Microsurgical subinguinal varicocelectomy.
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Humans↗
Biomedical subjects
T Ichikawa
Publications and source records attributed to T Ichikawa.
Changes in serum prostate-specific antigen following prostatectomy in patients with benign prostate hyperplasia.
PURPOSE: To investigate how prostatectomy for patients with benign prostate hyperplasia (BPH) affected the serum prostate-specific antigen (PSA) levels. METHODS: In 193 patients who underwent prostatectomy for BPH, serum PSA levels were measured before and three months after the operation. The total prostate weight measured by transrectal ultrasonography (TRUS) and the weight of the surgical specimen were examined in relation to the pretreatment PSA value and the changes in PSA levels after the operation. RESULTS: The transition zone volume measured by TRUS could well estimate the weight of the surgical specimen in patients who underwent subcapsular prostatectomy and transurethral resection of the prostate. The concentration of preoperative serum PSA showed a significant correlation with the prostatic volume and with the transition zone volume. Removal of 1 g of BPH tissue reduced serum PSA levels by an average of 0.18 ng/mL. The change in serum PSA levels after the prostatectomy correlated with the total prostatic gland volume and with the transition zone volume. CONCLUSIONS: The elevated PSA levels in patients with BPH were caused by the enlargement of the transition zone. After the resection of the adenoma, PSA levels should be expected to decrease to the normal range.
Adenoma↗
Abnormalities of the FHIT gene in human oral carcinogenesis.
The abnormalities of the fragile histidine triad (FHIT) gene in tissue samples of oral squamous cell carcinomas (SCCs) along with several leukoplakias and an erythroplakia were examined to determine whether the FHIT gene is actually a frequent target in vivo for alteration during oral carcinogenesis. Abnormal transcripts of the FHIT gene were found in eight of 15 oral SCCs. Although these abnormal transcripts varied widely, deletion patterns incorporating a deletion of exon 5 were the most common. Loss of heterozygosity (LOH) analysis demonstrated that the abnormal FHIT transcripts found in cancer cells were attributable to abnormalities of the FHIT gene. Abnormal FHIT transcripts were also observed in two of seven premalignant lesions. Interestingly, in the case of one patient with a premalignant lesion showing an abnormal FHIT transcript, subsequent oral SCC developed during a 3-year follow-up period. On the other hand, in the two patients from whom both leukoplakia and SCC samples were taken simultaneously, abnormal FHIT transcripts were found only in the SCCs. Although the functional role of FHIT remains to be clarified, these results suggest that the FHIT alteration is actually involved in carcinogenesis of the oral epithelium.
Acid Anhydride Hydrolases↗
Esophageal metastasis of hepatocellular carcinoma.
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Carcinoma, Hepatocellular↗
Isolation of Trichosporon asahii from environmental materials.
Trichosporon asahii is the most clinically important pathogenic yeast in the genus Trichosporon, as this species causes both deep-seated infection and summer-type hypersensitivity pneumonitis. We isolated 29 T. asahii colonies from environmental samples using the polymerase chain reaction (PCR) and dichloran rose bengal chloramphenicol (DRBC) medium. Our results suggest that T. asahii is common in nature.
Culture Media↗
Vitamin E inhibits cell proliferation and the activation of extracellular signal-regulated kinase during the promotion phase of lung tumorigenesis irrespective of antioxidative effect.
We have already reported that the activation of extracellular signal-regulated kinase (Erk) is critical in the stimulation of cell proliferation during the promotion stage of urethane-induced lung tumorigenesis in mice. Also, we have found that vitamin E suppresses lung tumorigenesis by inhibiting cell proliferation at the promotion stage. However, it is still unclear whether this inhibitory effect at the promotion stage is based on the antioxidative effect of vitamin E or not. In order to address this question, we examined the inhibitory effect of alpha-tocopheryloxybutyric acid (TSE), an ether derivative of vitamin E that cannot act as an antioxidant in vivo, on cell proliferation and the activation of Erk during promotion of lung tumorigenesis. On day 30 after urethane injection (750 mg/kg, i. p.) in A/J mice, TSE or vitamin E at 100 micromol/kg, p.o. was administered. Twenty-four hours after the final administration, the mice were killed to analyze cell proliferation and related parameters. The labeling index of proliferating cell nuclear antigen (a marker of cell proliferation) and ornithine decarboxylase activity (a marker of the promotion stage in lungs) were attenuated by treatment with TSE or vitamin E. TSE or vitamin E treatment also inhibited urethane-induced activation of Erk and suppressed the activation of other essential members of the Erk cascade (Ras, Raf and Mek). These results suggest that vitamin E inhibits cell proliferation and activation of the Erk cascade during promotion of urethane-induced lung tumorigenesis in mice, independent of its antioxidative effect.
Animals↗
Molecular characterization of a novel gamma-glutamyl transpeptidase homologue found in rat brain.
A cDNA clone for a novel homologue to gamma-glutamyl transpeptidase (gamma-GTP), termed GTPH, was isolated from a rat brain expression cDNA library using antisera against total brain synaptosomal fractions. The cloned GTPH consists of 641 amino acid residues (78 kDa) and exhibits structural similarity with a conventional type of gamma-GTP that is predominantly expressed in the liver: They share significant amino acid homology (33% identity, 73% similarity) spanning over the entire sequence. RNA analyses revealed that GTPH mRNA expression is found only in the nervous system, including all brain regions, eyes and peripheral ganglia, and increases during development. Endogenous GTPH protein is a membrane-bound glycoenzyme and migrates as 90-100 kDa in polyacrylamide gels. Taken together, GTPH is a novel form of a gamma-GTP-like molecule expressed exclusively in the nervous system.
Amino Acid Sequence↗
Increased activity in benign phyllodes tumor on Tc-99m MDP scintimammography.
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Adult↗
Various imaging modalities for the detection of salivary gland lesions: the advantages of 201Tl SPET.
The aim of this study was to compare dual-isotope (99Tc(m) and 201Tl) SPET imaging with computed tomography (CT) and magnetic resonance imaging (MRI) in the differentiation of various lesions of the major salivary glands. Twenty-two patients underwent dual-isotope SPET imaging, of whom 12 also had CT and 15 also had an MRI study. The uptake ratio and retention index for 99Tc(m) and 201Tl were calculated by drawing regions of interest on the involved and normal glands. Both CT and MRI were interpreted by two radiologists. All malignant tumours were detected by all three modalities. Warthin's tumours were detected by dual-isotope SPET imaging; however, MRI failed to differentiate Warthin's tumour from pleomorphic adenoma. Of 13 other benign tumours, dual-isotope SPET correctly diagnosed 12. Of 16 tumours showing a cold defect on the 99Tc(m) images, parametric analysis with 201Tl gave an accuracy of 94%, whereas CT gave an accuracy of 70-90%. MRI was 73-91% accurate in differentiating between benign (Warthin's) and malignant tumours. We believe that dual-isotope SPET imaging (99Tc(m) and 201Tl), together with semi-quantitative analysis, is the method of choice for differentiating between various lesions of the major salivary glands.
Adenolymphoma↗
The effects of DCG-IV and L-CCG-1 upon phencyclidine (PCP)-induced locomotion and behavioral changes in mice.
The behavioral changes of mice induced by acute and repeated i.p. injection of phencyclidine (PCP) were observed by measuring locomotor activity and stereotyped behavior. Then, the effects of metabotropic glutamate receptor (mGluR) agonists, DCG-IV and L-CCG-1, on the above behavioral changes induced by PCP were found. The effects of DCG-IV were very strong and completely depressed the PCP-induced hyperlocomotion. The effects of L-CCG-1 were not so strong. Repeated injection of PCP for 20 days into mice induced lower locomotor activity than that in acutely injected mice. These behavioral changes may be related with the negative symptoms of schizophrenia. In order to examine some molecular mechanisms of PCP-induced behavioral changes, Northern blot analysis of total RNA from prefrontal cortical tissues of mice treated with PCP, DCG-IV, and L-CCG-1 was carried out.
Amino Acids, Dicarboxylic↗
Complement depletion facilitates the infection of multiple brain tumors by an intravascular, replication-conditional herpes simplex virus mutant.
Intravascular routes of administration can provide a means to target gene- and virus-based therapies to multiple tumor foci located within an organ, such as the brain. However, we demonstrate here that rodent plasma inhibits cell transduction by replication-conditional (oncolytic) herpes simplex viruses (HSV), replication-defective HSV, and adenovirus vectors. In vitro depletion of complement with mild heat treatment or in vivo depletion by treatment of athymic rats with cobra venom factor (CVF) partially reverses this effect. Without CVF, inhibition of cell infection by HSV is observed at plasma dilution as high as 1:32, while plasma from CVF-treated animals displays anti-HSV activity at lower dilutions (1:8). When applied to the therapy of intracerebral brain tumors, in vivo complement depletion facilitates the initial infection (assayed at the 2-day time point) by an intra-arterial replication-conditional HSV of tumor cells, located within three separate and distinct human glioma masses. However, at the 4-day time point, no propagation of HSV from initially infected tumor cells could be observed. Previously, we have shown that the immunosuppressive agent, cyclophosphamide (CPA), facilitates the in vivo propagation of an oncolytic HSV, delivered intravascularly, within infected multiple intracerebral masses, by inhibition of both innate and elicited anti-HSV neutralizing antibody response (K. Ikeda et al., Nat. Med. 5:881-889, 1999). In this study, we thus show that the addition of CPA to the CVF treatment results in a significant increase in viral propagation within infected tumors, measured at the 4-day time period. The concerted action of CVF and CPA significantly increases the life span of athymic rodents harboring three separate and large glioma xenografts after treatment with intravascular, oncolytic HSV. Southern analysis of viral genomes analyzed by PCR reveals the presence of the oncolytic virus in the brains, livers, spleens, kidneys, and intestine of treated animals, although none of these tissues displays evidence of HSV-mediated gene expression. In light of clinical trials of oncolytic HSV for malignant brain tumors, these findings suggest that antitumor efficacy may be limited by the host innate and elicited humoral responses.
Adenoviridae↗
Hepatocellular adenoma: multiphasic CT and histopathologic findings in 25 patients.
PURPOSE: To evaluate multiphasic computed tomographic (CT) findings of hepatic adenomas and to correlate these findings with those of histopathologic analysis. MATERIALS AND METHODS: Multiphasic helical CT was performed in 25 patients with 44 hepatic adenomas. Nonenhanced scans were obtained in all cases, along with hepatic arterial-dominant phase (HAP) and portal venous-dominant phase (PVP) images at 25-28 and 60-70 seconds after intravenous contrast material injection at 3-5 mL/sec. Twelve patients with 24 adenomas also underwent delayed-phase (5-10-minute) CT. Two independent readers retrospectively reviewed each case for the number of detectable lesions in each CT phase, morphologic features of tumors, and degrees of enhancement. RESULTS: Thirteen patients had solitary adenomas; 12 patients had two or three adenomas. Both observers agreed on the numbers of lesions detected in all cases and in all phases of enhancement. The detection rate for all 44 adenomas per type of examination was as follows: nonenhanced, 86% (38 of 44); HAP, 100% (44 of 44); PVP, 82% (36 of 44), and delayed, 88% (21 of 24). Tumor margins were well defined in 38 adenomas (86%), and the surface was smooth in 42 adenomas (95%). The right hepatic lobe was the only site of adenoma or was a site along with the left lobe in 29 cases (66%). Tumor fat and calcifications were uncommon (three cases [7%] and two cases [5%], respectively). Other than areas of fat, hemorrhage, or necrosis, the adenomas enhanced nearly homogeneously, especially on PVP and delayed-phase scans. Five patients had coexistent hepatic masses, which were focal nodular hyperplasia (n = 3) or hepatocellular carcinoma (n = 2). CONCLUSION: Hepatic adenomas often have characteristic features at multiphasic CT that may allow their distinction from other hepatic masses.
Adenoma, Liver Cell↗
Islet cell tumor of the pancreas: biphasic CT versus MR imaging in tumor detection.
PURPOSE: To compare the effectiveness of biphasic computed tomography (CT) and magnetic resonance (MR) imaging in the detection of pancreatic islet cell tumors. MATERIALS AND METHODS: Retrospective quantitative, qualitative, and receiver operating characteristic analyses of biphasic CT and MR imaging were performed in 19 patients with 26 histopathologically proved islet cell tumors. Delayed arterial dominant-phase (AP) and portal venous-phase (PVP) biphasic CT was performed after the administration of contrast material. MR imaging included T1-weighted spin-echo (SE) and T2-weighted SE or fast SE imaging, fat-saturated T1-weighted SE imaging, dynamic contrast material-enhanced T1-weighted gradient-echo imaging, and delayed enhanced T1-weighted SE imaging with or without fat saturation. RESULTS: PVP CT and delayed enhanced T1-weighted MR imaging had the highest A(z) values (0.98 and 0.97, respectively; P <.05). Delayed enhanced T1-weighted MR imaging had the highest relative sensitivity (14-15 [74%-79%] of 19 lesions), followed by PVP CT (18-19 [69%-73%] of 26 lesions), AP CT (17-19 [65%-73%] of 26 lesions), fat-saturated T1-weighted MR imaging (eight to 10 [57%-71%] of 14 lesions), T2-weighted (16-17 [62%-65%] of 26 lesions), T1-weighted (15-18 [58%-69%] of 26 lesions) MR imaging, and dynamic MR imaging (nine [56%] of 16 lesions). CONCLUSION: Biphasic (especially PVP) CT and MR imaging have similar effectiveness in the detection of islet cell tumors if fat-saturated T1-weighted and delayed enhanced T1-weighted MR imaging are included.
Adenoma, Islet Cell↗
Liver adenomatosis: clinical, histopathologic, and imaging findings in 15 patients.
PURPOSE: To report and correlate the clinical, histopathologic, and imaging findings in 15 patients with liver adenomatosis. MATERIALS AND METHODS: Fifteen adult patients had more than 10 hepatic adenomas each and no history of glycogen storage disease or anabolic steroid use. Ten of them underwent bolus-enhanced dynamic computed tomography (CT) with or without magnetic resonance (MR) imaging, ultrasonography, and/or angiography. RESULTS: Clinical abnormalities included abdominal pain in 11 (73%) and hepatomegaly in 10 (67%) patients, and abnormal liver function in 10 (91%) of 11 patients. The number of adenomas in each patient was 10-50 at imaging, but many more lesions were found in the resected specimens. Hemorrhage was commonly found within adenomas at histopathologic analysis, but only four patients had clinical and imaging evidence of substantial hemorrhage. In all patients, the adenomas increased over time, and two patients developed hepatocellular carcinoma. CT and MR features of the adenomas included evidence of hypervascularity (63%), intratumoral fat (50% of patients at CT, 80% at MR), and decreased conspicuity at portal venous and delayed-phase imaging. Fifty percent of patients had congenital or acquired hepatic vascular abnormalities. CONCLUSION: The imaging and histopathologic features of individual adenomatous lesions are similar to those reported in young women who are taking oral contraceptives. However, the lesions in liver adenomatosis are not steroid dependent but rather multiple, progressive, and symptomatic, and they are more likely to lead to impaired liver function, hemorrhage, and perhaps malignant degeneration.
Abdominal Pain↗
Fibrolamellar hepatocellular carcinoma: pre- and posttherapy evaluation with CT and MR imaging.
PURPOSE: To determine the features of advanced hepatic and extrahepatic fibrolamellar hepatocellular carcinomas (HCCs) and their effects on immediate surgical management and tumor recurrence. MATERIALS AND METHODS: Thirty-one patients with fibrolamellar HCC underwent pretherapy computed tomography (CT); 11 underwent pretherapy magnetic resonance (MR) imaging. All 40 patients underwent posttherapy CT; four, follow-up MR imaging. Imaging, surgical, and histopathologic findings were correlated. RESULTS: Twenty-five (81%) patients had solitary tumors (mean maximum diameter, 13 cm). Thirteen (42%) patients had intrahepatic biliary obstruction; 27 (87%) patients had involvement of the portal or hepatic veins. Thirteen (42%) had extrahepatic tumor spread, nine (29%) had distant metastases on pretherapy images, and 20 (65%) had lymphadenopathy. Thirty-two (80%) of 40 patients underwent exploration surgery; curative resection was attempted in 25 (62%), including four patients who underwent liver transplantation. Only 17 patients were considered to have had hepatic and extrahepatic tumors completely excised. Tumor recurred in all eight of the 17 patients who had extrahepatic disease at pretherapy CT and in four of the seven patients who seemed to have tumor limited to the liver. A combination of repeat tumor resection and adjuvant chemotherapy resulted in prolonged tumor-free survival in some cases. CONCLUSION: Fibrolamellar HCC frequently demonstrates aggressive local invasion and nodal and distant metastases. Pretherapy and follow-up imaging are important for staging, surveillance, and optimal management. Aggressive surgical resection may be helpful to control fibrolamellar HCC and to prolong survival in appropriately selected cases.
Adolescent↗
CGRP modulates mucin synthesis in surface mucus cells of rat gastric oxyntic mucosa.
We examined the effects of the calcitonin gene-related peptide (CGRP), including the possible participation of nitric oxide (NO), on mucin biosynthesis in the surface epithelium and remaining deep mucosa as well as the entire mucosa and compared the distribution of CGRP and NO synthase (NOS) using a combination of double immunofluorescence labeling and multiple dye filter. Pieces of tissue obtained from the corpus and antrum were incubated in a medium containing [(3)H]glucosamine and CGRP, with or without the NOS inhibitor. CGRP dose-dependently enhanced [(3)H]glucosamine incorporation into the corpus mucin but had no effect on antral mucin biosynthesis. The CGRP receptor antagonist, CGRP-(8-37), prevented the increase in (3)H-labeled corpus mucin. This stimulation of corpus mucin synthesis disappeared after removal of the surface mucus cell layer. CGRP activated the mucin biosynthesis in the surface mucus cells. In the full-thickness corpus mucosa, CGRP-induced activation was completely blocked by the NOS inhibitor. CGRP-immunoreactive fibers were intertwined within the surface mucus cell layer with type I NOS immunoreactivity. These results show that CGRP-stimulated mucin biosynthesis mediated by NO is limited to surface mucus cells of the rat gastric oxyntic mucosa.
Animals↗
Optically active antifungal azoles. X. Synthesis and antifungal activity of N.
New optically active antifungal azoles, N-14-(azolyl)phenyl]- and N-14-(azolylmethyl)phenyl]-N'-[(IR,2R)-2(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(IH-1,2,4-triazol-1-yl)propyllazolones (1, 2, 3), were prepared in a stereocontrolled manner. Compounds 1-3 showed strong antifungal activity against Candida albicans in vitro. Among them, the imidazolidinones 3 showed a broad antifungal spectrum in vitro as well as potent in vivo activity against candidiasis and aspergillosis in mice. The imidazolidinones (3i, j, k) having 1H-1,2,3-triazol-1-yl, 2H-2-tetrazolyl and IH-1-tetrazolyl moieties were found to exert strong protective effect against aspergillosis.
Antifungal Agents↗
Optically active antifungal azoles. XI. An alternative synthetic route for 1.
New routes for the synthesis of the optically active antifungal triazoles 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1b) and the 3-14-(1H-1,2,3-triazol-1-yl)phenyl]-2-imidazolidinone analog (1a) that possess an imidazolidine nucleus were established. The key synthetic intermediates, (2R,3R)-3-(2,2-diethoxvethyl)amino-2-(2,4-difluorophenyl)-1-(1H1,2,4-triazol-1-yl)-2-butanol (8) and (2R,3R)-2-(2,4-difiuorophenyl)-3-(2-h ydroxyethyl)amino-1-(1H-1,2,4-triazol-1-yl)-2-butanol (14), were prepared by the ring-opening reaction of the oxirane (2) with the corresponding 2-substituted ethylamines. The acetal (8) was converted to the imidazolidinones (1a, b) by condensation with the carbamates (10a, b) followed by treatment with hydrochloric acid and subsequent catalytic hydrogenation. The candidate selected for the clinical trials, 1b (TAK-456), was alternatively prepared from the hydroxyethylamino intermediate (14) via two reaction steps: condensation with the carbamate (10b) to the urea (15) and subsequent cyclization to the imidazolidinones. This newly developed synthetic route could be applied to a large scale preparation of 1b.
Antifungal Agents↗