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Biomedical subjects

K Shimizu

Publications and source records attributed to K Shimizu.

At least 469 records · Page 26Linked to original sources
PubMed1998

Indocyanine green angiographic features of idiopathic submacular choroidal neovascularization.

PURPOSE: To clarify the indocyanine green angiographic features of idiopathic submacular choroidal neovascularization. METHODS: We performed fluorescein and indocyanine green angiography in 16 eyes of 16 patients (nine men, seven women; mean age +/- SD, 35.6 +/- 6.9 years; range, 24 to 48 years) with idiopathic submacular choroidal neovascularization. During the mean follow-up of 11.4 +/- 7.9 months (range, 1 to 28 months), angiography was repeated (mean, 2.6 +/- 0.5 times; range, 2 to 3 times) in 12 eyes and performed only once in four eyes. RESULTS: In the early phase of indocyanine green angiography, a network of choroidal neovascularization was observed in 11 of the 16 eyes with well-defined choroidal neovascularization seen by fluorescein angiography. Choroidal hyperfluorescent areas were noted in 10 of the 16 eyes in the late-phase angiography. Three of the 10 eyes showed focal dilatation of choroidal veins within the hyperfluorescent areas. Choroidal neovascular membrane was located within the hyperfluorescent areas in eight of the 10 eyes with choroidal hyperfluorescent areas. A dark rim surrounding choroidal neovascularization was observed in 13 of the 16 eyes at the initial examination. Indocyanine green angiography was repeated in nine of the 13 eyes and in the other three eyes without dark rim initially. During the follow-up period, the dark rim became prominent in eight of the nine eyes and developed in one eye without dark rim initially. Choroidal neovascular membrane regressed in these nine eyes. Choroidal neovascularization remained active or enlarged in three eyes in which the dark rim was stationary or invisible. CONCLUSIONS: The dark rim surrounding the choroidal neovascularization in indocyanine green angiograms appeared to reflect regression of idiopathic choroidal neovascularization. Choroidal vascular abnormalities such as hyperfluorescent areas or focal venous dilatation seem to be the background lesion predisposing to the choroidal neovascularization.

Adult↗
PubMed1998

Reperfusion of occluded capillary beds in diabetic retinopathy.

PURPOSE: To demonstrate the reperfusion of nonperfused capillary beds in diabetic retinopathy. METHODS: In a retrospective study, we reviewed 292 fluorescein angiograms of 94 eyes of 74 patients (mean age, 52 years; range, 20 to 68 years) with diabetic retinopathy. Fluorescein angiography was performed repeatedly (mean, three times; range, two to eight times) during a mean follow-up period of 2 years (range, 3 months to 12 years). None of the 94 eyes received laser photocoagulation. RESULTS: Reperfusion of occluded capillary beds was observed in 65 (69%) of 94 eyes. Reperfusion was characterized by recanalization in 22 (34%) of the 65 eyes or by intraretinal neovascularization in 54 (83%) of the 65 eyes. The former took place in small nonperfused areas and the latter in larger nonperfused areas. Reperfusion occurred throughout the entire fundus in six of 94 eyes, resulting in resolution of diabetic retinopathy. Reperfused capillary beds with intraretinal neovascularization left vascular remodeling, which was seen as twisted or kinked abnormal vessels. CONCLUSIONS: In diabetic retinopathy, occluded capillary beds may be reperfused. Twisted abnormal vessels may represent the reperfusion process through intraretinal neovascularization.

Adult↗
PubMed1998

Radiation choroidopathy with remodeling of the choroidal venous system.

PURPOSE: To describe a case of radiation choroidopathy manifesting drastic remodeling of choroidal drainage routes. METHOD: Case report. A 34-year-old man who had received radiation treatment for a tumor in the upper eyelid of his right eye 15 years earlier had floating black spots. He was examined ophthalmologically, including with indocyanine green angiography using a scanning laser ophthalmoscope. RESULTS: The right eye manifested classic features of radiation retinopathy in the superior fundus. Indocyanine green angiography showed vaso-occlusion of choroidal arteries, capillaries, and veins in a wider area than that affected by radiation retinopathy. The superotemporal vortex vein was obliterated, resulting in a remodeling of the choroidal veins in the same quadrant. The blood in this quadrant drained into the inferotemporal vortex vein through collateral venovenous drainage routes. CONCLUSION: The diagnosis in this eye was radiation retinopathy and radiation choroidopathy. Choroidal vascular lesions were more pronounced and involved a wider area than retinal vascular lesions did. This case illustrates that the choroidal veins may manifest a vast plasticity to remodel the drainage route after obliteration of a major vortex vein.

Adult↗
PubMed1998

Interferon-gamma-secreting T-cell populations in rejecting murine cardiac allografts: assessment by flow cytometry.

Interplay between T-helper-1 (Th1) and T-helper-2 (Th2) cells is considered important in the development of acute allograft rejection and many other immune-mediated disease processes. Existing methods for evaluating expression of Th1 and Th2 cytokines, including reverse transcriptase polymerase chain reaction (RT-PCR), RNase protection assay (RPA), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) all have limitations; alternate techniques to quantify cell populations expressing specific cytokine proteins, generate statistically analyzable data, and allow simultaneous identification of cytokine-secreting cell type are needed. To this end, we adapted a flow cytometric technique for intracellular cytokine immunofluorescence staining for use with cells isolated from solid tissue. To demonstrate the utility of the method, we determined the number of CD4+ and CD8+ cells secreting the prototypical Th1 and Th2 cytokines, interferon (IFN)-gamma, and interleukin (IL)-4 in acutely rejecting murine cardiac allografts. We also measured the cytokine production via ELISA, RPA, and semiquantitative competitive RT-PCR. The number of CD4+ cells producing IFN-gamma increased as rejection proceeded, in agreement with previous data; we detected no IL-4 production at any time, although relatively low numbers of IL-10-producing cells were identified. In addition, a high percentage of CD8+ cells, which outnumber CD4+ cells at day 6 after transplant, also produce IFN-gamma, suggesting that cytotoxic lymphocytes contribute significantly to the local cytokine milieu. This new application of intracellular cytokine staining provides a powerful methodology for studying transplantation immunology. The method may also be easily adapted to the study of other immune-mediated processes.

Animals↗
PubMed1998

Triterpenoid saponin from Vaccaria segetalis.

A new triterpenoid saponin, vaccaroid B, has been isolated from the seeds of Vaccaria segetalis and its structure was elucidated to be 3beta-hydroxyolean-12-en-23, 28-dioic acid-28-O-beta-D-glucopyranosyl-(1-->3)- beta-D-glucopyranosyl-(1-->6)-[6- O-(3-hydroxy-3-methylglutaryl)-beta-D-glucopyranosyl-(1-->2)]- beta-D-glucopyranoside by spectroscopic methods.

Carbohydrate Conformation↗
PubMed1998

Reduced dorsal hippocampal glutamate release significantly correlates with the spatial memory deficits produced by benzodiazepines and ethanol.

Memory deficits frequently occur after taking benzodiazepines and ethanol. We studied in vivo hippocampal presynaptic glutamate transmission in conjunction with memory deficits induced by benzodiazepines and ethanol in rats as an animal model of amnesia. These drugs potently impaired spatial memory formation as evaluated by the Morris water maze task, the rank order among tested treatments being the combination of triazolam (20 micrograms/kg) with ethanol (2 g/kg) > or = triazolam (100 micrograms/kg) > ethanol (2 g/kg) > or = triazolam (20 micrograms/kg) > rilmazafone (20 micrograms/kg). On the other hand, these drug treatments also reduced glutamate release in the dorsal hippocampus but not in the cerebellum measured by microdialysis: the combined administration of triazolam with ethanol potently inhibited glutamate release to 60% of basal output in the dorsal hippocampus. These decreases in hippocampal glutamate transmission closely correlated with the extent of impairment of spatial memory performance (r = 0.990). Thus, the present results strongly indicated that presynaptic dysfunction in dorsal hippocampal glutamatergic neurons would be critical for spatial memory deficits induced by benzodiazepines and ethanol.

Animals↗
PubMed1998

Florid reactive follicular hyperplasia in elderly patients. A clinicopathological study of 23 cases.

Florid reactive follicular hyperplasia (FRFH) of the enlarged lymph node in elderly patients requiring biopsy is a relatively uncommon phenomenon as compared with younger age groups. We experienced 23 patients, aged 60 years or more, from whom the biopsied lymph node specimens histologically showed inappropriate FRFH for their age, in the period between 1982 and 1996. These cases were morphologically subdivided into three groups, FRFH with interfollicular plasmacytosis, that with progressive transformation of germinal center, and FRFH without additional specific findings. FRFH with interfollicular plasmacytosis were observed in 11 cases, all of whom were accompanied with several immunological abnormalities (six with rheumatoid arthritis, three with multicentric Castleman's disease and one each with myoepithelial sialoadenitis and autoimmune hemolytic anemia). Three men with uncertain etiology exhibited an unusual histology of progressive transformed germinal centers which were clinically characterized by a bulky neck mass. Among the nine cases with nonspecific FRFH, only four had a specific etiology (one each with adult onset Still's disease, chronic sinusitis, Epstein-Barr virus infection and infectious lateral cervical cyst), while the other five with unknown etiology showed abnormal laboratory findings suggestive of an abnormal humoral immune response, i.e. hypergammaglobulinemia and seropositivities for some autoantibodies. None of our patients developed malignant lymphoma during the follow-up period. Of note, 16 (70%) of the 23 cases were found to be associated with various types of imbalances of the immune system, some of which appeared to be currently ill-defined as clinicopathological entities that were simply categorized as autoimmune disease.

Aged↗
PubMed1998

Occurrence of monocytoid B-cells in reactive lymph node lesions.

Benign monocytoid B-cells are a peculiar subset of B-cells. They are closely related to marginal zone B-lymphocytes, show cytological diversity and may be recognized in a variety of reactive lymph node conditions. To analyze the incidence, cytological spectrum and phenotypic features of benign monocytoid B-cells, we investigated a series of 301 consecutively biopsied and unselected cases of reactive lymph node change from 1988 and 1995. A monocytoid B-cell reaction was identified in 46 (15%) cases and could be cytologically subclassified into two groups: 31 (67%) cases with common-type cells and 15 (33%) cases with large, transformed cells, according to the description by Plank et al. [19]. These reactions were regularly associated with follicular hyperplasia (95%) and were part of an epithelioid cell response in 24 cases (50%). Immunohistologically, both types of benign monocytoid B-cells were negative for bcl-2 protein expression, which was in contrast to the bcl-2 positive reaction in marginal zone B-lymphocytes and their neoplastic counterpart in monocytoid B-cell lymphoma. An association of Epstein-Barr virus (EBV) with monocytoid B-cells was investigated by in situ-hybridization. EBV genomes were detected in five (15%) of 31 cases tested. In each of these five cases, positive cells were represented in both high and low numbers. The morphologic features of the EBV-positive cells were not consistent with monocytoid B-cells, but rather with medium-sized to large lymphoid cells. It appeared that the occurrence of monocytoid B-cell reaction in reactive lymph node lesions was not related to EBV infection in the majority of cases.

Adolescent↗
PubMed1998

In vitro study on intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) for meningeal dissemination of malignant brain tumors.

We investigated 5-fluoro-2'-deoxyuridine (FdUrd) as a potential agent for intrathecal treatment of malignant brain tumors with meningeal dissemination. We examined the neurotoxicity of FdUrd in vitro using primary cultures of neurons from C57BL/6 mice (ED14). Tumoricidal activity was also studied in four glioma cell lines and one medulloblastoma cell line. In addition, thymidine phosphorylase (TPase) and thymidine kinase (TK), which are key enzymes for FdUrd metabolism, were measured in the cerebrospinal fluid (CSF) of 36 patients with brain tumors. The antitumor activity of FdUrd for murine glioma cells was approximately 20- to 200-fold higher than that of 5-fluorouracil (5-FU). Against human cell lines, it was 3- to 500-fold higher than that of 5-FU. The neurotoxic effect of FdUrd on cultured neurons was far less than that of 5-FU or 5-fluorouridine (FUrd). Cerebrospinal fluid contained no detectable thymidine phosphorylase in most patients with brain tumors. Several studies have indicated that FdUrd is rapidly converted to 5-FU in the presence of thymidine phosphorylase, so that a high dose of FdUrd must be administered to obtain good efficacy. However, a high dose FdUrd frequently cause severe toxicity. In contrast, the data obtained here suggest that no enzymatic conversion of FdUrd to 5-FU should occur in the CSF. In addition, FdUrd has an excellent antitumor activity and minimal neurotoxicity. We therefore conclude that intrathecal FdUrd is a potential therapy for CSF dissemination of malignant brain tumors.

Animals↗
PubMed1998

Interferon yield and MHC antigen expression of human medulloblastoma cells and its suppression during dibutyryl cyclic AMP-induced differentiation: do medulloblastoma cells derive from bipotent neuronal and glial progenitors?

1. Human medulloblastoma (ONS-76), a central nervous system (CNS)-derived undifferentiated cell line, was found to possess glial characteristics as defined by responses in the interferon (IFN) system; ONS-76 cells produced as much IFN-beta as human fibroblast and glioma cells by viral infection and poly(I):poly(C) induction. 2. Major histocompatibility complex (MHC) class I antigens were also induced under IFN-beta stimulation. ONS-76 cells expressed neurofilament protein, as shown by Northern blot analysis, and morphological differentiation was induced by dibutyryl cyclic AMP (dcAMP). 3. Expression of IFN-beta and MHC class I antigens was suppressed in ONS-76 cells during the dcAMP-induced differentiation. 4. These results showed that ONS-76 cells possessed a glial property in IFN system responses and a neuronal property in cytoskeleton protein, suggesting that the precursors of medulloblastoma may be characterized as bipotent neuronal and glial progenitors in CNS.

Bucladesine↗
PubMed1998

Regulation of interferon responses in medulloblastoma cells by interferon regulatory factor-1 and -2.

Transcriptional activator interferon regulatory factor (IRF)-1 and repressor IRF-2 are known to play a critical role in the regulation of interferon (IFN) responses and oncogenesis in fibroblasts. Although these two factors are expressed in many tissues, including the brain, the role of IRFs in the central nervous system (CNS) has not been elucidated. We analysed a medulloblastoma cell line, ONS-76, as a CNS-derived model system and generated its derivatives, R1 and R2 cells, which constitutively expressed each mouse IRF-1 and IRF-2 cDNA at high levels. By viral infection, R1 and R2 cells showed IFN-beta gene expression 3 h earlier than the control ONS-76 (C-76) cells, with 2.46- and 2.24-fold increase in IFN-beta production respectively. In the presence of cycloheximide, virally induced IFN-beta gene expression of C-76 cells was suppressed, whereas R1 and R2 cells produced IFN-beta 7.5- and 2.2-fold higher than C-76 cells respectively. On the other hand, induction of IFN-inducible genes was enhanced in R1 cells but was suppressed in R2 cells compared with C-76 cells. These results demonstrate that IRF-1 and IRF-2 may play an important role in the regulation of IFN-beta and IFN-inducible genes and that IRF-2 may have dual functions as an activator and repressor in CNS-derived cells.

Animals↗
PubMed1998

Systemic interleukin 12 displays anti-tumour activity in the mouse central nervous system.

In various systemic cancers, interleukin 12 (IL-12) induces anti-tumour immunity mediated by T lymphocytes and natural killer cells. To determine whether IL-12 has anti-tumour activity against malignant gliomas in the central nervous system (CNS), which is considered to be an immunologically privileged site, we treated mice with meningeal gliomatosis by intraperitoneal (i.p.) or intrathecal (i.t.) administration of recombinant murine IL-12. Although untreated mice revealed symptoms, such as body weight loss or paraplegia as a result of the meningeal gliomatosis within 8 days after tumour inoculation, 80% of the mice treated with IL-12 at 0.5 microg i.p. were cured. Many lymphocytes, mostly CD4+ and CD8+ cells, infiltrated to the tumours of IL-12-treated mice. The numbers of these cells increased in the cervical lymph nodes, into which the cerebrospinal fluid drains, and there they secreted a considerable amount of interferon-gamma. Mice cured by IL-12 rejected subcutaneous or i.t. rechallenge with their original glioma cells, but the same mice were not able to reject other syngeneic tumour cells. These results indicate that the immune system recognizes malignant glioma cells in the subarachnoid space of the CNS and that systemic IL-12 may produce effective anti-tumour activity and long-lasting tumour-specific immunity.

Animals↗
PubMed1998

Peripheral blood stem cell autografts for the treatment of children over 1 year old with stage IV neuroblastoma: a long-term follow-up.

This is the first report of the long-term therapeutic results in 22 children more than 1 year old with stage IV neuroblastoma who were treated with autologous peripheral blood stem cell transplantation (PBSCT). The median age of the patients at PBSCT was 4 years (1 to 10 years) and seven of the 17 patients who were evaluated for N-myc amplification were positive. PBSC were collected by a median of four aphereses per patient. The patients underwent PBSCT from 6 to 21 months after the start of therapy (median 10.5 months) at which time 13 patients were in CR, seven were in PR, and two had refractory disease. Multi-drug therapy using the 'high-MEC' regimen consisting of carboplatinum (400 mg/m2) and VP-16 (200 mg/m2) on days -7 to -4, and melphalan (90 mg/m2) on days -3 and -2, was the primary cytoreductive regimen. The median number of infused MNC and CFU-GM was, respectively, 4.3 x 10(8)/kg and 2.4 x 10(5)/kg. After PBSCT, three patients died of regimen-related toxicities and one patient who was transplanted with refractory disease died of disease progression without any benefit from transplantation. Hematological recovery was evaluated in 21 patients, excluding one early death. The median number of days required to achieve an AGC of >0.5 x 10(9)/l and platelet count of >50 x 10(9)/l were, respectively, 11 and 46. Eleven patients relapsed 3 to 50 months after PBSCT, and currently seven patients (5/13 who were transplanted in CR and 2/7 in PR) are surviving disease-free at 52 to 84 months. Although the retrospective nature of this study and several variables prevent a meaningful analysis, the overall results still support the feasibility of developing a prospective study of PBSCT with a larger number of children with high-risk neuroblastoma.

Child↗
PubMed1998

Transduction of glioma cells using a high-titer retroviral vector system and their subsequent migration in brain tumors.

The intracranial migration of transduced glioma cells was investigated in order to improve the treatment of malignant glioma by gene therapy using retroviral vectors. In this study, about half the volume of the tumor mass could be transduced in 14 days after only a single implantation of 3 x 10(5) retrovirus-producing cells into a tumor mass with a diameter of 5 mm. Moreover, we were able to follow the migration of glioma cells transduced by the lacZ-harboring retroviruses originating from the high-titer retrovirus-producing cells. Besides the importance of using a high-titer retroviral vector system, our results also indicate that the implantation site of the virus-producing cells and the interval between the implantation of the virus-producing cells and the subsequent administration of ganciclovir are important factors for the efficient killing of glioma cells.

Animals↗
PubMed1998

Surgical treatment for ossification of the posterior longitudinal ligament and the yellow ligament in the thoracic and cervico-thoracic spine.

This study analyzed the postoperative results of surgical treatment for thoracic and cervicothoracic myelopathy caused by ossification of the posterior longitudinal ligaments (OPLL) or ossification of the yellow ligaments (OYL) in 22 patients using magnetic resonance imaging (MRI), myelography and computed tomography (CT). Anterior procedures were performed in 11 patients for OPLL, while posterior approaches were adopted for the management of 11 patients for both OYL and OPLL combined with OYL lesions. Clinical symptoms were improved using both anterior and posterior techniques. MRI and myelo-CT studies, which show the direction of cord compression, the form and extent of the lesion, and the degree of thoracic kyphosis, are very useful when the surgical procedure for OPLL and OYL in the thoracic and cervico-thoracic spine is selected.

Adolescent↗
PubMed1998

Inducible nitric oxide synthase is expressed in granuloma pyogenicum.

It is known that granuloma pyogenicum (GP) grows rapidly but cherry angioma (CA) does not, although they show the same histological features of hyperplasia of the capillary vessels. Although some cytokines have been thought to be angiogenic factors, a nitric oxide (NO) synthase-dependent effector mechanism is reported to be involved in macrophage-derived angiogenesis in humans. Under the hypothesis that this mechanism is also involved in the more rapid growth of GP, we examined the expression of inducible NO synthase (iNOS) in GP as compared with that in CA. The expression of iNOS mRNA was detected in GP, but not in CA, by reverse transcription-polymerase chain reaction (RT-PCR) analysis. In situ hybridization (ISH) demonstrated iNOS mRNA expression in endothelial cells and to a lesser extent round cells and spindle cells in the myxomatous stroma in GP. Immunohistochemical study showed that iNOS protein was expressed in endothelial cells, infiltrating round cells and spindle cells in the stroma in GP. These results suggested that a NOS-dependent mechanism may be involved in angiogenesis and the rapid growth of GP.

Adult↗
PubMed1998

The inhibitory components from Artocarpus incisus on melanin biosynthesis.

The inhibitory effects of methanol extracts of heartwood of 23 Papua New Guinean wood species on tyrosinase activity were examined. The extract of Artocarpus incisus showed the strongest tyrosinase inhibitory activity which was equivalent to kojic acid. The extract apparently inhibited melanin biosynthesis of both cultured B16 melanoma cells without any cytotoxicity and in the back of a brown guinea pig without skin irritation. Thus, the potentiality of the extracts of heartwood of A. incisus both as material of a useful skin whitening agent and as a remedy for disturbances in pigmentation is evident. Tyrosinase inhibitory activity-guided fractionation led to the isolation of seven active compounds including a new compound which has been characterized as 6-(3"-methyl-1"-butenyl)-5,7,2',4'-tetrahydroxyflavone, named isoartocarpesin. Other active compounds were (+)-dihydromorin, chlorophorin, (+)-norartocarpanone, 4-prenyloxyresveratrol, artocarbene, and artocarpesin, These compounds are probably responsible for the melanin biosynthesis inhibitory effects.

Animals↗