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Biomedical subjects

K Kawai

Publications and source records attributed to K Kawai.

At least 19 recordsLinked to original sources

Correlation in a Gaussian chain with the ends fixed.

We consider an ideal chain whose ends are fixed without fluctuation at different points, possibly by optical tweezers. We derive a two-point probability distribution of a corresponding random walk and explicitly calculate the scattering function. We find that the contour plot of the resulting function shows a kind of normal butterfly pattern, contaminated by wavy texture. These results are compared with some representative previous models.

Biophysics↗

Psychopathological features of patients with prolonged anorexia nervosa as assessed by the Minnesota Multiphasic Personality Inventory.

OBJECTIVE: The duration of illness is quite long in some anorexia nervosa (AN) patients. In the present study, we investigated the psychopathological features of patients with prolonged AN as assessed by the Minnesota Multiphasic Personality Inventory-1 (MMPI-1). METHODS: Fifty-five AN patients completed the MMPI-1 on admission to Kyushu University Hospital from 1999 to 2002. The patients were divided into three groups on the basis of their illness duration: a short-term group, less than 5 years of illness duration (n=31); a middle-term group, from 5 to 10 years (n=14); and a prolonged group, 10 years or more (n=10). RESULTS: The prolonged group scored significantly higher on the MPPI-1 scales of hysteria (Hy), low back pain (Lb) and family conflict than the short-term group. DISCUSSION: AN patients whose illness duration was prolonged characteristically had more hysteria with family conflict. This should be considered in their treatment.

Adolescent↗

Factors related to renal dysfunction in patients with anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) patients were surveyed to determine which disease factors were related to AN influenced renal dysfunction. METHODS: Data were from forty-five AN patients hospitalized in our department between 1995 and 2002. The patients were classified into three groups based on the type of anorexia: restricting (n=18), self-induced vomiting (n=13), and laxative abuse (n=14). Twenty-four hour-creatinine clearance (Ccr) was calculated within two weeks of hospitalization for comparison among the three groups. RESULTS: The Ccr level of the laxative abuse group was significantly lower than that of the restricting group (65.8+/-31.4 ml/min vs restricting type: 104+/-23.3 ml/min, p=0.002). The laxative abuse group had a significantly longer duration of illness than the restricting group (p<0.0001). Multiple regression analysis revealed the duration of illness to be a risk factor for renal function deterioration in AN patients (r=0.580, p<0.001). DISCUSSION: Renal function should be carefully followed during the treatment of AN patients with a long duration of illness, especially those with long-term laxative abuse.

Adolescent↗

Does informed consent exempt Japanese doctors from reporting therapeutic deaths?

The Japanese Medical Act section 21 states that doctors must report unnatural deaths to the police, even though the term "unnatural death" is not defined by law. However, many doctors are reluctant to report potential therapeutic deaths (PTDs). The Japanese Society of Legal Medicine has submitted guidelines for unnatural death, including PTD. These define a PTD as an unexpected death, the cause of which is unknown, but which is potentially related to medical practice. Such deaths are "reportable" to the coroner in the UK. In this study, we addressed the question of whether physicians would report each of eight hypothetical PTDs. Although the clinical societies (the Japan Society of Internal Medicine and the Japan Surgical Society) declare that doctors must report deaths due to gross negligence, 60% of the participants said that they would not report gross negligence involving an overdose in cases where they had obtained informed consent or had provided an explanation after the death occurred. This can be accounted for by the mistaken belief on the part of the participants that obtaining informed consent exempts Japanese physicians from the duty of reporting PTDs. The attitude of Japanese physicians is caused by the death investigation system, which is designed to discover whether a crime has been committed rather than focusing on the cause of death. Accordingly, the Japanese Government has decided to commission a pilot study from an independent organisation in which medical specialists will investigate PTDs in order to prevent deaths occurring as a result of gross negligence.

Accidental Falls↗

Single nucleotide polymorphisms in the gene encoding Krüppel-like factor 7 are associated with type 2 diabetes.

AIMS/HYPOTHESIS: Although genetic susceptibility plays an important role in the pathogenesis of type 2 diabetes, most of the genes that influence susceptibility to type 2 diabetes have yet to be identified. Krüppel-like transcription factors are known to play important roles in development and cell differentiation, and have recently been implicated in the pathogenesis of type 2 diabetes. The present study aimed to examine the associations of single nucleotide polymorphisms (SNPs) in genes encoding members of the Krüppel-like-factor (KLF) family with type 2 diabetes in a large cohort of Japanese subjects. METHODS: We genotyped 33 SNP loci found in 12 KLF genes in subjects with type 2 diabetes and in subjects from the general population using the PCR-Invader assay. We also examined the effects of the overexpression of KLF7 on adipogenesis in 3T3-L1 cells. RESULTS: We identified a significant association between an SNP in KLF7 and type 2 diabetes (A vs C: p=0.004 after Bonferroni's correction, odds ratio=1.59, 95% CI 1.27-2.00). The expression of Klf7 decreased in response to the differentiation of 3T3-L1 adipocytes, and the overexpression of KLF7 resulted in significant inhibition of adipogenesis in 3T3-L1 cells. CONCLUSIONS/INTERPRETATION: These results indicate that the gene encoding KLF7 is a novel candidate for conferring genetic susceptibility to type 2 diabetes.

3T3 Cells↗

Eradication of Helicobacter pylori increases platelet count in patients with idiopathic thrombocytopenic purpura in Japan.

BACKGROUND: The effect of Helicobacter pylori eradication on the platelet count in patients with thrombocytopenic purpura is controversial. In this multicentre study, we prospectively assessed the effect of H. pylori eradication therapy in idiopathic thrombocytopenic purpura patients. MATERIALS AND METHODS: Thirty-five consecutive patients with chronic idiopathic thrombocytopenic purpura (11 males and 24 females, a median age of 57) were assessed for H. pylori infection by use of a urea breath test. All patients received 1-week triple therapy (amoxicillin, clarithromycin, and lansoprazole) to eradicate H. pylori. At 6 months, idiopathic thrombocytopenic purpura patients with a platelet count recovery of greater than 100 x 10(9) L(-1) were defined as idiopathic thrombocytopenic purpura responders. RESULTS: Helicobacter pylori infection was observed in 25 (71%) of the 35 patients. All infected patients were cured. Eleven patients were identified as idiopathic thrombocytopenic purpura responders; 24 were considered nonresponders. Platelet counts improved by more than 100 x 10(9) L(-1) in 11 (44%) of the 25 patients cured of H. pylori infection, while none of the 10 patients H. pylori-negative patients experienced the same improvement (P = 0.015). Univariate analysis showed that H. pylori infection and its eradication were significant factors associated with platelet recovery (P = 0.015). CONCLUSIONS: Helicobacter pylori infection played a role in the pathogenesis of idiopathic thrombocytopenic purpura in approximately 30% of all patients assessed and 45% of the patients with H. pylori infection. Eradication of H. pylori in idiopathic thrombocytopenic purpura patients led to improved disease activity.

Adult↗

Overexpression of Ets-1 proto-oncogene in latent and clinical prostatic carcinomas.

AIMS: The high incidence of clinically diagnosed prostatic cancer is exceeded by the frequency of tumours detected at autopsy. The Ets-1 proto-oncogene is expressed by a variety of malignant and normal tissues. Therefore, in this study, expression of Ets-1 protein was investigated in 'latent' prostatic cancer detected at autopsy, compared with benign prostatic hyperplasia, normal prostatic tissues and clinical prostatic cancer. METHODS AND RESULTS: Using immunohistochemistry, we analysed Ets-1 expression in 95 prostatic specimens including 19 cases of latent prostatic carcinoma (LPC) and 55 cases of clinical prostatic carcinoma (CPC), 11 cases of benign prostatic hyperplasia (BPH) and 10 cases of normal prostate (NP). Differences in the incidence of LPC and CPC suggest different courses for the biological progression of prostatic cancer. There was a significant difference in the degree of Ets-1 expression in CPC and LPC (P < 0.05). Ets-1 was not expressed in BPH and NP, but in malignant cases (57 of 74; 77.0%) commonly demonstrated immunoreactivity in the tumour cells. In our study the expression of Ets-1 between benign and malignant, and well, moderately and poorly differentiated adenocarcinomas of prostatic cancer showed significant differences. The presence of Ets-1 mRNA was confirmed by in-situ hybridization in human prostatic tissues. CONCLUSION: Our results suggest that Ets-1 might play an important role in carcinogenesis and/or the progression of human prostatic carcinomas.

Humans↗

Combination of transconjunctival and endonasal-transantral approach in the repair of blowout fractures involving the orbital floor.

In the repair of orbital blowout fractures through eyelid or conjunctival incision, it is difficult to see the posterior edge of the fracture and the condition of the herniated tissue before reduction of the orbital contents. Prolapsed orbital tissue or infraorbital nerve and vessels may therefore be damaged in the reduction. The recently advocated combination of traditional transconjunctival approach and endoscopic transantral approach allows reduction and reconstruction under clear endoscopic vision without a facial skin incision. We modified this technique to make it less invasive and applied it to the repair of orbital blowout fractures involving the orbital floor. The use of a 70-degree straight endoscope through an enlarged ostium as for functional sinus surgery allowed clear sight of the roof of the antrum. During the repair of the orbital floor through a transconjunctival approach, reduction and reconstruction was assisted from the antrum. Twelve cases of fresh blowout fractures were treated with this approach. There were seven male and five female patients. Mean age was 23.5 years. Causes of injuries were fights, motor vehicle or bicycle accidents, and sports. Patients with concomitant fractures involving the orbital rim were excluded. Persistent diplopia was present in eight cases and enophthalmos of more than 2 mm was detected in five cases preoperatively. The average intervals from injury to surgery was 22.8 days.Exploration, reduction and reconstruction of the orbital floor fractures were precisely performed with this procedure. Large orbital floor defects were reconstructed with silicone sheets, thin iliac bone grafts or nasal septal cartilage. In all eight cases that showed diplopia, ocular movement recovered and symptomatic diplopia disappeared after surgery. Enophthalmos of more than 2 mm was also improved in all five cases. One early case showed temporary entropion. Transient numbness of the cheek appeared in five cases and temporary maxillary sinusitis recovered in one case. Postoperative infection was not observed.This method provides visualisation of posterior edge of the fracture and the condition of herniated orbital contents before initiation of reduction. Dual manipulation by two surgeons is also possible in reduction and reconstruction of the orbital floor.

Adolescent↗

A PLCdelta1-binding protein, p122RhoGAP, is localized in focal adhesions.

We have investigated the cellular distribution of p122RhoGAP, a GTPase-activating protein of Rho small GTPase and an activator of phospholipase C-delta(1). Immunofluorescence studies demonstrated that endogenous p122 is localized at the tips of actin stress fibres and co-localizes with vinculin in normal rat kidney cells. In immunoprecipitation studies, p122 co-precipitated with vinculin, indicating that p122 is localized at the sites of focal adhesion. We have also shown that the N-terminal half of p122 is responsible for this localization. It is conceivable, therefore, that p122 is involved in the reorganization of the actin cytoskeleton and focal adhesions that regulate cell-substratum adhesion and cell migration.

Animals↗

Effects of biotin supplementation on serum biotin levels and physical properties of samples of solar horn of Holstein cows.

Effects of dietary biotin supplementation on serum biotin levels and physical properties of sole horn of 40 Holstein cows were evaluated. The mean serum biotin level in biotin-supplemented cows after 10 mo of biotin supplementation (1163.2 +/- 76.2 pg/mL) was significantly higher (P = 0.007) than that in control cows (382.0 +/- 76.2 pg/mL). The sole horn of biotin-supplemented cows was significantly harder (P = 0.026) and had a significantly lower moisture content (P = 0.021) than that of control cows. No morphologic differences in horn tubules or intertubular horn were found between the biotin-supplemented and control cows. The total lipid content of sole horn was significantly higher (P = 0.030) in the biotin-supplemented cows than in the control cows. These results suggest that dietary biotin supplementation causes increases in serum biotin levels and changes in physical properties and fat content of sole horn.

Animal Nutritional Physiological Phenomena↗

Physiological changes in the concentrations of biotin in the serum and milk and in the physical properties of the claw horn in Holstein cows.

Physiological changes in the concentrations of biotin in the serum and milk and in the physical properties of the claw horn were examined in Holstein cows. A lower concentration of biotin in the serum and a higher concentration of biotin in milk were found during early and late lactation and during the dry period, and a significant (p<0.05) inverse correlation was found between serum and milk biotin concentrations. A high moisture content and a low level of hardness of the claw horn were found during mid-lactation. Our results indicate that change in the serum biotin concentration probably results from the loss of biotin in the milk of cows during each stage of lactation and also confirm that the moisture content and hardness of the claw horn undergo physiological changes.

Animals↗

Effect of infusing lactoferrin hydrolysate into bovine mammary glands with subclinical mastitis.

The therapeutic effect of administering lactoferrin hydrolysate (LFH) into the mammary glands of cows with subclinical mastitis was evaluated. Seven millilitres of a preparation of LFH (7% protein) was infused into 35 quarters of 25 cows with subclinical mastitis. The numbers of bacteria in the milk from infected quarters decreased, and bacteria disappeared by the 14th day after the administration of LFH. The mean somatic cell counts (SCC) peaked one day after administration of LFH and the counts were significantly p < 0.01) decreased on days 7, 14 and 21 compared to those before the administration of LFH. The mean lactoferrin concentration in the milk peaked on days 2 or 3 and then gradually decreased to day 14, returning to the level before the administration of LFH. It appears that administration of LFH may have a therapeutic effect when infused into the quarters of cows with subclinical mastitis.

Animals↗

Effect of different proton pump inhibitors, differences in CYP2C19 genotype and antibiotic resistance on the eradication rate of Helicobacter pylori infection by a 1-week regimen of proton pump inhibitor, amoxicillin and clarithromycin.

AIM: To investigate the effect of different proton pump inhibitors, S-mephenytoin 4'-hydroxylase (CYP2C19) genotype and antibiotic susceptibility on the eradication rate of Helicobacter pylori. METHODS: One hundred and eighty-seven H. pylori-infected peptic ulcer patients were randomly treated with either rabeprazole (10 mg b.d.) or lansoprazole (30 mg b.d.) plus amoxicillin (750 mg b.d.) and clarithromycin (400 mg b.d.) for 1 week. The antibiotic susceptibility and CYP2C19 genotype (extensive or poor metabolizer) were investigated. RESULTS: The eradication rates in the rabeprazole-amoxicillin-clarithromycin (RAC) and lansoprazole-amoxicillin-clarithromycin (LAC) groups were 75% and 69%, respectively, on an intention-to-treat basis, and 80% and 75%, respectively, on a per protocol basis. The eradication rate for clarithromycin-resistant strains was significantly lower than that for clarithromycin-sensitive strains (24% vs. 86%, P < 0.05). For clarithromycin-sensitive strains in the LAC group, there was a tendency for a lower eradication rate in extensive than poor metabolizers. The eradication rate in extensive metabolizers in the RAC group tended to be higher than that in extensive metabolizers in the LAC group (89% vs. 78%, P = 0.079726). CONCLUSIONS: The success of the 1-week proton pump inhibitor-amoxicillin-clarithromycin regimen depends on the susceptibility of H. pylori to clarithromycin. Moreover, differences in CYP2C19 genotype influence the eradication rates of lansoprazole-based therapy, and the rabeprazole-based regimen has an advantage especially in extensive metabolizers.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Clinical course and immune response of a renal cell carcinoma patient to adoptive transfer of autologous cytotoxic T lymphocytes.

The cytotoxic T lymphocyte (CTL) is a promising candidate for an effector cell in adoptive immunotherapy for renal cell carcinoma (RCC). Here we report the clinical course and in vivo immune responses of a RCC patient with bulky retroperitoneal lymph node (RPLN) metastases who received adoptive autologous CTL therapy. A 56-year-old woman diagnosed with RCC with multiple RPLN metastases underwent unilateral nephrectomy. Autologous RCC cells were primary-cultured from surgical specimens. Before addition of peripheral blood mononuclear cells (PBMC) for CTL induction, subconfluent RCC cells were irradiated with 50 Gy. The PBMCs were then cultured on RCC cells in the induction medium supplemented with four kinds of interleukins. The induced CTLs showed the potent killing activity against autologous RCC cells in a typical MHC-class I-restricted manner. The patient received three courses of CTL therapy with a total of 10.2 x 10(9) cells, and the RPLN mass decreased markedly in size after the second course. Eosinophilia and enhanced CTL inducibility from peripheral blood were observed after CTL administrations. The patient was progression free without further treatment; however, she developed rapidly progressive glomerulonephritis more than 1 year after the last treatment. The patient died of newly developed metastases 27 months after the start of CTL therapy. At autopsy, viable RCC cells were found in multiple metastatic sites. However, only diffuse fibrous tissue was observed in the responding RPLN mass. Apparent histological divergence was observed between primary and metastatic sites.

Carcinoma, Renal Cell↗

Cell signalling and gene expression mediated by RET tyrosine kinase.

Germline mutations of the RET proto-oncogene cause multiple endocrine neoplasia (MEN) 2A or 2B by different mechanisms. As is the case for other receptor tyrosine kinases, mutant RET recruits a variety of signalling molecules via phosphorylated tyrosine residues present in the kinase domain and carboxy-terminal tail. As we previously reported, the signaling via phosphorylated tyrosine 1062 plays a crucial role in the transforming activities of both RET-MEN2A and RET-MEN2B mutant protein. Interestingly, this single tyrosine residue represents a binding site for several signalling molecules including SHC, Enigma, SNT/FRS2, DOK and IRS1 and is responsible for activation of the RAS/ERK, PI3-K/AKT, JNK, p38MAPK and ERK5 signalling pathways. Amongst these, the PI3-K/AKT and JNK pathways appeared to be more strongly activated in the cells expressing RET-MEN2B than in the cells expressing RET-MEN2A, suggesting the possibility that these pathways may be involved in the disease phenotype. In addition, RET is alternatively spliced to produce three isoforms and the splicing site is present just downstream of tyrosine 1062. These isoforms play different roles for the tumour development associated with MEN 2 or the development of the kidney and the enteric nervous system. Moreover, using differential display analysis, we identified several genes whose expression is highly induced by RET-MEN2B mutant proteins. The differential gene expression by RET-MEN2A and RET-MEN2B may also be important for the development of their phenotypes.

Alternative Splicing↗

A novel radiopharmaceutical for detection of malignant melanoma, based on melanin formation: 3-iodo-4-hydroxyphenyl-L-cysteine.

The aim of this study was to develop a new artificial amino acid radiopharmaceutical labelled with radioiodine for detection of malignant melanoma, based on melanin formation. By considering the affinity for tyrosinase, a starting enzyme on the branching point to melanin biosynthesis, 3-[125I]iodo-4-hydroxyphenyl-L-cysteine (125I-L-PC) was synthesized and evaluated biologically. Labelling of 125I-L-PC using the chloramine-T method was carried out conveniently and efficiently in a short period of time, with high specific activity. In a biodistribution study, 125I-L-PC showed a low accumulation in normal tissue and relative retention in B16 melanoma. A high contrast image of peripheral tumour was obtained during autoradiography. During an in vitro accumulation study, inhibition of 125I-L-PC with a tyrosinase inhibitor suggested interaction of this tracer with tyrosinase. It indicates that the uptake mechanism of 125I-L-PC to melanoma tissue was dependent on high tyrosinase activity in melanoma cells. Thus, 125I-L-PC appears to be a promising radioiodinated amino acid radiopharmaceutical for imaging malignant melanoma in relation to melanin formation, namely specific metabolism with high tyrosinase activity.

Animals↗