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Biomedical subjects

Y Kitazawa

Publications and source records attributed to Y Kitazawa.

At least 19 recordsLinked to original sources

Changes in brain ECF amino acids in rats with experimentally induced hyperammonemia.

Using microdialysis, we studied brain extracellular fluid (ECF) amino acid metabolism in rats with experimentally induced hyperammonemia and regional elevation of brain ECF ammonia levels. The total brain ECF amino acid level was increased by an elevation of the blood ammonia level. Hyperammonemia elevated brain ECF aromatic amino acids and reduced arterial blood branched chain amino acids. When rats with hyperammonemia were intravenously administered norleucine, the brain ECF norleucine level rose markedly, suggesting increased permeability of the blood-brain barrier. When rats with hyperammonemia were infused with a branched chain amino acid-rich preparation, the elevated brain ECF aromatic amino acids level was not suppressed. Following local intracerebral ammonia infusion, only glutamate levels showed a marked elevation. These results suggest that impairment of the blood-brain barrier related to hyperammonemia increases the inflow of low molecular weight substances including amino acids. Furthermore, the ammonia-induced increase of glutamate in the cerebral ECF suggests that high ammonia levels may increase the excitability of the brain. Thus, ammonia may serve as a key factor in the onset of hepatic encephalopathy.

Amino Acids

Inhibition of corneal epithelial wound healing. A comparative study of mitomycin C and 5-fluorouracil.

PURPOSE: The purpose of this study is to assess the influence of the antiproliferative agents, 5-fluorouracil (5-FU) and mitomycin C (MMC), on the intact corneal epithelium and on epithelial wound healing in the rabbit cornea. METHODS: Using an eye cup made of polymethylmethacrylate, the intact rabbit corneas were bathed for 5 or 15 minutes with either MMC (in concentrations of 0.0016%, 0.008%, 0.04%, and 0.2%) or 5-FU (in concentrations of 1% and 5%). The same concentrations of MMC or 5-FU were applied to the cornea with the eye cup in which epithelial cells were mechanically removed. The contralateral fellow eyes, which were bathed in balanced salt solution in the eye cup, had the cornea intact or mechanically abraded and served as controls. Five to six animals were used only once for each concentration of MMC or 5-FU. RESULTS: Neither MMC nor 5-FU caused any discernible changes in the intact cornea of any of the eyes. The epithelial healing was retarded by mitomycin in a dose-related manner, and ID50 was calculated to be 0.06%. Five-fluorouracil 5% significantly delayed epithelial healing, but 1% failed to do so. Mitomycin C was estimated to be at least 125 times as potent as 5-FU in inhibiting corneal epithelial healing. CONCLUSION: These results indicate that particular care should be taken to minimize corneal contact with MMC in the clinical setting, particularly when epithelial defects are present.

Animals

Mitomycin concentration in rabbit and human ocular tissues after topical administration.

The authors measured mitomycin C (MMC) concentrations in ocular tissues with high-performance liquid chromatography. Mitomycin C concentration after a single subconjunctival injection of the drug in rabbit eyes showed a rapid decrease with a half-life of 0.18 to 0.30 hours for the conjunctiva and 0.20 to 0.45 hours for the sclera at the injection site. Irrigating the ocular surface with 200 ml of saline after MMC application reduced the initial drug concentration to one fifth in the sclera and to one fifteenth in the conjunctiva but did not change the half-life. The MMC concentration in human trabeculectomy specimens obtained immediately after MMC application (0.2 mg/0.5 ml) and irrigation was 5.4 to 12.0 micrograms/g with a mean of 8.4 micrograms/g, a level similar to that in the rabbit sclera immediately after the irrigation after administration of the same MMC dose. These results indicate that MMC disappears rapidly from the ocular tissues and that irrigating the tissues significantly reduces the tissue concentration of MMC.

Administration, Topical

[The influence of paraquat on cell cycle--analysis of cell kinetics using DNA/BrdU staining].

We examined the in vitro and in vivo effects of paraquat on the cell cycle. After we exposed paraquat to the cultured cell (MDCK), we examined cell kinetics by flow cytometry with BrdU-PI double staining. And we administered paraquat intravenously to the rats, we collected and separated rat's liver and pulmonary cells, and we examined the cell kinetics by same method. Consequently our study found that the cells in the S-phase were noted to be abundant, and we suggested that paraquat apparently arrested the cell cycle at S time, and that DNA damage was importance in the mechanism of paraquat toxicity.

Animals

[A case of nonbacterial thrombotic endocarditis presenting positive findings by two-dimensional echocardiography].

A 55-year-old woman was admitted to our hospital because of left hemiparesis. Brain CT and cerebral angiography demonstrated cerebral embolism due to occlusion of the sphenoidal part of the right middle cerebral artery. Two-dimensional echocardiography revealed mitral valve vegetation measuring 10 x 7 mm and slight mitral-valve regurgitation. Blood cultures were negative. She developed disseminated intravascular coagulation. Chest roentgenography and abdominal ultrasonography showed multiple liver and lung tumors, but she died before the primary lesion was detected. At autopsy, adenocarcinoma of the gall bladder was found. Friable vegetation was attached to the auricular surface of the mitral valve. Microscopic examination confirmed the diagnosis of nonbacterial thrombotic endocarditis. Although echocardiography is an important tool for diagnosing nonbacterial thrombotic endocarditis, few reports have described echocardiographic detection of nonbacterial thrombotic endocarditis. Because vegetation of nonbacterial thrombotic endocarditis is smaller than that of infective endocarditis (less than 3 mm), it is difficult for echocardiography to detect nonbacterial thrombotic endocarditis. Thus, a negative examination does not exclude the possibility of nonbacterial thrombotic endocarditis. To make an antemortem diagnosis of nonbacterial thrombotic endocarditis, we must perform echocardiography carefully in cases of cerebral infarction with carcinoma and/or DIC.

Adenocarcinoma

[The effect of the intraocular pressure reduction on glaucomatous disc changes and visual field defects].

The authors prospectively studied changes in the optic disc and visual field associated with intraocular pressure (IOP) reduction for one year after surgery in 12 primary open-angle glaucoma eyes of 7 patients who underwent trabeculectomy because of elevated IOP despite maximum tolerable medical therapy and whose cup volume was demonstrated to be decreased at 3 or 6 months after surgery. Topographic parameters including C/D ratio, rim area and cup volume were determined by the Optic Nerve Head Analyzer plus (Rodenstock). The 30-2 central threshold field was obtained with a Humphrey Field Analyzer at the same time. Mean deviation (MD), corrected pattern standard deviation (CPSD) and total deviation (TD) were used to evaluate visual field changes. Significant improvement of C/D ratio, rim area and cup volume and significant IOP reduction were noted at 1 year after surgery as compared with preoperative baseline value (p less than 0.01). Also the MD was significantly decreased at 1 year after surgery, compared with the preoperative baseline value (p less than 0.05). There was a significant negative correlation between the preoperative MD and the percent change of the MD at 1 year after surgery (r = -0.80, p less than 0.01). Our results suggest that the decrease of optic disc cupping can persist over one year after surgery and that the early visual field defects in glaucoma eyes can gradually improve in association with the decrease of cupping.

Adult

Determination of an appropriate laser setting for THC-YAG laser sclerostomy ab externo in rabbits.

To determine an appropriate setting for the THC-YAG laser (chromium-sensitized, thulium, and holmiumdoped YAG laser), we performed sclerostomy ab externo on 24 pigmented rabbits. The laser energy was delivered via a subconjunctivally-inserted fiberoptic probe that was placed at the limbus through a small conjunctival incision. We used four pulse-energy levels to perform the sclerostomies: 80 mJ, 120 mJ, 160 mJ, and 200 mJ. At all these levels, a new outflow pathway was easily created, a filtering bleb was formed, and intraocular pressure (IOP) was immediately reduced. Severe tissue damage around the sclerostomy site occurred with the 160-millijoule and 200-millijoule pulses. The 80-millijoule pulse created a relatively small patent sclerostomy, providing only relatively brief IOP reduction. We conclude that 120-millijoule is the most appropriate laser-pulse energy for use in pigmented rabbits.

Animals

[Visual field change and risk factors for progression of visual field damage in low tension glaucoma].

The authors carried out a prospective study in an attempt to determine the possible effect of intraocular pressure (IOP) and some clinical factors on the clinical course of low tension glaucoma (LTG). During the study period all the patients were followed without any antiglaucoma medication. The enrollment criteria for the study were reproducible, mild to moderate field loss as defined as a mean defect (MD) of greater than 2 dB and less than 10 dB or corrected loss variance (CLV) of greater than 7 dB revealed by the Octopus 201, G1 program. Forty-two consecutive patients (56 eyes) who fulfilled this criteria were enrolled. Baseline and follow-up examinations included applanation tonometry, perimetry with G1 program, blood pressure and pulse rate. When the MD increased by 4 dB or more on two consecutive perimetry examinations, the field defect was judged as "progressed". During the follow-up period (6-51 months, 25.1 +/- 12.5 months), the field defect progressed in 14 eyes of 12 patients. The life-table analysis (Kaplan-Meier) revealed that the rate of nonprogression of visual field defects was 55.5% at 48 months. The rate of nonprogression was significantly lower in 16 eyes with a mean IOP equal to or higher than 15 mmHg as opposed to 40 eyes with that lower than 15 mmHg (34.3% and 67.2% respectively, p less than 0.05). The results seem to indicate that IOP is likely to be responsible for the aggravation of visual fields in LTG. Canonical discriminant analysis revealed that the discriminant function containing four variables gives the best separation between the "progressed" and "nonprogressed" group (discriminant efficacy: 83.9%).

Adult

Trabeculectomy with mitomycin. A comparative study with fluorouracil.

We conducted a prospective, randomized study to compare mitomycin with fluorouracil for efficacy and safety as an adjunct to trabeculectomy in eyes with glaucoma with poor surgical prognosis. Thirty-two eyes of 32 patients were randomly allocated to either mitomycin (17 eyes) or fluorouracil therapy (15 eyes). Mitomycin (0.2 mg) was applied only once during trabeculectomy, and fluorouracil (5 mg) was subconjunctivally injected 10 times in the 2 weeks after surgery. Fifteen eyes (88%) in the mitomycin group and seven (47%) in the fluorouracil group achieved an intraocular pressure of less than or equal to 20 mm Hg without antiglaucoma medication. The follow-up period was 7 to 12 months. Corneal complications were less common in the group given mitomycin than in that given fluorouracil (12% vs 53%). The incidence of other complications was similar between the two groups.

Adult

The role of xanthine oxidase in paraquat intoxication.

The role of xanthine oxidase in the mechanism of paraquat toxicity was assessed by in vitro and in vivo experiments. Paraquat stimulated the reduction of cytochrome c by xanthine-xanthine oxidase system in vitro. Paraquat, when added in vitro, stimulated hypoxanthine-dependent superoxide production in the cytosol of rat lung. Tungsten-feeding inhibits xanthine oxidase activity in a variety of tissues in experimental animals. Its therapeutic effect on paraquat intoxication was studied in this paper. In rats fed a tungsten-enriched diet for 5 weeks prior to intraperitoneal injection of 50 mg/kg paraquat dichloride, the mortality decreased significantly compared with rats fed a standard diet. Pretreatment with oxypurinol (1000 mg/kg, s.c.) also ameliorated the paraquat toxicity in rats. We conclude that xanthine oxidase plays an important role in paraquat toxicity and that xanthine oxidase inhibitors may become antidotes for paraquat intoxication.

Animals

Diurnal variation of intraocular pressure of normal-tension glaucoma. Influence of sleep and arousal.

The measurement of the diurnal variation of intraocular pressure (IOP) is indispensable for the diagnosis of normal-tension glaucoma (NTG). To determine the diurnal variation of IOP, its measurement has to be made repeatedly for 24 hours, which interferes with patients's sleep at night and may influence the physiologic IOP variation. The authors studied the IOP variation in 82 NTG suspects, whose IOP was first measured every 2 hours for 24 hours. The following night they were suddenly aroused without any notice and IOP was measured. The diurnal IOP variation of NTG patients was found to be similar to that of the normal population and there was no significant difference in the IOP values at the same time points on the two successive nights. Sleep may have little, if any, influence on diurnal IOP variation in NTG patients.

Adult

Changes in gastric mucosal content of adenosine, xanthine and hypoxanthine induced by restrained water immersion stress: antiulcer effects of tetraprenylacetone.

The purpose of this study was to clarify the involvement of adenine nucleotide metabolism and substrates of the xanthine-xanthine oxidase system as the source of oxygen free radicals in a rat model of restrained water immersion stress ulceration. The gastric mucosal concentrations of adenine-5'-triphosphate (ATP), adenine-5'-diphosphate (ADP), adenine-5'-monophosphate (AMP) and thiobarbituric-acid (TBA)-reactant substances were measured after 4, 8 and 12 h restrained water immersion stress. The gastric mucosal concentrations of the nucleoside adenosine, the purine bases xanthine and hypoxanthine, and the final metabolic product uric acid, were measured after 4 h of restrained water immersion stress. The concentrations of ATP diminished significantly after 4, 8 and 12 h of restrained water immersion stress. However, the observed stress-induced changes in ADP were not significant. AMP concentrations increased significantly after 4, 8 and 12 h of stress. The adenylate pool (ATP + ADP + AMP) dropped significantly from the prestress value after 4, 8 and 12 h of stress, and the concomitant energy charge (EC = ATP + 0.5 ADP/ATP + ADP + AMP) decreased significantly after 4 and 8 h of stress compared with the prestress value. Gastric mucosal concentrations of TBA-reactant substances displayed a significant increase after 4 h of stress, and remained unchanged after 8 and 12 h of stress from the level after 4 h. Four hours of restrained water immersion stress induced an increase in adenosine and uric acid concentrations and a decrease in the hypoxanthine concentration of the gastric mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides

[Study on fluidized melt-granulation. I. Examination of the factors on the granulation].

The purpose of this study is to develop a new granulation method by using a fluidized-bed granulator, which requires a nucleus with a low melting point as a binder. This method was named as fluidized melt-granulation. The technique is very simple and useful. In this paper, the granulation mechanism and the effect of the physico-chemical properties of raw materials on the growth of the granules were investigated. The results were as follows: (1) The mixture of the nucleus and the other powder particles was heated up to the melting point of the nucleus by hot inlet air, immediately resulting in the generation of the adhesion of the powders on the melted nucleus. The granules grew as the melted material immersed into the void space among the adhered particles. (2) The lower the viscosity of the melted nucleus was, the faster the granule grew. (3) The shape and the size of the nucleus affected those of the products. (4) The optimum mixing ratio between the nucleus and the granulated materials existed and it depended on the ratio between the surface areas of these materials.

Adjuvants, Pharmaceutic

Epidemiology of glaucoma in Japan--a nationwide glaucoma survey.

A population-based, collaborative glaucoma survey was conducted in seven regions throughout Japan, during the years of 1988 and 1989. The total number of subjects examined was 8,126 out of 16,078 residents aged 40 years or older, representing a participation rate of 50.54%. There were no significant differences in background factors between participants and randomly sampled nonparticipants. A mainstay of the screening consisted of tonometry and fundus photography with nonmydriatic camera, followed by automatic perimetry as a recall examination. Overall prevalences obtained were primary open-angle glaucoma (POAG) 0.58%, low-tension glaucoma (LTG) 2.04%, primary angle closure glaucoma (PACG) 0.34%, other types of glaucomas 0.60%, and ocular hypertension (OH) 1.37% at the time of screening. The very high prevalence of LTG and extremely low prevalence of OH in the Japanese might reflect a racial peculiarity in the age-specific trend of the intraocular pressure. The prevalence of PACG was found much higher in Japanese than in Caucasians, with a predilection for women. Racial peculiarities as revealed in this study were discussed, with particular reference to the refractive status in the Japanese that showed progressive decrease in myopia with age.

Adult

[On factors related to the width of anterior chamber angle--multivariate analysis of biometrically determined values].

Primary angle-closure glaucoma (PACG) is associated with certain biometric ocular features such as shallow anterior chamber, axial hyperopia, increased thickness of the lens and small corneal diameter. The vast majority of previous studies on PAGG has shown that females are affected more frequently than males. In an attempt to study the relationship between the angle width and ocular dimensions, we carried out gonioscopic examination and biometric measurements (corneal diameter, corneal radius, anterior chamber depth, lens thickness, relative lens position and axial length) in 1,169 eyes of 585 adult subjects who participated in the glaucoma screening in Gifu Prefecture. It was found that the angle width significantly correlated with each biometric value. The coefficient of determination calculated by multiple regression analysis was 0.41, suggesting that factors other than these are involved in determining the angle width. When the angle width of females was compared to that of males with identical refractive errors and biometric values, the angle width of females was significantly narrower than that of males. Hence, the difference in ocular dimensions does not adequately explain the higher incidence of narrow angle in females. Increased asymmetry of angle width between a pair of eyes with aging appeared to be related to asymmetry of lens thickness, anterior chamber depth and lens position.

Adult

[Reproducibility of three-dimensional point by point measurements on the optic nerve head surface using a computerized image analysis system].

The reproducibility of topographic measurements of the optic nerve head was studied using a prototype Humphrey Retinal Analyzer system (Allergan Humphrey SKB, San Leandro, CA). Digital simultaneous stereographic images were obtained using programs in the Analyzer. The analyzer expressed the results in terms of microns of elevation at approximately 300 locations on the optic nerve head surface. At least 3 separate stereoscopic digital images were made of each of 8 eyes of 5 subjects. One randomly selected image of each disc was analyzed twice in order to determine intra-image reproducibility, and topographic analyses of two randomly selected images of each disc were compared to estimate the inter-image variability. We calculated the coefficients of variation (CV) of measurements at the center point of the optic disc. Further, we computed the absolute value of the difference in the degree of elevation among the measured locations on the optic disc and calculated the median and 95 percentile value of that group of approximately 300 differences. The CV, medians, and the 95 percentile values thus obtained for the 8 discs ranged from 0 to 6.1%, from 6 to 20 microns, and from 20 to 69 microns, respectively for intra-image reproducibility. Those for inter-image reproducibility ranged from 1.5 to 59.1%, from 6 to 33 microns, and from 36 to 92 microns, respectively.

Humans

[Chronic myelocytic leukemia induced into remission by interferon-alpha associated with early esophageal cancer].

A fifty-one-year-old male patient visited the Department of Dermatology of Toho University Ohashi Hospital with a complaint of generalized exanthema, which was diagnosed assyringoma; at that time his leukocytosis was recognized. He was admitted to our department on August 8, 1988. Physical examination on admission revealed slight hepatosplenomegaly. WBC count was elevated (50,700/microliters). He was diagnosed as having Ph1-positive CML in the chronic phase and was treated with IFN-alpha (HLBI, Sumitomo, 3 x 10(6) units/day, daily, I. M.) from August 12, but an elevated lesion was detected at the lower part of his esophagus by endoscopy, and it was diagnosed by biopsy as squamous cell carcinoma. Radical operation for esophageal cancer was performed on September 26; at that time his WBC count was 17,400/microliters. After discharge, his WBC level was maintained within normal range by IFN-alpha. On August 2, 1989, he was readmitted to our hospital because of lymphoblastic crisis. Although he attained transient complete remission, he died of pneumonia after the relapse on January 10, 1990. IFN-alpha therapy is suggested to be useful for the treatment of CML associated with gastrointestinal cancer because of its possible parenteral administration and mild toxicity.

Carcinoma, Squamous Cell

Biphasic intraocular pressure response to Q-switched Nd:YAG laser irradiation of the iris and the apparent mediatory role of prostaglandins.

In rabbits, laser irradiation of the iris causes an immediate rise in intraocular pressure (IOP), with a concomitant increase of prostaglandins (PGs) in the aqueous humor. We studied IOP responses to Q-switched Nd:YAG laser application to the iris in unanesthetized rabbits, and found that a prolonged IOP reduction lasting for 6-24 hr invariably followed the transient IOP rise of 0.5-2 hr duration. The magnitude of both the IOP rise and reduction was dependent on the level of laser energy. A masked, randomized study revealed that the intraperitoneal administration of indomethacin (50 mg kg-1) prior to laser application significantly reduced the ocular hypertensive and hypotensive responses to laser irradiation (energy: 24 mJ). The maximum IOP rise from baseline was 5.4 +/- 3.0 mmHg (n = 10) with the intraperitoneal vehicle and 1.5 +/- 4.2 mmHg (n = 10) with intraperitoneal indomethacin administration. Thus, the difference was statistically significant (P less than 0.025, Student's t-test). The maximum IOP reduction from baseline was -8.5 +/- 2.6 mmHg (n = 10) with the intraperitoneal vehicle and -4.0 +/- 2.4 mmHg (n = 10) with intraperitoneal indomethacin (P less than 0.001, Student's t-test). The concentration of PGE2 in the aqueous humor, as determined by radioimmunoassay on samples obtained at 2 and 4 hr after laser application, was found to be significantly increased in rabbits that received the vehicle solution but not in animals that were pretreated with intraperitoneal injection of indomethacin. This suggests that this PG or other cyclooxygenase products are involved with mediation of the initial IOP increase and the prolonged decrease in IOP that follows laser irradiation of the iris.

Animals