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Biomedical subjects

K Sunami

Publications and source records attributed to K Sunami.

At least 55 records · Page 3Linked to original sources

Time-dependent response of vestibular hair cells of guinea pigs following high-dose applications of streptomycin.

Apoptosis has been reported to occur in vestibular hair cells following aminoglycoside treatment and is suggested to play a predominant role in deletion of affected hair cells. However, the type of cell death occurring during an acute phase of vestibular damage following high-dose application of streptomycin has not yet been determined. Hence, in this study we examined the cell death mode of vestibular hair cells during the acute phase. The numbers of hair cell nuclei stained by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) method and residual hair cells were quantitatively analysed. Hoechst nuclear staining was used for analysis of the nuclear morphology of affected hair cells. TUNEL staining of hair cell nuclei and lost hair cells began to appear 6 h after streptomycin treatment and increased with more exposure time. Apoptotic nuclear features could also be found from 6 h after streptomycin treatment. These findings support the thesis that apoptosis is a predominant cell death mode in degeneration of vestibular hair cells due to streptomycin ototoxicity.

Animals↗

Cycloheximide blocks the toxic effect of streptomycin in guinea pig vestibular hair cells.

Apoptosis has been suggested to be a predominant cell death process for streptomycin-induced degeneration of vestibular hair cells. However, the biochemical aspects of this have not been studied. The purpose of this study was to examine the biochemical aspects of apoptosis of vestibular hair cells caused by streptomycin. Cycloheximide is a widely used protein synthesis inhibitor in studies of apoptosis. We therefore investigated cycloheximide effects on degeneration of vestibular hair cells following streptomycin applications. Supplements of cycloheximide significantly prevented DNA fragmentation in hair cell nuclei and reduced the loss of hair cells. This suggests that cycloheximide possibly inhibits apoptosis of hair cells and attenuates streptomycin-induced degeneration of the vestibular epithelium.

Animals↗

Brain stem contusion due to tentorial coup injury: case report and pathomechanical analysis from normal cadavers.

This report is in two parts. First, a case report on a 20-year-old man with a localized brain stem contusion. Second, in order to elucidate the mechanism of this injury, an anatomical study was performed. Ten cadaver heads were analysed to reveal the variations of spatial anatomy around the tentorial incisura. The lateral tentorial incisura (lateral to brain stem) was situated at the level of pontomesencephalic junction and nearest to the brain stem along its course. The shortest distance between them averaged 1.0 mm (0-4 mm). Based on these findings, primary brain stem injury caused by tentorial incisura occurs at its lateral portion due to the shortest distance to the brain stem and near the level of pontomesencephalic junction. In patients with a tentorial incisura closely related to or touching the brain stem, tentorial coup injury to the brain stem may occur even with a relatively minor injury. In our case, repeated CT and MRI proved that the location of contusion was at the pontomesencephalic junction, coinciding with the level of the tentorial edge. The injury started at the surface of brain stem. The tentorial edge was close to brain stem in this case. These radiological findings support the hypothesis that the brain stem contusion was caused by a tentorial coup injury.

Adult↗

Improvement with disodium cromoglycate of neutrophil phagocytosis and respiratory burst activity in a patient with hyperimmunoglobulin E syndrome.

We report a case of hyperimmunoglobulin E syndrome (HIE) complicated by neutrophil deficiency which was successfully treated with oral administration of disodium cromoglycate. A 48-year-old Japanese man with HIE developed Streptococcus pneumoniae meningitis. Laboratory tests after the meningitis revealed persistent neutropenia (300-800/mm3) and defects of phagocytosis and bacterial killing by neutrophils. Administration of disodium cromoglycate was started, and neutrophil counts gradually increased to 1200-1600/mm3. The impaired neutrophil activities returned to normal. The patient improved clinically; during the 2-year treatment, he had only two brief episodes of the common cold. Disodium cromoglycate may have potential clinical use in the treatment of cases of HIE even with neutrophil deficiency.

Cromolyn Sodium↗

Surgical indication after bromocriptine therapy on giant prolactinomas: effects and limitations of the medical treatment.

Bromocriptine (BC) is now an accepted primary therapeutic agent for patients with microadenoma. But, for patients with large or giant prolactinomas, the treatment choice is controversial. This report focuses on long-term results of the BC effect on 10 giant prolactinomas (maximum diameter more than 40 mm and the serum PRL level more than 1000 ng/ml) with particular emphasis on cases that needed surgical intervention due to unsatisfactory results from BC therapy alone. BC was effective in 6 cases (60%). They had the serum PRL level normalized in less than one year, with BC maintenance doses between 5-15 mg/day. MRI revealed complete or nearly total disappearance of the tumor. Discontinuation of the medicine was achieved in one patient. In the remaining 4 cases, surgery was needed for various reasons: 1) BC resistant prolactinomas in 2 cases, 2) large hematomas in one of the previous cases, 3) regrowth of tumor size, despite the nearly normalized PRL level due to bulk increase in non-secretory adenomatous portion in 1 case, and 4) intolerable side effect in 1 case. BC is effective even for giant prolactinomas in 60% of cases. But, this therapy needs surgical intervention more often than microadenomas. Surgical indications and timing should be decided on based on closer follow-up of neuroimaging and visual evaluation as well as the serum PRL level.

Adult↗

[Increased incidence of senile dementia in the Hansen's disease sanatoriums of Japan].

In 1973, Narita reported that the rate of demented patients above 65 years was about 2% at the sanatorium--Tama Zenshoen, which was much lower than that of the average aged people (4-5%). The reason for that was thought to be due to the acquirement of strong mind under loneliness and difficulties faced by the patients through social enforcement to live in isolation. From that report on the low percentage of dementia among the Japanese Hansen patients reemed to be widely accepted. Fifteen years later in 1988, Narita reported that the rate of demented patients above 65 years was 3.2% in males and 3.6% in females indicating still a low rate at Tama Zenshoen. In 1994, however, Narita found unexpectedly that the percentage of dementia among patients above 80 at Tama Zenshoen was higher than the average aged population. Therefore in this report, we tried to analyze the reason for this difference. In addition to Tama Zenshoen patients, we also investigated those of another Hansen disease sanatorium namely Nagashima Aiseien which has similar structural organization as Tama Zenshoen. A comparison of dementia between these two was carried out, taking patients above 65 years as the study group (Used GBS scale based on Karasawa's method). In Tama Zenshoen, the rate of patients with dementia was 18.6% in males and 31% in females. Above 80 years those were 54.4% in males and 75.9% in females. The reason for the above high rate of dementia may be probably due to the passage of long years (40 to 50 years) after the enforcement to live in isolation causing the weakening of the spirit. The patients might have got some mental support if they had offspring, but they had no way to have any under the forced contraception. On the contrary, in Nagashima Aiseisen, the percentage of patients with dementia was low, namely 3.6% in males and 9.1% in females. In those patients above 80 years, it was 2.7% in males and 6.8% in females, those were almost similar to the average normal population (6%). Such a big difference was quite surprising. The reason behind this difference, may be due to the construction of the houses for the disabled persons. Both Nagashima Aiseien and Tama Zenshoen, have small individual rooms. In Tama Zenshoen, patients are able to visit their close neighbor, only after changing their shoes or with the aid of wheel chairs, but in Nagashima Aiseien, the corridors connecting quarters allow the patients to move easily to his neighbors with bare feet or even with crawl. Therefore, in Nagashima Aiseien, the number of patients who have social contacts with their neighbors is much greater in number which make them mentally active, thus eliminating the major factors affecting dementia. We can conclude that such communication between friends and co-mates make them alert and keep the spirit in the aged.

Aged↗

Assessment of hair cell death using the dye extrusion method.

We examined the usefulness of the dye extrusion method for assessing cochlear hair cell death in guinea pigs. Unilateral temporal bones were incubated in sterile Dulbecco modified Eagle's medium for 1-6 h and then perfused with PBS/0.3% trypan blue to determine hair cell viability. Cells with nuclei stained with trypan blue were assumed to have died. The contralateral temporal bones of each animal were incubated with the same medium for 1-6 h and examined by transmission electron microscopy (TEM). This method revealed that hair cell viability under these conditions was maintained for at most 3 h. After incubation for more than 3 h, hair cell injury began and increased. After 6 h incubation, TEM revealed apoptotic death of outer hair cells. The results with this method agreed with the TEM findings. The dye extrusion method is simple, easy and useful for screening hair cell death in the cochlea under pathological conditions.

Animals↗

Cleavage product from the NO donor NOC-5 and inner ear hair cell damage.

Nitric oxide (NO) is a neurotoxic gas which causes neuronal cell death. NO ototoxicity has also been reported, 1-Hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene (NOC-5), NO donor, was used for studying NO. In this in vitro study, we examined whether NOC-5 and the cleavage products arising from it after production of No have ototoxic effects on the cochlea. The temporal bones of 55 guinea pigs were dissected and incubated in Dulbecco Modified Eagle's Medium (DMEM) with low glucose and 10% foetal bovine serum (FBS) perfused with various concentrations (100, 50, 10, 1 mM, 100 microM) of NOC-5 (pH 7.4) or the same concentrations of N-isopropyl 1-3 propanildiamine (R-NH2). Hair cell death was assessed using trypan blue staining. With NOC-5, percentages of outer hair cell death were 99.2, 98.0, 45.2, 40.5, and 20%, respectively, and percentages of inner hair cell death were 69.3, 70.2, 22.5. 11.1 and 0%, respectively. With R-NH2, percentages of outer hair cell death were 90.3, 81.1, 29.8, 21.0 and 19.3%, respectively, and percentages of inner hair cell death were 61.4, 48.1, 10.2, 5.4 and 0%, respectively. Ultramicroscopic examination showed that hair cell death was necrotic. Although NOC-5 is useful for study of NO, its cleavage products are also ototoxic.

Animals↗

Local substances regulating cochlear blood flow.

The regulation of cochlear lateral wall blood flow was investigated in rats using histochemistry, immunohistochemistry and transmission electron microscopy. The contractile protein, tropomyosin (TM) was localized in the pericyte around the vessels of spiral ligament but little was seen around strial capillaries. Prostaglandin I2 (PGI2) is a vasodilatory substance produced by PGI2 synthase (PGI2S), which is present in the endothelium of the vessels of spiral ligament but not much is present around strial capillaries. Endothelial nitric oxide synthase (eNOS) was present in the endothelium of both the vessels of spiral ligament and strial capillaries. These findings indicate that the blood flow of the cochlear lateral wall is regulated mainly in the spiral ligament by locally produced substances and that strial blood flow is not significantly regulated by pericytes responsible for enlargement or constriction of capillaries.

Animals↗

Surgical treatment of cancer extending from the retromolar fossa to the masticator space.

Cancer extending from the retromolar fossa to the masticator space with neck metastasis (T4N2M0, Stage IV) was surgically removed en bloc by maxillectomy using a mandibular swing technique. This approach allowed a wide surgical view and was useful as handling the external and internal pterygoid muscles and upper neck dissection could be combined. Though there have been several surgical approaches to the masticator space, in the case of tumors which are commonly malignant there, this approach is useful and satisfactory.

Carcinoma, Squamous Cell↗

Study of tuberculosis in the field of otorhinolaryngology in the past 10 years.

Over the 10 years from 1988 to 1997, a total of 18 cases of tuberculosis of the head and neck (8 of the cervical lymph node, 5 of the larynx, 2 of the salivary glands, and 1 each of the hypopharynx, tongue and middle ear) were diagnosed in our department. Four cases were diagnosed in 1996 and 8 in 1997, indicating a rapid increase over these 2 years. Definitive diagnosis was based on histopathological examination in 14 cases, detection of M. tuberculosis in 1 case and exclusion diagnosis, mainly using the tuberculin skin test, in 3 cases. The length of time from the first examination to obtaining a definitive diagnosis was 14.2 +/- 6.5 days in five subjects in whom tuberculosis was suspected from the beginning or in whom tuberculosis was suggested by the physician in making a differential diagnosis, 25.3 +/- 17.2 days in the group in whom malignant tumour was suspected and 64.3 +/- 57.3 days in other cases. Although no significant difference was found (p = 0.077), the length of time until diagnosis tended to be shorter in the cases that were suspected of having tuberculosis from the beginning. Family history and past history of tuberculosis, contact with a tuberculous patient and abnormal findings at chest X-ray were examined as background factors, and some of these were present in nine out of the 18 cases. In the five cases diagnosed in the early stage, some of the background factors were found in four cases. However, no significant difference in the time until definitive diagnosis was found between the groups with or without background factors in all cases (p = 0.675). These results suggest the importance of considering tuberculosis when performing differential diagnoses.

Adolescent↗

Apoptotic cell death in Kikuchi's disease: a TEM study.

The pathogenesis of Kikuchi's disease (Kikuchi-Fujimoto disease, histiocytic necrotizing lymphadenitis) remains unclear. However, some previous studies have suggested that a disorder in cellular immunity is responsible for this disease, and apoptotic cell death appears to be the principal finding in the histogenesis of this disease. In the present study, a lymph node from a female patient with Kikuchi's disease was examined by transmission electron microscopy (TEM). TEM revealed specific morphological features of apoptotic cells, such as nuclear chromatin condensation and fragmentation along the nuclear membrane with intact organelles, and the presence of histiocytes phagocytosing karyorrhectic debris (apoptotic bodies) in areas affected by Kikuchi's disease. Although neither the role nor the trigger of apoptosis in Kikuchi's disease has been clearly determined, our findings show that apoptotic cell death clearly plays a role in the pathogenesis of Kikuchi's disease.

Adult↗

Cell death caused by the acute effects of aminoglycoside and zinc in the ampullary cristae of guinea pigs.

We reported that apoptosis occurred in the guinea pig vestibular hair cells after chronic aminoglycoside treatments. In the present study, we used in situ nick-end labeling to determine whether apoptosis was also induced by the acute effects of aminoglycosides in guinea pig ampullar cristae. In addition, we evaluated the effect of zinc supplements upon these ototoxic treatments. After a local application of streptomycin directly to the round window, we found labeled bodies in the vestibular hair cells. The zinc supplement increased the number of labeled bodies resulting in severe hair cell loss. These findings indicate that the acute effects of aminoglycosides also induce apoptosis of the vestibular hair cells, and that zinc enhances aminoglycoside ototoxicity. Consequently, we propose that an interaction with ion channels may play a key mechanism in the processes of apoptosis affecting the vestibular hair cells.

Administration, Topical↗

Hemorrhagic type moyamoya disease.

The clinical picture of hemorrhagic type Moyamoya disease was analyzed in 20 cases. Hematoma at the basal ganglia was noted in 40% of cases, intraventricular hemorrhage (IVH) in 30%, thalamic hemorrhage with ventricular rupture in 15% and subcortical hemorrhage in 5%. The location was undetermined in two cases (10%) due to bleeding in the pre-computed tomography (CT) era. The frequencies shown above were correlated well to previous reports. In magnetic resonance imaging (MRI) performed 1 year or more after IVH, the primary bleeding site was demonstrated at the lateral wall of lateral ventricle, in portion density weighted and T2 weighted images. MRI can detect the site of old bleeding points and its chronological change if the study is repeated. In a follow-up period of 6.2 years, 35% of the cases had rebleeding once or twice. The second bleeding occurred seven times and the third twice. IVH occurred five times and the most common, basal ganglia hematoma three times while thalamic hemorrhage once. As a result, the rate of good outcome was 60% after the first bleeding and 40% after rebleeding. The mortality rate was 5% after the first 25% after rebleedings. Factors related to rebleedings and their poorer outcome are sex (with women being more susceptible), massive ICH and early recurrence. Rebleeding worsened the outcome. Therefore, prevention of rebleeding is important. From a therapeutic viewpoint, although a close relation between rebleeding and untreated hypertension could not be established, blood pressure control is critical at the both acute and chronic stages. Bypass surgery for bleeding type of Moyamoya disease seems to be less promising than ischemic type, even though a definite answer may not be obtained from our small number of cases.

Adolescent↗

Nitric oxide synthase and contractile protein in the rat cochlear lateral wall: possible role of nitric oxide in regulation of strial blood flow.

The present study demonstrated by histochemical and immunohistochemical methods that NADPH diaphorase reactivity, endothelial nitric oxide synthase (eNOS)-like immunoreactivity, and tropomyosin-like immunoreactivity, were located within the rat cochlear lateral wall. Both NADPH diaphorase reactivity and eNOS-like immunoreactivity were found mainly in the endothelium of the strial capillaries (ESC) and that of the vessels of the spiral ligament (ESL). These reaction products appeared to be somewhat more common in the ESC than in the ESL. On the other hand, tropomyosin-like immunoreactivity was localized in tissues outside the endothelium and its intensity was greater in the ESL than in the ESC. These findings suggest that nitric oxide (NO) produced by eNOS may play a role in regulating the blood flow of the cochlear lateral wall. In addition, NADPH diaphorase reactivity, eNOS-like immunoreactivity, and tropomyosin-like immunoreactivity showed different patterns of distribution between ESC and ESL. This suggests that in these two sites blood circulation is controlled by NO through two different mechanisms that are suitable for regulating strial blood flow.

Animals↗