-
[show abstract]
[hide abstract]
ABSTRACT: Milk fat globule-EGF factor 8 (MFG-E8) promotes the phagocytosis of apoptotic cells by serving as a bridging molecule between apoptotic cells and phagocytes. Many apoptotic cells are left unengulfed in the germinal centers of the spleen of MFG-E8(-/-) mice, which develop a human systemic lupus erythematosus (SLE)-like autoimmune disease. Here, we analyzed the MFG-E8 gene in human SLE patients, and found in two out of 322 female patients a heterozygous intronic mutation, which caused a cryptic exon from intron 6 to be included in the transcript. The cryptic exon contained a premature termination codon, generating a C-terminally truncated MFG-E8 protein. The mutant MFG-E8 was aberrantly glycosylated and sialylated, but bound to phosphatidylserine and enhanced the phagocytosis of apoptotic cells. When intravenously injected into mice, the mutant MFG-E8 was sustained longer in the blood circulation than wild-type MFG-E8. Repeated administrations of the mutant MFG-E8 protein induced the production of autoantibodies, such as anti-cardiolipin and anti-nuclear antibodies, at a lower dose than that required for the wild-type protein. These results suggested that the intronic mutation in the human MFG-E8 gene can lead to the development of SLE.
European Journal of Immunology 03/2010; 40(6):1778-85. · 5.10 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the response of patients with SS to mizoribine therapy in relation to histological features of minor salivary glands.
Forty patients definitely diagnosed as having SS were treated with mizoribine (150 mg/day). Thirty-four untreated patients matched for age, baseline salivary secretion, etc., served as controls. Salivary secretion volume (measured by the Saxon test) and serum IgG level were measured before and after 24 weeks of treatment. Each histological finding (lymphocytic infiltration, acinar atrophy and intralobular fibrosis) was graded at baseline and the therapeutic responses were compared with the grade at 24 weeks in both the groups.
There was a significant increase of the salivary secretion volume after treatment with mizoribine as compared with the untreated control group. The effect of mizoribine on salivary secretion was more marked in patients having moderate lymphocytic infiltration and moderate or less severe acinar atrophy and intralobular fibrosis at baseline.
Mizoribine was clinically effective in patients with SS whose minor salivary glands had moderate cell infiltration and were free of intralobular fibrosis. The drug was less effective in patients who presented intralobular fibrosis. Histological evaluation of the minor salivary glands may serve to predict the response of SS patients to mizoribine therapy.
Rheumatology (Oxford, England) 09/2009; 48(10):1279-82. · 4.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to investigate the atrophic change of tongue papilla in Sjögren syndrome (SjS) patients and the correlation with characteristic features of the disease.
Atrophic change of tongue papilla, investigated by a digital microscope, was classified from score 0 (normal) to score 6 (severe) and compared among 44 SjS patients, 20 xerostomia patients, and 20 healthy subjects. In SjS patients, correlation of the atrophic score of tongue papilla with characteristic changes in sialometry, sialography, lip biopsy, and serologic tests was also investigated.
The atrophic score of tongue papilla was significantly higher in SjS patients and correlated with the decrease of salivary secretion, the stage on sialography, and the histologic grade of the minor salivary gland.
Atrophic change of tongue papilla is significant in SjS patients and is correlated with the characteristic features of the disease.
Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics 07/2009; 107(6):801-5. · 1.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mouse milk fat globule epidermal growth factor 8 (MFG-E8), which is secreted by a subset of activated macrophages, binds to apoptotic cells by recognizing phosphatidylserine and promotes their engulfment. Many apoptotic cells are left unengulfed in the germinal centers of the spleen in MFG-E8(-/-) mice, and these mice develop an autoimmune disease resembling human systemic lupus erythematosus (hSLE). Here, we report that hMFG-E8 bound to phosphatidylserine and an integrin alpha(v)beta(3) complex. Increasing concentrations of MFG-E8 generated a bell-shaped response curve for the efficiency of phagocytosis. That is, in NIH3T3 and MFG-E8(-/-) thioglycollate-elicited peritoneal macrophages that do not express MFG-E8, hMFG-E8 enhanced engulfment at low concentrations but inhibited it at high concentrations. On the other hand, hMFG-E8 dose-dependently inhibited the engulfment of apoptotic cells by MFG-E8(+/+) thioglycollate-elicited peritoneal macrophages, indicating that an excess of MFG-E8 has an inverse effect on the engulfment of apoptotic cells. To investigate the role of MFG-E8 in human disease, we generated two mAb against MFG-E8 and screened human blood samples for MFG-E8 using an ELISA. We found that some childhood-onset and adult SLE patients carried a significant level of MFG-E8 in their blood samples. These results suggested that the aberrant expression of MFG-E8 is involved in the pathoetiology of some cases of hSLE.
Journal of Leukocyte Biology 06/2008; 83(5):1300-7. · 4.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: As the reason for insufficient control of blood pressure (BP), poor compliance of taking antihypertensive agents is an important issue. In Japan, no prospective study on the compliance of antihypertensive agents has been done. In this study we prospectively investigated the details of the relationship between the compliance of taking antihypertensive agents and living style and situation in hypertensive patients.
We prospectively examined 121 outpatients with essential hypertension treated with antihypertensive agents for 12 months. Using an oral interview based on the questionnaire sheet, the factors about living style and situations which worsen the compliance were assessed. Also we evaluated the relationship of BP control and season, which was compared between patients with poor compliance and those with good compliance.
As for the background of the poor compliance, many factors related to the patients' living style and situation were clarified. On average for 12 months the levels of the compliance and BP showed a significant negative correlation and BP was significantly higher in patients with poor compliance than those with good compliance. However, in the summer season BP did not differ between patients with poor and good compliance,
Many factors regarding the patients' living style and situation were related to poor compliance. The development of strategy that changes these factors is a future task for improving compliance. This study may also imply that unnecessary antihypertensive agents are prescribed in some patients with poor compliance in the summer season. Determination of the suitable prescription by which to attain optimal individual patients' compliance is important in the treatment of hypertensive patients.
Internal Medicine 02/2008; 47(19):1655-61. · 0.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We describe the case of a 61-year-old woman diagnosed with primary Sjögren's syndrome (SS) after an 8-year history of IgA nephropathy and a 3-year history of recurrent purpuric rashes. Her two daughters had previously been diagnosed with other autoimmune diseases. One daughter had Graves' disease and the other had Hashimoto's disease and systemic lupus erythematosus. The diagnosis of SS was made based on dryness of mucous membranes, Shirmer test, and parotid sialography. Thrombocytopenia, high platelet-aggregated IgG (PA-IgG) level, and normal megakaryocytes count in bone marrow suggested that her recurrent purpuric rashes were due to idiopathic thrombocytopenic purpura (ITP). Patients with SS may develop other autoimmune diseases. This case aids understanding of the immune pathogenesis and genetic background of SS.
Japanese Journal of Clinical Immunology 05/2002; 25(2):191-8.
-
[show abstract]
[hide abstract]
ABSTRACT: We report the case of a 57-year-old woman with systemic lupus eryth- ematosus associated with a ruptured sinus of Valsalva aneurysm. The physical examina- tion showed a holosystolic murmur at the left fourth intercostal space. Aortography revealed that the sinus of Valsalva aneurysm had ruptured into the right ventricle. Surgical closure of the ruptured aneurysm was successfully carried out. This aneurysm and its rupture may have been due to endocarditis involving the sinus of Valsalva.
-
[show abstract]
[hide abstract]
ABSTRACT: We treated a case of primary Sjören's syndrome with progressive central nervous systems manifestations. Central nervous system involvement in such patients is difficult to diagnose and rarely described. A 71-year-old man presenting with vertigo and vomiting was admitted to our hospital. Intension tremor developed in the left extremities and gradually spread to the right extremities, while an articulation disorder also appeared. Results of T2-weighted cranial magnetic resonance imaging on admission showed abnormally high intensity areas in the pons, medulla oblongata, and cerebellum, nearly all of which were on the left side. Laboratory findings showed a high level of serum γ-globulin, and were positive antinuclear antibodies, anti-Ro antibodies, and anti-La antibodies, while histological findings of a minor salivary gland biopsy revealed focal sialadenitis with marked lymphocytic infiltration. These serological and histopathological findings confirmed that the patient had primary Sjören's syndrome. The patient underwent pulsed intravenous methylprednisolone therapy, and blepharoptosis, miosis, kinetic tremors improved with the therapy. In addition, the intensities in T2-weighted cranial MR images in the pons and medulla oblongata disappeared, and cerebellar intensity improved. In view of the underlying autoimmune disorder, it seemed likely that the etiology of the CNS symptoms was related to inflammatory brain changes, such as from autoimmune-related vasculitis.
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the incidepce and clinicopathological characteristics of hypouricemia in patients with diabetes mellitus, we studied 473 consecutive hospitalized diabetic patients. The incidence of hypouricemia, defined as a serum urate concentration below 2.0 mg/dl, was 1.9% (9 patients). In this group (2 males, 7 females), there were no patients receiving drugs known to reduce serum urate concentration. Two of the 9 patients had neoplastic disease, while the others suffered from no other disorder known to affect serum urate levels. Four patients exhibited glomerular hyperfiltration. Three of the 9 patients were studied in more detail by renal biopsy, and all had mild to moderate glomer- ular diffuse lesions and tubulointerstitial lesions, such as interstitial fibrosis or mononuclear cell infiltration. These findings suggest that the glomerular hyperfiltration which accom- panies diabetic nephropathy and functional abnormality of tubular urate handling due to tubulointerstitial involvement contribute to hypouricemia in diabetic patients.
