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1.
Clin Pharmacokinet ; 58(11): 1445-1454, 2019 11.
Article in English | MEDLINE | ID: mdl-30997650

ABSTRACT

BACKGROUND: The 24-h area under the concentration-time curve (AUC24)/minimal inhibitory concentration ratio is the best predictive pharmacokinetic/pharmacodynamic (PK/PD) parameter of the efficacy of first-line anti-tuberculosis (TB) drugs. An optimal sampling strategy (OSS) is useful for accurately estimating AUC24; however, OSS has not been developed in the fed state or in the early phase of treatment for first-line anti-TB drugs. METHODS: An OSS for the prediction of AUC24 of isoniazid, rifampicin, ethambutol and pyrazinamide was developed for TB patients starting treatment. A prospective, randomized, crossover trial was performed during the first 3 days of treatment in which first-line anti-TB drugs were administered either intravenously or in fasting or fed conditions. The PK data were used to develop OSS with best subset selection multiple linear regression. The OSS was internally validated using a jackknife analysis and externally validated with other patients from different ethnicities and in a steady state of treatment. RESULTS: OSS using time points of 2, 4 and 8 h post-dose performed best. Bias was < 5% and imprecision was < 15% for all drugs except ethambutol in the fed condition. External validation showed that OSS2-4-8 cannot be used for rifampicin in steady state conditions. CONCLUSION: OSS at 2, 4 and 8 h post-dose enabled an accurate and precise prediction of AUC24 values of first-line anti-TB drugs in this population. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02121314).


Subject(s)
Antitubercular Agents/pharmacokinetics , Drug Monitoring/methods , Tuberculosis/blood , Adult , Antitubercular Agents/blood , Cross-Over Studies , Ethambutol/blood , Ethambutol/pharmacokinetics , Fasting/metabolism , Female , Humans , Isoniazid/blood , Isoniazid/pharmacokinetics , Male , Middle Aged , Pyrazinamide/blood , Pyrazinamide/pharmacokinetics , Rifampin/blood , Rifampin/pharmacokinetics , Tuberculosis/drug therapy , Young Adult
2.
BMC Public Health ; 19(1): 363, 2019 Apr 02.
Article in English | MEDLINE | ID: mdl-30940123

ABSTRACT

BACKGROUND: Establishing a correct diagnosis is challenging. We aimed to investigate the sensitivity and specificity of routine tuberculosis (TB) diagnostic work-up in lung clinics in Indonesia, a country with the third highest TB burden and the second highest gap between notifications of TB cases and the best estimate of incident cases in the world. METHODS: In the lung clinics of the Province of Yogyakarta, Indonesia, we recruited all consecutive patients with symptoms suggesting TB, aged ≥18 years. Routine TB examination consisted of clinical evaluation, sputum smear microscopy, and chest radiography. For research purposes, we added sputum culture, Human Immunodeficiency Virus (HIV) testing, and follow-up for 1.5 years or 2.5 years if culture results disagreed with the initial clinical diagnosis. The initial diagnosis was considered incorrect if patients did not respond to treatment. We calculated sensitivity and specificity of the TB routine examination using culture and a composite reference standard (CRS - a combination of routine examination, culture, and follow-up) as the reference standards. All analyses were conducted with IBM SPSS Statistics 25 (IBM Corp., Armonk, NY, USA). RESULTS: Between 2013 and 2015, we included 360 participants, and 21 were excluded due to incomplete data. Among those analyzed, 115 were initially diagnosed with smear-positive TB, 12 with smear-negative TB, and 212 non-TB. In 15 study participants, the diagnosis was changed after median 45 (range: 14-870) days; 14 participants initially not diagnosed with TB were later diagnosed with TB, while one subject initially diagnosed with TB actually did not have TB. Compared with culture and CRS, TB routine examination had sensitivity of 85% (95%CI: 77-91) and 90% (95%CI: 84-94), and specificity of 86.3% (95%CI: 81-91) and 99.5% (95%CI: 97-100), respectively. CONCLUSIONS: A combination of clinical evaluation with sputum microscopy and chest radiography provided high sensitivity and specificity in diagnosing TB in lung clinics; in only 4.4% the diagnosis was incorrect. There is a need to improve routine TB diagnostic work by using clinical evaluation, sputum smear microscopy, and chest radiography all together in other settings, such as in primary health centers. TRIAL REGISTRATION: NCT02219945 , clinicaltrials.gov . Registered 19 August 2014 (retrospectively registered).


Subject(s)
Diagnostic Tests, Routine/methods , Lung , Mycobacterium tuberculosis/growth & development , Tuberculosis, Pulmonary/diagnosis , Adult , Female , HIV Infections/virology , Humans , Indonesia , Lung/microbiology , Lung/pathology , Male , Microscopy , Middle Aged , Pneumonia/diagnosis , Radiography/methods , Reference Standards , Retrospective Studies , Sensitivity and Specificity , Sputum/microbiology , Thorax/diagnostic imaging , Tuberculosis/diagnosis , Tuberculosis/microbiology , Tuberculosis, Pulmonary/microbiology
3.
Opt Express ; 21(5): 5487-98, 2013 Mar 11.
Article in English | MEDLINE | ID: mdl-23482120

ABSTRACT

Software defined networking (SDN) and flexible grid optical transport technology are two key technologies that allow network operators to customize their infrastructure based on application requirements and therefore minimizing the extra capital and operational costs required for hosting new applications. In this paper, for the first time we report on design, implementation & demonstration of a novel OpenFlow based SDN unified control plane allowing seamless operation across heterogeneous state-of-the-art optical and packet transport domains. We verify and experimentally evaluate OpenFlow protocol extensions for flexible DWDM grid transport technology along with its integration with fixed DWDM grid and layer-2 packet switching.

4.
Opt Express ; 21(1): 789-95, 2013 Jan 14.
Article in English | MEDLINE | ID: mdl-23388971

ABSTRACT

We demonstrate the first 7-core multicore erbium-doped fiber amplified (MC-EDFA) transmission of 40 x 128-Gbit/s PDM-QPSK signals over 6,160-km 7-core multicore fiber (MCF). The crosstalk (XT) from all of the other 6 cores of a MC-EDFA and a 55-km length MCF are about -46.5 dB and -45.6 dB at center core, respectively. The core-to-core rotation approach at every amplified span is used to average the XT of all cores. The averaged optical signal-to-noise ratio (OSNR) after 6,160-km transmission is 15.6 dB with 0.1 nm resolution bandwidth. The Q-factor of all 40 channels surpasses the threshold of the forward-error-correction of 6.4 dB with 1 dB margin after 6,160 km. The total net capacity is 28.8 Tbit/s per fiber and achieved capacity-distance product is 177 Pbit/s.km per fiber. We confirmed the feasibility of MC-EDFA repeatered systems for trans-oceanic transmission.

5.
J Periodontal Res ; 48(5): 591-9, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23317284

ABSTRACT

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) is a new treatment method for the removal of infectious pathogens using a photosensitizer and light of a specific wavelength, e.g., toluidine blue with a wavelength of about 600 nm. We explored a new photosensitizer and focused on indocyanine green (ICG), which has high absorption at a wavelength of 800-805 nm. We investigated the bactericidal effect of PDT on Porphyromonas gingivalis using a new photosensitizer, ICG-loaded nanospheres with an 805 nm wavelength low-level diode laser irradiation. METHODS: We designed ICG-loaded nanospheres coated with chitosan (ICG-Nano/c) as a photosensitizer. A solution containing Porphyromonas gingivalis (10(8)  CFU/mL) with or without ICG-Nano/c (or ICG) was prepared and irradiated with a diode laser or without laser irradiation as a negative control. The irradiation settings were 0.5 W with a duty ratio of 10%, for 3-100 ms in repeated pulse (RPT) or continuous wave mode. CFU were counted after 7 d of anaerobic culture. RESULTS: We observed that ICG-Nano/c could adhere to the surface of P. gingivalis. When ICG-Nano/c was used for aPDT, irradiation with RPT 100 ms mode gave the lowest increase in temperature. Laser irradiation with ICG-Nano/c significantly reduced the number of P. gingivalis (i.e., approximately 2-log10 bacterial killing). The greatest bactericidal effect was found in the RPT 100 ms group. However, laser irradiation (RPT 100 ms) with ICG, as well as without photosensitizer, had no effect on the number of bacteria. CONCLUSIONS: Within the limits of this study, ICG-Nano/c with low-level diode laser (0.5 W; 805 nm) irradiation showed an aPDT-like effect, which might be useful for a potential photodynamic periodontal therapy.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Drug Delivery Systems , Indocyanine Green/administration & dosage , Lasers, Semiconductor/therapeutic use , Photochemotherapy/methods , Photosensitizing Agents/administration & dosage , Porphyromonas gingivalis/drug effects , Bacterial Adhesion , Bacterial Load/drug effects , Chitosan/chemistry , Humans , Microbial Viability/drug effects , Microscopy, Electron, Scanning , Microscopy, Fluorescence , Microscopy, Phase-Contrast , Nanospheres/chemistry , Periodontal Diseases/microbiology , Radiation Dosage , Temperature
6.
Opt Express ; 20(28): 29137-42, 2012 Dec 31.
Article in English | MEDLINE | ID: mdl-23388738

ABSTRACT

We present the implementation and validation of an Inter-layer Traffic Engineering (TE) architecture based on a hierarchical path computation element (PCE), where the parent PCE is notified of established optical layer Label Switched Paths that induce packet traffic engineering (TE) links, thus not requiring full topology visibility. We summarize the architecture, the control plane extensions and its experimental evaluation in a control plane testbed.

7.
J Dent Res ; 91(2): 161-6, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22157098

ABSTRACT

The objective of this study was to assess whether there is a bi-directional relationship between periodontal status and diabetes. Study 1 included 5,856 people without periodontal pockets of ≥ 4 mm at baseline. Relative risk was estimated for the 5-year incidence of periodontal pockets of ≥ 4 mm (CPI scores 3 and 4, with the CPI probe), in individuals with glycated hemoglobin (HbA1c) levels of ≥ 6.5% at baseline. Study 2 included 6,125 people with HbA1c < 6.5% at baseline. The relative risk was assessed for elevation of HbA1c levels in 5 years, with baseline periodontal status, assessed by CPI. Relative risk of developing a periodontal pocket was 1.17 (p = 0.038) times greater in those with HbA1c of ≥ 6.5% at baseline, adjusted for body mass index (BMI), smoking status, sex, and age. Relative risks for having HbA1c ≥ 6.5% at 5-year follow-up in groups with periodontal pockets of 4 to 5 mm and ≥ 6 mm at baseline were 2.47 (p = 0.122) and 3.45 (p = 0.037), respectively, adjusted for BMI, alcohol consumption, smoking status, sex, and age. The risk of developing periodontal disease was associated with levels of HbA1c, and the risk of elevations of HbA1c was associated with developing periodontal pockets of more than 4 mm.


Subject(s)
Diabetes Mellitus, Type 2/blood , Glycated Hemoglobin/analysis , Periodontal Index , Adult , Age Factors , Aged , Alcohol Drinking/epidemiology , Body Mass Index , Case-Control Studies , Cohort Studies , Dental Calculus/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Female , Follow-Up Studies , Gingival Hemorrhage/epidemiology , Humans , Incidence , Japan/epidemiology , Longitudinal Studies , Male , Middle Aged , Obesity/epidemiology , Periodontal Pocket/classification , Periodontal Pocket/epidemiology , Prospective Studies , Risk Assessment , Sex Factors , Smoking/epidemiology
8.
Community Dent Health ; 28(1): 111-5, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21485247

ABSTRACT

OBJECTIVE: The objective of this study was to clarify to what extent Japanese dentists recommend dental floss and what factors influence dentists in encouraging their patients to use dental floss. PARTICIPANTS: The subjects in this study were 291 dentists who were directors of dental clinics, selected by stratified sampling by age. RESULTS: Dentists whose teachers at dental school had demonstrated dental flossing tended to recommend patients to use dental floss 2.2 (1.0-4.6: 95% CI) times more frequently compared with those who did not see demonstrations of flossing at dental school. Respondents who considered that using dental floss was very easy and easy, moderate, and difficult recommended patients to use dental floss 45.4 (11.2-183.9), 17.4 (6.6-45.8) and 5.9 (2.5-14.1) times more frequently, respectively, compared with those who considered it very difficult. Respondents who considered that using dental floss was effective, fairly effective or very effective in preventing dental caries recommended patients to use dental floss 3.8 (1.7-8.6), 3.8 (1.7-8.8) and 9.1 (3.6-23.0) times more frequently respectively, compared with those who considered it ineffective or only slightly effective. CONCLUSIONS: The demonstration of the use of dental floss by teachers at their dental schools gave dentists a good impression and a positive opinion of dental flossing. This was closely associated with recommendations by dentists to their patients to use dental floss.


Subject(s)
Attitude of Health Personnel , Dental Devices, Home Care/statistics & numerical data , Dentists/psychology , Oral Hygiene/education , Practice Patterns, Dentists'/statistics & numerical data , Adult , Aged , Dental Hygienists/statistics & numerical data , Education, Dental/statistics & numerical data , Female , Humans , Japan , Logistic Models , Male , Middle Aged , Oral Hygiene/statistics & numerical data , Surveys and Questionnaires
9.
J Dent Res ; 90(2): 199-202, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21270462

ABSTRACT

Numerous cross-sectional epidemiological studies suggest that obesity is associated with periodontal disease. This longitudinal study tested whether body mass index (BMI) was related to the development of periodontal disease in a sample of employed Japanese participants. Data are from the statutory medical checkups routinely collected for employees in and around Nagoya, Japan. The authors tested the relationship between BMI at baseline and the 5-year incidence of periodontal disease in a sample of 2787 males and 803 females. The hazard ratios for developing periodontal disease after 5 years were 1.30 (P < .001) and 1.44 (P = .072) in men and 1.70 (P < .01) and 3.24 (P < .05) in women for those with BMIs of 25-30 and ≥ 30, respectively, compared to those with BMI < 22, after adjusting for age, smoking status, and clinical history of diabetes mellitus. These findings demonstrate a dose-response relationship between BMI and the development of periodontal disease in a population of Japanese individuals.


Subject(s)
Body Mass Index , Periodontitis/epidemiology , Periodontitis/physiopathology , Adult , Aged , Diabetes Complications , Female , Humans , Incidence , Japan/epidemiology , Longitudinal Studies , Male , Middle Aged , Periodontal Index , Periodontitis/complications , Proportional Hazards Models , Risk Factors , Smoking , Young Adult
10.
J Dent Res ; 89(5): 430-44, 2010 May.
Article in English | MEDLINE | ID: mdl-20348484

ABSTRACT

Hypoxia is an integral component of the inflamed tissue microenvironment. Today, the influence of hypoxia on the natural evolution of inflammatory responses is widely accepted; however, many molecular and cellular mechanisms mediating this relationship remain to be clarified. Hypoxic stress affects several independent transcriptional regulators related to inflammation in which HIF-1 and NF-kappaB play central roles. Transcription factors interact with both HATs and HDACs, which are components of large multiprotein co-regulatory complexes. This review summarizes the current knowledge on hypoxia-responsive transcriptional pathways in inflammation and their importance in the etiology of chronic inflammatory diseases, with the primary focus on transcriptional co-regulators and histone modifications in defining gene-specific transcriptional responses in hypoxia, and on the recent progress in the understanding of hypoxia-mediated epigenetic reprogramming. Furthermore, this review discusses the molecular cross-talk between glucocorticoid anti-inflammatory pathways and hypoxia.


Subject(s)
Cell Hypoxia/genetics , Gene Expression Profiling , Transcription, Genetic/genetics , Gene Expression Regulation/genetics , Histone Acetyltransferases/genetics , Histone Deacetylases/genetics , Humans , Hypoxia-Inducible Factor 1/genetics , Inflammation/genetics , NF-kappa B/genetics , Receptor Cross-Talk/physiology , Transcription Factors/genetics
11.
Neuroscience ; 164(4): 1685-94, 2009 Dec 29.
Article in English | MEDLINE | ID: mdl-19796667

ABSTRACT

The human natural killer-1 (HNK-1) glyco-epitope possesses a unique structural feature, a sulfated glucuronic acid attached to lactosamine on the non-reducing termini of glycans. The expression of HNK-1 is temporally and spatially regulated by glucuronyltransferase (GlcAT-P) in the brain. Our previous report showed that mice lacking GlcAT-P almost completely lost HNK-1 expression in the brain and exhibited reduced long-term potentiation (LTP) at hippocampal CA1 synapses. GlcAT-P-deficient mice also showed impaired hippocampus-dependent spatial learning. Although HNK-1 plays an essential role in synaptic plasticity and memory formation, it remains unclear how HNK-1 regulates these functions. In this study, we showed that loss of the HNK-1 epitope resulted in an increase of filopodium-like immature spines and a decrease of mushroom-like mature spines in both the early postnatal mouse hippocampus and cultured hippocampal neurons. However, HNK-1 had no influence on spine density or filopodium formation. Immunofluorescence staining revealed that loss of HNK-1 altered the distribution of postsynaptic proteins such as alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA)-type glutamate receptor subunit GluR2 and PSD-95 from spine heads onto dendritic shafts without affecting synapse formation, resulting in an increase of shaft synapses in cultured GlcAT-P-deficient neurons. GluR2, a major HNK-1 carrier glycoprotein in postsynaptic density, has the ability to promote spine morphogenesis. Overexpression of GluR2 promoted spine growth in both wild-type and GlcAT-P-deficient neurons, but the increase in GlcAT-P-deficient neurons was lower than that in wild-type neurons. This is the first evidence that HNK-1 is a key factor for normal dendritic spine maturation and is involved in the distribution of postsynaptic proteins.


Subject(s)
CD57 Antigens/physiology , Dendritic Spines/physiology , Hippocampus/cytology , Pyramidal Cells/ultrastructure , Animals , Animals, Newborn , Cells, Cultured , Culture Techniques , Epitopes , Glucuronosyltransferase/biosynthesis , Glucuronosyltransferase/genetics , Hippocampus/growth & development , Mice , Neurogenesis , Receptors, AMPA/metabolism , Synapses/physiology
12.
Acta Physiol (Oxf) ; 194(2): 149-59, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18429950

ABSTRACT

AIM: To examine the relations between specific fibroblast growth factors (FGFs) and satellite cell activation during muscle regeneration and hypertrophy in vivo, we measured mRNA expression of FGFs and myogenic markers in rat plantaris muscle after bupivacaine administration and synergist ablation. METHODS: mRNA levels for MyoD, myogenin, proliferating cell nuclear antigen (PCNA), p21, M-cadherin, Pax7, FGF-1, FGF-2, FGF-3, FGF-4, FGF-5, FGF-6, FGF-7, FGF-8 and hepatocyte growth factor (HGF) were measured continually for up to 72 h after bupivacaine administration and synergist ablation. FGF-5, FGF-7 and HGF proteins were immunostained at 72 h after bupivacaine administration. RESULTS: MyoD and PCNA mRNAs started increasing 24 h after bupivacaine administration. Myogenin, p21, M-cadherin and Pax7 mRNAs started to increase after 48 and 72 h. After synergist ablation, MyoD, PCNA, M-cadherin and Pax7 mRNAs had increased at 24 and 48 h, and myogenin and p21 mRNAs at 12 and 24 h. FGF-1, FGF-7 and HGF mRNAs after the treatments started to increase at the same time as MyoD and PCNA mRNAs. FGF-5 was expressed at the same time as MyoD and PCNA mRNAs after bupivacaine administration but did not after the ablation. FGF-2, FGF-3, FGF-4, FGF-6 and FGF-8 mRNAs were not associated with the expression of the myogenic markers. FGF-7 and HGF proteins were expressed in immature muscle fibre nuclei and the extracellular matrix, but FGF-5 protein was preferentially expressed in extracellular matrix. CONCLUSION: These results indicate that FGF-1, FGF-7 and HGF are associated with specific myogenic marker expression during muscle regeneration and hypertrophy.


Subject(s)
Fibroblast Growth Factors/biosynthesis , Muscle, Skeletal/metabolism , MyoD Protein/biosynthesis , Proliferating Cell Nuclear Antigen/biosynthesis , Regeneration/physiology , Animals , Bupivacaine/pharmacology , Fibroblast Growth Factors/genetics , Gene Expression Regulation/drug effects , Hypertrophy/metabolism , Male , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Muscle, Skeletal/physiology , MyoD Protein/genetics , Polymerase Chain Reaction/methods , Proliferating Cell Nuclear Antigen/genetics , RNA, Messenger/genetics , Rats , Rats, Wistar , Satellite Cells, Skeletal Muscle/physiology , Stress, Mechanical
13.
Oncogene ; 27(17): 2422-9, 2008 Apr 10.
Article in English | MEDLINE | ID: mdl-17952113

ABSTRACT

The proto-oncogene c-Jun plays an important role in regulating tumor progression. We previously reported that the serine/threonine phosphatase calcineurin (CaN, also called PP2B) dephosphorylates the C-terminus (Ser-243) of c-Jun, resulting in the increase in c-Jun and Sp1 interaction, and subsequent c-Jun-induced gene expression. Here, we demonstrate the interaction of c-Jun and CaN in the nucleus of living cells by fluorescence resonance energy transfer assay and that this interaction is mediated through the calmodulin-binding domain of CaN. Furthermore, c-Jun protein stability was altered by CaN-mediated dephosphorylation at the Ser-243 site of c-Jun. The half-life of the c-Jun mutant, c-Jun-S243A was longer than that of the wild-type c-Jun. Moreover, silencing of endogenous CaN expression led to increased c-Jun ubiquitination and decreased stability. In 46% of clinical cervical tissue samples obtained from patients with cervical cancer, enhanced c-Jun and CaN expression, as well as decreased phospho-Ser-243 expression levels were detected. Our results suggest that CaN stabilizes c-Jun by dephosphorylating c-Jun at Ser-243 to enhance its tumorigenic ability.


Subject(s)
Calcineurin/metabolism , Phosphoserine/metabolism , Proto-Oncogene Proteins c-jun/metabolism , Transgenes/genetics , Animals , Calcineurin/genetics , Cell Line , Cell Survival , Chlorocebus aethiops , Humans , Mutation/genetics , Protein Binding , Proto-Oncogene Mas , Proto-Oncogene Proteins c-jun/genetics
14.
Acta Neurochir Suppl ; 97(Pt 1): 403-7, 2007.
Article in English | MEDLINE | ID: mdl-17691403

ABSTRACT

Functional electrical stimulation (FES) techniques progress by adopting the developments in computers and engineering, but complete functional reconstruction is not yet possible to be achieved. The attachment of the devices to the body can be complex, and training to handle FES is not easy. FES systems are expensive and their coverage by medical insurance is limited with the exception of a few systems. Hence, recognition of FES by the medical community is limited and as a result, it is not a common therapy. However, FES is the main method available for reconstruction of motor function, at present. The improvement in activities of daily living (ADL) of patients using FES may not only improve the patient's quality of life (QOL) but also reduce the burden to persons who look after them, and hence, secure a valuable work force. The medical insurance should support the use of FES and reduce the patients' financial burden. Studies and developments based on a close collaboration of users (patients and care-givers), persons involved in therapy (doctors and nurses), and manufactures (engineers and technicians) are necessary. In addition to FES, other methods such as therapeutic electrical stimulation (TES) for prevention of atrophy and spasms of paralytic limbs show the therapeutic potential of neuromodulation.


Subject(s)
Electric Stimulation/methods , Motor Activity/radiation effects , Upper Extremity/physiology , Activities of Daily Living , Electric Stimulation/instrumentation , Electrodes, Implanted , Humans , Quality of Life
15.
Acta Neurochir Suppl ; 97(Pt 1): 455-9, 2007.
Article in English | MEDLINE | ID: mdl-17691409

ABSTRACT

Dorsal column stimulation (DCS) is described as a therapy for persistent deterioration of consciousness. The mechanism of its effect has not yet been elucidated. Various other methods, such as deep brain stimulation of the CM-p f complex, vagus nerve stimulation, and musical functional therapy, are being investigated as potential treatments of this problem. We present our series of DCS for persistent vegetative state and review the potential mechanisms of action and the relevant literature.


Subject(s)
Electric Stimulation Therapy , Persistent Vegetative State/therapy , Spinal Cord/physiology , Spinal Cord/radiation effects , Animals , Hippocampus/pathology , Humans , Magnetic Resonance Imaging/methods , Persistent Vegetative State/pathology , Tomography, Emission-Computed, Single-Photon/methods
16.
J Oral Rehabil ; 34(6): 428-32, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17518977

ABSTRACT

The objective was to assess the relationship between number of functional occluding natural pairs of teeth and health related functioning in older free living Japanese people using the SF-20. The participants were 107 elderly people aged 80 years. Health related functioning was measured with the SF-20. The numbers of functional occluding natural pairs of teeth (OPs) were calculated and scored as follows: 1, for each pair of anterior teeth and premolars in occlusion. Molar functional natural occluding pairs were scored 2 for each occluding pair. The number of functional occluding pairs was assessed separately as anterior natural occluding pairs (AOPs) and posterior occluding pairs (POPs). There were significant differences in the role functioning subscale of SF-20 between those who were edentulous and those with one to nine natural teeth and 10 or more natural teeth (P = 0.030). Those with one to six AOPs had significantly higher role functioning than the zero AOPs group (P = 0.042). Those with 1-12 POPs also had significantly higher role functioning scores than the zero natural POPs group (P = 0.007). However, there were no significant relationships between number of natural teeth, OPs or AOPs, and POPs on the one hand, and all other subscales of SF-20 on the other hand. The community-dwelling 80-year-old Japanese people in this study had overall good health related functioning. The number of functional occluding pairs of natural teeth, especially POPs, was related with the role functioning subscale of SF-20 but had no significant relationships to the other dimensions of SF-20.


Subject(s)
DMF Index , Dental Occlusion , Geriatric Assessment , Health Status , Jaw, Edentulous, Partially/psychology , Quality of Life/psychology , Aged, 80 and over , Female , Humans , Male
17.
Inflamm Res ; 55(12): 543-9, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17039283

ABSTRACT

OBJECTIVE AND DESIGN: Transforming growth factor- beta (TGF-beta) has not only a fibrogenic role, but also monocyte/ macrophage chemotactic properties in a synovial joint. However, little is known about the effects of TGF-beta on monocyte chemoattractant protein-1 (MCP-1) expression in human synovial cells under inflammatory status. The aim of this study was to determine whether TGF-modulates MCP-1 production under the chronic inflammation, and to elucidate the cell signaling mechanism involved. MATERIALS AND METHODS: Human synovial cells were exposed to IL-1beta, which mimics the environment of chronic inflammation. Production of MCP-1 protein and expression of MCP-1 mRNA were determined by ELISA and real-time PCR. RESULTS: TGF-beta upregulated the expression of MCP-1 mRNA and protein with or without IL-1beta. TGF-beta and IL-1beta synergistically enhanced MCP-1 gene expression, and an AP-1 binding site was involved in the signal transduction. In addition, MEK inhibitor completely suppressed TGF-beta-induced MCP-1 production. CONCLUSIONS: TGF-beta and IL-1beta synergistically enhance MCP-1 gene expression through the activation of the MEK/ERK1/2 pathways, which leads to AP-1 activation. The impairment of MCP-1 regulation by TGF-beta in resident synovial cells might represent an important mechanism of chronic inflammation and tissue fibrosis in a synovial joint. MCP-1 should be considered a valid target for therapeutic intervention.


Subject(s)
Chemokine CCL2 , Transforming Growth Factor beta , Cells, Cultured , Chemokine CCL2/metabolism , Humans , Interleukin-1beta/metabolism , RNA, Messenger/metabolism , Transcription Factor AP-1/metabolism , Transforming Growth Factors
18.
J Dent Res ; 85(5): 427-31, 2006 May.
Article in English | MEDLINE | ID: mdl-16632755

ABSTRACT

Hertwig's epithelial root sheath (HERS) is important for tooth root formation, but the molecular basis for the signaling of root development remains uncertain. We hypothesized that Sonic hedgehog (Shh) signaling is involved in the HERS function, because it mediates epithelial-mesenchymal interactions during embryonic odontogenesis. We examined the gene expression patterns of Shh signaling in murine developing molar roots. Shh and Patched2 transcripts were identified in the HERS, whereas Patched1, Smoothened, and Gli1 were expressed in the proliferative dental mesenchyme in addition to the HERS. To confirm whether Shh signaling physiologically functions in vivo, we analyzed mesenchymal dysplasia (mes) mice carrying an abnormal C-terminus of the PATCHED1 protein. In the mutant, cell proliferation was repressed around the HERS at 1 wk. Moreover, the molar eruption was disturbed, and all roots were shorter than those in control littermates at 4 wks. These results indicate that Shh signaling is important in tooth root development. Abbreviations used: BrdU, 5-bromo-2'-deoxyuridine; HERS, Hertwig's epithelial root sheath; NFI-C/CTF, nuclear factor Ic/CAAT box transcription factor; PCNA, proliferating cell nuclear antigen; Ptc, patched; Shh, sonic hedgehog; Smo, smoothened.


Subject(s)
Odontogenesis/genetics , Tooth Root/growth & development , Trans-Activators/genetics , Trans-Activators/physiology , Animals , Cell Proliferation , Epithelium , Gene Expression Regulation, Developmental , Hedgehog Proteins , In Situ Hybridization , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/physiology , Mesoderm/pathology , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Morphogenesis/genetics , Patched Receptors , Patched-1 Receptor , Patched-2 Receptor , Receptors, Cell Surface/genetics , Receptors, Cell Surface/physiology , Signal Transduction , Tooth Eruption/genetics , Zinc Finger Protein GLI1
19.
Acta Physiol (Oxf) ; 186(4): 291-300, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16634784

ABSTRACT

AIM: To determine the roles of myostatin and insulin-like growth factor-I (IGF-I) during postnatal growth, we examined IGF-I and myostatin mRNA expression in the skeletal muscles of hypophysectomized and underfed rats during postnatal growth. METHODS: Five-week-old rats were divided into four groups: freely fed control, moderately underfed, severely underfed and hypophysectomized. Four weeks later, blood and muscle samples were gathered to determine serum IGF-I, myosin heavy chain (MHC) isoforms, IGF-I Ea, IGF-I Eb and myostatin mRNA. RESULTS: The weights of soleus, plantaris and masseter muscles were decreased in underfed and hypophysectomized rats. Hypophysectomy resulted in significant increases of type I MHC at the expense of type IIx in plantaris muscle and of neonatal MHC at the expense of types IIx and IIb in masseter muscle. Serum IGF-I was decreased by underfeeding and hypophysectomy. Plantaris muscle IGF-I Ea mRNA in underfed and hypophysectomized rats was significantly lower than in normal controls. Plantaris muscle IGF-I Eb mRNA in underfed rats was significantly lower than in normal controls. Masseter muscle IGF-I Eb mRNA in severely underfed rats was significantly lower than in normal control and hypophysectomized rats. Soleus muscle myostatin mRNA in hypophysectomized rats was significantly higher than in normal and significantly underfed rats. No significant differences in plantaris and masseter muscle myostatin mRNA were observed between groups. CONCLUSION: Suppressed muscle growth caused by hypophysectomy and underfeeding may be attributed mainly to reduced circulating IGF-I and partially to reduced IGF-I mRNA, rather than to a change in myostatin.


Subject(s)
Insulin-Like Growth Factor I/genetics , Malnutrition/metabolism , Muscle, Skeletal/growth & development , Muscle, Skeletal/metabolism , RNA, Messenger/analysis , Transforming Growth Factor beta/genetics , Animals , Animals, Newborn , Body Weight , Hypophysectomy , Insulin-Like Growth Factor I/analysis , Male , Myostatin , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction
20.
Kyobu Geka ; 57(7): 555-9, 2004 Jul.
Article in Japanese | MEDLINE | ID: mdl-15285383

ABSTRACT

Five cases of surgically treated thymic carcinoma are reported. The patients (4 men and a woman) ranged in age from 46 to 76 years old with a mean of 64.6. Four patients were asymptomatic and an abnormal shadow on X-ray films was noted. One remaining patient suffered from hoarseness. One patient had stage II disease and the others had stage III. Surgical tumor resection was performed in all cases. Only 1 patient among the 5 underwent a successful complete resection. Histological examinations of the resected specimens revealed squamous cell carcinoma of thymus. Four specimens were poorly differentiated and 1 is moderately differentiated carcinoma. All patients received radiation therapy post operatively. Three patients are alive without any recurrence 6, 8 and 109 months after the surgery. Thymic carcinomas are frequently invasive or metastatic at the time of diagnosis. But poorly differentiated group, in squamous cell carcinoma, mucoepidermoid carcinoma and besaloid carcinoma, are characterized by a low incidence of local recurrence and distant metastasis. They also have a good sensitivity for the radiation. Therefore complete surgical resection combined with postoperative radiation therapy should be a choice in treating thymic carcinomas. We considered that complete resection and postoperative radiation therapy is a curative therapy for thymic carcinomas.


Subject(s)
Carcinoma, Squamous Cell/surgery , Thymus Neoplasms/surgery , Aged , Carcinoma, Squamous Cell/radiotherapy , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Radiotherapy, Adjuvant , Thymus Neoplasms/radiotherapy
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