Biomedical subjects
K Amemiya
Publications and source records attributed to K Amemiya.
[Preliminary study of pelvic CT with air enema].
In pelvic CT, several techniques (appropriate preparations) have been reported for the optimal diagnostic imagings. We demonstrated the usefulness and limitations of "Air Enema", which is one of preparations for hollow viscera in pelvic CT examination. From Oct. 1986 to Mar. 1987, 38 patients with gynecological abnormalities were evaluated by consecutive pre and post "Air Enema" CT. The patients aged 26-75 years with mean of 44.6 years. All patients were examined in prone position with 100 ml of 2% iopamidol in the urinary bladder and medical tampon in the vagina. Two consecutive scans were performed from the level of pubic symphysis to the 5th lumbar vertebra at 10 mm-15 mm intervals. The first scan was pre "Air Enema" CT, in which the rectum, entire colon and terminal ileum were not distended. The second scan was post "Air Enema" CT, in which the hollow viscera was distended by 1000 ml-1500 ml of air. Two images, each from pre and post "Air Enema" CT were evaluated on the efficacy for imaging diagnosis. In "Air Enema" CT, main useful effect was "replacement effect", which was that intrapelvic masses and/or intrapelvic paravascular spaces were clearly delineated by distended bowels. Detection and location of intrapelvic masses were correctly diagnosed when the masses were relatively small (5.3 cm in average diameter), but there were no advantages in cases in which the pelvic masses were large enough to occupy the pelvic cavity (12.7 cm in average diameter). Abdominal pain was the most common adverse reaction to this technique. But complaints usually disappeared in few hours after examination. Thus, "Air Enema" seems to be useful preparation for pelvic CT examination to detect relatively small intrapelvic masses and abnormalities.
Glial cells of the human developing brain and B cells of the immune system share a common DNA binding factor for recognition of the regulatory sequences of the human polyomavirus, JCV.
Cells of the nervous system and the immune system perform highly specialized functions which reflect the tissue-specific regulation of their genes. However there are some functions between these two cell systems such as antigen presentation, cytokine release, and expression of MHC molecules which suggest a common mechanism for regulation of certain genes. We present data that extend this observation to include the recognition of specific neurotropic viral DNA sequences by glial cells and B cells. The experiments here provide evidence that both human glial cells and B cells possess nuclear DNA binding proteins that interact with nucleotide sequences on the regulatory region of the JC viral genome. These DNA binding proteins are present in human lymphoma B cell lines and fetal glial cultures. The fetal glial cultures are characterized as astrocytes by unique cDNA expression and the presence of GFAP. Data are also presented that demonstrate the presence of JCV infected B cells in brain tissue derived from progressive multifocal leucoencephalopathy, the demyelinating disease caused by JCV infection. The possibility that the glial and B cell protein factor(s) responsible for recognition of the JCV genome belong to a family of proteins similar to known transcriptional control elements such as the Octamer binding proteins or Nuclear Factor-1 is discussed.
Effects of butenafine hydrochloride, a new benzylamine derivative, on experimental dermatophytosis in guinea pigs.
Butenafine hydrochloride, N-4-tert-butylbenzyl-N-methyl-1-naphthalenemethylamine hydrochloride (butenafine), is a novel antifungal agent of the class of benzylamine derivatives. Butenafine was investigated for its activity against guinea pig dermatophytosis caused by Trichophyton mentagrophytes or Microsporum canis in comparison with those of naftifine, tolnaftate, clotrimazole, and bifonazole. Topical butenafine showed excellent efficacy against dermatophytosis when it was applied once daily, and the effect was superior to those of all four reference drugs. When applied once at 24 or 48 h before infection, the drug exhibited excellent prophylactic efficacy against experimental T. mentagrophytes infection. The concentrations of butenafine in animal skin at 24 and 48 h after application of 0.2 ml of a 1% solution were several hundred times higher than those required to kill T. mentagrophytes and M. canis. The good efficacy of butenafine against dermatophytosis may be attributable to its fungicidal activity and long retention in the skin after topical application.
Effects of butenafine hydrochloride, a new benzylamine derivative, on experimental tinea pedis in guinea pigs.
Butenafine is a new antifungal benzylamine. The efficacy of butenafine was investigated in an experimental tinea pedis model in guinea pigs, which is pathologically similar to natural infections in humans. Butenafine (0.1 ml) in 0.2 to 1.0% solutions was applied to the site of infection. Treatment was started on day 10 postinfection and was continued for 20 days. Butenafine applied once daily exhibited excellent dose-related therapeutic efficacy. The efficacy of butenafine was significantly superior to those tolnaftate, clotrimazole, and bifonazole.
[Studies on metabolism and disposition of sizofiran (SPG), an anti-tumor polysaccharide. III. Degradation and excretion of SPG in rats].
Degradation and excretion of Sizofiran (SPG), an anti-tumor polysaccharide, were studied in rats after a single or multiple administration. After a single intravenous injection of [14C]SPG (3 mg/kg), SPG distributed in the liver was degraded at very slow rate to SPG-like substances (SPGLS) having lower molecular weight than that of SPG, while SPG in the spleen and mesenteric lymph node was metabolized at much slower rate than that in the liver. In the experiment with multiple subcutaneous administration, SPG was also found to be present mainly as SPGLS in the liver, but almost as an unchanged SPG in the spleen. SPG was excreted in the urine mainly as metabolites with a molecular weight of less than 10000. These results indicate that degradation of SPG to lower molecular weight-SPGLS is a prerequisite for efficient urinary excretion and the degradation occurs mainly in the liver.
[Non-quantitative analysis of the renography using 99mTc-DTPA; clinical efficacy and limitation].
The purpose of this paper is to evaluate the efficacy and limitation of the non-quantitative analysis of renography using 99mTc-DTPA, and to determine the clinical indication of the quantitative analysis of the study. We evaluated the clinical records of the patients and the findings of dynamic imagings and renograms. The non-quantitative analysis of the examination seemed to be useful to the selected cases, and quantitative analysis appeared to be dispensable except for the cases to evaluate the grade of parenchymal damages and causes of asymptomatic hematuria.
Conserved sequence elements upstream and downstream from the transcription initiation site of the Caulobacter crescentus rrnA gene cluster.
The nucleotide sequence and in vivo transcription start sites for rrnA, one of the two rRNA gene clusters of the eubacterium Caulobacter crescentus, have been determined. Two transcription start sites, a major and minor, for the rRNA gene cluster are located more than 700 nucleotides upstream from the 16 S rRNA gene. Transcription was detected from only the major start site in swarmer cells. But after the swarmer-to-stalked cell transition, transcription was detected from both rRNA start sites and continued throughout the developmental cell cycle when cells were grown in minimal medium. On the other hand, transcription from only the major start site was detected in cells growing in a complex medium. A small open reading frame was found upstream from the rRNA gene transcription start sites and was followed by an inverted repeat sequence. No sequence homology was found between the major rRNA gene transcription start site and the Escherichia coli sigma 70 promoters or the consensus sequence elements reported for C. crescentus fla promoters. However, there were two areas of homology when the major rRNA gene promoter was compared to the nucleotide sequence of the C. crescentus trpFBA promoter. There was a 12 nucleotide sequence centered around the -10 region of both promoters that was closely homologous. In addition, immediately downstream from the transcription start there was a sequence element that was identical in both promoters. These nucleotide sequence elements were not in the temporally expressed fla promoters of C. crescentus.
The use of serum TA-4 in monitoring patients with malignant transformation of ovarian mature cystic teratoma.
The development of cancer in mature cystic teratomas of the ovary is rare and sometimes difficult to detect because of sampling errors. Six cases of squamous cell carcinoma arising in ovarian mature cystic teratomas were studied, five of which showed an elevated level of a squamous cell carcinoma-associated antigen, TA-4, in the sera obtained preoperatively; the preoperative determination was not performed in the sixth case. However, no elevated TA-4 level was detected in the sera of 28 patients with mature cystic teratomas of the ovary. Moreover, serial determination of the serum TA-4 level showed a good correlation between the clinical course and the serum TA-4 level. Interestingly, an abnormal TA-4 level preceded the clinical detection of recurrence by 2 months in two patients. Thus, determination of the serum TA-4 concentration may be useful for diagnosing and monitoring patients with squamous cell carcinoma arising in mature cystic teratomas of the ovary.
Interaction of a nuclear factor-1-like protein with the regulatory region of the human polyomavirus JC virus.
We have initiated a study to identify host proteins which interact with the regulatory region of the human polyomavirus JC (JCV), which is associated with the demyelinating disease, progressive multifocal leukoencephalopathy. We examined the interaction of nuclear proteins prepared from different cell lines with the JCV regulatory region by DNA binding gel retardation assays. Binding was detected with nuclear extracts prepared from human fetal glial cells, glioma cells, and HeLa cells. Little or no binding was detected with nuclear extracts prepared from human embryonic kidney cells. Competitive binding assays suggest that the nuclear factor(s) which interacted with the JCV regulatory region was different from those which interacted with the regulatory region of the closely related polyomavirus SV40. We found three areas in the JCV regulatory region protected from DNase I digestion: site A, located just upstream from the TATA sequence in the first 98-base pair (bp) repeat; site B, located upstream from the TATA sequence in the second 98-bp repeat; and site C, located just following the second 98-bp repeat. There were some differences in the ability of the nuclear factor(s) from the two brain cell lines and HeLa cells to completely protect the nucleotides within the footprint region. The results from the DNase I protective studies and competitive DNA binding studies with specific oligonucleotides, suggest that nuclear factor-1 or a nuclear factor-1-like factor is interacting with all three sites in the JCV regulatory region. In addition, the results suggest that the nuclear factor which interacts with the JCV regulatory region from human brain cell lines is different from the factor found in HeLa cells.
Effect of 6-mercaptopurine on 65Zn distribution in the pregnant rat.
The effect of 6-mercaptopurine (6-MP) on the distribution of gavaged 65Zn in maternal and embryonic tissues of Sprague-Dawley rats was examined 24 hr after injection of the drug on day 13 of pregnancy. 6-MP injection resulted in a significantly higher retention of counts of 65Zn in maternal liver and lower counts in maternal plasma, uterus, placenta, and embryo than in controls. Compared to controls, gel chromatography of maternal liver from 6-MP injected dams showed higher counts associated with a protein peak of molecular weight 6,000-8,000, the approximate molecular weight of the zinc-binding protein metallothionein. These results support the idea that the zinc deficiency, which is observed in day 21 fetuses from dams injected with 6-MP during midgestation, may be the result of a drug-induced sequestering of zinc into maternal liver followed by a decrease in maternal plasma zinc and subsequent reduction in fetal zinc uptake. We suggest that this 6-MP-associated redistribution of zinc into maternal liver may be due to induction of maternal metallothionein synthesis by the drug.
Effect of beraprost sodium on peripheral circulation insufficiency in rats and rabbits.
Beraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is a chemically and biologically stable epoprostenol analogue which possesses both potent antiplatelet and peripheral vasodilating actions. Its effect on obstruction of the peripheral artery was studied in three different models: 1. acute thrombosis induced by electrical-stimulation of the femoral artery in rabbits, 2. occlusion induced by intra-arterial injection of sodium laurate in rats and 3. tail gangrene induced by subcutaneous injections of both ergotamine and epinephrine in rats. Oral administration of beraprost sodium resulted in suppression of thrombus formation in the acute thrombosis model, marked improvement of macroscopic and histological observations in the laurate-occlusion model and inhibition of tail gangrene extension. In contrast, ticlopidine improved thrombus formation in the acute thrombosis model and slightly improved histological observation in the laurate-occlusion model, but not in the tail gangrene model. Cilostazol suppressed lesions in the acute thrombosis model, but not in the tail gangrene model. These findings suggest that beraprost sodium may be very useful clinically for the therapy of peripheral circulation insufficiency diseases such as Buerger's disease and Raynaud's disease.
[Statistical analysis of trophoblastic disease in Kanagawa prefecture].
Two thousand one hundred and thirty-five cases of trophoblastic disease were registered in Kanagawa Prefecture in 7 years (from 1978 to 1984). The incidence of trophoblastic diseases, hydatidiform mole, partial mole, invasive mole, choriocarcinoma and persistent trophoblastic disease (PTD) was 3.22, 1.67, 1.20, 0.07, 0.06 and 0.20, respectively, per 1,000 live births. The incidence was constant for 7 years, and did not differ significantly from that of 16 prefectures in Japan. In Kanagawa, the incidence of hydatidiform mole was less and that of partial mole was more than those in the 16 prefectures. The incidence of invasive mole and choriocarcinoma was lower and that of PTD was higher than those in the 16 prefectures. Total incidence of invasive mole, choriocarcinoma and PTD was higher in the western part of Japan, and lower in the eastern and northern parts. Kanagawa Prefecture is between these two regions. The distribution by age of hydatidiform mole was high in 25-29 y.o. and over 40 y.o. The distribution by age of partial mole tended to be similar to that of hydatidiform mole, but less remarkable. The distribution by age of invasive mole and choriocarcinoma had 2 peaks of 30-34 y.o. and 45-49 y.o. The distribution by age of PTD was between that of hydatidiform mole and choriocarcinoma.
[A case of mixed müllerian tumor, usefulness of 67Ga-citrate scintigraphy].
Mixed Müllerian Tumor (M.M.T.) is a rare malignant neoplasm usually arising from uterine body in postmenoposal woman, and imaging diagnosis for the tumor has not been established. A 45-year-old female with pathologically confirmed M.M.T. was evaluated by 67Ga-citrate scintigraphy and CT on the basis of imaging diagnosis. 67Ga-citrate scintigraphy detected correctly not only primary lesions but also metastatic and recurrent-foci. The findings of 67Ga-citrate scintigraphy were confirmed to be correspond to autopsy findings. Generally, detectability of 67Ga-citrate scintigraphy for genito-urinary tract neoplasm was not appreciated, but in our case 67Ga-citrate scintigraphy was useful for detection of the primary lesion, metastatic and recurrent foci. The cellular components and grade of cell-differentiation of this tumor seemed to be responsible for good detection of the tumor. Thus, 67Ga-citrate scintigraphy was considered to be useful diagnostic imaging modality of M.M.T.
[67Ga-scintigraphic finding of colorectal carcinoma; the basis of clinicopathologic viewpoint].
Twenty-seven cases of colorectal carcinoma were evaluated by 67Ga-scintigraphy on the basis of clinicopathologic viewpoint. On each cases, 67Ga-scintigraphy was performed just before the operation, and resected specimen was also examined after the operation. In 17 cases (63%), the lesions were demonstrated on preoperative 67Ga-scintigraphy, on the other hand, all the lesions were clearly detected on images taken from resected specimen. Thus, it seems to be no doubt to accumulate 67Ga-citrate to colorectal carcinoma, and 67Ga-scintigraphy appears to be more useful imaging modality to detect the disease when the routine detectability becomes more higher because of some technical application.
Experimental studies on the pharmacokinetics and therapeutic effect of cefbuperazone in biliary infection.
A study was carried out using an experimental biliary infection model to investigate the pharmacokinetic characteristics and therapeutic effect of cefbuperazone in the rabbit. Thirty rabbits were divided into three equal groups; a control group of normal animals, a group of infected animals receiving no cefbuperazone, and a group of infected animals receiving 50 mg cefbuperazone/kg intramuscularly. The experimental infection was made by direct inoculation of a suspension of E. coli into the common bile duct after ligation. The results showed that extremely high levels of cefbuperazone were achieved in bile and tissues of the biliary tract and were higher than those in the blood. Moreover, the levels were maintained at effective concentrations even after 6 hours. Viable bacterial cells from bile and the gall-bladder were barely detectable 24 and 48 hours after infection in the cefbuperazone-treated group, whilst counts remained high in the other infected group. White blood cell counts were increased at 24 hours after infection but were significantly lower in the cefbuperazone-treated group. Histological examination revealed marked inflammatory changes in the gall-bladder and bile duct of infected, untreated animals but few, mild changes only were seen in cefbuperazone-treated animals. Similarly, total bilirubin and liver enzymes were markedly increased in infected animals, but transaminases and alkaline phosphatase were significantly lower in the treated compared to the untreated group. The findings indicate, therefore, that cefbuperazone can be a useful antibiotic in biliary infection.
[Preliminary study of patients with vertigo and dizziness using 123I-IMP].
To study the application of cerebral blood flow scintigraphy with 123I-IMP for the evaluation of central dizziness, the difference in 123I-IMP accumulation between the right and left cerebellar hemispheres was determined as an asymmetry index (A.I.) in 8 normal subjects and compared with A.I. from patients with central dizziness. According to estimated lesions, 123I-IMP findings were compared with CT findings. The normal subjects had A.I. of 5.8 +/- 2.1%, whereas 36 patients with central dizziness had A.I. of 12.7 +/- 7.5%. On the basis of an A.I. of 8% or more as an abnormal finding on IMP scintigraphy, 11 of the 14 patients with estimated lesions of cerebellar hemispheres and 16 of the 20 with those of the whole cerebellum including the vermis were evaluated to have had abnormalities. Seven of 11 with estimated lesions of the brainstem and 4 of 5 with vertebrobasilar arterial insufficiency were evaluated to have had abnormalities. The findings of 123I-IMP cerebral blood flow scintigraphy were in good agreement with clinical symptoms in patients with central dizziness with estimated lesions of the cerebellar hemispheres, suggesting the possibility that this method is more useful than CT.
Role of copper in the regulation and accumulation of superoxide dismutase and metallothionein in rat liver.
Weanling male Sprague-Dawley rats were fed one of four diets that varied in Cu, Zn or Cd content. To the control diet (I) Cu, Zn and Cd were added at 10, 100 and 0 mg/kg diet, respectively. Diets II and III also contained 10 mg/kg of dietary Cu, except that Zn was elevated to 1000 mg/kg for diet II, or Cd was added at 10 mg/kg for diet III. Diet IV was deficient in Cu (less than 1 mg/kg) with Zn at 100 mg/kg and no added Cd. At wk 6 postweaning, half of the rats fed diets I and IV were injected once with Cd acetate (5 mg Cd/kg body weight). The immediate response to Cd injection was an increase in metallothionein accumulation (three- to fourfold) and in Cu,Zn superoxide dismutase (SOD) accumulation (1.2- to 1.5-fold) in liver. SOD was estimated in an ELISA. These responses were not influenced by a change in Cu status (I vs. IV). However, in functional assays, SOD enzymatic activity was about half that of the control values. In this regard, SOD appears to be given high priority with respect to the utilization of cellular Cu, i.e., a 10-fold reduction in hepatic Cu only resulted in a twofold reduction in SOD activity and the amount of apoenzyme remained at normal levels.