Biomedical subjects

J Yoshida

Publications and source records attributed to J Yoshida.

At least 19 recordsLinked to original sources

PubMed2005

Balance of risk of therapeutic hypothermia.

The complications of therapeutic hypothermia sometimes undermine its clinical effects. In this study we investigated the efficacy and safety of therapeutic hypothermia based on analysis of 20 severe head injury cases from 6 institutions treated with therapeutic hypothermia in 1999. The twenty patients with severe head injury were enrolled prospectively based on the following indications; Glasgow Coma Scale of 7 or less on admission, age 60 or younger, and systric BP over 100 mmHg. A control group consisting of 21 patients with severe head injury met the same criteria but were treated without therapeutic hypothermia in other institutions. Clinical benefit were evaluated by a comparison of clinical result in the two groups defined according to the Glasgow Outcome Scale six months after injury. The hypothermia group was divided into two groups based on a target temperature [mild hypothermia group: 32-34 degrees C (n = 10); very mild hypothermia group: 35-36 degrees C (n = 10)]. The complication rate, clinical results and the duration of therapeutic hypothermia were analyzed between two groups. In the hypothermia group, 12 patients obtained a favorable outcome (Good Recovery or Moderate Disabled in GOS) and the mortality rate was 35%. In the control group, however only 5 patients had a favorable outcome and the mortality rate was 57%. Comparison between mild hypothermia and very mild hypothermia groups revealed no difference in clinical outcome. In the hypothermia group, severe pneumonia was seen in three patients, all in the mild hypothermia group with a hypothermic duration of over 120 hours. Mild hypothermia should be ended within 120 hours to avoid severe complication. When long-lasting therapeutic hypothermia of more than 120 hours is planned, very mild hypothermia is the treatment of choice.

Adult↗

PubMed2005

Structure-based design of an agonistic peptide targeting Fas.

A small agonistic peptide FRAP-4 (WEWT, Fas reactive peptide-4) that binds to the human Fas molecule was discovered using our computer screening strategy named the Amino acid Complement Wave (ACW) method, which is based on the complementarities of interacting amino acids between comprehensive testing peptides and a target protein surface pocket. In silico docking studies demonstrated the specific interaction of FRAP-4 with the main Fas ligand (FasL) binding domain in the Fas molecule. An octamer of this peptide produced by carboxyl terminal linkages of polylysine branches (MAP), (FRAP-4)8-MAP, effectively induced apoptosis in human ovarian cancer cell line NOS4 cells that was associated with the activation of caspases-8, -9 and -3, and the cleavage of PARP. Alanine substitution of the N-terminal W in FRAP-4 resulted in complete loss of FasL-mimetic action of (FRAP-4)8-MAP, suggesting that the aromatic functionality at the N-terminal position W appears to play an essentially important role in Fas binding ability. These observations indicate that the FasL-mimetic peptide should serve as an excellent starting point for the design of effective compounds with FasL-mimetic activity. Furthermore, the ACW method for the structure-based design of optimized small peptides against receptor molecules such as Fas could open new avenues for the development of peptide mimetic and nonpeptidic organic forms to generate novel effective pharmaceuticals.

Amino Acid Sequence↗

PubMed2004

Vascular supply of the subcutaneous pedicle of Nagata's method in microtia reconstruction.

Nagata's method is a two-stage method for total ear reconstruction in patients with microtia. In the first stage of this procedure, mastoid flap and posterior lobule flap are elevated with a subcutaneous pedicle. However, contribution to the vascular supply by this pedicle has been controversial. We investigated the presence or absence of apparent vessels in the subcutaneous pedicle in 14 primary cases of microtia in the first stage operation. In all cases some vessels were included in the pedicle. In lobular and small concha type microtia, the vessels originated from the parotid fascia or aponeurotic tissue behind the remnant cartilage. In concha type microtia, apparent vessels could be preserved by including the perichondrium of the conchal cartilage. These findings suggest that the mastoid and posterior lobule flaps or W-shaped flap in Nagata's first stage operation are actually the perforator-based flaps. The source vessel of the perforators seemed to be the posterior auricular artery because of its location although further dissection was not performed in order not to damage the vascular supply. The presence of the vessels can augment the blood supply of not only W-shaped flaps but also the skin flap cephalad to them. By confirming the preservation of the perforators in the subcutaneous pedicle the surgeon may be able to trim the covering skin more safely.

Blood Vessel Prosthesis Implantation↗

PubMed2004

Sequential delivery of interferon-alpha gene and DCs to intracranial gliomas promotes an effective antitumor response.

Effective presentation of tumor antigens by dendritic cells (DCs) is considered to be essential for the induction of antitumor T-cell responses. Apoptotic and necrotic tumors have been noted to be a robust antigen source for DCs. Because glioma cells undergo apoptosis after transfection with the type I interferon (IFN) gene and type I IFNs promote the stimulatory activity of DCs, we hypothesized that transfection of glioma cells with type I IFN genes and provision of DCs would promote particularly effective antitumor activity by both facilitating apoptosis of glioma cells and the presentation of the glioma antigens, thereby inducing specific immune responses against glioma cells. We have previously reported the proof of this hypothesis in vitro and in a subcutaneous tumor model. Here we report an extension of this approach in intracranial (i.c.) gliomas using adenoviral IFN-alpha (Ad-IFN-alpha) vector. Mice bearing day-5 i.c. GL261 glioma received sequential intratumoral (i.t.) delivery of Ad-IFN-alpha and bone marrow-derived syngeneic DCs. This treatment prolonged survival in that nine of 17 animals survived long term (> 60 days versus 0 of 10 control animals). Specific CTL activity was demonstrated following this regimen in the cervical lymph nodes, and the therapeutic efficacy was dependent upon CD8+ cells. Furthermore, these animals were protected against subsequent re-challenge with GL261 gliomas. DCs injected i.t. survived in the tumor and migrated into cervical lymph node. In vitro migration assays revealed the ability of DCs to migrate toward the tumor, suggesting that i.t. injected DCs migrate through the glioma. Taken together, this combination of gene therapy and cellular immunotherapy may be an effective future strategy for treating human gliomas.

Adenoviridae↗

PubMed2003

Effect of tactile interference stimulation of the ear in human primary somatosensory cortex: a magnetoencephalographic study.

OBJECTIVE: To confirm the somatotopic representation of the ear in the primary somatosensory cortex (SI), we studied the tactile interference effects on somatosensory evoked magnetic fields (SEFs) following stimulation of the ear (Helix, Lobulus and Tragus). METHODS: We applied tactile interference stimulation to the neck or face area continuously and concurrently while a time-locked electrical stimulation was applied to the ear. If the amplitude would be reduced by the interference, this would indicate that the cortical representation for both the time-locked electrical stimulation and the continuous interference stimulation overlapped. A two or 3-source model, Source 1 in the neck area of SI, Source 2 in the face area of SI, and Source 3 in the secondary somatosensory cortex (SII), was found to be the most appropriate by brain electric source analysis (BESA). RESULTS: Amplitudes of Sources 1 and 2 in most interference conditions were decreased. Source 1 following stimulation of all 3 sites was significantly reduced when the interference was applied to the neck area. Source 2 following stimulation of all 3 sites was significantly reduced when the interference was applied to the face area. CONCLUSIONS: These findings showed that the interference effect was found in both the neck and face areas of SI following the ear stimulation. SIGNIFICANCE: The representation of the ear in SI might be located in both the neck and face areas.

Adult↗

PubMed2002

Functional magnetic resonance imaging evidence for a representation of the ear in human primary somatosensory cortex: comparison with magnetoencephalography study.

Our previous study (T. Nihashi et al., 2001, Neuro- Image 13: 295-304), using magnetoencephalography (MEG), revealed somatotopy of the ear in the human primary somatosensory cortex (SI); that is, the signals following stimulation of the ear reach both the neck and face areas of the SI. However, since this was the first report on somatotopy of the ear in humans, we performed an fMRI activation study to confirm the somatotopic representation, and compared the electrical activity by MEG and the cerebral blood flow change by fMRI. We studied eight healthy subjects using 3-T MRI. We stimulated three parts of the left ear: the helix, the lobulus, and the tragus. First, we identified the location of the ear area in the SI based on our previous MEG study, in which equivalent current dipoles (ECDs) were located in the neck and/or face areas of the SI. Then, we determined the search volume as a sphere with a 15-mm radius, which was placed in the neck and/or face area. We analyzed whether or not fMRI activation occurred inside such spheres. Stimulation of the helix activated the neck area of the SI in four of eight subjects, and both the neck and face areas in two. No activation was observed in two subjects. Stimulation of the lobulus activated the neck area in one subject, the face area in two, both in four, and neither in one. Stimulation of the tragus activated the face in four, both in three, and neither in one. These fMRI findings confirm the result of MEG that the representation of the ear in the SI is separated into neck and face areas.

Adult↗

PubMed2002

Effect of early induction of hypothermia on severe head injury.

Although therapeutic hypothermia for patients with head injury has improved the outcome, the results in the most severe cases (GCS 3-6) have not been satisfactory so far. We induced hypothermia in head injury patients within 3 hours after the trauma, and compared the outcome of the treatment without hypothermia. Fourteen patients with GCS less than 6 were entered into this study (age range 13 to 58, mean 27.0 years). Seven of them were treated by hypothermia and 6 by the conventional method. The patients undergoing hypothermia were cooled to 34 degrees C within 3 hours after injury, kept at 32-34 degrees C for 48 hours, and then rewarmed. The outcome was evaluated at 6 months post-trauma, and the results were compared in the two groups. Therapeutic hypothermia dramatically suppressed brain swelling on CT in 3 of 7 patients. Four patients including these 3 showed a favorable outcome (good or moderate disability) and 3 died in the hypothermia group. In the conventional treatment group, only 1 patient was moderately disabled and 6 exhibited an unfavorable outcome (severely disabled, vegetative, or death). Early induction of hypothermia can improve the outcome in patients with severe head injury by reducing the severe brain swelling.

Craniocerebral Trauma↗

PubMed2002

Process of apoptosis induced by TNF-alpha in murine fibroblast Ltk-cells: continuous observation with video enhanced contrast microscopy.

Apoptosis is originally defined by unique morphological changes of dying cells, and the biochemical hallmark associated with apoptosis is internucleosomal DNA fragmentation. However, few report has shown the precise time course of the apoptotic events. The present study was designed to try to clarify apoptotic processes using a video-enhanced contrast-differential interference contrast (VEC-DIC) microscopy. The morphological changes of murine fibroblast Ltk-cells treated with TNF-alpha were divided into four stages: (i) pre-apoptotic, (ii) cytoplasmic shrinkage, (iii) membrane blebbing, and (iv) ballooning. Almost of the cells underwent cytoplasmic shrinkage and membrane blebbing within 6 hours after TNF-alpha exposure, and at about 9 hours, they were in the ballooning stage. Based on these data, we investigated the relationship between morphological changes and other biochemical features. The earliest event was exposure of phosphatidyl-serine at the cytoplasmic membrane, which was already observed in the pre-apoptotic stage. Loss of mitochondrial membrane potential was observed in the cytoplasmic shrinkage stage. Caspase-8/-3 activities already started increasing in the pre-apoptotic stage, and reached their peak at 6 hours after TNF-alpha exposure. DNA fragmentation occurred in the late phase of the membrane blebbing.

Animals↗

PubMed2002

[Salvage operation for esophageal cancer after radical chemoradiotherapy].

We reviewed salvage surgery cases for esophageal cancer following radical chemoradiotherapy. From January 1998 through January 2001, 6 patients (4 men, 2 women) underwent salvage operation at our department. Mean age was 56 years (range: 46-66). According to the Japanese Society for Esophageal Diseases localization schema, there was one case in the upper third of the thoracic esophagus, 3 cases in the middle third and 2 cases in the lower third. The histology was squamous cell carcinoma in all cases. Our radical chemoradiotherapy regimen for esophageal cancer was fluorouracil (5-FU) 400 mg/m2/24 hours i.v. on days 1 to 5 and 8 to 12, cisplatin (CDDP) 40 mg/m2/2 hours i.v. on days 1 and 8, and concurrent radiation therapy (2 Gy/day on days 1 to 5, 8 to 12 and 15 to 19). This regimen was repeated in 5 weeks, followed by 5-FU 800 mg/m2/24 hours i.v. on days 1 to 5 and CDDP 80 mg/m2/2 hours i.v. on day 1, which was repeated in 4 weeks. After these chemoradiotherapy, patients who were confirmed to have local recurrence or esophagobronchial fistula underwent salvage operation. Postoperative complications were anastomosis leakage in 1 patient, and anastomosis stenosis in 2 and esophagobronchial fistula in 1. Although no postoperative hospitalized death occurred, 1 patient died because of empyema 3 months after salvage operation. Another patient died due to respiratory failure 15 months later. The salvage operation outcomes are not acceptable. Salvage procedure and indication for salvage intervention need to be changed.

Aged↗

PubMed2001

Diversity-oriented synthesis of multisubstituted olefins through the sequential integration of palladium-catalyzed cross-coupling reactions. 2-pyridyldimethyl(vinyl)silane as a versatile platform for olefin synthesis.

A novel strategy for the diversity-oriented synthesis of multisubstituted olefins, where 2-pyridyldimethyl(vinyl)silane functions as a versatile platform for olefin synthesis, is described. The palladium-catalyzed Heck-type coupling of 2-pyridyldimethyl(vinyl)silanes with organic iodides took place in the presence of Pd2(dba)3/tri-2-furylphosphine catalyst to give beta-substituted vinylsilanes in excellent yields. The Heck-type coupling occurred even with alpha- and beta-substituted 2-pyridyldimethyl(vinyl)silanes. The one-pot double Heck coupling of 2-pyridyldimethyl(vinyl)silane took place with two different aryl iodides to afford beta,beta-diarylated vinylsilanes in good yields. The palladium-catalyzed Hiyama-type coupling of 2-pyridyldimethyl(vinyl)silane with organic halides took place in the presence of tetrabutylammonium fluoride to give di- and trisubstituted olefins in high yields. The sequential integration of Heck-type (or double Heck) coupling and Hiyama-type coupling produced the multisubstituted olefins in regioselective, stereoselective, and diversity-oriented fashions. Especially, the one-pot sequential Heck/Hiyama coupling reaction provides an extremely facile entry into a diverse range of stereodefined multisubstituted olefins. Mechanistic considerations of both Heck-type and Hiyama-type coupling reactions are also described.

Alkenes↗

PubMed2001

Unusually accelerated silylmethyl transfer from tin in stille coupling: implication of coordination-driven transmetalation.

The palladium-catalyzed cross-coupling reaction of 2-PyMe2SiCH2SnBu3 with aryl iodide (Ar-I) exclusively produced the 2-PyMe2SiCH2 transferred product 2-PyMe2SiCH2Ar. The relative transfer ability of organic group from tin was found to be 2-PyMe2SiCH2 >> Ph > Me > Bu >> PhMe2SiCH2, which implies the beneficial pyridyl-to-palladium coordination effect. Thus, the transfer of the silylmethyl group from tin to palladium was remarkably accelerated by simply appending the 2-pyridyl group on silicon. The pyridyl-to-palladium coordination was validated in the palladium(II) complex 2-PyMe2SiCH2PdClPPh3 by 1H NMR and X-ray crystal structure analysis. The cross-coupling product was used for further transformations. The C-Si oxidation of the cross-coupling product 2-PyMe2SiCH2Ar afforded ArCH2OH in high yield. The fluoride ion-catalyzed 1,2-addition of 2-PyMe2SiCH2Ar to carbonyl compound (RR'C=O) gave ArCH2C(OH)RR' in high yield.

Journal Article↗

PubMed2001

Growth-inhibitory effect of a streptococcal antitumor glycoprotein on human epidermoid carcinoma A431 cells: involvement of dephosphorylation of epidermal growth factor receptor.

An antitumor glycoprotein [streptococcal acidic glycoprotein (SAGP)] purified from an extract of Streptococcus pyogenes inhibited the growth of human epidermoid carcinoma A431 cells overexpressing epidermal growth factor receptor (EGFR) in a time- and a concentration-dependent manner. The antiproliferative effect of SAGP was diminished by preincubating the cells with pertussis toxin and by coadministration of sodium orthovanadate, an inhibitor of protein tyrosine phosphatases (PTPases). Western blot analysis showed that the immunoreactivity of a M(r) 170,000 band of cell lysate to antiphosphotyrosine antibody was reduced by SAGP, and the effect was abolished by sodium orthovanadate. The phosphotyrosine level of the precipitant with anti-EGFR antibody was reduced by SAGP, which was abolished by preincubation with pertussis toxin or by a coadministration with sodium orthovanadate. The PTPase activity transiently increased in the lysate of cells incubated with SAGP and was inhibitable by sodium orthovanadate. Additionally, preincubation of serum-starved A431 cells with SAGP decreased the epidermal growth factor-induced tyrosine phosphorylation of EGFR, and the effect of SAGP was sodium orthovanadate sensitive. These findings indicate that dephosphorylation of the M(r) 170,000 EGFR by activation of PTPase(s) may be responsible in part for the antiproliferative effect of SAGP on A431 cells.

Antibiotics, Antineoplastic↗

PubMed2001

Synthetic and theoretical studies on group-transfer imidoylation of organotellurium compounds. remarkable reactivity of isonitriles in comparison with carbon monoxide in radical-mediated reactions.

Imidoylation of organotellurium compounds with isonitriles has been investigated in conjunction with the radical-mediated C1 homologation reaction by using CO and isonitriles. Carbon-centered radicals generated photochemically or thermally from organotellurium compounds react with isonitriles in a group-transfer manner to give the corresponding imidoylated products. Organotellurium compounds have been found to serve as effective precursors of a wide variety of stabilized radicals, namely benzyl, alpha-alkoxy, alpha-amino, and acyl radicals, which take part in the imidoylation with high efficiency. The reactions are compatible with various functional groups, and can be carried out in various solvents including environmentally benign water. The reactivity of isonitriles has been compared with that of CO through competition experiments, and the results indicate that isonitriles are superior to CO as radical acceptors in reactions with stabilized radicals. The origin of the differences has been addressed in theoretical studies with density functional theory calculations using the B3LYP hybrid functional. The calculations suggest that both carbonylation and imidoylation proceed with low activation energies, and that there are virtually no differences in the kinetic sense. Instead, it indicates that thermodynamic effects, namely differences in the stability of the acyl and the imidoyl radicals, control the overall course of the reactions.

Journal Article↗

PubMed2001

Rat glioma cell death induced by cationic liposome-mediated transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment.

BACKGROUND AND OBJECTIVES: We studied antitumor effects and cell death induced by cationic liposome-mediated gene transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene followed by ganciclovir treatment in cultured rat T9 glioma cells and in experimental gliomas produced from this cell line. METHODS: To transfer genes we used small unilamellar cationic liposomes containing N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride. Video-enhanced contrast differential interference contrast microscopy was used for morphologic observations of cultured cells. RESULTS: When we treated the cells or implanted gliomas with the liposomes and ganciclovir, a strong effect was seen against tumor cells, and survival of tumor-implanted rats was increased. Morphologically, cell death observed after HSV-tk gene/liposome and ganciclovir treatment in the cultured glioma cells included both apoptosis and necrosis. CONCLUSIONS: Introduction of the HSV-tk gene in a DNA-liposome complex followed by ganciclovir treatment induced both apoptosis and necrosis, which together resulted in a potent antitumor effect.

Animals↗

PubMed2001

Clinicopathological characteristics of surgically resected lung cancer associated with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is well known to be associated with lung cancer. It is important to clarify the clinical and pathological features of lung cancer with IPF in understanding the pathogenesis of lung cancer in IPF patients. We compared clinicopathological factors of lung cancer in patients with and without IPF. METHODS: A retrospective study was conducted in 711 surgically resected lung cancer patients. Medical records were compared of IPF and non-IPF patients. RESULTS: Of the 711 patients, 53 (7.5%) were IPF patients. Lung cancer in IPF patients was more frequent in elderly male smokers. Most lung cancers in IPF (79%) arose in peripheral areas involving fibrosis (P < 0.01). The incidence of squamous cell carcinoma in the IPF patients (46%) was significantly higher than that in non-IPF patients (22%) (P < 0.01). The incidence of multiple lung cancer in IPF cases (17%) was also significantly higher. CONCLUSIONS: These results suggest that IPF has the potential to develop into lung cancer, especially peripheral squamous cell carcinoma. Further molecular analyses are necessary to clarify the relationship between IPF and lung cancer.

Adenocarcinoma↗

PubMed2001

Representation of the ear in human primary somatosensory cortex.

We studied 13 healthy subjects with a multichannel magnetoencephalography (MEG) system to investigate the somatotopic representation of the ear in the primary somatosensory cortex (SI). We stimulated three parts of the left ear: the helix, the lobulus, and the tragus. The somatosensory-evoked magnetic fields (SEFs) were successfully measured in 7 of 13 subjects. Short-latency responses were analyzed using both single dipole and multidipole models (brain electric source analysis, BESA). From the single dipole model, the equivalent current dipole (ECD) following the helix stimulation was estimated to be near the neck area of SI in all the subjects. In the lobulus stimulation, the ECDs were estimated around the neck area of SI in four subjects, in the face area in one subject, and in the deep white matter in two subjects. In the tragus stimulation, the ECDs were estimated around the neck area of SI in three subjects, in the hand area of SI in two subjects, and in the deep white matter in two subjects. When the ECDs were estimated to be located in unlikely sites (hand area and deep white matter), a two-dipole model, (1) the neck area of SI and (2) face area of SI, was found to be the most appropriate. Although this might be a preliminary study due to a relatively small number of subjects, it revealed that receptive fields of some part of the ear, such as the lobulus and tragus, might be present in both the neck and face areas of SI. These findings suggested that the "ear area" of SI has variability between subjects, unlike the other areas of SI, possibly because the ear is located on the border between the neck and face.

Adult↗

PubMed2001

Intratumoral microinfusion of nimustine (ACNU) for recurrent glioma.

We investigated stereotactic intratumoral microinfusion of nimustine (ACNU) in recurrent brain tumors. Eligibility required histologic confirmation of glioma recurrence despite standard radiotherapy and chemotherapy as well as enhancement of the recurrence with gadolinium on magnetic resonance imaging (MRI). A total intratumoral dose of 10 mg of ACNU was administered continuously with a microinfusion pump over an average of 13h. Fifteen infusions were given in nine patients. All patients completed the treatment safely. On MRI, necrotic changes surrounded the infusion area in all patients, and tumor progression was inhibited or performance score was improved in seven of nine patients. No symptomatic systemic toxicity was evident, although one patient developed permanent left oculomotor palsy locally after treatment of a left medial temporal tumor. It is concluded that direct microinfusion of ACNU into recurrent gliomas can induce tumor necrosis and inhibit tumor growth.

Adult↗

PubMed2001

Extrapleural pneumonectomy for diffuse malignant pleural mesothelioma. A treatment option in selected cases?

OBJECTIVE: There is no standard treatment for diffuse malignant pleural mesothelioma. Sporadic extrapleural pneumonectomy for the disease in off-protocol set has been performed when the disease was judged as being confined to a hemithorax. SUBJECT: To evaluate the role of extrapleural pneumonectomy in the treatment for the disease, cases that underwent surgery in a single institution are reported with descriptions of the stages based on the system from the International Mesothelioma Interest Group. METHODS: Patients with diffuse malignant pleural mesothelioma treated with extrapleural pneumonectomy from 1989 to 1995 at the National Cancer Center Hospital East were reviewed. RESULTS: Five patients underwent extrapleural pneumonectomy. All were male. Their ages ranged from 48 to 68 years. The disease was right-sided in two and left-sided in three. The histologic subtype was epithelial in three, and mixed epithelial and sarcomatous in the other two. Post-surgical pathologic stage was Ib (T1bN0M0) in three, III (T3N1M0) in one, and IV (T4N2M0) in one. There was no treatment-related death. Two cases with epithelial histology were alive with local recurrence on the chest wall at 75 months and at 51 months after surgery, respectively. A case with mixed epithelial and sarcomatous histology died of an esophageal cancer at 25 months after surgery. The two other cases died of the progressed disease at ten months and at four months after surgery, respectively. CONCLUSION: Extrapleural pneumonectomy for diffuse malignant pleural mesothelioma was concluded to be a treatment option in stage Ib cases with epithelial histology. To evaluate precisely the efficacy of surgery for the disease, a randomized control trial must be organized multi-institutionally.

Aged↗