[Progress in diagnosis and treatment of kidney diseases. III. Hereditary kidney diseases and others. 2. Alport syndrome].
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Biomedical subjects
Publications and source records attributed to T Harada.
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BACKGROUND: Urothelial carcinoma is one of the most common malignant neoplasms of the urinary tract and is characterized by a high local recurrence rate. However, no specific and reliable tumor marker has been identified for the diagnosis and follow-up of patients with urothelial carcinoma. METHODS: Urinary basic fetoprotein (U-BFP) levels were measured by enzyme immunoassay in 119 patients with urothelial carcinoma, 64 patients with other urologic malignancies, 144 patients with benign diseases, and 166 healthy individuals to evaluate it clinical efficacy as a marker of urothelial carcinoma. The histologic logic localization of BFP was also studied. A cutoff value was set at 14 ng/mL based on the maximum diagnostic efficiency. RESULTS: The specificity and sensitivity of U-BEP for urothelial carcinoma was 91.7% and 58%, respectively. THe U-BFP positive rate increased significantly with the histologic grade. The U-BFP positive rate was higher in both Tis and T2-4 than in Ta, 1 disease. The U-BFP level exceeded the cutoff value before curative therapy in 32 patients; U-BFP was normalized in 97% of these patients within 2 weeks after therapy. There was a total of 11 recurrences and the U-BFP level returned to abnormally high levels in all instances. Histologic localization of U-BFP was demonstrated in the cytoplasm of the tumor cells in 80% of the patients. CONCLUSION: Based on these results, U-BFP is a potential tumor maker of urothelial carcinoma. In particular, the test could be used to monitor patients whose U-BFP value is positive before therapy.
Substituted 2-sulfinylimidazoles were synthesized and investigated as potential inhibitors of gastric H+/K(+)-ATPase. The 4,5-unsubstituted imidazole series 6-11 and the 1,4,5,6-tetrahydrocyclopent[d]imidazole series 12 were found to be potent inhibitors of the acid secretory enzyme H+/K(+)-ATPase. Structure-activity relationships indicate that the substitution of 2-pyridyl groups at the 1-position of the imidazole moiety combined with (2-aminobenzyl)-sulfinyl groups at the 2-position leads to highly active compounds with a favorable chemical stability. Other substitution patterns in the imidazole moiety result in reducing biological activities. 2-[(2-Aminobenzyl) sulfinyl]-1-[2-(3-methylpyridyl)]-1,4,5,6-tetrahydrocyclopent++ ++ ++ [d]-imidazole (12h, T-776) was selected for further development as a potential clinical candidate. Extensive study on the acid degradation of 12h indicates a mechanism of action different from that of omeprazole, the first H+/K(+)-ATPase inhibitor introduced to the market.
STUDY DESIGN: This study analyzed immunohistological features of the extruded or sequestrated intervertebral disc of the lumbar spine. To clarify the pathogenesis of neovascularization, cells isolated from herniated disc were cultured and examined biologically. OBJECTIVES: The objectives of this study were to characterize the histologic features of extruded or sequestrated discs and inflammatory cells that infiltrate along the margins of the disc tissue and to clarify the pathogenesis of neovascularization observed at the edge of the disc tissue. SUMMARY OF BACKGROUND DATA: When some of the contents of the disc extrudes into the epidural space and is considered "foreign," an autoimmune response develops, which can lead to a chronic inflammatory response. However, the pathogenesis of inflammatory cell infiltrations and neovascularization are not clearly defined. METHODS: The herniated discs were obtained during surgery and were stained with anti-interleukin-1, intercellular adhesion molecule-1, lymphocyte function-associated antigen, and basic fibroblast growth factor antibodies by using an indirect immunoperoxidase method. Cells isolated from herniated disc were cocultured with human endothelial cells and basic fibroblast growth factor contained by cultured disc cells were measured by radioimmunoassay. RESULTS: The ingrowth of granulation tissue with vascularization, occurring at the edge of fibrocartilage fragment, was present at 11 of 16 of extruded and 3 of 5 of sequestrated discs. Anti-interleukin-1, intracellular adhesion molecule-1, lymphocyte function-associated antigen, and basic fibroblast growth factor were expressed on most of mononuclear cells infiltrating into the extruded or sequestrated disc. Cells from the extruded or sequestrated disc demonstrated significantly greater levels of basic fibroblast growth factor than those from the protruded disc, and they enhanced the proliferation of endothelial cells. CONCLUSIONS: This study showed that mononuclear cells infiltrating along the margins of extruded discs expressed inflammatory mediators and might induce neovascularization and persistence of inflammation.
The possibility of active specific immunotherapy using interleukin-1 (IL-1) plus sonicated tumor supernatant (SS) was examined in a murine tumor model. The growth of intraperitoneally or subcutaneously inoculated plasmacytoma MOPC104E, which is syngeneic to BALB/c mice, was significantly suppressed by intraperitoneal pretreatment with IL-1 and SS from MOPC104E cells (MOPC-SS), on days 10, 7, and 4 before tumor inoculation. Pretreatment with IL-1 plus MOPC-SS or MethA-SS (SS from MethA cells) suppressed the growth of subcutaneous tumor of only the corresponding tumor cells, indicating the development of tumor-specific immunity in vivo. The splenic cells of immunized mice with IL-1 and MOPC-SS showed tumor neutralizing activity. However, their tumor neutralizing activity was abrogated when they were treated in vitro with anti-Thy1.2 or anti-L3T4 plus complement. Moreover, when combined with indomethacin per oral, IL-1 plus MOPC-SS significantly suppressed the growth of established subcutaneous tumor and prolonged survival of post-operative mice. These results suggest that this new type of active specific immunotherapy could be a useful method for cancer immunotherapy, especially when combined with oral indomethacin.
Serum levels of the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and the carboxy-terminal propeptide of type I procollagen (PICP) were measured in 95 patients with renal hyperparathyroidism who had undergone a total parathyroidectomy and autotransplantation of a small portion of the resected gland. The results were compared with the serum levels of other bone metabolic markers and bone mineral densities in the distal radius (R-BMD) and lumbar vertebrae (L-BMD), which were measured by dual energy x-ray absorptiometry and converted to the percentage of the mean value of sex- and age-matched healthy controls. The preoperative mean values of ICTP and PICP were 142.4 ng/ml and 187.8 ng/ml, respectively. Although the serum levels of PICP levels exceeded the normal range in 42.1% of the patients, those of ICTP exceeded it in all of them. The serum levels of ICTP correlated positively not only with those of tartrate-resistant acid phosphatase (TRACP), total alkaline phosphatase (ALP), and osteocalcin but also negatively with the values of %R-BMD and %L-BMD and seemed to manifest specifically the disturbance of bone metabolism. On the other hand, the serum levels of PICP correlated with those of ALP and TRACP but not with values of %BMDs. After surgery, the serum levels of ICTP decreased gradually, but those of PICP increased immediately up to peak values at 7 days and then decreased gradually after 14 days, reaching the normal range at 3 months. These changes in the bone metabolic markers seemed to reflect the change in bone metabolism that was converting from bone resorption to bone formation. The percent change in the PICP/ICTP ratio at 7 days correlated significantly with the percent change in R-BMD at 12 months, and it was suggested that postoperative bone gain might be predicted using a combination of postoperative changes in PICP and ICTP.
We examined the diurnal variation of c-fos gene expression during a 12:12 light/dark cycle in developing rat retinas by in situ hybridization histochemistry. c-fos Gene was not expressed before postnatal day 10 (P10) but was expressed on P15 in the outer nuclear layer throughout the dark period and in the inner nuclear layer and the ganglion cell layer during the light period. These results demonstrated that the earliest c-fos gene expression occurred between P11 and P15. The good correlation between the expression of c-fos gene and the genes coding for proteins involved in phototransduction, in terms of their diurnal variation and in their development, suggested that c-fos gene may play a role in the regulation of these genes in retinal cells during the light/dark cycle.
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OBJECTIVE: To investigate the effect of earlier administration of hCG according to serum concentrations of P on the outcome of IVF-ET in cycles in which a subtle rise in serum P (1.0 to 2.0 ng/mL; conversion factor to SI unit, 3.180) occurred during the follicular phase. DESIGN: Retrospective study. PATIENTS: A total of 110 infertile women underwent 124 cycles of IVF-ET at Tottori University Hospital. MAIN OUTCOME MEASURES: Serum was obtained daily or every 12 hours from day 7 until the administration of hCG. Serum E2 and P concentrations were measured by RIA. In 19 of 36 subtle P rise cycles, hCG injection was given when the levels of serum P exceeded 1.0 ng/mL ("rescued" subtle P rise). Parameters of IVF outcomes for the no P rise, the subtle P rise, and the rescued subtle P rise cycles were compared. RESULTS: The mean day of hCG administration in the rescued cycles was 1 day earlier than those of the subtle P rise and no P rise cycles. The mean number of oocytes collected was significantly higher in the subtle P rise and rescued P rise cycles than in the no P rise cycles. The mean follicular diameter on the day of hCG administration was 13.9 mm in the rescued cycles, significantly smaller than those of the no P rise and subtle P rise cycles. However, there was no significant difference in the cleavage rates between the three groups. The rate of embryonic development beyond four-cell stage was increased significantly in the rescued cycles and no P rise cycles versus the subtle P rise cycles. Embryos obtained in the no P rise and rescued cycles were of better morphological quality than those obtained in the P rise cycles. The implantation rate was significantly higher in the rescued cycles than in the P rise cycles. CONCLUSION: The data suggest that, if hCG is administered when a subtle P rise is detected, embryo quality and subsequent implantation rate can be improved.
BACKGROUND: Detailed information on the depth of invasion of superficial esophageal cancer is required for endoscopic mucosal resection. As a pretherapeutic diagnostic procedure, endoscopic ultrasonography using conventional 7.5 MHz systems has been ineffective at providing sufficient details. A newly developed, thin ultrasound probe system provides both radial and linear scanning for evaluation of superficial esophageal cancer. METHODS: Endoscopic ultrasonography was performed in 16 patients using a switchable probe driven at 20 MHz. Seventeen lesions of superficial esophageal cancer were evaluated for depth of invasion to discriminate mucosal from submucosal penetration. RESULTS: The overall accuracy of staging was 64.7%. In all six errors, mucosal cancers were overstaged as submucosal invasion. The diagnostic accuracy was 80% when the muscularis mucosae was visualized. CONCLUSION: A 20 MHz linear-radial switchable probe is a useful new method in the staging of superficial esophageal cancer.
Aging effects on the susceptibility to chemical endometrial carcinogenesis were investigated in ICR female mice. The animals were divided into 3 groups of different ages: 1 month (young), 6 months (middle), and 12 months (old) at initiation of treatment. They received weekly oral administration of mixture of ETU (100 mg/kg body weight) and sodium nitrite (70 mg/kg body weight) for 6 months followed by a withdrawal period of 3 months. All animals were subjected to histopathology. The incidence of endometrial adenocarcinomas was highest in the middle age group (8/20), secondary in the old age group (4/20), and lowest in the young group (1/20). The incidence of atypical glandular hyperplasia, a precursor lesion of the tumor, was also higher in the middle age group. The endometrial adenocarcinomas showed morphological similarities among all age groups and the nuclei of tumor cells lost almost all staining reactivity to estrogen receptors. The labeling indices with bromodeoxyuridine (BrdU) were notably higher in the old age group than in the young and middle age groups. A further investigation on the aging process of female genital organs in control mice revealed that their senility seemed to be preceded by the formation of ovarian cysts which first appeared at 6 months of age with a concomitant elevation of plasma 17 beta-estradiol level. These results indicate that the susceptibility of the mouse endometrium to the carcinogenic effects of N-nitroso ETU could be closely linked with the stage of aging process of the genital organs and it appears to be most susceptible when initiated at around 6 months of age. However, the mitotic activity of neoplastic endometrial glandular cells seems to be higher in older mice than younger ones.
OBJECTIVE: To evaluate the heating effect of microwave irradiation on the dog adrenal gland and to assess the clinical feasibility of microwave ablation of adrenal tumours. MATERIALS AND METHODS: The thermal distribution and histology were evaluated after dog adrenal glands were irradiated at different intensities with microwaves. Irradiation at 70 W for 30 s was also performed after laparotomy, on the adrenal tumour of a patient with primary aldosteronism. RESULTS: Microwave irradiation at 70 W for 30 s provided a sufficiently high temperature to produce coagulation within a 5 mm radius of the microwave electrode. The adrenal tumor in the patient with primary aldosteronism was coagulated successfully by this dose of microwave irradiation. CONCLUSION: Microwave ablation of the adrenal gland may be clinically applicable in the treatment of adrenal tumours.
Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. However, the relationship between the vascularity of HCC and the expression of angiogenic factors has not been investigated. In addition, no detailed studies have examined the possible involvement of angiogenic factors in the grade of malignancy of HCC. The aim of this study was to determine which angiogenic factors regulate tumor angiogenesis and contribute to the invasive ability of liver tumors, especially of HCC. Northern blot analysis was used to examine the transcriptional expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), and acidic FGF in resected surgical specimens (20 HCC and 9 metastatic liver tumors). Correlations between messenger RNA (mRNA) expression and arteriographic findings, as well as histopathological findings, were evaluated. Immunohistochemistry was performed to identify the localization of cells expressing VEGF in HCC. Higher levels of VEGF mRNA were observed in 12 of 20 HCC and 2 of 9 metastatic liver tumors than in corresponding nontumorous tissues. The degree of VEGF mRNA expression was significantly correlated with the intensity of tumor staining in angiograms (P<.01). On immunohistochemical observation, VEGF protein was intensely detected in HCC cells. Furthermore, basic FGF mRNA was detected in 9 of 20 HCC and was related to the capsular infiltration of cancer cells (P<.05). In contrast, no significant difference was observed in the very low levels of acidic FGF mRNA found in the tumorous and nontumorous portions of the liver. In conclusion, these results suggest that VEGF contributes to angiogenesis of liver tumors, whereas basic FGF may be involved in the invasion of HCC into the surrounding tissues.
The prognosis for hepatocellular carcinoma (HCC) depends mainly on the clinicopathological characteristic regarding invasion and metastasis. In addition, another distinguishing feature of HCC is the high incidence of concomitant liver cirrhosis, in which the extracellular matrix proliferates markedly. Therefore, the present study was designed to investigate the molecules responsible for the invasion potential of HCC by focusing on matrix metalloproteinase (MMP) in particular, MMP-2 and MMP-9 and the corresponding tissue inhibitor of metalloproteinase (TIMP-2 and TIMP-1), because these enzymes participate in the degradation of the extracellular matrix including the basement membrane. Tumorous and adjacent nontumorous liver samples were obtained from 23 HCC patients who underwent a partial hepatectomy. In 16 of the 23 HCC samples, transcripts for MMP-9 were detected in the tumorous tissues, and 15 of 16 of these samples showed stronger expression in the tumorous tissues than in the nontumorous tissues. On the other hand, MMP-2 messenger RNA (mRNA) was detected in 18 of the 23 cases. Eight of these 18 cases showed more intense expression in the tumorous tissues than in the nontumorous tissues, whereas the expression levels were lower in the tumorous tissues than in the nontumorous tissues in 7 of 18 samples. With respect to the correlation between the clinicopathological features and mRNAs expression, it was found that the expression of MMP-9 mRNA in HCC with capsular infiltration was significantly higher than in HCC without capsular infiltration. HCC with capsular infiltration also tended to have a higher ratio of MMP-9 mRNA expression to TIMP-1 mRNA expression. In addition, the expression of MMP-2 mRNA in nontumorous cirrhotic tissues was significantly higher than in nontumorous tissues from patients with chronic hepatitis. Immunohistochemical examinations revealed that MMP-9 immunoreactivity was the most intense in the HCC cells, particularly in those cells in the marginal areas of the tumorous tissues. In conclusion, the present study shows that MMP-9 is closely participated in capsular infiltration in HCC.
We identified kan-1 complementary DNA (cDNA), the sequence of which is identical to bile acid CoA:amino acid N-acyltransferase (BAT), a liver enzyme that catalyzes the conjugation of bile acids with glycine or taurine. Kan-1(BAT) messenger RNA (mRNA) levels of the resected specimens obtained from 37 hepatocellular carcinoma (HCC) patients were studied in an attempt to evaluate prognostic significance in HCC patients after partial hepatectomy. Using Northern blot hybridization, kan-1(BAT) mRNA levels were quantified in tumorous and nontumorous tissues, and the ratio of the former to the latter was defined as the kan-1(BAT) ratio. Twelve patients had a kan-1(BAT) ratio < 0.5 (low kan-1[BAT] ratio), and 25 patients had a ratio >0.5 (high kan-1[BAT] ratio). The patients with a low kan-1(BAT) ratio demonstrated poorer survival than the patients with a high kan-1(BAT) ratio (P = .0013). The overall estimated hazard ratio for death in patients with a low kan-1(BAT) ratio was 68.05 according to a multivariate model (P = .0005). Thus, the kan-1(BAT) ratio may serve as a new molecular prognostic marker in HCC patients, following hepatic resection.
The aim of this study was to investigate the relationship between chlamydia infection and adnexal adhesion. A total of 131 infertile women who were otherwise asymptomatic underwent chlamydia antibody testing and laparoscopy. These women had additional infertility factors. Serum concentration of anti-Chlamydia trachomatis immunoglobulins G and A were determined prospectively by means of an enzyme-linked immunosorbent assay (ELISA). Results were compared with the tubal patency and severity of adnexal adhesion. Sensitivity, specificity, positive and negative predictive value, and likelihood ratios of anti-C.trachomatis antibody titres for the presence of adnexal adhesion were calculated. Patients who were positive for chlamydia antibody had a significantly higher incidence of tubal occlusion than those who were negative (47.1 versus 25.0%). Adnexal adhesion scores were significantly higher in the patients who were positive for chlamydia antibody than those in patients who were negative (17.1 versus 8.5). Adnexal adhesion scores were significantly correlated with anti-chlamydia antibody titre by ELISA [immunoglobulin (Ig) G: r = 0.60, Ig A: r = 0.61]. As the antibody titre by ELISA rose, the specificity, positive predictive value and the positive likelihood ratio all increased. In conclusion, C.trachomatis antibody testing is a simple and inexpensive means of predicting pelvic damage and laparoscopic examination may be recommended for patients with high anti-C.trachomatis antibody titres by ELISA.
OBJECTIVE: The value of preoperative transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) has not been duly appreciated. The authors assessed the advantages and disadvantages of preoperative TACE by reviewing their experience with the procedure. METHODS: A total of 140 patients who underwent hepatectomy for HCC were entered into the study (105 received preoperative TACE and 35 did not). The authors investigated the reduction of tumor size and the complications after TACE, as well as the relationship between the interval from TACE to resection and the occurrence of complications. They compared postoperative morbidity and mortality between the TACE and non-TACE groups. They also compared survival and disease-free survival between the two groups, as well as between subgroups, defined by the extent of tumor necrosis achieved with TACE. RESULTS: A distinct reduction of tumor size was observed in approximately half of the TACE group. However, there were 68 appreciable complications of TACE in 56 patients (53.3%), and the interval between TACE and resection was significantly prolonged in the patients with complications. The postoperative morbidity and mortality rates of the TACE group were not different from those of the non-TACE group. Preoperative TACE did not improve the survival or disease-free survival of the whole patient group after hepatectomy. In addition, the survival and disease-free survival rates of the three TACE subgroups were not different from those of the non-TACE group. CONCLUSIONS: Preoperative TACE should only be performed to reduce tumor bulk in patients with HCC with borderline resectability. In such patients, increased tumor resectability appears to improve the survival rate. Preoperative TACE does not promote tumor recurrence.
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