Lingual squamous cell carcinoma in an ocelot (Felix pardalis).
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Animals↗
Biomedical subjects
N Hama
Publications and source records attributed to N Hama.
[Interstitial pneumonia].
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Collagen Diseases↗
Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats.
Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) both have diuretic, natriuretic, and hypotensive effects, and both are involved in cardiovascular homeostasis as cardiac hormones. To study the effects of HHE on the natriuretic peptide synthesis system, 170 male Wistar rats were housed in a chamber at the equivalent of the 5500-m altitude level for 1-12 weeks. After 1 week of HHE, pulmonary arterial pressure was significantly raised, and the ratio of left ventricle plus septum over right ventricle of the heart showed a significant decrease (compared with those of ground-level control rats). In both ventricular tissues, the expression of ANP messenger (m)RNA and BNP mRNA increased after exposure to HHE. The amounts of ANP and BNP had decreased significantly in right atrial tissue at 12 weeks of HHE (compared with those of the controls), whereas in ventricular tissues at the same time point, both levels had increased significantly. In in situ hybridization and immunohistochemical studies, the staining of the mRNAs for ANP and BNP and of ANP and BNP themselves was more intense in both ventricular tissues after exposure to HHE than before (i.e., in the controls). The results suggest that, in response to HHE, the changes in ventricular synthesis are similar for ANP and BNP. These changes may play a role in modulating pulmonary hypertension in HHE. However, under our conditions, pulmonary hypertension increased progressively throughout the HHE period.
Altitude Sickness↗
[Minocycline for the treatment of bronchiolitis obliterans associated with rheumatoid arthritis].
We discribe a rare case of rheumatoid arthritis (RA) complicated with bronchiolitis obliterans that was successfully treated with minocycline. Sixty four-year old woman with a four-years history of RA was admitted to the hospital because of dyspnea on exertion and polyarthritis. Pulmonary function test revealed marked decrease in V25 (0.10 l/s: 6.9%) and MMFR (12.6%). High resolution CT of the lung showed scattered centri-lobular micronodules in both lung fields, mucoid impaction, and hyperinflation. These findings indicated the presence of bronchiolitis obliterans. After 3 months of the treatment with minocycline, the patient showed a significant improvement of both arthritis and pulmonary function. Chest CT findings also improved after 1 year. The present case suggests that minocycline is effective for the treatment of bronchiolitis obliterans seen in patients with RA.
Anti-Bacterial Agents↗
Expression of C-type natriuretic peptide during development of rat lung.
C-type natriuretic peptide (CNP), recently found to be secreted from vascular endothelial cells, is now viewed as a novel endothelium-derived relaxing peptide. However, the distribution and expression of CNP during cardiopulmonary development is unclear. To follow changes in the expression of CNP during lung development, we examined rat embryos and neonates using Northern blot analysis and in situ hybridization for CNP mRNA and radioimmunoassay and immunohistochemistry for CNP protein. A substantial expression of CNP mRNA was first detected on postnatal day 2, and it thereafter remained fairly steady. The level of CNP protein also increased rapidly after postnatal day 1, reaching a settled level on postnatal day 4. CNP protein and mRNA were detected in the endothelium and smooth muscle cells of blood vessels and in bronchial airway and alveolar epithelia. Immunoreactivity for CNP protein in the endothelium of blood vessels increased to an intense level after the saccular stage. These results suggest that the changes in CNP levels may be related to the occurrence of pulmonary vasodilation after birth.
Animals↗
[Synthetic glucocorticoid in the treatment of connective tissue diseases].
Synthetic glucocorticoids are the most potent anti-inflammatory and immunosuppressive drugs, which have been used for almost 50 years as a core drug for the treatment of connective tissue diseases. The mechanism of action of glucocorticoids as anti-inflammatory or immunosuppressive drug is considered as the repression of inflammatory cytokines, receptors of cytokines, and adhesion molecules. When 60 mg of prednisolone is administered in 3 divided doses, the plasma concentrations are around 20-30 micrograms/dl during the day time, in which condition around 90% of GC receptors are occupied. However, the concentration will decrease almost to 0 microgram/dl in the next early morning. In case of methyl prednisolone pulse therapy, about 40 micrograms/dl of the steroid is present in the next morning. These kinetics are important when we consider the glucocorticoid therapy. In the treatment of connective tissue diseases, the combination of the steroid therapy with the immunosuppressive therapy should always be considered. In diffuse proliferative lupus nephritis, glucocorticoid dosage, started at high level to suppress the clinical activity of SLE, decrease rather rapidly while cytotoxic drugs are administered at least for 2 years. In the treatment of systemic sclerosis, normotensive scleroderma kidney is treated with moderate dose of glucocorticoid and cytotoxic drugs. It is our clinical impression that low dose glucocorticoid is quite effective in the treatment of rheumatoid arthritis. However, low dose glucocorticoid therapy is effective for the patient's sense of well-being, but is scarsely effective for the articular symptoms itself and shows intense rebound phenomenon when glucocorticoid is withdrawn.
Connective Tissue Diseases↗
Effects of intravenously administered C-type natriuretic peptide in humans: comparison with atrial natriuretic peptide.
We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells and suggested that CNP might be a local regulator of vascular tone and growth. To evaluate the biological actions of CNP as compared with human atrial natriuretic peptide (hANP), we intravenously administered synthetic CNP (0.43 nmol/kg) and alpha-hANP (0.43 and 0.043 nmol/kg) to healthy humans. The experiments were done on different days in the same five healthy volunteers (31+/-1 yr old). CNP injection caused a transient but significant decrease in both systolic and diastolic blood pressure (-4.3+/-1.3, -4.1+/-1.0 mmHg) with a significant increase in heart rate (+7.6+/-2.6 bpm), and exerted significant diuretic and natriuretic activities (+130+/-80%, +160+/-100% over the basal level). These effects of CNP (0.43 nmol/kg) were comparable to, or less than, those of alpha-hANP (0.043 nmol/kg). CNP injection also significantly suppressed aldosterone secretion (22% reduction as compared with the basal level). Our results demonstrate that intravenously-administered CNP acts as a natriuretic peptide with less potency than ANP.
Adult↗
[A case of systemic lupus erythematosus associated with spinal epidural hematoma].
A 47 year-old Japanese female who showed transverse myelopathy (TM) due to spinal epidural hematoma diagnosed by MRI in the course of systemic lupus erythematosus (SLE) was reported. She was admitted to Keio University Hospital due to paraplegia, anesthesia of lower extremity, urinary disturbance. Neurological examination revealed transverse disturbance of Th 10. Lumbar spinal cord MRI showed irregular mass that located at epidural region of 9th-11th thoracic vertebrae. When the laminectomy of 9th-11th thoracic vertebrae was performed, hematoma (4.5 cm x 1.5 cm in size) was confirmed and removed completely. Post operative condition was stable and symptoms had been improving gradually. It has been reported that TM associated with SLE was closely related to myelitis. In this case, epidural hematoma was a major cause of TM and MRI was very useful for her diagnosis and treatment. This is the rare case of SLE associated with spinal epidural hematoma and was thought as a important case to consider the cause of neurological complication of SLE.
Female↗
[The efficacy of combination therapy with prednisolone (PSL) and methotrexate (MTX) on radiographic progression in patients with rheumatoid arthritis (RA)].
A case-controlled study was performed, based on early active RA patients treated with MTX; Prednisolone (PSL) was also given in sixteen patients (PSL + MTX group) and each of them was matched for age and sex with a control who have never received PSL (MTX group). No significant differences in radiographic progression were found between the 2 groups. Analysis of radiographic parameters showed that CRP, erythrocyte sedimentation rate, and titers of serum rheumatoid factors after 6 months treatment and their integral amounts during cource were significantly high in the patients with marked radiographic progression. There was no relationship between radiographic progression and treatment with PSL. These results suggested that the indication of PSL therapy for RA is limited for patients with the poor decrease in the level of CRP, erythrocyte sedimentation rate, and rheumatoid factor by MTX treatment.
Anti-Inflammatory Agents↗
Clinical characteristics related to methotrexate-induced pancytopenia.
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Adult↗
Advanced gastric carcinoma in a de Brazza's guenon (Cercopithecus neglectus).
A necropsy case of advanced gastric carcinoma in a 20-year-old female de Brazza's guenon (Cercopithecus neglectus) was studied, Grossly, an excavated carcinoma mass, 60 x 55 x 35 mm in size, was located in the cardiac region of the stomach. Multiple disseminated nodules had implanted on the diaphragm and omentum. The tumor consisted of intestinal-type adenocarcinoma cells and showed infiltrative growth beyond the serosa. The morphologic features of this tumor closely resembled those of advanced gastric carcinomas in human patients.
Adenocarcinoma↗
[An adult case of dermatomyositis complicated with cecum perforation and panniculitis].
The case of dermatomyositis complicated with cecum perforation and panniculitis occurred in a 62-year-old woman was reported. She was admitted to Keio University Hospital with a history of proximal muscular weakness, and dysphagia. Physical examination showed erythema over the face and shoulder. Serum level of muscle enzymes was remarkably increased. The diagnosis of dermatomyositis was made based on proximal muscular weakness, elevated serum level of muscle enzymes and myogenic change of electromyocardiogram. The treatment with 60 mg/day of prednisolone was started, and was a good response. However, 7 months later the disease became active again when the amount of prednisolone was reduced to 13 mg/day. Subsequently she complained of abdominal pain on the right lower quadrant. The surgical findings included peritonitis due to the perforation of the cecum and multiple ulcers of the cecum. After operation, azathioprine was added. Four years and 9 months later, she noticed skin erythema with ulceration and subcutaneous nodule. Skin biopsy indicated the findings of the panniculitis with membrano-cystic lesion. It was thought that both cecum perforation and panniculitis were caused by angiopathy which was often seen in childhood dermatomyositis.
Cecal Diseases↗
Coexistence of serum anti-DNA topoisomerase I and anti-Sm antibodies: report of 3 cases.
We describe 3 Japanese patients having both serum anti-DNA topoisomerase I and anti-Sm antibodies. All 3 patients had typical features of systemic lupus erythematosus, such as glomerulonephritis, in addition to skin thickening and systemic sclerosis related organ involvement, including pulmonary interstitial fibrosis and renal crisis. This is the first report of the coexistence of these 2 disease specific autoantibodies.
Adolescent↗
[Toxicity of low-dose methotrexate in rheumatoid arthritis--clinical characteristics in patients with MTX-induced pancytopenia and interstitial pneumonitis].
Pancytopenia and interstitial pneumonitis are one of the most serious and unpredictable adverse effects of low dose, pulse methotrexate (MTX) in treating rheumatoid arthritis (RA). It is important to investigate the historical, clinical or immunologic features associated with the development of such toxicity, in order to use MTX more appropriately. Two hundred eighty four patients (female 230 male 54) with rheumatoid arthritis had been treated with pulse weekly oral MTX with a mean follow-up of 33.2 months. Adverse effects which required the discontinuation of MTX occurred in 47 patients (16.5%). Gastrointestinal toxicity occurred most frequently (14 patients) and liver dysfunction occurred in 9 patients. Four patients (1.4%) developed pancytopenia, and six patients (2.1%) developed interstitial pneumonitis. All patients who developed pancytopenia were old female with long history of active, deforming rheumatoid arthritis, The cumulative dose of MTX ranged from 15 mg to 760 mg at the time pancytopenia developed. Impaired renal function, hypoalbuminemia, and multiple medication were observed, and antinuclear antibodies were positive in most patients. It should be noted that severe stomatitis preceded or accompanied with pancytopenia in all patients. Blood counts returned to the normal level in 7 to 14 days. All patients who developed interstitial pneumonitis were old female. The cumulative dose ranged from 65 mg to 580 mg. Pre-existance of lung diseases, history of adverse effects of other DMARDs, the presence of Raynaud's phenomenon, and antinuclear antibodies appeared to be risk factors for interstitial pneumonitis. All patients recovered with high dose of corticosteroid and mechanical ventilation. Such clinical characteristics that are associated with MTX-induced pancytopenia or interstitial pneumonitis should be reminded in the treatment of rheumatoid arthritis with MTX.
Aged↗
Clinical characteristics of patients with rheumatoid arthritis and methotrexate induced pneumonitis.
OBJECTIVE: To determine the clinical features of methotrexate (MTX) pneumonitis in patients treated for rheumatoid arthritis (RA). METHODS: The medical records of 284 patients with RA who had been treated with oral MTX (mean followup 33.2 mo) were reviewed retrospectively. RESULTS: MTX induced interstitial pneumonitis developed in 6 patients (2.1%). The affected patients were significantly older than those without MTX pneumonitis (67.3 +/- 9.8 vs 52.4 +/- 12.6 yrs, respectively; p < 0.005). The cumulative MTX dose ranged from 65 to 580 mg at the time pneumonitis developed. Five of the patients (83%) had preexisting interstitial abnormalities, while only 29 of the 278 patients without MTX pneumonitis (10%) had such abnormalities (p < 0.001). The frequency of adverse effects due to previous treatment with disease modifying antirheumatic drugs (DMARD) was 66.7% in MTX pneumonitis patients and 14.3% in the other 278 patients (p < 0.01). CONCLUSION: Advanced age, preexisting interstitial abnormalities, and previous adverse reactions to DMARD may be associated with MTX pneumonitis. Patients with these characteristics require careful monitoring during MTX therapy.
Adult↗
Glucocorticoids modulate CD28 mediated pathways for interleukin 2 production in human T cells: evidence for posttranscriptional regulation.
In T cells stimulated through the T cell receptor (TCR), both cyclosporine (CsA) and glucocorticoids (GC) inhibit the transcription of the IL-2 gene. In these cells costimulation via the CD28 cell surface molecule further increases the transcription of IL-2 and stabilizes its mRNA, resulting in a 20-30 fold induction in IL-2 production. This pathway is relatively resistant to the inhibitory effect of CsA. In this study, we asked whether GC interfere with CD28-mediated costimulatory signals for T cell activation. Primary human T cells or Jurkat T cells were stimulated with anti-CD28 and phorbol myristate acetate (PMA) in the presence of dexamethasone (Dex, 10(-10)-10(-5) M). Dex inhibited both the mRNA for IL-2 and IL-2 production in a dose-dependent fashion (minimum effective dose 10(-9) M). In similar experiments employing anti-CD3 mAb and PMA, a 7-20 fold higher concentration of Dex was required to obtain comparable inhibition. To determine if transcriptional modulation is occurring, Jurkat T cells were transfected with a plasmid containing the IL-2 promoter linked to the chloramphenicol acetyl transferase reporter gene. Following stimulation with ionomycin and PMA, high doses (10(-6) M) of Dex inhibited the activity of the IL-2 promoter (approximately 50% inhibition). However, in the presence of anti-CD28 mAb, this promoter became resistant to Dex (< or = 10% inhibition). These results suggest that GC inhibit accessory pathways for IL-2 production via CD28 by predominantly posttranscriptional mechanisms. Inhibition of the CD28 pathway may be an important mechanism for the T cell directed immunosuppressive effects of low-to-moderate doses of GC.
Antibodies↗
Signal requirements for interleukin 4 promoter activation in human T cells.
We have studied the signal requirements for human IL-4 promoter activation in Jurkat T cells by the use of DNA transfection assays with vectors carrying the IL-4 promoter linked to a reporter gene. Stimulation with calcium (Ca2+) ionophores (ionomycin), but not with phorbol esters (phorbol myristate acetate, PMA) or cyclic AMP elevating agents (prostaglandin E2, PGE2), induced the transcriptional activity of the IL-4 promoter by approximately 3-fold. Costimulation with ionomycin and PGE2 resulted in the same level of IL-4 promoter activity as the stimulation with ionomycin alone. In contrast, costimulation with ionomycin and PMA decreased the activity of the IL-4 promoter by approximately 40% compared to stimulation with ionomycin alone. Induction of Il-4 promoter by ionomycin was partially inhibited (approximately 50% inhibition) in the presence of as high as 2 microgram/ml cyclosporin A (CsA), an inhibitor of the Ca+/calmodulin-dependent phosphatase calcineurin. Under the same conditions, only 0.1 microgram/ml of CsA inhibited by >95% the transactivation of the IL-2 promoter in response to ionomycin and PMA. Transfection of a deletion mutant of the calcineurin catalytic subunit (delta CaM-AI) known to have Ca2+-independent, constitutive phosphatase activity increased IL-4 promoter activity by approximately 14-fold. Stimulation with ionomycin of cells transfected with low doses of delta CaM-AI, further induced IL-4 promoter activity by approximately 2-fold. These results identify the Ca2+-signaling system as a key component of the signal transduction pathway leading to IL-4 promoter activation in Jurkat T cells and suggest a major role of calcineurin in its regulation.
Calcineurin↗
Regulation of endothelial production of C-type natriuretic peptide in coculture with vascular smooth muscle cells. Role of the vascular natriuretic peptide system in vascular growth inhibition.
Recently, we have demonstrated that C-type natriuretic peptide (CNP) is produced in vascular endothelial cells (ECs). In the present study, we investigated the interaction of ECs and vascular smooth muscle cells (SMCs) for endothelial production of CNP and its action on vascular growth, using the EC/SMC coculture system. The concentration of CNP-like immunoreactivity in the medium was increased 60-fold within 48 hours in the EC/SMC coculture with direct contact compared with that in EC alone. Northern blot analysis revealed the augmented expression of CNP mRNA in the EC/SMC coculture. The accumulation of intracellular cGMP in the coculture was concomitantly increased, and this response was blocked by anti-CNP monoclonal antibody and HS-142-1, a nonpeptide atrial natriuretic peptide receptor antagonist. The concentration of biologically active transforming growth factor-beta (TGF-beta) in the culture medium of the coculture with direct contact of ECs and SMCs was elevated to the level to stimulate endothelial production of CNP. Actually, the neutralizing antibody against TGF-beta abrogated the cGMP accumulation in the coculture. These results show that endothelial production of CNP in the EC/SMC coculture is at least in part regulated by TGF-beta. Furthermore, the conditioned medium from ECs stimulated by TGF-beta was demonstrated to have a growth-inhibitory effect on SMCs, which was abolished by anti-CNP monoclonal antibody and HS-142-1. The treatment with anti-CNP monoclonal antibody and HS-142-1 also significantly increased the cell number of the EC/SMC coculture. The present study reveals the pathophysiological significance of endothelial CNP as a paracrine/autocrine vascular regulator for vascular growth in the interaction of ECs and SMCs.
Animals↗