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Biomedical subjects

T Ichikawa

Publications and source records attributed to T Ichikawa.

At least 235 records · Page 13Linked to original sources

Functional coupling of the nociceptin/orphanin FQ receptor with the G-protein-activated K+ (GIRK) channel.

Nociceptin/orphanin FQ is a heptadecapeptide which was recently isolated from brains. It induces hyperalgesia, in contrast to the analgesic effects of opioid ligands, although it and its receptor structurally resemble opioid peptides and opioid receptors, respectively. To investigate the molecular mechanism underlying nociceptin/orphanin FQ actions, we performed Xenopus oocyte expression assays, in situ hybridization histochemistry and electrophysiological analyses of neurons. We found that the nociceptin/orphanin FQ receptor is functionally coupled with the G-protein-activated K+ (GIRK) channel in Xenopus oocytes, and that the receptor mRNA and GIRK1 mRNA co-exist in various neurons, including hippocampal pyramidal cells. Furthermore, we found that nociceptin/orphanin FQ induces hyperpolarizing currents via inward-rectifier K+ channels in hippocampal pyramidal cells, suggesting that the nociceptin/orphanin FQ receptor couples with the GIRK channel in this region. We conclude that the nociceptin/orphanin FQ receptor couples with the GIRK channel in various neurons, including hippocampal pyramidal cells, thereby modulating neuronal excitability.

Animals↗

Localization of two cholinergic markers, choline acetyltransferase and vesicular acetylcholine transporter in the central nervous system of the rat: in situ hybridization histochemistry and immunohistochemistry.

Choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) are proteins that are required for cholinergic neurotransmission. Present knowledge concerning the organization of cholinergic structures has been derived primarily from immunohistochemistry for ChAT. In the present study, we investigated the distribution of mRNAs and the corresponding proteins for ChAT and VAChT by in situ hybridization histochemistry and immunohistochemistry. The patterns of distribution of perikarya containing ChAT mRNA. ChAT protein, VAChT mRNA and VAChT protein were similar in most regions, and co-localization in the same neuron of mRNAs for ChAT and VAChT, that of ChAT mRNA and ChAT protein, and that of VAChT mRNA and VAChT protein were demonstrated. However, in the cerebral cortex and hypothalamus, ChAT-immunoreactive perikarya were present, but they did not contain mRNAs for ChAT and VAChT, and VAChT protein. On the other hand, in the cerebellum, Purkinje cell bodies contained VAChT mRNA and VAChT protein, but they did not contain either ChAT mRNA or ChAT protein. Axon bundles were clearly revealed by immunohistochemistry for ChAT, but they were not detected by that for VAChT. Both ChAT and VAChT antibodies revealed preterminal axons and terminal-like structures. In the forebrain, they were present in the olfactory bulb, nucleus of the lateral olfactory tract, olfactory tubercle, lateral septal nucleus, amygdala, hippocampus, neocortex, caudate-putamen, thalamus and median eminence of the hypothalamus. In the brainstem, they were localized in the superior colliculus, interpeduncular nucleus and some cranial nerve motor nuclei, and further in the ventral horn of the spinal cord. These results indicate strongly that ChAT and VAChT are expressed in most of the cholinergic neurons, and that immunohistochemistry for VAChT is as useful to detect cholinergic terminal fields as that for ChAT.

Amino Acid Sequence↗

Telomerase activity in neuroblastoma: is it a prognostic indicator of clinical behaviour?

Neuroblastomas show remarkable biological heterogeneity, resulting in favourable prognosis or unfavourable prognosis due to aggressive growth despite multimodal therapy. Recently, we proposed that aggressive tumours express telomerase at a high level while the favourable tumours lack or have low telomerase expression. To evaluate the correlation between telomerase activity and other biological characteristics reported as prognostic markers (MYCN gene amplification, loss of heterogeneity (LOH) in the short arm of chromosome 1, trk-A expression, Ha-ras p21 expression, and DNA ploidy), we investigated these biological features in 105 untreated neuroblastomas. In these cases, 23 showed high telomerase activity, 78 showed low activity, and telomerase activity was undetectable in 4 cases. Most tumours with genetic alterations (MYCN amplification or 1p32 LOH) showed high telomerase activity. Most tumours with low or undetectable activity were aneuploid, and showed trk-A and Ha-ras expression. Three of the four tumours with undetectable telomerase activity regressed. In 2 of the tumours with low telomerase activity, the residual tumours maturated and showed repression of telomerase activity. Thus, the level of telomerase activity correlated with other genetic alterations and/or gene expression and may be a useful prognostic indicator in neuroblastoma.

Age Factors↗

Structural requirements for roxatidine in the stimulant effect of rat gastric mucin synthesis and the participation of nitric oxide in this mechanism.

1. The structural requirements of the histamine H2-receptor antagonist, roxatidine (2-acetoxy-N-(3-[m-(1-piperidinylmethyl)phenoxy]-propyl)acetamide hydrochloride), for the stimulant effect on mucin biosynthesis and their relation to histamine H2-receptor antagonism were identified by considering the structural analogues of this drug using an organ culture system of the rat stomach and competition studies with [125I]iodoaminopotentidine ([125I]-APT) binding to membranes of the guinea pig striatum. 2. [3H]Glucosamine incorporation into mucin during 5 h incubation period was stimulated by roxatidine and its structural analogues A (2-hydroxy-N-(3-[m-(1-piperidinylmethyl)phenoxy]-propyl)acetamide) and B (N-(3-[m-(1-piperidinylmethyl)phenoxy]-propyl)acetamide). This effect was seen in mucosal cultures of the corpus, but not antrum, region. 3. Structural analogues, in which the length of the flexible chain between the benzene ring and the amide structure differs from that of roxatidine, failed to activate mucin synthesis. No significant change in mucus synthesis occurred with the addition of analogues in which the piperidine ring attached to the benzene ring via a methylene bridge was changed. 4. Specific [125I]-APT binding to the histamine H2 receptor of guinea pig brain membranes was inhibited by roxatidine and all structural analogues used in this study, except F (N-(3-[m-(N, N-dimethyl-aminomethyl)phenoxy]-propyl)acetamide). 5. Ranitidine at 10(-4) M did not suppress the roxatidine-induced increase in [3H]glucosamine incorporation into mucin. 6. Roxatidine-induced stimulation of [3H]glucosamine incorporation into mucin was completely blocked by the addition of either NG-nitro-L-arginine (10(-5) M) or 2-(4-carboxyphenyl)-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide sodium salt (10(-5) M). The inhibitory action of NG-nitro-L-arginine was totally reversed by L-arginine (5 x 10(-3) M). 7. These results suggest that the cardinal chemical features of roxatidine for the activation of mucin biosynthesis in the corpus region of the rat stomach are the appropriate length of the flexible chain between the amide structure and the aromatic ring system bearing the methylpiperidinyl group at the meta position. The activity of roxatidine and its analogues to stimulate mucin synthesis is not related to their histamine H2 receptor antagonistic activity. Roxatidine-induced activation of mucin biosynthesis in the corpus tissue is mediated by nitric oxide.

Animals↗

Effects of histamine on mucin biosynthesis in rat gastric mucosa.

Mucin biosynthesis is stimulated by gastrin during the process of glycosylation in the corpus mucosa of the rat stomach. The purpose of this study was to clarify, using an organ culture technique, whether biosynthetic responses to histamine in the rat gastric mucin are the same as that to gastrin. Radiolabeled mucin was obtained from the corpus and antral mucosa of the rat stomach after in vitro incubation for 5 h with [3H]glucosamine (GlcN), [14C]threonine (Thr), and [35S]sulfate. Addition of histamine (10(-7)-10(-5) M) to the culture medium increased [3H]GlcN-labeled mucin in the corpus tissue in a concentration-dependent manner. In the antrum, there was no significant change in the biosynthetic activity of mucin in response to histamine. Histamine at 10(-5) M also increased the incorporation of both [35S]sulfate and [14C]Thr into the corpus mucin. These results indicate that histamine stimulates the biosynthesis of the mucin peptide, as well as the glycosylation step in the corpus, and suggest that the effect of histamine on mucin synthesis is distinct from that of gastrin.

Animals↗

Prostate-specific antigen levels from a mass screening program using highly sensitive RIA kits.

BACKGROUND: This study was designed to evaluate the distribution of prostate-specific antigen (PSA) levels of men in a mass screening program for prostatic disease. METHODS: A total of 763 men over 40 years of age underwent mass screening for prostatic disease in a Japanese prefecture using the highly sensitive Eiken kit and the Hybritech (Tandem-R) kit. The screening tests consisted of serum PSA determination, digital rectal examination, a questionnaire on symptoms, evaluation of prostate volume, and determination of the obesity rate. RESULTS: Serum PSA levels of all subjects were measured with both kits. The correlation between the values obtained by the Eiken kit and those of the Tandem-R kit was high (r = 0.990), but the values of the former were slightly higher than those of the latter. Serum PSA weakly correlated with age, however, when estimated within decade age brackets, the levels of PSA showed significant differences among only 1 pair of groups stratified by age. In contrast, the levels of PSA showed significant differences among 9 pairs of groups stratified by prostate volume. CONCLUSION: A highly sensitive assay kit is useful to evaluate both the distribution of PSA levels and the relationship of PSA values to age and prostate volume of men in mass screening programs for prostatic disease, since approximately 40% of the subjects who underwent the present mass screening showed PSA values under 1.0 ng/mL, which have been the the lower limit of detection of many PSA kits.

Adult↗

Influence of bone quality on the stress distribution. An in vitro experiment.

Adequate bone quality and stress distribution to the bone are of decisive importance for implant success. The purpose of this in vitro study was to investigate the influence of bone quality on the stress distribution using 2 implant-bone mimicking models, simulating compact and cancellous bone quality. The resin model was made of an acrylic resin only simulating compact bone quality. The hybrid model was made of 2 kinds of materials, acrylic resin covered with a 1-mm layer of urethane to simulate cancellous bone quality. An implant was embedded in each model, and the abutment and suprastructures were connected to the implant. A strain gauge was placed perpendicular to the implant on the surface of the model and a small accelerometer was attached to the abutment. When an impact load was applied to the suprastructure, both strain and acceleration were measured. Both abutment acceleration and surface strain in the hybrid model decreased rapidly as time progressed when compared to the resin model. Abutment accelerations in the resin model were significantly lower than those in the hybrid model. In the hybrid model, the strain increased as the loading site was moved closer to the strain gauge. The influence of loading sites on strain in the resin model was greater than in the hybrid model. Therefore, the occlusal stress was distributed more widely in the hybrid model than in the resin model. This may indicate that occlusal stress in compact bone may have a tendency to concentrate in particular regions.

Acrylic Resins↗

Pancreatic ductal adenocarcinoma: preoperative assessment with helical CT versus dynamic MR imaging.

PURPOSE: To compare helical computed tomography (CT) and dynamic, magnetic resonance (MR) imaging in the evaluation of pancreatic ductal adenocarcinoma. MATERIALS AND METHODS: Dynamic MR images obtained with breath holding, 256 phase- and 512 frequency-encoding steps, 5-mm section thickness, phased-array multicoil, and double-dose gadolinium were available from 21 patients. Dynamic MR images were retrospectively compared with helical CT images in the evaluation of tumor detection, local tumor extension, and vascular involvement. RESULTS: Tumors were detected on dynamic MR images of 19 of 21 (90%) patients and on helical CT scans of 16 (76%) patients. Dynamic MR imaging had equal or better sensitivity, accuracy, and agreement of tumor grade than did helical CT in the comparison of imaging findings and histopathologic findings. Dynamic MR imaging also had equal or better specificity than had helical CT in determination of local tumor extension and vascular involvement, except in the factors of duodenal invasion and portal venous system involvement. However, there was no statistically significant difference among any of these measurements. CONCLUSION: Dynamic MR imaging may be better than helical CT in the preoperative detection and evaluation of local tumor extension and of vascular involvement of pancreatic ductal adenocarcinomas.

Adult↗

Stimulation of mucin metabolism in rat gastric mucosa by histamine.

We examined the effects of histamine on mucin localized in the different regions and layers of rat gastric mucosa by determining the changes in the content as well as the biosynthetic activity of the mucin. In vivo administration of 0.8 mg/kg of histamine, which could not induce a concomitant gastric acid secretion, caused a significant increase in the mucin content in the corpus mucosa, but not in the antral mucosa. This increase was due to a significant accumulation of the mucin in the mucus gel and surface mucosa of the corpus region, whereas that in the deep mucosa did not significantly change. In the in vitro incubation system of rat gastric mucosa, histamine and dibutyryl cyclic AMP significantly increased [3H]-labeled mucin in the corpus. The histamine-induced acceleration of mucin biosynthesis was suppressed by ranitidine, but not pyrilamine. In the antrum, the biosynthetic activity showed no significant change by histamine. These results suggest that histamine promotes mucin metabolism via histamine H2 receptors in the surface mucosal layer of the corpus.

Animals↗

The value of emergency CT studies in spontaneous rupture of hepatocellular carcinoma. Analysis for tumor protrusion and hemorrhagic ascites.

CT characteristics of spontaneous rupture of HCC (n = 13) were reviewed retrospectively, and the value of emergency CT studies in this disease was evaluated. Especially, tumor protrusion ratio (TPR) and ascitic CT numbers were measured to for comparison with the data for unruptured HCCs and ordinary (e.g. non hemorrhagic) ascites (n = 13). As a result, except for diffuse type HCCs, the TPR was significantly higher than for the unruptured HCCs. Nine cases had intraperitoneal HDAs, and the laterality of the HDAs corresponded with that of the ruptured tumors in 8 cases. Also, the ascitic CT numbers apart from the HDA were still higher than the ordinary ascites. Therefore, a high TPR, HDAs adjacent to the tumor, and elevated ascitic CT numbers are important CT manifestations indicating HCC rupture. Diffuse HCCs, however, require careful clinical evaluation.

Adult↗

Perfusion-weighted MR imaging in the upper abdomen: preliminary clinical experience in 61 patients.

OBJECTIVE: We quantitatively analyzed the potential usefulness of perfusion-weighted (PW) MR imaging of the upper abdomen performed with a single-shot gradient-recalled echo echoplanar (GRE EP) sequence. SUBJECTS AND METHODS: PW imaging of the upper abdomen with a GRE EP sequence was performed in 61 patients who had suspected liver or pancreatic disease. PW imaging was started at the time of administration of 0.1 mmol/kg of gadopentetate dimeglumine, and images were obtained every 2 sec for 88 sec. Time-intensity curves for the liver, pancreas, spleen, and kidney, and for subgroups of patients with various pathologic conditions, were constructed for quantitative analysis. RESULTS: The signal-intensity changes seen throughout the PW imaging process differed for each abdominal organ and pathologic condition. In the spleen, pancreas, and renal cortex, a transient signal-intensity decrease was seen in the perfusion phase (42%, 39%, and 78%, respectively). In the liver and renal medulla, the maximum signal-intensity decrease occurred in the later phase rather than in the perfusion phase. Signal-intensity recovery in the spleen and pancreas occurred soon after the maximum signal-intensity decrease, whereas such recovery was delayed in the liver and renal cortex. In cirrhotic livers, the signal-intensity change seen throughout the examination was minimal. CONCLUSION: Unlike conventional MR imaging, PW imaging with a GRE EP sequence can provide detailed hemodynamic information about upper abdomen organs and about disorders of these organs because of its excellent temporal resolution and susceptibility to contrast enhancement.

Abdomen↗

The inhibitory effect of vitamin E on arachidonic acid metabolism during the process of urethane-induced lung tumorigenesis in mice.

It is known that change in the arachidonic acid metabolism plays an important role in the development of tumors. This study was undertaken to understand the relationship of changes in lipoxygenase, cyclooxygenase and ornithine decarboxylase (ODC) to the inhibitory effect of vitamin E on urethane-induced lung tumorigenesis in mice. We analyzed the inhibitory effect of vitamin E on ornithine decarboxylase, cyclooxygenase and lipoxygenase activities at a promotion phase of lung tumorigenesis in mice. An increase in the ODC of urethane treated-mice and no significant change in the ODC of VE-treated mice were observed. An increase in the production of PGE2 and all HETES tested in the lungs of the urethane-treated mice was observed at week 8 after injection (promotion phase), showing a significant difference compared to the control group. Excessive vitamin E feeding during the initiation or promotion phases inhibited the increase in PGE2 and HETES produced by urethane treatment. These results suggest that the suppression of prostagrandin metabolism and ODC may be associated with the inhibitory effect of vitamin E against urethane-induced lung tumorigenesis.

Animals↗

[Significance of rectal contractions during multichannel urodynamic study].

BACKGROUND: The influence of rectal contractions on urination was examined using multichannel urodynamic study. METHODS: We reviewed a total of 246 consecutive urodynamic studies. Each study consisted of a uroflow measurement and multi-channel urodynamic study, evaluating total vesical pressure, abdominal (rectal) pressure, subtracted detrusor pressure and perianal electromyography. Rectal contractions were defined as periodic fluctuations over 5 cmH2O in abdominal pressure detected by a rectal balloon catheter. No relationship of these contractions with cough and breathing was observed. RESULTS: Of the 246 patients, 17 (6.9%) had a positive study for rectal contractions. The patients, who had positive rectal contractions, averaged 70-year-old were older than negative subjects averaged 62-year-old. In multichannel urodynamics, the flow rate was significantly decreased, and electromyographic activity was increased at the moment of each rectal contractions. CONCLUSIONS: The rectal contractions are not artifactual and may be regarded as one of causes responsible for urinary difficulty in the elderly.

Adult↗

[A study of 44 patients with Kirisawa type uveitis].

We studied 50 eyes of 44 patients with acute retinal necrosis, Kirisawa type uveitis (KU), in order to examine clinical symptoms, pathogenic viruses, clinical grading, therapy and prognosis for this disease. Varicella-zoster virus (VZV) was the pathogenic organism in 37 eyes of 31 patients, while herpes simplex virus (HSV) was responsible in 13 eyes of 13 patients. There were more elderly patients in the VZV-KU group than in the HSV-KU group. In addition, mutton fat keratic precipitates and retinal exudates were more common in VZV-KU than in HSV-KU. We divided KU eyes into 3 clinical grades: severe, serious, and mild. Using statistical analysis, we found that the VZV-KU group had a significantly greater number of severe and serious cases than the HSV-KU group. Furthermore, some HLA antigens were found to be statistically more common in the VZV-KU group, although no associations were found in the HSV-KU group. 32% of VZV-KU and 67% of HSV-KU eyes had a final visual acuity (fVA) of greater than 0.5. When eyes with an fVA of greater than 0.1 were compared to eyes with an fVA of less than 0.1, we found that combined therapy using acyclovir, interferon beta, and prednisolone was especially effective for VZV-KU, although no significant difference was found for HSV-KU. Thus, it is essential to determine the pathogenic virus causing KU, in order to understand the disease pathogenesis as well as to select appropriate treatment.

Adult↗

[Active MR tracking system at 0.2T MR, a preliminary report: real time position tracking on interventional MR].

An active MR tracking system was installed in a 0.2 T open-type MRI. Interventional devices with a receive-only microcoil at their tips were newly developed for tracking at 0.2T. The low signal-to-noise ratio at 0.2T required the microcoils to have a diameter of about 2 mm and 20 turns for stable tracking. Simulation of MR-guided biopsy using biplane images with tracking in the gelatin phantom was performed. MR tracking in the aorta and IVC of a dog by a catheter with a microcoil at its tip was successful.

Animals↗