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Biomedical subjects

K Kawano

Publications and source records attributed to K Kawano.

At least 181 records · Page 10Linked to original sources

Fourier-transform infrared spectroscopic studies on the coordination of the side-chain COO- groups to Ca2+ in equine lysozyme.

Interactions between Ca2+ and the Asp side chains in the Ca2+-binding site of equine lysozyme were investigated by Fourier-transform infrared (FT-IR) spectroscopy. In the spectrum of equine lysozyme, the intensities of the bands at about 1595 cm-1 and 1578 cm-1 in the region of the COO antisymmetric stretches increased upon Ca2+ binding. In the region of the COO- symmetric stretches, the loss of intensity at about 1388 cm-1 and gains of intensities at about 1423 cm-1 and 1403 cm-1 were observed due to Ca2+ binding to equine lysozyme. The spectral changes for equine lysozyme indicate that the COO- groups of Asp85, Asp90 and Asp91 in the Ca2+-binding site coordinate to Ca2+ in the pseudo-bridging mode, where divalent metal cation is bound to one of the two oxygens in the COO- group and a water molecule is hydrogen bonded to the other oxygen. The results presented here provide further evidence for a high degree of similarity between Ca2+-binding lysozyme and alpha-lactalbumin. The effects of Ca2+ binding on the main-chain conformation of equine lysozyme were compared with those of bovine alpha-lactalbumin and hen egg-white lysozyme.

Animals↗

FT-IR study of the Ca2+-binding to bovine alpha-lactalbumin. Relationships between the type of coordination and characteristics of the bands due to the Asp COO- groups in the Ca2+-binding site.

Fourier-transform infrared spectroscopy (FT-IR) was applied to examine relationships between the type of coordination and the COO- antisymmetric and symmetric stretches of the COO- groups in the Ca2+-binding site of bovine alpha-lactalbumin. The peaks at 1593, 1578, 1425, and 1403 cm(-1) were assigned to the COO- groups of Asp-82, 87, and 88 coordinating to Ca2+ in the pseudo bridging mode, according to the results of X-ray crystallography. The bands due to the COO- groups were quite similar to each other between alpha-lactalbumin and EDTA which is the model compound for the pseudo bridging state.

Animals↗

Epstein-Barr virus in gastric carcinoma in Suzhou, China and Osaka, Japan: association with clinico-pathologic factors and HLA-subtype.

Information on geographic differences of Epstein-Barr virus (EBV) positivity and association with HLA in gastric carcinoma are limited. Therefore, the association of gastric carcinoma with EBV was examined in 118 patients from Suzhou, China, where the incidence of nasopharyngeal carcinoma (NPC) is high, and in 216 patients from Osaka, Japan, where the incidence of NPC is low, NPC being one of the EBV-associated carcinomas. Expression of HLA-A2 was also examined in some of these cases. The EBV genome was evidenced by PCR and in the tumor cells by in situ hybridization in 7/90 and 9/151 of cases from Suzhou and Osaka, respectively. Immunohistochemistry revealed that cancer cells in all cases with EBV did not express latent membrane protein-I. Type A was found in all cases positive for EBV. Among several histologic and clinical factors, only age of patients showed a correlation with EBV positivity: patients over 60 showed a higher frequency than patients below 60 years of age (p < 0.05). Typing of the HLA-A locus was possible in 16 cases positive for the EBV genome: 3 of 4 cases from Suzhou and 4 of 7 from Osaka were positive for HLA-A2 products. Severe lymphoid cell infiltration was found in 2 of 7 cases and 1 of 4 cases with and without the HLA-A2 type, respectively. The reported frequency of EBV positivity in Chinese living in Taiwan and in Japanese living in Hawaii is higher than in Suzhou, China, and Osaka, Japan, respectively. Our findings suggest that EBV association with gastric carcinoma is influenced by environmental and cultural factors.

Adenocarcinoma↗

Serum protein standardization project in Japan: evaluation of an IFCC reference material (RPPHS/CRM470) and establishment of reference intervals.

Reference preparation for proteins in human serum (RPPHS), also called Certified Reference Material 470 (CRM 470), was prepared by the international Federation of Clinical Chemistry (IFCC) and is intended to serve as a new international plasma protein reference material. It is now being introduced into Japan. RPPHS possesses many excellent properties, including safety, stability, and accuracy in value assignment. Moreover, the physicochemical properties of its proteins are identical to those of fresh serum, giving it immunochemical behavior that is commutable with that of existing reference materials and calibrators in given immunoassays. Reference intervals of 13 serum proteins were determined for the first time using nephelometry and a new working calibrator assigned from RPPHS, which seems certain to play a critical role in the global standardization of specific protein immunoassays.

Age Factors↗

Increased cardiac sympathetic activity in patients with hypothyroidism as determined by iodine-123 metaiodobenzylguanidine scintigraphy.

Clinical manifestations of hypothyroidism, such as bradycardia, suggest decreased sympathetic tone. However, previous studies in patients with hypothyroidism have suggested that increased plasma noradrenaline (NA) levels represent enhanced general sympathetic activity. As yet, cardiac sympathetic activity (CSA) in hypothyroidism has not been clarified. To evaluate CSA in patients with hypothyroidism, iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed in eight patients with hypothyroidism before therapy and in ten normal control patients. Planar images were obtained at 15 min and 4 h after injection of MIBG. The ratio of early myocardial uptake to the total injected dose (MU) and myocardial clearance of MIBG within 4 h p.i. (MC) were calculated. Plasma NA was also measured, and echocardiography was performed in all patients. Those patients with hypothyroidism in the euthyroid state after medical therapy were also evaluated in a similar manner. Left ventricular ejection fraction, measured by echocardiography, did not differ significantly between the groups. NA, MU and MC were significantly higher in patients with hypothyroidism than in controls, and all parameters were decreased after therapy. MC was well correlated with NA in hypothyroidism (r=0.86) before therapy. We conclude that CSA is increased in patients with hypothyroidism, in parallel with the enhanced general sympathetic activity.

3-Iodobenzylguanidine↗

A mathematical model that reproduces vertical ocular following responses from visual stimuli by reproducing the simple spike firing frequency of Purkinje cells in the cerebellum.

A mathematical model that accurately reproduces eye movements from visual stimuli and incorporates intermediate neural signals is useful for quantitative analysis of the neural mechanisms involved in transforming visual stimuli to eye movements. Here we describe a mathematical model consisting of two systems: a non-linear system that relates retinal slip to simple spike firing frequency of Purkinje cells in the ventral paraflocculus (VPFL) and a linear system that relates VPFL simple spike firing frequency to eye movement. This model accurately reproduced the firing frequency of Purkinje cells and ocular following responses from visual stimulation paradigms used in physiological experiments.

Action Potentials↗

Platelet-dependent thrombin generation in patients with hyperlipidemia.

OBJECTIVES: We evaluated coagulability as determined by platelet-dependent thrombin generation in hypercholesterolemic patients before and after treatment with pravastatin and in hypertriglyceridemic patients to investigate the usefulness of coagulability as an index of atherosclerosis and to determine the importance of treating hyperlipidemia. BACKGROUND: An understanding of the interaction between platelets and the plasma coagulation system is important for clarifying the mechanism of the procoagulant process. METHODS: We assessed coagulability in 58 patients with hypercholesterolemia (serum total cholesterol level > or = 220 mg/dl, age 56.5 +/- 1.5 years [mean +/- SEM]), 37 patients with hypertriglyceridemia (serum triglyceride level > or = 200 mg/dl, age 59.5 +/- 1.7 years), 13 patients with hypercholesterolemia plus hypertriglyceridemia (age 51.4 +/- 3.1 years) and 75 normal subjects (age 52.2 +/- 1.7 years). We also studied platelet-dependent thrombin generation in patients with hypercholesterolemia before and after treatment with pravastatin. Calcium chloride was added to 0.5 ml of platelet-rich plasma (150 x 10(9)/liter) to initiate coagulation. Ten microliters of the sample was transferred into 90 microliters of 3.8% sodium citrate at 10-min intervals for 30 min. A chromogenic substrate, S-2238, was added to each sample, and absorbance was measured spectrophotometrically at a wavelength of 405 nm to determine thrombin generation. RESULTS: Platelet-dependent thrombin generation was increased in patients with hypercholesterolemia and patients with hypercholesterolemia plus hypertriglyceridemia (p < 0.01) compared with patients with hypertriglyceridemia and control subjects. Treatment with pravastatin normalized thrombin generation. CONCLUSIONS: Hypercholesterolemia, but not hypertriglyceridemia, was associated with increased platelet-dependent thrombin generation. Pravastatin normalized the generation of thrombin.

Adult↗

Body mass index variations by age and sex, and prevalence of overweight in Japanese adults.

OBJECTIVE: To determine the reference value of BMI for Japanese subjects and to estimate the prevalence of overweight based on this reference value. DESIGN: Epidemiological analysis with the LMS method, which provides a way of obtaining normalized BMI distributions. SUBJECTS: 7508 Japanese subjects aged 18-69 y in 1993. MEASUREMENTS: Height, age and body weight. CALCULATION: BMI was calculated and tables for percentiles of BMI were plotted against age and sex. Furthermore, the prevalence of overweight was estimated based on 85th percentile of BMI in the men and women 20-29 y of age, who were considered the reference group. RESULTS: The geometric mean BMI and the prevalence of overweight in men was highest in the 30-39 y age group. For women the maximum BMI and prevalence of overweight occurred in the decade 50-59 y. The cut-off points for overweight in this sample were 24.7 kg/m2 for men and 22.6 kg/m2 for women. These are considerably lower than the figures of 27.8 kg/m2 and 27.3 kg/m2 estimated for Americans. CONCLUSIONS: The prevalence of obesity in Japanese populations should be estimated using ethnic specific values of BMI, rather than those drawn from Caucasians who tend to have higher BMI in each age group. The prevalence of overweight is increased as age increased in both sexes, especially in women.

Adolescent↗

Improving effect of carteolol on bodyweight and carbohydrate and lipid metabolic responses in the OLETF rat.

1. Carteolol, a non-selective beta-blocker with intrinsic sympathomimetic activity, admixed in a pellet diet was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneous non-insulin-dependent diabetes mellitus with mild obesity. A high dose of carteolol (0.02%) suppressed bodyweight gain without affecting food and water consumption until the appearance of glycosuria. Carteolol tended to reduce the cumulative incidence of glycosuria at 26 weeks after the beginning of administration (55, 17 and 25% in control rats, and in rats fed a low (0.002%) and high dose of carteolol, respectively). 2. At the 26th week of administration, the high dose of carteolol decreased visceral fat weight, such as that of retroperitoneal and epididymal adipose tissue, whereas the liver and the kidney were not affected. 3. Although plasma glucose and triglyceride levels in non-fasted rats were elevated with age, carteolol tended to delay the increases in those parameters. Carteolol suppressed the increase in plasma glucose levels, which indicate the diabetic pattern, in a 25th week oral glucose tolerance test. 4. These findings indicate that carteolol induces improvements in bodyweight and carbohydrate and lipid metabolism in an obese condition. Consequently, carteolol may be useful for the treatment of hypertension with obesity in order to prevent cardiovascular events.

Adipose Tissue↗

Hepatitis C virus RNA present in saliva but absent in breast-milk of the hepatitis C carrier mother.

In order to examine whether saliva and breast-milk are mediators of the vertical transmission of hepatitis C virus (HCV) from an HCV carrier mother, serum, saliva, and breast-milk samples from 11 HCV carrier mothers were collected at the time of delivery, and at approximately 1- to 3-months intervals for as long as 30 months postpartum. Serum was also sampled from their children. All samples were analysed for the presence of HCV RNA, using the nested polymerase chain reaction method. No HCV RNA was detected in any breast-milk samples. In saliva, HCV RNA was detected in four of the 11 mothers (36%). These four mothers also had liver function abnormalities. Hepatitis C virus RNA was not detected in any serum samples of the children, and all children had normal liver function. The children were monitored for periods from 2 to 44 months. During this period, there was no evidence of virus transmission. Breast-milk is not likely to be a source of mother-to-child transmission of HCV. Maternal saliva may harbour HCV, but it may not result in infant infection.

Child, Preschool↗

Genotype distribution of estrogen receptor polymorphisms in men and postmenopausal women from healthy and coronary populations and its relation to serum lipid levels.

The cardiovascular protective effects of estrogen are known to be mediated by its beneficial effects on lipid metabolism and its direct actions on the vessel wall. The latter can be mediated by a specific receptor for estrogen present on smooth muscle cells and endothelial cells. The gene for the receptor (the classic estrogen receptor [ER]) has three known polymorphisms, Pvu II, Xba I, and B-variant polymorphisms, which are reportedly associated with receptor expression and altered receptor function and with some disorders including breast cancer, hypertension, and spontaneous abortion. However, the significance of genetic variations of the ER in vascular diseases has not been reported. We have examined the association between coronary artery disease (CAD) and the three polymorphisms in ER. Genotypes (P1/P2, X1/X2, and B-wild type/B-variant type) were determined in 87 men and postmenopausal women with myocardial infarction or angina pectoris whose lesions were confirmed by coronary angiography, as well as from 94 control individuals from the general population with no coronary heart disease and normal resting ECG. For B-variant polymorphism, all individuals examined had B-wild type, which contrasts with the reported allele frequency for B-variant type (0.1) in the white population. Genotype distributions and allele frequencies of Pvu II or Xba I polymorphisms were not significantly different between control subjects and patients (P > .05 for Pvu II or Xba I genotypes; P > .05 for Pvu II or Xba I allele frequencies). When the allele frequencies were analyzed separately by sex, there was still no statistically significant difference for both polymorphisms (P > .05 for men; P > .05 for women). No association was found between the polymorphisms and the angiographic severity of CAD. Total cholesterol, triglyceride, or HDL-cholesterol levels were not significantly different among ER genotypes. These findings suggest that the three polymorphisms in ER are not associated with the prevalence and severity of CAD and that the polymorphisms are unrelated to the serum lipid levels in control subjects and patients.

Adult↗

A 192Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese.

Recent reports have suggested that polymorphisms in the human paraoxonase (HUMPONA) gene may be a genetic risk factor for coronary artery disease (CAD) in white populations. However, this association has not yet been confirmed in other ethnic populations. We studied 75 Japanese patients with CAD, whose coronary lesions were confirmed by angiography, and 115 Japanese control subjects with no history of CAD and a normal resting electrocardiogram. The assays for genotyping the two polymorphisms in the HUMPONA gene (192Arg/Gln and 55Leu/Met) were based on changes in restriction enzyme digestion patterns. For codon 192, the frequencies of the Arg-coding allele (B allele) in both patients and control subjects were much higher than those from published results of whites (.26 to .31), and the difference between patients (.74) and control subjects (.59) was statistically significant (P = .002). The patient group had a higher proportion of Arg/Arg (B/B) homozygotes (52.0% vs 32.2%, P = .006). For codon 55, the frequencies of the Leu-coding allele in control subjects and patients were much higher (.91 and .93, respectively) than those published results for whites, but there was no difference between Japanese control subjects and Japanese patients. When subjects with the 55Leu/Leu genotype only were analyzed, 192Arg/Arg homozygotes were still significantly more frequent in the patients than in the control subjects (55.4% vs 37.2%, P = .024), and the frequency of the 192Arg allele was also higher in patients than control subjects (P = .013). Logistic regression analysis including conventional coronary risk factors revealed that 192Arg is an independent risk factor for CAD. Thus, in the Japanese, the association of CAD with the 192Arg variant of HUMPONA (B-type enzyme) is similar to that reported for whites, although the allele frequencies for 192Arg and 55Leu are much higher in the former than the latter population.

Adult↗

Loss of glycosylation at Asn144 alters the substrate preference of the N8 influenza A virus neuraminidase.

Role of asparagine-linked (N-linked) oligosaccharide side chains in the maturation and the function of influenza virus neuraminidase (NA) subtype N8 was examined by site-directed mutagenesis and vaccinia virus expression system. Mutations in the consensus sequence for N-linked glycosylation at Asn 84 or 398 prevent the proper maturation of mutant NAs. On the contrary, mutation at Asn 144, that is conserved in all except two strains of influenza virus NA ever sequenced, did not affect the proper maturation and the transport of the mutant NA to the cell surface. Furthermore, this mutation led the alternation of substrate preference of this enzyme. These observations indicate that N-glycosylation at Asn 144 of N8 NA may be conserved from the functional requirement, but not from the structural necessity.

Amino Acid Sequence↗

Stage-dependent distribution of calreticulin in oocytes of the frog, Rana rugosa.

We studied immunohistologically the distribution of a Ca2(+)-binding protein, calreticulin (CLT), at different stages of growing oocytes in the frog, Rana rugosa. Northern blot analysis showed that the CLT gene expression in gonads of metamorphosing tadpoles was low, but was extremely strong in the ovary, but not in the testis, of 2-month post-metamorphosis frogs, followed by decline to a lower level in adult frogs. On the contrary, the beta-actin gene expression did not increase in the same ovary. As for the distribution of CLT protein, a weak immunostaining was observed in indifferent gonads of tadpoles at stage I. The CLT distribution in oocytes from stage A to F was stage-dependent. In addition, Western blot analysis revealed that the CLT level was low in gonads of tadpoles at stage I, but increased at stage XVI. It still increased in the ovary of frogs 2 months after metamorphosis, and then dropped to a lower level in adult frogs. The results indicate that CLT gene expression occurs in the early stage of growing oocytes, and that CLT is synthesized actively in oocytes in the ovary of frogs after metamorphosis. Based on these findings, the role of CLT is discussed.

Actins↗

Impaired beta-cell function and deposition of fat droplets in the pancreas as a consequence of hypertriglyceridemia in OLETF rat, a model of spontaneous NIDDM.

Hypertriglyceridemia is known to be a feature of obesity-related NIDDM, but the patho-etiological significance of this association is obscure. The effects of triglycerides (TGs) on beta-cell function and morphological changes in pancreas were examined using in vivo and in vitro approaches in male OLETF rats at ages 6, 12, and 30 weeks, with their diabetes-resistant counterpart, LETO rats, as normal controls. The results showed that, in the fasting state, plasma TGs in OLETF rats were increased 2.5-fold at age 6 weeks, 3.3-fold at age 12 weeks, and 6.2-fold at age 30 weeks, compared with age-matched LETO rats. The TG content in islets from 12-week-old OLETF rats was significantly increased when compared with those from their age-matched counterparts, but this was not the case with the 6-week-old OLETF rats. Therefore, the islets from 6-week-old rats were cultured with either free fatty acids (FFAs; 1.0 mmol/l sodium oleate) or TG (5.0 mmol/l Intralipide) for 72 h. Several abnormalities in OLETF rats were evident, in contrast to the results from control LETO rats: 1) glucose-induced insulin secretion was more inhibited by either FFAs or TGs in the presence of 27.7 mmol/l glucose, a result associated, at least in part, with reduced glucokinase activity in the islets; 2) a marked elevation in TG content was found in the islets; and 3) the deposition of fat droplets in the enlarged islets, even in the beta-cells, was found by Oil Red O-insulin double staining at age 30 weeks. In conclusion, hypertriglyceridemia resulted in significant TG stores in the islets, which subsequently inhibited glucose-induced insulin secretion, at least in part, via reduced glucokinase activity in the islets. Fat droplets in islets, therefore, may play an important role in hastening the development of NIDDM in this rat model.

Animals↗

[A case of foramen magnum meningioma in which case enhanced three-dimensional CT scan was valuable for preoperative evaluation of the surgical approach].

We report a case of foramen magnum meningioma in which case enhanced three-dimensional CT scan was valuable for preoperative evaluation of the surgical approach. A 53-year-old woman had suffered from stiffness and pain in the left occipital region and numbness of the left side of the face for about 2 years before admission. She had also weakness and numbness of the left side of her body for about 2 months before admission, and dysphagia and pain in the occipital region and in the posterior region of the neck produced by straining for about 1 month before admission. Neurological examination revealed left hemiparesis, and hypalgesia and tactile hypesthesia of the left side of the body, including the face. Plain X-P was normal. Enhanced CT scan and gadolinium enhanced MRI revealed a well-enhanced mass attached to the left anterolateral part of the foramen magnum. The left occipital condyle was observed at the lateral side of the attachment part of this mass. Angiography revealed tumor feeders from the meningeal branches of the left vertebral artery and the left ascending pharyngeal artery. Enhanced three-dimensional CT scan clearly showed that the tumor was attached to the left anterolateral part of the foramen magnum, that the left occipital condyle was at the lateral side of the attachment part of this mass and that the jugular foramen and jugular tubercle were situated superolateral to the attachment part of this mass. Considering these factors, we decided that removal of the posterior part of the left occipital condyle was necessary, but removal of the left jugular tubercle was not necessary for a good operative view from the left posterior lateral direction. The tumor was totally removed successfully and good results were obtained by the transcondylar approach without removal of the jugular tubercle. Histology of the tumor revealed meningothelial meningioma. In this case, preoperative evaluation with enhanced three-dimensional CT scan was helpful for deciding the surgical approach. With enhanced three-dimensional CT scan, it is easy to judge whether removal of the posterior part of the occipital condyle and/or the jugular tubercle is necessary for a good operative view, and we can get good images revealing the relationships between the tumor and surrounding structures. Preoperative evaluation with enhanced three-dimensional CT scan is very useful especially in this kind of situation.

Female↗

A diabetogenic gene, ODB2, identified on chromosome 14 of the OLETF rat and its synergistic action with ODB1.

Genetic analysis of diabetogenic genes involved in developing spontaneous diabetes of NIDDM type in the OLETF rat was performed in (OLETF female X B N male)F2 and (OLETF female X BN male)F1 female X OLETF male backcross male offspring. In the F2 and/or backcross offspring, a high frequency of diabetes was found to be associated with a coat color gene, H (hooded). Since it is know that H gene is located on chromosome 14. an attempt was made to examine the linkage association of the gene responsible for elevating plasma glucose with various microsatellite markers of chromosome 14 in male F2 and/or backcross offspring. The results show that a high linkage exists with a microsatellite marker, D14Mit4 (LOD > 2). The gene was designated Odb2. It was also found that both genes, Odb1 which was previously found on chromosome X, and homozygous Odh2 are required to cause elevated plasma glucose in OGTT.

Animals↗

Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinoma.

Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is unique in its ability to promote vascular permeability and endothelial cell growth, and its role in tumor development has received considerable attention. In this report, we describe the elevation of VPF/VEGF transcript expression in human hepatocellular carcinoma. Surgical samples of 23 patients with hepatocellular carcinoma were studied using reverse transcription-PCR analysis. The oligonucleotide primers were designed to amplify all four known splicing variants that could be expressed in the samples studied. Sixteen cases showed VPF/VEGF transcript expression in the tumor (16/23, 69.6%), whereas only 9 of the 23 patients showed it in the corresponding nontumoral part. There was no difference between the pattern of expression of VPF/VEGF isoforms in tumoral and nontumoral tissues. VPF/VEGF mRNA expression in the liver tumors was associated with fibrous capsule formation and septal formation (P < 0.05 respectively, Fisher's exact P test). In situ hybridization confirmed the presence of VPF/VEGF mRNA expression in tumor cells and less intensely in hepatocytes of nontumoral liver. We also found that VPF/VEGF expression in the tumor cell was increased in the area adjacent to necrotic regions (presumably hypoxic regions). As a regulator of vascular permeability and endothelial cell growth factor, VPF/VEGF may play an important role in the development of hepatocellular carcinoma.

Adult↗