Biomedical subjects

Hiroshi Kitamura

Publications and source records attributed to Hiroshi Kitamura.

At least 37 records · Page 2Linked to original sources

PubMed2006

Retroperitoneal extragonadal germ cell tumor presenting as a bulky pelvic mass of the obturator fossa.

Extragonadal germ cell tumors (EGGCT) are commonly found in the midline of the body. We report a rare case of a retroperitoneal EGGCT presenting as a bulky pelvic mass located between the left internal and external iliac arteries in a 29-year-old man. His alpha-fetoprotein level was 12946.2 ng/mL and the biopsy of the tumor revealed a nonseminomatous germ cell tumor. After three cycles of chemotherapy (bleomycin/etoposide/cisplatin) followed by resection of all residual tumors, one cycle of salvage chemotherapy (etoposide/ifosphamide/cisplatin) was added. The patient was disease free at 21-month follow up.

Adult↗

PubMed2006

[Pulmonary infection of Pneumocystis carinii and Cytomegalo virus in the treatment of cholesterol crystal embolism].

Cholesterol crystal embolism (CCE) is a multivisceral disease caused by occlusion of small arteries with cholesterol crystal emboli deriving from eroded atherosclerotic plaques of the aorta and/or large feeder arteries. The factors precipitating CCE are manipulation of the aorta or other large arteries during arteriography or surgery, and anticoagulant or thrombolytic therapy. CCE has been reported to be a life threatening condition involving multiple vital organ dysfunction, including renal failure, cardiac failure, skin ischemic lesions such as livedo reticularis, patchy skin necrosis, and purple toes, gastrointestinal ischemia, and/or visual disturbance. We report a 63-year-old male patient of CCE after percutaneous transluminal coronary angioplasty, who contracted severe pneumonia of Pneumocystis carinii and Cytomegalo virus during steroid therapy (prednisolone 20 mg for 3 months). He was treated successfully with mechanical ventilation, hemodialysis, and appropriate antibiotic therapy. Although corticosteroid therapy has been reported to be effective in some CCE patients, the indications of steroid therapy, dosage of corticosteroids, duration of the treatment, or efficacy of prophylactic administration of antibiotics are not yet established. Further interventional studies are required in order to evaluate the benefit of corticosteroid therapy for CCE.

Angioplasty, Balloon, Coronary↗

PubMed2005

Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis.

Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of kappaB-alpha, thereby suppressing proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.

Acute Disease↗

PubMed2005

Valpha14 NK T cell-triggered IFN-gamma production by Gr-1+CD11b+ cells mediates early graft loss of syngeneic transplanted islets.

Pancreatic islet transplantation is a highly promising approach for the treatment of insulin-dependent diabetes mellitus. However, the procedure remains experimental for several reasons, including its low efficiency caused by the early graft loss of transplanted islets. We demonstrate that Gr-1+CD11b+ cells generated by transplantation and their IFN-gamma production triggered by Valpha14 NKT cells are an essential component and a major cause of early graft loss of pancreatic islet transplants. Gr-1+CD11b+ cells from Valpha14 NKT cell-deficient (Jalpha281-/-) mice failed to produce IFN-gamma, resulting in efficient islet graft acceptance. Early graft loss was successfully prevented through the repeated administration of alpha-galactosylceramide, a specific ligand for Valpha14 NKT cells, resulting in dramatically reduced IFN-gamma production by Gr-1+CD11b+ cells, as well as Valpha14 NKT cells. Our study elucidates, for the first time, the crucial role of Gr-1+CD11b+ cells and the IFN-gamma they produce in islet graft rejection and suggests a novel approach to improving transplantation efficiency through the modulation of Valpha14 NKT cell function.

Animals↗

PubMed2005

Long-term functional outcome and late complications of Studer's ileal neobladder.

OBJECTIVE: The purpose of this study was to evaluate the long-term functional outcome and late complications of Studer's ileal neobladder. METHODS: The study included 57 patients who underwent radical cystectomy and bladder reconstruction with Studer's ileal neobladder, and were followed-up for at least 3 months after surgery. The voiding and storage function, and late complications were evaluated. The times of evaluation after surgery were categorized into periods I (3-23 months), II (24-59 months), III (60-95 months) and IV (> or =96 months). RESULTS: Daytime and night-time continence rates were 95.6 and 88.6%, respectively. The averages of functional capacity (439 ml), maximum flow rate (15.7 ml/s) and residual urine (35 ml) evaluated in period I were maintained in period IV. Of the 57 patients, intermittent self-catheterization was needed in five (8.8%) due to incomplete emptying or urinary retention. Urethroileal anastomotic stricture was found in two patients (3.5%), who were successfully treated by transurethral intervention. Inguinal hernia was found in seven patients (12.8%), five of whom developed it within 2 years after surgery. CONCLUSIONS: Our results indicate that Studer's ileal neobladder had a favorable long-term functional outcome. Although late complication rates were low, the incidence of inguinal hernia was relatively high, and this was considered as a definite late complication in our study.

Adult↗

PubMed2005

Aberrant expression and potency as a cancer immunotherapy target of inhibitor of apoptosis protein family, Livin/ML-IAP in lung cancer.

CD8(+) CTLs have an essential role in immune response against tumor. Although an increasing number of tumor-associated antigens that can be recognized by CTLs have been identified from human tumors, a limited number of tumor-associated antigens is known in lung cancer. In addition, because some of them are expressed in noncancerous tissues, there exist limitations in their application to tumor immunotherapy. Livin/ML-IAP is one of recently identified inhibitor of apoptosis protein (IAP) family, which is overexpressed in melanoma cells. In this report, we show that Livin/ML-IAP is aberrantly expressed in many lung cancer cell lines and primary lung cancer tissues, whereas it is not detectable in normal tissues, including lung by reverse transcription-PCR methods. To identify HLA-A24-restricted T-cell epitopes of Livin/ML-IAP, eight peptides were selected from the amino acid sequence of this protein and screened for their binding affinity to HLA-A24. It was revealed that Livin7 peptide (amino acid sequence, KWFPSCQFLL) had the highest affinity to HLA-A24. By stimulating peripheral blood lymphocytes of HLA-A24-positive lung cancer patients with Livin7 peptide in vitro, the peptide-specific CTLs were successfully induced from four of five patients with Livin/ML-IAP-positive lung cancer but not from any of four patients without Livin/ML-IAP expression in their cancer tissues. Furthermore, the CTLs induced by Livin7 peptide showed cytotoxicity against Livin/ML-IAP(+) lung cancer cell lines in an HLA-A24-restricted manner. Our data suggest that Livin/ML-IAP may be an excellent target antigen in immunotherapy for lung cancer and Livin7 peptide may serve as a potent peptide vaccine for HLA-A*2402(+)/Livin(+) lung cancer patients.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Occurrence of hyaline droplets in renal biopsy specimens: an ultrastructural study.

Hyaline droplets are apical cytoplasmic vesicles containing an accumulation of electron-dense amorphous materials surrounded by a unit membrane. Hyaline droplets may originate from apical vesicles after conversion to osmotic vesicles and loss of internally lined glycocalyx. They are found in the proximal tubular epithelium in biopsies from patients with renal diseases; however, their biological importance is not well understood. We reviewed ultrastructural pathology records of 140 renal biopsy patients to determine the occurrence and relevance of hyaline droplets. Of the cases, 14 (10%) showed the presence of hyaline droplets in proximal tubular epithelium. The distribution of cases were 8 of the 19 (42%) with minimal change nephritic syndrome, 2 of the 37 (5%) with IgA nephropathy, 2 of the 4 (50%) with membranous glomerulonephropathy, 1 of the 4 (25%) with tubulointerstitial nephritis, and 1 of the 1 (100%) with acute renal failure. The droplets were frequently found in male patients (86%), never in children, and were mostly associated with tubular necrosis (8 of 14 cases; 56%). Many hyaline droplets were observed in the cytoplasm of necrotic proximal tubular epithelial cells, and even when tubular necrosis was not evident, the proximal tubular epithelial cells containing hyaline droplets showed degenerated microvilli and decreased basal interdigitations. These results suggest that hyaline droplets could be one marker of renal tubular necrosis and a sign of functional disorder of protein reabsorption by degenerating proximal tubular epithelium.

Adult↗

PubMed2005

Ligands for peroxisome proliferator-activated receptor gamma have potent antitumor effect against human renal cell carcinoma.

OBJECTIVES: To examine whether peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in human renal cell carcinoma (RCC) cells, and whether activation of PPARgamma by its ligands can have multiple antitumor effects on human RCC cells in vitro. METHODS: We examined the expression of PPARgamma in four human RCC cell lines by reverse transcriptase-polymerase chain reaction and immunocytochemical staining. The effects of two PPARgamma ligands, pioglitazone and 15-deoxy-Delta12,14-prostaglandin J2, on cell proliferation were investigated by 3-[4,5-dimethylthiazol-2-thiazoly]-2,5-diphenyltetrazolium bromide assay. The induction of apoptosis by the ligands was examined using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method and Annexin V assay. Furthermore, we investigated whether these ligands suppressed the production of angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, by enzyme-linked immunosorbent assay. RESULTS: PPARgamma and retinoid X receptor, which forms a heterodimer with PPARgamma, were expressed in all RCC cell lines. In addition, immunocytochemical studies showed expression of PPARgamma protein in the RCC cells. PPARgamma ligands inhibited the cell growth in all cells in a dose-dependent manner. These ligands also induced apoptosis. Furthermore, secretion of both vascular endothelial growth factor and basic fibroblast growth factor was inhibited by these ligands in a dose-dependent and time-dependent manner. CONCLUSIONS: Ligands for PPARgamma have multiple antitumor effects in human RCC cells in vitro. Activation of the PPARgamma pathway may be a new strategy for treatment of patients with RCC.

Carcinoma, Renal Cell↗

PubMed2005

Dislocation of the cervical oesophagus: a rare cause of oesophageal obstruction.

We describe a case of obstruction of the cervical oesophagus in which ultrasonography and computed tomography revealed characteristic dislocation of the cervical oesophagus and food impaction in a segmental canal. Although the patient presented with complete obstruction initially, spontaneous recovery of passage was achieved with conservative therapy. One recurrent episode was noted during her remaining life span. To our knowledge, no similar case has been described previously.

Aged↗

PubMed2005

Sudden death in a case of cardiac amyloidosis immediately after pacemaker implantation for complete atrioventricular block.

We report a patient with cardiac involvement associated with primary amyloidosis presenting marked left ventricular (LV) wall thickening, severely decreased systolic and diastolic function, and complete atrioventricular block (CAVB), who died suddenly of cardiac arrest caused by electro-mechanical uncoupling occurring immediately after permanent pacemaker implantation. Post mortem examination showed no procedural complications such as cardiac or venous perforation. The heart was densely infiltrated with amyloid fibrils, especially in the extracellular tissues surrounding the papillary vessels.

Aged↗

PubMed2005

CDNA library construction from a small amount of RNA: adaptor-ligation approach for two-round cRNA amplification using T7 and SP6 RNA polymerases.

In this study, we developed a method that allows cDNA library construction from a small amount of RNA without causing serious size bias in the resulting cDNA population. For this purpose, we adopted two-round cRNA amplification by T7 and SP6 RNA polymerases. The first-round cDNAs, flanked by the promoter sequences of T7 and SP6 RNA polymerases, were synthesized from 1 microg total RNA and then subjected to two rounds of cRNA amplification. Comparison of the sizes of the first-round and the second-round cRNAs indicated that the size-bias effect of the second-round cRNA synthesis was not serious. The resultant double-stranded cDNAs were cloned into a plasmid by in vitro lambda phage recombination with an efficiency of 1.2 x 10(11) colony-forming unit/microgram of starting total RNA. Characterization of the resultant cDNA library in terms of the insert size, clone redundancy, and integrity of 3' ends of cDNAs indicated that the amplified library was comparable to a library constructed by a conventional method, although large cDNAs tend to be slightly truncated in the amplified library. This method enables the construction of a library from a small amount of RNA, and calculations suggest that the strategy would be efficient enough to use even a single cell as starting material.

Cloning, Molecular↗

PubMed2005

Impairment of change in diameter of the hepatic portion of the inferior vena cava: a sonographic sign of liver fibrosis or cirrhosis.

OBJECTIVE: We propose a new sonographic technique for detecting parenchymal stiffness of the liver. This technique measures the physiologic change in the diameter of the hepatic inferior vena cava (IVC). The hepatic portion of the IVC is extensively attached to the hepatic parenchyma so that changes in diameter of the venous lumen could not occur without changes in the shape of the surrounding parenchyma. Therefore, increased parenchymal stiffness due to cirrhosis or fibrosis may result in an impaired change in venous diameter. METHODS: Thirty patients with histologically proven cirrhosis and 30 patients with normal livers were examined. A commercial ultrasound system was used in conjunction with a convex probe at a center frequency of 4.0 MHz. The major axis of the IVC was measured during normal breathing. The patients were then requested to take a deep breath to produce negative intrathoracic pressure, and the same measurement as that during normal breathing was repeated immediately. RESULTS: In the normal liver group, the maximal diameter of the vena cava was 2.35 +/- 0.34 cm (mean +/- SD), and this was reduced by 1.30 +/- 0.67 cm (range, 0.4-2.85 cm) during deep inspiration. In the cirrhotic patient group, the maximal diameter was 1.74 +/- 0.35 cm, and this was reduced by 0.03 +/- 0.09 cm (range, 0.0-0.4 cm) (P < .0001). CONCLUSIONS: The physiologic change in the diameter of the hepatic portion of the IVC enhanced by deep respiration may reflect the stiffness of hepatic parenchyma.

Humans↗

PubMed2005

[Case of ANCA-associated glomerulonephritis detected at an early phase].

A 71-year-old man was admitted with low-grade fever, a high titer of CRP and ANCA. He was diagnosed as MPO-ANCA-associated vasculitis. On admission, his renal function was normal. Proteinuria and extra renal symptoms were not recognized. Only hematuria and hyaline cast were detected. A high titer of CRP and MPO-ANCA persisted. After obtaining informed consent, a renal biopsy was performed, revealing cellular crescentic glomerulonephritis and necrotizing vasculitis. The findings of the renal biopsy indicated an early phase of ANCA-associated nephritis. After MPSL pulse therapy, renal function was in the nomal range and proteinuria and hematuria disappeared. This present case demonstrated that early diagnosis and treatment are very important to sustain normal renal function if a high titer of MPO-ANCA is recognized in an elderly person without proteinuria.

Aged↗

PubMed2005

[Tumor size and regional lymph node metastasis in patients with M0 renal cell carcinoma: analysis in those having regional lymph node dissection].

We evaluated the relationship between regional lymph node metastasis and tumor size in patients with M0 renal cell carcinoma who received regional lymph node dissection. The study involved 234 of the 247 patients with localized renal cell carcinoma who underwent radical nephrectomy with lymph node dissection at our institute between 1985 and 1999. Patients were arbitrarily classified into 3 groups by the greatest diameter of the tumor on preoperative computed tomography (CT): 4.0 cm or less (group A), 4.1 to 7.0 cm (group B), and 7.1 cm or more (group C). The incidence of lymph node metastasis was assessed in each group. The current study showed that 11 (4.7%) of the 234 patients with lymph node dissection together with radical nephrectomy were lymph node positive. The incidences of lymph node metastasis were 4.0% in group A, 2.3% in group B, and 8.4% in group C (p = 0.79). Of these 11 patients with lymph node metastasis, 2 (18.2%) have so far survived for over 5 years following surgery. Although the role of regional lymph node dissection with radical nephrectomy might be limited and controversial in renal cell carcinoma, urological surgeons should always be aware of possible metastasis for any tumor size.

Adult↗

PubMed2004

Post-transcriptional effects of phorbol 12-myristate 13-acetate on transcriptome of U937 cells.

To identify post-transcriptionally modulated genes at the translational level by phorbol 12-myristate 13-acetate (PMA), we investigated mRNA profiles in the polysomal and the cytoplasmic fractions of U937 cells before and after PMA stimulation using microarrays with 15017 oligonucleotide probes. Global comparison of the profiles showed that the cytoplasmic distribution of mRNAs was considerably modulated upon PMA stimulation. The results also indicate that PMA post-transcriptionally regulated at least 0.7% of detectable genes in U937 cells. Thus, besides transcriptional modulation by PMA, changes in the translational state of transcripts seem to play a critical role in PMA-induced differentiation of U937 cells.

Gene Expression Profiling↗

PubMed2004

Transcriptional regulation of the MAIL gene in LPS-stimulated RAW264 mouse macrophages.

IkappaB inhibits nuclear factor kappa B (NF-kappaB), which is known to regulate the expression of various genes, including genes involved in inflammation. Recently, a novel IkappaB family protein, 'molecule possessing ankyrin repeats induced by lipopolysaccharide' (MAIL), was identified. MAIL is a nuclear-acting, inducible protein, unlike typical IkappaB proteins. However, the mechanism of its induction by lipopolysaccharide (LPS) is unclear. Using the LPS-reactive region located upstream from the MAIL gene, we investigated the mechanism of MAIL induction. MAIL expression was strongly regulated by NF-kappaB and partly regulated by CREB. Furthermore, deletion, point mutation and binding analyses revealed that the NF-kappaB binding site located at -229 to -220 bp is an essential target of MAIL expression. Overexpression of MAIL protein suppressed the LPS-induced promoter activity of the MAIL gene. These data indicate that MAIL expression is strongly upregulated by NF-kappaB, and it is controlled, at least in part, by an autoregulation mechanism.

Adaptor Proteins, Signal Transducing↗

PubMed2004

A simple and robust method for preparation of cDNA nylon microarrays.

DNA array technology has made remarkable progress in recent years and has become an indispensable tool in molecular biology research. However, preparing high-quality custom-made DNA arrays at a reasonable cost is still an important concern because we cannot abandon the use of DNA array systems designed for specific purposes. To address these problems, we here report the use of rolling circle amplification products of cDNA plasmids dissolved in 80% formamide as DNA probes immobilized on a nylon membrane. First, because formamide is practically non-volatile under ambient conditions and nucleic acids are easily dissolved in it, the use of formamide as a DNA solvent ensures that the DNA concentration of the solution will not change during arraying, which often takes several hours to a day depending on the number of DNA spots and arrays to produce. Secondly, the use of rolling circle amplification technology greatly reduced the labor needed to prepare the spotted DNA. The results in this study demonstrate that the introduction of these two modifications in preparation of nylon DNA array greatly improved its quality.

Cost Control↗

PubMed2004

Targeted disruption of MAIL, a nuclear IkappaB protein, leads to severe atopic dermatitis-like disease.

MAIL (molecule-possessing ankyrin repeats induced by lipopolysaccharide) is a nuclear IkappaB protein that is also termed interleukin-1-inducible nuclear ankyrin repeat protein or inhibitor of nuclear factor kappaB (IkappaB) zeta. In this study, we generated Mail-/- mice to investigate the roles of MAIL in whole organisms. Mail-/- mice grew normally until 4-8 weeks after birth, when they began to develop lesions in the skin of the periocular region, face, and neck. MAIL mRNA and protein were constitutively expressed in the skin of wild type controls, especially in the keratinocytes. Serum IgE was higher in Mail-/- mice than in normal. Histopathological analysis indicated that the Mail-/- skin lesions appeared to be atopic dermatitis (AD) eczema with inflammatory cell infiltration. In addition, markedly elevated expression of some chemokines such as thymus and activation-regulated chemokine was detected in the Mail-/- skin lesions, similar to that observed in the skin of patients with AD. In Mail-/- mice, MAIL-deficient keratinocytes might be activated to produce chemokines and induce intraepidermal filtration of inflammatory cells, resulting in the onset of the AD-like disease. These findings suggest that MAIL is an essential molecule for homeostatic regulation of skin immunity. The Mail-/- mouse is a valuable new animal model for research on AD.

Adaptor Proteins, Signal Transducing↗