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M Nagayama

Publications and source records attributed to M Nagayama.

At least 55 records · Page 3Linked to original sources
PubMed1999

Induction of sister chromatid exchanges in cultured human lymphocytes with methylsulphonyl PCB congeners.

Methylsulphonyl polychlorinated biphenyls (MSF-PCBs) have already contaminated at relatively high concentration in the lungs and blood of Yusho patients and healthy Japanese people. Therefore, we should give due attention to their biological and toxicological effects to man. In this study, in order to evaluate S-dependent genotoxicity of five MSF-PCB congeners, namely, 3-MSF-4,5,3',4'-tetrachlorobiphenyl (TCB), 3-MSF-4,5,2',3'-TCB, 3-MSF-2,5,2',4',5'-pentachlorobiphenyl (PenCB), 4-MSF-2,5,2',3',4'-PenCB and 4-MSF-2,5,2',3',5',6'-hexachlorobiphenyl (HCB), we have examined their effects on the induction of sister chromatid exchanges (SCEs), which has been frequently used to estimate the dose of S-dependent clastogens, in cultured human lymphocytes in the absence or presence of 2,3,4,7,8-pentachlorodibenzofuran (PenCDF), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 3,4,5,3',4'-pentachlorobiphenyl (Co-PenCB) and the following results were obtained. 1) 4 x 10(-5)M, 7,8-benzoflavone (ANF) and two of the five MSF-PCB congeners, namely, 3-MSF-2,5,2',4',5'- and 4-MSF-2,5,2',3',4'-PenCB at respective doses of 5.2 and 5.8 ppm, which were about 35,000 times higher than the concentrations in the lungs and adipose tissue of healthy Japanese people, significantly enhanced the frequency of SCEs. 2) In the simultaneous treatment of one of the five MSF-PCB congeners and PenCDF (3.9 ppb), TCDD (1.5 ppb) or Co-PenCB (8.8 ppb), the combination of 3-MSF-4,5,3',4'-TCB (6.8 ppb) or 4-MSF-2,5,2',3',5',6'-HCB and one of the three highly toxic chemicals significantly promoted the formation of SCEs. We have already studied whether these MSF-PCBs are non-S-dependent genotoxic compounds or not and have obtained the results that they seemed not to be or very weak ones. Therefore, based on the results of this and our former studies, the five MSF-PCB congeners examined are considered rather potent S-dependent genotoxic chemicals than non-S-dependent ones.

Cells, Cultured↗
PubMed1999

[Sarcoidosis with hypercalcemia, urolithiasis, renal insufficiency, and heart failure].

A 65-year-old man was admitted to our hospital because of thirstyness and left lower abdominal pain. On admission, he was found to have urolithiasis, renal insufficiency (BUN: 73 mg/dl, Crt: 4.4 mg/dl), and hypercalcemia (13.2 mg/dl). Chest X-ray films and computed tomograms showed enlargement and calcification of the hilar lymph nodes, and thickened interlobar fissures in both lungs. Levels of angiotensin converting enzyme (30.2 IU/l) and 1.25 (OH)2VitD3 (66.4 pg/ml) were elevated. Histologic examination of the specimen obtained from transbronchial lung biopsy showed non-caseous epithelioid cell granulomas. Because the level of parathyroid hormone was normal and no malignancies were detected, a diagnosis of sarcoidosis was made. Treatment with extracorporeal shock wave lithotripsy, transurethral lithotomy, saline infusion, and prednisolone (30 mg/day) alleviated the urolithiasis, renal insufficiency, and hypercalcemia. After discharge, the patient was followed up and given prednisolone therapy. About 1 month after the prednisolone dose had been tapered to 15 mg/day, the patient experienced dyspnea and facial and pedal edema. Because congestive heart failure was diagnosed, he was re-admitted to our hospital for a second time. Although he was then placed on intensive therapy, he died of ventricular tachycardia associated with sarcoidosis of the heart.

Aged↗
PubMed1998

Interaction between inducible nitric oxide synthase and cyclooxygenase-2 after cerebral ischemia.

Focal cerebral ischemia is associated with expression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), enzymes whose reaction products contribute to the evolution of ischemic brain injury. We tested the hypothesis that, after cerebral ischemia, nitric oxide (NO) produced by iNOS enhances COX-2 activity, thereby increasing the toxic potential of this enzyme. Cerebral ischemia was produced by middle cerebral artery occlusion in rats or mice. Twenty-four hours after ischemia in rats, iNOS-immunoreactive neutrophils were observed in close proximity (<20 micrometer) to COX-2-positive cells at the periphery of the infarct. In the olfactory bulb, only COX-2 positive cells were observed. Cerebral ischemia increased the concentration of the COX-2 reaction product prostaglandin E2 (PGE2) in the ischemic area and in the ipsilateral olfactory bulb. The iNOS inhibitor aminoguanidine reduced PGE2 concentration in the infarct, where both iNOS and COX-2 were expressed, but not in the olfactory bulb, where only COX-2 was expressed. Postischemic PGE2 accumulation was reduced significantly in iNOS null mice compared with wild-type controls (C57BL/6 or SV129). The data provide evidence that NO produced by iNOS influences COX-2 activity after focal cerebral ischemia. Pro-inflammatory prostanoids and reactive oxygen species produced by COX-2 may be a previously unrecognized factor by which NO contributes to ischemic brain injury. The pathogenic effect of the interaction between NO, or a derived specie, and COX-2 is likely to play a role also in other brain diseases associated with inflammation.

Animals↗
PubMed1998

Effects of added antibiotics on the basic properties of anti-washout-type fast-setting calcium phosphate cement.

The effect of added antibiotics on the basic properties of anti-washout-type fast-setting calcium phosphate cement (aw-FSCPC) was investigated in a preliminary evaluation of aw-FSCPC containing drugs. Flomoxef sodium was employed as the antibiotic and was incorporated into the powder-phase aw-FSCPC at up to 10%. The setting time, consistency, wet diametral tensile strength (DTS) value, and porosity were measured for aw-FSCPC containing various amounts of flomoxef sodium. X-ray diffraction (XRD) analysis was also conducted for the identification of products. To evaluate the drug-release profile, set aw-FSCPC was immersed in saline and the released flomoxef sodium was determined at regular intervals. The spread area of the cement paste as an index of consistency of the cement increased progressively with the addition of flomoxef sodium, and it doubled when the aw-FSCPC contained 8% flomoxef sodium. In contrast, the wet DTS value decreased with increase in flomoxef sodium content. Bulk density measurement and scanning electron microscopic observation revealed that the set mass was more porous with the amount of flomoxef sodium contained in the aw-FSCPC. The XRD analysis revealed that formation of hydroxyapatite (HAP) from aw-FSCPC was reduced even after 24 h, when the aw-FSCPC contained flomoxef sodium at > or = 6%. Therefore, the decrease of wet DTS value was thought to be partly the result of the increased porosity and inhibition of HAP formation in aw-FSCPC containing large amounts of flomoxef sodium. The flomoxef sodium release from aw-FSCPC showed the typical profile observed in a skeleton-type drug delivery system (DDS). The rate of drug release from aw-FSCPC can be controlled by changing the concentration of sodium alginate. Although flomoxef sodium addition has certain disadvantageous effects on the basic properties of aw-FSCPC, we conclude that aw-FSCPC is a good candidate for potential use as a DDS carrier that may be useful in surgical operations.

Biocompatible Materials↗
PubMed1998

Quantitative measurements of cerebral blood flow in rats using the FAIR technique: correlation with previous iodoantipyrine autoradiographic studies.

Flow-sensitive alternating inversion recovery (FAIR) is a recently introduced MRI technique for assessment of perfusion that uses blood water as an endogenous contrast agent. To characterize the FAIR signal dependency on spin tagging time (inversion time (TI)) and to validate FAIR for cerebral blood flow (CBF) quantification, studies were conducted on the rat brain at 9.4 T using a conventional gradient-recalled echo sequence. The T1 of cerebral cortex and blood was found to be 1.9 and 2.2 s, respectively, and was used for CBF calculations. At short TIs (<0.8 s), the FAIR signal originates largely from vascular components with fast flows, resulting in an overestimation of CBF. For TI > 1.5 s, the CBF calculated from FAIR is independent of the spin tagging time, suggesting that the observed FAIR signal originates predominantly from tissue/capillary components. CBF values measured by FAIR with TI of 2.0 s were found to be in good agreement with those measured by the iodoantipyrine technique with autoradiography in rats under the same conditions of anesthesia and arterial pCO2. The measured pCO2 index on the parietal cortex using the FAIR technique was 6.07 ml/100 g/min per mmHg, which compares well with the pCO2 index measured by other techniques. The FAIR technique was also able to detect the regional reduction in CBF produced by middle cerebral artery occlusion in rats.

Animals↗
PubMed1998

Initial histological evaluation of anti-washout type fast-setting calcium phosphate cement following subcutaneous implantation.

Anti-washout-type fast-setting calcium phosphate cement using chitosan (aw-FSCPC(chi)), conventional CPC (c-CPC), CPC mixed with citric acid (CPC(citric)) and CPC mixed with polyacrylic acid (CPC(acrylic)) were implanted subcutaneously in rats immediately after mixing to shed some light on the understanding of the appearance of excellent tissue response to CPC. CPC(citric) and CPC(acrylic) set quickly, similar to aw-FSCPC(chi), but the former two stopped their transformation to apatitic minerals. The c-CPC, which required a long setting time, was found to be crumbled, but the other CPCs maintained the shape at implantation. The aw-FSCPC(chi) and CPC(citric) showed no inflammatory response whereas c-CPC and CPC(acrylic) showed an inflammatory response one week after implantation. A component of the aw-FSCPC(chi) and c-CPC was an apatitic mineral whereas CPC(citric) and CPC(acrylic) showed no transformation to apatite. We concluded that the non-crumbling property plays a more dominant role in the appearance of excellent tissue response to CPC than the transformation to apatite. Also, a non-crumbling property is not a sufficient condition, but a necessary condition for the appearance of the excellent tissue response to CPC.

Animals↗
PubMed1998

Delayed treatment with aminoguanidine decreases focal cerebral ischemic damage and enhances neurologic recovery in rats.

Delayed treatment with aminoguanidine (AG), a relatively selective inhibitor of inducible nitric oxide synthase, ameliorates brain damage produced by occlusion of the rat's middle cerebral artery (MCA). We investigated whether the protection exerted by AG is dose-dependent and whether it is associated with improved neurologic outcome. We also studied the effect of the timing of administration of AG relative to the induction of cerebral ischemia. Halothane-anesthetized spontaneously hypertensive rats underwent permanent MCA occlusion distal to the lenticulostriate branches. Neurologic deficits were assessed daily by the postural reflex test and beam balance test. Infarct volume was determined in thionin- stained sections 96 hours after ischemia and values corrected for swelling. Treatment with AG (intraperitoneally, twice daily), starting 24 hours after MCA occlusion, decreased neocortical infarct volume in comparison to vehicle-treated rats. After correction for swelling, the decrease was 8 +/- 12% at 50 mg/kg (n = 8; P > .05; analysis of variance), 25 +/- 13% at 100 mg/kg (n = 7; P < .05), 30 +/- 16% at 200 mg/kg (n = 7; P < .05) and 32 +/- 9% at 400 mg/kg (n = 5; P < .05). Twenty-four hours after induction of ischemia neurologic deficits scores did not differ between treated and untreated rats (P > .05). However, from 48 to 96 hours after ischemia, neurologic deficits improved significantly in rats treated with AG (100 to 400 mg/kg) compared to rats in which vehicle was administered (P < .05). The decrease in neocortical infarct volume was greatest when AG (100 mg/ kg; twice daily) was administered 12 (26 +/- 17%; n = 9) or 24 hours (25 +/- 13, n = 7) after MCA occlusion. The findings show that AG decreases ischemic brain damage dose-dependently and improves neurologic recovery. Delayed treatment with AG may be a therapeutic strategy to selectively target the evolution of ischemic damage that occurs in the post-ischemic period.

Animals↗
PubMed1997

Tissue response to fast-setting calcium phosphate cement in bone.

Fast-setting calcium phosphate cement (FSCPC) is a promising new bioactive cement with a significantly short setting time (approximately 5-6 min) compared to conventional calcium phosphate cement (c-CPC) (30-60 min) at physiologic temperatures. As a result of its ability to set quickly, it is applicable in surgical procedures where fast setting is required. In this study, FSCPC was implanted in rat tibiae to evaluate tissue response and biocompatibility. FSCPC was converted to hydroxyapatite (HAP) in bone faster than c-CPC in the first 6 h. By 24 h, significant amounts of both FSCPC and c-CPC had been converted to HAP. The conversion of FSCPC into HAP further proceeded gradually, reaching 100% within 8 weeks. Infrared spectroscopic analysis disclosed the deposition of B-type carbonate apatite, which is a biological apatite contained in human dentin or bone, on the surface of the FSCPC. Histologically, FSCPC showed a tissue response similar to that of c-CPC. A slight inflammatory reaction was observed in the soft tissue apposed to both cements in the early period, and new bone was formed along the surface of the FSCPC at the adjacent bone. However, no resorption of either cement by osteoclasts or macrophages was observed within 8 weeks. We conclude that FSCPC is superior to c-CPC in clinical applications in oral and maxillofacial, orthopedic, plastic, and reconstructive surgery, since it shows a faster setting time and higher mechanical strength in the early period that are required in these surgical procedures, as well as osteoconductivity and excellent biocompatibility similar to that of c-CPC.

Animals↗
PubMed1997

Delayed reduction of ischemic brain injury and neurological deficits in mice lacking the inducible nitric oxide synthase gene.

Inducible nitric oxide synthase (iNOS), an enzyme that produces toxic amounts of nitric oxide, is expressed in a number of brain pathologies, including cerebral ischemia. We used mice with a null mutation of the iNOS gene to study the role of iNOS in ischemic brain damage. Focal cerebral ischemia was produced by occlusion of the middle cerebral artery (MCA). In wild-type mice, iNOS mRNA expression in the post-ischemic brain begun between 24 and 48 hr peaked at 96 hr and subsided 7 d after MCA occlusion. iNOS mRNA induction was associated with expression of iNOS protein and enzymatic activity. In contrast, mice lacking the iNOS gene did not express iNOS message or protein after MCA occlusion. The infarct and the motor deficits produced by MCA occlusion were smaller in iNOS knockouts than in wild-type mice (p < 0.05). Such reduction in ischemic damage and neurological deficits was observed 96 hr after ischemia but not at 24 hr, when iNOS is not yet expressed in wild-type mice. The decreased susceptibility to cerebral ischemia in iNOS knockouts could not be attributed to differences in the degree of ischemia or vascular reactivity between wild-type and knockout mice. These findings indicate that iNOS expression is one of the factors contributing to the expansion of the brain damage that occurs in the post-ischemic period. iNOS inhibition may provide a novel therapeutic strategy targeted specifically at the secondary progression of ischemic brain injury.

Animals↗
PubMed1997

Non-decay type fast-setting calcium phosphate cement: hydroxyapatite putty containing an increased amount of sodium alginate.

A hydroxyapatite [(HAP) Ca10(PO4)6(OH)2] putty that behaves like a putty or self-curing resin was made by increasing the amount of sodium alginate in non-decay type fast-setting calcium phosphate cement (nd-FSCPC). nd-FSCPC became viscous as the sodium alginate concentration was increased. The best handling properties were obtained when nd-FSCPC contained 8% sodium alginate in its liquid phase. When a 2-kg glass plate was placed on the paste, HAP putty spread to form an area three times that of FSCPC paste. Thus, HAP putty is expected to be easier to use than FSCPC in the filling of bone defects. HAP putty did not decay; in fact, it set within approximately 20 min when immersed in distilled water immediately after mixing. The wet diametral tensile strength value of HAP putty was approximately 12 MPa after 24 h, the same as that for nd-FSCPC containing 0.5% sodium alginate in its liquid phase, or FSCPC that is free from sodium alginate. The elements constituting set HAP putty were examined using powder X-ray diffraction and found to be predominantly apatitic minerals after 24 h. Since the handling properties of a putty or self-curing resin-like cement are very useful in certain surgical procedures, HAP putty made by increasing the sodium alginate concentration in nd-FSCPC is potentially a valuable new biomaterial for use in plastic and reconstructive surgery, as well as oral and maxillofacial surgery.

Alginates↗
PubMed1997

Blast coating method: new method of coating titanium surface with hydroxyapatite at room temperature.

When a titanium plate was blasted with hydroxyapatite [HAP; Ca10[x](HPO4)[x](PO4)[6-x](OH)[2-x]] powder at room temperature using an ordinary sandblaster, the surface of the titanium plate was found to be coated with HAP homogeneously and completely. The coated layer was examined with energy dispersive X-ray spectroscopy and X-ray diffraction and was found to be the same as the HAP powder used with respect to composition and crystallographic structure. The coated HAP layer was tightly attached to the surface of the titanium plate, at least at the level of scanning electron microscopy. Interestingly, the HAP particles stuck together at room temperature as if they were sintered. The coating was stable against ultrasonication in water for at least 5 min, and it was difficult to remove by nail scratching. Thus, the bonding strength between the HAP powder and the titanium plate was much higher than that achieved with currently employed room temperature coating processes such as dipping, electrophoretic deposition, and electrochemical deposition. Therefore, the blast coating method is potentially valuable for the fabrication of useful biomaterials for hard tissue replacement.

Biocompatible Materials↗
PubMed1997

The association of platelet-derived growth factor (PDGF) receptor tyrosine phosphorylation to mitogenic response of human osteoblastic cells in vitro.

OBJECTIVES: The purpose of this study was to make clear the relationship of human osteoblastic cell growth, induced by platelet-derived growth factor (PDGF), to PDGF receptor tyrosine phosphorylation. MATERIALS AND METHODS: Osteoblastic cells derived from human maxilla were cultured with human PDGF. The cell growth was evaluated by cell number and DNA synthesis. PDGF receptor tyrosine phosphorylation was detected by immunoblot analysis using anti-PDGF receptor alpha, beta subunits and anti-phosphotyrosine antibodies. Genistein, a tyrosine kinase inhibitor, was added to the culture to investigate the effect on osteoblastic cell growth and PDGF receptor tyrosine phosphorylation induced by PDGF. RESULTS AND CONCLUSIONS: PDGF stimulated the proliferation of human osteoblastic cells and this effect was synergetic with serum stimulation. DNA synthesis of osteoblastic cells was elevated by PDGF in a dose dependent manner at the minimum concentration of 1 ng ml-1. PDGF also induced PDGF receptor tyrosine phosphorylation within 1 min on osteoblastic cells, and tyrosine phosphorylation occurred on PDGF receptor subunits alpha and beta. Genistein inhibited cell growth and receptor tyrosine phosphorylation, which was induced by PDGF on these cells. In conclusion, human osteoblastic cell growth induced by PDGF is shown to relate to tyrosine kinase of PDGF receptors.

Becaplermin↗
PubMed1997

Effects of fenthion, isoxathion, dichlorvos and propaphos on the serum cholinesterase isoenzyme patterns of dogs.

The serum cholinesterase (ChE) isoenzyme patterns consist of 5 bands for normal beagle dogs. We examined the ChE isoenzyme patterns and ChE activities of 4 groups, each of which consisted of 4 dogs, given the organophosphate (OP) compounds fenthion (P = S type), isoxathion (P = S type), dichlorvos (P = O type) or propaphos (P = O type) po at 220, 75, 120 or 90 mg/kg respectively. Blood samples were collected for 30 d after the OP administrations. ChE isoenzyme bands 4 and 5 were inhibited 12 h after fenthion and isoxathion administration; dichlorvos and propaphos produced suppression of main bands 4 and 5 20 min after administration. This change was effective to differentiate the type of OP administered (P = S and P = O), while the main ChE isoenzyme bands of dog serum reflected inhibition of serum ChE activity.

Animals↗
PubMed1997

[Systemic sarcoidosis with involvement of the spermatic cord].

A 49-year-old man presented with an enlarging, painful, right inguinal mass and small red nodules around his nose and upper lip. He had undergone an operation for a right inguinal hernia in childhood. Because malignancy was suspected, the right spermatic cord, testis, and epididymis were resected. Histological examination of the lesion in the spermatic cord revealed non-caseating epithelioid-cell granuloma and no acid-fast bacilli, which was compatible with sarcoidosis. A chest X-ray film and computed tomograms showed enlarged hilar lymph nodes and reticular infiltrates. Histological examination of specimens obtained by transbronchial lung biopsy and by skin biopsy also showed non-caseating epithelioid-cell granulomas. After resection of the spermatic cord, the activity of angiotensin-converting enzume was 29.9 IU/L, which was above the reference range. Systemic sarcoidosis with involvement of the spermatic cord was diagnosed. Because he had no respiratory symptoms and his skin lesions resolved without treatment, he is currently under observation and is not receiving corticosteroid therapy.

Genital Diseases, Male↗
PubMed1997

Induction of micronuclei in cultured human lymphocytes with the mixture of highly toxic organochlorine compounds retained in human body.

In this study, we investigated the effect of mixture of the organochlorine compounds, which very resembled their contamination profile of healthy Japanese people in its composition, on the induction of micronuclei in human whole-blood cultures in order to clarify their genotoxicity as a whole. The following results were obtained. Regardless of the presence or absence of 7, 8-benzoflavone (ANF) in the blood culture system, we observed a fairly good dose-response relationship between the concentration of the mixture and the induction of micronuclei. In particular, we found that 50% effective concentration of the mixture of the organochlorine chemicals was considered only about 7 times greater level over the average concentration in the healthy people, namely 70ppt as 2, 3, 7, 8-TCDD, in the absence of ANF and about 5 times more than that in the presence of ANF. Based on these results, the mixture was regarded as extremely genotoxic. Our human bodies, however, have already been contaminated with a variety of chemicals including PCDDs, PCDFs and Co-PCBs and accordingly one of the most important problems to be solved is a further comprehensive genotoxicity and health consequences due to these chemicals to the descendants.

Adult↗
PubMed1997

Laparoscopic adrenalectomy: comparison with the conventional approach.

Laparoscopic adrenalectomy (LA) was performed on 14 patients with adrenal tumors. Herein we describe the laparoscopic procedure and the patients' clinical course compared with those of patients who underwent the conventional posterior or transabdominal approach (PA, TA). The 14 patients included four men and 10 women aged 28 to 69 years. Clinical diagnoses in this series were primary aldosteronism in seven patients, Cushing's adenoma in four patients, and nonfunctioning tumor in three patients. Maximum diameters of the adrenal tumors ranged from 10 to 48 mm. In all patients, the adrenal tumors were removed successfully. The mean operating time was longer for LA- than for PA- or TA-treated patients (185 versus 99 and 143 min), whereas the mean blood loss was smaller for LA- or PA-treated (92 and 126 ml) than for TA-treated patients (407 ml). The patients' postoperative condition, as assessed in terms of the number of febrile days, leucocytosis, and elevation of C-reactive protein value, was significantly better with LA. In addition, the frequency of administration of analgesics was lower and the time required until the patient could walk were shorter after LA than after PA and TA. In conclusion, laparoscopic adrenalectomy appears to be a minimally invasive and safe therapeutic option that may become a standard procedure for adrenal surgery.

Adrenal Gland Neoplasms↗