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Biomedical subjects

Kazuo Suzuki

Publications and source records attributed to Kazuo Suzuki.

At least 19 recordsLinked to original sources

Protective effects of glutathione on 5-fluorouracil-induced myelosuppression in mice.

The protective effects of glutathione (GSH) administration on myelosuppression induced by 5-fluorouracil (5-FU) were investigated in female BALB/c mice. Animals were allocated to four groups (16 mice/group). GSH was given orally at a dose of 800 mg/kg to groups 3 and 4 for 21 consecutive days (day 0 to day 20). 5-FU was repeatedly administered at a dose of 40 mg/kg to groups 2 and 3 for 1 week (day 7 to day 13) by gavage. Group 3 served as a combined treatment group and group 1 as a non-treated control group. The total observation period was 3 weeks. Body weight was measured once a week. A decrease in body weight due to 5-FU treatment was observed in groups 2 and 3 on day 14. Although the body weight in group 2 had not increased by 1-week after cessation of 5-FU treatment, the value in group 3 markedly recovered. Hematology, total nucleated myelocyte count and histopathology of bone marrow were carried out on day 14 and day 21. In groups 2 and 3, these examinations showed thrombocytopenia, leukopenia, reticulocytopenia and myelosuppression on day 14. However, platelets and bone marrow were less affected in group 3 than in group 2. On day 21, the thrombocytopenia in groups 2 and 3 was resolved. The myelosuppression, leukopenia and reticulocytopenia resolved in group 3, but not in group 2. Although simple microcytic anemia occurred delayed on day 21, it was less severe in group 3 than in group 2. Therefore, GSH may have preventive effects against 5-FU-induced hematopoietic toxicity, and accelerate recovery after cessation of 5-FU treatment.

Administration, Oral↗

No increase in protease resistance and a decrease in reverse transcriptase resistance mutations in primary HIV-1 infection: 1992-2001.

Rates of antiretroviral resistance in recently transmitted virus in Sydney, Australia fluctuated over the past decade, influenced by treatment trends. Current rates of drug resistance are not high in historical terms or compared with those reported. Rates of resistance to reverse transcriptase inhibitors peaked in the mid-1990s, fell dramatically with the introduction of combination therapy and appear to have plateaued at 10-15% over the past 3 years. Primary resistance mutations in the protease gene are still rare.

Acute Disease↗

Surgical outcome of laparoscopic radical prostatectomy: summary of early multiinstitutional experience in Japan.

BACKGROUND: Because laparoscopic radical prostatectomy requires significant laparoscopic expertise, it needs to be evaluated critically before being accepted as a standard therapeutic option for localized prostate cancer. METHODS: A total of 148 men diagnosed as having clinically resectable prostate cancer underwent laparoscopic radical prostatectomy at seven different institutions in Japan. Early biochemical and oncological outcomes were investigated. RESULTS: Policies underlying the selection of laparoscopic radical prostatectomy did not appear to be consistent among the participating institutions. Pathologically organ-confined disease was found in 64.0% of the patients who had undergone neoadjuvant therapy and in 77.2% of those who had not. Positive surgical margins were found in 36.0% and 34.1%, respectively, of the specimens. The most common site was the apex, which accounted for 77.8% of positive margins in patients who had undergone neoadjuvant therapy and 50.0% in those who had not. Seven patients have experienced biochemical failure at a median follow-up of 9.0 months. No clinical progression has been reported. CONCLUSIONS: Continuing improvements in each step of laparoscopic radical prostatectomy, especially apical dissection, should be sought as we pursue the goal of still better oncological outcomes. A systematic approach and therapeutic guidelines should help to reduce the learning curve for competent performance of this procedure.

Aged↗

The trend of imported mycoses in Japan.

Pathogenic fungi that are non-native in Japan are highly virulent and present a significant health hazard to persons in the environment into which they are introduced. Little is known, however, about the precise trend of infection by imported mycoses in Japan. To clarify this issue, all available cases were collected through a search of MEDLINE and Japana Centra Revuo Medicine and analyzed. Also included in this analysis were cases not reported in the literature for which the authors provided identification of the fungi, diagnosis, or treatment. The analysis revealed that, for three diseases, the number of imported mycoses cases in Japan is much higher than previously reported: 31 cases of coccidioidomycosis, 34 cases of histoplasmosis, and 17 cases of paracoccidioidomycosis. Additionally, one case of penicilliosis marneffei was found. The most rapid increase in the incidence of these mycoses occurred from 1991 to 1995. Analysis of the patients' profiles provided the following information: (1) coccidioidomycosis infection in Japan is increasing very rapidly, (2) Japan might be an endemic area of histoplasmosis infection, (3) histoplasmosis is a potentially fatal disease; and (4) reliable serodiagnostic methods have been used only infrequently. Because of the increase of international travel and immigration, the incidence of imported mycoses in Japan is expected to continue rising, and mycoses that have never been reported in Japan, such as blastomycosis, might also be encountered in the near future. To cope with this newly emerging health problem to residents of Japan, the Japanese medical system must train its members to identify and treat mycoses.

Adolescent↗

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↗

Expression, oxidative refolding, and characterization of six-histidine-tagged recombinant human LECT2, a 16-kDa chemotactic protein with three disulfide bonds.

Human LECT2 is a 16-kDa chemotactic protein that consists of 133 amino acids and three intramolecular disulfide bonds. Here, we present the oxidative refolding of (His)(6)-LECT2, an N-terminally (His)(6)-tagged recombinant protein of human LECT2. (His)(6)-LECT2 was overproduced in Escherichia coli in the form of insoluble aggregates, solubilized with 8 M urea in the presence of 10 mM DTT, and purified and refolded on Ni-NTA agarose by lowering the urea concentration before the elution. This process, however, gave a mixture of oligomers of (His)(6)-LECT2 as well as the monomer, whose composition was as low as 36%. The oligomers formed as a result of incorrect intermolecular disulfide bonds. After the refolding on Ni-NTA agarose (step 1), the disulfide bonds were shuffled using a glutathione redox buffer (step 2) and the remaining thiols were completely oxidized (step 3) to improve the yield of correctly folded, monomeric (His)(6)-LECT2. The monomer composition was significantly improved to 81% by the three-step refolding method and the monomer thus obtained was shown to have the same conformation as the authentic LECT2 produced in CHO cells by CD and NMR spectroscopies. The yield of (His)(6)-LECT2 was 1.0 mg/L E. coli culture and was 16 times as high as that in our previous report, in which (His)(6)-LECT2 was purified from the soluble fractions of E. coli cell lysates.

Animals↗

Rates of transmission of antiretroviral drug resistant strains of HIV-1.

BACKGROUND: It is clear that transmission of drug resistant HIV-1 is possible and occurs regularly. However, there is a lack of clarity concerning the true rate of this transmission in a given population, the impact of combination therapies on this rate, and the contribution of transmitted resistant virus to treatment failure either in an individual or on a population basis. OBJECTIVES: To provide a review of our current understanding of rates of transmission of drug resistant HIV-1 in various populations and to report the results of a study conducted to determine this rate in Sydney, Australia in the years 1992-2000. STUDY DESIGN: A review of the literature combined with a prospective study of antiretroviral drug resistance in 130 individuals who were diagnosed with symptomatic primary infection at St. Vincent's Hospital, Sydney, Australia between 1992 and 2000. Sequencing of reverse transcriptase (RT) and protease (PR) was performed by the TruGene HIV-1 genotyping kit (Visible Genetics Inc.). RESULTS: The results found in the Sydney population contrast with much of the literature. The prevalence of mutations that conferred primary resistance to protease inhibitors (PIs) was only 0.8% at position V82I. Secondary mutations/polymorphisms were seen in the PR at position L10I/V, K20R, M36I, L63P, A71T/V, or V77I in 60%. L63P was the most frequently found mutation (46.3%). The incidence of protease-resistant strains of HIV in primary HIV-1 infection did not change after the introduction of PIs in 1996. The distribution of the most common resistance mutations in the RT was as follows; M41L (8.5%) and T215Y (8.5%) and K70R (4.8%). The frequency of mutations associated with NRTI resistance was significantly lower in the post 1995 samples (43.9 vs. 19.1%, P < 0.05). Moreover, both M41L and K70R, but not T215Y, occurred with significantly decreased frequency in the post 1995 samples. CONCLUSIONS: In contrast to other studies we found no increase in the rate of PR resistance and a decrease in the rate of RT resistance in recently transmitted virus over the period 1992-2000. The reasons for the differences between these results and those reported from elsewhere may relate to treatment regimens used in the transmitting population and may have implications for treatment policies in this country.

Anti-HIV Agents↗

Morbidity of laparoscopic radical prostatectomy: summary of early multi-institutional experience in Japan.

AIM: Laparoscopic radical prostatectomy is being evaluated throughout the world. The aim of the present study is to report early multi-institutional experience of the procedure in Japan. METHODS: A total of 148 men who were diagnosed with clinically localized prostate cancer underwent laparoscopic radical prostatectomy at seven different institutions in Japan. Early complications (within 30 days postoperatively) and postoperative convalescence were reviewed retrospectively. The median age of patients was 68.0 years (range, 51-80). RESULTS: The median operative time was 403 minutes (range, 167-925; average, 427). Blood loss ranged from 50 to 5000 mL (median, 540; average, 856). A total of 66 complications were reported in 55 patients (37.2%). Intraoperative complications were noted in 25 of 148 patients (16.9%): 10 rectal injuries (6.8%); five bladder injuries (3.4%); five cases of subcutaneous emphysema (3.4%); two intestinal injuries (1.4%); one major vessel injury (0.7%); one ureteral injury (0.7%); and one obturator nerve injury (0.7%). Overall, 16 of 148 patients (10.8%) required open conversion or postoperative open surgical repair. The most common postoperative complications were anastomotic leakage (6.8%), wound-related complications (4.7%) and perineal pain (4.7%). The bladder catheter was removed on day 7 or earlier in 73 cases (49.3%). The median time to ambulation was 1 day (mean 1.4, range 1-5). Oral intake was started on postoperative day 1 in 67 patients (45.2%) and on postoperative day 2 in 65 (43.9%). CONCLUSION: Although laparoscopic radical prostatectomy is technically demanding, reduced blood loss and shorter convalescence periods can be expected from the procedure. Surgeons should be aware of the disturbingly high morbidity rate related to early experience. By mastering laparoscopic skills and sharing knowledge, surgeons could reduce the impact of the learning curve required to complete this procedure competently.

Aged↗

Beta2-microglobulin-selective adsorbent column (Lixelle) for the treatment of dialysis-related amyloidosis.

Lixelle is a direct hemoperfusion-type adsorbent column developed for selective elimination of beta2-microglobulin (beta2-m) from the circulating blood of patients with dialysis-related amyloidosis (DRA). Lixelle S-35, that has a column volume of 350 mL, efficiently eliminates beta2-m and improves symptoms of DRA such as joint pain and nocturnal awakening. The performance of Lixelle S-15, that has a column volume of 150 mL, is dependent on the dialysis membrane used in combination with the adsorbent column in a hemodialysis circuit. The combination of S-15 and a dialysis membrane with a high beta2-m clearance eliminates an amount of beta2-m that is nearly equal to the amount removed by using S-35. Treatment with S-15 for 6 months improved joint pain with an efficacy similar to that observed when using S-35. The major adverse effects were hypotension and decrease in hematocrit, and these incidences were much less in S-15 compared to S-35.

Adsorption↗

Myeloperoxidase has directly-opposed effects on nitration reaction--study on myeloperoxidase-deficient patient and myeloperoxidase-knockout mice.

Myeloperoxidase (MPO) catalyzes a nitration reaction to form nitrotyrosine in the presence of high nitrite, the metabolite of NO. Human leukocyte was shown to cause phenolic nitration using released MPO as a catalyst in the presence of nitrite. It opposes our previous finding that inhibition of MPO was essential for phenol nitration in human leukocyte study. To clarify the role of MPO, we utilized MPO-deficient human leukocytes and MPO-knockout mice. Even in the absence of exogenously added nitrite, high nitration product was observed in MPO-deficient leukocytes. In liver subjected to ischemia/reperfusion injury, a significantly higher amount of nitrotyrosine was produced in MPO-knockout mice than in normal mice. These results clearly demonstrate that MPO inhibits the accumulation of nitration products in vivo. Further experiments showed that MPO could degrade nitrotyrosine in the presence of glutathione. Thus, MPO-induced degradation of nitration products may cause the underestimation of the nitration product generated in vivo. We conclude that MPO may act predominantly to scavenge nitrotyrosine under physiological nitrite condition, and protect against injurious effect of nitrotyrosine.

Adult↗

CD69-null mice protected from arthritis induced with anti-type II collagen antibodies.

CD69, known as an early activation marker antigen on T and B cells, is also expressed on platelets and activated neutrophils, suggesting certain roles in inflammatory diseases. In order to address the role of CD69 in the pathogenesis of arthritis, we established CD69-null mice. CD69-null mice displayed a markedly attenuated arthritic inflammatory response when injected with anti-type II collagen antibodies. Cell transfer experiments with neutrophils, but not T cells or spleen cells, from wild-type mice into CD69-null mice restored the induction of arthritis. These results indicate a critical role for CD69 in neutrophil function in arthritis induction during the effector phase. Thus, CD69 would be a possible therapeutic target for arthritis in human patients.

Adoptive Transfer↗

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↗

Prevalence of inherited myeloperoxidase deficiency in Japan.

The microbicidal activity of the myeloperoxidase (MPO)-hydrogen peroxide-halide system has been implicated as the most efficient, oxygen-dependent antimicrobial component of neutrophil host defense. Unexpectedly, individuals with MPO deficiency suffer few clinical consequences. In order to understand better the clinical impact of MPO deficiency, we surveyed several clinical hematology laboratories in Japan to assess the prevalence of MPO deficiency in the general population. MPO activity was determined by flow cytometry using the Technicon H series of automated systems. We identified 26 cases of complete MPO deficiency, prevalence 1 in 57,135, and 129 cases of partial deficiency, prevalence 1 in 17,501. The distribution of complete and partial deficiencies differed among the laboratories studied.

Flow Cytometry↗

Effects of benidipine and candesartan on kidney and vascular function in hypertensive Dahl rats.

We examined the effect of the dihydropyridine calcium channel blocker (CCB) benidipine, the angiotensin II type 1 receptor blocker (ARB) candesartan, and the combination of these drugs on blood pressure and kidney and vascular function in rats with salt-induced hypertension. Dahl salt-sensitive (DS) rats were fed with a high-salt (8% NaCl) diet from 7 weeks of age. Benidipine (1, 3 mg/kg), candesartan (1, 3 mg/kg), benidipine (3 mg/kg) combined with candesartan (3 mg/kg), or vehicle was administered orally after the start of the feeding. Relaxant responses to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) were measured to examine the vascular function. DS rats fed the high-salt diet showed an increase in systolic blood pressure (SBP), which was accompanied by glomerular sclerosis and an increase in urinary albumin excretion. Relaxant responses to acetylcholine and sodium nitroprusside were impaired in superior mesenteric arterial rings from the hypertensive DS rats. SBP was significantly lower in all of the drug-treated groups than in the vehicle-treated group. The antihypertensive effect of benidipine at 3 mg/kg was more potent than that of candesartan at 3 mg/kg. The albuminuria was significantly decreased in the benidipine and benidipine plus candesartan groups, but not in the candesartan group. The level of SBP in the benidipine plus candesartan group was lower than that by either drug alone. In addition, benidipine alone and benidipine plus candesartan inhibited the glomerular sclerosis and the impairment of relaxant responses in the arteries. These results demonstrate that benidipine is more effective than candesartan in lowering blood pressure and preventing the impairment of kidney and vascular function in salt-sensitive hypertensive rats. In addition, the results suggest that combination therapy with benidipine and an ARB decreases blood pressure more effectively than either drug alone and may be useful for the treatment of hypertension.

Albuminuria↗

[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↗