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Biomedical subjects

K Mishima

Publications and source records attributed to K Mishima.

At least 73 records · Page 4Linked to original sources
PubMed2000

Supplementary administration of artificial bright light and melatonin as potent treatment for disorganized circadian rest-activity and dysfunctional autonomic and neuroendocrine systems in institutionalized demented elderly persons.

Increased daytime napping, early morning awakening, frequent nocturnal sleep interruptions, and lowered amplitude and phase advance of the circadian sleep-wake rhythm are characteristic features of sleep-waking and chronobiological changes associated with aging. Especially in elderly patients with dementia, severely fragmented sleep-waking patterns are observed frequently and are associated with disorganized circadian rhythm of various physiological functions. Functional and/or organic deterioration of the suprachiasmatic nucleus (SCN), decreased exposure to time cues such as insufficient social interaction and reduced environmental light, lowered sensitivity of sensory organs to time cues, and reduced ability of peripheral effector organs to express circadian rhythms may cause these chronobiological changes. In many cases of dementia, the usual treatments for insomnia do not work well, and the development of an effective therapy is an important concern for health care practitioner and researchers. Recent therapeutical trials of supplementary administration of artificial bright light and the pineal hormone melatonin, a potent synchronizer for mammalian circadian rhythm, have indicated that these treatments are useful tools for demented elderly insomniacs. Both bright light and melatonin simultaneously ameliorate disorganized thermoregulatory and neuroendocrine systems associated with disrupted sleep-waking times, suggesting a new, potent therapeutic means for insomnia in the demented elderly. Future studies should address the most effective therapeutic design and the most suitable types of symptoms for treatment and investigate the use of these tools in preventive applications in persons in early stages of dementia.

Aged↗
PubMed2000

Levels of beta-human chorionic gonadotropin in cerebrospinal fluid of patients with malignant germ cell tumor can be used to detect early recurrence and monitor the response to treatment.

BACKGROUND: Tumor marker-producing germ cell tumors of the central nervous system are malignant and require radiation and/or chemotherapy. Although serum beta-human chorionic gonadotropin (hCG) has been used to monitor the course of treatment, the levels of beta-hCG in the cerebrospinal fluid (CSF) have not been measured routinely in the clinic. To determine whether they can be used to evaluate parameters of tumor status, such as progression or response to therapy, levels of beta-hCG in the serum and CSF of patients with germ cell tumors were studied. METHODS: Fifty-four paired samples of CSF and serum were taken from seven patients with germ cell tumor and their beta-hCG levels were measured. Beta-hCG was negative in both serum and CSF in 11 instances and the levels in the other 43 paired samples were analyzed for any correlation or relationship to therapy. They were also compared with the clinical courses. RESULTS: The mean CSF beta-hCG level was 11.5 mIU/ml, which was significantly higher than the level in serum (3.5, p = 0.002). In all the paired samples except for one time point, the level in CSF was higher than that in serum. Out of 43 instances where the beta-hCG level in CSF was elevated, the level in serum was elevated in only 16 (37.2%). Among cases of recurrent malignant germ cell tumor, there were nine instances of recurrence or progression despite therapy. In all five instances where beta-hCG CSF levels were measured, the levels were elevated prior to any increase or detectability of the serum values. CONCLUSION: It seems likely that the level of beta-hCG in CSF is a good marker for monitoring tumor recurrence or evaluation of treatment results.

Adolescent↗
PubMed2000

The scopolamine-induced impairment of spatial cognition parallels the acetylcholine release in the ventral hippocampus in rats.

We investigated the relationship between the induction of spatial cognition impairment in the 8-arm radial maze task and regional changes (ventral hippocampus (VH), dorsal hippocampus, frontal cortex, and basolateral amygdala nucleus) in brain acetylcholine (ACh) release using microdialysis in rats treated with muscarinic (M) receptor antagonists. In a behavioral study, two M1 antagonists, scopolamine (0.5 mg/kg, i.p. and 20 microg, i.c.v.) and pirenzepine (80 microg, i.c.v.), but not an M2 antagonist, AF-DX116 (40-80 microg, i.c.v.), disrupted spatial cognition in the 8-arm radial maze task. In brain microdialysis with Ringer's solution containing 0.1 mM eserine sulfate, scopolamine and AF-DX116, but not pirenzepine, increased ACh release in the VH. Moreover, in the bilateral injection of scopolamine (2 microg/side), the VH and dorsomedial thalamus nucleus were important regions for scopolamine-induced impairment of spatial cognition. A simultaneous determination of the behavioral changes revealed that scopolamine (0.5 mg/kg, i.p.) markedly decreased the ACh contents and also increased the ACh release in all regions tested. Especially, the changes in the ACh release of the VH closely paralleled the induction of the scopolamine-induced impairment of spatial cognition. These results suggest that the blocking balance between M1 and M2 muscarinic receptor in the VH therefore plays a major role in the spatial cognition impairment induced by scopolamine in the 8-arm radial maze task.

Acetylcholine↗
PubMed2000

Unfolding of poly-L-glutamic acid by microbubbling of supercritical carbon dioxide.

The conformational changes in alpha-helical poly-L-glutamic acid caused by microbubbling supercritical CO2 were investigated with circular dichroism spectra. After microbubbling using a micropore filter at 35 and 30 MPa for 30 min, alpha-helix content decreased to 37%, while without the filter it was 68%. The alpha-helix structure was significantly decomposed by a high density of CO2. No important changes were observed in heating, autoclaving, or pH-lowering.

Carbon Dioxide↗
PubMed2000

Comparison between palatal configurations in UCLP infants with and without a Hotz plate until four years of age.

OBJECTIVE: To evaluate the efficacy of presurgical orthopedic treatment three dimensionally, we previously developed a novel measuring system and described the efficacy of the treatment until 18 months of age. The aim of this study was to compare palatal configuration in complete unilateral cleft lip and palate (UCLP) infants fitted with a Hotz plate to those without it until four years of age using the same measuring system. PATIENTS: Twenty complete UCLP infants were divided into two groups. A Hotz plate was used with 12 patients who first visited our clinic from January 1990 to March 1992 and was not used with an additional eight patients who first visited from April 1992 to July 1993. MAIN OUTCOME MEASURES: Palatal casts taken from birth until four years of age were measured three dimensionally and were compared between the two groups. RESULTS AND CONCLUSIONS: The width of the palate was larger in the group with a Hotz plate than in the group without it at four years of age. No difference was observed between the anteroposterior distance of the palate in the two groups at four years of age. Similarly, the alveolar arch form did not differ between the two groups. The degree of curvature of the palatal surface was smaller in the group with a Hotz plate than in the group without it. These data were similar to data obtained at 18 months of age.

Child, Preschool↗
PubMed2000

[Histological identification of brainstem neurons related to generation of rhythmical jaw movements in the rat].

Rhythmical jaw movements (RJM) were induced by stimulation of the oral cavity or the cerebral peduncle in the anesthetized rat. We found that the phase-dependent rhythmical (RJM-phasic) neuronal activities were necessary for the generation of RJM and iontophoretic application of glutamate activated a small number of these neurons rhythmically in phase with simultaneous RJM (Glu-RJM-phasic neurons) although it activated most RJM-phasic neurons tonically without RJM. N-(2-aminoethyl) biotinamide hydrochloride was iontophoretically applied to visualize these neurons. An identified Glu-RJM-phasic neuron had the complicated outline of soma with eight or more short and long dendrites. The RJM-phasic neurons had the simple outlines of soma (fusiform, triangular or rhomboid) with several short dendrites. Differential activation by glutamate corresponded to differential morphological characteristics of the brainstem neurons related to RJM-generation.

Animals↗
PubMed1999

VHL gene inactivation in an endolymphatic sac tumor associated with von Hippel-Lindau disease.

The authors present a case of endolymphatic sac tumor, a rare adenomatous tumor of the temporal bone, in a patient with von Hippel-Lindau (VHL) disease. Sequencing and microsatellite analysis of DNA samples from the tumor showed a 1-base pair deletion in exon 1 of the VHL gene and loss of heterozygosity at chromosome 3p25.5, the locus for the VHL gene. The results indicate that VHL gene inactivation contributed to the oncogenesis of endolymphatic sac tumor and provide molecular genetic proof that this tumor is associated with VHL disease.

Adult↗
PubMed1999

Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer's type with disturbed sleep-waking.

BACKGROUND: There is growing evidence that the dysregulation of circadian rhythms may play an important role in irregular sleep-waking in demented elderly. In this study, we investigated daily variation of the pineal hormone melatonin, which has been reported to possess hypnogenic and synchronizing effects, in patients with senile dementia of Alzheimer's type. METHODS: Serum melatonin secretion rhythms in inpatients with senile dementia of Alzheimer's type (SDAT group, n = 10, average age = 75.7 years) with disturbed sleep-waking and nondemented elderly (ND group, n = 10, age = 78.3 years) without clinical sleep disorders in the same facility were monitored under a dim light condition without excessive physical exercise. RESULTS: The SDAT group showed a significantly higher degree of irregularities in actigraphically recorded rest-activity (R-A) rhythm during the 7-day baseline period compared with the ND group. The SDAT group simultaneously showed significantly reduced amplitude, larger variation of peak times, and diminished amount of total secretion in the melatonin secretion rhythm compared with the ND group. There were significantly positive correlations between the severity of R-A rhythm disorder and the reduced amplitude as well as diminished amount of total melatonin secretion. CONCLUSIONS: The SDAT patients with disturbed sleep-waking possessed melatonin secretion rhythm disorders that may play an important role in irregular sleep-waking in demented elderly.

Aged↗
PubMed1999

X-ray microanalysis of melanin granules of retinal pigment epithelium and choroid in hereditary copper deficient mice (macular mice).

The role of trace elements in vivo has not been completely clarified. Trace elements were studied in melanin granules in the retinal pigment epithelium (RPE) and choroid of hereditary copper-deficient macular mice as a model of Menkes' disease. The analysis of elements in these melanin granules was done by new methods: freeze-embedding and an energy dispersive X-ray microanalysis (EDX). We used 14-day- and 1-month-old male hemizygote macular mice for the experiments and normal litter-mates as controls. Melanin granules in RPE and choroid contained sulfur, chloride, calcium, iron, copper and zinc. Calcium and copper were especially abundant in 14-day-old hemizygote macular mice, although there were few melanin granules in their RPE. The fact that copper was most abundant in the melanin granules in the RPE of 14-day-old macular mice suggests that the synthesis of melanin granules in the RPE and choroid of the hemizygote macular mice cannot be completed because of the lower activity of copper-containing enzymes such as tyrosinase and the abnormal copper distribution in various organs. Therefore, the melanin granules in the RPE and choroid of hemizygote macular mice are irregular in shape and few in number. Large amounts of copper concentrated in melanin granules in the RPE and choroid of hemizygote macular mice might induce quantitative abnormalities of trace elements.

Aging↗
PubMed1999

Levels of human defensin-1, an antimicrobial peptide, in saliva of patients with oral inflammation.

OBJECTIVE: The purpose of this study was to investigate the presence of an antimicrobial peptide, human defensin-1, in the saliva of patients with oral inflammation. STUDY DESIGN: Whole saliva samples were collected from patients with oral inflammation and from healthy volunteers. Human defensin-1 in saliva was isolated and purified by reversed-phase high-performance liquid chromatography. The amino acid sequence and molecular weight of defensin-1 were determined. The concentration of defensin-1 in saliva was quantified by high-performance liquid chromatography. Serum C-reactive protein concentration was measured by particle-enhanced turbidimetric immunoassay. RESULTS: The salivary defensin-1 concentration was significantly higher in patients with oral inflammation than in healthy volunteers; furthermore, in patients with oral inflammation, the concentration was significantly higher before treatment than after treatment. In the patients with oral inflammation, there was a strong positive correlation between salivary defensin-1 concentration and serum C-reactive protein concentration. CONCLUSIONS: The findings suggest that defensin-1 in saliva may be a convenient marker of inflammation associated with oral disease.

Adult↗
PubMed1999

Preoperative concurrent chemoradiotherapy plus radical surgery for advanced squamous cell carcinoma of the oral cavity: an analysis of long-term results.

Locoregionally advanced squamous cell carcinomas of the head and neck continue to be a major clinical problem. We demonstrated in 1996 that preoperative concurrent cisplatin- or carboplatin-based chemotherapy and radiotherapy plus radical surgery in advanced oral cancer had minimal toxicity, had high clinical tumor response rates, was well tolerated and produced impressive complete response rates and a high 5-year survival rate. The purpose of the present study was the long-term follow-up of this treatment regimen for advanced oral carcinoma. Forty-eight patients with squamous cell carcinoma of the oral cavity (including soft palate) were treated preoperatively with cisplatin- or carboplatin-based chemotherapy in combination with simultaneous irradiation to a target volume of 40 Gy, and 2-6 weeks later underwent curative surgery. All patients with advanced Stage II (n=7), Stage III (n=22) and Stage IV (n=19) were treated and followed for an average of 7.2 years (range: 61-144 months). The overall actuarial survival of all patients was 81.3% at 5 years and also at 10 years. Progression-free survival at both 5 and 10 years was 84.8% for all patients, and 85.7% for Stage II, 90.0% for Stage III, and 78.9% for Stage IV patients. Progression-free survival rates according to the histopathologic regression grade of primary tumor following preoperative chemoradiotherapy at 10 years were 40. 0% for Grade IIa, 88.9% for Grade IIb, 100% for Grade III, and 87.5% for Grade IV. Patients who achieved good responses histopathologically (Grades IIb, III, IV) had superior survival rates in comparison to patients with extensive residual tumor (Grade IIa) in surgically resected specimens (p=0.0012). A better histologic regression grade was also associated with a higher survival rate even in the long-term analysis. This treatment regimen for advanced oral cancer produced high clinical and pathologic complete response and survival rates with an acceptable acute toxicity profile and lack of late therapeutic complications. The long-term follow-up showed gratifying results even for advanced oral cancers without a substantial increase in distant metastasis and second primary malignancy.

Adult↗
PubMed1999

Encapsulation of lysozyme in a biodegradable polymer by precipitation with a vapor-over-liquid antisolvent.

Lysozyme was encapsulated in biodegradable polymer microspheres which were precipitated from an organic solution by spraying the solution into carbon dioxide. The polymer, either poly(l-lactide) (l-PLA) or poly(DL-lactide-co-glycolide) (PGLA), in dichloromethane solution with suspended lysozyme was sprayed into a CO2 vapor phase through a capillary nozzle to form droplets which solidified after falling into a CO2 liquid phase. By delaying precipitation in the vapor phase, the primary particles became sufficiently large, from 5 to 70 microm, such that they could encapsulate the lysozyme. At an optimal temperature of -20 degrees C, the polymer solution mixed rapidly with CO2, and the precipitated primary particles were sufficiently hard such that agglomeration was markedly reduced compared with higher temperatures. More uniform particles were formed by flowing CO2 at high velocity in a coaxial nozzle to mix the droplets at the CO2 vapor-liquid interface. This process offers a means to produce encapsulated proteins in poly(DL-lactide-co-glycolide) microspheres without earlier limitations of massive polymer agglomeration and limited protein solubility in organic solvents.

Animals↗
PubMed1999

Spontaneous regression of a residual pineal tumor after resection of a cerebellar vermian germinoma.

A case of multiple intracranial germ cell tumor in which a pineal tumor regressed spontaneously after resection of the cerebellar mass is reported. Immunohistochemical staining of the cerebellar mass showed that most of the infiltrating lymphocytes were positive for CD3 and CD8. The anti-Ki-67 monoclonal antibody MIB-1 staining of the resected tumor revealed a high MIB-1 positivity ratio (36.1%) among the large tumor cells, and TUNEL staining demonstrated that positivity in up to 6% of the tumor cells. Possible mechanisms responsible for this spontaneous regression including immunological responses and apoptosis induced by T lymphocytes are discussed.

Adult↗
PubMed1999

Double-blind test on the efficacy of methylcobalamin on sleep-wake rhythm disorders.

The therapeutic effect of methylcobalamin (Met-12) on sleep-wake rhythm disorders was examined in a double-blind test. In the test group which was given a large dosage, a higher percentage of improvement was found compared to the control group with a small dosage, although the difference was not significant. The test group inconsistently showed significant improvement in both the sleep-wake cycle parameters and in clinical symptoms. The tendency was for the results to show a beneficial effect of Met-12 on rhythm disorders. However, because the percentage of improvement was low and significant improvement was inconsistent, Met-12 might be considered to have a low therapeutic potency and possible use as a booster for other treatment methods of the disorders.

Affect↗
PubMed1999

Computer aided three-dimensional analysis of nostril forms: application in normal and operated cleft lip patients.

The appearance of the nostril in cleft lip patients is very important in the subjective assessment of naso-labial forms and patient satisfaction. To improve the outcome of plastic surgery, a computer aided diagnostic system was developed. Facial forms were measured with a three-dimensional optical scanner (Ogis Range Finder RFX-IV) XYZ coordinates (256x240) and RGB (red, green, blue) image (512x480) data sets were then obtained with the apparatus. The nostril area was determined by discriminant analysis of the RGB data, and the landmarks of the nostril were extracted under geometric conditions. To assess the reliability of this technique with head inclination, five volunteers were measured in seven postures. Landmark stability was within approximately 1 mm when the Frankfort plane was 45-60 degrees. Subsequently, this system was applied to two cleft lip patients who had undergone a secondary nasal correction. For control data, 37 healthy adults (22 males and 15 females) were measured in the same manner. Nasal asymmetry in the unilateral case and wide and flat nostrils in the bilateral case were greatly improved after surgery. Conversely, the volume of the nasal tip decreased. This system was a great help in the diagnosis of nostril abnormalities.

Adolescent↗
PubMed1999

The gene for heparin-binding epidermal growth factor-like growth factor is stress-inducible: its role in cerebral ischemia.

The functions of the epidermal growth factor (EGF) family members in the adult brain are not known. This study investigated the changes in the expression of members of the EGF family following global ischemia employing in situ hybridization and immunohistochemical techniques to elucidate their roles in pathological conditions. EGF mRNA was not detected in either the control or the postischemic rat brain. Although transforming growth factor-alpha (TGF-alpha) mRNA was widely expressed in the normal brain, its expression did not change appreciably following ischemia. By contrast, heparin-binding EGF-like growth factor (HB-EGF) mRNA expression was rapidly increased in the CA3 sector and the dentate gyrus of the hippocampus, cortex, thalamus, and cerebellar granule and Purkinje cell layers. EGF receptor mRNA, which was widely expressed, also showed an increase in the CA3 sector and dentate gyrus. Conversely, HB-EGF mRNA did not show any increase prior to ischemic neuronal injury in the CA1 sector, the region most vulnerable to ischemia. Immunohistochemical detection of HB-EGF in the postischemic brain suggested a slight increase of immunostaining in the dentate gyrus of the hippocampus and the cortex. These findings showed that the gene encoding HB-EGF is stress-inducible, indicating the likelihood that HB-EGF is a neuroprotective factor in cerebral ischemia.

Animals↗
PubMed1999

A case of Pai syndrome.

A fourth patient suspected of having Pai syndrome is described. The female baby had a median cleft of the upper lip, a polypoid skin mass in the right nostril, and a conjunctival lipoma in the right eye. A median alveolar cleft was in the oral cavity. The polypoid skin mass was attached to the nasal septum, and a histologic examination disclosed mature adipose tissue with normal skin and no cartilaginous tissue. A computed tomographic scan revealed a lipoma of the corpus callosum. However, the patient was neurologically normal, and her electroencephalogram was also normal. Her growth and development have been within normal limits, and no convulsions have occurred.

Brain Neoplasms↗