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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 181 records · Page 10Linked to original sources

A novel gene "Niban" upregulated in renal carcinogenesis: cloning by the cDNA-amplified fragment length polymorphism approach.

A modified AFLP (amplified fragment length polymorphism) method was employed to isolate genes differentially expressed in renal carcinogenesis of Tsc2 gene mutant (Eker) rats. One gene, selected for further investigation, was named "Niban" "second" in Japanese), because it is the second new gene to be found after Erc (expressed in renal carcinoma) in our laboratory. Importantly, "Niban" is well expressed even in small primary rat Eker renal tumors, more than in progressed cell lines, and is also expressed in human renal carcinoma cells, but not in normal human or rat kidneys. Chromosome assignment was to RNO 13 in the rat, and HSA 1. This "Niban" gene is a candidate as a marker for renal tumor, especially early-stage renal carcinogenesis.

Amino Acid Sequence↗

Fatty acid synthase is expressed mainly in adult hormone-sensitive cells or cells with high lipid metabolism and in proliferating fetal cells.

Animal fatty acid synthase (FAS) is a homodimer protein which synthesizes long-chain fatty acids and is rich in liver, brain, breast, and lung. However, the precise cellular localization of FAS in human tissues has not been elucidated. Immunohistochemistry with a new antibody to human FAS revealed that in adult human tissues FAS is distributed mainly in cells with high lipid metabolism (adipocytes, corpus luteum, hepatocytes, sebaceous glands, and Type II alveolar cells), in hormone-sensitive cells (anterior pituitary, apocrine gland, breast, endometrium, prostate, seminal vesicle, and adrenal cortex), and in a subset of epithelial cells of duodenum and stomach, colon absorptive cells, cerebral neurons, basket cells of cerebellum, decidua, uroepithelium, and epidymis. In fetal cells at 20 weeks of gestation, FAS was mainly present in proliferative epithelial cells of the digestive and respiratory systems, proximal renal tubules, adrenocortical cells, and mesenchymal and hematolymphoid cells. Staining was significant in nonproliferating cells, as observed in adult, and in sympathetic ganglion cells, Leidig cells of testis, and Langhans cells of chorionic villi. FAS is maintained in hormone-sensitive cells and/or cells active in lipid metabolism in the adult and is expressed in proliferating cells in the fetus, suggesting active fatty acid synthesis for energy utilization or membrane lipids.

Adipocytes↗

Effects of aging on surfactant forms in rats.

Surfactant present in the alveolar space exists in two major forms: functional large aggregate forms (LA) and nonfunctional small aggregate forms (SA), but there is no information about the changes of surfactant forms and the rate of conversion of LA to SA in the aged lungs. The purpose of the present study was to investigate the developmental aspects of surfactant forms in newborn, young, middle-aged and aged rats, LA and SA were recovered from alveolar lavages of rats. The rate of conversion from LA to SA was then analysed using a surface-area cycling technique. Age-related changes of saturated phosphatidylcholine (Sat-PC) and surfactant protein A (SP-A) pool sizes were also evaluated in alveolar lavages. The alveolar lavages recovered from aged rats contained a significantly higher proportion of LA than did those obtained from young or newborn rats. There was also an age-related decrease in the rate of conversion from LA to SA in vitro. The Sat-PC pool sizes in the alveolar lavages decreased with age, but the SP-A contents were similar between young and aged rats. These results suggested that decreased form conversion may contribute to maintaining functional surfactant pool sizes in the lungs of aged rats.

Aging↗

Increased levels of surfactant protein A and D in bronchoalveolar lavage fluids in patients with bronchial asthma.

Surfactant proteins (SP)-A and SP-D are collagen-like glycoproteins belonging to the "collectin" class of C-type lectins, which are primarily synthesized in type II cells. Recent studies reported the possibility of local production of SP-A and SP-D in the airways, but the amounts of surfactant proteins in patients with bronchial asthma have not been studied. The composition of surfactant proteins in mild, stable asthmatics in the first lavage as bronchial lavage (BL) and the second and third lavages consecutively as alveolar lavages (AL) were therefore, analysed separately. The co-relationships in the BL between the amounts of surfactant proteins and those of fucose, which is one of the markers of submucosal secretion were also analysed. Increased amounts of SP-A in BL and AL of in asthmatics were found as compared with those in controls. A high concentration of SP-D in the AL asthma patients was also found. The levels of SP-A correlated with those of fucose in patients with bronchial asthma (r=0.849, p<0.01). The observations in the present study suggested that surfactant protein A may be secreted from the airways with allergic inflammation in a different manner from the alveoli. The increased levels of surfactant proteins A and D may play a protective role in an allergic inflammation in the pathogenesis of bronchial asthma.

Adult↗

Effect of calcimimetic agent, KRN568, on gastrin secretion in healthy subjects.

KRN568 is a calcimimetic compound which acts on the calcium sensing receptors (CaR) on the parathyroid gland to suppress secretion of PTH. A recent report has demonstrated that CaRs are expressed on cultured human antral gastrin cells and that gastrin secretion is stimulated by an increase in extracellular calcium level. However, the effect of KRN568 on serum gastrin levels has yet to be clinically assessed. We therefore studied the effect of this calcimimetic on gastrin secretion in healthy subjects enrolled in the phase 1 study for KRN568 currently carried out in Japan. Single doses of KRN568, ranging from 25 mg to 400 mg, were orally administered to 6 healthy male volunteers at fasting and after meal. One subject proved to be a poor metabolizer (PM) for this compound and showed more than 10-fold high concentrations of plasma KRN568 (fasting Cmax 90.8 and non-fasting 83.8 ng/ml) compared to the other 5 individuals (Cmax 6.5 +/- 2.2 and 7.4+/- 1.6 ng/ml, respectively). Plasma gastrin levels showed mild but apparent increase (from 30 to 125 pg/ml) in this particular subject, while there were no significant increases in the other five people (from 34 +/- 6 to 63 +/- 3 pg/ml) after oral administration of 400 mg KRN568 at fasting. In the PM, administration of KRN568 resulted in extraordinarily high serum drug levels associated with transient increase of gastrin levels. This observation suggested that calcium-induced stimulation of gastrin secretion in human was mediated by a mechanism involving CaR. Potential side effects related to the increased gastrin secretion may be warranted in the practical use of this compound.

Administration, Oral↗

Peripheral occluding effects of non-absorbable membranes on ingrowth of cultured gingival connective tissue cells.

BACKGROUND: The success of periodontal regenerative procedures, i.e., using regenerative cells to repopulate wounds, is enhanced by using barrier materials, such as expanded polytetrafluoroethylene (ePTFE) membranes, to provide a barrier to the proliferation of epithelial cells and gingival connective tissue cells at the healing site. However, several animal and clinical studies have demonstrated the difficulties of avoiding thin connective tissue ingrowth under the ePTFE membrane used for bone regeneration procedures. We investigated the peripheral occluding effects of ePTFE membranes on ingrowth of cultured gingival connective tissue cells in vitro. METHODS: The ePTFE membrane was divided into 4 pieces, fixed, and immobilized on a culture dish. Human connective tissue cells from clinically healthy gingiva were isolated and cultured. Low passages (2 through 3) of these cells, 5 x 105, were seeded and cultured in each dish. At weeks 1, 2, and 4, the ingrowth cells under the membranes were stained with Giemsa and photographed. The percentage of cell ingrowth as an area measurement and the cell ingrowth score as a linear measurement were determined using computer-assisted interactive image processing. RESULTS: There were no measurable spaces between the membranes and the dishes at x40 magnification using the stereomicroscope. However, the percentage of cell ingrowth under the membrane gradually increased from 1 to 4 weeks, reaching approximately 70% by week 4. There was a statistically significant difference between the 1 - and 4-week percentage of cell ingrowth (P <0.05). The cell ingrowth score also increased gradually, and cells invaded the center from all peripheral borders. There was a statistically significant difference for the lower right and left margins of the membrane between the 1-week and 4-week cell ingrowth scores. Furthermore, there was a statistically significant difference for the 4-week cell ingrowth score between the upper and lower margins (P <0.05). CONCLUSION: The use of ePTFE membranes placed over the culture dish plate cannot prevent ingrowth of cultured gingival connective tissue cells in vitro.

Adolescent↗

Remnant-like particle cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients.

OBJECTIVE: The aim of the study was to investigate the relationships between remnant-like particle (RLP) cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 86 nonobese Japanese type 2 diabetic patients (72 men and 14 women, aged 40-83 years, BMI 20.1-26.6 kg/m2) were studied. BMI, HbA1c levels, and fasting concentrations of plasma glucose, serum lipids (RLP cholesterol, total cholesterol, HDL cholesterol, and triglycerides), and serum insulin were measured. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). The subjects were divided into two groups according to the value of HOMA-IR. Values >2.5 were indicative of the insulin-resistant state, and values <2.5 were indicative of the insulin-sensitive state. RESULTS: The insulin-resistant group had significantly higher RLP cholesterol and triglyceride levels and lower HDL cholesterol levels compared with the insulin-sensitive group. Univariate regression analysis showed that insulin resistance was positively correlated with BMI (r = 0.254, P = 0.019), HbA1c levels (r = 0.278, P = 0.011), RLP cholesterol levels (r = 0.315, P = 0.004), and triglyceride levels (r = 0.332, P = 0.002) and was negatively correlated with HDL cholesterol levels (r = -0.301, P = 0.006) in our diabetic patients. Multiple regression analysis showed that insulin resistance was independently associated with serum triglyceride levels, which explained 13.5% of the variability of insulin resistance in our nonobese Japanese type 2 diabetic patients. CONCLUSIONS: These results indicate that 1) nonobese Japanese type 2 diabetic patients with insulin resistance are characterized by high RLP cholesterol and triglyceride levels, and low HDL cholesterol levels; and 2) the level of serum triglycerides is an independent predictor of insulin resistance in these patients.

Apolipoproteins↗

[Usefulness of Doppler echocardiography in patients with ischemic cerebrovascular disease].

We carried out transthoracic Doppler echocardiography on 213 patients with ischemic cerebrovascular disease to examine cardiac functions. The prevalence of valvular regurgitation, left ventricular diastolic function (E/A ratio), and ejection fraction (EF) of each patient were studied by transthoracic Doppler echocardiography. In patients with embolic strokes, the prevalence of valvular regurgitation of the left ventricular system such as mitral regurgitation was significantly higher than that of normal controls. In contrast, there was no significant difference in the prevalence of valvular regurgitation in the right ventricular system. Although there was no significant difference in the ejection fraction between groups, the E/A ratio in patients with ischemic cerebrovascular disease showed a significantly lower value than that in normal controls. Patients with ischemic cerebrovascular disease showed a tendency to have an atherosclerotic change in the systemic arteries including cerebral and coronary arteries, reflecting an aggravation of cardiac wall compliance and diastolic dysfunction resulting in lowering of the E/A ratio. Thus, transthoracic Doppler echocardiography was useful to evaluate cardiac diastolic dysfunction and valvular regurgitation in patients with ischemic cerebrovascular disease.

Acute Disease↗

Slow N-acetyltransferase 2 genotype affects the incidence of isoniazid and rifampicin-induced hepatotoxicity.

SETTING: Japanese in-patients with pulmonary tuberculosis and normal liver function receiving treatment with isoniazid and rifampicin (INH + RMP). OBJECTIVE: To elucidate the relationship between N-acetyltransferase 2 (NAT2) genotype and the incidence of isoniazid + rifampicin-induced hepatotoxicity. DESIGN: Prospective study. After NAT2* genotyping, 77 patients were classified into three groups according to their NAT2* genotypes: rapid-type (a homozygote of NAT2*4), intermediate-type (a heterozygote of NAT2*4 and mutant alleles) and slow-type (a combination of mutant alleles). Their biochemical profiles of liver function test were investigated for 3 months to assess the development of serum aminotransferase elevation. RESULT: Of the 77 patients, 18.2% developed adverse hepatic reaction within the first month of INH + RMP treatment. A significant association was observed between hepatotoxicity and NAT2* genotype: compared with rapid-type, the relative risk was 4.0 (95% CI 1.94-6.06) for intermediate-type and 28.0 (95%CI 26.0-30.0) for slow-type. Especially in slow-type, the incidence of hepatotoxicity and serum aminotransferase elevation was significantly higher than in the other two types. CONCLUSION: Slow NAT2* genotype significantly affected the development of INH + RMP-induced hepatotoxicity. This suggests the possibility that NAT2* genotyping prior to medication may be useful in evaluating patients with high risk for INH + RMP-induced hepatotoxicity.

Adult↗

[Quantitative evaluation for scatter and attenuation correction in 99mTc SPECT--multicenter cooperation phantom study].

A multicenter cooperation phantom study was conducted to evaluate the accuracy of a triple energy window scatter correction technique in combination with various attenuation correction methods for 99mTc single photon emission computed tomography (SPECT) imaging. Six centers participated in this research and the data obtained with seven SPECT instruments were analyzed. The phantom used in the experiment was a 20 x 10 cm cylinder filled with homogeneous 99mTc solution, containing two kinds of cold spots (cold rod phantoms). One had a water-filled cylinder 5.5 cm in diameter positioned 2.5 cm from the center. The other contained 6 water-filled cylinders of various sizes. Contrasts of cold regions were in the range from 74% to 120% (true 100%). Another phantom had the shape of a pie-chart divided into six chambers symmetrically positioned in a cylinder 20 cm in diameter and 10 cm in height. Each chamber had volume of 480 ml and contained homogeneous 99mTc solution of different concentrations. This phantom was used to test for linearity between the radio activity concentration and reconstructed count density (linearity phantom). The intercept of the regression line obtained from the linearity phantom was 8.4 kBq ml-1 without scatter correction and -6.8 kBq ml-1 with scatter correction. Contrast was in the range from 78% to 132% (true 100%). The mean relative error for the measured activity concentration was 4.9% +/- 3.5% (mean +/- sd).

Phantoms, Imaging↗

[Cardiac function estimated by Doppler echocardiography in patients with hypertensive intracerebral hemorrhage].

We carried out transthoracic Doppler echocardiography on 38 patients with hypertensive intracerebral hemorrhage(ICH) to examine cardiac functions. The ratio of myocardial hypertrophy and the prevalence of valvular regurgitation were investigated. The E/A ratio which reflects left ventricular diastolic function and the ejection fraction(EF) of each patient were also studied to demonstrate cardiac functions in patients with hypertensive ICH. Myocardial hypertrophy was found in 39.5% of patients with hypertensive ICH. The aortic regurgitation showed a trend to have a higher prevalence in patients with hypertensive ICH when compared to normal volunteer group. Although there was no significant differences in the ejection fraction between groups, the E/A ratio in patients with hypertensive ICH showed a significantly lower value than in normal volunteer group. Therefore, transthoracic Doppler echocardiography demonstrated that patients with intracerebral ICH showed a trend to have a myocardial hypertrophy, aortic valvular regurgitation, and the lower ventricular diastolic function. Thus, transthoracic Doppler echocardiography is useful to evaluate cardiac functions in patients with hypertensive ICH.

Adult↗

[Balloon-occluded retrograde transvenous obliteration (B-RTO) for portal hypertension].

We reviewed the current techniques and published results of balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices (GV) and hepatic encephalopathy. The portal hemodynamics of gastric varices were classified into three types according to their feeding vessels, and the development of collateral veins under balloon occlusion of gastro-renal shunt was classified into five grades. The main draining veins of gastric varices were gastro-renal and gastro-inferior phrenic shunts. Preprocedural diagnosis of portal hemodynamics is important in selecting the technique for B-RTO. The rate of disappearance or marked reduction of GV was 98%, and the rate of recurrence of GV was 2%. Hepatic encephalopathy due to gastro-renal shunt improved markedly. In contrast, esophageal varices were aggravated at rates of 10% to 62.5% by the post-procedural elevation of portal pressure. Common adverse effects were hemoglobinuria, abdominal pain, and low-grade fever, but ascites and pleural effusion were also reported. Severe complications such as cardiogenic shock, atrial fibrillation, and pulmonary embolism were reported. We await technical improvements and further indications for this procedure.

Catheterization↗

[Complications of hysteroscopical myomectomy: a report of two cases].

Hysteroscopical myomectomy has recently become popular in Japan. We present two patients who developed water intoxication and air embolism during surgery. [Case 1] Hysteroscopical myomectomy was performed under general anesthesia in a 37-yr-old woman (ASA I). Three hours after the start of the surgery, the patient's serum sodium concentration dropped to 118 mEq.l-1. She was treated with furosemide and recovered without sequelae. [Case 2] A 39-yr-old woman (ASA I) was scheduled to have hysteroscopical myomectomy under spinal and epidural anesthesia. Forty-five minutes after the start of the surgery, the patient complained of severe back pain, her blood pressure decreasing to 40 mmHg, SpO2 decreased to 80%, and ECG showed atrial fibrillation. After administration of ephedrine 5 mg, she recovered within 20 min. No abnormality was observed in echocardiogram, although some negative spots were detectable in a lung scintigraphy. She was discharged without sequelae. The hysteroscopical procedure is considered a non-invasive surgery, but the cases presented here emphasize the necessity for close attention to complications, especially pulmonary embolism.

Adult↗

[Estimating cost functions of cancer screening programs provided by municipalities].

OBJECTIVE: To estimate cost functions of cancer screening programs for stomach, lung, colorectal, cervical, and breast cancers provided by municipalities and to describe the relationship between the costs and the scale of cancer screening programs. METHODS: Subjects were all the municipalities in Japan. Questionnaires were sent to 3,182 subjects and 1,860 responses were received. Data obtained from questionnaires were the number of persons screened and the total cost of each program in the 1998 fiscal year. A cost function of each program was specified as a linear model, a power model, and a cubic model, and the fitness of each model was estimated. RESULTS: Long-run cost functions of all the cancer screening programs allowed better explanation of the relationship between the number of persons screened and the total cost than short-run cost functions. The average costs of stomach, colorectal, and cervical cancer screening programs increased and the average cost of the lung cancer screening program decreased, as the number of persons screened increased. The cost function of the breast cancer screening program could not be identified. CONCLUSIONS: It is necessary to estimate not only cost functions but also production functions of cancer screening programs using the data related to products, costs, and factors of production to evaluate the efficiency of cancer screening programs.

Cities↗

[A study on resource based relative values for visiting nursing services].

PURPOSE: The purpose of this study was to investigate the resource based relative values of visiting nursing services, and to analyze the relationships between the relative values and the dimensions of nursing service(time, mental effort and physical effort). METHODS: We interviewed nurses at 20 Home-visit nursing care stations (HVNCS) in the Metropolitan area using the resource based relative value questionnaires. We asked nurses about relative values of "Total Work", and also measured relative weight of 3 dimensions of nursing services. Total Work was defined as comprehensive evaluation of nursing services, with careful consideration of intensity as well as duration. With the dependent variable as Total Work and independent variables as the 3 dimensions, multiple regression analyses were carried out. Furthermore we examined the degree of influence on Total Work by service type and individual respondent. To examine the validity of the results, we timed nursing services and compared the measured time with the answered time. RESULTS: The 107 respondents were all female and their average age was 36.6 years old. They had HVNCS experience of 2.2 years and 95.3% nurses had experience of hospital nursing. "Total Work" and 3 dimension scores were standardized using common logarithms. "Total Work" of every service significantly differed among service types. The 3 dimensions explained 54.6% of Total Work in the multiple regression analysis. Service type explained 3.3% of Total Work. Individual respondent explained 16.0% of Total Work. Answered time and measured time were not significantly different with nursing services. CONCLUSIONS: Although Total Work was somewhat influenced by individual respondent, most of variation was explained by 3 dimensions. Thus, it could be concluded that Total Work is an index of nursing resource input. A further investigation about influence of patients' condition on Total Work is necessary in the future.

Adult↗