Biomedical subjects
Publications and source records attributed to H Sano.
Synovial osteochondromatosis of the foot is a rare disorder. We present the first report of synovial osteochondromatosis of the intermetatarsal/tarsometatarsal joints. When a mass develops in the sole of the foot and heterotopic ossifications are revealed radiographically, synovial osteochondromatosis should be considered in the differential diagnosis.
We investigated the effect of high dose methotrexate (HDMTX) therapy on plasma hypoxanthine (Hx) and uridine (UR) concentrations in 12 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). The initial plasma Hx level before the first administration of HDMTX (1 g/m2) was significantly higher in patients (25.5 +/- 17.5 microM) than that in healthy adult controls (4.0 +/- 1.4 microM). By 48 or 72 hours after the beginning of MTX infusion, the Hx concentration had decreased to 7.9 +/- 7.7 microM and 4.7 +/- 4.1 microM, respectively. This decrease of plasma Hx concentration after MTX infusion was also observed with the second course of HDMTX (3 g/m2) therapy. On the other hand, the plasma UR level did not change significantly. The in vitro treatment with 2 microM MTX of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient mutant cells selected from HL-60 lowered the excretion of Hx into the culture medium. These data suggest a possible new explanation of the synergism of HDMTX and 6-thiopurines, for example 6-mercaptopurine and 6-thioguanine, since plasma Hx is considered to counteract 6-thiopurine toxicity through competition at the level of HGPRT.
Recent clinical and experimental studies have suggested that blood transfusion decreased immunological responsiveness. In order to investigate this mechanism, we performed following studies. In vivo experiments, we investigated the effect of blood transfusion on tumor growth and survival rate in mice, and added the comparative studies about the timing of blood transfusion and blood cell component transfusion. In vitro experiments, we studied on the responses of CTL and NK activity by the experimental model of postoperative blood transfusion. These experiments led to the following results: 1) Accelerated tumor growth and reduced survival rate were observed in allogeneic transfused mice. 2) These effects were seen independently of the timing of blood transfusion. 3) A transfusion of lymphocytes was capable of inducing this effect of blood transfusion. 4) Blood transfusion induced both suppression of anti-tumor CTL, TNP-CTL and NK activity. 5) The suppression of CTL was mediated by suppressor cells. From these results, it was suggested that allogenic blood transfusion induced immunosuppression in mice independently of its timing.
In this paper we reported a familially occurred cavernous angiomas (CA) of the central nervous system (CNS). Case 1 was a 14-year-old female with an initial symptom of transient motor and sensory disorders of the right upper extremity. On examination she had a cutaneous angioma and no neurological deficit. CT and MRI revealed two lesions in the brain. These lesions were removed surgically and were diagnosed histologically as CA. Case 2 was a 45-year-old female, the mother of case 1, with a long standing headache. She had a cutaneous angioma and no neurological deficit. CT and MRI revealed a CA in the brain and a one in the cervical cord. Case 3 was an 11-year-old female, the cousin of case 1, with an initial symptom of left hemiparesis. On examination, she had a cutaneous angioma and left hemiparesis. CT revealed two lesions in the brain. These lesions were removed surgically and were diagnosed histologically as CA. Familial CA of the CNS is relatively rare and the reported cases were 24 families consisted of 70 cases. We analyzed the reported cases to clarify the specificities of the familial cases. In the familial cases, CAs were apt to be multiple and were located more frequently in the posterior fossa than in the non-familial cases. In some familial cases, the vascular anomalies of the CNS other than CA or CA of the skin or retina were also revealed. Because of high incidence (89%) of the hemorrhage from the histologically verified CA, operation should be carried out even in the cases of CA with mild or no symptom, if the lesion is accessible surgically.
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Corticotropin-releasing hormone (CRH) functions as a regulator of the hypothalamic-pituitary-adrenal axis and coordinator of the stress response. CRH receptors exist in peripheral sites of the immune system, and CRH promotes several immune functions in vitro. The effect of systemic immunoneutralization of CRH was tested in an experimental model of chemically induced aseptic inflammation in rats. Intraperitoneal administration of rabbit antiserum to CRH caused suppression of both inflammatory exudate volume and cell concentration by approximately 50 to 60 percent. CRH was detected in the inflamed area but not in the systemic circulation. Immunoreactive CRH is therefore produced in peripheral inflammatory sites where, in contrast to its systemic indirect immunosuppressive effects, it acts as an autocrine or paracrine inflammatory cytokine.
We observed that in hypoxic myocardial cells prostacyclin and arachidonic acid release increased and that during hypoxia phospholipid degradation also occurred. In order to clarify the mechanism of phospholipid degradation, we determined the activity of phospholipases A2 and C. We found that phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were markedly decreased and that lysophosphatidylcholine and lysophosphatidylethanolamine were increased. In contrast, there was only slight phosphatidylinositol degradation and no lysophosphatidylinositol elevation was observed. These results show that phospholipase A2 was activated in hypoxic myocytes and had substrate specificity towards PC and PE. To study phospholipase C activity, membrane phospholipids were labeled with [3H]choline, [3H]inositol or [3H]ethanolamine. The release of inositol was observed, but neither choline nor ethanolamine was released. In hypoxia, myocardial-cell phospholipase C has high substrate specificity towards phosphatidylinositol. The activation of phospholipases is closely related to the intracellular Ca2+ concentration; it is though that inositol polyphosphatides may regulate intracellular Ca2+. We determined how Ca2+ influx occurs in hypoxia. beta-Adrenergic blockade and Ca2+ antagonists markedly suppressed Ca2+ influx, phospholipase A2 activity, phospholipase C activity and cell death. However, the alpha 1-adrenergic blockade was less effective in suppressing these phenomena. These results suggest that in hypoxic myocardial cells Ca2+ influx mediated by beta-adrenergic stimulation activates phospholipases A2 and C, and that phospholipid degradation and prostacyclin release then occur.
The cytotoxicity and DNA lesions induced by methotrexate (MTX) were compared in wild-type, hypoxanthine-guanine phosphoribosyltransferase-deficient (HGPRT-) and thymidine-kinase-deficient (TK-) HL-60 cells. TK- and HGPRT- cells were approximately 10 and 3 times more sensitive to MTX than wild-type cells, respectively. Following incubation with 2 microM MTX for 16 hr, TK- cells showed a significantly higher number of DNA strand breaks. Concomitantly, DNA fragmentation at the nucleosomal linker region was detected more prominently in TK- cells. Although MTX tended to decrease TTP pools similarly in all 3 cells types, the initial TTP level in TK- cells was only about one-fifth of that found in the wild type. These results indicate that the thymidine salvage pathway has a pivotal role in mediating MTX-induced toxicity and DNA lesions.
Endothelial cells play a fundamental role in the pathogenesis of chronic inflammatory arthritis in humans such as rheumatoid arthritis (RA), as well as experimental animal models such as streptococcal cell wall (SCW) arthritis in Lewis (LEW/N) rats. This review summarizes data in support of this concept. The earliest apparent abnormalities in synovial tissues of patients with RA and Lewis rats with SCW arthritis appear to reflect microvascular endothelial cell activation or injury. At the molecular level, the abnormalities include enhanced expression by endothelial cells of activation markers such as class II major histocompatibility complex antigens, phosphotyrosine, leukocyte adhesion molecules, oncoproteins such as c-Fos and c-Myc, and metalloproteinases such as collagenase and transin/stromelysin. The development of severe, chronic, destructive arthritis is dependent upon thymic-derived lymphocytes and is accompanied by tumorlike proliferation of cells in the synovial connective tissue stroma (blood vessels and fibroblastlike cells), which results in resorptive destruction of bone and cartilage. Multiple criteria support the analogy to a neoplastic process. Paracrine and autocrine factors such as interleukin-1 (IL-1), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), and heparin-binding fibroblast growth factors (HBGF, FGF) appear to play important roles in the generation of these lesions. Finally, in addition to the autocrine and paracrine regulatory factors, neuroendocrine factors, particularly the hypothalamic-pituitary-adrenal axis, appear to be involved in the counterregulation of the inflammatory process. The counterregulatory effects are mediated, in part, by inhibition of endothelial cell activation by corticosteroids.
Exposure of normal, tall rice (Oryza sativa) seedlings to 5-azacytidine, a powerful inhibitor of DNA methylation in vivo, induced both demethylation of genomic DNA and dwarf plants. Genes that had been affected by treatment were identified by differential screening of a cDNA library, and a ras-related gene, rgp1, was subsequently isolated. The cDNA of rgp1 was found to encode a deduced protein sequence of 226 amino acids with a relative molecular mass of 24850, which was most closely related to the ras-related ypt3 protein of fission yeast, Schizosaccharomyces pombe. The rgp1 protein, expressed in transformed Escherichia coli, clearly showed GTP-binding activity. During seedling rgp1 expression was first observed 14 days after germination, reaching a maximum level between 28 and 42 days, and gradually decreased thereafter until 63 days when it attained the same level of expression as in 14-day-old seedlings. Expression of rgp1 was found to be markedly reduced throughout the growth period of both 5-azacytidine-induced dwarf plants and their progenies, relative to levels in untreated tall control plants. These results suggest that expression of rgp1 may be influenced, either directly or indirectly, by DNA methylation, and that the rgp1 protein may play an important role in plant growth and development.
The pathology of rheumatoid arthritis (RA) is characterized by massive tumor like hyperplasia of synovial connective tissues. Fibroblast like cells and microvascular endothelial cells are the predominant cell types present in this invasive tissue, particularly at sites of bone erosions. Identification of growth factors or cytokines that drive this process is an important goal of current research. Here we review evidence that platelet-derived growth factor (PDGF)-like and heparin-binding fibroblast growth factor (HBGF)-like polypeptides play a significant role in this process. For example, messenger RNA transcripts for PDGF-A, PDGF-B, HBGF-1, and HBGF-2 are present in RA synovial tissue specimens, and immunoreactive PDGF-like and HBGF-1- and -2-like polypeptides are present in RA synovia. Levels of expression are significantly higher in RA synovia than in osteoarthritis (OA) synovia, and their expression correlates with the extent and intensity of mononuclear cell infiltration. Similarly, PDGF-receptor expression is elevated in RA synovia compared with OA synovia. High levels of tyrosine phosphorylation and Fos and Myc expression are also characteristic of RA synovia and occur in cells after PDGF- and HBGF-receptor interaction. These and other observations strongly support the view that PDGF-like and HBGF-like factors are involved in stimulating the proliferative and invasive phenotype of RA synovial connective tissue cells.
The structure of several T-DNAs of Agrobacterium tumefaciens was determined by molecular cloning and Southern hybridization. The T-DNAs cloned in Escherichia coli vectors from four different nopaline type strains (PyTE1, PO31, PO22, and AKE10) showed various sizes of restriction enzyme fragments. Comparative analysis of the restriction maps revealed that the T-DNAs were composed of three distinct structural domains: (1) the region proximal to the right border (Domain I) containing the portion essential for tumorigenicity, (2) the proximity to the left border (Domain II), and (3) the region between the two domains (Domain III) to both of which no functional assignments have yet been made. The restriction map indicated that the Domains I and II were conserved in the most clones, including the well-characterized T37 T-DNA. The only exception was AKK1 (obtained from AKE10) which differed in Domain I. In the Domain III, insertions of 1.5- or 1.6-kb DNA were found in four clones, whereas an additional 2.5-kb insertion was found in one clone (PO22P1). The individual T-DNAs including Domain III with insertions was demonstrated in petunia and poplar tumors induced by the referred A. tumefaciens strains. However, resulting tumors differed in morphology and growth. These results suggest that the length polymorphism of the nopaline type T-DNA can be accounted by DNA insertions, and that diverse T-DNAs reflect their different roles in tumorigenicity.
The effects of high-speed cutting by use of a diamond bur with or without water coolant or sanding by 80-grit SiC paper on dentin permeability, before and after surface treatment, and dentin bonding of adhesive resins were compared. Three different bonding systems were used: Scotchbond DC, which requires no removal of smear layers, and two others, Clearfil Photobond and Superbond C&B, both of which remove smear layers (phosphoric acid gel or 10% citric acid containing 3% ferric chloride, respectively). Creation of smear layers by bur cutting or sanding reduced dentin permeability to levels that were only 1-3% of the maximum permeability values. Scotchbond DC gave low but consistent bond strengths (3.7-6.1 MPa) to dentin covered with smear layers. Clearfil PHotobond also produced consistent bond strengths (8.6-9.4 MPa). The increase in the permeability of dentin after phosphoric acid treatment was higher when the SiC paper was used (146%) than when the high-speed bur was used (87-90%). The smear layer and smear plugs produced by the diamond bur were more resistant to 10-3 treatment than were the SiC-created smear layers. The bond strengths of Superbond showed the highest bond strengths to the conditioned dentin when the high-speed cutting was used with water coolant (16.3 MPa), compared with the other two groups (12.2-12.5 MPa).
The effect of calcium and magnesium supplementation and the role of opioidergic system was examined in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The rats were divided into four groups receiving standard laboratory rat diet (control group; n = 9); a calcium-rich diet with 2% CaCl2 added (Ca-group; n = 12); a magnesium-rich diet with 0.5% MgO added (Mg-group; n = 11); and a calcium and magnesium-rich diet with 2% CaCl2 and 0.5% MgO added (Ca/Mg-group; n = 11); each diet contained 7% NaCl. After four weeks on these diets, the rats were decapitated and blood was obtained for the measurement of plasma electrolytes, intraerythrocyte sodium, potassium and magnesium content (RBC-Na, -K, in mEq/L cells and RBC-Mg, in mg/dL cells) and plasma beta-endorphin concentration (beta-END, in pg/mL). In the control group, systolic blood pressure and RBC-Na were obviously higher than in the other groups. Plasma beta-endorphin concentration was 45.1 +/- 13.4 in the control group, 70.7 +/- 17.4 in the Ca-group (P less than .05 v control group), 58.0 +/- 20.1 in the Mg-group and 83.8 +/- 24.8 in the Ca/Mg-group (P less than .01 v control group). The blood pressure correlated significantly with both RBC-Na (r = 0.416, P less than .01) and beta-END (r = 0.436, P less than .005). A negative correlation was also observed between RBC-Na and beta-END (r = 0.437, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)
The purpose of this study was to examine the effect of the sulfate ion on blood pressure in DOCA-salt hypertension, which involves increased sympathetic nervous activity. Male Wistar rats were divided into four groups, and received one of the following drinking solutions: distilled water [control], 171 mmol/L sodium chloride [NaCl group], 171 mmol/L sodium chloride plus 12 mmol/L magnesium sulfate [S(+) group], or 171 mmol/L sodium chloride plus 12 mmol/L magnesium chloride [S(-) group]. In the S(+) group, the elevation of systolic blood pressure (SBP; mm Hg) was significantly attenuated (168 +/- 17 v 213 +/- 26, P less than .005) and intraerythrocyte calcium concentration (R-Ca; mumol/L cells) was significantly lower (11.5 +/- 3.0 v 17.4 +/- 6.5, P less than .05) than in the S(-) group. The cardiac norepinephrine content (H-NE; ng/100 g tissue) of the S(+) group was significantly lower than that of the S(-) group. SBP was correlated negatively with H-NE (r = -0.70, P less than .001) and positively with R-Ca (r = 0.45, P less than .005). R-Ca was negatively correlated with H-NE (r = -0.36, P less than .05). These results suggest that the replacement of chloride with sulfate ion suppresses the development of hypertension in DOCA-salt rats at least in part by its inhibitory effect on sympathetic nervous activity through the decreased intracellular calcium concentration.
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To clarify the mechanism of the antihypertensive effect of oral Ca loading, we studied the effect of Ca supplementation on salt-induced blood pressure elevations in patients with essential hypertension and DOCA-salt hypertensive rats. When the diet was changed from low to high salt (300 mEq/day), the percent increase in mean blood pressure was smaller (p less than 0.01) in the Ca-supplemented (2,160 mg/day) patients than in the Ca-restricted (250 mg/day) ones. Oral Ca loading resulted in a smaller weight gain, a greater urinary sodium excretion, and an increase in red cell Mg. In the experimental study, high Ca (4% CaCl2) intake attenuated the blood pressure elevation in DOCA-salt-treated rats, accompanied with an increase in urinary sodium excretion, with the resultant attenuation in intra- and extracellular sodium retention. The decrease in catecholamine contents of hearts was improved, and a higher survival rate was observed in Ca-supplemented DOCA-salt rats. The results suggest that Ca supplementation may prevent a rise in BP in salt-dependent hypertension by inducing natriuresis with the resultant attenuation in sodium retention. The altered intracellular Mg level in hypertensive patients and the normalization of enhanced sympathetic nervous activity in DOCA-salt rats may, in part, be involved in its mechanism.
We demonstrated that the activities of phosphatidylinositide-specific phospholipase C, inositol 1,4,5-trisphosphate (IP3) kinase, and IP3 phosphatase were enhanced in cardiomyopathic hamster hearts (BIO 14.6 and BIO 53.58) in comparison to control hamsters (F1b). Release of both arachidonic acid and prostacyclin was markedly enhanced by norepinephrine in the cardiomyopathic hamsters. Phospholipase C in heart has high substrate specificity to phosphatidylinositol. IP3 production was markedly enhanced in the cardiomyopathic hamsters. We also determined the intracellular calcium concentration, which was higher in BIO 53.58 hamsters than in BIO 14.6 hamsters at 5-20 weeks of age. There was no significant difference in the intracellular calcium level between F1b and BIO 14.6 hamsters at 5 weeks of age. These results suggest that phosphatidylinositol turnover stimulated by norepinephrine may produce high intracellular calcium levels in both BIO 14.6 and BIO 53.58 myocytes. In addition, in BIO 53.58 hamsters, some mechanism such as the sarcoplasmic reticulum, which controls the intracellular calcium level, may deteriorate in function. We concluded from these results that a prolonged high intracellular calcium level may lead to the death of BIO 53.58 myocytes.