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Biomedical subjects

M Monden

Publications and source records attributed to M Monden.

At least 217 records · Page 12Linked to original sources
PubMed1997

Expanded polytetrafluoroethylene (ePTFE) vascular graft loses its thrombogenicity six months after implantation.

Although expanded polytetrafluoroethylene (ePTFE) has been believed to be an inert material for vascular prosthesis, it shows less tendency of graft maturation by means of endothelialization. The aim of this study is to evaluate long-term alteration in thrombogenicity of ePTFE grafts after implantation. Serial levels of thrombin-antithrombin III complex (TAT), D-dimer, C-reactive protein (CRP), and prothrombin time (PT) were examined in 77 patients following ePTFE Y-graft implantation for up to five years. TAT showed biphasic elevation after implantation; TAT increased from 16.4+/-8.6 ng/ml to 27.4+/-10.5 ng/ml at one day, decreased to 18.5+/-4.5 ng/ml at one week, and increased again to 25.3+/-8.5 ng/ml at two weeks. Elevated TAT gradually decreased after the second peak to reach a lower level than that before surgery after six months. There was no significant difference in TAT level after six months due to the difference in diagnosis or anti-thrombotic therapy. We suggest that ePTFE grafts lose their thrombogenicity six months after implantation, after which anti-thrombotic therapy might be unnecessary.

Adult↗
PubMed1997

Awareness of donor alloantigens in antiadhesion therapy induces antigen-specific unresponsiveness to islet allografts.

BACKGROUND: Antiadhesion therapy using monoclonal antibodies (mAbs) to adhesion molecules in vivo has been shown to produce significant prolongation of graft survival in various transplantation models. However, it remains unclear whether antiadhesion therapy operates by merely blocking adhesion between antigen-presenting cells and T cells physically and/or by blocking costimulatory signals while preserving signals mediated through T-cell receptors in vivo. We examined antigen-specific T-cell responses during and after antiadhesion therapy. METHODS: BALB/c islets were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 mice given anti-lymphocyte function-associated antigen (LFA)-1 and/or anti-intercellular adhesion molecule-1 mAb treatment. The animals bearing surviving islet allografts were challenged with BALB/c or third-party islets on day 7 or more than 100 days after transplantation. RESULTS: Islet allografts were acutely rejected in untreated animals, with a mean survival time (MST) of 19+/-8 days. Administration of anti-LFA-1 mAb induced significant prolongation of graft survival with a mean survival time of 72+/-33 days, and half of the allografts showed indefinite survival. The animals given anti-LFA-1 mAb alone 7 days before transplantation showed acute rejection of BALB/c islets, whereas a significant number of animals given anti-LFA-1 mAb and the BALB/c islet allograft simultaneously accepted secondary BALB/c islets, but rejected third-party islets. Likewise, most of the animals bearing long-term functioning BALB/c allografts for more than 100 days accepted secondary BALB/c islets, but rejected C3H islets acutely. Interestingly, the spleen cells from these animals transferred unresponsiveness to BALB/c islets into the 2.5-Gy x-irradiated recipients, whereas those from naive animals induced acute rejection. CONCLUSIONS: These results indicate that anti-LFA-1 mAb treatment prevents T-cell activation leading to rejection, but results in a T-cell receptor engagement leading to antigen-specific unresponsiveness maintained by transferrable suppressor cells.

Animals↗
PubMed1997

The release mechanism of platelet-activating factor during shear-stress induced platelet aggregation.

We previously reported that 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor, PAF), released from activated platelets stimulated with thrombin plus collagen, is associated with platelet microparticles. In the present study, we found that PAF is concentrated and associated with microparticles released from high shear stress-induced activated platelets. The total amount of PAF released from 3 x 10(8) platelets under high shear stress (108 dyne/cm2) was 3.2 +/- 0.6 x 10(-15)mol (n = 5, mean +/- S.D.). Eighty percent of the PAF released from the platelets was recovered in the microparticle fraction after ultracentrifugation in the presence of albumin. Under high shear stress, PAF was not released from platelets within 3 minutes, although microparticles were released. In conclusion, microparticles released from activated platelets in the rheological condition of high shear stress are major carriers of PAF.

Animals↗
PubMed1997

Hypercholesterolemia as a risk factor for deep-vein thrombosis.

Our retrospective study has shown that hyperlipidemia is a novel etiologic factor in deep-vein thrombosis (DVT) and that most of the idiopathic DVT patients were hyperlipidemic (Thrombosis Research 79, 147-151, 1995). The aim of our current study is to analyze the interrelationship between hyperlipidemia and DVT by means of a case-control study. A series of lipid parameters were analyzed using serum from 109 patients with deep vein thrombosis (DVT). One hundred nine age- and sex-matched subjects served as controls. Diagnosis of hyperlipidemia was made if the serum cholesterol level was above 220 mg/dL or if the triglyceride level was above 150 mg/dL. Among several types of hyperlipidemia examined, the risk factor associated with the highest estimated odds ratio was carriage of hypercholesterolemia associated with hypertriglyceridemia (odds ratio 5.1) followed in order by hypercholesterolemia without hypertriglyceridemia (odds ratio 2.6) and hypertriglyceridemia without hypercholesterolemia (odds ratio 0.9). These findings support the hypothesis that hypercholesterolemia plays an important role in the pathogenesis of DVT.

Adult↗
PubMed1997

Identification of mu-, m-calpains and calpastatin and capture of mu-calpain activation in endothelial cells.

The presence of the calpain-calpastatin system in human umbilical vein endothelial cells (HUVEC) was investigated by means of ion exchange chromatography, Western blot analysis, and Northern blot analysis. On DEAE anion exchange chromatography, calpain and calpastatin activities were eluted at approximately 0.30 M and 0.15-0.25 M NaCl, respectively. For half-maximal activity, the protease required 800 microM Ca2+, comparable to the Ca2+ requirement of m-calpain. By Western blot analysis, the large subunit of mu-calpain (80 kDa) was found to be eluted with calpastatin (110 kDa). Both the large subunit of m-calpain (80 kDa) and calpastatin were detected in the respective active fractions. By Northern blot analysis, mRNAs for large subunits of mu- and m-calpains were detected in single bands, each corresponding to approximately 3.5 Kb. Calpastatin mRNA was observed in two bands corresponding to approximately 3.8 and 2.6 Kb. Furthermore, the activation of mu-calpain in HUVEC by a calcium ionophore was examined, using an antibody specifically recognizing an autolytic intermediate form of mu-calpain large subunit (78 kDa). Both talin and filamin of HUVEC were proteolyzed in a calcium-dependent manner, and the reactions were inhibited by calpeptin, a cell-permeable calpain specific inhibitor. Proteolysis of the cytoskeleton was preceded by the appearance of the autolytic intermediate form of mu-calpain, while the fully autolyzed postautolysis form of mu-calpain (76 kDa) remained below detectable levels at all time points examined. These results indicate that the calpain-calpastatin system is present in human endothelial cells and that mu-calpain may be involved in endothelial cell function mediated by Ca2+ via the limited proteolysis of various proteins.

Antibody Specificity↗
PubMed1997

Detection of pancreatic and gastric cancer cells in peripheral and portal blood by amplification of keratin 19 mRNA with reverse transcriptase-polymerase chain reaction.

Reverse transcriptase-polymerase chain reaction (RT-PCR) targeted at keratin 19 mRNA was applied to detect circulating cancer cells in the peripheral and portal blood of pancreatic and gastric cancer patients. Keratin 19 mRNA expression was studied by RT-PCR in cancer tissues (12 pancreatic and 15 gastric cancers) and in peripheral and/or portal blood samples from patients with pancreatic cancer (stage I, n = 5; stage II, n = 1; stage III, n = 15; stage IV, n = 19), gastric cancer (stage la,b, n = 28; stage II, n = 9; stage IIIa,b, n = 5; stage IVa,b, n = 7) and benign pancreatic diseases (n = 7). Peripheral blood samples from 50 healthy volunteers served as controls. RT-PCR was conducted in duplicate in each sample, and only samples showing keratin 19 transcript in both determinations were considered as being positive. All the pancreatic and gastric cancers, but none of the control blood samples, were found to be positive. Dilution study using pancreatic cancer cells serially mixed against peripheral blood showed that detection sensitivity was more than one cancer cell in 10(6) peripheral blood mononuclear cells. In pancreatic cancer patients, RT-PCR analysis of the portal blood samples gave positive results in one stage III and one stage IV patient, and that of peripheral blood samples gave positive results in 2 stage IV patients. No positive results were obtained in any of the blood samples from gastric cancer patients. Our results indicate that incidence of circulating cancer cells is unexpectedly very low even in advanced pancreatic and gastric cancer patients.

Humans↗
PubMed1997

Calpain activation in shear-induced platelet aggregation.

Fluid shear stress has been known to activate platelet reaction such as aggregation, but the exact mechanism of shear-induced platelet aggregation (SIPA) has not been fully understood. Calpain, an intracellular calcium-activated cysteine protease, is abundant in platelets and is considered to be activated and involved in the proteolytic processes during platelet activation. A possible activation of calpain in SIPA was investigated, employing a newly developed aggregometer and specific monoclonal antibodies to detect activation of calpain. When a shear stress gradient varying between 6 and 108 dyn/cm2 was applied to platelets, activation of mu-calpain was observed only in high-shear-stressed platelets, resulting in the proteolysis of talin. At 1 min after the onset of constant high shear stress of 108 dyn/cm2, mu-calpain activation and proteolysis of talin were detected and increased in a time-dependent manner. Constant shear stress more than 50 dyn/cm2, applied for 5 min, caused mu-calpain activation and proteolysis of talin, which were increased in a shear-force-dependent manner. Calpeptin, a calpain-specific peptide antagonist, caused the complete inhibition of both mu-calpain activation and proteolysis of talin, while SIPA profiles with calpeptin showed almost no change compared to those without calpeptin. These results suggest the possibility of calpain involvement in late phases of shear-induced platelet activation such as cytoskeletal reorganization.

Calpain↗
PubMed1997

CYP1A1, CYP2E1 and GSTM1 polymorphisms are not associated with susceptibility to squamous-cell carcinoma of the esophagus.

We investigated the genetic polymorphisms of CYP1A1, CYP2E1 and GSTM1 in Japanese esophageal cancer patients (n = 53) with a histological diagnosis of squamous-cell carcinoma, to determine whether susceptibility to esophageal cancer is associated with these polymorphisms. There were no significant differences in the frequency distribution of any one of the 3 polymorphisms between esophageal cancer patients and 132 healthy Japanese controls. The genotype distributions in tobacco smokers or alcohol drinkers were also quite similar for male patients and male controls. The age at onset of esophageal cancer was also similar for patients with any genotype of the 3 polymorphisms. We conclude that the 3 polymorphisms are unlikely to be associated with esophageal cancer susceptibility.

Adult↗
PubMed1997

Signal transduction system in epinephrine stimulated platelets; comparison between epinephrine sensitive and insensitive platelets.

We recently reported the high prevalence of impaired platelet responsiveness only to epinephrine in healthy Japanese. This abnormality was associated with a 50% decrease in the number of alpha 2-adrenergic receptors. Platelets from non-responders (NR) do not undergo secondary platelet aggregation even after exposure to 100 microM epinephrine, but they can potentiate the effect of ADP to provoke platelet aggregation. To further define the nature of the defect and to delineate controversial steps of epinephrine stimulated signal transduction, a signaling pathway of epinephrine was investigated in platelets from NR and R(normal responder to epinephrine). In a unique particle counting apparatus, epinephrine initially triggered the formation of small platelet aggregates composing of 10-1000 cells from both R and NR, but the aggregates became larger (4600 > cells) only in platelets from R. Thus, platelets from NR lack the ability to form larger aggregates. A similar defect was reproduced by treating normal platelets with aspirin. In the presence of fibrinogen, platelets from NR lacked phospholipase A2 activation, determined by arachidonic acid liberation in the presence of inhibitors to cyclooxygenase and lipoxygenase. In the absence of fibrinogen, aggregation and phospholipase A2 activation were not evident in R and NR. The surface expression of GPIIb/IIIa was markedly decreased in platelets from NR after stimulation by epinephrine, in comparison with those from R. The resting level and epinephrine stimulated increase in cAMP were not significantly different between NR and R. Incubating R platelets with a half saturating dose of yohimbine rendered them insensitive to epinephrine. These results indicated that the impaired platelet aggregation induced by epinephrine was due to the impaired surface exposure of glycoproteins GPIIbIIIa integral to the activation of phospholipase A2, which requires the full and normal occupancy of the alpha 2-adrenergic receptor by epinephrine.

Adenosine Triphosphate↗
PubMed1997

Prognostic factors in patients with recurrent differentiated thyroid carcinoma.

BACKGROUND: Approximately 20% of patients with thyroid carcinoma have relapse. To evaluate the factors affecting their disease-free survival and prognosis, we studied 68 patients with recurrent differentiated thyroid carcinoma, ranging in age from 5 to 73 years (mean: 47.6 years). Three-fourths of patients were followed for >10 years. Thirty-nine patients were treated with total or subtotal thyroidectomy at first operation; the remainder underwent lesser operations. Fifty-six patients had local recurrence, mostly lymph node infiltration. Twenty-six patients died. METHODS: Survival curves were constructed using the Kaplan-Meier method. Factors affecting relapse and survival were tested by univariate or multivariate analysis. RESULTS: Univariate analysis identified age at diagnosis, local tumor extension, and surgical method as significant factors for disease-free survival. These three factors and histology were significant prognostic factors. Multivariate analysis showed age, histology, and disease-free interval as significant and independent variables. CONCLUSIONS: In high-risk patients, complete resection of thyroid tissue and cervical lymph nodes is critical.

Adolescent↗
PubMed1997

Prostacyclin analog-suppressed ischemia-reperfusion injury of the rat liver: evaluation by calpain mu activation.

Prostaglandin I2 has a protective effect on hepatic ischemia-reperfusion injury. However, the exact intracellular mechanisms of this effect have not been elucidated. Calpain micro, a Ca2+-dependent protease, has been found to play a role in the ischemia-reperfusion injury of various organs. The hilar area of the left lateral and median lobes of rat livers was clamped for 60 min. A prostaglandin I2 analog (OP2507, C35H41NO4) was intravenously administered at 0.1, 0.32, or 1.0 microg/kg/min from 20 min before the ischemia. In addition to biochemical and microscopic analyses, the activation of calpain mu was investigated using specific antibodies against the intermediate (activated) and preactivated forms of calpain mu. The degradation of talin was also studied by Western blotting. When OP2507 was infused at 0.32 and 1.0 microg/kg/min, bile flow significantly increased after reperfusion compared with the control group, consistent with the decrease in serum transaminase levels. Membrane bleb formation and the appearance of the intermediate form of calpain mu were observed at 60 min of ischemia in the control and OP2507 (0.1 microg/kg/min) groups and remained present until 120 min after reperfusion. OP2507 (1.0 microg/kg/min) markedly suppressed not only membrane bleb formation but also calpain mu activation and the degradation of talin. In conclusion, OP2507 suppresses ischemia-reperfusion injury of the rat liver, and its cytoprotective effect is closely associated with the inhibition of calpain mu activation.

Alanine Transaminase↗
PubMed1997

Sclerotherapy for varicose veins of the lower legs in patients with dysplasminogenemia.

Sclerotherapy combined with ligation has become a widely accepted treatment for varicose veins; however, it is associated with some risk of the serious complications of deep vein thrombosis (DVT). We investigated the incidence of thrombophilia in 164 consecutive patients undergoing treatment for varicose veins and determined the activities of antithrombin-III, protein C, and plasminogen. Of the 164 patients, 10 were diagnosed as having dysplasminogenemia (DPG), showing an incidence of 6.1%, in accordance with previous reports. DVT was not found to be caused by DPG in any patient, and no difference was found between patients with and those without DPG, suggesting that DPG is not a risk factor for varicose veins. We also investigated the activation of coagulation by measuring the thrombin-antithrombin III complex (TAT). The activation of coagulation after sclerotherapy was inhibited when ligation was performed 1 month prior to sclerotherapy, whereas it was increased when sclerotherapy and ligation were performed simultaneously. Of the 10 patients with DPG, 5 were treated uneventfully, and their TAT level increased to 4.0 micrograms/l, which was comparable to the level after sclerotherapy and ligation. These findings indicate that sclerotherapy can be performed safely in the majority of patients with DPG, and that the temporal separation of sclerotherapy and surgery is an alternative for these patients to prevent the activation of coagulation.

Adult↗
PubMed1997

Augumentation of splenic antitumor immunity by local immunotherapy in gastric cancer patients.

We previously reported that the antitumor effect of OK-432, a streptococcal preparation, was markedly augmented when this agent was injected into tumors together with fibrinogen. In order to elucidate the effect of this treatment on the spleen, we assessed splenic function in gastric cancer patients receiving preoperative local immunotherapy with OK-432 and fibrinogen. Immunohistochemical studies of the spleen at 7 days after intratumoral injection therapy revealed numerous macrophages phagocytizing OK-432 in the splenic sinuses. Phenotypic analysis of splenocytes by flow cytometry revealed an increase in the CD4/CD8 ratio and in the expression of HLA-DR, CD25, and Leu M3 by splenic T cells of the patients treated with OK-432 plus fibrinogen when compared to patients treated with OK-432 alone or untreated patients. Splenic T cells from patients treated with OK-432 plus fibrinogen showed significantly higher cytotoxicity against Daudi and K562 cells than T cells from control patients (p < 0.05), and culture of these splenic T cells with recombinant IL-2 induced the expansion of lymphokine-activated killer cells. These results demonstrate that local immunotherapy with a mixture of OK-432 and fibrinogen effectively augumented splenic antitumor immunity in gastric cancer patients.

Antineoplastic Agents↗
PubMed1997

Effect of low concentration of epinephrine on human platelet aggregation analyzed by particle counting method and confocal microscopy.

The effect of a physiologic concentration of epinephrine (Ep) on platelet activation was studied by using a novel method that simultaneously measures platelet aggregation by changes in light transmission and counts particles of various sizes by using light scattering. Detailed morphologic changes associated with activation process were studied by using confocal laser scanning microscopy (CLSM). A low concentration of Ep (20 nmol/L) corresponding to a high physiologic concentration triggered the formation of small platelet aggregates (diameter 7 to 30 microm) without any change in light transmission. The redistribution of filamentous actin (F-actin) and the expression of activated glycoprotein IIb-IIIa complex (GPIIb-IIIa), detected by PAC-1 binding, were also observed in the platelets comprising the small aggregates. Attempts were then made to detect changes in cytoplasmic ionized Ca2+ ((Ca2+)i) in individual platelets involved in the aggregate formation by CLSM with fluo-3, a Ca2+-indicating dye. Ep caused a weak (Ca2+)i increase in some individual platelets involved in the formation of small aggregates. This (Ca2+)i increase was associated with platelet aggregation, because no (Ca2+)i rise was detected in single platelets. Furthermore, platelets stimulated by Ep in the presence of RGDS or Ro 44-9883, a GPIIb-IIIa antagonist, did not form small aggregates or trigger a (Ca2+)i rise. Prior incubation with low concentrations of Ep (20, 100 nmol/L) enhanced the initial formation of small (diameter 7 to 30 microm), medium (diameter 30 to 50 microm), or large (diameter 50 to 70 microm) aggregates induced by a subthreshold concentration of adenosine diphosphate (0.25 micromol/L) as determined by the particle counting method. However, no apparent synergistic (Ca2+)i increase was observed in platelets involved in aggregate formation. From these observations the following conclusions have been reached. (1) A high physiologic concentration of Ep (20 nmol/L) is capable of triggering the formation of small aggregates, resulting in the redistribution of F-actin and the expression of activated GPIIb-IIIa complex. (2) An increase in (Ca2+)i is observed in platelets comprising the small aggregates. This increase is not related to the binding of Ep to its receptor but most likely is triggered by platelet-platelet association. (3) The characteristic potentiating effect of Ep is not due to the synergistic increase in (Ca2+)i.

Actins↗
PubMed1997

Shear-stress causes polarized change in cytoplasmic calcium concentration in human umbilical vein endothelial cells (HUVECs).

Using a newly developed, parallel-plate flow-chamber for confocal laser scanning microscopy (CLSM), we studied the distribution and temporal changes in intracellular Ca2+ concentration ([Ca2+]i) in individual HUVECs stimulated by shear-stress. In the presence of ATP, shear-stress (1-10 dyne/cm2) caused a rise in [Ca2+]i, whereas no such response was observed in the absence of ATP or in the presence of Ni2+, a nonspecific, plasma membrane Ca2+ channel blocker. These results suggest that both ATP and Ca2+ influx are essential for the increase in [Ca2+]i in response to shear stress at less than 10 dyne/cm2. Analysis of [Ca2+]i distribution revealed a repetitive intracellular 'Ca2+ wave' originating from the upstream edge of the cell in some populations of HUVECS, which was transmitted to the downstream of the cell. The polarized [Ca2+]i response induced by shear-stress might be integral to polarized cellular reactions such as remodeling of endothelial lining.

Adenosine Triphosphate↗
PubMed1997

Role of supplementation of a nucleic acid solution on the intestinal mucosa under total parenteral nutrition.

Since dietary nucleotides play an important role in the growth and development of the intestine, supplementation of a nucleic acid solution (OG-VI) may support the optimal growth and integrity of the intestine under total parenteral nutrition (TPN). Supplementation of OG-VI to a TPN solution improved mucosal morphologic and functional changes, increased mucosal proliferation, and decreased mucosal permeability of the intestine. After 80% small bowel resection, OG-VI supplementation to a TPN solution attenuated the initial mucosal atrophy and improved intestinal cell turnover. Nucleic acid supplementation may be clinically beneficial in certain situations.

Animals↗
PubMed1997

Midkine expression in human breast cancers: expression of truncated form.

The expression of midkine (MK), a growth/differentiation factor, was assessed in 34 surgically resected specimens of primary breast cancer or mastopathy. Using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, all of the non-cancerous and cancerous tissues were found to express MK except for one breast cancer specimen. Northern blot analysis revealed that MK mRNA was also expressed in the normal breast tissues examined. Immunohistochemical analysis of the MK protein was performed on a limited number of the specimens, showing that some cancerous tissues were immunoreactive with anti-MK antibodies. Furthermore, using RT-PCR analysis, expression of not only the wild-type but also a truncated form of MK, which was recently found in various human tumor cell lines, was detected in 6 of 26 cancerous tissues but not in non-cancerous tissues.

Blotting, Northern↗