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Biomedical subjects

K Fukuda

Publications and source records attributed to K Fukuda.

At least 73 records · Page 4Linked to original sources

Predominance of Th1 immune response in diffuse proliferative lupus nephritis.

OBJECTIVE: Lupus nephritis, which shows various histologic patterns, is a serious complication of systemic lupus erythematosus (SLE). We previously demonstrated the importance of Thl cell-mediated immune response in patients with diffuse proliferative lupus nephritis (DPLN). The aim of this study was to examine the relationship between the peripheral blood Th1/Th2 balance and the intrarenal immune response. METHODS: The Th1:Th2 ratio in peripheral blood was measured by intracellular staining for cytokines with flow cytometry. Immunohistochemical analysis of renal biopsy specimens was performed to clarify the characterization of local infiltrating cells in 3 groups of subjects: SLE patients with World Health Organization (WHO) class IV nephritis (DPLN) (group I; n = 13), SLE patients with WHO class V nephritis (group II; n = 9), and patients with minor glomerular lesions (group III; n = 7). In addition, the histologic activity index and chronicity index were evaluated and correlated with the Th1:Th2 ratio. RESULTS: Immunohistochemical studies showed higher numbers of CD68+ macrophages, CD3 + T cells, and interferon-gamma-positive cells in group I than in groups II or III. Renal tissues from patients in group I also showed up-regulation of expression of osteopontin and CD40, with a small number of infiltrating T cells expressing interleukin-4. Overall, the Thl:Th2 ratio in group I patients (SLE with DPLN) was high and correlated significantly with the histologic activity index, but not with the chronicity index. CONCLUSION: We have identified a predominance of Thl-type response in both peripheral and renal tissues of patients with DPLN, suggesting that the peripheral blood Thl:Th2 ratio directly reflects the local histopathologic findings. In patients with lupus nephritis, the peripheral blood Th1:Th2 ratio could be useful as a parameter that reflects the renal histologic activity or the strength of the local Thl response.

Adult↗

Micro-lymph node metastasis and its correlation with cathepsin D expression in early gastric cancer.

BACKGROUND AND OBJECTIVES: Limited operations for early gastric cancer (EGC) have been recommended based on data from lymph node (LN) metastasis detected by hematoxylin and eosin (HE) staining. Recently, the clinical importance of micro-LN metastasis has been reported. In this study, the indication of limited operations for EGC was re-evaluated based on the data from micro-LN metastasis detected by cytokeratin (CK) immunostaining. Also, the correlation between micro-LN metastasis and lysosomal acidic protease cathepsin D (CD) expression in primary tumors was evaluated. METHODS: A total of 5,949 LNs from 160 patients with EGC were stained by anti-CK monoclonal antibody (CAM 5.2). Also, the 160 primary EGCs were stained by CD. RESULTS: The incidence of LN metastasis increased from 7.5% (12/160) by HE-staining to 27.5% (44 of 160) by CK immunostaining. The incidence of micro-LN metastasis increased according to the depth of tumor invasion (mucosal cancer: 19% and submucosal cancer: 36.8%) and the size of tumors (< or = 1.0 cm: 5.9%, 1.1-2.0 cm: 25.6%, and > 2.1 cm: 31.7%). The CK-staining patterns were classified into the three subgroups (CK-negative, n = 116; single cell type, n = 27; and clustered type, n = 17). The occurrence of cancer recurrence was significantly higher in clustered type (17.6%) than in single cell type (3.7%) and in CK-negative (0%, P < 0.0001). The mean percentage of CD-positive cancer cells of primary tumors in clustered type (17.2%) was significantly higher than in single cell type (12.3%) and in CK-negative (7.5%, P = 0.0036). CONCLUSIONS: The acidic protease CD may play an important role of cancer metastasis in EGC. The limited operation without lymphadenectomy should be indicated for EGC with CD-negative.

Cathepsin D↗

The effect of nulliparity on survival in endometrial cancer at different ages.

OBJECTIVE: Nulliparity is a major independent risk factor for endometrial cancer in Japan. We examined the effect of nulliparity on survival in endometrial cancer at different ages. METHODS: A retrospective study of 328 Japanese women with endometrial cancer was performed. The subjects were divided into two groups: a younger age group (women < 50 years) and an older age group (women >/= 50 years). Parity was analyzed for its influence on survival. RESULTS: No effect of nulliparity was observed on survival in the younger group. In the older women, nulliparity did not affect survival in 189 subjects with surgical stage I and II tumors (P < 0.27). In contrast, the cumulative 10-year survival rates associated with nulliparity, a parity of 1 or 2, and a parity of 3 or more were 7.7, 48.0, and 56.2% in 54 subjects with surgical stage III and IV tumors, respectively (P < 0.03). In these 54 subjects, the cumulative 10-year survival rates associated with < 6-month and > 7-month delays in diagnosis were 57.1 and 16.6%, respectively (P < 0.02). The prognostic impact of parity disappeared after adjustment for delay in diagnosis. Multivariate analysis including histopathological variables, parity, and delay in diagnosis showed no independent prognostic variable in the older subjects with surgical stage III and IV tumors. CONCLUSIONS: The negative effect of nulliparity on survival was observed in the older subjects with advanced-surgical-stage tumors. Delay in diagnosis contributed to the prognostic impact of nulliparity.

Adenocarcinoma, Clear Cell↗

Accessory spleen in the pelvis diagnosed by Tc-99m phytate scintigraphy.

We report a 58-year-old woman with an accessory spleen in the left side of the pelvis. She visited our outpatient clinic complaining of lower abdominal discomfort. Abdominal ultrasonography revealed a tumor 4 cm in diameter in the left side of the pelvis. Color Doppler ultrasonography demonstrated plentiful pulsating blood flow. Magnetic resonance angiography revealed that the blood supply for the tumor was from a branch of the splenic artery. Scintigraphy with Tc-99m phytate revealed accumulation of radioactivity concordant with a mass in the left side of the pelvis, and the spleen was normally visualized. These findings suggested that this tumor was an accessory spleen, and the patient underwent no further invasive procedures.

Female↗

Hydrogen peroxide induces apoptosis of chondrocytes; involvement of calcium ion and extracellular signal-regulated protein kinase.

OBJECTIVE: Recent observations demonstrated that reactive oxygen species facilitate cartilage degradation. We demonstrated that hydrogen peroxide (H2O2) caused inhibition of proteoglycan synthesis, induction of apoptosis and stimulation of extracellular signal-regulated protein kinase (ERK) of the chondrocytes (Inflamm Res 48: 399-403, 1999). To determine whether activation of ERK is involved in the induction of chondrocyte apoptosis, we examined the signal transduction pathways in this hydrogen peroxide induced apoptosis. DESIGN: Bovine articular chondrocytes were cultured. To determine the induction of apoptosis, Annexin V staining and terminal deoxynucleotidyl transferase were used. The activity of caspase-3 was measured using an apopain assay kit. Intracellular Ca2+ imaging was observed after fura2-AM loading. RESULTS: Hydrogen peroxide enhanced annexin V positive apoptotic cells and caspase-3 activity, which is an executor of apoptosis. Hydrogen peroxide also enhanced intracellular Ca2+ and preincubation with the intracellular Ca2+ chelator protected chondrocytes against hydrogen peroxide-induced cell apoptosis, indicating that an increase in the cytosolic Ca2+ plays a decisive role in this action. When ERK activity was blocked with geldanamycin and PD098059, increased apoptosis was evident. CONCLUSION: Hydrogen peroxide induces chondrocyte apoptosis via Ca2+ signaling, and ERK is involved in these signal transduction pathways.

Animals↗

Lower limb amputation for diabetic foot.

We amputated 35 limbs of 27 patients with diabetic foot from March 1988 to March 1998. The mean age of the patients at the time of operation was 67 years, and the mean follow-up period was 27 months. Thirteen patients died in the period from 1 day to 39 months after the operation. All patients suffering from diabetic foot were referred to our department for surgical procedures after failure of conservative treatment conducted elsewhere. Their feet were classified into grade 2-3 in 18 limbs, grade 4-5 in 11 limbs, and gangrene of the lower leg and entire foot in 2 limbs, as classified by the Wagner system. Two patients had cellulitis of the foot and two other limbs had infectious gonarthritis. All patients had type 2 diabetes with poor blood sugar control, and 90% were treated by insulin. All patients suffered from diabetic neuropathy. Half of the patients were put on hemodialysis because of diabetic nephropathy. More than 60% of the patients suffered from arteriosclerosis obliterans. The amputation level of the limb was determined by skin thermography, but the patient's will was critical. The initial amputation levels were: débridement and synovectomy in 4 limbs, toe and digital ray in 15 limbs, transmetatarsal in 3 limbs, transtibial in 9 limbs, transfemoral amputations in 4 limbs. Upper level reamputation was conducted on 15 limbs. Logistic regression analysis revealed that lower temperature of the amputation site, being female, and being elderly were significant risk factors in reamputation. Skin thermography was one of the effective determinants of amputation level, in order to avoid reamputation.

Aged↗

Pancreatitis induced by valproic acid: report of a case.

A 22-year-old woman with intellectual impairment, who had been taking valproic acid continuously for 19 years since being diagnosed with epiloia at the age of 3 years, presented to our hospital following the sudden development of epigastric pain. An abdominal computed tomography scan revealed acute exacerbation of chronic pancreatitis. Conservative treatment was initiated, despite which the pancreatitis became exacerbated, necessitating resection of the pancreatic head and duodenum. Histological examination of the resected specimens revealed a large number of pancreatic calculi in the main pancreatic duct, suggesting chronic pancreatitis with fibrosis at the periphery. The incidence of pancreatitis developing in association with valproic acid is unclear; however, only 40 such cases have been reported in the English literature. Most of the patients previously described presented with acute pancreatitis in the initial stage. However, the clinical course of our patient, with acute exacerbation following a relatively chronic course, was different from those previously described, suggesting the presence of chronic pancreatitis related to valproic acid.

Adult↗

Cyst fluid levels of carcinoembryonic antigen, carbohydrate antigen 19-9, squamous cell carcinoma antigen, and amylase in thyroglossal duct and branchial cleft cysts.

Cyst fluid was aspirated from five thyroglossal duct cysts (TDCs) and four branchial cleft cysts (BCCs). The cyst fluid levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, squamous cell carcinoma antigen (SCC), and amylase were measured and compared between the two types of cyst. The enzyme immunoassay technique was used for CEA and CA19-9, while SCC and amylase levels were measured by the immunoradiometric assay and nitrophenol method, respectively. Immunostaining for CEA, CA19-9, and amylase was also performed. The serum levels of these markers in both groups of patients were within the normal ranges. In contrast, their cyst fluid levels were extremely high. There was no significant difference in the cyst fluid levels of CEA and SCC between the two types of cyst; however, the cyst fluid from the TDCs showed significantly higher levels of CA19-9 and significantly lower levels of amylase compared with that from the BCCs. Immunostaining revealed expression of CA 19-9 in nearly half the columnar epithelial cells in the TDCs, but not in the squamous epithelial cells in the BCCs. CEA and amylase were not found in the epithelial cells of either type of cyst. These findings seem to reflect the difference in etiology between TDCs and BCCs.

Adult↗

Primary subclavian venous thrombosis which developed after sleeping with the arm in an outstretched position: report of a case.

Primary subclavian venous thrombosis is more rare than secondary thrombosis. This type of thrombosis is called "effort thrombosis" or Paget-Schroetter syndrome, and develops after a strenuous effort of the superior limb. A day after a 55-year-old man got drunk and slept in the left lateral position in combination with an abducted and elevated position of the left superior limb, he became aware of swelling and an oppressive feeling in his left superior limb and was admitted 9 days later. Thrombus of the left axillary-subclavian vein was confirmed by venography, and thrombolytic therapy with urokinase was performed immediately. The left arm symptoms improved for the most part. Venography after the therapy revealed thrombolysis at the site of the axillary vein, while the subclavian vein enhanced the collateral vessel pathway. The patient was discharged on the seventh hospital day, and anticoagulant therapy with oral warfarin sodium has since been continued. This is considered to be a rare case of subclavian venous thrombosis caused by sleeping in an abnormal position with the arm outstretched.

Alcoholic Intoxication↗

Combined resection of invaded organs in patients with T4 gastric carcinoma.

BACKGROUND: To understand the efficacy of gastrectomy combined with the resection of other organs and to refine the indications for this type of surgery, the records of 156 patients with carcinoma of the stomach directly invading adjacent organs or structures (T4 gastric carcinoma) were analyzed retrospectively. METHODS: The patients were divided into three groups, as follows: in group A, curative resection was performed by the combined resection of invaded organs or structures; in group B, although combined resection was performed, curative resection could not be performed because of the extent of lymph node metastasis, liver metastasis, and/or peritoneal metastasis; in group C, combined resection was not performed. RESULTS: In patients with peritoneal or liver metastasis, there was no significant difference in prognosis among the three groups. In patients without peritoneal and liver metastasis, the prognosis of group A was significantly better than that of group B or group C, irrespective of the extent of lymph node metastasis or the number of invaded organs. In these group A patients, the 5-year survival rates of those with localized tumors and no lymph node metastasis, those with localized tumors and lymph node metastasis, those with infiltrating tumors and no lymph node metastasis, and those with infiltrating tumors and lymph node metastasis were 100%, 56.2%, 57.1%, and 13.6%, respectively. CONCLUSIONS: Combined resection of involved organs should be carried out with curative intent in patients with localized gastric cancer or infiltrating gastric cancer without lymph node metastasis.

Adenocarcinoma↗

Eye blinks: new indices for the detection of deception.

Eyeblink variables were investigated while subjects performed a guilty knowledge test (Experiment 1) and a dual modality attention task (Experiment 2). In both experiments, the temporal distribution of blinks was analyzed using an automatic video based blink analysis system [Matsuo and Fukuda, Jpn. J. Physiol. Psychol. Psychophysiol., 14 (1996), 17]. In experiment 1, the blink rate pattern discriminated between relevant and irrelevant stimuli. In experiment 2, the blink rate peak after the auditory stimulus disappeared during visually attended tasks whereas the blink rate peak after the visual stimulus was significant during auditory attended tasks. It was suggested that eye blinks could be related to the selective attention and that eye blinks could provide an additional index for the detection of deception.

Acoustic Stimulation↗

PC reporting system for radiologists: practical use under PACS environment.

To evaluate the practical usefulness of several types of the reporting system especially for radiologists, we have developed and employed several reporting systems. We categorized those reporting systems as follows (1) stand alone PC reporting system; (2) linked reporting system with PACS environment; (3) integrated three-dimensional (3D) imaging workstation (WS) with the intranet. We have evaluated the advantages and disadvantages of those three systems, and compared between the reporting system without PACS and network reporting system with PACS. Using linked reporting system with PACS, radiologists could easily reference both previous reports and archived diagnostic images, and also make their teaching files quickly. In conclusion, the reporting system under PACS environment is found to be practical and helpful for Japanese radiologists.

Humans↗

Increased von Willebrand factor in the endocardium as a local predisposing factor for thrombogenesis in overloaded human atrial appendage.

OBJECTIVES: We investigated immunoreactive von Willebrand factor (vWF), a platelet adhesion molecule, in the endocardial endothelium and its relationship to thrombogenesis in the human atrial appendage. BACKGROUND: Intra-atrial thrombogenesis is generally thought to be induced by blood stasis in the atrial appendage involved with atrial fibrillation (AF). Little attention has been paid to alterations of the endocardial endothelium on which the thrombus develops. METHODS: Atrial appendage tissue was obtained at heart surgery or at autopsy from AF and non-AF cardiac patients and from noncardiac patients. Immunohistochemistry for endothelial cell markers including vWF, CD31, CD34 and endothelial nitric oxide synthase (eNOS) and platelet glycoprotein Ib/IX or IIb/IIIa was performed and semiquantitatively graded. RESULTS: In contrast to the apparent immunostaining for CD31, CD34 and eNOS, only focal or little immunoreactive vWF was seen in the endocardium of noncardiac patients. Immunoreactive vWF in the endocardial endothelium was increased in most cardiac patients, particularly in the left, but not in the right, atrial appendage of patients with mitral valvular disease, irrespective of whether AF was present. Platelet adhesion/thrombus formation in the endocardium was found in limited sites in which the overlying endothelium was deficient in eNOS and CD34. When warfarin-treated cases were excluded, there was a significant correlation between the immunohistochemical grade for vWF and the degree of platelet adhesion/thrombus formation in the endocardium. CONCLUSIONS: Immunoreactive vWF in the endocardial endothelium was increased in overloaded human atrial appendage, which may be a local predisposing factor for intraatrial thrombogenesis.

Adult↗

Cyclic tensile stretch inhibition of nitric oxide release from osteoblast-like cells is both G protein and actin-dependent.

Recent reports indicate the alteration of nitric oxide (NO) synthesis with mechanical stress loaded on the osteoblast and NO is considered to have a significant role in mechanotransduction. We found the involvement of guanine-nucleotide-binding regulatory proteins (G proteins), especially Gi, in stress-inhibited NO release of osteoblast-like cells (JOR:17;593-597, 1999). To determine further the mechanism involved in this process, we measured c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activity under cyclic tensile stretch loaded on osteoblast-like cells. Cyclic stretch significantly enhanced JNK/SAPK activity and pertussis toxin clearly reversed stress-enhanced JNK/SAPK activity. Cytochalasin D, actin microfilament disrupting reagent, also abolished the stress activation of JNK/SAPK. We propose a model for signaling events induced by cyclic tensile stretch, namely a transmembrane mechanosensor which couples Gi-protein, actin cytoskeleton and finally activates JNK/SAPK activity of osteoblasts.

Actins↗

Ultrasound virtual endoscopic imaging.

Volume data acquisition, three dimensional (3D) imaging, and multiplanar reformatting have become widely used for computed tomography (CT) and magnetic resonance imaging (MRI). As an extension of this technology, virtual endoscopic visualization of hollow organs has become a reality that is now finding its way into clinical CT practice. The same methods of computer processing as are used for CT and MRI can be applied to an ultrasound (US) volume image data set with the same potential output; namely, 3D, multiplanar, and virtual endoscopic images. The use of this image processing technology for US applications has lagged behind the CT and MRI applications, but considerable progress in applying these methods to US has occurred in recent years. As a result, US virtual endoscopic imaging now can be performed on a clinical basis by using standard US instruments and commercially available computer software. The use of newer US imaging methods, such as tissue harmonic and power Doppler imaging, has enhanced the potential for US virtual endoscopy. This article reviews the technology of US virtual endoscopy. In addition, our preliminary experience of using this method for abdominal and vascular diagnosis is described. Finally, we speculate on technical improvements and potential applications that are likely in the future.

Acoustics↗

Interleukin-4 reversed the Interleukin-1-inhibited proteoglycan synthesis through the inhibition of NO release: a possible involvement of intracellular calcium ion.

Interleukin-1 (IL-1) causes cartilage degradation through nitric oxide (NO) synthesis. Although Interleukin-4 (IL-4) antagonizes the IL-1-mediated cartilage degradation, the precise mechanisms are not clear. We examined the effect of IL-4 on NO synthesis in parallel with intracellular Ca levels ([Ca(2+)]i) and proteoglycan (PG) synthesis. IL-4-inhibited IL-1-enhanced NO release in a dose-dependent manner. IL-1-enhanced [Ca(2+)]i in the chondrocytes, and IL-4 attenuated this increase. IL-4 reversed IL-1-inhibited PG synthesis. Accordingly, IL-4 reversed the IL-1-inhibited PG synthesis through the inhibition of NO release. An increase in [Ca(2+)]i with IL-1 is possibly involved in this action.

Journal Article↗

Intraarterial low-dose cisplatin via an indwelling port and concurrent radiotherapy for invasive bladder cancer.

Thirteen patients with invasive bladder cancer who had residual tumor after transurethral resections, were treated with consecutive intraarterial (IA) cisplatin (15 mg/d; total, 150 mg) and concurrent radiation (1.8 Gy/d; total, 30.6 Gy). All patients received unilateral or bilateral placement of vascular access devices (VAD) to perform daily cisplatin infusion after alteration of intrapelvic blood flow by coil embolizations. Tumor response was evaluated by transurethral biopsy 2 weeks after treatment. Complete response, defined as no viable tumor cell in the biopsy specimen, was achieved in seven patients (54%). After a median follow-up of 30 months (range, 12-48 months), 10 patients (77%) were alive, five (38%) of whom had no recurrence. Two cancer-related deaths were observed. All complete response cases survived with a median follow-up of 35 months (range, 25-48 months). Cause-specific and disease-free survival rates at 4 years were 85% and 28%, respectively. The regimen was well-tolerated, with no dose-limiting toxic events. There were no VAD-related complications. Consecutive IA low-dose cisplatin and concurrent radiation may be an acceptable alternative treatment for patients with bladder cancer who are not suitable for systemic chemotherapy. The use of a VAD contributed to successful consecutive IA infusions.

Aged↗

A case of disseminated extrahepatic hepatocellular carcinoma after US-guided biopsy and percutaneous ethanol injection therapy.

A case of disseminated extrahepatic hepatocellular carcinoma (HCC) occurring after ultrasound (US)-guided biopsy and percutaneous ethanol injection therapy is presented. A 72-year-old man with hepatitis-C-virus-related cirrhosis underwent percutanous ethanol injection therapy (PEIT) two times with complete remission: the first for moderately-differentiated HCC in segment six (S6), and the second for well-differentiated HCC in another part of S6. Imaging studies including carbon dioxide (CO(2))-US angiography, incremental computed tomography, and dynamic magnet resonance imaging showed that both HCCs were hypovascular. Twenty-one months after the first PEIT and 7 months after the second, a 5.5x4.5 cm extrahepatic mass interfaced with S6 of the liver was detected by imaging studies. The patient underwent surgery for extrahepatic HCC. Grossly, the main tumor was 5.5x4.5 cm with capsule and septum; the disseminated tumors were detected on the surface of the liver, including the right diaphragm and the falx ligamentosa. Histologically, it was moderately- to poorly-differentiated HCC, which, although not attributed to direct track seeding, was suspected of being induced by the percutaneous US-guided biopsy procedure or by PEIT, irrespective of a hypovascular tumor. Further studies may provide insight into the risk factor engendered by these procedures.

Journal Article↗