Effects of glucocorticoids on rat thymus and apoptosis.
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Animals↗
Biomedical subjects
M Fujimoto
Publications and source records attributed to M Fujimoto.
The effect of deoxyspergualin on rat thymocytes and thymic epithelial cells.
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Animals↗
Serum levels of tissue inhibitor of metalloproteinases 2 in patients with systemic sclerosis.
BACKGROUND: The serum tissue inhibitor of metalloproteinases 1 (TIMP-1) level was reported to be a useful indicator of disease activity, especially of lung fibrosis in patients with systemic sclerosis. TIMP-2 is also an important inhibitor of matrix metalloproteinases (MMPs), such as interstitial collagenase, gelatinase, and stromelysin, which control the metabolism of the extracellular matrix. However, serum levels of TIMP-2 in patients with systemic sclerosis (SSc) have not been investigated. OBJECTIVE: We sought to determine the clinical significance of serum levels of TIMP-2 and MMP-2 in patients with SSc. METHODS: Serum samples were obtained from 128 patients with SSc (68 with limited cutaneous SSc and 60 with diffuse cutaneous SSc). Twenty-seven serum samples from healthy age- and sex-matched individuals were also examined as controls. The TIMP-2 and MMP-2 levels were determined by means of sandwich enzyme-linked immunosorbent assays. RESULTS: The serum TIMP-2 levels were elevated in 29 (22.7%) of the 128 patients with SSc and were significantly higher than those of the healthy control subjects. The serum TIMP-2 levels were significantly correlated with the extent of skin sclerosis in the patients with SSc. The incidence of decreased percentage of the diffusing capacity of lung for carbon monoxide (DLCO ) and that of an elevated erythrocyte sedimentation rate were significantly greater in the patients with elevated TIMP-2 levels compared with the patients with normal TIMP-2 levels (P <.05). When these patients were classified into 2 groups by disease activity, TIMP-2 levels were significantly more elevated in the high active group than in those low active group (P <.001). The serum MMP-2 levels of the patients with SSc were not significantly higher than those of the healthy control subjects. CONCLUSION: These findings suggest that the serum TIMP-2 level is a useful marker of the extent of skin sclerosis and disease activity in patients with SSc. The balance of TIMP-2 and MMP-2 may play an important role in patients with SSc. Furthermore, TIMP-2 may be thought to contribute to the development of disease in patients with SSc.
Adolescent↗
CD19 regulates Src family protein tyrosine kinase activation in B lymphocytes through processive amplification.
CD19 regulates constitutive and antigen receptor-induced signaling thresholds in B lymphocytes through its unique cytoplasmic domain. Herein, we demonstrate a novel molecular mechanism where interactions between CD19 and Lyn amplify basal and antigen receptor-induced Src family kinase activation. Lyn expression was required for CD19 tyrosine phosphorylation in primary B cells. Experiments with purified proteins demonstrated that CD19-Y513 was Lyn's initial phosphorylation and binding site. This led to processive phosphorylation of CD19-Y482, which recruited a second Lyn molecule, allowing for transphosphorylation and amplification of Lyn activation. In vivo, CD19 deficiency impaired, and CD19 overexpression enhanced, Lyn kinase activity. Thus, CD19 functions as a specialized adapter protein for the amplification of Src family kinases that is crucial for intrinsic and antigen receptor-induced signal transduction.
Amino Acid Sequence↗
Characterization of autoantibodies to endothelial cells in systemic sclerosis (SSc): association with pulmonary fibrosis.
To determine the prevalence and the characterization of antibodies to endothelial cells in patients with SSc, serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 20 healthy control subjects were examined by ELISA using cultured human umbilical vein endothelial cells (HUVEC), indirect immunofluorescence analysis (IIF), and immunoblotting using cytoplasmic extract of HUVEC. IgG and/or IgM isotype anti-endothelial cell antibodies (AECA) were demonstrated by ELISA in 43 of 80 patients with SSc (54%), in 15 of 20 patients with SLE (75%), and in none of 20 healthy control subjects. Immunofluorescence analysis on HUVEC substrate showed homogeneous cytoplasmic staining. Immunoblotting demonstrated that these patients had antibodies directed to one or several antigens of approximately 60, 90, 110 and 140 kD, and the most common responses were to the 90-kD antigen. By the immunofluorescence method using HUVEC, affinity-purified anti-90-kD antibodies showed identical cytoplasmic staining to that produced by sera positive for AECA. Furthermore, AECA were closely correlated with pulmonary fibrosis in patients with SSc. These findings suggest that patients with SSc have abnormal antibodies to endothelial cell antigens, and support the hypothesis that endothelial dysfunction is involved in the development of this disease.
Adult↗
Penetration by a giant gastric ulcer induced by a nonsteroidal anti-inflammatory drug.
A patient presented with penetration by a giant gastric ulcer resulting from treatment with a nonsteroidal anti-inflammatory drug. A test for Helicobacter pylori proved negative. Treatment with a combination of an inhibitor of gastric acid secretion and prostaglandin substitution therapy with misoprostol resulted in closure of the perforation and cicatrization of the gastric ulcer without the need for laparotomy.
Anti-Inflammatory Agents, Non-Steroidal↗
Eradication of metastatic angiosarcoma of the lower extremity. Case report.
A 47-year-old man with an angiosarcoma of the right lower extremity was cured with mainly surgery and radiotherapy despite an inguinal metastasis. Histologically, the amputation stump of the metastatic tumour showed invasion by tumour. Radiotherapy, chemotherapy, and treatment with interleukin-2 was added. Ten years later he has had no recurrence.
Hemangiosarcoma↗
A short region containing an AP-1 binding site is essential for transforming growth factor-beta-induced c-jun gene expression in osteoblastic cells.
Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory peptide that elicits different responses in different cell types. Much remains unknown about the pathway of intracellular TGF-beta signal transduction, but TGF-beta is known to induce expression of several genes by way of the transcription factor AP-1. We studied the mechanism that mediates TGF-beta-induced gene expression of c-jun, a component of AP-1, in MC3T3-E1 osteoblastic cells. To map in detail the corresponding responsive elements in the rat c-jun promoter, we generated a series of 5' deletion promoter/luciferase reporter gene constructs. Transient cell transfection assays identified the region located between positions -79 and -59 as being critical for the TGF-beta response and for the basal activity of the promoter. Gel mobility shift assays indicated specific binding of nuclear proteins to this 21-bp region of the c-jun promoter containing an AP-1 binding site. These results show that the AP-1-dependent mechanism is involved in TGF-beta-induced increase of c-jun induction, suggesting positive autoregulation of AP-1.
3T3 Cells↗
A long-term follow-up study of cervical lesions in rheumatoid arthritis.
To determine the natural history of cervical lesions in rheumatoid arthritis, 161 patients who had been followed for a minimum of 5 years were enrolled in this study. The average follow-up period was 10.2 years (range, 5 to 20 years). The severity of the rheumatoid arthritis was classified into three types based on the multiplicity of peripheral joint rheumatoid involvement: a least erosive subset, a more erosive subset, and a mutilating disease subset. Ninety-two patients (57%) had upper cervical involvement, which progressed in the order of anterior atlantoaxial subluxation, anterior atlantoaxial subluxation combined with vertical subluxation, and vertical subluxation alone. Subaxial subluxation was found in 18 patients (11%). In 17 of these 18 patients, upper cervical lesions were also noted. The incidence of cervical involvement in each disease subset was 39% in the least erosive group, 83% in the more erosive group, and 100% in the mutilating disease group. Fifty percent of the patients with cervical involvement had neck pain, and the remaining patients were asymptomatic. Neural involvement occurred in 10 patients. In 7 of these 10 patients, vertical subluxation of the atlas was responsible for the neural deficit. Six patients required surgical intervention because of progressive myelopathy.
Adolescent↗
False localization of rupture site in patients with multiple cerebral aneurysms and subarachnoid hemorrhage.
OBJECTIVE: Patients with subarachnoid hemorrhage and multiple intracranial aneurysms present a unique challenge to the neurosurgeon. Unless all aneurysms can be clipped through a single craniotomy, the surgeon must accurately determine which aneurysm has ruptured. Misjudgment may result in disastrous postoperative rebleeding from the untreated but true ruptured lesion. We assessed the risk of false localization of the rupture site and subsequent rebleeding and documented the problems in predicting the true rupture site when patients have multiple intracranial aneurysms. METHOD: We reviewed the records of a consecutive series of 93 patients treated over a period of 12 years who presented with their first subarachnoid hemorrhage and who had multiple intracranial aneurysms. The rupture site was determined on the basis of computed tomographic and angiographic findings, and the supposed ruptured aneurysm was clipped within 2 days of hemorrhage in each patient. Additional aneurysms that could not be accessed in the same surgical session were operated on at a later stage. All patients' records were reviewed, and all computed tomographic scans and angiograms, including repeat studies performed in some patients, were retrospectively reevaluated by the authors, who had no knowledge of the patients' clinical information. RESULTS: The location of the aneurysm that ruptured was verified at the time of surgery or during the autopsy in 76 patients (82%). The aneurysm that ruptured was the one predicted as ruptured by the surgeon before surgery in 69 patients (91%) and in retrospect in 72 patients (95%). Five of the 6 patients in whom the ruptured aneurysm was not correctly identified were thought to have only a single aneurysm. Four patients rebled after surgery, and 2 patients died as a result of the rebleeding. CONCLUSION: In the reported series, the most common cause of rebleeding soon after aneurysm surgery was failure to obliterate the ruptured aneurysm, usually because it was missed on the initial angiogram. The results support not only meticulous radiological investigation of all intracranial arteries before surgery but also thorough surgical inspection of the target aneurysm in all cases of subarachnoid hemorrhage even after one candidate lesion has been discovered.
Adult↗
Recurrent craniopharyngioma with nasopharyngeal extension.
We report the case of a 10-year-old boy having a recurrent craniopharyngioma with nasopharyngeal extension during a course of growth hormone therapy, in whom the nasopharyngeal craniopharyngioma was totally resected despite its extensive growth by using a transbasal approach. There has been no evidence of recurrence during 6 years of follow-up. A literature review was made with respect to nasopharyngeal extension of craniopharyngiomas, and the efficacy of the transbasal approach for those tumors is discussed.
Child↗
Complex systems in technology and policy: telemedicine and telecare in Japan.
We have examined aspects of the development of telemedicine and telecare in Japan. Despite Japan's reputation as an integrated and technocratic country, the diffusion of telemedicine has fallen below expectations, notwithstanding the urgent need to solve the problems of an ageing society. There has been a fragmentation of objectives and perspectives within the corporate (manufacturing) sector and within the policy sector of central and local government. There has also been a broader fragmentation between manufacturers, government and users (doctors and hospitals). As a result, the success or failure of individual projects appears to depend not on the quality of the technology, and often not on the evident importance of the social need, but on the overall coherence of a complex socio-technical system.
Financing, Government↗
CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification.
The fate of B lymphocytes is dependent on intrinsic and B cell antigen receptor (BCR)-induced signals. These signals are interpreted and modified by response regulators such as CD19 that govern mature B cell activation. The current understanding of how CD19 governs B lymphocyte signaling is outlined in this review. Primarily, CD19 establishes a novel Src-family kinase amplification loop that regulates basal signal transduction thresholds in resting B cells. Moreover, CD19 amplifies Src-family kinase activation following BCR ligation. CD19 amplification of Lyn activity leads to processive phosphorylation of CD19 and downstream substrates including CD22. Phosphorylated CD19 recruits other effector molecules including Vav, Grb2, phosphoinositide 3-kinase, phospholipase Cgamma2, and c-Abl, which may contribute to CD19 regulation of B cell function. CD19/Lyn complex formation also regulates phosphorylation of CD22 and FcgammaRIIB, which inhibit B cell signal transduction through the recruitment of the SHPI and SHIP phosphatases. These observations provide insight into how CD19 governs the molecular ordering and intensity of signals transduced in B cells, and how perturbations in CD19 expression or signaling function may contribute to autoimmunity.
Animals↗
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and adrenal insufficiency induced by rathke's cleft cyst: a case report.
We report a case of a seventy-year-old woman with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and adrenal insufficiency induced by Rathke's cleft cyst. She experienced nausea, vomiting, diarrhea, and headache and disturbance of consciousness induced by hyponatremia at a serum sodium level of 100 mEq/l. In spite of severe hyponatremia, urinary sodium excretion was not suppressed and serum osmolality (270 mOsm/kg) was lower than urine osmolality (304 mOsm/kg), and arginine vasopressin (AVP) remained within normal range. SIADH was diagnosed because she was free from other diseases known to cause hyponatremia such as dehydration, cardiac dysfunction, liver dysfunction, renal dysfunction, hypothyroidism, and adrenal insufficiency. Cranial computed tomographic (CT) scan and cranial magnetic resonance (MR) imaging showed a cystic lesion of approximately 2 cm in diameter in the pituitary gland. These images suggested that the cystic lesion was a Rathke's cleft cyst, which was the cause of SIADH. Water restriction therapy normalized her serum sodium concentration and improved her symptoms. After one year, she suffered from general fatigue, appetite loss, fever, and body weight loss (5 kg/2 months). She had neither hypotension nor hypoglycemia, but her serum sodium level was low and serum cortisol, ACTH, and urine free cortisol were very low. Therefore, secondary adrenal insufficiency was suspected and diagnosed by stimulation tests. After start of hydrocortisone replacement therapy (10 mg/day), her symptoms disappeared. In conclusion, Rathke's cleft cyst should be kept in mind as a potential cause in a patient with SIADH, hypopituitarism, and/or adrenal insufficiency.
Adrenal Insufficiency↗
CD19 and CD22 regulate a B lymphocyte signal transduction pathway that contributes to autoimmunity.
The fate of B lymphocytes is dependent on intrinsic and B cell antigen receptor (BCR)-induced signals. These signals are modified and interpreted by other cell-surface molecules such as CD19 and CD22 that govern mature B cell activation. This review assesses our current understanding of how CD19 and CD22 regulate B lymphocyte signaling and how alterations in these response-regulators contribute to autoimmunity in mice and humans. We propose that CD19 functions as a specialized adapter protein that regulates B lymphocyte signaling and autoantibody production. Overexpression of CD19 by B cells in systemic sclerosis patients correlates with autoantibody production and transgenic mice that overexpress CD19 produce similar autoantibodies. CD19 establishes a novel Src-family kinase activation loop that regulates basal signal transduction thresholds in resting B cells and amplifies Src-family kinase activation following BCR ligation. Reciprocally, CD22 is a potent regulator of CD19 function. These observations provide insight into how CD19 and CD22 govern the molecular ordering and intensity of signals transduced in B cells that may contribute to autoimmunity.
Animals↗
Structures and comparison of genomic and complementary DNAs of mouse MSSP, a c-Myc binding protein.
Two cDNAs encoding mouse MSSP and Scr3 were cloned. Both proteins, like those in humans, share significant homology of the region near the N-terminus containing the RNA-binding protein, RNP, while little homology exists near the C-terminal region of the proteins. Expression of mouse MSSP and Scr3 in mouse tissues were examined by Northern blot hybridization and both mRNAs were ubiquitously expressed in all the tissues except for testis, where the smaller sizes of MSSP mRNAs, but not Scr3 mRNA, were highly expressed. Then, the genomic DNA of mouse MSSP was cloned. Mouse genomic MSSP gene was comprised of at least 13 exons over the region spanning 60 kb. Furthermore, a chromosome location of human MSSP gene was identified at 2q24 by FISH mapping.
Amino Acid Sequence↗
[Bone marrow transplantation-associated thrombotic microangiopathy manifested by visual disturbance].
In October 1996, a 26-year-old woman was given a diagnosis of acute myeloblastic leukemia, FAB subtype M1. Treatment with combined chemotherapy achieved a complete remission (CR). In May 1997, the patient received an allogenic bone marrow transplant (BMT) from an HLA-identical sibling donor. Cyclosporine (CsA) and short-term methotrexate were given for graft-versus-host disease (GVHD) prophylaxis. Successful engraftment was obtained and signs of acute or chronic GVHD never developed. Five months after BMT, the patient experienced low-grade fever and blurred vision. Retinal examination demonstrated intraretinal hemorrhages, cotton-wool spots, and retinal detachments, which were presumably attributable to multiple thrombosis of retinal microvessels. The patient also exhibited hemolytic anemia with red cell fragmentation, thrombocytopenia, elevated lactate dehydrogenase, and renal impairment, and was thus given a diagnosis of BMT-associated thrombotic microangiopathy (BMT-TM). Discontinuation of CsA and administration of ticlopidine and prednisolone induced successful recovery from BMT-TM. Three months after the onset of BMT-TM, however, the patient experienced generalized clonic-tonic seizures with consciousness loss. Single-photon-emission computed tomography revealed blood-flow disturbances in the brain, suggesting the recurrence of microthrombosis. Accordingly, multiple transfusions of fresh frozen plasma were administered together with dipyridamole and aspirin. The patient gradually recovered and remained asymptomatic through the following 13 months. Currently, early diagnosis of BMT-TM is considered to be difficult. We suggest that careful examination of the ocular base may be useful for the early detection of BMT-TM.
Adult↗
Circulating levels of soluble CD30 are increased in patients with localized scleroderma and correlated with serological and clinical features of the disease.
OBJECTIVE: To determine serum soluble CD30 (sCD30) levels in patients with localized scleroderma. METHODS: Serum soluble CD30 levels were assayed by a sensitive ELISA in 55 patients with localized scleroderma, in 15 with systemic sclerosis (SSc), and in 20 healthy controls. RESULTS: Serum levels of sCD30 were significantly higher in patients with localized scleroderma than in healthy controls. Serum levels of sCD30 were correlated with the number of sclerotic lesions, the number of involved areas, levels of anti-histone antibody IgM, and levels of interleukin 6. sCD30 levels in sera from patients with SSc were also significantly higher than in healthy controls. CONCLUSION: These results suggest possible involvement of Th2 cells in the immunopathogenesis in localized scleroderma, and serum sCD30 levels may be helpful in following the outcome of the disease.
Adolescent↗