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Biomedical subjects

T Ichikawa

Publications and source records attributed to T Ichikawa.

At least 163 records · Page 9Linked to original sources

Influence of L-365,260, a CCK-B/gastrin receptor antagonist, on tetragastrin-stimulated mucin metabolism in rat gastric mucosa.

The effect of L-365,260, a CCK-B/gastrin receptor antagonist, on gastric mucus metabolism induced by tetragastrin was investigated in rats. In vivo application of L-365,260 at a dose of 3 mg/kg p.o. significantly reduced the tetragastrin (12 microg/kg s.c. )-stimulated gastric acid secretion, but 0.3 mg/kg of L-365,260 did not affect the gastric acid secretion induced by the tetragastrin administration. A single administration of 12 microg/kg of tetragastrin caused an increase in gastric mucin content in the soluble mucus (175% of control), the mucus gel (155% of control) and the surface mucosa (125% of control). L-365,260 at the doses of 0.3 and 3 mg/kg considerably inhibited the tetragastrin-induced mucus secretion in the soluble mucus (70-80% of tetragastrin) and the mucus gel (45-70% of tetragastrin) and resumed the mucus accumulated in the surface mucosa to the control situation (80% of tetragastrin). In the in vitro incubation system of rat gastric mucosa, L-365,260 (0.1-10 micromol/l) caused no significant change in gastric mucin synthesis. An in vivo study also showed that the increase in total gastric mucin content and the distributional changes in mucin content induced by 12 microg/kg of tetragastrin reverted with 3 mg/kg of L-365,260 pretreatment to the control situation. It is evident from these results that the CCK-B/gastrin receptor is involved in the mechanism of the stimulation of mucus secretion and/or mucus accumulation in rat gastric mucosa and not directly concerned with the action of gastrin-induced gastric acid secretion.

Animals↗

Expression of N-acetyllactosamine and beta1,4-galactosyltransferase (beta4GalT-I) during adenoma-carcinoma sequence in the human colorectum.

We set out to determine the expression profiles of glycoproteins possessing N-acetyllactosamine, a precursor carbohydrate of sialyl Le(x), during colorectal cancer development. We immunohistochemically analyzed the distribution of N-acetyllactosamine as well as of beta4GalT-I, a member of the beta1, 4-galactosyltransferase family responsible for N-acetyllactosamine biosynthesis, in normal mucosa and in adenoma and carcinoma of the human colorectum. Using monoclonal antibody H11, N-acetyllactosamine was barely detectable in the normal mucosa. In low-grade adenoma, however, N-acetyllactosamine was weakly but definitely expressed on the cell surface, and its expression level was moderately increased in high-grade adenoma and markedly increased in carcinoma in situ as well as in advanced carcinoma. To detect beta4GalT-I, we used a newly developed polyclonal antibody (designated A18G), which is specific for the stem region of human beta4GalT-I. Faint expression of beta4GalT-I was detectable in normal mucosa, and the expression level was moderately increased in low-grade adenoma and in high-grade adenoma and markedly increased in carcinoma in situ and advanced carcinoma. The expression of N-acetyllactosamine was highly correlated with the expression of beta4GalT-I in these tumor cells. These results indicate that the expression level of beta4GalT-I is apparently enhanced during tumorigenesis in the colorectum and that beta4GalT-I mostly directs the carcinoma-associated expression of N-acetyllactosamine on the colorectal tumor cell surface. (J Histochem Cytochem 47:1593-1601, 1999)

Adenocarcinoma↗

Cytotoxicity and pharmacokinetics of 1-beta-D-arabinofuranosyl-2-thiocytosine, a 2-sulphur substituted derivative of cytarabine.

1-(beta-D-Arabinofuranosyl)-2-thiocytosine (araSC), a 2-substituted derivative of cytarabine (araC), has been investigated for its cytotoxicity, enzymatic stability, plasma concentration-time profile in mice, and cytokinetics. This derivative showed strong cytotoxicity in several mammalian cell lines, although activity (IC50s) was weaker than araC. Greater stability to mouse cytidine deaminase was observed; the half-life in the presence of the enzyme was about 4-times longer than that of araC. The plasma concentration-time profile in mice in vivo showed prolonged retention of araSC when compared with araC. Cytokinetic study using flow cytometry indicated a non-S-phase specific effect of this compound.

Animals↗

Perfusion MR imaging with a superparamagnetic iron oxide using T2-weighted and susceptibility-sensitive echoplanar sequences: evaluation of tumor vascularity in hepatocellular carcinoma.

OBJECTIVE: The study purpose was to examine the usefulness of perfusion echoplanar MR imaging with a superparamagnetic iron oxide (SHU-555A) for evaluating the vascularity of hepatocellular carcinomas. SUBJECTS AND METHODS: Twenty-two patients with 32 hepatocellular carcinomas underwent perfusion imaging with bolus injection (0.7-1.1 ml) of SHU-555A. Echoplanar sequences included multishot spin-echo (17 patients) and single-shot gradient-echo (five patients) imaging. Image acquisition was repeated every 30 sec for 3 min with the multishot spin-echo sequence and every 2 sec for 100 sec with the single-shot gradient-echo sequence. Lesion signal intensity versus time curves were created for quantitative analysis. RESULTS: Transient decreases in tumor signal intensity (28.8% with multishot spin-echo and 63.3% with the single-shot gradient-echo) were seen in the perfusion phase. These decreases in signal intensity were statistically significantly (p < .01) different for each histologic type of hepatocellular carcinoma (poorly differentiated, 43.3%; well differentiated, 18.4%; and moderately differentiated, 24.8%). After the perfusion phase, the tumor signal intensities rapidly recovered. The multishot spin-echo sequence could detect some signal changes even in lesions smaller than 1 cm. CONCLUSION: Hepatocellular carcinoma vascularity can be evaluated with perfusion echoplanar imaging with SHU-555A. Because of its excellent temporal resolution, the single-shot gradient-echo echoplanar sequence detects the transient signal decrease in most lesions. The high image quality of the multishot spin-echo echoplanar sequence allows evaluation of the vascularity of even very small lesions.

Aged↗

[Cyclophosphamide-induced bladder cancer in a patient with Wegener granuromatosis].

Cyclophosphamide (CPM) has been considered to be a factor of bladder carcinogen. A 60-years old woman had been received a total dose of 370 g of CPM for the treatment of Wegener's granulomatosis since August, 1977. She was consulted to our department with chief complaint of macrohematuria in August, 1986. Hemorrhage cystitis was diagnosed and cystoscopy and urine cytology were performed as follow-up schedule in every year. In 1996, urine cytology showed class IV and cystoscopy revealed multiple nonpapillary tumors. Abdominal computerized tomography demonstrated a low density mass on the posterior wall of the bladder. A transurethral cold cup biopsy showed G3 transitional cell carcinoma (TCC). Radical cystectomy and tubeless cutaneous ureterostomy was performed on December 6, 1996 and histopathological diagnosis was TCC, G 3, pT3 bNXM0. She died of liver failure due to metastatic bladder cancer after seven months postoperatively.

Carcinoma, Transitional Cell↗

New types of liposidomycins produced by Streptomyces that inhibit bacterial peptidoglycan synthesis. Structure elucidation of fatty acid components by tandem mass spectrometry.

The structures of the fatty acid components of various new liposidomycins were determined using tandem mass spectrometry; the negative FAB/MS/MS/MS technique for liposidomycins with a 3-methylglutaric acid moiety and the negative FAB/MS/MS technique for liposidomycins without a 3-methylglutaric acid moiey. This structural information was obtained by analysis of peaks due to charge-remote fragmentations for 3-hydroxycarboxylate anions or carboxylate anions which were generated from liposidomycin molecules in a mass spectrometer. The MS/MS/MS technique that can exclude the matrix-derived and/or interfering ions showed higher sensitivity than the MS/MS technique.

Aminoglycosides↗

[3D-CT cystography of submucosal elevated lesion of the bladder: report of two cases].

We report 2 cases of rare inflammatory disease of the bladder arising from the bladder submucosa: eosinophilic cystitis in a 33-year-old woman and inflammatory pseudotumor of the bladder in a 41-year-old man. 3D-CT cystography demonstrated submucosal tumorous lesions clearly and enabled the evaluation of mucosae of lesions especially showed the bridging fold-like appearance of the submucosal tumorous lesion in eosinophilic cystitis.

Adult↗

Three-dimensional CT angiographic assessment of vascular diseases using various postprocessing techniques: the voxel transmission and cruising eye view methods and their respective merits.

BACKGROUND: To assess the clinical usefulness of three-dimensional CT angiography (3D-CTA) with newly-developed three-dimensional reconstruction techniques; voxel transmission (VT) and cruising eye view (CEV) methods, for performing minimally invasive diagnostic imaging of vascular diseases. METHODS DESIGN: retrospective comparative study. SETTING: University Hospital, Japan. PATIENTS: fifty-five patients with vascular lesions confirmed by catheter angiography (20 patients with aortic aneurysms, 10 patients with aortic dissection, and 25 patients with peripheral arterial occlusive disease). MAIN OUTCOME MEASURES: minimally invasive, three-dimensional diagnosis of vascular diseases. RESULTS: Angiogram-like images with a diagnostic quality similar to that of catheter angiography were obtained by the three-dimensional CT angiography/voxel transmission (3D-CTA/VT) method. This method is useful for treatment planning and also valuable for assessing the effectiveness of treatment. Three-dimensional endoscopic images of the vessel interior were obtained by the three-dimensional CT angiography cruising eye method (3D-CTA/CEV). This also yielded precise information about the relationship between the vascular lesions and the aortic orifices. CONCLUSIONS: Three-dimensional CTA/VT and three-dimensional-CTA/CEV enable visualisation of vascular lesions from an infinite number of viewing angles, and are useful as minimally invasive diagnostic techniques for imaging the vasculature.

Aged↗

Identification of a I-cM region of common deletion on 13q14 associated with human prostate cancer.

Frequent allelic losses on chromosome arm 13q are observed in carcinomas of the head and neck, breast, ovary, and pituitary gland. We analyzed 59 primary prostate tumors (stage B, 18 patients; C, 12 patients; D1, 4 patients; and endocrine therapy-resistant cancer death, 25 patients), as well as 18 metastatic tissues from 14 of the 25 cancer death patients for loss of heterozygosity (LOH) using 35 microsatellite markers on chromosome arm 13q. Of the 59 primary tumors, 31 (53%) showed LOH involving at least one locus. Detailed deletion mapping identified a distinct commonly deleted region in the I-cM interval flanked by D13S153 and D13S273 on 13q14 and this region overlapped a part of the RB1 gene. Paired DNAs were available from both primary and metastatic tumors in the 14 cases of cancer death; among those pairs, we detected LOH on 13q in seven (50%) primary tumors, and in all metastatic foci (P = 0.0029). Moreover, the regions lost in metastatic tissues were more extensive than those seen in the corresponding primary tumors. These results suggest that inactivation of a putative tumor suppressor gene(s) including the RB1 gene on 13q14 plays an important role in human prostate cancer.

Adrenal Gland Neoplasms↗

[Sertoli cell tumor of the testis: a case report].

A case of Sertoli cell tumor of the testicle is reported. A 33-year-old man visited the Chiba University Hospital with the chief complaint of a painless right testicular swelling on May 1990. The right testis was hard and swollen on palpation. Gynecomastia was not present. Serum levels of tumor markers and hormones including alphafetoprotein, human chorionic gonadotropin-beta, carcinoembryonic antigen, testosterone, prolactin, estradiol, luteinizing hormone, and follicle stimulating hormone were within normal limits. Ultrasonic examination showed a high echoic lesion in the right testis. Computerized tomography and magnetic resonance imaging showed no evidence of retroperitoneal lymph node enlargement. A high right orchiectomy was performed under a diagnosis of right testicular tumor. The right testis was elastic hard and measured 9 x 10 x 7 cm, weighing 450 g. The cut surface was light yellowish white and was completely displaced by the tumor. No normal tissue was seen. Histological examination showed a Sertoli cell tumor. No adjuvant therapy was performed. Neither recurrence nor evidence of metastasis has been detected for 8 years postoperatively.

Adult↗

Calcium channel antagonistic effects of AH-1058, a novel antiarrhythmic drug, on guinea-pig myocardium.

Effects of AH-1058, a novel cyproheptadine derivative with high antiarrhythmic activity in in vivo arrhythmia models, were studied in guinea-pig myocardium. In coronary-perfused right ventricular tissue preparations, AH-1058 (10(-5) M) shortened the action potential duration with little effect on the resting membrane potential, maximum rate of rise and overshoot. AH-1058, 10(-7) M to 10(-5) M, concentration-dependently decreased the contractile force. The increase in contractile force by Ca2+ was markedly inhibited by 3 x 10(-6) M AH-1058 while that by isoproterenol was only slightly affected. In isolated ventricular myocytes, AH-1058 concentration-dependently decreased the nicardipine sensitive transient inward current with no effect on steady state currents, and decreased the amplitude of the evoked Ca2+ transient. These results suggest that AH-1058 has Ca2+ channel antagonistic effects which may contribute to its antiarrhythmic activity.

Action Potentials↗

Herpes simplex virus type 1 DNA amplified as bacterial artificial chromosome in Escherichia coli: rescue of replication-competent virus progeny and packaging of amplicon vectors.

Herpes simplex virus type 1 (HSV-1)-based amplicon vectors contain only approximately 1% of the 152-kb HSV-1 genome, and consequently, replication and packaging into virions depends on helper functions. These helper functions have been provided conventionally by a helper virus, usually a replication-defective mutant of HSV-1, or more recently, by a set of five cosmids that overlap and represent the genome of HSV-1 deleted for DNA cleavage/packaging signals (pac). In the absence of pac signals, potential HSV-1 genomes that are reconstituted from the cosmids via homologous recombination are not packageable. The resulting amplicon stocks are, therefore, virtually free of contaminating helper virus. To simplify this packing system, the HSV-1 genome was cloned and maintained stably as a single-copy, F plasmid-based bacterial artificial chromosome in E. coli. Such a plasmid containing the HSV-1 genome deleted for the pac signals (fHSV delta pac) did not generate replication-competent progeny virus on transfection into mammalian cells, but rather, it was able to support the packaging of cotransfected amplicon DNA that contained a functional pac signal. The resulting amplicon vector stocks had titers of up to 10(7) transducing units per milliliter of culture medium and efficiently transduced neural cells in the rat brain, as well as hepatocytes in the rat. The capacity of generating infectious and replication-competent HSV-1 progeny following transfection into mammalian cells was restored after insertion of a pac signal into fHSV delta pac.

Animals↗

Overview and initial results of the very long baseline interferometry space observatory programme

High angular resolution images of extragalactic radio sources are being made with the Highly Advanced Laboratory for Communications and Astronomy (HALCA) satellite and ground-based radio telescopes as part of the Very Long Baseline Interferometry (VLBI) Space Observatory Programme (VSOP). VSOP observations at 1.6 and 5 gigahertz of the milli-arc-second-scale structure of radio quasars enable the quasar core size and the corresponding brightness temperature to be determined, and they enable the motions of jet components that are close to the core to be studied. Here, VSOP images of the gamma-ray source 1156+295, the quasar 1548+056, the ultraluminous quasar 0014+813, and the superluminal quasar 0212+735 are presented and discussed.

Journal Article↗

Distribution of prepro-nociceptin/orphanin FQ mRNA and its receptor mRNA in developing and adult mouse central nervous systems.

Nociceptin/orphanin FQ (N/OFQ) and its receptor share similarities to opioids and their receptors in terms of the molecular structure and signaling pathway, but the two systems exhibit different actions in vivo. To understand the mechanism of N/OFQ-system actions, we examined, by in situ hybridization analysis, the distribution of preproN/OFQ and N/OFQ receptor mRNAs in the developing and adult mouse central nervous systems (CNS). In most neural regions, preproN/OFQ mRNA was mainly expressed in a small population of middle-sized neurons. These neurons were scattered between large projection-type neurons or within the neuropil, suggestive of interneurons. In some other nuclei (lateral septum, bed nucleus of the stria terminalis, reticular thalamic nucleus, inferior colliculus, and rostral periolivery nucleus), preproN/OFQ mRNA was expressed in a number of large projection-type neurons. By contrast, N/OFQ receptor mRNA was evenly expressed in most neurons of the adult CNS. Considering the inhibitory actions of N/OFQ, the distinct cellular expression pattern of the N/OFQ system suggests that the release of N/OFQ from interneurons may lower neuronal and synaptic activities of neighboring neurons, leading to integration or modulation of local circuits. Furthermore, the cellular expression pattern, distinct from that of the opioid system, may provide a possible molecular/cellular basis for the different in vivo actions of N/OFQ and opioids. In embryonic stages, both preproN/OFQ and N/OFQ receptor mRNAs were highly and widely expressed in the mantle zone, suggesting the possible importance of N/OFQ signaling in CNS development.

Age Factors↗

Morphology of single primary spindle afferents of the intercostal muscles in the cat.

A reconstruction was made of the trajectory of primary spindle afferents from the intercostal muscles in the spinal cord of the cat. Intraaxonal recordings were performed from the primary spindle afferents that were identified by their response to lung inflation and stimulus threshold to activate the action potentials. The afferents were stained by using intraaxonal injection of horseradish peroxidase (HRP). Results were obtained mainly from internal intercostal Ia fibers, which entered the spinal cord and bifurcated into ascending and descending branches. The ascending branches could be traced up to 10.7 mm, and the descending branches could be traced up to 7.3 mm. The ascending branches extended to the next segment. Collaterals ranging from one to six were given off from these branches. The distances between adjacent collaterals ranged from 0.9 mm to 4.7 mm. Each collateral had similar morphological characteristics. The collaterals entered the dorsal horn and ran toward lamina IX through the medial half of the gray matter. Fine branches and boutons were given off in laminae V, VII, VIII, and IX. The aggregations of these branches were found in lamina VII, mainly in the region of Clarke's column and in the ventral and ventrolateral regions thereof and in lamina IX, mainly in the nucleus lateromedialis. Most terminals did not contact the somata of target neurons in all laminae in which terminals were found. However, a few terminals were found to contact large neurons in lamina IX. In addition to these aggregates, there were some terminals scattered throughout the ventral horn. Thus, it was concluded that single intercostal Ia afferents project to the region of Clarke's column, to the intercostal motor nucleus, and to the intermediate regions.

Afferent Pathways↗

Identification of a novel metastasis-suppressor region on human chromosome 12.

There is a critical need for markers that can be used to predict accurately the malignant potential of histological prostate cancers (J. T. Isaacs. Am. J. Pathol., 150: 1511-1521, 1997). Metastasis-suppressor genes are attractive candidates for marker development because, by definition, their loss should be associated with the acquisition of metastatic ability. In an effort to identify such genes, a single copy of human chromosome 12, tagged with the neomycin resistance gene, was introduced into highly metastatic Dunning AT6.1 prostate cancer cells by microcell-mediated chromosomal transfer. Thirty-two AT6.1-12 clonal cell lines were established and the region(s) of chromosome 12 retained was determined by sequence tagged site-based PCR analysis. Representative AT6.1-12 clones containing overlapping regions of chromosome 12 were characterized cytogenetically and were shown to have a normal complement of parental AT6.1 rat chromosomes. Fluorescence in situ hybridization, performed on representative AT6.1-12 hybrids, demonstrated a single human chromosome 12-specific signal. The metastatic ability of six representative clones was tested in immunodeficient mice. All of the AT6.1-12 clones showed the same in vivo growth rates as the control AT6.1-neo cells. Clonal cell lines that contained a conserved approximately 70-cM portion of chromosome 12 (e.g., AT6.1-12-8, -8-1, and -8-3), showed a >30-fold suppression in the number of macroscopic surface lung metastases. Mice that received injections of these cells developed a mean number 4 lung metastases whereas mice that received injections of other AT6.1-12 hybrids (lacking the approximately 70-cM region) or AT6.1-neo control cells, developed a mean number of 140 metastases. Interestingly, histological examination of the lungs of the mice that received injections of AT6.1-12-8 cells showed essentially no microscopic metastases. These findings suggest that a gene(s) encoded by the approximately 70-cM portion of human chromosome 12 suppresses an early step in the metastatic cascade.

Animals↗