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Biomedical subjects

S Hori

Publications and source records attributed to S Hori.

At least 37 records · Page 2Linked to original sources

Characterization of tissue- and cell-type-specific expression of a novel human septin family gene, Bradeion.

Expression changes in subsets of genes occur in the course of altering cell fates, i.e., aging, cell death, and carcinogenesis. These changes simultaneously provide the good candidate as a biomarker for monitoring cancer. We have identified a novel human septin family gene, Bradeion, from adult brain cDNA library by a monoclonal antibody CE5. Northern blot and in situ hybridization analysis showed that Bradeion has two distinct transcripts, approximately 2.2 and 1.7 kb length (alpha and beta, respectively) mainly in brain and slightly in heart, and no expression in any fetal organs. Haplotype analysis placed the gene location at 17q23. The gene contains GTPase motifs highly conserved in the septin family genes that are essential for cytokinesis and cell separation. The transcript of beta form lacks a hydrophobic region, which suggests that this form arises from a single Bradeion gene through unique RNA splicing. Interestingly, this brain-specific Bradeion gene is also expressed in two human cancers, colorectal cancer and malignant melanoma. Ectopic expression of normal Bradeion alpha and beta transcripts were confirmed both in patients' tumor samples and in in vitro cultured human cancer cell lines. Thus the Bradeion provides valuable tools as a tumor-specific and selective marker.

Amino Acid Sequence↗

Tumor growth inhibition by arsenic trioxide (As2O3) in the orthotopic metastasis model of androgen-independent prostate cancer.

Arsenic trioxide (As2O3) induces clinical remission of patients with acute promyelocytic leukemia. As a novel anticancer agent for treatment of solid cancers, As2O3 is promising, but no in vivo experimental investigations of its efficacy on solid cancers have been done at clinically obtained concentrations. In addition, the cell death mechanism of As2O3 has yet to be clarified, especially in solid cancers. In this study, human androgen-independent prostate cancer cell lines, PC-3, DU-145, and TSU-PR1 were examined as cellular models for As2O3 treatment, and As2O3-induced cell death and inhibition of cell growth and colony formation were evaluated. The involvement of p38, c-Jun NH2-terminal kinase (JNK), caspase-3, and reactive oxygen species (ROS) were investigated in As2O3-induced cell death. Finally, As2O3 was administered to severe combined immunodeficient mice inoculated orthotopically with PC-3 cells to estimate in vivo efficacy. In all three of the cell lines, at high concentrations, As2O3 induced apoptosis and, at low concentrations, growth inhibition. As2O3 activated p38, JNK, and caspase-3 dose dependently. Treatment with the p38 inhibitor and over-expression of dominant-negative JNK did not guard against As2O3-induced cell death. In contrast with partial protection by the caspase-3 inhibitor, the antioxidant N-acetyl-L-cysteine gave marked protection from As2O3-induced apoptosis and eliminated the activation of p38, JNK, and caspase-3, and the generation of ROS. The orthotopic murine metastasis model showed in vivo tumor growth inhibition in orthotopic and metastatic lesions with no signs of toxicity. This study establishes that As2O3 provides a novel, safe approach for treatment of androgen-independent prostate cancer. Generation of ROS as a therapeutic target for the potentiation of As2O3-induced apoptosis also was shown.

Androgens↗

Estimation of absorption rate of alpha-human atrial natriuretic peptide from the plasma profile and diuretic effect after intranasal administration to rats.

The absorption rate of alpha-human atrial natriuretic peptide (alpha-hANP) after intranasal (i.n.) administration to rats was estimated from the plasma profile and pharmacological effect (diuretic effect) using a pharmacokinetic (PK) model and a PK-pharmacodynamic (PD) model involving data obtained after intravenous (i.v.) bolus injection. The plasma concentrations of alpha-hANP after i.v. administration at different doses were fitted to a two-compartment PK model with zero-order excretion and input of endogenous alpha-rat atrial natriuretic peptide (alpha-rANP) and two elimination processes represented by Michaelis-Menten and first-order kinetics. However, the saturable process was ignored at low doses. The plasma concentrations after low doses via the i.n. route could also be expressed by this model, but with first-order absorption, so that an absorption rate constant was calculated using a deconvolution method. In addition, the diuretic effect plotted against the i.v. dose was represented by the Hill equation and showed an anti-clockwise hysteresis loop versus the plasma concentration. These results suggest that the diuretic effect could be estimated by a PK-PD model having an 'effect' compartment or a homeostatic system. Such a PK-PD model accurately expressed the diuretic effect of alpha-hANP at all doses after i.v. and i.n. administrations. The resulting absorption rate constant calculated using the PK-PD model agreed closely with that obtained by the PK model alone. The absorption rate and simulated diuretic effect suggest that, for i.n. administration of alpha-hANP, a higher absorption rate constant causes a more potent diuretic effect (a dramatic effect over the early period), whereas greater bioavailability is associated with a better hypotensive effect (sustained effect).

Absorption↗

Continuous surveillance of organochlorine compounds in human breast milk from 1972 to 1998 in Osaka, Japan.

The presence of chlorinated organic compounds in breast milk of lactating women living in Osaka Prefecture, Japan, has been followed since 1972. Following the highest concentration found at the start of the measurements, contamination by polychlorinated biphenyls (PCBs) and organochlorine pesticides, such as beta-HCH and DDT declined to about 3-13% of the peak levels by the mid-1970s and continued to decrease to low-level equilibrium states. This decline varies greatly with the chemical compound. In comparison with 1970s, when the contamination of breast milk was highest, the beta-HCH level fell to about 3%, DDT to about 7%, and PCBs to about 13%, representative of different half-lives in the environment and the particular persistence of PCB. In the case of chlordane, a termite insecticide, more than 10 years have passed since its use was prohibited in Japan, but it continues to be found in human breast milk, although at a low level.

Adult↗

Localization of endothelin-A and -B receptors during the postnatal development of rat cerebellum.

Intense expression of mRNA of endothelin-B receptor (ETBR) has been detected in the Bergmann glia of cerebellum by in situ hybridization, but the intracellular localization has not been reported because of the absence of a useful antibody for immunohistochemical investigations. We made polyclonal antibodies against the carboxyl terminus of human ETBR (420-442) and ETAR (403-427), and performed light- and electron-microscopic immunohistochemistry of the wild-type and ETBR-deficient (sl/sl) rat cerebella. Localization of ETBR during postnatal development was examined by double-staining immunofluorescence using antibodies against ETBR and S-100 beta. In the wild-type rats, ETBR immunoreactivity appeared from postnatal day 5 (P5) and was distributed diffusely in the processes and cell bodies of S-100 beta-positive glial cells. By P14, ETBR immunoreactivity was concentrated in the Golgi apparatus of Bergmann glial cell soma and the plasma membrane of its processes. The ETBR-positive astrocytes in the granular layer decreased in number during P7-14 and had disappeared by week 3. At 3 weeks, ETBR immunoreactivity was restricted to the Golgi apparatus of Bergmann glia. In the sl/sl rats, ETBR immunoreactivity was not observed at all. In contrast to ETBR, ETAR immunoreactivity appeared transiently in the cytoplasm of all astrocytes (Bergmann glia and astrocytes in the granular layer) in the 9- to 14-day-old wild rats and 7- to 14-day-old sl/sl rats, and disappeared within 3 weeks in both. Granule cells did not express immunoreactivity for ETBR and ETAR from the neonatal stage to adulthood. Changes in the intracellular localization of ETBR and transient expression of ETAR may be correlated with the changes of glial functions and proliferation during postnatal development of rat cerebellum.

Amino Acid Sequence↗

Long-term outcomes of immunosuppressed renal transplant recipients with malignancies.

This study analyzes ten cases of malignancy in a cohort of 183 renal transplant recipients, examining surgical management, postoperative immunosuppressive therapy, and long-term outcome. One of these ten patients, who had malignant lymphoma of the jejunum, died of the neoplasm, but the other nine patients did not show any signs of tumor recurrence after removal. All of these nine patients, except for one who had transplant renal cell carcinoma (RCC), received the same dose of immunosuppressive agents after surgery for the malignant disease. Seven patients were still alive at the time of this report, six of whom had good transplant renal function. The findings of this study indicate that even if immunosuppressive agents predispose to the development of cancer, it is not necessary to reduce their dose after removal of the tumor.

Adult↗

Successful surgical treatment of renal cell carcinoma in a transplanted kidney from a cadaveric donor: report of a case.

Posttransplant renal cell carcinoma (RCC) usually arises in the native kidneys of renal transplant recipients rather than in the transplanted kidney. This report describes a case of RCC that developed in the transplanted cadaveric kidney in a 37-year-old male recipient 9 months after transplantation. An en bloc radical transplant nephrectomy was performed, and he has subsequently remained stable on hemodialysis for 3 years without any sign of recurrence.

Adenocarcinoma↗

Glycemic control and lens transparency in patients with type 1 diabetes mellitus.

PURPOSE: To assess quantitatively the cumulative effect of hyperglycemia on lens transparency in patients with juvenile type 1 diabetes mellitus. METHODS: Subjects were 30 patients (30 eyes) with type 1 diabetes mellitus who had well-documented records on the duration of diabetes mellitus and condition of glycemic control from the onset. They were 35 years of age or younger (mean, 26.0 years), had a history of type 1 diabetes mellitus at least 5 years (mean, 8.4 years), had corrected visual acuity of 20/20 or better, and showed no clinically apparent cataract on slit-lamp examination. Twenty-one eyes of 21 subjects served as age-matched normal controls. They were 35 years of age or younger (mean, 25.7 years), had no diabetes mellitus, had corrected visual acuity of 20/20 or better, and showed no signs of cataract on slit-lamp examination. The degree of lens opacity was quantified using the anterior eye segment analysis system based on the Scheimpflug principle. An index was created to represent the cumulative effect of long-term glycemic control (hyperglycemic accumulation) by multiplying the average hemoglobin A(1c) value and the number of months from the onset. RESULTS: The patients with diabetes mellitus exhibited significantly greater degree of lens opacity than the normal controls (P =.017, Mann-Whitney U-test). Among the patients with diabetes mellitus, the lens opacity was greater in eyes with retinopathy than those without retinopathy (P =.011). Multiple regression analysis revealed that only the index of hyperglycemic accumulation significantly correlated with the degree of lens opacity (P =.042). CONCLUSION: Accumulated effect of hyperglycemia is related to the lens transparency in patients with diabetes.

Adult↗

GC/MS analysis of polybrominated diphenyl ethers in fish collected from the Inland Sea of Seto, Japan.

Development of an analytical method for polybrominated diphenyl ethers (PBDEs) in fish and their concentration in Japanese marine fish were investigated. Fish homogenate was extracted with diethyl ether/hexane (1 + 3). The extract was cleaned up by automated gel permeation chromatography (GPC) and then by mini-column chromatography, which consisted of three layers of silica gel and sulfuric acid-impregnated silica gel. The PBDE fraction was concentrated and injected into a GC/MS with negative chemical ionization (NCl). Recoveries of the 15 individual PBDEs (BDE-15, 28, 37, 47, 66, 71, 75, 77, 85, 99, 100, 119, 153, 154, and 209) each at a fortification level of 4 ng/g lipid were in the range of 88-128% and the relative standard deviations (RSD) were 0.43-7.6% (n = 4). Seven species of marine fish (conger eel, flounder, gray mullet, horse mackerel, red sea bream, sea bass, and yellowtail) were collected from the Inland Sea of Seto, and were analyzed with the developed method. Seven PBDEs (BDE-28, 47, 66, 99, 100, 153, and 154) were detected in all the samples. The most abundant PBDE congener was BDE-47 found in all the samples. Relatively high levels of PBDEs were found in the gray mullets and yellowtails.

Animals↗

Survival of a subarachnoid hemorrhage patient who presented with prehospital cardiopulmonary arrest: case report and review of the literature.

A 63-year-old woman was admitted to the intensive care unit after resuscitation from prehospital cardiopulmonary arrest (CPA). A brain CT scan revealed a subarachnoid hemorrhage (SAH), which was considered to be the cause of the CPA. The patient recovered neurologically after admission, and the elevated intracranial pressure (ICP) was controlled by inducing mild hypothermia. The day after admission, cerebral angiography revealed a ruptured cerebral aneurysm. The aneurysm was successfully treated with detachable coils by an endovascular technique. Mild hypothermia was continued for 3 days, and the patient was gradually rewarmed. After rehabilitation, the patient was discharged to her home with severe disability. Although aneurysmal SAH is one of the most common causes of CPA, survival of SAH patients after CPA is rare. This case illustrates the ability and possibility of multidisciplinary treatment, including the use of endovascular techniques and mild hypothermia, to improve the outcome of SAH patients with CPA who have been considered to be inoperable and untreatable.

Cardiopulmonary Resuscitation↗

Selective paralysis of the upper extremities after odontoid fracture: acute central cord syndrome or cruciate paralysis?

A patient presented with selective paralysis of the arms after having sustained a fall. X-ray of the cervical spine showed a type II odontoid fracture with posterior atlantoaxial dislocation. The diagnosis in the emergency room was cruciate paralysis, which is frequently associated with fractures of axis and/or atlas. However, magnetic resonance imaging (MRI) of the cervical spine revealed a lesion consistent with the acute central cord syndrome (CCS) at the C2-C6 level. The patient underwent posterior atlantoaxial arthrodesis to correct instability and was discharged, without much neurological improvement. Cruciate paralysis has been reported to be associated with fractures of axis and/or atlas, and acute CCS has rarely been associated with the fractures. However, this case illustrates that the lesion responsible for selective paralysis of the upper extremities is not as specific as it had been thought to be, and that it is difficult to accurately identify the level of the cervical cord injury by neurological diagnosis and X-rays alone. Supplementary diagnostic modalities, particularly MRI, are required to make a correct diagnosis and develop a therapeutic strategy.

Acute Disease↗

Regulatory T cells: the physiology of autoreactivity in dominant tolerance and "quality control" of immune responses.

Little progress has been achieved over the last 20 years on the clinical management of several conditions that relate to self-tolerance and to the regulation of immune responses: autoimmune diseases, transplantation tolerance, tumor immunity, allergy and vaccine development in chronic infections. These failures, it is argued, are due to the inability of the prevalent "recessive tolerance" concepts to accommodate physiological autoreactivity and the regulatory potential it embodies. In this review, the advantages of "dominant tolerance" models are underlined in the light of critical evidence and in the general context of the natural autoimmune activities. The role of regulatory T cells is discussed, notably in the regulation of inflammatory reactions and, more generally, in the "quality control" of immune responses. It is anticipated that progress will be brought about by dominant tolerance approaches, and through an increased knowledge of the differentiative pathways, repertoires, mechanisms of activation and effector functions of autoreactive, regulatory T cells.

Animals↗

VCP/p97 in abnormal protein aggregates, cytoplasmic vacuoles, and cell death, phenotypes relevant to neurodegeneration.

Neuronal cell death, abnormal protein aggregates, and cytoplasmic vacuolization are major pathologies observed in many neurodegenerative disorders such as the polyglutamine (polyQ) diseases, prion disease, Alzheimer disease, and the Lewy body diseases, suggesting common mechanisms underlying neurodegeneration. Here, we have identified VCP/p97, a member of the AAA+ family of ATPase proteins, as a polyQ-interacting protein in vitro and in vivo, and report on its characterization. Endogenous VCP co-localized with expanded polyQ (ex-polyQ) aggregates in cultured cells expressing ex-polyQ, with nuclear inclusions in Huntington disease patient brains, and with Lewy bodies in patient samples. Moreover, the expression of VCP mutants with mutations in the 2nd ATP binding domain created cytoplasmic vacuoles, followed by cell death. Very similar vacuoles were also induced by ex-polyQ expression or proteasome inhibitor treatment. These results suggest that VCP functions not only as a recognition factor for abnormally folded proteins but also as a pathological effector for several neurodegenerative phenotypes. VCP may thus be an ideal molecular target for the treatment of neurodegenerative disorders.

Adenosine Triphosphatases↗

Multiresidue analysis of pesticides in vegetables and fruits using two-layered column with graphitized carbon and water absorbent polymer.

A high-throughput multiresidue analysis of pesticides in non-fatty vegetables and fruits was developed. The method consisted of a single extraction and a single clean-up procedure. Food samples were extracted with ethyl acetate and the mixture of extract and food dregs were poured directly into the clean-up column. The clean-up column consisted of two layers of water-absorbent polymer (upper) and graphitized carbon (lower), which were packed in a reservoir (75 ml ) of a cartridge column. The polymer removed water in the extract while the carbon performed clean-up. In a recovery test, 110 pesticides were spiked and average recoveries were more than 95% from spinach and orange. Most pesticides were recovered in the range 70-115% with RSD usually < 10% for five experiments. The residue analyses were performed by the extraction of 12 pesticides from 13 samples. The two methods resulted in similar residue levels except chlorothalonil in celery, for which the result was lower with the proposed method. The results confirmed that the proposed method could be applied to monitoring of pesticide residue in foods.

Food Contamination↗

Epidermal growth factor induces expression of decay-accelerating factor in human colonic cancer cells via the mitogen-activated protein kinase pathway.

The expression of decay-accelerating factor (DAF), a complement regulatory protein, is enhanced in colorectal cancer. In this study, to elucidate mechanisms for enhanced DAF expression, we studied the effects of growth factors on DAF expression in HT-29 human colonic cancer cells. Cells were treated with epidermal growth factor (EGF), insulin-like growth factor-I, platelet-derived growth factor, and transforming growth factor-beta. DAF protein expression and mRNA expression were determined with enzyme immunoassay and Northern blot analysis. The signaling pathways that target DAF expression in response to growth factor stimulation were characterized by using various inhibitors of the signal transduction pathway. EGF induced significant increases in DAF protein and mRNA expression in HT-29 cells; the other growth factors had a weak effect or no effect. The EGF-induced DAF expression was inhibited by mitogen-activated protein (MAP) kinase kinase inhibitor PD 98059 but not by phosphatidylinositol-3 kinase inhibitor, phospholipase Cgamma inhibitor, or protein kinase C inhibitor. When we analyzed the phosphorylation state of the MAP kinase by immunoblot analysis, phosphorylated p44/p42 MAP kinase was detected in EGF-stimulated HT-29 cells, and the addition of PD 98059 abrogated the phosphorylation. These results indicate that EGF regulates DAF expression in HT-29 cells via the signaling pathway that depends on the activation of MAP kinase.

Blotting, Northern↗

Relationship between vascular endothelial growth factor and interleukin-6 in diabetic retinopathy.

PURPOSE: To determine the relationship between the severity of diabetic retinopathy and the levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in aqueous humor and plasma. METHODS: Forty-four eyes of 34 diabetic patients were studied. The concentrations of VEGF and IL-6 in plasma samples and in aqueous specimens obtained from the eyes during cataract surgery were measured by enzyme-linked immunosorbent assay. RESULTS: Aqueous levels of VEGF and IL-6 were significantly correlated with the severity of diabetic retinopathy (p = 0.793 and p = 0.744, respectively). Vascular endothelial growth factor and IL-6 levels in aqueous humor were significantly correlated with the aqueous protein concentration (p = 0.641 and p = 0.646, respectively). The aqueous level of VEGF was significantly correlated with that of IL-6 (p = 0.627). Aqueous levels of VEGF and IL-6 were also significantly correlated with the grade of fundus findings. Vascular endothelial growth factor and IL-6 concentrations were higher in the aqueous than in the plasma. CONCLUSION: The results of the current study suggest that there is a relationship between VEGF and IL-6 but the role of IL-6 in diabetic retinopathy is unclear and may warrant further investigation.

Adult↗