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Biomedical subjects

K Niwa

Publications and source records attributed to K Niwa.

At least 127 records · Page 7Linked to original sources

[Oligospermia improved by switching an anticonvulsant from phenytoin to valproate].

We report a case of 30-year-old man with generalized seizure, who had received phenytoin (PHT) for more than 6 years, but developed decrease in sperm count and motility. After PHT had been discontinued and valproate (VPA) had been administered for 3 months, his sperm activity became normalized. The decrease in sperm motility was the most important cause of his infertility. Sperm motility has been reported to be inversely correlated with the ratio of the concentrations of antiepileptic drugs in the plasma and semen. In our case, the ratio was 0.21 for PHT and 0.08 for VPA. We wish to emphasize the importance of measuring the concentration of antiepileptic drugs in the semen of infertile young males if they are on anticonvulsants.

Adult↗

Effects of tinted intraocular lens on contrast sensitivity.

We evaluated contrast sensitivity and glare in 64 pseudophakic eyes. An ultraviolet-absorbing intraocular lens (IOL) was implanted in 32 eyes and a noncyanopsia yellow-tinted IOL was implanted in 32 eyes. The latter lens was designed to effectively absorb light below a wave-length of 500 nm. Contrast sensitivity was measured at a pupil diameter of 3 mm using an artificial pupil. The implanted yellow-tinted IOL showed improved contrast sensitivity in the middle spatial frequencies of 6 and 12 c/deg in photopic and mesopic vision. In addition, the yellow-tinted IOL decreased the effect of central glare on the contrast sensitivity.

Aged↗

Overexpressions of c-fos/jun mRNA and their oncoproteins (Fos/Jun) in the mouse uterus treated with three natural estrogens.

To further understand hormonal carcinogenesis of natural estrogens (estrone, 17 beta-estradiol (E2) and estriol), we determined the expressions of c-fos/jun mRNA, and their oncoproteins (Fos/Jun) with intracellular localization in the uterus of ovarectomized mice treated with these estrogens. Mid-term chronic, as well as short-term assays were examined. Of three estrogens examined, mid-term chronic E2-treatment significantly increased the expression of c-fos/jun mRNA, and their oncoproteins (Fos/Jun). These were most prominently expressed in glandular cells of E2-treated mouse endometrium. Therefore, mid-term chronic E2-treatment might partially induce glandular cell transformation of uterine endometrium via overexpression of Fos/Jun.

Animals↗

Rare occurrence of p53 and ras gene mutations in preneoplastic and neoplastic mouse endometrial lesions induced by N-methyl-N-nitrosourea and 17 beta-estradiol.

To examine K-, H-, or N-ras and p53 gene mutations in mouse endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17 beta-estradiol, we performed polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) in 13 adenocarcinomas and 11 other preneoplastic lesions. A significant shifted band in exon 5 of p53 using PCR-SSCP was detected in one of 13 adenocarcinomas. Direct sequencing showed that the mutation was TCA-to-TGA (Ser-to-End) transition. These results suggest that ras gene mutations were not related to carcinogenesis and inactivation of p53 may occur with low frequency during the mouse endometrial carcinogenesis in this model.

Adenocarcinoma↗

Ca(2+)-regulating mechanisms that modulate bull sperm capacitation and acrosomal exocytosis as determined by chlortetracycline analysis.

We have used chlortetracycline (CTC) analysis to investigate mechanisms that may play important roles during bull sperm capacitation in a culture medium (containing glucose, heparin, and caffeine) known to promote capacitation and fertilization in vitro. In initial experiments employing the Ca2+ ionophore A23187, we identified three discrete CTC patterns so similar to those described for mouse and human sperm that we have employed the same nomenclature: "F," characteristic of uncapacitated, acrosome-intact cells; "B," characteristic of capacitated, acrosome-intact cells; "AR," characteristic of capacitated, acrosome-reacted cells. Over a 60-min period, A23187 stimulated significant increases in B and AR pattern cells, with concomitant decreases in F pattern cells, suggesting a very rapid transition from the uncapacitated to the capacitated state and then on to exocytosis. Without ionophore, significant changes in the proportions of F and B pattern cells were also observed, but the maximum responses required 4 hr; the proportion of AR cells was consistently approximately 15% throughout, indicating a low incidence of spontaneous acrosome loss. Analysis of cells in media with altered composition indicated that the inclusion of either heparin or caffeine significantly promoted capacitation to about the same extent, but together, heparin plus caffeine had an even more stimulatory effect. Despite this, none of these treatments triggered acrosome loss above the levels seen in media lacking these constituents. In the presence of caffeine, with or without heparin, the inclusion of glucose had little effect on responses, but in the presence of heparin there were fewer B cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗

Successful pregnancy in a patient with pseudomyxoma peritonei arising from ovarian mucinous cystadenocarcinoma treated with cisplatin.

A 24-year-old Japanese woman clinically showing pseudomyxoma peritonei arising from ovarian mucinous cystadenocarcinoma FIGO stage Ic is reported. She received intra-abdominal administrations of cisplatin five times following left oophorectomy. After being free of disease for 6 months, she conceived and carried two pregnancies to successful deliveries at 34 and 37 weeks, respectively. At the Cesarean sections, there were no abnormal findings except for right ovarian mucinous cystadenoma. She has had no evidence of recurrence by the time of the 60-month postoperative examination.

Abdomen↗

Synergetic effects of epidermal growth factor and gonadotropins on the cytoplasmic maturation of pig oocytes in a serum-free medium.

Cumulus-enclosed or cumulus-free pig oocytes were cultured for 48 h in a serum-free maturation medium, TCM-199B containing 1 mg/ml polyvinylalcohol, supplemented with gonadotropins (PMSG + hCG) and/ or epidermal growth factor (EGF), and inseminated with frozen-thawed ejaculated spermatozoa. Fourteen hours after insemination, the ability of oocytes to form male pronucleus (MPN) was examined. EGF significantly increased the ability of cumulus-enclosed oocytes to form MPN irrespective of the concentrations (1-100 ng/ml) tested. Gonadotropins had a greater effect than EGF on MPN formation in cumulus-enclosed oocytes, and a synergetic effect was observed when EGF and gonadotropins were added together. However, neither EGF nor gonadotropins exhibited a stimulatory effect on MPN formation in cumulus-free oocytes. These results indicate that the role(s) of both EGF and gonadotropins in stimulating cytoplasmic maturation of pig oocytes is mediated by cumulus.

Animals↗

Inhibitory effects of medroxyprogesterone acetate on mouse endometrial carcinogenesis.

The present study was undertaken to examine the effects of cyclic administration of low-dose progestogen on endometrial carcinogenesis in mice. A total of 115 female ICR mice, 10 weeks of age, were divided into four experimental and control groups. Mice in groups 1-3 received laparotomy and were injected with N-methyl-N-nitrosourea (MNU) solution at a dose of 1 mg/100 g body weight to the left uterine tube and with normal saline to the right uterine tube. From one week after the MNU exposure, groups 1 and 2 were given 5 ppm 17 beta-estradiol (E2)-containing diet throughout the experiment. Mice in group 1 received 5 s.c. injections of medroxyprogesterone acetate (MPA) (2 mg/mouse) at intervals of 4 weeks from week 7. Group 3 was treated with MNU/normal saline alone. Group 4 consisted of mice treated with MPA alone. At the termination of the experiment (week 30), all animals were killed and autopsied for pathological examinations. It was found that adenocarcinomas and preneoplastic lesions developed in the bilateral uterine corpora in mice of groups 1-3. MPA treatment significantly decreased the weight of the uterine corpus (P < 0.05) and the incidences of endometrial adenocarcinoma and atypical or adenomatous (P < 0.001) but not cystic glandular hyperplasias in the MNU/E2-treated groups. Additionally, MPA treatment tended to decrease the proliferating cell nuclear antigen-labeling index in endometrial glandular cells. These data indicate that MPA, even at low dose, has an inhibitory effect on mouse endometrial carcinogenesis induced by MNU and E2.

Animals↗

Development of a colon delivery capsule and the pharmacological activity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in beagle dogs.

A peroral dosage form was examined to deliver recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the colon in beagle dogs. A new gelatin capsule with its inside surface coated with ethylcellulose was prepared for this purpose. RhG-CSF was dissolved with propylene glycol and was filled in the capsule. Several kinds of ethylcellulose-gelatin capsules with an ethylcellulose layer of thickness 46 to 221 mm were used. The capsule was filled with propylene glycol solution containing fluorescein as an absorption marker, castor oil derivative and citric acid. The hardness of the capsule was tested after the gelatin layer was dissolved using a hardness tester and was dependent on the thickness of the ethylcellulose layer of the capsule. The time, Tmax, at which plasma fluorescein level reaches its maximum following oral administration of ethylcellulose capsules was used as a parameter for the in-vivo disintegration time of the ethylcellulose capsule into the colon. Capsules of thickness 84 mm with a Tmax of 4-6 h were filled with rhG-CSF solution containing fluorescein and were administered to dogs. After administration, blood samples were collected for 96 h and the blood total leucocyte (BTL) counts were measured as a pharmacological index of rhG-CSF. The maximum BTL count appeared at 10 h then gradually decreased and returned to its normal level at 48 h. These results suggest the usefulness of ethylcellulose capsules for the delivery of rhG-CSF to the colon and the possibility of a new oral rhG-CSF dosage form has been elucidated.

Animals↗

Perfusion imaging of the brain by B-mode ultrasonography. An experimental study in rabbits.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the ultrasonic imaging of normal rabbit brain by using echocontrast enhancer to identify the brain tissue perfusion. METHODS: A solution of SH/TA-508 (containing microbubbles of mean size 2 to 4 microns; n = 4) was used for contrast enhancement of rabbit brain tissue and was administered through the left internal carotid artery. Contrast enhancement in the ipsilateral parietal area was examined by placing a 7.5-MHz transducer on the dura after a craniectomy. Throughout the experiment, we measured parameters including arterial blood pressure, arterial blood gases, and serum glucose and hematocrit levels. We investigated whether the administration of an echocontrast enhancer would be safe for the brain tissue (n = 4). RESULTS: After injection of 100 mg/mL SH/TA-508, contrast enhancement was clearly observed within approximately 1 second in the left hemisphere (especially in the left cerebral cortex) in all animals and disappeared within 3 seconds after the end of injection. All physiological parameters remained within the normal range throughout the experiment. No focal abnormalities were observed on hematoxylin-eosin staining of the brain tissue. CONCLUSIONS: Contrast enhancement was observed in the ipsilateral hemisphere with the administration of SH/TA-508. Contrast enhancement on B-mode brain imaging would be useful for real-time identification of brain tissue perfusion and should become a promising method for bedside clinical assessment of brain tissue perfusion.

Animals↗

Effects of osmolarity and amino acids in a chemically defined medium on development of rat one-cell embryos.

Rat one-cell embryos, recovered from naturally mated females, were cultured in a chemically defined medium (R1ECM) under different experimental conditions. When the osmolarity of the medium with a reduced concentration (63.8 mmol l-1) of NaCl was varied by adding different amounts of D-sorbitol, more (79-91%) of the one-cell embryos developed to the four-cell stage at 212-278 mosmol than at 306 mosmol (13%). The greatest proportions of morulae (74%) and blastocysts (60%) were obtained at 246 mosmol. When the medium was supplemented with amino acids in various combinations and the osmolarity adjusted to about 246 mosmol, more (80-98%) of the embryos developed to the morula stage. More blastocysts were obtained in medium supplemented with glutamine (Gln: 80%), minimal essential medium (MEM) essential amino acids (EAA) (90%), Gln+EAA (83%), EAA+MEM nonessential amino acids (NEAA) (83%) or EAA+Gln+NEAA (90%) than in medium without amino acids (59%). Few (3-10%) hatching or hatched blastocysts were observed 120 h after the start of culture in the medium with EAA plus Gln or NEAA. The mean number of cells in blastocysts developed in the medium with EAA+Gln+NEAA was 46.7 +/- 7.2. When a total of 82 morulae or early blastocysts that had developed in culture were transferred to eight pseudopregnant rats on day 4, six recipients into which 62 embryos were transferred maintained their pregnancies beyond day 23, although no deliveries had occurred by day 25 or 26. When the rats were killed, 42 (68%) implantation sites and eight (13%) full-term fetuses with no gross abnormality were observed in the uterine horns.

Amino Acids↗

Functional analysis using chlortetracycline fluorescence and in vitro fertilization of frozen-thawed ejaculated boar spermatozoa incubated in a protein-free chemically defined medium.

Cumulus-enclosed pig oocytes were matured in vitro, freed from cumulus cells, and inseminated with frozen-thawed ejaculated spermatozoa in a chemically defined protein-free medium containing 37.0 mmol NaHCO3 l-1 and 5 mmol caffeine l-1. When the medium was supplemented with 1 mg polyvinylalcohol (PVA) ml-1, more penetrated oocytes were observed 14 h after insemination with 7-12 x 10(6) cells ml-1 than with 4-5 x 10(6) cells ml-1 and the incidence of polyspermy reflected the sperm concentration used. Varying the NaHCO3 concentration but maintaining the sperm concentration at 8 x 10(6) cells ml-1 resulted in significantly more oocytes being penetrated in media containing 45.83-50.25 than 37.0-41.42 mmol NaHCO3 l-1; there were no significant differences in the incidence of either male pronuclear formation or polyspermy. In medium containing 45.83 mmol NaHCO3 l-1, the inclusion of PVA at 0-5 mg ml-1 had no effect on proportions of penetrated oocytes, male pronuclear formation or polyspermy. However, when spermatozoa from three different boars were evaluated, the penetration and male pronuclear formation rates were highly variable, unlike the incidence of polyspermy. Penetration of cumulus-free oocytes was first detected at 6 h. When spermatozoa were incubated for 6 h in the absence of oocytes, motility, but not vitality, decreased whether or not PVA was included in the medium. Chlortetracycline (CTC) fluorescence analysis of the capacitation state indicated a rapid decline in the proportion of live uncapacitated, acrosome-intact cells and a rapid rise in the proportion of live capacitated, acrosome-reacted cells during the first hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Preparation and evaluation of a time-controlled release capsule made of ethylcellulose for colon delivery of drugs.

A novel ethylcellulose (EC) capsule which releases drug with a time-controlled fashion has been prepared. This capsule is composed of four parts, drug container, swellable substance, capsule body and cap. At the bottom of the body, micropores are made. As water penetrates through these micropores, the swellable substance such as low substituted hydroxypropyl cellulose (L-HPC) swells. When the cap made of water-insoluble macromolecular substance such as EC cannot persist the swelling pressure, the EC cap disintegrates and the drug in the container is released from the capsule. The lag-time is utilized for the delivery of drug to the colon. The release time of the drug from the capsule was measured both in vitro and in vivo experiments. In the case of an in vitro experiment, after 12mg of fluorescein as a model drug and 238mg of starch were filled into the container, caps having different thickness were attached to the capsule body and release study was performed. The release time of the drug was mainly dependent on the thickness of the cap. Using test capsules of which mean cap thickness were 39.1 +/- 2.3 (SE)microns, 63.1 +/- 5.0 microns and 75.6 +/- 4.1 microns, the in vivo release time was estimated after administration to beagle dogs. As a parameter, the peak time (tmax) when plasma fluorescein concentration reached to its maximum level was determined for the estimation of the release time of the drug from the capsule in the gastrointestinal tract. The in vivo tmax was well correlated with the cap thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Relationship between kinetic visual acuity and visual acuity with limited exposure].

Using a kinetic vision tester which we developed, kinetic visual acuity (KVA) at target velocity of 0-100 km/h was measured at background luminance of 0.1-200 cd/m2 in 19 eyes of 10 normal volunteers ranging in age from 20 to 31 years. The decrease in KVA was slow at a target velocity of 30 km/h or more as reported before. KVA was best at background luminance of 100 cd/m2. In 3 eyes of 2 normal subjects, 3 eyes of 2 patients with tonic accommodation and 1 eye of 1 patient with central serous chorioretinopathy, visual acuity at limited exposure times was also measured. In patients with tonic accommodation, visual acuity at limited exposure times was good, but KVA was poor as compared to normal eyes. In the eyes of patients with central serous chorioretinopathy, results were poor for both. The quantity of light required to obtain the same visual acuity was similar for both normal eyes and eyes with central serous chorioretinopathy in terms of both KVA and visual acuity at limited exposure times. In eyes with tonic accommodation, difference was seen in the required quantity of light. We conclude that functions of accommodation are involved in kinetic vision and that higher visual functions are required than those for visual acuity at limited exposure times.

Adult↗

Changes in the number of silver-stained nucleolar organizer regions in the normal, preneoplastic, and neoplastic endometrium.

The number of silver-stained nucleolar proteins (AgNORs) were counted in preneoplastic and neoplastic endometrial lesions and compared with those of the normal endometrium in the menstrual cycle. In glandular cells in the normal menstrual cycle, the mean number of AgNORs in the proliferative phase endometrium (3.4) was significantly higher than that in the secretory phase endometrium (2.5, p < 0.01). The mean number of AgNORs in well-differentiated endometrioid type adenocarcinoma (4.2) was significantly greater than that in simple hyperplasia (3.0, p < 0.001) and complex hyperplasia without cytological atypia (3.6, p < 0.05). The average number of AgNORs showed an increased tendency according to the neoplastic changes in the endometrium. These findings suggest that the one-step colloid method for AgNORs may therefore be a simple and partially useful technique for examining the proliferative activity in neoplastic and preneoplastic endometrial cells, but no clear distinction in each preneoplastic and neoplastic endometrial lesion can be drawn so far from our measurements.

Endometrial Neoplasms↗

[Measurement of temporal summation of visual acuity with the use of a trial tachistoscope].

Visual acuity was measured in eighteen normal eyes of 10 subjects ranging from 20 to 30 years of age, using a modified tachistoscope. We changed the exposure time of the target (1-1,000 msec) or background luminance (0.1-200 cd/m2). The visual acuity rose with increasing exposure time. At background luminance over 10 cd/m2, the critical duration time was about 500 msec. However, at low luminance below 10 cd/m2, the critical duration was prolonged. This tendency was also seen when the pupil diameter was fixed at 3 mm with an artificial pupil. Similar by luminance detection, visual acuity was also determined by the product of background luminance and exposure time. From theses findings, we concluded that Bloch-Bunsen-Roscoe law was statisfied.

Adult↗