Biomedical subjects

K Fukuda

Publications and source records attributed to K Fukuda.

At least 37 records · Page 2Linked to original sources

PubMed2004

An intraductal papillary component is associated with prolonged survival after hepatic resection for intrahepatic cholangiocarcinoma.

BACKGROUND: The outcome after surgery for intrahepatic cholangiocarcinoma (ICC) is dismal and data on long-term survival are not available. This study evaluated prognostic indicators and characteristic features of long-term survivors after hepatic resection for ICC. METHODS: Thirty-one patients who had undergone hepatic resection for ICC were studied. Univariate and multivariate survival analyses of clinicopathological data included an intraductal papillary carcinoma component (IDPCC) in the tumour, which was defined as the histological demonstration of cancer cells growing in a papillary fashion into the lumen of the large bile duct. RESULTS: The overall cumulative survival rate after hepatic resection for ICC was 51.2 per cent at 1 year and 24.5 per cent at 5 years, with a mean(s.d.) survival time of 11(4) months. The presence of IDPCC (P = 0.003), curative resection (P = 0.009) and the absence of perineural invasion (P = 0.040) were identified as favourable independent prognostic factors in multivariate analysis. Eight patients with IDPCC had a 5-year survival rate of 87.5 per cent and a mean(s.d.) survival time of 69(13) months. All seven patients who survived for more than 5 years after surgery had IDPCC, regardless of the gross appearance of the tumour. CONCLUSION: An IDPCC in the tumour resulted in long-term survival after hepatic resection for ICC.

Adult↗

PubMed2004

Combination of transconjunctival and endonasal-transantral approach in the repair of blowout fractures involving the orbital floor.

In the repair of orbital blowout fractures through eyelid or conjunctival incision, it is difficult to see the posterior edge of the fracture and the condition of the herniated tissue before reduction of the orbital contents. Prolapsed orbital tissue or infraorbital nerve and vessels may therefore be damaged in the reduction. The recently advocated combination of traditional transconjunctival approach and endoscopic transantral approach allows reduction and reconstruction under clear endoscopic vision without a facial skin incision. We modified this technique to make it less invasive and applied it to the repair of orbital blowout fractures involving the orbital floor. The use of a 70-degree straight endoscope through an enlarged ostium as for functional sinus surgery allowed clear sight of the roof of the antrum. During the repair of the orbital floor through a transconjunctival approach, reduction and reconstruction was assisted from the antrum. Twelve cases of fresh blowout fractures were treated with this approach. There were seven male and five female patients. Mean age was 23.5 years. Causes of injuries were fights, motor vehicle or bicycle accidents, and sports. Patients with concomitant fractures involving the orbital rim were excluded. Persistent diplopia was present in eight cases and enophthalmos of more than 2 mm was detected in five cases preoperatively. The average intervals from injury to surgery was 22.8 days.Exploration, reduction and reconstruction of the orbital floor fractures were precisely performed with this procedure. Large orbital floor defects were reconstructed with silicone sheets, thin iliac bone grafts or nasal septal cartilage. In all eight cases that showed diplopia, ocular movement recovered and symptomatic diplopia disappeared after surgery. Enophthalmos of more than 2 mm was also improved in all five cases. One early case showed temporary entropion. Transient numbness of the cheek appeared in five cases and temporary maxillary sinusitis recovered in one case. Postoperative infection was not observed.This method provides visualisation of posterior edge of the fracture and the condition of herniated orbital contents before initiation of reduction. Dual manipulation by two surgeons is also possible in reduction and reconstruction of the orbital floor.

Adolescent↗

PubMed2004

Unresponsiveness to factor VIII inhibitor bypassing agents during haemostatic treatment for life-threatening massive bleeding in a patient with haemophilia A and a high responding inhibitor.

We report a case of haemophilia A with a high responding inhibitor of factor VIII (FVIII) who had a serious retroperitoneal haematoma caused by penetration of a duodenal ulcer. Inhibitor-bypassing therapy was commenced immediately on admission. On the 17th day of treatment with activated prothrombin complex concentrate (APCC; FEIBA, re-bleeding occurred and thrombelastography (TEG) demonstrated resistance to therapy. Treatment was changed to recombinant activated factor VII (rFVIIa; NovoSeven and resulted in clinical improvement together with an improvement in TEG parameters. On the 10th day of continuous infusion with NovoSeven, however, TEG again showed resistance to therapy. FEIBA infusions were re-introduced and TEG results remained satisfactory for 7 days. On day 34, however, further retroperitoneal bleeding was evident and a decline in the haemostatic efficiency of FEIBA was recorded by TEG. NovoSeven was again successfully administered for 7 days. There were no laboratory findings to indicate disseminated intravascular coagulation (DIC), hypercoagulability or abnormal fibrinolysis. The plasma-based clotting tests did not show any additional prolongation on the occasions when the TEG demonstrated unresponsiveness to FEIBA or NovoSeven. These findings suggested that some component of whole blood, other than plasma might have governed the TEG data. The long-term use of APCC such as FEIBA or rFVIIa, requires careful monitoring in terms of FVIII inhibitor bypassing activity as well as the tendency to DIC.

Adolescent↗

PubMed2003

Cyclic tensile stretch loaded on bovine chondrocytes causes depolymerization of hyaluronan: involvement of reactive oxygen species.

OBJECTIVE: We have previously demonstrated that reactive oxygen species (ROS) are involved in cartilage degradation. Decreased size of hyaluronan (HA), the major macromolecule in synovial fluid, to which it imparts viscosity, is reported in patients with arthritis. The purpose of this study was to determine the alteration in the molecular weight range of HA as a result of mechanical deformation loaded on the chondrocytes, as well as the involvement of ROS in this action. METHODS: ROS were generated via the oxidation of hypoxanthine by xanthine oxidase. Cyclic tensile stretch was loaded using a vacuum-operated instrument. Levels of HA were measured using a sandwich enzyme-binding assay. Superoxide dismutase (SOD) activity and ROS were measured using water-soluble tetrazolium and a chemiluminescent probe, respectively. RESULTS: ROS depolymerized HA molecules. Cyclic tensile stretch depolymerized HA and induced ROS. SOD inhibited not only ROS induction but also HA depolymerization caused by the mechanical stress. CONCLUSION: ROS play an important role in mechanical stress-induced HA depolymerization.

Animals↗

PubMed2003

Effects of an aldose reductase inhibitor on gastroenteropathy in streptozotocin-diabetic rats.

We investigated the effects of epalrestat, an aldose reductase inhibitor (ARI), on gastric emptying, fecal water content, and electrolyte transport in distal colon in streptozotocin (STZ)-induced diabetic rats. We measured gastric emptying time by acetaminophen method and short-circuit-current (Isc) in colonic mucosa using an Ussing chamber. The Isc in response to electric-field-stimulation (EFS) was decreased in untreated rats due to suppression by Cl- secretion. ARI treatment alleviated this suppression (2.7 +/- 0.6 vs. 7.4 +/- 1.1 microA/0.38 cm2 at 8 weeks after treatment, 1.1 +/- 0.2 vs. 7.0 +/- 1.0 at 12 weeks after treatment, P<0.05). In addition, the percentage of fecal water content in untreated rats was significantly lower than in ARI-treated rats (58.0 +/- 2.0 vs. 67.6 +/- 0.8% at 8 weeks, 56.9 +/- 2.1 vs. 63.4 +/- 1.4 at 12 weeks, P<0.05). From STZ injection to 8 weeks, the serum levels of acetaminophen in the diabetic rats were significantly lower than in controls, indicating delayed gastric emptying. At 12 weeks in the diabetic rats treated with ARI, the serum levels of acetaminophen were significantly higher than in the untreated diabetic rats (6.6 +/- 0.4 vs. 3.5 +/- 0.5 microg/ml, P<0.05). ARI-treatment ameliorated delayed gastric emptying without improving glycemic control. These findings show that ARI partially prevented progression of impaired gastric emptying, ion transport, and water transport, and suggest that epalrestat might be useful in the treatment of diabetic gastroenteropathy.

Acetaminophen↗

PubMed2003

Use of adult marrow mesenchymal stem cells for regeneration of cardiomyocytes.

Bone marrow cells have been suggested to have multilineage plasticity including formation of cardiac tissue. We have established a cardiomyogenic (CMG) cell line from mouse bone marrow stromal cells that can be induced to differentiate into cardiomyocytes in vitro by 5-azacytidine treatment. A number of lines of evidence confirm the cardiomyocyte characteristics of CMG cells.

Action Potentials↗

PubMed2003

Simultaneous genotyping of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 by single-strand conformation polymorphism analysis.

Alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3) have important roles in the elimination of ingested ethanol. These enzymes have polymorphisms resulting from single-point mutations that cause kinetic differences in their respective enzyme activities. Simultaneous observation of these enzymes would be useful in investigating the association between these enzyme polymorphisms and alcohol-related problems. In this study amplified genomic DNA was amplified from nail clippings with two sets of primers for ADH2 and ALDH2 genes, respectively, in a micro test tube and the accuracy of the amplification was verified by direct sequencing. The PCR products were separated into four distinct bands by single-strand conformation polymorphism analysis. This genotyping method is fast, accurate. reliable and inexpensive, and requires the same amount of template DNA as non-simultaneous methods. In other words, the required amount of template DNA for this method is only half that required for the separate genotyping of ADH2 and ALDH2.

Alcohol Dehydrogenase↗

PubMed2003

Inhibition of hepatitis C virus serine protease in living cells by RNA aptamers detected using fluorescent protein substrates.

Hepatitis C virus is one of the causative agents of non-A non-B hepatitis. Since one of viral proteins, NS3, has serine protease activity indispensable for virus maturation. NS3 serine protease is considered to be a suitable target for anti-HCV reagents. We report an assay of HCV NS3 protease in living cells. We designed peptide substrates bearing one of the sequences of HCV NS3 protease cleavage sites sandwiched with fluorescent proteins CFP and YFP. Substrates were expressed and cleaved efficiently in HeLa cells by cotransfection with HCV NS3 protease. The relationship between the progress of cleavage reaction and the change in fluorescence of the substrate emitted from living cells was confirmed. As a group of candidates for inhibitor of HCV NS3 protease, we chose RNA aptamers, nucleic acid ligands selected from a completely random RNA pool by in vitro selection. We found that 3 classes of aptamers, G9-I, II and III, bound NS3 protease specifically and inhibited cleavage in vitro. We studied the effect of RNA aptamers introduced into HeLa cells. The addition of G9-II RNA in the medium at a concentration of 2.5 micro g/ml reduced cleavage by one-third that of control.

Blotting, Western↗

PubMed2003

Strong polarization toward Th1 immune response in ANCA-associated glomerulonephritis.

AIM: Human immune response can be classified into 2 different subsets of T helper cells (Th1 and Th2) based on the pattern of cytokine production. In modern immunology, Th1/Th2 paradigm helps to explain the different inflammatory effector pathways and outcomes in human diseases. The present study was designed to determine the type of immunological response that influences anti-neutrophil cytoplasmic antibody-(ANCA) associated glomerulonephritis (GN) using cytokine analysis of peripheral T cells and diseased kidney tissues. PATIENTS AND METHODS: We analyzed peripheral blood Th1/Th2 ratio in 91 patients with primary GN, including 10 cases of ANCA-associated GN. Tissues were immunostained with markers of T cells and macrophages and osteopontin (OPN). Intrarenal expression of IFN-gamma and IL-4 mRNAs was evaluated by reverse transcriptase (RT)-PCR. RESULTS: Peripheral Th1/Th2 ratio was significantly higher in ANCA-associated GN (19.4 +/- 9.4, mean +/- SD, n = 10), than those in healthy controls (7.6 +/- 4.1, n = 27), IgA nephropathy (9.6 +/- 5.6, n = 45), membranous nephropathy (7.1 +/- 4.4, n = 13), minimal-change nephrotic syndrome (8.2 +/- 4.5, n = 13) and focal segmental glomerulosclerosis (8.3 +/- 3.9, n = 10) (p < 0.01, each). In 7 of 10 cases of ANCA-associated GN, Th1/Th2 ratio decreased significantly after treatment with corticosteroid from 21.0 +/- 12.0 to 9.0 +/- 6.6 (p < 0.05). Immunohistochemical staining showed numerous infiltrating T cells, macrophages and OPN-positive cells in both glomerular tuft and cellular crescent; OPN-positive cell distribution was similar to that of macrophages. Intrarenal expression of IFN-gamma mRNA was strongly enhanced whereas a weak expression of IL-4 mRNA was observed especially in advanced cases showing tubulointerstitial injury. CONCLUSION: Both peripheral and renal immune responses are strongly polarized toward Th1 type immune response in ANCA-associated GN. Peripheral Th1/Th2 ratio may reflect the immune responses in renal injury of ANCA-associated GN.

Adult↗

PubMed2002

Effects of N-methyl-N'-nitro-N-nitrosoguanidine on the human colorectal polyps consecutively maintained in SCID mice.

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatments for a long period induced morphological and molecular alterations in the benign human colorectal polyps which were maintained in the severe combined immunodeficient C.B17/N-scid/scid mice. Thirty four xenografts of colorectal polyps from five solitary polyp and three familial polyposis patients were examined for K-ras and p53 mutations. Six K-ras mutations were induced in 16 grafts treated with MNNG more than five times, while no K-ras mutations were detected in 14 untreated grafts (P<0.05). Additional and new K-ras mutations were also induced in two polyps in which K-ras mutation had pre-existed. p53 mutations were not observed in both MNNG-treated and untreated groups. The mutations in K-ras gene were induced at codon 12 (GGT-->GAT) except one at codon 13 (GGC-->GGT). The results indicate that K-ras mutation plays an important role in human colorectal carcinogenesis as is the case in experimental animals.

Animals↗

PubMed2002

Hydrogen peroxide induces apoptosis of osteocytes: involvement of calcium ion and caspase activity.

We hypothesized that reactive oxygen species play an important role in avascular/ischemic osteonecrosis. When isolated chick osteocytes were cultured with hydrogen peroxide, annexin V binding, which is the earliest marker of apoptosis, increased in a dose-dependent fashion. Hydrogen peroxide also induced the activation of caspase-3 and increase in cytosolic Ca2+. Treatment with BAPTA/AM (cheletor of cytosolic Ca2+) and Ac-DEVD-cho (caspase inhibitor) attenuated hydrogen peroxide-induced apoptosis. These data demonstrated the signal transduction pathways that participate in this hydrogen peroxide-induced cell damage.

Animals↗

PubMed2002

Possible mechanisms of panic attack and schizophrenia via APUD system.

Psilocybin poisoning produces biphasic reactions composed of a schizophrenic phase and a panic attack-like phase. There is a time lag of several hours between phases, which may be considered an accumulation time in certain sites between the gut and the brain. So far as 5-hydroxytryptamine (5-HT) congeners are concerned, no sites are to be found except the amine precursor uptake and decarboxylation (APUD) system. It is postulated that argyrophil cells (AC) in the foregut, neuroepithelial bodies (NEB) in the lung, and raphe nuclei (RN) in the brainstem axis are relevant to mental disorders. Schizophrenia might be due to the massive destruction of APUD cells, and the paroxysmal release of 5-HT with peptides and panneuroendocrine markers from NEB might be the cause of panic attack.

APUD Cells↗

PubMed2002

Effects of propofol on lactate accumulation and oedema formation in focal cerebral ischaemia in hyperglycaemic rats.

BACKGROUND: In cerebral ischaemia, hyperglycaemia brings about severe lactate accumulation and neuronal damage when compared with normoglycaemia. Propofol has been known to suppress glucose metabolism in the brain and possess neuroprotective properties in cerebral ischaemia. Therefore, in this study we examined if propofol could attenuate lactate accumulation and neuronal damage in cerebral ischaemia under hyperglycaemic conditions. METHODS: Ten male wistar rats were divided into two experimental groups: low-dose (approximately 12 mg kg(-1) h(-1)) and high-dose (approximately 60 mg kg(-1) h(-1)) propofol groups (n=5 for each). Following injection of 2 g kg(-1) glucose intraperitoneally, the middle cerebral artery was occluded for 1 h, and then reperfused for the following 2 h. Lactate accumulation and oedema formation were estimated consecutively using nuclear magnetic resonance (NMR) techniques. RESULTS: Lactate accumulation and oedema formation increased continuously during ischaemia and reperfusion in the low-dose propofol group, which was attenuated in the high-dose propofol group. Lactate/NAA (N-acetylaspartate) ratio (as an index of lactate accumulation) 60 and 120 min after reperfusion were 2.67 and 3.26 in low-dose group and 0.30 and 0.10 in high-dose group. For NMR images the number of pixels with a low average diffusion coefficient (an index of the oedema formation), 60 and 120 min after reperfusion were 250.0 and 317.8 in low-dose group, and 16.0 and 12.4 in high-dose group. CONCLUSION: High-dose propofol attenuated lactate accumulation and oedema formation in cerebral ischaemia in hyperglycaemic rats.

Anesthetics, Intravenous↗

PubMed2002

Effects of xenon on acetylcholine release in the rat cerebral cortex in vivo.

BACKGROUND: We have reported previously the effects of several anaesthetics on cholinergic activity in the central nervous system (CNS). In this study, we report the effects of xenon on cholinergic cell activity. METHODS: Using in vivo brain microdialysis, we measured acetylcholine (ACh) release in the rat cerebral cortex in vivo during xenon anaesthesia. RESULTS: Xenon induced an initial increase in ACh release, followed by a gradual decrease. The level of Ach release at 40 min of xenon administration was significantly higher than the control. CONCLUSIONS: Xenon activates CNS cholinergic cell activity followed by development of acute tolerance.

Acetylcholine↗

PubMed2002

Correlation between cathepsin D expression and p53 protein nuclear accumulation in oesophageal squamous cell carcinoma.

AIM: The lysosomal protease cathepsin D has been reported to be associated with tumour progression in malignant tumours. Expression of the gene encoding cathepsin D is known to be stimulated by oestrogen in mammary cancer cells. Recent experiments revealed that a p53 DNA binding site is located in the promoter region of the cathepsin D gene. This fact indicates that cathepsin D expression may correlate with p53 protein expression. The purpose of this study is to evaluate the expression patterns of the cathepsin D and p53 proteins in oesophageal squamous cell carcinoma (SCC). METHODS: In 154 patients with oesophageal SCC, expression of the cathepsin D and p53 proteins was measured in tumours by means of immunohistochemistry using monoclonal antibodies against cathepsin D (clone, 1C11) and p53 (clone, BP53-12). RESULTS: Cathepsin D was detected in tumour cells, although it was not found in normal oesophageal epithelium adjacent to carcinoma. High cathepsin D expression (positive tumour cells > 10%) was detected in 76 of 154 cases (49%) and high p53 nuclear expression (positive tumour cells > 50%) was detected in 70 cases (46%). High cathepsin D expression was significantly associated with invasive tumour growth (p = 0.002), poor prognosis (p = 0.049), and nuclear accumulation of p53 protein (p = 0.001). Overexpression of both p53 and cathepsin D was seen in 45 of the 154 cases (29.2%). In addition, there was a positive correlation between the cathepsin D index (percentage of cathepsin D positive tumour cells) and Ki-67 labelling index (percentage of Ki-67 positive tumour cells) in 154 oesophageal SCCs (rho = 0.257; p = 0.009). However, in multivariate survival analysis, cathepsin D expression by the tumours was not an independent prognostic factor in patients with oesophageal SCC (p = 0.236). CONCLUSIONS: The expression of cathepsin D by cancer cells may play an important role in the invasive growth of oesophageal SCC. Overexpression of both p53 and cathepsin D was seen frequently in tumours; p53 gene abnormalities may correlate with cathepsin D overexpression in oesophageal SCC.

Aged↗

PubMed2002

Superimposition of post-streptococcal acute glomerulonephritis on the course of IgA nephropathy: predominance of Th1 type immune response.

A 23-year-old man was admitted with macrohematuria and systemic edema appearing after an acute upper respiratory tract infection. He had been diagnosed 6 years earlier with IgA nephropathy (IgA-N). On admission, hypertension, nephrotic syndrome and hypocomplementemia were evident together with a high titer of anti-streptokinase (ASK). Renal biopsy showed severe glomerular mesangial proliferation, segmental endocapillary proliferation and crescent formation. Immunofluorescence microscopy (IF) showed strong deposition of C3 and reduced deposition of IgA. Electron microscopy showed a so-called "hump" on the epithelial side of the glomerular basement membrane. These features were consistent with post-streptococcal acute glomerulonephritis (PSAGN) superimposed on IgA-N. Following 2 weeks of observation, blood pressure, C3 level and ASK titer returned to normal ranges, although nephrotic syndrome was still evident, which necessitated oral prednisolone (30 mg/day) therapy. Another biopsy taken 2 months later demonstrated regression of endocapillary proliferation and IF showed decreased deposition of C3. Immunohistochemical staining of the specimen taken on admission revealed the presence of numerous T cells and macrophages in the interstitium. Macrophages were also seen in the glomerular tuft. Many interstitial infiltrating cells were positive for interferon-gamma, but their number diminished after treatment. Our findings suggest that PSAGN complicating pre-existing IgA-N activates cellular immunity and augments renal tissue injury.

Adult↗

PubMed2002

Diffuse proliferative glomerulonephritis after bone marrow transplantation.

A 15-year-old boy developed nephrotic syndrome and acute renal failure 4 years after allogenic bone marrow transplantation (BMT) for lymphoid crisis of chronic myelocytic leukemia. On admission, he presented with clinical features of chronic GVHD including transient exacerbation of cholestatic liver injury. Renal biopsy showed diffuse proliferative glomerulonephritis with cellular crescents. The patient was treated with methylprednisolone pulse therapy (1 g/day, for 3 days) followed by oral prednisolone. Renal function gradually improved but nephrotic state was persistent. A second renal biopsy showed improvement of acute tubular necrosis and endocapillary proliferation and transformation of crescents into a fibrous form. After tapering of oral prednisolone, cyclophosphamide was started, which resulted in a gradual improvement of proteinuria. Several cases of nephrotic syndrome occurring after BMT have already been reported, but most cases had membranous nephropathy. In our case, renal biopsy revealed diffuse proliferative glomerulonephritis with findings of active cellular immunity, and aggressive treatment resulted in attenuation of these findings. Moreover, chronic GVHD-related liver injury was noted at the time of this episode. Our findings suggest that chronic GVHD may be complicated with diffuse proliferative glomerulonephritis through unknown cellular immune mechanism.

Adolescent↗

PubMed2001

Immunological characterization of factor VIII autoantibodies in patients with acquired hemophilia A in the presence or absence of underlying disease.

The development of a factor VIII autoantibody results in a severe hemorrhagic diathesis known as acquired hemophilia A. Underlying pathologies, such as autoimmune disease or chronic inflammatory disease, are observed in about half of the patients. We have investigated a total of 16 cases with acquired hemophilia A and divided the patients into two groups according to the presence or absence of other clinical conditions. Group A comprised nine cases with no detectable associated pathology. Group B consisted of seven cases with other clinical diagnoses. Significant levels of factor VIII activity (FVIII:C) and factor VIII antigen (FVIII:Ag) were detected in Group A and the pattern of FVIII:C inactivation was characteristic of Type 2 inhibitors. In contrast, no FVIII:C was detected in Group B and, in five of seven cases, the inhibitory pattern was Type 1. IgG(4) antibody subclass specificity was dominant in both groups. IgG1 antibody reactivity was higher in Group B than in Group A. Our results suggested a close relationship between the presence of underlying disease and immunological and coagulation characteristics in acquired hemophilia A.

Adult↗