Biomedical subjects

Hiroshi Yamada

Publications and source records attributed to Hiroshi Yamada.

At least 19 recordsLinked to original sources

PubMed2025

An adjuvant database for preclinical evaluation of vaccines and immunotherapeutics.

Adjuvants are immunostimulators used to enhance vaccine efficacy against infectious diseases. However, current methods for evaluating their efficacy and safety are limited, hindering large-scale screening. To address this, we developed a prototype Adjuvant Database (ADB) containing transcriptome data, generated using the same protocols as the widely used Open TG-GATEs (OTG) toxicogenomics database, covering 25 adjuvants across multiple species, organs, time points, and doses. This enabled cross-database integration of ADB and OTG. Transcriptomic patterns successfully distinguished each adjuvant regardless of organs or species. Using both databases, we built machine learning models to predict adjuvanticity and hepatotoxicity. Notably, we identified colchicine's adjuvant activity and FK565's liver toxicity through data-driven analysis. Overall, ADB combined with OTG offers a framework for transcriptomics-based, data-driven screening of adjuvant candidates.

Animals↗

PubMed2003

Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation.

Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-tetrads. Colocalization of CpG DNA with Toll-like receptor 9 in endosomal vesicles is disrupted by these repetitive elements, although cellular binding and uptake remain unchanged. These findings are the first to establish that specific host-derived molecules can down-regulate the innate immune response elicited by a TLR ligand.

Adjuvants, Immunologic↗

PubMed2003

Ubiquitin-positive inclusions in ependymal cells.

Ubiquitin-positive inclusions (UbIs) have not been well studied in ependymal cells. Since we detected such UbIs in the central canals of the medulla and spinal cord while investigating UbIs in neurodegenerative diseases, we studied UbIs in the entire ependymal system of 42 patients with various neurological diseases and of 10 non-neurological controls. UbIs were located in the cytoplasm of the ependymal cells, and were round to oval in shape, measuring 4-11 microm in diameter. The UbIs were non-argyrophilic and undetectable by hematoxylin and eosin staining, but mildly reactive to periodic acid-Schiff staining with and without digestion. The UbIs were variably immunoreactive for anti-epithelial membrane antigen (EMA) antibody, but did not react with several other antibodies. The co-existence of ubiquitin and EMA was confirmed by confocal laser microscopy. Throughout the ependymal system, UbIs were variably found in ependymal cells as well as in subependymal cells. There was no significant difference in the overall incidence of either ependymal or subependymal UbIs between the patients with neurological diseases and controls. However, ependymal UbIs in the central canal were more frequent in the neurological disease patients than in controls, although there was no disease specificity. This is the first comprehensive report to show common occurrence of UbIs in the ependymal cells of adult human brains.

Adolescent↗

PubMed2003

Goal-directed, serial and synchronous activation of neurons in the primate striatum.

To study roles of cortico-basal ganglia loops in action planning, we examined interactions between the activities of simultaneously recorded neurons in the striatum of monkeys performing sequence motor tasks by cross-correlation analysis. Serial activation occurred between projection neurons in a motor sequence-dependent manner, and was in the direction of a neuron encoding an early event in the sequence to a neuron encoding the same event or later, but closer event to the reward. Synchronous activation occurred between pairs of interneurons. The serial activation seems to originate through the cortico-basal ganglia loops, because projection neurons are inhibitory. We propose that the task-dependent serial and synchronous activation of striate neurons may be a neural substrate for goal-directed planning through the basal ganglia.

Animals↗

PubMed2003

Severe neutropenia with gelatinous bone marrow transformation in anorexia nervosa: a case report.

A 28-year-old woman with a history of anorexia nervosa was admitted with excessive weight loss, edema, and amenorrhea. She had lost 34% of her previous body weight within 2 years, and her body mass index was 12.3 kg/m(2). The leukocyte count on admission was 2150/microl and gradually decreased to 980/microl (neutrophils; 276/microl). Bone marrow biopsy disclosed gelatinous transformation with hypocellularity. After the patient was treated with intravenous nutritional support, the severe neutropenia improved to the level on admission. Hematological abnormalities seem to be common in anorexia nervosa, but severe neutropenia with gelatinous bone marrow transformation has rarely been reported.

Adult↗

PubMed2003

Relationships between the changes in compound muscle action potentials and selective injuries to the spinal cord and spinal nerve roots.

OBJECTIVE: Compound muscle action potentials (CMAPs) evoked by transcranial electrical stimulation have been widely introduced to monitor motor function during spinal surgery. They may reflect segmental injuries as well as injuries to motor-related tracts in the spinal cord. However, we have experience with some patients who developed postoperative segmental motor weakness without any potential changes during surgery. To evaluate the efficacy of this method, we used a cat model to observe the relationships between potential changes and selective injuries to the white and gray matters of the spinal cord and spinal nerve roots. METHODS: Ten CMAPs were obtained before and after injury to the spinal cord and spinal nerve roots in 20 cats. Changes in the amplitude, latency, and duration of CMAPs were analyzed. RESULTS: CMAPs decreased in amplitude significantly after the insult to the motor-related tracts in the spinal cord in all cats, while the potentials did not always change when the insult was restricted to a limited area in the anterior horn of the spinal cord or to the single spinal nerve root. CONCLUSIONS: CMAPs may not exactly reflect segmental injury, and careful attention should be paid to the interpretation of CMAPs.

Action Potentials↗

PubMed2003

[Host cellular proteases trigger the infectivity of the influenza virus in the airway and brain].

The pathogenesis of the influenza and Sendai viruses is primarily determined by host cellular trypsin-type processing proteases that activate viral fusion activity and infectivity. We isolated three secretory trypsin-type proteases from rat lungs, such as tryptase Clara, mini-plasmin, and ectopic anionic trypsin, candidates for the processing proteases of viral envelope glycoproteins. These enzymes specifically cleave the precursor of fusion glycoprotein hemagglutinin (HA) of influenza virus at Arg(325) and the F(0) of Sendai virus at Arg(116) in the consensus cleavage motif, Gln(Glu)-X-Arg, resulting in the induction of infectivity of these viruses. These proteases show different localization in the airway and susceptibility for the processing of various subtypes of influenza virus HA, suggesting that these processing proteases determine the viral pathogenicity. Influenza virus readily infects and replicates in the airway epithelial cells but occasionally replicates in the central nervous system, particularly in children below 5-6 years of age and Reye's syndrome patients. We found an invasion by a non-neurovirulent influenza virus in cerebral capillaries with progressive brain edema of mice having impaired mitochondrial fatty acid metabolism congenitally or posteriorly in the newborn period. In the brain of these mice, mini-plasmin, which potentiates viral-multiplication in vivo and destroys the blood-brain barrier, accumulated with virus antigen in the brain capillaries but only a little in the control mice without impaired mitochondrial fatty acid metabolism.

Animals↗

PubMed2003

[The effects of inhaled carbon monoxide on lung injury in rats caused by lipopolysaccharide].

BACKGROUND: Carbon monoxide (CO) has long been considered a toxic substance. Recent studies have revealed that CO may play an important role in intercellular signaling. We hypothesized that CO modulates the inflammatory mechanisms. METHODS: SD rats (each study group consisting of 7 animals) inhaled 250 ppm of CO one hour prior to LPS challenges. These animals were incubated for a particular period of time (four different length of time; 1, 2, 4, and 8 hours). The control group (each study group consisting of 6 animals) had been left in the room air. Both groups were instilled with LPS (1 mg) into the lungs. At the end of each period, animals were exsanguinated, broncho-alveolar lavage (BAL) and blood sampling were performed, and a part of the small intestine was harvested. PMN numbers, protein, TNF, and IL-10 concentrations in BAL fluid were measured. Plasma TNF and IL-10 were also measured. The Wet/Dry ratio of a small intestine was calculated. RESULTS: In the CO-inhalation group, the anti-inflammatory cytokine IL-10 concentration in the BAL fluid was higher at 8 hours after LPS challenge than the counterpart of room air group (37.6 +/- 11.4 pg.ml-1 vs. 92.8 +/- 31.5 pg.ml-1, P < 0.05). W/D ratio decreased (3.29 +/- 0.2 vs. 2.94 +/- 0.06, P < 0.05). CONCLUSION: These findings indicated that CO inhalation might modulate the inflammatory response to LPS. Further study is needed to prove the therapeutic role of CO inhalation without serious adverse effects.

Acute Disease↗

PubMed2002

Influence of stability on range of motion after cruciate-retaining TKA.

BACKGROUND: A loosely balanced total knee arthroplasty (TKA) is reported to produce a good postoperative range of motion (ROM), but too much laxity is thought to be the cause of persistent pain and worsened functionality. METHODS: The anteroposterior and mediolateral laxity values were measured to evaluate the influence of stability after cruciate-retaining (CR) TKA on ROM and the modified Knee Society score at 4-8 years after the operation. Twenty-one knees in 15 patients with an average age of 68 years who had undergone a CR TKA for osteoarthrosis were examined. The mean preoperative and postoperative ROM was 124 degrees and 112 degrees, respectively. The mean anteroposterior and mediolateral laxity values were 9.7 mm and 10.6 degrees, respectively. RESULTS: No correlation was found between the postoperative ROM and laxity or between the modified Knee Society score and laxity. A loosely balanced TKA did not produce a good postoperative ROM. No parameters suggested that lax knees showed a higher pain score and lower functional score than stable knees.

Aged↗

PubMed2002

Effect of suppressive DNA on CpG-induced immune activation.

Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs stimulate a strong innate immune response. This stimulation can be abrogated by either removing the CpG DNA or adding inhibitory/suppressive motifs. Suppression is dominant over stimulation and is specific for CpG-induced immune responses (having no effect on LPS- or Con A-induced activation). Individual cells noncompetitively internalize both stimulatory and suppressive ODN. Studies using ODN composed of both stimulatory and suppressive motifs indicate that sequence recognition proceeds in a 5'-->3' direction, and that a 5' motif can block recognition of immediately 3' sequences. These findings contribute to our understanding of the immunomodulatory activity of DNA-based products and the rules that govern immune recognition of stimulatory and suppressive motifs.

Adjuvants, Immunologic↗

PubMed2002

Secretory granule-mediated co-secretion of L-glutamate and glucagon triggers glutamatergic signal transmission in islets of Langerhans.

L-Glutamate is believed to function as an intercellular transmitter in the islets of Langerhans. However, critical issues, i.e. where, when and how L-glutamate appears, and what happens upon stimulation of glutamate receptors in the islets, remain unresolved. Vesicular glutamate transporter 2 (VGLUT2), an isoform of the vesicular glutamate transporter essential for neuronal storage of L-glutamate, is expressed in alpha cells (Hayashi, M., Otsuka, M., Morimoto, R., Hirota, S., Yatsushiro, S., Takeda, J., Yamamoto, A., and Moriyama, Y. (2001) J. Biol. Chem. 276, 43400-43406). Here we show that VGLUT2 is specifically localized in glucagon-containing secretory granules but not in synaptic-like microvesicles in alpha TC6 cells, clonal alpha cells, and islet alpha cells. VGLUT1, another VGLUT isoform, is also expressed and localized in secretory granules in alpha cells. Low glucose conditions triggered co-secretion of stoichiometric amounts of L-glutamate and glucagon from alpha TC6 cells and isolated islets, which is dependent on temperature and Ca(2+) and inhibited by phentolamine. Similar co-secretion of L-glutamate and glucagon from islets was observed upon stimulation of beta-adrenergic receptors with isoproterenol. Under low glucose conditions, stimulation of glutamate receptors facilitates secretion of gamma-aminobutyric acid from MIN6 m9, clonal beta cells, and isolated islets. These results indicate that co-secretion of L-glutamate and glucagon from alpha cells under low glucose conditions triggers GABA secretion from beta cells and defines the mode of action of L-glutamate as a regulatory molecule for the endocrine function. To our knowledge, this is the first example of secretory granule-mediated glutamatergic signal transmission.

Animals↗

PubMed2002

Does reconstruction of posterior ligamentous complex with extensor musculature decrease axial symptoms after cervical laminoplasty?

STUDY DESIGN: The authors retrospectively determined the prevalence of neck and shoulder symptoms (axial symptoms) after expansive laminoplasty with reattachment of spinous process and extensor musculature in patients with cervical myelopathy. OBJECTIVES: To determine the prevalence of both preoperative and postoperative axial symptoms of expansive laminoplasty when they occur after expansive laminoplasty. SUMMARY OF BACKGROUND DATA: Several clinical reports have noted that laminoplasty for cervical myelopathy produces positive clinical outcomes. However, recent reports have pointed out that complications from laminoplasty, such as axial symptoms, may be severe enough to interfere with daily activities. METHODS: The authors used a modified spinous process-splitting laminoplasty, which involved reattaching the spinous process with extensor musculature after enlarging the spinal canal by use of the French window method. Postoperative axial symptoms were investigated in 173 of 214 patients (80.1%) who underwent expansive laminoplasty between January 1989 and December 1998. The patients included 121 men and 52 women, and their average age was 61.5 years. The presence or absence and grade of axial symptoms before and after laminoplasty were investigated. The severity and duration of complications were also recorded, along with differences between age, sex, spinal alignment, and cervical diseases. RESULTS: Neck and/or shoulder stiffness worsened in 15% of the patients and declined in 21%. Neck pain worsened in 10% of the patients and improved in 11%. Neck and/or shoulder stiffness worse than moderate was recognized in 14.4% of the patients. Neck pain worse than moderate was recognized in 5% of the patients. In the 137 patients who had no axial pain before surgery, only 13 patients experienced such symptoms after surgery, and in most cases these symptoms were minimal. In only 1 case, significant postoperative neck pain arose de novo as a result of this surgery. In 88 patients who had no neck and/or shoulder stiffness before surgery, only 16 patients experienced such symptoms after surgery, and in most cases these were minimal. A similar pattern held true for each of the other grades of preoperative axial symptoms. The recovery rate score (Japanese Orthopedic Association) was 47.5 +/- 32.3 in the patients whose axial symptoms were worse than moderate and 60 +/- 28.9 in patients whose axial symptoms were less than mild. This difference was significant (P < 0.05). CONCLUSION: Laminoplasty is an appropriate operation for cervical spondylotic myelopathy and did not, in this study, seem to have any significant influence on the development or resolution of axial symptoms.

Adult↗

PubMed2002

Distribution of dynamins in testis and their possible relation to spermatogenesis.

Dynamin 2 and dynamin 3 are highly expressed in testis. However, their functions in the tissue remain unclear. Considering that dynamin 1, neuron-specific isoform of dynamin, plays a pivotal role in endocytosis, functions of dynamin 2 and dynamin 3 in testis must be essential. Cellular expression and subcellular localization of dynamin 2 and dynamin 3 in testis were investigated. Dynamin 2 and dynamin 3 were highly expressed in germ cells and Sertoli cells, constituents of seminiferous tubules. By immunofluorescence it was revealed that dynamin 2 colocalizes with clathrin both at the plasmamembrane and at Golgi in a cell line of Sertoli cells. Immunoreactivity for dynamin 3, on the other hand, appeared as finer puncta, which did not colocalize with clathrin, suggesting that these two dynamins have distinct functions in Sertoli cells. In the klotho deficient mouse testis, which demonstrates disorder in spermatogenesis, expression of dynamin 2 and dynamin 3 was drastically reduced indicating possible association of these proteins with spermatogenesis.

Animals↗

PubMed2002

Phosphatidylinositol 4,5-bisphosphate stimulates vesicle formation from liposomes by brain cytosol.

As a step toward the elucidation of mechanisms in vesicle budding, a cell-free assay that measures cytosol-induced vesicle generation from liposomes was established. This assay then was used to explore the role of phosphoinositides in vesicle formation. Liposomes incubated with brain cytosol in the presence of ATP and GTP massively generated small vesicles, as assessed both quantitatively and qualitatively by a dynamic light-scattering assay. Both ATP and GTP were required. Vesicle formation was inhibited greatly by the immunodepletion of dynamin 1 from the cytosol, indicating a major contribution of this GTPase in this reaction and suggesting that it mimics endocytic vesicle fission. Increasing the concentration of l-alpha-phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] but not of l-alpha-phosphatidylinositol 4-monophosphate or l-alpha-phosphatidylinositol in the lipid membranes enhanced vesicle formation. Lipid analysis revealed rapid degradation of PtdIns(4,5)P2 to l-alpha-phosphatidylinositol during the incubation with the reaction reaching a maximum within 5 sec, whereas vesicle formation proceeded with a longer time course. PtdIns(4,5)P2 degradation was independent of vesicle formation and occurred also in the presence of guanosine 5'-O-(thiotriphosphate), where few vesicle formations occurred. These results suggest that PtdIns(4,5)P2 plays a critical role in the early step of vesicle formation, possibly in the recruitment of coats and fission factors to membranes.

Adenosine Triphosphate↗

PubMed2002

Lumbar sagittal balance influences the clinical outcome after decompression and posterolateral spinal fusion for degenerative lumbar spondylolisthesis.

STUDY DESIGN: This study was designed to assess both lumbar sagittal balance and clinical outcomes of decompression and posterolateral fusion for degenerative lumbar spondylolisthesis. As an index for the radiologic evaluation of sagittal alignment, the L1 axis S1 distance was used (i.e., the horizontal distance from the plumbline of the center in the L1 to the back corner of the S1). OBJECTIVE: To determine whether lumbar sagittal balance affected the clinical outcome after posterolateral fusion. SUMMARY OF BACKGROUND DATA: Little is known about whether the sagittal vertical axis influences clinical outcomes in cases of degenerative lumbar spondylolisthesis. METHODS: A retrospective review of 47 patients (15 men and 32 women), ranging in age from 41 to 79 years, was conducted. The mean follow-up period was 3.6 years. Relations among outcomes including the visual analog pain scale, recovery rate, L1 axis S1 distance, slippage, and lumbar lordosis were evaluated. RESULTS: Recovery rates were 44% and 62% in patients whose preoperative L1 axis S1 distance, respectively, was more than 35 mm (Group A, n = 16) and less than 35 mm (Group B, n = 31) (P < 0.05). Follow-up assessment found a positive correlation between only lordosis and recovery rate. Severe low back pain and lower recovery rate were observed in patients with in situ fusion in Group A (n = 9), as compared with patients with reduced slippage in Group A (n = 7) and patients in Group B. CONCLUSIONS: Both preoperative L1 axis S1 distance and lordosis at follow-up assessment affected surgical outcome. Reduction of slippage may improve clinical outcomes of posterolateral fusion for degenerative lumbar spondylolisthesis with an L1 axis S1 distance more than 35 mm.

Adult↗

PubMed2002

Reduction of CpG-induced arthritis by suppressive oligodeoxynucleotides.

OBJECTIVE: Bacterial DNA contains immunostimulatory CpG motifs that cause inflammation when injected into the knee joints of normal mice. We examined whether synthetic oligodeoxynucleotides (ODN) that suppress CpG-induced immune responses prevent CpG-induced arthritis. METHODS: CpG, suppressive, and/or control ODN were injected into the knees of BALB/c mice. Joint swelling and inflammation were evaluated by physical measurement, by histologic analysis of joint tissue, and by magnetic resonance imaging. RESULTS: Immunostimulatory CpG DNA induced local arthritis, characterized by swelling of the knee joints, the presence of inflammatory cell infiltrates, the perivascular accumulation of mononuclear cells, and hyperplasia of the synovial lining. Administering suppressive (but not control) ODN reduced the manifestations and severity of arthritis up to 80%. CONCLUSION: Suppressive ODN may be useful for the prevention or treatment of arthritis induced by bacterial DNA.

Animals↗

PubMed2002

Discrepancy between decreases in the amplitude of compound muscle action potential and loss of motor function caused by ischemic and compressive insults to the spinal cord.

We examined the relationship between decreases in the amplitude of the compound muscle action potential (CMAP), caused by ischemic and compressive insults to the spinal cord, and postoperative motor deficits. Results were compared with those for other evoked potentials commonly used for multimodal monitoring of the spinal cord. CMAP was more sensitive than the other evoked potentials employed to ischemic and compressive insults to the spinal cord, although the disappearance of CMAP did not always result in a residual motor deficit. A decrease of more than 50% in the amplitude of the motor-evoked potential (MEP) from the spinal cord correlated well with the postoperative motor deficit. CMAP is a sensitive tool for the early detection of spinal cord impairment caused by ischemic or compressive insults to the spinal cord. The time after the disappearance of the CMAP amplitude was important for predicting postoperative motor deficit, but it is also necessary to employ CMAP concomitantly with other conductive potentials in spinal cord monitoring.

Action Potentials↗

PubMed2002

Identification of ectopic anionic trypsin I in rat lungs potentiating pneumotropic virus infectivity and increased enzyme level after virus infection.

Extracellular cleavage of virus envelope fusion glycoproteins by host cellular proteases is a prerequisite for the infectivity of mammalian and nonpathogenic avian influenza viruses, and Sendai virus. In search of such target processing proteases in the airway, we recently found a new candidate trypsin-like processing protease in rat lungs, which was induced by Sendai virus infection, and identified as ectopic rat anionic trypsin I. On SDS/PAGE under reducing and nonreducing conditions, the purified enzyme gave protein bands corresponding to 29 and 22 kDa, respectively, i.e. at the same positions as rat pancreatic anionic trypsin I. It exhibited an apparent molecular mass of 31 kDa on molecular sieve chromatography and its isoelectric point was pH 4.7. The amino-acid sequences of the N-terminus and proteolytic digest peptides of the purified enzyme were consistent with those of rat pancreatic anionic trypsin I. Its substrate specificities and inhibitor sensitivities were the same as those of the pancreatic enzyme. The purified enzyme efficiently processed the fusion glycoprotein precursor of Sendai virus and hemagglutinin of human influenza A virus, and potentiated the infectivity of Sendai virus in the same dose-dependent manner as the pancreatic one. Immunohistochemical studies revealed that this protease is located in the stromal cells in peri-bronchiolar regions. These results suggest that ectopic anionic trypsin I in rat lungs induced by virus infection may trigger virus spread in rat lungs.

Amino Acid Sequence↗