[Slowly progressive insulin-dependent (type 1) diabetes mellitus].
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Diabetes Mellitus, Type 1↗
Biomedical subjects
Tetsuro Kobayashi
Publications and source records attributed to Tetsuro Kobayashi.
[Diabetes associated with infection].
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Antibodies, Viral↗
Mitochondrial complex I activity is significantly decreased in a patient with maternally inherited type 2 diabetes mellitus and hypertrophic cardiomyopathy associated with mitochondrial DNA C3310T mutation: a cybrid study.
Mitochondrial respiratory function in a patient with maternally inherited type 2 diabetes mellitus and hypertrophic cardiomyopathy associated with heteroplasmic mitochondrial DNA (mtDNA) C3310T mutation, which replaces the second amino acid of NADH dehydrogenase 1 (ND1) from a hydrophobic Proline to a hydrophilic Serine, was investigated. Mitochondrial respiratory function solely due to mtDNA C3310T mutation was investigated in cybrid system by the fusion of mtDNA-deleted (rho(0)) HeLa cells and exogenous mtDNA either from the proband or from controls. Total oxygen consumption of the proband cybrid cells was significantly decreased compared with those of controls (2.468+/-0.475 versus 2.871+/-0.484 micromol/h/10(7) cells, p=0.0392). Mitochondrial respiratory chain complex I activity of the proband cybrid cells was also significantly decreased compared with those of controls (0.191+/-0.080 versus 0.288+/-0.113 micromol/h/mg protein, p=0.0223). Furthermore, ATP content in the proband cybrid cells was also significantly decreased compared with those in controls (1.119+/-0.344 versus 1.419+/-0.378 pmol/10(5) cells, p=0.044). The present study indicates that mtDNA C3310T mutation may be a pathogenic mutation of maternally inherited type 2 diabetes mellitus and hypertrophic cardiomyopathy in the proband and the family.
Blotting, Southern↗
Systematic search for single nucleotide polymorphisms in a lymphoid tyrosine phosphatase gene (PTPN22): association between a promoter polymorphism and type 1 diabetes in Asian populations.
The protein tyrosine phosphatase, nonreceptor 22 gene (PTPN22) maps to human chromosome 1p13.3-p13.1 and encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase (Lyp). Recently, the minor allele of a single-nucleotide polymorphism (SNP) at nucleotide position 1858 (rs2476601, +1858C > T) was found to be associated with type 1 diabetes. However, the degree of the association is variable among ethnic populations, suggesting the presence of other disease-associated variants in PTPN22. To examine this possibility, we carried out a systemic search for PTPN22 using direct sequencing of PCR-amplified products in the Japanese population. Association and linkage studies were also conducted in 1,690 Japanese samples, 180 Korean samples, and 472 Caucasian samples from 95 nuclear families. We identified five novel SNPs, but not the +1858C > T SNP. Of these two frequent SNPs, -1123G > C, and +2740C > T were in strong linkage disequilibrium (LD), and the -1123G > C promoter SNP was associated with acute-onset but not slow-onset type 1 diabetes in the Japanese population (odds ratio [OR] = 1.42, 95% CI = 1.07-1.89, P = 0.015). This association was observed also in Korean patients with type 1 diabetes (Mantel-Haenszel chi2= 6.543, P = 0.0105, combined OR = 1.41 95% CI = 1.09-1.82). Furthermore, the affected family-based control (AFBAC) association test and the transmission disequilibrium analysis of multiplex families of European descent from the British Diabetes Association (BDA) Warren Repository indicated that the association was stronger in -1123G > C compared to +1858C > T. In conclusion, the type 1 diabetes association with PTPN22 is confirmed, but it cannot be attributed solely to the +1858C > T variant. The promoter -1123G > C SNP is a more likely causative variant in PTPN22.
Alleles↗
Electro-optic transparent frequency conversion of a continuous light wave based on multistage phase modulation.
Frequency conversion of a continuous light wave based on multistage phase modulation has been investigated both analytically and numerically. The proposed frequency-conversion process consists of three stages: (i) phase modulation and chirp compression to generate a pulse train, (ii) Doppler shift of the pulse center frequency in a second phase modulation, and (iii) demodulation of the pulse train. By controlling the modulation power we can select the destination frequency from an equally spaced grid separated by the modulation frequency. A conversion efficiency of approximately 40% has been numerically confirmed with respect to a destination frequency of +/- 50 channels. Carrier frequency conversion of an analog data stream is numerically demonstrated.
Journal Article↗
A sensitive radioimmunoassay of insulin autoantibody: reduction of non-specific binding of [125I]insulin.
There has been a lack of consensus among results of assays for insulin autoantibody (IAA) carried out by different laboratories, despite a reduction in the non-specific effect using a cold insulin competitor in radioimmunoassays (RIAs) for IAA in type I diabetes. We speculated that the discrepancies are partly a result of the non-specific binding (NSB) of [125I]insulin to unidentified molecules in serum on polyethylene glycol separation, and tried to improve IAA RIAs. The molecular weight of a candidate for the factor causing NSB was estimated to be about 700 kDa by gel filtration analysis, resembling that of alpha 2-macroglobulin (a2M). Further, the addition of purified a2M to the assay resulted in an increase in NSB. Screening revealed that heterocyclic compounds, such as isothiazolinone derivatives (ProClin300), were greatly effective at reducing NSB in control subjects from 2.904+/-0.909% to 1.347+/-0.254% (n=283, mean+/-SD, p<0.0001). Using our newly developed IAA RIA with ProClin300, the sensitivity for newly diagnosed type I diabetes patients (n=55) was 32.7% and 30.9% with or without insulin competition, respectively, whereas that of the former assay without ProClin300 was only 20.0%.
Adolescent↗
Focal segmental glomerulosclerosis associated with essential thrombocythemia.
Focal segmental glomerulosclerosis (FSGS) is a primary glomerular disease that is characterized by progressive proteinuria and declining renal function. Secondary FSGS is known to be associated with various diseases. However, an association of FSGS with essential thrombocythemia (ET) has been reported in few cases. We report a 76-year-old man who presented with nephrotic syndrome and hepatosplenomegaly. He had thrombocythemia after a splenectomy, which had been carried out at a nearby hospital. A renal biopsy showed that he had focal segmental glomerulosclerosis (FSGS), while assessment of the bone-marrow specimen revealed that he had ET. A possible relationship between FSGS, which occurred in association with a dramatic increase of thrombocytes after a splenectomy in a patient with ET, and increased serum levels of transforming growth factor (TGF)-beta, basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF)-BB was suggested.
Aged↗
Immunopathological and genetic features in slowly progressive insulin-dependent diabetes mellitus and latent autoimmune diabetes in adults.
In 1982 we proposed the presence of a subtype of type 1 diabetes [slowly progressive insulin-dependent diabetes mellitus (SPIDDM)], which was characterized by persistently positive islet cell antibody, late age of onset, noninsulin-dependent diabetes, and slowly progressive beta cell failure. Since then many studies demonstrated that this subtype of type 1 diabetes is prevalent in many ethnic groups and was later called the latent autoimmune diabetes in adults (LADA). Recent epidemiological studies reported that about 10% of patients with apparent type 2 diabetes have at least one autoantibodies against islet-specific antigen with high potential to progress to insulin-dependent state. Between SPIDDM and LADA some differences are reported in terms of some genetic predispositions including HLA class II and class I genes, vitamin D receptor gene, and CTLA4 genes. Common features in SPIDDM and LADA including preserved beta cells at the onset of diabetes and weak T cell response to residual beta cells suggest that these subtypes of type 1 diabetes are suitable candidates for prevention treatment for further progression of beta cell failure.
Adult↗
The association of CTLA4 polymorphism with type 1 diabetes is concentrated in patients complicated with autoimmune thyroid disease: a multicenter collaborative study in Japan.
CONTEXT: Transracial studies are a powerful tool for genetic association studies of multifactorial diseases, such as type 1 diabetes. The low incidence of type 1 diabetes in Asian countries, however, makes it difficult to perform large-scale studies in Asia. OBJECTIVE: To overcome this, we have assembled a multicenter study group in Japan and studied the association of CTLA4 polymorphisms with type 1 diabetes relative to autoimmune thyroid disease (AITD) phenotypes. SUBJECTS: Subjects included a total of 1837 samples, including 1114 cases (769 with type 1 diabetes and 345 with AITD) and 723 control subjects. METHODS: The +6230G>A and +49G>A polymorphisms of CTLA4 as well as HLA-DRB1 and -DQB1 were genotyped. RESULTS: The +6230G>A polymorphism was significantly associated with type 1 diabetes complicated with AITD (odds ratio, 1.54; P = 0.027) and with AITD alone (odds ratio, 1.31; P = 0.045) but not with type 1 diabetes without AITD. The association with type 1 diabetes positive for autoantibodies to both pancreatic islets and thyroid was particularly strong (odds ratio, 1.87; P = 0.001). Type 1 diabetic patients with the disease-associated GG genotype were characterized by a significantly higher frequency of AITD (P = 0.013), of positivity for both AITD and antiislet autoantibody (P = 0.00086), and of high-risk HLA genotypes (P = 0.034). CONCLUSIONS: Given the high frequency of AITD in patients with type 1 diabetes, these data suggest the possibility that the association of CTLA4 with type 1 diabetes in previous studies may have been secondary to AITD, suggesting the importance of subclassification of type 1 diabetes relative to AITD in genetic studies.
Adult↗
Serum level of macrophage colony-stimulating factor and atherosclerosis in hemodialysis patients.
BACKGROUND/AIMS: Atherosclerosis and its related complications are the leading causes of death in the hemodialysis (HD) population. Aortic calcification index (ACI), intima-media thickness (IMT) in common carotid arteries, and electrocardiogram (ECG) are atherosclerotic parameters that are available in usual clinical outpatient settings. Macrophage colony-stimulating factor (MCSF) and monocyte chemoattractant protein-1 (MCP-1) play important roles in atherosclerosis. METHODS: We performed a cross-sectional study of 133 outpatients on maintenance HD in a single HD outpatient center. We measured serum levels of MCSF and MCP-1, determined the ACI using computed tomography scan and the IMT using high-sensitivity ultrasound B-mode imaging, and performed ECGs. RESULTS: Stepwise multivariate regression analysis revealed that the MCSF level correlated with age-adjusted mean and maximum IMT (F = 10.811, p = 0.001, and F = 6.784, p = 0.010, respectively) as well as with the diastolic blood pressure. Age and MCSF level (F = 4.866, p = 0.029) were independently related to an increased ACI. High-sensitivity C-reactive protein (hsCRP) was not related to IMT and ACI. The hsCRP level (chi2 = 5.002, p = 0.025) correlated with ECG changes followed by MCSF (chi2 = 3.940, p = 0.047). MCP-1 was not related to the above atherosclerotic parameters. CONCLUSION: A head-to-head comparison between MCSF and hsCRP revealed that MCSF was more closely associated with IMT and ACI in HD patients.
Adolescent↗
Generation of flat power-envelope terahertz-wide modulation sidebands from a continuous-wave laser based on an external electro-optic phase modulator.
Flat power-envelope terahertz-wide modulation sidebands are generated by only electro-optic phase modulation of continuous-wave laser light. Generation and power equalization of widespread sidebands are realized simultaneously by spatial distribution of the modulation index within a laser beam cross section by use of simple domain-engineering processes in LiTaO3 electro-optic crystal. Generation of 46 sidebands spaced by 16.25 GHz within a -3-dB bandwidth (over a 1-THz span for a +/- 3-dB bandwidth) is demonstrated.
Journal Article↗
Extensive pancreatic necrosis in microscopic polyangiitis.
We encountered an 84-year-old woman with microscopic polyangiitis who was found to have pancreatitis on autopsy. The patient was admitted to Yamanashi University Hospital because of fever and progressive renal failure. She was diagnosed with anti-myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-related microscopic polyangiitis (MPA) and was treated successfully with prednisolone pulse therapy. Two months later, she was found unconscious at home and was transferred to hospital, where she died of cardiac arrest after 6 days. Autopsy revealed systemic vasculitis with fibrinoid necrosis (with the most severe form found in the pancreas), interstitial pneumonia, and crescentic glomerulonephritis. A review of the literature revealed that pancreatic involvement in vasculitis, although rare, is one of the complications of MPA; however, the present study is the first report to focus on the pancreatic involvement of MPA. We recommend that nephrologists consider the possibility of pancreatic involvement in this disease.
Aged, 80 and over↗
Distinct diagnostic criteria for ultrasonographic examination of papillary thyroid carcinoma: a multicenter study.
Recent advances permitting high-resolution ultrasonography have made ultrasonographic examination of nodular thyroid diseases an accessible examination for routine practice. However, diagnostic criteria for ultrasonographic examination of thyroid nodules are not surely established. To identify the optimal strategy for well standardized differential diagnosis of papillary thyroid carcinoma and benign nodules, we evaluated the significance of individual ultrasonographic characteristics of thyroid nodules in a multicenter study. Ten characteristics in ultrasonograms from 53 patients scored by 17 investigators from 15 centers were analyzed by t tests and logistic regression analyses. Between benign and papillary thyroid cancer groups, all characteristics but not size or multiplicity of strong echoes, which suggest calcifications, were significant parameters. Logistic regression analyses showed that border character, shape, and internal echo level are highly significant parameters (p < 0.0005). A multiple logistic regression showed to be the most important predictors of pathologic diagnosis. The diagnostic criterion with border character and internal echo level yielded 93% sensitivity and 92% specificity. In conclusion, univariate and multivariate analyses identified border character, shape, internal echo level, but not strong echoes (calcifications), as important characteristics in differentiating papillary thyroid carcinoma from benign nodules. These results will contribute to standardization of accurate ultrasonographic diagnosis of papillary thyroid carcinoma.
Adenocarcinoma, Papillary↗
Colonic lipoma with florid vascular proliferation and nodule-aggregating appearance related to repeated intussusception.
A unique case of repeatedly intussuscepted colonic lipoma mimicking an epithelial tumor in a 50-year-old man is reported. The tumor was located in the ascending colon and was approximately 5 cm in diameter. Colonoscopic and barium-enema examinations suggested a huge epithelial tumor because of its nodule-aggregating appearance. In contrast, computed tomography examination showed a fatty element in the core of the lesion. The biopsy specimens suggested a primary angiomatous lesion because of its pronounced vascular proliferation. Because the presumed diagnoses based on the examinations were different, the preoperative diagnosis was not confirmed. The tumor was composed of intramural lipoma with a multiple polypoid mucosa overlay. This lesion was unique in that the lipoma appeared to be within the muscularis propria and the multiple polypoid appearance of its covering mucosa. The mucosal changes including florid vascular proliferation, fibromuscular obliteration and epithelial regeneration suggested a reparative process, with ischemic damage due to the effects of intussusception being the most likely event. It should be kept in mind that even a simple lipoma can have a unique appearance reminiscent of epithelial tumor when it repeatedly experiences intussusception.
Colonic Neoplasms↗
[A case of colon cancer with multiple liver, lung and bone metastases successfully treated with combined weekly high-dose 5-FU (WHF) chemotherapy with UFT and CPT-11].
A 54-year-old woman who had ascending colon cancer with multiple liver and lung metastases underwent rt. hemicolectomy and catheter insertion into the gastroduodenal artery for arterial infusion chemotherapy. On postoperative day 7, she had nausea and vomiting due to the enlarged multiple liver metastases on lateral segment. Intraarterial infusion of 5-FU 1,000 mg/m(2) for 5 hours weekly (WHF: weekly high-dose 5-FU) was started at first. After 3 courses, her symptoms improved, oral intake could be started, and liver metastases showed significant reduction on abdominal CT. Three months after surgery, bone scinti revealed multiple bone metastases. Combined HAI (5-FU: 600 mg/m(2)/3 hr) chemotherapy with UFT (400 mg/body) + CPT-11(80/body) and UFT (400 mg/body)/LV (75 mg/body) + CPT-11(100 mg/body) were effective for highly advanced colon cancer in terms of QOL. Eight months after surgery, she was doing well and the chemotherapy was continued. WHF therapy was effective for digestive symptoms due to liver metastasis.
Adenocarcinoma↗
Adenovirus-mediated transfer of thyroid transcription factor-1 induces radioiodide organification and retention in thyroid cancer cells.
Loss of thyroid-specific gene expression and functions accompanied by loss of thyroid transcription factors render them unresponsive to radioiodide therapy in poorly differentiated and anaplastic thyroid cancer. In anticipation of reactivation of thyroid functions, we investigated the effect of thyroid transcription factor-1 (TTF-1) gene transfer on thyroid cancer cells. Reexpression of thyroperoxidase (TPO) and thyroglobulin (Tg) mRNA and protein was detected in poorly differentiated human thyroid cancer cells that were infected with an adenovirus vector containing TTF-1 (AdTTF-1). Although TTF-1 gene transfer faintly induced iodide uptake, the induction of sodium/iodide symporter (NIS) mRNA was not observed in AdTTF-1-infected cells. To analyze the effect of TTF-1 on iodide metabolism, we transfected an NIS expression vector into BHP18-21v cells and cloned a cell line (N-BHP18-21v) that stably expressed NIS. The treatment of N-BHP18-21v cells with AdTTF-1 significantly increased the amount of protein-bound radioiodide and prolonged the iodide efflux. AdTTF-1 injections significantly induced iodide retention and organification in tumors formed from N-BHP18-21v cells in nude mice. These results indicate that AdTTF-1 specifically induces iodide organification and retards iodide efflux in thyroid cancer cells in vitro and in vivo.
Adenoviridae↗
WRN gene and other genetic factors affecting immortalization of human B-lymphoblastoid cell lines transformed by Epstein-Barr virus.
The immortalization of human B-lymphoblastoid cell lines (LCL) transformed by Epstein-Barr virus (EBV) is accompanied by two major events: increase in telomerase activity and change in karyotype from normal diploid to aneuploidy. We investigated the effect of genetic factors on the incidence of immortalization by putting old and new data together to collect enough samples for statistical analysis. Among 50 LCL from normal individuals, 5 LCL (10.0%) were immortalized and the remaining 45 LCL were mortal. None of the 44 LCL (0%; P < 0.031 against normal individuals by chi square test) from patients having Werner syndrome (WS), a recessive genetic disorder showing premature aging, were immortalized. Among 11 LCL from a family with a tendency to have hereditary type 2 diabetes mellitus, 5 LCL (45.5%; P < 0.0040 against normal individuals, P < 0.00001 against WS patients) were immortalized. Duplicated measurements of the lifespan of 33 LCL showed a good coincidence (r=0.785) between the first and second estimations, indicating that each mortal LCL has a predetermined lifespan. These results strongly suggest that the normal WRN gene, the causative gene of WS, is essential for LCL to immortalize, and genetic factor(s) of a family having diabetes mellitus increases immortalization, implicating that host genetic factors affect immortalization of EBV and probably carcinogenesis by EBV.
Adolescent↗