Biomedical subjects
Publications and source records attributed to Hiroyuki Yamada.
The inferior alveolar nerve is sometimes affected by periapical pathoses and mandibular cysts. However, mandibular intraosseous lesions have not been reported to disturb the lingual nerve. A case of simultaneous paresthesia of the right lingual nerve and the right inferior alveolar nerve is presented. The possible mechanisms of this extremely uncommon condition are discussed.
The variations of plasma concentrations of 5-fluorouracil (5-FU) were investigated in 30 esophageal cancer patients treated with repetitive protracted venous infusion (PVI) of 5-FU-based chemoradiotherapy, and in an attempt to find a new possible candidate that explains their variations, CLOCK T3111C genetic polymorphism was examined. The patients have received 2 courses of chemoradiotherapy consisting of 2 cycles of 5-day PVI of 5-FU (400 mg/m/d) with cisplatin and concurrent radiation. The plasma concentrations of 5-FU were determined at 5 PM on day 3 and 5 AM on day 4 after the beginning of each 5-FU infusion. The CLOCK T3111C genotype was determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) and by direct sequencing. Plasma concentrations were measured in 239 samples. In the first course, the plasma concentrations of 5-FU at 5 AM were significantly lower than those at 5 PM in the first cycle, whereas a similar tendency was observed in the second cycle, although not significantly (Wilcoxon signed-rank test). The plasma concentrations of 5-FU at 5 PM and 5 AM in the second cycle were both significantly higher than those in the first cycle, and their coefficient of variation in the former was also significantly smaller than that in the latter. These phenomena in the first course were also observed in the second one. These results revealed the elevation of plasma drug concentration and its reduced circadian variation during repetitive PVI of 5-FU. In 5-FU-based chemotherapy, its administration schedule should be made in consideration of these phenomena. The CLOCK T3111C genotype did not have a significant impact on the variation of the plasma concentrations of 5-FU in this study population. Further studies are needed to clarify the mechanism of these phenomena and to identify an easy-to-assess marker of circadian rhythms for use in individualizing delivery of 5-FU.
We report a case of gastric remnant carcinoma (GRC) that was successfully treated by laparoscopy-assisted gastrectomy. A 69-year-old man was referred to our department for management of GRC. Preoperative investigations revealed a slightly elevated tumor, 5.0 cm in maximal diameter, confined to the gastric mucosa. Computed tomography and endoscopic ultrasonography identified no lymph node metastasis. Laparoscopy-assisted gastrectomy was performed including perigastric and mesenteric lymph node dissection. The postoperative course was uneventful. This is the first reported case of laparoscopically treated GRC. In cases with little adhesion from previous surgery, laparoscopic procedure might represent the treatment of choice for early GRC in terms of minimal invasiveness.
Guinea pigs are often used as an animal model of human tuberculosis (TB). However, there are few methods available for pursuing the immunological processes involved in guinea pig TB. In this study, we developed for the first time systematic reverse transcription (RT)-PCR for evaluation of guinea pig mRNA expression. RT-PCR primer sets were newly designed for detection of cytokines and inducible nitric oxide synthase (iNOS) mRNA in guinea pig TB. Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, interleukin (IL)-1beta, IL-2, IL-10, IL-12p40, granulocyte-macrophage-colony stimulating factor (GM-CSF) and iNOS mRNA expression were detected significantly and reproducibly when these primer sets were used. The data by real-time PCR were comparable with those of RT-PCR. We showed that these RT-PCR primer sets could be used to examine mRNA expression semi-quantitatively in guinea pig tissues, and conclude that these newly designed primer sets for conventional RT-PCR will be useful for studying the immunological processes in guinea pig tuberculosis experiments to investigate and evaluate efficacy of new vaccines or anti-mycobacterial drugs.
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Pituitary adenylate cyclase-activating polypeptide (PACAP) potentiates glucose-induced insulin release and increases cytosolic Ca2+ concentration ([Ca2+]i) in islet beta-cells in a concentration-dependent manner with two peaks at 10(-13) and 10(-9) M. PAC1 receptor (PAC1-R) and VPAC2 receptor (VPAC2-R) are expressed in pancreatic beta-cells and thought to be involved in insulin release. We aimed to determine the receptor types involved in the [Ca2+]i responses to 10(-13) and 10(-9) M PACAP. We measured [Ca2+]i in beta-cells and examined comparative effects of PAC1-R-selective agonist maxadilan, its antagonist M65, VPAC2-R-selective agonist Ro25-1553, and native ligands of PACAP and VIP. In the presence of 8.3 mM glucose, maxadilan, Ro25-1553, PACAP, and VIP at 10(-13) and 10(-9) M all increased [Ca2+]i. PACAP and maxadilan elicited greater effects at 10(-9) M than at 10(-13) M both in the incidence and amplitude of [Ca2+]i responses. For VIP and Ro25-1553, in contrast, the effects at 10(-9) and 10(-13) M were comparable. Furthermore, the amplitude of [Ca2+]i responses to 10(-9) M PACAP, but not 10(-13) M PACAP, was suppressed by M65. The results suggest that VPAC2-R and PAC1-R contribute equally to [Ca2+]i responses to sub-picomolar concentrations of PACAP, while PAC1-R has greater contribution to [Ca2+]i responses to nanomolar concentrations of this peptide.
Interface-selective probing of magnetism is a key issue for the design and realization of spin-electronic junction devices. Here, magnetization-induced second-harmonic generation was used to probe the local magnetic properties at the interface of the perovskite ferromagnet La(0.6)Sr(0.4)MnO3 with nonmagnetic insulating layers, as used in spin-tunnel junctions. We show that by grading the doping profile on an atomic scale at the interface, robust ferromagnetism can be realized around room temperature. The results should lead to improvements in the performance of spin-tunnel junctions.
PURPOSE: Expression of thymidylate synthase (TS) and the 5-fluorouracil (5-FU) metabolic enzymes, including dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), thymidine phosphorylase (TP), and uridine phosphorylase (UP), has been reported to be associated with the sensitivity to 5-FU-based chemotherapy in colorectal cancer. We evaluated the correlation of the expression of these genes between primary tumors and corresponding liver metastases. METHOD: The mRNA levels of TS, DPD, OPRT, TP, and UP were measured by real-time quantitative RT-PCR in samples from 23 consecutive patients with both primary colorectal adenocarcinoma and liver metastasis. RESULTS: The DPD, OPRT, TP, and UP mRNA levels were significantly higher in liver metastases than in primary tumor (expression in relation to that of beta-actin mRNA: 0.42 vs 0.16, P=0.00053; 1.4 vs 0.92, P=0.016; 23 vs 11, P=0.00014; 0.36 vs 0.25, P=0.0026; respectively). However, the TS mRNA level did not differ significantly between liver metastases than primary tumor (0.20 vs 0.16, P=0.28). No correlation was observed for any gene between primary tumor and liver metastases. In both primary tumor and liver metastasis, the TS mRNA levels correlated significantly with the OPRT mRNA level (primary rS=0.83, P=0.00000081; liver metastasis rS=0.49, P=0.017), while the DPD mRNA level correlated significantly with the TP mRNA level rS=0.81, P=0.0000024; rS=0.63, P=0.0014; respectively). CONCLUSIONS: The differential gene expression of 5-FU metabolic enzymes between primary colorectal cancer and corresponding liver metastases should be taken into consideration when estimating the sensitivity to 5-FU-based chemotherapy in colorectal cancer. The gene expression of TS and OPRT, which are involved in de novo pyrimidine synthesis, and that of DPD and TP, may be coregulated.
Extensive structural studies using high-pressure NMR spectroscopy have recently been carried out on proteins, which potentially contribute to our understanding of the mechanisms of protein folding. Pressure shifts the conformational equilibrium from higher to lower volume conformers. If the pressure is varied, starting from the folded native structure, in many cases we observe intermediate conformers before the onset of total unfolding. This enables the investigation of details of the structure and thermodynamic characteristics of various intermediate conformers of proteins under equilibrium conditions. We can also examine pressure effects on the structure and stability of some typical denatured states such as helical denatured, molten globule, and unfolded states. The high-pressure NMR method can also be used to investigate association/dissociation equilibria of oligomeric or aggregated proteins. Beside direct observation of kinetic intermediates upon pressure jump, NMR structural investigations of equilibrium conformers under pressure provide information about the structures of kinetic intermediates during folding/unfolding reactions.
To investigate the pathological and immunological profiles of rat tuberculosis, Lewis female rats were infected aerially with Mycobacterium tuberculosis. Histopathology, immunological profiles of mononuclear cells from M. tuberculosis-infected rat lung tissue, and the expression patterns of cytokine and iNOS mRNAs were examined over time. M. tuberculosis induced granulomatous lesions in the lungs, spleen, lymph nodes and liver, but these lesions lacked central necrosis. Multinucleate giant cells were observed in late-phase tuberculosis. CD4(+) and CD8(+) T cells increased with time and reached a peak 5 weeks after infection, decreasing gradually thereafter. ED1 antigen, suggestive of alveolar macrophages, was expressed at a high level in early phase tuberculosis and remained at the same level even in the late phase. OX62 antigen increased gradually and reached a peak 5 weeks after infection. Interferon-gamma, tumour necrosis factor-alpha and iNOS mRNAs were expressed strongly over time, but their expression decreased 12 weeks after infection. Because rat tuberculosis is very similar to murine tuberculosis and it is easy to obtain mononuclear cells from M. tuberculosis-infected rat lung tissue, the rat tuberculosis model appears to be suitable for immunological studies in vivo.
Guinea pig eosinophils were positively identified in bronchoalveolar lavage populations and in the lung granulomas of Mycobacterium tuberculosis-infected guinea pigs. It is possible that the rapid influx of these cells, and their subsequent degranulation during acute pulmonary tuberculosis, may play a key role in the susceptibility of this animal model.
To understand the role of neutrophils in the development of rat tuberculosis in vivo, we utilized lipopolysaccharide (LPS)-induced neutrophilia in the lungs. LPS (50 micro g/ml) was administered intratracheally to male Fischer rats. Rats were then infected with Mycobacterium tuberculosis by an airborne route. Intratracheal injection of LPS significantly blocked the development of pulmonary granulomas and significantly reduced pulmonary CFU (P < 0.01). LPS treatment with amphotericin B (an LPS inhibitor) or neutralizing anti-rat neutrophil antibody reversed the development of pulmonary lesions. LPS-induced transient neutrophilia prevented early mycobacterial infection. The timing of LPS administration was important. When given intratracheally at least 10 days after aerial infection, LPS did not prevent development of tuberculosis. Neutrophils obtained by bronchoalveolar lavage killed M. tuberculosis cells. These results indicate clearly that neutrophils participate actively in defense against early-phase tuberculosis.
UNLABELLED: We evaluated the effect of transdermal lidocaine on differential sensory nerve block in 15 healthy volunteers. Lidocaine 10% gel was applied topically to a forearm and covered with a plastic film. Three types of sensory nerve fibers (Abeta, Adelta, and C fibers) were evaluated with a series of 2000-, 250-, and 5-Hz stimuli using current perception threshold (CPT) testing. Sensations of touch, pinprick, cold, and warmth were also measured. These measurements were made before the topical lidocaine (baseline), 60 min after the draping (T0), and at 1-h intervals until 5 h after T0 (T1 to T5). A significant increase in CPT compared with baseline was observed until T2 at 5 Hz and T4 at 250 Hz, whereas the increase in CPT at 2000 Hz continued throughout the study period. All subjects experienced the disappearance of pinprick and cold sensations, whereas touch and warmth sensations were detectable during the study period. We conclude that when lidocaine is applied transdermally, the sensitivity of nerves to local anesthetics is proportional to the axon diameters. However, pinprick and cold sensation are affected more strongly than other sensations at receptor sites. IMPLICATIONS: We evaluated the effect of transdermal lidocaine on differential sensory nerve block in healthy volunteers. Our results show that the sensitivity of nerves to local anesthetics is proportional to the axon diameter.
This study was designed to determine the roles of STAT1 protein in defense against mycobacterial infection. Airborne infection of STAT1 knockout (KO) mice with a Mycobacterium tuberculosis Kurono strain induced multiple necrotic lesions in lungs, spleen and liver, while that in wild-type (WT) mice did not. The STAT1 KO mice succumbed to mycobacterial infection by the 35th day after infection. Compared with the levels in WT mice, inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha, interferon-gamma and IL-12 mRNA levels were significantly lower in the lung of STAT1 KO mice. Interestingly, granulomatous lesion development in STAT1 KO mice was inhibited significantly by treatment with exogenous recombinant murine IL-12. Therefore, STAT1 regulates IL-12 expression and appears to be a critical transcription factor in controling mycobacterial infection.
As a clinical association is thought to exist between diabetes and tuberculosis, this study was set up to examine whether GK/Jcl diabetic rats are more susceptible to Mycobacterium tuberculosis infection than non-diabetic rats. GK/Jcl diabetic rats were infected aerially with M. tuberculosis and their capacity to control mycobacterial growth, granuloma formation, cytokine secretion by alveolar macrophages and nitric oxide (NO) production was examined. The rats developed large granulomas but not necrotic lesions in their lungs, liver or spleen. This is consistent with a significant increase in number of colony-forming units of M. tuberculosis in the lungs (p<0.01). Expression levels of interferon-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-12 mRNA were lower in GK/Jcl diabetic rats than those in control Wistar rats. Alveolar macrophages from GK/Jcl rats secreted less TNF-alpha and IL-12, and produced less NO compared with those from Wistar rats. No significant difference was observed between phagocytosis of tubercle bacilli by alveolar macrophages from GK/Jcl or Wistar rats. These data show that there is a close association between experimental tuberculosis and diabetes in animals, and that alveolar macrophages from GK/Jcl diabetic rats are not fully activated by M. tuberculosis infection.
Recently, the treatment of gastric cancer is becoming diversified. In Japan, gastrectomy with D2 lymphadenectomy has been recognized as a standard operation and has been performed widely for years. However, instead of D2 conventional gastric resection, various treatments using endoscopic or laparoscopic methods have been developed. Their usefulness and safety have been established, and the rate of detection of early gastric cancer has risen with the progress of medical technology and systems. The treatment suitable for the given stage must be chosen. In our department, we introduced laparoscopic operations and considered their usefulness and indication. Now, laparoscopic gastrectomy is recommended for cases in cStage I A and cStage I B of the guideline proposed by the Japanese Gastric Cancer Society. Future randomized controlled trials consisting of open surgery and laparoscopic gastrectomy are warranted.
Efforts to find the magnetic monopole in real space have been made in cosmic rays and in particle accelerators, but there has not yet been any firm evidence for its existence because of its very heavy mass, approximately 10(16) giga-electron volts. We show that the magnetic monopole can appear in the crystal momentum space of solids in the accessible low-energy region (approximately 0.1 to 1 electron volts) in the context of the anomalous Hall effect. We report experimental results together with first-principles calculations on the ferromagnetic crystal SrRuO3 that provide evidence for the magnetic monopole in the crystal momentum space.