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Biomedical subjects

K Nakano

Publications and source records attributed to K Nakano.

At least 289 records · Page 16Linked to original sources
PubMed1996

Prolongation of survival period and improvement of cancer cachexia by long-term administration of UFT.

We assayed the antitumoral and anticachectic activity of an oral fluoropyrimidine, UFT using the Colon-26-bearing murine cachexia model in terms of the survival period and parameters corresponding to clinical symptoms. Tumor growth was inhibited by UFT dose-dependently at the dose range of 12.5-25.0 mg/kg per day. Although UFT did not show significant growth inhibition at 15.0 and 12.5 mg/kg to which UFT gave little toxicity, the survival period was shown to be superior to the case of maximum tolerated dose (25.0 mg/kg per day). Next, we compared the maximum increase of life span (ILS) value for an administration schedule of continuous 9 days and 5 weeks which mimics the clinical schedule and found that the ILS value in the latter group was superior to the former and UFT improved cachexia, in the same manner. In the following experiments, we have clarified that UFT decreased the level of both plasma interleukin-6 (IL-6) and tumorous prostaglandin E2 (PGE2) and it highly accelerated IL-6 production from Colon-26. These findings suggest that UFT therapy, in low-toxic dose, could be useful to cachectic patients with poor performance status.

Animals↗
PubMed1996

Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats.

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.

Adenocarcinoma↗
PubMed1996

CD40 expression by human peripheral blood eosinophils.

In this study, we have investigated CD40 expression in human peripheral blood eosinophils and in human chronically inflamed nasal tissues, i.e., nasal polyps. We show by both reverse transcriptase-PCR and Northern blot analysis that eosinophils from allergic subjects express human CD40 mRNA. We also show that constitutive CD40 mRNA expression in eosinophils could be upregulated by exposure to IgA immune complexes and downregulated by IL-10 and the synthetic steroid budesonide. In addition, we demonstrate that eosinophils express CD40 protein by flow cytometry. Such expression is biologically functional as cross-linking CD40 with CD40 mAbs enhances eosinophil survival in a dose-dependent fashion; in addition, CD40 ligation stimulates eosinophils to release GM-CSF. CD40-mediated eosinophil survival was largely inhibited by an anti-GM-CSF neutralizing antibody suggesting GM-CSF involvement in the survival enhancing mechanism. CD40 mRNA was also detected in total RNA extracted from nasal polyp tissues but not in RNA isolated from normal nasal mucosa (inferior turbinate); by immunohistochemistry, we were able to detect immunoreactive CD40 protein in a variety of cell types in the polyp stroma, but primarily in eosinophils. These observations suggest previously unforeseen interactions between eosinophils and cells expressing the CD40 ligand and, thus, novel pathways by which eosinophils may contribute to the regulation of airway inflammation.

Antibodies, Monoclonal↗
PubMed1996

Ciliary neurotrophic factor attenuates spatial cognition impairment, cortical infarction and thalamic degeneration in spontaneously hypertensive rats with focal cerebral ischemia.

Ciliary neurotrophic factor (CNTF) has been shown to exhibit potent neurotrophic activity on peripheral and central neurons in vitro and in vivo. However, it remains to be determined whether or not CNTF rescues neuronal loss due to focal cerebral ischemia and prevents ischemia-induced disability of space navigation in rats. In the present in vivo study, we infused CNTF continuously for 4 weeks into the lateral ventricle, starting just after permanent occlusion of the left middle cerebral artery (MCA) of stroke-prone spontaneous hypertensive rats. CNTF infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner in rats subjected to the Morris water maze task. Subsequent histological examinations showed that cortical infarction and retrograde degeneration of the ipsilateral thalamic neurons in ischemic rats infused with CNTF were significantly less severe than those in ischemic rats infused with vehicle alone. These findings suggest that postischemic CNTF treatment prevents the occurrence of spatial learning disability in rats with permanent MCA occlusion, possibly by reducing neuronal damage within the cerebral cortex and secondary retrograde degeneration of the thalamus.

Analysis of Variance↗
PubMed1996

Motility-related protein-1 (MRP-1/CD9) reduction as a factor of poor prognosis in breast cancer.

The application of reliable markers is of major importance for predicting the prognosis of and instituting the appropriate postsurgical treatment of patients with breast cancer. Previously we showed that motility-related protein-1 (MRP-1), which is identical to CD9, regulates cell motility, and that cultured tumor cells transfected with MRP-1/CD9 cDNA have low motility and low metastatic potential. In addition, MRP-1/CD9 immunoblotting and immunohistochemical study with breast cancer revealed that MRP-1/CD9 expression diminished as the clinical stage of a given breast cancer advanced and that the MRP-1/CD9 gene and protein expression in the metastatic lymph nodes was strikingly lower than in the primary breast cancers. In this study, we also investigated the expression of MRP-1/CD9 by immunoblotting and immunohistochemical analysis in 143 freshly resected invasive ductal carcinomas of the breast: 52 tumors were stage I, 61 were stage II, and 30 were stage III. Tumors were classified as MRP-1/CD9 positive when a band intensity of >30% compared with positive control cells, ZR-75-30 were evaluated with the antibody M31-15, and those with intensities <30% as negative. Moreover, these results were ascertained by immunostaining. Tumor specimens classified as MRP-1/CD9 positive using Western blotting had >50% of the cancer cells immunostained with M31-15, and those classified as MRP-1/CD9 reduced had <50% of the cancer cells immunostained with M31-15. There were 97 patients with MRP-1/CD9 positive tumors and 46 patients whose tumors had reduced MRP-1/CD9 levels. The disease-free rate of the former group of patients was strikingly higher than that of the latter (84.7% versus 51.4%, P<0.001). Similarly, the overall survival rate was also significantly different between the two groups (93.6% versus 69.6%, P=0.004). Multivariate analysis with the Cox regression model indicated that MRP-1/CD9 positively correlated better with disease-free survival (P<0.001) than estrogen receptor, tumor, and lymph node status. Our data suggest that low MRP-1/CD9 expression by tumors of the breast may be associated with poor prognosis. It is conceivable that testing for MRP-1/CD9 may identify node-negative breast cancer patients who are at high risk for early disease recurrence.

Antigens, CD↗
PubMed1996

Pallido-thalamo-motor cortical connections: an electron microscopic study in the macaque monkey.

We combined the retrograde transport of horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) technique and degenerating electron microscopic investigations to confirm the motor cortical area projection from the medial pallidal segment (GPm) via the thalamic nucleus ventralis lateralis pars oralis (VLo). We found first degenerated boutons arising from the GPm make synaptic contact with the somata and proximal dendrites of VLo neurons containing WGA-HRP reaction products transported retrogradely from motor area.

Animals↗
PubMed1996

Modulation of endotoxin-induced histamine synthesis by cytokines in mouse bone marrow-derived macrophages.

The aim of this study was to examine the roles of various cytokines in histamine synthesis by macrophages in bone marrow. Pure (> 99% nonspecific esterase-, CD14-, and Mac-1-positive) macrophage populations were obtained after long term culture of bone marrow cells (bone marrow-derived macrophages). Culture of the cells in the presence of Escherichia coli LPS caused a slight, but dose-dependent, increase in histidine decarboxylase-associated histamine synthesis with a concomitant increase in the expression of CD14, a LPS receptor, as well as the Mac-1 Ag on their surface. Granulocyte/macrophage CSF (GM-CSF) or IL-3 strongly enhanced LPS-induced histamine formation and expression of CD14 on bone marrow-derived macrophages, without affecting the expression of Mac-1 Ag. GM-CSF and IL-3 also caused a marked accumulation of both histidine decarboxylase and IL-6 mRNAs in the cells. Macrophage CSF and IL-1-alpha also potentiated LPS-dependent histamine formation when it was stimulated with GM-CSF or IL-3. In contrast to these cytokines, IFN-gamma suppressed LPS-induced histamine production regardless of whether it was stimulated by GM-CSF or IL-3, and inhibited CD14 expression. Neither IL-6 nor granulocyte CSF had any appreciable effect on LPS-induced histamine production even in combination with GM-CSF or IL-3. These results suggest that GM-CSF and IL-3 enhance LPS-induced histamine production in bone marrow-derived macrophages and that macrophage CSF and IL-1 alpha augment the actions of GM-CSF and IL-3. Possible implication of CD14 molecule in the reactions is discussed.

Animals↗
PubMed1996

Self-control and the Type A behavior pattern.

A laboratory experiment was conducted to investigate self-control features of the Type A behavior pattern. The results indicated that the Type A subjects, high on the speed/impatient factor, had more difficulty in waiting for the larger delayed reward than non-Type As and chose the small reward available immediately. The results are discussed in terms of a conceptualization of Type As' poor self-control skills.

Adolescent↗
PubMed1996

Correlation between occurrence of exudative epidermitis and exfoliative toxin-producing ability of Staphylococcus hyicus.

Staphylococcus hyicus was isolated from healthy pigs and pigs affected with exudative epidermitis (EE). Thirty seven strains (P-7 to P-43) were isolated from pigs affected with EE on 8 farms while 131 strains were isolated from healthy pigs bred on 2 farms in Japan. Isolation rate for pigs affected with EE was 100% while that for healthy pigs was 35.4%. The biochemical and cultural characteristics of the isolates from healthy and diseased pigs were identical except for the Voges-Proskauer reaction. The culture supernatant of many isolates caused skin exfoliation in 1-day-old chickens. Therefore, many isolates were considered to produce S. hyicus exfoliative toxin (shET). The rate of shET production by the isolates from piglets affected with EE was 87.5%, while that of the isolates from healthy pigs was 76.1%. shETs were divided in two serotypes by immunodiffusion. Piglets experimentally infected with shET-producing and nonproducing strains were observed. Local skin erythema at the inoculation site was observed with nonproducing strains and disappeared within 48 h, while the skin erythema at the sites inoculated with shET-producing strains did not disappear until 7 days after inoculation. Typical clinical signs, such as exfoliation, exudation and crusting were observed only in the piglets inoculated with shET-producing strains.

Animals↗
PubMed1996

Serial doppler echocardiographic evaluation of bioprosthetic valves in the tricuspid position.

OBJECTIVES: This study sought to evaluate bioprosthetic valve dysfunction in the tricuspid position by serial Doppler echocardiography. BACKGROUND: Few reports on the long-term results of tricuspid valve replacement with bioprosthetic valves are evaluated by serial Doppler echocardiography. METHODS: Between September 1979 and December 1993, 95 patients underwent tricuspid valve replacement with bioprosthetic valves at our facility. Sixty patients who underwent serial Doppler echocardiographic examination at intervals of at least 2 years after operation were included in the final analysis. These patients were followed up from 1.5 to 13.0 years (mean 5.8 +/- 2.5). RESULTS: The actuarial rates of freedom from bioprosthetic valve stenosis and regurgitation at 10 years were 46% and 51%, respectively. The prevalence of bioprosthetic valve stenosis and regurgitation increased progressively in a linear manner beginning 1 or 2 years after tricuspid valve replacement. Right heart failure developed during follow-up in 20 of the 25 patients with bioprosthetic valve dysfunction. CONCLUSIONS: The long-term durability of bioprosthetic valves in the tricuspid position was substantially lower in our study than that reported in previous studies. Tricuspid bioprosthetic valve dysfunction increased progressively in a linear manner beginning 1 to 2 years after tricuspid valve replacement.

Actuarial Analysis↗
PubMed1996

Rationale of the Cox maze procedure for atrial fibrillation during redo mitral valve operations.

OBJECTIVE: The frequency of reoperation for mitral valve diseases with chronic atrial fibrillation has increased steadily. This study examined the rationale for using the Cox maze operation for atrial fibrillation during redo mitral valve operations. METHODS: Between June 1992 and July 1995, we performed the maze procedure in 42 patients as a concomitant operation with redo mitral valve surgery (maze group). Associated procedures were tricuspid valve surgery in 27 patients and aortic valve surgery in 15 patients. The mean age at operation was 57.3 +/- 9.7 years, and the mean interval from the previous operation was 14.3 +/- 10.5 years. The mean follow-up period after the maze procedure was 25.5 +/- 10.8 months. Atrial fibrillation was present at the time of the previous operation in 29 patients (69%). RESULTS: Neither hospital death nor late death occurred. Sinus rhythm was regained in 28 patients (67%), and an atrial A-wave was detected in 21 patients (50%) by pulsed Doppler study. Patients in whom sinus rhythm was restored had a shorter history of atrial fibrillation (9.0 +/- 6.0 years vs 15.9 +/- 4.6 years, p = 0.0009), a larger f-wave on lead V1 of the electrocardiogram (0.18 +/- 0.10 mV vs 0.10 +/- 0.08 mV, p = 0.017), and a smaller cardiothoracic ratio (63% +/- 8% vs 67% +/- 5%, p = 0.049) than patients with persistent atrial fibrillation. During the same period, 54 patients underwent mitral valve reoperation without the maze procedure (control group). The aortic crossclamp and cardiopulmonary bypass times were slightly longer (p = 0.048 and p = 0.012) in the maze group (133 +/- 28 minutes and 221 +/- 43 minutes) than in the control group (126 +/- 65 minutes and 197 +/- 78 minutes). There was no significant difference in the amount of chest tube drainage or transfusion between the two groups (890 +/- 510 ml and 2120 +/- 1600 ml, respectively, in the maze group and 840 +/- 480 ml and 2140 +/- 1760 ml, respectively, in the control group). It was not necessary to reopen the chest for bleeding significantly more often in one group than in the other (14% in the maze group and 7% in the control group), and it was possible to operate without transfusion with the same frequency in the two groups (17% in the maze group and 20% in the control group). CONCLUSION: These results suggest that the maze procedure should be considered in selected patients who have a high possibility of regaining sinus rhythm during redo mitral valve operations.

Adult↗
PubMed1996

Ten-year experience with the Carpentier-Edwards pericardial xenograft in the tricuspid position.

We reviewed the cases of 66 patients who underwent 67 tricuspid valve replacements with Carpentier-Edwards pericardial xenografts between April 1985 and January 1994. Average patient age at time of operation was 52 years (range 8 to 71 years). Concomitant mitral or aortic valve replacements were performed in 46 patients. There were 10 operative deaths and 6 late deaths. Actuarial survival at 9 years was 75.4% +/- 5.7%. Prosthetic valve endocarditis occurred twice in one patient. Reoperations for tricuspid regurgitation and for concomitant procedures (maze operation and repair for leak of the mitral prosthesis) were performed in two patients. In both cases, examination of the explanted prostheses showed that the tricuspid regurgitation was the result of nonstructural dysfunction caused by fibrous pannus formation on the cusps of the ventricular side. Among the survivors, 47 patients (92%) were in functional class I or II. Prosthetic valve function was studied by color Doppler echocardiography. Among 38 patients, tricuspid regurgitation more than grade 3/4 or transprosthetic gradient more than 5 mm Hg was found in 11. One patient had right heart failure and the others had no symptoms. In 10 years of experience with the Carpentier-Edwards pericardial xenograft, mortality and morbidity after tricuspid valve replacement were satisfactory. Echocardiographic examination revealed subclinical prosthetic dysfunction in 35% of patients who were followed up for longer than 5 years, however, and we believe that these patients should receive careful follow-up.

Adolescent↗
PubMed1996

Risks and benefits of combined maze procedure for atrial fibrillation associated with organic heart disease.

OBJECTIVES: This study sought to identify the risks and benefits of adding the maze procedure in patients with atrial fibrillation (AF) undergoing operation for underlying organic cardiac disorders. BACKGROUND: Persistent AF often leaves patients symptomatic even after otherwise successful cardiac surgery. METHODS: Fifty-one patients undergoing valvular operation and the maze procedure (n = 43) or repair of congenital anomalies (n = 8) combined with the maze procedure were compared with 51 patients (control group) matched for underlying diseases and procedures except for the maze operation. Each group, including 31 patients with a concomitant tricuspid annuloplasty and 12 undergoing reoperation, were similar in age, duration of arrhythmia, degree of cardiomegaly and New York Heart Association functional class. RESULTS: Patients undergoing the maze procedure had longer cardiopulmonary bypass time (213 vs. 144 min, p < 0.0001), longer cardiac arrest (134 vs. 93 min, p < 0.0001) and greater blood loss with longer respiratory care (39 vs. 18 h p = 0.021) and intensive care unit stay but no mortality. No significant differences were found in catecholamine or transfusion requirements immediately after operation. Sustained AF was much less frequent in the maze group (12% at 1 year) than the control group (86%, p < 0.0001), with an average follow-up period of 32 months (range 25 to 42). Atrial contraction was documented in 41 (80%) and 40 (78%) patients for right and left ventricular filling, respectively, after the maze procedure, resulting in a significantly smaller cardiac size and improved functional capacity. Medication was discontinued in seven patients in the maze group compared with two in the control group. CONCLUSIONS: Improved restoration of atrial rhythm and contraction with combined maze operation appeared to justify the increased operative time and complexity and postoperative care.

Atrial Fibrillation↗
PubMed1996

Surgical stratification of patients with atrial fibrillation secondary to organic cardiac lesions.

BACKGROUND: While the maze procedure does not always eliminate atrial fibrillation (AF) secondary to organic cardiac lesions, concomitant performance of the procedure is associated with increased surgical complexity and potential risks. METHODS: To stratify the surgical approach for patients with AF secondary to underlying cardiac lesions, we analyzed 24 preoperative and perioperative variables in 115 consecutive patients with AF undergoing a modified maze procedure combined with valvular intervention (101), repair of congenital anomalies (13) and coronary revascularization (1). RESULTS: Patients who remained in AF (18) compared to patients with restored atrial rhythm (97), had a higher incidence of giant left atrium (56% vs 10%, P < 0.0001), larger cardiothoracic ratio (70 +/- 13 vs 62 +/- 8%, P = 0.001) and left atrial dimension (64 +/- 12 vs 55 +/- 12 mm, P = 0.004), a longer history of AF (13.7 +/- 6.8 vs 8.3 +/- 6.9 years, P = 0.003) and lower f-wave voltage (0.10 vs 0.15 mV, P = 0.004). Multivariate logistic regression analysis of 24 preoperative and perioperative variables identified the presence of giant left atrium, cardiothoracic ratio and age at operation as the significant risk factors predisposing patients to persistent postoperative AF. Retrospective estimation identified 73 (63.5%) patients with a high probability of atrial defibrillation (97.3%) and 42 (36.5%) patients with a high risk of failure (38.1%). Regardless of the preoperative risk analysis or the performance of left atrial plication, every patient with a postoperative left atrial dimension less than 40 mm or cardiothoracic ratio below 55% was successfully defibrillated. CONCLUSION: The results suggest performing the maze procedure before "risk factors" develop for patients with predicted maze-amenable AF. While omitting the maze procedure may be prudent for patients with suspected maze-refractory AF, the simultaneous reduction of left atrial size may offset the increased risk from preoperative size factors. A prospective study seems warranted to examine the effects of left atrial plication on postoperative rhythm.

Adult↗
PubMed1996

Ca2+/calmodulin-dependent transcriptional activation of neuropeptide Y gene induced by membrane depolarization: determination of Ca(2+)- and cyclic AMP/phorbol 12-myristate 13-acetate-responsive elements.

Membrane depolarization stimuli (high potassium concentration and veratridine) increased neuropeptide Y (NPY) mRNA abundance time-dependently, without a change in beta-actin mRNA level, in NG108-15 and PC12 cells. Although the induction by veratridine was blocked completely by tetrodotoxin, the induction by potassium was suppressed minimally. Voltage-dependent Ca channel blockers and calmodulin antagonists inhibited the increases by both depolarization stimuli completely, suggesting involvement of Ca2+/calmodulin-dependent kinases (CaM kinases). Transient assay using chloramphenicol acetyltransferase reporter genes containing the rat NPY gene promoter indicated that membrane depolarization and Ca entry stimulate transcription of the NPY gene. The depolarization-induced transactivation was also blocked by CaM kinase inhibitors. The 200-bp 5'-upstream region (-344/-145) was localized as a Ca2+/ calmodulin-responsive element (CaMRE), which confers depolarization-induced transactivation. It is interesting that this CaMRE did not contain the canonical Ca-responsive elements such as CRE, SRE, NF-AT, or the C/EBP beta-binding site and was separated from a 64-bp cyclic AMP/ phorbol 12-myristate 13-acetate-responsive element (-144/-81). These findings suggested that membrane depolarization regulates the NPY gene transcription positively through the unique CaMRE by activation of CaM kinases following Ca entry through L-type Ca channels.

Animals↗
PubMed1996

Determination of interferon-alpha-producing capacity in whole blood cultures from patients with various diseases and from healthy persons.

To assess the clinical value of determination of the interferon (IFN)-producing capacity of patients, IFN production induced by Sendai virus (HVJ) in vitro was measured in cell cultures of whole blood from patients with various diseases. IFN production in patients with lung cancer, myelodysplastic syndromes, noninsulin-dependent diabetes mellitus, pulmonary tuberculosis, and asymptomatic HIV-1 infection was lower than that in healthy persons. Furthermore, periodic measurements of IFN production revealed decreasing IFN producing capacities in patients with lung cancer with progression of the tumor stage. However, increased IFN-producing capacities were observed in patients with tuberculosis after standard therapy. Further experiments showed that the main type of IFN induced in whole blood cultures was IFN-alpha, and decreased IFN production in patients did not result from a decreased number of leukocytes but rather from an impairment of cellular IFN production. The evaluation of IFN production in whole blood cell cultures may be a feasible method of assessing the impaired immune status.

Adult↗
PubMed1996

Characterization of transendothelial migratory lymphokine-activated killer cells.

We examined the killing activity of transmigrated lymphokine-activated killer (LAK) cells and their surface molecules associated with both transendothelial migration and cytotoxicity, using human umbilical vein-derived endothelial cell (HUVEC) monolayers on fibronectin with gelatin separating the upper chamber from the lower chamber. Migratory LAK cells were significantly more cytotoxic to Daudi target cells, expressed more LFA-1, and were more likely to be positive for CD2, compared to those LAK cells not adherent to the HUVEC monolayer. In contrast, in the absence of the HUVEC monolayer, there was no difference in LAK activity between migratory and non-adherent LAK cells. These results indicate that the interaction between LAK cells and the HUVEC monolayer allows selective migration of LAK cells with cytotoxic activity that is enhanced with respect to some surface molecules.

Antigens, Surface↗