Correction: A unique ectonucleotide pyrophosphohydrolase associated with porcine chondrocyte-derived vesicles.
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Biomedical subjects
Publications and source records attributed to J Hamada.
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We studied the effect of generally applied calcium antagonist on endothelin (ET-1) treated rabbit eyes. Nicardipine (20 micrograms/kg) was injected intravenously 15 minutes before intravitreal injection of 10 microliters of ET-1 at 10(-6) M. We measured the relative caliber of the retinal artery (the caliber of the retinal artery at the edge of the optic nerve head (ONH)/that of ONH), the capillary blood flow in ONH, visual evoked potential (VEP), intraocular pressure (IOP), and blood pressure (BP). In the control group (0.4 ml/kg of saline), administration of ET-1 caused contraction of the retinal artery, decrease of the capillary blood flow in ONH, prolongation of the VEP latency, and reduction of IOP. But these effects were significantly reduced in the calcium antagonist group. These results showed that generally applied calcium antagonist inhibits the disturbance of ocular circulation induced by ET-1. However, it also caused significant reduction of BP until 45 minutes after application, so we will have to work to find the optimum dose of calcium antagonist.
Analysis was conducted on calcific deposits from 5 patients with calcific periarthritis. These calcific deposits were dried, immersed in hydrazine, or heated to 1000 degrees C for 1 hour, to prepare 3 kinds of samples. The samples were classified as dried samples, hydrazine-deproteinated samples, or as heated samples. All samples were analyzed by X-ray diffraction (XRD). Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy (Raman), and by electron probe microanalysis (EPMA). Although the XRD patterns of the dried samples and of the deproteinated samples were similar to that of hydroxyapatite (HAp), it was still unclear whether or not the calcific deposits were HAp. FTIR then revealed that the dried samples contained carbonate. Raman showed that the dried samples and the deproteinated samples do not have an OH-group. The dried samples were then heated to 1000 degrees C for one hour and analyzed by all 4 methods. The heated samples were found to be HAp. From these results, the calcific deposits from the 5 patients with calcific periarthritis were found to be carbonate apatite: Ca10-x-y/2 (PO4)6-x (CO3) x (OH) 2-y (CO3)y/2.nH2O.
A novel spectrophotometric nitrite (NO2-)/nitrate (NO3-) assay system for a small quantity (5 microliter) of dialysate sample obtained by in vivo brain microdialysis was developed based on the diazotization reaction. The system has the advantage of in vivo consecutive measurement, high precision, good reproducibility, technical simplicity, relatively short resolution time (2.5-20 min), and wide availability. The NO3- level in the rat striatum was found to be 3 times higher than the NO2- level. A nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester, reduced striatal NO2-/citrulline formation in a dose-related manner and increased arginine, indicating that the tissue NO2- level detected by this assay system adequately reflects the striatal NO synthase activity.
An important clinical endpoint in patients with cancer is formation of metastases in the brain. Understanding this phenomenon is important in several types of malignancies, including melanoma, lung and breast cancers. Metastatic tumor cells use specific adhesion molecules to home to brain, and there they must attach to microvessel endothelial cells and respond to brain endothelial cell-derived motility factors and brain invasion factors to invade the CNS. Neurotrophins are important invasion factors in this process, and the ability to invade into the brain may well depend on metastatic cell responses to neurotrophins and production of basement membrane-degradative enzymes capable of locally destroying the blood-brain barrier. Brain-metastatic human melanoma cells express low-affinity p75 receptor for neurotrophins such as nerve growth factor, but they do not express the high-affinity-type receptors for nerve growth factor encoded by the protooncogene trkA. Tumor cells can proliferate in the CNS in response to local paracrine growth factors and inhibitors, but their growth also depends on their producing and responding to autocrine growth factors. A major organ-derived (paracrine) growth factor has been isolated that differentially stimulates the growth of cells metastatic to the brain. Characterization of this mitogen demonstrated that it is a transferrin-like glycoprotein; cells that are metastatic to brain express greater numbers of transferrin receptors on their surfaces than cells that are poorly metastatic or metastatic to other sites. Transferrin-like factors are expressed in fetal brain and could represent the transferrin-like factors that stimulate growth of brain-metastatic melanoma and breast cancer cells. These and other factors are probably important in determining whether metastatic cells can successfully invade, colonize, and grow in the CNS.
We studied the relationship between dietary salt intake, urinary salt excretion, blood pressure and anthropometric measurements in 322 Japanese schoolchildren, aged between 6 and 11 years. Two surveys were carried out: one among a small group of 22 children from the 322, and one involving all 322. In the former group, both a detailed and a simplified dietary questionnaire were used, and nocturnal and 24 hr urinary salt excretion samples were collected. The latter group's survey used only the simplified questionnaire and nocturnal salt excretion measurements. The surveys from the two different groups were then compared to each other. It was found that the simplified questionnaire and nocturnal urinary samples were statistically accurate enough to be used for the purpose of this study. From the latter survey, dietary salt intake among the children was 7.5 +/- 2.7 g per day, (mean +/- SD), and 65 pupils (20%) consumed more than 10 g of salt per day. It was also found that nocturnal urinary salt excretion levels were 1.47 +/- 0.82 g per day, with 30 pupils (9.3%) registering levels of more than 2.5 g per day. There was a significant correlation between these dietary and urinary salt levels. Systolic blood pressure (SPB) among the schoolchildren showed significant correlation with age, height, weight and BMI. For diastolic blood pressure (DBP), a significant correlation was seen in age only. SBP and DBP showed little relation with either dietary salt intake or urinary salt excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Two cases of moyamoya disease associated with repeated intraventricular hemorrhage are reported. The origin of bleeding was thought to be a distal aneurysm of the choroidal artery. The aneurysms were confirmed radiologically and histologically. The relationship between moyamoya disease and aneurysms is discussed, and a treatment proposed.
The Meiji government that modernized Japan decided the direction which adopted western medicine positively and eliminated Oriental medicine, and carried out the policy to inhibit acupuncture (1874). However, there was no concrete system until 1885, when the Ministry of Home Affairs issued a report to entrust the permission and superintendance of acupuncture to each prefecture. On the other hand, modern education for the blind was begun in various parts of the country in 1878, and acupuncture was adopted as a vocational course. The Rakuzenkai Blind School began Anma and acupuncture in 1881, but in 1885 acupuncture was removed from the curriculum and put under the direct control of the Ministry of Education. The principal of the school, Ryokichi Yatabe, had doubts about this and sent a question to Tokyo Imperial University. The answer to it (1887) was to recognize acupuncture, and this recognition became an admission of the revival of acupuncture in the course of blind education and the basis of the thought in legislation for modern Japanese acupuncture. There is a high possibilty that the reply to Yatabe was influenced by the article of Sansaku Okumura (1864-1912), a blind man in Kanazawa City, which appeared in the 157th issue of "Iji Shimbun" (1885).
We report a 14-year-old girl who had been diagnosed incidentally as having a cerebral arteriovenous malformation (AVM) in the left thalamus. The AVM disappeared spontaneously without treatment. Follow-up angiography performed 6 years after the original angiograms confirmed the complete disappearance of the AVM. Some possible mechanisms giving rise to the thrombosis of an AVM are discussed.
We have examined the differentiation-inducing effects of ONO-4007, a new synthetic lipid A derivative with low endotoxic activities, on a rat myelomonocytic cell line, c-WRT-7, in vitro and in vivo. ONO-4007 induced the differentiation of c-WRT-7 cells into macrophage-like cells and inhibited the proliferation of c-WRT-7 cells in vitro. Stimulation with ONO-4007 induced messenger RNA expression of interleukin-1 alpha (IL-1 alpha), IL-6, and tumor necrosis factor-alpha (TNF-alpha), which have been reported to induce differentiation of several leukemia cell lines. However, autocrine production of these cytokines may not be involved in the mechanisms of differentiation induced by ONO-4007, because the treatment with IL-1 alpha, IL-6, or TNF-alpha does not induce the differentiation of c-WRT-7 cells. In vivo treatment by intravenous administration of ONO-4007 resulted in a significant prolongation of survival time of the rats inoculated intravenously with c-WRT-7 cells compared with that of untreated rats. These results suggest that ONO-4007 can be therapeutically useful for the treatment of leukemia.
By means of an immunohistochemical technique, we examined the neuronal induction of 72-kDa heat shock protein (HSP72) in response to methamphetamine-induced hyperthermia in the mouse hippocampus. Strong HSP72 immunoreactivity (ir) was found in the neurons of hippocampus proper, particularly in the CA1/2 and medical CA3 subfields, at 10 h after drug injection. By 18 h, those neurons still revealed HSP72-ir, while neurons of the dentate gyrus also appeared positive for HSP72. At this stage, intense HSP72-ir was first detected in non-neuronal cells, i.e. glial and vascular endothelial cells. At 24 h, no apparent HSP72-ir was found in the hippocampal neurons, while only non-neuronal cells still revealed immunoreactivity for HSP72. In addition, no morphological evidence of cell degeneration or loss was noted in the CA1 sector or other hippocampal regions at 5 days after hyperthermic insult. In conclusion, (1) methamphetamine-induced hyperthermia per se is a stressful stimulant causing neuronal induction of HSP72 in the hippocampus neurons, particularly of CA1/2 and medial CA3 sectors, but does not prove fatal to the cells; (2) there is a cell type-specific difference in response to hyperthermic insult by inducing HSP72 and the timing of the induction response in the hippocampal formation; and (3) the animals that underwent drug-induced hyperthermia may be useful as an experimental model for the study of the protective mechanism of heat shock proteins against subsequent harmful stimuli.
Selective malignant cell invasion at secondary sites mediated by organ-specific (paracrine) motility factors may be of importance in preferential organ colonization of metastatic cells. In this study we isolated and examined a migration-stimulating activity present in mouse hepatic sinusoidal endothelial cell-conditioned medium (HSE-CM). HSE-CM contains migration-stimulating activity for highly liver-metastatic (RAW117-H10) and highly lung- and liver-metastatic (RAW117-L17) mouse large cell lymphoma sublines but not for the poorly metastatic parental line (RAW117-P). A migration-stimulating factor for H10 cells was purified from HSE-CM by hydroxylapatite affinity and DEAE anion exchange chromatography, Sephacryl S-200 gel filtration, and preparative native gel electrophoresis. The activity in each of the purification fractions was measured in a Transwell chamber assay using 3-microns diameter pore filters. Upon sodium dodecyl sulfate polyacrylamide gel electrophoresis, the component migrated as a single component of M(r) > 200,000 (nonreducing conditions) or as two components or M(r) approximately 110,000 and approximately 67,000 (reducing conditions). The factor was bound to Concanavalin A-Sepharose but not to heparin- or gelatin-Sepharose affinity columns, induced mainly H10 chemotactic cell activity and some chemokinetic activity, and preferentially stimulated the chemotaxis of liver-colonizing RAW117 sublines (H10 > L17 > P). NH2-terminal amino acid sequence analysis of each subunit indicated that the HSE-CM-derived migration-stimulating factor was a proteolytic fragment of complement component C3. HSE-derived migration-stimulating factors may be important in determining the ability of RAW117 tumor cells to invade and colonize the liver.
Although overexpression of the low-affinity p75 neurotrophin receptor (p75NTR) is frequently associated with advanced stages of human melanoma progression, the functional significance of this finding is unknown. We examined whether the degree of cell surface expression of p75NTR in human melanoma cell variants determines their extent of invasion stimulated by nerve growth factor (NGF). Treatment of MeWo melanoma cells or a metastatic spontaneous wheat germ agglutinin-resistant variant subline (70W) of MeWo cells with 2.5S NGF resulted in a dose-dependent enhancement of invasion through a reconstituted basement membrane. This effect was most pronounced with the 70W subline that exhibits brain-metastasizing potential in nude mice but was not found with a poorly metastatic MeWo variant subline (3S5). The expression of p75NTR as determined by Northern blotting and immunoprecipitation analysis of 125I-labeled cell surface proteins correlated with NGF-stimulated invasion. The MeWo melanoma sublines used in this study did not express p140proto-trkA mRNA or any p140proto-trkA variant transcripts including p70trkA as determined by Northern analysis and RT-PCR analysis. Thus, these melanoma cells would not be expected to form functional p75-p140 heterodimers or p140-p140 homodimers capable of transducing an NGF-generated signal to p140proto-trkA cytoplasmic substrates. These cells did express authentic p145trkC transcripts. However, NGF did not catalytically activate p145trkC receptors via increased tyrosine phosphorylation as would be expected if p145trkC participated in the signaling established by NGF. Furthermore, a NGF-stimulated purine-analogue-sensitive kinase activity was found to coimmunoprecipitate with p75NTR. This p75NTR-associated kinase may coordinate initial signaling events evoked by p75NTR ligand interaction. Addition of 2.5S NGF, at concentrations that should saturate cell surface p75NTR, to matrix-adherent cultures of human MeWo and 70W but not 3S5 melanoma cells suppressed the expression of 92-kDa type IV collagenase and stimulated the production of 72-kDa type IV collagenase in its fully active 68-kDa form. In the absence of p140proto-trkA, the matrix-dependent effects of NGF on metalloproteinase expression of brain-metastatic 70W melanoma cells suggest a signaling role for the low-affinity melanoma p75NTR receptor and its associated purine-analogue-sensitive kinase in signaling enhanced matrix penetration of NGF-rich stromal microenvironments such as the brain.
We have studied the effects of growth factors and cytokines on the tumorigenicity and invasion capacity of tumor cells by using regressor and progressor tumor cell lines (ER-1 and ERpP, respectively) derived from an SHR rat mammary adenocarcinoma. ER-1 cells regress spontaneously whereas ERpP cells show invasive growth and high metastasis to lung and other organs in syngeneic SHR rats. When ER-1 cells were pretreated with either epidermal growth factor (EGF) or transforming growth factor-beta (TGF-beta) for 24 h in vitro, and intraperitoneally transplanted into SHR rats, they grew and killed the host, whereas ER-1 cells pretreated with tumor necrosis factor-alpha did not. Tumorigenicity and invasion capacity of ERpP cells were also enhanced by treatment with EGF and TGF-beta. The ER-1 cells pretreated with EGF, once grown in vivo, had acquired irreversible tumorigenicity and invasion capacity without requiring further EGF treatment, and the enhanced malignancy was irreversible. These findings suggest that growth factors play an important role in acquisition of malignancy of tumor cells.
To elucidate tumor progression-enhancing factor(s), we examined the effects of host inflammation and host immunological status on in vivo tumor progression. One x 10(4) cells of QR clones (QR-32, -20 and -18), regressor tumor clones of 3-methylcholanthrene-induced fibrosarcoma, were unable to grow when injected s.c. into C57BL/6 mice in cell suspension form. However, QR clones grew and were lethal when s.c. implanted, attached to plastic plates. Furthermore, the tumor lines (QRpP) obtained from the tumors which had arisen from the plate-attached QR-32 clone cells no longer required plastic plates for their growth in normal mice, and had acquired stable malignant phenotypes. Although QR-32 cells became lethal when injected at the site of plastic plate implantation 1, 5 and 10 days before tumor injection, few tumors developed when plastic plates had been implanted 20 or 30 days before tumor injection. We established culture clones from the tumors arising in normal mice and mice immunosuppressed by irradiation. Clones derived from the tumors which had arisen in normal mice after implantation with plastic plates were lethal when re-implanted in normal mice (71%). On the other hand, clones derived from the tumors that arose in irradiated mice with or without plastic plates were lethal in only a few normal mice, when re-implanted (20 and 8%, respectively). These results indicate that QR clone cell progression is enhanced by the early phase of inflammation at the site of plastic plate implantation and that the progression-enhancing activity of co-implantation with a plastic plate is inhibited by previous whole-body irradiation of hosts.
To evaluate the usefulness of measuring lumbar intraspinal epidural pressure (ISEDP) measurements for the estimation of intracranial pressure, we studied the relationship between ISEDP and intracranial epidural pressure (ICEDP) in 12 patients with high intracranial pressure after neurosurgical procedures. ISEDP was measured with a Gaeltec catheter-tip pressure transducer placed percutaneously in the lumbar epidural space with a Touhy needle. ICEDP was determined by the conventional method. During the measurement, some manipulations were carried out. ISEDP and ICEDP measurements exhibited a linear correlation. In all but one patient with normal cerebrospinal fluid, ISEDP was 84 to 100% of ICEDP. In patients with mild subarachnoid hemorrhage, ISEDP was 82 to 86% of ICEDP. In patients with severe subarachnoid hemorrhage, ISEDP was 45 to 57% of ICEDP and always fluctuated in parallel with ICEDP. ISEDP accurately reflected ICEDP in response to manipulations such as breath holding, neck compression, compression at the cranial defect, mannitol administration, and coughing. These data suggest that ISEDP measurement is useful in monitoring intracranial pressure in patients with intracranial hypertension. In addition, the measurements can be obtained easily and safely.
To evaluate the usefulness of lumbar intraspinal epidural pressure (ISEDP) measurements for the estimation of intracranial pressure, we studied the relationship between ISEDP and intracranial epidural pressure (ICEDP) in 25 adult mongrel dogs. ICEDP and ISEDP were measured simultaneously with Gaeltec catheter-tip pressure transducers placed in the parietal epidural space and in the lumbar epidural space. Groups 1 and 2 dogs served as normal cerebrospinal fluid condition models. Group 1 received sequential steady-state normal saline infusions (0.5, 1.0, and 1.5 ml/min) into the cisterna magna. ISEDP and ICEDP measurements exhibited a linear correlation, and ISEDP was 80 to 90% of ICEDP at any pressure level. There was no significant difference in the pressure curves obtained at the different infusion rates. Group 2 dogs were subjected to rapid pressure changes by a cisternal bolus injection. Although compliance calculated from the change in ISEDP was slightly greater than that from ICEDP at resting pressure, the compliance calculated from both ISEDP and ICEDP decreased at 20 and 30 mm Hg of ICEDP and the values became almost equivalent. Groups 3 and 4 dogs were mild and severe experimental subarachnoid models, respectively. The ISEDP and ICEDP measurements also showed a linear correlation; however, ISEDP was about 70% of ICEDP in Group 3 and about 50% of ICEDP in Group 4. Although there are varying degrees of discrepancy between ISEDP and ICEDP in the normal or subnormal pressure range and in the presence of severe spinal block, our findings suggest that ISEDP measurements can be used to estimate intracranial pressure in a clinical practice.
An 11-month-old boy presented with a huge subdural empyema in the left hemisphere associated with a subsequent contralateral chronic subdural hematoma. Burr-hole drainage and antibiotic therapy achieved a successful outcome. Subdural empyema may result from hematogenous seeding of infection into a pre-existing chronic subdural hematoma.