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Biomedical subjects

T Ichikawa

Publications and source records attributed to T Ichikawa.

At least 127 records · Page 7Linked to original sources

Enzymatic reactivity and anti-tumor activity of 1-(beta-D-arabinofuranosyl)-2-thiocytosine derivatives.

Sixteen derivatives of 1-(beta-D-arabinofuranosyl)-2-thiocytosine (araSC), including five 5'-esters, three 3'-esters, five N4-amides and three 5'-phosphodiesters, were synthesized and their reactivity to mouse tissue homogenates, including plasma, liver and intestine, and antitumor activity in mice bearing P388 cells were measured. The ester derivatives had a potent effect on the enzyme systems while the amide and phosphodiester derivatives were less active. The reactivity of ester derivatives was highly dependent on their chemical structure. The reactivity of amides and phosphodiester derivatives on mouse plasma and intestinal homogenate was also dependent on the chemical structure, although their action on intestinal enzymes was very similar. Two of eight ester derivatives showed considerable antitumor activity in vivo, although they also showed serious toxicity indicated by a weight loss in the mice. Four out of five amides and two out of three phosphodiesters showed antitumor activity, and two were highly effective (>200% in T/C, the ratio of the mean survival time of the treated group to that of the control group) with only a very slight weight loss.

Animals↗

Inhibitory mechanism of papaverine on the smooth muscle of guinea pig urinary bladder.

In guinea pig urinary bladder, the hyperosmotic 65 mM KCI (H-65K+)- or carbachol (CCh)-induced contraction was inhibited by an addition of papaverine in a concentration-dependent manner. The cAMP content of the muscle in the presence of H-65K+ or CCh was increased by papaverine only at the higher concentration of 100 microM, but cGMP content was not affected by papaverine. Forskolin, compared with papaverine, increased cAMP content in a concentration-dependent manner, and nitroprusside did not significantly increase cGMP content. In a fura 2 loaded muscle, papaverine did not affect an increase of [Ca2+]i level by high K+ or CCh. The increase of oxidized flavoprotein (FPox) fluorescence and muscle contraction in the presence of H-65K+ or CCh was decreased by papaverine (1 - 100 microM), and the increase of pyridine nucleotide (PNred) fluorescence was not affected by papaverine. In summary, it was concluded that papaverine induced relaxation by inhibiting mitochondrial respiration in guinea pig urinary bladder as well as ileum. Moreover, it is proposed that the mechanism of papaverine-induced relaxation in the smooth muscle, which shows predominantly a metabolic dependency on its contraction, is an inhibition of mitochondrial respiration.

Animals↗

Clinical usefulness of computed tomography arteriography and computed tomography during arterial portography for the diagnosis of early and early advanced hepatocellular carcinoma.

OBJECTIVE: We examined the clinical usefulness of two techniques of Angio Computed tomography (CT), namely, CT arteriography (CTA) and CT during arterial portography (CTAP), for the diagnosis of early hepatocellular carcinoma (HCC) and early advanced HCC. MATERIALS AND METHODS: The subjects were six patients with a total of seven lesions: three had one early HCC lesion each, and three had four early advanced HCC lesions between them. There were five men and one woman, aged 61 approximately 73 years (mean: 65 years). A catheter was inserted into each inguinal artery according to Seldinger's method, and the results of CTA and CTAP were compared with those of conventional CT. RESULTS: Visualization of tumor borders, arterial blood feeding areas, and portal blood flow areas gave results equal to or better than those of conventional CT. CONCLUSIONS: A combination of CTA and CTAP is useful for the diagnosis of early HCC and early advanced HCC.

Aged↗

4D-CT: a new development in three-dimensional hepatic computed tomography.

OBJECTIVE: Addition of contrast dynamics to three-dimensional hepatic tumor CT imaging. MATERIALS AND METHODS: Six patients with hepatic cavernous hemangioma with a mean age of 57 years were included in the study. Two of the patients were male and four were female. Contrast enhanced computed tomography (CT) was carried out on the tumors in six phases by helical CT, using bolus injection of contrast medium intravenously. Using maximum intensity projection (MIP), a separate three-dimensional image was then reconstructed for each phase, and rotational images around the longitudinal axis of the torso were observed using the CRT monitor. RESULTS: The patterns of contrast enhancement of hepatic cavernous hemangiomas were obtained on 3D-images. In all patients, the reciprocal relations between the tumor and the portal veins and the hepatic veins were clearly imaged three-dimensionally. CONCLUSIONS: We have succeeded in adding the dynamic observation of a contrast medium to static three-dimensional imaging. This will be valuable for the diagnosis of hepatic tumors, and it opens up new prospects for diagnostic imaging.

Aged↗

Intracranial lipomas: demonstration by computed tomography and magnetic resonance imaging.

We present two cases of a very rare tumor, intracranial lipoma, diagnosed by computed tomography (CT) and magnetic resonance imaging (MRI). In one case, the lipoma was in the superior cerebellar cistern, the other was in the periphery of the corpus callosum. In the case in which MRI was used, identification of the lipoma using a routine MRI examination was difficult. These cases are reported now because the incidental diagnosis of intracranial lipoma is likely to increase due to advanced neuroradiological techniques such as CT and MRI.

Brain Neoplasms↗

Histological change after interferon therapy in chronic hepatitis C in view of iron deposition in the liver.

We examined the efficacy of interferon (IFN) therapy for chronic hepatitis C (CHC) in view of the change of liver histology and iron staining before and after IFN therapy. Enrolled in this study were 109 patients with CHC who completed IFN treatment and were followed for at least 1 yr after the end of IFN therapy. Serum iron, unsaturated-iron-binding capacity (UIBC), and total-iron-binding capacity (TIBC) were assessed before IFN therapy. Knodell's histological activity index (HAI) score and iron staining were examined in 55 patients in whom liver biopsy was performed at two points: before and. 1 yr after IFN therapy. Serum iron levels before IFN therapy did not correlate with the response to IFN. The HAI score significantly decreased after IFN therapy in complete responders (p < 0.01) and biochemical responders (p < 0.01). Three factors in the HAI, periportal necrosis, intralobular necrosis, and portal inflammation, but not fibrosis, were significantly decreased in complete responders (p < 0.01) and biochemical responders (p < 0.01). Of 55 patients, 23 (41.8%) were positive for iron staining before IFN therapy and 14 of 55 (25.5%) after IFN therapy. The positive rate for iron staining tended to decrease after IFN therapy, not correlating to the response to IFN, but the change was not statistically significant. In conclusion, the histological improvement by IFN therapy was mostly seen in necroinflammatory changes but not in fibrosis at least 1 yr after IFN, and iron staining tended to decrease after IFN therapy.

Adult↗

Calbindin D-28k immunoreactive nerve fibers in the carotid body of normoxic and chronically hypoxic rats.

The distribution and ultrastructural characteristics of calbindin D-28k immunoreactive nerve fibers were examined in the carotid body of the normoxic control rats by light and electron microscopy, and the abundance of calbindin D-28k fibers in the carotid body was compared in normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). Calbindin D-28k immunoreactivity was recognized in nerve fibers within the carotid body. Calbindin D-28k immunoreactive nerve fibers appeared as thin processes with many varicosities. They were distributed around clusters of glomus cells, and around blood vessels. Immunoelectron microscopy revealed that the calbindin D-28k immunoreactive nerve terminals are in close apposition with the glomus cells, and membrane specialization is visible in some terminals. Some dense-cored vesicles in the glomus cells were aggregated in this contact region. The chronically hypoxic carotid bodies were found to be enlarged several fold, and a relative abundance of calbindin D-28k fibers was lesser than in the normoxic carotid bodies. When expressed by the density of varicosities per unit area of the parenchyma, the density of calbindin D-28k fibers associated with the glomus cells in chronically hypoxic carotid bodies was decreased by 70%. These immunohistochemical findings indicate a morphological basis for involvement of calcium binding protein in the neural pathway that modulates carotid body chemoreception.

Animals↗

Bone changes around hydroxyapatite and titanium implants after abutment placement in rabbits-observations using histological and three-dimensional examinations.

We have previously developed a computer-aided system for examination of the three-dimensional bone structure around implants and observed the bone changes in the healing period after implant placement. This paper describes the bone changes around hydroxyapatite (HA) and titanium (Ti) implants after abutment placement using histological and three-dimensional examinations. Twenty-four HA and Ti implants were embedded in the tibias of adult male New Zealand white rabbits. After 8 weeks, the abutment had passed through periosteum and was placed under the skin. Rabbits were sacrificed 4 and 8 weeks following abutment placement. In conclusion, histological examination showed that, at 4 weeks after abutment placement, bone resorption around the implant neck was seen in both HA and Ti implants, and at 8 weeks, excessive bone formation was seen around the implant neck. Three-dimensional bone examination showed that abutment placement may affect bone formation and cause additional bone hypertrophy in the bone marrow area.

Animals↗

[Herpes simplex type-1 virus-based vectors for gene therapy].

Recent advances in recombinant nucleic acid technologies and the understanding of the molecular biology of diseases provide the basis for gene therapy's ability to impact on the clinical practice of medicine. Herpes simplex virus type 1 (HSV-1) has features that make it suitable as a vector for gene therapy. These properties include: 1) wide host range and high efficiency of gene transfer; 2) large transgene capacity which is provided by deletion of genes unnecessary for viral replication; 3) unique ability of entering a state of latency in neurons; 4) specific oncolytic effect of some mutants by deletion of certain early genes. Three types of vectors designed for gene therapy have been developed from this virus, termed replication-defective vectors, replication-conditional vectors and amplicon vectors. In this review, we describe the recent advances in HSV-1-based vector systems and their applications for gene therapy.

Animals↗

Interleukin-16 in synovial fluids from cases of various types of arthritis.

OBJECTIVES: To examine the characteristic relationship between interleukin-16 (IL-16) and clinical data in various types of arthritis. METHODS: We measured IL-16 levels of the synovial fluids (SF) of patients with various types of arthritis, which included rheumatoid arthritis, traumatic arthritis, pseudogouty arthritis, gouty arthritis, and osteoarthritis, by an enzyme immunosorbent assay, and examined their correlations with clinical parameters. RESULTS AND CONCLUSIONS: Higher levels of IL-16 in synovial fluid from patients with rheumatoid arthritis, traumatic arthritis, and pseudogouty arthritis, compared to those with osteoarthritis, and gouty arthritis were indicated. Also, synovial IL-16 levels in patients with rheumatoid arthritis correlated significantly, especially with synovial matrix metalloproteinase-3 levels. But the IL-16 levels of both synovial fluid and peripheral blood did not correlate with conventional inflammatory parameters such as C-reactive protein, erythrocyte sedimentation rate, or rheumatoid factor. Although the function of IL-16 in inflammatory arthritis has not yet been defined, these data indicated some essential features of IL-16.

Adult↗

Mapping of metastasis suppressor genes for prostate cancer by microcell-mediated chromosome transfer.

AIM: To identify the metastasis suppressor genes for prostate cancer. METHODS: A copy of human chromosomes was introduced into the highly metastatic Dunning R-3327 rat prostate cancer cells by the use of microcell-mediated chromosome transfer. Relationships between the size of human chromosomes introduced into microcell hybrid clones and the number of lung metastases produced by the clones were analyzed to determine which part of human chromosomes contained the metastasis suppressor gene(s) for prostate cancer. To determine portions of human chromosomes introduced, G-banding chromosomal analysis, fluorescence in situ hybridization analysis, and polymerase chain reaction analysis were performed. RESULTS: Each of microcell hybrid clones containing human chromosomes 7, 8, 10, 11, 12, or 17 showed decreased ability to metastasize to the lung without any loss of tumorigenicity. This demonstrates that these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portions of human chromosomes was observed in the human chromosome 7, 10, 11, 12, and 17 studies. In the human chromosome 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletions of human chromosome 8. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasis suppressor genes on human chromosomes were located on 7q21-22, 7q31.2-32, 8p21-12, 10q11-22, 11p13-11.2, 12p11-q13, 12q24-ter, and 17pter-q23. KAI1 and MKK4/SEKI were identified as metastasis suppressor genes from 11p11.2 and 17p12, respectively. CONCLUSION: This assay system is useful to identify metastasis suppressor gene (s) for prostate cancer.

Animals↗

Temporal characteristics of response integration evoked by multiple whisker stimulations in the barrel cortex of rats.

We investigated the responses of 114 cells in the barrel cortex of rats to describe the temporal characteristics of excitatory interactions among neurons serving two vibrissae. To examine these interactions, the principal whisker and one adjacent whisker in the same row were stimulated simultaneously or serially at various interstimulus intervals (ISIs). In 37% of the cells tested, combined stimulation of two whiskers exhibited response facilitation; the response to the combined stimulus was larger than the sum of the responses to stimulation of the individual whiskers. The occurrence and magnitude of the facilitation were strongly dependent on the ISI. The ISI capable of producing facilitation for a particular cell was tuned to a narrow range (mean +/- SD, 5.3 +/- 2.3 msec). The ISI that evoked the maximal facilitation was 1.3 +/- 1.3, 3.4 +/- 2.3, and 2.8 +/- 4.5 msec for neurons in layers II/III, IV, and V/VI, respectively. These ISIs corresponded to the difference in latencies between the responses to the individual stimulations of the principal and adjacent whiskers. A significant response facilitation was observed in the regular-spiking cells but not in the fast-spiking cells. When the ISI was longer than the range that evoked facilitation, a suppression of the response to the second whisker stimulation was observed. Facilitation was observed predominantly in layer II/III cells (69%) and to a lesser extent in cells of layers IV (15%) and V/VI (24%). Our results suggest that, in the barrel cortex, the temporal relationships among tactile stimuli are coded by facilitatory and inhibitory interactions among neurons located in neighboring barrel columns.

Animals↗

Synchronous firing patterns of a set of insect neurosecretory cells.

The number of active cells in each synchronous firing event in a set of 10 neurosecretory cells in the silkmoth Bombyx mori was estimated from the amplitude and waveform of compound action potentials. One to 10 cells discharged an action potential within a period of 30 ms and one to two or nine to 10 units became active more frequently in a synchronous firing event. Numbers of active cells fluctuated like a sequence of pseudo random numbers, though the same number of cells tended to fire in two successive firing events of a short interval. These patterns suggest that electrical coupling may mediate synchronous firings in the insect neurosecretory cell system.

Action Potentials↗

Age-related stimulation by tetragastrin of gastric mucin biosynthesis in rat.

The effects of tetragastrin on gastric mucin biosynthesis in middle-aged rats were compared with those in young rats. The incorporation of [3H]glucosamine and [35S]sulfate into mucin was stimulated by tetragastrin in cultured corpus mucosa from 7-week-old rats. In contrast, tetragastrin could not enhance mucin biosynthesis in stomachs from 52-week-old rats. The isosorbide dinitrate-induced stimulation of corpus mucin biosynthesis observed in middle-aged rats was essentially the same as that seen in young rats. Nitric oxide (NO) synthase activity of the corpus was significantly reduced in the middle-aged rats compared to the young rats. NO synthase-immunoreactivity was observed at surface mucous cells in the corpus mucosa of young, but not of middle-aged, rats. These results suggest that aging decreases the effect of gastrin on gastric mucin biosynthesis through the age-related loss of NO synthase function in the surface mucous cell layer of rat stomach.

Aging↗

Suppression of the tumorigenicity of prostatic cancer cells by gene(s) located on human chromosome 19p13.1-13.2.

BACKGROUND: In previous reports, we used microcell fusion-mediated chromosomal transfer to introduce normal human chromosomes into highly metastatic rat prostatic cancer cells to map the location of tumor and metastasis suppressor genes. The gene for prostate-specific antigen as well as several classes of genes, including cell adhesion molecules, previously demonstrated to be altered during prostate cancer progression, were mapped to human chromosome 19. METHODS: A normal human chromosome 19 was introduced into Dunning-R3327 AT6.1 rat and TSU-prl human prostatic cancer cells by microcell-mediated chromosome transfer to test the suppressive effects of this chromosome on prostate cancer. Five independent hybrid clones from Dunning-R3327 AT6.1 rat prostatic cancer cells and four independent hybrid clones from TSU-pr1 human prostatic cancer cells were isolated, karyotyped, allelotyped, and analyzed for in vitro and in vivo growth characteristics. RESULTS: Introduction of human chromosome 19 into both the rat and human prostatic cancer cells resulted in alteration of cell morphology in vitro and suppression of tumorigenicity in vivo in athymic nude mice. Highly polymorphic SSR2 markers mapped to human chromosome 19 were used to determine the portions of human chromosome 19 retained in the hybrids. These analyses identified a region localized on human chromosome 19p13.1-13.2 that is responsible for the tumor suppression of both rat and human prostatic cancer cells. The expression of several genes previously mapped to this human chromosome 19p13.1-13.2 region (i.e., ICAM-1, Notch3, and Stau) were analyzed to evaluate if they could be candidate suppressor genes for prostate cancer cell growth in vivo, but no expression patterns consistent with those predicted for a suppressor gene were observed. CONCLUSIONS: Human chromosome 19p13.1-13.2 contains potential tumor suppressor gene(s) for prostate cancer.

Animals↗

Metastasis suppressor gene(s) for rat prostate cancer on the long arm of human chromosome 7.

Allelotype analyses of human prostate cancer indicate that allelic losses on human chromosome arms 7q, 8p, 10q, 13q, 16q, 17q, and 18q are observed frequently. For the study of the possible biological significance of the frequently observed deletions on chromosome arm 7q in human prostate cancer, human chromosome 7 was introduced into highly metastatic rat prostate cancer cells by use of a microcell-mediated chromosome transfer technique. The introduction of human chromosome 7 resulted in the suppression of metastatic ability of the microcell hybrids, whereas no suppression of tumorigenicity was observed. To identify the portion of chromosome 7 containing the metastasis-suppressive function gene, the derivative chromosome 7 that was generated with the initial transfer was retransferred into rat prostate cancer cells. Human chromosome 7-containing rat prostate cancer cells could be used as the donor cells, because rodent cells produced a sufficient number of microcells with colchicine treatment. Cytogenetic and molecular analyses of these clones demonstrated that loss of segments on 7q was related to the reexpression of the metastatic phenotype. These results show that human 7q contains a metastasis suppressor gene or genes for rat prostate cancer. The findings also suggest that this gene may play an important role in the progression of human prostate cancer.

Animals↗

Progressive bone resorption after pathological fracture of the femoral neck in Hunter's syndrome.

We report a case of Hunter's syndrome associated with a transverse fracture of the left femoral neck after minor trauma, followed by progressive resorption of the femoral head at 12 years of age and a stress fracture of the right femoral neck at 16 years of age. MRI performed at 15 years of age revealed intra-articular low intensity on T1-weighted and T2-weighted images of both hip joints. The MR finding may represent fibrous synovial thickening, which caused pressure erosion of the femoral neck, resultant pathological and/or stress fractures, and subsequent osteonecrosis with rapid absorption of the femoral head.

Bone Resorption↗