Biomedical subjects
Publications and source records attributed to H Takeda.
A case of a 61 year old man who developed early esophageal cancer on top of a leiomyoma located in the upper third of the esophagus is described. Both lesions were successfully treated by endoscopic resection, without recurrence on short-term-follow-up.
The cause of gastric cell injury induced by Helicobacter pylori was investigated in vitro using gastric mucosal cells derived from male Japanese white rabbits. To evaluate the contribution of the potent urease activity of H. pylori to gastric mucosal cell injury, the supernatant of the H. pylori bacterial pellet, solubilized with N-octyl-glucoside, was added to the gastric mucosal cell suspension. Cell injury was assessed by lactate dehydrogenase (LDH) release into the extracellular fluid. Treatment of cells with H. pylori extracts together with urea resulted in high levels of LDH release, suggesting definite gastric mucosal cell injury, and elevation of ammonia concentration was also observed. In contrast, incubation with H. pylori extracts alone or urea solution alone did not result in increased LDH release or elevated ammonia concentrations. The degree of LDH release from gastric mucosal cells due to H. pylori extracts in the presence of urea was similar to that induced by administration of the same amount of exogenous ammonia. The addition of acetohydroxamic acid, a potent specific urease inhibitor, remarkably inhibited ammonia production, the elevation of pH of extracellular fluid, and LDH release in a dose-dependent manner. These results suggest that ammonia produced by potent urease activity of H. pylori in the presence of urea plays an important role in the pathogenesis of gastric mucosal cell injury.
To determine the mechanisms of gastric mucosal injury associated with Helicobacter pylori infection, we investigated the contents of cytokines and inflammatory cell infiltration in the gastric mucosa. Ninety-six patients with dyspepsia were studied (58 gastric ulcer, 38 nonulcer dyspepsia). Of the 96 patients, 63 were infected with H. pylori as determined by microscopic examination with HE staining, culture of H. pylori, or the rapid urease test. Endoscopic biopsy specimens were obtained from both the antrum and the body to examine interleukin (IL)-8, IL-6, IL-1 beta, and tumor necrosis factor-alpha contents in the gastric mucosa by enzyme-linked immunosorbent assay. Inflammatory cell infiltration was assessed according to the Sydney system. IL-8 content was enhanced in both the antral and body mucosa of the H. pylori-positive patients compared with the H. pylori-negative patients. Furthermore, IL-8 content correlated well with the infiltration of both mononuclear cells and polymorphonuclear cells. These results suggest that IL-8 plays important roles in the pathogenesis of gastric mucosal injury associated with H. pylori infection.
As power sources for rehabilitation equipment, electric, hydraulic, and pneumatic actuators have been used. However a more human-sized and higher powered actuator that can reduce the equipment size is desired. A new metal hydride (MH) actuator that uses the reversible reaction between the heat energy and mechanical energy of a hydrogen absorbing alloy has recently attracted much attention. The MH actuator is characterized by its small size, low weight, noiseless operation and a compliance similar to that of the human elbow joint. Therefore, the MH actuator has the characteristic of being light and easy to use and so is suitable for use in medical and rehabilitation applications. Some lifting devices using this actuator have already been developed and are being used for the care of the aged and disabled. The characteristics of the MH actuator are presented and then some applications are introduced in this paper. It is our opinion that in our aging society the MH actuator will play an important role in the development of medical and rehabilitation equipment.
Toxic epidermal necrolysis (TEN) is a severe blistering skin disease of high mortality. TEN may occur after bone marrow transplantation (BMT). In such cases, TEN have been attributed to graft-versus-host disease (GVHD) or an adverse drug reaction. It is very difficult to distinguish the causes of TEN after BMT. We report a 21-year-old Japanese man who developed TEN eight days after BMT, evaluate the differential diagnosis of hyperacute GVHD and an adverse drug reaction, and deduce that hyperacute GVHD was the more likely pathogenesis of TEN in this patient.
For the development of a totally implantable ventricular assist system (VAS), we have been developing the vibrating flow pump (VFP), which can generate oscillated blood flow with a relatively high frequency (10-50 Hz) for a totally implantable system. In this study, effects of left ventricular assistance with this unique oscillated blood flow were analyzed by nonlinear mathematics for evaluation as the entire circulatory regulatory system, not as a separate part of the system. Left heart bypasses using VFPs from the left atriums to the descending aortas were performed in chronic animal experiments using healthy adult goats. Electrocardiogram (ECG), arterial blood pressure, VFP pump flow, and flow of the descending aorta data taken while the goats were awake were recorded in the data recorder and analyzed in the personal computer system through the AD convertor. Using nonlinear mathematics, time series data were embedded into the phase space, and the Lyapunov numerical method, fractal dimension analysis, and power spectrum analysis were performed to evaluate the nonlinear dynamics. During left ventricular assistance with the VFP, Mayer wave fluctuations were decreased in the power spectrum, the fractal dimension of the hemodynamics was significantly decreased, and peripheral vascular resistance was significantly decreased. These results suggest that nonlinear dynamics, which mediate the cardiovascular dynamics, may be affected during LV bypass with oscillated flow. Decreased power of the Mayer wave in the spectrum caused the limit cycle attractor of the hemodynamics and decreased the peripheral resistance. Decreased sympathetic discharges may be the origin of the decreased Mayer wave and fractal dimension. These nonlinear dynamical analyses may be useful to design the optimal VAS control.
Pulmonary arterial impedance is an important and interesting characteristic that can be used to evaluate the physiological properties of the pulmonary vessel. However, power spectrum analysis of the pulmonary artery pressure and flow pattern have suggested that peak power in the relatively high frequency range (> 10 Hz) is significantly low; thus, we cannot analyze the vessel properties in the high frequency range. In this study, we used the newly developed vibrating flow pump (VFP), which can generate oscillated blood flow with a relatively high frequency (10-50 Hz) for right heart bypass, to evaluate the pulmonary arterial impedance pattern in the high frequency range. Acute animal experiments of the right heart bypass from the right atrium to the pulmonary artery using 6 healthy adult goats were performed. The flow pattern and pressure of the pulmonary artery, electrocardiograms (ECGs), and arterial and right atrial pressures were continuously monitored during the experiments. Spectral analysis of the hemodynamic parameters using the fast Fourier transform (FFT) method was performed to evaluate the spectral properties. The coherence function, transfer function, and phase patterns were calculated to analyze the impedance pattern in the relatively high frequency area. Previously, various investigators had tried to analyze the impedance patterns of the pulmonary artery; however, they could not analyze the impedance patterns over 10 Hz because the spectral patterns of the pulmonary flow do not have high power at high frequencies. These physiological analyses may be useful in designing the optimal pulmonary circulation.
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In the present study, we examined mechanisms of Porphyromonas gingivalis lipopolysaccharide (P-LPS)-stimulated bone resorption via CD14, one of the lipopolysaccharide (LPS) receptors, and also assessed the inhibitory action of several kinds of antibiotics on the LPS-induced stimulation. First, we observed by using mouse embryonic calvarial cells that P-LPS stimulated bone resorption through the action of endogenous interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) via CD14 because (i) P-LPS-stimulated expression of IL-1beta and IL-6 genes in calvarial cells was inhibited by an anti-mouse CD14 antibody, (ii) stimulated bone resorption was markedly inhibited by both IL-1beta and IL-6 antibodies, and (iii) P-LPS-stimulated bone resorption was clearly neutralized by an anti-mouse CD14 antibody. Next, we examined the effects of several kinds of antibiotics on P-LPS-stimulated bone resorption via CD14. Two of them, chloramphenicol and erythromycin, inhibited P-LPS-stimulated bone resorption in a dose-dependent manner. In an additional experiment, we observed that chloramphenicol clearly inhibited P-LPS-stimulated expression of the CD14, IL-1beta, and IL-6 genes in calvarial cells. These results suggest that chloramphenicol might be a useful antibiotic as an anti-inflammatory agent against P-LPS-stimulated periodontal destruction occurring via CD14 in periodontal disease.
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This study was undertaken to examine whether a sulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor, captopril, improves postischemic cardiac function and myocardial metabolism in the perfused working rat heart, and to elucidate the mechanism by which captopril protects the myocardium from postischemic damage. Isolated rat hearts were perfused by the working heart technique for 15 min. Ischemia was then induced for 30 min by lowering the afterload pressure and coronary flow to zero. After ischemia, hearts were reperfused for 30 min by returning afterload pressure to 60 mmHg. Captopril, a non-sulfhydryl-containing ACE inhibitor, enalapril, or a type 1 angiotensin II receptor antagonist, DuP 753, was added to the perfusate 5 min before ischemia, and the treatment was continued during the first 10-min period of reperfusion. In all groups there was no significant difference in pressure-rate product, coronary flow, tissue levels of ATP, total adenine nucleotides (TANs), energy charge potential (ECP), or creatine phosphate (CrP) before and during ischemia. During reperfusion following ischemia, captopril significantly improved the recovery of pressure-rate product, coronary flow, and tissue levels of ATP, TAN, ECP, and CrP, but neither enalapril nor DuP 753 had an effect. In conclusion, captopril improved postischemic cardiac function and myocardial metabolism in the perfused rate heart and its effect was independent of the blunting of angiotensin II formation.
To examine the effects of a specific cysteinyl leukotriene (cysLT) antagonist, pranlukast, on allergic rhinitis, antigen-induced rhinitis in guinea pigs was modified by pretreatment with an cyclooxygenase inhibitor (indomethacin) followed by an H1-blocker (pyrilamine). Intranasal ovalbumin (OVA) administration in actively sensitized guinea pigs resulted in concentration-dependent increases in nasal permeability and nasal airway resistance (NAR). Although pyrilamine (1 mg/kg, i.v.) abolished these antigen-induced changes, pretreatment with indomethacin (5 mg/kg, i.v.) followed by pyrilamine enhanced these responses to a degree similar to that observed with OVA challenge alone. Analyses of nasal perfusate in indomethacin/pyrilamine-pretreated animals showed that cysLTs increased by 270.8%, whereas thromboxane B2 decreased by 88.3% as compared with those on challenged with OVA alone. Oral administration of pranlukast (1-10 mg/kg) dose-dependently prevented increases in nasal permeability and NAR of indomethacin/pyrilamine-pretreated animals. However, an anti-allergic agent, azelastine, did not affect these responses. These results indicate that pranlukast suppresses antigen-induced cysLT-mediated responses of allergic rhinitis in actively sensitized guinea pigs. A cysLT antagonist, pranlukast, may thus prevent cysLT-mediated symptoms of allergic rhinitis.
To examine whether cysteinyl leukotrienes (cysLTs: LTC4, LTD4 and LTE4) induce symptoms of allergic rhinitis via their receptors, we studied the following: i) the specific binding of radiolabeled cysLTs to guinea pig nasal mucosa membrane and ii) effects of nasal LTD4 challenge in normal guinea pigs. The binding study indicated that there was a single population of binding sites for LTC4, LTD4 and LTE4 with Kd and Bmax values of 34.9+/-2.0, 0.252+/-0.015 and 0.589+/-0.039 nM and 10, 140+/-490, 122+/-11 and 306+/-23 fmol/mg protein, respectively. The in vivo study showed that topical nasal challenge of LTD4 (0.1-30 microg/nose) increased nasal secretion, nasal airway resistance and nasal eosinophil infiltration without inducing sneezing. While the increases in nasal secretion and nasal airway resistance were transient, peaking 10 to 20 min after LTD4 challenge, nasal eosinophil infiltration persisted at least until 24 hr post-challenge. These nasal symptoms were dose-dependently suppressed by oral administrations of pranlukast (0.3-3 mg/kg). The results suggest that cysLTs cause not only early-phase symptoms but also nasal eosinophil migration, a characteristic associated with the late-phase symptom of allergic rhinitis, via a receptor-mediated mechanism. Cysteinyl leukotrienes, thus, may be important mediators in allergic rhinitis.
A 68-year-old man with a 28-year history of non-insulin dependent diabetes mellitus (NIDDM) was admitted to our hospital because of foot gangrene. He had previously suffered from cerebral infarction resulting in right hemiplegia and his right foot was amputated because of right femoral lesion presenting diabetic foot gangrene 5 years previously. The diabetic foot gangrene gradually became worse, although he had received various medications. Then, we attempted to treat the patient with low density lipoprotein (LDL)-apheresis ten times a month. The foot gangrene itself and the local circulation around the gangrene lesion were remarkably improved after treatment with LDL-apheresis. We present here the first case of diabetic foot gangrene improved by LDL-apheresis. LDL-apheresis therapy is anticipated to be a new therapeutic approach for treatment of fatal foot gangrene associated with diabetes mellitus.
Bosniak classification of renal cystic massesis an extremely useful management tool. Of category I-IV by Bosniak, category III lesion is moderately complicated cyst, which cannot be confidently distinguished from malignancy radiologically. Here, we reviewed the clinical course of 5 patients with pathologically proven category III mass by Bosniak in order to evaluate the usefulness of magnetic resonance imaging (MRI) and renal angiography. Two of the 5 lesions were benign (hemorrhagic cyst) and the other were malignant (RCC). On MRI, the results of 5 lesions were true positive in 1 and false negative in 2. On angiography, the results were true positive in 2 and false negative in 1. MRI has an important role in detection of mass. Angiography is necessary for making a definitive diagnosis of the indeterminate renal cystic masses on US and CT as RCC, but cannot increase enough diagnostic confidence in small cystic renal masses. We experienced indeterminate 2 masses (case 1 and 4) on these four imaging techniques, which were RCC and hemorrhagic cyst, respectively. In category III lesions, if malignant finding was detected by MRI or angiography, we believe that surgical exploration should be performed. But, an absolute decision tree for management of the complicated renal cystic mass has not been published, and further investigation should be required.
The purpose of this study was to assess the limitations of the head and lumbar movements in relation to the center of gravity which is needed to maintain standing balance with aging. The subjects of the study were 22 healthy volunteers. The subjects were divided into two age categories, the young group (mean 21.7 +/- 2.9 years, 7 males and 6 females); and the elderly group (mean 71.3 +/-2.6 years, 3 males and 4 females). The instruments for measuring lumbar and head movements and the center of pressure (COP) were a three-dimensional motion analysis system and a force plate. In addition, the peak foot pressure was measured during standing using the F-Scan system. The subjects were first asked to stand relaxed for 10 s. They then shifted from the starting position to the four directions (sways); anterior, posterior, right, and left. They tried to maintain standing balance at the maximal possible distance position for each sway for 10 seconds. Analyzing parameters were performed by measuring the average maximal linear displacement (cm) of the head and lumbar markers, the COP (cm), and the peak foot pressure (percent of body weight per squared centimeters; BW%/cm2) in each subject. The data of the young group for lumbar maximal displacement were greater than those of the elderly group in the anterior, posterior, and lateral sways. A significant difference between the young and elderly data was found in the posterior sway. According to the data of the head's maximal displacement, the elderly group was greater than the young group in all sways except for the anterior side. For the data of peak foot pressure in the posterior sway, the elderly group's data was greater than the young group's data. The forefoot area data of the young group was significantly greater than that of the elderly group and the heel area data of the elderly was significantly greater than that of the young group in the right sway. The results suggest that evaluating the maximal displacement of head and lumbar positions and toe's activity in the forefoot are all important factors associated with the center of gravity in healthy adults.
Adenosine deaminase (ADA) is one of the enzymes in the purine metabolism and divided into two isozymes, ADA-1 and ADA-2. It is known that the activity of this enzyme is elevated in the sera of patients with pulmonary tuberculosis, sarcoidosis and other diseases, however there are few reports about the change of the activity of this enzyme under treatment. It is often said that this enzyme may have its origin in T lymphocyte, but it remains to be proved. That goes for each of two isozymes, too. In this study, we investigated the activity of serum total ADA, ADA-1 and ADA-2 in patients with pulmonary tuberculosis on admission and after three months' treatment. We also studied the correlation of lymphocyte subpopulation with these enzymes. The activity of total ADA, ADA-1 and ADA-2 was significantly higher in the sera of patients with pulmonary tuberculosis than in those of healthy persons. ADA-2 activity correlated significantly and negatively with the number of CD3+ lymphocytes and CD4+ lymphocytes. The change rate of ADA-2 activity during three months' treatment correlated significantly and negatively with the change rate of CD4/8. These results may suggest that there is a close correlation between the activity of ADA-2 and lymphocyte subpopulation in the sera of patients with pulmonary tuberculosis. ADA-1 activity did not correlate with lymphocyte subpopulation significantly, but it decreased significantly after three months' treatment. The activity of ADA-1 also may have certain relations with the disease process of pulmonary tuberculosis.
Laparoscopic splenectomy has been accepted as a feasible extension of minimally invasive surgery, which has undergone dramatic improvements in both technology and instrumentation. We performed a laparoscopic splenectomy in a 7-year-old girl with hereditary spherocytosis. The patient recovered rapidly and returned to unrestricted activities quickly. The appropriate positioning of each laparoscopic port is essential for a good operative view and smooth access. It is also important to dissect the hilum of the spleen meticulously. Laparoscopic splenectomy in the pediatric age group appears to be another promising extension of laparoscopic surgery.