Biomedical subjects

S Kishi

Publications and source records attributed to S Kishi.

At least 55 records · Page 3Linked to original sources

PubMed1998

A combination chemoendocrine therapy of mitoxantrone, doxifluridine, and medroxyprogesterone acetate for anthracycline-resistant advanced breast cancer.

Between January 1993 and October 1995, 34 patients with anthracycline-resistant advanced breast cancer were treated with a combination chemoendocrine therapy of mitoxantrone (MIT), doxifluridine (5'-DFUR) and medroxyprogesterone acetate (MPA). Of 34 patients, 28 were evaluable for efficacy of this combination therapy, and 30 including 2 for whom data were incomplete were assessed for adverse drug reactions. Adriamycin (ADM) was used for pretreatment in 12 patients, 4'-epi-ADM in 6, and THP-ADM in 12. In the eligible patients, 8.0 mg/m2 MIT was administered intravenously every 4 weeks, and 600 mg MPA and 600 mg 5'-DFUR were given orally every day. The median follow-up period was 25 weeks (range 2-90 weeks). The median cumulative dose of mitoxantrone was 66 mg (range 12-121 mg). Of the 28 patients, 11 (39.3%) responded to this combination therapy. As for response in relation to predominant site of lesion, 1 of 5 soft tissue lesions (20%) and 8 of 12 bone metastases (66.7%) showed a partial response, and one complete response and one partial response (25.0%) were seen in eight lung lesions. None of three pleural lesions responded to this therapy. The median duration of response was 31 +/- weeks (range 12-82 weeks). Adverse drug reactions were controllable or tolerable. Combined chemoendocrine therapy with a low dose of MIT is a well-tolerated and moderately effective regimen for the treatment of anthracycline-resistant advanced breast cancer.

Adult↗

PubMed1998

Serous detachment of the ciliary body in Harada disease.

PURPOSE: To evaluate the involvement of the anterior ocular segment in Harada disease. METHODS: In a prospective study, ultrasound biomicroscopy was performed in 18 consecutive eyes of nine patients with Harada disease in its acute phase before and after onset of systemic corticosteroid therapy. Examination was repeated every 3 days until the resolution of serous retinal detachment. RESULTS: Serous detachment of the ciliary body was present in 11 (61%) of 18 eyes before treatment. The circumference of the ciliary body was detached in 10 of the 11 eyes. The height of ciliary detachment ranged from 20% to 250% of the scleral thickness. Ciliary detachment was more prominent in eyes with more extensive retinal detachment. There was no relation between the frequency of ciliary detachment and the severity of iritis. On day 3 of treatment, ciliary detachment had disappeared in seven eyes. In the other four eyes, it diminished in height to less than 10% of scleral thickness. Retinal detachment disappeared on days 6 through 17 (mean, day 11) of treatment. Two eyes of one patient showed very shallow anterior chambers. These eyes showed high ciliary detachment at 250% of scleral thickness. In another patient, both eyes developed -5.0 diopters of transient myopia. CONCLUSION: Ciliary detachment was a frequent finding in the acute stage of Harada disease. Its resolution was more prompt than that of serous retinal detachment after treatment. Ciliary detachment may be related to the development of a shallow anterior chamber.

Acute Disease↗

PubMed1998

Formation of retinochoroidal collaterals in central retinal vein occlusion.

PURPOSE: To demonstrate the drainage routes that compensate the venous congestion in central retinal vein occlusion. METHODS: Indocyanine green angiography was performed in 13 eyes of 13 patients with central retinal vein occlusion at the involutional stage using a scanning laser ophthalmoscope. The interval between onset of central retinal vein occlusion and indocyanine green angiography ranged from 1.0 to 9.3 years (mean, 3.6 years). Panoramic indocyanine green angiograms that covered the entire choroidal vasculature were produced by composing regional angiograms. RESULTS: Retinochoroidal collateral routes were found in 10 eyes that had papillary vascular loops. They were not observed in three eyes that did not have the vascular loops. Papillary vascular loops served as the collaterals to connect retinal veins and choroidal veins. The blood in the retinal veins was drained through the papillary vascular loops into the choroidal veins. These choroidal veins were selectively dilated and acted as drainage routes to the vortex veins. Nasal vortex veins served as extraocular exits of the drainage routes in all 10 eyes, and temporal vortex veins served as extraocular exits of the drainage routes in three of the 10 eyes. CONCLUSIONS: In central retinal vein occlusion with papillary loops, blood in the retinal veins ultimately drained into the vortex veins through the retinochoroidal collaterals.

Aged↗

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

Idarubicin and idarubicinol are less affected by topoisomerase II-related multidrug resistance than is daunorubicin.

We investigated the cytotoxicity and cellular pharmacology of idarubicin (IDA), idarubicinol (IDAol) and daunorubicin (DNR) in K562/VP-H2 cells, which show topoisomerase II-related multidrug resistance but do not overexpress P-glycoprotein. K562/VP-H2 cells were less resistant to IDA and IDAol than to DNR. There was no significant difference in the accumulation of each drug between K562 and K562/VP-H2 cells. The cleavage of DNA induced by each drug was decreased in K562/VP-H2 cells, however, the decrease in cleavage in K562/VP-H2 cells was less with IDA and IDAol than with DNR. These results suggest that IDA and IDAol have more cytotoxic potency than DNR in topoisomerase II-related multidrug-resistant leukemia cells.

Antineoplastic Agents↗

PubMed1998

Effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga mice.

The effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga (NC) mice was examined. FK506 ointment (0.1-1%) suppressed the development of dermatitis and was also therapeutically effective against established dermatitis. Increases in CD4-positive T cells (helper T cells), mast cells, eosinophils and immunostaining of interleukin (IL)-4, IL-5 and IgE were confirmed in the skin of the NC mice, and FK506 ointment suppressed all of these changes. Increased plasma IgE was also confirmed in the NC mice, and treatment with FK506 ointment reduced the plasma IgE level. These results suggested that FK506 suppressed the dermatitis by inhibiting the activation of inflammatory cells and by blocking the cytokine network in the skin of the NC mice. The commercially available steroid ointments showed only marginal effect on the development of dermatitis and showed some signs of side effects such as alopecia or atrophy of the skin. The effect of the steroids might have been masked by these side effects because the steroids showed similar inhibitory effects on the skin histopathological changes and the increase of plasma IgE. From these results, FK506 ointment can be expected to be a useful drug for atopic dermatitis.

Animals↗

PubMed1998

Diagnostic pearls in the management of vitreomacular disorders.

The posterior precortical vitreous pocket is a premacular liquefied lacuna that is physiologically present in adult eyes. The posterior wall of the pocket consists of a thin layer of the vitreous, and its anterior border is delineated by vitreous gel. This peculiar structure of the premacular vitreous cortex plays a key role in the development of various vitreomacular disorders. In diabetic retinopathy, fibrovascular tissue tends to develop along the outer margin of the pocket, resulting in a ring- or c-shaped structure. Tangential contraction of the posterior wall of the pocket or premacular cortex causes the formation of macular holes. The posterior wall of the pocket serves as a major structural component of idiopathic premacular fibrosis. The concept of the posterior precortical vitreous pocket provides a guideline to manage vitreoretinal disorders occurring in the macular area.

Adult↗

PubMed1997

The proteolytic cleavage of protein kinase C isotypes, which generates kinase and regulatory fragments, correlates with Fas-mediated and 12-O-tetradecanoyl-phorbol-13-acetate-induced apoptosis.

Protein kinase C (PKC) has been implicated in signaling induced by diverse sets of stimuli regulating growth, differentiation, and apoptosis. The present study focused on the fate of PKC isotype proteins during Fas-mediated apoptosis of human leukemic cell lines. Among the PKC isotypes expressed in different cell types, such as Jurkat, HPB-ALL, U937, and HL60, all the nPKC isotypes including nPKCdelta, nPKC epsilon, and nPKCtheta, but not cPKC alpha and betaII and aPKCzeta (n, c, and a represent novel, conventional and atypical, respectively), showed limited proteolytic cleavage during Fas-mediated apoptosis. The limited proteolysis of nPKC isotypes means the disappearance of the intact protein band concomitant with the appearance of two fragments, most likely containing the kinase and regulatory domains, in contrast to the so-called down-regulation known for both cPKC and nPKC isotypes following exposure to stimuli such as 12-O-tetradecanoyl-phorbol 13-acetate (TPA). The time course of Fas-mediated apoptosis in Jurkat cells parallels that of the activation of a 32-kDa cysteine protease (CPP32)-like protease and also closely parallels the proteolytic cleavage of nPKC isotypes. A peptide inhibitor of the CPP32-like protease, Ac-DEVD-CHO, blocked the proteolytic cleavage of nPKC isotypes as well as apoptosis mediated by Fas. Transfection of recombinant protein coding for the catalytic fragment of nPKCdelta to COS1 cells resulted in the apoptotic morphology of cells and nuclei. The effect of TPA on apoptosis depends on the cell type. TPA significantly suppressed Fas-mediated apoptosis in Jurkat, whereas TPA alone caused apoptosis in HPB-ALL, U937, and HL60, only slight apoptosis in Jurkat. The proteolytic fragmentation of nPKC isotypes again closely correlated with the degree of apoptosis even in apoptosis induced by TPA. Separation of TPA-treated cells into apoptotic and non-apoptotic differentiating cells revealed that the proteolytic fragmentation of nPKC isotypes occurs only in apoptotic cells and, in adherent differentiating cells, nPKC isotypes as well as cPKC alpha were down-regulated without the generation of nPKC fragments. These results are consistent with the idea that nPKC isotypes meet two different fates, down-regulation and proteolytic cleavage generating kinase and regulatory fragments, and that the proteolytic cleavage of nPKC isotypes is a step in the signaling pathway involved in Fas-mediated and TPA-induced apoptosis.

Animals↗

PubMed1997

Resistance to fas-mediated apoptosis of peripheral T cells in human T lymphocyte virus type I (HTLV-I) transgenic mice with autoimmune arthropathy.

Transgenic mice carrying the env-pX region of human T lymphocyte virus type I (HTLV-I) develop autoimmune arthropathy in high incidence. Adopting the approach that Fas-mediated apoptosis has a critical function in the elimination of self-reactive T cells, we examined the involvement of this apoptosis in the induction of autoimmunity in HTLV-I transgenic mice. Splenic T cells derived from the transgenic mice were more resistant to apoptosis induced by anti-Fas mAb than those of the nontransgenic mice, whereas no appreciable difference in apoptosis was detected for thymocytes from either mouse's type. The resistance of transgenic T cells may be due to Tax coded in the pX region, since Tax mediates the inhibition of anti-Fas- induced apoptosis in mature T cell line, Jurkat. Among the transgenic mice, the extent of the resistance to Fas-mediated apoptosis was further enhanced in transgenic T cells with disease. These results suggest that the escape of self-reactive T cells from Fas-mediated apoptosis in the periphery, is critical for the development of autoimmune arthropathy in HTLV-I transgenic mice.

Animals↗

PubMed1997

Affinity labeling displays the stepwise activation of ICE-related proteases by Fas, staurosporine, and CrmA-sensitive caspase-8.

The activation of multiple interleukin-1beta converting enzyme-related proteases (caspases) in apoptotic mammalian cells raises questions as to whether the multiple active caspases have distinct roles in apoptotic execution as well as how these proteases are organized in apoptotic signaling pathways. Here we used an affinity-labeling agent, YV(bio)KD-aomk, to investigate the caspases activated during apoptotic cell death. YV(bio)KD-aomk identified six distinct polypeptides corresponding to active caspases in Fas-stimulated Jurkat T cells. On staurosporine treatment, four polypeptides were detected. Competition experiments showed that the labeled caspases have distinct substrate preferences. Stepwise appearance of the labeled caspases in each cell death event was consistent with the view that the activated caspases are organized into protease cascades. Moreover, we found that stepwise activation of caspases similar to that induced by Fas ligation is triggered by exposing non-apoptotic Jurkat cell extracts to caspase-8 (MACH/FLICE/Mch5). Conversely, CrmA protein, a viral suppressor of Fas-induced apoptosis, inhibited the protease activity of caspase-8. Overall, these findings provide evidence that caspase-8, a CrmA-sensitive protease, is responsible for initiating the stepwise activation of multiple caspases in Fas-stimulated cells.

Affinity Labels↗

PubMed1997

Ceramide-induced translocation of protein kinase C-delta and -epsilon to the cytosol. Implications in apoptosis.

Ceramide is now recognized as an intracellular lipid signal mediator, which induces various kinds of cell functions including apoptosis. Ceramide-induced apoptosis was reported to be blocked by 12-O-tetradecanoylphorbol 13-acetate, a protein kinase C (PKC) activator, but its mechanism remained unclear. Therefore, we investigated whether ceramide has any effects on PKC in the induction of apoptosis. We here report that N-acetylsphingosine (synthetic membrane-permeable ceramide) induced translocation of PKC-delta and -epsilon isozymes from the membrane to the cytosol within 5 min in human leukemia cell lines. Treatment with sphingomyelinase, tumor necrosis factor-alpha, or anti-Fas antibody, all of which can induce apoptosis by generating natural ceramide, similarly induced cytosolic translocation of PKC-delta and -epsilon. In Fas-resistant cells anti-Fas antibody did not induce cytosolic translocation of PKC-delta and -epsilon because of no generation of ceramide, whereas N-acetylsphingosine induced apoptosis with cytosolic translocation of PKC-delta and -epsilon. Furthermore, both 12-O-tetradecanoylphorbol 13-acetate and a nonspecific kinase inhibitor, staurosporine, prevented ceramide-induced apoptosis by inhibiting cytosolic translocation of PKC-delta and -epsilon. These data suggest that cytosolic translocation of PKC-delta and -epsilon plays an important role in ceramide-mediated apoptosis.

Antibodies, Monoclonal↗

PubMed1997

Fas ligand-mediated depletion of CD4 and CD8 lymphocytes by monomeric HIV-1-gp120.

In order to determine in what condition and by what mechanism gp 120 can deplete not only CD4 but also CD8 T cells, an in vitro system was established in which peripheral blood lymphocytes from healthy donors were treated with recombinant gp 120. We found that gp 120 can deplete both CD4 and CD8 T cells when they have recently been activated and are exposed to IL-2-deficient conditions. Bioassay of the Fas ligand (FasL) demonstrated augmented expression and release of soluble FasL by CD4 T cells in the supernatant of this culture. The administration of anti-FasL mAb and anti-Fas mAb, both of which exhibit neutralizing activity, completely abolished the depletion of these two T cell populations in culture. Based on these findings, we concluded that FasL depletes Fas antigen expressing CD4 and CD8 T cells by programmed cell death.

Antibodies, Monoclonal↗

PubMed1997

White dot fovea.

PURPOSE: To describe a newly identified clinical entity tentatively named white dot fovea. METHODS: We examined by scanning laser ophthalmoscopy 58 eyes of 30 patients (mean age, 64 years) who had white dots in the fovea (anatomically defined as the foveola) simulating macular hole. In addition, the retinal surfaces of 30 autopsy eyes from donors aged 70 years or older were observed by scanning electron microscopy. RESULTS: White dot fovea was bilateral in 28 of 30 patients (93%). It was characterized by the presence of numerous white dots on the foveal surface distributed either diffusely or along the foveal margin, forming a gray ring. There was no subjective symptom or visual disturbance. The condition was best seen by a scanning laser ophthalmoscope using argon blue laser as the light source. The white dots numbered from 100 to 300 per eye. Each dot was approximately 5 microns in diameter. Scanning electron microscopy showed foveal granules simulating the white dots in five of 30 autopsy eyes (17%). The granules had multiple protrusions with cilia-like structures resembling glial cells. This glia-like structure seemed to be a counterpart of clinically observed white dot fovea. CONCLUSION: White dot fovea is a new, frequent, and apparently innocuous clinical entity. It merits due attention in the differential diagnosis of macular holes.

Aged↗

PubMed1997

Ciliary body and choroidal detachment after laser photocoagulation for diabetic retinopathy. A high-frequency ultrasound study.

OBJECTIVE: The purpose of the study is to clarify the manifestation of the ciliary body after retinal photocoagulation for diabetic retinopathy. DESIGN: Ultrasound biomicroscopy (UBM) was applied to obtain the tomographic features of the anterior ocular segment. PARTICIPANTS: Twenty-one eyes of 17 consecutive patients with diabetic retinopathy were included in this study. INTERVENTION: These eyes were treated by panretinal photocoagulation divided in four sessions. In the first session, the nasal quadrant of the fundus was treated with argon or dye (590 nm) laser totaling 208 to 331 spots per eye. MAIN OUTCOME MEASURES: The eyes were examined by UBM before, immediately after, 3, and 7 days after the first session of photocoagulation. RESULTS: Three days after photocoagulation, ciliochoroidal detachment was observed in 19 eyes (90%). The detachment was present along the whole circumference. The ciliary detachment was most prominent in the pars plana in 19 eyes and extended to the pars plicata in 9 eyes. It spontaneously had disappeared 7 days after photocoagulation. CONCLUSIONS: Ciliochoroidal detachment was a very frequent feature after sector photocoagulation in diabetic eyes. Although this complication was asymptomatic and transient so far, this potential hazard merits due attention in the planning of panretinal photocoagulation in diabetic eyes.

Adult↗

PubMed1997

Characterization of zinc effect to inhibit osteoclast-like cell formation in mouse marrow culture: interaction with dexamethasone.

The inhibitory effect of zinc compounds on osteoclast-like cell formation in mouse marrow culture in vitro was characterized. The bone marrow cells were cultured for 7 days in alpha-minimal essential medium containing a well-known bone resorbing agent, 1,25-dihydroxyvitamin D3[1,25(OH)2D3] or prostaglandin E2 (PGE2). Osteoclast-like cell formation was estimated by staining for tartrate-resistant acid phosphatase (TRACP), a marker enzyme of osteoclasts. The presence of 1,25(OH)2D3 (10(-8) M) or PGE2 (10(-6) M) induced a remarkable increase in osteoclast-like multinucleated cells. These increases were enhanced by the presence of dexamethasone (10(-9) to 10(-6) M). The dexamethasone (10(-7) M)-enhanced osteoclast-like cell formation was not inhibited by the presence of zinc sulfate (10(-6) M) or zinc-chelating dipeptide (beta-alanyl-L-histidinato zinc; 10(-6) M), although the zinc compounds had an inhibitory effect on osteoclastic formation in the absence of the steroid. The effect of dexamethasone was not seen, when the steroid was added at the later stage of culture with bone-resorbing agents. In this case, the inhibitory effect of zinc compounds was clearly revealed. This effect of zinc compounds disappeared in the presence of Ca2+-chelating agent (0.5 mM EGTA). The present study suggests that zinc compounds have an inhibitory effect at the stage of differentiation of preosteoclastic cells in bone marrow cell culture system.

Animals↗

PubMed1997

Experimental chronic compression on the spinal cord of the rabbit by ectopic bone formation in the ligamentum flavum with bone morphogenetic protein.

This study was conducted to induce chronic spinal cord compression myelopathy in rabbits. The L5 lumbar lamina was cut partially in 70 rabbits, and bone morphogenetic protein (BMP) was implanted on the ligamentum flavum in 35 of them. In the BMP group, new bone formed on the dorsal side of the spinal canal and flattened the spinal cord in an anteroposterior direction. No pathological changes were detected in the intramedullary tissues by light microscopic examination. In rabbits it is possible to induce compression of the cord by using BMP, although sufficient cord compression to induce myelopathy was not achieved.

Animals↗