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1.
PLoS One ; 19(6): e0305062, 2024.
Article in English | MEDLINE | ID: mdl-38905210

ABSTRACT

In Ontario, despite the increasing prevalence of Parkinson's disease (PD), barriers to access-to-care for people with Parkinson's disease (PwP) and their caregivers are not well understood. The objective of this study is to examine spatial patterns of health care utilization among PwP and identify factors associated with PD-related health care utilization of individuals in Ontario. We employed a retrospective, population-based study design involving administrative health data to identify PwP as of March 31, 2018 (N = 35,482) using a previously validated case definition. An enhanced 2-step floating catchment area method was used to measure spatial accessibility to PD care and a descriptive spatial analysis was conducted to describe health service utilization by geographic area and specialty type. Negative binomial regression models were then conducted to identify associated geographic, socioeconomic, comorbidity and demographic factors. There was marked spatial variability in PD-related service utilization, with neurology and all provider visits being significantly higher in urban areas (CMF>1.20; p<0.05) and family physician visits being significantly higher (CMF >1.20; p<0.05) in more rural areas and remote areas. More frequent visits to family physicians were associated with living in rural areas, while less frequent visitation was associated with living in areas of low spatial accessibility with high ethnic concentration. Visits to neurologists were positively associated with living in areas of high spatial accessibility and with high ethnic concentration. Visits to all providers were also positively associated with areas of high spatial accessibility. For all outcomes, less frequent visits were found in women, older people, and those living in more deprived areas as years living with PD increased. This study demonstrates the importance of geographic, socioeconomic and individual factors in determining PwP's likelihood of accessing care and type of care provided. Our results can be expected to inform the development of policies and patient care models aimed at improving accessibility among diverse populations of PwP.


Subject(s)
Parkinson Disease , Patient Acceptance of Health Care , Humans , Parkinson Disease/therapy , Parkinson Disease/epidemiology , Ontario/epidemiology , Female , Male , Aged , Patient Acceptance of Health Care/statistics & numerical data , Middle Aged , Retrospective Studies , Aged, 80 and over , Health Services Accessibility/statistics & numerical data , Adult , Rural Population/statistics & numerical data , Socioeconomic Factors
2.
PLoS One ; 16(6): e0251430, 2021.
Article in English | MEDLINE | ID: mdl-34101744

ABSTRACT

Income polarization is a pressing issue which is increasingly discussed by academics and policymakers. The present research examines income polarization in Canada's eight largest Census Metropolitan Areas (CMAs) using data at the census-tract (CT) level between 1971 and 2016. Generally, there are significant decreasing trends in the middle-income population with simultaneously increasing trends in low-income groups. The high-income groups have been relatively stable with fewer significant increasing population trends. Using conventional mapping and cartograms, patterns of the spatial evolution of income inequality are illustrated. Every CMA examined contains an increasing trend of spatial fragmentation at the patch level within each CMA's landscape mosaic. The results of a spatial autocorrelation analysis at the sub-patch, CT level, exhibit significant spatial clustering of high-income CTs as one process that dominates the increasingly fragmented landscape mosaic.


Subject(s)
Economic Status , Income , Poverty , Canada , Censuses , Cities , Family Characteristics , Female , Humans , Male
3.
J Laryngol Otol ; : 1-9, 2020 Dec 03.
Article in English | MEDLINE | ID: mdl-33267923

ABSTRACT

OBJECTIVE: Socioeconomic risk factors may contribute to geographic variation in diseases, but studies are limited due to lack of large available cohorts. METHOD: A geographic analysis was performed of the association between socioeconomic risk factors and the distribution of vestibular schwannomas in adults diagnosed with sporadic vestibular schwannomas through the National Health Services in the West of Scotland from 2000 to 2015. RESULTS: A total of 511 sporadic vestibular schwannomas were identified in a population of over 3.1 million. Prevalence of vestibular schwannomas were lowest in cases with good health (-0.64, 95 per cent confidence interval: -0.93,-0.38; p = 0.002) and level 1 qualifications (-0.562, 95 per cent confidence interval: -0.882 to -0.26; p = 0.01). However, these risk factors did not demonstrate consistent linearity of correlations. Prevalence was lower in people originating from European Union accession countries from April 2001 to March 2011 (-0.63, 95 per cent confidence interval: -0.84 to -0.43; p = 0.002). No correlation between distribution of vestibular schwannomas and socioeconomic risk factors met our threshold criteria (± 0.7). CONCLUSION: This study demonstrated that there is little variation in distribution of vestibular schwannomas by socioeconomic risk factors.

4.
J Phys Condens Matter ; 32(44): 445801, 2020 Jul 20.
Article in English | MEDLINE | ID: mdl-32688353

ABSTRACT

La based Co-Fe combined double perovskite (La1.8Pr0.2CoFeO6) was synthesized and the dielectric (zero-field and in-field), magnetic, x-ray absorption and Raman spectroscopy measurements have been investigated for La1.8Pr0.2CoFeO6 double perovskite. The existence of re-entrant cluster glass state is observed. The magneto-dielectric (MD) is found in two temperature regions (25-80 K and 125-275 K). It has been demonstrated that the observed MD at low and high temperatures are respectively due to the spin freezing and the spin-lattice coupling. Furthermore, the very large dielectric constant and the low loss suggest that La1.8Pr0.2CoFeO6 is very important from the application point of view.

5.
PLoS One ; 14(3): e0212814, 2019.
Article in English | MEDLINE | ID: mdl-30865701

ABSTRACT

Gentrification is multidimensional and complex, but there is general agreement that visible changes to neighbourhoods are a clear manifestation of the process. Recent advances in computer vision and deep learning provide a unique opportunity to support automated mapping or 'deep mapping' of perceptual environmental attributes. We present a Siamese convolutional neural network (SCNN) that automatically detects gentrification-like visual changes in temporal sequences of Google Street View (GSV) images. Our SCNN achieves 95.6% test accuracy and is subsequently applied to GSV sequences at 86110 individual properties over a 9-year period in Ottawa, Canada. We use Kernel Density Estimation (KDE) to produce maps that illustrate where the spatial concentration of visual property improvements was highest within the study area at different times from 2007-2016. We find strong concordance between the mapped SCNN results and the spatial distribution of building permits in the City of Ottawa from 2011 to 2016. Our mapped results confirm those urban areas that are known to be undergoing gentrification as well as revealing areas undergoing gentrification that were previously unknown. Our approach differs from previous works because we examine the atomic unit of gentrification, namely, the individual property, for visual property improvements over time and we rely on KDE to describe regions of high spatial intensity that are indicative of gentrification processes.


Subject(s)
Residence Characteristics , Social Change , Canada , Cities/statistics & numerical data , Deep Learning , Geographic Mapping , Humans , Spatial Analysis
6.
J Phys Condens Matter ; 31(27): 275802, 2019 Jul 10.
Article in English | MEDLINE | ID: mdl-30921773

ABSTRACT

Electronic structure of Pr2CoFeO6 (at 300 K) was investigated by x-ray photoemission spectroscopy (XPS) and x-ray absorption spectroscopy techniques. All three cations, i.e. Pr, Co and Fe were found to be trivalent in nature. XPS valance band analysis suggested the system to be insulating in nature. The analysis suggested that Co3+ ions exist in low spin state in the system. Moreover, Raman spectroscopy study indicated the random distribution of the B-site ions (Co/Fe) triggered by same charge states. In temperature-dependent Raman study, the relative heights of the two observed phonon modes exhibited anomalous behaviour near magnetic transition temperature T N ~ 270 K, thus indicating towards interplay between spin and phonon degrees of freedom in the system. Furthermore, clear anomalous softening was observed below T N which confirmed the existence of strong spin-phonon coupling occurring for at least two phonon modes of the system. The line width analysis of the phonon modes essentially ruled out the role of magnetostriction effect in the observed phonon anomaly. The investigation of the lattice parameter variation across T N (obtained from the temperature-dependent neutron diffraction measurements) further confirmed the existence of the spin-phonon coupling.

10.
Int J Health Geogr ; 16(1): 6, 2017 02 16.
Article in English | MEDLINE | ID: mdl-28209210

ABSTRACT

BACKGROUND: With the expansion and growth of research on neighbourhood characteristics, there is an increased need for direct observational field audits. Herein, we introduce a novel direct observational audit method and systematic social observation instrument (SSOI) for efficiently assessing neighbourhood aesthetics over large urban areas. METHODS: Our audit method uses spatial random sampling stratified by residential zoning and incorporates both mobile geographic information systems technology and virtual environments. The reliability of our method was tested in two ways: first, in 15 Ottawa neighbourhoods, we compared results at audited locations over two subsequent years, and second; we audited every residential block (167 blocks) in one neighbourhood and compared the distribution of SSOI aesthetics index scores with results from the randomly audited locations. Finally, we present interrater reliability and consistency results on all observed items. RESULTS: The observed neighbourhood average aesthetics index score estimated from four or five stratified random audit locations is sufficient to characterize the average neighbourhood aesthetics. The SSOI was internally consistent and demonstrated good to excellent interrater reliability. At the neighbourhood level, aesthetics is positively related to SES and physical activity and negatively correlated with BMI. CONCLUSION: The proposed approach to direct neighbourhood auditing performs sufficiently and has the advantage of financial and temporal efficiency when auditing a large city.


Subject(s)
Cities/epidemiology , Environment Design/standards , Geographic Information Systems/statistics & numerical data , Residence Characteristics , Urban Population , User-Computer Interface , Humans , Ontario/epidemiology
11.
Rev Sci Instrum ; 87(11): 11D503, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27910640

ABSTRACT

The Hitomi Soft X-ray Spectrometer (SXS) was a pioneering non-dispersive imaging x-ray spectrometer with 5 eV FWHM energy resolution, consisting of an array of 36 silicon-thermistor microcalorimeters at the focus of a high-throughput soft x-ray telescope. The instrument enabled astrophysical plasma diagnostics in the 0.3-12 keV band. We introduce the SXS calibration strategy and corresponding ground calibration measurements that took place from 2012-2015, including both the characterization of the microcalorimeter array and measurements of the x-ray transmission of optical blocking filters.

12.
Eur J Gynaecol Oncol ; 35(1): 11-5, 2014.
Article in English | MEDLINE | ID: mdl-24654454

ABSTRACT

PURPOSE: To review the outcome in patients with atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) who received MPA treatment in the present hospital. MATERIALS AND METHODS: Patients with AEH or EC were administered MPA for 12 weeks followed by endometrial curettage. The rates of effect, recurrence, pregnancy, and complications were evaluated. The changes in progesterone receptors and FOXO-1, known as a target of MPA treatment, were examined by immunostaining. RESULTS: Four of seven patients with endometrial cancer and three of three patients with AH had complete response. Four of seven patients had recurred within one year after the treatment and had to undergo hysterectomy. None of the patients showed changes in progesterone receptors. Although six of seven patients were negative for FOXO-1 before and after treatment, all the patients showed increased developments of FOXO-1 during MPA treatment. CONCLUSION: Progestin as a fertility-preserving treatment is expected to be effective for endometrial cancer, but judicious use might be required because it shows high rate of recurrence. Further studies regarding the mechanism may be necessary to achieve high efficacy.


Subject(s)
Endometrial Hyperplasia/drug therapy , Endometrial Neoplasms/drug therapy , Fertility Preservation/methods , Medroxyprogesterone Acetate/therapeutic use , Organ Sparing Treatments/methods , Adult , Endometrial Hyperplasia/metabolism , Endometrial Neoplasms/metabolism , Female , Forkhead Box Protein O1 , Forkhead Transcription Factors/analysis , Forkhead Transcription Factors/chemistry , Forkhead Transcription Factors/metabolism , Humans , Immunohistochemistry , Japan , Receptors, Progesterone/analysis , Receptors, Progesterone/chemistry , Receptors, Progesterone/metabolism , Treatment Outcome
13.
Eur J Gynaecol Oncol ; 35(1): 48-51, 2014.
Article in English | MEDLINE | ID: mdl-24654461

ABSTRACT

PURPOSE: Primary prophylaxis with G-CSF has been used to minimize myelosuppression caused by anticancer agents and to avoid severe neutropenia. The authors retrospectively examined the value of primary prophylaxis using granulocyte colony-stimulating factor (G-CSF) for epithelial ovarian cancer. MATERIALS AND METHODS: From 2001 to 2010, 105 patients with ovarian cancer receiving chemotherapy in the present hospital were divided into two groups: one received primary prophylaxis with G-CSF and the other did not receive it in compliance with the guidelines for G-CSF usage. The incidence of febrile neutropenia (FN), degree of neutropenia, frequency of G-CSF administration, number of days of hospitalization, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: Neutrophils decreased almost equally and the length of hospitalization was not significantly lower between the groups. Five-year PFS or OS showed no significant difference either. CONCLUSIONS: Primary prophylaxis with G-CSF in chemotherapy for epithelial ovarian cancer could be of low significance.


Subject(s)
Granulocyte Colony-Stimulating Factor/therapeutic use , Immunologic Factors/therapeutic use , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Antibiotic Prophylaxis , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Carcinoma, Ovarian Epithelial , Chemotherapy-Induced Febrile Neutropenia/etiology , Chemotherapy-Induced Febrile Neutropenia/prevention & control , Female , Humans , Incidence , Kaplan-Meier Estimate , Middle Aged , Retrospective Studies
14.
J Eur Acad Dermatol Venereol ; 27(12): 1514-20, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23198869

ABSTRACT

BACKGROUND: DAV-interferon (IFN)-ß therapy is a combination chemotherapy of dacarbazine (DTIC), nimustine (ACNU) and vincristine (VCR) with local subcutaneous injection of IFN-ß that is widely employed as postoperative adjuvant chemotherapy to treat malignant melanoma in Japan. However, the efficacy of DAV-IFN-ß therapy has not been confirmed by randomized controlled trials and the benefit of DAV-IFN-ß therapy has not been established yet. This study evaluated the contribution of DAV-IFN-ß therapy to improve survival of postoperative patients with cutaneous melanoma. Methods Patients with stage II or III cutaneous melanoma seen at Nagoya University Hospital from January 1998 to December 2009 were eligible for this study. Disease-free survival rates and melanoma-specific survival rates were evaluated. A propensity score was calculated to control for the effects of variables related to decisions regarding the application of DAV-IFN-ß therapy. RESULTS: Eighty-two stage II and 60 stage III melanoma patients were included. In the post-matched stage II patients (17 matched pairs), the mean (± SE) disease-free survival rates were 39.9 ± 13.7% for DAV-IFN-ß therapy and 73.1 ± 11.7% for non-use (hazard ratio for recurrence, 2.06; 95% CI, 0.63-6.69; P = 0.23), and the melanoma-specific survival rates were 66.2 ± 20.0% for DAV-IFN-ß therapy and 86.2 ± 9.1% for non-use (hazard ratio for death, 1.09; 95% CI, 0.17-6.82; P = 0.93). In the post-matched stage III patients (nine matched pairs), the disease-free survival rates were 29.6 ± 16.4% for DAV-IFN-ß therapy and 33.3 ± 15.7% for non-use (0.69; 95% CI, 0.22-2.17; P = 0.53), and the melanoma-specific survival rates were 55.6 ± 16.6% for DAV-IFN-ß therapy and 44.4 ± 16.6% for non-use (0.67; 95% CI, 0.18-2.50; P = 0.55). CONCLUSIONS: DAV-IFN-ß therapy brought no significant improvement in either disease-free survival rates or melanoma-specific survival rates of patients with stage II or III cutaneous melanoma. A randomized controlled trial would be required to further evaluate the efficacy of DAV-IFN-ß therapy as an adjuvant chemotherapy.


Subject(s)
Interferon-beta/therapeutic use , Melanoma/drug therapy , Survival Rate , Aged , Female , Humans , Male , Melanoma/pathology , Middle Aged , Neoplasm Staging , Postoperative Period
15.
Epidemiol Infect ; 140(4): 655-64, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21733250

ABSTRACT

Recent epidemiological data suggest a link between the consumption of bovine offal products and Shiga toxin-producing Escherichia coli (STEC) infection in Japan. This study thus examined the prevalence of STEC in various types of these foods. PCR screened 229 bovine offal products for the presence of Shiga toxin (stx) gene. Thirty-eight (16·6%) samples were stx positive, of which eight were positive for rfbE(O157) and three were positive for wzy(O26). Four O157 and one O26 STEC isolates were finally obtained from small-intestine and omasum products. Notably, homogenates of bovine intestinal products significantly reduced the extent of growth of O157 in the enrichment process compared to homogenates of beef carcass. As co-incubation of O157 with background microbiota complex from bovine intestinal products in buffered peptone water, in the absence of meat samples, tended to reduce the extent of growth of O157, we reasoned that certain microbiota present in offal products played a role. In support of this, inoculation of generic E. coli from bovine intestinal products into the homogenates significantly reduced the extent of growth of O157 in the homogenates of bovine intestinal and loin-beef products, and this effect was markedly increased when these homogenates were heat-treated prior to inoculation. Together, this report provides first evidence of the prevalence of STEC in a variety of bovine offal products in Japan. The prevalence data herein may be useful for risk assessment of those products as a potential source of human STEC infection beyond the epidemiological background. The growth characteristic of STEC O157 in offal products also indicates the importance of being aware when to test these food products.


Subject(s)
Cattle/microbiology , Escherichia coli Infections/epidemiology , Meat Products/microbiology , Shiga-Toxigenic Escherichia coli/growth & development , Animals , Escherichia coli Infections/etiology , Escherichia coli O157/genetics , Escherichia coli O157/growth & development , Escherichia coli O157/isolation & purification , Humans , Intestines/microbiology , Japan/epidemiology , Molecular Sequence Data , Polymerase Chain Reaction , Prevalence , Shiga-Toxigenic Escherichia coli/genetics , Shiga-Toxigenic Escherichia coli/isolation & purification
16.
Eur J Gynaecol Oncol ; 32(3): 269-73, 2011.
Article in English | MEDLINE | ID: mdl-21797114

ABSTRACT

PURPOSE: This study was designed to assess the safety and efficacy of a splenectomy and to analyze the prognostic factors of Müllerian carcinoma with spleen metastasis. METHODS: We reviewed the medical records of 11 patients with Müllerian carcinoma who underwent a splenectomy between 1997 and 2007. The treatment outcome of these patients was examined and the possible prognostic factors were investigated by univariate analysis. RESULTS: Four and seven patients underwent a splenectomy for primary and recurrent disease, respectively. A complete resection was achieved in eight patients. A blood transfusion was not required and only two mild postoperative complications were observed. The median and five-year survivals of all patients following treatment were 39 months and 39%, respectively. Older patients (> or = 60 years old) and patients with a poor performance status (PS2) had a poorer prognosis by univariate analysis. CONCLUSIONS: A splenectomy can be performed safely and effectively during debulking surgery for appropriately selected patients with primary or recurrent Müllerian carcinoma.


Subject(s)
Carcinoma/surgery , Fallopian Tube Neoplasms/surgery , Mullerian Ducts/pathology , Ovarian Neoplasms/surgery , Peritoneal Neoplasms/surgery , Spleen/surgery , Splenectomy/adverse effects , Adult , Aged , Carcinoma/pathology , Fallopian Tube Neoplasms/pathology , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/pathology , Prognosis , Retrospective Studies , Spleen/pathology , Treatment Outcome
17.
Eur J Gynaecol Oncol ; 32(3): 325-7, 2011.
Article in English | MEDLINE | ID: mdl-21797126

ABSTRACT

Lymphoepithelioma-like carcinoma (LELC) of the uterine cervix is a rare variant of squamous cell carcinoma of the uterine cervix. This tumor is characterized by nests of poorly differentiated epithelial cells surrounded by a prominent lymphocytic infiltration. Despite the poorly differentiated pathological findings, it appears to have a better outcome than the usual squamous cell carcinoma of the uterine cervix. Therefore, it is quite important to differentiate this tumor from poorly differentiated squamous cell carcinoma and lympho-proliferative disorders of the cervix. LELC arising from the nasopharynx has been suggested to be associated with Epstein-Barr virus (EBV), whereas the involvement of EBV in LELC of the uterine cervix is still controversial. In addition, the role of high-risk human papilloma virus (HPV) in this type of tumor remains unknown. We report a case of LELC of the cervix with diagnosis on the basis of histopathology in a 52-year-old Japanese woman who presented with a history of continuous bleeding post menopause. We also examine the association of EBV and HPV in this case.


Subject(s)
Carcinoma, Squamous Cell/pathology , Cervix Uteri/pathology , Uterine Cervical Neoplasms/pathology , Carcinoma, Squamous Cell/virology , Cervix Uteri/virology , Diagnosis, Differential , Female , Humans , Middle Aged , Papillomaviridae , Uterine Cervical Neoplasms/virology
18.
Br J Cancer ; 100(9): 1400-5, 2009 May 05.
Article in English | MEDLINE | ID: mdl-19401699

ABSTRACT

A retrospective analysis was carried out to identify risk factors for survival and relapse in patients with FIGO stage I-IIB cervical adenocarcinoma (AC), who underwent radical hysterectomy, and to compare outcome and spread pattern with those of squamous cell carcinoma (SCC). One hundred and twenty-three FIGO stage I-IIB patients with AC and 455 patients with SCC, who all underwent primary radical hysterectomy, were reviewed. Among the patients with AC, Cox model identified tumour size (95% CI: 1.35-30.71) and node metastasis (95% CI: 5.09-53.44) as independent prognostic factors for survival, and infiltration to vagina (95% CI: 1.15-5.76) and node metastasis (95% CI: 6.39-58.87) as independent prognostic factors for relapse. No significant difference was found in survival or relapse between the AC and SCC groups, after adjusting for other clinicopathological characteristics using Cox model. No significant difference was found in the positive rates of lymph nodes or location of initial failure sites between the two groups, but ovarian metastatic rate was significantly higher in patients with pathologic stage IIB AC (P=0.02). Positive node is a common independent prognostic factor for survival and relapse of patients with AC. FIGO stage I-IIB patients with AC or SCC, who underwent radical hysterectomy, have similar prognosis and spread pattern, but different ovarian metastasis rates.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/surgery , Hysterectomy , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/radiotherapy , Combined Modality Therapy , Female , Humans , Lymphatic Metastasis/pathology , Neoplasm Staging , Prognosis , Recurrence , Retrospective Studies , Survivors , Time Factors , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/radiotherapy , Vaginal Neoplasms/pathology
19.
Br J Pharmacol ; 155(5): 767-74, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18660829

ABSTRACT

BACKGROUND AND PURPOSE: Substance P (SP), a representative member of the tachykinin family, is involved in nociception under physiological and pathological conditions. Recently, hemokinin-1 (HK-1) was identified as a new member of this family. Although HK-1 acts on NK(1) tachykinin receptors that are thought to be innate for SP, the roles of HK-1 in neuropathic pain are still unknown. EXPERIMENTAL APPROACH: Using rats that had been subjected to chronic constrictive injury (CCI) of the sciatic nerve as a neuropathic pain model, we examined the changes in expression of SP- and HK-1-encoding genes (TAC1 and TAC4, respectively) in the L4/L5 spinal cord and L4/L5 dorsal root ganglia (DRGs) in association with changes in pain-related behaviours in this neuropathic pain state. KEY RESULTS: The TAC4 mRNA level was increased on the ipsilateral side of the dorsal spinal cord, but not in DRGs, at day 3 after CCI. In contrast, the TAC1 mRNA level was significantly increased in the DRGs at day 3 after CCI without any changes in the dorsal spinal cord. Analysis of a cultured microglial cell line revealed the presence of TAC4 mRNA in microglial cells. Minocycline, an inhibitor of microglial activation, blocked the increased expression of TAC4 mRNA after CCI and inhibited the associated pain-related behaviours and microglial activation in the spinal cord. CONCLUSIONS AND IMPLICATIONS: The present results suggest that HK-1 expression is increased at least partly in activated microglial cells after nerve injury and is clearly involved in the early phase of neuropathic pain.


Subject(s)
Pain Threshold , RNA, Messenger/biosynthesis , Sciatica/metabolism , Spinal Cord/metabolism , Tachykinins/biosynthesis , Animals , Cell Line , Disease Models, Animal , Gene Expression/drug effects , Immunohistochemistry , Lumbosacral Region , Male , Microglia/drug effects , Microglia/metabolism , Minocycline/pharmacology , Pain Threshold/drug effects , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Spinal Cord/drug effects , Tachykinins/genetics
20.
J Neural Transm Suppl ; (72): 113-20, 2007.
Article in English | MEDLINE | ID: mdl-17982884

ABSTRACT

Biochemical studies on postmortem brains of patients with Parkinson's disease (PD) have greatly contributed to our understanding of the molecular pathogenesis of this disease. The discovery by 1960 of a dopamine deficiency in the nigro-striatal dopamine region of the PD brain was a landmark in research on PD. At that time we collaborated with Hirotaro Narabayashi and his colleagues in Japan and with Peter Riederer in Germany on the biochemistry of PD by using postmortem brain samples in their brain banks. We found that the activity, mRNA level, and protein content of tyrosine hydroxylase (TH), as well as the levels of the tetrahydrobiopterin (BH4) cofactor of TH and the activity of the BH4-synthesizing enzyme, GTP cyclohydrolase I (GCHI), were markedly decreased in the substantia nigra and striatum in the PD brain. In contrast, the molecular activity (enzyme activity/enzyme protein) of TH was increased, suggesting a compensatory increase in the enzyme activity. The mRNA levels of all four isoforms of human TH (hTH1-hTH4), produced by alternative mRNA splicing, were also markedly decreased. This finding is in contrast to a completely parallel decrease in the activity and protein content of dopamine beta-hydroxylase (DBH) without changes in its molecular activity in cerebrospinal fluid (CSF) in PD. We also found that the activities and/or the levels of the mRNA and protein of aromatic L-amino acid decarboxylase (AADC, DOPA decarboxylase), DBH, phenylethanolamine N-methyltransferase (PNMT), which synthesize dopamine, noradrenaline, and adrenaline, respectively, were also decreased in PD brains, indicating that all catecholamine systems were widely impaired in PD brains. Programmed cell death of the nigro-striatal dopamine neurons in PD has been suggested from the following findings on postmortem brains: (1) increased levels of pro-inflammatory cytokines such as TNF-alpha and IL-6; (2) increased levels of apoptosis-related factors such as TNF-alpha receptor R1 (p 55), soluble Fas and bcl-2, and increased activities of caspases 1 and 3; and (3) decreased levels of neurotrophins such as brain-derived nerve growth factor (BDNF). Immunohistochemical data and the mRNA levels of the above molecules in PD brains supported these biochemical data. We confirmed by double immunofluorescence staining the production of TNF-alpha and IL-6 in activated microglia in the putamen of PD patients. Owing to the recent development of highly sensitive and wide-range analytical methods for quantifying mRNAs and proteins, future assays of the levels of various mRNAs and proteins not only in micro-dissected brain tissues containing neurons and glial cells, but also in single cells from frozen brain slices isolated by laser capture micro-dissection, coupled with toluidine blue, Nissl staining or immunohistochemical staining, should further contribute to the elucidation of the molecular pathogenesis of PD and other neurodegenerative or neuropsychiatric diseases.


Subject(s)
Corpus Striatum/pathology , Dopamine/metabolism , Parkinson Disease/pathology , Substantia Nigra/pathology , Biopterins/analogs & derivatives , Biopterins/genetics , Biopterins/metabolism , Dopamine/genetics , Dopamine beta-Hydroxylase/genetics , Dopamine beta-Hydroxylase/metabolism , Epinephrine/genetics , Epinephrine/metabolism , Forecasting , GTP Cyclohydrolase/genetics , GTP Cyclohydrolase/metabolism , Humans , Interleukin-6/genetics , Interleukin-6/metabolism , Microdissection , Norepinephrine/genetics , Norepinephrine/metabolism , Parkinson Disease/genetics , RNA, Messenger/genetics , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Tyrosine 3-Monooxygenase/genetics , Tyrosine 3-Monooxygenase/metabolism
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