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Biomedical subjects

Masahiro Shin

Publications and source records attributed to Masahiro Shin.

At least 19 recordsLinked to original sources

Negative regulation of primitive hematopoiesis by the FGF signaling pathway.

Hematopoiesis is controlled by multiple signaling molecules during embryonic and postnatal development. The function of the fibroblast growth factor (FGF) pathway in this process is unclear. Here we show that FGF plays a key role in the regulation of primitive hematopoiesis in chicks. Using hemoglobin mRNA expression as a sensitive marker, we demonstrate that timing of blood differentiation can be separated from that of initial mesoderm patterning and subsequent migration. High FGF activity inhibits primitive blood differentiation and promotes endothelial cell fate. Conversely, inhibition of FGFR activity leads to ectopic blood formation and down-regulation of endothelial markers. Expression and functional analyses indicate that FGFR2 is the key receptor mediating these effects. The FGF pathway regulates primitive hematopoiesis by modulating Gata1 expression level and activity. We propose that the FGF pathway mediates repression of globin gene expression and that its removal is essential before terminal differentiation can occur.

Animals↗

FGF10 is required for cell proliferation and gland formation in the stomach epithelium of the chicken embryo.

The development of digestive organs in vertebrates involves active epithelial-mesenchymal interactions. In the chicken proventriculus (glandular stomach), the morphogenesis and cytodifferentiation of the epithelium are controlled by the inductive signaling factors that are secreted from the underlying mesenchyme. Previous studies have shown that Fgf10 is expressed in the developing chicken proventricular mesenchyme, whereas its receptors are present in the epithelium. In our present study, we show that FGF10 is an early mesenchymal signal that is critically associated with the developmental processes in the proventricular epithelium. Furthermore, virus-mediated Fgf10 overexpression in ovo results in a hypermorphic epithelial structure and an increase in epithelial cell number. In contrast, the overexpression of a secreted FGFR2b (sFGFR2b), an FGF10 antagonist, blocks cell proliferation and gland formation in the proventricular epithelium in ovo. This downregulation of proliferative activity was subsequently found to retard gland formation and also to delay differentiation of the epithelium. These results demonstrate that FGF10 signaling, mediated by FGFR1b and/or FGFR2b, is required for proliferation and gland formation in the epithelium in the developing chick embryo.

Animals↗

Identification, characterization, and expression pattern of the chicken EKLF gene.

EKLF/KLF1 was the first of the Krüppel-like factors (KLFs) to be identified in mammals and plays an important role in primitive and definitive erythropoiesis. Here, we identify and characterize EKLF in the chicken (cEKLF). The predicted amino acid sequence of the zinc finger region of cEKLF is at least 87.7% similar to mammalian EKLF proteins and is 98.8% and 95% similar to the EKLF orthologues in Xenopus and zebrafish, respectively. During early embryonic development, cEKLF expression is seen in the posterior primitive streak, which gives rise to hematopoietic cells, and then in the blood islands and in circulating blood cells. cEKLF mRNA is expressed in blood cells but not in brain later in chicken embryonic development. cEKLF mRNA is increased in definitive compared with primitive erythropoiesis. The conserved sequence and expression pattern of cEKLF suggests that its function is similar to its orthologues in mammals, Xenopus, and zebrafish.

Amino Acid Sequence↗

Endoscopic microneurosurgery: usefulness and cost-effectiveness in the consecutive experience of 210 patients.

OBJECTIVE: Indications, usefulness, and cost-effectiveness of the endoscope in routine microneurosurgery are not clear. To delineate such aspects, we assessed our experience of endoscopic application and additional cost to use an endoscope. METHODS: Endoscopes were used in 210 patients with cranial base and cisternal pathological features in the previous 7 years. Lesions were located in the extradural cranial base in 78 patients and in the cistern in 132 patients. Rigid lens endoscopes 2.7 to 4 mm in width, 11 to 20 cm in length, and 0 to 70 degrees in angle were used. RESULTS: Endoscopes were used for primary or a significant part of the surgery in 64% of the extradural cranial base procedures. Although endoscopes were used only for visual assistance in 82% of cisternal pathological features, significant benefit was noted in 9% and was not different from cranial base lesions. Eleven patients may have had complications if the endoscope had not been used, and 10 procedures would have been impossible without endoscopic use. Therefore, the number of patients need to treat to experience significant benefits by endoscope was 10. Endoscopic equipment costs an additional 326 US dollars per patient and, hence, significant benefit was the equivalent of 3260 US dollars. No permanent complications resulted from the use of the endoscope. CONCLUSION: The endoscope can be applied safely in routine microsurgery with specific equipment and has proven useful in 1 of 10 patients. To perform more effective procedures using endoscopes, we need to develop specially designed instruments usable through a narrow corridor and in an angled field.

Cisterna Magna↗

The risk of hemorrhage after radiosurgery for cerebral arteriovenous malformations.

BACKGROUND: Angiography shows that stereotactic radiosurgery obliterates most cerebral arteriovenous malformations after a latency period of a few years. However, the effect of this procedure on the risk of hemorrhage is poorly understood. METHODS: We performed a retrospective observational study of 500 patients with malformations who were treated with radiosurgery with use of a gamma knife. The rates of hemorrhage were assessed during three periods: before radiosurgery, between radiosurgery and the angiographic documentation of obliteration of the malformation (latency period), and after angiographic obliteration. RESULTS: Forty-two hemorrhages were documented before radiosurgery (median follow-up, 0.4 year), 23 during the latency period (median follow-up, 2.0 years), and 6 after obliteration (median follow-up, 5.4 years). As compared with the period between diagnosis and radiosurgery, the risk of hemorrhage decreased by 54 percent during the latency period (hazard ratio, 0.46; 95 percent confidence interval, 0.26 to 0.80; P=0.006) and by 88 percent after obliteration (hazard ratio, 0.12; 95 percent confidence interval, 0.05 to 0.29; P<0.001). The risk was significantly reduced during the period after obliteration, as compared with the latency period (hazard ratio, 0.26; 95 percent confidence interval, 0.10 to 0.68; P=0.006). The reduction was greater among patients who presented with hemorrhage than among those without hemorrhage at presentation and similar in analyses that took into account the delay in confirming obliteration by means of angiography and analyses that excluded data obtained during the first year after diagnosis. CONCLUSIONS: Radiosurgery significantly decreases the risk of hemorrhage in patients with cerebral arteriovenous malformations, even before there is angiographic evidence of obliteration. The risk of hemorrhage is further reduced, although not eliminated, after obliteration.

Adult↗

Expression of Fgf10 and Fgf receptors during development of the embryonic chicken stomach.

Fibroblast growth factor 10 (FGF10) is involved in numerous different aspects of embryonic development and especially in active epithelial-mesenchymal interactions during morphogenesis of many organs as a mesenchymal regulator by activating its receptors (FGFR1b and FGFR2b) expressed in the epithelial tissue. FGFR2b is also activated by FGF7 although FGF7 does not bind to FGFR1b. To provide basic data to analyze function of FGFs in the developing gut, here we cloned Fgf7 and studied expression patterns of Fgf7, Fgf10 and Fgfr1-4 during the development of chicken stomach (glandular stomach; proventriculus and muscular stomach; gizzard). Fgf10 is expressed both in the proventricular and gizzard mesenchyme while Fgf7 is expressed only in gizzard mesenchyme. Fgfr1-4 are expressed both in the epithelium and mesenchyme with a different spatial expression patterns. Furthermore, RT-PCR analysis reveals that Fgfr1b and Fgfr2b are expressed only in epithelia of both organs.

Amino Acid Sequence↗

Integration of three-dimensional corticospinal tractography into treatment planning for gamma knife surgery.

OBJECT: In the radiosurgical treatment of critically located lesions, the effort to minimize the risk of complication is essential. In this study the integration of diffusion-tensor (DT) imaging-based tractography was clinically applied to treatment planning for gamma knife surgery (GKS). METHODS: Seven patients with cerebral arteriovenous malformations located adjacent to the corticospinal tract (CST) underwent this technique. Data provided by DT imaging were acquired before the frame was affixed to the patient's head and the CST of the DT tractography was created using our original software. Stereotactic three-dimensional imaging studies were obtained after frame fixation and then coregistered with the data from DT tractography. After image fusion of the two studies, the combined images were transported to a GKS treatment-planning workstation. The spatial relationship between the dose distribution and the CST was clearly demonstrated within the 2 hours it took to complete the entire imaging process. The univariate logistic regression analysis of transient or permanent motor complications revealed a significant independent correlation with the volume of the CST that received 25 Gy or more and with a maximum dose to the CST (p < 0.05). CONCLUSIONS: The integration of DT tractography into the GKS treatment planning was highly useful in confirming the dose to the CST during treatment planning.

Adult↗

Risk of hemorrhage from an arteriovenous malformation confirmed to have been obliterated on angiography after stereotactic radiosurgery.

OBJECT: Radiosurgery has been widely adopted for the treatment of cerebral arteriovenous malformations (AVMs) in which the practical endpoint is angiographic evidence of obliteration, presumed to be consistent with elimination of the risk of hemorrhage. To test this unverified assumption, the authors followed 236 radiosurgery-treated AVMs between 1 and 133 months (median 77 months) after angiographic evidence of obliteration. METHODS: Four patients experienced hemorrhage between 16 and 51 months after angiographic confirmation of AVM obliteration, and two underwent resection. The histological findings in these patients showed occlusion of the AVM by thickening of the intimal layer with dense hyalinization as well as a small amount of residual AVM vessels and a tiny vasculature. The risks of hemorrhage from these presumaby obliterated AVMs were 0.3% for the annual bleeding risk and 2.2% for the cumulative risk over 10 years. Continuous enhancement of the nidus on computerized tomography (CT) or magnetic resonance (MR) imaging was the only significant factor positively associated with hemorrhage in the statistical analysis (p = 0.0212). CONCLUSIONS: Because the study was based on limited follow-up data, its significance for defining predictive features of hemorrhage after angiographic evidence of obliteration is still indeterminable. Nevertheless, disappearance of the AVM on angiography after radiosurgery does not always indicate total elimination of the disease, especially when CT or MR imaging continues to demonstrate an enhancing lesion. The authors therefore recommend continual follow up even after evidence of AVM obliteration on angiography.

Adolescent↗

Gamma knife surgery for arteriovenous malformations involving the corpus callosum.

OBJECT: The purpose of this study was to evaluate the safety and efficacy of gamma knife surgery (GKS) for the treatment of arteriovenous malformations (AVMs) involving the corpus callosum. METHODS: Thirty-two patients aged from 7 to 65 years (median 25 years) with AVMs of the corpus callosum underwent GKS between 1990 and 2002. The maximum AVM diameter was more than 3 cm in 11 patients (34%). The AVM volume ranged from 0.1 to 19.1 cm3 (median 1.6 cm3). The median dose to the AVM margin was 20 Gy (range 17-28 Gy). Patients were followed for 1 to 12 years (median 9 years). The angiographically confirmed actuarial obliteration rate was 64% and 74% at 4 and 6 years, respectively. Younger patient age (p < 0.05) and lower radiosurgery-based grading score (calculated from the patient age and AVM volume; p < 0.01) were the significant factors affecting successful AVM obliteration. No patient suffered a hemorrhage after GKS, although 28 patients (88%) had a history of hemorrhage from their AVMs. Radiation-induced neurological deficit was observed only in one patient (3%) who had undergone previous radiotherapy (50 Gy). No patient experienced complications of occlusion or stenosis of the normal vascular structures adjacent to the AVM. CONCLUSIONS: Gamma knife surgery is a safe and effective treatment for selected patients with AVMs involving the corpus callosum, and it carries a low risk of damaging adjacent critical vascular structures. Even ruptured AVMs with relatively large diameter can be successfully treated, especially in younger patients, with minimal morbidity and a low risk of repeated hemorrhage.

Adolescent↗

Gamma knife surgery for hemangioblastomas.

OBJECT: The authors reviewed their 14-year experience using stereotactic radiosurgery for the treatment of hemangioblastomas and define the role and the proper strategy for radiosurgery of this condition. METHODS: This is a retrospective study of 38 hemangioblastomas in 13 patients. Seven patients had von Hippel-Lindau disease. All patients have undergone at least one follow-up visit. The median and mean tumor volumes were 0.23 cm3 and 0.72 cm3 respectively (range 0.004::4.84 cm3). Twenty-eight tumors received 20 Gy to the margin, and the remainder received 18 Gy. The median clinical follow-up period was 36 months (range 3-159 months). No patient died. The survival rate was 84.6% (11 of 13 patients). The actuarial 5- and 10-year survival rates were both 80.8%. The median radiological follow-up period was 35 months (range 7-147 months). Only one tumor increased in volume 24 months after treatment in association with an intratumoral hemorrhage. The tumor control rate was 97.4% (37 of 38 tumors). Actuarial 5- and 10-year control rates were both 96.2%. New lesions and/or those increasing in size outside the irradiated area were discovered in five patients (38.5%). Nine tumors revealed peritumoral contrast enhancement which was seen more frequently in larger tumors with a volume greater than 0.5 cm3 (p = 0.0034). CONCLUSIONS: Gamma knife surgery is a safe and effective method to control hemangioblastomas for as many as 10 years. Higher doses and smaller tumors probably contribute to good outcomes. Recurrence outside the original irradiated area is common. Peritumoral contrast enhancement may be seen in larger tumors. The authors recommend regular imaging follow up and early repeated treatment in the face of new or growing tumors.

Adult↗

Proposed treatment strategy for cavernous sinus meningiomas: a prospective study.

OBJECTIVE: To establish a safe and effective treatment strategy for cavernous sinus (CS) meningiomas, we prospectively analyzed the outcome of a treatment protocol combining surgery and radiosurgery during the past 7 years. METHODS: Tumors confined to the CS and distant from the optic apparatus and the brainstem were treated with radiosurgery alone. Tumors attached to or compressing the optic apparatus and brainstem and that were larger than 3 cm in mean diameter, extended into the multiple cranial fossae, and were suspected of being malignant were treated with combined nonradical microsurgery and radiosurgery. RESULTS: In accordance with this treatment protocol, 40 patients aged 26 to 72 years (median, 51 yr) with primary (n = 27) or recurrent (n = 13) CS meningiomas (volume range, 0.9-39.3 cm(3); median volume, 5.4 cm(3)) were treated with combined surgery and radiosurgery (n = 23) or radiosurgery alone (n = 17). During radiosurgery, 12 to 18 Gy (median, 16 Gy) was delivered to the tumor margin. The follow-up period ranged from 14 to 79 months (median, 47 mo). The actuarial tumor control rate was 94.1% at 5 years. The improvement of cranial nerve function was significantly frequent in patients with primary CS meningiomas (P < 0.05). Permanent cranial nerve dysfunction was significantly frequent in patients with tumors compressing the brainstem or smaller than 10 cm(3) (P < 0.05). All 36 patients with a pretreatment Karnofsky Performance Scale score of 90 or more maintained the same range after treatment. CONCLUSION: Proper combination of microsurgery and radiosurgery for CS meningiomas provides excellent growth control with favorable functional state. Outcomes were better when this protocol was adopted at the initial diagnosis for patients with smaller tumors that did not compress the brainstem.

Adult↗

Analysis of nidus obliteration rates after gamma knife surgery for arteriovenous malformations based on long-term follow-up data: the University of Tokyo experience.

OBJECT: A large number of clinical studies have been made on treatment outcomes of radiosurgery for arteriovenous malformations (AVMs), but the reported obliteration rates following this treatment vary significantly, perhaps reflecting the different methods and timings of the imaging studies used. METHODS: The authors retrospectively analyzed their experience with gamma knife surgery in 400 patients with AVMs (follow-up period 1-135 months, median 65 months), with special reference to the imaging modality used in each case. The calculated obliteration rates varied from 68.2 to 92%, depending on imaging modality and timing of evaluation. When only unquestionable imaging data such as demonstrations of a residual nidus on computerized tomography (CT) or magnetic resonance (MR) images or findings on angiograms were used in the calculation, the obliteration rates were 72% at 3 years and 87.3% at 5 years. Factors leading to a better obliteration rate were previous hemorrhage (p = 0.0084), smaller nidus (p = 0.0023), and higher radiation dose to the lesion's margin (p = 0.0495), as determined in a multivariate analysis. Factors leading to an earlier obliteration of the nidus were male sex (p = 0.0001), previous hemorrhage (p = 0.0039), smaller nidus diameter (p = 0.0006), and dose planning using angiography alone (p = 0.0201). CONCLUSIONS: After the introduction of CT and MR images into dose planning, the conformity and selectivity of dosimetry improved remarkably, although the latency intervals until obliteration were prolonged. Imaging outcomes for AVMs should be evaluated using data provided by longer follow-up periods. The timing of additional treatments for residual AVMs should be decided cautiously, considering the size of the AVM, the patient age and sex, and the history of hemorrhage before radiosurgery.

Adolescent↗

Expression of DDSG1, a novel gene encoding a putative DNA-binding protein in the embryonic chicken nervous system.

In an attempt to clone genes expressed in the gizzard of the chicken embryo by differential display, we obtained a cDNA of a gene encoding a protein with a putative nuclear localization signal and a DNA-binding motif and designated it DDSG1 (differential display-screened gene expressed in the gizzard-1). Besides its expression in the gizzard, the gene is expressed in central and peripheral nervous systems such as brain, spinal cord and dorsal root ganglia in specific patterns.

Amino Acid Sequence↗

Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery.

Stereotactic radiosurgery is used to treat benign tumours, but its long-term effects are not fully understood. Here we describe a vestibular schwannoma that underwent malignant transformation 6 years after gamma knife radiosurgery applied to the tumour remnant after a primary resection. Histological specimens of the original specimen did not show any atypical features. Genotyping showed a TP53 mutation in the recurrent tumour, which did not exist in the original tumour. Our results suggest that radiosurgery induced the malignant transformation, and we propose a cautious application of this treatment for benign tumours.

Adult↗

Gamma knife radiosurgery for pituitary adenoma.

For the treatment of pituitary adenomas, transsphenoidal surgery is established as a first choice of treatment. However, pituitary adenomas are often not curable with surgery alone, and further treatment including radiation therapy is required to control the disease. In this report, we review the literature of gamma knife radiosurgery for pituitary adenomas and discuss the efficacy of this modern technology. Radiosurgery achieved 85-100% of growth control rates with only mild and transient neurological complications in most cases. Endocrinological normalization was obtained in more than 65% of GH producing tumors. These hormonal control rates seemed to be slightly better in GH producing tumors compared to ACTH producing tumors. To normalize the excessive GH or ACTH levels, radiosurgery for functioning adenomas requires a relatively higher dose, ideally more than 35 Gy at tumor margin. However, the adjacent optic apparatus is less tolerable for irradiation, and the tumors have to be sufficiently separated from it to prevent the radiation-induced visual deficits. Therefore, the role of surgery should not be underevaluated, and even if radiosurgery alone may be able to achieve an excellent outcome in some cases, surgical resection will remain the primary treatment for pituitary adenomas. For high-risk patients or patients with residual tumors after transsphenoidal surgery, gamma knife radiosurgery can be a first choice of treatment, achieving both growth control and hormonal remission with minimum neurological complications, which is equivalent to conventional radiation therapy but with much less risk of radiation injury to the surrounding structures.

Humans↗

Retrospective analysis of a 10-year experience of stereotactic radio surgery for arteriovenous malformations in children and adolescents.

OBJECT: To obtain information essential to the decision to perform radiosurgery for arteriovenous malformations (AVMs) in children and adolescents, the authors retrospectively analyzed their experience with gamma knife surgery for AVMs in 100 patients ranging in age from 4 to 19 years. METHODS: Follow-up periods ranged from 6 to 124 months (median 71 months), and the actuarial obliteration rates demonstrated by angiography were 84.1, 89.4, and 94.7% at 3, 4, and 5 years, respectively. Factors associated with better obliteration rates in univariate analysis included the following: a patient age of 12 years or younger; a mean nidus diameter of 2 cm or less; a nidus volume of 3.8 cm3 or less; a maximum diameter of the nidus less than 3 cm; and a Spetzler-Martin grade of III or less. Radiation-induced neuropathy was seen in four patients, and the risk factors were considered to be a nidus in the brainstem and a maximum radiation dose greater than 40 Gy. Hemorrhage developed during the latency interval in four patients, and one patient with a cerebellar AVM died of the hemorrhage. The annual bleeding rate was 1.5%. Feeding arteries located in the posterior cranial fossa and an AVM nidus located in the cerebellum were significantly associated with the risk of hemorrhage. After angiographically verified obliteration of the nidus, 51 patients continued to be observed from 1 to 110 months (median 67 months); hemorrhage developed in one patient 38 months after nidus obliteration. CONCLUSIONS: Radiosurgery is an acceptable treatment for small AVMs in children and adolescents in whom a higher obliteration rate can be achieved with lower risks of interval hemorrhage compared with the reported results in the general population. Careful follow-up observation seems to be required, however, even after angiographically verified obliteration.

Adolescent↗

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗