Correspondence re: J. Mora et al., Neuroblastic and Schwannian stromal cells of neuroblastoma are derived from a tumoral progenitor cell. Cancer Res., 61: 6892-6898, 2001.
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Publications and source records attributed to Hiroyuki Shimada.
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Orthotopic brain tumor growth is inhibited in athymic mice by the daily systemic administration of the alpha v-integrin antagonist EMD 121974. This compound, a cyclic RGD-penta-peptide, is a potent inhibitor of angiogenesis, which induces apoptosis of growing endothelial cells through inhibition of their alpha v-integrin interaction with the matrix proteins vitronectin and tenascin. Here we show that EMD 121974 also induces apoptosis in the alpha v-integrin-expressing tumor cell lines U87 MG and DAOY by detaching them from vitronectin and tenascin, matrix proteins known to be essential for brain tumor growth and invasion. These matrix proteins are shown to be produced by the brain tumor cells in vitro and in vivo. Furthermore, only tumor cells expressing alpha v-integrins responded to the treatment with EMD 121974, after xenotransplantation into the forebrain of nude mice, supporting the importance of tumor cell-matrix interactions in tumor cell survival in the brain. Thus, the alpha v-antagonist EMD 121974 suppresses brain tumor growth through induction of apoptosis in both brain capillary and brain tumor cells by preventing their interaction with the matrix proteins vitronectin and tenascin. The dual action of this peptide explains its potent growth suppression of orthotopically transplanted brain tumors.
BACKGROUND: After the establishment of the International Neuroblastoma Pathology Classification system, the authors studied retrospectively the prognostic impact of morphologic features in a series of two clinically distinct subsets of patients with peripheral neuroblastic tumors (NTs), i.e., tumors in the neuroblastoma category. METHODS: Forty-seven NTs categorized into either clinically favorable or unfavorable subgroups were selected randomly from 100 NTs for a histologic review that included the evaluation of 14 morphologic characteristics. The review was performed individually followed by a group review. The correlations of the prognostic significance of the individual morphologic features and the correlations among them were determined by use of odds ratios (ORs) with corresponding 95% confidence intervals (95%CIs). The inter-rater agreement was determined by using the Cohen kappa coefficient. RESULTS: Ten of 14 morphologic features, including nuclear size, cellularity, prominent nucleoli in undifferentiated or poorly differentiated neuroblasts, and the number of mitotic and karyorrhectic cells (MKI), showed a significant correlation with the clinical groups (ORs between 36.9 and 10.5 and P values between < 0.001 and 0.002). In addition to the patient's age at diagnosis (OR, 7.4; 95%CI, 1.9-28.9; P = 0.002), 8 of 14 features also provided prognostic information (ORs between 35.1 and 7.9 and P values between < 0.001 and 0.039). CONCLUSIONS: This study again confirmed the prognostic impact of the criteria used in the Shimada system and revealed that some other morphologic features, such as prominent nucleoli in undifferentiated and poorly differentiated neuroblasts, identify unfavorable tumor biology, partly independent from the patient's age at diagnosis. However, the prognostic impact of these features needs to be confirmed by analysis of a large series of neuroblastic tumors.
The hSNF5/INI1 gene, which encodes a subunit of the SWI/SNF family of chromatin-remodeling complexes and is located at 22q11.2, has been reported as a tumor suppressor gene inactivated in malignant rhabdoid tumors (MRTs). We analyzed this gene in varieties of pediatric solid tumors including MRTs, using the reverse transcription-polymerase chain reaction (PCR) and PCR-single strand conformation polymorphism method. We found 5 homozygous deletions, 2 truncated mutations, one missense mutation, and one silent mutation of the hSNF5/INI1 gene in 7 MRT cell lines, and one homozygous deletion, one microdeletion, one splicing acceptor site mutation, and one absence of expression in 7 fresh tumor tissues of MRT and atypical teratoid (AT)/rhabdoid tumors (RTs). Homozygous deletions were also found in one (KYM-1) of 8 rhabdomyosarcoma (RMS) cell lines. To investigate characteristics of the KYM-1 cell line, we have established KYM-1 tumors in nude mice into which KYM-1 cells were transplanted. Notably, we found that MyoD1, known as a marker for RMS, was not expressed in the KYM-1 cell line as well as MRT cell lines and fresh tumors. Histopathologic, cytogenetic, and molecular studies of the KYM-1 cell line and KYM-1 tumors in nude mice have revealed that this RMS cell line should be MRT rather than RMS. RMS-carrying aberrations of the hSNF5/INI1 gene should be reevaluated. No aberrations of this gene were found in the other 34 cell lines or 80 fresh tumor specimens except the single nucleotide polymorphisms in the 3' noncoding region. These results suggest that alterations of the hSNF5/INI1 gene were restricted to MRTs or AT/RTs in pediatric solid tumors.
The purpose of this study was to examine the relationship between outdoor-activity areas and physical functions such as muscle strength, postural balance, gait function, and to identify the physical functions related to accomplishment of outdoor activity in elderly persons utilizing outpatient rehabilitation facilities. Furthermore, we investigated the relationship among physical, social and intellectual activities and physical functions. The subjects were 265 elderly persons (average age: 80.3 +/- 7.0). They were classified into the indoor-activity group, neighborhood outdoor-activity group and long-distance outdoor-activity group, and functional differences among the three groups were examined. The Barthel index, one-leg standing time, timed up-and-go test and performance-oriented mobility assessment were significantly different among the three groups. These results suggested that physical functions have a close relationship with extension of the activity area. Based on 95% confidence intervals, elderly subjects with more than 95 points on the Barthel index seemed able to do neighborhood outdoor activities. Those who can finish timed up-and-go test in less than 18 seconds, and obtain 26 points in performance-oriented mobility assessment may be able to do long-distance outdoor-activities using a bus. Furthermore, it was found that physical function was largely affected by physical activity such as exercise habituation and house keeping. In conclusion the difference of the activity area as well as extended activities of ADL influenced the physical function, which was critical to prevent functional decline in elderly persons.
PURPOSE: We investigated the relations between ingrowth site and visual results in patients undergoing surgical removal of subfoveal choroidal neovascular membranes (CNV) caused by age-related macular degeneration (AMD). MATERIALS AND METHODS: The subjects were 70 eyes(69 patients), which underwent surgical removal of CNV for AMD and were followed up for 6 months or more. The eligibility criteria were active subfoveal choroidal neovascular membrane 3 disc diameters (DD) or less in size located above the retinal pigment epithelium, and visual acuity of 0.3 or worse. We analyzed the relationships between postoperative best-corrected visual acuity and preoperative factors: ingrowth site of CNV, distance between the fovea and the CNV edge, CNV size, and fluorescence pattern in indocyanine green angiography (IA). RESULTS: Patients 1) with feeder vessels located outside the foveal avascular zone (FAZ) rather than inside the FAZ and/or unknown feeder vessels, 2) with a distance between the fovea and the CNV edge 0.2 DD or less than 0.2 DD versus larger, than 0.2 DD 3) with a 1 DD or smaller CNV versus 1.5 DD or larger, and 4) type I, II, or III findings in IA rather than type IV had good postoperative best-corrected visual acuity. CONCLUSIONS: To achieve better postoperative visual acuity after surgical removal of CNV associated with AMD, it is important to select CNV with ingrowth sites outside the FAZ, small and large CNV with a relatively short distance between the fovea and the CNV edge closest to the fovea, and type I, II, and III findings in IA.
PURPOSE: To analyze the histopathology of polypoidal choroidal vasculopathy (PCV) and choroidal neovascularization (CNV) developing from PCV, the authors evaluated correlations between pathological findings and the findings of preoperative indocyanine green angiography (IA). METHODS: Two specimens were obtained during CNV excision associated with PCV. PCV tissue was excised with the CNV. The specimens were examined by light microscopy. RESULTS: In one case, IA revealed polypoidal lesions exhibiting hyperfluorescence in both the early and the late phase, and in the affected area, abnormally dilated vessels were identified histologically underneath relatively healthy retinal pigment epithelium (RPE). In the other case, the polypoidal lesions seen on IA showed early hyperfluorescence and late isofluorescence, and dilated vessels were observed under the RPE; perivascular amorphous material was present. The RPE adhered to the side of the choroid, and there was CNV under the neurosensory retina in both cases. The CNV had numerous vascular lumens, was not surrounded by the RPE, and exhibited few fibrous components. CONCLUSIONS: IA findings vary depending on the condition of the RPE located above the PCV and the extent of amorphous material around the PCV.
PURPOSE: To describe a new 20-gauge transconjunctival vitrectomy procedure that we designed, to evaluate its usefulness, and to compare two different methods of use. METHODS: The records of 431 patients (433 eyes) who underwent 20-gauge transconjunctival vitrectomy at the Surugadai Hospital of Nihon University between March 2003 and January 2004 were studied retrospectively. In surgical method 1, 20-gauge wounds were made through the conjunctiva and sclera together. In surgical method 2, 20-gauge conjunctival openings were made 2 mm posterior to the sclerotomies. Absorbable sutures were used to stitch the scleral and conjunctival openings simultaneously in both methods. RESULTS: A 20-gauge transconjunctival vitrectomy has various benefits and is indicated for nearly all ocular diseases. Moreover, it is not limited by the intraocular instruments required. However, since cannulas were not placed in all ports, conjunctival edema occurred more easily with surgical method 2 owing to the leakage of perfusion fluid. CONCLUSIONS: This new 20-gauge transconjunctival vitrectomy procedure has various benefits and is indicated for nearly all ocular diseases. It is not limited by the intraocular instruments required.
PURPOSE: To evaluate the visual acuity outcome and the various factors influencing visual outcome in patients undergoing surgical removal of type 1 + 2 choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD). METHODS: We studied the records of 54 patients (54 eyes) followed for at least 1 year after surgical excision of CNV associated with AMD. RESULTS: The final visual acuity was 0.4 or better in 4%, 0.1 to 0.3 in 46%, and worse than 0.1 in 50% of the patients. Final visual acuity was improved in 39%, stable in 37%, and worse in 24%. Stepwise regression showed that the distance between the center of the foveal avascular zone and the CNV margin had the greatest effect on final visual acuity. CONCLUSIONS: Surgical excision of type1 + 2 CNV due to AMD may be indicated for preserving preoperative visual acuity. The distance between the center of the foveal avascular zone and the CNV margin is the most important factor affecting final visual acuity.
PURPOSE: To evaluate the visual acuity outcome and the influence of various factors on visual outcome in patients undergoing surgical removal of type 2 choroidal neovascular neovascularization (CNV) caused by age-related macular degeneration (AMD). METHODS: We studied the records of 92 patients (92 eyes) who were followed for at least 1 year after surgical excision of CNV associated with AMD. RESULTS: The final visual acuity was 0.4 or better in 21%, 0.1 to 0.3 in 66%, and worse than 0.1 in 13% of the patients. Final visual acuity was improved in 62%, stable in 29%, and worse in 9%. Stepwise regression identified CNV size as a significant factor influencing final visual acuity (R = 0.287, P = 0.0045). CONCLUSIONS: Surgical excision of CNV for AMD is indicated for patients with subfoveal active type 2 CNV with a visual acuity of 0.3 or worse. To achieve better postoperative visual acuity it is important to operate on AMD patients in the early stage of CNV.
PURPOSE: We conducted 25-gauge (25G) transconjunctival vitrectomy to treat patients with various ocular diseases, and examined the possibility of expanding the indications for this system through combined use with 20G devices when needed. METHODS: The records of 167 patients (169 eyes) who underwent vitrectomy in our hospital between April and June 2004 were studied. Vitrectomy had been conducted using the 20G or 25G transconjunctival vitrectomy system. RESULTS: In 7 of the 169 eyes (4%), the 20G system was initially selected. Vitrectomy could be performed using the 25G system alone in 150 eyes (89%), while 20G devices were used in combination with the 25G system in 12 (7%). None of the 25G scleral wounds were sutured, while all the 20G scleral wounds were sutured at the completion of surgery. Low intraocular tension was noted in 15 of 162 eyes (9%), but all these eyes recovered within 2 to 4 days. In two eyes with macular hole, retinal detachment occurred, but reattachment was achieved after reoperation. No extensive vitreoretinal hemorrhage or postoperative infection was observed. CONCLUSIONS: By combining the use of 20G devices, indications for the 25G system can be expanded. However, postoperative low ocular tension must be addressed by carefully considering surgical indications and prevention measures.
PURPOSE: We evaluated the effects of the peeling of the internal limiting membrane (ILM) during vitrectomy in diabetic cystoid macular edema (CME) patients. METHODS: Visual outcome and intraoperative and postoperative complications were evaluated retrospectively in 84 CME patients (100 eyes), all of whom had been followed for at least 1 year postoperatively. Before January 2001, we did not perform ILM peeling at our hospitals; 57 patients (66 eyes) treated before 2001 were included in this retrospective study as the non-peeling group. After January 2001, ILM peeling was performed in 27 (34 eyes) CME patients, who were included in this study as the peeling group. In the peeling group, indocyanine green (ICG) staining was performed at the time of ILM peeling. RESULTS: Visual acuity improved significantly after vitrectomy regardless of ILM peeling. Visual acuity improved gradually from 6 months to 1 year after the operation, and improved further at the final observation point in both groups. Visual acuity did not differ significantly between the two groups at any time point. There was no difference in the incidence of intraoperative and postoperative complications between the two groups. There were no adverse events associated with ICG-assisted ILM peeling. CONCLUSIONS: Visual acuity improved with vitrectomy for diabetic cystoid macular edema in both groups. ILM peeling was not found to improve visual acuity postoperatively.
PURPOSE: To shorten the duration of prone positioning after macular hole surgery from 1 week to 1 day, and to evaluate preoperative factors and the initial hole closure rate. METHODS: The subjects were 33 patients (34 eyes) who underwent macular hole surgery between April 1998 and August 1999, and maintained the prone position for 1 week (1-week group) and 21 patients (21 eyes) who underwent this operation between September 1999 and March 2000, and maintained the prone position for only 1 day (1-day group). The criteria for macular hole surgery were no more than 6 months since symptom development and no flattening of the fluid cuff. Eyes treated by removal of the retinal pigment epithelium (RPE) or internal limiting membrane (ILM) were excluded. In all phakic eyes, cataract surgery was combined with macular hole surgery. In the 1-day group, the patients maintained the prone position for 1 day and were instructed to avoid only the supine position for the subsequent 1 week. RESULTS: Preoperative factors possibly affecting the hole closure rate did not differ significantly between the two groups. Initial hole closure rates were similar in the 1-week (91.2%) and 1-day (90.5%) groups. CONCLUSION: In eyes without symptoms of long duration, the duration of prone positioning after macular hole surgery may be shortened to 1 day even without using special techniques, such as removal of the RPE or ILM, in combination with macular hole surgery.
PURPOSE: We evaluated visual outcomes following vitrectomy for diabetic cystoid macular edema. METHODS: Visual outcomes and factors possibly influencing final visual acuity were assessed and documented retrospectively in 45 eyes of 40 patients, all of whom were followed up for at least 6 months postoperatively. RESULTS: Compared with the preoperative logarithm of the minimum angle of resolution (logMAR) visual acuity, final logMAR visual acuity improved 0.2 or more in 51% of the eyes, was unchanged in 47%, and decreased 0.2 or more in 2%. A final postoperative visual acuity of 0.5 or better was achieved in 38%. Preoperative visual acuity and the extent of the cystoid space on fluorescein angiography were significantly related to final visual acuity. A final postoperative visual acuity of 0.5 or better was noted in 8% of eyes with a preoperative visual acuity below 0.1, in 50% of eyes with a preoperative visual acuity of 0.1 or better, in 71% of eyes with a cystoid space smaller than 5 disc areas, and in 20% of eyes with a cystoid space of 5 disc areas or more. The state of the posterior vitreous membrane did not influence final visual acuity. There were no complications that decreased visual acuity. CONCLUSIONS: We conclude that diabetic cystoid macular edema is a good indication for vitrectomy, regardless of the state of the posterior vitreous membrane. A preoperative visual acuity of 0.1 or better and/or a cystoid space smaller than 5 disc areas may be indications for surgery aimed at achieving a final postoperative visual acuity of 0.5 or better.