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Biomedical subjects

K Sakurai

Publications and source records attributed to K Sakurai.

At least 19 recordsLinked to original sources

Effect of palate covering on bolus-propulsion time and its contributory factors.

The aim of this study was first to investigate whether the covering of the palatal mucosa with a denture base affects or not the bolus-propulsion time, and second if there was such an effect then investigate the possible contributory factors which have influence on the propulsion time. The propulsion time was measured in 21 young normal edentulous subjects under five different conditions: a complete palatal covering, non-covered palate, anterior palatal covering, posterior palatal covering and surface anaesthetized palate. As possible contributory factors palatal morphometric parameters, as well as tongue pressure were also measured. The data were analysed on the following way: changes when the palate was complete covered and non-covered, effects of sensation reduction after topic anaesthesia, effects of differences in the covering site, effects of palatal morphometric parameters and effects of tongue pressure. Ten subjects exhibited significant differences in the propulsion time when comparing the data between the complete palatal covering and the non-covered palate condition (change group). Eleven subjects did not show changes (unchanged group). Effects in the propulsion time were also recognized with posterior palatal covering-palate and superficially anaesthetized palate. With regard to the tongue pressure, significant differences during swallowing were observed. These results indicated that the bolus propulsion time into the oropharynx was affected by the palatal covering in some subjects. Moreover, the sensation in the posterior region of the hard palate, as well as the tongue pressure were also factors which affected the propulsion time during swallowing.

Adult↗

Individual difference in the number of chewing strokes and its determinant factors.

This study was carried out to clarify the distribution and individual variation of the number of chewing strokes before last swallowing (NCS), as well as to assess the factors that affect NCS, when dentulous adults masticate the same type of food. NCS was measured in 75 dentulous adults using gummy candies. Measurements were repeated five times to obtain the average and variation. Moreover, the correlation of NCS with various physiological factors (lateral width and vertical distance of chewing loop, angle of opening and closing path, opening and closing time, occlusal time, masticatory performance, number of occlusal contact points, occlusal contact area, occlusal force, flow rate of whole saliva and viscosity of whole saliva) and 28 personality factors were analysed by both of the single variate analysis and the multivariate analysis. The results showed that the average NCS was 41.0 +/- 16.0, and the coefficient of variation was 0.090 +/- 0.040. Additionally, the correlation between NCS and each factor was investigated, and found that any of these factors did not function as a single determinant for NCS. Following, determinant factors were further examined by the stepwise method of linear multiple regression analysis. From these analysis we found that when opening and closing time and four personality factors were combined, they were significantly involved in determining NCS (P < 0.01). Therefore, we conclude that individual NCS until last swallowing is not determined by a sole, specific physiological factor but is affected by multiple factors including personality.

Adult↗

Insulin resistance and increased pancreatic beta-cell proliferation in mice expressing a mutant insulin receptor (P1195L).

Several mutations of the tyrosine kinase domain of insulin receptor (IR) have been clinically reported to lead insulin resistance and insulin hypersecretion in humans. However, it has not been completely clarified how insulin resistance and pancreatic beta-cell function affect each other under the expression of mutant IR. We investigated the response of pancreatic beta-cells in mice carrying a mutation (P1195L) in the tyrosine kinase domain of IR beta-subunit. Homozygous (Ir(P1195L/P1195L)) mice showed severe ketoacidosis and died within 2 days after birth, and heterozygous (Ir(P1195L/wt)) mice showed normal levels of plasma glucose, but high levels of plasma insulin in the fasted state and after glucose loading, and a reduced response of plasma glucose lowering effect to exogenously administered insulin compared with wild type (Ir(wt/wt)) mice. There were no differences in the insulin receptor substrate (IRS)-2 expression and its phosphorylation levels in the liver between Ir(P1195L/wt) and Ir(wt/wt) mice, both before and after insulin injection. This result may indicate that IRS-2 signaling is not changed in Ir(P1195L/wt) mice. The beta-cell mass increased due to the increased numbers of beta-cells in Ir(P1195L/wt) mice. More proliferative beta-cells were observed in Ir(P1195L/wt) mice, but the number of apoptotic beta-cells was almost the same as that in Ir(wt/wt) mice, even after streptozotocin treatment. These data suggest that, in Ir(P1195L/wt) mice, normal levels of plasma glucose were maintained due to high levels of plasma insulin resulting from increased numbers of beta-cells, which in turn was due to increased beta-cell proliferation rather than decreased beta-cell apoptosis.

Animals↗

Initial functional status predicts infections during steroid therapy for renal diseases.

BACKGROUND AND AIM: Corticosteroid therapy is an effective way of treatment for many renal diseases, however, it is sometimes associated with infections. Our aim is to identify useful predictive markers of infection during steroid therapy. METHODS: We examined 121 patients (M/F = 71/50, mean age 43.8, range 15 - 82 years) who were treated with corticosteroids (IgA nephropathy in 51, minimal-change disease in 17, membranous nephropathy in 16 rapidly progressive glomerulonephritis (RPGN) in 13, lupus nephritis in 12 and other disorders in 12). Karnofsky's performance score (KPS) was employed to assess the physical functional status at the time of diagnosis. Infections were defined as conditions that required more than 1-week care, and those that caused the patient's death. RESULTS: Nineteen patients (15.7%) had infections during treatment. A logistic multivariate analysis showed significant correlations between infection and the use of immunosuppressive agents (relative risk RR = 7.7, p = 0.0265), ages of 52.9 years or more (RR = 13.5, p = 0.0026), initial number of lymphocytes (Lym) less than 1.250/microl (RR = 14.2, p = 0.0011), and KPS less than 77.4 (RR = 12.1, p = 0.0020). All correlations with infection were independent of all the other variables listed above. CONCLUSION: KPS, along with age, Lym and the use of immunosuppressive agents, are useful for the prediction of infectious complications during steroid therapy.

Activities of Daily Living↗

Brain transplantation of genetically modified bone marrow stromal cells corrects CNS pathology and cognitive function in MPS VII mice.

Current therapies for lysosomal storage diseases (LSDs), enzyme replacement therapy and bone marrow transplantation are effective for visceral organ pathology of LSD, but their effectiveness for brain involvement in LSDs is still a subject of controversy. As an alternative approach, we transplanted genetically modified bone marrow stromal (BMS) cells to lateral ventricle of newborn mucopolysaccharidosis VII (MPS VII) mice. MPS VII is one of LSDs and caused by deficiency of beta-glucuronidase (GUSB), resulting in accumulation of glycosaminoglycans (GAGs) in brain. At 2 weeks after transplantation, the GUSB enzyme-positive cells were identified in olfactory bulb, striatum and cerebral cortex, and the enzymatic activities in various brain areas increased. The GAGs contents in brain were reduced to near normal level at 4 weeks after transplantation. Although GUSB activity declined to homozygous level after 8 weeks, the reduction of GAGs persisted for 16 weeks. Microscopic examination indicated that the lysosomal distention was not found in treated animal brain. Cognitive function in MPS VII animals as evaluated by Morris Water Maze test in treated mice showed a marked improvement over nontreated animals. Brain transplantation of genetically modified BMS cells appears to be a promising approach to treat diffuse CNS involvement of LSDs.

Animals↗

A method of measuring salivary flow rate in the lower labial mucosal region.

To measure resting whole saliva, draining and spitting methods have been commonly used. However, these methods require the patients' understanding and cooperation. The aim of this study was to establish a method for measuring the salivary flow rate that does not rely on patient's cooperation or the state of the mouth and does not cause any discomfort to patients when performing the measurements. The salivary flow rate in the lower labial mucosal region was measured by means of strips that incorporated the iodo-starch reaction. The salivary flow rate was then calculated on the basis of the number of spots and area of discoloration on the strip. In order to test the validity of these methods, the correlation between these results and resting whole saliva measured by the draining method was also investigated. A positive correlation was found between the salivary flow rate estimated from the area of discoloration on the strip and the resting whole saliva (r=0.678, P=0.01). Therefore, these findings indicate that this is a valid method of measuring the salivary flow rate in the lower labial mucosal region.

Adult↗

No nephropathy in Type 2 diabetic patient with POEMS syndrome with an elevated plasma VEGF.

Vascular endothelial growth factor (VEGF) is considered to have a role in the pathogenesis of diabetic retinopathy. Recent experimental observations that anti-VEGF neutralizing antibody fully abolished the hyperfiltration and the increase in urinary albumin excretion suggested the contribution of VEGF to the development of diabetic nephropathy, as well. Here, we present a case of POEMS (Crow-Fukase) syndrome with Type 2 diabetes, which was associated with elevated plasma VEGF level, but no sign of diabetic nephropathy. The findings obtained from this case did not support the hypothesis that VEGF may enhance the development of diabetic nephropathy.

Diabetes Mellitus, Type 2↗

Mucinous adenocarcinoma with neuroendocrine differentiation of the mandibular ramus: report of a case.

A rare case of mucinous adenocarcinoma with neuroendocrine differentiation of the mandibular ramus is presented. The patient, an 80-year-old man, was referred to our hospital with chief complaint of swelling and pain in the left buccal mucosa. CT and MRI examination showed an osteolytic tumor mass occupying the upper region of the left mandibular ramus. Macroscopically, the excised tumor was a relatively well-defined, solid mass with diffuse bone resorption, measuring 3 cm x 3.2 cm x 3 cm. Microscopical examination showed that the tumor forming glandular structures with abundant mucous production and high cellular atypia. Immunohistochemical studies demonstrated the positive reactivities for pan-keratin, cytokeratin 7, vimentin,alpha-amylase, alpha-smooth muscle actin, neuron-specific enolase, glial fibrillary acid protein, calcitonin, and somatostatin in tumor cells. These findings suggested that the tumor was originated from heterotopic or misplaced salivary gland in the mandible.

Actins↗

Clinical evaluation of response to long-term treatment with Pranlukast in patients with bronchial asthma.

BACKGROUND: Short-term treatment with pranlukast, a leukotriene receptor antagonist, has shown to be effective for the management of asthma. The effectiveness and safety of long-term treatment with pranlukast remains to be established. OBJECTIVES: The aim of this study was to determine the effects of pranlukast on morning peak expiratory flow rates (PEFRs), the diurnal variation of these values, and disease severity. METHODS: Fifteen men with bronchial asthma were studied for 5 years. During the first year, the subjects were treated with a bronchodilator; some also received inhaled and oral corticosteroids. During the next 4 years, the subjects received pranlukast in addition. RESULTS: Mean PEFR increased after the start of treatment with pranlukast. The increase in PEFR occurred later in subjects with more severe disease. Diurnal variation of PEFR was unchanged, but subsequently decreased. The condition of all subjects improved, but the greatest improvement was obtained in patients with mild to moderate asthma. CONCLUSIONS: Long-term treatment with pranlukast is effective for the management of bronchial asthma, particularly in patients with mild to moderate disease. Our results suggest that the effectiveness of antiasthmatic drugs should be evaluated over a period of years, rather than on a short-term basis.

Adrenal Cortex Hormones↗

Investigation of the factors related to the formation of the buccal mucosa ridging.

The aim of this study was to clarify the factors related to the formation of the buccal mucosa ridging, which has been mentioned to be a clinical sign of clenching. Twenty-one individuals were investigated and divided into three groups: (i) those without buccal mucosa ridging, (ii) the buccal mucosa ridging located in all the posterior teeth region, and (iii) the buccal mucosa ridging corresponding only to the molar teeth region. A pressure sensor was used and placed at two points: first upper premolar and second upper molar. The recording tasks were: (i) silent reading at rest, (ii) light voluntary clenching, (iii) maximum voluntary clenching, (iv) holding the cheeks tightly against the teeth while light voluntary clenching, (v) holding the cheeks tightly against the teeth without tooth contact, (vi) pulling angle of mouth laterally while light voluntary clenching, (vii) pulling angle of mouth laterally without tooth contact and (viii) swallowing. No significant differences were found between groups in all the recording tasks except for the swallowing, at which significant difference (P < 0.05) was found between the groups of individuals having buccal mucosa ridging and without it. Based on these results it became clear that the buccal mucosa pressure exerted on the buccal aspect of teeth during swallowing plays an important role in the formation of buccal mucosa ridging.

Adult↗

Stem cell gene therapy for chronic renal failure.

Recently, stem cell research has attracted considerable attention because it could be used for the regeneration of damaged organs that are untreatable by conventional techniques, and several stem cells (or progenitor cells), such as endothelial stem cells and neural stem cells have been discovered. Following the progression of this field of research, the potential for stem cell gene therapy has increased and several therapeutic benefits have already been reported. Although this approach was originally investigated for fatal or hereditary diseases, chronic renal failure is also a candidate for stem cell gene therapy. We have proposed two different therapeutic strategies for chronic renal failure depending on whether the bone marrow stem cells differentiate and commit into mesenchymal or hematopoietic stem cells. In the case of diseases, which need reconstitution of residential renal cells, such as congenital enzyme deficiency diseases, mesenchymal stem cells should be transplanted, and in contrast, hematopoietic stem cells may be used for gene delivery for diseases, which need foreign cytokines and growth factors, such as glomerulonephritis. This article reviews the recent investigation on this tailor-made stem cell gene therapy for chronic renal failure and discusses the potential of this novel strategy and the major practical challenges of its clinical application.

Genetic Therapy↗

Insulin resistance highly associates with hypertension in IgA nephropathy.

BACKGROUND: Insulin resistance has been reported to induce hypertension. Previous studies described that there was no relationship between insulin resistance and hypertension in patients with chronic renal diseases with mild to moderate renal dysfunction. The aim of the present study is to clarify the relationship between insulin resistance and blood pressure, renal function, histopathological changes and other characteristics in IgA nephropathy (IgAN). METHODS: Eighty-eight IgAN patients were included in this cross-sectional study. Hypertension was diagnosed according to the WHO/ISH criteria. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR). RESULTS: Male gender, age, body mass index, serum creatinine, urinary protein excretion, triglycerides and HOMA-IR were positively correlated with hypertension. C(Cr), serum albumin and HDL cholesterol were negatively correlated with blood pressure by Spearman's simple correlation test. By logistic multivariate analysis, C(Cr), insulin resistance, age and male gender were significantly correlated with hypertension, independently of all other variables. CONCLUSIONS: Insulin resistance is not directly related to renal dysfunction, but is also independently associated with hypertension in IgAN. Since hypertension is considered as a risk factor for renal disease progression, insulin resistance may be an indirect deteriorating factor for IgAN. To identify and improve insulin resistance may be another therapeutic target in the clinical management of IgAN.

Adult↗

An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia.

Morphological alterations in the brains of schizophrenia patients suggest that neurodevelopmental dysfunction is involved in the etiology of the disease.(1) Such dysfunction may be due to functional alterations of cell adhesion molecules, which play important roles in cell migration, axonal growth, fasciculation, synaptogenesis, and synaptic remodeling. We screened for mutations in the coding region of the close homologue to L1 gene (CHL1), which is located on human chromosome 3p26, in 24 Japanese patients with schizophrenia. A missense polymorphism (Leu17Phe) in the signal peptide region was identified. A case-control comparison revealed significantly higher frequencies of the Leu/Leu genotype (P = 0.004) and the Leu allele (P = 0.006) in 282 Japanese schizophrenic patients than in 229 Japanese control subjects. The estimated odds ratio for schizophrenia was 1.83 (95% CI, 1.28-2.26) for the Leu/Leu genotype compared with the other genotypes. An association between this CHL1 gene polymorphism and schizophrenia supports the notion that cell adhesion molecules are involved in the etiology of schizophrenia.

Adult↗

Changes of blood flow in the mucosa underlying a mandibular denture following pressure assumed as a result of light clenching.

The aim of this study was to investigate the influence of the continuous compression assumed as a result of light clenching on the blood flow of the denture underlying mucosa in tissue-supported or tooth-tissue-supported denture wearers. Measurements were carried out on eight removable partial denture wearers (three males and five females, from 50 to 72 years, mean age: 61.5 years). The blood flow in the denture underlying mucosa was measured at the unilateral mandibular first molar region using an experimental denture base equipped with a laser Doppler flowmeter. The area of the experimental denture base was 2 cm2, and the loading force was 1 kgf. The loading time was set at 5, 10, 20, 30 and 60 s. The blood flow after 20 s loading was <15% in rest. The times from release of loading to the maximum blood flow and from release of loading to recovery up to 110% of the blood flow at pre-loading were significantly prolonged by an increase in the loading time. Even if it is light, a continuous clenching results in ischaemia and delays the recovery of blood flow in the mucosa underlying the denture after release of compression.

Aged↗

[Experience of coronary artery bypass grafting on the beating heart with right heart bypass; 3 cases of octogenarian].

Right heart bypass (RHB) yields more stable hemodynamics by increasing left ventricular preload and collapse right ventricular chamber during the displacement of the heart on beating heart coronary artery bypass grafting (CABG). Recently beating heart CABG gaining popularity, and the indications for CABG have increasingly expanded to elderly person. Using RHB while exposing posterior branches by displacing the beating heart, we have attempted to make total revascularization in beating heart CABG. We performed beating heart CABG with RHB in 3 cases of octogenarian. All patients had left main trunk lesion and needed revascularization of posterior vessels. Introduction of RHB enabled us to approach to posterior target vessels in better exposure and under greater hemodynamic stability. All three patients had no complications postoperatively. Strictly speaking CABG with RHB is not off-pump CABG, but RHB system does not include either artificial lung or manipulation of the aorta. Therefore we think it is very effective support system which enables multiple coronary revascularization for elderly person.

Aged↗

Alloxan-induced mitochondrial permeability transition triggered by calcium, thiol oxidation, and matrix ATP.

In addition to their critical function in energy metabolism, mitochondria contain a permeability transition pore, which is regulated by adenine nucleotides. We investigated conditions required for ATP to induce a permeability transition in mammalian mitochondria. Mitochondrial swelling associated with mitochondria permeability transition (MPT) was initiated by adding succinate to a rat liver mitochondrial suspension containing alloxan, a diabetogenic agent. If alloxan was added immediately with or 5 min after adding succinate, MPT was strikingly decreased. MPT induced by alloxan was inhibited by EGTA and several agents causing thiol oxidation, suggesting that alloxan leads to permeability transition through a mechanism dependent on Ca(2+) uptake and sulfhydryl oxidation. Antimycin A and cyanide, inhibitors of electron transfer, carbonyl cyanide m-chlorophenylhydrazone, and oligomycin all inhibited MPT. During incubation with succinate, alloxan depleted ATP in mitochondria after an initial transient increase. However, in a mitochondrial suspension containing EGTA, ATP significantly increased in the presence of alloxan to a level greater than that of the control. These results suggest the involvement of energized transport of Ca(2+) in the MPT initiation. Addition of exogenous ATP, however, did not trigger MPT in the presence of alloxan and had no effect on MPT induced by alloxan. We conclude that alloxan-induced MPT requires mitochondrial energization, oxidation of protein thiols, and matrix ATP to promote energized uptake of Ca(2+).

Adenosine Triphosphate↗