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Biomedical subjects

Hiroshi Kitamura

Publications and source records attributed to Hiroshi Kitamura.

At least 55 records · Page 3Linked to original sources

Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries.

We have been conducting a mouse cDNA project to predict protein-coding sequences of mouse homologues of human KIAA and FLJ genes since 2001. As an extension of these projects, we herein present the entire sequences of 500 mKIAA cDNA clones and 4 novel cDNA clones that were incidentally identified during this project. We have isolated cDNA clones from the size-fractionated mouse cDNA libraries derived from 7 tissues and 3 types of cultured cells. The average size of the 504 cDNA sequences reached 4.3 kb and that of the deduced amino acid sequences from these cDNAs was 807 amino acid residues. We assigned the integrity of CDSs from the comparison with the corresponding human KIAA cDNA sequences. The comparison of mouse and human sequences revealed that two different human KIAA cDNAs are derived from single genes. Furthermore, 3 out of 4 proteins encoded in the novel cDNA clones showed moderate sequence similarity with human KIAA proteins, thus we could obtain new members of KIAA protein families through our mouse cDNA projects.

Animals↗

Prediction of the coding sequences of mouse homologues of FLJ genes: the complete nucleotide sequences of 110 mouse FLJ-homologous cDnas identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries.

We have been conducting a mouse cDNA project to predict protein-coding sequences of mouse KIAA-homologous genes since 2001. As an extension of this project, we also started to accumulate mouse cDNA clones homologous to the human FLJ cDNA clones which are another long cDNA resource produced in our institute. We have isolated the cDNA clones from size-fractionated cDNA libraries derived from five different mouse tissues and natural killer T-cells. Although the human FLJ cDNA clones were originally derived from human spleen libraries, one-third of their mouse homologues were obtained from the brain library. We designated these homologues "mFLJ" plus a 5-digit number and herein characterized 110 mFLJ cDNA clones. We assigned an integrity of the CDSs from the comparison of the 110 cDNA clones with the corresponding human FLJ cDNA clones. The average size of the 110 mouse cDNA sequences was 3.8 kb and that of the deduced amino acid sequences from their longest CDS in each cDNA was 663 amino acid residues. Homology and/or motif search against public databases revealed new domains and/or motifs in 26 mFLJ gene products which provide additional speculation regarding the function of FLJ genes.

Animals↗

Successful treatment of Fournier's gangrene with the assistance of preoperative computed tomography in an elderly man: report of a case.

An 87-year-old man presented with inguinal pain and swelling, and was later diagnosed as having Fournier's gangrene. The information gained from preoperative computed tomography (CT) proved very useful for defining the extent of necrosis, and emergency surgery saved his life. Thus, CT should be performed prior to treatment of Fournier's gangrene, even in an emergency situation.

Aged↗

Membranous nephropathy complicated by renal cell carcinoma.

We experienced a patient with membranous nephropathy (MN) and renal cell carcinoma (RCC). Although MN is known to be commonly associated with malignant tumors, association with RCC is rare. In our patient, no malignant focus was found in the major organs examined, except for a small lesion in the right kidney. Diagnosis of a small RCC (1.6 x 1.6 cm), which was made by renal biopsy and histology, was impossible by other, imaging, methods. As surgical treatment for the patient, laparoscopic partial nephrectomy was performed successfully, alleviating the symptoms of nephrotic syndrome for up to 21 months.

Biopsy↗

Aneurysmal subarachnoid hemorrhage in a patient with Wegener's granulomatosis.

A 34-year-old Japanese man admitted to hospital with pneumonia had previously undergone surgery for paranasal sinusitis and also for the clipping of an aneurysm at the origin of the anterior choroidal artery after subarachnoid hemorrhage. Laboratory tests performed at the present admission showed renal insufficiency and serological findings of raised proteinase 3 antineutrophil cytoplasmic antibody level. A renal biopsy was performed that showed diffuse necrotizing glomerulonephritis with fibrocellular crescents. The diagnosis of Wegener's granulomatosis(WG) was confirmed on the basis of the clinical picture, laboratory findings, and biopsies of renal tissues. The disease responded to prednisolone and cyclophosphamide. The association of WG with a ruptured intracranial aneurysm is rare and has not previously been confirmed.

Adult↗

Antiproliferative and antiangiogenic activities of genistein in human renal cell carcinoma.

OBJECTIVES: To determine whether genistein, an isoflavone that is plentiful in soy beans, could inhibit the growth of human renal cell carcinoma (RCC) cells in vitro, induce apoptosis, and suppress neovascularization in vivo induced by human RCC cells. METHODS: We investigated the effect of genistein on cell proliferation in four human RCC cell lines, SMKT R-1, R-2, R-3, and R-4. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay was performed to examine whether genistein could induce apoptosis in SMKT R-1 cells. To evaluate the effect of genistein on in vivo angiogenesis, we used a new mouse dorsal air sac model in which we could evaluate it simply and quantitatively. Radioisotope-labeled red blood cells were injected into a tail vein in mice bearing a Millipore filter chamber containing genistein, and the vascular volume was examined by measuring the radioactivity of the mouse dorsal skin. RESULTS: Treatment with genistein for 48 hours inhibited cell proliferation in a dose-dependent manner and 100 microg/mL genistein inhibited it in a time-dependent manner. A dose of 50 microg/mL genistein clearly induced cell apoptosis. The vascular volume after implantation of the Millipore filter chamber containing RCC cells increased to threefold that without RCC cells. Genistein in the Millipore filter chamber significantly decreased the neovascularization induced by human RCC cells in vivo. CONCLUSIONS: The results of this study demonstrated that genistein inhibited cell proliferation, induced apoptosis, and suppressed in vivo angiogenesis in human RCC cells. Genistein may be a promising antitumorigenic and antiangiogenic agent for the treatment and prevention of RCC.

Angiogenesis Inhibitors↗

Cloning of bovine MAIL and its mRNA expression in white blood cells of Holstein cows.

Molecule possessing ankyrin-repeats induced by lipopolysaccharide (MAIL) is known as an IkappaB protein induced after administration of bacterial lipopolysaccharide (LPS) to mice. In the present study, we cloned bovine MAIL cDNA and examined its mRNA expression in white blood cells isolated from Holstein cows. Bovine MAIL had more than 80% amino acid identities with murine and human MAILs, highly conserved ankyrin-repeat motifs and PEST-like sequences. Bovine MAIL mRNA was undetectable in isolated peripheral white blood cells, but rapidly induced (<1h) after stimulation by LPS and lipid A in vitro in a dose-dependent manner. The lipid A-induced MAIL mRNA expression was found in polymorphonuclear cells, monocytes/macrophages and total lymphocytes, but not in T-lymphocytes. MAIL mRNA was also induced in vivo in peripheral blood leukocytes of cows after intramammary injection of Escherichia coli derived from coliform mastitis. Thus, bovine MAIL, as rodent MAILs, is induced by inflammatory stimuli in specific immune cells in vitro and in vivo, suggesting a role in inflammatory responses to bacterial infection in cattle.

Amino Acid Motifs↗

Dynamic computed tomography and color Doppler ultrasound of renal parenchymal neoplasms: correlations with histopathological findings.

BACKGROUND: We evaluated whether color Doppler ultrasound (US) had diagnostic accuracy equal to dynamic computed tomography (CT) and whether performing dynamic CT and Doppler US together would be more informative in preoperative diagnosis of renal solid tumors. METHODS: A total of 110 renal solid tumors smaller than 7 cm were evaluated with dynamic CT and Doppler US. We compared the enhancement and the color flow patterns with the histopathological subtypes. RESULTS: Eighty-seven (95.6%) of 91 clear cell carcinomas showed rich enhancement in the cortical nephrographic phase (CNP) and 82 (90.1%) of them had color flow in the Doppler US. Of the total of 110 tumors, nine (8.1%) did not show color flow in spite of rich enhancement in the CNP. Conversely, eight (7.2%) of the 110 tumors showed color flow in spite of poor enhancement, including two chromophobe cell carcinomas and two metastatic renal tumors. CONCLUSIONS: The enhancement pattern in dynamic CT and the color flow pattern in Doppler US were different among the subtypes of RCC. Color Doppler US had diagnostic accuracy equal to dynamic CT in most patients with renal solid tumors. Although Doppler US may play a unique role in the diagnosis of some renal parenchymal solid tumors, it is sufficient to perform dynamic CT alone for diagnosis of clear cell carcinoma.

Adenocarcinoma, Clear Cell↗

Treatment of invasive bladder cancer: lessons from the past and perspective for the future.

Radical cystectomy with lymphadenectomy is the gold standard for treatment of invasive bladder cancer. However, the treatment alone does not always provide a satisfactory result for the disease extending outside the bladder. In this review we discuss several clinical issues in the diagnosis and treatment of this invasive disease. Although the quality of diagnostic imaging modalities has improved, they are still not sensitive enough for the staging of the disease, especially for early invasive disease. In addition, lack of serum markers hinders appropriate monitoring of patients with the disease. Regarding the surgical aspect of lymphadenectomy, the area of its dissection, the standard number of nodes retrieved and the method of pathological examination should be established so that the clinical benefits of surgery can be more clearly defined. Neoadjuvant chemotherapy for invasive disease is promising for improvement of survival of patients. A chemotherapy regimen as effective as, but less toxic than, MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) has been reported and several phase III clinical trials have been launched to determine the benefits of adjuvant or neoadjuvant chemotherapy with newly developed agents. However, we still lack a chemotherapy regimen more effective than MVAC, which is the most crucial issue in the treatment of this invasive disease. An alternative option for such disease may be bladder preservation with transurethral resection of tumor followed by chemoradiotherapy. However, patients who are indicated for this treatment may be limited to those with early invasive disease having certain favorable clinical and pathological features.

Antineoplastic Combined Chemotherapy Protocols↗

Vascular endothelial growth factor165 resolves glomerular inflammation and accelerates glomerular capillary repair in rat anti-glomerular basement membrane glomerulonephritis.

Vascular endothelial growth factor (VEGF) is essential for maintenance of the glomerular capillary network. The present study investigated the effects of VEGF in rats with progressive crescentic glomerulonephritis (GN). Necrotizing and crescentic GN was induced in rats by injection of anti-rat glomerular basement membrane (GBM) antibody. The alterations of glomerular capillaries and glomerular VEGF expression were assessed. In addition, the effects of continuous VEGF165 administration (10 microg/100 g per d) on glomerular capillaries, glomerular inflammation, and the course of crescentic GN were examined. The appropriate timing of VEGF administration in progressive GN also was evaluated. In anti-GBM GN, necrotizing and crescentic glomerular lesions occurred by day 7, and newly formed necrotizing lesions reoccurred by week 3. Expression of VEGF was markedly reduced in necrotizing and crescentic lesions. Capillary repair was impaired after capillary destruction in necrotizing and crescentic glomeruli, which rapidly progressed to sclerotic glomeruli with chronic renal failure. In contrast, in the rats that received VEGF165 administration from day 7, the necrotizing and crescentic lesions recovered and renal function significantly improved in week 4. This was evident by proliferating endothelial cells and glomerular capillary repair. In addition, VEGF administration decreased intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 expression in glomeruli (particularly on endothelial cells), reduced glomerular infiltrating CD8-postive and ED-1-positive cells, and inhibited the newly formed necrotizing lesions. VEGF administration was apparently effective against both the inflammatory and necrotizing glomerular lesions. These results suggest that VEGF administration resolves glomerular inflammation and accelerates glomerular recovery in the progressive necrotizing and crescentic GN. The therapeutic application of VEGF may be clinically useful for severe GN accompanied by extensive glomerular inflammation and endothelial injury.

Animals↗

Microscopic polyangiitis presenting with liver dysfunction preceding rapidly progressive necrotizing glomerulonephritis.

The authors describe a 52-year-old woman diagnosed with microscopic polyangiitis. She presented with abnormal liver function tests accompanied by fever, headache, and fatigue. Two months later, rapidly progressive necrotizing glomerulonephritis developed together with seropositivity for perinuclear antineutrophil cytoplasmic antibody. Although liver dysfunction from microscopic polyangiitis is very rare, especially at presentation, this diagnostic possibility should be kept in mind to permit prompt consideration of steroid therapy.

Antibodies, Antineutrophil Cytoplasmic↗

Predictive value of urinary micro-cholesterol (mCHO) levels in patients with progressive glomerular disease.

BACKGROUND: Trace amounts of lipids are present in the urine of patients with glomerular disease, raising the possibility that the excess lipids reabsorbed by tubule cells may be toxic to these cells. In the present study, we assessed the prognostic value of micro-cholesterol (mCHO) levels in patients with chronic glomerular disease. METHODS: The urinary mCHO levels of healthy subjects and patients with chronic kidney disease were measured by the enzymatic cholesterol cycling (ECC) method with a minimum detection level of 0.10 x 10(-3) mmol/L. First, the urinary mCHO levels of healthy subjects and 320 patients with various glomerular diseases with proteinuria >1000 mg/gCr were measured. Second, correlations of urinary mCHO levels with those of various other molecules, including albumin, IgG, IgM, transferrin, phospholipid, alpha1-microglobulin (alpha1MG), Apo A1, Apo A2, and Apo B, and urinary fatty body counts, were determined. Third, urinary mCHO, total protein (TP), albumin, and N-acetyl-beta-D-glucosaminidase (NAG) levels were measured longitudinally over 12 months (20.5 +/- 5.8 months) in 68 nondiabetic patients with impaired renal function [serum creatinine (Cr) > or = 1.5 mg/dL]. Correlations of the concentrations of urinary parameters in the initial 3-month period with the slopes of the reciprocal of creatinine versus time for the entire follow-up period were assessed by the ROC method and multiple regression analysis. RESULTS: Urinary mCHO levels of the healthy subjects were 0.06 to 0.72 mg/gCr for males and 0.16 to 2.34 mg/gCr for females. Urinary mCHO levels in subjects with minimal change nephrotic syndrome were significantly lower than those in the patients with other glomerular diseases with massive proteinuria. Urinary mCHO levels correlated significantly with Apo A1 and Apo A2 levels, but not with urinary Apo B levels, in the latter subjects. The correlation coefficient of urinary fatty body counts (a marker of lipoprotein loading tubulopathy) with mCHO was higher than those with TP, albumin, IgG, IgM, and alpha1MG. The urinary mCHO elevation was significantly greater in patients who had a nonselective index of proteinuria than in those with a highly or moderately selective index. In nondiabetic patients with impaired renal function, the urinary mCHO level had a higher predictive value for rapid decline of renal function than TP, albumin, or NAG. CONCLUSION: The urinary cholesterol level corresponds to the magnitude of urinary HDL excretion, and correlates with the degree of lipoprotein loading tubulopathy. Measurement of urinary mCHO by the ECC method is a simple and useful tool for predicting progression of chronic glomerular disease.

Acetylglucosaminidase↗

The expression of src-suppressed C kinase substrate (SSeCKS) and uptake of exogenous particles in endothelial and reticular cells.

Src-suppressed C kinase substrate (SSeCKS), a potent tumor suppressor, plays a role in membrane-cytoskeletal remodeling to regulate mitogenesis, cell differentiation, and motility. Our previous study showed that lipopolysaccharide (LPS) induced a selective and strong expression of SSeCKS in the vascular endothelial cells of several organs, such as hepatic sinusoids, and in the reticular cells of lymphoid organs. In the present immunocyto-chemical study, we determined the detailed cellular and subcellular localization of SSeCKS in mouse tissues after LPS administration, and examined the involvement of SSeCKS in the uptake of exogenous particles. SSeCKS immunoreactivity in the liver and lymph nodes was below the detectable level under normal conditions. After LPS stimulation, an intense immunoreactivity for SSeCKS became noticeable in sinusoidal endothelial cells of the liver and medullary reticular cells of the lymph node. Electron-microscopically, the immunoreactivity was localized predominantly along the cytoplasmic membrane of both cell types. These cells in normal mice incorporated a small amount of injected particles (carbon particles and latex beads), while after LPS stimulation, the uptake of particles increased in terms of the amount and extent of the uptaking sites. Endothelial cells and reticular cells without SSeCKS expression could not incorporate any particles even after LPS stimulation. The subcellular localization of SSeCKS in endothelial cells correlated with some pinocytic pits and phago-lysosomes, although a diffuse distribution of SSeCKS in the cytoplasm was also visible. Taken together, these findings indicate that SSeCKS expression in endothelial cells and reticular cells is a functional index of the reticulo-endothelial system and is involved in the uptake of particles from blood and lymph circulation.

A Kinase Anchor Proteins↗

Adrenocortical responses to tumor necrosis factor-alpha and interferon-gamma in cattle.

The responses of plasma cortisol and adrenocorticotropic hormone (ACTH) were examined to intravenous injection of recombinant bovine tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (INF-gamma) in Holstein cows. INF-gamma induced dose-dependent rises in the plasma levels of both cortisol and ACTH, while TNF-alpha induced comparable plasma cortisol responses with much smaller rises in plasma ACTH. The results suggest a direct stimulatory action of TNF-alpha on cortisol secretion from the adrenal gland in cattle.

Adrenal Cortex↗

Thymic transplantation in miniature swine: III. Induction of tolerance by transplantation of composite thymokidneys across fully major histocompatibility complex-mismatched barriers.

BACKGROUND: This study determines whether composite thymokidney (TK) grafts, created by implantation of autologous thymic tissue beneath the donor's renal capsule before transplantation, could induce allogeneic transplantation tolerance across two-haplotype fully major histocompatibility complex (MHC)- mismatched barriers in juvenile MGH-miniature swine. METHODS: TK grafts were prepared by implanting autologous thymic tissue under the renal capsule of donor animals 2 to 3 months before transplantation. Four recipients were treated with a T-cell-depleting immunotoxin and received fully MHC-mismatched TK grafts plus a 12-day course of cyclosporine A (CsA). Control animals were treated with CsA alone or both CsA and immunotoxin, but with a normal kidney or a kidney implanted with autologous lymph node rather than thymus. Renal graft function was assessed by plasma creatinine levels and histologic analyses. Immunologic status was monitored by cell-mediated lympholysis assays. RESULTS: All four recipients of fully MHC-mismatched TK transplants treated with immunotoxin and a 12-day course of CsA accepted their composite renal allografts long-term. All control recipients receiving a TK and CsA alone, a normal kidney or a composite kidney containing lymph node tissue acutely rejected their grafts. CONCLUSIONS: To our knowledge, this is the first demonstration that functional vascularized thymic grafts can induce transplantation tolerance across fully MHC-mismatched barriers in a large animal model.

Animals↗