Search PubMed⌕ Search

Biomedical subjects

Takashi Harada

Publications and source records attributed to Takashi Harada.

At least 37 records · Page 2Linked to original sources
PubMed2004

A clinical study on serum prostaglandin E2 with low-level laser therapy.

METHODS: The subjects of this investigation consisted of 83 female patients that were treated in this department during the 2-year period from January 1999 to December 2002. Laser irradiation was applied for 3 min either every day or every other day for a total of 10 times. A diode semi-conductor laser with a wavelength of 830 nm and a photointensity of 1 W was used. Evaluations were performed before and after the series of 10 exposures to laser irradiation. The evaluation included the measurement of pain using the visual analog scale (VAS) and serum prostaglandin E(2) (pg/mL) measured by RIA-PEG. RESULTS: The analgesic effects were observed in 67 of 83 cases, or 80.7%. The VAS scores for the effective cases decreased after the irradiation series from 8.5 +/- 0.2, to 2.8 +/- 0.2 ( p < 0.001). The post-irradiation PGE(2) levels were lower than the pre-irradiation PGE(2) levels in the effective cases, which were 5.8 +/- 0.3 and 7.1 +/- 0.4 pg/mL, respectively ( p < 0.05). The postirradiation PGE(2) levels for the effective cases were lower than those for the ineffective cases, which were 5.8 +/- 0.3 and 7.3 +/- 0.9 pg/mL, respectively ( p < 0.05). CONCLUSIONS: Based on the above findings, the analgesic effects of LLLT were found to be valid. The serum PGE(2) levels are therefore considered to directly reflect nociceptive pain.

Adult↗
PubMed2004

TNP-470, an angiogenesis inhibitor, suppresses the progression of peritoneal fibrosis in mouse experimental model.

BACKGROUND: In patients on long-term peritoneal dialysis (PD), angiogenesis and vasculopathy are observed in the peritoneum, and the degree of vascularization correlates with the area of fibrotic tissue, suggesting the involvement of angiogenesis in the progression of peritoneal fibrosis. The aim of the present study was to evaluate the effect of TNP-470, an anti-angiogenic compound, on the development of peritoneal fibrosis induced by chlorhexidine gluconate (CG). METHODS: Peritoneal fibrosis was induced by injection of CG into peritoneal cavity of Institute for Cancer Research (ICR) mice. TNP-470 was injected subcutaneously with CG. Mice were sacrificed, and peritoneal tissues were dissected out at days eight and 16 after CG and TNP-470 injection. The expression patterns of CD31 (as a marker of endothelial cells), vascular endothelial cell growth factor (VEGF), alpha-smooth muscle actin (as a marker of myofibroblasts), heat shock protein 47 (HSP47), type III collagen, F4/80 (as a marker of mice macrophages), proliferating cell nuclear antigen (PCNA), and cyclin-dependent kinase 2 (Cdk2) were examined by immunohistochemistry. RESULTS: CG-injected mice showed thickening of the submesothelial zone and increased number of vessels, myofibroblasts, and infiltrating macrophages. The expression levels of VEGF, type III collagen, and HSP47 were increased, and a large number of PCNA-positive cells and Cdk2-expressing cells were observed in the thickened submesothelial area. Treatment with TNP-470 suppressed the submesothelial zone thickening and reduced collagen III expression as well as angiogenesis. TNP-470 also decreased the number of VEGF-expressing cells, myofibroblasts, macrophages, PCNA-positive cells, and Cdk2-expressing cells. CONCLUSION: Our results indicate the involvement of angiogenesis in the progression of peritoneal fibrosis, and suggest that TNP-470 may be potentially useful for the prevention of peritoneal fibrosis through inhibition of angiogenesis and suppression of myofibroblast proliferation.

Actins↗
PubMed2004

Synthesis and characterization of a native, oligomeric form of recombinant severe acute respiratory syndrome coronavirus spike glycoprotein.

We have expressed and characterized the severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein in cDNA-transfected mammalian cells. The full-length spike protein (S) was newly synthesized as an endoglycosidase H (endo H)-sensitive glycoprotein (gp170) that is further modified into an endo H-resistant glycoprotein (gp180) in the Golgi apparatus. No substantial proteolytic cleavage of S was observed, suggesting that S is not processed into head (S1) and stalk (S2) domains as observed for certain other coronaviruses. While the expressed full-length S glycoprotein was exclusively cell associated, a truncation of S by excluding the C-terminal transmembrane and cytoplasmic tail domains resulted in the expression of an endoplasmic reticulum-localized glycoprotein (gp160) as well as a Golgi-specific form (gp170) which was ultimately secreted into the cell culture medium. Chemical cross-linking, thermal denaturation, and size fractionation analyses suggested that the full-length S glycoprotein of SARS-CoV forms a higher order structure of approximately 500 kDa, which is consistent with it being an S homotrimer. The latter was also observed in purified virions. The intracellular form of the C-terminally truncated S protein (but not the secreted form) also forms trimers, but with much less efficiency than full-length S. Deglycosylation of the full-length homotrimer with peptide N-glycosidase-F under native conditions abolished recognition of the protein by virus-neutralizing antisera raised against purified virions, suggesting the importance of the carbohydrate in the correct folding of the S protein. These data should aid in the design of recombinant vaccine antigens to prevent the spread of this emerging pathogen.

Animals↗
PubMed2004

[A case of tinea capitis with a couple of nodular lesions possibly resulting from topical application of tacrolimus].

We herein report a case of tinea capitis initially showing a couple of nodular lesions. The patient was a 66-year-old woman who had seen a nearby dermatologist for itching on her head and had been treated with a topical steroid followed by tacrolimus application for one month. Because pseudolymphoma-like erythematous nodules developed at two sites, she visited us. Two weeks after stopping all medication, some slight scaling was found around these nodules. On KOH direct microscopic examination, many filamentous elements around hair shafts were observed. Biopsy of the nodules confirmed the destruction of hair follicles surrounded by granulomatous inflammation histologically. Grocott staining of the same specimen revealed a few short fungal hyphae as well as spores. She was also diagnosed as tinea pedis by direct microscopic examination of her feet. Trichophyton rubrum was isolated from scales of both her head and feet on Sabouraud's dextrose agar at 25 degrees C. Kerion celsi (KC) is usually clinically preceded by a gray patch or black dots. Such a typical course of KC, however, was not observed in our patient. Tacrolimus was thought to have possibly played an important role in modifying tinea capitis.

Administration, Topical↗
PubMed2004

[A case of chronic renal insufficiency due to vascular injury of systemic sclerosis].

A 48-year-old woman with systemic sclerosis (SSc) and rheumatoid arthritis was admitted to our hospital because of renal dysfunction. She had no hypertension at the time of admission and mild hypertension for only one and a half months until the time of admission. After admission, she received angiotensin-converting enzyme-inhibitor, but her renal dysfunction did not improve. She then had thrombotic microangiopathy with thrombocytopenia, and was treated with plasma exchange five times, but her renal dysfunction persisted. The renal biopsy specimens showed an arteriosclerotic lesion with intimal thickening and luminal narrowing and ischemic glomerular changes. These findings suggest that there is chronic vascular injury in a patient who has no hypertension with SSc and that once hypertension supervenes, whether severe or not, exacerbation of the vascular injury and renal dysfunction may occur.

Arthritis, Rheumatoid↗
PubMed2003

Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome.

Kindler syndrome is an autosomal recessive disorder characterized by neonatal blistering, sun sensitivity, atrophy, abnormal pigmentation, and fragility of the skin. Linkage and homozygosity analysis in an isolated Panamanian cohort and in additional inbred families mapped the gene to 20p12.3. Loss-of-function mutations were identified in the FLJ20116 gene (renamed "KIND1" [encoding kindlin-1]). Kindlin-1 is a human homolog of the Caenorhabditis elegans protein UNC-112, a membrane-associated structural/signaling protein that has been implicated in linking the actin cytoskeleton to the extracellular matrix (ECM). Thus, Kindler syndrome is, to our knowledge, the first skin fragility disorder caused by a defect in actin-ECM linkage, rather than keratin-ECM linkage.

Abnormalities, Multiple↗
PubMed2003

Detection of nuclear factor-kappaB in IgA nephropathy using Southwestern histochemistry.

BACKGROUND: The transcription factor nuclear factor-kappaB (NF-kappaB) is involved in inflammatory and immune responses through induction of various cytokines and growth factors. The aim of this study is to examine the correlation between NF-kappaB expression and severity of tissue injury in immunoglobulin A (IgA) nephropathy and the mechanism of such correlation. METHODS: The study included 43 renal tissue samples from 28 patients, including 28 samples of IgA nephropathy, 5 samples of non-IgA mesangial proliferative glomerulonephritis (non-IgA nephropathy), and 10 samples with nonproliferative glomerulonephritis (membranous nephropathy [MN] n = 5; minimal change nephrotic syndrome [MCNS]; n = 5). Tissue sections were examined by Southwestern histochemistry and immunohistochemistry for monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and intercellular cell adhesion molecule-1 (ICAM-1), which are regulated by NF-kappaB. Normal portions of surgically resected kidney with adenocarcinoma served as controls. RESULTS: In normal kidney, MCNS, and MN sections, NF-kappaB expression was detected in a few mesangial cells and tubular epithelial cells. In IgA nephropathy and non-IgA nephropathy samples, NF-kappaB was expressed in mesangial, glomerular endothelial and epithelial cells, tubular epithelial cells, and infiltrating cells. Expression in both glomeruli and interstitium correlated with progression of tissue injury. In IgA nephropathy samples, MCP-1 and GM-CSF expression was increased in both glomeruli and interstitium and correlated with progression of tissue injury. Glomerular ICAM-1 expression was weaker in severe lesions, whereas interstitial expression correlated with progression of tissue injury. CONCLUSION: Our results indicate that NF-kappaB is involved in the progression of tissue injury in IgA nephropathy through the induction of transcriptionally regulated genes.

Adenocarcinoma↗
PubMed2003

Antisense oligonucleotides against collagen-binding stress protein HSP47 suppress peritoneal fibrosis in rats.

BACKGROUND: Peritoneal fibrosis is a serious complication in patients on continuous ambulatory peritoneal dialysis (CAPD), but the molecular mechanism of this process remains unclear. Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for biosynthesis and secretion of collagen molecules, and is expressed in the tissue of human peritoneal fibrosis. In the present study, we examined the effect of HSP47 antisense oligonucleotides (ODNs) on the development of experimental peritoneal fibrosis induced by daily intraperitoneal injections of chlorhexidine gluconate (CG). METHODS: HSP47 antisense or sense ODNs were injected simultaneously with CG from day 14, after injections of CG alone. Peritoneal tissue was dissected out 28 days after CG injection. The expression patterns of HSP47, type I and type III collagen, alpha-smooth muscle actin (alpha-SMA), as a marker of myofibroblasts, ED-1 (as a marker of macrophages), and factor VIII were examined by immunohistochemistry. RESULTS: In rats treated with CG alone, the submesothelial collagenous compact zone was thickened, where the expression levels of HSP47, type I and type III collagen and alpha-SMA were increased. Marked macrophage infiltration was also noted and the number of vessels positively stained for factor VIII increased in the CG-treated group. Treatment with antisense ODNs, but not sense ODNs, abrogated CG-induced changes in the expression of HSP47, type I and III collagen, alpha-SMA, and the number of infiltrating macrophages and vessels. CONCLUSION: Our results indicate the involvement of HSP47 in the progression of peritoneal fibrosis and that inhibition of HSP47 expression might merit further clinical investigation for the treatment of peritoneal fibrosis in CAPD patients.

Actins↗
PubMed2003

Effect of high glucose on nitric oxide production and endothelial nitric oxide synthase protein expression in human glomerular endothelial cells.

BACKGROUND: Hyperglycemia directly contributes to the development of diabetic nephropathy. Nitric oxide (NO), a potent endothelium-derived vasodilator, has been suggested to participate in the regulation of renal blood flow, glomerular filtration rate, and mesangial matrix accumulation. Human vascular endothelial cells are known to exhibit functional heterogeneity, this prompted us to do the first study of NO bioavailability in human glomerular endothelial cells (HGECs), in response to high glucose exposure. METHODS: NO release was examined by detecting nitrite generation by the Griess assay in HGECs exposed to control-level (5.5 mM) and high-level (15, 30 and 60 mM) glucose solutions at various time periods (24, 48 and 72 h) in the presence or absence of L-arginine (1 mM), or superoxide dismutase (SOD) (250 U/ml). In addition, we evaluated the effect of glucose on the expression of endothelial nitric oxide synthase (eNOS) in HGECs by Western blotting. RESULTS: Final levels of nitrite generated in HGECs were reduced significantly, in a time- and concentration-dependent manner, after high glucose exposure. However, Western blot analysis revealed that eNOS protein expression was significantly upregulated at 12 h after exposure to high glucose concentrations (30 mM), reaching a peak at 48 h (twofold increase over baseline levels). The inhibitory effect of high glucose on NO production was restored by the addition of SOD. Addition of L-arginine (1 mM) to external media also reversed the inhibitory effect of high glucose on NO production of HGECs as well. CONCLUSIONS: The present study demonstrated that high glucose increased eNOS protein expression, but decreased NO release finally. Decreased NO bioavailability seems to be associated with overproduction of superoxide and L-arginine deficiency. These findings provide an important clue in clarifying the molecular basis of the mechanisms by which elevated glucose leads to an imbalance between NO and superoxide, resulting in impaired endothelial function. In addition, restoration of NO function by both administration of L-arginine and adequate intake of antioxidants suggests a potential supportive treatment for patients with diabetic nephropathy.

Arginine↗
PubMed2003

Temperament, character, and eating attitudes in Japanese college women.

The present study investigated associations between dimensions of personality characteristics and eating attitudes in Japanese college women. 91 college women with a mean age of 20.7 yr. (SD=2.3 yr.), attending a School of Nursing or a School for Kindergarten Teachers, voluntarily responded to the Japanese version of the Temperament and Character Inventory and the Eating Attitudes Test. A significant positive correlation was found between the scores on the Temperament and Character Inventory subscale of Harm Avoidance and the Eating Attitudes Test total scores (Spearman p = .24, p = .02) and the scores on the Eating Attitudes Test subscale of Food Preoccupation (Spearman p = .33, p =.002). The scores on the Temperament and Character Inventory subscale of Self-directedness showed significant negative correlations with the Eating Attitudes Test total scores (Spearman p = -.35, p = .001) and the scores on the Eating Attitudes Test subscales of Dieting (Spearman p = -.29, p = .005) and Food Preoccupation (Spearman p = -.43, p = .0001). The present results suggest that Japanese college women who score high on Harm Avoidance and low on Self-directedness may be more likely to develop inappropriate eating attitudes.

Adult↗
PubMed2003

[Guidelines for clinical evaluation of topical antifungal agents].

The Japanese Society for Medical Mycology (JSMM) decided in 2002 to establish guidelines for the clinical evaluation of antifungal agents. The JSMM committee presents here guidelines for the clinical evaluation of topical antifungal agents in the dermatology field. Guidelines for the Clinical Evaluation of Antibiotic Agents established by the Japanese Society of Chemotherapy were referred to, and the diseases subjected to clinical evaluation include tinea (tinea pedis and tinea glabrosa), cutaneous candidiasis, and pityriasis versicolor. Among superficial mycoses, tinea pedis is viewed as the pivotal disease because it is intractable and is the most common. Therefore, the clinical efficacy of antifungal agents for external use in this condition should be established, and tinea pedis is subjected to phase III clinical studies. If efficacy of the antifungal agents is confirmed in the treatment of tinea pedis, a comparative study need not necessarily be performed for tinea glabrosa. If the number of patients is adequate for statistical analysis, a comparative study should be considered for both cutaneous candidiasis and pityriasis versicolor. However, if the number of patients is low, the efficacy of the agents should be evaluated based on their antifungal activity on pathogens and the results of open trials, and a comparative study is not necessarily performed for such diseases. The safety should be strictly evaluated.

Anti-Infective Agents, Local↗
PubMed2003

[Two cases of tinea capitis by Microsporum ferrugineum believed infected in Myanmar].

We report two cases of tinea capitis by Microsporum (M) ferrugineum. A two year old boy (case 1) visited our hospital 3 months after his return from Myanmar. About a year later, we observed the same symptom on the scalp of his mother (case 2). In both cases itraconazole was effective clinically and mycologically. In Japan, although M. ferrugineum was the most common organism of tinea capitis before the 1960s, no cases of tinea are found caused by this species nowdays. We believe these cases to have been infected in Myanmar, and suggest the possibility that tinea caused by M. ferrugineum may become a re-emergent infection or an imported fungal disease in Japan.

Adult↗
PubMed2002

Severe arteriolar lesion mimicking drug-induced arteriolopathy in a long-term surviving renal allograft.

We report severe arteriolar lesion mimicking drug-induced arteriolopathy in a renal allograft of a 37-year-old Japanese male, who has been treated by conventional immunosuppressive therapy but not administered cyclosporin or tacrolimus for 16 years after renal transplantation. Renal biopsy also showed glomerular changes including transplant glomerulopathy and features of chronic vascular rejection. The cause of the arteriolar lesion remains uncertain. Although its pathogenesis may be multi-factorial, long-term usage of conventional immunosuppressive agents and/or vascular rejection may contribute to the occurrence of the arteriolar lesion. We propose that biopsy study is needed for further understanding of histopathological behaviours of renal grafts in long-term survivors.

Adult↗
PubMed2002

Expression profiling of liver cell lines expressing entire or parts of hepatitis C virus open reading frame.

Although hepatitis C virus (HCV) is a causative agent of liver diseases, its mechanism of pathogenesis is still unclear, mainly because of the lack of adequate cell culture systems to support HCV infection and replication. In this report, we describe development and characterization of human hepatoma cell lines constitutively expressing entire (Hep394) or parts (Hep352, Hep3294) of the HCV open reading frame (ORF). The viral and cellular proteolytic machinery involved in the viral precursor processing was consistently functional, and processed HCV proteins were synthesized in these established cell lines. By using a cDNA microarray analysis coupled with semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), we identified 12 genes up-regulated and 4 genes down-regulated in Hep394 cells. With regard to genes related to cell growth regulation, we found up-regulation of forkhead transcription factor FREAC-1, poly (A) binding protein PABP2, and Ras suppressor Rsu-1. Another category of changes in gene expression includes MHC antigens, which play an important role in the T-cell-mediated immune reaction in the liver. In conclusion, functional genomic approaches comparing expression among the different cell lines expressing parts of the HCV genome may promote our understanding of the molecular basis of pathogenicity of HCV infection.

Carcinoma, Hepatocellular↗
PubMed2002

Acute renal failure in neuroleptic malignant syndrome.

We report a patient with neuroleptic malignant syndrome (NMS) who developed acute renal failure and was successfully treated by hemodialysis. A 60-year-old man with a 26-year history of schizophrenia had been treated with thioridazine and sulpiride. He was admitted to our hospital for muscular rigidity and oliguria. After the diagnosis of NMS with acute renal failure was established, thioridazine and sulpiride were discontinued and hemodialysis was instituted. Renal function gradually improved and hemodialysis was discontinued after 17th treatment. We also reviewed 57 cases of NMS with acute renal failure reported in the literature. To our knowledge, 26 years is the longest latency between initiation of neuroleptic drug treatment and onset of NMS. Our review of reported NMS cases with acute renal failure identified those risks for poor prognosis as high level of BUN, age and female gender.

Acute Kidney Injury↗