Search PubMed⌕ Search

Biomedical subjects

T Akimoto

Publications and source records attributed to T Akimoto.

At least 91 records · Page 5Linked to original sources
PubMed2000

Continuously maintaining positive flow avoids endocardial suction of a rotary blood pump with left ventricular bypass.

This study showed the usefulness of maintaining positive pump flow to avoid endocardial suction and as an assist bypass. Three calves were implanted with centrifugal pumps. Hemodynamics and pump parameters were measured at varying pump speeds (from 1,100 to 2,300 rpm). In each test pump, speed was adjusted to create 3 hemodynamic states: both positive and negative flow (PNF), positive and zero flow (PZF), and continuously positive flow (CPF). The pump flow volume was determined during systole (Vs) and diastole (Vd). Vs in PNF was 29.6 ml and was not significantly different from Vs in PZF (p > 0.15). Vd in PNF was significantly different from Vd in PZF (p < 0.05). All bypass rates of PNF were over 30% of pulmonary flow. All PZF bypass rates were between the PNF rate and the CPF rate. These data showed that PZF satisfied the minimum requirement of assist flow and was under 100% bypass. Thus, PZF may avoid endocardial suction.

Analysis of Variance↗
PubMed2000

Quantitative analysis of the kinetic constant of the reaction of N,N'-propylenedinicotinamide with the hydroxyl radical using dimethyl sulfoxide and deduction of its structure in chloroform.

N,N'-Propylenedinicotinamide (Nicaraven) is presently being developed for the treatment of cerebral stroke including subarachnoid hemorrhage. This drug is promising because some data suggest it to have an ability to scavenge the hydroxyl radical under physiological conditions in vivo, while it also has a high permeability through the blood brain barrier. Using the kinetic constant of the reaction between the hydroxyl radical and dimethyl sulfoxide, the formula derived by Babbs and Griffin (Free Rad. Biol. Med., 6 1989) was applied to obtain the kinetic constant of Nicaraven with the hydroxyl radical using a dimethyl sulfoxide-xanthine oxidase-hypoxanthine-Fe system, and this yielded the kinetic constant 3.4x10(9) M(-1) s(-1) (1 M=1 mol dm(-3)) for Nicaraven. Structurally related compounds were also investigated. The amide group of Nicaraven was thus found to play an important part in the reaction with the hydroxyl radical. Methanesulfinic acid, which was obtained from the reaction between dimethyl sulfoxide and the hydroxyl radical, was found to be stable under this adopted experimental condition and therefore was used to quantify the kinetic constant of Nicaraven. The structure of Nicaraven has also been investigated in CDCl3 using IR spectra, computer calculations and 1H-NMR analysis, and Nicaraven was thus shown to have an intramolecular hydrogen bond which forms a 7-membered ring that resembles a part of the 1H-1,4-benzodiazepines. This structure may play an important role in the penetration through the blood brain barrier.

Antioxidants↗
PubMed2000

Locus of dominant hairless gene (Ht) causing abnormal hair and keratinization maps to rat chromosome 10.

The rat dominant hairless gene (Ht) of the WBN/Ila-Ht rat causes atrichosis in Ht/Ht and hypotrichosis in Ht/+. Furthermore the Ht/Ht shows signs of abnormal keratinization and almost all of the Ht/Ht die in an immature stage before weaning in the conventional environment. Ht/+ was affected by dermatitis caused by Staphylococcus aureus, suggesting that the gene Ht might involve defense mechanisms against infection. In this study, we performed the linkage analysis of the gene Ht by outcross with the Brown Norway rat in the SPF environment. Ninety-six backcross progeny of (BN x WBN/Ila-Ht/Ht) F1 x WBN/Ila-Ht/Ht were typed with microsatellite markers and the gene Ht was mapped on chromosome 10 between Asgr1 and Nos2 within the map distance of 6.2 cM.

Alopecia↗
PubMed2000

Efficacy of directional coronary atherectomy before stent implantation for coronary ostial lesions.

We evaluated stent implantation following directional coronary atherectomy (DCA) for coronary ostial lesions. The subjects were 27 patients (27 lesions) who underwent stent deployment after DCA, and 47 patients (47 lesions) who underwent stent deployment alone as the control group. There were no differences in numbers of lesions with multi-vessel disease, left anterior descending artery lesions, de novo lesions or reference vessel diameters in the two groups. The percent diameter stenosis after stent implantation was lower in the DCA-stent group than in the stent-alone group (9 +/- 10% versus 17 +/- 14%, respectively; p < 0.01). The initial procedural success rate was 92.6% in the DCA-stent group and 91.4% in the stent-alone group. The initial clinical success rate was 100% in the DCA-stent group and 95.7% in the stent-alone group. The restenosis rate was lower in the DCA-stent group (20% versus 43% in the stent-alone group). This study showed that debulking by DCA before stenting is more effective compared to stenting alone.

Aged↗
PubMed2000

[Comparison of plasma exchange (PEX) vs. double filtration plasmapheresis (DFPP) with or without steroid administration in a case of MPO-ANCA-positive immune complex type crescentic glomerulonephritis].

The effect of plasmapheresis(PP) monotherapy and PP with corticosteroid administration were evaluated in a male with crescentic glomerulonephritis(CrGN). On the first admission, since he was positive for both anti-neutrophil cytoplasmic myeloperoxydase autoantibody(MPO-ANCA) and circulating immune complex(IC), the treatment was started with PP alone to reduce these autoantibodies immediately. During two months, three series of PP were performed: three sessions of plasma exchange (PEX) with fresh frozen plasma(FFP), two sessions of double filtration plasmapheresis(DFPP), and then, another two sessions of PEX, respectively. ANCA remained suppressed for 4 weeks after the first series of PEX, and increased thereafter. Subsequent DFPP caused a rebound of ANCA titer while the second PEX suppressed ANCA, at least, for 1 week. Though creatinine clearance(Ccr) improved after the first PEX and this level was maintained, ANCA increased again after the second PEX. Therefore the patient was treated with methyl-prednisolone(m-PSL) semipulse therapy followed by mild cocktail therapy including prednisolone(PSL) at 20 mg/day and mizoribine at 100 mg/day. In two weeks, ANCA and IC became negative and Ccr improved further. When PSL was tapered off, the ANCA became positive again. Since ANCA was not suppressed and Ccr declined gradually even after re-administration of oral PSL at 30-40 mg/day, PP was superimposed on steroid therapy with 3 sessions of DFPP and PEX, respectively. Ccr was improved, but ANCA was not sufficiently decreased by DFPP. Subsequent PEX was more efficient than DFPP in reducing the ANCA level. However, m-PSL semipulse was eventually required for complete suppression of ANCA. Thus PP was partially effective, but not sufficient as monotherapy. However it was considered advantageous as an adjunct therapy to reduce the dose of immunosuppressive drugs in CrGN. As to the mode of PP, PEX with FFP appeared to be more effective than DFPP in reducing the plasma ANCA level.

Aged↗
PubMed1999

Potentially lethal damage repair and its inhibitory effect of caffeine in two yolk sac tumor cell lines with different radiosensitivities.

PURPOSE: In order to investigate the role of potentially lethal damage repair (PLDR) in cellular radiosensitivity, PLDR and its inhibitory effect by caffeine was examined. In addition, cell cycle distribution was also examined. MATERIALS AND METHODS: Two rat yolk sac tumor cell lines, NMT-1 and NMT-1R, with different radiosensitivities in vitro were used. The capacity for PLDR was examined using confluent-phase cells, and evaluated by calculating the recovery ratio. Inhibitory effect of caffeine on PLDR was examined with doses of 1, 5 and 10 mM. RESULTS: The capacity of PLDR in two cell lines reflected radiosensitivity. The recovery ratio after irradiation of 5 Gy was 2.8 in the radiosensitive NMT-1 and 5.2 in the radioresistant NMT-1R, and recovery reached its peak level at 6 h in both cell lines. The degree of inhibition of PLDR was weaker in NMT-1R than that in NMT-1 at the same dose level, and was correlated with reduction of G2-arrested cells by caffeine. CONCLUSIONS: The results of this study suggest that the capacity of PLDR may be one of the determinant factors for radiosensitivity in the two cell lines used, and the inhibitory effect of caffeine on PLDR was in part attributable to the modification of the cell cycle progression.

Animals↗
PubMed1999

Is radiosensitive cell line cross-sensitive to heat?: Effect of heat on two rat yolk sac tumor cell lines with different radiosensitivity.

The differences between two rat yolk sac tumor cell lines, which are of the same origin but differ in their response to irradiation, in thermal sensitivity and development of thermotolerance were investigated. A radiosensitive cell line NMT-1 is consistently less heat sensitive than the radioresistant cell line NMT-1R. The thermotolerances in NMT-1 and in NMT-1R preheated at 43 degrees C for 30 min, respectively, reached peaks at 6 h and at 12 h, but did not completely disappear at 48 h. Thermotolerance with a good correlation between both cell lines with HSP70 accumulation was observed in a different time course after a primary heating.

Animals↗
PubMed1999

Association of increased radiocurability of murine carcinomas with low constitutive expression of p21(WAF1/CIP1) protein.

PURPOSE: The study investigated whether basal, constitutive levels of p21(WAF1/CIP1) protein in murine carcinomas are related to in vivo tumor radioresponse. The study is based on recent observations demonstrating that in vitro cancer cell lines are resistant to cytotoxic drugs when they express high basal levels of p21(WAF1/CIP1) protein, and that the loss of the p21 gene in the HCT116 human colorectal cancer cell line results in increased radioresponse of xenografts derived from that cell line. METHODS AND MATERIALS: Protein levels of p21(WAF1/CIP1), p53, bax, and bcl-2 were determined in 8 carcinomas (3 mammary carcinomas designated MCa-4, MCa-29, and MCa-35, 2 squamous cell carcinomas designated SCC-IV and SCC-VII, ovarian adenocarcinoma OCa-I, hepatocarcinoma HCa-I, and adenosquamous carcinoma ACa-SG) syngeneic to C3Hf/Kam mice using Western blot analysis. The tumors, growing in the right hind legs of mice, were 8 mm in diameter at the time of analysis. These tumors greatly differ in their radioresponse, assessed by TCD50 assay, and in their susceptibility to radiation-induced apoptosis. RESULTS: Protein levels of these oncogenes varied among tumors, with p21(WAF1/CIP1) showing the greatest variation: its mean densitometric value ranged from 1 to 19. Bcl-2 levels also showed broad variation in densitometric values, from 1 to 10. In comparison, bax and p53 (7 of 8 tumors contained wild-type p53) varied much less among different tumor types; their variation was within a 5-fold range, and the level of p53 was similar in 6 of 8 tumors. Tumor radioresponse correlated significantly (R = 0.77, p = 0.02) only with the magnitude of p21(WAF1/CIP1)expression: tumors with high levels of p21(WAF1/CIP1)were less radiocurable than those with lower levels. Tumor radiocurability showed a significant positive correlation (p = 0.02) with the extent of radiation-induced apoptosis, indicating that tumors that responded to radiation with higher percentages of apoptosis were more curable by radiation. Despite a strong trend to correlation, (p = 0.15), p21(WAF1/CIP1) expression did not correlate significantly with radiation-induced apoptosis, which suggested that p21(WAF1/CIP1) influenced tumor radioresponse by mechanisms beyond that of apoptosis induction. CONCLUSION: Our findings showed that murine tumors exhibit wide variation in constitutive levels of p21(WAF1/CIP1) which had a significant relationship with tumor radioresponse: tumors with high levels of p21(WAF1/CIP1) were less radiocurable than those with lower levels. These findings support the concept that p21(WAF1/CIP1) is a major determinant of tumor radioresponse in vivo, and may have important clinical implications. The pretreatment assessment of p21(WAF1/CIP1) protein could serve as a useful predictor of radiotherapy outcome and may assist in selecting an effective treatment modality.

Animals↗
PubMed1999

Role of platelet activating factor on severity of ischemic colitis.

PURPOSE: Ischemic colitis develops after a sudden decrease in colonic blood supply and has a variety of clinical manifestations. The aim of this study was to assess the role of platelet activating factor in the pathogenesis of ischemic colitis with use of the platelet activating factor antagonist TCV-309. METHODS: Rats were randomly divided into four groups. Rats in Group RV underwent ring attachment around the rectum to induce partial obstruction and ligation of the marginal vessels of the left colon. As control, rats in Group R underwent the ring attachment and rats in Group V underwent the vascular ligation. Rat in Group C underwent sham operation. The effects of TCV-309 on lesion formation in the colon were evaluated. Thiobarbituric acid reactant level was determined in colonic mucosa, and the incidence and severity of ischemic lesions were also determined. RESULTS: Lesions of colitis were frequently observed in Group RV. TCV-309 did not prevent lesion formation, nor did it suppress the increase in thiobarbituric acid reactant level in Group RV. However, TCV-309 mitigated the severity of the lesion. CONCLUSIONS: Partial obstruction of the colon tends to induce ischemic colitis, and additional ischemia completes lesion formation. Platelet activating factor may play a role in the progression of ischemic lesions.

Animals↗
PubMed1999

Low E-cadherin and beta-catenin expression correlates with increased spontaneous and artificial lung metastases of murine carcinomas.

This study examined the relationship between the expression of E-cadherin or beta-catenin in murine adenocarcinomas and their hematogenous metastatic propensity, assessed by both spontaneous and artificial lung metastasis. Seven different carcinomas, syngeneic to C3Hf/Kam mice were used: 4 mammary carcinomas (MCa-4, MCa-29, MCa-35, and MCa-K), ovarian carcinoma OCa-I, hepatocarcinoma HCa-I, and adenosquamous carcinoma ACa-SG. These tumors vary widely in their ability to spontaneously metastasize to the lung (from 0 to 100% metastatic incidence), and their cells greatly differ in their ability to form artificial lung nodules when injected i.v. Primary tumors in the leg were assessed for E-cadherin and beta-catenin expression by western blotting. The expression of both proteins showed wide variation among the tumors; however, the expression of E-cadherin correlated well with that of beta-catenin. There was significant inverse correlation between the expression of E-cadherin, as well as beta-catenin, and the incidence of both spontaneous and artificial lung metastases from these tumors. Spontaneous metastases of highly metastatic HCa-I and moderately metastatic MCa-35 were significantly lower in E-cadherin and beta-catenin expression than their corresponding primary tumors were. Thus, the propensity of murine carcinomas for hematogenous spread is highly related to E-cadherin and beta-catenin levels in primary tumors. The inverse correlation between the expression of these molecules and spontaneous and artificial metastases implies that tumor cells with low E-cadherin and beta-catenin content have increased ability to enter the vascular circulation at the primary tumor site and to colonize distant tissues.

Adenocarcinoma↗
PubMed1999

Vascular endothelial growth factor overproduced by tumour cells acts predominantly as a potent angiogenic factor contributing to malignant progression.

To elucidate the role of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, in tumour angiogenesis and malignant progression, an expression vector harboring human VEGF cDNA was stably transfected into three human cancer cell lines with poor VEGF productivity. Though their in vitro growth rate and intrinsic productivity of another angiogenic factor, basic fibroblast growth factor (bFGF), were not changed by transfection, those clones with higher VEGF production were endowed with tumorigenic and angiogenic potentials as follows: firstly, nontumorigenic, lung carcinoma QG90 cells having lower bFGF productivity acquired tumorigenicity as well as significant in vivo angiogenesis-inducing ability, secondly, tumorigenic colorectal carcinoma RPMI4788 cells having higher potency for bFGF production could form more vascularized solid tumour with faster growth rate and thirdly, oestrogen-dependent breast carcinoma MCF-7 cells, which did not produce detectable bFGF, acquired tumorigenicity even in the absence of oestrogen and the solid tumour growth rate was remarkably enhanced, accompanied with increased vascularization, in the presence of oestrogen. These results suggest that tumour progression closely depends on angiogenesis, and VEGF significantly contributes to malignant progression of a variety of tumour cells through its potent angiogenic activity, independent on the bFGF productivity of tumour cells.

Animals↗
PubMed1999

Rotary blood pump flow spontaneously increases during exercise under constant pump speed: results of a chronic study.

Many types of rotary blood pumps and pump control methods have recently been developed with the goal of clinical use. From experiments, we know that pump flow spontaneously increases during exercise without changing pump control parameters. The purpose of this study was to determine the hemodynamics associated with the long-term observation of calves implanted with centrifugal blood pumps (EVAHEART, Sun Medical Technology Research Corporation, Nagano, Japan). Two healthy female Jersey calves were implanted with devices in the left thoracic cavity. A total of 22 treadmill exercise tests were performed after the 50th postoperative day. During exercise, the following parameters were compared with conditions at rest: heart rate, blood pressure, central venous oxygen saturation (SvO2), pump speed, and pump flow. The pump flow in a cardiac cycle was analyzed by separating the systole and diastole. Compared to the base data, statistically significant differences were found in the following interrelated parameters: the heart rate (66.8 +/- 5.2 vs. 106 +/- 9.7 bpm), mean pump flow (4.8 +/- 0.2 vs. 7.0 +/- 0.3 L/min), and volume of pump flow in diastole (26.0 +/- 1.8 vs. 13.5 +/- 2.5 ml). During exercise, the volume of pump flow in systole was 3 times larger than that measured in diastole. Blood pressure, SvO2, and pump speed did not change significantly from rest to exercise. These results suggested that the mean pump flow depends on the systolic pump flow. Therefore, the increase in the mean pump flow during exercise under constant pump speed was caused by an increase in the heart rate.

Animals↗
PubMed1999

Interaction between low dose-rate irradiation, mild hyperthermia and low-dose caffeine in a human lung cancer cell line.

PURPOSE: To investigate cell killing by means of low dose-rate irradiation (LDRI) combined with concurrent mild hyperthermia and to determine the effect of low-dose caffeine on this combination treatment. MATERIALS AND METHODS: Human lung adenocarcinoma cells, LK87, were treated with LDRI (50 cGy/h) in combination with mild hyperthermia at 41 degrees C and low-dose caffeine (1 mM). Cell survival was estimated by clonogenic assay. Flow-cytometry was performed with PI staining using FACScan. Heat-shock protein (HSP72/73) was measured by the Western blotting method. All treatments were simultaneously performed for up to 48 h (24 Gy). RESULTS: LDRI cytotoxicities were enhanced by hyperthermia at 41 degrees C. D0 calculated from the dose-response curve for LDRI combined with 41 degrees C was 3.46 Gy whereas it was 6.55 Gy for LDRI alone. The survival curve for LDRI +41 degrees C demonstrated no chronic thermotolerance up to 48 h. For LDRI + simultaneous low-dose caffeine, cell killing was also enhanced, where D0 was 3.38 Gy at 37 degrees C. Radiosensitization caused by caffeine was enhanced by combination with simultaneous mild hyperthermia at 41 degrees C, where D0=1.78 Gy. Cell cycle analysis demonstrated remarkable G2 and mild G1 arrest for LDRI alone, but only G1 arrest was observed for LDRI combined with 41 degrees C and for LDRI combined with caffeine. Strong and early G1 arrest was observed in the treatment with LDRI + caffeine at 41 degrees C. The amount of HSP72/73 in the combination of LDRI with caffeine at 41 degrees C was less than that at 41 degrees C alone. CONCLUSION: LDRI cytotoxicity was enhanced by non-lethal hyperthermia. Low dose caffeine produced further cell killing in the combination of LDRI with mild hyperthermia.

Caffeine↗
PubMed1999

Human recombinant erythropoietin inhibits interleukin-1beta-stimulated nitric oxide and cyclic guanosine monophosphate production in cultured rat vascular smooth-muscle cells.

BACKGROUND: Recently rat vascular smooth-muscle cells (VSMC) have been shown to possess Epo receptor, and respond to various cytokines for producing nitric oxide (NO). In the present study we examined the effect of pharmacological dose of human recombinant erythropoietin (rHuEpo) on the IL-1beta-induced NO and cGMP production as well as inducible nitric oxide synthase (iNOS) in cultured rat VSMC. METHODS: Nitrite, a stable metabolite of NO, and intracellular cGMP contents were assayed by Griess method and enzyme immunoassay. iNOS mRNA expression was analysed by Northern blotting. RESULTS: RHuEpo inhibited IL-1beta-induced nitrite production in a dose- and time-dependent manner with concomitant changes of intracellular cGMP contents. On the other hand, rHuEpo did not inhibit atrial natriuretic peptide- (ANP) or sodium nitroprusside (SNP)-induced nitrite and cGMP production at all. While rHuEpo inhibited IL-1beta-induced iNOS mRNA expression, rHuEpo vehicle did not affect IL-1beta-induced iNOS mRNA expression. CONCLUSIONS: It is suggested that a pharmacological dose of rHuEpo inhibits IL-1beta-induced NO and cGMP production as well as iNOS mRNA expression, presumably via the Epo receptor.

Animals↗
PubMed1999

The effect of erythropoietin on interleukin-1beta mediated increase in nitric oxide synthesis in vascular smooth muscle cells.

OBJECTIVE: Recently, we observed that recombinant human erythropoietin (rHuEPO) inhibits the interleukin (IL)-1beta induced nitric oxide (NO) production and inducible NO synthase (iNOS) expression in cultured rat vascular smooth muscle cells (VSMC). The mechanisms of these inhibitory effects of rHuEPO were evaluated. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was performed to identify a specific erythropoietin receptor (EpoR). Tyrosine phosphorylation of phospholipase C (PLC) was analyzed by combination of immunoprecipitation and Western blotting. Protein kinase C (PKC) activities were analyzed by phosphorylation assay of myelin basic protein (MBP4-14). VSMC were incubated with test agents for 24 h and nitrite as a stable NO metabolite was measured. iNOS mRNA and protein expression was analyzed by Northern and Western blotting, respectively. RESULTS: RT-PCR analysis revealed that EpoR m-RNA was expressed; furthermore, it might be alternatively spliced in VSMC. rHuEPO induced tyrosine phosphorylation of PLC-gamma1 and activation of PKC. rHuEPO inhibited not only IL-1beta induced nitrite production, but also the expression of iNOS mRNA and protein. These inhibitory effects of rHuEPO were reversed in the presence of PKC inhibitors, calphostin C (1 pmol/l) or staurosporine (10 nmol/l). PKC activation by phorbol myristate acetate inhibited nitrite production. The inhibitory effect of rHuEPO on IL-1beta induced nitrite production was also eliminated in PKC depleted cells or in the existence of anti-EpoR antibody. CONCLUSION: rHuEPO inhibits IL-1beta induced NO production by suppressing iNOS mRNA and protein expressions through EpoR, and the PLC-gamma1 and PKC pathway may be involved.

Animals↗
PubMed1999

Stereotactic radiotherapy for locally recurrent nasopharyngeal carcinoma.

OBJECTIVE: To determine the efficacy of stereotactic radiotherapy (SRT) in the treatment of recurrent nasopharyngeal carcinoma. STUDY DESIGN: A retrospective review of the outcome of SRT for patients with recurrent nasopharyngeal carcinomas following definitive conventional radiation therapy. METHODS: Five patients were treated with daily static multiportal irradiation. Two Gy was administered with eight isocentric portals in a single plane 5 days a week, and the plane was changed for every 20 to 30 Gy. Of these patients, three had poorly differentiated squamous cell carcinoma. Tumor sizes ranged from 1 to 15 cm3, with a median size 3.2 cm3. Median follow-up time from SRT was 34 months (range, 4-61 mo). RESULTS: Four of five recurrent tumors responded well and achieved complete regression. Three patients have survived without evidence of local recurrence with a median follow-up time of 34 months. Marginal recurrence was observed at the posterosuperior wall in a patient with adenoid cystic carcinoma at 30 months after SRT. One patient who received SRT after the two complete courses of radiation therapy died 6 months after SRT as a result of rupture of a branch of the left carotid artery, but autopsy revealed no local residual tumor. CONCLUSIONS: Stereotactic radiotherapy with isocentric multiportals in one plane, which is changed at every 20 to 30 Gy, can provide local control with acceptable toxicity in patients with recurrent nasopharyngeal carcinoma, but increased clinical experience and longer follow-up will be necessary to evaluate the overall role of this technique in nasopharyngeal carcinoma.

Adult↗