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K Amemiya

Publications and source records attributed to K Amemiya.

At least 19 recordsLinked to original sources
PubMed1992

Adjacent nuclear factor-1 and activator protein binding sites in the enhancer of the neurotropic JC virus. A common characteristic of many brain-specific genes.

JC virus is a neurotropic virus that causes the demyelinating disease progressive multifocal leukoencephalopathy in humans. In order to understand the neurotropic nature of this virus, we examined the binding of nuclear proteins to the viral regulatory region. A close association of nuclear factor-1 (NF-1) and Jun protein binding sites was found. These binding sites were either adjacent or overlapped each other. Depending on the order of binding, there was some interference of binding of the NF-1 protein by Jun even at a non-Jun binding site. This suggests that there may be a direct interaction between these proteins. Examination of the regulatory region of a number of genes expressed in the central and peripheral nervous systems revealed that many of these genes apparently have adjacent NF-1 and activator protein binding sites immediately upstream from the mRNA start site. Since it had been demonstrated that nuclear proteins from brain and non-brain cells could interact with these sites, it is probable that the NF-1- and Jun-related proteins which interact at these sites are involved in the basal activity of these genes. It appears that adjacent binding sites for NF-1 and Jun immediately upstream from the mRNA start site may be a characteristic of many genes expressed in the nervous system.

Base Sequence↗
PubMed1992

Combination therapy of radiation and Sizofiran (SPG) on the tumor growth and metastasis on squamous-cell carcinoma NR-S1 in syngeneic C3H/He mice.

The efficacy of Sizofiran(SPG), a highly purified beta-1,3-D-glucan from the culture broth of basidiomycetes Schizophyllum commune Fries, in combination with local irradiation was investigated using squamous-cell carcinoma NR-S1 and syngeneic hosts of C3H/He mice. NR-S1 tumor was implanted sc in the thigh of C3H/He mice. When tumor grew to 4 mm in diameter, the local irradiation of 55 Gy was delivered. SPG was injected im at a dose of 5 mg/kg. When SPG was administered after irradiation, remarkable inhibition of tumor growth was observed in comparison with the radiation alone group. Furthermore, the combination effect of radiation and active immunotherapy using mitomycin C-treated NR-S1 cells as vaccine was examined. When radiotherapy and active immunotherapy were combined with SPG, suppression of tumor growth was observed from an early stage in comparison with the group which was not administered SPG. SPG also inhibited the pulmonary metastasis of NR-S1 tumor after radiotherapy.

Animals↗
PubMed1992

Re-appraisal of clinical usefulness of 67Ga-citrate scintigraphy for primary colorectal carcinoma: with evaluation of scintigram obtained from resected specimens.

Clinical usefulness of 67Ga-citrate scintigraphy for the diagnosis of colorectal carcinoma was reappraised at the standpoint of clinicopathological diagnosis. Fifty-eight patients with colonic carcinoma were subjected to this study. They underwent 67Ga scintigraphy before surgery. Colorectal carcinomas were detected in 38 patients, 65.5% by this procedure. Surgical specimens from thirty-seven patients underwent postoperative scanning. The scanning of the surgical specimen revealed accumulation of 67Ga-citrate in all 37 patients, suggesting that 67Ga-citrate accumulated in the carcinoma of the colon. The results suggested that detectability of carcinoma of the colon by 67Ga scintigraphy in this series was better than generally considered. 67Ga scintigraphy was considered to provide useful information in cases of severe stenosis and dolichocolon which were difficult to diagnose with a Barium enema and fiberscope. The problem is that abnormal accumulation is sometimes hard to distinguish from physiological excretion in the stools. However we believe that images should be carefully evaluated, keeping in mind the fact that 67Ga-citrate could accumulate in a colorectal carcinoma, and also believe that we radiologists should actively promote Ba-enema examination in positive cases rather than to devote time to the differentiation between physiological excretion of 67Ga in the stools and accumulation in a colorectal carcinoma.

Adenocarcinoma↗
PubMed1992

Interaction of the human polyomavirus, JCV, with human B-lymphocytes.

The human polyomavirus, JCV, is the causative agent of the central nervous system demyelinating disease progressive multifocal leukoencephalopathy (PML). The principal target of JCV infection in the central nervous system (CNS) is the myelinating oligodendrocyte. However, the site of JCV multiplication outside of the CNS and the mechanism by which virus gains access to the brain are not known. Recently, JCV infected B-lymphocytes have been demonstrated in PML patients in several lymphoid organs, in circulating peripheral lymphocytes, and in brain, suggesting a possible role of B-lymphocytes in the dissemination of virus to the brain. The experiments reported here were undertaken to understand more about the interactions of JCV with human B-lymphocytes. The data show that JCV is able to multiply in either Epstein-Barr virus transformed (EBV) or EBV negative human B cell lines resulting in production of infectious, progeny virions. In addition, nuclear proteins extracted from these B cells bind to similar nucleotides within the JCV regulatory region that are bound by nuclear proteins extracted from human fetal glial cells, the most susceptible host and principal target cell for JCV infection in vitro. It is not known, however, whether these DNA binding proteins from susceptible B cells and glial cells are similar.

B-Lymphocytes↗
PubMed1992

Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain.

Studies of the pathogenesis and molecular biology of JC virus infection over the last two decades have significantly changed our understanding of progressive multifocal leukoencephalopathy, which can be described as a subacute viral infection of neuroglial cells that probably follows reactivation of latent infection rather than being the consequence of prolonged JC virus replication in the brain. There is now sufficient evidence to suggest that JC virus latency occurs in kidney and B cells. However, JC virus isolates from brain or kidney differ in the regulatory regions of their viral genomes which are controlled by host cell factors for viral gene expression and replication. DNA sequences of noncoding regions of the viral genome display a certain heterogeneity among isolates from brain and kidney. These data suggest that an archetypal strain of JC virus exists whose sequence is altered during replication in different cell types. The JC virus regulatory region likely plays a significant role in establishing viral latency and must be acted upon for reactivation of the virus. A developing hypothesis is that reactivation takes place from latently infected B lymphocytes that are activated as a result of immune suppression. JC virus enters the brain in the activated B cell. Evidence for this mechanism is the detection of JC virus DNA in peripheral blood lymphocytes and infected B cells in the brains of patients with progressive multifocal leukoencephalopathy. Once virus enters the brain, astrocytes as well as oligodendrocytes support JC virus multiplication. Therefore, JC virus infection of neuroglial cells may impair other neuroglial functions besides the production and maintenance of myelin. Consequently our increased understanding of the pathogenesis of progressive multifocal leukoencephalopathy suggests new ways to intervene in JC virus infection with immunomodulation therapies. Perhaps along with trials of nucleoside analogs or interferon administration, this fatal disease, for which no consensus of antiviral therapy exists, may yield to innovative treatment protocols.

Animals↗
PubMed1992

Effect of 15-deoxyspergualin on lupus nephropathy in New Zealand black/white F1 mice.

Fourteen-week-old female New Zealand B/W F1 mice were treated subcutaneously with 15-deoxyspergualin (DSP) at 0.3 mg-6.0 mg/kg body weight, 4 times/week. They were sacrificed at 36 weeks of age to determine the minimal effective dose as well as the lowest maximally effective dose without toxicity of DSP required to suppress the development of nephropathy. The life span of the animals was significantly prolonged with 0.6 mg/kg or more DSP. Additionally, glomerular (immuno)histological improvement of the kidney at 36 weeks was observed with 0.6 mg/kg DSP, although a higher dose was required to lower serum anti-DNA activity or to decrease proteinuria. In addition, DSP produced a decrease of L3T4+ splenocytes without affecting the number of Lyt 2+ cells, while the level of IL-2 generated in vitro was somewhat elevated. It may be concluded that DSP has a therapeutic range within an order of ten, but its exact mechanism of immunosuppression remains to be determined.

Animals↗
PubMed1992

[81mKr scintigraphic evaluation of hemodynamics in gynecologic malignancies under condition of angiotensin II-induced hypertension].

Transcatheter arterial infusion chemotherapy is one of the most useful therapeutic procedures for gynecologic malignancies. Recently, several reports have been published about Angiotensin II-induced hypertension chemotherapy and the efficacy of the method, but there have been no reports to evaluate an application for gynecologic malignancies. We evaluate the usefulness of the method for gynecologic malignancies demonstrating the changes of hemodynamics of the tumor using 81mKr scintigraphy. Thirteen patients with pathologically confirmed gynecologic malignancies were evaluated by angiography and continuous infusion of 81mKr via the catheter with and without Angiotensin II. At first, continuous infusion of 81mKr was performed under the superselective catheterization of the uterine artery. The radioactivities in the ROI were counted. Then, withdrew the catheter from the uterine artery to the internal iliac artery, and again continuously infused 81mKr and counted the radioactivities in the same ROI. Finally, keeping the catheter in the internal iliac artery, Angiotensin II and 81mKr were infused simultaneously. And counted the radioactivities. The radioactivities were highest when the catheter tip was placed in uterine arteries and lowest when the catheter tip was placed in internal iliac arteries. But radioactivities in the ROIs were definitely increased when Angiotensin II was used, even if the catheter tip was keeping in the internal iliac arteries. The optimal catheter position of transcatheter arterial chemotherapy for gynecologic malignancies is at proximal uterine artery. Since Angiotensin II-induced hypertension may increase blood flow of tumors, it seems to have indication for post-operative cases, highly advanced cases and cases with difficulties to perform superselective catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Involvement of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vitro.

Although transforming growth factor (TGF) alpha and epidermal growth factor (EGF) receptor (EGFR) autocrine mechanism is widely demonstrated in many kinds of cancers, its biological significances still remain circumstantial. We critically assessed the significance of this mechanism on the growth of an ovarian cancer cell line. Northern blot analysis in polyadenylated RNA isolated from cells by using 32P-labeled pre-TGF alpha, EGRF, and prepro-EGF complementary DNAs as probes revealed that pre-TGF alpha and EGFR but not prepro-EGF gene transcripts were expressed in the cell. TGF alpha and EGFR but not EGF proteins were observed by immunocytochemical stainings, using monoclonal antibodies against human TGF alpha, EGFR, and EGF, respectively. This cell line possessed a class of high affinity EGF receptor by 125I-EGF binding studies; Kd being 2.9 x 10(-10) M and Bmax to be 7.7 x 10(4) sites/cell. As much as 1.12 +/- 0.14 ng (SD; n = 3)/10(7) cells/24 h of TGF alpha was secreted in the conditioned media. These results suggested the expression of a TGF alpha/EGFR autocrine mechanism in this cell line. We, therefore, assessed the biological significance of this mechanism on the growth of this cell line in serum-free monolayer cell cultures. Although 0.1, 1.0, and 10 nM concentrations of TGF alpha did not show significant growth promotion, monoclonal antibodies against TGF alpha and EGFR but not EGF significantly inhibited cell growth. All these data suggested the biological importance of a TGF alpha/EGFR autocrine mechanism on the growth of this cell line in vitro.

Antibodies, Monoclonal↗
PubMed1991

Importance of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vivo.

We have elucidated the importance of a transforming growth factor (TGF) alpha and epidermal growth factor receptor autocrine mechanism on the growth of a human ovarian serous cystadenocarcinoma-derived cell line (SHIN-3) in vitro. In this study, we studied the biological significance of this autocrine mechanism in vivo using female athymic nude (nu/nu) mice. We measured the mouse plasma epidermal growth factor and TGF alpha levels by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Plasma epidermal growth factor concentrations were remarkably decreased by sialoadenectomy (Sx): 410 +/- 65 (SE) pg/ml (n = 10) in intact animals; and undetectable in Sx mice (n = 5). Plasma TGF alpha levels were 90 and 40 pg/ml in intact and in Sx animals, respectively. Ten million SHIN-3 cells inoculated into nu/nu mice formed tumors in 100% of mice, and tumors grew progressively. Implantabilities and tumor growth rates of inoculated cells were not affected by Sx and even by Sx and anti-mouse epidermal growth factor antibody treatment. However, anti-TGF alpha monoclonal antibody (mAb) administered to SHIN-3 cell-inoculated Sx animals drastically reduced the tumor growth. Although 10(7) SHIN-3 cells formed tumors in this group, tumor growth was significantly inhibited by 10 micrograms of anti-TGF alpha mAb given 3 times a week, and growth inhibitions were more by 20 micrograms of anti-TGF alpha mAb. Moreover, as aggressive tumor growth as that in Sx animals was resumed by the cessation of anti-TGF alpha mAb treatments. All these data suggested the biological importance of a TGF alpha/epidermal growth factor receptor autocrine mechanism on the growth of this cell line in vivo.

Animals↗
PubMed1991

Evidence for the involvement of transforming growth factor alpha and epidermal growth factor receptor autocrine growth mechanism in primary human ovarian cancers in vitro.

We examined 35 primary human ovarian adenocarcinomas for the presence of epidermal growth factor (EGF) receptor (EGFR) in plasma membranes from cancer tissues by using 125I-EGF as a ligand. Specific 125I-EGF bindings were observed in 20 (57%) of these 35 cases. Scatchard analysis showed a class of high affinity EGF receptor: Kd 5.0 +/- 1.0 x 10(-10) M; Bmax, 83.3 +/- 12.1 fmol/mg protein (mean +/- SE, n = 20). Northern analysis in polyadenylated RNA from 15 EGFR(+) cancers using pretransforming growth factor alpha (pre-TGF alpha), prepro-EGF complementary DNA, and pE7, a complementary DNA clone of human EGFR, as probes revealed that pre-TGF alpha and EGFR mRNAs but not prepro-EGF mRNA were expressed in all cases examined. Immunocytochemical studies using monoclonal antibodies (mAbs) against TGF alpha, EGF, and EGFR showed that TGF alpha and EGFR but not EGF proteins were present on ovarian cancer cells in all cases. These data suggested a possible TGF alpha/EGFR autocrine mechanism in EGFR(+) ovarian cancers. We, therefore, examined the biological significance of this autocrine mechanism by using primary monolayer cell cultures. In primary cultures from EGFR (+) cancers, TGF alpha added to the culture medium stimulated the [3H]thymidine incorporation dose dependently. Moreover, the addition of mAbs against TGF alpha and EGFR but not EGF inhibited [3H]thymidine incorporation dose dependently in EGFR(+) cancer cells. On the other hand, in primary cultures from EGFR(-) cancers, TGF alpha and anti-TGF alpha, -EGFR, and -EGF mAbs did not show any effects on [3H]thymidine incorporation. All these results suggested the possible crucial role of a TGF alpha/EGFR autocrine growth mechanism in primary human ovarian cancers which express EGFR.

Adenocarcinoma↗
PubMed1991

Persistent human immunodeficiency virus type 1 infection in human fetal glial cells reactivated by T-cell factor(s) or by the cytokines tumor necrosis factor alpha and interleukin-1 beta.

Human immunodeficiency virus type 1 (HIV-1) infection of the brain has been associated with a severe dementing illness in children and adults. However, HIV-1 antigens are most frequently found in macrophages and microglial cells. To determine the extent of susceptibility of neuroglial cells to infection, the HIV-1 genome was introduced into cells cultured from human fetal brain tissue. Astroglial cells rapidly transcribed the viral genome producing high levels of p24 protein and infectious virions which peaked two to three days posttransfection. Thereafter HIV-1 genome expression progressively diminished and a persistent phase of infection developed during which neither virus nor viral proteins could be demonstrated by immunodetection methods. Cocultivation with CD4+ T cells at any time during the persistent infection resulted in resumption of p24 synthesis and virus multiplication. The release of persistence did not require direct cell-cell contact between the glial and T cells, since separation of the two cell types across a permeable membrane resulted in a delayed but similar resumption of p24 synthesis and virus multiplication. The persistently infected glial cells could also be stimulated to produce viral p24 protein if either tumor necrosis factor alpha or interleukin-1 beta was added to the medium without T cells present. These results suggest that astrocytes may serve as an undetected reservoir for HIV-1 and disseminate the virus to other susceptible cells in the brain upon triggering by some cellular or biochemical signal.

Astrocytes↗
PubMed1991

Decrease in epidermal growth factor receptor and its messenger ribonucleic acid levels in intrauterine growth-retarded and diabetes mellitus-complicated pregnancies.

We measured the amounts of epidermal growth factor receptor (EGFR) in plasma membranes from human placentas at term delivery in three groups: appropriate for gestational age (AGA), intrauterine growth-retarded (IUGR), and diabetes mellitus-complicated (DM) pregnancies. At the same time, EGFR mRNA levels were examined in three groups by dot and Northern blot analyses. Binding studies were performed using 125I-labeled human EGF as a ligand, and two classes (high and low) of binding sites were found in all specimens. Although dissociation constants (Kd) were not significantly different among three groups, the number of binding sites was significantly decreased in IUGR and DM placentas compared to that in the AGA group. Total cellular RNA was isolated from a part of the placentas used for binding studies using the guanidinium CsCl method, denatured, and dot blotted onto nitrocellulose filter. Poly(A)+ RNA was selected from the total RNA, electrophoresed in 1% agarose gel, and transferred onto nitrocellulose filters. Then, hybridization with 32P-labeled pE7 (a cDNA of EGFR), autoradiography, and densitometry were performed. The amounts of mRNA hybridized with pE7 were reduced in IUGR and DM placentas compared to that in the AGA group. The molecular sizes of EGFR mRNA were 10 and 5.6 kilobases in all three groups. These results suggest possible physiological actions of EGF on adequate feto-placental growth and development in human pregnancy.

Diabetes Mellitus↗
PubMed1991

[Synthesis and antifungal activity of butenafine hydrochloride (KP-363), a new benzylamine antifungal agent].

In screening of new antifungal agents, bis(naphthalenemethyl)amines were found to have more potent antifungal activity than clotrimazole. Studies on their structure-activity relationships indicated that benzylamines had potent antifungal activity. Among them, butenafine hydrochloride (N-p-tert-butylbenzyl-N-methyl-1-naphthalenemethylamine hydrochloride, KP-363) has proved to show the strongest activity. It exhibits a wide spectrum activity in vitro against particularly dermatophytes (87 strains; minimal inhibitory concentration (MIC) range, 0.0015 to 0.05 microgram/ml), and also against Aspergillus (15 strains; MIC range, 0.025 to 0.78 microgram/ml), Cryptococcus neoformans (4 strains; MICs 0.78 and 1.56 micrograms/ml) and yeasts of genus Candida (67 strains; MIC range, 3.13 to greater than 100 micrograms/ml).

Animals↗
PubMed1990

[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.

Adult↗
PubMed1990

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.

Astrocytes↗
PubMed1990

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.

Animals↗