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Biomedical subjects

T Kikuchi

Publications and source records attributed to T Kikuchi.

At least 181 records · Page 10Linked to original sources
PubMed1999

Antitumor activity of killer cells stimulated with both interleukin-2 and interleukin-12 on mouse glioma cells.

Interleukin-12 (IL-12), originally called natural killer cell stimulatory factor or cytotoxic lymphocyte maturation factor, has potential for use as an immunomodulator in cancer therapy because it significantly retards the growth of some murine tumors. In this study, we analyzed the antitumor effects of lymphocytes stimulated in vitro with both recombinant IL-2 (rIL-2) and rIL-12. When IL-12 was added to mouse splenocytes (SPCs) or human peripheral blood monocytes (PBMCs) incubated with IL-2 for > 4 days, IL-2-induced cytotoxicity against glioma cells was augmented. In contrast, IL-12 inhibited IL-2-induced lymphokine-activated killer (LAK) cell activity when added concurrently to cultures. The concentration of IL-10 induced by IL-12 increased in the supernatant of human PBMCs costimulated with IL-2 and IL-12. Endogenous IL-10 augmented the cytotoxicity of SPCs stimulated with IL-2 or IL-12 or both. However, tumor-bearing mice treated with PBMCs stimulated with both IL-2 and IL-12 did not survive longer than those treated with PBMCs stimulated with IL-2 alone (LAK cells).

Animals↗
PubMed1999

Kinetic parameter estimation from compartment models using a genetic algorithm.

Kinetic parameters were estimated from a three-compartment fluorodeoxyglucose model with three rate constants using a genetic algorithm. The performance of the genetic algorithm was investigated by simulation studies, in which brain time-activity data (TAD) were generated using cited mean values of rate constants and the plasma TAD obtained from positron emission tomographic studies. The accuracy of kinetic parameter estimation using the genetic algorithm was compared with that using the non-linear least-squares (NLSQ) method. The margin of error in the parameters estimated using the genetic algorithm tended to be smaller than that obtained by the NLSQ method. Although not statistically significant at a noise level of 5% in the brain TAD, the difference between the two methods became significant for all parameters at a noise level of 15% or higher. Our results suggest that the genetic algorithm is a promising means of estimating kinetic parameters from compartment models, because it is more robust against statistical noise than the NLSQ method and it can be rendered highly parallel for processing.

Algorithms↗
PubMed1999

In vitro activity of HSR-903, a new oral quinolone, against bacteria causing respiratory infections.

The in vitro activity of HSR-903, an oral quinolone, against 196 recent clinical isolates of respiratory pathogens was evaluated. HSR-903 was 2 to 32 times more active than ofloxacin, ciprofloxacin, and sparfloxacin against Staphylococcus aureus, including methicillin-resistant strains, and Streptococcus pneumoniae and was at least as active as the other quinolones against gram-negative pathogens.

Anti-Infective Agents↗
PubMed1999

ATP binding cassette transporter retina genotypes and age related macular degeneration: an analysis on exudative non-familial Japanese patients.

AIM: To determine whether mutations in the Stargardt's disease gene, ATP binding cassette transporter retina (ABCR) affect the occurrence of age related macular degeneration (AMD) in Japanese non-familial patients. METHODS: 80 unrelated Japanese patients with AMD (67 males and 13 females; mean age, 67.2 years) diagnosed by indocyanine green angiography and 100 age matched control subjects were studied. Among the AMD patients, 70 (87.5%) had choroidal neovascularisation of exudative type. Genomic DNA was purified from the total blood and 10 exons (exons 11, 23, 29, 32, 34, 37, 41, 43, 44, and 49) that have been reported to contain AMD associated mutations were amplified by polymerase chain reaction (PCR). The amplicons were analysed by the single strand conformation polymorphism (SSCP) method. The nucleotide sequencing of the amplicons was determined when necessary. RESULTS: Of the 10 exons, aberrant patterns of SSCP were detected in three exons-exons 29, 41, and 43. In exon 29, an aberrant pattern was found in seven of 80 patients (8.8%) and eight of 100 controls (8%). Sequencing of the PCR products revealed a heterozygous T1428M mutation which has been previously reported as one of the AMD associated mutations. Statistical analysis showed that there was no significant difference in the occurrence of this mutation between these AMD patients and the control groups (p = 0.86). In exons 23, 41, and 43, polymorphisms and sequence variations were found. CONCLUSION: No data to support the association between the ABCR gene mutations and AMD of Japanese patients, especially that of the exudative type, were obtained in this molecular genetic analysis.

ATP-Binding Cassette Transporters↗
PubMed1999

Interleukin-11 therapy selectively downregulates type I cytokine proinflammatory pathways in psoriasis lesions.

Psoriasis is a chronic inflammatory skin disease in which epidermal hyperplasia results from skin infiltration by type I T lymphocytes and release of associated cytokines. A multifunctional cytokine, rhIL-11, modulates macrophage and type I T-lymphocyte function in cell culture and shows anti-inflammatory activity in animal models. We are testing subcutaneous delivery of rhIL-11 to patients with psoriasis in a phase 1 open-label dose-escalation clinical trial. Tissue was obtained from lesional and uninvolved skin before and during treatment with rhIL-11 and was examined by histology/immunohistochemistry and quantitative RT-PCR. Expression of over 35 genes was examined in all patients, and multiple genetic markers of psoriasis were identified. Expression of numerous proinflammatory genes was elevated in psoriatic tissue compared with nonlesional skin. Seven of 12 patients responded well to rhIL-11 treatment. Amelioration of disease by rhIL-11, as shown by reduced keratinocyte proliferation and cutaneous inflammation, was associated with decreased expression of products of disease-related genes, including K16, iNOS, IFN-gamma, IL-8, IL-12, TNF-alpha, IL-1beta, and CD8, and with increased expression of endogenous IL-11. We believe that this is the first study in humans to indicate that type I cytokines can be selectively suppressed by an exogenous immune-modifying therapy. The study highlights the utility of pharmacogenomic monitoring to track patient responsiveness and to elucidate anti-inflammatory mechanisms.

Antigens, Surface↗
PubMed1999

Complete atrioventricular septal defect associated with tetralogy of fallot: surgical indications and results.

Complete atrioventricular septal defect (AVSD) associated with tetralogy of Fallot is a rare condition that still has problems in the postoperative period. The authors report their surgical experiences over the past 10 years. Nine children underwent total correction. The defect was repaired by the 2-patch technique and the ATrioventricular valve was reconstructed by suturing the cleft and annuloplasty. A transannular right ventricular outflow patch was used in 5 patients. All patients had Down syndrome and a free-floating superior bridging lEAflet. One patient died from cardiac failure. Although there was no reoperation or death in the late postoperative periods, mild mitral regurgitation occurred in 4 patients and there was moderate or severe pulmonary regurgitation in 2 patients. All survivors currently have no critical symptoms in their daily lives. With the standard of patient selection used, the optimal body weight was around 8 kg and PA index was 200 or more. Right ventriculotomy provided a better view for complete closure of the ventricular septal defect (VSD). In order to avoid re-regurgitation of the atrioventricular valve, the 2-patch technique is the most suitable procedure for total repair.

Aortic Valve Insufficiency↗
PubMed1999

Opportunistic Pneumocystis carinii infection in red-bellied tamarins (Saguinus labiatus).

P. carinii infection in red-bellied tamarins (Saguinus labiatus), born and maintained in a laboratory breeding colony, was examined by histopathologic examination postmortem. P. carinii cysts were detected in 6 of 10 red-bellied tamarins examined, by using Grocott's, toluidine blue O and immunostaining with avidin-biotin complex using antisera for rat-, simian-, and human-P. carinii. The results obtained from the present studies imply that P. carinii may be an important pathogen in this species.

Animals↗
PubMed1999

Pneumococcal psoas abscess.

A 47-year-old woman was admitted to our hospital because of severe low back pain. A computed tomography (CT) scan revealed a left sided psoas muscle abscess. On the first hospital day, US-guided drainage was performed. Streptococcus pneumoniae was isolated from the pus. Thereafter, the open drainage of the abscess and antibiotic treatment were given with subsequent clinical improvement. Only 10 cases of pneumococcal psoas abscess have been previously reported in the world literature.

Female↗
PubMed1999

Antibodies to a microbial peptide sharing sequence homology with betaA3-crystallin damage lens epithelial cells in vitro and in vivo.

Circulating auto-antibodies (Abs) against lens antigens (Ags) are highly prevalent in patients with cataract, but their origin and pathogenic significance are unknown. We hypothesized that Abs raised after exposure to infectious microbes could cross-react with lens Ags. To test this hypothesis, we generated a monoclonal Ab to human betaA3-crystallin. Epitope analysis indicated that the ETQAE sequence in the N-terminus region of betaA3-crystallin was critical for mounting a humoral response. Similar sequences were found in three microbial Ags. Mice injected with a microbial oligopeptide containing ETQAE emulsified with complete Freund's adjuvant (CFA) raised Abs which cross-reacted with betaA3-crystallin and developed lens epithelial cell (LEC) damage in vitro. We also genetically engineered an betaA3-crystallin-expressing E. coli. Mice immunized with the recombinant E. coli developed LEC damage. These results support the hypothesis that exposure to microbes having Ags homologous to self Ags can trigger a humoral immune response that leads to LEC damage in mice.

Amino Acid Sequence↗
PubMed1999

Comparison of various phosphate salts as the dietary phosphorus source on nephrocalcinosis and kidney function in rats.

The effects of various phosphate salts as the dietary phosphorus sources on the development of nephrocalcinosis and kidney function were examined in rats fed diets containing monophosphate salts (sodium dihydrogenphosphate, NaH2PO4, or potassium dihydrogenphosphate, KH2PO4) or polyphosphate salts (sodium tripolyphosphate, Na5P3O10, or potassium tripolyphosphate, K5P3O10), at levels representing normal phosphorus (normal phosphorus diet) or high phosphorus (high phosphorus diet) contents for 21 d. High phosphorus diet-feeding increased the kidney calcium and phosphorus concentrations. Kidney calcium and phosphorus concentrations were higher in rats fed the high phosphorus diet containing Na5P3O10 or K5P3O10 than in rats fed the high phosphorus diet containing NaH2PO4 or KH2PO4. Nephrocalcinosis was observed in all rats fed a high phosphorus diet, and the degree of nephrocalcinosis was more severe in rats fed Na5P3O10 or K5P3O10 than in rats fed NaH2PO4 or KH2PO4. In rats fed the high phosphorus diet, creatinine clearance was higher in rats fed Na5P3O10 or K5P3O10 than in rats fed NaH2PO4 or KH2PO4. In rats fed Na5P3O10 or K5P3O10, urinary albumin excretion and N-acetyl-beta-D-glucosaminidase (NAG) activity in the urine were increased in rats fed the high phosphorus diet. These were higher in rats fed the high phosphorus diet containing Na5P3O10 than in rats fed the high phosphorus diet containing NaH2PO4 or KH2PO4. This study observed that the development of nephrocalcinosis and kidney function in rats fed the high phosphorus diet was influenced by the difference in monophosphate or polyphosphate salts provided as the dietary phosphorus source, while the effects of sodium and potassium salts were not evident. We suggest that the development of nephrocalcinosis and kidney function in rats fed a high phosphorus diet was altered depending on the form of phosphate salts provided as the dietary source of phosphorus. Additionally, the development of nephrocalcinosis and diminished kidney function in rats fed the high phosphorus diet was more severe for polyphosphate salts as compared to monophosphate salts.

Acetylglucosaminidase↗
PubMed1999

Inhibition of plasminogen activator inhibitor-1 by 11-keto-9(E),12(E)-octadecadienoic acid, a novel fatty acid produced by Trichoderma sp.

We have recently found a novel fatty acid, 11-keto-9(E),12(E)-octadecadienoic acid (KOD), that enhances fibrinolytic activity of endothelial cells. The mechanism of action of KOD has been investigated. KOD increased 2-fold the plasmin activity of bovine aortic endothelial cells at 250 microM. The stimulation was dependent on plasminogen and was inhibited by anti-urokinase, whereas KOD did not enhance the urokinase-catalyzed plasminogen activation and the resulting plasmin activity in a cell-free system. Neither the production of urokinase nor the conversion of pro-urokinase to the active, two-chain form was elevated by KOD, but it decreased plasminogen activator inhibitor-1 (PAI-1) activity of cells and inactivated PAI-1 irreversibly in a purified system. These results demonstrated that the KOD enhancement of endothelial fibrinolytic activity was mediated, at least in part, by inactivation of PAI-1.

Animals↗
PubMed1999

Esculetin (dihydroxycoumarin) inhibits the production of matrix metalloproteinases in cartilage explants, and oral administration of its prodrug, CPA-926, suppresses cartilage destruction in rabbit experimental osteoarthritis.

OBJECTIVE: To investigate the in vitro effects of 6,7-dihydroxycoumarin (esculetin) on the production of matrix metalloproteinases (MMP) in rabbit articular cartilage, and the in vivo effects of orally administered CPA-926, a prodrug of esculetin, on cartilage destruction in rabbit experimental osteoarthritis (OA). METHODS: In vitro studies were performed using rabbit articular cartilage explants. Esculetin 10-100 microM was added to cartilage explants in the presence or absence of interleukin 1alpha (IL-1alpha). Effects of esculetin on cartilage metabolism were assessed. Proteoglycan release into medium was determined by dye precipitation with 1,9-dimethylmethylene blue, synthesis of proMMP-1 (interstitial procollagenase) and proMMP-3 (prostromelysin 1) by Western blotting, and collagen degradation activity using FITC labeled collagen. In vivo experimental OA was induced in the knee joints of 15 Japanese adult white rabbits by partial lateral meniscectomy. Ten rabbits were orally administered 200 or 400 mg/kg/day of CPA-926 from the day of surgery for 14 days. The size of the macroscopic erosive area on the femoral condyle and tibial plateau was measured, and cartilage destruction was histologically evaluated. Collagenolytic activities in synovial fluid were measured using FITC labeled collagen as a substrate. RESULTS: In vitro, esculetin inhibited the IL-1alpha induced release of proteoglycan into the medium in a dose dependent manner. The collagenolytic activities in cartilage explant medium induced by IL-1alpha were also suppressed with the addition of 33-100 microM esculetin (p = 0.0209 at 33 and 100 microM, p = 0.0202 at 66 microM). Western blotting of cartilage explant medium showed a decrease in the levels of proMMP-1 and proMMP-3 in the medium by treatment with esculetin. In vivo: At 14 days after surgery, the femoral condyle and tibial plateau in the control group showed macroscopic erosions of cartilage. Compared with the control group, the rabbits treated with CPA-926 at the dose of 400 mg/kg exhibited reduction of the size of the erosive area on the tibial plateau (p = 0.009). Histological evaluation indicated protection against the development of destructive changes in the tibial plateau cartilage at a dose of 200 mg/kg (p = 0.0442) and 400 mg/kg (p = 0.0446) of CPA-926. CONCLUSION: These results indicate that esculetin inhibits matrix degradation in rabbit joint cartilage explants through the suppression of MMP synthesis, secretion, or activity. Prophylactic administration of its prodrug, CPA-926, appears to provide some protection against cartilage destruction in a short term rabbit experimental OA model.

Administration, Oral↗
PubMed1999

[Exercise capacity in children late after aortic valve replacement using the Konno procedure].

Between 1980 and 1996, aortic valve replacements using the Konno procedure were performed in 10 patients. In order to assess the latent problems after this procedure, the exercise capacity was evaluated in 6 patients (3 males and 3 females). Exercise stress tests by a bicycle ergometer with ramp protocol were performed and gas exchange responses using the mixing chamber method were measured. The mean age at the time of operation was 6.6 years (range 3 to 11) and the mean age at the time of exercise test was 11.4 years (range 8 to 15). All patients were NYHA class I except 2 patients who had residual PH. Maximum oxygen consumptions were 37 to 39 ml/kg/min in males and 23 to 34 ml/kg/min in females. Maximum heart rates ranged from 166 to 184 bpm and O2 pulses ranged from 4.6 to 7.1 ml/beat/BSA. In the 2 patients who had residual pulmonary hypertension, HR bursting and O2 pulse plateau & decline occurred, which may indicate presence of decreased stroke volume. In conclusion, all patients late after the Konno procedure could tolerate exercise beyond respiratory compensation and there were no arrhythmia during exercise. HR was satisfactorily increased but maximum oxygen consumption was lowered at about 70% of the normal level.

Aortic Valve↗
PubMed1999

Caspaselike proteases activated in apoptotic photoreceptors of Royal College of Surgeons rats.

PURPOSE: To study the role of caspase-like proteases, especially roles of more extensively characterized caspase-1 and caspase-2, in apoptotic photoreceptor cell degeneration in Royal College of Surgeons (RCS) rats. METHODS: Both RCS and Sprague-Dawley rats were used. Cryosections of the retinas at various postnatal times were immunostained with antibodies against caspase-1 (interleukin-1beta-converting enzyme, ICE) and caspase-2 (Nedd2/Ich-1). Double staining with TdT-dUTP terminal nick-end labeling (TUNEL), propidium iodide, and the antibodies was also performed. To evaluate the time course of protein expression, western blot analysis was carried out. The temporal profile of caspase-like protease activity was studied using a fluorogenic tetrapeptide substrate, acetyl-tyrosyl-valyl-alanyl-aspartic acid alpha (4-methyl-coumaryl-7-amide) (Ac-YVAD-MCA). Intravitreal injection of a caspase-1 inhibitor, acetyl-tyrosyl-valyl-alanyl-aspartic-aldehyde (Ac-YVAD-CHO), at postnatal days 21 (P21) and P26 was performed to see if this caused a decrease in apoptotic cell number at P28. RESULTS: TUNEL-positive photoreceptors of RCS rats stained strongly with antibodies against caspase-1 and caspase-2. Double staining studies revealed that caspase-1 and caspase-2 were coexpressed in apoptotic cells. Western blot analysis showed that active forms of caspase-1-like and caspase-2-like proteases were upregulated at P28, concurrent with the peak in TUNEL-positive cells. The enzymatic activity of caspase-1-like protease was elevated in RCS rat retinas at P28, and the inhibitor of caspase-1 transiently reduced the number of the apoptotic photoreceptors. CONCLUSIONS: Activation of caspase-like proteases plays an important role in photoreceptor apoptosis of RCS rats.

Animals↗
PubMed1999

[The expression of chemokines and the dynamics of inflammatory cell infiltration before and after H. pylori eradication].

We attempted to evaluate the relationship between the expression of IL-8 and RANTES and the dynamics of their target cells in human gastric mucosa of H. pylori associated gastritis, including their changes after H. pylori eradication. We performed the measurement of the mucosal level of IL-8 and RANTES protein by ELISA and immunohistochemistry. The neutrophil infiltration into the gastric mucosa was identified by the histological examination based on the Updated Sydney system and the measurement of MPO activity. The memory T lymphocyte and eosinophil were indicated by immunohistochemistry of CD45RO that is one of surface markers indicating memory T lymphocytes and MBP that is contained in the granules of eosinophils. H. pylori positive gastric mucosa demonstrated a remarkable increase in neutrophils. CD45RO positive cells and eosinophils, compared to H. pylori negative gastric mucosa. Gastric mucosal level of IL-8 and RANTES protein and MPO activity was significantly higher in H. pylori positive cases than that in H. pylori negative controls after H. pylori eradication, both of the level of IL-8 protein and MPO activity reduced at the same levels as negative controls. However, RANTES expression, CD45RO positive T lymphocytes and eosinophils remained in H. pylori eradicated gastric mucosa at the significantly high level, compared with H. pylori negative cases. Therefore, it seems possible that IL-8 might enhance the inflammation by facilitating the neutrophil infiltration into H. pylori infected gastric mucosa and that RANTES might play an important role in the specific immune response against H. pylori and the maintenance of the immune memory after H. pylori eradication.

Adult↗
PubMed1999

[The efficacy of SEMS for malignant upper gastrointestinal stenosis, evaluated by a "home index"].

We used a self expandable metalic stent (SEMS) on 24 patients (average age 68.6 years, 20 males, 4 females) with malignant upper gastrointestinal stenosis from August, 1997 to March, 1999. The primary diseases of the 24 patients were gastric cancer (13 cases: 54%), esophageal cancer (10 cases: 42%) and paraesophageal lymph node metastasis of breast cancer (one case: 4%). In this study, we present a "Home Index" as an indicator to evaluate a patient's quality of life, and investigated the efficacy and problem of SEMS.

Adult↗