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Biomedical subjects

Kimio Fujita

Publications and source records attributed to Kimio Fujita.

16 recordsLinked to original sources

Resistance index in benign prostatic hyperplasia using power Doppler imaging and clinical outcomes after transurethral vaporization of the prostate.

BACKGROUND: Using power Doppler ultrasonography (PDUS), we investigate the change of resistance index (RI) before and after transurethral vaporization of the prostate (TUVP) in benign prostatic hyperplasia (BPH) patients. METHODS: In all, 49 patients underwent transrectal PDUS before receiving TUVP, three were excluded because of cancer and three could not be followed up. The remaining 43 were enrolled in the present study. Patients were assessed before and 1, 3 and 6 months after surgery, giving a mean duration of follow-up of 9.1 months. International prostate symptom scores (IPSS), quality of life (QOL) scores, postvoiding residual urine volumes (PVR) and maximum urinary flow rates (Qmax) were evaluated and total prostatic volume (TPV) and RI were measured using PDUS. RESULTS: Resistance index ranged from 0.64 to 0.91. The postoperative parameters except for RI, such as TPV, PVR, IPSS and QOL scores improved significantly at the follow-up assessment after surgery. The elevated RI decreased significantly 1, 3 and 6 months after the treatment. Resistance index significantly decreased after TUVP and IPSS and other urodymamics parameters improved. CONCLUSIONS: The present study suggested that RI could evaluate the severity of BPH and the degree of intraprostatic pressure or bladder outlet obstruction.

Aged↗

Oral clonidine advances spermatogenesis in oligozoospermic patients with spermatogenetic maturation arrest.

BACKGROUND: Growth hormone (GH) plays an important role in the pubertal development of males and females, and influences the male reproductive function after puberty. The purpose of this study was to investigate the cause of GH deficiency in infertile men with spermatogenetic maturation arrest using the clonidine loading test (GH stimulation test). Based on the results of the loading test, we tried to con fi rm whether clonidine might be usable as a male infertility remedy. METHODS: We studied 75 infertile men (55 oligozoospermic and 20 azoospermic men) and 25 normal fertile volunteers. We used the oral clonidine (0.15 mg/m2) loading test to evaluate the GH secretory reserve. Histological diagnoses were performed using testicular biopsy and testicular sperm extraction specimens. RESULTS: The most important finding was that the clonidine loading test caused a good response in 41 out of 55 (74.6%) patients with oligozoospermia. We treated these 41 good-response patients with oral clonidine, and the sperm count improved in 34 (82.9%) cases, increasing to 12-79 million/mL. Spontaneous pregnancy was subsequently achieved by 10 (24.4%) couples. CONCLUSIONS: These findings also suggest that GH is necessary for spermatogenesis, at least for the process of spermatozoa maturation. Oral clonidine therapy improved the sperm count in patients who showed an excessive response to the clonidine loading test.

Administration, Oral↗

BK virus subtype 1 infection associated with tubulointerstitial nephritis in a renal allograft recipient.

The BK polyomavirus (BKV) infects most of the human population, but clinically relevant infections are usually limited to individuals who are in an immunosuppressed state. The significance of BKV infection was investigated in a 50-year-old man who underwent cadaveric kidney transplantation and was treated with tacrolimus, mycophenolate mofetil and prednisolone. By staining renal biopsy specimens with a monoclonal antibody against BK large T antigen, we were able to observe the relationship between the appearance of the BKV antigen and the extent of immunosuppression in this patient. We also determined that BKV belonged to genotype I by analysis of viral DNA from the patient's urine.

BK Virus↗

[Economical aspects on the treatments of urolithiasis by surgical methods: comparison of surgical method selections and world status].

Economical elements including surgical fee and hosipital stay become larger in the selection of surgical methods for the treatment of urinary stones. Then, urologists need to explain to patients the treatment cost to obtain informed consent. By comparing the data from participants' answer to Debate 1 at the 82th annual meeting of the Japanese Urological Association (April 2002, Tokyo) and questionnaire responses from the members of the annual meeting of central division of Japanese Urological Association (November 2002, Nagoya), we surveyed the trends of surgical methods on the treatments of staghorn caliculi and lower ureter stones. Furthermore, we clarified the cost of these methods. Based on the status of world countries, we demonstrate the ideal selection including economical aspects on the selection of endourological method.

Global Health↗

Thymidine phosphorylase and dihydropyrimidine dehydrogenase in renal cell carcinoma: relationship between histological parameters and chemosensitivity to 5-fluorouracil.

OBJECTIVES: Thymidine phosphorylase (TdR-Pase) and dihydropyrimidine dehydrogenase (DPD) are thought to be key enzymes in the metabolic pathway of 5-fluorouracil (5-FU). Theoretically, cancer cells which have high TdR-Pase activity and/or low DPD activity should be sensitive to 5-FU. TdR-Pase is also known to have angiogenic activity which helps tumor progression and metastasis. On the other hand, little is known concerning the relationship of DPD activity with clinical malignant potential in renal cell carcinoma (RCC). In this study, we measured both TdR-Pase and DPD activities in surgically obtained RCC tissues and examined the relationship between these enzymatic activities and histological parameters. In addition, the results of in vitro chemosensitivity testing were also analyzed to determine whether TdR-Pase and/or DPD activity in carcinoma cells can predict the efficacy of 5-FU. METHODS: RCC tissues from 53 patients were obtained. TdR-Pase and DPD activities were measured by ELISA and radioenzyme assay, respectively. Sensitivity to 5-FU was assessed by histoculture drug response assay (HDRA), an in vitro chemosensitivity test, for 20 of the 53 specimens. RESULTS: Both TdR-Pase and DPD activities of RCC increased with histological grade. There was a significant positive correlation between the TdR-Pase activity and 5-FU sensitivity. In addition, a stronger positive correlation was found between TdR-Pase / DPD ratio and 5-FU sensitivity. DPD exhibited no correlation with 5-FU sensitivity. CONCLUSIONS: The activity of both enzymes increased with malignant potential of RCC. TdR-Pase appeared to be the enzyme regulating activation of 5-FU in RCC.

Antimetabolites, Antineoplastic↗

Control of oxalate formation from L-hydroxyproline in liver mitochondria.

Serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT) is largely located in mitochondria in carnivores, whereas it is entirely found within peroxisomes in herbivores and humans. In rat liver, SPT/AGT is found in both of these organelles, and only the mitochondrial enzyme is markedly induced by glucagon. Although SPT/AGT is a bifunctional enzyme involved in the metabolism of both L-serine and glyoxylate, its contribution to L-serine metabolism is independent of mitochondrial or peroxisomal localization (Xue HH et al., J Biol Chem 274: 16028-16033, 1999). Therefore, the species-specific and food habit-dependent organelle distribution might be required for proper metabolism of glyoxylate at the subcellular site of its formation. Glyoxylate formation from glycolate and that from L-hydroxyproline have been shown to occur in peroxisomes and mitochondria, respectively. The present study found that urinary excretion of oxalate was markedly increased when a large dose of L-hydroxyproline or glycolate was administered to rats. Oxalate formation from L-hydroxyproline but not that from glycolate was significantly reduced when mitochondrial SPT/AGT had been induced by glucagon. The hydroxyproline content of collagen is 10 to 13%, and collagen accounts for about 30% of total animal protein; therefore, these results suggest that an important role of mitochondrial SPT/AGT in carnivores is to convert L-hydroxyproline-derived glyoxylate into glycine in situ, preventing undesirable overflow into the production of oxalate.

Animals↗

[Laparoscopic adrenalectomy using telementoring system].

We report on our experience in telementoring during laparoscopic adrenalectomy. An experienced laparoscopic surgeon supervised a less experienced surgeon from a control room about 100 meter away. Mentoring was accomplished over a fiber optic cable employing real-time video imaging, two-way audio communication, OES ImageTrac Video System used to control the laparoscopic image, and a telestrator. The patient was a 52-year-old male with primary aldosteronism due to a left adrenal adenoma 2 cm in diameter. The procedure was successfully performed in 195 minutes with minimal blood loss. The patient recovered without complications and returned home on postoperative day 7. As broadband telecommunication expands, telementoring will become an important method for the training and supporting of laparoscopic surgery.

Adrenalectomy↗

Clinical significance of thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in transitional cell cancer.

PURPOSE: Thymidine phosphorylase (TdR-Pase) and dihydropyrimidine dehydrogenase (DPD) are thought to be key enzymes in the metabolic pathways of 5-fluorouracil (5-FU). Theoretically, tumors which have low DPD and/or high TdR-Pase expression should be 5-FU-sensitive. TdR-Pase also has angiogenic expression which aids tumor progression and metastasis. However, little is known concerning the relationship between DPD expression and clinical malignant potential, especially in urological cancer. MATERIALS AND METHODS: Transitional cell cancer (TCC) tissues were obtained from 50 patients, and TdR-Pase and DPD expression was measured by ELISA and radioenzyme assay, respectively. The sensitivity of 23 of the 50 specimens to 5-FU was assessed in a histoculture drug response assay (HDRA), an in vitro chemosensitivity test. RESULTS: TdR-Pase and DPD expression in TCC tissues was higher than in normal urothelial tissues. The expression of both TdR-Pase and DPD in TCC increased with histological grade and stage. Superficial bladder cancer patients who had undergone transurethral resection were divided into two groups, a recurrent and a nonrecurrent group. The expression of TdR-Pase and DPD was higher in the recurrent group than in the nonrecurrent group, but the differences were not significant. There was a significant inverse correlation between DPD expression and 5-FU sensitivity. However, TdR-Pase exhibited no correlation with 5-FU sensitivity. CONCLUSIONS: The expressions of both enzymes may be a good indicator of the malignant potential of TCC. Although DPD may be a good indicator of sensitivity of TCC to 5-FU, TdR-Pase appeared not to regulate the sensitivity of TCC to 5-FU.

Carcinoma, Transitional Cell↗

The value of power Doppler imaging to predict the histologic components of benign prostatic hyperplasia.

BACKGROUND: The response of symptoms caused by benign prostate hypertrophy (BPH) to alpha blockade is related to the area density of the smooth muscle of the prostate. If this density could be determined by ultrasound examination, ultrasound might be useful in predicting the efficacy of alpha-blocker therapy. In this study, various ultrasonographic parameters obtained by transrectal method (TRUS) were compared with histologically measured components. METHODS: Before surgery, ultrasonic power Doppler imaging (PDI) of the prostate was performed using a transrectal probe. The volume of total prostate, transition zone (TZ), and the presumed circle area ratio (PCAR) [1,2] were calculated. Pulsatile blood flow was recorded, and the resistive index (RI) was calculated. Based on the serum concentration of total prostate specific antigen (PSA), ratio of PSA to prostate volume (PSAD), and ratio of PSA to TZ (PSAT) were calculated. Prostate tissues were obtained from 26 patients undergoing transurethral resection, suprapubic prostatectomy, or radical cystectomy, and were analyzed by quantitative morphometry. Computer image analysis was used to determine the mean area densities of the smooth muscle (SM), connective tissue (CT), glandular epithelium (GE) and lumen (GL), and vascular lumen (V). Correlations between ultrasonographic parameters and morphometric data were studied. RESULTS: On microscopic examination, the specimens showed a wide variety, ranging from normal prostate to typical glandular hyperplasia. There was a correlation between RI and the ratios of the four components (SM: r = -0.42 P = 0.034; CT: r = -0.42 P = 0.030; GE: r = 0.42 P = 0.032; GL: r = 0.46 P = 0.018). However, correlations between the other five transrectal parameters and the composition of the prostate were not so clear. This may have been because the blood vessels are compressed within the surgical capsule together with the urethra. CONCLUSIONS: The present study demonstrates that when RI is calculated by PDI, it can be quite useful for predicting component ratios, thereby making it possible to predict the therapeutic efficacy of alpha-blockers in individual patients.

Aged↗

Analyses in transfected cells and in vitro of a putative peroxisomal targeting signal of rat liver serine:pyruvate aminotransferase.

Serine:pyruvate aminotransferase (SPT; EC 2.6.1.51) of rat liver is a unique enzyme in that it is located in both mitochondria and peroxisomes. To analyze a peroxisomal targeting signal (PTS) of SPT, we constructed in this study various peroxisomal SPT clones having mutations at the C-terminal 20-amino acid region in which a putative PTS is located, and we examined subcellular localization of mutated products expressed in transfected COS-1 cells. When the mutant SPTs were unstable in transfected COS-1 cells, their translocation into peroxisomes was examined using an in vitro peroxisomal import system. Deletion of the C-terminal tripeptide, NKL, and amino acid substitution of K2 (the second lysine from the C-terminus), K4, or E15 abolished or impaired the peroxisomal import of the translated product, resulting in cytosolic accumulation in the cell. In the cases of mutation of R18G, D19A, or K2Q and the conversion to proline of L9, L13, V17, or A20, no products were detected in transfected cells. However, the results of an in vitro peroxisomal import experiment showed that the mutation of L9P, L13P, V17P, and A20P caused loss of the PTS function. When serine was introduced instead of N3 to generate a typical PTS1, the SKL motif, at the C-terminus, all of the proteins having mutations at P5, E11, R12, or E15 showed extensive localization in peroxisomes. These results suggest that the putative C-terminal PTS of SPT is not equivalent to the typical PTS1 shown in acyl-CoA oxidase and urate oxidase, because the PTS of SPT is not restricted to the C-terminal tripeptide. The results also suggest that the alpha-helical structure of the C-terminal region of SPT is important for the stable conformation of the enzyme and the peroxisomal targeting function of its PTS.

Animals↗

Thymidine phosphorylase activity in renal cell carcinoma: relationship between histological parameters and chemosensitivity to fluorouracil-related drugs.

Thymidine phosphorylase (TdR-Pase) is an essential enzyme in the metabolism of fluorouracil-related drugs and is also a potent angiogenic factor. We measured the TdR-Pase activity in human renal cell carcinomas (RCCs) to assess the relationship between TdR-Pase activity and the degree of tumor malignancy. We also investigated the relationship between TdR-Pase activity and chemosensitivity to fluorouracil-related drugs. A total of 61 RCC tissue specimens and 39 normal kidney tissue specimens were obtained. TdR-Pase activity was measured by enzyme-linked immunosorbent assay. The in vitro histoculture drug response assay was also performed to examine tumor sensitivity to 5-fluorouracil (5-FU) and doxifluridine (5'-DFUR). The TdR-Pase activity of RCCs was 13-fold that of the normal tissues. Activity increased with histological grade, and,was significantly higher in high-stage tumors (T3 or higher). TdR-Pase activity exhibited a significant positive correlation with sensitivity to 5-FU and 5'-DFUR. High TdR-Pase activity in human RCC was confirmed to predict high tumor grade and stage. RCCs with high TdR-Pase activity were also sensitive to FU-related drugs.

Antimetabolites, Antineoplastic↗

Primary signet ring cell carcinoma of the urinary bladder successfully treated with intra-arterial chemotherapy alone.

A 65-year-old man presented with the complaint of gross hematuria. Cystoscopy revealed a sessile tumor on the left bladder wall. It was diagnosed as primary signet ring cell carcinoma of the bladder (T3bN0M0). The patient did not want surgical treatment. Therefore, three courses of arterial infusion of carboplatin were administered at 3-week intervals. Complete remission was obtained and has been maintained for 44 months. Our case appears to be the first report of successful treatment with chemotherapy alone of an infiltrating signet ring cell carcinoma of the bladder.

Aged↗

Role of Doppler ultrasound and resistive index in benign prostatic hypertrophy.

BACKGROUND: The aim of the present study was to assess the resistive index in patients with benign prostatic hypertrophy (BPH) and the role of power Doppler ultrasonography. METHODS: From April 1996 to December 1997, a total of 214 men aged 48-86 years with symptoms of BPH were prospectively enrolled to participate in our study. All patients presented to our clinic with lower urinary tract symptoms. Transrectal ultrasonography was used to calculate the total prostate volume (TPV), transition zone (TZ) volume, transition zone index (TZI = TZ volume/TPV) and presumed circle area ratio (PCAR). Power Doppler imaging was used to identify the capsular and urethral arteries of the prostate and measure its resistive index (RI) value. RESULTS: The RI of capsular arteries significantly correlated with theTPV, TZ volume, TZI (r = 0.470; P < 0.0001) and PCAR (r = 0.334; P < 0.0001). Correlations were found between the RI of capsular arteries and the International Prostatic Symptom Score (IPSS) (r = 0.389; P < 0.0001), peak flow rate of uroflowmetry (r = -0.393; P < 0.0001). CONCLUSION: We demonstrated that an increase of the RI of capsular arteries correlated with increases in the TZI and PCAR in BPH. The lower IPSS and peak flow rate correlated with the high RI of capsular arteries; however, no correlation between the RI of urethral arteries and prostatic parameters was found. The findings suggested that the RI of capsular arteries may become the index for measuring lower urinary obstruction in the future.

Aged↗

Histologically benign but telomerase positive adrenal pheochromocytoma.

Adrenalectomy was performed on a 37-year-old woman with right adrenal pheochromocytoma. Although the histological diagnosis was benign, telomerase repeat amplification protocol (TRAP) demonstrated positive telomerase activity. Thirty-five months after adrenalectomy, a recurrent tumor was found. Forty-seven months after adrenalectomy, bone metastases also appeared. Malignant pheochromocytoma was clinically diagnosed. Our experience suggests that telomerase-positive tumor cells are highly likely to repeat cell proliferation when they are left in the patient's body, and lead to recurrence. Therefore, telomerase-positive tumors should be clinically treated as malignant even if they have been histologically diagnosed as benign.

Adrenal Gland Neoplasms↗

[Sling suspension of incontinent urinary reservoir].

We report a case and surgical technique of successful sling suspension of insufficient efferent limb of continent urinary reservoir, which has occurred urinary incontinence. A 64-year-old male, who received radical cystectomy with continent urinary reservoir, had been suffered urinary incontinence from the reservoir about one year after surgery. Various procedures, such as the repair of the efferent limb of the reservoir, addition of the ileal patch, instillation of scopolamine, oxybutynin into the reservoir and an injection of GAX collagen in the efferent limb, were not effective for his urinary incontinence. Finally, anti-incontinence procedure of sling at an efferent limb using abdominal rectus muscle fascia was employed and obtained a continence for 2 years after operation. The principle of this surgery is same with that of sling suspension for female stress incontinence. It is advisable for the incontinent urinary reservoir when it has an enough length of efferent limb.

Humans↗

[Repeat prostate biopsy in patients with previous negative biopsies].

We retrospectively analyzed the results of 104 patients who underwent a second prostate needle biopsy. Between January 1993 and September 2000, 654 needle biopsies were performed and cancer was found in 239 patients. Among the other 415 patients, 104 patients underwent a second biopsy. The average prostate specific antigen (PSA) value was 9.6 ng/ml (2.0-30.9) (Tandem R conversion value). Cancer was detected in 16 out of 104 cases (15%) at the second biopsy, 4 out of 39 (10%) at the third biopsy, and 3 out of 10 (30%) at the fourth biopsy. The age, PSA value, digital examination, echography, and magnetic resonance imaging (MRI) were not helpful in distinguishing the patients with prostate cancer and atypical histological findings at the previous biopsy were the most important information. Among the 9 patients who showed atypical findings at the previous biopsy, 6 (67%) had cancer.

Aged↗