[Therapeutic potential of DPP-IV inhibitor for the treatment of Type 2 diabetes].
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Biomedical subjects
Publications and source records attributed to Takashi Inoue.
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Lymphatic recovery of cholesterol infused into the duodenum as bile salt micelles containing phosphatidylcholine (PC) was accelerated by the co-administration of phospholipase A2 in bile and pancreatic juice diverted rats. Previously we observed that cholesterol esterase, which has the ability to hydrolyze PC, caused the same effect under a similar experimental condition (Ikeda et al., Biochim. Biophys. Acta, 1571, 34-44 (2002)). Accelerated cholesterol absorption was also observed when a part of micellar PC was replaced by lysophosphatidylcholine (LysoPC) and oleic acid. Phospholipase A2 facilitated the incorporation of micellar cholesterol into Caco-2 cells in a dose-dependent manner. There was a highly negative correlation between the incorporation of cholesterol into Caco-2 cells and the content of micellar PC remaining in the culture medium. The release of cholesterol as a monomer from bile salt micelles was enhanced when a part of micellar PC was replaced with LysoPC and oleic acid. These results strongly suggest that the release of monomer cholesterol from bile salt micelles is accelerated by hydrolysis of PC in bile salt micelles and hence that cholesterol absorption is enhanced.
A 33-year-old man presented with a minute tumor incidentally detected by magnetic resonance (MR) imaging screening. 1.5 Tesla MR spectroscopy indicated normal brain tissue whereas 3.0 Tesla MR spectroscopy indicated neoplasm. The tumor was completely resected. The histological diagnosis was fibrillary astrocytoma. Minute glioma, measuring less than 15 mm in diameter on MR imaging, can be completely resected, resulting in a good prognosis. 3.0 Tesla MR spectroscopy can establish the diagnosis in the early stage of glioma.
A 67-year-old woman with a recent history of recurrent ischemic stroke secondary to right vertebral artery stenosis suffered acute onset of left homonymous hemianopsia and the medial longitudinal fasciculus syndrome, which resolved with hyperdynamic therapy. However, consciousness deteriorated 6 hours later. Perfusion computed tomography (CT) revealed regions of prolonged mean transit time in the bilateral cerebellar hemispheres, vermis, brainstem, and right occipital lobe, which were more extensive than the ischemic lesions demonstrated by diffusion-weighted magnetic resonance (MR) imaging. Subsequent cerebral angiography showed occlusion of the right vertebral artery. The patient underwent emergent left superficial temporal artery to left superior cerebellar artery bypass. Postoperatively she demonstrated resolution of the preoperative perfusion CT/diffusion-weighted MR imaging mismatch and improved neurological deficits. Early revascularization in a patient with perfusion CT/diffusion-weighted MR imaging mismatch following acute vertebrobasilar stroke can lead to improvement in cerebral perfusion and neurological function.
Magnetic resonance (MR) imaging is an important diagnostic tool for neurosurgical diseases but susceptibility artifacts caused by biomaterial instrumentation frequently causes difficulty in visualizing postoperative changes. The susceptibility artifacts caused by neurosurgical biomaterials were compared quantitatively by 0.5, 1.5, and 3.0 Tesla MR imaging. MR imaging of uniform size and shape of pieces ceramic (zirconia), pure titanium, titanium alloy, and cobalt-based alloy was performed at 0.5, 1.5, and 3.0 Tesla. A linear region of interest was defined across the center of the biomaterial in the transverse direction, and the susceptibility artifact diameter was calculated. Susceptibility artifacts developed around all biomaterials at all magnetic field strengths. The artifact diameters caused by pure titanium, titanium alloy, and cobalt-based alloy increased in the order of 0.5, 1.5, to 3.0 Tesla magnetic fields. The artifact diameter of ceramic was not influenced by magnetic field strength, and was the smallest of all biomaterials at all magnetic field strengths. The artifacts caused by biomaterials except ceramic increase with the magnetic field strength. Ceramic instrumentation will minimize artifacts in all magnetic fields.
A blood examination was carried out in order to assess the serum zinc level in a patient with taste dysfunction. A blood cell count was also performed simultaneously and promyelocytic leukemia was identified. This case provides an example of leukemia being detected at the time of a blood test being given to assess taste dysfunction.
The purpose of this study was to investigate the relationship between Merkel cells and nerve elements during tissue regeneration after receiving dental implants. Golden hamsters were divided into 3 groups and titanium alloy implants were fixed in their left-side maxilla through the third palatine rug. Animals were sacrificed at 1, 2, 3, 4, 5, 6, and 7 days after the implantation and tissues were characterized at the immunohistochemical and morphological levels. CK 20 and PGP 9.5 antibodies which react with Merkel cells and nerve fibers were used. Immunohistochemically, no CK 20-positive Merkel cells were seen in the peri-implant epithelium throughout the 7 days. However, starting at day 4, PGP 9.5-positive nerve fibers appeared in the connective tissue, and by day 7, nerve fibers had invaded the more superficial layer of the peri-implant epithelium compared to the mucosa removal control group. At the electron microscopic level, the intercellular spaces of the regenerating epithelium in the mucosa removal control group were small. In contrast, intercellular spaces of the peri-implant epithelium tended to be wide and regenerating nerve fibers invaded those intercellular spaces. In both the mucosa removal control group and the implantation group, the basal lamina and connective tissues regenerated completely. However, clear Merkel cells containing neurosecretory granules were not observed. Taken together, our results indicate that Merkel cells in the hamster palatine mucosa do not regenerate in the peri-implant epithelium. However, regenerative nerve fibers seem to play essential roles as part of the defense and sensory systems around the peri-implant epithelium to compensate for the weakened defense mechanism.
The purpose of the current study was to evaluate the bone formation when beta-tricalcium phosphate (TCP) was implanted in bone defects of rat femurs. beta-TCP granules were applied to defects created in the femurs of 65 male rats who were sacrificed 3, 7, 10, 14 or 30 days later. Bone tissues were embedded in paraffin, serial sections were cut and then stained with hematoxylin-eosin. Histomorphometric analyses were also conducted. Furthermore, total mRNAs were extracted, homogenized, and reverse transcribed, after which quantitative PCR assays were conducted with a LightCycler using the double-stranded DNA dye Syber Green I with primers for either rat osteopontin or osteocalcin. Tissues in defects without beta-TCP were used as controls. The amount of newly formed bone tissue in the beta-TCP implanted group was significantly greater in both the side areas and the central area of defects than in the control group. Expressions of osteopontin and osteocalcin mRNAs of cells in the defects of the experimental group were up-regulated compared with the control group at all time periods. Taken together, these results prove that beta-TCP is an appropriate material for osteoconduction and promotes bone formation in bone defects.
To investigate the direct effect to the cartilage caused by the meniscal repair, we examined patients who underwent an isolated meniscal repair without any other abnormalities by arthroscopic examination. A total of 17 patients were examined by second-look arthroscopy after an average interval of 9 months from the meniscal repair, and have been evaluated the status of the repaired meniscus and of the relative femoral condylar cartilage. Changes in the severity of the cartilage lesion between at the time of meniscal repair and the time of the second-look arthroscopy were considered based on the status of the repaired meniscus. Regardless of the healing status of the repair site, it was possible to prevent degeneration in the cartilage in 9 of the 10 patients who demonstrated no degeneration in the meniscal body. Of the 7 patients who demonstrated degeneration in the meniscal body, progression in cartilage degeneration was noted as 1 grade in 2 patients and 2 grades in another 3 patients. Even in those in which stable fusion of the repair site was achieved, the condition of the inner meniscal body was not necessarily maintained favorably in all cases, indicating that degeneration in the meniscal body was a risk factor for cartilage degeneration. It was concluded that recovery could not be expected even at 9 months after the repair if the lesion had already demonstrated degeneration in the meniscal body at the time of repair.
OBJECT: Cognitive impairment occurs in 20 to 30% of patients following carotid endarterectomy (CEA). The purpose of the present study was to determine whether postoperative cerebral hyperperfusion is associated with impairment of cognitive function in patients undergoing that procedure. METHODS: Cerebral blood flow (CBF) was measured using single-photon emission computerized tomography scanning before and immediately after CEA and on the 3rd postoperative day in 92 patients with ipsilateral internal carotid artery stenosis of 70% or greater. Hyperperfusion post-CEA was defined as a 100% increase or greater in CBF compared with preoperative values. Neuropsychological testing was also performed preoperatively and at the 1-, 3-, and 6-month follow-up examinations. At the 1-month postoperative neuropsychological assessment, 11 patients (12%) displayed evidence of cognitive impairment. In addition, the incidence of postoperative cognitive impairment in patients with post-CEA hype perfusion (seven [58%] of 12 patients) was significantly higher than that in patients without post-CEA hyperperfusion (four [5%] of 80 patients; p < 0.0001). A logistic regression analysis demonstrated that post-CEA hyperperfusion was the only significant independent predictor of postoperative cognitive impairment. Of the seven patients in whom post-CEA hyperperfusion and cognitive impairment were identified 1 month postoperatively, four (including three patients with hyperperfusion syndrome) remained cognitively impaired at the 3- and 6-month follow-up examinations. CONCLUSIONS: Postoperative cerebral hyperperfusion is associated with impairment of cognitive function in patients undergoing CEA. Furthermore, the development of hyperperfusion syndrome is associated with the persistence of postoperative cognitive impairment.
OBJECT: This study investigated the changes in the valve pressure setting of several magnetic pressure-programmable valves after exposure to a 3-tesla magnetic field. METHODS: Five each of four types of pressure-programmable shunt valves were tested: Sophy Polaris, Sophy SM8, Codman-Hakim, and Medtronic Strata. First, the valves were advanced toward the 3-tesla static magnetic field. Second, T1-, T2-, and diffusion-weighted magnetic resonance (MR) images were generated with a radiofrequency magnetic field. Any changes in the pressure setting were observed by visual inspection with a compass or radiography. The pressure settings were changed after exposure to the static magnetic field in all programmable valves except for the Sophy Polaris. All pressure settings studied were unchanged after exposure to both static and radiofrequency magnetic fields (T1-, T2-, and diffusion-weighted MR imaging) in the Sophy Polaris. CONCLUSIONS: The Sophy Polaris valve allows shunt-dependent patients who need a programmable valve to undergo 3-tesla MR imaging.
BACKGROUND AND PURPOSE: Cerebral hyperperfusion syndrome is a rare but serious complication of carotid endarterectomy (CEA). The aim of the present study was to determine whether intraoperative blood flow velocity (BFV) monitoring in the middle cerebral artery (MCA) by using transcranial Doppler ultrasonography (TCD) could be used as a reliable technique to detect cerebral hyperperfusion following CEA by comparing findings with those of brain single photon emission CT (SPECT). METHODS: Intraoperative BFV monitoring was attempted in 67 patients undergoing CEA for treatment of ipsilateral internal carotid artery (ICA) stenosis (> or =70%). Cerebral blood flow (CBF) was also assessed using SPECT, which was performed before and immediately after CEA. RESULTS: Intraoperative BFV monitoring was achieved in 60 patients. Of the 60 patients, post-CEA hyperperfusion (CBF increase > or =100%, compared with preoperative values) was observed in six patients. The sensitivity, specificity, and positive predictive value of the BFV increases immediately after declamping of the ICA for detecting post-CEA hyperperfusion was 100%, 94% and 67%, respectively, with a cut-off point 2.0-fold that of preclamping BFV. The sensitivity and specificity of the BFV increases at the end of the procedure for detecting post-CEA hyperperfusion were 100% for both parameters, with cut-off points of 2.0- to 2.2-fold BFV of preclamping value. Hyperperfusion syndrome developed in two patients with post-CEA hyperperfusion, but intracerebral hemorrhage did not occur. In one of these two patients, BFV monitoring was not possible because of failure to obtain an adequate bone window. CONCLUSION: Intraoperative MCA BFV monitoring by using TCD is a less reliable method to detect cerebral hyperperfusion following CEA than postoperative MCA BFV monitoring, provided adequate monitoring can be achieved.
Colorectal cancer patients with central venous catheters (CVC) for pharmacokinetic modulating chemotherapy (PMC) have a substantial risk of venous thromboembolism (VTE). PMC, designed as a hybrid of lower metronomic and higher shorter plasma 5-FU concentrations, has been clinically successful. To determine the effectiveness and safety of D-dimer tests and multidetector-row CT (MDCT) for diagnosis in cancer patients with suspected VTE, we carried out a clinical outcome study on PMC outpatients. Patients received a D-dimer test before and after commencing the PMC regimen. MDCT was performed additionally if the D-dimer test appeared positive or showed signs of VTE. When CT results were positive for thromboembolism, anticoagulation was started. The overall prevalence of VTE in PMC patients was 2.0% (7 of 350 patients). In this study, 34 out of 102 colorectal cancer patients gave a positive D-dimer test (33.3%). CT identified venous thrombi in 2 of the 102 patients (2.0%), mural thrombosis on catheterized veins in another 3 patients (2.9%), and endothelial hyperplasia on catheterized veins in 8 patients (7.8%). The catheters of these patients did not show any significant abnormalities. Patients with negative D-dimer tests showed no signs or symptoms of VTE. In colorectal cancer patients receiving continuous 5-FU infusion via CVC, a D-dimer test can be safely used as the primary diagnostic test for ruling out VTE. We suggest 7.0 microg/ml as the D-dimer cut-off value. Thromboprophylaxis should be considered in the patients showing values >7.0 microg/ml.
We conducted this study to evaluate the clinical significance of preoperative concurrent chemoradiotherapy (CRT) followed by esophagectomy in the management of T3 and T4 esophageal cancer. Thirty patients with squamous cell carcinoma of the esophagus received CRT followed by surgery. Preoperative CRT consisted of 5-fluorouracil (500 mg/m(2) by 24 h infusion for 5 days), cisplatin (15 mg/m(2) on days 1-5), and concurrent radiotherapy (a total dose of 40 Gy delivered in daily fractions of 2 Gy, 5 times per week). Esophagectomy was planned for 4-6 weeks after treatment and restaging. All 30 patients completed preoperative CRT. A clinical response (PR+CR) of the primary tumor was obtained in 82.8%, and a response of metastatic nodes was seen in 23.1%. Radical resection was possible in 17 of 29 operated patients (58.6%). The postoperative mortality rate was 6.9%, and the hospital mortality rate was 10.3%. Ten out of 29 operated patients (34.5%) had no residual cancer in the resected esophagus, corresponding to pathological CR. The 1-year survival rate was 80.6%, the 2-year survival rate was 62.7%, and the 3-year survival rate was 53.8%. The clinical response group and the R0 or R1 group showed better survival than other patients. Preoperative CRT should be given to patients with squamous cell carcinoma, while esophagectomy remains the standard therapy for responders and has a tolerable mortality.
It is well-known that secondary hyperparathyroidism of uremia influences not only bone and mineral metabolism but also cardiovascular complications. Here we reported the effects of the level of serum intact PTH and its gene polymorphism on cardiovascular and non-cardiovascular mortality in hemodialysis patients. We analyzed the association between clinico-molecular parameters and 3-year survival in 508 hemodialysis patients among whom 90 patients died. The multivariate Cox proportional hazards models showed that the presence of diabetes mellitus, levels of albumin and intact PTH, and BstB I genotype were indicated as independent predictors of cardiovascular mortality, whereas age and albumin level were indicated as those of non-cardiovascular mortality, suggesting that the level of intact PTH and its gene polymorphism effect cardiovascular mortality in hemodialysis patients.
The Zic-family proteins control various developmental processes. Previous studies have shown that Zic1, Zic2, and Zic3 can act as transcriptional regulators, and that their functions are repressed by I-mfa, which has been identified as a repressor for basic helix-loop-helix-type transcriptional factors. Here, we investigated the molecular properties of the Zic4 and Zic5 proteins. Zic4/Zic5 showed DNA-binding activity to the Gli-binding sequence, similar to Zic1/Zic2/Zic3 proteins. However, Zic4/Zic5 did not exhibit any significant transcriptional activation ability nor they bind to I-mfa differently from Zic1/Zic2/Zic3. The nuclear localization of Zic4/Zic5 was not affected by the presence of the I-mfa protein, whereas the Zic1/Zic2/Zic3 proteins were translocated to the cytoplasmic compartment in the presence of I-mfa. The difference may be attributable to the dissimilarity of the N-terminal region between the Zic1/Zic2/Zic3 and Zic4/Zic5 proteins, since the binding of the Zic1/Zic2/Zic3 proteins to I-mfa occurs through their N-terminal regions.
We investigated hippocampal substructure in the rat, cat, dog, and human by means of magnetic resonance imaging to elucidate phylogenetic differences in longitudinal organization. Multidirectional high-resolution images obtained with a 3 T scanner revealed that the dorsal part of the hippocampus was well developed in the rat, cat, and dog brain, and was homologous to the hippocampal tail, a poorly-developed posterior part, in the human. We conclude that the dorsal hippocampus of laboratory animals corresponds to the hippocampal tail in the human brain, which is considered to be hypoplastic and of less importance clinically than more anterior regions. These data may help in understanding phylogenetic, and in correlating results from animal experiments with clinical findings on the functions and pathologies of the human hippocampus.
The temperature change of the fractional dissociation of imidazole (alpha-imidazole) in resting human lower leg muscles was measured noninvasively using (1)H-nuclear magnetic resonance spectroscopy at 3.0 and 1.5 T on five normal male volunteers aged 30.6 +/- 10.4 yr (mean +/- SD). Using (1)H-nuclear magnetic resonance spectroscopy, water, carnosine, and creatine in the muscles could be simultaneously analyzed. Carnosine contains imidazole protons. The chemical shifts of water and carnosine imidazole protons relative to creatine could be used for estimating temperatures and alpha-imidazole, respectively. Using the chemical shift, the values of temperature in gastrocnemius (Gast) and soleus muscles at ambient temperature (21-25 degrees C) were estimated to be 35.5 +/- 0.5 and 37.4 +/- 0.6 degrees C (means +/- SE), respectively (significantly different; P < 0.01). The estimated values of alpha-imidazole in these muscles were 0.620 +/- 0.007 and 0.630 +/- 0.013 (means +/- SE), respectively (not significant). Alternation of the surface temperature of the lower leg from 40 to 10 degrees C significantly changed the temperature in Gast (P < 0.0001) from 38.1 +/- 0.5 to 28.0 +/- 1.2 degrees C, and the alpha-imidazole in Gast decreased from 0.631 +/- 0.003 to 0.580 +/- 0.011 (P < 0.05). However, the values of alpha-imidazole and the temperature in soleus muscles were not significantly affected by this maneuver. These results indicate that the alpha-imidazole in Gast changed significantly with alternation in muscle temperature (r = 0.877, P < 0.00001), and its change was estimated to be 0.0058/ degrees C.