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Biomedical subjects

J Hamada

Publications and source records attributed to J Hamada.

At least 73 records · Page 4Linked to original sources
PubMed1998

Reversible and irreversible tumor progression of a weakly malignant rat mammary carcinoma cell line by in vitro exposure to epidermal growth factor.

We examined the effects of epidermal growth factor (EGF) on tumor progression of a weakly malignant rat mammary carcinoma cell line, ER-1. In vitro treatment with EGF enhanced tumorigenicity, metastatic capacity and in vitro invasive capacity of ER-1 cells. The increased malignancy of ER-1 cells was reversible, when the cells were pretreated with EGF for 24 h, whereas it was irreversible when pretreated with EGF for 1 month. EGF treatment elevated the intracellular peroxide level in ER-1 cells. When ER-1 cells were treated with EGF in the presence of N-acetylcysteine, a chemical antioxidant, the reversible or irreversible EGF-induced progression was inhibited. These results suggest that the reversible or irreversible tumor progression in ER-1 cells occur in accordance with the duration of exposure to EGF, and that reactive oxygen species may be involved in the progression.

Acetylcysteine↗
PubMed1998

Hepatocyte growth factor enhances the invasion activity of human hepatocellular carcinoma cell lines.

We investigated whether hepatocyte growth factor (HGF) enhances the invasion activity of three human HCC cell lines, HLF, HLE, and HC-4, in vitro. The analysis of the invasiveness consisted of the production of u-PA and the chemotaxis for fibronectin. Invasion activity of all cell lines was enhanced by the addition of recombinant human hepatocyte growth factor (rhHGF) to the medium. HGF stimulated the production of u-PA in HLF cells. HGF accelerated the chemotaxis of HC-4 and HLE. These data suggest that HGF increase the invasion activity of human HCC cell lines by affecting the production of u-PA or the chemotaxis for fibronectin.

Carcinoma, Hepatocellular↗
PubMed1997

Distribution of N(omega)-nitro-L-arginine following topical and intracerebroventricular administration in the rat.

The distribution of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine (L-NA), in the rat brain following either topical or intracerebroventricular application was examined using 14C-labeled L-NA. Two hours after topical application, the concentration of L-NA 1 mm below the surface was approximately 20% of the concentration at the surface, and less than 3% at 2 mm below the cortical surface. L-NA infused into the lateral cerebral ventricle distributes only in regions in close proximity to the ventricle even 8 h after administration. Consequently, intracerebroventricular administration of nitric oxide synthase inhibitors may not be useful if global inhibition of nitric oxide synthase is desired.

Administration, Topical↗
PubMed1997

Follow-up evaluation of dissecting aneurysms of the vertebrobasilar circulation by using gadolinium-enhanced magnetic resonance imaging.

The authors assessed the reliability of magnetic resonance (MR) imaging contrast enhancement for the detection and follow-up evaluation of dissecting aneurysms of the vertebrobasilar circulation. Twenty consecutively admitted patients who underwent both gadolinium-enhanced MR imaging and conventional angiography were reviewed. Enhancement of the dissecting aneurysm was seen in all but one of the 20 patients, including 10 (71%) of 14 patients examined in the chronic phases, when the T1-hyperintensity signal that corresponded to the intramural hematoma was unrecognizable. The enhanced area corresponded to the "pearl sign" or aneurysm dilation noted on the comparable angiogram. On follow-up MR studies enhancement had spontaneously disappeared in four patients at a time when comparable vertebral angiograms revealed disappearance of the aneurysm dilation. The enhancement persisted in five of nine patients examined more than 24 weeks after symptom onset; in all five patients the aneurysm dilation remained on comparable angiograms. Dynamic MR studies showed rapid and remarkable enhancements with their peaks during the immediate dynamic phase after injection of the contrast material. The authors conclude that gadolinium-enhanced MR imaging is useful for the detection and follow-up evaluation of dissecting aneurysms of the vertebrobasilar circulation.

Adult↗
PubMed1997

Nucleotide pyrophosphohydrolase in human synovial fluid.

OBJECTIVE: To identify the molecular forms of ectonucleotide pyrophosphohydrolase (NTPPHase) in human synovial fluid (SF). METHODS: We examined synovial fluids from 32 patients with various joint diseases [10 calcium pyrophosphate dihydrate (CPPD) deposition disease; 7 osteoarthritis (OA); 6 rheumatoid arthritis (RA); 3 after total knee arthroplasty (TKA); 6 olecranon bursa] and 3 normal joint fluids. Joint fluids were analyzed after sequential centrifugation for NTPPHase activity and by Western blot using polyclonal antibodies against 127 kDa porcine articular cartilage vesicle-associated NTPPHase and against PC-1 and 58 kDa, 2 other ecto-NTPPHases. Lysate from human synoviocytes, porcine chondrocytes, and their conditioned media were examined using antibodies to these ecto-NTPPHases. Radiographs of joints from which fluid was obtained were graded for degenerative changes 0-4 using a standard method. RESULTS: NTPPHase activity was found in all pathological and normal SF tested and correlated with the degree of radiographic degeneration (r = 0.55, p < 0.05). NTPPHase specific activity in ultracentrifugation pellets was highest in CPPD deposition disease fluids (p < 0.05). 127 kDa enzyme was found in both sedimentable and soluble fractions from CPPD, OA, TKA, and normal fluids, and was extensively degraded in all inflammatory fluids. Intact 115 kDa PC-1 was found only in the 2 CPPD fluids with the highest NTPPHase activity. 58 kDa enzyme was found in most fluids, predominantly in the soluble fraction. 127 kDa protein was identified in human synoviocyte conditioned media but not in cell lysate, while PC-1 and 58 kDa proteins were found in the cell lysate but not in the conditioned media. CONCLUSION: There was no disease specific association with any one ecto-NTPPHase. Total enzyme activity correlated with the degree of degenerative change. The specific activity of pelletable 127 kDa enzyme was higher in fluids containing CPPD crystals. All 3 ecto-NTPPHases or their presumed degradation products were detectable in some pathologic and normal fluids. A 200 kDa reactive band often accompanied reactivity to the 127 kDa enzyme. PC-1 and 127 kDa proteins were extensively degraded in inflammatory SF, while 58 kDa protein was not. The relative contribution of each of these enzymes to inorganic pyrophosphate production by human joint tissues remains unclear.

Animals↗
PubMed1997

[Calcification of cervical ligamentum flavum--analysis of calcium compounds and histopathological findings].

We operated 3 patients with cervical myelopathy due to calcification of ligamentum flavum (CLF). Specimens collected surgically were subjected to X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy (Raman) analysis and also histopathological examination. The calcium compounds deposited were calcium pyrophosphate dihydrate (CPPD) in Case 1, apatite in Case 2, and a double-layer structure with an outer CPPD layer and an inner carbonate apatite layer in Case 3. Histopathologically, CPPD deposition in Case 1 could be distinguished from apatite deposition in Case 2 and 3 by hematoxylin-eosin stain. Chondrocytes were observed in all 3 cases, suggesting the chondrocytes may have played a role in calcification in these three cases. To date, 62 cases of CLF (including the present cases) have been reported, and analysis of calcium compound has been performed for 29 of them. Of these 29, 15 were analyzed as calcium phosphate compounds, 9 as CPPD and 4 cases as mixed crystals like Case 3. However the analysis method and result about CPPD are no problem, the analysis result of calcium phosphate compounds depends on the using methods. Calcium phosphate or undetectable compounds was identified by XRD as hydroxyapatite (HAp), and by FTIR as calcium phosphate or undetectable compound. Analysis of calcium phosphate compounds should be condacted and identified by XRD, FTIR, and Raman. We propose two possible mechanisms for the formation of the double-layer structure in Case 3: one is formation of apatite first followed by deposition of CPPD outside, and the other is formation of CPPD first followed by conversion of CPPD in the central region to apatite. What the process of formation of the double-layer was in this cases remains unclear.

Aged↗
PubMed1996

Brain nitrite production during global ischemia and reperfusion: an in vivo microdialysis study.

Nitric oxide (NO) is considered to be associated with the pathogenesis of cerebral ischemic injury. In the present study, NO production was continuously monitored employing in vivo microdialysis. A microdialysis probe was inserted into the stratum. Levels of the major NO metabolite, NO-2, in the dialysate were determined using the Griess reaction. Rats were subjected to global cerebral ischemia produced by occlusion of both common carotid arteries together with induced hypotension. Cerebral ischemia induced a decrease in NO production, which was interrupted by a transient increase in NO synthesis. This increment was abolished in the presence of a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), suggesting that NO synthase activity is transiently activated during ischemia. Following reperfusion, NO synthesis was enhanced. To our knowledge, this is the first report concerning the continuous temporal profile of NO production during global cerebral ischemia and reperfusion.

Animals↗
PubMed1996

Nitric oxide regulates NMDA-induced dopamine release in rat striatum.

We investigated the effect of nitric oxide (NO) on N-methyl-D-aspartate (NMDA)-induced changes in levels of dopamine (DA) and its metabolite in the striatum using in vivo microdialysis. Local administration of 1mM NMDA into the striatum significantly augmented DA release in the striatum. Simultaneous administration of -5mM N(G)-nitro-L-arginine methyl ester (-NAME), a NO synthase inhibitor, into the striatum significantly potentiated NMDA-induced DA release. This effect of L-NAME was completely reversed in the presence of 50mM L-arginine (L-Arg). Administration of 1 mM NMDA significantly decreased the levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This effect of NMDA was not affected by concurrent administration of L-NAME. This study provides in vivo evidence for the involvement of NO in NMDA-induced DA release.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Correlation of in vivo nitric oxide and cGMP with glutamate/glutamine metabolism in the rat striatum.

We have examined how the suppression of endogenous production of nitric oxide (NO) in the striatal tissue affects release of glutamate (GLU) and glutamine (GLN) in pentobarbital-anesthetized male Sprague-Dawley rats. For the quantitative measurement of tissue NO production and amino acid release, an in vivo assay system for extracellular nitrite (NO2-) and amino acids was employed using an in vivo microdialysis technique. An NO synthase inhibitor (NG-nitro-L-arginine methyl ester, L-NAME) in concentrations ranging between 4-40 mM was perfused into the rat striatum using the assay system. Tissue NO production was found to be inversely proportional to the L-NAME concentration. L-NAME likewise decreased striatal levels of GLU and GLN. Furthermore, tissue NO production showed a positive correlation with GLU (R = 0.62, P < 0.02) and GLN (R = 0.86, P < 0.001) concentrations. Exogenous application of NO and cGMP by intrastriatal perfusion with 0.1-2.5 mM hydroxylamine and 0.4-10 mM 8-bromo-cGMP, respectively, increased striatal GLU release in a dose-related manner. Hydroxylamine reduced GLN release, and 8-bromo-cGMP showed a tendency to decrease GLN. In conclusion, striatal GLU/GLN metabolism is a function of the tissue concentration of NO. Normal endogenous concentration of NO causes GLU to be released at a consistent basal level, and enhanced tissue NO production facilitates GLU release via pathways including cGMP formation. We hypothesize that NO may suppress GLN formation by astrocytes.

Animals↗
PubMed1996

Enhancing effects of epidermal growth factor on human squamous cell carcinoma motility and matrix degradation but not growth.

In order to ascertain the effects of epidermal growth factor (EGF) on human cancer invasion abilities, three cell lines of human oral squamous cell carcinoma were studied using a phagokinetic track assay and zymography. EGF (1-100 ng/ml) was found to inhibit the growth but enhance the random motility of all three cell lines in a concentration-dependent fashion. Exposure to EGF, dose-dependently, led to an increased production of urokinase-type plasminogen activator and M(r) 92 kD matrix metalloproteinase by the same cells. These results strongly suggest that EGF may promote human squamous cell carcinoma invasion and metastasis.

Carcinoma, Squamous Cell↗
PubMed1996

Reconstruction of the posterior inferior cerebellar artery in the treatment of giant aneurysms. Report of two cases.

Two techniques of revascularizing the posterior inferior cerebellar artery (PICA) during aneurysm surgery are presented. One involves transposition of the PICA to the vertebral artery proximal to the aneurysm using a superior temporal artery (STA) as a graft. This is used in cases in which the PICA has branched off from the wall of the giant vertebral artery aneurysm. The other technique involves end-to-end anastomosis of the PICA after excision of a giant distal PICA aneurysm located at the cranial loop near the roof of the fourth ventricle. The reconstructions of the PICA described here are surgical procedures designed to preserve normal blood flow in the PICA in patients treated for giant aneurysms involving that artery.

Aged↗
PubMed1995

Enhanced effect of epidermal growth factor on pulmonary metastasis and in vitro invasion of rat mammary carcinoma cells.

We examined the effects of epidermal growth factor (EGF) on metastatic and in vitro invasive capacity of weakly malignant ER-1 cells derived from a rat mammary carcinoma cell line, c-SST-2. EGF enhanced the metastatic capacity and in vitro invasiveness to reconstituted basement membrane, Matrigel, of ER-1 cells in a dose-dependent fashion. EGF-stimulated invasiveness was inhibited by anti-EGF antibody, which is able to neutralize the binding of EGF to EGF receptor, in the invasion assay system. EGF stimulated chemotactic migration toward fibronectin, laminin or newborn rat fibroblast-conditioned medium which was used as a chemoattractant in the in vitro invasion assay, but showed neither adhesion to Matrigel nor production of gelatinase and plasminogen activators. These results suggested that the increased metastatic and invasive capacity of ER-1 cells by EGF might be due to the increase in cell motility.

Animals↗
PubMed1995

Prediction of sleep disorders induced by beta-adrenergic receptor blocking agents based on receptor occupancy.

beta-adrenergic receptor blocking agents (beta-blocking agents) have been widely used clinically for the treatment of various cardiovascular conditions. However, beta-blocking agents are liable to cause sleep disturbance, such as vivid dreams, nightmares, increased waking, and insomnia. The mechanisms of the sleep disorders are not known, but several may conceivably be responsible for these CNS-related side effects. In the present study, we hypothesized that the sleep disorders are induced by the blockade of central or peripheral beta 2 receptors and/or central serotonin (5-HT) receptors. To verify the hypothesis, we retrospectively analyzed the relationships between the extent of the sleep disorders and the beta 1, beta 2, or 5-HT receptor occupancies for four beta-blocking agents (atenolol, metoprolol, pindolol, and propranolol). No significant correlations were observed among pharmacokinetic/physicochemical parameters (therapeutic dose, plasma concentration, plasma unbound concentration, cerebrospinal fluid concentration, and lipid solubility) and pharmacodynamic parameters (the scores of the sleep disorders such as the number of dreams). Furthermore, no significant relationship (correlation coefficient: r < 0.3) was observed between beta 1 receptor occupancies of the drugs and the number of dreams. On the other hand, good relationships (r > 0.95) were observed between central and peripheral beta 2 or central 5-HT receptor occupancies and the number of dreams. These findings suggest that beta 2 and/or 5-HT receptor occupancy is superior to beta 1 receptor occupancy as an index for the sleep disorders.

Adrenergic beta-Antagonists↗
PubMed1995

Effects of central inhibition of nitric oxide synthase on focal cerebral ischemia in rats.

We have investigated whether central inhibition of nitric oxide synthase (NOS) could modify the tissue damage of focal cerebral ischemia produced by occlusion of the middle cerebral artery (MCA) in rats. NG-Nitro-L-arginine methyl ester (L-NAME) was administered intracerebroventricularly at two doses 15 min prior to occlusion of the MCA, as well as 4 and 24 h following occlusion. After the injection of L-NAME, the catalytic activity of the constitutive NOS, considered to be mainly neuronal, was effectively suppressed in the subcortical gray matter bilaterally, but not in the ischemic territory. Seven days after the MCA occlusion, the brains were evaluated for histopathologic damage. High-dose administration of L-NAME (120 micrograms/kg 15 min prior to MCA occlusion, followed by 150 micrograms/kg 4 and 24 h after occlusion) produced an enlargement of the infarct area and increased the volume of ischemic damage. These results indicate that extensive inhibition of NOS by a central route can increase the cerebral infarct size in focal ischemia even if NOS is not inhibited in the ischemic tissue and suggest that NO may also play a potentially beneficial role as well as a neurodestructive role in the pathophysiological mechanisms of focal cerebral ischemia.

Amino Acid Oxidoreductases↗
PubMed1995

Differing distribution of hepatocyte growth factor-positive cells in the liver of LEC rats with acute hepatitis, chronic hepatitis and hepatoma.

Using anti-rat hepatocyte growth factor (HGF) antibody, we investigated the distribution of HGF-positive cells in the liver tissues of LEC rats at various phases of liver diseases. During the phase of fulminant hepatitis, HGF-positive cells increased remarkably, and many of them were localized at the portal triads; these cells were identified from their shape as non-epithelial cells. A reduced number of HGF-positive cells was observed during the phase of chronic hepatitis, while no HGF-positive cells were seen in the tissue of cholangiofibrosis. During the phase of carcinoma, staining revealed that both the hepatocellular carcinoma cells and the non-epithelial cells in cancerous liver tissue were HGF-positive. These results suggest that, in LEC rats, HGF may play an important role in the regeneration of hepatocytes as well as in the development of hepatocellular carcinoma.

Acute Disease↗
PubMed1995

A possible role of 92 kDa type IV collagenase in the extramedullary tumor formation in leukemia.

Production of metalloproteinases such as collagenases has been reported to be involved in the metastasis of cancer cells. Granulocytic sarcoma in extramedullary sites can be formed by similar steps to other cancers. In this study, we have examined the secretion of type IV collagenases and a tissue inhibitor of metalloproteinase-1 (TIMP-1) in several human leukemia cell lines, including a granulocytic sarcoma-derived cell line established from a patient with granulocytic sarcomas in dermal tissues. We have also examined the invasive capacity of these leukemia cell lines into reconstituted basement membrane, Matrigel, which was used for in vitro invasion assay. Among the human leukemia cell lines used in this study, only the granulocytic sarcoma cell line was found to secrete type IV collagenase constitutively. Other myeloid leukemia cell lines such as HL-60 and U-937 produced type IV collagenase only after treatment with 12-O-tetradecanoylphorbol-13-acetate. All the cell lines secreted similar amounts of the tissue inhibitor of metalloproteinases. In vitro invasion assay revealed that the granulocytic sarcoma cell line showed higher invasive capacity than the other cell lines. These results suggest that the secretion of 92 kDa type IV collagenase plays a role in the leukemia cells' invasion of extramedullary tissues.

Collagenases↗
PubMed1995

A unique ectonucleotide pyrophosphohydrolase associated with porcine chondrocyte-derived vesicles.

Previous studies have shown increased nucleotide pyrophosphohydrolase (EC 3.6.1.8) (NTPPHase) activity in detergent extracts of degenerated human cartilage containing calcium pyrophosphate dihydrate (CPPD) crystals relative to those from osteoarthritis or normal cartilage. NTPPHase was later shown to be an ectoenzyme and its activity was increased in synovial fluid from patients with CPPD crystal deposits relative to fluids from other types of arthritis. We have purified a soluble 61-kD NTPPHase from conditioned media of organ-cultured porcine articular cartilage to electrophoretic homogeneity. Its NH2-terminal sequence through 26 cycles showed < 30% homology to any previously reported protein sequence. An antibody raised to a synthetic peptide corresponding to this sequence reacted with denatured but not native enzyme. This antibody reacted against a sedimentable vesicle-associated 127-kD protein in conditioned media from cultured articular cartilage or from chondrocytes in primary monolayer culture and against a series of soluble proteins in conditioned media supernatant, including a 61-kD protein representing our original isolate. No reactivity was found in 1% SDS extracts of washed cultured chondrocytes, although these contained greater NTPPHase activity than the conditioned media. Antibody to PC-1, another ectoNTPPHase, reacted with 1% SDS extracts of whole chondrocytes but not against those chromatographic fractions containing the major portion of NTPPHase activity. Release of the vesicle-associated 127-kD enzyme into conditioned medium was stimulated three- to sevenfold by TGF beta 1. The antibody also reacted with a series of soluble proteins and with 127-kD sedimentable protein in human synovial fluid. Kinetic studies supported the existence of a unique vesicle-associated NTPPHase; apparent Km (mM) of chondrocyte membrane NTPPHase was 1.5 and 3.0 at pH 7.3 and 9.88, respectively; apparent Km (mM) of vesicle associated NTPPHase was 0.83 and 1.28 at pH 7.3 and 9.88. The data suggest the existence of a unique ecto-NTPPHase associated with vesicles derived from normal articular cartilage.

Amino Acid Sequence↗