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N Fukushima

Publications and source records attributed to N Fukushima.

At least 37 records · Page 2Linked to original sources
PubMed2002

Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer.

BACKGROUND: The aim of this study was to assess the implications of positive peritoneal washing cytology for management of patients with potentially resectable pancreatic cancer. METHODS: Cytological examination of peritoneal washings was performed in 134 patients who underwent surgical resection for pancreatic adenocarcinoma. The clinicopathological findings and the relationship between cytology results (including cytomorphology) and survival were investigated. RESULTS: One hundred and fourteen patients (85 per cent) had negative cytology results (group 1). Excluding one patient with atypical cells, positive cytology results were obtained in 19 patients (14 per cent): 16 patients without macroscopic peritoneal metastases (group 2) and three patients with minimal macroscopic peritoneal metastases (group 3). The patients in group 2 had significantly larger (P < 0.001) and more advanced (P = 0.022) tumours than those in group 1. However, there were no significant differences in postoperative cumulative survival rates between groups 1 and 2 (P = 0.347). Two patients in group 2 are long-term survivors (40 and 58 months). In cytomorphological analyses, the presence of clusters with ragged edges and isolated carcinoma cells can be considered to indicate a high risk of peritoneal recurrence. CONCLUSION: Positive cytology does not directly predict peritoneal carcinomatosis and, while associated with advanced disease, does not contraindicate radical surgery.

Adenocarcinoma↗
PubMed2002

The minimum number of neurons in the central olfactory pathway in relation to its function: a retrograde fiber tracing study.

The present study was aimed at determining the functionally essential size of the neuronal population in the central olfactory nervous system. Using conditioned rats who had learnt to avoid repellent (cycloheximide) solution by olfaction, varying degrees of injuries were made to the lateral olfactory tract, a major central olfactory pathway connecting the olfactory bulb to the olfactory cortex. After examining their olfactory ability to discriminate cycloheximide solution from water, intact bulbar projection neurons (mitral cells) with fiber connections to the olfactory cortex were quantified using a retrograde fiber tracing technique. The numbers of retrogradely labeled mitral cells from the rats with normal olfaction ranged between 20 and 92% of the control value, while those numbers from the anosmic rats ranged between 0 and 22%. We conclude that the functionally essential neuronal population is approximately one-fifth of the total in the central olfactory pathway, a presumed threshold value in terms of the ability to avoid cycloheximide solution by olfactory discrimination.

Animals↗
PubMed2001

Regulation of Schwann cell morphology and adhesion by receptor-mediated lysophosphatidic acid signaling.

In peripheral nerves, Schwann cells (SCs) form contacts with axons, other SCs, and extracellular matrix components that are critical for their migration, differentiation, and response to injury. Here, we report that lysophosphatidic acid (LPA), an extracellular signaling phospholipid, regulates the morphology and adhesion of cultured SCs. Treatment with LPA induces f-actin rearrangements resulting in a "wreath"-like structure, with actin loops bundled peripherally by short orthogonal filaments. The latter appear to anchor the SC to a laminin substrate, because they colocalize with the focal adhesion proteins, paxillin and vinculin. SCs also respond to LPA treatment by forming extensive cell-cell junctions containing N-cadherin, resulting in cell clustering. Pharmacological blocking experiments indicate that LPA-induced actin rearrangements and focal adhesion assembly involve Rho pathway activation via a pertussis toxin-insensitive G-protein. The transcript encoding LP(A1), the canonical G-protein-coupled receptor for LPA, is upregulated after sciatic nerve transection, and SCs cultured from lp(A1)-null mice exhibit greatly diminished morphological responses to LPA. Cultured SCs can release an LPA-like factor implicating SCs as a potential source of endogenous, signaling LPA. These data, together with the previous demonstration of LPA-mediated SC survival, implicate endogenous receptor-mediated LPA signaling in the control of SC development and function.

Actins↗
PubMed2001

Continual replacement of newly-generated olfactory neurons in adult rats.

It has been known that stem cells do exist in the central nervous system, and adult neurogenesis is continually taking place in the olfactory bulb during life. We report here, with the combined method of autoradiography using (3)H-thymidine and immunohistochemistry for a neuronal marker, that 65.3-76.9% of calretinin-immunoreactive bulbar neurons are replaced during the short period of 6 weeks in the adult rodent. The results indicate that neuronal replacement is a common phenomenon in the olfactory bulb during life.

Aging↗
PubMed2001

Two novel Xenopus homologs of mammalian LP(A1)/EDG-2 function as lysophosphatidic acid receptors in Xenopus oocytes and mammalian cells.

Lysophosphatidic acid (LPA) induces diverse biological responses in many types of cells and tissues by activating its specific G protein-coupled receptors (GPCRs). Previously, three cognate LPA GPCRs (LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7) were identified in mammals. By contrast, an unrelated GPCR, PSP24, was reported to be a high affinity LPA receptor in Xenopus laevis oocytes, raising the possibility that Xenopus uses a very different form of LPA signaling. Toward addressing this issue, we report two novel Xenopus genes, xlp(A1)-1 and xlp(A1)-2, encoding LP(A1) homologs (approximately 90% amino acid sequence identity with mammalian LP(A1)). Both xlp(A1)-1 and xlp(A1)-2 are expressed in oocytes and the nervous system. Overexpression of either gene in oocytes potentiated LPA-induced oscillatory chloride ion currents through a pertussis toxin-insensitive pathway. Injection of antisense oligonucleotides designed to inhibit xlp(A1)-1 and xlp(A1)-2 expression in oocytes eliminated their endogenous response to LPA. Furthermore, retrovirus-mediated heterologous expression of xlp(A1)-1 or xlp(A1)-2 in B103 rat neuroblastoma cells that are unresponsive to LPA conferred LPA-induced cell rounding and adenylyl cyclase inhibition. These results indicate that XLP(A1)-1 and XLP(A1)-2 are functional Xenopus LPA receptors and demonstrate the evolutionary conservation of LPA signaling over a range of vertebrate phylogeny.

Adenylate Cyclase Toxin↗
PubMed2001

Effects of gene transfection of human bcl-2 on concordant cardiac xenografts in hamster to rat model.

OBJECTIVES: Concordant cardiac xenografts are known for delayed vascular rejection. Therapy combining with FK506 and cobra venom factor prolongs graft survival. The proposed underlying mechanism holds that cytoprotective proteins such as Bcl-2 play a role here. We studied the effects of gene transfection of human-bcl-2 on graft survival and coronary artery lesions in concordant cardiac xenografts, and discuss the role of cytoprotective genes in vascular xenograft rejection. METHODS: Golden-Syrian-hamster hearts were heterotopically transplanted into Lewis rats given FK506 (1 mg/kg daily) and cobra venom factor (0.2 mg/kg; day 0 and 1) intramuscularly. They were divided into 2 groups--grafts transfected vector with the human-bcl-2 gene (Group-B(+)) and vector without the gene (Group-B(-)) using the HVJ liposome method; 4 or 5 grafts from each group were explanted 1, 2, 3, or 4 weeks and more than 1 month after transplantation and evaluated by H-E, Elastic-Van-Gieson and immunohistochemical staining of Bcl-2. Coronary arterial lesions were examined using a scoring method. RESULTS: Bcl-2 expression in endothelial cells in Group-B(+) was confirmed within 2 weeks after transplantation but not thereafter. The coronary score in Group-B(+) was significantly lower than that in Group-B(-) within 2 weeks after transplantation but not thereafter. CONCLUSIONS: In this hamster-to-rat cardiac xenograft model, the bcl-2 gene was successfully transfected to the coronary endothelium and lasted 2 weeks. During Bcl-2 expression, coronary vascular lesions were suppressed more than in the untransfected group.

Animals↗
PubMed2001

Invasive carcinoma derived from intraductal papillary-mucinous carcinoma of the pancreas: clinicopathologic and immunohistochemical study of eight cases.

Most intraductal papillary-mucinous carcinomas (IPMCs) of the pancreas are resectable and curable, but some develop into frankly invasive carcinomas. We studied the clinicopathologic features of eight cases of invasive carcinoma derived from IPMC (IC-IPMC) of the pancreas. The patients were aged 54-75 years (mean, 66.6 years); six were male and two were female. The mean tumor size was 7.7 cm (range 5.5-10.5 cm). Two patients without lymph node metastasis had no peripancreatic invasion, and survived longer (115 and 20 months). Three out of four patients with extrapancreatic invasion died of their tumors or developed tumor recurrence within a year. One patient with evidence of liver and lymph node metastasis at the time of first surgery again showed metastatic tumor 21 months later. One patient died of another cause. We also performed a comparative study of the immunohistochemical features of IC-IPMCs in 9 IPMCs (including minimally invasive cases) and 15 ductal adenocarcinomas. CEA cytoplasmic positivity was observed in most of the IC-IPMCs (87.5%) and ductal adenocarcinomas (93.3%), but in only 1 IPMC (11.1%). The frequency of p53 nuclear staining in ductal adenocarcinoma (73.3%) was higher than in IPMC (33.3%) or IC-IPMC (37.5%). In conclusion, IC-IPMC with extrapancreatic invasion should be treated as ductal carcinoma because of its aggressive behavior after resection. Some IPMCs might progress to invasive carcinoma via pathways that are different from those followed by ductal adenocarcinomas.

Adenocarcinoma, Mucinous↗
PubMed2001

STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas.

Despite the growing awareness of intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas among clinicians, the molecular features of IPMNs have not been well characterized. Previous reports suggest that inactivation of the STK11/LKB1, a tumor-suppressor gene responsible for Peutz-Jeghers syndrome (PJS), plays a role in the pathogenesis of gastrointestinal hamartomas as well as several cancers, including pancreatic adenocarcinoma. Using polymerase chain reaction amplification of five microsatellite markers from the 19p13.3 region harboring the STK11/LKB1 gene, we analyzed DNA from 22 IPMNs for loss of heterozygosity (LOH). LOH at 19p13.3 was identified in 2 of 2 (100%) IPMNs from patients with PJS and 5 of 20 (25%) from patients lacking features of PJS (7 of 22, 32% overall). Sequencing analysis of the STK11/LKB1 gene in these IPMNs with LOH revealed a germline mutation in one IPMN that arose in a patient with PJS and a somatic mutation in 1 of the 20 sporadic IPMNs. None of the 22 IPMNs showed hypermethylation of the STK11/LKB1 gene. These results suggest that the STK11/LKB1 gene is involved in the pathogenesis of some IPMNs.

AMP-Activated Protein Kinase Kinases↗
PubMed2001

A vitamin D analog ameliorates glomerular injury on rat glomerulonephritis.

OCT (22-oxa-calcitriol), a vitamin D analog, has been reported to show strong inhibitory effects on mesangial cell proliferation in vitro. In the present study, we report a study of the effect of OCT on anti-thy-1 glomerulonephritis. Both OCT and 1,25(OH)(2)D(3) significantly inhibited mesangial cell proliferation, the degree of glomerulosclerosis, and albuminuria at day 8 compared to the disease control group. The OCT-treated group showed normal calcium levels but the 1,25(OH)(2)D(3)-treated group showed higher levels. The disease control group showed a marked increase of type I and type IV collagens, and alpha-smooth muscle actin (alpha-SMA) compared to the normal group. The treatment of OCT or 1,25(OH)(2)D(3) significantly reduced the expression of these proteins. The mRNA of the glomeruli of anti-thy-1 model expressed significantly higher levels of type I and type IV collagens, and alpha-SMA at day 8 compared to normal rats. Treatment with OCT or 1,25(OH)(2)D(3) inhibited the mRNA expressions of type I and type IV collagens, as well as that of alpha-SMA. These data demonstrate that OCT inhibits mesangial cell proliferation and extracellular matrix expansion with a low calcemic activity. Disease control rats showed significantly increased levels of transforming growth factor-beta1 protein in the glomeruli, but treatment with OCT or 1,25(OH)(2)D(3) markedly reduced this expression. The levels of mRNA in glomeruli were also consistent with these protein levels. Therefore, the suppressive effect of OCT may be mediated by inhibition of transforming growth factor-beta1. The present results suggest that OCT has potential for use in therapeutic strategy for the treatment of glomerulonephritis without inducing hypercalcemia.

Actins↗
PubMed2001

A novel strategy of decoy transfection against nuclear factor-kappaB in myocardial preservation.

BACKGROUND: Nuclear factor-kappaB (NFkappaB) is critical for the transcription of multiple genes involved in myocardial ischemia-reperfusion injury. Therefore, we hypothesized that blocking NFkappaB would attenuate ischemia-reperfusion injury after prolonged myocardial preservation, resulting in an improvement in cardiac function. METHODS: Double-stranded oligodeoxynucleotides with a specific affinity for NFkappaB (NFkappaB decoy group) or a scrambled decoy group were transfected into rat hearts using a hemagglutinating virus of Japan-liposome method. After 16 hours of preservation in Euro-Collins solution at 4 degrees C, the cardiac grafts were heterotopically transplanted into recipient rats of the same strain. RESULTS: Fluorescein isothiocyanate staining showed introduction of double-stranded oligonucleotides into the nuclei of endothelial cells and cardiomyocytes. After 1 hour of reperfusion the NFkappaB decoy group showed significantly higher degrees of recovery of left ventricular function as well as significantly lower levels of serum creatine phosphokinase, myocardial water content, tissue IL-8, and neutrophil infiltration than did the scrambled decoy group (p < 0.05). CONCLUSIONS: Gene transfection of the NFkappaB decoy attenuates ischemia-reperfusion injury after prolonged heart preservation. As a result, this method appears to be a novel strategy for enhanced myocardial preservation.

Animals↗
PubMed2001

The LPA receptors.

Lysophosphatidic acid (LPA) is a growth factor-like lipid that produces many cellular responses. These responses, including actin cytoskeletal rearrangements, cell proliferation and inhibition of gap junction communication, have been documented in many cell types over the last 2 decades. Both non-receptor and receptor-mediated mechanisms had been implicated to explain these responses. A clear advance in this field was the cloning and functional identification of LPA receptors, and there are currently three high-affinity members, LPA1, LPA2 and LPA3 (synonymous with orphan receptor names edg-2, edg-4 and edg-7, respectively). Here we review the gene structure, expression and functions of LPA receptors. We also discuss the in vivo roles mediated by a single LPA receptor type, based on studies of the nervous system, a major locus of LPA receptor expression.

Lysophospholipids↗
PubMed2001

Analysis of sympathetic nerve activity in end-stage cardiomyopathy patients receiving left ventricular support.

BACKGROUND: The left ventricular assist system (LVAS) has been used increasingly for patients with end-stage heart failure who are awaiting transplantation. Sympathetic nerve activity is known to correlate with cardiac function in chronic heart failure patients, but little is known about sympathetic nerve activity during LVAS support. In this study, we examined the status of sympathetic nerve activity in relation to mechanical support. METHODS: In this study, we included 10 consecutive patients with end-stage cardiomyopathy who were on LVAS support for at least 2 months (duration, 222 +/- 59 days). None of these patients achieved enough functional recovery to be taken off LVAS. In these patients, we used iodine-125-metaiodobenzylguanidine (125I-MIBG) scintigraphy to examine the change of sympathetic nerve activity after LVAS implantation, and compared the results with the change of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels as well as with histologic optional findings. Samples for ANP and BNP measurement were obtained before and 30 days after LVAS implantation. Specimens for histologic analysis were obtained at the time of LVAS implantation and at the time of cardiac transplantation or autopsy. RESULTS: We observed marked decrease in serum levels of ANP and BNP 1 month after LVAS implantation. But myocardial sympathetic nerve function, which was evaluated with 125I-MIBG scintigraphy and expressed as the heart-to-mediastinum activity ratio, remained below normal even 2 months after the LVAS implantation (1.57 +/- 0.19; normal, 2.34 +/- 0.36). Serial histologic analysis in these 10 patients showed continuous increase in percentage of fibrosis and cell diameter despite ventricular unloading by the LVAS. CONCLUSIONS: Sympathetic nerve function, which was evaluated on 125I-MIBG scintigraphy, did not improve during left ventricular support. Because none of the patients included in our study showed improvement in cardiac function or histologic findings, the recovery of myocardial sympathetic nerve function may be an important factor in myocardial recovery for cardiomyopathy patients on LVAS support.

3-Iodobenzylguanidine↗
PubMed2001

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children.

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) was established in July 1994 with the chief aim to improve the quality of therapy for type 1 diabetes in children, an entity far less common in Japan than in Europe. We proposed four initial research topics: (i) to determine the current status of medical care and glycemic control in Japanese children with type 1 diabetes mellitus; (ii) to standardize the measurement of hemoglobin A1c; (iii) to establish a registry of a large cohort of patients in order to enable prospective studies to improve the quality of therapy for children with type 1 diabetes in Japan; and (iv) to enable participants of the JSGIT to hold a workshop twice annually. We registered a total of 736 patients from 45 hospitals throughout Japan. Intervention via insulin treatment was instituted after 2 yr for those patients whose hemoglobin A1c level was more than 8.1%. The proportion of patients receiving multiple insulin injections increased after intervention; however, average hemoglobin A1c in females remained significantly higher than in males. We identified two forms of diabetes in Japanese children: a rapidly progressive form and a more slowly progressive form. There was a significantly higher prevalence of a family history of diabetes in first-degree relatives in the slowly progressive form. These preliminary findings are the result of the first collaborative study of childhood diabetes in Japan.

Journal Article↗
PubMed2001

Expression of laminin-5-gamma-2 chain in intraductal papillary-mucinous and invasive ductal tumors of the pancreas.

The laminin-5-gamma-2 chain is expressed in various invasive carcinoma cells. To clarify the relationship between laminin-5 expression and the development of intraductal papillary-mucinous tumors (IPMTs), we performed an immunohistochemical study of 26 IPMTs and 30 invasive ductal adenocarcinomas. Cases were classified into five groups: intraductal papillary-mucinous adenoma (Group A; n = 8), adenocarcinoma without invasion (Group B; n = 3), adenocarcinoma with minimal invasion (Group C; n = 5), adenocarcinoma with macroscopically evident invasion (Group D; n = 10), and invasive ductal adenocarcinoma (conventional type; Group E; n = 30). In the invasive components of Groups D and E, laminin-5 was expressed in 80% and 100% of cases, respectively. In the intraductal components of IPMTs, expression of laminin-5 was not seen in Groups A and B, whereas they were seen in one case in Group C (20%) and in seven in Group D (70%). Most of the staining patterns of the intraductal components were focal and scattered. Laminin-5-gamma-2 expression in the intraductal components of IPMTs tends to increase as tumors develop and may be a indicator of the potential invasiveness of the tumor cells.

Adenocarcinoma, Mucinous↗
PubMed2001

Intraductal papillary components in invasive ductal carcinoma of the pancreas are associated with long-term survival of patients.

Most patients with pancreatic ductal carcinoma have a poor prognosis. However, in certain cases, 5-year survival can be achieved after surgical resection. Analysis of the pathologic findings associated with good survival rates will assist in identifying the optimum treatment. The clinicopathologic features of 67 patients who underwent surgical resection of ductal adenocarcinoma of the pancreas between 1990 and 1996 were reviewed and correlated with survival rates. There were 42 men and 25 women, with a mean age of 62.1 years (range, 44 to 82 years). The mean greatest diameter of the tumor was 4.3 cm (range, 1.5 to 11 cm). Nineteen patients (29.4%) survived more than 3 years, and 9 (13.2%) survived more than 5 years after surgical resection. The intraductal papillary component (IDPC) of the carcinoma was the main focus of the pathologic observations. IDPC was defined as intraductal papillary proliferative lesions seen in the tumor nodule with proliferative cells consistent with carcinomatous cellular atypia. IDPC was clearly present (++) in 24 patients and vaguely present (+) in 9 patients. Using the Mantel-Cox test, a statistically significant correlation was found between the presence of IDPC (either + or ++) and postoperative patient survival (P =.002). IDPC is a morphologic feature associated with longer patient survival and should be taken into consideration in assessing the pathway of tumor progression.

Adult↗
PubMed2001

Sevelamer hydrochloride (Renagel), a non-calcaemic phosphate binder, arrests parathyroid gland hyperplasia in rats with progressive chronic renal insufficiency.

BACKGROUND: It has been demonstrated that dietary phosphate restriction suppresses parathyroid hormone (PTH) secretion and parathyroid cell proliferation in experimental animals with chronic renal insufficiency (CRI) independently of serum calcium and 1,25(OH)(2)D3 levels. This study was conducted to examine whether sevelamer hydrochloride (Renagel); hereafter referred to as sevelamer), a non-calcaemic phosphate binder could inhibit the parathyroid gland (PTG) hyperplasia in rats with progressive CRI. METHODS: Male Sprague-Dawley rats were injected twice with low doses of adriamycin (ADR). Two weeks after the last injection of ADR, rats were fed a diet containing 1 or 3% sevelamer for 84 days. Time course changes of serum levels of calcium, phosphorus, and PTH were measured. At the end of study, serum 1,25(OH)(2)D3 levels were measured and the maximal two-dimension area of the PTG in paraffin section was calculated using an imaging analyser. RESULTS: Dietary sevelamer treatment inhibited the elevations of serum phosphorus, calciumxphosphorus product, and PTH levels that occurred as the study progressed. Sevelamer also suppressed maximal PTG area and there existed positive strong correlation between maximal PTG area and serum PTH levels at the end of the study. Serum phosphorus levels positively correlated well with serum PTH levels and maximal PTG area. In contrast, serum calcium or 1,25(OH)(2)D3 levels did not show any correlation with serum PTH levels and maximal PTG area. CONCLUSIONS: Sevelamer treatment arrested hyperphosphataemia and PTG hyperplasia accompanied by the elevation of serum PTH levels. The correlation analysis suggests that reduced serum phosphorus levels contributed to the suppression of PTG hyperplasia and resulted in the reduction of PTH levels in this animal model after the sevelamer treatment. The management of phosphorus control started from early stage of CRI could prevent PTG hyperplasia and facilitate later management of secondary hyperparathyroidism.

Animals↗