Search PubMed⌕ Search

Biomedical subjects

T Ichikawa

Publications and source records attributed to T Ichikawa.

At least 91 records · Page 5Linked to original sources
PubMed2000

Effects of substance P and calcitonin gene-related peptide on axonal transport in isolated and cultured adult mouse dorsal root ganglion neurons.

Substance P and calcitonin gene-related peptide (CGRP) released from primary sensory neurons are known to play important roles in nociception and nociceptive transmission. In the present study, we attempted to clarify the roles of these neuropeptides in the regulation of axonal transport in sensory neurons. Cells were isolated from adult mouse dorsal root ganglia and cultured in F-12 medium containing fetal bovine serum for 48 h until their neurites were grown. These isolated and cultured DRG cells were mostly (>98%) small (diameter <25 microm) and medium (diameter, 25-40 microm) in size, and were immunoreactive for substance P and CGRP (85.9 and 66. 0% of total cells, respectively). Video-enhanced microscopy was applied to observe particles transported within neurites. Application of substance P (100 nM) decreased the number of particles transported in both anterograde and retrograde directions in each of DRG neurons tested (n=5). The instantaneous velocities of individual particles transported in anterograde and retrograde directions were also reduced by substance P. In contrast, alpha-CGRP (100 nM) increased the number of particles transported in both directions in each of DRG neurons tested (n=5), and also increased the instantaneous velocities of particles transported bidirectionally. Application of beta-CGRP (100-1000 nM) did not elicit any effect on axonal transport. Therefore, axonal transport in sensory neurons seems to be modulated by substance P and alpha-CGRP, both of which can be derived from its own and adjacent sensory neurons.

Animals↗
PubMed2000

Physiological and anatomical organization of multiwhisker response interactions in the barrel cortex of rats.

To understand the physiological properties and anatomical organization of the spatiotemporal interaction of the responses to multiwhisker stimulation in neurons of the rat barrel cortex, single-unit recordings of 114 neurons were performed across all layers (layer II/III, n = 39; IV, n = 33; V/VI, n = 42) of the posteromedial barrel subfield of the primary somatosensory cortex of anesthetized rats. Two neighboring principal and adjacent whiskers (PW and AW, respectively) in the same row were deflected rostrally or caudally at varying interstimulus intervals (ISIs). In 37% of the neurons, the response to the combined stimulus was significantly larger than the sum of the responses to stimulation of the individual whiskers. In instances in which response facilitation was observed, selectivity was noted for the combination (75%) of the PW with a particular AW or for a particular direction (60%) of whisker deflection. The direction bias of the responses to multiwhisker stimulation was well correlated with that of the sum of the responses to single whisker stimulation (r = 0.83; p < 0.001). The pattern and magnitude of the response interaction in the neurons of the superficial layers were closely related to the location of the recorded cell in the barrel columns. Multiwhisker stimulation at short ISIs (</=3 msec) evoked prominent response facilitation in cells located close to the border between two columns (p < 0.05, one-way ANOVA), where two excitatory inputs were expected to arrive at the same time. Our results suggest that the spatiotemporal patterns of multiwhisker stimulation, such as whisker combination, direction of deflection, and timing, are expressed as different magnitudes of response interaction, which depends on the proximity of cells to home and adjacent barrel columns.

Animals↗
PubMed2000

The effect of 6-methylthiohexyl isothiocyanate isolated from Wasabia japonica (wasabi) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-buatnone-induced lung tumorigenesis in mice.

The present study was undertaken to estimate the effect of 6-methylthiohexyl isothiocyanate (6MHITC) isolated from Wasabia japonica (wasabi) pretreatment on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK)-induced lung tumorigenesis in mice. Pretreatment with 6MHITC for 4 consecutive days at a daily dose of 5 micromol significantly inhibited NNK-induced O(6)-methylguanine formation in lungs at 4 h after the injection. In conjugation with this inhibitory effect, 6MHITC suppressed the increase in proliferating nuclear cell antigen level as well as ornithine decarboxylase activity at a promotion stage of NNK-induced lung tumorigenesis. Finally, this treatment of 6MHITC suppressed the NNK-induced lung tumorigenesis in mice. These results suggest that 6MHITC inhibits the development of lung tumors in mice treated with NNK, due to the suppression of initiation stage.

Animals↗
PubMed2000

Cloning of a novel murine gene Sfmbt, Scm-related gene containing four mbt domains, structurally belonging to the Polycomb group of genes.

A novel cDNA clone encoding a protein structurally related to the transcriptional repressor Polycomb group (PcG) proteins, which regulate homeotic genes and others, was isolated from mouse and rat brain. The coding protein contained the SPM domain and mbt repeats, both of which are characteristic of the PcG proteins, and showed significant similarity in amino acid sequence to the Drosophila Sex comb on midleg (Scm) protein. Since this novel protein contains the mbt repeats in four tandem copies, we designated this murine gene as Sfmbt for Scm-related gene containing four mbt domains. Cloning and characterization of the mouse Sfmbt gene revealed that the coding sequence comprised 20 exons, dispersed along approximately 40kb, and mapped to the proximal part of Chromosome 14. Northern blot analysis showed that the Sfmbt mRNAs were expressed most abundantly in the adult testis, and less intensively in all other tissues examined.

Amino Acid Sequence↗
PubMed2000

Hepatocyte growth factor region specifically activates mucin synthesis in rat stomach.

We investigated the effects of hepatocyte growth factor (HGF) on mucin biosynthesis and the expression of its receptor in distinct sites and layers of rat gastric mucosa. HGF stimulated the mucin biosynthesis in the surface and gland mucus cells of corpus, but not in the antrum, without its trophic effects. The HGF-receptor mRNA expression was high in the surface and deep corpus mucosa, but low in the antrum. These results demonstrate that HGF has distinct effects on mucin biosynthesis in a specific region of rat stomach, suggesting different regulatory mechanisms underlying the mucus metabolism of distinct mucus-producing cells.

Animals↗
PubMed2000

Digital fluorescence imaging of trafficking of endosomes containing low-density lipoprotein in brain astroglial cells.

We have used digital fluorescence microscopy to examine transport of LDL-containing endosomes in rat brain astroglial cells to show that individual middle endosomes undergo rapid transitions between forward/backward movements and immobile states over short distances. The population of rapidly moving endosomes (>0.04 microm/sec) was 35. 9%, and the remaining endosomes were slowly moving or temporarily immobile (<0.04 microm/sec). The averaged motion was, however, a very slow perinuclear motion with a velocity of 3.25 microm/h. This small velocity is mainly due to frequent changing of directions in movements, requiring 6 h for a significant concentration around the circumference of the cell nuclei. The application of both anti-dynein antibodies and vanadate in permeabilized cells resulted in peripherally concentrated distribution of endosomes, probably due to inhibition of perinuclear motion by dynein-like motor proteins. These results imply that both dynein-like and kinesin-like proteins bind to the same endosome resulting in both perinuclear and peripherally directed movements.

Animals↗
PubMed2000

Experimental gene therapy for brain tumors using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene with 5-fluorocytosine.

Transduction of the cytosine deaminase (CD) gene into tumor cells followed by administration of 5-fluorocytosine (5-FC), called 5-FC/CD gene therapy, was created as suicide gene therapy for various cancers. The uracil phosphoribosyltransferase (UPRT) gene, which is absent from mammalian cells, directly converts 5-fluorouracil (5-FU) to 5-fluorouridine 5'-monophosphate. We evaluated whether the coexpression of CD and UPRT genes could generate a synergistic antitumor effect on experimental brain tumors. In vitro study showed that 9L cells, transduced with the UPRT gene by an adenovirus, were 16 times more sensitive to 5-FU, and CD + UPRT-transduced cells were 6,000 times more sensitive to 5-FC than parent cells, indicating that the acquisition of CD and UPRT further increased the 5-FC sensitivity of 9L cells compared with cells transduced with CD alone. In a rat brain tumor model, decreased amounts of CD and UPRT vectors were inoculated into the tumors to detect any additional effect of UPRT. CD and UPRT coexpression followed by 5-FC administration showed an antitumor effect as detected by sequential magnetic resonance imaging. This therapy significantly prolonged animal survival. These results suggest that 5-FC/CD + UPRT gene therapy can enhance the antitumor effect of 5-FC/CD gene therapy. Consequently, this approach might be a more feasible modality for the treatment of malignant brain tumors.

Adenoviridae↗
PubMed2000

Long-term overexpression of human granulocyte colony-stimulating factor in transgenic mice: persistent neutrophilia with no increased mortality for more than one year.

To investigate possible adverse consequences of persistent neutrophil overproduction, mice transgenic for human granulocyte colony-stimulating factor (hG-CSF) were studied for more than 1 year. They showed marked granulocytopoiesis and neutrophilia. Continuous medullary and extramedullary granulocytopoiesis resulted in marked changes in bone and liver. In the liver, haemorrhage and focal necrosis and a few haemangiosarcomas were present, presumably caused by the destructive granulocytopoiesis. Despite the high incidence of lung infiltration by mature neutrophils, lung lesions rarely appeared. Although there was a persistent increase in neutrophils, mortality of the mice did not differ from that of non-transgenic littermates at least within 1 year after birth. Factors other than overproduction of G-CSF and extensive neutrophilia could be required for the development of neutrophil-mediated acute and chronic tissue damage.

Animals↗
PubMed2000

Effect of hyperthermia on the viability and the fibrinolytic potential of human cancer cell lines.

The effects of heat treatment on the viability and fibrinolytic potential of four cultured human carcinoma cell lines, fibrosarcoma cells (HT-1080), lung adenocarcinoma cells with highly metastatic potential (HAL-8), melanoma cells (Bowes) and osteosarcoma cells (NY), determined by measuring their levels of urokinase-type plasminogen activator (u-PA) and its specific receptor (u-PAR), were investigated by comparing them with those of human umbilical vein endothelial cells (HUVECs). HUVECs incubated at 43 degrees C for 120 min exhibited no decrease in viability but exhibited an increase in both u-PA and u-PAR. HT-1080 and HAL-8 showed a moderately high heat-resistance (viability, 60-90%) that correlated with the reduction of u-PAR but not u-PA. On the other hand, Bowes and NY cells, with poor heat-resistance (viability, 20-50%), exhibited stronger cell-associated u-PA activity when they survived at 43 degrees C for 120 min. Since the u-PA/u-PAR system is directly involved in the invasiveness and metastatic potential of carcinoma cells, hyperthermia would alter the biological activity of these carcinoma cells.

Adenocarcinoma↗
PubMed2000

The mucin biosynthesis stimulated by epidermal growth factor occurs in surface mucus cells, but not in gland mucus cells, of rat stomach.

Although epidermal growth factor (EGF) accelerates gastric mucin biosynthesis, information on whether its activation is limited to the specific mucus-producing cells is lacking. In this paper, we investigated the effects of EGF on mucin biosynthesis and the expression of its receptor in distinct layers of rat gastric mucosa, including the possible participation of nitric oxide (NO). EGF enhanced the incorporation of [3H]glucosamine and [14C]threonine into the mucin in the full-thickness tissues of the gastric mucosa. This stimulation disappeared on the removal treatment of the surface mucosal layer chiefly consisting of surface mucus cells. The EGF-induced increase in [3H]-labeled mucin in the full-thickness mucosa was not suppressed by either NG-nitro-L-arginine (10(-5) M) or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (10(-5) M). The EGF-receptor-mRNA expression was high in the surface mucosal layer but low in the deep and muscle layers of the stomach. These results suggest that EGF-induced stimulation of mucin biosynthesis is limited to the surface mucus cells of the rat gastric mucosa and is independent of the NO pathway.

Animals↗
PubMed2000

Prostaglandin E(2) enhances axonal transport and neuritogenesis in cultured mouse dorsal root ganglion neurons.

The effects of prostaglandin E(2) on axonal transport in cultured mouse dorsal root ganglion neurons were investigated by analysing the number of axonally transported particles under video-enhanced microscopy. Application of prostaglandin E(2) increased the number of particles transported in anterograde and retrograde directions. The EP(2) prostaglandin receptor agonist butaprost mimicked the effect of prostaglandin E(2), but the EP(1)/EP(3) prostaglandin receptor agonist 17-phenyl trinor prostaglandin E(2) and the EP(3) prostaglandin receptor agonist M&B 28767 had no effect. The membrane-permeable cyclic AMP analogue dibutyryl cyclic AMP and the adenylate cyclase activator forskolin mimicked the effect of prostaglandin E(2). The protein kinase A inhibitor H-89 reversibly reduced the number of particles in both anterograde and retrograde directions. The effects of prostaglandin E(2) and dibutyryl cyclic AMP were blocked by H-89. Taken together with previous biochemical studies showing that prostaglandin E(2) increases cyclic AMP levels, the present results suggest that prostaglandin E(2) enhances axonal transport via the EP(2) receptor and cyclic AMP-dependent protein kinase A pathway. We further investigated the role of prostaglandin E(2) in neurite growth. Prostaglandin E(2) increased both the number of cells exhibiting neurites and the neurite growth rate, operating by a similar mechanism to stimulation of axonal transport. Prostaglandin E(2) may modulate axonal transport to supply materials for morphogenesis as well as other functions in sensory neurons.

Animals↗
PubMed2000

Laparoscopic adrenalectomy for functioning adrenal tumors: clinical experiences with 38 cases and comparison with open adrenalectomy.

We reviewed 38 cases of transperitoneal or retroperitoneal laparoscopic adrenalectomy for unilateral benign functioning adrenal tumors and compared the results with those of a recent series of 36 patients undergoing an open adrenalectomy. The tumors were removed successfully in all but two cases with laparoscopy that required open laparotomy. In the other 36 cases of the laparoscopy group, mean operative time and blood loss were 225 minutes and 138 mL, respectively. Mean operative time was significantly longer for the laparoscopy group (122 minutes for open surgery: P < 0.0001), whereas mean blood loss of the laparoscopy group was almost equal to that of the open surgery group. Mean intervals to first ambulation and oral intake, and postoperative hospital stay of the laparoscopy group were significantly less than those of the open surgery group (1.4 vs 2.0 days: P = 0.014; 1.8 vs 2.9 days: P < 0.0001; and 8.5 vs 12.9 days: P < 0.0001, respectively). We conclude that laparoscopic adrenalectomy is equally effective and less invasive than open adrenalectomy. and that it should be considered as the first-choice therapy for benign adrenal tumors.

Adrenal Gland Neoplasms↗
PubMed2000

Effects of ecabet sodium, a novel gastroprotective agent, on mucin metabolism in rat gastric mucosa.

The effects of ecabet sodium (ecabet), 12-sulfodehydroabietic acid monosodium salt, on gastric mucin biosynthesis in rat antrum were compared with those in the corpus. Intragastric administration of ecabet significantly increased [3H]glucosamine incorporation into antral mucin as well as into corpus mucin during five successive hours of organ culture. In contrast, mucin biosynthesis in either antrum or corpus was not susceptible to the addition of ecabet to the culture medium. Ecabet-induced stimulation of prostaglandin E2 production in the antrum was essentially the same as that seen in the corpus. In antrum treated with 100 mg/kg ecabet, immunoreactivity with three distinct anti-mucin monoclonal antibodies was found not only in the specific mucus-producing cells, but also in the secreted mucus present at the surface gel layer. These results suggest that ecabet enhances the mucin metabolism, and this stimulation occurs in both the corpus and antrum, suggesting that ecabet might be a useful tool for the further clarification of the regulatory mechanism of antral mucin synthesis.

Abietanes↗
PubMed2000

Demonstration of hydroxyindole-O-methyltransferase (HIOMT) mRNA expression in pineal parenchymal tumors: histochemical in situ hybridization.

The expression of hydroxyindole-O-methyltransferase (HIOMT), an enzyme catalyzing the final step of melatonin biosynthesis, was examined in three pineoblastomas and five pineocytomas by in situ hybridization analysis. Distinct hybridization signals for HIOMT mRNA, though weaker than in normal pineal gland pinealocytes, were detected in two of the three pineoblastoma and three of the five pineocytoma cases. Of the pineoblastomas, hybridization signals were observed in most tumor cells of one case, while in another, signals were detected in occasional cells clustered or scattered throughout the neoplastic field. Of the pineocytomas, signals were detected in most tumor cells of two cases, while in one case, signals were detected only in occasional cells. Among these specimens, one pineoblastoma and one pineocytoma were also analyzed using northern blot and reverse transcription polymerase chain reaction (RT-PCR) analyses. In the northern blot analysis, an apparently single band corresponding to the size of HIOMT mRNA was detected in both pineoblastoma and pineocytoma RNA blots. In the RT-PCR analysis, three species of HIOMT mRNA generated via alternative splicing were detected in both tumors. These results suggest that the neoplastic cells of pineoblastomas and pineocytomas often retain the ability to express HIOMT mRNA, as in normal pinealocytes, and that HIOMT is a useful tumor marker for the diagnosis of pineal parenchymal tumors.

Acetylserotonin O-Methyltransferase↗
PubMed2000

In vivo efficacy and toxicity of 5-fluorocytosine/cytosine deaminase gene therapy for malignant gliomas mediated by adenovirus.

We evaluated the therapeutic efficacy and neurotoxicity of adenovirus-mediated transduction of the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) for experimental malignant brain tumors. The 5-FC sensitivity in 9 L cells infected by an adenovirus vector expressing CD (AdexCACD) was increased 1700-fold compared with control cells. Rats bearing 9 L brain tumors were treated with an intratumoral injection of AdexCACD followed by intraperitoneal administration of 5-FC. The rats demonstrated remarkable inhibition of tumor growth by magnetic resonance imaging, and 7 of 10 rats survived for >90 days. To evaluate the potential side-effects of the 5-FC/CD gene therapy, rats were treated with an intracerebral injection of AdexCACD into the right basal ganglia and with 5-FC. The magnetic resonance imaging showed a highly enhanced area on the gadollinium-enhanced T1-weighted image at 18 days postinjection. Pathologically, this corresponded to an area of necrosis with surrounding apoptotic cells. In addition, there was demyelination and gliosis with enlargement of the lateral ventricles. These results suggest that the 5-FC/CD gene therapy may provide an anticancer effect for malignant brain tumors in humans, but also show that there are neurotoxic effects on normal brain tissue.

Adenoviridae↗
PubMed2000

Flexural strength of rebased denture polymers.

The properties of denture base and reline resins may be affected by daily changes between room temperature and mouth temperature. The purpose of the study was to evaluate the effect of thermocycling on the flexural strength of the relined denture base polymer with reline resin. Three denture base resins, three hard reline resins and their combinations were tested. Fourteen specimens, 65x10x2.5 mm, were fabricated for each material. Polymer combination specimens were made using 1.5 mm hard reline resin on 1.0 mm cured denture base resins. Half of the specimens were stored for 50+/-2 h in distilled water at 37 degrees C, while the other half were thermocycled for 20 000 cycles between 4 and 60 degrees C. Three point bending tests were conducted on a universal testing machine at a cross-head speed of 0.5 cm/s. The flexural strengths were measured and a statistical analysis was performed on the data using three-way ANOVA (P<0.05). The results showed that the flexural strength of relined denture base polymer was significantly higher than that of hard reline polymer. Thermocycling did not affect the flexural strength of the relined denture base polymers, whereas the denture base polymer and reline polymer alone showed a decrease in strength after thermocycling.

Acrylic Resins↗
PubMed2000

Effect of prostatic biopsy on free-to-total prostate-specific antigen ratio in patients with prostate cancer.

BACKGROUND: We determined the effect of prostatic biopsy on the changes in total and free prostate-specific antigen (PSA) and free-to-total PSA ratio (F/T ratio) and examined if there are differences in these parameters between patients with benign and malignant histologic findings. METHODS: The concentration of total and free PSA and the F/T ratio were determined in 35 men before and 1 h after prostatic biopsy. The level of PSA was measured with a chemiluminescent enzyme assay. Of 35 patients, nine were diagnosed as having prostate cancer. RESULTS: In patients whose biopsy revealed cancer, the F/T ratio was lower than those without cancer, although there were no differences in total and free PSA value before prostatic biopsy. One hour after prostatic biopsy, there was an increase in the level of total and free PSA and the F/T ratio in all men. The increase in the F/T ratio was greater in patients whose biopsies revealed no prostate cancer. In patients with stage B cancer, these parameters increased more than those with stage C/D cancer. CONCLUSION: Prostatic biopsy causes a dramatic increase in total and free PSA. The F/T ratio also increased after biopsy. The PSA response to prostatic biopsy might be different in patients with and without prostatic malignancy. The response might also be different according to stage of prostate cancer.

Aged↗