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Biomedical subjects

N Kasai

Publications and source records attributed to N Kasai.

At least 91 records · Page 5Linked to original sources

[Middle cerebral artery occlusion with unilateral moyamoya like vessels and with ruptured anterior cerebral artery aneurysm--its relation to the antiphospholipid antibody syndrome].

We report a case of right middle cerebral artery occlusion associated with ipsilateral basal moyamoya like vessels and ruptured anterior cerebral artery aneurysm. A 59-year old man suddenly developed a consciousness disturbance and was brought to our hospital by ambulance. On admission, computed tomography (CT) of the head revealed a diffuse dense high-density lesion in the basal cistern and in the bilateral sylvian fissures, and a round homogeneous high-density area in the interhemispheric fissure. Subsequent angiography showed a large anterior cerebral artery aneurysm and occlusion of the right middle cerebral artery with moyamoya-like vessels. We made a diagnosis of subarachnoid hemorrhage due to aneurysm rupture. An emergency bifrontal free bone craniotomy was performed, utilizing the interhemispheric approach and the neck of the aneurysm was clipped. On the 68th postoperative day the patient was ambulatory and discharged from the hospital. Hemodynamic stress was thought to be the main cause of the anterior cerebral artery aneurysm. Because the laboratory data on admission included a false-positive serological test for syphilis, we tested the patient for antiphospholipid antibodies, and repeatedly found anticardiolipin antibody in the patient's serum. The antiphospholipid antibody syndrome may have been responsible for the occlusion of the middle cerebral artery, in this patient and we think that testing for serum antiphospholipid antibodies is important in occlusive cerebral artery disease, especially in moyamoya disease or when moyamoya-like vessels are present.

Aneurysm, Ruptured↗

[A case of polycystic kidney associated with new growth of cerebral aneurysm after aneurysmal operation].

We have encountered a 66-year-old woman with a polycystic kidney (PCK). This was combined with the fact that the new growth of an aneurysm at the left anterior cerebral artery (A2-A3 junction) had ruptured 3 years after an operation for a right IC-PC aneurysm in 1985. The cause of the neogenesis and enlargement of an intracranial aneurysm is important because of the changes in the arterial wall due to congenital factors, hypertension, arteriosclerosis, etc, or hemodynamic stress caused by hypertension. We suspected that intracranial aneurysm formation was caused by hypertension due to PCK and the intracranial aneurysm is explained as being due to maldevelopment. In patients with PCK, it should be kept in mind that intracranial aneurysms may be present, and it is advisable to use cerebral angiography and MRA to see whether this is so or not. It should be also stressed that the control of hypertension is very important for the prognosis of patients with PCK. Not only new growth of cerebral aneurysms but also intracerebral hemorrhage is to be prevented.

Aged↗

[Structure and regulation of human thyroid-stimulating hormone (TSH) gene].

This article describes the structure of human thyroid-stimulating hormone (TSH) gene and the regulation of its expression. TSH is a heterodimer composed of common alpha subunit and unique beta subunit encoded by genes located on different chromosomes. It is known that the expression of these subunit genes is regulated in different mechanism by several extracellular factors. The DNA sequencing data of the gene demonstrated that these genes were regulated by interaction of several potential regulatory elements with transcription factors. This transcriptional regulation was analyzed by transient expression of chimeric gene fragments and DNA-protein binding assay, in vitro. To identify the essential DNA regulatory elements of the human TSH beta gene in vivo, we introduced 1.1 kbp of the 5' flanking region of the human TSH beta gene-simian virus 40 T-antigen (SVT) fusion gene into the mouse. This region could direct pituitary-specific expression of SVT and tumorigenesis in transgenic mice.

Animals↗

High level expression of human alpha-fetoprotein in transgenic mice.

Transgenic mice were produced by the microinjection of the cDNA of human alpha-fetoprotein (AFP) under control of the enhancer/promoter of the human beta-actin gene. Among the 4 mouse lines where the transgene were stable transmitted to the progeny, 3 produced human AFP. The expression was not developmental stage-specific nor tissue-specific as predicted from the properties of enhancer/promoter. The serum human AFP levels of adult mice were 30-600-fold higher than those of mouse AFP. These mice could be useful for the studies of possible biological functions of AFP during development as well as in malignancies.

Actins↗

Inhibition of mouse hepatitis virus multiplication by antisense oligonucleotide, antisense RNA, sense RNA and ribozyme.

Antisense nucleic acids against specific sequences of mouse hepatitis virus (MHV)-RNAs were tested for their inhibitory effects on viral multiplication in mouse DBT cells. An antisense oligonucleotide containing a sequence complementary to leader RNA was synthesized and shown to induce a significant inhibitory effect on the multiplication of MHV-JHM. A vector which expressed the antisense or sense mRNA7 of MHV was transfected into DBT cells. A decreased multiplication of MHV was observed in both cell lines. The transfected cell line which expressed ribozyme against the 5'-end of the MHV genome was established. The rate of inhibition of MHV-multiplication and the quantity of synthesized virus-specific mRNAs in this transfected cell line were the same for both antisense and sense RNA. These results show that antisense nucleic acids might be eligible for use as antiviral agents against MHV multiplication.

Animals↗

Ganglioside distribution in the liver of inbred strains of rats and the cancerous liver of LEC rats.

The gangliosides in the livers of various inbred strains of rats and hepatoma of LEC rats were purified and analyzed by thin-layer chromatography. The patterns of ganglioside distribution in these rat livers were classified into three phenotypes depending on the strain, that is, a-type (ACI, LEA, LEW, BUF), b-type (WKAH, SHR/SP), and LEC type, which are characterized by dominance of a- or b-series of gangliosides, or a variation of a-type, respectively. A sex difference was also recognized in the molar ratio of GM3 which was much higher in males (60-75%) than in females (33-56%) except in LEC rats. In addition, the content of a-series gangliosides was lower and the content of b-series gangliosides was higher in a-type male rats than in a-type female rats. The opposite was true in b-type rats. LEC rats were an exception, characterized by no sex difference and a quite low content of b-series gangliosides. The LEC rat is a mutant strain that spontaneously develops fulminant hepatitis around 14 to 20 weeks of age and hepatoma at 1 to 1.5 years old. The gangliosides of the hepatoma were characterized by the appearance of the newly synthesized gangliosides, fucosyl-GM1 and alpha-galactosyl alpha-fucosyl GM1 (BGM1). In particular, BGM1 ganglioside accumulated in the hepatoma of female rats.

Animals↗

Absence of linkage between the retinoblastoma gene and hts gene in the LEC rat: a model of human Wilson's disease.

The LEC rat is an authentic model of human Wilson's disease (WD) with an autosomal recessively inherited hepatitis. We investigated linkage between the hepatitis gene (hts) and the rat retinoblastoma gene (RB), that is closely linked to the WD gene in humans, to see whether or not the hts gene is located on the syntenic region of WD and is the counterpart of the WD gene. Polymerase chain reaction-single strand conformation polymorphism analysis with backcross progenies from LEC and TM strains showed that the recombination rate between these two loci was 55.6%, demonstrating that the hts and RB genes are not linked to each other. These data indicate that the hts gene is not the counterpart of the WD gene and that the human syntenic region on which the WD locus and human RB gene are located, is not conserved in the rat genome.

Animals↗

Hypersensitivity of LEC strain rats in radiation-induced acute bone-marrow death.

LEC strain rats, which have been known to develop hereditarily spontaneous fulminant hepatitis 4 to 5 months after birth, were highly sensitive to whole-body X ray-irradiation as compared to WKAH strain rats. Radiation-induced acute bone-marrow death occurred at doses higher than 2.0 Gy in LEC rats, and at doses higher than 7.4 Gy in WKAH rats, respectively. By probit analysis of survival data, it was shown that the LD50/30 value for LEC rats was 3.0 Gy which was significantly lower than that (7.8 Gy) of WKAH rats. Histopathological examinations of the bone marrows from both strains after irradiation at a dose of 4.0 Gy revealed that a number of hemopoietic cells were recovered in WKAH rats on day 8 after irradiation, but not in LEC rats. These results suggested the hypersensitivity of LEC rats to ionizing radiation in connection with acute bone-marrow death.

Animals↗

Transgenic mice with antisense RNA against the nucleocapsid protein mRNA of mouse hepatitis virus.

In this study transgenic mice which expressed antisense RNA against the nucleocapsid protein gene of mouse hepatitis virus (MHV) under the control of RSV LTR were produced. These transgenic mice were able to transmit the foreign gene to their progeny in a Mendelian fashion. Antisense RNA was detected in various tissues from the transgenic mice including liver and brain, the target organs of MHV infection. One strain of transgenic mice derived from founder mouse No. 19 was more resistant to the lethal challenge of MHV than non-transgenic mice. The results of the present study show the ability of antisense RNA against the viral gene to protect against viral infection in vivo.

Animals↗

Three-dimensional structure of ferricytochrome c' from Rhodospirillum rubrum at 2.8 A resolution.

The structure of ferricytochrome c' extracted from Rhodospirillum rubrum has been determined by the X-ray crystallographic method. Crystals in hexagonal space group P6(1), with unit-cell dimensions a = b = 51.72 A and c = 155.49 A, contain one dimer molecule composed of chemically identical polypeptide chains (monomer I and monomer II) per asymmetric unit. An electron density map has been calculated at a resolution of 2.8 A by the multiple isomorphous replacement method using four-circle diffractometer data from native crystals and two heavy-atom derivatives. The quality of the map was improved by averaging the electron density about the non-crystallographic 2-fold axis relating the two monomers. The initial three-dimensional model of monomer I was built on a computer graphics system and that of monomer II was derived from monomer I using the non-crystallographic symmetry matrices. The dimer structure has been refined using a combination of simulated annealing and conventional restrained least-squares crystallographic refinement. The current model includes 244 amino acid residues (122 x 2) and 2 hemes, with a root-mean-square deviation in bond lengths from ideal values of 0.022 A. The current crystallographic R-factor is 23.3% for 4,481 independent reflections [magnitude of Fo greater than or equal to sigma (F)] between 5.0 and 2.8 A resolution. The monomer molecule is structurally organized as an array of four nearly parallel alpha-helices which construct a left-twisted bundle. One end of the bundle, in which a covalently bound protoheme IX prosthetic group is incorporated, is more divergent than the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Inherited copper toxicity in Long-Evans cinnamon rats exhibiting spontaneous hepatitis: a model of Wilson's disease.

The copper concentrations in organs of developing Long-Evans Cinnamon (LEC) rats (2 d to 13 mo) were measured to elucidate the pathogenesis of their hereditary hepatitis. Hepatic copper contents of LEC rats were significantly higher than those of control rats (26 to 92 times higher). The subcellular distribution of hepatic copper indicated that the nuclear and large granular fractions had been saturated and the cytosol fraction contained about 70% of all the hepatic copper in LEC rats. The serum concentrations of copper and ceruloplasmin were significantly lower than those of control rats from the 4th wk (10-12% and 5-19%, respectively). Copper contents in kidney of LEC rats did not exhibit an increase over those of control rats until 12 wk, but then increased to nearly 40 times higher during fulminant hepatic failure. Accumulation of copper was not detected in the brain or small intestines of LEC rats until 13 mo. The hepatic copper concentration, its subcellular distribution, and serum copper concentration of F1 rats (LEC x Long-Evans Agouti) exhibited the same levels as those of Long-Evans Agouti rats. In addition to their similarity concerning inheritance of autosomal recessive means and clinical course, we found causality relating copper accumulation to the pathogenesis of the disease. We propose that LEC rats will be the most promising animal model for the study of Wilson's disease.

Age Factors↗

Higher sensitivity of LEC strain rat in radiation-induced acute intestinal death.

LEC strain rats (LEC rats), which have been known to develop hereditarily spontaneous fulminant hepatitis 4-5 months after birth, were highly sensitive to whole-body X-irradiation as compared to WKAH strain rats (WKAH rats). Radiation-induced acute intestinal death occurred at doses higher than 6.5 Gy in LEC rats, and at doses higher than 12.8 Gy in WKAH rats, respectively. By the probit analysis of survival data, it was shown that the LD50/7 value of LEC rats was estimated to be 7.03 Gy which was significantly lower than that (12.99 Gy) of WKAH rats. Histopathological examinations of small intestines from LEC rats 2 days after irradiation at the dose of 8.5 Gy showed severe epithelial death together with edema, whereas little or no significant changes were noted in intestinal epithelium of 8.5 Gy-irradiated WKAH rats. These results suggest that the radiosensitivity of LEC rats to ionizing radiation appears to be higher than that of other strains of rats.

Animals↗

Inconsistent expression of glycolipid sulfotransferase activity between hepatoma and serum.

Glycolipid sulfotransferase activity in human and rat hepatocellular carcinoma tissues was studied, since an elevated level of the enzyme activity in serum had been demonstrated in cancer patients. The level of the enzyme activity in carcinoma tissues, however, could not be distinguished from that of normal controls. Similar observations were made for rat hepatoma. A higher level of enzyme activity was observed in the female than in the male. Inconsistent expression between hepatoma tissue and serum suggests that humoral factor(s) derived from hepatoma tissue stimulates production of the sulfotransferase, which is released into the blood-stream in the host.

Animals↗

Useful short-range transport of mouse embryos by means of a nonfreezing technique.

The survival of mouse morulae to be implanted on the uterine wall of a recipient after storage at 0 degree C in sucrose-containing medium has shown tendencies similar to those of blastocysts developing in vitro. The pregnancy rate, as defined by implantation sites per embryos transferred, has varied from 52.9 to 77.2% and decreased depending on the duration of storage (0 to 72 h), and was lower than the rate of blastocyst formation in vitro (57.2 to 87.3%). Regarding the birth rate, 56.0 to 59.4% of implanted embryos were delivered as live pups regardless of storage duration, with the exception of controls (78.9%, 0 h). Eventually, 37.0, 32.8, or 29.9% of embryos were obtained as live pups when preserved by our system for 24, 48, or 72 hours, respectively. This viable, highly reproducible nonfreezing technique is useful for embryo preservation. Embryos were transported to evaluate the efficacy of the nonfreezing method. Mouse morulae were kept in a thermos bottle filled with ice-water and packaged in polystyrene foam. The package was transported from Kochi to Sapporo, about 1300 km, within 48 hours during which it was possible to maintain 0 degree C in the bottle and deliver to most areas in Japan. After shipping, the survival of embryos was 46.8% for development to blastocysts in vitro, and 37.1% for the pregnancy rate, with a final birth rate of 14.1%. Transport factors other than storage may have contributed to the lower birth rate; however, our system is cheaper, more convenient, and more practical than others for short-range transport.

Animals↗

Unidirectional distribution of mosaicism in chimeric rats.

Experimental rat chimeras were produced by aggregation of eight-cell embryos from two inbred strains, ACI/Hkm and WKAH/Hkm, which differ from each other in their major histocompatibility complexes and coat colors, and their mosaicism was analyzed. The existence of the isozyme Es-1, a serum cholinesterase specifically produced by WKAH-derived cells, and the agouti coat color due to ACI cells, indicated that all of the rats analyzed were unequivocal chimeras. The proportion of ACI cells in the red blood cell populations of the chimeras varied from 45% to 98%, as determined with a fluorescence-activated cell sorter and a monoclonal antibody against class I (RT1) antigen. Digital analysis of the coat color revealed that the proportion of the ACI type of coat color ranged from 72% to 98% in these chimeric rats. Each phenotype expressed in the coat color was complex and varied in size. The ratios of red blood cells and the coat color inclined toward the ACI type of cell population. Conversely, the rate of the WKAH-cell-type population was less than 50%. A breeding test disclosed chimerism of germ cells in two chimeric rats, and there were more pups with agouti coats than with albino coats. Taken together, it was shown in most of the phenotypes analyzed that the ACI type of cells was predominant in all of the chimeric rats. We discuss the possible causes for this unbalanced distribution in the rats.

Animals↗

Effects of sex hormones on fulminant hepatitis in LEC rats: a model of Wilson's disease.

LEC rats, which have hereditary hepatitis and have recently been proposed as an animal model for Wilson's disease, were examined to determine the effects of sex hormones on fulminant hepatitis. After the rats had undergone ovariectomies or orchidectomies (castration) and were compared with intact rats, the age at the onset of fulminant hepatitis was not substantially altered but the survival rates decreased from 50% to 12.5% for females and 75% to 14.3% for males, indicating that sex hormones did not influence the occurrence of fulminant hepatitis but influenced mortality due to fulminant hepatitis. When testosterone was administered to the ovariectomized or orchidectomized rats, the survival rate increased to over 90% in both sexes. In contrast, estradiol did not affect the survival rate of either sex but affected the onset of fulminant hepatitis. That is, with the administration of estradiol, the age at which serum GPT activity reached its maximum was delayed 4 weeks in ovariectomized rats and 6 weeks in orchidectomized rats as compared with intact rats. A similar but somewhat weaker tendency appeared in rats given progesterone. The results of our study indicate that sex hormones have no effect on the rate of occurrence of hepatitis but affect the progression of hepatitis. In particular, testosterone increased the survival rate of rats with fulminant hepatitis, and exogenous estradiol delayed the onset of hepatitis for several weeks.

Alanine Transaminase↗