Biomedical subjects

Hiroshi Furukawa

Publications and source records attributed to Hiroshi Furukawa.

At least 19 recordsLinked to original sources

PubMed2007

Prediction of metastases in melanoma patients with positive sentinel node: histological and molecular approach.

It is now established that sentinel node (SN) biopsy is a minimally-invasive procedure that accurately indicates the regional nodal status. In our institute, 14 consecutive patients had only one node micrometastases after elective lymph node dissection or positive SN for primary cutaneous melanoma. These 14 patients could be clearly divided into two groups: (i) patients who developed distant metastases or in-transit metastases (metastasized group); and (ii) and patients who remains free from metastases (non-metastasized group). The purpose of this study was to identify the histological and molecular factors that might predict the further dissemination beyond the SN. We assessed the maximum depth from the capsule to the deepest melanoma cells and the maximum diameter of melanoma nests in the lymph nodes as histological parameters and also evaluated the quantitative expression of tyrosinase mRNA as a molecular approach. The mean maximum depth and the maximum diameter were significantly smaller in the metastasized group than those in the non-metastasized group. Tyrosinase mRNA expression was strongly correlated with the histological tumor burden. Tyrosinase mRNA expression was higher in the former group than that in the latter group but there were no significant differences between them. Melanoma patients with small micrometastases (<0.5 mm deep, <1 mm in diameter) and a low level of tyrosinase mRNA had less chances for hematogenous metastases via lymph nodes.

Adult↗

PubMed2006

Influence of overweight on surgical complications for gastric cancer: results from a randomized control trial comparing D2 and extended para-aortic D3 lymphadenectomy (JCOG9501).

BACKGROUND: The impact of overweight on the outcome of gastrectomy with lymphadenectomy is controversial, and data from a well-controlled, randomized study are needed to identify a possible relationship. METHODS: We used data from 523 patients registered for a prospective randomized trial comparing D2 and extended para-aortic D3 lymphadenectomy to compare the effects of body mass index (BMI) and the extent of lymphadenectomy for the development of general or major surgical complications (anastomotic leakage, abdominal abscess, and pancreatic fistula). RESULTS: Seventy-seven patients were classified as overweight with BMI >or= 25, and 38 and 39 of these patients underwent a D2 or D3 lymphadenectomy, respectively. Among the 446 patients classified as nonoverweight with BMI < 25, 225 received D2 and 221 received D3 lymphadenectomy. Surgical complications, operation time, and blood loss were statistically significantly associated with BMI, and logistic regression analysis revealed that overweight directly affected the occurrence of surgical complications even after considering operation time and blood loss as intermediate factors instead of outcome variables. Among patients undergoing D2 lymphadenectomy, being overweight increased the risk for surgical complications and blood loss, whereas overweight was associated with only blood loss and operation time among patients receiving D3 lymphadenectomy. CONCLUSIONS: Overweight increased the risk of surgical complications in patients undergoing gastrectomy both directly and indirectly through operation time and blood loss. The impact of overweight on surgical complications was more evident in patients undergoing a D2 dissection.

Aged↗

PubMed2006

Spinal gene transfer using ultrasound and microbubbles.

Spinal gene therapy is a promising option for treating various spinal-related disorders. Several previous studies using viral vectors reported successful transfer of therapeutic genes into the spinal nerve system. However, because of the considerable immunogenicity related to the use of viruses, non-viral gene transfer still needs to be developed. One possible approach is the combined use of ultrasound and echo-contrast microbubbles. The present study shows that this method can be applied for targeted intrathecal gene delivery. We intrathecally injected a mixture of plasmid-DNA encoded with luciferase and commercially available albumin microbubbles by needle puncture at the lower lumbar intervertebral space in mice. Subsequent percutaneous ultrasonication on the lumbar vertebrae significantly enhanced the luciferase expression, analyzed by imaging luciferin bioluminescence, in the dorsal meningeal cells at the insonated region. No apparent neurological damages were induced by the present spinal interventions. In addition to the general benefits of the combined use of ultrasound and microbubbles, our approach can offer some advantages specific to spinal gene transfection including minimal invasiveness of simple percutaneous dural puncture, targetability due to the limited access of ultrasound waves through anatomical apertures of the vertebrae, and possible paracrine delivery of therapeutic molecules to the spinal nerve system.

Animals↗

PubMed2006

Phase II study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer.

AIM: To test protracted irinotecan infusion plus a low-dose cisplatin in this Phase II trial to decrease its toxicity. METHODS: The eligibility criteria were: (1) histologically proven measurable gastric cancer; (2) performance status of 0 or 1; (3) no prior chemotherapy or completion of prior therapy at least 4 wk before enrollment; (4) adequate function of major organs; (5) no other active malignancy; and (6) written informed consent. The regimen consisted of irinotecan (60 mg/m(2)) on d 1 and 15 by 24-h infusion and cisplatin (10 mg/m(2)) on d 1, 2, 3, 15, 16, and 17. Treatment was repeated every 4 wk. RESULTS: Thirty-one patients were registered between April 2000 and January 2001. The response rate for all 31 patients, 20 patients without prior chemotherapy, and 11 patients with prior chemotherapy was 52% (16/31), 60% (12/20), and 36% (4/11), respectively. The median survival time was 378 d. The median number of courses given to all patients was 2. Grade 4 neutropenia occurred in 11 (35%) patients, while grade 3 to 4 diarrhea or nausea occurred in 1 (3%) and 3 (10%) patients, respectively. Fatigue was minimal as grade 1 fatigue was found only in 3 (10%) patients. Other adverse events were mild and no treatment-related deaths occurred. CONCLUSION: This regimen showed a high level of activity and acceptable toxicity in patients with metastatic gastric cancer.

Adult↗

PubMed2006

Comparison of the effects of nicorandil versus verapamil on the incidence of slow flow/no reflow during rotational atherectomy.

In rotational atherectomy, the slow-flow/no-reflow phenomenon is a common complication, which usually results in myocardial injury. We prospectively randomized 111 patients with successful rotational atherectomy into a verapamil group (group V, n = 56) and a nicorandil group (group N, n = 55). We compared final burr size, total ablation time, maximum decrease in revolutions per minute, incidence of slow flow/no reflow, creatine kinase-MB increase, and cardiac troponin T increase between the 2 groups. Patient and procedural characteristics were not significantly different between groups. The incidence of no reflow/slow flow was significantly lower in group N than in group V (3.6% vs 17.9%, respectively, p <0.05). The incidence of a minor increase in cardiac markers was also significantly lower in group N than in group V (creatine kinase-MB 3.6% vs 16.1%, p <0.05; cardiac troponin T 5.5% vs 21.4%, p <0.05). In conclusion, our results showed that nicorandil decreases the incidence of slow flow/no reflow during rotational atherectomy.

Aged↗

PubMed2006

A non-major histocompatibility locus determines tissue specificity in the pathogenic process underlying synovial proliferation in a mouse arthropathy model.

BACKGROUND: The incidence and characteristics of spontaneous ankylosis in the ankle of specific F(1) mice descended from two Fas-deficient strains were reported. Here the coincidence of synovial proliferation and ankylosis in the descendent F(2) mice is reported. AIM: To clarify whether the two distinct manifestations are genetically different. METHODS: An arthropathic group of mice (MCF(2)) were bred by intercrossing MRL/Mp.Fas(lpr)-sap(-)/sap(-) and C3H/He.Fas(lpr) mice. All mice were killed by bleeding under anaesthesia when they were 6 months old. Pathological grades for synovial proliferation were determined by microscopical examination. To obtain a linkage locus, the whole genome of male MCF(2) mice was scanned by using 73 microsatellite markers. RESULTS: Synovial proliferation was equally observed in male and female MCF(2) mice. No correlation was observed between the grades of synovial proliferation and the ankylosis occurring in the MCF(2) mice. A suggestive susceptibility locus was shown in the middle of chromosome 11. This locus was an MRL allele with a recessive inheritance mode. CONCLUSION: The pathogenic mechanisms of synovial proliferation and ankylosis are genetically different. The present locus is overlapped with some loci associated with rheumatoid arthritis and with others associated with experimental arthritides.

Animals↗

PubMed2006

Melanoma of thumb: retrospective study for amputation levels, surgical margin and reconstruction.

For the treatment of melanoma of thumb, the evidence about amputation level (IP joint or MP joint) and cutaneous excision margin has not been fully presented. And reconstructions for lost thumbs need to be balanced against functional and aesthetic requirements of individual patients and overall prognosis. We report 15 patients, who underwent primary excision and reconstruction for thumb melanoma between 1986 and 2004 at Department of Plastic and Reconstructive Surgery, University of Hokkaido at Sapporo, Graduate School of Medicine. The patients were reviewed to evaluate the prognostic significance of variables including age and sex of the patient, tumour thickness, staging, level of amputation, and cutaneous excision margin. Our 15 cases were divided into two groups according to amputation level (MP or IP) and cutaneous excision margin (<40 mm or >or =40 mm) and prognosis was analysed statistically. The stage and thickness were identified as prognostic factors for disease-free survival; however, IP amputation and 10-30 mm margin did not compromise disease-free survival. Amputated thumb was reconstructed by pollicization, free toe to thumb transfer, reverse forearm flap, local flap, and skin graft. No major complication of reconstructed thumb occurred. Seven of eight cases of MP amputation were reconstructed by pollicization. On the other hand, five cases of IP amputation were reconstructed by volar skin flap in two cases, reverse forearm flap in two cases, and trimmed first toe transfer in one case. Although a small number of cases, our study is the first attempt focussing on melanoma of thumb, and evaluating amputation level and cutaneous margin separately. The reconstructive algorithm for the amputated thumb is proposed and has various tools including free toe to thumb transfer.

Adult↗

PubMed2006

Bilateral dermal thymus of neck in branchio-oculo-facial syndrome.

Dermal thymus in bilateral sides of neck is very rare, probably unique anomaly of branchio-oculo-facial syndrome (BOF). We report a case of BOF with cleft lip and non-healing erosions on bilateral sides of neck. The thymus of neck in our case showed unusual clinical course that appeared at 1 year and half of age after the repair of cleft lip deformity. The lesions of neck were completely excised, and the histopathologic examination for neck lesion confirmed ectopic dermal thymus. Ectopic thymus can be excised completely after careful evaluation of haematologic, immunologic status if normal thymic shadow cannot be identified on chest X-p.

Branchio-Oto-Renal Syndrome↗

PubMed2006

Epidermal-type fatty acid binding protein as a negative regulator of IL-12 production in dendritic cells.

Fatty acids and their metabolites have recently been shown to modulate various functions of dendritic cells (DCs) including their differentiation and cytokine production, although the mechanisms underlying their cellular functions are not fully understood. In view of our previous finding that epidermal-type fatty acid binding protein (E-FABP) was exclusively expressed in splenic DCs among FABP family, we examined the phenotype of E-FABP-null mutant mice in order to elucidate the functional significance of E-FABP expression in DCs. Although E-FABP-null mutant mice showed no apparent abnormalities in the population density and subset distribution of DCs as well as the microscopic morphology in the spleen, DCs isolated from E-FABP-null spleen showed enhanced production of IL-12p70, a key cytokine for innate immune responses, in response to appropriate stimuli as compared with wild-type. In real-time PCR, the expression level of IL-12p35 mRNA after LPS stimuli was much higher in mutant DCs when compared with wild-type, while no apparent change of IL-12p40 mRNA level was detected. Phosphorylated forms of p38 mitogen-activated protein kinase (p38MAPK) and IkappaB-alpha, molecules critical for IL-12 production, were detected at higher levels in E-FABP-null-mutant DCs after LPS stimuli when compared with wild-type counterparts. Collectively, it is suggested that E-FABP may be a novel negative regulator of IL-12 production in DCs, and this regulation may be exerted via its involvement in the p38MAPK-mediated transcription of IL-12p35.

Animals↗

PubMed2006

A signal adaptor SLAM-associated protein regulates spontaneous autoimmunity and Fas-dependent lymphoproliferation in MRL-Faslpr lupus mice.

Autoantibody production and lymphadenopathy are common features of systemic autoimmune disease. Targeted or spontaneous mutations in the mouse germline have generated many autoimmune models with these features. Importantly, the models have provided evidence for the gene function in prevention of autoimmunity, suggesting an indispensable role for the gene in normal immune response and homeostasis. We describe here pathological and genetic characterizations of a new mutant strain of mice, the mutation of which spontaneously occurred in the Fas-deficient strain, MRL/Mp.Faslpr (MRL/lpr). MRL/lpr is known to stably exhibit systemic lupus erythematosus-like diseases. However, the mutant mice barely displayed autoimmune phenotypes, though the original defect in Fas expression was unchanged. Linkage analysis using (mutant MRL/lpr x C3H/lpr)F2 mice demonstrated a nucleotide insertion that caused loss of expression of small adaptor protein, signaling lymphocyte activation molecule (SLAM)-associated protein (SAP). SAP is known to be a downstream molecule of SLAM family receptors and to mediate the activation signal for tyrosine kinase Fyn. Recent studies have shown pleiotropic roles of SAP in T, B, and NK cell activations and NKT cell development. The present study will provide evidence for an essential role for SAP in the development of autoimmune diseases, autoantibodies, and lymphadenopathy in MRL/lpr lupus mice.

Amino Acid Sequence↗

PubMed2006

Cappuccino mutation in an autoimmune-prone strain of mice suggests a role of platelet function in the progression of immune complex crescentic glomerulonephritis.

OBJECTIVE: Crescent formation in the renal glomerulus is a typical manifestation of progressive glomerulopathy associated with fatal renal failure; therefore, its prevention is of clinical importance. Little is known about the pathogenic mechanism for crescent formation. This study was undertaken in an attempt to identify the events that are critical for crescent formation in immune complex crescentic glomerulonephritis (CGN) by analyzing a novel mutant strain of mice. METHODS: A spontaneous mutant strain of mice was isolated from the autoimmune-prone strain EOD, which stably develops fatal CGN. The mutant phenotypes were assessed histopathologically, hematologically, and immunologically. The mutation was searched for with positional cloning using microsatellite markers. RESULTS: Compared with wild-type EOD (WT-EOD) mice, mutant EOD (mut-EOD) mice showed marked improvement in CGN in conjunction with an improvement in spontaneous mortality. In WT-EOD mice, an inverse correlation between blood urea nitrogen concentration and blood platelet count and massive accumulation of platelets in the glomerulus were evident, suggesting that an accumulation of platelets in the glomerulus contributes to the progression of CGN. The mutant platelets showed an abnormal aggregation in response to collagen and thrombin, associated with a bleeding tendency in mut-EOD mice. Genetic analysis revealed a deleterious mutation in the cappuccino gene (cno), which encodes a protein that belongs to a complex called the biogenesis of lysosome-related organelle complex 1 and is profoundly involved in platelet function. Morphologic examination revealed a partial defect in dense body formation in the delta-granule of platelets. CONCLUSION: The present findings suggest that platelet functions have a critical role in crescent formation in autoimmune GN.

Amino Acid Sequence↗

PubMed2006

NK026680, a novel suppressant of dendritic cell function, prevents the development of rapidly progressive glomerulonephritis and perinuclear antineutrophil cytoplasmic antibody in SCG/Kj mice.

OBJECTIVE: NK026680 is a newly identified type of immunosuppressive agent that inhibits dendritic cell (DC) functions and consequently reduces the mortality of mice with experimental acute graft-versus-host disease. This study was undertaken to evaluate NK026680 suppression of DC functions in preventing development of rapidly progressive glomerulonephritis (RPGN) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) in SCG/Kj mice. METHODS: Oral administration of NK026680 to SCG/Kj mice began when mice were 8-10 weeks old, before the onset of disease, and continued for 56 days. The efficacy of NK026680 was evaluated using the mortality of mice, the results of urinalysis, histopathologic evaluation for glomerular injury, and immunofluorescence staining for the detection of immune complex (IC) deposition in glomeruli, and by assessing lymphadenopathy and measuring autoantibody titers. RESULTS: Oral administration of NK026680 at a dosage of 25 mg/kg once daily or 50 mg/kg once daily significantly suppressed 1) spontaneous mortality, 2) proteinuria and hematuria, 3) blood urea nitrogen levels, 4) glomerular damage characterized histopathologically, 5) IC deposition in glomeruli, 6) the development of pANCA and anti-DNA antibodies, and 7) lymphadenopathy. CONCLUSION: The newly identified DC inhibitor, NK026680, prevented the onset of RPGN, autoantibody production, and lymphadenopathy in SCG/Kj mice, suggesting a crucial role for DC function in these autoimmune phenotypes. NK026680 may be a potent immunosuppressive agent for the treatment of ANCA-associated renovascular disorders.

Animals↗

PubMed2006

Multicenter phase II study of antimicrobial prophylaxis in low-risk patients undergoing distal gastrectomy for gastric cancer.

BACKGROUND: In Japan, antimicrobial prophylaxis (AMP) is typically administered for 3 to 4 days postoperatively for clean-contaminated operations such as distal gastrectomy. This far exceeds the recommended 2h or less laid out by the Centers for Disease Control (CDC) guidelines for the prevention of surgical-site infections (SSIs), after a clean-contaminated operation. METHODS: Patients with gastric cancer, which was curable by distal gastrectomy with D2 lymphandectomy, were assigned to a multicenter phase II study. One gram of cefazolin within 3 min of the first surgical incision and intraoperative supplements of g of cefazolin every h were administered. AMP was not administered after skin closure unless postoperative infection occurred. The occurrence of SSIs was monitored until postoperative day 30 as the primary endpoint of this study. RESULTS: In 56 patients, three SSIs (5.4%) and one remote site infection (1.8%) developed. No other postoperative infections were observed. CONCLUSION: Our data indicate that the CDC guidelines regarding AMP may also be sufficient for patients undergoing clean-contaminated operations in Japan.

Anti-Bacterial Agents↗

PubMed2006

Isoflavonoids with antiestrogenic activity from Millettia pachycarpa.

Three new isoflavonoids, named millewanins G (1) and H (2) and furowanin B (3), were isolated from the leaves of Millettia pachycarpa. Their structures were elucidated on the basis of spectroscopic analyses. The antiestrogenic activity in the yeast two-hybrid assay of these isoflavonoids was examined and shown to be comparable with that of 4-hydroxytamoxifen.

Estrogen Receptor Modulators↗

PubMed2006

Induction of apoptosis by isoflavonoids from the leaves of Millettia taiwaniana in human leukemia HL-60 cells.

We have isolated two new isoflavonoids, millewanin-F (1) and furowanin-A (2), together with five known isoflavonoids from the leaves of Millettia taiwaniana Hayata (Leguminosae) and examined their effects on the growth of human leukemia HL-60 cells. Among the isolated isoflavonoids, furowanin-A (2), warangalone (3), isoerysenegalensein-E (4), and euchrenone b10 (6) showed significant cytotoxicity against HL-60 cells. After treatment with three of the cytotoxic isoflavonoids, furowanin-A (2), warangalone (3), and isoerysenegalensein-E (4), fluorescence microscopy with Hoechst 33,342 staining revealed that the percentage of apoptotic cells with fragmented nuclei and condensed chromatin increased in a time-dependent manner. In addition, the activities of caspase-9 and caspase-3 were also enhanced in a time-dependent manner upon treatment with the isoflavonoids 2, 3, and 4. Caspase-9 and caspase-3 inhibitors suppressed apoptosis induced by isoflavonoids 2, 3, and 4. These results suggest that the isoflavonoids induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, which is triggered by mitochondrial dysfunction.

Antineoplastic Agents, Phytogenic↗

PubMed2006

Apoptosis inducing activity of 4-substituted coumarins from Calophyllum brasiliense in human leukaemia HL-60 cells.

With the objective of identifying anti-tumour-promoting agents, we carried out a primary screening of ten 4-substituted coumarins isolated from Calophyllum brasiliense Camb. (Guttiferae), to determine the ability of these compounds to inhibit proliferation of the human leukaemia cell line HL-60. Among the 4-substituted coumarins isolated, calophyllolide (2) and mammea B/BB (3) showed significant cytotoxicity against HL-60 cells. Fluorescence microscopy with Hoechst 33342 staining revealed that the percentage of apoptotic cells with fragmented nuclei and condensed chromatin increased in a time-dependent manner after treatment with calophyllolide (2) or mammea B/BB (3). In addition, the activity of caspase-9 and caspase-3 was also enhanced in a time-dependent manner upon treatment with the 4-substituted coumarins 2 and 3. Caspase-9 and caspase-3 inhibitors suppressed apoptosis induced by 4-substituted coumarins 2 and 3. These results suggest that calophyllolide (2) and mammea B/ BB (3) induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, which is triggered by mitochondrial dysfunction.

Antineoplastic Agents↗

PubMed2006

Recyclable polymeric pi-acid catalyst effective on Mannich-type reaction in water.

Polymer-supported dicyanoketene acetal (poly-DCKA-1), synthesized by copolymerization of a DCKA bearing a 4-vinylbenzyl group with ethyleneglycol dimethacrylate, was found to be an excellent recyclable catalyst for the three-component Mannich-type reaction of aldehydes, aromatic amines, and TMS enolate of ethyl isobutyrate in water as the sole solvent.

Acetals↗

PubMed2006

[Pulmonary vein orifice cryoablation for atrial fibrillation with mitral valve disease using a specially designed cryo-probe].

OBJECTIVES: To evaluate the effectiveness of pulmonary vein orifice cryoablation (PVOC) for atrial fibrillation during mitral valve surgery. METHODS: Twenty-two patients (12 men and 10 women) with mitral valve disease complicated with atrial fibrillation have been treated by PVOC since March 2000. During the mitral valve operations, all four pulmonary vein orifices were ablated using a ball-shaped cryo-probe. A newly designed cryo-probe was used for the last seven patients. Success was defined as atrial defibrillation within 6 months after the operation. RESULTS: The success rate was 72.7% (16/22) of all patients, and improved from 66.6% to 85.7% (6/7) in the patients treated with the new cryo-probe. The mean left atrial dimension was smaller (50.2 +/- 4.1 vs. 61.5 +/- 9.4 mm, p < 0.01), and the duration of atrial fibrillation was also shorter (27.2 +/- 42.8 vs. 138.0 +/- 95.6 months, p < 0.01) in the successful group. CONCLUSIONS: PVOC with mitral valve surgery is a simple and less invasive procedure, so could be an effective option for atrial fibrillation.

Adult↗