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Biomedical subjects

K Kaga

Publications and source records attributed to K Kaga.

At least 91 records · Page 5Linked to original sources

Keratinocyte growth factor and receptor mRNA expression in cholesteatoma of the middle ear.

Keratinocyte growth factor (KGF) is synthesized and secreted exclusively by stromal cells in epithelialized organs, and specifically promotes proliferation of cells of epithelial origin, including keratinocytes. Cholesteatoma is a proliferative form of keratinocyte dysregulation with aggressive growth that often leads to destruction of adjacent bone. We examined the expression of KGF, closely related peptides and their receptors in the development of cholesteatoma by comparing cholesteatoma with normal ear skin using the reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. All surgical specimens of cholesteatoma and most normal ear skin samples expressed detectable levels of KGF and KGF receptor (KGFR). Semiquantitative RT-PCR using beta-actin mRNA as an internal standard revealed significantly higher expression of KGF mRNA in cholesteatoma than in normal skin, while no significant difference in KGFR mRNA expression was noted between cholesteatoma tissue and normal skin. These results suggest that excessive KGF synthesis may contribute to the hyperproliferative state in cholesteatoma.

Blotting, Southern↗

Origin of auditory brainstem responses in cats: whole brainstem mapping, and a lesion and HRP study of the inferior colliculus.

In order to identify the origin of five waves of auditory brainstem responses (ABRs) in cats, we designed three experiments. In particular, we focused on the inferior colliculus (IC). Experiment 1: Evoked potential maps of the frontal sections of the brainstem from the level of the cochlear nuclei to the level of the ICs were constructed from the results of whole brainstem field-potential analysis comparing ABR peaks. Experiment 2: Both ICs were aspirated and the brainstem and midbrian were transected along the midline. Experiment 3: HRP was injected to the central nucleus of the IC to cause phase reversal of field potentials, and localization of brainstem auditory neurons projecting to the IC was studied. The results of these experiments suggest that each wave of the ABR is elicited from multiple sources of auditory brainstem nuclei and tracts only.

Animals↗

Central auditory information processing in patients with bilateral auditory cortex lesions.

Severe auditory cognitive disorders in 10 patients who had bilateral lesions either to the auditory cortex and/or auditory radiations were studied audiologically with special attention to residual hearing. This auditory cognitive problem is called "auditory agnosia or cortical deafness". Our study revealed that auditory information processing for pure tones, monosyllable discrimination, environmental sound perception, and auditory comprehension is commonly but differently affected by bilateral lesions of auditory cortex or auditory radiation. In summary, these patients can discriminate loudness of pure tones and some environmental sounds but cannot clearly perceive any sounds of monosyllables and sentences. Generally their residual hearing is useful for auditory awareness and is often enhanced by lip reading.

Adult↗

Comparison of interaural time and intensity difference discrimination in patients with temporal lobe lesions.

We studied the sound lateralization in 15 patients with left (12 patients) or bilateral (3 patients) temporal lobe cerebrovascular lesions. The lesions included the auditory cortex. Interaural time difference (ITD) and interaural intensity difference (IID) discriminations were separately measured by using a self-recording apparatus. All 12 patients with left temporal lobe lesions could discriminate ITD, and their IID thresholds were significantly higher than those in healthy volunteers. None of the 3 patients with bilateral temporal lobe lesions could discriminate ITD. On the other hand, all patients with either unilateral or bilateral temporal lobe lesions could discriminate IID and their IID thresholds were significantly higher than those in healthy volunteers. The present findings indicate that the auditory cortex plays an important role in discriminating both cues, but that the role may not be essential for IID.

Auditory Cortex↗

[Thoracoscopic unilateral fold plication method in lung volume reduction surgery for diffuse pulmonary emphysema].

We have devised a 'Fold Plication Method', which helps ensure safe and simple lung volume reduction surgery (LVRS) for pulmonary emphysema and prevent air leakage from pulmonary stumps, which is most crucial problem, in addition to postoperative interstitial pneumonia that is occasionally caused by the use of the bovine pericardium. We performed LVRS on seven patients with the disease, using this method and the thoracoscopic surgery, which is based on the 'Two Windows Method' we had previously developed. The operation was performed without observable bleeding within approximately one hour for all patients, who then recovered favorably.

Aged↗

Influence of chronic kanamycin administration on basement membrane anionic sites in the labyrinth.

We studied the effect of chronic treatment with kanamycin on the basement membrane (BM) anionic sites in the cochlea and endolymphatic sac using polyethyleneimine (PEI) as a cationic tracer. Albino guinea pigs weighing 250-300 g received kanamycin (400 mg/kg/day, i.m.) for 10 or 17 consecutive days. The number of BM anionic sites as derived from the PEI area was not affected in Reissner's membrane, spiral prominence, basilar membrane or endolymphatic sac, whereas it was significantly decreased in the stria vascularis and spiral limbus, being more marked in the guinea pigs treated for 17 days than in those treated for 10 days. The number of BM anionic sites in these regions did not recover until 6 weeks after kanamycin treatment. These findings suggest that chronically administered kanamycin may selectively and progressively affect the BM anionic sites in the stria vascularis and spiral limbus, resulting in disruption of a barrier function in the cochlea, and that severely impaired BM anionic sites in the cochlea may not recover.

Analysis of Variance↗

Sound lateralization in patients with lesions including the auditory cortex: comparison of interaural time difference (ITD) discrimination and interaural intensity difference (IID) discrimination.

We examined sound lateralization using dichotic presentation of noises in 15 patients with left unilateral (12 patients) or bilateral (3 patients) temporal lobe lesions, that included the auditory cortex, and evaluated their abilities to discriminate interaural time and intensity difference (ITD, IID) separately. On the ITD discrimination test, discrimination thresholds in patients with left unilateral lesions were significantly higher than those in normal subjects, but all patients with left unilateral lesions could detect ITD. However, none of 3 patients with bilateral lesions could detect ITD. On the IID discrimination test, all patients with either unilateral or bilateral lesions could detect IID. IID discrimination thresholds in these patients were significantly higher than those in normal subjects. The auditory cortex plays an important role in discriminating both cues, but appears to be necessary for discriminating ITD.

Adolescent↗

Effect of cisplatin on the negative charge barrier in strial vessels of the guinea pig. A transmission electron microscopic study using polyethyleneimine molecules.

The anionic sites on the basement membrane in the cochlea are believed to act as a charge barrier. Using polyethyleneimine (PEI) as a cationic tracer, we examined the effects of cisplatin (CDDP) on anionic sites in the basement membrane in the cochlea. Eight Hartley-strain guinea pigs were separated into control (buffer administration) and CDDP groups. Ultrathin sections of the basal and third turns of the cochlear ducts were examined using a transmission electron microscope. A marked decrease of PEI distribution was noted in the strial vessels of the CDDP group compared to the control group. However, the two groups showed no significant differences in PEI particles on the basement membranes in the basilar and Reissner's membranes, or in the basal and third turns. These findings suggest that the charge barrier in the stria vascularis may be easily injured by the administration of CDDP.

Animals↗

Metastatic hypopharyngeal carcinoma to the temporal bone.

Two cases of temporal bone metastasis by hypopharyngeal carcinomas are reported. One patient was a 43-year-old Japanese male who developed palsy of left oculomotor, trochlear, trigeminal, abducens and facial nerves. Carcinoma infiltrated the petrous portion of the left temporal bone. Tumor had destroyed a part of the facial canal and invading tumor cells were in contact with the perineurium. The other patient was a 59-year-old male who had no obvious facial nerve or otologic symptoms during the clinical course of his disease. Postmortem findings showed that carcinoma had invaded the right temporal bone and had produced extensive destruction of the facial canal. Degenerative findings were evident in the nerve. In the cases presented here, tumor resulted either from metastatic lymph nodes or had invaded through the suture of the temporal and sphenoid bones around the foramen lacerum to the middle cranial fossa and then infiltrated the temporal bone.

Adult↗

Temporal bone and brain stem histopathological findings in Cornelia de Lange syndrome.

The temporal bone and the brain stem of an infant with Cornelia de Lange syndrome, aged 9 months, were studied histopathologically. Abnormalities in the inner ear included short cochlea, dilated vestibule, and mesenchyme-filled perilymphatic spaces of the vestibule and semicircular canals. The inner and outer hair cells were normal. Many spiral ganglion cells, which normally would be located in the canal of Rosenthal, were seen in the internal auditory meatus. Some of the vestibular ganglion cells intruded into the facial nerve. The facial nerve formed a loose curve and the geniculum was difficult to recognize. The middle ear was filled with mesenchyme, and there was marked dehiscence of the facial canal. The brain stem, particularly the pons, was smaller than normal, while the fourth ventricle was dilated. The microscopic observation of the pons revealed weak staining with Luxol Fast Blue and decreased number of oligodendroglia. These findings suggested the malformation of the myelin of transverse fibers.

Brain Stem↗

Auditory brainstem responses in infants and children with anoxic brain damage due to near-suffocation or near-drowning.

We studied auditory brainstem responses (ABRs) of sixteen infants and children with brain damage after anoxic accidents due to near-suffocation or near-drowning. The patients manifested cerebral palsy, mental retardation and/or epilepsy and showed poor responses in the behavioral audiometry. Auditory brainstem responses were abnormal in five of the patients in the near-drowning group (waves I, II and III only were present in three patients and the amplitudes of waves IV and V were low in two patients) but normal in most of the patients in the near-suffocation group. This difference in the ABRs between the two groups suggest that in infants and children anoxic brain damage due to near-drowning might involve not only the cerebral cortex and subcortical white matter but also the upper brainstem and midbrain.

Brain Injuries↗

Safe and effective topical application dose of lidocaine for surgery with laryngomicroscopy.

A clinical case of a patient in whom seizure developed after topical application of lidocaine to the oropharyngeal region was described. The exploratory studies on the optimal dosage of lidocaine in the surgery under laryngomicroscope was performed in 22 patients. During the application of 2% lidocaine viscous and 4% lidocaine solution to the oropharyngeal region, the patient was instructed to expectorate the excess intermittently to avoid absorption. In addition, the oropharyngeal region was swabbed with gauze. The serum lidocaine concentrations after application were less than 1.8 micrograms/ml. The total application dose of the drug was within the range of 324 to 640 mg, and the total recovery rate from the saliva and gauze was 52% to 81%. We found a good correlation between net application dose (total application dose minus excessive lidocaine dose) and serum lidocaine concentration. In this study, it was shown that the safe and effective net application dose of lidocaine for the surgery may be within the range of 127 to 260 mg.

Administration, Topical↗

Expression of epidermal growth factor family proteins and epidermal growth factor receptor in human endometrium.

The biological significance of epidermal growth factor (EGF)-related proteins in the development and progression of endometrioid endometrial carcinoma was studied. Expression of EGF-related proteins including EGF, transforming growth factor-alpha (TGF-alpha), cripto (CR), amphiregulin (AR), and EGF receptor (EGFR) were immunohistochemically examined. Results were then correlated with clinicopathologic findings and steroid receptor status in 12 specimens with normal endometrium, 13 with endometrial hyperplasia, and 40 with endometrioid endometrial carcinoma. EGFR, EGF, TGF-alpha, and CR immunoreactivities were observed in 58.3%, 66.7%, 91.6%, and 66.7% of normal endometrial specimens; 100%, 15.4%, 100%, and 30.8% of endometrial hyperplasia specimens; and 67.5%, 32.5%, 65.0%, and 65.0% of endometrial carcinoma specimens, respectively. AR immunoreactivity was not observed in any of the normal, hyperplastic, or neoplastic endometrium. The presence or absence of EGFR or TGF-alpha in endometrial carcinoma correlated with surgical stage, depth of myometrial invasion, and findings from peritoneal washing cytology. EGF expression significantly correlated with the age of the patients and that of CR with surgical stage and peritoneal washing cytological findings. There was a significant correlation between EGFR and TGF-alpha expression, and between EGF and TGF-alpha. Co-expression of EGFR and TGF-alpha, EGFR and CR, and TGF-alpha and CR in carcinoma specimens significantly correlated with advanced surgical stage, deeper myometrial invasion, and positive peritoneal washing cytology. In normal as well as hyperplastic endometrium, endometrial glands immunohistochemically positive for TGF-alpha were generally positive for ER, but in poorly differentiated endometrial carcinoma, cells positive for TGF-alpha tended to be negative for ER. The results of the present study show that among EGF-related proteins, expression of TGF-alpha and CR seem to be associated with the progression of human endometrioid endometrial carcinoma. Additionally, expression of TGF-alpha became increasingly estrogen independent with increasing histological carcinoma grades.

Adult↗

Adrenal 4-binding protein in common epithelial and metastatic tumors of the ovary.

Adrenal 4-binding protein (Ad4BP) is a transcription factor that regulates the expression of steroidogenic enzymes. Ovarian tumors other than sex cord stromal tumors are occasionally associated with functioning stroma or hormonal abnormalities. To determine the steroidogenic potential of these tumors, the authors determined the immunohistochemical distribution of Ad4BP in 75 patients with primary common epithelial tumors (20 cystadenomas, 15 carcinomas of low malignant potential, and 40 carcinomas), and seven patients with metastatic carcinoma of the ovary. Ad4BP immunoreactivity was observed in intratumoral stromal cells in 3 of 15 (20%) carcinomas of low malignant potential, 26 of 40 (65%) carcinomas, and three of seven (43%) metastatic carcinomas. Ad4BP immunoreactivity was not observed in the stroma of cystadenomas. Among the positive cases, Ad4BP-positive stromal cells were particularly distributed adjacent to invasive carcinomatous glands. Among ovarian carcinomas, mucinous carcinoma showed a significantly higher number of Ad4BP-positive intratumoral stromal cells than did other histological types. Results suggest that invasion of primary or metastatic carcinoma into the ovarian stroma, especially in the case of mucinous carcinoma, may render the stromal cells to acquire the potential of metabolizing and synthesizing steroid hormones.

Breast Neoplasms↗

Aromatase cytochrome P450 gene expression in endometrial carcinoma.

We analysed aromatase gene expression and its regulation in seven cases of endometrioid endometrial carcinoma. Immunohistochemistry revealed the presence of strong aromatase immunoreactivity in the stromal cells of carcinoma in five out of seven cases. A polymerase chain reaction after reverse transcription (RT PCR) revealed varying levels of aromatase transcripts (0.1-27.0 amol ng(-1) total mRNA) in five cases. The alternative use of multiple exons 1 was also examined by identifying various human aromatase transcripts specific for exons 1 in RT-PCR products. Gonadal type or exon 1d was primarily used in three cases in which aromatase overexpression was not detected. The two cases in which fibroblasts type or exon 1b was used with other exons 1 as minor transcripts demonstrated aromatase overexpression in immunohistochemistry and RT PCR analysis. Further studies are required, but alternative splicing as well as use of multiple exons 1 transcripts may result in increased aromatase expression in stromal cells observed in endometrial carcinoma.

Adult↗

Auditory findings in patients with maternally inherited diabetes and deafness harboring a point mutation in the mitochondrial transfer RNA(Leu) (UUR) gene.

Five patients with sensorineural hearing loss, who harbored a point mutation in the mitochondrial transfer RNA (tRNA) gene tRNA(Leu) (UUR), from five unrelated family pedigrees were examined. In these families diabetes and deafness were maternally inherited. Bilateral hearing was more severely impaired at higher frequencies. Audiometric test results revealed that hearing loss involved the cochlea. Hearing gradually deteriorated; the progression rate ranged from 1.5 to 7.9 dB per year. Proportion of mutant mitochondrial DNAs (mtDNAs) in the leukocytes was not related to the rate or degree of hearing loss, although hearing loss appeared at a younger age in patients with higher heteroplasmy. We speculate that after the proportion of damaged mtDNAs, mostly as a result of mutation, exceeds the expression threshold for deficiencies in mitochondrial protein synthesis and oxygen consumption, a drop in adenosine triphosphate level could lead to an imbalance of ion concentration, resulting in cell death in the cochlea.

Adult↗

Lack of effect of vancomycin and gentamicin on auditory function in guinea pigs.

The dispositions of vancomycin (VCM) and gentamicin (GM) in plasma and perilymph after single and multiple administrations and the effects of multiple administrations of VCM or GM alone and the combination of both drugs on auditory function were studied in male guinea pigs. The pharmacokinetic parameters of VCM and GM obtained from plasma drug concentration-time data after single and multiple (22 days) intramuscular administrations of VCM (200 mg/kg of body weight) alone and GM (50 mg/kg) alone were not significantly different from those after combined administration of VCM (200 mg/kg) and GM (50 mg/kg). There was no change in the penetration ratio of VCM and GM into perilymph between administration of VCM or GM alone and the combination of both drugs. Furthermore, the hearing threshold of guinea pigs was not affected by VCM or GM alone or the combination of both drugs within the range of therapeutic VCM and GM levels in plasma in humans.

Animals↗

Abnormalities of ABR and auditory perception test findings in acquired palatal myoclonus.

An auditory test battery consisting of pure tone audiometry, the auditory brainstem response (ABR), the nonsense monosyllable perception test, the dichotic listening test and the Token test were administered to three patients with palatal myoclonus. All patients had ABR abnormalities correlated with the location of brainstem lesions, despite relatively normal pure-tone threshold. In two of the three patients, both the nonsense monosyllable test and the dichotic listening test revealed dominance on the side ipsilateral to the lesion, while ABR abnormalities were present on the contralateral side. In one patient who had bilateral ABR abnormalities, both the monosyllable perception and dichotic listening test scores were poor for bilateral ears. These results suggest that brainstem lesions producing palatal myoclonus could have an effect on auditory perception.

Adult↗