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Biomedical subjects

Koichi Kobayashi

Publications and source records attributed to Koichi Kobayashi.

At least 37 records · Page 2Linked to original sources
PubMed2006

[Prognosis of surgically treated thymic epithelial tumors].

This study was performed to clarify the prognosis of patients with surgically treated thymic epithelial tumors. The records of 131 patients who underwent surgical treatment during 1985-2005 were retrospectively reviewed. Pathologic review was done according to the WHO classification of tumors of the thymus. Patients characteristics were: 76 male and 55 fimale; average age 53 (range 20-80) years; tumor stage was stage I in 42, stage II in 43, stage III in 23, stage IVa in 15, stage IVb in 1, and thymic carcinoma (squamous cell carcinoma) in 7 based on Masaoka's staging. There were 7 cases of type A, 23 of type AB, 30 of type B1, 27 of type B2, 29 of type B3, and 15 of type C. Surgical procedures performed were 5 partial resections, 5 tumoretomies, 5 thymectomies, 65 extended thymectomies, 4 tumorectomies plus adjunctive resections of surrounding tissue, and 51 extended thymectomies plus tumorectomies plus adjunctive resections of surrounding tissue including the pleura, pericardium, lung, and great vessels. Five-, 10-, and 15-year survival rates by Masaoka stage were 100%, 100%, and 100% in stage I; 100%, 100%, and 87.5% in stage II; 100%, 87.5%, and 87.5% in stage III; 71.1%, 53.3%, and 53.3% in stage IVa; and 42.9%, 42.9%, and 0% in thymic carcinoma. The prognosis of patients with stage IVa and thymic carcinoma was thus significantly poorer compared with that in the other groups. According to the WHO classification, the 5-year survival rate of type A was 100%, and the 5-, 10-, and 15-year survival rates were 100%, 100%, and 100% in type AB; 100%, 100%, and 75.0% in type B1; 92.6%, 86.4%, and 86.4% in type B2; 95.5%, 95.5%, and 81.8% in type B3; and 57.1%, 42.9%, and 0% in type C. The survival rate of patients with type C was the poorest and there was a significant difference between type C and all other groups. The prognosis of patients with thymic epithelial tumors after resection is thought to be determined by histologic classification and clinical invasiveness. In particular, patients with type B3 and type C thymomas should be considered for multidisciplinary treatment.

Adult↗
PubMed2005

12-oxo-phytodienoic acid triggers expression of a distinct set of genes and plays a role in wound-induced gene expression in Arabidopsis.

Jasmonic acid (JA) and methyl jasmonate (MeJA), collectively known as JAs, regulate diverse physiological processes in plants, including the response to wounding. Recent reports suggest that a cyclopentenone precursor of JA, 12-oxo-phytodienoic acid (OPDA), can also induce gene expression. However, little is known about the physiological significance of OPDA-dependent gene expression. We used microarray analysis of approximately 21,500 Arabidopsis (Arabidopsis thaliana) genes to compare responses to JA, MeJA, and OPDA treatment. Although many genes responded identically to both OPDA and JAs, we identified a set of genes (OPDA-specific response genes [ORGs]) that specifically responded to OPDA but not to JAs. ORGs primarily encoded signaling components, transcription factors, and stress response-related genes. One-half of the ORGs were induced by wounding. Analysis using mutants deficient in the biosynthesis of JAs revealed that OPDA functions as a signaling molecule in the wounding response. Unlike signaling via JAs, OPDA signaling was CORONATINE INSENSITIVE 1 independent. These results indicate that an OPDA signaling pathway functions independently of JA/MeJA signaling and is required for the wounding response in Arabidopsis.

Acrolein↗
PubMed2005

Therapeutic angiogenesis with intramuscular injection of low-dose recombinant granulocyte-colony stimulating factor.

OBJECTIVE: In vivo administration of granulocyte colony-stimulating factor (G-CSF) has been shown to facilitate regeneration of cardiovascular tissues. However, G-CSF causes marked leukocytosis that potentially induces adverse cardiovascular events. Earlier studies showed that G-CSF had direct stimulatory actions on mature endothelial cells, resulting in promotion of angiogenesis. We thus examined whether low doses of recombinant human G-CSF (rhG-CSF) locally injected into ischemic tissues would stimulate angiogenesis without inducing severe leukocytosis. METHODS AND RESULTS: Reverse-transcription polymerase chain reaction (PCR) revealed expression of G-CSF receptor in human umbilical vein endothelial cells (HUVECs). rhG-CSF (100 ng/mL) enhanced migration and tube formation but not proliferation of HUVECs in vitro. We then examined the effects of rhG-CSF on angiogenesis in a rat model of hindlimb ischemia. Nude rats received in their ischemic skeletal muscles either rhG-CSF (2, 10, 20 microg/kg per day) or saline (control) for 6 days. Laser Doppler blood flowmetry (LDBF) revealed an augmented ischemic/normal limb LDBF ratio and an increased capillary density in the rhG-CSF-treated groups compared with the control at days 14, 21, and 28 (P<0.05). These doses of rhG-CSF induced only mild leukocytosis ( approximately 1.4-fold increases versus baseline). CONCLUSIONS: rhG-CSF promoted endothelial migration and tube formation in vitro. Local injection of low doses rhG-CSF effectively augmented ischemia-induced angiogenesis in vivo. This treatment regimen of low-dose rhG-CSF may become a new and safe modality for therapeutic angiogenesis.

Animals↗
PubMed2005

Superficial contact cryoablation attenuates experimentally created lung air leakage.

Previously, we, and others found that cryoablation on normal lung produced localized pulmonary hemorrhage and edema, causing obliteration of air space. Therefore, we hypothesized that lung air leakage may be diminished by this procedure. In the present study, we examined if cryoablation can attenuate experimentally created lung air leakage. Male domestic pigs (n=4) underwent a thoracotomy. The lung was resected approximately 5 mm in diameter and 1mm in depth to create air leakage lesions. An argon gas cryoprobe with a copper plate attached to its tip was used to cryoablate the lesions superficially. After cryoablation, the positive airway pressure that produced macroscopic bubbles from each lesion site was compared between cryoablated and untreated lesions. Also, cryoablation of the lung surface was carried out in male Donryu rats (n=20) which were sequentially sacrificed to observe the histological changes over a time course. In the pigs, the air leakage pressure was significantly increased with cryoablation (40 cmH2O <) compared to no treatment (19+/-5 cmH2O) (p=0.021, Mann-Whitney U test). Histologically, cryoablation produced acute pulmonary hemorrhage and edema. In the rats, the region with extensive hemorrhage progressed to fibrosis in 1 month, and the areas with edema recovered. This study provides supportive evidence that cryoablation has the potential to stop air leakage from surface pulmonary injury. This procedure may provide a useful adjunct to surgical resection for spontaneous pneumothorax, and the control of air leakage from dissected raw lung surfaces during lung resection.

Animals↗
PubMed2005

Effect of packing on orientation and cis-trans isomerization of azobenzene chromophore in Langmuir-Blodgett film.

Photoactive film material of long-chain azobenzene derivative, p-(omega-trimethylammoniodecyloxy)-p'-octyloxyazobenzene bromide (TAOAB), was fabricated into a Langmuir-Blodgett (LB) film by a polyion-complex technique using poly(sodium 4-styrenesulfonate) as a polyanion. To investigate the effect of the packing state of the azobenzene chromophore on its orientation and cis-trans isomerization, TAOAB was mixed with methyl stearate in the LB film matrix at various mole fractions (X(TAOAB)), and structural characterizations were subsequently carried out by means of Fourier transform infrared and ultraviolet-visible spectroscopies, X-ray diffraction analysis, and atomic force microscopy. The results obtained show that as the degree of packing increases, both the azobenzene chromophores and the hydrocarbon chains orient more perpendicularly to the surface of the LB film. In addition, reversible cis-trans photoisomerization of TAOAB took place upon alternate irradiation with UV and visible light even in a mixed LB film with the chromophores in a dense lateral packing state. In the process of thermal cis-to-trans isomerization, we found that the reaction rate is strongly affected by the packing state of TAOAB at 20 degrees C, reflecting the differences in steric hindrance among LB films of various X(TAOAB). In addition, higher activation energy was obtained for thermal cis-to-trans isomerization when the free volume around the chromophores became smaller.

Journal Article↗
PubMed2005

Role of Rho-kinase in reexpansion pulmonary edema in rabbits.

Reexpansion of a collapsed lung increases the microvascular permeability and causes reexpansion pulmonary edema. Neutrophils and their products have been implicated in the development of this phenomenon. The small GTP-binding proteins Rho and its target Rho-kinase (ROCK) regulate endothelial permeability, although their roles in reexpansion pulmonary edema remain unclear. We studied the contribution of ROCK to pulmonary endothelial and epithelial permeability in a rabbit model of this disorder. Endothelial and epithelial permeability was assessed by measuring the tissue-to-plasma (T/P) and bronchoalveolar lavage (BAL) fluid-to-plasma (B/P) ratios with (125)I-labeled albumin. After intratracheal instillation of (125)I-albumin, epithelial permeability was also assessed from the plasma leak (PL) index, the ratio of (125)I-albumin in plasma/total amount of instilled (125)I-albumin. T/P, B/P, and PL index were significantly increased in the reexpanded lung. These increases were attenuated by pretreatment with Y-27632, a specific ROCK inhibitor. However, neutrophil influx, neutrophil elastase activity, and malondialdehyde concentrations in BAL fluid collected from the reexpanded lung were not changed by Y-27632. In endothelial monolayers, Y-27632 significantly attenuated the H(2)O(2)-induced increase in permeability and mitigated the morphological changes in the actin microfilament cytoskeleton of endothelial cells. These in vivo and in vitro observations suggest that the Rho/ROCK pathway contributes to the increase in alveolar barrier permeability associated with reexpansion pulmonary edema.

Actin Cytoskeleton↗
PubMed2005

The acute effects of transthoracic cryoablation on normal lung evaluated in a porcine model.

PURPOSE: Percutaneous transthoracic cryoablation of lung parenchymal tumors offers a potentially less invasive alternative to thoracoscopic tumor resection. In the present study, we investigated the feasibility of transthoracic cryoprobe insertion into the lung parenchyma. DESCRIPTION: Cryoablation was performed in porcine lung through a thoracotomy. A 2-mm diameter cryoprobe was inserted to a depth of 3 cm from the pleura. Cryoablation was performed as one or two cycles of 15-minute freeze followed by 5-minute thaw. Bleeding time and amount, and air leakage pressure from the insertion site was measured and compared between cycles. EVALUATION: The bleeding time and amount significantly increased, and air leakage pressure significantly decreased with two cycles of cryoablation compared with one cycle. Histologically, the primary finding in the cryolesion was localized pulmonary hemorrhage. CONCLUSIONS: Bleeding time, bleeding amount, and air leakage from the insertion site after two cycles (453 +/- 202 s, 1.3 +/- 0.6 g, and 28 +/- 12 cm H2O, respectively) were considered unlikely to cause acute serious complications. Although long-term studies are needed, the present study provides support for transthoracic cryoablation.

Air↗
PubMed2005

The sealing effect of fibrin glue against alveolar air leakage evaluated up to 48 h; comparison between different methods of application.

OBJECTIVE: There is little experimental evidence to show how much positive airway pressure fibrin sealants can actually withstand, and in particular, how this effect changes over time. In the present study, we experimentally evaluated the sealing effect of fibrin glue against alveolar air leakage up to 48 h after application. METHODS: Beagles were used (n = 48). Under thoracotomy, approximately 5 x 10 mm defects (2 mm depth) were made on the lung surface. Fibrin glue sealants were applied to this defect in three ways. In rubbing and spray method, fibrinogen was rubbed, followed by spraying of both fibrinogen and thrombin solutions. In double layer method, fibrinogen was dripped, followed by thrombin. Collagen fleece, coated with fibrinogen and thrombin (TachoComb) was also tested. The minimum positive airway pressure which produced air leakage was measured for each sealed defect (seal breaking pressure, cmH2O) at 0, 3, 6, 12, 24, and 48 h after application (n = 6 at each time point). RESULTS: The seal-breaking pressure increased over time in all of the application methods. At 6 h, differences between methods were not significant but three defects in RS reached 70 cmH2O, the maximum pressure tested, compared with none in other two methods. At 12h, the seal-breaking pressure was significantly higher in RS compared with the other two methods (rubbing and spray method vs TachoComb; 66+/-3 vs 47+/-17, P = 0.047, rubbing and spray method vs double layer method; 66+/-3 vs 42+/-18, P = 0.024). Beyond 24 h, sealing pressure reached close to 70 cmH2O in all the methods. CONCLUSIONS: The results show that the sealing effect of fibrin glue is relatively unstable up to 12h after its application. Rubbing and spray method may help the fibrin seal to reach its full strength faster compared with the other two methods.

Aerosols↗
PubMed2005

Bcl-2 overexpression enhances in vitro sensitivity against docetaxel in non-small cell lung cancer.

Taxanes (docetaxel and paclitaxel) as well as cisplatin (CDDP) are key chemotherapeutic agents in the treatment of non-small cell lung cancer (NSCLC). Although some indicators of taxane resistance, such as beta-tubulin mutations, P-glycoprotein (P-gp) and Bcl-2, have been reported in malignant cells, the mechanisms of taxane resistance in NSCLCs have yet to be fully elucidated. We evaluated in vitro chemosensitivity to docetaxel (DOC) and CDDP in 87 surgically-resected specimens of NSCLC by collagen gel-droplet embedded culture drug sensitivity test (CD-DST). Bcl-2 and P-gp expression in these specimens were also investigated by immunohistochemistry. We examined the association between Bcl-2 and P-gp expression and in vitro chemosensitivity to DOC and CDDP. Out of the 87 NSCLCs that were examined, Bcl-2 and P-gp were expressed in 32 (36.8%) and 28 (32.2%) of the tumors, respectively. Positive Bcl-2 expression was significantly associated with enhanced DOC sensitivity in NSCLCs (p=0.007) while no apparent association was observed between DOC sensitivity and P-gp expression. Interestingly, although DOC, but not CDDP has been reported to be a substrate of P-gp, P-gp expression was significantly inversely correlated with CDDP sensitivity in pulmonary adenocarcinomas (p=0.03). Positive Bcl-2 expression may be a promising indicator in determining in vitro taxane sensitivity in NSCLCs. On the other hand, positive P-gp expression may be an indicator of enhanced in vitro resistance to CDDP in pulmonary adenocarcinomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

[Artificial blood].

To prepare for shortage of blood components and to avoid side effects such as blood borne infectious disease, blood substitutes such as artificial red cell (artificial oxygen carrier) and artificial platelet are being developed. As for oxygen carriers, there are several candidates such as perfluorochemicals, modified hemoglobins and liposome encapsulated hemoglobins and albuimin heme. Perfluorochemicals have limited oxygen carrying capacity and oxygen inhalation is mandatory when they are used. Modified hemoglobins such as intermolecular or intramolecular cross linked hemoglobins have side effect to cause hypertension by scavenging nitro oxide (NO) which is produced by endothelial cells, because the size of these hemoglobins are small enough to go to the adjacent place near endothelial surface. Hemoglobin vesicles (HbV) in which hemoglobins are encapsulated in liposome is most possible candidate for oxygen carrier. Usefulness and safety of the HbV is evidenced by animal shock model or exchange transfusion model and they are now being prepared for clinical trials as red blood substitutes or oxygen therapeutics. Albumin heme in which recombinant human serum albumin incorporating synthetic heme is thought an ideal resuscitation fluid as this material has colloid oncotic pressure. Short time storage and viral infection are serious concern in platelet transfusion therapy for bleeding thrombocytopenic patients. Adhesion of the platelet to the collagen surface and aggregation at the bleeding sites to plug holes in blood vessels, and to facilitate the function of the remaining platelets is a starting point in developing platelet substitutes and several platelet substitutes have been proposed on this theory.

Albumins↗
PubMed2004

Exchange transfusion with synthetic oxygen-carrying plasma protein "albumin-heme" into an acute anemia rat model after seventy-percent hemodilution.

Recombinant human serum albumin (rHSA) incorporating the synthetic heme "albumin-heme" is an oxygen-carrying plasma protein that has the potential to be a red blood cell substitute. The physiological responses to a 30% exchange transfusion with two types of albumin-heme (rHSA-FecycP, rHSA-FepivP) solutions after 70% isovolemic hemodilution with 5 g/dL rHSA were investigated using anesthetized rats. The circulation parameters, blood parameters, renal cortical oxygen pressure (pO2), and muscle tissue pO2 were carefully monitored for 60 min after the injection. The declined mean arterial pressure and the mixed venous partial pO2 significantly recovered to 70.8 and 91.9% of the basal values by intravenous infusion of albumin-hemes, respectively. The lowered renal cortical pO2 also increased, indicating oxygen transport by this synthetic hemoprotein. The administration of albumin-heme into the acute anemia rat model after hemorrhage improved the circulatory volume and resuscitated the shock state. Both rHSA-FecycP and rHSA-FepivP transported oxygen through the body.

Anemia↗
PubMed2004

Exchange transfusion with entirely synthetic red-cell substitute albumin-heme into rats: physiological responses and blood biochemical tests.

Recombinant human serum albumin (rHSA) incorporating 2-[8-[N-(2-methylimidazolyl)]octanoyloxymethyl]-5,10,15,20-[tetrakis[alpha,alpha,alpha,alpha-o-(1-methylcyclohexanoyl)amino]phenyl]porphinatoiron(II) [albumin-heme (rHSA-heme)] is an artificial hemoprotein which has the capability to transport O(2) in vitro and in vivo. A 20% exchange transfusion with rHSA-heme into anesthetized rats has been performed to evaluate its clinical safety by monitoring the circulation parameters and blood parameters for 6 h after the infusion. Time course changes in all parameters essentially showed the same features as those of the control group (without infusion) and rHSA group (with administration of the same amount of rHSA). Blood biochemical tests of the withdrawn plasma at 6 h after the exchange transfusion have also been carried out. No significant difference was found between the rHSA-heme and rHSA groups, suggesting the initial clinical safety of this entirely synthetic O(2)-carrier as a red-cell substitute.

Albumins↗
PubMed2004

Importance of tumor necrosis factor-alpha cleavage process in post-transplantation lung injury in rats.

Tumor necrosis factor-alpha (TNF-alpha) has two forms with apparently different biological activities: a membrane-associated form and a soluble form. TNF-alpha-converting enzyme (TACE) mediates a cleavage of membrane-associated TNF-alpha to induce its bioactive soluble form. We hypothesized that inhibition of TACE might prevent TNF-alpha-induced tissue injury while preserving the benefits of TNF-alpha. In this study, we evaluated the role of TACE in acute inflammation using an inhibitor of the enzyme in a rat model of lung transplantation. Inbred Lewis rats underwent left lung isotransplantation, and the donor lungs were kept in Euro-Collins solution with or without the inhibitor. After 6 hours of ischemia, the left lung was transplanted into the recipient rat and reperfused for 4 hours. Inhibition of TACE significantly attenuated endothelial and alveolar septal damage, as assessed by radiolabeled albumin leakage after transplantation. The inhibition also attenuated neutrophil accumulation in the alveolar space and other histopathologic findings, including intercellular adhesion molecule-1 expression. In addition, significantly lower levels of monocyte chemotactic protein-1, cytokine-induced neutrophil chemoattractant-1, high mobility group box-1, and soluble epithelial cadherin and decreased neutrophil elastase activity were observed in bronchoalveolar lavage fluid from the rats treated with the inhibitor. We conclude that TACE mediates a critical step in the development of post-transplantation lung injury.

ADAM Proteins↗
PubMed2004

Physiological capacity of the reticuloendothelial system for the degradation of hemoglobin vesicles (artificial oxygen carriers) after massive intravenous doses by daily repeated infusions for 14 days.

A hemoglobin vesicle (HbV; diameter 252 +/- 53 nm) or liposome-encapsulated Hb is an artificial oxygen carrier developed for use as a transfusion alternative, and its oxygen-transporting capacity has been well characterized, although critical physiological compartments for the Hb degradation after a massive infusion of HbV and the safety outcome remain unknown. In this study, we aimed to examine the compartments for its degradation by daily repeated infusions (DRI) of HbV, focusing on its influence on the reticuloendothelial system (RES). Male Wistar rats intravenously received the HbV suspension at 10 ml/kg/day for 14 consecutive days. The cumulative infusion volume (140 ml/kg) was equal to 2.5 times the whole blood volume (56 ml/kg). The animals tolerated the DRI well and survived, and body weights continuously increased. One day after DRI, hepatosplenomegaly occurred significantly through the accumulation of large amounts of HbV. Plasma clinical chemistry was overall normal, except for a transient elevation of lipid components derived from HbV. These symptoms subsided 14 days after DRI. Hemosiderin deposition and up-regulation of heme oxygenase-1 coincided in the liver and spleen but were not evident in the parenchyma of these organs. Furthermore, the plasma iron and bilirubin levels remained unchanged, suggesting that the heme-degrading capacity of the RES did not surpass the ability to eliminate bilirubin. In conclusion, phospholipid vesicles for the encapsulation of Hb would be beneficial for heme detoxification through their preferential delivery to the RES, a physiological compartment for degradation of senescent RBCs, even at doses greater than putative clinical doses.

Animals↗