Biomedical subjects

K Kawasaki

Publications and source records attributed to K Kawasaki.

At least 19 recordsLinked to original sources

PubMed2006

PTEN activity could be a predictive marker of trastuzumab efficacy in the treatment of ErbB2-overexpressing breast cancer.

Trastuzumab is the only HER2/neu-directed therapy to have received Food and Drug Administration approval for the treatment of patients with metastatic breast cancer. The efficacy of trastuzumab depends on the HER2/neu status of the tumour and the patient's prior treatment, but even when patients are selected on the basis of HER2/neu gene amplification, the single-agent response rate ranges from 12 to 30% and few patients respond to trastuzumab monotherapy. Here, we propose PTEN as a predictive biomarker for trastuzumab efficacy. Human breast cancer SKBR3 and drug-resistant SKBR3/R cells were investigated. We also examined clinical samples from patients who had been treated with trastuzumab and analysed the relationship between trastuzumab efficacy and PTEN level. The PI3K/Akt signalling pathway was observed to be highly active in the drug-resistant cells, and their level of PTEN was low. Delivery of antisense PTEN duplex siRNA significantly decreased the trastuzumab chemosensitivity of parental SKBR3 cells, and marked activation of Akt signalling pathway was also recognised. Moreover, immunohistochemical investigation revealed that trastuzumab treatment was remarkably successful in cells with elevated PTEN expression. Along with the immune-system-associated cytotoxic mechanism, several mechanisms have been proposed for the effect of trastuzumab. PTEN activity might play an important and major role in its HER2/PI3K/Akt-mediated antitumour effect, and could be a useful biomarker for predicting the efficacy of trastuzumab in the treatment of breast cancer.

Antibodies, Monoclonal↗

PubMed2006

Effects of aging on RANKL and OPG levels in gingival crevicular fluid during orthodontic tooth movement.

OBJECTIVES: To compare the levels of the receptor activator of NFkB ligand (RANKL) and osteoprotegerin (OPG) in the gingival crevicular fluid (GCF) during orthodontic tooth movement in juvenile and adult patients. DESIGN: Fifteen juveniles and 15 adults served as subjects. GCF was collected from the distal cervical margins of the experimental and control teeth at 0, 1, 24, and 168 h after application of a retracting force. Enzyme-linked immunosorbent assay kits were used to determine RANKL and OPG levels in the GCF samples. RESULTS: The amount of tooth movement for juveniles was larger than for adults after 168 h. Further, after 24 h RANKL levels were increased and those of OPG decreased in GCF samples from the compression side during orthodontic tooth movement in both juveniles and adults. The RANKL/OPG ratio in GCF from adult patients was lower than that in the juvenile patient samples. CONCLUSION: Our results suggest that the age-related decrease in amount of tooth movement may be related to a decrease in RANKL/OPG ratio in GCF during the early stages of orthodontic tooth movement.

Adolescent↗

PubMed2006

Decrease in anterior knee laxity by electrical stimulation of normal and reconstructed anterior cruciate ligaments.

We have investigated the changes in anterior laxity of the knee in response to direct electrical stimulation of eight normal and 45 reconstructed anterior cruciate ligaments (ACLs). In the latter, the mean time from reconstruction was 26.7 months (24 to 32). The ACL was stimulated electrically using a bipolar electrode probe during arthroscopy. Anterior laxity was examined with the knee flexed at 20 degrees under a force of 134 N applied anteriorly to the tibia using the KT-2000 knee arthrometer before, during and after electrical stimulation. Anterior tibial translation in eight normal and 17 ACL-reconstructed knees was significantly decreased during stimulation, compared with that before stimulation. In 28 knees with reconstruction of the ACL, in 22 of which the grafts were found to have detectable somatosensory evoked potentials during stimulation, anterior tibial translation was not decreased. These findings suggest that the ACL-hamstring reflex arc in normal knees may contribute to the functional stability and that this may not be fully restored after some reconstructions of the ACL.

Adolescent↗

PubMed2005

Gastric mucosal hyperplasia via upregulation of gastrin induced by persistent activation of gastric innate immunity in major histocompatibility complex class II deficient mice.

BACKGROUND AND AIMS: Major histocompatibility complex class II deficient (Aalpha0/0) mice have decreased CD4+ T cells, making them immunologically similar to patients with acquired immunodeficiency syndrome (AIDS). Both patients with AIDS and Aalpha0/0 mice have hypertrophic gastric folds. To clarify the mechanism of gastric mucosal hyperplasia, we investigated the pathophysiology and the role of the innate immunity in the stomach of Aalpha0/0 mice. METHODS: Stomachs from 1-6 month old Aalpha0/0 mice, kept under specific pathogen free conditions, were examined at 1 month intervals histologically and immunohistochemically. Gene expression of proinflammatory cytokines, Toll-like receptors (TLRs), cyclooxygenase (COX)-2, and myeloperoxidase (MPO) activity in the gastric mucosa was investigated. Serum gastrin levels and gastric acidity were measured. Bacterial culture of the stomach was performed. To clarify the roles of hypergastrinaemia in the gastric mucosa, a gastrin receptor antagonist (AG041R) was administered. RESULTS: Aalpha0/0 mice had a diffusely thick corpus mucosa with infiltration of CD11b+ granulocytes and macrophages. Anti-Ki67 staining demonstrated expansion of the proliferating neck zone. Gene expression of interleukin 1beta, interferon gamma, TLR-2, TLR-4, and COX-2 were upregulated, and MPO activity was increased. Only a small amount of non-pathogenic bacteria was detected in the stomach. Serum gastrin levels and Reg-Ialpha positive cells in the gastric mucosa increased, despite normal gastric acidity. After treatment with AG041R, gastric mucosal thickness was significantly reduced. CONCLUSION: Persistent activation of innate immunity in the stomach induced gastric mucosal hyperplasia through upregulation of gastrin synthesis in Aalpha0/0 mice, suggesting a pathophysiology similar to the gastric changes in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Determination of a misfit dislocation complex in SiGe/Si heterostructures by image deconvolution technique in HREM.

The core structure of a dislocation complex in SiGe/Si system composed of a perfect 60 degrees dislocation and an extended 60 degrees dislocation has been revealed at atomic level. This is attained by applying the image deconvolution technique in combination with dynamical diffraction effect correction to an image taken with a 200kV field-emission high-resolution electron microscope. The possible configuration of the dislocation complex is analyzed and their Burgers vectors are determined.

Journal Article↗

PubMed2004

One-year clinical evaluation of two composite materials used for anterior class V restorations.

The purpose of the current study was to evaluate the clinical performance of two composite materials used for filling anterior cavity preparations. A total of 100 class V cavities of anterior tooth were restored with two different composite materials (Palfique Estelite and Palfique Toughwell, 50 cavities each, respectively) in combination with the same bonding agent (Mac Bond II). Colour match, cavosurface marginal discolouration, recurrent caries, wear, marginal integrity and surface texture were evaluated clinically for all restorations on the basis of the United States Public Health Service (USPHS) criteria immediately after insertion (baseline), after 6 months and after 1 year. In the comparison of baseline to 1-year evaluation, the Palfique Toughwell material showed significant changes in all factors except recurrent caries. The Palfique Estelite material, however, showed neither significant cavosurface marginal discolouration nor recurrent caries. No significant difference (P > 0b05) was observed between the two materials in clinical performance after 1 year, with the exception of caries rate, which was found to be significantly lower in the Palfique Estelite material. It was concluded that both composites were clinically reliable materials when used for anterior class V restorations.

Composite Resins↗

PubMed2004

Effects of alendronate on restoration of biomechanical properties of periodontium in replanted rat molars.

OBJECTIVE: We examined the effect of the pretreatment of roots with alendronate on the restoration of the support function of the healing periodontal ligament in replanted rat molars. METHODS: The left maxillary first molars were extracted, placed in 0.9% NaCl containing 1 mm alendronate (alendronate group) or 0.9% NaCl (control group) for 5 min, and were replanted into their sockets. Groups of animals were killed at 7, 14, and 21 days after replantation. Normal control rats were also killed on the same days. The force required to extract the replanted or normal tooth from its socket was measured, and a load-deformation curve was developed and analyzed. Micro-computed tomography and histologic analyses were also made. RESULTS: The mechanical properties of the healing periodontal ligament in the alendronate group were gradually restored from 7 to 21 days. However, fractures of the roots and bones during mechanical testing occurred in most of the replanted teeth in the control group at 21 days. The rates of restoration of the mechanical strength, extensibility, stiffness, and toughness for the alendronate group at 21 days were 67, 98, 74, and 68% of the normal controls, respectively. Micro-computed tomography and histologic observations revealed that bone-like structures within the pulp and ankylosis between the roots and socket bones occurred commonly in the control group, but were uncommon in the alendronate group. CONCLUSIONS: Our findings suggest that the pretreatment with alendronate inhibits the formation of abnormal mineralized tissues and results in better restoration of the support function of the healing periodontal ligament in replanted teeth.

Alendronate↗

PubMed2004

Minimization of sludge production and stable operational condition of a submerged membrane activated sludge process.

Modification of conventional activated sludge process by adding microfiltration type hollow fiber membrane module offers various advantages. The membrane module is immersed directly in the bioreactor to separate the treated water from the sludge and the modified process is called submerged membrane activated sludge process (SMASP). Bench scale SMASP units were operated at constant flux to study the possibility of minimizing the excess sludge production and stable operation at different SRT and BOD loading. The long SRT developed high stabilized MLSS concentration in the bioreactor and decreased the sludge loading rate [kg-BOD/kg-MLSS-d]. In SMASP, very low sludge yield coefficients (0.04-0.09 kg-MLSS/kg-BOD) were obtained at long SRT (500 d) and small BOD loading (< or =0.5 kg/(m3 x d)) as compared to conventional activated sludge process and these coefficients showed considerable minimization in excess activated sludge production. At the same operation conditions, suction pressure was also maintained low (<25 kPa), and then SMASP was operated stably for long time (approximately 200 d).

Biomass↗

PubMed2003

Temporary amniotic membrane patching for acute chemical burns.

PURPOSE: To describe the surgical technique, and its usefulness, of temporary amniotic membrane patching (AMP) in the acute phase of ocular chemical injury. METHODS: Temporary AMP with modification in suture placement was performed on five eyes of five consecutive patients inflicted with acute chemical injury having a greater than grade II injury by the Roper-Hall classification. RESULTS: All patients reported herein presented with a large epithelial defect on the cornea and conjunctiva. Case 3 was classified as grade III while the other four cases were classified as grade II. The causative chemical agents were anhydrous acetic acid in Case 1, calcium oxide in Case 2, sodium hydroxide in Case 3, sodium silicate in Case 4, and sulphuric acid in Case 5. All cases experienced rapid relief of pain after AMP. Epithelialization of the cornea with improvement of visual acuity was observed in all cases when the amniotic membrane was removed within 2 weeks after surgery. During the mean follow-up of 19.6 months, the ocular surface remained stable and no cicatricial complications were noted. CONCLUSIONS: These results suggest that immediate AMP is quite useful for managing moderately severe acute ocular chemical injury by facilitating rapid epithelialization and pain relief, and securing ocular surface integrity.

Acute Disease↗

PubMed2003

Protein adsorption at polymer-grafted surfaces: comparison between a mixture of saliva proteins and some well-defined model proteins.

Grafting a dense layer of soluble polymers onto a surface is a well-established method for controlling protein adsorption. In the present study, polyethylene oxide (PEO) layers of three different grafting densities were prepared, i.e. 10-15 nm2, 5.5 nm2 and 4 nm2 per polymer chain, respectively. The adsorption of different proteins on the PEO grafted surfaces was measured in real time by reflectometry. Furthermore, the change of the zeta-potential of such surfaces resulting from adsorption of the proteins was determined using the streaming potential method. Both the protein adsorption and the zeta-potential were monitored for 1 h after exposure of the protein solution to the surface. The adsorption pattern for a mixture of saliva proteins was compared to those observed for a number of well-defined model-proteins (lysozyme, human serum albumin, beta-lactoglobulin and ovalbumin). The results of the adsorption kinetics and streaming potential measurements indicate that the effect of the PEO layer on protein adsorption primarily depends on the size and the charge of the protein molecules. The saliva proteins are strongly blocked for adsorption, whereas the change in the zeta-potential is larger than for the other proteins (except lysozyme). It is concluded that positively charged protein molecules, having dimensions larger than those of lysozyme, are involved in the initial stage of adsorption from saliva onto a negatively charged surface.

Adsorption↗

PubMed2003

Inhibitory effects of Helicobacter pylori infection on murine autoimmune gastritis.

BACKGROUND AND AIM: Long term Helicobacter pylori infection leads to atrophic gastritis but the relation between H pylori infection and autoimmune related atrophic gastritis (AIG) remains unclear. We studied the effects of H pylori infection on the pathophysiology of AIG in mice. MATERIALS AND METHODS: BALB/c nu/nu mice (n=40) with or without H pylori infection received splenocytes from neonatally thymectomised mice to induce AIG. Half of the mice were orally infected with H pylori prior to AIG induction. Histological findings, and local and systemic immune responses were serially evaluated. RESULTS: Two and six months after transfer, parietal cells in uninfected mice were depleted while those in infected mice were well preserved. The degree of gland atrophy (p<0.01), hyperplasia (p<0.01), gastric pH (p<0.05), and serum gastrin levels of infected mice were significantly lower than those of uninfected mice. Serum antiparietal cell antibody levels gradually decreased in infected mice, and were significantly lower than those of uninfected mice at six months (p<0.05). Real time polymerase chain reaction studies revealed significantly higher interleukin 4 (p<0.05) and transforming growth factor beta (p<0.05) gene expression in the gastric mucosa in infected mice than in uninfected mice at both two and six months after AIG induction. CONCLUSIONS: H pylori infection inhibited the development of AIG in mice. Th2-type immune responses and transforming growth factor beta in the gastric microenvironment might be involved in the inhibitory effects of H pylori infection on the development of AIG, in which Th1-type responses have an important role.

Animals↗

PubMed2002

Effects of low-intensity pulsed ultrasound on proliferation and chondroitin sulfate synthesis of cultured chondrocytes embedded in Atelocollagen gel.

The effects of low-intensity pulsed ultrasound (US) on the proliferation and chondroitin sulfate synthesis of cultured chondrocytes embedded in Atelocollagen gel in vitro were examined. Articular cartilage was harvested from the hip, knee, and shoulder joints of 10-week-old Japanese white rabbits. Chondrocytes isolated by collagenase digestion were embedded in type I collagen gel, Atelocollagen gel, and were cultured in Dulbecco's modified eagle's medium for 3 weeks. The US apparatus, SAFHS, was used to deliver an ultrasound signal with spatial and temporal average intensities of 30 mW/cm(2) (US group). The frequency was 1.5 MHz with a 200-microsecond tone burst repeated at 1.0 kHz. US treatments were administered for 20 min per day under culture dishes, with the medium replaced twice a week. Another group of cells was exposed to sham ultrasound as a control. Cell number, histological findings, synthesis of isomers of chondroitin sulfate, and stiffness of the chondrocyte-collagen gel composites were analyzed. US exposure promoted synthesis of chondroitin sulfate, especially chondroitin 6-sulfate, although it did not significantly enhance cell number and stiffness. In this three-dimensional culture model, these results suggest that US exposure may be clinically useful in improving the quality of chondrocyte-Atelocollagen implants for transplantation into articular cartilage defects.

Animals↗

PubMed2002

Atomic configuration in core structure of Lomer dislocation in Si0.76Ge0.24/Si.

The core structure of a Lomer dislocation in SiGe/Si system has been revealed at atomic level. This is attained by applying the image deconvolution technique in combination with dynamical diffraction effect correction to the high-resolution image taken with a 200 kV field-emission gun high-resolution electron microscope. The Lomer dislocation has a Hornstra-like core. The contrast of the image simulated on the basis of derived atomic configuration is in agreement with that of the experimental image.

Journal Article↗

PubMed2002

Arthroscopic assessment of human cartilage stiffness of the femoral condyles and the patella with a new tactile sensor.

We measured the stiffness of the cartilage of the human femoral condyles via an ultrasonic tactile sensor under arthroscopic control. The stiffness and the degeneration of articular cartilage were assessed in 105 knees in 74 patients (39 men, 35 women, age: 9-72 years) who underwent arthroscopic observation or surgery. Twenty-five knees suffered from traumatic cartilage injury, 14 from osteochondritis dissecans, 13 from osteoarthritis, 11 from meniscal injury and six from ligamentous injury, bipartita patellae (three knees), and symptomatic plica synovialis (two knees). The degeneration of cartilage was classified according to Outerbridge's grading system. The relationships between the stiffness and the grade of cartilage degeneration, and gender were analyzed. The stiffness of grade I (softening) and II (fissuring less than 0.5 inches in length) was significantly lower than that of intact cartilage. In contrast, the stiffness of grade IV (exposed subchondral bone) was significantly higher than that of any other group. The cartilage stiffness of the patella in women was significantly lower than that in men. The tactile sensor was useful for determining the intraoperative stiffness of healthy and diseased human cartilage in all grades.

Adolescent↗

PubMed2002

Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee.

We investigated the clinical, arthroscopic and biomechanical outcome of transplanting autologous chondrocytes, cultured in atelocollagen gel, for the treatment of full-thickness defects of cartilage in 28 knees (26 patients) over a minimum period of 25 months. Transplantation eliminated locking of the knee and reduced pain and swelling in all patients. The mean Lysholm score improved significantly. Arthroscopic assessment indicated that 26 knees (93%) had a good or excellent outcome. There were few adverse features, except for marked hypertrophy of the graft in three knees, partial detachment of the periosteum in three and partial ossification of the graft in one. Biomechanical tests revealed that the transplants had acquired a hardness similar to that of the surrounding cartilage. We conclude that transplanting chondrocytes in a newly-formed matrix of atelocollagen gel can promote restoration of the articular cartilage of the knee.

Adolescent↗

PubMed2002

Induction of somatosensory evoked potentials by mechanical stimulation in reconstructed anterior cruciate ligaments.

We have determined whether somatosensory evoked potentials (SEPs) were detectable after direct mechanical stimulation of normal, injured and reconstructed anterior cruciate ligaments (ACLs) during arthroscopy. We investigated the position sense of the knee before and after reconstruction, and correlated the SEP with instability. Reproducible SEPs were detected in all 19 normal ACLs and in 36 of 38 ACLs reconstructed during a period of 13 months. Of the 45 injured ACLs, reproducible SEPs were detected in 26. The mean difference in anterior displacement in the SEP-positive group of the injured ACL group was significantly lower than that in the SEP-negative group. In the reconstructed group, the postoperative position sense was significantly better than the preoperative position sense. Our results indicate not only that sensory reinnervation occurs in the reconstructed ACL, but also that the response to mechanical loads can be restored, and is strongly related to improvement in position sense.

Adolescent↗

PubMed2001

Molecular cloning of a member of the facilitative glucose transporter gene family GLUT11 (SLC2A11) and identification of transcription variants.

We isolated a member of the facilitative glucose transporter (GLUT) gene family (GLUT11; SLC2A11 as a HGMW-approved symbol) based on the analysis of a human genomic BAC clone KB1125A3 located on band q11.2 of human chromosome 22. The gene GLUT11/SLC2A11 consists of 12 exons spanning over 29 kb in size and is located between two genes, SMARCB1 and MIF. The deduced amino acid sequence indicated the topological features of transmembrane helices and sequence motifs which are common to the GLUT protein family. The cDNA cloning revealed the presence of three types of variation in its transcripts. The first variation is caused by the existence of three distinct first exons (SLC2A11-a, -b, and -c). PCR analysis of multi-tissue-derived cDNA panels indicated the differential expression of these transcript variants. The second variation is caused by skipping over one exon (exon 6). The third variation is caused by the premature transcription termination at a site between exon 8 and exon 9. Both exon skipping and premature termination caused frameshift, resulting in the production of truncated GLUT11/SLC2A11 transcripts. These results suggested that transcription of GLUT11/SCL2A11 gene is controlled in a complex manner.

Amino Acid Motifs↗

PubMed2001

Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency.

Holocarboxylase synthetase (HLCS) is an enzyme that catalyzes the incorporation of biotin into apo-carboxylases, and its deficiency causes biotin-responsive multiple carboxylase deficiency. The reported sequences of cDNA for human HLCS from liver, lymphocyte, and KG-1 myeloid cell lines differ at their 5' regions. To elucidate variations of the human HLCS mRNA and longer 5' cDNA ends, we performed screening of the human liver cDNA library and rapid amplification of the cDNA ends (RACE). Our results suggest the existence of three types of HLCS mRNA that start at different exons. The first type starts at exon 1, and the second type starts at exon 3, and both are found in various human tissues. The third type, corresponding to the cDNA from the KG-1 cell, starts at exon 2 of the HLCS gene. Various splicing patterns from exons 3-6 were also observed. None of the variations of cDNA found created a new initiation codon. Mutation screening from exons 6-14, therefore, was sufficient to detect amino acid changes in HLCS in patients. Our direct sequencing strategy for screening mutations in the HLCS gene revealed mutations in five Japanese patients and seven non-Japanese patients. Our analyses involving 12 Japanese and 13 non-Japanese patients and studies by others indicate that (1) there is no panethnically prevalent mutation; (2) the Arg508Trp, Gly581Ser, and Val550Met mutations are found in both Japanese and non-Japanese populations; (3) the IVS10+5G-->A mutation is predominant and probably a founder mutation in European patients; (4) the 655-656insA, Leu237Pro, and 780delG mutations are unique in Japanese patients; (5) the spectrum of the mutations in the HLCS gene may vary substantially among different ethnic groups.

Base Sequence↗