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Biomedical subjects

Masaaki Nakano

Publications and source records attributed to Masaaki Nakano.

At least 19 recordsLinked to original sources

Outcome of patients with reactive amyloidosis associated with rheumatoid arthritis in dialysis treatment.

The aim was to analyze the clinical outcome of a group of 51 patients diagnosed with systemic amyloidosis associated with rheumatoid arthritis who received hemodialysis (HD) as renal replacement therapy. We monitored the clinical course of the disease and factors that could influence survival. Determination of the onset of the underlying disorder was made retrospectively by reviewing the patient's chart when a diagnosis of amyloid was confirmed. During a 96.9 person-year follow-up, 42 patients died. Survival of these 51 patients from the initiation of HD at 251 days was 50%. Poor prognosis in amyloid patients was mainly due to a large number of sudden deaths immediately following HD therapy. Out of 51 patients 21 needed unplanned initiation of HD. The unplanned initiation was significantly associated with poor survival. Seventy-five percentile of creatinine clearance (Ccr) was 9.7 ml/min, and 75% of these patients who initiated HD had highly impaired renal functional states. These data indicated that amyloidotic patients with HD showed a high mortality rate; therefore, planned initiation of HD was highly recommended to improve the patient's survival. Particular attention was given to the Ccr levels, because the levels of serum creatinine may not be a useful marker for some patients with amyloidosis.

Adult↗

A case of Takayasu arteritis complicated with glomerulonephropathy mimicking membranoproliferative glomerulonephritis: a case report and review of the literature.

In this report, we describe the case of a 50-year-old Japanese woman with Takayasu arteritis who developed severe proteinuria and renal dysfunction. Abdominal computed tomography did not show narrowing of both renal arteries. Although her levels of C-reactive protein were negative, plasma vascular endothelial growth factor (VEGF) and serum interleukin (IL)-6 levels were elevated. Renal biopsy showed glomerulonephropathy mimicking membranoproliferative glomerulonephritis (MPGN) with glomerular capillary wall thickening (double contour). This was accompanied by mesangial cell proliferation and moderate increase of mesangial matrix without deposits of C3. These findings are quite different from MPGN as electron microscopy did not show subendothelial deposit and circumferential mesangial interposition. Here, we present the case of Takayasu arteritis associated with MPGN-like renal manifestation and elevated VEGF and IL-6. The presence of elevated VEGF and IL-6 could be factors that might contribute to MPGN-like appearance.

Biopsy↗

Efficient methods for sample processing and cDNA synthesis by RT-PCR for the detection of grapevine viruses and viroids.

Template preparation is important in reverse-transcription polymerase chain reaction (RT-PCR)-based detection methods. A TissueLyser with tungsten carbide beads was used for simultaneous processing of up to 48 samples under the same conditions in the development of a simple and rapid procedure to prepare a plant extract for RT reaction. A sandpaper method was also developed by which wood tissue of dormant cuttings could be macerated easily to process with minimal time and effort. It was also demonstrated that the combination use of random primers and oligo dT primer in an RT reaction was efficient for simultaneous cDNA synthesis of viral and viroid RNAs in plant extracts. These template preparation methods were used for the amplification of Grapevine leafroll-associated virus-1,-2, and -3; Grapevine virus A and B; Grapevine rupestris stem pitting-associated virus; Grapevine fleck virus; and Grapevine fanleaf virus. All these viruses tested in this study were reliably detected up to a 10(3)-fold or higher dilution of the original extract. Besides, Hop stunt viroid and Grapevine yellow speckle viroid 1 were well amplified in the same manner as the template preparation and following PCR for virus detection. These methods would contribute to cost-effective testing of a large number of samples through the year and help to detect viral pathogens in grapevine.

DNA Primers↗

A case of mixed connective tissue disease complicated with thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a rare complication of mixed connective tissue disease (MCTD). In this report, we describe the case of a 73-year-old Japanese woman with MCTD who developed fever, thrombocytopenia, and microangiopathic hemolytic anemia and was diagnosed with MCTD together with TTP. The activity of von Willebrand factor (vWF) cleaving metalloprotease ADAMTS13 was low and considered to have contributed to the disease activity of TTP. The patient died despite intensive treatment of plasma exchange (PEX) and steroid pulse therapy. Autopsy results revealed that the kidneys had platelet and fibrin thrombi, which occluded capillaries and arterioles. These findings were compatible with TTP and the decreased activity of ADAMTS13 was considered to be associated with the disease activity of TTP.

ADAM Proteins↗

SAA1 gene polymorphisms and the risk of AA amyloidosis in Japanese patients with rheumatoid arthritis.

To investigate the precise modality of association between SAA1 gene polymorphisms and the development of AA amyloidosis in patients with rheumatoid arthritis (RA), Japanese patients with RA (n=153), among whom 29 were histologically diagnosed as having amyloidosis, were genotyped for three single nucleotide polymorphisms (SNPs), C-13T, C2995T, and C3010T, in the SAA gene. Pairwise linkage disequilibrium coefficients between each pair of SNPs were calculated and estimated haplotype frequencies were compared between patients with and without amyloidosis. Possible associations between these SNPs and amyloidosis were analyzed by a case-control study and by the Kaplan-Meier method, in which the endpoint was defined as the time of diagnosis of AA amyloidosis. The -13T and 2995C alleles, which were in a tight linkage disequilibrium, were more frequent in the patients with amyloidosis, and the groups with the -13TT and 2995CC genotype had worse survival curves than patients without these genotypes, whereas C3010T was not associated with amyloidosis. Moreover, the haplotype containing -13C and 2995T was found to be protective. Both C-13T and C2995T were associated with the development of amyloidosis. Examining both polymorphisms may be more useful than examining only one of them for estimating the risk of the development of amyloidosis.

Aged↗

Long-term mortality outcome in patients with reactive amyloidosis associated with rheumatoid arthritis.

It is well established that amyloidosis is a serious clinical complication that can influence the prognosis of patients with rheumatoid arthritis (RA). The purpose of the study was to obtain information on the survival and the hemodialysis (HD) of patients with amyloidosis. Eighty patients (9 men and 71 women) who were diagnosed with amyloidosis by biopsy and definite or classical RA were studied retrospectively. The average duration of RA prior to the diagnosis of amyloidosis was 15.4+/-9.4 years. The average period from the diagnosis of amyloidosis to death was 67.4 months. Forty-nine patients died of the disease (32 cases with HD and 17 cases without HD). Thirty-one patients lived (7 cases with HD and 24 cases without HD). Regarding the survival of these patients, 49 (61.3%) of the 80 patients have died. Survival rate at 28 months was 75%; at 67 months, it was 50%; and at 111 months, it was down to 25%. Mortality rate was 11.9% per year. Survival rate in dialysis at 9.8 months was 75%; at 60.6 months, it dropped to 50%; and at 100.0 months, to 25%. As for patients' survival, high onset age of amyloidosis was the major determining factor for poor survival in these patients (p<0.001). Furthermore, male patients also had poor survival (p=0.07). The long-term results were very encouraging to initiate HD in patients with end-stage renal disease due to reactive amyloidosis associated with RA.

Age of Onset↗

Systemic lupus erythematosus in identical twins: a case report.

In this report we describe the case of identical twin sisters that developed systemic lupus erythematosus (SLE). These patients have in common major histocompatibility complex class I and class II alleles and identical red blood cell antigens, which is a clear indication of monozygotic twins. Both twins showed high titers of anti-dsDNA antibody. However, only one of them manifested signs of lupus psychosis and was positive for the LE test, rheumatoid factor, anti-Scl 70, anti-SSA, and antiribosomal P antibodies. Both sisters lived together; therefore, the environmental factors were considered to be the same. Interestingly, these patients expressed different types of autoantibodies and the manifestation of disease was also quite different. When one of the twins was diagnosed with SLE, we began to closely follow up signs of the disease in the other twin periodically. This enabled us to promptly diagnose the second twin with SLE and she was successfully treated without progression of the disease. It is important to mention that following up the subsequent history of an identical twin diagnosed with SLE allowed early detection of the disease in the other twin.

Journal Article↗

Mixed connective tissue disease associated with antineutrophil cytoplasmic antibodies against proteinase-3 and systemic atherosclerosis: a case report.

A 47-year-old woman presented with facial spasm, swollen fingers and Raynaud's phenomenon due to cerebrovascular disorder and mixed connective tissue disease (MCTD). Although she was positive for both antineutrophil cytoplasmic antibodies against proteinase-3 (PR3-ANCA) and anti-U1 RNP antibodies, she did not meet the American College of Rheumatology classification criteria for Wegener's granulomatosis (WG). Physical and histopathological examinations revealed severe systemic atherosclerosis without any of the traditional risk factors. Elevated levels of malondialdehyde-modified LDL and antioxidized LDL autoantibodies, which are considered to be key factors in the pathogenesis of atherosclerosis, were also detected in the serum of this patient. In this case, systemic atherosclerosis might have been linked to these autoimmune reactions.

Antibodies, Antineutrophil Cytoplasmic↗

A case of Takayasu arteritis complicated with glomerulonephropathy mimicking membranoproliferative glomerulonephritis.

We report on a 65-year-old Japanese woman with Takayasu arteritis who developed severe proteinuria, hypertension, and renal dysfunction. Renal angiography demonstrated moderate irregular narrowing of both renal arteries. Renal biopsy showed glomerulonephropathy mimicking membranoproliferative glomerulonephritis (MPGN) with glomerular capillary wall thickening ("double contour") accompanied by mesangial cell proliferation and moderate increase of mesangial matrix without deposits of C3. Electron microscopy showed no subendothelial deposit and no circumferential mesangial interposition (CMI), and these findings are different from MPGN. In this report we present a case of Takayasu arteritis associated with glomerulonephropathy mimicking MPGN.

Aged↗

A case of pneumatosis cystoides intestinalis in a patient with polymyositis and interstitial pneumonia.

We report the case of a 49-year-old man who presented with pneumatosis cystoides intestinalis associated with polymyositis and interstitial pneumonia. Three months after the administration of prednisolone and cyclosporine, he noticed mild abdominal distension, and a radiographic examination showed intraperitoneal free gas and intramural gas, suggestive of pneumatosis cystoides intestinalis (PCI). Additional treatment with a combination of doxycycline and high-dose oxygen therapy was effective in relieving the clinical symptoms and reducing the intramural gas.

Journal Article↗

Increase in the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 in saliva from patients with primary Sjögren's syndrome.

BACKGROUND: To investigate the ratio of matrix metalloproteinase (MMP) to tissue inhibitor of metalloproteinase (TIMP) in primary Sjögren's syndrome (PSS), patients and healthy subjects MMP-2, 9 and TIMP-1, 2 levels were measured in saliva. METHODS: Stimulated whole-mixed saliva was collected from 32 patients and 26 healthy subjects. MMP-2, 9 and TIMP-1, 2 levels were measured using enzyme-linked immunosorbent assay (ELISA) and the sandwich enzyme immunoassay (sandwich EIA). Zymography and reverse zymography were used to identify MMPs and TIMPs. RESULTS: MMP-9 (gelatinase-B) level in saliva was significantly increased in the patients. MMP-9 (ng/ml): patients 231.02 +/- 151.77 (mean +/- S.D.), healthy subjects 145.87 +/- 111.65 (p < 0.05). MMP-2 levels were not detected with this system kit in either healthy subjects or patients. The differences in TIMPs were only trends and not statistically significant (p > 0.05). Accordingly, MMP-9/TIMP-1 was greatly increased in the patients (2.60 +/- 1.18) than in the healthy subjects (1.28 +/- 1.11) (p < 0.01). CONCLUSION: This study found that MMP-9/TIMP-1 and MMP-9 levels in the saliva were significantly higher in pSS patients than those in healthy subjects. Our results indicate that the increase in MMP-9/TIMP-1, rather than the increase in MMP-9, in pSS patients' saliva is strongly involved in destruction of glandular and salivary duct tissues.

Enzyme-Linked Immunosorbent Assay↗

Renal outcome and predictors of clinical renal involvement in patients with silent lupus nephritis.

OBJECTIVES: We investigated the development of clinically overt nephritis in patients with silent lupus nephritis in an effort to determine predictors of onset. METHODS: We selected 31 patients with systemic lupus erythematosus (SLE) who were diagnosed as having silent lupus nephritis between 1985 and 1995. Urinalysis, blood cell count, serum creatinine, complement levels, and anti-double-stranded DNA antibody (anti-dsDNA antibody) levels were followed retrospectively for at least 60 months in each patient. RESULTS: During the follow-up period, 8 patients developed clinical renal disease and 23 had no renal impairment. The mean time of overt nephritis onset was 58 months and renal function deteriorated mildly in 3 patients. Although clinical and laboratory findings were not significantly different at SLE onset, patients with overt nephritis showed both persistent elevation of anti-dsDNA antibodies and persistently low levels of serum C3 and CH50 for at least 24 months before the onset of overt nephritis. CONCLUSIONS: Although the renal prognosis was relatively favorable, 25.8% of patients developed overt nephritis during the follow-up period. Elevation of anti-dsDNA antibodies with hypocomplementemia was persisted in these patients, suggesting the utility of these factors as predictors of clinical renal involvement in silent lupus nephritis.

Adolescent↗

Patient with diffuse mesangial and endocapillary proliferative glomerulonephritis with hypocomplementemia and elevated anti-streptolysin O treated with prednisolone, angiotensin-converting enzyme inhibitor, and angiotensin II receptor antagonist.

A 24-year-old woman was admitted to Toyosaka Hospital with proteinuria, hematuria, lymphopenia, hypocomplementemia, positive anti-nuclear antibody (ANA), and elevation of anti-streptolysin O (ASO). Renal biopsy specimen revealed diffuse mesangial and endocapillary glomerulonephritis with crescent formation and duplication of the capillary loop on light microscopic examination. Mild to moderate proliferation of mesangial matrix and cells were observed. On immunofluorescence (IF) examination, deposition of IgG, IgA, IgM, C1q, C3, and C4 to the mesangium and capillary wall were observed. By electron microscopy (EM), mesangial, subendothelial, and subepithelial deposits were recognized. However, microtubular structure in glomerular endothelial cells, fingerprint structures, and circumferential mesangial interposition were not observed by EM. The patient was referred to our hospital, but there was no change in her proteinuria 3 weeks after admission. The elevation of ASO, hypocomplementemia, and endocapillary proliferation suggested acute glomerulonephritis, while lymphocytopenia, positive ANA, the persistent hypocomplementemia, and various deposits detected by IF and EM suggested lupus nephritis; however, she did not fulfill the classification criteria of systemic lupus erythematosus. We started prednisolone (40 mg/day) with the diagnosis of chronic glomerulonephritis revealing diffuse mesangial and endocapillary proliferative glomerulonephritis, but it was not effective for the proteinuria. Quinapril (10 mg/day) and losartan (25 to 50 mg/day) were administered and the proteinuria decreased. It is possible that this use of an angiotensin converting-enzyme inhibitor and an angiotensin II receptor antagonist was effective in reducing the proteinuria in this patient.

Adult↗

Bronchoalveolar lavage fluid cells in mixed connective tissue disease.

OBJECTIVE: Patients with mixed connective tissue disease (MCTD) exhibit clinical features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and polymyositis and dermatomyositis (PM-DM). The objective of this study was to clarify differences in BAL findings and immunophenotypes of BAL fluid (BALF) cells of patients with interstitial lung disease associated with these diseases. METHODOLOGY: We were unable to recruit a sufficient number of SLE patients with lung disease. We compared immunophenotypes of lymphocytes and alveolar macrophages (AM) in BALF of 20 MCTD patients with those of 21 SSc and 27 PM-DM patients and tested the relationships between immunophenotypes and pulmonary function in MCTD. RESULTS: MCTD patients had a significantly higher CD4/CD8 ratio with more CD4 positive lymphocytes than PM-DM patients (P = 0.025). In AM phenotypes, MCTD patients had a significantly lower percentage of CD71 positive AM compared with SSc patients (P = 0.023). DLCO was negatively related to absolute numbers of CD8 positive lymphocytes (R = -0.517, P= 0.033). CONCLUSIONS: CD4 positive lymphocytes in BALF were increased in MCTD compared to PM-DM patients, while CD71 positive AM were decreased in MCTD compared to SSc patients. CD8 positive lymphocytes correlated negatively with DLCO measurements in MCTD patients.

Adult↗

Risk of periodontitis in systemic lupus erythematosus is associated with Fcgamma receptor polymorphisms.

BACKGROUND: Leukocyte Fc receptors for immunoglobulin G (FcgammaR) play a major role in the handling of immune complexes and pathogens in systemic lupus erythematosus (SLE) and periodontitis. Both diseases have been shown to be partly influenced by genetic components including FcgammaR genotype. The aim of this study was therefore to evaluate whether FcgammaR gene polymorphisms are associated with periodontitis risk in SLE patients. METHODS: The study subjects consisted of 42 SLE patients with periodontitis (SLE/P), 18 SLE patients without periodontitis (SLE/H), 42 healthy subjects with periodontitis (H/P), and 42 healthy subjects without periodontitis (H/H), who were all unrelated Japanese non-smokers. Genomic DNA was isolated from peripheral blood, and FcgammaR genotypes for 3 biallelic polymorphisms (FcgammaRIIa-R131/H131, FcgammaRIIIa-158V/158F, FcgammaRIIIb-NA1/NA2) were determined by allele-specific polymerase chain reactions. RESULTS: The SLE/P group was found to have more mild levels of periodontal destruction than the H/P group (P < 0.01). There was a significant difference in the distribution of FcgammaRIIa genotypes between SLE/P and H/H groups (P = 0.004). A significant overrepresentation of the FcgammaRIIa-R131 allele was found in the SLE/P group compared to the H/H group (SLE/P versus H/H: odds ratio [OR] 3.13, 95% confidence interval [CI] 1.46-6.77, P = 0.0013). Furthermore, the prevalence of periodontitis was found to be 70% in SLE patients. The FcgammaRIIa-R131 allele was also found to be overrepresented in the SLE/P group compared to the SLE/H group (SLE/P versus SLE/H: OR 3.40, 95% CI 1.18-10.25, P = 0.011). CONCLUSION: These results show the FcgammaRIIa-R131 allele to be associated with periodontitis risk in SLE patients.

Adolescent↗

A patient with Takayasu's arteritis treated with corticosteroids who developed primary biliary cirrhosis.

A 40-year-old woman with a history of fever and arthralgia since age 17 had received long-term prednisolone (PSL) therapy. She was diagnosed with Takayasu's arteritis in 1980 and given PSL. The symptoms were well controlled until she developed itching in 1998. Laboratory tests showed elevated levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, total cholesterol, and immunoglobulin M (IgM). She tested positive for anti-mitochondria antibody and for both IgG and IgM anti-pyruvate dehydrogenases. Liver biopsy findings were typical of primary biliary cirrhosis (PBC). Our patient's clinical course suggested that an adequate amount of PSL to control Takayasu's arteritis does not necessarily prevent the development of PBC.

Adult↗