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Biomedical subjects

R Ikeda

Publications and source records attributed to R Ikeda.

At least 55 records · Page 3Linked to original sources

Reversal of P-glycoprotein and multidrug-resistance protein-mediated drug resistance in KB cells by 5-O-benzoylated taxinine K.

A newly synthesized taxoid originally from the Japanese yew Taxus cuspidata, 5-O-benzoylated taxinine K (BTK) was examined for its ability to reverse P-glycoprotein (P-gp) and multidrug resistance protein (MRP)-mediated multidrug resistance. BTK reversed the resistance to paclitaxel, doxorubicin (ADM), and vincristine (VCR) of KB-8-5 and KB-C2 cells that overexpress P-gp by directly interacting with P-gp. BTK also moderately reversed the resistance to ADM of KB/MRP cells that overexpress MRP. However, BTK neither inhibited the transporting activity of MRP nor reduced intracellular glutathione levels in KB/MRP cells. BTK shifted the distribution of ADM in KB/MRP cells from punctate cytoplasmic compartments to the nucleoplasm and cytoplasm by inhibiting acidification of cytoplasmic organelles. These two functions of BTK make it able to reverse both P-gp- and MRP-mediated MDR. BTK in combination with ADM should be useful for treating patients with tumors that overexpress both P-gp and MRP.

ATP Binding Cassette Transporter, Subfamily B↗

Serological relationships of Cryptococcus spp.: distribution of antigenic factors in Cryptococcus and intraspecies diversity.

The antigenic formulas of 34 species in the genus Cryptococcus were determined by using type strains and eight factor sera prepared from adsorption experiments with Cryptococcus neoformans serotypes. These antigenic factors were shared by 19 species. The strains used could be divided into eight serological groups. The patterns of groups 1, 2, 3, 5, and 6 were the same as the patterns of C. neoformans serotypes A, D, A-D, B, and C, respectively. The species belonging to group 4 reacted to factor sera 1, 2, and 3. Group 7 contained one species that reacted only to factor serum 1. The 15 species in group 8 did not react to any of the factor sera used. Compared to the reported molecular phylogenetic tree, the serological and phylogenetic data were correlated in the Filobasidium lineage. All the members of the albidus clade in the Filobasidium lineage had antigens 1, 2, and 3, and all the strains in the magnus clade belonged to serogroup 8. Moreover, intraspecies diversity was examined using strains of C. curvatus, C. humicolus, and C. laurentii. Serological heterogeneity was observed in the species C. humicolus and C. laurentii, as well as in phylogenetic relationships previously published. Using serological features, similarities and differences between Cryptococcus species were demonstrated. Our study contributes to a better description of the genus Cryptococcus and related species phenotypically and phylogenetically.

Agglutination Tests↗

Intraspecies diversity of Cryptococcus laurentii as revealed by sequences of internal transcribed spacer regions and 28S rRNA gene and taxonomic position of C. laurentii clinical isolates.

The intraspecies diversity of an opportunistic yeast pathogen, Cryptococcus laurentii, was revealed by analysis of the sequences of the internal transcribed spacer regions and the 28S rRNA gene. Ten strains of C. laurentii were grouped into two major phylogenetic groups and were further divided into at least seven species. Four of the strains isolated from patients did not represent a single species but showed heterogeneity. These results suggest that C. laurentii is a genetically heterogeneous species, and this must be taken into consideration when identifying C. laurentii clinical isolates.

Cryptococcosis↗

Hypoparathyroidism potentiates cardiovascular complications through disturbed calcium metabolism: possible risk of vitamin D(3) analog administration in dialysis patients with end-stage renal disease.

BACKGROUND/AIM: Progressive cardiovascular calcification in dialysis patients with end-stage renal disease (ESRD) is a serious complication; however, the precise mechanism remains uncertain. We tested whether metabolic calcium abnormalities and hypoparathyroidism might have a correlation with cardiovascular complications in ESRD patients. METHODS: A series of 48 ESRD patients with cardiovascular diseases and/or congestive heart failure, aged 36-82 (61 +/- 12) years, 23 male and 25 female, were enrolled in this study. Serum total calcium (Ca, mmol/l), inorganic phosphate (mmol/l), and intact parathyroid hormone (iPTH, pg/ml) levels were determined in all cases. RESULTS: Organic heart disease was confirmed in 28 patients (58.3%), including 15 with coronary artery disease: 8 with aortic aneurysm, 8 with stenotic valvular heart disease, 9 with excessive mitral annular calcification, 3 with dialysis cardiomyopathy, and 7 with obstructive arterial disease. Serum iPTH measurement revealed hypoparathyroidism (iPTH <60) in 20 of 48 (41.7%) and hyperthyroidism (iPTH >/=200) in 13 of 48 (27.1%) subjects. The 20 patients with low iPTH had a higher prevalence of valvular heart disease, a higher total Ca level corrected for serum albumin (2.70 +/- 0.30 in low iPTH vs. 2.47 +/- 0.30 in normal iPTH, 2.35 +/- 0.20 in high iPTH, p = 0.003) and a higher tendency of vitamin D(3) analog use (65% in low iPTH vs. 33% in normal iPTH and 46% in high iPTH, p = 0.078). Moreover, corrected serum Ca exhibited a negative logarithmic correlation with serum iPTH: corrected Ca = -0.284x log (iPTH) + 3.021 (r = 0.637, p = 0.0001). Multiple logistic regression analysis revealed diabetes and hypoparathyroidism (iPTH <60) as risk factors for cardiovascular complications in ESRD. CONCLUSION: These results suggest that hypercalcemia and hypoparathyroidism in conjunction with vitamin D(3) use might play an important role in cardiovascular complications of chronic dialysis patients.

Adult↗

Telomerase activity in giant condyloma acuminatum.

A 46-year-old male came to our hospital 1 month after noticing a 2-cm penile tumor. Since malignant findings such as atypical cells and mitosis were not observed in the frozen sections obtained at operation, the pathological diagnosis of this tumor was giant condyloma acuminatum. This tumor was analyzed by a telomeric repeat amplification protocol method, and telomerase activity was revealed. For comparison, a case of squamous cell carcinoma and a case of condyloma acuminatum were examined. Telomerase activity was observed in our case and in the case of squamous cell carcinoma. To our knowledge, this is the first case of telomerase activity in giant condyloma acuminatum ever reported. In addition to the histological examination, measurement of telomerase activity may provide valuable objective diagnostic information on evaluating the degree of malignancy of giant condyloma acuminatum and in obtaining a differential diagnosis between the benign and malignant.

Biomarkers, Tumor↗

Immunoreactive pit-1 protein in hyperplastic pars intermedia induced by calcitonin of the rat pituitary gland.

To elucidate the effects of synthetic salmon calcitonin (sCT) on the cells in the rat pituitary gland, we histopathologically and immunohistochemically examined the early changes after 4 or 13 weeks treatment with sCT 120 IU/kg. Focal proliferative lesions of the anterior pituitary glands were consistently found after treatment with sCT for 13 weeks. Histologically, the cells with the focal proliferative lesions were classified into the following three groups: 1) enlarged basophilic cell focus, 2) vacuolated cell focus and 3) chromophobe cell focus. These focal proliferative lesions had positive staining only for the alpha-subunit and failed to show Pit-1 protein immunoreactivity. The sCT treatment also increased the thickness of the pars intermedia. Hypertrophy of the pars intermediate cells was characteristically seen. Furthermore, Pit-1 protein immunoreactivity was clearly detected in the nuclei of the hyperplastic pars intermediate cells. All pars intermediate cells were equally stained by alpha- or beta-MSH and beta-endorphin in both vehicle- and sCT-treatment. No difference was seen. These findings strongly suggest a very close relationship between Pit-1 protein immunoreactivity and cellular proliferation induced by sCT.

Animals↗

Atrophic effects of antiandrogen, chlormadinone acetate (CMA) on dog prostate with spontaneous benign prostatic hyperplasia.

The atrophic effect of a synthetic steroidal antiandrogen, chlormadinone acetate (CMA), on spontaneous benign prostatic hyperplasia (BPH) in dogs was investigated. Male beagle dogs (5-8 years old) were divided into four experimental groups. Group 1 consisted of untreated controls. Groups 2 to 4 received CMA 0.03, 0.1, and 0.3 mg/kg/day, p.o., respectively, for 6 months. In group 1, glandular hyperplasia of the prostate was clearly detected. The glandular epithelial cells showed uniformly intense nuclear staining for androgen receptor (AR). AR was also localized in the nuclei of the fibro-muscular stromal cells. Immunoreactivity of 5 alpha-reductase type I was positive in most glandular epithelial cells. No fibro-muscular stromal cells were stained. Immunolocalization of 5 alpha-reductase type II was clearly detected in the interacinar fibro-muscular stromal cells, but not in the glandular epithelial cells. In groups 2 to 4, CMA produced marked atrophy of the glandular epithelium. The interacinar fibro-muscular stroma was prominent. The nuclear staining for AR in both epithelial and stromal cells was remarkably decreased. Furthermore, the immunoreaction for 5 alpha-reductase type I in most glandular epithelial cells was negative or very weak. The immunoreaction of 5 alpha-reductase type II in the interacinar fibro-muscular stromal cells was negative or very weak. These results indicate that the uptake of testosterone and/or its androgenic effect on the prostate may be suppressed by CMA. The decreased AR-immunostaining may be explained by the decrease in the number of AR and/or antibody binding sites for AR. Therefore, the atrophy after treatment with CMA may be due to shrinkage of both glandular and stromal compartments in the prostate tissue.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

[Mycological and serological diagnosis of cryptococcosis].

Methods for the diagnosis of cryptococcosis have been established, including serotyping and serodiagnosis. Slide agglutination tests with factor sera, the phenol oxidase test, and the growth test at 37C are used for rapid identification of Cryptococcus neoformans. We identified 140 strains and found that 86, 10, and 4% of the isolates were serotypes A, D, and A-D, respectively. Twelve of 14 serotype D strains were isolated from cutaneous cryptococcosis. The most reliable method of serodiagnosis is the latex agglutination (LA) test for detection of polysaccharide antigen combined with protease pretreatment. The LA test is also used for prognosis. The clearance of cryptococcal polysaccharide antigen often takes a few years after treatment. To model the persistence of cryptococcal polysaccharides, we examined the clearance of antigen from the blood of rabbits injected with polysaccharide. The distribution and elimination half-lives of the antigen suggest the prolonged survival of C. neoformans. Recently, the number of cases of C. albidus and C. laurentii has been increasing. The antigenic pattern and the sensitivity of C. albidus in the LA test are the same as that of C. neoformans serotype A. In contrast, C. laurentii does not react with factor sera for C. neoformans and the reactivity with sensitized latex is extremely low. These results were supported by the chemical structures of polysaccharides from these species. We should consider non-neoformans cases in both the identification of isolates and in serodiagnosis.

Animals↗

DNA ploidy analysis of urinary tract epithelial tumors by laser scanning cytometry.

OBJECTIVE: To evaluate a rapid and simple method for DNA content analysis of urinary tract epithelial tumors with laser scanning cytometry (LSC). STUDY DESIGN: The subjects were 25 patients (37 specimens) who underwent surgery for urinary tract epithelial tumors. Tissue specimens of such tumors were frozen immediately after tumor resection and stored at -80 degrees C until used. Touch preparations were made and fixed in ethanol at room temperature. The cell nucleus was stained with propidium iodide solution containing RNase, and DNA ploidy was analyzed by LSC. Nuclear debris and overlapping nuclei were gated out by special statistical filters. In LSC, a normal diploid reference peak was determined by observing lymphocytes morphologically on the computer display of the instrument and/or under the microscope. RESULTS: DNA ploidy could be evaluated in all tumor tissues. The time it took from preparing the tumor specimen to the last measurement was about 40 minutes at the shortest, and measurement of all the specimens was completed within one hour. The coefficient of variation was 2.8-7.8% (mean, 4.4%). All eight specimens (100%) at grade 1 (G1) were DNA diploid, but 20% and 85.7% of the G2 and G3 cells, respectively, were DNA aneuploid. In total, 15 of the 37 specimens were DNA aneuploid. All 17 pTa-pT1 specimens (100%) were DNA diploid, but 100% and 50% of the T2 and T3 tumors, respectively, were DNA aneuploid. CONCLUSION: One can now supplement a morphologic diagnosis with useful information using LSC of touch preparations of tumors obtained at surgery or of imprints of archived, frozen specimens. LSC provides excellent DNA histograms for surgical specimens and has great potential for clinical application in pathology.

Aged↗

[Chromophobe cell renal carcinoma: a case report].

Chromophobe cell renal carcinoma is an uncommon subtype of renal cell carcinoma and the number of cases studied is still limited in Japan. We here report a case of chromophobe cell renal carcinoma in a 41-year-old Mexican male. He visited our branch hospital with the symptom of upper abdominal pain. Ultrasound examination showed a left renal mass. He was admitted to our hospital for treatment of a left renal mass. Radiological examinations revealed a hypervascular tumor in the left kidney. Under the clinical diagnosis of possible renal cell carcinoma, left radical nephrectomy was performed. This tumor was diagnosed as chromophobe cell renal carcinoma with a microscopic examination of H & E stained specimens, histochemical staining using Hale's colloidal iron and an ultrastructural study.

Adult↗

Persistence of cryptococcal antigenemia in an infected dog and uninfected rabbits.

A case of cryptococcosis in a dog is reported. The titers of polysaccharide antigen in sera were monitored by latex agglutination (LA) tests during and after treatment with antifungal therapy. Although the LA titers decreased in response to therapy, it took about 3.5 years to achieve a negative LA test. To model the persistence of cryptococcal polysaccharides, we examined the clearance of antigen from the blood of rabbits injected with sterile, cryptococcal capsular polysaccharide isolated from culture supernatant. The distribution half-lives were between 2.6 and 3.9 days and the elimination half-lives were between 10.4 and 39 days. These results suggest that polysaccharide antigen may be stored in tissues. However, we think that slow clearance of antigen cannot explain the extraordinarily slow clearance found in this dog, and that prolonged survival of Cryptococcus neoformans is a more plausible explanation.

Animals↗

Intranuclear localization of proliferating cell nuclear antigen during the cell cycle in renal cell carcinoma.

OBJECTIVE: To investigate, with laser scanning cytometry (LSC), proliferating cell nuclear antigen (PCNA) expression during the cell cycle in renal cell carcinoma. STUDY DESIGN: DNA ploidy and intracellular localization of PCNA in renal cell carcinoma were determined using LSC and immunohistochemistry. The subjects were nine patients who had received surgery for renal cell carcinoma. After DNA ploidy analysis, the glass slides were restained by immunohistochemistry of PCNA. LSC allowed direct observation of PCNA localization during the cell cycle because we could obtain immunohistochemical staining of PCNA as a function of cell cycle phase for individual cells. RESULTS: PCNA was not demonstrated in the nuclei of G0/G1 cells. PCNA expression increased from the S phase of the cell cycle. PCNA rapidly degraded at the end of the G2 phase. In the late G2 and M phase, PCNA was not detected in almost any nucleus. CONCLUSION: LSC allows morphologic observation of the intracellular distribution of PCNA during the cell cycle in renal cell carcinoma.

Adult↗

[Intracardiac floating thrombi in patients with acute pulmonary thromboembolism].

The mortality and morbidity associated with residual intracardiac floating thrombi in patients with acute pulmonary thromboembolism remain uncertain. Thirteen patients (2 men and 11 women, mean age 56 +/- 15 years) with pulmonary thromboembolism underwent echocardiography within 24 hours from onset of symptoms. Four patients (31%) had floating intracardiac thrombi in the right heart: 3 in the right atrium and one in the inferior vena cava. The time to evaluation by echocardiography was shorter than in the patients without thrombi. The thrombi disappeared shortly (3.2 +/- 2.4 hr) after thrombolysis without adverse effects in these patients. After thrombolysis, clinical symptoms improved and pressure gradient between the right ventricle and right atrium decreased significantly (p < 0.01) from baseline 47 +/- 6 to 26 +/- 5 mmHg. Major bleeding complications occurred in 3 (43%) of the patients who underwent thrombolysis. Right-side intracardiac floating thrombus was easily detectable by early echocardiography. Thrombolytic agents are likely to be effective in patients with intracardiac floating thrombi.

Acute Disease↗

[The relationships among DNA ploidy type determined by laser scanning cytometry, the overexpression of p53 protein and the numerical aberrations of chromosome 7 in bladder cancer].

The cellular DNA content of certain malignancies is regarded as a prognostic parameter. The mutant p53 is thought to destabilize centrosome replication, which leads to aberrant mitosis and chromosome instability. We investigated the relationship among DNA ploidy pattern type, numerical aberrations of chromosome 7 and p53 overexpression in 20 transitional cell carcinomas of the urinary bladder. The DNA ploidy pattern type was determined by laser scanning cytometry, while p53 overexpression was investigated immunohistochemically. Using fluorescence in situ hybridization with chromosome-specific probes, the copy number of chromosome 7 was counted by touch preparations of interphase nuclei. The cytometric analysis revealed that the DNA patterns were highly correlated with both the numerical aberrations of chromosome 7 (p = 0.0002) and the overexpression of p53. The incidences of p53 overexpression in DNA aneuploid tumors and DNA diploid ones were 78% and 10%, respectively (p = 0.0017). Our results suggest that the overexpression of abnormal p53 protein induces DNA aneuploidy in bladder cancer.

Aged↗

Histopathological studies of subcutaneous implantation of chlormadinone acetate (CMA) for preventing estrus in queens.

The efficacy and clinical safety of chlormadinone acetate (CMA) in preventing estrus were assessed in queens on condition that CMA was subcutaneously implanted in siliastic rubber. Thirteen queens were divided into the following four groups according to dose of CMA-administered: group 1 (n = 3), control; group 2 (n = 3), 2.5 mg/kg; group 3 (n = 3), 5 mg/kg; group 4 (n = 4), 20 mg/kg. The implants were left in these queens for 12 months after implantation. All control animals showed signs of estrus during the experiment, with periods of anestrus of normal duration. In contrast, estrus was completely inhibited in the CMA-treated groups. Histopathologically, the uterus from group 4 had coiled branched glands with little secretion in the endometrium. Mammary glands from the CMA-treated groups showed mild lobular development with acinar proliferation and secretion. Sections through the other organs (pituitary gland, adrenal gland, ovary, and implant site) had no distinct or consistent changes that could be related to the CMA-treated. It was concluded, therefore, subcutaneous implantation of CMA could be the good drug-delivery system for reducing changes due to the antigonadotropic and glucocorticoid-like activities and serious condition in the uterine and mammary gland due to progestagenic activity.

Animals↗

[Multimodality therapy for synchronous liver metastases of gastric cancer--significance of aggressive hepatic resection of liver lesions].

We analyzed 15 gastric cancer patients with synchronous liver metastases, and studied the significance of hepatic resection with multimodality therapy. 1. Both gastric and hepatic resections followed by intra-arterial or systemic chemotherapy were performed for six patients, two of whom had intra-operative MCT or EIT. The survival time of four patients without recurrence was 5 Y 4 M, 4 Y 5 M, 2 Y 4 M and 11 M. Two patients died of recurrence in the retroperitoneum or residual liver 3 Y 10 M and 8 M after therapy, respectively. The three-year survival rate was 83%. 2. The longest survival among the five patients treated with gastric resection without hepatic resection followed by intra-arterial or systemic chemotherapy was 1 Y 1 M. 3. Four patients with non-curative factors (P, N, M) were treated with systemic chemotherapy only, and the longest survival was 1 Y 1 M. In conclusion, when local control is obtained during surgery in patients with gastric cancer with synchronous liver metastasis, aggressive hepatic resection supported with MCT or EIT should be performed on liver lesions to improve the prognosis.

Aged↗

[Acquired renal cystic disease].

In 1977, Dunnill et al. described a new disorder, bilateral multiple renal cystic disease. It occurred among hemodialysis patients whose original illness had not been cyst-related. Acquired cystic disease of the kidney (ACDK) is commonly observed in patients undergoing hemodialysis. The incidence of ACDK is 40-50% in reports of autopsy and surgical specimens, rising to more than 90% after 5-10 years of dialysis. The volume of the kidneys decreases in the first 3 years of dialysis and then increases as the rate of cyst formation increases. In male patients undergoing long-term hemodialysis the incidence of ACDK is markedly high. ACDK is also found in patients before hemodialysis. The primary concern in patients with ACDK is the increased incidence (5-19%) of renal cell carcinoma (RCC). The incidence is about twelve to eighteen times higher than that in the general population and the cancers may be asymptomatic. Therefore, screening is essential if carcinomas are to be detected early. Regular screening by ultrasonic examination or CT scan is needed. A patient requires nephrectomy when the kidney cancer exists or is suspected by dynamic CT scan. Nephrectomy is performed only on the side with renal mass. It has been argued that RCC associated with ACDK are innocuous and do not predispose the patient to an increased risk of death from RCC. RCC arising from ACDK is considered to be a tumor of low malignant potential, compared with classic RCC. However, RCC has been reported to metastasize in 16% of the patients on dialysis and to be the cause of death in 2% of the kidney transplant recipients. The etiology of ACDK is unclear and its incidence increases with the duration of dialysis. ACDK patients have a propensity to develop adenocarcinoma. The increased incidence of RCC in ACDK patients warrants careful radiologic monitoring of end-stage kidneys in selected patients.

Carcinoma, Renal Cell↗

Histopathological study of female beagle dogs for four year treatment with subcutaneous implantation of chlormadinone acetate (CMA).

The histopathological changes related to chlormadinone acetate (CMA) implantation were examined using female beagle dogs given 10mg/kg for four years. All control animals showed sign of estrus during the experiment, with periods of anestrus of normal duration. In contrast, estrus was completely inhibited in the CMA-implanted animals. Histopathologically, uterine sections from the CMA-implanted animals showed cystic glandular hyperplasia, but no histologic evidence of endometritis, myometritis, and pyometra was found. In the ovaries of the CMA-implanted animals, developing ovarian follicles were observed but no mature follicles were noted in addition to an absence of corpus luteum. No remarkable changes were observed in the liver, adrenal, mammary gland, gallbladder and implanted site. Furthermore, the intensity of staining and number and size of ACTH-and LH-positive cells in the pituitary sections of CMA-implanted animals were not different from control animals. It was concluded, therefore, that subcutaneous implantation of CMA is a potential drug-delivery system for reducing changes due to antigonadotropic and glucocorticoid-like activities and characteristic histopathological changes in the uterus due to progestagenic activity.

Animals↗