Biomedical subjects

F Sasaki

Publications and source records attributed to F Sasaki.

At least 19 recordsLinked to original sources

PubMed2006

MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening.

MYCN is the most powerful prognostic factor in cases of older children. However, how MYCN is related to the prognosis of infantile cases is not clear. A mass screening program was carried out by measuring urinary catecholamine metabolites (VMA and HVA) from 6-month-old infants. Of 2084 cases detected by the screening program, MYCN amplification (MNA) was examined by Southern blot analyses in 1533 cases from 1987 to 2000. Of the 1533 cases examined, 1500 (97.8%) showed no MNA, 20 cases (1.3%) showed MNA from three to nine copies, and 13 (0.8%) cases showed more than 10 copies. The 4-year overall survival rates of these three groups (99, 89 and 53%, respectively) were significantly different (P<0.001), indicating that MYCN copy number correlates with the prognosis. Cases with MNA more than 10 copies were more advanced than those without amplification (stage III, IV vs I, II, IVs; P<0.001). Patients with MNA more than 10 copies had significantly higher serum levels of neuron-specific-enolase (NSE) and ferritin than non-amplified patients (P=0.049, P=0.025, respectively). MYCN amplification was strongly correlated with a poor prognosis in infantile neuroblastoma cases. Therefore, for the selection of appropriate treatment, an accurate determination of MNA is indispensable.

Biomarkers, Tumor↗

PubMed2006

Management of childhood and adolescent thyroid carcinoma: long-term follow-up and clinical characteristics.

AIM: This analysis was performed to evaluate clinical factors such as local tumor control, control of distant metastasis, survival, and complications in children and adolescents with thyroid carcinoma. MATERIALS AND METHODS: From 1960 to 2003, 21 children and adolescents (16 girls and 5 boys, aged 4 to 15 years) were treated for thyroid carcinoma in our departments. Clinical data, operative findings, pathological findings, operative procedures, intra- and postoperative complications and follow-up were evaluated. Follow-up of patients ranged from 3 to 42 years (median, 20 years). RESULTS: Papillary carcinoma was found in 20 patients (95%) and follicular carcinoma in one patient. Cervical lymph node metastases were found in 12 out of 21 patients (57.1%) when thyroid carcinoma was diagnosed, and 5 patients (23.8%) had pulmonary metastasis. In patients with pulmonary metastasis, total thyroidectomy and bilateral radical lymph node resection was performed in 3 patients, lobectomy of the thyroid and radical lymph node resection in one patient, and partial thyroidectomy in one patient. All three patients who underwent total thyroidectomy are still alive. Internal irradiation by 131I and thyroid hormone replacement therapy was administered to 2 of 3 patients with pulmonary metastasis. CONCLUSION: Despite metastasis in the lymph nodes and even the lungs, the prognosis for patients with papillary carcinoma is good. Total thyroidectomy and positive 131I therapy are recommended for childhood and adolescent thyroid carcinoma with pulmonary metastasis.

Adenocarcinoma, Follicular↗

PubMed2006

Histological differentiation between prenatally diagnosed choledochal cyst and type I cystic biliary atresia using liver biopsy specimens.

Because it is difficult to distinguish preoperatively between prenatally diagnosed choledochal cyst (CC) and type I cystic biliary atresia (BA) by ultrasound scanning or magnetic resonance imaging (MRI), some modality of discrimination for the 2 entities is required. The aim of this study was to investigate the histological differences between prenatally diagnosed CC and type I cystic BA using liver biopsy specimens. Four children with prenatally diagnosed CC and two children with prenatally diagnosed type I cystic BA were identified by fetal ultrasonography between 1985 and 2003. The control group included two children who were operated on at an earlier period due to postnatally diagnosed BA. Liver wedge biopsy in the right lobe was performed at the time of the radical operation. Histological findings of the H & E-stained liver biopsy specimens were classified into 4 grades (Grade 0, no abnormality; Grade 1, ductular proliferation without bridging fibrosis; Grade 2, ductular proliferation with bridging fibrosis; and Grade 3, liver cirrhosis). The CC group consisted of one case of Grade 0 and three cases of Grade 1. The type I cystic BA group consisted of one case each of Grade 2 and Grade 3. In the control group, both cases were Grade 2. The authors suggest that exploratory laparotomy might be avoided and, instead, histologic examination using liver biopsy specimens can be a reliable test for the differential diagnosis of CC and type I cystic BA in prenatally diagnosed neonates.

Biliary Atresia↗

PubMed2006

Effective esophageal balloon dilation for esophageal stenosis in recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited disorder of squamous epithelium that results in dystrophic scarring of the skin after minor trauma. RDEB is classified into two subtypes: Hallopeau-Siemens (HS) and non-Hallopeau-Siemens (nHS). Although severe scarring of the skin is the most common and obvious complication of the disease, esophageal scarring with formation of long strictures may also develop. Treatment options for esophageal stenosis in patients with RDEB include steroids, hyperalimentation, esophageal dilation and replacement. This report describes a child who was dilated immediately after diagnosis of severe esophageal stenosis subsequent to nHS-RDEB and managed successfully. Endoscopic esophageal balloon dilation under fluoroscopic control was very useful for detecting the region of stenosis and bougienage. The literature on such injuries is reviewed here, and the problems associated with the treatment of children with esophageal stenosis associated with RDEB are discussed.

Catheterization↗

PubMed2006

Management and algorithm for focal nodular hyperplasia of the liver in children.

PURPOSE: The aim of this study was to determine an appropriate management plan for childhood and adolescent FNH, in particular to establish an algorithm for preoperative diagnosis and treatment. PATIENTS AND METHODS: Between 1985 and 2003, 4 children with FNH were diagnosed. Of these 4 patients, 3 (Group A) underwent tumor resection, and 1 (Group B) was treated by conservative management. Clinical data, pathological findings and follow-up were evaluated retrospectively. RESULTS: The 3 patients in Group A were symptomatic, while the 1 patient in Group B was asymptomatic. In 3 of 4 patients, a homogeneous tumor with a central stellate area was noted on abdominal ultrasonography, CT scan and MR imaging. In case 2, SPIO-enhanced MR imaging was useful for differentiating FNH from hepatocellular carcinoma. Though percutaneous needle biopsy was performed in case 3, a pathologically definitive diagnosis was impossible. An open biopsy was performed in case 4 and FNH was diagnosed. In case 4 treated by conservative management, the tumor size did not change during the 7 years after the diagnosis of FNH. CONCLUSION: FNH is usually treated conservatively because of the good evolutionary outcome of the lesion. Surgery is indicated in cases of complications, compressed adjacent organs, lesion progression, or for symptomatic patients. We advocate the use of less invasive SPIO-enhanced MR imaging instead of open biopsy when the diagnosis of focal liver lesions is not clear after contrast-enhanced CT scan and non-enhanced MR imaging.

Adolescent↗

PubMed2005

Delay of gastric emptying measured by 13C-acetate breath test in neurologically impaired children with gastroesophageal reflux.

Delayed gastric emptying often occurs in patients, including children, with gastroesophageal reflux (GER) due to neurological impairment (NI). The aim of this study was to evaluate gastric emptying of liquids in children with symptomatic GER using the (13)C- acetate breath test (ABT), and to compare the gastric emptying rates between children without and with NI. Thirteen patients were divided into 2 groups: group I without NI (5 patients) and group II with NI (8 patients). The liquid test meal consisted of Racoltrade mark (5 ml/kg) mixed with (13)C- acetate (50 mg for infants, 100 mg for children, and 150 mg for adolescents). Breath samples were collected for (13)CO (2) measurement before the intake of the meal, every 15 minutes during the first 2 hours after the meal and every 30 minutes thereafter to assess the ingestion of (13)C- acetate and Racoltrade mark. (13)CO (2) was measured using a gas chromatograph-isotope ratio mass spectrometer. The results were expressed as % of (13)C expired per hour and cumulative (13)C excretion over a 3-hour period. The half excretion time in (13)C- ABT(t (1/2) ex) was 1.095 hour for group I and 1.817 hour for group II (p = 0.0045). The lag time (t lag), which reflected the initial delay of gastric emptying, was 0.666 h for group I and 1.002 h for group II (p = 0.0045). Gastric emptying studies can be easily and reliably carried out in children with NI using (13)C- ABT. We showed that we were able to determine the gastric emptying rate by (13)C- ABT in patients with GER due to NI.

Acetates↗

PubMed2005

Bleeding disorder as the first symptom of biliary atresia.

Biliary atresia (BA) is occasionally diagnosed in infants whose first symptom is a bleeding disorder, such as intracranial bleeding, nasal bleeding or gastrointestinal bleeding. The authors describe 3 cases in which a bleeding disorder was the first symptom of BA. The presenting symptom was intracranial bleeding in a male on day 55 after birth, nasal bleeding in a female at 65 days, and gastrointestinal bleeding in a female at 25 days. Coagulation studies revealed a vitamin K deficiency in all patients. After the administration of vitamin K, the results of coagulation tests normalized and the bleeding tendency of the infants ceased. Subsequently, BA was suspected to be the cause of these bleeding disorders based on imaging findings. BA should therefore be considered in all infants with sudden onset of a tendency to bleed.

Biliary Atresia↗

PubMed2004

High expression of telomerase is an independent prognostic indicator of poor outcome in hepatoblastoma.

Telomerase, an enzyme related with cellular immortality, has been extensively studied in many kinds of malignant tumours for clinical diagnostic or prognostic utilities. Telomerase activity is mainly regulated by the expression of hTERT (human telomerase reverse transcriptase), which is a catalytic component of human telomerase. To evaluate whether the levels of hTERT mRNA provides a molecular marker of hepatoblastoma malignancy, we examined hTERT mRNA expression levels in the primary hepatoblastoma tissues by fluorescent RT-PCR using LightCycler technology and followed up the clinical outcomes in 63 patients listed in the Japanese Study Group of Pediatric Liver Tumor between 1991 and 2002. The hTERT mRNA expression was detected in 61 (96.8%) specimens and their expression levels ranged between 0.1/1000 and 745.1/1000 copies of PBGD gene that was used as an internal control. Among these cases, frozen 39 tumour samples and 14 adjacent noncancerous liver tissues were analysed for semiquantitative telomerase assay. In the 39 tumour samples, the levels of telomerase activity ranged between 0.11 and 2709 TPG and 12 (30.7%) had high telomerase activity (>100 TPG), whereas only nine of 14 noncancerous liver tissue samples showed telomerase activity which was less than 1.0 TPG. The levels of telomerase activity were significantly correlated with the levels of hTERT mRNA expression (P<0.001). The frequency of high hTERT mRNA expression and/or high telomerase activity did not significantly associate with the clinicopathological factors except for stage of disease. The prognosis of the patients with high hTERT mRNA expression was significantly worse than that of others (P<0.01), as was the patients with high telomerase activity (P<0.01). Multivariate analysis indicated that high levels of hTERT mRNA expression as well as telomerase activity are independent prognosis-predicting factors in patients with hepatoblastoma.

Adolescent↗

PubMed2004

Perforation of the piriform recessus by a swallowed glass splinter presenting as pneumomediastinum in a child.

The swallowing of sharp glass splinters is rare due to the difficulty of swallowing such objects, and perforation of the piriform recessus and mediastinitis are unusual complications. Perforation of the piriform recessus due to a swallowed sharp glass splinter requires prompt treatment. This report describes a child who was operated on immediately after the diagnosis of perforation of the piriform recessus and was managed successfully. Light-guided pharyngoscopy was very useful for detecting the region of perforation. The literature on such injuries is reviewed here, and the problems associated with treating children with perforation of the piriform recessus and mediastinitis caused by swallowed glass splinters are discussed.

Deglutition↗

PubMed2002

Outcome of hepatoblastoma treated with the JPLT-1 (Japanese Study Group for Pediatric Liver Tumor) Protocol-1: A report from the Japanese Study Group for Pediatric Liver Tumor.

PURPOSE: Hepatoblastoma is the most common malignant liver tumor in childhood. Multicenter studies elucidate the optimal pre- or postoperative chemotherapeutic regimens. This report reviews the results of the Japanese Study Group for Pediatric Liver Tumor Protocol-1 (JPLT-1) and compares its outcomes with published reports of other studies. METHODS: From March 1991 to December 1999, 154 patients with malignant liver tumor including 145 cases of hepatoblastomas were enrolled in the JPLT study. Data from 134 cases were analyzed in this study. JPLT-1 protocol 91A was used for patients with stage I or II hepatoblastoma. The chemotherapy regimen consisted of repeated courses of cisplatin (CDDP), 40 mg/m(2), and tetrahydropyranyl (THP)-Adriamycin, 30 mg/m(2). JPLT-1 protocol 91B was administered to patients with stage IIIA, IIIB, or IV hepatoblastoma. The chemotherapy regimen consisted of repeated courses of CDDP, 80 mg/m(2), and THP-Adriamycin, 30 mg/m(2)/day for 2 days. Courses were repeated every 4 weeks as tolerated. RESULTS: Seven patients died of chemotherapy-related side effects. Six of them died of sepsis caused by leukopenia and 1 case of liver failure. Overall survival rate (3-year/6-year) was 100%/100% for stage I (n = 9), 100%/95.7% for stage II (n = 32), 76.6%/73.8% for stage IIIA (n = 48), 50.3%/50.3% for stage IIIB (n = 25), 64.8%/38.9% for stage IV (n = 20), and 77.8%/73.4% overall. For stage IIIA and B disease, intravenous chemotherapy was better than intraarterial chemotherapy (66.4% v 38.1% for event-free survival and 69.3% v. 57.1% for overall survival). Patients less than 1 year of age had a better prognosis than older patients, but age was not a significant prognostic factor by multivariate analysis. CONCLUSIONS: The overall and event-free survival rates of the JPLT-1 study of hepatoblastoma were comparable with the results of other multicenter studies in Europe and the United States. The event-free survival rate at 3 years for stage IIIB and IV disease was under 50%. New treatment strategies are needed for patients with advanced hepatoblastoma.

Adolescent↗

PubMed2001

Frequent beta-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm.

Significance of Wnt signaling with beta-catenin mutations on solid-pseudopapillary neoplasm (SPN) of the pancreas was studied by immunohistochemistry and molecular analysis. On immunohistochemistry, all 18 SPNs tested showed diffuse cytoplasmic/nuclear positivity for beta-catenin. Upon direct DNA sequencing of exon 3 of the beta-catenin gene, 15 (83%) of the 18 SPNs showed 1-bp missense mutation in codons 32 (5 cases), 33 (3 cases), 34 (3 cases), 37 (3 cases), and 41 (1 case). Immunoreactivity for cyclin D1, one of the intranuclear targets of beta-catenin complexes, was found in tumor cells of more than half the tumor cells of all of the 18 SPNs. The present study strongly suggested a significant role of Wnt signaling, mostly associated with beta-catenin mutations in the tumorigenesis of SPN.

Adolescent↗

PubMed2001

Caveolar and intercellular channels provide major transport pathways of macromolecules across vascular endothelial cells.

Serum macromolecules are transported through the vascular endothelial layer to the interstitium via the caveolae and interendothelial clefts, but the nature of the permeability of these structures is unknown, and the manner of caveola-vesicle transport is controversial. We have developed a method of detecting macromolecular channels using an in situ HRP perfusion into arteries previously perfused with aldehyde and random conventional sectioning for electron microscopy. Using unbiased morphometry, 4.75% of the abluminal caveolae and 15.13% of the intercellular clefts were the tracer-positive in rat aortic endothelium. In rat aortas treated with N-ethylmaleimide, all caveolae and most free vesicles in the cytoplasm except those around the Golgi area were HRP-positive in the endothelial cells; 1.48% of abluminal caveolae were structurally recognized as caveolar channels through the endothelial layer in a plane of single section. The length density of the abluminal caveolae was decreased to about 80% to the physiological control level whereas the larger invaginations were more frequently observed. Moreover 96.17% of the intercellular clefts were HRP-positive. We suggest that a flexible channel-system functions extensively as a macromolecular transport pathway in the arterial endothelium in vivo because the tracer-labeled abluminal caveolae and intercellular clefts should be opened to the luminal surfaces methodologically. We therefore propose that caveolar channels, rather than transcytosis, provide a mechanism of caveola-vesicle transport in the endothelial cells, because free vesicles involved in transcytosis were few in number.

Animals↗

PubMed2001

Role of the gonads in sex differentiation of growth hormone-releasing hormone and somatostatin neurons in the mouse hypothalamus during postnatal development.

We clarify the mechanism of sexual dimorphism of growth hormone releasing hormone (GHRH) neurons in the arcuate nucleus (ARC) and somatostatin (SS) neurons in periventricular nucleus (PeN), by studying the role of the gonads during the neonatal period and after puberty using immunohistochemical and morphometric methods. As in our previous works the numbers of ARC GHRH-ir and PeN SS-ir neurons were significantly greater in adult normal male (NM) mice than in adult normal female (NF) mice. Adult female mice that were ovariectomized neonatally (NOF) increased the expression of GHRH-ir neurons to the male pattern, but adult female mice ovariectomized after puberty (APO) did not change. Adult male mice castrated neonatally and after puberty (NCM and APC, respectively) were not significantly different from NM mice. However, NCT male mice, which were castrated neonatally and transplanted with ovary just before puberty, showed a significantly reduced number of GHRH-ir neurons compared with NCM mice, but no significant difference from NM and NF mice. On the other hand, the PeN SS-ir neuron expression in NCM mice and APC mice showed a significant reduction compared with NM mice, but no significant difference from NF mice. The number of PeN SS-ir neurons in NOF increased to match that of NM mice. Our results suggest that the presence of the ovary during postnatal life inhibits the development of ARC GHRH-ir neurons. The presence of the testis during postnatal life may stimulate the development of PeN SS-ir neurons, while the presence of the ovary during neonatal period may inhibit the development of PeN SS-ir neurons; the presence of ovary after puberty does not inhibit.

Animals↗

PubMed2001

Adrenomedullin suppresses fMLP-induced upregulation of CD11b of human neutrophils.

In this study we investigated the effect of adrenomedullin (AM) on fMLP-mediated activation of human neutrophils. AM partially, but significantly, suppressed fMLP-induced upregulation of CD11b expression. The inhibitory effects of AM upon fMLP-induced upregulation of CD11b expression were completely blocked by CGRP [8-37], a CGRP receptor antagonist. AM significantly increased cAMP content in neutrophils and SQ-22,536, an adenylate cyclase inhibitor, and KT-5720, a PKA inhibitor, significantly blocked the inhibitory effects of AM upon fMLP-induced upregulation of CD11b expression. This study indicates that binding of AM to the CGRP receptor suppresses fMLP-induced upregulation of CD11b expression of human neutrophils by increasing intracellular cAMP levels. AM may play an important role in the regulation of inflammatory processes, especially in the binding of neutrophils to vascular endothelial cells and subsequent neutrophil emigration evident in acute pulmonary inflammation.

Adenine↗

PubMed2001

Perinatal development of the rat kidney: proliferative activity and epidermal growth factor.

The immunolocalization of proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF) and its receptor (EGFR) was examined in the perinatal rat kidney. As the index of proliferative activity, PCNA-positive cell ratios in glomeruli and proximal tubules were determined. The PCNA-positive ratios in both glomeruli and proximal tubules decreased significantly during the perinatal period and tended to decrease as the glomerular developmental stage proceeded as well. PCNA-positive cells were seen predominantly in the nephrogenic zone of the kidney throughout the period examined. They were noted in the collecting ducts of the nephrogenic zone and were rarely seen in those of the central zone of the kidney. On the other hand, PCNA-positive cells were noted in the straight portion of the proximal tubules and were rarely seen in the convoluted one. EGF-positive cells were seen in the proximal tubules, distal tubules and collecting ducts, though EGF-positive cells in the proximal tubules decreased after birth. EGFR-positive cells were seen along the entire length of the proximal tubules and collecting ducts as well as in immature glomeruli, not in mature ones. These results indicate that marked cell proliferation occurs in the collecting ducts in the peripheral area and in the proximal tubules in the central area of the kidney, that the proliferative activity decreases with age during the perinatal days and that EGF plays an important role in the proliferation of glomerular cells, and in both proliferation and maturation of the cells in the proximal tubules and collecting ducts.

Animals↗

PubMed2001

The role of gicerin, a novel cell adhesion molecule, in development, regeneration and neoplasia.

Neurite outgrowth factor (NOF) is an extracellular matrix (ECM) protein in the laminin family and its ligand, gicerin, is a novel cell adhesion molecule in the immunoglobulin superfamily. Gicerin has a homophilic adhesive activity as well as a heterotypic manner to NOF. In the nervous systems, gicerin is expressed during developmental stage when neurons migrate or extend neurites to form a neural network. Gicerin promotes neurite extension and migration of embryonic neurons in vitro by its homophilic and heterophilic adhesion activities. Introduction of antigicerin antibody into early developing eyes perturbs the layer formation of neural retina. These data suggest that gicerin participates in the formation of neural tissues. Gicerin is also expressed in other non-neural tissues; in epithelia of trachea, kidney and oviduct, gicerin expression is restricted in the developmental period. In contrast, muscular tissues and endothelial cells express gicerin continuously even after maturation. Interestingly, gicerin re-appears strongly in the regenerating epithelia of trachea, kidney and oviduct, and also anti-gicerin antibody disrupts the healing process of trachea. Furthermore, gicerin and NOF are overexpressed in the chicken nephroblastomas (Wilm's tumor) and oviductal adenocarcinomas. In vitro analyses show that gicerin adhesive activities can promote binding among tumor cells and adhesion of tumor cells to NOF. A polyclonal antibody against gicerin also perturbs the re-attachment of cancer cells onto metastasizing sites. It is clear from these studies that gicerin is a potential effector for pathological tissue formation as well as for normal development.

Animals↗

PubMed2001

Acute severe alcohol-induced bronchial asthma.

We report the case of a severe bronchial asthma attack 15 minutes after the ingestion of food containing small amounts of alcohol. Although an ethanol inhalation test was negative, an acetaldehyde inhalation test was positive. Furthermore, it was discovered that the patient was homozygous for a mutation of the aldehyde dehydrogenase-2 (ALDH-2) gene. We subsequently diagnosed his attack as acute severe alcohol-induced asthma. Since bronchial asthma patients who are homozygous for mutant ALDH-2 genes are susceptible to acute severe alcohol-induced asthma attacks, strict clinical attention is thought a necessity.

Acetaldehyde↗

PubMed2001

Japanese red-bellied newts in Space--AstroNewt experiment on Space Shuttle IML-2 and Space Flyer Unit.

Biological effects of gravity was examined in embryonic development of Japanese red bellied newt. Two space newt missions were conducted in 1994 and 1995. The Second International Microgravity Laboratory was flown in 1994 as one of the SpaceLab missions. Space Flyer Unit, a Japanese space platform, was delivered to the earth orbit by the third launch of the H-II rocket and retrieved by Space Shuttle in 1996. Female newts were induced to lay eggs in orbit at these two space missions. Eggs were successfully obtained on both missions, and exposed to space environment from its early developmental stages. Morphology of the embryos was found not deviated from those developed on ground, as long as in the images taken in orbit or the examined specimen retrieved to ground. On the other hand, pathological changes were discovered in several organs of the adult newts that returned alive from their space flight.

Adaptation, Physiological↗