Biomedical subjects

Junji Uchida

Publications and source records attributed to Junji Uchida.

At least 19 recordsLinked to original sources

PubMed2006

Clinical experience with autofluorescence imaging system in patients with lung cancers and precancerous lesions.

BACKGROUND: It is important to detect preinvasive bronchial lesions before they become invasive cancer, because detection of early cancer is expected to lead to a cure. Autofluorescence bronchoscopy is a useful device in the detection of preinvasive and cancerous lesions. Recently, a new autofluorescence bronchoscopic system, autofluorescence imaging (AFI) system, has been developed. OBJECTIVES: We evaluated the efficacy of AFI in the diagnosis of precancerous and cancerous lesions. METHODS: A total of 31 patients underwent both conventional white-light bronchoscopy (WLB) and AFI from January 2002 to September 2004. We evaluated autofluorescence findings using a four-point scale: AFI-I, II, III, and B. The findings in WLB were evaluated on a three-point scale: WLB-I, II, and III. Abnormal areas by WLB and AFI were biopsied for histopathological examinations. RESULTS: A total of 64 lesions were evaluated. When the AFI-III finding was regarded as positive in AFI and WLB-III as positive in WLB, sensitivity for severe dysplasia or worse was 94.7% with AFI and 73.7% with WLB, respectively. CONCLUSIONS: AFI is an effective system for the detection of precancerous and cancerous lesions.

Aged↗

PubMed2006

Molecular mechanisms and therapeutic strategies of chronic renal injury: the role of nuclear factor kappaB activation in the development of renal fibrosis.

Tubulointerstitial fibrosis is a common feature of many progressive renal diseases and is a main determinant that leads to an irreversible loss of renal function. In chronic cyclosporin A nephrotoxicity, we previously reported that inflammatory responses such as macrophage infiltration preceded interstitial fibrosis. This inflammation was accompanied by an elevation in renal nuclear factor kappaB (NF-kappaB) activity. Similar findings were obtained in chronic tacrolimus nephrotoxicity and obstructive nephropathy. Inhibition of NF-kappaB markedly attenuated renal inflammation and interstitial fibrosis in these models. Furthermore, administration of oral adsorbent (Kremezin) significantly attenuated the increase in renal NF-kappaB activity and concomitantly reduced interstitial inflammation and renal fibrosis in chronic renal failure rats. Elimination of indoxyl sulfate by this adsorbent is likely involved in this mechanism since it is known that indoxyl sulfate activates NF-kappaB in renal tubular cells. It is suggested that strategy aiming at NF-kappaB inhibition is important to prevent the progression of renal fibrosis.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2006

High-dose-rate brachytherapy for small-sized peripherally located lung cancer.

BACKGROUND: The demand for minimally invasive therapies is increasing in the treatment of small peripheral non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Twelve patients with T1-2 N0 M0 peripheral NSCLC were treated by high-dose-rate brachytherapy with (192)Ir radioactive source. RESULTS: A (192)Ir source was introduced into the tumors percutaneously in five patients (percutaneous brachytherapy) or transbronchially in seven patients (transbronchial brachytherapy). Whereas irradiation was performed with a single fraction of 20 Gy in percutaneous brachytherapy, it was hypofractionated from 5 x 5 Gy to 2 x 12.5 Gy in transbronchial brachytherapy. Complications were generally mild in all patients, although focal radiation pneumonitis was observed in most patients. Primary recurrence occurred in three patients, including one with a T2 tumor and one treated by brachytherapy as a salvage treatment for recurrence after conformal radiotherapy. When brachytherapy is evaluated as a primary treatment for T1 N0 M0 NSCLC, local control rate is 88.9% and estimated 5-year survival rate is between 60% and 70%. CONCLUSION: Brachytherapy has a potential to be a method to treat peripheral T1 N0 M0 NSCLC.

Aged↗

PubMed2006

Modified extravesical ureteroneocystostomy for completely duplicated ureters in renal transplantation.

INTRODUCTION: Completely duplicated ureters are the most common congenital malformation of the upper urinary tract. However, there are very few reports on transplantation using kidneys with double ureters, and the technique of ureterocystoneostomy for completely duplicated ureters has not yet been established. PATIENTS AND METHODS: We treated 3 patients with completely duplicated ureters at our institutions from January 1998 to October 2005. We modified the extravesical technique for treating these 3 cases and evaluated the 52-month follow-up period for possible urological complications. RESULTS: Neither urological complications nor urinary tract infections occurred in the follow-up period after using our new technique. CONCLUSION: We conclude that this technique is an appropriate procedure for the transplantation of kidneys with completely duplicated ureters.

Cystostomy↗

PubMed2006

B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis.

Systemic sclerosis (scleroderma) is an autoimmune disease characterized by excessive extracellular matrix deposition in the skin. A direct role for B lymphocytes in disease development or progression has remained controversial, although autoantibody production is a feature of this disease. To address this issue, skin sclerosis and autoimmunity were assessed in tight-skin mice, a genetic model of human systemic sclerosis, after circulating and tissue B-cell depletion using an anti-mouse CD20 monoclonal antibody before (day 3 after birth) and after disease development (day 56). CD20 monoclonal antibody treatment (10 to 20 microg) depleted the majority (85 to 99%) of circulating and tissue B cells in newborn and adult tight-skin mice by days 56 and 112, respectively. B-cell depletion in newborn tight-skin mice significantly suppressed (approximately 43%) the development of skin fibrosis, autoantibody production, and hypergammaglobulinemia. B-cell depletion also restored a more normal balance between Th1 and Th2 cytokine mRNA expression in the skin. By contrast, B-cell depletion did not affect skin fibrosis, hypergammaglobulinemia, and autoantibody levels in adult mice with established disease. Thereby, B-cell depletion during disease onset suppressed skin fibrosis, indicating that B cells contribute to the initiation of systemic sclerosis pathogenesis in tight-skin mice but are not required for disease maintenance.

Aging↗

PubMed2005

Increased antitumor activity in combined treatment TS-1 and docetaxel. A preclinical study using gastric cancer xenografts.

As TS-1 and docetaxel (TXT) have different mechanisms of antitumor activity, the combination therapy is expected to have a higher response. Human gastric cancer xenografts SC-2, St-40, and SC-4 inoculated into nude rats were treated with TS-1 alone (TS-1 12 mg/kg/day, day 1-14), TXT alone (TXT 2 mg/kg/day, day 1 or day 8), and combination of both drugs. TS-1 alone showed antitumor activity against three tumors (growth inhibition rate (IR): SC-2 (38.6 and 40.5%), St-40 (54.5%), SC-4 (55.1%)). TXT was effective with minimal toxicity, especially on day 1 of administration (IR at day 1 administration: SC-2 (51.7%), St-40 (42.1%), SC-4 (46.3%)). In the combined TS-1 and TXT group, antitumor activity increased at day 1 and at day 8 TXT administration (IR at day 1 administration: SC-2 (68.4%), St-40 (72.5%), SC-4 (76.0%)). Weight loss of TS-1 and day 1 TXT administration was the same as that of TS-1 alone. TS-1 and TXT showed no pharmacokinetic interaction. Compared with 5-fluorouracil and cisplatin treatment, combined therapy with TS-1 and TXT showed the same antitumor activity and toxicity. Combined therapy with TS-1 and TXT showed enhanced antitumor activity compared with monotherapy of each drug. The outpatient-based treatment of this combination is worth investigating.

Animals↗

PubMed2005

The peritoneal cavity provides a protective niche for B1 and conventional B lymphocytes during anti-CD20 immunotherapy in mice.

Although anti-CD20 immunotherapy effectively treats human lymphoma and autoimmune disease, the in vivo effect of immunotherapy on tissue B cells and their subsets is generally unknown. To address this, anti-mouse CD20 mAbs were used in a mouse model in which the extent and kinetics of tissue B cell depletion could be assessed in vivo. CD20 mAb treatment depleted most mature B cells within 2 days, with 95-98% of B cells in the bone marrow, blood, spleen, lymph nodes, and gut-associated lymphoid tissues depleted by day 7, including marginal zone and follicular B cells. The few spleen B cells remaining after CD20 mAb treatment included pre-B, immature, transitional, and some B1 B cells that expressed CD20 at low levels. By contrast, peritoneal cavity B cells expressed normal CD20 densities and were coated with CD20 mAb, but only 30-43% of B1 cells and 43-78% of B2 cells were depleted by day 7. Spleen B cells adoptively transferred into the peritoneal cavity were similarly resistant to mAb-induced depletion, while transferred B cells that had migrated to the spleen were depleted. However, peritoneal B1 and B2 cells were effectively depleted in mAb-treated wild-type and C3-deficient mice by thioglycolate-induced monocyte migration into this otherwise privileged niche. Inflammation-elicited effector cells did not promote peritoneal cavity B cell depletion in FcR-deficient mice treated with CD20 mAb. Thus, the majority of CD20(+) cells and B cell subsets within lymphoid tissues and the peritoneum could be depleted efficiently in vivo through Fc-dependent, but C-independent pathways during anti-CD20 immunotherapy.

Animals↗

PubMed2005

Silent cerebral infarction predicts vascular events in hemodialysis patients.

BACKGROUND: Cardiovascular disease is the leading cause of death in hemodialysis (HD) patients. We have previously reported a higher incidence of silent cerebral infarction (SCI) in HD patients compared with the control group using MRI studies. In the present study, we examined whether or not SCI could predict vascular events in HD patients. METHODS: Cranial magnetic resonance imaging (MRI) was performed on 119 HD patients without symptomatic cerebrovascular disease. SCI was detected by MRI, and the patients were prospectively followed up. The end points of the study were the incidence of major events related to vascular events (cerebral events, cardiac events, and sudden deaths). We investigated the prognostic role of SCI in cerebral, cardiac, and vascular events by using the Kaplan-Meier method and Cox proportional hazards analysis. RESULTS: The prevalence of SCI was 49.6% in HD patients. During a follow-up period of maximum 60 months, vascular events, which included 13 cerebral events, 5 cardiac events, and 3 sudden deaths, occurred in 21 patients. The presence of SCI was predictive for a higher cerebral and vascular morbidity compared to the absence of SCI [18.6% (N= 11) vs. 3.3% (N= 2), P= 0.0169, and 30.5% (N= 18) vs. 5.0% (N= 3), P= 0.0006, respectively]. By multivariate Cox proportional hazards analysis, SCI remained a powerful independent predictor of cerebral and vascular events (hazard ratio for cerebral events 7.33, 95% CI 1.27-42.25: for vascular events 4.48, 95% CI 1.09-18.41). CONCLUSION: The findings of the present study indicate that the presence of SCI is a new risk factor for vascular events in HD patients.

Adult↗

PubMed2004

The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy.

Anti-CD20 antibody immunotherapy effectively treats non-Hodgkin's lymphoma and autoimmune disease. However, the cellular and molecular pathways for B cell depletion remain undefined because human mechanistic studies are limited. Proposed mechanisms include antibody-, effector cell-, and complement-dependent cytotoxicity, the disruption of CD20 signaling pathways, and the induction of apoptosis. To identify the mechanisms for B cell depletion in vivo, a new mouse model for anti-CD20 immunotherapy was developed using a panel of twelve mouse anti-mouse CD20 monoclonal antibodies representing all four immunoglobulin G isotypes. Anti-CD20 antibodies rapidly depleted the vast majority of circulating and tissue B cells in an isotype-restricted manner that was completely dependent on effector cell Fc receptor expression. B cell depletion used both FcgammaRI- and FcgammaRIII-dependent pathways, whereas B cells were not eliminated in FcR common gamma chain-deficient mice. Monocytes were the dominant effector cells for B cell depletion, with no demonstrable role for T or natural killer cells. Although most anti-CD20 antibodies activated complement in vitro, B cell depletion was completely effective in mice with genetic deficiencies in C3, C4, or C1q complement components. That the innate monocyte network depletes B cells through FcgammaR-dependent pathways during anti-CD20 immunotherapy has important clinical implications for anti-CD20 and other antibody-based therapies.

Animals↗

PubMed2004

Severely impaired B lymphocyte proliferation, survival, and induction of the c-Myc:Cullin 1 ubiquitin ligase pathway resulting from CD22 deficiency on the C57BL/6 genetic background.

Understanding the molecular mechanisms through which CD22 regulates B lymphocyte homeostasis, signal transduction, and tolerance is critical to defining normal B cell function and understanding the role of CD22 in autoimmunity. Therefore, CD22 function was examined in vivo and in vitro using B cells from CD22-deficient (CD22(-/-)) mice. Backcrossing of founder CD22(-/-) mice onto the C57BL/6 (B6) genetic background from a B6/129 mixed background resulted in a dramatically reduced B cell proliferative response following IgM ligation, characterized by a paucity of lymphoblasts and augmented apoptosis. Also, the phenotype of splenic B6 CD22(-/-) B cells was uniquely HSA(high) and IgD(low)/CD21(low) with intermediate levels of CD5 expression, although the percentages of mature and transitional B cells were normal. That B6 CD22(-/-) B cells predominantly underwent apoptosis following IgM ligation correlated with this unique tolerant phenotype, as well as defective induction of the c-Myc:Cullin 1 (CUL1) ubiquitin ligase pathway that is necessary for progression to the S phase of cell cycle. CD40 ligation compensated for CD22 deficiency by restoring lymphoblast development, proliferation, c-Myc and CUL1 expression, and protein ubiquitination/degradation in IgM-stimulated B6 CD22(-/-) B cell cultures. Thereby, this study expands our current understanding of the complex role of CD22 during B cell homeostasis and Ag responsiveness, and reveals that the impact of CD22 deficiency is dictated by the genetic background on which it is rendered. Moreover, this study defines CD22 and CD40 as the first examples of lymphocyte coreceptors that influence induction of the c-Myc:CUL1 ubiquitin ligase pathway.

Adjuvants, Immunologic↗

PubMed2004

Mouse CD20 expression and function.

CD20 plays a role in human B cell proliferation and is an effective target for immunotherapy. In this study, mouse CD20 expression and biochemistry were assessed for the first time using a new panel of CD20-specific mAb, with CD20 function assessed using CD20-deficient (CD20(-/-)) mice. CD20 expression was B cell restricted and was initiated during late pre-B cell development. The frequency and density of CD20 expression increased during B cell maturation in the bone marrow, with a subpopulation of transitional IgM(hi) B cells expressing higher CD20 levels than the majority of mature recirculating B cells. Transitional T1 B cells in the spleen also expressed high CD20 levels, providing a useful new marker for this B cell subset. In CD20(-/-) mice, immature and mature B cell IgM expression was approximately 20-30% lower relative to B cells from wild-type littermates. In addition, CD19-induced intracellular calcium responses were significantly reduced in CD20(-/-) B cells, with a less dramatic effect on IgM-induced responses. These results reveal a role for CD20 in transmembrane Ca(2+) movement in mouse primary B cells that complements previous results obtained using human CD20 cDNA-transfected cell lines. Otherwise, B cell development, tissue localization, signal transduction, proliferation, T cell-dependent antibody responses and affinity maturation were normal in CD20(-/-) mice. Thus, mouse and human CD20 share similar patterns of expression and function. These studies thereby provide an animal model for studying CD20 function in vivo and the molecular mechanisms that influence anti-CD20 immunotherapy.

Animals↗

PubMed2004

Kidney transplants from living related donors having double inferior vena cava.

We performed four living related kidney transplantations from donors with double inferior vena cava (D-IVC), in which the left kidney was selected in two cases and the right in two cases. By dissecting the right internal iliac vein and isolating the right external iliac vein, the surgical procedure of the recipient side was so devised as to avoid any complications. In one patient, the surgical procedure of the donor side was modified to extend the donor left renal vein by anastomosis of part of the donor IVC to the renal vein. In the other case, no special treatment was necessary due to the patient's slender physique. In all four cases, transplants were successfully performed. The following conclusions can be made from these results: If the donor has D-IVC, it is essential to carefully conduct pre-operative examinations including angiography and venography to investigate other possible anomalies and blood flow of the renal vein. In addition, the graft must be carefully selected so that it is not disadvantageous to the donor. If there is no disadvantage to the donor as to which kidney is selected, the kidney with the longer renal vein should be transplanted.

Adolescent↗

PubMed2003

Renal transplantation for the hemodialysis patient with axillofemoral bypass.

BACKGROUND: Axillofemoral bypass grafts are used in the treatment of aortoiliac occlusive disease caused by atherosclerosis. There have been no previous reports on renal transplantation used as treatment for chronic renal failure after an axillofemoral bypass graft being placed because of atypical coarctation of the aorta. METHODS: The patient was a 47-year-old woman who had received regular hemodialysis for 15 years. Axillofemoral bypass surgery was performed because of atypical coarctation of the aorta in October 1999. Three years after surgery, she underwent renal transplantation. RESULTS: Renal transplantation was successful, and helical computed tomography demonstrated patent graft bypass and good nephrographic effects of the renal artery. CONCLUSIONS: Even though dialysis patients with atypical coarctation of the aorta are treated with an axillofemoral bypass, it is possible for them to undergo regular renal transplantation, if part of the external or internal iliac artery is intact.

Aortic Coarctation↗

PubMed2003

Renal allograft arteriovenous fistula and large pseudoaneurysm.

The patient was a 51-year-old female. Post-biopsy arteriovenous fistula (AVF) and pseudoaneurysm in a renal allograft were diagnosed 5 yr and 4 months after she received a renal transplantation. Four years after the diagnosis, interventional treatment for the AVF and pseudoaneurysm was performed because of a high risk of pseudoaneurysm rupture. Although the longitudinal diameter of the pseudoaneurysm was more than 5 cm, this AVF and pseudoaneurysm were treated successfully by a percutaneous transluminal embolization, and renal function has remained stable after embolization. A selective interventional procedure proved effective for the large pseudoaneurysm in the renal allograft. Therefore, when a transcutaneous needle biopsy of the renal allograft is performed, although there are no apparent symptoms or signs of vascular complications during the clinical course, periodical examinations such as echo-Doppler imaging should be made on the allograft.

Aneurysm, False↗

PubMed2003

Xanthogranulomatous pyelonephritis with acquired cystic disease of the kidney in a haemodialysis patient.

A 54-year-old-female patient who had received regular haemodialysis therapy for 12 years was referred to our hospital for evaluation of a left renal mass. Imaging examinations revealed acquired cystic disease of the kidney (ACDK) and a tumour-like lesion in the left kidney. Because of the preoperative diagnosis of the left renal cell carcinoma, the patient underwent a left nephrectomy. Pathological examination revealed xanthogranulomatous pyelonephritis. It was difficult to distinguish xanthogranulomatous pyelonephritis from renal cell carcinoma in our case, because it is very rare for xanthogranulomatous pyelonephritis to occur in ACDK.

Female↗

PubMed2003

Unruptured intracranial aneurysms in haemodialysis patients.

While the mortality rate of subarachnoid haemorrhage is very high in haemodialysis (HD) patients, the prevalence of unruptured intracranial aneurysms in HD patients has not yet been elucidated. We performed cerebral magnetic resonance angiography (MRA) on 123 HD patients who did not have symptomatic cerebrovascular disease, and on 52 control subjects. On the basis of these images, the prevalence of unruptured intracranial aneurysms was evaluated. Unruptured aneurysms were found in three HD patients (2.4%). There were no aneurysms found in the healthy control group. There was no significant difference in the prevalence of unruptured aneurysms between HD patients and healthy controls. Therefore, the incidence of intracranial aneurysms is not associated with chronic renal failure.

Adult↗

PubMed2003

Advanced ureteral cancer with complete remission achieved by taxan containing systemic chemotherapy.

We report a case of advanced ureteral cancer successfully treated with systemic chemotherapy combined with irradiation. A 47-year-old man was diagnosed as having a right ureteral cancer at the clinical stage of T4, N2 and M1 (liver). A papillary tumor was also found in the bladder and the resected specimen showed a grade 1 transitional cell carcinoma. Although three cycles of methotrexate, vinblastine, pirarubicin and cisplatin (MVAC) gave partial response to the ureteral tumor, new metastases to the lung and pelvic bone were observed. The patient received 50 Gy external irradiation to the pelvis, 11 cycles of paclitaxel (270 mg) and cisplatin (60-80 mg) followed by four cycles of docetaxel (100 mg) and cisplatin. Thereafter, he underwent bone biopsy, partial hepatectomy, total nephroureterectomy and lymph node resection, by which a complete response was achieved pathologically. The patient has been alive without evidence of disease for 12 months.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Asymptomatic occlusive lesions of cerebral arteries in Japanese hemodialysis patients.

While cerebrovascular diseases (CVD) are very common in hemodialysis (HD) patients, the prevalence and risk factors of asymptomatic occlusive lesions (AOL) of cerebral arteries in HD patients have not yet been elucidated. We performed cerebral magnetic resonance angiography (MRA) on 123 HD patients without symptomatic cerebrovascular disease and on 52 control subjects. On the basis of these images, we investigated the prevalence and risk factors of AOL. Stenosis greater than 25% narrowing of the cerebral arteries was found in 27 HD patients. The prevalence of AOL of cerebral arteries in HD patients was significantly higher than in the control group [27 (22.0%) versus 4 patients (7.7%), chi.2=4.2, p=0.0411]. Multiple logistic regression analysis showed that independent risk factors of AOL of cerebral arteries were uremic state, dyslipidemia, and age in all subjects and dyslipidemia and age in HD patients (R.2=0.162, p=0.0004; R.2 =0.138, p=0.0145, respectively). Our findings suggest that chronic renal failure maintained by hemodialysis increases the prevalence of AOL, and that age and dyslipidemia are also significantly associated with AOL in HD patients.

Adult↗