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Toshimitsu Suzuki

Publications and source records attributed to Toshimitsu Suzuki.

At least 37 records · Page 2Linked to original sources
PubMed2003

Morphologic and angiographic assessment of the macula after macular translocation surgery with 360 degrees retinotomy.

PURPOSE: To compare the optical coherence tomographic assessment of retinal thickness and the fluorescein angiographic appearance after macular translocation surgery for subfoveal choroidal neovascularization. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twenty-three consecutive eyes. INTERVENTION AND TESTING: Optical coherence tomography and fluorescein angiography were performed before and 6 to 15 months (mean +/- standard error [SE], 10.4+/-0.7) after macular translocation surgery with a 360 degrees retinotomy in 23 patients, ages 48 to 79 years, with age-related macular degeneration (12 eyes), polypoidal choroidal vasculopathy (2 eyes), and high myopia (9 eyes). The diameter of the choroidal neovascularizations ranged from 0.3 to 2.6 disc diameters (mean +/- SE, 1.2+/-0.2), and the angle of rotation of the retina ranged from 11 degrees to 45 degrees (mean +/- SE, 29.1+/-2.1 degrees ). RESULTS: The preoperative best-corrected visual acuity ranged from hand motions to 20/100, and the postoperative best-corrected visual acuity ranged from 20/667 to 20/25. Optical coherence tomography demonstrated a concave foveal configuration after surgery in all 23 eyes, with a mean foveal thickness of 150+/-11 micro m (mean +/- SE). Fluorescein angiography showed various degrees of fluorescein leakage with a pattern similar to cystoid macular edema in 16 of 23 eyes (70%). CONCLUSIONS: The newly located macula after macular translocation surgery with a 360 degrees retinotomy had cystoid macular edema on fluorescein angiography and normal macular configuration with normal thickness in optical coherence tomography.

Aged↗
PubMed2003

Intra-epithelial neuroendocrine carcinoma of the nasal cavity.

We describe a distinctive neuroendocrine carcinoma (NEC) that proliferated intra-epithelially. The tumor was 35 mm in diameter and arose from the right superior turbinate of a 46-year-old woman. Histologically, the tumor exhibited papillary growth and the tumor cells were localized in the thickened mucosal epithelium. The tumor cells had round to oval and vesicular or hyperchromatic nuclei, and cohered without any specific structure such as a fibrillary background, rosette or glandular structure. No stromal invasion by the tumor was observed. Immunohistochemically, the tumor cells were positive for neuron-specific enolase focally. In addition, many tumor cells expressed cytokeratin (AE1/AE3 and CAM 5.2), mostly with characteristic perinuclear dot-like patterns. Electron microscopy revealed focal but well-eveloped cytoplasmic processes containing arrays of microtubules and a few dense core granules. The tumor was considered to be a poorly differentiated neuroendocrine carcinomas (NEC) that exhibited exceptional intra-epithelial proliferation. The tumor completely disappeared after the stereotactic radiosurgery and has not recurred for 40 months. It might be difficult to distinguish a poorly differentiated NEC in the sinonasal region from other neuroectodermal tumors, including olfactory neuroblastoma, but the differential diagnosis is important because each tumor has different clinicopathological characteristics.

Biomarkers, Tumor↗
PubMed2003

Polyangitis overlap syndrome: a fatal case combined with adult Henoch-Schönlein purpura and polyarteritis nodosa.

Henoch-Schönlein purpura (HSP) is a rather common disease characterized by systemic hypersensitivity vasculitis in the skin and other visceral organs. It has a favorable prognosis unless it is complicated by severe glomerular disease. We report a distinctive fatal case of systemic vasculitis combined with HSP and polyarteritis nodosa (PN) in a 56-year-old man who died of progressive renal failure one month after the onset of the disease. He complained of arthralgia, purpura of both lower extremities, nasal bleeding and tarry stool, and acute renal failure was noted at the time of admission to hospital. A skin biopsy from the purpura lesion exhibited leucocytoclastic vasculitis with IgA deposition, and HSP was considered. However, renal failure progressed rapidly and subsequently was complicated by acute myocardial infarction. Postmortem examination revealed PN type necrotizing vasculitis in the kidneys, heart and mesentery resulting in acute multiple infarctions of these organs. We think the current case was a polyangitis overlap syndrome. It is important to suspect the polyangitis overlap syndrome positively when progressive acute renal failure is seen in a patient with HSP and to begin appropriate therapy immediately.

Fatal Outcome↗
PubMed2003

Recent developments in the quest for myoclonic epilepsy genes.

Understanding the latest advances in the molecular genetics of the epilepsies is important, as it provides a basis for comprehending the new practice of epileptology. Epilepsies have traditionally been classified and subtyped on the basis of clinical and neurophysiologic concepts. However, the complexity and variability of phenotypes and overlapping clinical features limit the resolution of phenotype-based classification and confound epilepsy nosology. Identification of tightly linked epilepsy DNA markers and discovery of epilepsy-causing mutations provide a basis for refining the classification of epilepsies. Recent discoveries regarding the genetics surrounding certain epilepsy types (including Lafora's progressive myoclonic epilepsy, the severe myoclonic epilepsy of infancy of Dravet, and idiopathic generalized epilepsies) may be the beginning of a better understanding of how rare Mendelian epilepsy genes and their genetic architecture can explain some complexities of the common epilepsies.

Epilepsies, Myoclonic↗
PubMed2003

Function and morphology of macula before and after removal of idiopathic epiretinal membrane.

PURPOSE: To study the function and morphology of the macula of the eye before and after the removal of unilateral idiopathic epiretinal membrane (ERM). METHODS: Focal macular electroretinograms (fmERGs) elicited by a 15 degrees stimulus were recorded in 37 eyes of 37 patients with a unilateral ERM. The amplitudes of the a- and b-waves and the oscillatory potentials (OPs) were compared with the corresponding waves in the normal fellow eyes before and after removal of the ERM. In 29 eyes followed up for more than 6 months after surgery, the fmERGs and foveal and parafoveal thicknesses, measured by optical coherence tomography (OCT), were evaluated. RESULTS: Before surgery, the mean amplitudes of all components of the fmERGs were significantly smaller than in the fellow eyes, with the decrease largest for the OPs, followed by the b-waves and then the a-waves. The eyes with less severely reduced a-wave amplitude (>70% of the fellow eyes) had significantly lower b-wave to a-wave (b/a) ratios. After surgery, the amplitudes of the b-wave and OPs were still significantly smaller in the affected eyes. The mean foveal and parafoveal thicknesses were significantly less after surgery; however, the thickness was still more in the affected eyes. The decrease of the OPs remained after surgery and correlated with increased parafoveal thickness (r = -0.460, P = 0.011). CONCLUSIONS: The decreased fmERGs indicate that macular function is impaired in eyes with ERM. The decrease of the b-wave and OPs in the 29 eyes examined after vitrectomy may be due to the still thickened macular retina.

Aged↗
PubMed2002

Targeted disruption of the Epm2a gene causes formation of Lafora inclusion bodies, neurodegeneration, ataxia, myoclonus epilepsy and impaired behavioral response in mice.

Mutations in the EPM2A gene encoding a dual-specificity phosphatase (laforin) cause Lafora disease (LD), a progressive and invariably fatal epilepsy with periodic acid-Schiff-positive (PAS+) cytoplasmic inclusions (Lafora bodies) in the central nervous system. To study the pathology of LD and the functions of laforin, we disrupted the Epm2a gene in mice. At two months of age, homozygous null mutants developed widespread degeneration of neurons, most of which occurred in the absence of Lafora bodies. Dying neurons characteristically exhibit swelling in the endoplasmic reticulum, Golgi networks and mitochondria in the absence of apoptotic bodies or fragmentation of DNA. As Lafora bodies become more prominent at 4-12 months, organelles and nuclei are disrupted. The Lafora bodies, present both in neuronal and non-neural tissues, are positive for ubiquitin and advanced glycation end-products only in neurons, suggesting different pathological consequence for Lafora inclusions in neuronal tissues. Neuronal degeneration and Lafora inclusion bodies predate the onset of impaired behavioral responses, ataxia, spontaneous myoclonic seizures and EEG epileptiform activity. Our results suggest that LD is a primary neurodegenerative disorder that may utilize a non-apoptotic mechanism of cell death.

Animals↗
PubMed2002

Genotype-phenotype correlations for EPM2A mutations in Lafora's progressive myoclonus epilepsy: exon 1 mutations associate with an early-onset cognitive deficit subphenotype.

Mutations in the EPM2A gene encoding a dual-specificity phosphatase (laforin) cause an autosomal recessive fatal disorder called Lafora's disease (LD) classically described as an adolescent-onset stimulus-sensitive myoclonus, epilepsy and neurologic deterioration. Here we related mutations in EPM2A with phenotypes of 22 patients (14 families) and identified two subsyndromes: (i) classical LD with adolescent-onset stimulus-sensitive grand mal, absence and myoclonic seizures followed by dementia and neurologic deterioration, and associated mainly with mutations in exon 4 (P = 0.0007); (ii) atypical LD with childhood-onset dyslexia and learning disorder followed by epilepsy and neurologic deterioration, and associated mainly with mutations in exon 1 (P = 0.0015). To understand the two subsyndromes better, we investigated the effect of five missense mutations in the carbohydrate-binding domain (CBD-4; coded by exon 1) and three missense mutations in the dual phosphatase domain (DSPD; coded by exons 3 and 4) on laforin's intracellular localization in HeLa cells. Expression of three mutant proteins (T194I, G279S and Y294N) in DSPD formed ubiquitin-positive cytoplasmic aggregates, suggesting that they were folding mutants set for degradation. In contrast, none of the three CBD-4 mutants showed cytoplasmic clumping. However, CBD-4 mutants W32G and R108C targeted both cytoplasm and nucleus, suggesting that laforin had diminished its usual affinity for polysomes. Our data, thus, represent the first report of a novel childhood syndrome for LD. Our results also provide clues for distinct roles for the CBD-4 and DSP domains of laforin in the etiology of two subsyndromes of LD.

Adolescent↗
PubMed2002

Alternative splicing modulates subcellular localization of laforin.

Laforin is a dual-specificity phosphatase coded by the EPM2A gene defective in Lafora's progressive myoclonus epilepsy. We reported earlier that laforin is a cytoplasmic protein associated primarily with polyribosome. In the present study we characterized the expression of an EPM2A splice variant, named C-terISO, originating from the usage of a novel exon located in the 3'-untranslated region of exon 4 and encoding a laforin isoform containing unique sequences at its carboxyl terminus. Transfection studies demonstrate that, in addition to cytoplasm, the protein coded by C-terISO was targeted to the nucleus, a distinctive feature that was not observed for laforin coded by the major transcript of the EPM2A gene. The unique C-terminal sequence did not affect laforin's affinity for polysome, but sequestered nearly an equal amount of the protein into the nucleus. Our results are significant in light of the finding that laforin is an active phosphatase; therefore, isoforms targeted to different cellular compartments might dephosphorylate and regulate distinct cellular substrates.

Alternative Splicing↗
PubMed2002

An invasion-independent pathway of blood-borne metastasis: a new murine mammary tumor model.

It is generally believed that active invasion by cancer cells is essential to the metastatic process. In this report, we describe a murine mammary tumor (MCH66) model of metastasis that does not require invasion into the vascular wall of both the primary tumor and the target organ, in this case, the lung. The process involves intravasation of tumor nests surrounded by sinusoidal blood vessels, followed by intravascular tumor growth in the lung, without penetration of the vascular wall during the process. Comparative studies using a nonmetastatic MCH66 clone (MCH66C8) and another highly invasive metastatic cell line (MCH416) suggested that high angiogenic activity and sinusoidal remodeling of tumor blood vessels were prerequisites for MCH66 metastasis. Differential cDNA analysis identified several genes that were overexpressed by MCH66, including genes for the angiogenesis factor pleiotrophin, and extracellular matrix-associated molecules that may modulate the microenvironment toward neovascularization. Our analyses suggest that tumor angiogenesis plays a role in the induction of invasion-independent metastasis. This model should prove useful in screening and development of new therapeutic agents for cancer metastasis.

Animals↗
PubMed2002

Collateral vessels around the esophageal wall in patients with portal hypertension: comparison of EUS imaging and microscopic findings at autopsy.

BACKGROUND: In patients with portal hypertension, EUS reveals the presence of collateral vessels within and outside the esophageal wall such as esophageal varices, periesophageal collateral veins (peri-ECVs), paraesophageal collateral veins (para-ECVs), and perforating veins. This study retrospectively compared radial EUS images of these collateral vessels with histopathologic findings. METHODS: Four patients with esophageal varices treated by endoscopic injection sclerotherapy were studied. EUS was performed to evaluate the effects of endoscopic injection sclerotherapy. After endoscopic injection sclerotherapy, the segment of the esophagus from the esophagogastric junction to a point 5 cm proximal to junction was imaged with a 20-MHz radial scanning catheter US probe. Esophageal collateral veins outside the esophageal wall were identified as peri-ECVs (veins lateral to muscularis propria or within adventitia) and para-ECVs (veins lateral and separate from muscularis propria) along with perforating veins (veins connecting extramural collateral veins to submucosal varices). At autopsy, the esophagus with surrounding tissue was removed and cross-sectioned at 1-cm intervals from the esophagogastric junction to a point 5 cm proximal to the junction. Radial EUS images were correlated with histopathologic findings. RESULTS: Radial EUS after endoscopic injection sclerotherapy demonstrated peri-ECVs and perforating veins in all cases and para-ECVs in 3 cases. Based on histopathologic findings, veins associated with the esophageal wall were divided into 3 groups: those adjacent to the muscularis propria, veins separated from the wall without contact with the muscularis propria, and veins perforating the muscularis propria. All 3 groups of veins were observed in all cases. These 3 types of veins identified by histopathologic examination corresponded, respectively, to the peri-ECVs, para-ECVs, and perforating veins observed by EUS. CONCLUSION: Collateral esophageal veins demonstrated by radial EUS in patients with portal hypertension correspond to collateral veins identified histopathologically. In patients with portal hypertension, EUS is useful for assessment of vascular anatomy around the esophageal wall.

Aged↗
PubMed2002

Identification and mutational analysis of candidate genes for juvenile myoclonic epilepsy on 6p11-p12: LRRC1, GCLC, KIAA0057 and CLIC5.

Juvenile myoclonic epilepsy (JME) is one of the most frequent hereditary epilepsies characterized by myoclonic and tonic-clonic convulsions beginning at 8-20 years of age. Genetic studies have revealed four major chromosomal loci on 6p21.3, 6p11-12, 6q24, and 15q14 as candidate regions harboring genes responsible for JME. Previously we reported the region on 6p11-p12 (EJM1), and here we report the identification and mutational analysis of candidate genes for EJM1. One of those is a leucine-rich repeat-containing 1 (LRRC1) gene that is composed of 14 exons and codes for 524 amino acid residues. In Northern analysis, 7 kb transcripts of LRRC1 gene were detected in multiple tissues, most strongly, in heart, lung, and kidney. Mutation analysis of LRRC1 gene in 20 JME patients from ten families revealed one nucleotide substitution that lead to amino acid exchange (c.577 A>G; Ile193Val). This variation, however, did not co-segregate with the disease phenotype. We further performed mutational analyses of CLIC5, KIAA0057 and GCLC genes in or flank to the EJM1 region. These analyses did not provide any evidences that these genes are responsible for the JME phenotype, and suggested that these may not be the EJM1 gene.

Base Sequence↗
PubMed2002

Molecular cytogenetic characterization of drug-resistant leukemia cell lines by comparative genomic hybridization and fluorescence in situ hybridization.

Resistance to chemotherapeutic drugs is one of the major difficulties encountered during cancer chemotherapy. To detect genomic aberrations underlying the acquired drug resistance, we examined three cultured human myelomonocytic leukemia cell sublines each resistant to adriamycin (ADR), 1-beta-1-D-arabinofuranosylcytosine (ara-C), or vincristine (VCR), using comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), RT-PCR, and western blot techniques. Chromosomes 7, 10 and 16 most conspicuously showed frequent aberrations among the resistant sublines as compared to the parental KY-821 cell line. In ADR-resistant cells, gains at 7q21, 16p12, 16p13.1-13.3, 16q11.1-q12.1, and losses at 7p22-pter, 7q36-qter, 10p12, 10p11.2-pter, 10q21-q25, 10q26-qter were notable. In ara-C-resistant cells, no remarkable gain or loss on chromosome 7, but losses at 10p14-pter, 10q26-qter and 16p11.2-p11.3 were observed. In VCR-resistant cells, gain at 7q21 and losses at 10p11-p13, 10p15 and 16p11.2-p13.3 were found. FISH identified amplified signals for the MDR-1 gene located at 7q21.1 in ADR- and VCR- but not ara-C-resistant cells, and for the MRP-1 gene located at 16p13.1 in ADR-resistant cells. These findings were validated at the mRNA and protein levels. Overlapping of the amplified MRP-1 gene with MDR-1 gene may play a critical part in the acquisition of resistance to ADR. Resistance to ara-C excluded MDR-1 gene involvement and highlighted other key genes such as MXR gene. Several other genes putatively involved in the development of drug resistance might lie in other aberrated chromosomal regions.

Antimetabolites, Antineoplastic↗
PubMed2002

Change in full-field ERGs after macular translocation surgery with 360 degrees retinotomy.

PURPOSE: One of the methods used in macular translocation (MT) surgery for subfoveal neovascularization is to create a temporary total retinal detachment followed by a 360 degrees retinotomy. The whole retina is then shifted from the original surface of the retinal pigment epithelium (RPE), resulting in an unusual retina and RPE complex. The purpose of this study was to assess retinal function after MT surgery. METHODS: Full-field electroretinograms (ERGs) were recorded before and 4 to 8 months (mean, 5.4 months) after MT surgery with a 360 degrees retinotomy in 15 consecutive patients with age-related macular degeneration (10 eyes), high myopia (4 eyes), and polypoidal choroidal vasculopathy (1 eye). Their ages ranged from 57 to 74 years. The angle of rotation of the retina ranged from 18 degrees to 45 degrees (mean +/- SE, 30 +/- 2 degrees). In addition to the recording of the standard rod and mixed rod-cone ERGs after 30 minutes of dark adaptation, the cone single flash and 30-Hz flicker ERGs were recorded immediately after a light-adapting background was turned on (LA(0)) and also after 10 minutes of light adaptation (LA(10)). RESULTS: The mean amplitude of the full-field ERGs was reduced after surgery by 44% for the rod response, by 24% for the mixed rod-cone b-wave, by 12% and 35% for the cone single-flash b-wave at LA(0) and 30-Hz flicker ERGs at LA(0), respectively. The mean implicit times were delayed by 8 msec for the rod response, by 2 msec for the mixed rod-cone oscillatory potential (OP1), by 4 msec for the cone single-flash b-wave at LA(0), and by 6 msec for the 30-Hz flicker at LA(0). CONCLUSIONS: These results demonstrated a functional alteration in both the rod and cone components of the ERGs for the entire retina after MT surgery.

Aged↗
PubMed2002

Focal macular electroretinograms before and after removal of choroidal neovascular lesions.

PURPOSE: To evaluate the changes in focal macular electroretinograms (fmERGs) after surgical removal of choroidal neovascular (CNV) lesions. METHODS: Fourteen patients (14 eyes) with subfoveal or juxtafoveal CNV associated with age-related macular degeneration and 1 patient with idiopathic CNV underwent vitrectomy and removal of the lesions. fmERGs elicited by a 15 degree stimulus were recorded before and 3 months after surgery. Optical coherence tomography (OCT) was performed to measure the foveal and parafoveal thickness before and 3 months after surgery. RESULTS: Preoperative fmERGs were markedly reduced in all eyes. The mean amplitude of the b-wave in 15 eyes recorded 3 months after surgery increased significantly (P = 0.0022, Wilcoxon signed rank test). In all eyes except two with nearly nonrecordable a- and b- waves, the mean b-wave-to-a-wave ratio after surgery increased significantly in all eyes (P = 0.0330, Wilcoxon signed rank test). The percentage increase in the b-wave amplitude correlated significantly with the percentage decrease in the mean parafoveal retinal thickness (r = 0.688, P = 0.0076). CONCLUSIONS: The decreased macular ERGs were partially recoverable in the early postoperative period. The decreased retinal edema after surgery may have contributed to this recovery.

Adult↗
PubMedDate not supplied

Preoperative electroretinogram and postoperative visual outcome in patients with diabetic vitreous hemorrhage.

PURPOSE: To determine whether the single-flash electroretinogram (ERG) can predict the postoperative outcome in diabetic cases where massive vitreous hemorrhage precludes fundus observation. METHODS: Eighty-five diabetic patients (105 eyes) who underwent vitrectomy due to dense vitreous hemorrhage were studied retrospectively. Eyes with postoperative complications were excluded. Preoperative ERGs (mixed cone-rod ERG with maximum flash intensity) were classified as: Group A, the b-wave/a-wave ratio (b/a ratio) was > or =1.0 and the oscillatory potentials (OPs) were clearly recordable (22 eyes); Group B, the b/a ratio was > or =1.0 and the OPs were markedly reduced (33 eyes); and Group C, the b/a ratio was <1.0 (50 eyes). RESULTS: The postoperative visual acuity in Group C (hand motion to 1.5) was significantly worse than in Group A (0.4-.2) (P<.01) or Group B (0.08-1.0) (P<.01). Thick preretinal membrane causing retinal traction around the optic disc was found intraoperatively in 1 eye (4.5%) in Group A, 9 eyes (27.3%) in Group B, and 28 eyes (56.0%) in Group C (P=.0132). CONCLUSION: Our findings suggested that the configuration of the single-flash ERG can provide important preoperative information for a functional prognosis following vitrectomy in diabetic patients with vitreous hemorrhage.

Adult↗
PubMedDate not supplied

Osteosarcoma arising in the breast.

We report on a 49-year-old woman with osteosarcoma arising in the breast. She had undergone two consecutive excision biopsies for right breast tumors at ages 40 and 42 years. The tumors were diagnosed as a fibroadenoma and a benign phyllodes tumor, respectively. At age 46 years, she noticed a gradually enlarging mass in the same breast. After 3 years, at age 49 years, total mastectomy was performed. The tumor occupied the entire breast and measured 12x9x8.5 cm. The tumor cells were spindle-shaped and pleomorphic, with large, irregular nuclei and distinct nucleoli. Many tumor cells had characteristics of osteoblastic and chondroblastic elements producing osteoid, osseous, and cartilaginous intracellular substances. Pathologic mitoses and apoptotic cells were frequent. Neoplastic cells had infiltrated the skin. Blood and lymph vessel invasion was present. Tumor cells expressed vimentin, osteopontin, vascular endothelial growth factor, CD10, and alkaline phosphatase, but did not express keratin. Chemotherapy was not effective. The patient died of multiple pulmonary metastases 9 months after mastectomy.

Adult↗