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Biomedical subjects

T Katakura

Publications and source records attributed to T Katakura.

At least 19 recordsLinked to original sources

Immunological control of methicillin-resistant Staphylococcus aureus (MRSA) infection in an immunodeficient murine model of thermal injuries.

Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is a major cause of sepsis in patients who are immunosuppressed by their burns. In this study, an immunological regulation of MRSA infection was attempted in a mouse model of thermal injury. SCIDbg mice were resistant to MRSA infection, while SCIDbgMN mice (SCIDbg mice depleted of neutrophils and macrophages (Mphi)) were susceptible to the same infection. Also, thermally injured SCIDbg mice were shown to be susceptible to MRSA infection. On the other hand, the resistance of SCIDbgMN mice to the infection was completely recovered after an inoculation with Mphi from normal mice. However, anti-MRSA resistance was not shown in SCIDbgMN mice inoculated with Mphi from thermally injured mice. Mphi from MRSA-infected thermally injured mice were identified as alternatively activated Mphi, and Mphi from MRSA-infected unburned mice were characterized as classically activated Mphi. Mphi from thermally injured SCIDbg mice previously treated with 2-carboxyethylgermanium sesquioxide (Ge-132) protected SCIDbgMN mice against MRSA infection. Ge-132 has been described as an inhibitor of alternatively activated Mphi generation. These results suggest that MRSA infection in thermally injured patients is controlled immunologically through the induction of anti-MRSA effector cells and elimination of burn-associated alternatively activated Mphi, which are cells that inhibit the generation of classically activated Mphi.

Animals↗

Low-concentration lidocaine rapidly inhibits axonal transport in cultured mouse dorsal root ganglion neurons.

BACKGROUND: Axonal transport plays a critical role in supplying materials for a variety of neuronal functions such as morphogenetic plasticity, synaptic transmission, and cell survival. In the current study, the authors investigated the effects of the analgesic agent lidocaine on axonal transport in neurites of cultured mouse dorsal root ganglion neurons. In relation to their effects, the effects of lidocaine on the growth rate of the neurite were also examined. METHODS: Isolated mouse dorsal root ganglion cells were cultured for 48 h until full growth of neurites. Video-enhanced microscopy was used to observe particles transported within neurites and to measure the neurite growth during control conditions and in the presence of lidocaine. RESULTS: Application of 30 microM lidocaine immediately reduced the number of particles transported in anterograde and retrograde axonal directions. These effects were persistently observed during the application (26 min) and were reversed by lidocaine washout. The inhibitory effect was dose-dependent at concentrations from 0.1 to 1,000 microM (IC50 = 10 microM). In Ca2+-free extracellular medium, lidocaine failed to inhibit axonal transport. Calcium ionophore A23187 (0.1 microM) reduced axonal transport in both directions. The inhibitory effects of lidocaine and A23187 were abrogated by 10 microM KN-62, a Ca2+-calmodulin-dependent protein kinase II inhibitor. Application of such low-concentration lidocaine (30 microM) for 30 min reduced the growth rate of neurites, and this effect was also blocked by KN-62. CONCLUSIONS: Low-concentration lidocaine rapidly inhibits axonal transport and neurite growth via activation of calmodulin-dependent protein kinase II.

Anesthetics, Local↗

The Gln27Glu beta2-adrenergic receptor variant is associated with obesity due to subcutaneous fat accumulation in Japanese men.

The Trp64Arg beta3-adrenergic receptor (AR) variant is associated with visceral obesity probably due to decreased lipolysis in visceral fat (H. Kim-Motoyama et al., Diabetologia 40, 469-472, 1997). Functional alteration of beta2AR may also change fat distribution. We investigated the influence of the Gln27Glu beta2AR variant upon obesity and fat distribution. We screened 278 unrelated Japanese men and detected 249 wild-type Gln27 homozygotes, 28 Gln27/Glu27 heterozygotes, and one mutant Glu27 homozygote. The frequency of mutant Glu27 allele was significantly higher in obese subjects than in nonobese/intermediate subjects (0.11 vs 0.04, P = 0. 004). The Gln27/Glu27 heterozygotes had a significantly higher mean age-adjusted body-mass index (BMI) and mean age-adjusted subcutaneous fat area assessed by CT scan than the wild-type homozygotes but not the mean age-adjusted visceral fat areas. In summary, we have found that in Japanese men the Gln27Glu beta2AR variant is associated with obesity due to subcutaneous fat accumulation.

Adipose Tissue↗

Axonal transport is inhibited by a protein kinase C inhibitor in cultured isolated mouse dorsal root ganglion cells.

We investigated roles of protein kinase C (PKC) and Ca2+/calmodulin-dependent protein II (CAM II) kinase activities in the maintenance of axonal transport in cultured isolated mouse dorsal root ganglion (DRG) cells. Video-enhanced microscopic recordings revealed that the PKC inhibitor chelerythrine (1 microM) reduced anterograde and retrograde axonal transport, while the CAM II kinase inhibitor KN-62 (10 microM) had no effect. Morphological observation showed that neurite growth was prevented by the presence of chelerythrine (1 microM). From these results, we conclude that PKC activity is required to maintain axonal transport and thereby neurite growth.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Extracellular potassium rapidly inhibits axonal transport of particles in cultured mouse dorsal root ganglion neurites.

Changes in extracellular potassium concentration ([K+]o) modulate a variety of neuronal functions. However, whether axonal transport, which conveys materials to the appropriate destination for morphogenesis and other neuronal functions, depends on the extracellular K+ environment remains unclear. We therefore examined the effects of changes in [K+]o on axonal transport of particles visualized by video-enhanced microscopy in cultured mouse dorsal root gan-glion neurites. Increases in [K+]o (delta[K+]o > or = 2.5 mM) from control concentration (5 mM) inhibited both anterograde and retrograde axonal transport within a few minutes in a concentration-dependent manner. Conversely, removal of extracellular K+ induced the rapid facilitation of transport in both directions. These inhibitory and facilitatory responses were completely blocked by the K+ channel blocker tetraethylammonium (TEA), suggesting that the effect of changes in [K+]o involves the TEA-sensitive K+ channels. Increases in [K+]o provoked membrane depolarization in the absence and presence of TEA. Another depolarizing agent, veratridine, did not produce an effect on axonal transport. These results suggest that the extracellular K+-mediated inhibition of axonal transport does not depend on membrane depolarization. The inhibitory effect of increasing [K+]o on axonal transport was retained in calcium (Ca2+)-free extracellular medium, indicating that the inhibitory effect of extracellular K+ does not result from Ca2+ influx through voltage-dependent Ca2+ channels. In chloride (CI-)-free medium, increasing [K+]o failed to inhibit axonal transport, implying that the extracellular K+-mediated inhibition of axonal transport may be due to an increase in intracellular Cl- concentration associated with increases in the net inward movement of K+ and CI- across the membrane. Our results suggest that the extracellular K+ environment is involved in the rapid modulation of axonal transport of particles in dorsal root ganglion neurites.

Animals↗

Lidocaine inhibits neurite growth in mouse dorsal root ganglion cells in culture.

Recent clinical and experimental studies suggest the effectiveness of lidocaine in blocking neuropathic pain. Because it has been demonstrated that the pathogenetic mechanisms of neuropathic pain involve morphological changes in afferent neuronal terminals onto spinal cord, we examined the effects of lidocaine on neurite growth in isolated mouse dorsal root ganglion cells in culture. Incubation for 2-42 h with various concentrations of lidocaine (0.006 mM, 0.6 mM, and 30 mM) reduced the number of cells exhibiting neurites. The effects were time- and dose-dependent. Lidocaine therefore may exert its pharmacological effect, at least in part, by changing neuronal structures derived from sensory neurons.

Animals↗

Effect of the Pro12Ala variant of the human peroxisome proliferator-activated receptor gamma 2 gene on adiposity, fat distribution, and insulin sensitivity in Japanese men.

To examine the role of the Pro12Ala variant of the human PPARgamma2 gene on adiposity and insulin resistance, we studied the effect of the variant on fat distribution assessed by CT scan, plasma glucose, and insulin levels during a 75g oral glucose load in 215 non-diabetic Japanese men. The allele frequency of the variant was 0. 03 in this population. There were no differences in body mass index (BMI), subcutaneous fat area (S), visceral fat area (V), V/S ratio, fasting plasma insulin levels, or insulin resistance index in homeostatic model assessment between 203 subjects who were homozygous for the wild-type Pro12 allele and 12 subjects with the variant Ala12 allele (11 heterozygotes and one homozygote). These data suggest that the Pro12Ala variant is not a major contributor to adiposity, fat distribution, or insulin resistance in Japanese men.

Adipose Tissue↗

Regulation by an extract of embryonic chick brain of the densities of voltage-dependent Na+ and Ca2+ channels in embryonic chick skeletal muscle cells during their development in culture.

We studied the chronic effects of a brain extract (BE) prepared from chick embryonic brains on voltage-dependent Na+ channels (VDNCs) and Ca2+ channels (VDCCs) during the development of chick skeletal muscle cells in culture. The maximum rates of rise of Na+ and Ca2+ action potentials were measured electrophysiologically in an attempt to determine the effects of BE on the densities of these channels. The basic culture medium was supplemented with chick transferrin instead of whole-embryo extract and skeletal muscle cells were grown in the absence or in the presence of crude BE or fractionated BE. Long-term inclusion of BE to the culture medium increased the densities of both VDNCs and L-type VDCCs. By contrast, BE apparently decreased the density of T-type VDCCs. Our results indicate that BE contains some protein(s) that has a negative effect on the density of T-type VDCCs of skeletal muscle cells at a less differentiated stage and that this effect of BE is closely associated with subsequent regulation of the densities of VDNCs and L-type VDCCs. Possible roles of the influx of Ca2+ ions through T-type and L-type VDCCs in the control of the densities of VDNCs and L-type VDCCs are discussed.

Animals↗

[Immunohistochemical studies in depressed type adenomas of the stomach--comparison with protruded type adenomas and depressed type well differentiated mucosal gastric cancers].

In this study, we performed immunohistochemical studies using p53 and Ki-67 immunostaining in 48 depressed type adenomas, and compared with protruded type adenomas (n = 28) and depressed type well differentiated mucosal gastric cancers (mcancer: n = 46). Focal and diffuse p53 staining patterns were not noticed in depressed type adenomas and in protruded type adenomas, but were noticed in mcancers (focal: 4.3%, diffuse: 41.3%). Ki-67 positive cells were noticed in surface epithelium in 24.4% of depressed type adenomas, in 21.4% of protruded type adenomas and in 87.0% of mcancers. Ki-67 positive rate in foveolar epithelium (superior, middle, inferior) were noticed in (31.1%, 12.9%, 6.1%) of depressed type adenomas, in (33.4%, 15.4%, 6.9%) of protruded type adenomas and in (33.4%, 31.4%, 20.4%) of mcancers. These results suggest that from the point of immunohistochemistry, depressed type adenomas were similar to protruded type adenomas, but were different from mcancers.

Adenoma↗

Serum leptin levels are associated with hyperinsulinemia independent of body mass index but not with visceral obesity.

To examine the relationship between leptin levels and visceral obesity or plasma insulin levels, we studied serum leptin levels, fat distribution assessed by CT scan, and plasma insulin levels during 75 g oral glucose load in 100 Japanese men. Regression analysis adjusted by age and body mass index (BMI) showed leptin levels to be associated with visceral fat area(V)(p = 0.003), subcutaneous fat area(S)(p < 0.0001), and V + S(p < 0.0001), but not with V/S ratio(p = 0.897). By regression analysis adjusted by age, BMI, and V + S, serum leptin levels were still highly and positively correlated with plasma insulin levels during 75 g oral glucose load (p < 0.001), insulin resistance index(p < 0.001), and beta cell function index(p = 0.009) in homeostasis model assessment. These data suggest that hyperinsulinemia, but not visceral obesity, may be regulators of serum leptin levels independent of BMI.

Adult↗

A mutation of the beta 3-adrenergic receptor is associated with visceral obesity but decreased serum triglyceride.

The Trp64Arg mutation of the beta 3-adrenergic receptor (beta 3AR) is prevalent in several ethnic groups and is associated with weight gain, and some features of syndrome X such as insulin resistance and dyslipidaemia. Nevertheless, it is not known at present whether this mutation is associated with visceral obesity, which is an important risk factor for the development of hypertension, dyslipidaemia, insulin resistance, non-insulin-dependent diabetes mellitus, and atherosclerosis. To investigate whether this mutation may contribute to visceral obesity, we studied the relationships between beta 3AR genotypes and clinical phenotypes. The Trp64Arg allele of beta 3AR was examined in 278 Japanese men with respect to variables relating to visceral obesity assessed by computerised tomography. To detect the Trp64Arg mutation, polymerase chain reaction-restriction fragment length polymorphism analysis using Bst NI digestion was performed. This mutation was more frequently observed in subjects with higher body mass index (BMI) (p = 0.02). Moreover, in 120 subjects with a moderate degree of obesity (22 < or = BMI < 26.4 kg/m2), the mutation (homozygotes and heterozygotes) was associated with visceral obesity (higher ratio of visceral to subcutaneous fat area; V/S) (p = 0.03). Furthermore, the Trp64Arg allele was more frequent in subjects with lower serum triglyceride levels (p = 0.02) and the Trp64Arg homozygotes, but not heterozygotes, exhibited lower triglyceride levels. Thus, this mutation appears to be associated with visceral obesity but with lower serum triglyceride. It is suggested that those with the mutation may describe a subset of subjects characterized by decreased lipolysis in visceral adipose tissue.

Adult↗

The effect of a collagenous implant on deep dermo-periosteal defects in the rabbit.

In plastic surgery, extensive wounds with exposed bone and loss of the periosteum (i.e., deep dermo-periosteal defects) are difficult to treat, even with split-thickness skin grafts, because such grafts rarely survive. Even when these grafts do survive, functional impairment often occurs subsequently. The application of a collagen sponge (Terudermis, Terumo, Tokyo) to such wounds has previously been reported to accelerate granulation tissue formation, resulting in would healing and graft survival. However, this previous report only presented data relating to gross morphological appearance. In this paper, we present histological evidence to demonstrate the beneficial effect of the collagen sponge on experimental dermo-periosteal scalp defects in rabbits. About two weeks after the application of collagen sponge to the experimental wounds, a well-vascularized granulation tissue was formed. Autologous split-thickness skin grafts applied to this new granulation tissue were found to be viable one week after grafting. The results confirm histologically that collagen sponge is effective for the treatment of deep dermo-periosteal defects which would not have regenerated skin cover with conventional therapies such as skin grafting or the temporary use of dermoprotective materials followed by skin grafting.

Animals↗

[Gastric mucosal atrophy and prevalence of Helicobacter pylori in reflux esophagitis of the elderly].

This study is aimed at a role of Helicobacter pylori (HP) infection in reflux esophagitis of the elderly. 46 patients with reflux esophagitis aged at older than 60 years are selected for this study with informed consent. 43 patients without reflux esophagitis, peptic ulcer, and gastric cancer are used as a control group. In reflux esophagitis, gastric mucosal atrophy is judged as closed type of endoscopic findings in all cases. In control, 27 of 43 patients were judged as open type. Serum pepsinogen I, II ratio is 4.73 +/- 1.28 which is higher significantly than 3.39 +/- 1.69 in control. Serological positive rate of HP antibody is 39.1% in reflux esophagitis. This rate is significantly lower than 62.7% in control. In conclusion, low frequency of chronic HP infection protects gastric mucosa from atrophy, and keeps secretion of gastric acid, resulting in reflux esophagitis of the elderly accompanied with various abnormal esophago-gastric functions.

Aged↗

A new type of biomaterial for artificial skin: dehydrothermally cross-linked composites of fibrillar and denatured collagens.

A new type of biomaterial for artificial skin was developed as a form of sponge by combining fibrillar collagen (F-collagen) with gelatin. The sponge was physically and metabolically stabilized by introducing dehydrothermal cross links. To get the final product, various conditions in the preparation of sponges were evaluated by in vitro cellular responses and in vivo tissue reactions. Fibroblasts placed on a sponge of gelatin attached themselves to it, migrated well into the sponge, and remained inside it for at least 7 days. However, sponges of gelatin showed structural instability for hydrolytic degradation by the cells. Most fibroblasts appeared not to penetrate into the interior of a sponge of F-collagen but to remain on its surface when fibroblasts were placed on the sponge, suggesting poor attraction of F-collagen toward cells. Implantation experiments of sponges of F-collagen revealed an intense infiltration of neutrophils into the sponge, indicating F-collagen as an inducer of the inflammatory reaction. These aggravating characters of F-collagen sponges were greatly improved by blending gelatin with F-collagen. The new type of collagen-based biomaterials developed in the present study is expected to become a useful matrix substance for artificial skin.

Animals↗

Helical volume CT and its clinical significance.

Helical Volume CT (HVCT) is an X-ray CT scanning technique in which the patient is scanned continuously while the couch-top is moved in the axial direction. It is performed using the Toshiba TCT-900S CT scanner jointly developed by the authors and Toshiba Corporation. This scanner features a large central opening, the inner surface of which is lined with a circular array of 2,304 detectors. The X-ray tube rotates outside the detector array at the rate of one revolution per second. Electrical power is supplied to the X-ray tube through a slip ring mechanism, permitting the X-ray to be continuously generated without any interscan delay. The X-ray tube and detectors move in a "nutate/rotate" pattern. The maximum scanning time is 30 seconds (equivalent to a single breath-hold). To improve image quality, the slice thickness can be selected to equal the distance over which the couch-top moves in one second. The clinical advantages of HVCT are as follows: (1) the examination time is significantly reduced (to minimize the patient's discomfort), (2) continuous data of anatomical structures can be obtained without artifacts due to respiratory motion, and (3) it is possible to obtain superior images for multiplanar reconstruction (MPR), cine-display, and three-dimensional reconstruction.

Humans↗

Transitory cardiovascular responses to rapid infusion of blood into aorta of rabbit.

Blood (5 to 15 ml) was infused into aorta of the anesthetized rabbit through the carotid artery or femoral artery at a constant rate (0.55 to 8.3 ml/s). The carotid sinuses were occluded. The systemic arterial pressure (SAP) began to rise immediately at the onset of the infusion and dropped gradually in most cases during the infusion. SAP continued to decline after the infusion and in many cases became lower than the preinfusion pressure. Within seconds, SAP tapered off to its lowest point and resumed a gradual rise, leveling off higher than its initial pressure. A depressor effect caused by the rapid infusion of blood into the aorta (DRIA) was observed in every rabbit. DRIA was not suppressed much by the section of aortic or vagal nerves. DRIA was markedly suppressed by the administration of alpha-adrenergic blockade, but beta-adrenergic blockade had little effect on DRIA. By using a hydraulic model of the closed circulatory system, a theoretical analysis was made on the basis of the "theory of active fluid element," a theory developed by Hatakeyama, one of the authors, and it was demonstrated that DRIA must not be considered to be a passive hemodynamic phenomenon. The results obtained suggest that a nervous regulatory mechanism--rather than the reflex via the carotid sinus or aortic baroreceptors, or other mechanoreceptors--plays an important part in the venous and the cardiac regions.

Adrenergic alpha-Antagonists↗