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Biomedical subjects

N Fukushima

Publications and source records attributed to N Fukushima.

At least 55 records · Page 3Linked to original sources
PubMed2001

Abdominal pain in patients with resectable pancreatic cancer with reference to clinicopathologic findings.

Abdominal and/or back pain is one of the most common symptoms in patients with pancreatic cancer. However, the cause of the pain and the clinicopathologic features of patients with pain have not been fully elucidated. We retrospectively determined the factors related to preoperative abdominal and/or back pain in 95 patients with resectable pancreatic cancer. Pancreatic tumor size, invasion of the intrapancreatic nerves, invasion of the anterior pancreatic capsule, and lymph node metastasis were determined to be variables related to the pain. Pancreatic tumor size, invasion of anterior pancreatic capsule, and lymph node metastasis were also variables significantly correlating to pain intensity. Survival also correlated with pain intensity: the median survival periods were 29 months in patients without pain, 19 months in those with mild pain, and 9 months in those with severe pain who required analgesics. Larger pancreatic tumors, invasion of the intrapancreatic nerves, and invasion of the anterior pancreatic capsule may cause abdominal and/or back pain in patients with resectable pancreatic cancer. This study also suggests clinical implications of the pain intensity as a prognostic factor in patients with resectable pancreatic cancer.

Abdominal Pain↗
PubMed2001

Lysophospholipid receptors.

Lysophospholipids (LPs), including lysophosphatidic acid and sphingosine 1-phosphate, produce many cellular effects. However, the prolonged absence of any cloned and identified LP receptor has left open the question of how these lipids actually bring about these effects. The cloning and functional identification of the first LP receptor, lp(A1)/vzg-1, has led rapidly to the identification and classification of multiple orphan receptors/expression sequence tags known by many names (e.g. edg, mrec1.3, gpcr26, H218, AGR16, nrg-1) as members of a common cognate G protein-coupled receptor family. We review features of the LP receptor family, including molecular characteristics, genomics, signaling properties, and gene expression. A major question for which only partial answers are available concerns the biological significance of receptor-mediated LP signaling. Recent studies that demonstrate the role of receptor-mediated LP signaling in the nervous system, cardiovascular system, and other organ systems indicate the importance of this signaling in development, function, and pathophysiology and portend an exciting time ahead for this growing field.

Animals↗
PubMed2001

Renal mineral handling in normal rats treated with sevelamer hydrochloride (Renagel), a noncalcemic phosphate binder.

The effects of sevelamer hydrochloride (Renagel); hereafter referred to as sevelamer), a noncalcemic phosphate binder, on renal mineral handling were examined in rats. Normal rats were fed a diet containing 0.3, 1, 3, and 5% sevelamer for 8 days, and serum, urine, and the immunohistochemical localization of the type II Na/Pi cotransporter protein in the kidney were analyzed. Rats treated with 3 or 5% sevelamer showed significant decreases in serum phosphorus (P) and parathyroid hormone (PTH) levels, with no changes in serum calcium (Ca), magnesium (Mg), or 1,25(OH)2D3 levels. Increases were observed in urinary excretions of Ca and Mg associated with a reduction in the PTH level in rats treated with 3 or 5% sevelamer. Rats treated with 1% or higher concentrations of sevelamer showed significant dose-dependent and marked reductions of the urinary P excretion, and the tubular reabsorption of P was maximized to almost 100% in the 5% sevelamer group. The hypophosphaturia in rats treated with 3 or 5% sevelamer was accounted for by the reductions in serum PTH and P per se, and immunohistochemical analysis showed that the expression of type II Na/Pi cotransporter protein was markedly increased at the brush border membranes of the deep and superficial nephrons in rats treated with 5% sevelamer as compared with rats given a normal diet. In conclusion, sevelamer rapidly lowered serum P and PTH levels in normal rats. Sevelamer treatment also produced a marked hypophosphaturia associated with translocation of type II Na/Pi cotransporter protein and increased urinary Ca and Mg excretions by the reduction of PTH.

Administration, Oral↗
PubMed2001

Investigation of patients' demand for community pharmacies: relationship between pharmacy services and patient satisfaction.

We performed an investigation on the patients' demand for community pharmacy based on the analysis of questionnaire responses on community pharmacy services from the patients at 32 pharmacies in Tokyo and Osaka. In the previous study, we developed seven evaluation indices for pharmacy services, and showed that the functions most sought by patients in the "ideal pharmacies" were "Attitude of pharmacy/pharmacist", "Convenient hours" and "Information management". The objective of this study is to determine the relationship between these pharmacy functions and patient satisfaction by analyzing responses from the same questionnaire survey. Overall satisfaction score with the "pharmacy used today" was employed as the dependent variable, while the six factors derived from the 26-item evaluation scale in the questionnaire by factor analysis were used as the independent variables. As a result of analysis, it was found that four variables had a significant positive correlation with patient satisfaction, one had a significant inverse correlation, and one showed no significant correlation (p < 0.05). These results suggest that: attitude of the pharmacists such as general attitude and specialized activities of pharmacy/pharmacist such as providing information and explanations, and convenience of hours are not only judged to be important by patients, but also influence their satisfaction; comfortable facilities and availability of OTC drugs, while rated relatively low by patients in terms of importance, do influence their satisfaction; and convenience of location does not influence patient satisfaction. It was also indicated that insufficient inventories of prescribed medications have an impact upon patient satisfaction. This investigation offers evidence to provide patient-based pharmacy services.

Adult↗
PubMed2001

Angiogenesis and mast cells in non-Hodgkin's lymphoma: a strong correlation in angioimmunoblastic T-cell lymphoma.

Mast cells are likely to play a role in angiogenesis under pathological conditions. Solid tumor growth is dependent on angiogenesis, but the influence of mast cells on angiogenesis in non-Hodgkin's lymphoma, (NHL) is not clear. We investigated mast cell number and vessel count in 61 cases of NHL. We also evaluated expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), both important cytokines for angiogenesis. The number of mast cells was greater in T-cell lymphomas than in B-cell lymphomas. Of the T-cell lymphomas, the greatest number of mast cells was observed in the angioimmunoblastic T-cell lymphoma (AIL). In all NHLs, significant correlation was found between vessel count and the number of mast cells (p < 0.0001) and between vessel count and the number of VEGF-expressing cells (p < 0.05) but not between vessel count and bFGF-expressing cells. Strong correlation was detected between the number of mast cells and the number of VEGF-expressing cells (p < 0.0001) in all NHLs. Double fluorescence staining of VEGF mRNA and mast cell tryptase revealed that mast cells expressed VEGF mRNA. Our data suggest that mast cells play a very important role in angiogenesis by expressing VEGF in NHL, especially in AIL.

Cell Count↗
PubMed2001

[A study on the isolation period of patients with metastatic thyroid cancer treated by 131I according to a new guideline].

In Japan, a new guideline for the release of patients administered 131I was issued by the Ministry of Welfare on June, 1998: The dose rate is under 30 microSv/h at 1 m or the activity in the body is under 500 MBq. This study was designed to set the appropriate isolation period enough to satisfy these limits. A total of 28 patients with the history of total thyroidectomy and metastasis were selected for this study. In these patients, 28 patients were treated with oral administration of 3.7 GBq of Na131I (72 times), and one of 28 patients was once treated with 5.55 GBq of Na131I. Two of them were also received a total of 4 courses of a split dose therapy of 3.7 GBq of Na131I (740 MBq once a week for 5 consecutive weeks = one course). Measurements of the external exposure dose (microSv/h) at 1 m and the urinary excretory radioactivity (MBq) were performed at various times. There was a good correlation of the external exposure dose between standing (x microSv/h) and sitting (y microSv/h) postures (y = 0.99x + 0.406, r = 0.99, p < 0.0001, n = 169). The difference in the external exposure dose before and after urination (x microSv/h) had a significant correlation with the urinary excretory radioactivity (y MBq); y = 16.6x + 24.8, r = 0.96, p < 0.001, n = 41. Also, there was a significant correlation between the predicted value of residual radioactivity in the body (y' MBq) and the external exposure dose (x' microSv/h); y' = 20.8x' + 31.5, r = 0.98, p < 0.001, n = 77. In the patients treated with 3.7 GBq of Na131I, the mean and S.D. values of the external exposure dose (microSv/h) changed as follow: After 6 hr, 168 +/- 40; 24 hr, 52 +/- 23; 48 hr, 20 +/- 15; 72 hr, 10 +/- 9; and 96 hr, 8 +/- 9. The percentages of the patients satisfied the new guideline were as follow; 21.7% at 24 hr, 81.2% at 48 hr and 100% after 72 hr. Therefore the 3-day isolation is sufficient for the patients administered 3.7 GBq of Na131I.

Adult↗
PubMed2001

[Guideline of antimicrobial therapy in the area of cardiovascular surgery].

Although cardiovascular surgery is considered to be aseptic, prolonged hospital stay before and after surgery, the use of artificial materials and cardiopulmonary bypass, long-term use of intratracheal tubes or intravenous catheters, and an increase in surgeries on high-risk patients increase the incidence of postoperative infections. Therefore meticulous management to minimize bacterial contamination before and after surgery and identification of patient risk factors are important to reduce their incidence and severity, in addition to optimal antimicrobial therapy. As the targets of prophylactic antibiotics are usually superficial and environmental bacteria, those of choice are first or second-generation cephalosporins or penicillin with sulbactam. If postoperative infection is suspected, identification of the infectious site and pathogens and their susceptibility to anitimicrobials is useful to control infections. The use of broad-spectrum antibiotics is not recommended because these drugs induce bacterial resistance to antibiotics. Infectious endocarditis (IE) and deep wound infections, such as mediastinitis, are major serious infections after cardiovascular surgery. Antibiotics should be selected by considering the susceptibility of pathogens and pharmacokinetic properties of antibiotics, such as concentration in infected tissue. In patients reluctant to medical therapies, surgical intervention such as valve repair or replacement in IE and debridement and omental flap in mediastinitis should be considered.

Cardiovascular Surgical Procedures↗
PubMed2000

Lysophosphatidic acid (LPA) is a novel extracellular regulator of cortical neuroblast morphology.

During cerebral cortical neurogenesis, neuroblasts in the ventricular zone (VZ) undergo a shape change termed "interkinetic nuclear migration" whereby cells alternate between fusiform and rounded morphologies. We previously identified lp(A1), the first receptor gene for a signaling phospholipid called lysophosphatidic acid (LPA) and showed its enriched expression in the VZ. Here we report that LPA induces changes in neuroblast morphology from fusiform to round in primary culture, accompanied by nuclear movements, and formation of f-actin retraction fibers. These changes are mediated by the activation of the small GTPase, Rho. In explant cultures, where the cerebral cortical architecture remains intact, LPA not only induces cellular and nuclear rounding in the VZ, but also produces an accumulation of rounded nuclei at the ventricular surface. Consistent with a biological role for these responses, utilization of a sensitive and specific bioassay indicates that postmitotic neurons can produce extracellular LPA. These results implicate LPA as a novel factor in cortical neurogenesis and further implicate LPA as an extracellular signal from postmitotic neurons to proliferating neuroblasts.

Actins↗
PubMed2000

Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior.

Although extracellular application of lysophosphatidic acid (LPA) has been extensively documented to produce a variety of cellular responses through a family of specific G protein-coupled receptors, the in vivo organismal role of LPA signaling remains largely unknown. The first identified LPA receptor gene, lp(A1)/vzg-1/edg-2, was previously shown to have remarkably enriched embryonic expression in the cerebral cortex and dorsal olfactory bulb and postnatal expression in myelinating glia including Schwann cells. Here, we show that targeted deletion of lp(A1) results in approximately 50% neonatal lethality, impaired suckling in neonatal pups, and loss of LPA responsivity in embryonic cerebral cortical neuroblasts with survivors showing reduced size, craniofacial dysmorphism, and increased apoptosis in sciatic nerve Schwann cells. The suckling defect was responsible for the death among lp(A1)((-/-)) neonates and the stunted growth of survivors. Impaired suckling behavior was attributable to defective olfaction, which is likely related to developmental abnormalities in olfactory bulb and/or cerebral cortex. Our results provide evidence that endogenous lysophospholipid signaling requires an lp receptor gene and indicate that LPA signaling through the LP(A1) receptor is required for normal development of an inborn, neonatal behavior.

Animals↗
PubMed2000

Serum-free induced neuronal apoptosis-like cell death is independent of caspase activity.

Cultured cortical neurons survived in a density-dependent manner under serum-free conditions. Low-density cultured cells died in an aurintricarboxylic acid (ATA)-sensitive manner, which was accompanied with marked chromatin condensation and nuclear fragmentation. These features, characteristic for apoptosis, were not attenuated by DEVD-CHO, a caspase-3-specific inhibitor, or zVAD-FMK, a broad range caspase inhibitor, while zVAD-FMK showed a marked inhibition of camptothecin-induced cell death. Therefore, cortical neurons died in an apoptosis-like and a caspase-independent manner under serum-free conditions.

Amino Acid Chloromethyl Ketones↗
PubMed2000

G(i1) and G(oA) differentially determine kinetic efficacies of agonists for kappa-opioid receptor.

We examined the diversity of single receptor function by measuring receptor-G protein coupling in the baculovirus-Sf21 expression system. In comparative studies using Sf21 cell membranes expressing kappa-opioid receptor (KOR) plus Galpha(i1)beta(1)gamma(2) or KOR plus Galpha(oA)beta(1)gamma(2), there was no significant difference between both preparations in the K(i) values of various kappa-opioid ligands for the displacement of [(3)H]U69593 binding. However, a marked difference in the rank order of agonists to stimulate [(35)S]GTPgammaS binding was observed between both preparations. These findings suggest that agonist efficacy is dependent on the population of different G proteins expressed in various tissues.

Animals↗
PubMed2000

Nucleotide variations amongst V(H)Genes of AMA-producing B cell clones in primary biliary cirrhosis.

Primary biliary cirrhosis, a chronic liver disease characterized by progressive inflammatory destruction of intrahepatic bile ducts, is also characterized by the presence of antimitochondrial antibodies (AMA). The predominant autoantibody is directed at the E2 component of pyruvate dehydrogenase (PDC-E2). Recent studies of this autoantibody response have analysed immunoglobulin-variable regions of human monoclonal antibodies and provided evidence for antigen-driven clonal selection. However, the number of clones analysed has been very limited and the presence of somatic mutations not formally proven. In this study, we took advantage of three stable B cell lines producing human IgG anti-PDC-E2 mAbs from a patient with PBC. We analysed the V(H)and V(L)gene structure of these reagents and, in addition, analysed 10 V(H)-D and D-J(H)sequences over a period of nearly 3 years. The expressed Ig V regions of the heavy chain (V(H)) and the light chain (V(L)) genes of mAb18, mAb37, and mAb82 utilized the V(H)III-VlambdaI, V(H)IV-VlambdaIII, and V(H)IV-V(k)IV gene families, respectively. The utilized gene elements were Ig gene elements that were found frequently in other antibodies with different specificity and affinity. Presence of somatic point-mutations was confirmed in mAb82 by comparison of the expressed V(H)gene sequence with that of corresponding germline V(H)gene obtained from the granulocyte genomic DNA of the same patient. Interestingly, clonally related B cells were consistently found throughout the observation period and nucleotide variations among the V(H)genes were very few, ranging from 0.19 to 0.72% per base. These findings suggest that long-lived B cell clones can exist and may contribute, at least in part, to maintenance of autoantibodies in humans.

Amino Acid Sequence↗
PubMed2000

Coronary artery bypass graft in a renal transplant recipient.

A 47-year-old woman receiving predonine after renal transplantation underwent coronary artery bypass graft (CABG) surgery because of medically angina uncontrollable since 1996. Although she had an episode of acute renal rejection successfully treated with steroid pulse therapy, she had no angina or hemodialysis for over 2 years after CABG. We discuss postoperative management of renal recipient after cardiac surgery using lymphocyte-subpopulation monitoring.

Coronary Artery Bypass↗
PubMed2000

Primary intestinal T-cell lymphoma resembling lymphomatous polyposis: report of a case.

We report an interesting case of primary intestinal T-cell lymphoma (ITL) resembling lymphomatous polyposis (LP) in a 24-year-old man. The neoplasm macroscopically showed numerous small polyps throughout the colon and microscopically showed diffuse proliferation of small-sized tumor cells with occasionally cleaved or irregularly shaped nuclei. The tumor cells were immunohistochemically positive for CD3, CD8, TIA-1, and CD56, and a polymerase chain reaction study showed a single band, indicating monoclonal rearrangement of the T-cell receptor beta gene. The phenotypic features in the current case are consistent with those of ITL derived from cytotoxic CD56+ CD8+ intraepithelial lymphocytes. This is the second documented case of primary ITL with a morphologic pattern of LP.

Adult↗
PubMed2000

Association of vascular endothelial growth factor and mast cells with angiogenesis in laryngeal squamous cell carcinoma.

We investigated the expression of vascular endothelial growth factor (VEGF) and microvascular density in 54 cases of invasive laryngeal squamous cell carcinoma (SCC) and in ten samples of normal laryngeal tissue using immunohistochemistry methods. The study also focused on the distribution of mast cells in and around the SCCs. The microvascular density in laryngeal carcinoma tissue was higher than that in normal tissue (P = 0.02). VEGF was localized in SCCs, stromal cells, endothelial cells, minor salivary glands, and non-cancer epithelium adjacent to the tumor. VEGF expression in the tumor cells was found in 13 of 54 cases (24.1%), whereas mast cells around the carcinomas were VEGF positive in all 54 cases. Staining of VEGF in SCCs was strong in the area of high microvascular density (P = 0.0002). Using a multi-labeling subtraction immunostaining method, VEGF-positive stromal cells were classified mostly as mast cells and, in a few instances, as macrophages. VEGF staining in SCCs was associated with the mast cell count (P = 0.0001). There was no distinct correlation between VEGF expression and pTNM stage of an SCC. In conclusion, the results suggest that VEGF might be an important angiogenic factor in cancer invasion. Laryngeal cancer cells and mast cells may control the angiogenic response by releasing VEGF.

Adult↗