Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-one patients with acute schistosomiasis were evaluated clinically and immunologically. Cytokine levels were determined in peripheral blood mononuclear cell (PBMC) supernatants. Levels of total and antigen-specific IgE, tumor necrosis factor (TNF)-alpha, and immune complexes were measured in serum samples. Clinical findings included general symptoms, liver damage, pulmonary involvement, and pericarditis. All patients had eosinophilia. Immune complexes were detected in 55% of the patients (mean+/-SD, 7.8+/-7.6 microg Eq/mL) and were associated with cough, dyspnea, and abnormal chest radiographic findings. Levels (mean +/- SD) of TNF-alpha (1349.3+/-767.6 pg/mL), interleukin (IL)-1 (2683+/-1270 pg/mL), and IL-6 (382 +/- 52.3 pg/mL) were elevated in PBMC. Serum TNF-alpha levels were elevated in 87% of the patients and were associated with abdominal pain. Higher interferon-gamma levels were detected in PBMC of patients with acute disease than in those of patients with chronic schistosomiasis; IL-5 levels were higher in those with chronic disease. Low IL-5 levels were associated with weight loss. Proinflammatory cytokines and immune complexes with low Th2 responses might explain the immunopathogenesis of acute schistosomiasis.
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PMID:Clinical and immunologic evaluation of 31 patients with acute schistosomiasis mansoni. 1175 87

A 42-year-old familial Mediterranean fever (FMF) patient who was treated with cisplatin-based chemotherapy for adenocarcinoma of the lung developed severe and frequent attacks of FMF during treatment. Abdominal pain, arthralgia and fever occurred for a few days following each cisplatin cycle. His FMF worsened, the abdominal pain and fever lasted longer and treatment with colchicine was ineffective. It has been hypothesized that the link between cisplatin treatment and FMF attacks lies in an increased production of serotonin, IL-6, IL-1, IL-8 and TNF-alpha. These inflammatory cytokines have been reported to be overproduced during cisplatin treatment and are known to play an important role in FMF relapse. The oncologist should be made aware of the possibility of disease aggravation in FMF patients during cisplatin-based chemotherapy.
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PMID:Cisplatin treatment triggers familial Mediterranean fever attacks. 1272 67

Thalidomide has several targets and mechanisms of action: a hypnosedative effect, several immunomodulatory properties with an effect on the production of TNF-alpha and the balance between the different lymphocyte subsets and an antiangiogenic action. Thalidomide has been used in several cutaneous inflammatory disorders (e.g., erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus and severe aphtosis), cancers (e.g., relapsed/refractory multiple myeloma, malignant melanoma and systemic signs in cancer) and inflammatory conditions (e.g., Crohn's disease and rheumatoid arthritis). Several side effects are associated with thalidomide. Some are major, such as teratogenicity, peripheral neuropathy and deep vein thrombosis. Somnolence and rash are frequently reported when thalidomide is used at higher doses as an anticarcinogenic agent and can lead to dose reduction or treatment discontinuation depending on severity. Minor side effects include abdominal pain and endocrine disturbances. To prevent the teratogenicity, use of thalidomide is strictly controlled in western countries with close adherence to a birth control programme. Close monitoring for early development of peripheral neuropathy is also recommended.
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PMID:Thalidomide: an old drug with new clinical applications. 1468 Apr 61

Locoregional administration of the streptococcal preparation OK-432 is effective in treating malignant ascites from gastric cancer. In order to enhance the efficacy, we conducted a pilot study of locoregional immunotherapy for malignant ascites using host-oriented doses of OK-432. Moreover, action mechanisms of OK-432 were further explored in view of the T-helper type 1 (Th1)-Th2 concept. Gastric cancer patients with cytologically determined malignant ascites were locoregionally administered with OK-432. The dose of OK-432 was selected according to the delayed-type hypersensitivity (DTH) reaction levels to OK-432. Cytokine production profiles of ascites cells were determined using whole ascites assay by stimulation with OK-432. IL-10 mRNA expression was analyzed using RT-PCR. It was found that a positive clinical response was observed in 37 of the 51 (73%) patients with the DTH-oriented approach, showing a significantly higher efficacy than traditional dosage methods using empirical doses (31/58, 53%) (p=0.0487). The DTH-oriented administration of OK-432 produced adverse effects such as fever elevation (p<0.0001) and abdominal pain (p=0.0013) to a significantly lesser extent compared with the traditional treatment. Analysis of the action mechanism of OK-432 revealed that the DTH reaction in responders (19+/-6 mm) was stronger than that in non-responders (6+/-4 mm) (p<0.0001). Tumor necrosis factor (TNF)-alpha production of ascites cells was also higher in responders (3943+/-1247 pg/ml) than in non-responders (1217+/-939 pg/ml) (p=0.0002). There was a significant positive correlation (p=0.0085) between the levels of DTH reaction and TNF-alpha production of ascites cells, but not of blood cells. Responders appeared to polarize on the Th1 axis when clinical responses were plotted on Th1-Th2 dimensions according to the cytokine production profiles of TNF-alpha, IFN-gamma, IL-4 and IL-6 of ascites cells. In vitro culture with IL-2 of ascites cells after OK-432 administration demonstrated an almost clonal expansion of CD4+ lymphocytes, which produced TNF-alpha and IFN-gamma, but did not produce IL-4 or IL-6. IL-10 mRNA expression was detectable in ascites cells from non-responders before treatment. These results suggest that the DTH-oriented locoregional administration of OK-432 may be both effective and less toxic in treating malignant ascites from gastric cancer, showing a possibility of the tailored immunotherapy for malignant ascites. Th1 dysfunction exists in the microenvironment of malignant ascites from gastric cancer, in which IL-10 may, in part, play a role. The up-regulation of Th1 responses by OK-432 may result in positive clinical responses. The DTH reaction to OK-432 may be a useful tool not only for predicting clinical response but also for selecting the optimal dose of OK-432.
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PMID:Locoregional immunotherapy of malignant ascites from gastric cancer using DTH-oriented doses of the streptococcal preparation OK-432: Treatment of Th1 dysfunction in the ascites microenvironment. 1501 Aug 36

An adolescent boy had had recurrent episodes of fever, abdominal pain, and arthralgias since the age of 7 years. Progressive renal failure due to renal amyloidosis developed, leading to renal transplant at the age of 14.5 years. Five years later, he developed AA amyloidosis in the transplant as well as the thyroid gland. His father had had similar symptoms including systemic amyloidosis since the age of 6 years. DNA sequence analysis revealed a heterozygous mutation in the TNFRSF1A (TNFa-receptor 1) gene (T50M) in both father and son causing tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Previous phenotype/genotype analyses have proposed that this mutation is usually not associated with the occurrence of amyloidosis. This difference in the clinical course in different families may indicate a strong influence of modifier genes. Treatment with a TNFRSF1B fusion protein TNF antagonist (etanercept) favorably influenced the disease course.
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PMID:Two familial cases with tumor necrosis factor receptor-associated periodic syndrome caused by a non-cysteine mutation (T50M) in the TNFRSF1A gene associated with severe multiorganic amyloidosis. 1557 Jun 62

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autosomal dominant inherited condition of periodic fever and pain. TRAPS is caused by mutations of the TNFRSF1A gene localized at 12p13. The gene encodes extracellular region of the p55 TNF-alpha receptor, resulting in impaired cleavage and down-regulation of the membrane expressed form of the receptor, a diminished shedding of potentially antagonistic soluble form of the receptor and, as a consequence, an unbalanced TNF-alpha action. Most affected patients are from northern Europe. Fever, sterile peritonitis, pleural pain, arthralgia, myalgia, skin rash, and/or conjunctivitis occur during the syndrome episodes; some patients also develop systemic amyloidosis, with some differences among patients. An acute-phase response occurs during the episodes. We describe a case of a 23-year-old Moldavian woman, living in Italy presenting recurrent fever episodes with abdominal pain and skin rash. A biopsy showed small vessel vasculitis. The genetic analysis showed a TNFRSF1A gene (R92Q) mutation. In this paper we report also a literature review on this rare disease.
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PMID:[TRAPS syndrome, a rare cause of fever of unknown origin: case report and review of the literature]. 1585 96

The prevention of the recurrence of Crohn's disease after surgery remains difficult. The monoclonal antibody anti-TNF-alpha, infliximab, is very effective in inducing and maintaining the remission of uncomplicated, active Crohn's disease. We present here the case of a 23-year-old white woman who underwent resection for a sigmoid stricture caused by Crohn's disease. Surgery removed the involved colon, and pathology confirmed the stricture to be fibrotic. Two weeks after the operation she was given infliximab at the dose of 5 mg/kg body weight and followed in time. Since then, she has been disease free for approximately 4 years after surgery on clinical, radiological and endoscopic/histological grounds (Crohn's Disease Activity Index < or = 110 on all occasions). Up to now, she has had no increase in inflammatory indices, no anaemia and no abnormal blood tests. In contrast, all of five control patients operated in the same period with colonic or ileocolonic resection for symptomatic strictures and treated with mesalamine or no medication developed endoscopic or clinical recurrence (abdominal pain or diarrhoea) by year 3. This is the first case, to our knowledge, in which infliximab has been successfully used to prevent the postsurgical recurrence of Crohn's disease, an event so far considered to be inescapable. We believe that, with this aim in mind, clinical trials with this drug are warranted.
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PMID:Prevention of postoperative recurrence of Crohn's disease by infliximab. 1653 23

We describe a patient with a long history of familial Mediterranean fever who developed proteinuria as a result of secondary AA amyloidosis. In this patient, the inflammatory process, including recurrent attacks of arthritis, abdominal pain, nephrotic syndrome secondary to amyloidosis, and high sedimentation rate, was rapidly suppressed by treatment with infliximab and there was remarkable improvement of the proteinuria.Because TNF-alpha is a proinflammatory cytokine that plays a major role in FMF and secondary amyloid, it is an appropriate target for therapy. Our case is the first case of reactive systemic amyloidosis secondary to familial Mediterranean fever, which responded favorably to infliximab.
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PMID:Infliximab treatment of Familial Mediterranean fever and its effect on secondary AA amyloidosis. 1704 87

Toll-like receptors (TLRs) are important molecules that stimulate the innate immunity in order to eradicate microbial pathogens, after which the adaptive immunity emerges. The involvement of TLRs in the action mechanism of OK-432, a bacterial preparation, was investigated in the locoregional treatment of malignant ascites from gastric cancer. The expression of TLRs in ascites cells was analyzed using reverse-transcription polymerase chain reaction specific for TLRs and by flow cytometry using anti-TLR2, -TLR4, -CD4, -CD8, and -CD11c antibodies. These measurements were compared with the locoregional response of OK-432 immunotherapy for malignant ascites, as well as TNF-alpha producing potential, which was measured by ELISA, of ascites cells stimulated in vitro with OK-432. It was observed that OK-432 immunotherapy for malignant ascites showed 8 positive (67%) and 4 negative responses with the tolerable adverse effects of fever elevation and abdominal pain. The TNF-alpha production of ascites cells by in vitro OK-432 stimulation was significantly higher in responder patients than in non-responders. The clinical responses were correlated with the expression of the TLR4 gene of ascites cells. The TNF-alpha-producing potential of ascites cells by in vitro OK-432 stimulation was dependent on the existence of a CD11c + TLR-4+ cell population in ascites cells. OK-432 was highly stimulatory for TNF-alpha production of ascites cells compared with other biological response modifiers of PSK and LEM. These results suggest that TLR-4 expression on ascites cells of a macrophage lineage is essential for ascites cells to produce TNF-alpha in relation to OK-432 stimulation and for subsequent positive clinical responses in locoregional immunotherapy using OK-432 for malignant ascites from gastric cancer.
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PMID:Essential requirement of toll-like receptor 4 expression on CD11c+ cells for locoregional immunotherapy of malignant ascites using a streptococcal preparation OK-432. 1709 88

We sought to study Toll-like receptor 4 (TLR4) expression on peripheral blood mononuclear cells (PBMCs) during the early stage of human acute pancreatitis (AP). Thirty consecutive patients with acute pancreatitis admitted within 24 hr of onset of abdominal pain were enrolled prospectively in this study. Blood samples were taken by venipuncture at admission and on the third and seventh days after admission. PBMCs were isolated, and TLR4 and CD14 expression on PBMCs was detected by flow cytometer. Serum tumor necrosis factor (TNF)-alpha, interleukin, and lipase were detected simultaneously. Relations among these parameters were analysis. In mild AP, TLR4 expression increased on the first day of admission and then continued to decline for several days. On the seventh day, TLR4 expression was almost normal compared with that of the normal control. The alteration of serum TNF-alpha was coincidence with TLR4. We conclude that mononuclear-macrophages might be ignited through TLR4 (the gatekeeper of the innate immune system) and lead to production of TNF-alpha.
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PMID:Alterations of Toll-like receptor 4 expression on peripheral blood monocytes during the early stage of human acute pancreatitis. 1741 54


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