Biomedical subjects

T Kikuchi

Publications and source records attributed to T Kikuchi.

At least 127 records · Page 7Linked to original sources

PubMed2000

Age-related modifications of effects of ketamine and propofol on rat hippocampal acetylcholine release studied by in vivo brain microdialysis.

BACKGROUND: We sometimes encounter impairment of learning and memory after general anesthesia in elderly patients. The aim of this study was to examine age-related modifications of the effects of ketamine and propofol on rat hippocampal acetylcholine (ACh) release because hippocampal cholinergic neurons are supposed to be involved in learning and memory. METHODS: The experiments were performed on male Wistar young rats (2 months old) and old rats (18 months old), using in vivo brain microdialysis technique under freely moving condition. After initial sampling of three collections, test drugs were administered. The ACh release was determined by the HPLC-ECD method. RESULTS: In old rats, the hippocampal basal ACh release was significantly lower than in young rats. Ketamine (25 and 50 mg kg(-1) i.p.) increased and propofol (25 and 50 mg kg(-1) i.p.) decreased the hippocampal ACh release in both young and old rats. Furthermore, ketamine 50 mg kg(-1) i.p. (anesthetic dose) produced facilitatory effects on the hippocampal ACh release in young rats (193% of the basal release), while in old rats the same dose of ketamine i.p. produced more pronounced facilitatory effects on the hippocampal ACh release (317% of the basal release). On the other hand, propofol 50 mg kg(-1) i.p. (anesthetic dose) produced inhibitory effects on the hippocampal ACh release in young rats (56% of control) and in old rats (77% of control). Although the maximal inhibitory peak effects of propofol 50 mg kg(-1) i.p. did not differ significantly between young rats and old rats, decrease of the hippocampal ACh release in old rats persisted longer than in young rats. CONCLUSION: Ketamine produced more pronounced facilitatory effects on the hippocampal ACh release in old rats, as compared with young rats. On the other hand, propofol has inhibitory effects on the hippocampal ACh release in young and old rats. The aging process may suppress the ability to recover from the inhibitory anesthetic state induced by propofol.

Acetylcholine↗

PubMed2000

Dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can initiate antigen-specific humoral immunity independent of CD4+ T cells.

We have investigated whether dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can trigger B cells to produce antigen-specific antibodies without CD4+ T-cell help. Dendritic cells modified with a recombinant adenovirus vector to express CD40 ligand and pulsed with heat-killed Pseudomonas induced naive B cells to produce antibodies against Pseudomonas in the absence of CD4+ T cells in vitro, initiated Pseudomonas-specific humoral immune responses in vivo in wild-type and CD4-/- mice, and protected immunized wild-type and CD4-/-, but not B-cell -/- mice, from lethal intrapulmonary challenge with Pseudomonas. Thus, genetic modification of dendritic cells with CD40 ligand enables them to present a complex mixture of microbial antigens and establish CD4+ T cell-independent, B cell-mediated protective immunity against a specific microbe.

Animals↗

PubMed2000

Association of serum low-density lipoprotein metabolism with oestrogen receptor gene polymorphisms in healthy children.

The aim of this study was to reveal the association of serum lipid and apolipoprotein levels with oestrogen receptor (ER) Xba I and Pvu II polymorphisms in 102 healthy Japanese school children (56M, 46F) aged 10-15 y. Each genotype of the genomic DNA extracted from peripheral leukocytes was determined using polymerase chain reaction and digestion with Xba I or Pvu II. The genotypes were coded as either X1 or X2 (Xba I) and P1 or P2 (Pvu II), when XI, P1 signified the absence of and X2, P2 the presence of restriction sites. The fasting serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride and apolipoproteins A1, B and E were measured. In the Xba I polymorphism, LDL cholesterol, apolipoprotein B levels of the XI/XI genotype were significantly higher than those of the others. The other lipid and apolipoprotein levels were not significantly different among the three genotypes. In the Pvu II polymorphism, there were no significant differences in serum lipids and lipoproteins among the three genotypes. This study reveals that Xba I polymorphisms are related to LDL metabolism. These findings support previous reports that the LDL-lowering effects of oestrogen occur through the ER (alpha) pathway. The Xba I polymorphism may be one of the genetic factors in the control of LDL metabolism.

Adolescent↗

PubMed2000

NOx- concentrations in the rat hippocampus and striatum have no direct relationship to anaesthesia induced by ketamine.

Using microdialysis, we have examined the effects of ketamine on concentrations of total nitric oxide oxidation products (NOx-) in the rat hippocampus and striatum in vivo to investigate the relationship between anaesthesia and NOx- production in the brain. Ketamine 25, 50 and 100 mg kg-1 i.p. increased NOx- concentrations to mean 125 (SD 13)%, 165 (11)% and 193 (13)% of basal, respectively, in the hippocampus and to 122 (12)%, 147 (7)% and 177 (14)% of basal in the striatum. Local perfusion with ketamine 50 and 100 mumol litre-1 into the hippocampus or striatum increased NOx- concentrations to 212 (32)% and 291 (17)% of basal, respectively, in the hippocampus and to 148 (20)% and 201 (18)% of basal in the striatum. Ketamine 50 and 100 mg kg-1 i.p. caused dose-dependent prolongation of loss of the righting reflex (LRR) and 100 mg kg-1 i.p. also caused loss of the corneal reflex (LCR). Local perfusion of ketamine did not provoke LRR or LCR. Inhibition of NOS by L-NAME 100 mg kg-1 i.p. decreased hippocampal NOx- concentrations to 58 (7)% of basal and did not provoke LRR or LCR. Although the effect of ketamine-induced increases in hippocampal NOx- concentrations was significantly depressed by L-NAME, LRR was not affected. These data imply that NOx- concentrations in the hippocampus or striatum have no direct relationship to the anaesthetic efficacy of ketamine, although this requires further investigation.

Anesthetics, Dissociative↗

PubMed2000

Molecular cloning and characterization of a new neuron-specific homologue of rat polypyrimidine tract binding protein.

Cancer-associated retinopathy (CAR) is a rare form of retinal degeneration and also one of the paraneoplastic neurologic disorders. Sera of CAR patients usually contain high titers of antibodies against retinal proteins, and CAR is believed to be an autoimmune disease. Using serum from a CAR patient as a molecular probe, a homologue of the polypyrimidine tract-binding protein (PTB) was isolated from a cDNA library of rat neonatal retina. This homologue, named PTB-like protein (PTBLP), encodes a 532 amino acid residue protein and has 73.5 and 68.8% homology with PTB and with a regulator of differentiation 1, respectively. Functional domains in the PTB, such as nuclear localization signals and four RNA recognition motifs (RRMs), were highly conserved. The expression of PTBLP mRNA was observed in the retina and brain but not in liver, kidney, spleen, or lung. The expression of PTBLP protein in rat retina was distributed in most of the cells in the ganglion cell layer and some cells in the inner nuclear layer. The PTBLP protein was localized in the nuclei of these cells. These results suggest that PTBLP is a new member of the PTB gene family and a neuron-specific homologue.

Amino Acid Sequence↗

PubMed2000

The Colletotrichum lagenarium MAP kinase gene CMK1 regulates diverse aspects of fungal pathogenesis.

The infection process of Colletotrichum lagenarium, the causal agent of cucumber anthracnose disease, involves several key steps: germination; formation of melanized appressoria; appressorial penetration; and subsequent invasive growth in host plants. Here we report that the C. lagenarium CMK1 gene encoding a mitogen-activated protein (MAP) kinase plays a central role in these infection steps. CMK1 can complement appressorium formation of the Pmk1 MAP kinase mutant of Magnaporthe grisea. Deletion of CMK1 causes reduction of conidiation and complete lack of pathogenicity to the host plant. Surprisingly, in contrast to M. grisea pmk1 mutants, conidia of cmk1 mutants fail to germinate on both host plant and glass surfaces, demonstrating that the CMK1 MAP kinase regulates conidial germination. However, addition of yeast extract rescues germination, indicating the presence of a CMK1-independent pathway for regulation of conidial germination. Germinating conidia of cmk1 mutants fail to form appressoria and the mutants are unable to grow invasively in the host plant. This strongly suggests that MAP kinase signaling pathways have general significance for infection structure formation and pathogenic growth in phytopathogenic fungi. Furthermore, three melanin genes show no or slight expression in the cmk1 mutant when conidia fail to germinate, suggesting that CMK1 plays a role in gene expression required for appressorial melanization.

Amino Acid Sequence↗

PubMed2000

Two cases of pediatric bone disease (eosinophilic granuloma and Brodie's abscess) showing similar scintigraphic and radiographic findings.

Two 9-year-old patients with femoral bone lesions were referred to the authors' institution within a few days of each other. Both showed similar radiographic, magnetic resonance imaging, and scintigraphic findings. The radiographs showed osteolytic lesions in the right femoral diaphyses, and gadolinium-DTPA-enhanced magnetic resonance imaging revealed inhomogeneous enhancement. Tc-99m HMDP showed marked linear accumulation with relatively low central uptake in the right femoral shafts, and TI-201 scintigraphy showed considerable uptake corresponding to the area seen with Tc-99m HMDP. Histologic analysis confirmed eosinophilic granuloma in the first patient and Brodie's abscess in the second. The radiographic and scintigraphic findings in Brodie's abscess may be similar to those in eosinophilic granuloma.

Child↗

PubMed2000

Tc-99m PMT hepatobiliary scintigraphy in the differential diagnosis of extrahepatic metastases and hepatocellular carcinoma.

PURPOSE: The authors evaluated the utility of hepatobiliary scintigraphy for tissue characterization of extrahepatic metastases from hepatocellular carcinoma (HCC) using Tc-99m N-pyrydoxyl-5-methyltriptophane (Tc-99m PMT). METHODS: We examined 13 patients with HCC (29 extrahepatic metastases and 3 benign bone lesions) and 5 patients with other cancers (15 extrahepatic metastases). Thirty minutes to 6 hours after intravenous administration of Tc-99m PMT, planar (all 47 lesions) and SPECT (42 lesions) images were obtained. Accumulation of Tc-99m PMT in the lesion was evaluated visually by comparing bone scintigraphy, computed tomography, magnetic resonance imaging, or all of these. RESULTS: Findings were positive in 12 of 13 patients with HCC and extrahepatic metastases (16 of 29 on planar imaging and 21 of 26 on SPECT). Findings in all three benign bone lesions and 15 metastatic lesions from non-HCC primary lesions were negative (0 of 18 on planar imaging, 0 of 16 on SPECT). There were no false-positive findings in these lesions. Lesion-by-lesion sensitivity, specificity, accuracy, and positive and negative predictive values were 55%, 100%, 72%, 100%, and 58% by planar imaging and 81%, 100%, 88%, 100%, and 76% by SPECT, respectively. CONCLUSIONS: Because of the high specificity and reasonable sensitivity, Tc-99m PMT appears to be useful for the differential diagnosis of extrahepatic metastases from HCC. SPECT improves the detectability of small or faint accumulation in metastases from HCC.

Aged↗

PubMed2000

Five cases of MRSA-infected patients with cerebrovascular disorder and in a bedridden condition, for whom bu-zhong-yi-qi-tang (hochu-ekki-to) was useful.

The herbal formula bu-zhong-yi-qi-tang (hochu-ekki-to, 5 grams per day) was administered to five MRSA-infected bedridden patients with cerebrovascular disorder, dementia and, in two cases, bed sores, who had resistance to several antibacterial drugs. After hochu-ekki-to the patients showed an excellent result; disappearance of MRSA, improvement of their general condition, and no side effects. Therefore, it is thought that hochu-ekki-to may be a useful drug for MRSA-infected patients.

Cerebrovascular Disorders↗

PubMed2000

Acid instillation enhances the inflammatory response to subsequent lipopolysaccharide challenge in rats.

Aspiration of gastric contents is one of leading causes of the acute respiratory distress syndrome (ARDS). The pathogenesis of acid aspiration-induced acute lung injury is well understood. Less clear is why patients who have suffered acid aspiration are susceptible to ARDS. We studied the effects of acid instillation on the inflammatory response to subsequent lipopolysaccharide (LPS) challenge in rats. Instillation of acid into the right lung worsened the pathology induced by LPS that was administered 24 h after acid instillation. This included worsened oxygenation, increased pulmonary edema, increased production of tumor necrosis factor-alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant, neutrophil accumulation and mobilization to the alveolar spaces, and nitric oxide (NO) production. Of interest, neutrophil mobilization, NO production, and protein permeability were also magnified in the left lung. These effects were attenuated by administration of the protein tyrosine kinase (PTK) inhibitors genistein and tyrphostin AG556. These data suggest that acid instillation primes the rat to enhance the inflammatory response to subsequent endotoxin challenge and that at least part of the augmented inflammatory response depends on PTK.

Animals↗

PubMed2000

Regulation of T-helper type 2 cell and airway eosinophilia by transmucosal coadministration of antigen and oligodeoxynucleotides containing CpG motifs.

The characteristic features of bronchial asthma, including airway eosinophilia and elevated immunoglobulin (Ig)E levels, are known to be orchestrated by T-helper (Th) 2 cells. Oligodeoxynucleotides containing CpG motifs (CpG) have recently been highlighted as an immunomodulator that biases toward a Th1-dominant phenotype. However, CpG may incur nonspecific Th1 activation and toxic effects. In this study we report a novel inhibition of Th2 cells by transmucosal inoculation of antigen and CpG. Intratracheal instillation of CpG inhibited airway eosinophilia and Th2 cytokine production in antigen-sensitized mice. The inhibition was observed when CpG was given at the same time or in advance of antigen challenge. Notably, concomitant administration of CpG and antigen (as opposed to either one alone) was essential for the inhibitory effects. The antigen dose could be minimized to avoid a harmful boost of eosinophilia. CpG had few effects on systemic anti-ovalbumin IgE responses. These results demonstrate that a synergism between transmucosally administered allergen and CpG inhibits Th2 cells in parallel with an improvement in airway eosinophilia and hyperresponsiveness without impeding systemic immune responses. Our data imply that inhalation of a minimal amount of allergen plus CpG could be a novel desensitization therapy for patients with bronchial asthma.

Animals↗

PubMed2000

Secretory leukoprotease inhibitor augments hepatocyte growth factor production in human lung fibroblasts.

Secretory leukoprotease inhibitor (SLPI), an 11.7-kD nonglycosylated serine protease inhibitor, is produced and released into the fluids of mucosal surfaces including human lung. It comprises two domains with homologous amino acid sequences: the N-terminal domain possessing antibacterial activity, and the C-terminal domain with antiprotease activity. Here we report the positive regulation of hepatocyte growth factor (HGF) production in human lung fibroblasts exerted by SLPI or its C-terminal domain under physiologic concentrations (1 to 10 microM). This HGF production by SLPI was unaffected by the addition of interleukin (IL)-1 receptor antagonist. In contrast, human skin fibroblasts exerted no SLPI-stimulated increase in HGF production, despite the fact that IL-1beta increased HGF production with an intensity similar to that of human lung fibroblasts. Both the time-course and dose-response studies in human lung fibroblasts revealed that the induction of HGF messenger RNA (mRNA) and protein occurred in parallel, indicating that the mechanism existed at the steady-state mRNA level. A synthetic elastase inhibitor failed to induce HGF, but alpha(1)-antitrypsin also stimulated HGF production in lung fibroblasts. Inactivation of the antiprotease activity of SLPI or its C-terminal domain by an oxidizing agent (N-chlorosuccinimide) abolished their stimulatory effect on HGF production. These findings demonstrate that SLPI exerts a novel HGF induction and functions as an anti-inflammatory and regenerative factor in addition to its role in protease inhibition.

Binding Sites↗

PubMed2000

Activation and transforming growth factor-beta production in eosinophils by hyaluronan.

To investigate whether extracellular matrix glycosaminoglycan hyaluronan (HA) modulates eosinophil activation and transforming growth factor (TGF)-beta production by eosinophils, human peripheral blood eosinophils (purity > 99%) from 12 patients with mild to moderate asthma or six healthy subjects were isolated and incubated with increasing concentrations of low molecular weight (mol wt) HA ( approximately 0.2 x 10(6) D) or high mol wt HA (3.0 to approximately 5.8 x 10(6) D). We found that the low mol wt HA has a pronounced effect on eosinophil survival in both patients with asthma and healthy subjects in a dose-dependent fashion on Days 2 and 4. Whereas the high mol wt HA had a smaller effect on eosinophil survival than did the low mol wt HA. The HA-mediated eosinophil survival was partially but significantly inhibited ( approximately 50% inhibition) by a blocking monoclonal antibody for CD44, a specific receptor of HA, and largely inhibited by an anti-granulocyte macrophage colony-stimulating factor (GM-CSF) neutralizing antibody but not by an anti-interleukin (IL)-3 or anti-IL-5 neutralizing antibody. In addition, the low mol wt HA increased GM-CSF messenger RNA (mRNA) expression and protein secretion by eosinophils in a dose-dependent fashion, suggesting that the HA-mediated eosinophil survival is due mainly to induction of GM-CSF release through partial CD44 signaling. Furthermore, we demonstrated that the low mol wt HA results in morphologic changes in eosinophils such as transforming from a round to a spindle shape and in homotypic aggregation, upregulates intercellular adhesion molecule-1 expression, and increases TGF-beta mRNA expression and protein secretion by eosinophils. These observations suggest previously unforeseen interactions between eosinophils and low mol wt extracellular matrix and, thus, novel pathways by which eosinophils may contribute to the regulation of airway inflammation and airway remodeling.

Asthma↗

PubMed2000

Antipituitary antibodies as pathogenetic factors in patients with pituitary disorders.

Our previous reports showed detection of antipituitary antibodies (APA) by immunoblot analysis and enzyme linked immunosorbent assay (ELISA) by using rat pituitary tissue as antigen in patients with certain endocrine disorders. In the present report, we evaluated APA by using our immunoblot and ELISA technique in 76 patients with various pituitary disorders. The prevalence of a 22 kDa band of APA detected by immunoblot was found to be significantly higher (P<0.01) in patients with pituitary disorders (20 of 76, 26%) than in the controls (3 of 209, 1%). APA levels detected by ELISA were significantly higher in patients with GH deficiency, isolated ACTH deficiency, acromegaly, and idiopathic panhypopituitarism compared with control (mean +/- SD; 2.40+/-2.66, 2.36+/-1.87, 2.09+/-1.87, 3.10+/-1.96 versus 1.42+/-0.64 (C.I.) P<0.05, respectively). APA levels detected by ELISA in 7 patients with GH deficiency showed a statistically significant decrease (p<0.05) after administration of GH replacement therapy. APA detection by immunoblot is useful in examining as pathogenesis, while ELISA may be useful as an objective index of pathological state in patients with autoimmune-related pituitary disorders.

Adolescent↗

PubMed2000

Dehydroepiandrosterone suppresses elevated hepatic glucose-6-phosphatase mRNA level in C57BL/KsJ-db/db mice: comparison with troglitazone.

Dehydroepiandrosterone (DHEA) is known to improve hyperglycemia of diabetic C57BL/KsJ-db/db mice that are obese and insulin resistant. In a previous study, we reported that DHEA as well as troglitazone suppresses the elevated hepatic gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and fructose-1,6-bisphosphatase (FBPase) activities in C57BL/KsJ-db/db mice. In the present study, we evaluated the changes in mRNA of G6Pase and FBPase in db/db mice. Despite hyperinsulinemia, the G6Pase mRNA level of db/db mice was elevated as compared to their heterozygote littermate db/+m mice. In contrast, the FBPase mRNA level was not elevated in db/db mice. Administration of DHEA for two weeks significantly decreased the blood glucose level and the elevated G6Pase mRNA level in db/db mice. No significant changes were seen in the FBPase mRNA level after the administration of DHEA. Administration of troglitazone also decreased the blood glucose and G6Pase mRNA level in db/db mice although no changes were seen in the FBPase mRNA level. These results suggest that the elevation of G6Pase mRNA is important in elucidating the cause of insulin resistance, and that the G6Pase gene is at least one target for the hypoglycemic effects of DHEA as an insulin sensitizing agent in db/db mice.

Animals↗

PubMed2000

Variability of bio-optical factors influencing the seasonal attenuation of ultraviolet radiation in temperate coastal waters of Japan

The study identifies the relative contribution of various bio-optical factors to the total attenuation of ultraviolet radiation (UVR) wavelengths and photosynthetically active radiation (PAR) in temperate coastal waters of Japan by surveying the physical properties of the water column, UVR and PAR penetration, and the absorption characteristics of dissolved and particulate material. Spectral absorbance properties of pigment (aph), detritus (ad) and chromophoric dissolved organic material (aCDOM) displayed both seasonal and wavelength specific variability. On an annual basis, absorbance by aCDOM was the highest absorbing fraction (47-59%) for the UVR wavelengths measured (305, 320, 340 and 380 nm) but decreased (32%) at 450 nm. Contribution of pigments to total absorbance was highest (40-60%) during a spring bloom for both UVR and PAR. A large variability (C.V. > 42%) for annual average attenuation coefficients (Kd[lambda]) at respective wavelengths observed suggests that the spectral composition of the water column changes throughout the year in this region. A significant relationship was observed between Kd(lambda) and aCDOM at 305, 320, 340 and 380 nm only (P < 0.01) but not for 450 nm (PAR) indicating the role of CDOM in regulating variations in Kd(lambda), particularly in the UVR range. The slope S, obtained from a natural-log plot of the absorption coefficient of CDOM against wavelength, ranged between 0.014 and 0.036 nm-1 annually (average = 0.020 +/- 0.007, C.V. = 35%) and suggests seasonal changes in the origin of CDOM between terrestrial (low S) and biogenous (high S) CDOM.

Journal Article↗

PubMed2000

[Epirubicin-based combination chemotherapy combined with G-CSF for the elderly patients with non-Hodgkin's lymphoma].

We devised a new epirubicin-based combination chemotherapy (Epi-COP) regimen for the patients with elderly non-Hodgkin's lymphoma and have treated 30 patients aged 66 years and older who had measurable diseases. In Epi-COP therapy, epirubicin was used as a substitute for doxorubicin in the CHOP regimen, and some dose modifications were made for the other agents. Combined modality treatment (CMT; chemotherapy plus radiotherapy) was adopted for 9 patients with localized disease. Complete response was obtained in 21 of all the 30 patients (70%), 8 in 9 (89%) of the CMT group and 13 in 21 (62%) of the patients with chemotherapy only (chemotherapy group). The median follow up time is 350 days, ranging from 2 to 77 months. The 2 year survival rate was 56% in all patients, 67% in the CMT group and 52% in the chemotherapy group. Granulocyte colony-stimulating factor (G-CSF) was administered when the leucocyte count decreased below 2,000/microliter, and 16 patients received it in the first course. The regimen could be repeated every three weeks in most cases. Although we encountered two early deaths, the overall toxicity level seemed to be acceptable. Even when we take account of the small number of patients and the short observation period, it might be concluded that Epi-COP was effective in inducing a good remission rate with moderate toxic effect in elderly patients with non-Hodgkin's lymphoma and CMT should be adopted if it is localized. A randomized comparative study with the CHOP regimen is necessary.

Aged↗

PubMed2000

[A case of heart surgery without homologous transfusion for complete atrioventricular septal defect associated with tetralogy of Fallot].

We performed intracardiac repair in an 11-month-old infant, weighing 5.1 kg, with complete atrioventricular septal defect and tetralogy of Fallot, who had been on a respirator, preoperatively, because of congestive heart failure due to severe common atrioventricular valve regurtitation. The preoperative angiogram revealed a very narrow and hypoplastic left pulmonary artery. Autologous blood donation after induction of anesthesia and minimalization of the cardiopulmonary bypass circuit (priming volume: 230 ml) made it possible to perform open-heart surgery without homologous blood transfusion in this case. The perioperative hemodynamics and respiratory status were satisfactory. An angiogram taken 1 year after surgery showed a well-developed left pulmonary artery.

Blood Transfusion, Autologous↗