Search PubMed⌕ Search

Biomedical subjects

Hiroaki Kimura

Publications and source records attributed to Hiroaki Kimura.

At least 19 recordsLinked to original sources
PubMed2007

Autoimmune thyroid diseases.

PURPOSE OF REVIEW: Interesting clinical and basic studies have been published in the field of autoimmune thyroiditis (represented by Graves' disease and Hashimoto's thyroiditis) since January 2005. The review is organized into four main areas: genetics, environment, adaptive immune system, and innate immune system. RECENT FINDINGS: The quest continues for the identification of susceptibility genes for autoimmune thyroiditis. In addition to the classical major histocompatibility complex class II genes and cytotoxic T cell antigen-4, new studies have appeared on CD40 the protein tyrosine phosphatase-22. Too much iodine increases the incidence of Hashimoto's thyroiditis, perhaps by augmenting the antigenicity of thyroglobulin. T regulatory cells, Toll-like receptors and presentation of lipid antigens by CD1 molecules are new areas of basic immunological investigation that have been applied to autoimmune thyroiditis. SUMMARY: Overall, the studies have greatly expanded our understanding of the pathogenesis of thyroiditis. They have opened new lines of investigations that will ultimately result in a better clinical practice.

Adaptation, Physiological↗
PubMed2006

Stable top-up operation at SPring-8.

Top-up operation allows SPring-8 to provide highly stable X-ray beams with arbitrary filling patterns. The implementation of top-up operation is described, with a focus on the simultaneous achievement of stability of stored current, beam orbit, purity of an isolated single bunch, and beam injection efficiency. Stored-current fluctuations have been routinely reduced to a level of 10(-3). Stored-beam oscillation on frequent beam injection, which was originally regarded as the most serious problem, has been successfully suppressed to a sufficiently low level that it never perturbs imaging experiments. Current impurities in nominally empty buckets have been reduced to a level of 10(-9) over more than one week of operation, making possible the measurement of time-resolved spectra using high-current bunches. Finally, excellent injection efficiency, higher than 80%, is routinely obtained, even for small undulator gaps, which is critical for preventing radiation damage to insertion-device magnets and to reduce leakage radiation. The process of achieving highly stabilized top-up operation at SPring-8 and its utility for user experiments are described.

Electrons↗
PubMed2006

IL-12 overexpression in mice as a model for Sjögren lung disease.

Interleukin-12 (IL-12), a Th1 proinflammatory cytokine, is reported to be increased in Sjögren syndrome. To evaluate the effects of local Th1/Th2 deregulation, we generated a transgenic mouse model that overexpresses IL-12 in the lungs. IL-12 transgenic mice developed bronchial and alveolar abnormalities strikingly similar to those found in the lungs of Sjögren patients. Pathologically, lung abnormalities began at approximately 4 mo of age and were characterized by lymphocytic infiltrates around the bronchi, intraluminal periodic acid Schiff-positive debris, increased cell proliferation in the alveolar region, and increased interstitial and alveolar macrophages. Functionally, these abnormalities translated into decreased mucociliary clearance (P<0.05 vs. wild-type littermates) and increased oxidative stress (P<0.01). The pathological and functional abnormalities were accompanied by significant changes in lung natural killer (NK) cells. The number of NK cells was fourfold higher in IL-12 transgenic than wild-type lungs (20% of all lymphoid cells vs. 5%) during the first month of life. NK cells then decreased within a narrow window of time (from 30 to 50 days of age), reaching a nadir of approximately 2% on day 50, and remained at these low levels thereafter. This new mouse model highlights the role of IL-12 in the initiation of Sjögren syndrome.

Animals↗
PubMed2006

Efficacy of neurotropin in chronic fatigue syndrome: a case report.

Chronic fatigue syndrome (CFS) is a disorder that causes general fatigue and chronic widespread pain. A 28-year-old male visited an outpatient department due to general fatigue and pain involving the entire body. He did not suffer from fibromyalgia, but he was diagnosed with CFS. At the initial visit, he complained of lack of concentration, memory decline, frequent urination, insomnia and occasional difficulty of emotional control, as well as general fatigue and pain involving the entire body. Four tablets of Neurotropin per day alone were administered. General fatigue and pain were gradually alleviated one week later. His sleep condition, concentration power, and memory also improved two weeks later. Medication was discontinued from 11 weeks based on the patient's judgment as he felt little general fatigue and pain involving the entire body. Treatment was completed 3 months later. The symptoms disappeared and did not recur five months after the discontinuation of Neurotropin. He was looking for a job without fatigue and pain 8 months later (5 months after the cessation of treatment). The functional mechanisms of Neurotropin in CFS are unknown.

Adult↗
PubMed2005

Nerve tolerance to high-dose-rate brachytherapy in patients with soft tissue sarcoma: a retrospective study.

BACKGROUND: Brachytherapy, interstitial tumor bed irradiation, following conservative surgery has been shown to provide excellent local control and limb preservation in patients with soft tissue sarcomas (STS), whereas little is known about the tolerance of peripheral nerves to brachytherapy. In particular, nerve tolerance to high-dose-rate (HDR) brachytherapy has never been properly evaluated. In this study, we examined the efficacy and radiation neurotoxicity of HDR brachytherapy in patients with STS in contact with neurovascular structures. METHODS: Between 1995 and 2000, seven patients with STS involving the neurovascular bundle were treated in our institute with limb-preserving surgery, followed by fractionated HDR brachytherapy. Pathological examination demonstrated that 6 patients had high-grade lesions with five cases of negative margins and one case with positive margins, and one patient had a low-grade lesion with a negative margin. Afterloading catheters placed within the tumor bed directly upon the preserved neurovascular structures were postoperatively loaded with Iridium-192 with a total dose of 50 Gy in 6 patients. One patient received 30 Gy of HDR brachytherapy combined with 20 Gy of adjuvant external beam radiation. RESULTS: With a median follow-up of 4 years, the 5-year actuarial overall survival, disease-free survival, and local control rates were 83.3, 68.6, and 83.3%, respectively. None of the 7 patients developed HDR brachytherapy-induced peripheral neuropathy. Of 5 survivors, 3 evaluable patients had values of motor nerve conduction velocity of the preserved peripheral nerve in the normal range. CONCLUSION: In this study, there were no practical and electrophysiological findings of neurotoxicity of HDR brachytherapy. Despite the small number of patients, our encouraging results are valuable for limb-preserving surgery of unmanageable STS involving critical neurovascular structures.

Adolescent↗
PubMed2005

Interleukin (IL)-12-driven primary hypothyroidism: the contrasting roles of two Th1 cytokines (IL-12 and interferon-gamma).

IL-12, a prototypic T helper 1 cytokine, has been implicated in the pathogenesis of organ-specific autoimmune diseases, such as Hashimoto's thyroiditis, but reported to give conflicting results in murine models of lymphocytic thyroiditis. To determine the effects of chronic, local production of IL-12 within the thyroid gland, we created transgenic mice that express IL-12 p70 under the transcriptional control of the thyroglobulin promoter. Transgenics developed growth retardation, moderate primary hypothyroidism, and mild lymphocytic infiltration of the thyroid gland. The hypothyroidism was associated with increased mRNA levels of the sodium-iodide symporter, an increase partly due to a direct effect of IL-12 on the thyrocyte. Upon immunization with a suboptimal dose of mouse thyroglobulin, IL-12 transgenic mice developed a lymphocytic thyroiditis that was more frequent and severe than that observed in wild-type littermates. The disease-promoting effect of IL-12 was independent of interferon-gamma, as shown by the similar interferon-gamma levels in transgenics and controls. These findings highlight the contrasting roles of two T helper 1 cytokines and report a novel role of IL-12 on thyroid hormonogenesis.

Animals↗
PubMed2005

Increased thyroidal fat and goitrous hypothyroidism induced by interferon-gamma.

Summary Hashimoto's thyroiditis is associated with a diffuse lymphocytic infiltration of the stroma and a production of several cytokines, such as interferon-gamma (IFN-gamma). We previously reported that transgenic mice expressing IFN-gamma under the control of the thyroglobulin promoter develop primary hypothyroidism. In order to determine the long-term changes induced by IFN-gamma in the thyroid gland, we analysed cross-sectionally 202 mice (96 transgenic mice and 106 controls) of 0-650 days of age. Multiple linear regression analysis showed that, after adjusting for age and sex, thyr-IFN-gamma transgenic mice were 14% (3 g) smaller (P < 0.0001) and had a 5- to 6-fold bigger thyroid (P < 0.0001) than wild-type littermates. Transgenic thyroids showed striking histopathological changes in follicles, thyrocytes and stroma. Follicles were enlarged, irregular and were lined by thickened, granular and oxyphilic thyrocytes. The stroma contained a moderate and diffuse mononuclear infiltrate--mainly composed of macrophages--and, interestingly, a clear increase in the content of fat. These findings indicate that, in addition to hypothyroidism, chronic exposure of the thyroid to IFN-gamma leads also to macrophage infiltration and subsequent adipocyte expansion, suggesting a link between inflammation and fat accumulation.

Adipose Tissue↗
PubMed2005

Frequency of gouty arthritis in patients with end-stage renal disease in Japan.

OBJECTIVE: The purpose of this study was to investigate gouty arthritis in Japanese patients with end-stage renal disease (ESRD). METHODS: Questionnaires plus patient interviews and reviews of medical records were used to investigate gouty arthritis in 493 Japanese patients with ESRD receiving maintenance dialysis. RESULTS: The frequency of gouty arthritis was 4.1% for female patients and 15.4% for male patients greater than 2 years before the start of dialysis, and 0.6% for female patients and 7.7% for male patients less than 2 years before the start of dialysis. After the start of dialysis the frequency was 3.4% for the first 2 years and 1.2% thereafter in male patients, but no gouty arthritis appeared in female patients. Although the annual number of gouty attacks was 2.0+/-4.2 greater than 2 years before the start of dialysis, and 1.9+/-6.6 less than 2 years before the start of dialysis, the annual number of attacks decreased significantly after the start of dialysis to 0.2+/-0.7 in the first 2 years and 0.1+/-0.6 thereafter. CONCLUSIONS: The frequency of gouty arthritis in Japanese patients with ESRD is similar to that of patients with hyperuricemia in the general population and it is decreased slightly before dialysis; however, the frequency decreases markedly after dialysis.

Aged↗
PubMed2004

Expression of class II major histocompatibility complex molecules on thyrocytes does not cause spontaneous thyroiditis but mildly increases its severity after immunization.

Class II major histocompatibility complex (MHC) molecules are classically expressed on antigen-presenting cells of the hematopoietic lineage but have also been described on epithelial cells in association with autoimmunity. In this context, however, it remains debatable whether class II MHC molecules are the initiating event or rather the consequence of the autoimmune attack. In addition, the role of epithelial class II expression once the autoimmune attack has begun is unknown. We generated transgenic mice expressing in the thyroid follicular cells the class II transactivator, the master regulator of all the genes in the class II MHC pathway. The study used a cohort of 245 CBA/J mice (127 wild-type and 118 transgenic), both in basal conditions (n = 63) and at different time points after immunization with mouse thyroglobulin (n = 182). In basal conditions, transgenic mice were similar to wild-type controls and did not develop spontaneous autoimmune thyroiditis, despite the aberrant expression of class II MHC molecules on thyrocytes. After immunization, thyroiditis was 8% more severe in transgenics than controls (95% confidence interval from 1.8-13.4%; P = 0.033), especially during the florid stages of disease. These findings suggest that expression of class II MHC molecules on epithelial cells is not sufficient to initiate autoimmunity but mildly modulates an already established autoimmune attack against the target organ.

Animals↗
PubMed2004

Early chemokine expression induced by interferon-gamma in a murine model of Hashimoto's thyroiditis.

Chemokines represent a group of small, secreted proteins mainly involved in navigating leukocytes towards site of inflammation. Some chemokines have been implicated in the pathogenesis of autoimmune diseases, which are characterized by an ectopic retention of leukocytes within the target organ, ultimately leading to loss of function. To determine the chemokines profile expressed in the thyroid gland upon chronic exposure to interferon-gamma (IFNgamma), we analyzed C57BL6 transgenic mice that aberrantly express IFNgamma under control of the thyroglobulin promoter. We compared by reverse transcriptase PCR the thyroidal expression of 10 chemokines (CCL1 through 5 and CXCL9 through 13) in thyr-IFNgamma transgenics and wild-type littermates. We found that transgenics exclusively expressed CCL4, CXCL9, and CXCL11, and showed increased expression of CCL5 and CXCL10. This chemokine profile was associated with moderate mononuclear cell infiltration of the thyroid stroma that, however, decreased significantly after 2 months of age and did not organize into lymphoid structures. Our findings indicate that the isolated expression of IFNgamma is capable of recruiting mononuclear cells but they do not progress to full lymphoid transformation of the thyroid.

Animals↗
PubMed2004

Comparison of current perception threshold between each side in unilateral complex regional pain syndrome patients does not measure the patient's pain.

The current perception threshold (CPT) test has been developed as one of the neuroselective sensory nerve conduction threshold tests. The score of the CPT of the affected side subtracted from the score of the CPT of the unaffected side in complex regional pain syndrome (CRPS) is expected to show pain objectively. The purpose of this study is to examine first whether the CPT of the affected side is generally lower than that of the unaffected side, and second, whether the greater score shows the more intense pain. The CPT of each side in 25 patients with unilateral CRPS type I was measured and compared. For the 2000 Hz stimulus, the CPT of the affected side was 2677 +/- 262 microAmp (mean +/- standard error) and the CPT of the unaffected side was 2194 +/- 247 microAmp (p = 0.0149). For the 250 Hz stimulus, the CPT was 876 +/- 117 microAmp and 721 +/- 73 microAmp respectively (p > 0.05). For the 5 Hz stimulus, the CPT was 730 +/- 105 microAmp and 448 +/- 56 microAmp respectively (p = 0.0018). In 2000 Hz, 250 Hz, and 5 Hz stimuli, the CPT of the affected side was higher than that of the unaffected side. This shows that generally the affected side is less sensitive than the unaffected side in terms of current perception. The score of the CPT of the affected side subtracted from the score of the CPT of the unaffected side in CRPS does not measure the patient's pain.

Adult↗
PubMed2003

Multiple mechanisms involved in the inhibition of proinflammatory cytokine production from human monocytes by N-(p-coumaroyl)serotonin and its derivatives.

We have reported that N-(p-coumaroyl)serotonin(CS) isolated from safflower oil cake (Carthamus tinctorius L.) inhibits the production of proinflammatory cytokines by endotoxin (LPS)- stimulated human monocytes. In this study, the effects of CS and its three derivatives, N-(trans-cinnamoyl)serotonin (Cin.S), N-(trans-cinnamoyl)tryptamine (Cin.T), and N-(p-coumaroyl)tryptamine (CT) on the production of proinflammatory cytokines were compared. Cin.S possessed radical scavenging activity at a comparable level to CS, while CT and Cin.T exhibited lower activity, suggesting that hydroxyl group in serotonin is essential for the antioxidative activity. CS and CT strongly inhibited the production of proinflammatory cytokines (IL-1alpha, IL-1beta, IL-6, IL-8, and TNF-alpha) from LPS-stimulated human monocytes. However, Cin.S inhibited the production of only IL-1alpha and IL-1beta, and Cin.T inhibited none of these cytokines production. CS and CT markedly inhibited the protein synthesis in monocytes, the inhibitory effect of Cin.S was moderate, and that of Cin.T was quite weak. These results indicate that CS and its derivatives inhibit the production of proinflammatory cytokines through multiple mechanisms.

Antioxidants↗
PubMed2003

Urate transport via human PAH transporter hOAT1 and its gene structure.

BACKGROUND: We recently cloned the human organic anion transporter 1 (hOAT1) as a p-aminohippurate (PAH) transporter. Whether urate is transported by the PAH transporter in humans remains unclear. Familial juvenile gouty nephropathy (FJGN) is thought to develop as a result of an abnormality in the urate transporter. METHODS: To determine if hOAT1 transported urate, the cellular uptakes of PAH and urate were determined, as were the inhibition profiles of inorganic anions, and uricosuric and antiuricosuric agents using a mouse S2 cell line expressing hOAT1. The hOAT1 gene was cloned from a genomic library using full-length hOAT1-1 cDNA as a probe. The coding regions of the hOAT1 genes of two sisters with FJGN were sequenced. Also, immunohistochemical fluorescence analysis of hOAT1 in the kidney of the younger sister with FJGN was performed. RESULTS: The Km and Vmax values of urate transport via hOAT1 were 943 +/- 84 micromol/L and 1286 +/- 162 pmol/mg protein/min, respectively. The order of the IC50 of urate transport via hOAT1 was benzbromarone < probenecid < salicylate or pyrazine carboxylic acid. The 10.9 kb hOAT1 gene was found to be interrupted by nine introns. Mutations in the coding region of the hOAT1 gene from the two sisters with FJGN were undetectable. Immunohistochemical fluorescent staining showed that hOAT1 in the kidney of the younger sister was similar to that of control individuals. CONCLUSIONS: Our data show that hOAT1 transports urate, and the inhibition profiles of uricosuric and antiuricosuric agents are defined. hOAT1 is not responsible for FJGN in the two sisters examined in this study.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Studies on murine thyroiditis: new insights from organ flow cytometry.

The pathogenesis of autoimmune diseases is frequently studied in murine models, in which disease outcome is traditionally assessed by light microscopy. To determine whether digital imaging improves reliability of the histopathologic assessment, and whether flow cytometry is applicable directly on the murine thyroid, we studied 395 CBA/J mice 3 weeks after thyroglobulin immunization, and 192 nonimmunized CBA/J mice. Digital imaging significantly improved reliability of the histopathological assessment (r = 0.988, 95% confidence interval: 0.980-0.992, p < 0.0001), and flow cytometry on the murine thyroid could be performed successfully. We also found that normal thyroids contained a higher than expected number of hematopoietic cells in the interstitium. We suggest that digital imaging offers a better means of estimating disease outcome, and that flow cytometry performed at the target organ levels reflects the autoimmune pathogenesis more closely than when performed on peripheral lymphoid organs. These methods should also be applicable to other organ systems targeted by autoimmune attack, such as heart, exocrine, and other endocrine glands.

Animals↗
PubMed2003

Does a viral infection cause complex regional pain syndrome?

In 1990 Omura, Y. reported that Herpes Simplex Virus Type 1 as the major cause of chronic intractable pain and its effective treatment using mixture of EPA & DHA with Selective Drug Uptake Enhancement Method. Subsequently among the other causes of pain, he included Chlamydia Trachomatis, Borrelia Burgdorferi, Mycobacterium Tuberculosis, human Herpes Virus type 6, and Circulatory Disturbances. In order to test possible involvement of viral infection in Complex Regional Pain Syndrome (CRPS), a disease which usually occurs in the extremities, we did a study of 17 patients with CRPS. They were examined for Herpes Simplex Virus (HSV) and Varicella Zoster Virus (VZV) by measuring IgG and IgM antibody titers, and 14 of these patients were also examined for Cytomegalo-Virus (CMV). As a control group 100 healthy Japanese employees at SRL, Inc. were also studied. In CRPS group, HSV IgG was positive in 12 of the 17 patients with an average antibody titer of 90.0 EIA value. VZV IgG was positive in all 17 patients with an average antibody titer of 26.8 EIA value. CMV IgG was positive in all 14 patients with an average antibody titer of 66.6 UA/ml. In control group, HSV IgG was positive in 54 subjects with an average antibody titer of 42.3 EIA value. VZV IgG was positive in 97 subjects with an average antibody titer of 26.2 EIA value. CMV IgG was positive in 82 subjects. There were no significant differences of positive rate of IgG antibody for the three viruses between patient and control groups. Although the difference was not significant, the average antibody titers of HSV in CRPS group were more than twice of those in healthy group. Antibody titers were almost equal in both groups for VZV. Possibly, some people in the control group who had latent virus, were also asymptomatic. In 2000, Takasaki, I. et al. in a separate animal study, inoculated with HSV Type-I the shin of the mouse causing allodynia and hyperalgesia (which are some of the characteristic findings seen in CRPS in humans). Also, VZV, which causes shingles which is sometimes followed by Post-Herpetic Neuralgia (PHN), is in the same family of HSV. As PHN resembles CRPS in symptoms, it is possible that HSV contributes to CRPS. Therefore, virus infection theory is an attractive hypothesis that accounts for many enigmas of CRPS.

Adolescent↗
PubMed2003

A patient with MRSA infection to prosthesis of femoral head diagnosed non-invasively using bi-digital O-ring test: a clinical case report.

Prosthesis of femoral head is a common surgical procedure, but the diagnosis of infection associated with the prosthesis remains difficult. We diagnosed non-invasively methicillin resistant Staphylococcus aureus (MRSA) infection of prosthesis of femoral head with Bi-Digital O-Ring Test (BDORT). BDORT uses the resonance phenomenon between 2 identical substances, and electromagnetic field principle. The method can non-invasively detect viral & bacterial infection. Accuracy of the BDORT findings was confirmed through bacterial culture & sensitivity test to antibiotics. Patient was successfully treated with operation of evulsion of the prosthesis of femoral head and administration of antibiotics and Cilantro. The drug compatibility was tested with BDORT. BDORT was an effective technique for non-invasively detecting infection of prosthesis and selecting the most effective antibiotics.

Aged↗