activity of the promoter construct containing a mutation in the C/EBPbeta binding site was significantly decreased in HepG2 cells. This study suggests that C/EBPbeta (-356 to -343) may regulate the liver expression of the MRP2 gene.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

Effects of the antihistaminergic drugs diphenhydramine and zolantidine on vestibular-induced hypothalamic neuronal activity in the guinea pig.

The mode of action of diphenhydramine in treating motion sickness is unknown. Using an electrophysiologic technique, we investigated the effects of intravenous diphenhydramine and zolantidine on the changes in neuronal activity produced by caloric stimulation in the hypothalamic paraventricular nucleus (PVN) in the guinea pig. Changes in neuronal activity were modulated by the administration of diphenhydramine in a high percentage of the neurons tested (71%), while zolantidine affected only a small number (29%). This finding reinforces the involvement of a histaminergic system in vestibular autonomic responses. The modulatory effect of diphenhydramine on PVN neuron activity may explain in part this drug's efficacy in treating motion sickness.

Animals↗
PubMed1999

The role of the labyrinth, proprioception and plantar mechanosensors in the maintenance of an upright posture.

The maintenance of an upright posture in man requires information from vision, the labyrinth, proprioception and plantar mechanosensors. In order to evaluate the role of the labyrinth, proprioception and plantar mechanosensors, stabilometry was performed in subjects with closed eyes. Ten patients with bilateral severe or complete labyrinthine paresis were studied, as well as 9 patients with severe proprioceptive disorders and 10 normal healthy persons whose plantar mechanosensors were anesthetized by hypothermia. Both the area of sway and the total locus length (accumulated shift distance length) were evaluated. On closing eyes, in patients with labyrinthine disorders demonstrated that the area of sway increased more than length. On the other hand, in patients with proprioceptive disorders, length increased more than the area. In plantar anesthetized subjects, similar to the labyrinthine disorder cases, the area of sway increased more than length. These findings suggest that the labyrinth is a main monitor of the area of body sway, while proprioception is a principle monitor of the velocity of body movement of sway (or locus length). The plantar mechanosensor monitors the area of body sway similar to the labyrinth, but works less than the labyrinth. The locus length is the distance per minute and reflects the velocity of body sway. Thus, the length per area is a parameter for the velocity of body sway per area. Since proprioceptive disorders increase both the locus length and the length per area, present findings suggest that if proprioception is damaged, the body begins to move faster. Compensated labyrinthine disorders have a tendency to increase the length per area, indicating that if a labyrinthine disorder is compensated, the body adapts and moves faster to maintain an upright posture.

Achilles Tendon↗
PubMed1999

Huge hamartoma with inverted papilloma in the nasal cavity.

We report clinical experience in managing a 46-year-old Japanese man with long-standing nasal obstruction resulting from a huge left nasal mass. Computed tomography, magnetic resonance imaging and biopsy were used to make a provisional diagnosis of inverted papilloma. The mass was resected via a frontal approach combined with rhinotomy. Histopathologic examination of the resected specimen was consistent with a hamartoma that included an inverted papilloma on a portion of its surface. In addition to being rare tumors in the nasal cavity, we believe that our patient's tumor the largest nasal hamartoma ever reported.

Biopsy↗
PubMed1999

Magnetic sensory cortical responses evoked by tactile stimulations of the human face, oral cavity and flap reconstructions of the tongue.

Magnetoencephalography (MEG) is a procedure that analyzes the magnetic responses of neurons. An MEG system with a 37-channel superconductivity quantum interference device (SQUID) was used to record magnetic signals from the human brain in response to tactile stimulations of the face and oral cavity. Six normal individuals were studied as well as three patients who had undergone hemiglossectomies as treatment for carcinoma of the tongue and reconstruction with a pectoralis major myocutaneous flap. When the locations of the magnetic responses having latencies of 40 ms from onset of tactile stimulation were identified, these corresponded to the primary somatosensory cortex. In patients whose tongues had been reconstructed with a pectoralis major myocutaneous flap, the magnetic response upon stimulation of the flap was recorded in a sensory cortical area identical to that corresponding to the tongue. MEG systems such as the one described permit functional mapping of the cerebral cortex on stimulating the face and oral cavity.

Adult↗
PubMed1999

Overexpression of p53 nuclear protein in premalignant and malignant laryngeal lesions.

To investigate the role of p53 nuclear protein mutations in the initiation and progression of laryngeal carcinoma, 111 premalignant and malignant laryngeal lesions (19 specimens with hyperkeratosis and 92 with carcinoma) were studied immunohistochemically. Over-expression of p53 was observed in 8 cases (42%) of laryngeal hyperkeratosis and 44 cases (47%) of laryngeal carcinoma. However, the expression of p53 showed no relationship to patients' clinical courses. Our study confirms that p53 overexpression can be found in laryngeal carcinogenesis and is an early event but not a useful prognostic marker.

Carcinoma, Squamous Cell↗
PubMed1999

Comparison of survival rates of patients with nasopharyngeal carcinoma treated with radiotherapy, 5-fluorouracil and vitamin A ("FAR" therapy) vs FAR therapy plus adjunctive cisplatin and peplomycin chemotherapy.

The overall survival rate (OSR) of 36 patients with nasopharyngeal carcinomas (NPC) treated at Kyushu University hospital between 1983 to 1992 was analyzed. As primary treatment, 16 patients received a combination therapy of 5-fluorouracil, vitamin A, and radiation (FAR therapy); two patients received radiotherapy only; 18 patients received FAR therapy plus adjunctive systemic chemotherapy consisting of cisplatin and peplomycin. The radiation dose to the nasopharynx was 6000 to 7050 cGy while that to the neck was 4000-6000 cGy. The 5-year OSR of all the patients was 49%. Histological type (moderately differentiated squamous cell carcinoma) and patient age (> or = 55) were found to be significant prognostic factors for a worse OSR. Although survival decreased with increasing T stage, no significant difference was observed. The 5-year OSR of the patients treated with FAR therapy was 53% and was 51% with FAR therapy plus chemotherapy. Compared to FAR therapy alone, adjunctive chemotherapy did not increase OSR of the patients with NPC.

Adult↗
PubMed1999

Induction of apoptosis in maxillary sinus cancer cells by 5-fluorouracil, vitamin A and radiation (FAR) therapy.

The triple combination of 5-fluorouracil (5-FU), vitamin A and radiation (FAR therapy) has been used since 1972 to treat malignant tumors of the head and neck at Kyushu University. Using nick end labeling of tumor specimens, cells of human maxillary sinus carcinomas were observed previously to undergo apoptosis in response to FAR therapy. The present study evaluated the in vitro effects of FAR therapy on a human maxillary sinus cancer (IMC-4) cell line. We further compared the effects of FAR therapy on this cell line with those effects seen on tissue samples taken from patients with maxillary sinus cancers. DNA electrophoresis and electron microscopic examination of the IMC-4 cells after treatment with FAR therapy revealed typical apoptotic features. The effects of 50-100 micrograms/ml 5-FU, 10(-4) M all-trans-retinoic acid and radiation to 6 Gy on IMC-4 cells were evaluated by trypan blue dye exclusion and a cell colony formation assay. 5-FU and radiation caused direct cell death, while vitamin A mainly inhibited cell growth. The combination of these treatment as FAR therapy synergistically enhanced cell death and inhibited cell growth. Flow cytometry demonstrated that FAR-treated cells were arrested in the G1 phase of the cell cycle before undergoing apoptosis. To further investigate possible biological parameters influencing a tumor's apoptotic sensitivity, we also examined the expression of p53 in human maxillary sinus cancer cells and analyzed the relationship between p53 expression and apoptosis. However, no relationship was found between these two markers at the time point studied.

Antineoplastic Agents↗
PubMed1999

Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome.

Dubin-Johnson syndrome (DJS) is an autosomal recessive disease characterized by conjugated hyperbilirubinemia. Previous studies of the defects in the human canalicular multispecific organic anion transporter gene (MRP2/cMOAT) in patients with DJS have suggested that the gene defects are responsible for DJS. In this study, we determined the exon/intron structure of the human MRP2/cMOAT gene and further characterized mutations in patients with DJS. The human MRP2/cMOAT gene contains 32 exons, and it has a structure that is highly conserved with that of another ATP-binding-cassette gene, that for a multidrug resistance-associated protein. We then identified three mutations, including two novel ones. All mutations identified to date are in the cytoplasmic domain, which includes the two ATP-binding cassettes and the linker region, or adjacent putative transmembrane domain. Our results confirm that MRP2/cMOAT is the gene responsible for DJS. The finding that mutations are concentrated in the first ATP-binding-cassette domain strongly suggests that a disruption of this region is a critical route to loss of function.

ATP-Binding Cassette Transporters↗
PubMed1998

[A case of adenoid cystic carcinoma in epipharynx which responded to radiation and chemotherapy].

A 45-year-old man visited our hospital complaining of a right hearing loss. The head and neck examination was unremarkable except for right secretory otitis media. Fiberoptic examination of the nose and the epipharynx revealed a mass. Transnasal biopsy was performed and histologic analysis revealed adenoid cystic carcinoma. Invasion of the sphenoid sinus was identified by MRI. He was treated with FAR therapy (5-FU, Vit A, Radiation) and chemotherapy (intra-arterial infusion of ADM). Severe side effects were not seen during treatment. After treatment, the majority of the tumor mass disappeared on fiberoptic examination and MRI. On repeat biopsy specimens, no cancer cells were found. The patient was alive with no evidence of disease as of August 1997.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Neuronal responses to vestibular stimulation in the guinea pig hypothalamic paraventricular nucleus.

We investigated the effects of caloric stimulation on neuronal activity in the hypothalamic paraventricular nucleus (PVN) in anesthetized guinea pigs. Hot water stimulation of the contralateral labyrinth produced excitation in 29.4% of the PVN neurons tested, while cold water produced excitation in 22.2% of the neurons. Hot water resulted in inhibition of 22.4% of the neurons and cold water inhibition of 24.7% of the neurons. Intracranial vestibular nerve section greatly reduced responsiveness of the PVN neurons to caloric stimulation, indicating that the majority of the responses observed were vestibular in origin. The response pattern of the individual PVN neurons was similar following hot and cold water stimulation and after stimulation of the contralateral and ipsilateral labyrinths. These results suggest that the PVN neurons receive vestibular afferents bilaterally according to the intensity of vestibular stimulation, with the information received probably integrated in the hypothalamus to participate in vestibulo-autonomic reflexes.

Animals↗
PubMed1997

[Changes in arterial blood pressure and hypothalamic neural activity in response to caloric stimulation in guinea pigs].

We investigated the effects of caloric stimulation on arterial blood pressure (AP) and neural activity in the hypothalamic paraventricular nucleus (PVN) in anesthetized guinea pigs. Hot water stimulation of the labyrinth produced a decrease in AP in 56 of 73 cases tested, and AP decrease followed by increase in 12 cases. In the cases where AP initially decreased and then increased, 92% of PVN neurons responded as excitatory or inhibitory to caloric stimulation. When the AP change was a decrease alone, the responsive rate of the PVN neurons was 63%, and no change in PVN neural activity was seen in the group which showed no AP change after caloric stimulation. The ratio of the PVN neurons showing inhibition in the group that showed AP decrease-increase sequence was significantly higher than that in the group showing AP decrease alone. AP changes following caloric stimulation were greatly reduced after electric destruction of the anterior and middle parts of the hypothalamus. This indicates that the activation of the hypothalamic neurons by the vestibular input is important to produce the vestibulovasomotor response and its pattern. When the same amount of stimulus was applied periodically to the labyrinth, the AP increment component was increased with time. It is suggested that the pattern of AP changes is greatly influenced by level of consciousness. It is suggested that the basal activity level of the autonomic nervous system, and the variety and magnitude of the vestibular stimuli should be synthetically evaluated when the autonomic nerve function test is applied to patients suffering dizziness.

Animals↗
PubMed1997

[Quantitative analysis of the gustatory evoked potentials in the guinea pig].

Gustatory evoked potentials were studied in anesthetized guinea pigs to develop an objective and quantitative taste examination for patients with taste disorders. A positive wave was recorded by the application of NaCl, HCl or quinine hydrochloride solution. There was little difference in latency, duration and waveform among these three solutions. No apparent change in activity was seen after the application of sucrose solution or distilled water. The gustatory evoked potentials that excluded the influence of the trigeminal nerve innervating the tongue surface were able to be reproducibly recorded on either the cortical surface or the skull surface. There was a linear relationship between logarithmic values of potential amplitude and those of taste solution concentration. Therefore, it is suspected that the quantitative evaluation of taste detection is possible by measuring the taste solution concentration-potential amplitude relationship.

Animals↗
PubMed1995

Disturbance of regulation of sodium by cis-diamminedichloroplatinum in perilymph of the guinea pig cochlea.

We studied the acute effects of cis-diamminedichloroplatinum (CDDP) on the cochlear partition and inner ear fluid in the guinea pig. At 48 hours after the administration of a single intramuscular injection of CDDP, 12.5 mg/kg of body weight, the endocochlear resting potential (EP) was significantly decreased to 32.1 +/- 1.8 mV in the treated animals, versus 80.6 +/- 1.0 mV in the control animals. There was a significant rise in potassium (K+), sodium (Na+), and chlorine (Cl-) in the endolymph of the animals treated with CDDP as compared with the control animals. Only Na+ was found to increase significantly in the perilymph, reaching more than twice the level of the control animals; both K+ and Cl- remained within the normal range. Serum electrolytes also remained within the normal range. Evaluation of modified ionic permeabilities across the endolymph-perilymph barrier showed an apparent increase in Na+ permeability and a normal range of K+ and Cl- permeabilities. Histopathologic examination of the cochlea showed a moderate collapse of the endolymphatic space, with atrophy of the stria vascularis and destruction of the outer hair cells. The findings suggest that the acute changes produced in the cochlea by administration of CDDP were attributable to a breakdown in the regulation of Na+ metabolism in the perilymph.

Animals↗
PubMed1993

Purification and characterization of membrane-bound CO-reactive hemoprotein from Tetrahymena pyriformis mitochondria.

A CO-reactive hemoprotein was purified from the mitochondrial membrane fraction of Tetrahymena pyriformis. It showed absorption peaks at 615 and 455 nm in the reduced form and an alpha peak at 565 nm in the pyridine ferrohemochrome spectrum. Although the spectral properties were apparently similar to those of 'cytochrome a620' which was previously proposed as a mitochondrial terminal oxidase in T. pyriformis, it did not contain any molecules of heme a or copper atoms. Further, it showed neither cytochrome c oxidase nor cytochrome c peroxidase activity. These results suggest that 'cytochrome a620' may not be the terminal oxidase in the mitochondrial respiratory chain of T. pyriformis.

Animals↗
PubMed1993

Convergence of olfactory and nasotrigeminal inputs and possible trigeminal contributions to olfactory responses in the rat thalamus.

To elucidate the role of trigeminal input on the olfactory system, field-evoked potentials were measured following electrical stimulation of the nasociliary branch of the trigeminal nerve in the olfactory-related structures in the rat brain. Significant potential changes were recorded in the mediodorsal nucleus of the thalamus and the lateral hypothalamic area. In the mediodorsal nucleus of the thalamus, the neurons responding to olfactory bulb electrical stimulation also responded to trigeminal nerve stimulation. Single neuronal responses of mediodorsal thalamic neurons following odorant stimulation were enhanced by blockade of the trigeminal nerve with procaine. These results suggest that olfactory and trigeminal pathways converge on the same neural elements within the mediodorsal nucleus of the thalamus and that the trigeminal input may modulate olfactory input in this nucleus.

Animals↗
PubMed1991

Vestibular evoked potentials to angular acceleration in the guinea pig. A preliminary report.

Rotational evoked potentials were studied in the guinea pig under urethane anesthesia. The stimulus events were triangular velocity changes produced by abrupt reversals of acceleration, and horizontal semicircular canals were stimulated. A positive-negative-positive wave was recorded in the vestibular nuclei and the potential was totally abolished after bilateral labyrinthectomy. Single unit recordings revealed that the peak latency of the negative wave is almost coincident with the peak latency of the excitation of type I vestibular nucleus neurons. It is concluded that the recorded potential to the rotational stimuli in this experiment is of vestibular origin.

Acceleration↗