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Ken-ichi Harada

Publications and source records attributed to Ken-ichi Harada.

At least 19 recordsLinked to original sources
PubMed2006

Naked gene therapy of hepatocyte growth factor for dextran sulfate sodium-induced colitis in mice.

Ulcerative colitis (UC) is progressive and relapsing disease. To explore the therapeutic effects of naked gene therapy of hepatocyte growth factor (HGF) on UC, the SRalpha promoter driving HGF gene was intrarectally administered to the mice in which colitis was induced by dextran sulfate sodium (DSS). Expression of the transgene was seen in surface epithelium, lamina propria, and muscularis mucosae. The HGF-treated mice showed reduced colonic mucosal damage and increased body weights, compared with control mice (P < 0.01 and P < 0.05, respectively). The HGF-treated mice displayed increased number of PCNA-positive cells and decreased number of apoptotic cells than in control mice (P < 0.01, each). Phosphorylated AKT was dramatically increased after HGF gene administration, however, phosphorylated ERK1/2 was not altered. Microarray analysis revealed that HGF induced expression of proliferation- and apoptosis-associated genes. These data suggest that naked HGF gene delivery causes therapeutic effects through regulation of many downstream genes.

Animals↗
PubMed2006

Degradation of microcystins using immobilized microorganism isolated in an eutrophic lake.

The final purpose of our series of studies is to establish a biological removal method of cyanobacteria and their toxic products using immobilized microorganisms that can lyse cyanobacteria and decompose microcystins. To establish the biological removal method in non-point areas and water purification plants, as the first step, we explored bacteria active against the cyanobacterial hepatotoxin microcystin in the present study. Eleven active bacteria were isolated from samples taken from Lakes Tsukui and Sagami, Japan. Among 3 strains (B-9 to B-11) with degradative activity, strain B-9 exhibited the strongest activity. The 16S rDNA sequence of the strain B-9 showed the highest similarity to that of Sphingomonas sp. Y2 (AB084247, 99% similarity). Microcystins-RR and -LR were completely degraded by strain B-9 (SC16) within 1d, which led to an immobilized microorganism with a polyester resin. The degradation of microcystin-RR in a bioreactor using the immobilized strain B-9 was observed and microcystin-RR (> 90%) was completely degraded after 24 h. Microcystin-RR was added to the lake water at regular intervals and the degradation after 24 h was observed in the bioreactor over a 72-d period. An over 80% removal efficiency continued for 2 months, showing that the life of the immobilized B-9 in terms of activity was at least 2 months under the optimized conditions. From these results, this immobilized B-9 is feasible for the practical treatment of microcystins in non-point areas and water purification plants.

Bacteria↗
PubMed2006

Radiofrequency ablation of small breast cancer followed by surgical resection.

BACKGROUND: With the growing demand from patients for less-invasive procedures, the shift from surgical extirpation to ablative local control of breast tumors is an emerging focus in breast cancer care. This study was performed to determine the feasibility and safety of treating small breast cancer with radiofrequency (RF) ablation. METHODS: Patients with biopsy-proven invasive or non-invasive breast cancer underwent RF ablation under general anesthesia. Before RF ablation, all patients were confirmed to have a localized lesion using imaging modalities. Wide excision or total mastectomy with sentinel lymph node biopsy or axillary lymph node dissection was performed. The resected tumor was examined histologically with hematoxylin-eosin (H&E) and nicotinamide adenine dinucleotide-diaphorase (NADH) staining. RESULTS: Ten patients completed the treatment without RF ablation-related complications. The mean tumor size was 1.1 cm (range: 0.5-2.0 cm). Histological evaluation of the ablated tissue using H&E staining revealed a spectrum of changes ranging from complete coagulation necrosis of tumor cells to normal-appearing tumor cells. However, NADH-diaphorase showed no staining of viable tumor cells in the RF-ablated region in all of the patients. CONCLUSIONS: RF ablation is promising as a minimally invasive ablation technique in the local treatment of invasive or non-invasive breast cancer. However, further study is necessary before RF ablation can replace conventional breast conservation therapy for patients with small breast cancer.

Adult↗
PubMed2006

Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam and quazepam.

OBJECTIVE: Grapefruit juice (GFJ) inhibits cytochrome P450 (CYP) 3A4 in the gut wall and increases blood concentrations of CYP3A4 substrates by the enhancement of oral bioavailability. The effects of GFJ on two benzodiazepine hypnotics, triazolam (metabolized by CYP3A4) and quazepam (metabolized by CYP3A4 and CYP2C9), were determined in this study. METHODS: The study consisted of four separate trials in which nine healthy subjects were administered 0.25 mg triazolam or 15 mg quazepam, with or without GFJ. Each trial was performed using an open, randomized, cross-over design with an interval of more than 2 weeks between trials. Blood samples were obtained during the 24-h period immediately following the administration of each dose. Pharmacodynamic effects were determined by the digit symbol substitution test (DSST) and utilizing a visual analog scale. RESULTS: GFJ increased the plasma concentrations of both triazolam and quazepam and of the active metabolite of quazepam, 2-oxoquazepam. The area under the curve (AUC)(0-24) of triazolam significantly increased by 96% (p<0.05). The AUC(0-24) of quazepam (+38%) and 2-oxoquazepam (+28%) also increased; however, these increases were not significantly different from those of triazolam. GFJ deteriorated the performance of the subjects in the DSST after the triazolam dose (-11 digits at 2 h after the dose, p<0.05), but not after the quazepam dose. Triazolam and quazepam produced similar sedative-like effects, none of which were enhanced by GFJ. CONCLUSION: These results suggest that the effects of GFJ on the pharmacodynamics of triazolam are greater than those on quazepam. These GFJ-related different effects are partly explained by the fact that triazolam is presystemically metabolized by CYP3A4, while quazepam is presystemically metabolized by CYP3A4 and CYP2C9.

Adult↗
PubMed2006

Clinicopathological features of recurrence after radical cystectomy for patients with transitional cell carcinoma of the bladder.

BACKGROUND: The objective of this study was to investigate the clinicopathological features of recurrent transitional cell carcinoma (TCC) of the bladder in patients who had previously undergone radical cystectomy. MATERIALS AND METHODS: This study included 124 patients who underwent radical cystectomy for transitional cell carcinoma (TCC) of the bladder in our institution. Several clinicopathological factors were analyzed to characterize differences between patients with and without disease recurrence, and determined predictive factors for disease recurrence using multivariate analysis. We further analyzed prognostic parameters that affect survival after disease recurrence was diagnosed. RESULTS: Of the 124 patients, 24 (19.5%) developed recurrence, and the median time to recurrence was 9.5 months (range, 1-44 months). The 5-year recurrence-free survival in these 124 patients was 75.6%. The incidence of disease recurrence was significantly associated with gender, pathological stage, lymph node metastasis, lymphatic invasion and blood vessel invasion. Multivariate analysis identified gender, pathological stage and lymph node metastasis as independent predictors of disease recurrence following radical cystectomy. After disease recurrence, the 1-year cancer-specific survival of the 24 patients was 16.7%; that is, 23 of the 24 patients had died of progressive recurrent diseases, while the remaining 1 who survived had developed recurrence in the upper urinary tract. CONCLUSIONS: These findings suggest that careful follow-up should be performed after radical cystectomy for TCC of the bladder considering gender, pathological stage and nodal involvement; however, once recurrent disease develops, the prognosis of such patients is extremely poor. Therefore, it would be potentially important to establish a multimodal therapeutic approach targeting recurrent TCC of the bladder.

Aged↗
PubMed2006

Transvalencin Z, a new antimicrobial compound with salicylic acid residue from Nocardia transvalensis IFM 10065.

Transvalencin Z was isolated from a culture broth of Nocardia transvalensis IFM 10065, a clinical isolate from a Japanese patient with actinomycotic mycetoma. The transvalencin Z structure was determined using NMR and mass spectrometric analyses. The structure is similar to a partial structure of siderophores such as mycobactins and nocobactins, but the compound has no cytotoxic activity. Transvalencin Z shows a strong antimicrobial activity against Gram-positive bacteria, but shows no activity against Gram-negative bacteria, fungi and tumor cells.

Anti-Bacterial Agents↗
PubMed2006

Analysis of differences in clinicopathological features between prostate cancers located in the transition and peripheral zones.

BACKGROUND: The objective of this study was to retrospectively characterize differences in the clinicopathological features of prostate cancer according to the zonal origin. METHODS: Among 185 consecutive patients who underwent radical prostatectomy without any neoadjuvant hormonal therapies, this study included 134 patients who were diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer according to the following criteria: TZ or PZ cancers were considered when more than 70% of the cancer area was located in the TZ or PZ, respectively. The various clinicopathological features were then compared according to this classification. RESULTS: In this series, 27 patients were diagnosed as having TZ cancer, while the remaining 107 were diagnosed as having PZ cancer. The percent of positive biopsy cores in TZ cancers was significantly lower than that in PZ cancers; however, there were no significant differences in the anatomical location of positive cores between these two groups except for the middle of prostate where TZ cancer showed a significantly lower rate of positive biopsies than PZ cancer. The preoperative serum prostate-specific antigen (PSA) value in patients with TZ cancer was significantly higher than that in those with PZ cancer. Furthermore, tumor volume in TZ cancers was significantly greater than that in PZ cancers. However, there was no significant difference in biochemical recurrence-free survival between patients with TZ and PZ cancers. CONCLUSIONS: Despite the significantly high PSA value as well as great tumor volume compared with those of PZ cancers, TZ cancers had similar biochemical cure rates following radical prostatectomy, suggesting a less aggressive phenotype of TZ cancers than that of PZ cancers.

Aged↗
PubMed2006

Reconstruction of urinary tract combined with surgical management of locally advanced non-urological cancer involving the genitourinary organs.

INTRODUCTION: The objective of this study was to review our experience with urinary reconstruction in patients undergoing surgical management for locally advanced pelvic cancer, and to evaluate the role of urologists in these procedures. MATERIALS AND METHODS: This study included a total of 37 patients undergoing some type of urinary reconstruction due to invasion of the urological organs by locally advanced pelvic cancers, including 17 rectal cancers, 9 cervical cancers, 4 sigmoid cancers, 4 retroperitoneal sarcomas, 2 ovarian cancers and 1 appendiceal cancer. Among these 37, 18 were recurrent cancers following initial surgery for primary tumors. The clinical outcomes of these approaches were retrospectively analyzed. RESULTS: Of the 37 patients, 9 underwent cystectomy (group A) with the following urinary diversions: ileal neobladder in 3, ileal conduit in 5 and colon conduit in 1, and 12 underwent partial cystectomy (group B), among whom 11 received additional urinary reconstruction as follows: bladder flap repair in 5, psoas hitch in 2, ileal ureter in 2, bladder augmentation in 1 and ureteroureterostomy in 1, while the remaining 16 (group C), in whom complete bladder preservation was possible, underwent the following types of urinary reconstruction: bladder flap repair in 6, psoas hitch in 3, en bloc removal of the rectum with prostate in 3, ileal ureter in 2, and ureteroureterostomy in 2. There were 10 early urological complications, including leakage of urine in 7 and acute pyelonephritis in 3. As a late urological complication, hydronephrosis was observed in 8 patients, but ureteral stent was not required in any of these 8. There were no significant differences in the incidence of postoperative complications, the status of surgical margin and the survival among groups A-C. CONCLUSION: Our experience with extended surgical management of non-urological pelvic cancer with reconstruction of the urinary tract suggests that the urological portion of this procedure can be performed with acceptable morbidity, and that the role of the urological surgeon during this procedure is potentially important.

Adult↗
PubMed2006

Usefulness of the nadir value of serum prostate-specific antigen measured by an ultrasensitive assay as a predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer.

INTRODUCTION: The objective of this study was to determine whether the nadir value of serum prostate-specific antigen (PSA) measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: This study included 127 patients who underwent radical prostatectomy for clinically localized prostate cancer without neoadjuvant hormonal therapy and were pathologically diagnosed as negative for lymph node metastasis. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and the findings were analyzed with respect to several clinicopathological factors. In this series, biochemical recurrence was defined as PSA persistently >0.2 ng/ml. RESULTS: Based on the nadir PSA value, we divided 127 patients into three groups as follows: group A (n=99): or=0.05 ng/ml. The nadir PSA value was significantly associated with preoperative PSA value, but not other conventional clinicopathological prognostic parameters. During the observation period (median 31 months, range 6-75 months), biochemical recurrence occurred in 16 patients, that is, 1 in group A (6.3%), 4 in group B (25.0%), and 11 in group C (91.7%). Multivariate analysis using the Cox proportional hazards regression model indicated that the nadir PSA value was an independent predictor for biochemical recurrence after radical prostatectomy. CONCLUSION: These findings suggest that the nadir serum PSA value measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer, and that careful follow-up should be considered in cases demonstrating a nadir PSA value>0.01 ng/ml because of the significantly higher probability of biochemical recurrence in such cases.

Aged↗
PubMed2006

Melophlins P, Q, R, and S: four new tetramic acid derivatives, from two Palauan marine sponges of the genus Melophlus.

Four new tetramic acid derivatives, named melophlins P, Q, R, and S (1-4), were isolated from two marine sponges of the genus Melophlus collected at Palau, together with seven known melophlins A, D, E, G, H, I, and O. The structures of the new compounds were elucidated on the basis of their spectral data. The absolute stereochemistries at the tetramic acid moieties of the new compounds were determined as 1 : 1 mixtures (racemic) by ESI-LC/MS analysis of derivatives obtained by oxidation and hydrolysis of the respective parent compounds. Melophlins P-S (1-4) showed cytotoxicity against the murine leukemia cell line L1210 with IC(50) values of 20.0, 10.5, 0.85, and 5.13 microM, respectively.

Animals↗
PubMed2005

Electromagnetically induced diffraction in sodium vapor.

By using a sodium atomic vapor we have observed a honeycomb-type multiple-diffraction pattern that was due to a grating induced optically by three noncollinear bichromatic excitation beams. In particular, when the two incident frequencies satisfy the two-photon resonance condition and the atomic density is high, the diffraction is enhanced by electromagnetically induced transparency, and strong Stokes and anti-Stokes components are generated in well-defined directions.

Journal Article↗
PubMed2005

Clinicopathological features of prostate cancer in Japanese men diagnosed on repeat transrectal ultrasound-guided biopsy.

BACKGROUND: The objective of this study was to analyze the clinicopathological features of prostate cancer detected on repeat transrectal ultrasound-guided random biopsy in comparison with those detected on initial biopsy. METHODS: Between January 1999 and March 2004, 132 Japanese men underwent radical retropubic prostatectomy without neoadjuvant therapy at our institution. In 109 patients (group A) prostate cancer was detected on initial biopsy, while in the remaining 23 (group B), it was diagnosed on repeat biopsy. We retrospectively characterized differences in clinicopathological features between these two groups. RESULTS: There were no significant differences in age, serum prostate specific antigen (PSA) value, or biopsy Gleason score between groups A and B. However, prostate volume in group A was significantly smaller than that in group B, while PSA density, the percentage of positive biopsy cores, and the percentage of cancers in the biopsy set in group A were significantly higher than those in group B. Pathological examination of the radical prostatectomy specimens showed that there were no significant differences in the distribution of pathological T stage or in the Gleason score; or in the incidences of lymphatic invasion, vascular invasion, and perineural invasion between groups A and B. Despite there being a significantly larger tumor volume in the radical prostatectomy specimens in group A compared to that in group B, there was no significant difference in the incidence of insignificant disease between these two groups. CONCLUSION: These findings suggest that missing the cancer on the initial needle biopsy may be due to a small cancer focus in a large prostate; however, there were no significant differences in the final pathological features of prostate cancers detected on the initial and repeat biopsies, suggesting similar biological behaviors. Thus performance of a repeat biopsy in cases negative for malignancy on the initial biopsy is advocated. Missing prostate cancer on the initial biopsy may be due to a small cancer focus in a large prostate; however prostate cancers detected on initial and repeat biopsies may have similar biological behavior.

Aged↗
PubMed2005

Clinical outcome of combined immunotherapy with low-dose interleukin-2 and interferon-alpha for Japanese patients with metastatic renal cell carcinoma who had undergone radical nephrectomy: a preliminary report.

BACKGROUND: The objective of this study was to evaluate the clinical outcome of combined immunotherapy with interferon-alpha (IFN-alpha) and low-dose interleukin-2 (IL-2) for Japanese patients with metastatic renal cell carcinoma (RCC) who had undergone radical nephrectomy. METHODS: This study included 13 patients who were diagnosed as having metastatic RCC following radical nephrectomy. These patients received a subcutaneous injection of IFN-alpha (6 x 10(6) IU per day) three times per week and an intravenous injection of IL-2 (1.4 x 10(6) IU per day) twice per week. Tumor response was evaluated every 16 weeks, and as a rule, this weekly regimen was repeated 50 times in patients with evidence of objective response or stable disease. RESULTS: One of the 13 patients dropped out because of severe toxicity; hence, 12 patients were evaluable, with a median follow-up period of 18 months after the start of this combined therapy. Six patients (50.0%) achieved objective responses, with 1 complete response (CR), while only 2 (16.7%) demonstrated progressive disease. The median duration of response in the 6 responders was 13.5 months. Toxicity associated with this combined immunotherapy was limited to WHO grade 1 or 2 in these 12 patients. All patients were alive at last follow-up, and 2 remain disease-free after 1 additional patient showed a CR following surgical resection of the remaining metastatic disease. CONCLUSION: Our preliminary experience suggests that long-term, repeated treatment with IFN-alpha and low-dose IL-2 is feasible in Japanese patients with metastatic RCC who have undergone radical nephrectomy. Although it will be necessary to accumulate data from a larger number of patients with a longer follow-up period, the combined immunotherapy tested in this study may become the preferred therapy for Japanese patients with metastatic RCC.

Aged↗
PubMed2005

Significance of the percentage of prostate needle biopsy cores with cancer as a predictor of disease extension in radical prostatectomy specimens in Japanese men.

OBJECTIVES: To evaluate the significance of the percent of positive biopsy cores (PPBC) with cancer, which has been shown to be one of the most useful predictors of prostate cancer extension in patients undergoing radical prostatectomy. MATERIALS AND METHODS: This study included 120 patients who underwent radical prostatectomy for prostate cancer without any neoadjuvant therapies. All of these patients were diagnosed by random prostate biopsy targeting 8 cores; that is, standard sextant cores and 2 additional cores from the bilateral anterior lateral horns. We evaluated the appropriate cut-off points of PPBC for predicting disease extension according to the number of biopsy cores. Based on these criteria, multivariate analysis was then performed to determine whether PPBC could be an independent factor differentiating organ-confined disease from extraprostatic disease. RESULTS: The most suitable PPBC cut-off value using findings targeting 8 cores for predicting disease extension was 37.5%. If PPBC was calculated based on the outcome of standard sextant cores alone, it is most appropriate to use 33.3% as the cut-off point. Multivariate analysis showed that PPBC calculated based on the standard sextant cores and percent of cancer in the biopsy set could be used as independent factors predicting disease extension irrespective of other biopsy-associated factors. CONCLUSIONS: For predicting disease extension, it may be useful to calculate PPBC based on the outcomes of standard sextant biopsy cores alone even if additional cores were taken, and that PPBC calculated in such a way may be the strongest preoperative predictor of prostate cancer extension in Japanese men scheduled for radical prostatectomy.

Aged↗
PubMed2005

Exaggerated liver injury induced by ischemia-reperfusion in spontaneously hypertensive rats.

BACKGROUND: The functions of polymorphonuclear leukocytes (PMNs), which play a critical role in organ damage, are primed in patients with essential hypertension and spontaneously hypertensive rats (SHR). Hepatic ischemia-reperfusion (I/R) injury is shown to be caused and aggravated by the PMNs. We examined whether the hepatic I/R injury was exaggerated in SHR. METHODS: The portal vein and artery were partially occluded for 60 min. Blood samples were obtained to determine the degree of liver damage during 48 h after reperfusion. RESULTS: The increase in serum transaminase concentration and hepatic myeloperoxidase content, which reflects the number of PMNs in liver tissue, in SHR were significantly greater than those of their control rats, Wistar-Kyoto rat (WKY). However, the elevations in hepatic transaminases induced by I/R did not differ between other hypertensive animal models (N-nitro-L-arginine methyl ester [L-NAME]-treated and deoxycorticosterone acetate [DOCA]/salt-treated rats) and their controls. CONCLUSIONS: These results suggest that the elevated PMNs, but not high blood pressure per se, contributes to the exaggerated hepatic I/R injury in SHR.

Alanine Transaminase↗
PubMed2005

Bacterial degradation of microcystins and nodularin.

Microcystins and nodularins produced by cyanobacteria are potent hepatotoxins and tumor promoters. They are, respectively, cyclic heptapeptides and cyclic pentapeptides containing a characteristic beta-amino acid residue, (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4(E ),6(E)-dienoic acid (Adda). Strain B-9 isolated from Lake Tsukui, Japan, degrades microcystin-LR, which is the most toxic among the microcystins, to nontoxic Adda as an end product. In the present study, we characterized the bacterial degradation process of the cyclic peptide hepatotoxins by liquid chromatography/ion trap tandem mass spectrometry. The use of protease inhibitors with a B-9 cell extract indicated that the degradation process of microcystin-LR consists of sequential enzymatic hydrolyses of Arg-Adda, Ala-Leu, and then Adda-Glu peptide bonds into two known nontoxic intermediate degradation products and then Adda, respectively. Subsequently, additional microcystins and nodularin were compared with microcystin-LR on substrate specificity. The cyclic peptides containing the Arg-Adda peptide bond were almost completely degraded to Adda as well as microcystin-LR, whereas microcystin-LF containing the Phe-Adda peptide bond instead of Arg-Adda peptide bond and 6(Z)-Adda-microcystin-LR and -RR which are geometrical isomers of the Adda residue were barely degraded. These results indicated that the degrading enzymes selectively hydrolyzed the Arg-Adda peptide bond as the initial ring opening of the cyclic peptide hepatotoxins, microcystins and nodularin.

Bacterial Toxins↗
PubMed2005

Biotransformation of bile acids by pathogenic actinomycetes Nocardia otitidiscaviarum and Amycolatopsis sp. strains.

Three sterol-type compounds (compounds 4, 5 and 6) were isolated from culture broth of pathogenic Nocardia otitidiscaviarum IFM 0988 and Amycolatopsis sp. IFM 0703 strains which were isolated from Japanese patients. The structures of the compounds were determined by NMR and mass spectrometric analyses. The structural studies indicated that compound 4 is a biotransformation product from cholic acid derivative in a nutrient culture medium constituent by a reductase-type enzyme, and the remaining two compounds 5 and 6 are also biotransformation ones by oxidase-type enzymes.

Actinobacteria↗