Biomedical subjects

Shigenori Tanaka

Publications and source records attributed to Shigenori Tanaka.

At least 19 recordsLinked to original sources

PubMed2006

Molecular interactions between estrogen receptor and its ligand studied by the ab initio fragment molecular orbital method.

The ab initio fragment molecular orbital calculations were performed for molecular interactions of the whole estrogen receptor (ER) ligand-binding domain with a natural ligand, 17beta-estradiol (EST). The interaction energies of the ligand at the residue level were calculated using HF and MP2 methods with several basis sets. The charge-transfer (CT) interactions were also analyzed based on configuration analysis for fragment interaction. Strong electrostatic interactions were observed between the EST and surrounding charged/polarized residues, Glu353, Arg394, His524, and Thr347. Weak electrostatic and significant van der Waals dispersion interactions were observed between the EST and the many surrounding hydrophobic residues. Together with the experimental interpretations, both interactions equally contributed to the total binding energies, and it was found that the inclusion of electron correlation was essential to obtain an appropriate picture of the interaction. The strongest interaction energy was observed between Glu353 and the EST, and the CT interactions from the lone-pair orbital of the carbonyl oxygen of Glu353 to the sigma(OmicronEta) orbital of the hydroxyl group of EST were found to be important. The CT interactions from the lone-pair orbital of EST to the sigma(NuEta) of Arg394 and from the lone-pair orbital of EST to the sigma(NuEta) of His524 were also observed. These CT interactions occurred through the hydrogen-bond networks between the ER and EST. Therefore, electron donations from the ER to the EST and electron back-donations from EST to the ER were characteristic of ER-ligand binding. Our approach provides a powerful tool to understanding detailed molecular interactions at the quantum mechanical level.

Estradiol↗

PubMed2006

Surgical anatomy of the innervation of pylorus in human and Suncus murinus, in relation to surgical technique for pylorus-preserving pancreaticoduodenectomy.

AIM: To clarify the innervation of the antro-pyloric region in humans from a clinico-anatomical perspective. METHODS: The stomach, duodenum and surrounding structures were dissected in 10 cadavers, and immersed in a 10mg/L solution of alizarin red S in ethanol to stain the peripheral nerves. The distribution details were studied to confirm innervations in the above areas using a binocular microscope. Similarly, innervations in 10 Suncus murinus were examined using the method of whole-mount immunohistochemistry. RESULTS: The innervation of the pyloric region in humans involved three routes: One arose from the anterior hepatic plexus via the route of the suprapyloric/supraduodenal branch of the right gastric artery; the second arose from the anterior and posterior gastric divisions, and the third originated from the posterior-lower region of the pyloric region, which passed via the infrapyloric artery or retroduodenal branches and was related to the gastroduodenal artery and right gastroepiploic artery. For Suncus murinus, results similar to those in humans were observed. CONCLUSION: There are three routes of innervation of the pyloric region in humans, wherein the route of the right gastric artery is most important for preserving pyloric region innervation. Function will be preserved by more than 80% by preserving the artery in pylorus-preserving pancreaticoduodenectomy (PPPD). However, the route of the infrapyloric artery should not be disregarded. This route is related to several arteries (the right gastroepiploic and gastroduodenal arteries), and the preserving of these arteries is advantageous for preserving pyloric innervation in PPPD. Concurrently, the nerves of Latarjet also play an important role in maintaining innervation of the antro-pyloric region in PPPD. This is why pyloric function is not damaged in some patients when the right gastric artery is dissected or damaged in PPPD.

Aged↗

PubMed2006

Intra- and intermolecular interactions between cyclic-AMP receptor protein and DNA: ab initio fragment molecular orbital study.

The ab initio fragment molecular orbital (FMO) calculations were performed for the cAMP receptor protein (CRP) complexed with a cAMP and DNA duplex to elucidate their sequence-specific binding and the stability of the DNA duplex, as determined by analysis of their inter- and intramolecular interactions. Calculations were performed with the AMBER94 force field and at the HF and MP2 levels with several basis sets. The interfragment interaction energies (IFIEs) were analyzed for interactions of CRP-cAMP with each base pair, DNA duplex with each amino acid residue, and each base pair with each residue. In addition, base-base interactions were analyzed including hydrogen bonding and stacking of DNA. In the interaction between DNA and CRP-cAMP, there was a significant charge transfer (CT) from the DNA to CRP, and this CT interaction played an important role as well as the electrostatic interactions. It is necessary to apply a quantum mechanical approach beyond the "classical" force-field approach to describe the sequence specificity. In the DNA intramolecular interaction, the dispersion interactions dominated the stabilization of the base-pair stacking interactions. Strong, attractive 1,2-stacking interactions and weak, repulsive 1,3-stacking interactions were observed. Comparison of the intramolecular interactions of free and complexed DNA revealed that the base-pairing interactions were stronger, and the stacking interactions were weaker, in the complexed structure. Therefore, the DNA duplex stability appears to change due to both the electrostatic and the CT interactions that take place under conditions of DNA-CRP binding.

Algorithms↗

PubMed2005

Functionally relevant protein motions: extracting basin-specific collective coordinates from molecular dynamics trajectories.

Functionally relevant motion of proteins has been associated with a number of atoms moving in a concerted fashion along so-called "collective coordinates." We present an approach to extract collective coordinates from conformations obtained from molecular dynamics simulations. The power of this technique for differentiating local structural fluctuations between classes of conformers obtained by clustering is illustrated by analyzing nanosecond-long trajectories for the response regulator protein Spo0F of Bacillus subtilis, generated both in vacuo and using an implicit-solvent representation. Conformational clustering is performed using automated histogram filtering of the inter-C(alpha) distances. Orthogonal (varimax) rotation of the vectors obtained by principal component analysis of these interresidue distances for the members of individual clusters is key to the interpretation of collective coordinates dominating each conformational class. The rotated loadings plots isolate significant variation in interresidue distances, and these are associated with entire mobile secondary structure elements. From this we infer concerted motions of these structural elements. For the Spo0F simulations employing an implicit-solvent representation, collective coordinates obtained in this fashion are consistent with the location of the protein's known active sites and experimentally determined mobile regions.

Amino Acid Sequence↗

PubMed2005

Surgical anatomy of the innervation of the major duodenal papilla in human and Suncus murinus, from the perspective of preserving innervation in organ-saving procedures.

OBJECTIVES: Few studies have focused on the detailed surgical anatomy of the innervation of the major duodenal papillary region, especially in relation to duodenum-preserving pancreatic head resection (DPPHR) and its modified procedures, which is crucial to preserving the innervation of the papillary region. The aim of this study is to clarify the neural distribution of the major duodenal papilla in humans. METHODS: The pancreas, duodenum, and surrounding structures were dissected in 10 cadavers and immersed in a 0.001% solution of alizarin red S in ethanol to stain the peripheral nerves. The details of the innervation in the above areas were confirmed using a binocular microscope. Similarly, the distribution in 10 Suncus murinus was examined by whole mount immunohistochemistry method with antineurofilament protein antibody. RESULTS: The innervation of the papillary region in humans involved 2 systems. One arose from the celiac plexus, which through the anterior hepatic plexus running along the arcades of the superior pancreaticoduodenal arteries and through the posterior hepatic plexus running along or accompanying the common bile duct (CBD) or Wirsung's duct, innervated the papillary region. The other arose from the superior mesenteric plexus wound around the arcades of the inferior pancreaticoduodenal arteries innervating the papillary region. The results in S. murinus supported those in humans. CONCLUSIONS: We emphasize the importance of the nervus-preserving of the major duodenal papilla and CBD by a suitable pancreatic head remnant, preserving the pancreaticoduodenal arterial arcades and avoiding kocherization of the CBD in DPPHR and its modified procedures.

Aged↗

PubMed2005

Nerve supply to the soft palate muscles with special reference to the distribution of the lesser palatine nerve.

OBJECTIVE: Descriptions of the innervation of the soft palate muscles in previous studies have varied according to the author. In the present study, distribution of the lesser palatine nerve, through which motor fibers of the facial nerve are considered to reach soft palate muscles, and that of the pharyngeal plexus in the soft palate were investigated in order to reexamine the innervation of the soft palate muscles according to anatomical evidence. RESULTS: Observations suggested that the levator veli palatini and palatopharyngeus were doubly innervated by branches of the lesser palatine nerve and pharyngeal plexus, and that the musculus uvulae was innervated by only the lesser palatine nerve. CONCLUSION: The soft palate is considered to be located in the border region between the areas of distribution of the lesser palatine nerve and pharyngeal plexus. This may be why controversies exist in previous studies about the innervation of the soft palate muscles.

Cadaver↗

PubMed2004

The solubilization and biological activities of Aspergillus beta-(1 --> 3)-D-glucan.

We have recently demonstrated that the cell wall beta-glucan of Candida albicans could be solubilized by sodium hypochlorite, followed by dimethylsulfoxide-extraction (NaClO-DMSO method). In this study, applying this method to Aspergillus spp., we prepared mycelial cell wall beta-glucan and examined its physical properties and immunotoxicological activity. The acetone-dried mycelia of Aspergillus spp. were oxidized by the NaClO-DMSO method. An analysis of (13)C NMR spectra revealed the preparations to be composed of alpha-(1 --> 3) and beta-(1 --> 3)-D-glucan. Also, the proportion of alpha-(1 --> 3) and beta-(1 --> 3)-D-glucan varied. Furthermore, a solubilized Aspergillus beta-glucan (ASBG) was prepared from OX-Asp by urea-autoclave treatment. ASBG showed limulus activity similar to Candida solubilized beta-glucan (CSBG), and there was little difference in the activity of ASBG between various Aspergillus spp. ASBG affected the production of IL-8 by human peripheral blood mononuclear cells (PBMC). ASBG should be useful for analyzing the clinical role of beta-glucan.

Animals↗

PubMed2004

Penetration of muscles by branches of the mandibular nerve: a possible cause of neuropathy.

We carried out detailed dissections of the branches of the mandibular nerve and muscles innervated by these branches to investigate their positional relationships. We made the following observations: 1) small branch of the auriculotemporal nerve penetrated the lateral pterygoid muscle; 2) the entire lingual nerve penetrated the medial pterygoid muscle; and 3) branch of the mylohyoid nerve penetrated the mylohyoid muscle and communicated with the submandibular ganglion. No detailed descriptions of these nerve branches have been reported previously. The existence of these nerve branches that penetrate muscles might result in the neuralgic pain in the trigeminal region when such pain is of unknown origin.

Cadaver↗

PubMed2004

Contributions of the hypoglossal nerve to the innervations of the recti capiti lateralis and anterior.

We dissected five Japanese cadavers (three males, two females) to investigate the innervations of the anterior vertebral muscles. According to our observations, it could be considered that the hypoglossal nerve would participates in the innervations of the recti capiti lateralis and anterior. In addition, we observed the small muscle bundle spanning between the recti capiti lateralis and anterior, which was not reported in previous studies as far as we know. This bundle received a branch of the hypoglossal nerve or the first cervical nerve. Based on the morphology and the innervation pattern, this bundle was considered to have close relationships with the recti capiti lateralis and anterior, especially with the former muscle.

Cadaver↗

PubMed2004

DNA array analysis of altered gene expression in human leukocytes stimulated with soluble and particulate forms of Candida cell wall beta-glucan.

We previously reported that 1,3-beta-d-glucan derived from Candida albicans, a pathogenic fungus was obtained by oxidation of the cell wall with sodium hypochlorite (NaClO). It could be solubilized by treatment with dimethylsulfoxide (DMSO). We found that OX-CA and CSBG showed significantly different levels of activity toward leukocytes. Here, we have used cDNA microarrays to analyze the mRNA expression of 1176 genes in PBMCs stimulated with Candida cell wall glucan and considered the difference in the activation mechanism of OX-CA and CSBG. Total mRNA showed a significant change for 147 out of 1176 arrayed genes on stimulation with OX-CA and CSBG for 4 h. Among those genes, 62 were common, 26 were OX-CA-specific and 59 were CSBG-specific. Many of these up-regulated genes encode effectors with well-characterized proinflammatory properties. The expression of genes related with signal transduction differed in the particulate and soluble glucans derived from C. albicans having exactly the same primary structure. This fact suggested that each glucan induced specific biological activity through a different activation mechanism. This study using cDNA microarrays to analyze a broad spectrum of mRNA expression provides information on the biological activity of Candida cell wall glucan as a potential pathogenic factor.

Candida albicans↗

PubMed2004

Cellular localization of endocrine cells in the adult pancreas of the house musk shrew, Suncus murinus: a comparative immunocytochemical study.

The right and left lobes of the pancreas in the house musk shrew, Suncus murinus, were found to be completely separated. A morphologic study of the pancreas in S. murinus in terms of the blood supplies and innervation of the right and left lobes was performed in our previous study. It revealed clearly different blood supply and innervation patterns in the right and left lobes, suggesting that the right lobe of the pancreas corresponded to the ventral pancreas, and the left lobe related to the dorsal pancreas. To test this perspective from the histology, in this study, we investigated the immunolocalization of the cells of Langerhans islets in the pancreas of the animal. The distribution of insulin-, glucagon-, somatostatin-, and pancreatic polypeptide (PP)-secreting cells of the right and left lobes of the pancreas was examined in 10 animals. The glucagon-immunoreactive cells were distributed in both the right and left lobes. The PP-immunoreactive cells were extremely abundant in the right lobe and distributed throughout almost all the islets of Langerhans in the right lobe. By contrast, in the left lobe, immunoreactive PP cells were absent in the islets of Langerhans, and only very few immunoreactive PP cells were scattered in the exocrine parenchyma in part of the specimens. Therefore, these findings support our previous studies, and showed that the right and left lobes of the S. murinus pancreas could be related to an embryological origin from the ventral and dorsal pancreatic primordium, respectively, and that the S. murinus pancreas is suitable as a new experimental model to study the development of the human pancreas.

Animals↗

PubMed2004

Characterization of beta-glucan recognition site on C-type lectin, dectin 1.

Dectin 1 is a mammalian cell surface receptor for (1-->3)-beta-d-glucans. Since (1-->3)-beta-d-glucans are commonly present on fungal cell walls, it has been suggested that dectin 1 is important for recognizing fungal invasion. In this study we tried to deduce the amino acid residues in dectin 1 responsible for beta-glucan recognition. HEK293 cells transfected with mouse dectin 1 cDNA could bind to a gel-forming (1-->3)-beta-d-glucan, schizophyllan (SPG). The binding of SPG to a dectin 1 transfectant was inhibited by pretreatment with other beta-glucans having a (1-->3)-beta-d-glucosyl linkage but not by pretreatment with alpha-glucans. Dectin 1 has a carbohydrate recognition domain (CRD) consisting of six cysteine residues that are highly conserved in C-type lectins. We prepared 32 point mutants with mutations in the CRD and analyzed their binding to SPG. Mutations at Trp(221) and His(223) resulted in decreased binding to beta-glucan. Monoclonal antibody 4B2, a dectin- 1 monoclonal antibody which had a blocking effect on the beta-glucan interaction, completely failed to bind the dectin-1 mutant W221A. A mutant with mutations in Trp(221) and His(223) did not have a collaborative effect on Toll-like receptor 2-mediated cellular activation in response to zymosan. These amino acid residues are distinct from residues in other sugar-recognizing peptide sequences of typical C-type lectins. These results suggest that the amino acid sequence W221-I222-H223 is critical for formation of a beta-glucan binding site in the CRD of dectin 1.

Amino Acid Sequence↗

PubMed2004

Limitation of polymyxin B on suppression of endotoxin shock induced by Salmonella infection in mice.

The protective effects of an antibiotic polymyxin B (PLB), having lipopolysaccharide (LPS)-binding activity, on infection-induced endotoxin shock in mice were investigated. Infection with 10(8) colony forming units of an attenuated Salmonella typhimurium aroA strain caused lethal endotoxin shock to ddY mice. Treatment with PLB 1 h post infection (p.i.) resulted in significant reduction of mortality and bacterial numbers in livers. In addition, treatment with PLB 1 h p.i. resulted in a transient increase at the early stage and gradual decline in plasma LPS levels. Although plasma levels of sCD14 and high mobility group box chromosomal protein-1 (HMGB-1) increased according with progression of infection, increases in plasma levels of sCD14 and HMGB-1 were downregulated by treatment with PLB 1 h p.i. However, the lethal shock was not blocked by treatment with anti-CD14 monoclonal antibody at 3 h and 6 h p.i. Interestingly, administration of PLB 6 h p.i. did not show any protective activities, indicating that a time window for effective PLB action is present.

Animals↗

PubMed2003

Nuclear quantum effects on electron transfer reactions in DNA hairpins.

The driving force dependence of photoinduced electron transfer rate constant in synthetic DNA hairpins in aqueous solutions has been analyzed by means of molecular dynamics simulations. The quantum energy gap law has thus been investigated from a fully atomistic point of view, well reproducing the experimental results with reduced ambiguities in the parameter fitting. Although the contribution from the high-frequency vibrational modes of DNA and water solvent to the reorganization energy is fairly small, their quantum effect on the electron transfer rate constant is significant, well accounting for the deviation from the Marcus parabola observed in the experiments.

Base Sequence↗

PubMed2003

Anatomical study of the pancreas in the house musk shrew (Suncus murinus), with special reference to the blood supply and innervation.

To examine the macroscopic structure, blood supply, and innervation of the pancreas in the house musk shrew (Suncus murinus), we performed gross anatomical dissection and whole-mount immunostaining of the autonomic nerve of Suncus pancreases based on neurofilament protein (NFP) immunoreactivity. The adult Suncus pancreas is clearly separated into right and left lobes that are not fused. The right lobe of the Suncus pancreas is located in the dorsum of the duodenum and to the right of the common bile duct independently. The right lobe is supplied by branches of the superior mesenteric artery, and is innervated by branches that originate from the superior mesenteric plexus and run along the arterial branches of the superior mesenteric artery. The left lobe occupies 9/10 of the entire pancreas and is located to the left of the common bile duct. It is supplied mainly by branches of the splenic and common hepatic arteries, and is innervated by branches that originate from the celiac plexus and run along the splenic and common hepatic arteries. According to previous studies on the blood supply and innervation of the human pancreas, the right and left lobes of the Suncus pancreas correspond to the pancreatic parts derived from the ventral and dorsal pancreatic buds. The current results suggest that the Suncus pancreas is a suitable experimental model for studying the development of the human pancreas.

Animals↗

PubMed2003

Morphological study on the rootlets comprising the root of the intermediate nerve.

The number and arising sites of the rootlet comprising the intermediate nerve root were investigated in 100 sides of human brains. The arising sites of the rootlets were the pons halfway between the facial and vestibulocochlear nerves (31.9%), the arising portion of the vestibulocochlear nerve on the pons (28.8%) and the stem of the vestibulocochlear nerve (15.9%). The number of roots varied from one to five, with the most common being one root (58%). The number of rootlets per root also varied from one to five. Most of the roots had one rootlet (63%), while 2% of the roots had five rootlets. The variation of the arising sites of the intermediate nerve rootlets and its clinical significance were also discussed.

Adult↗

PubMed2003

Innervation of the pancreas from the perspective of perineural invasion of pancreatic cancer.

INTRODUCTION: Pancreatic cancer invasion via neural routes (perineural invasion) has been studied extensively, but detailed research on the morphology of innervation of the pancreas related to perineural invasion is scarce. AIMS: To clarify the morphology of neural distribution in the human pancreas. METHODOLOGY: The pancreas and surrounding structures were dissected in 9 cadavers, the specimens were immersed in a 0.001% solution of alizarin red S in ethanol to stain the peripheral nerves, and the detailed distribution was studied to confirm the extrapancreatic and intrapancreatic plexus using a binocular microscope. RESULTS: The innervation of the uncinate process of the pancreas originated from the superior mesenteric plexus (SMPlx) along the inferior pancreaticoduodenal artery (IPDA), but did not form a wide offshoot of nerve bundles as reported. Concerning the innervation of the body and tail, it was found that the nerve fibers entered the pancreas immediately after leaving the celiac plexus, and were distributed around the pancreatic duct in a twig-like manner. CONCLUSION: It was emphasized that the nerve originating from SMPlx to the uncinate process chiefly ran along the IPDA and it was necessary to focus one's attention not only on the extrapancreatic perineural invasion but also on the intrapancreatic perineural invasion in carcinoma of the body and tail of the pancreas.

Aged↗

PubMed2003

Innervation of calf muscles in relation to calf reduction.

Plump and muscular calves, a so-called radish-like leg, embarrass young women and cause a feeling of inferiority in Korea. Damage to motor nerves innervating a muscle makes the muscle paralyzed and dystrophic, with loss of muscle volume. The authors studied the morphometry of the motor branches of the tibial nerve innervating the gastrocnemius and soleus muscle and sensory medial sural cutaneous nerve in popliteal fossa. Dissection and exploration of the tibial nerve were performed in the popliteal fossae of 70 legs (of 18 males and 17 females) of embalmed Korean cadavers. The main branch of the tibial nerve innervating medial and lateral gastrocnemius muscle originated 3 cm above and below the popliteal crease. The medial gastrocnemius muscle had an additional nerve (49%). The medial sural cutaneous nerve came off the nerve into the medial gastrocnemius muscle (30%) and diverged 5.5 mm from the tibial nerve. The nerve into the soleus muscle originated from the nerve innervating the lateral gastrocnemius muscle (30%) and was 12.3 mm away from it. Surgeons should keep in mind that the medial sural cutaneous nerve originates from the nerve to medial gastrocnemius in 30% and the nerve to soleus muscle originates from the nerve to lateral gastrocnemius in 30%.

Cadaver↗