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Biomedical subjects

T Dohi

Publications and source records attributed to T Dohi.

At least 37 records · Page 2Linked to original sources

Effect of the sinus of valsalva on the closing motion of bileaflet prosthetic heart valves.

Conventional bileaflet prosthetic mechanical heart valves close passively with backflow. Naturally, the valve has problems associated with closure, such as backflow, water hammer effect, and fracture of the leaflet. On the other hand, in the case of the natural aortic valve, the vortex flow in the sinus of Valsalva pushes the leaflet to close, and the valve starts the closing motion earlier than the prosthetic valve as the forward flow decelerates. This closing mechanism is thought to decrease backflow at valve closure. In this study, we propose a new bileaflet mechanical valve resembling a drawbridge in shape, and the prototype valve was designed so that the leaflet closes with the help of the vortex flow in the sinus. The test valve was made of aluminum alloy, and its closing motion was compared to that of the CarboMedics (CM) valve. Both valves were driven by a computer controlled hydraulic mock circulator and were photographed at 648 frames/s by a high speed charge-coupled device (CCD) camera. Each frame of the valve motion image was analyzed with a personal computer, and the opening angles were measured. The flow rate was set as 5.0 L/min. The system was pulsed with 70 bpm, and the systolic/diastolic ratio was 0.3. Glycerin water was used as the circulation fluid at room temperature, and polystyrene particles were used to visualize the streamline. The model of the sinus of Valsalva was made of transparent silicone rubber. As a result, high speed video analysis showed that the test valve started the closing motion 41 ms earlier than the CM valve, and streamline analysis showed that the test valve had a closing mechanism similar to the natural one with the effect of vortex flow. The structure of the test valve was thought to be effective for soft closure and could solve problems associated with closure.

Alloys↗

Mice deficient in Th1- and Th2-type cytokines develop distinct forms of hapten-induced colitis.

BACKGROUND & AIMS: Most experimental models for inflammatory bowel disease in mice are associated with production of interferon (IFN)-gamma and other proinflammatory cytokines. We hypothesized that T-helper 2 (Th2)-type cells could also contribute to the colitis and cause inflammation different than that mediated by Th1-type cells. METHODS: Trinitrobenzene sulfonic acid (TNBS)-induced colitis in C57BL/6 background mice genetically deficient in interleukin (IL)-12 p40 (IL-12(-/-)), IFN-gamma (IFN-gamma(-/-)), or IL-4 (IL-4(-/-)) was examined in comparison with control mice (C57BL/6(+/+)). RESULTS: C57BL/6(+/+), IFN-gamma(-/-), and IL-12(-/-) mice developed patterns of colitis characterized by distortion of crypts, loss of goblet cells, and mononuclear cell infiltration with fibrosis of the mucosal layer. IL-4(-/-) mice had greater mortality than other groups because of penetrating ulcers; however, survivors developed milder lesions that were limited to focal acute ulceration. Colonic CD4(+) T cells from normal, IFN-gamma(-/-), or IL-12(-/- )mice produced both IL-4 and IL-5. CONCLUSIONS: In TNBS colitis, Th1-like cytokine responses induce fatal, acute, transmural, and focal types of lesions, whereas Th2-like cytokine responses play a significant role in the diffuse atrophic changes in crypts and the mucosal layer that occur in the late stages of this disease.

Animals↗

Evidence for GABA(A) receptor agonistic properties of ketamine: convulsive and anesthetic behavioral models in mice.

UNLABELLED: We examined the potentiation by ketamine of the gamma-aminobutyric acid(A) (GABA(A)) receptor function using convulsive and anesthetic behavioral models in adult male ddY mice. General anesthetic potencies were evaluated by a rating scale, which provided the data for anesthetic scores, loss of righting reflex, duration, and recovery time. All drugs were administered intraperitoneally. Small subanesthetic doses of ketamine did inhibit tonic seizures induced by a large dose of the GABA(A) receptor antagonist bicuculline (8 mg/kg). The 50% effective dose value was 15 (95% confidence limits 10-22) mg/kg. Even large anesthetic doses (100-150 mg/kg) did not suppress clonic seizures in 50% of the animals. The GABA(A) receptor agonist, muscimol (0.32-1.12 mg/kg), potentiated ketamine-induced anesthesia in a dose-dependent fashion (P < 0.05). Similarly, the benzodiazepine receptor agonist, diazepam (1-3 mg/kg), augmented ketamine anesthesia in a dose-dependent manner (P < 0.05). Bicuculline (2-5 mg/kg) dose-dependently antagonized ketamine-induced anesthesia (P < 0.05). Neither the benzodiazepine receptor antagonist, flumazenil (2-20 mg/kg), nor the GABA synthesis inhibitor, L-allylglycine (200 mg/kg), affected the anesthetic action of ketamine. These results suggest that ketamine has GABA(A) receptor agonistic properties and that ketamine-induced anesthesia is mediated, at least in part, by GABA(A) receptors. IMPLICATIONS: We examined the potentiation by ketamine of the gamma-aminobutyric acid(A) receptor function using convulsive and anesthetic behavioral models in mice. Subanesthetic doses of ketamine-inhibited tonic convulsions induced by the gamma-aminobutyric acid(A) receptor antagonist bicuculline. The gamma-aminobutyric acid(A) receptor agonist, muscimol, potentiated ketamine-induced anesthesia. Bicuculline antagonized ketamine anesthesia, but the benzodiazepine receptor antagonist, flumazenil, and the gamma-aminobutyric acid synthesis inhibitor, L-allyglycine, did not. The effects of ketamine on the gamma-aminobutyric acid(A) receptors appear to correlate with its anesthetic actions.

Allylglycine↗

Changes in seizure susceptibility to local anesthetics by repeated administration of cocaine and nomifensine but not GBR12935: possible involvement of noradrenergic system.

We examined cross-sensitization of cocaine and synthetic local anesthetics to their seizure susceptibility after repeated administration. Seizure susceptibility of procaine and lidocaine increased after the end of two days of treatment with a subconvulsive dose of cocaine. Acute treatment with nomifensine but not GBR12935, a specific inhibitor of the dopamine transporter, facilitated lidocaine-induced convulsion. Furthermore, daily treatment with nomifensine for two days enhanced lidocaine-induced convulsion. These results suggest the possible involvement of the brain noradrenergic system in the changes in seizure susceptibility after repeated administration of some local anesthetics.

Anesthetics, Local↗

[A case of hypothyroidism found by delayed awakening after the operation].

We report a case of hypothyroidism found by delayed awakening after surgery. A 55-year-old male patient had been suffering from elevated creatine phosphokinase (CPK) and cartinoembryonic antigen (CEA) of unknown origin before the operation. Laparoscopic cholecystectomy was performed under general anesthesia combined with epidural block. Hypotension, low arterial oxygen saturation, hypothermia and metabolic acidosis developed and continued during the operation. Awakening was delayed for about two hours postoperatively. Specific examination resulted in a definitive diagnosis of hypothyoidism. We should pay careful attention to any patient with elevated CPK and CEA of unknown origin before surgery, continuous hypotension, respiratory and circulatory failure and metabolic disorder during surgery, and delayed awakening after surgery that may be the result of hypothyroidism.

Aged↗

Hapten-induced colitis is associated with colonic patch hypertrophy and T helper cell 2-type responses.

To investigate the potential involvement of T helper (Th)2-type responses in murine models of intestinal inflammation, we used trinitrobenzene sulfonic acid (TNBS)-hapten to induce inflammatory bowel disease in situations where Th1-type responses with interferon (IFN)-gamma synthesis are either diminished or do not occur. Intracolonic administration of TNBS to either normal (IFN-gamma+/+) or Th1-deficient IFN-gamma knockout (IFN-gamma-/-) BALB/c mice resulted in significant colitis. In IFN-gamma-/- mice, crypt inflammation was more severe than in IFN-gamma+/+ mice and was accompanied by hypertrophy of colonic patches with a lymphoepithelium containing M cells and distinct B and T cell zones resembling Peyer's patches. Hapten-specific, colonic patch T cells from both mouse groups exhibited a Th2 phenotype with interleukin (IL)-4 and IL-5 production. TNBS colitis in normal mice treated with anti-IL-4 antibodies or in IL-4(-/-) mice was less severe than in either IFN-gamma+/+ or IFN-gamma-/- mice. Our findings now show that the Th2-type responses in TNBS colitis are associated with colonic patch enlargement and inflammation of the mucosal layer and may represent a model for ulcerative colitis.

Animals↗

Dominant negative isoform of rat norepinephrine transporter produced by alternative RNA splicing.

We have cloned from rat brain a family of alternatively spliced cDNAs from a single gene, which encodes a norepinephrine transporter (NET) having variations at the 3'-region including both coding and noncoding regions. This produces two transporter isoforms, rNETa and rNETb, which differ at their COOH termini. The rNETa isoform reveals a COOH terminus homologous to human NET and transports norepinephrine. In contrast, rNETb revealed no detectable transport function but reduced functional expression of rNETa when both isoforms were expressed in the same cell. Thus, rNETb potentially functions as a dominant negative inhibitor of rNETa activity. Co-expression of rNETb with a gamma-aminobutyric acid transporter (rGAT1), a serotonin transporter (rSERT), and a dopamine transporter (rDAT) reduced their transport activity. No reduction was found with the glutamate/aspartate transporter (rGLAST). Alternative RNA splicing of NET suggests a novel mechanism for the regulation of synaptic transmission.

Alternative Splicing↗

Molecular cloning and characterization of rat trp homologues from brain.

Identification of trp (transient receptor potential) gene from Drosophila photoreceptor and subsequent molecular cloning of the human cDNA homologues suggest its participation in capacitative calcium entry (CCE) or so called store-operated Ca2+ channel (SOC). We identified five different trp-related amplifications of reverse-transcription-polymerase chain reaction (RT-PCR) from rat brain; these corresponded to mouse trp homologues, mtrp1,3,4,5,6 and were distributed in various tissues with multiple expression levels. Two cDNAs, homologous to Drosophila trp from rat brain, designated rtrp3 and rtrp6, were isolated and characterized. By RT-PCR analysis, mRNAs of rtrp3 and rtrp6 were found to be expressed differently in brain and other tissues. In situ hybridization analysis revealed that rtrp6 mRNA was preferentially expressed in hippocampal dentate gyrus and cortical layers II and III. Expression of rat TRP3 and TRP6 in COS cells revealed an increase in CCE, as compared to that in the mock-transfected COS cells of the control. Isolation of cDNAs of rat trp gene family provides a useful model for studying mechanism of CCE.

Animals↗

A new safe laparoscopic manipulator system with a five-bar linkage mechanism and an optical zoom.

This paper describes a new type of laparoscopic manipulator system designed with regard to its safety and sterilization in medical settings. It consists of a laparoscope manipulator using a five-bar linkage mechanism, an optical zoom called the automatic microzoom laparoscope, and a man-machine interface called the Head-Mouse system. The movement of the laparoscope manipulator in the X-Y plane determines the angle of the laparoscope, and the optical zoom substitutes for back-and-forth movements. This system achieves intrinsic safety and ease of sterilization due to limitations in the range of movement. The system achieves high reliability because of the simplicity of both its mechanism and its software. The newly developed optical zoom avoids the possibility of contact with organs by eliminating the back-and-forth movements of the laparoscope required for close-up observation while preserving a high-quality laparoscopic image. The Head-Mouse system for man-machine interface was designed to avoid incorrect inputs by the surgeon. To evaluate the performance of this newly developed system, an experiment was conducted in which a surgeon used the system to perform an in vivo laparoscopic cholecystectomy on a pig.

Animals↗

Phospholipid turnover in the inflamed intestinal mucosa: arachidonic acid-rich phosphatidyl/plasmenyl-ethanolamine in the mucosa in inflammatory bowel disease.

Cytosolic phospholipase A2 (PLase A2) is activated by low Ca2+ concentrations and translocates from the cytosol to the cell membrane, releasing arachidonic acid; the arachidonic acid cascade then leads to the production of many inflammatory mediators. The aim of this study, accordingly, was to investigate the role of phospholipid metabolism in the intestinal mucosa in inflammatory bowel disease (IBD). Surgically resected specimens from patients with Crohn's disease (CD), ulcerative colitis (UC), and colrectal cancer (non-cancerous tissue; as a control) were submitted to phospholipid analysis and a PLase A2 assay, which measures the degradation of endogenous mucosal phospholipids. A high percentage of plasmenylethanolamine (plas.E) was detected in the glycerophospholipid fraction of CD mucosa. The arachidonic acid content of the phosphatidylethanolamine plus plas.E subfraction was higher in inflamed than in intact mucosa in CD. PLaseA2 activity, resulting in lysophosphatidyl ethanolamine production, was detected only in inflamed mucosa from CD and UC patients, but not in normal mucosa from controls. PLaseA2 activity was highest in moderately inflamed mucosa adjacent to a severely ulcerated area. The PLaseA2 that reacts with endogenous phosphatidylcholine (PC) to form lysoPC was found irrespective of the presence of inflammation. The PLaseA2 that reacts with ethanolamine-containing phospholipids is more closely related to inflammation than other PLaseA2 isoenzymes in IBD mucosa.

Adult↗

Preliminary study on the new self-closing mechanical mitral valve.

Anatural mitral valve starts closing before systole. Conventional mechanical mitral valves start their closing motion after systole. In order to let the mechanical mitral valves start closing before systole, we propose a new self-closing valve by adjusting the center of gravity of the leaflet. As a first step, we adjusted the center of gravity by attaching a block of lead to the leaflet of a CarboMedics bileaflet valve and evaluated it using a pulse duplicator and an x-ray high-speed video camera. Comparative study was conducted under 60 bpm and 4 L/min as the mean flow rate. It was clarified that the self-closing valve started closing before systole, no influence on inflow volume was found, the final closing speed of the self-closing valve just before complete closure was slower than the conventional valve (1.9-0.34 m/s), a design strategy of a self-closing valve (sewing ring diameter 29 mm) was obtained from the experiment that momentum of inertia of the leaflet should be less than 14.9 x 10-9 kg.m2 and the torque caused by gravity should be more than 4.2 x 10-6 N. m, and only one leaflet should be designed as self-closing, and surgeons need to pay attention to the positioning of the two leaflets. In conclusion, the preliminary study showed the ability of starting to close before systole and the design strategy for future prototyping.

Biocompatible Materials↗

Experimental study on hemolysis in centrifugal blood pumps: improvement of flow visualization method.

To evaluate rotary blood pumps, flow visualization is commonly applied to determine the flow patterns in a centrifugal blood pump, which have a relationship to its hemolytic performance. However, it is very troublesome to visualize the flow near the vanes due to the high rotational speed of the impeller. The rotational speed of the impeller in a centrifugal blood pump is usually several hundred revolutions per minute. In this study, we combined a high-speed video camera based imaging method and an optical system in which the image of the rotating impeller was kept stationary. In the optical system, a prism rotating at half the speed of the impeller reflected the image of the impeller. The resultant reflected image was observed by a high-speed video camera through a half mirror. With this optical setup, the image through the half mirror became stationary, and the path of a specific tracer particle could be traced for a longer duration. A longer duration of measurements and better quality of the obtained images were realized through this improvement. Movement of a specific tracer from the inlet portion to the outlet portion of the impeller could be examined using the developed method.

Acrylic Resins↗

Propofol anaesthesia in mice is potentiated by muscimol and reversed by bicuculline.

We have examined the role of gamma-aminobutyric acid (GABA) neurones in propofol anaesthesia in mice using the righting reflex. Propofol i.p. increased the percentage of loss of the righting reflex in a dose-dependent manner with an ED50 value of 140 (95% confidence limits 123-160) mg kg-1 (n = 40; eight animals per dose, five doses per dose-response curve). The ED50 for propofol decreased significantly to 66 (58-75) mg kg-1 in the presence of the GABAA receptor agonist muscimol 1 mg kg-1 i.p. (n = 40) (P < 0.05). In contrast, the ED50 increased significantly to 240 (211-274) mg kg-1 in the presence of the antagonist bicuculline 5 mg kg-1 i.p. (n = 40) (P < 0.05). Our results suggest that propofol anaesthesia may be mediated, at least in part by GABA neurons.

Anesthetics, Local↗

gammadelta T cells regulate mucosally induced tolerance in a dose-dependent fashion.

We used gammadelta TCR-deficient (TCRdelta(-/-)) mice to examine the role of gammadelta T cells for induction of mucosal responses and systemic tolerance to high versus low doses of oral antigen. When either TCRdelta(-/-) or TCRdelta(+/+) mice were immunized orally with a high dose of ovalbumin (OVA) prior to parenteral challenge, systemic IgG and IgE antibody responses were markedly reduced in both types of mice, while mucosal IgA responses were reduced only in the TCRdelta(-/-) mice. Reduced T cell proliferative responses and delayed-type hypersensitivity were seen in TCRdelta(-/-) and TCRdelta(+/+) mice given the high dose of OVA. Antigen-induced T(h)1 and T(h)2 cytokine production by splenic CD4(+) T cells was severely inhibited in orally tolerized TCRdelta(-/-) and TCRdelta(+/+) mice. In contrast, while oral tolerance associated with increased levels of IL-10 synthesis was induced by a low dose of OVA in TCRdelta(+/+) mice, the TCRdelta(-/-) mice were not tolerized and failed to produce IL-10. Our findings indicate that gammadelta T cells play a significant immunoregulatory role in IL-10-mediated, low-dose oral tolerance induction, but are not essential participants in the induction of systemic tolerance to orally introduced antigens given in larger doses.

Animals↗

[Prospect of computer aided surgery].

To develop the new surgical fields of minimally invasive surgery, noninvasive surgery, virtual reality microsurgery, telesurgery, fetal surgery and others in the next century, it is necessary to use various advanced technologies; surgical robots, three-dimensional medical images etc. based on computer technology. Therefore, this new surgical field is called Computer Aided Surgery (CAS). Three-dimensional medical images provide the most recognizable information for medical doctors and the most advanced visualization for surgeons. Surgical robots function as advanced hands for surgeons, but do not perform the same actions as surgeons wielding scissors or scalpel. The advanced vision and hands available to surgeons are creating a new surgical environment. The philosophy behind the development of surgical robots is to assist surgeons in difficult procedures and extend the greatest possible help to patients with incurable disease.

Surgical Procedures, Operative↗

MPP+ toxicity and plasma membrane dopamine transporter: study using cell lines expressing the wild-type and mutant rat dopamine transporters.

The Parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium (MPP+) causes specific cell death in dopaminergic neurons after accumulation by the dopamine transporter (DAT). COS cells, a non-neuronal cell line insensitive to high doses of MPP+, becomes sensitive to MPP+ when transfected with the rat DAT cDNA. We analyzed the bi-directional transport of MPP+ and its toxicity in several cell lines expressing wild or mutant DATs. Cell death in COS cells expressing wild DAT by exposure to MPP+ was concentration-dependent and cocaine-reversible. Increased wild DAT expression caused higher sensitivities to the toxin in HeLa cells. Although several mutant DATs demonstrated greater transport activity than the wild-type, they displayed similar or lower sensitivity to MPP+ toxicity. Reverse transport of preloaded [3H]MPP+ through DAT was facilitated in COS cells expressing certain mutant DATs, which consistently displayed less sensitivity to MPP+ toxicity. These results suggest that re-distribution of MPP+ due to influx/efflux turnover through the transporter is a key factor in MPP+ toxicity.

1-Methyl-4-phenylpyridinium↗

Dihydroheptaprenyl and dihydrodecaprenyl monophosphates induce apoptosis mediated by activation of caspase-3-like protease.

Dolichyl phosphate, an essential carrier lipid in the biosynthesis of N-linked glycoprotein, has been found to induce apoptosis in rat glioma C6 cells and human monoblastic leukemia U937 cells. In the present study, dolichyl phosphate and structurally related compounds were examined regarding their apoptosis-inducing activities in U937 cells. Dihydroheptaprenyl and dihydrodecaprenyl phosphates, of which isoprene units are shorter than that of dolichyl phosphate, induced apoptosis in U937 cells. This phenomenon occurred in a dose- and time-dependent manner, as seen with dolichyl phosphate-induced apoptosis. Derivatives of the same isoprene units of dolichyl phosphate, such as dolichol, dolichal or dolichoic acid, did not induce DNA fragmentation. Farnesyl phosphate and geranylgeranyl phosphate also failed to induce apoptosis. During apoptosis, the caspase family of cysteine proteases play important roles. We observed that apoptosis induced by dihydroprenyl phosphate was mediated by caspase-3-like (CPP32-like) activation but not by caspase-1-like (ICE-like) activation. This caspase-3-like activation was inhibited by a specific inhibitor of caspase-3, DEVD-CHO, but not by an caspase-1 inhibitor YVAD-CHO. We interpret these results to mean that dihydroprenyl phosphates with more than seven isoprene units have apoptosis-inducing activity and that their signal is mediated by caspase-3-like activation.

Apoptosis↗