Gene/Protein Disease Symptom Drug Enzyme Compound
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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results of clinical observation of 35 patients with aortitis syndrome (AS) in childhood, obtained by a nationwide survey in Japan, are reported. The male to female ratio was 1:2.5, the estimated age of onset averaged 10.2 years, and the duration from the estimated age of onset to the diagnosis averaged 15 months. In HLA examination A24, Bw52, Cw7 and DR2 were relatively common. Arterial lesions tended to extensively involve the aortic arch and its branches. Fever was the most frequently noted clinical symptom, followed by abdomen, joint and muscle pain. The physical findings in order of frequency were impaired circulation of the upper extremities, cardiac and vascular murmurs, hypertension, impaired cerebral circulation, visual disorder and impaired circulation of the pulmonary artery. The murmurs were found not only over the chest wall but also over the cervical area and abdomen. Pulselessness of the upper extremities occurred in 66% of patients. Percutaneous retrograde aortography and/or intravenous digital subtraction angiography to make the final diagnosis was employed except for three cases. There were not any specific abnormal signs in laboratory data. Steroid hormones were administered in 34 cases, and immunosuppressive agents in 8 cases. Five cases had percutaneous transluminal angioplasty to the right renal artery as an interventional treatment. The high frequency of abdominal pain is considered to be one of the characteristics of AS in childhood. The high frequency of pulselessness of the upper extremities and cardiac and vascular murmurs in this report is considered significant for the diagnosis of AS in childhood.
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PMID:Aortitis syndrome in children: clinical observation of 35 cases in Japan. 914 Dec 73

The concept of predictive medicine based on the detection of genetic markers for disease susceptibility stemmed from the finding that many diseases are associated with specific HLA alleles. This model suggested that similar associations probably existed with other genes located all along the human genome. The Human Specimen Study Center (HSSC) was created to assist in investigating this possibility and has contributed significantly to the knowledge contained in current genetic and physical human genome maps. Predictive medicine is intended not for patients but for healthy individuals, its goal being to determine whether their susceptibility to a specific disease is increased or not. Fetuses with evidence of disease are excluded from the province of predictive medicine, which can, however, determine whether a healthy fetus is at high risk for developing a disease in adolescence or adulthood. Predictive medicine is based on probabilities: it evaluates diseases susceptibility but cannot predict with 100% certainty that a specific disease will occur. Whereas many preventive interventions are directed at groups (e.g., immunization programs), predictive medicine is conducted on an individualized basis. For instance, glaucoma is a monogenic disease whose early detection can allow to prevent permanent loss of vision. The fruits of predictive medicine are expected to be greatest, however, in the polygenic multifactorial diseases that are prevalent in industrialized countries, such as diabetes mellitus, hypertension, myocardial infarction, hyperlipidemia, and arteriosclerosis. An ability to detect subjects who are susceptible to breast cancer would be extraordinarily useful, and may be a goal within reach since two breast cancer susceptibility genes have already been identified. Genes associated with increased susceptibility to colon cancer have also been reported. Predictive medicine raises a number of sensitive ethical issues. Individuals should be free to accept or decline disease susceptibility testing after having been fully informed. Confidentiality is vital. The results of susceptibility tests should not be made available to employers or insurance agencies. Susceptibility testing should be offered only if the disease requires a specific treatment or lifestyle modification. Unnecessary anxiety may be one of the main adverse effects of susceptibility testing. A large number of disease susceptibility or resistance genes will probably be identified in the near future, and this will inevitably have an impact on the way physicians approach their patients. Physicians in the XXIst century will spend an increasingly large proportion of their time counselling their patients on how to stay healthy. This trend can be expected to translate into a marked increase in life expectancy. Rather than seeking to add years to life, physicians will strive to add life to years.
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PMID:[Predictive medicine and its ethics]. 929 63

There are only few data available regarding the immunological mechanisms for cerebral infarction. The aim of this study was to find out the humoral and cell-mediated immunity under the conditions of focal brain ischemia (CI). As a method for humoral immunity, the complement consumption test against a panel of 8 antigens, quantitative analysis of immunoglobins and fractionized sedimentation of erythrocytes were used in the group of pts with CI, and the group of atherosclerotics (AS) and hypertonics (VH), potential victims of focal brain ischemia. It was found that the occurrence of antibodies against the whole panel of antigens in the group of CI is significantly higher as compared with the healthy controls, but it is lower than that in the group of AS and VH. The occurrence of antibodies exclusively against only brain antigens and that in CSF is similar. No correlation to the location of ischemic lesion and the degree of neurological deficit score was found. These findings didn't change in 2 and 4 weeks as well as in 1 year after the onset of CI. The quantitative analysis of immunoglobins revealed statistically higher levels of IgA and lower levels of IgM in comparison with the controls. IgG were higher, but without statistical significance. Statistically significant higher levels of all immunoglobins in CSF were found. As similar trend of changes found also in the group of AS and VH. These results of humoral immunity confirmed by the results of fractionized sedimentation of erythrocytes with EP. The results can be interpreted as a possible change or disorder of central regulation of immunizing processes due to the latent (in AS and VH) of manifest (in CI) lesions of the brain. But the quality and quantity of this response might have been affected by the entire case history of the patients who survived cerebral infarction. The changes in immunity response of the organism in CI was shown also in cell-mediated immunity. The results a statistically significant increase in stimulatory (SI) as well as in immunoregulatory (IRI) indices in stroke patients under the age of 40. These findings didn't change 2 and 4 weeks after the onset of CL. An increase in IRI was due to the increase in Th lymphocytes. In the immune response of the organism in CI, the antiphospholipid antibodies (aPLs = anticardiolipin antibodies (aCL) and lupus anticoagulant--LA) play an important role. aCLs were present in 9.8% of the first stroke pts when compared to 4.3% in controls. The most common isotype of the antibodies we IgG. Of all first-stroke pts who were aCL positive only 8% had no other stroke risk factors (atrial fibrillation, diabetes, hypertension and other). aCLs are an important risk factor for the first stroke, mainly in the young, but also in the elderly. The presence of aCLs increases the risk for recurrent strokes. aPLs are not necessarily associated with the specific location of clinical stroke syndrome but they are in significant correlation to the occurrence of multiple strokes on CT (30:18%). None of the initially aCL-negative patients became aCL-positive during the time course of CI. These data support the idea that aCLs play a causal role in stroke (PROPTER HOC changes) rather than vice versa (POST HOC changes). From the therapeutic point of view, currently there do not exist any good treatment guidelines for preventing the second stroke. The analysis of HLA. antigen showed an increase in some HLA (A2, A28 etc.) and a decrease in others (A3, A9 etc.) in comparison with the controls. This might refer to the participation of genetic factors in the onset of CI.
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PMID:[Cerebral infarct and the immune response]. 933 23

Membranous nephropathy is the most frequent cause of glomerulonephritis in adults with nephrotic syndrome. Approximately one quarter of the patients develop end-stage renal disease. Another quarter enters complete remission during follow-up. Treating all patients with membranous nephropathy with immunosuppressive drugs would unnecessarily expose at least one quarter of the patients to these toxic drugs. Identifying patients at highest risk would allow tailor-made treatment. Many risk factors have been found, such as male sex, HLA type DR3+/B8+, white race, advanced age, and tubulointerstitial changes or focal sclerosis found with renal biopsy. In addition, nephrotic syndrome, elevation of immunoglobulin G excretion or beta2-microglobulin excretion, low serum albumin, high serum cholesterol, an elevation of urinary excretion of complement activation products, impaired renal function at diagnosis, and, finally, hypertension are associated with a higher risk of renal function deterioration during follow-up. We have critically reviewed the literature and summarized the clinical significance of the above-mentioned risk factors in predicting subsequent renal function deterioration in patients with membranous nephropathy.
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PMID:Prognostic factors in idiopathic membranous nephropathy. 942 45

To determine how well tacrolimus (FK506) and cyclosporin A (CsA) are tolerated after HLA-identical blood stem cell transplantation, we performed a retrospective review of 87 adults transplanted consecutively who received FK506 (n = 40) or CsA (n = 47) in a nonrandomized fashion in combination with methylprednisolone for graft-versus-host disease (GVHD) prophylaxis and compared the incidences of complications potentially related to the immunosuppressive agents. Pre-transplant demographic characteristics, drug compliance and rates of acute GVHD were comparable for the two groups. Following first discharge, fewer patients in the FK506 group required antihypertensive therapy (32 vs 59%, P = 0.022), but more required insulin (34 vs 10%, P = 0.014). There was also a trend for more hyperkalemia and less moderate-to-severe venoocclusive disease in the FK506 group. However, nephrotoxicity, neurotoxicity, hemolytic-uremic syndrome, and cytomegaloviral or fungal infections through the first 100 days post-transplant did not differ significantly between the two groups. We conclude that for allogeneic blood stem cell transplant recipients, the incidence of complications related to FK506 and CsA in equally effective dose schedules in combination with methylprednisolone are similar with the exception of the risks of hypertension and hyperglycemia.
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PMID:Toxicities of tacrolimus and cyclosporin A after allogeneic blood stem cell transplantation. 946 84

We describe a Thai family with three children, two of whom presented with Wolfram syndrome, which is a rare syndrome characterised by diabetes insipidus, diabetes mellitus, optic atrophy, deafness and urinary tract dilatation. A girl and her younger brother had insulin-dependent diabetes mellitus at 11 years old with early onset of renal impairment, proteinuria and hypertension. Urinary tract dilatation was demonstrated in both patients. Kidney biopsies were compatible with diabetic nephropathy. Both children also had bilateral sensorineural hearing loss. Optic atrophy with severe loss of vision was detected in the girl and bilateral cataract in her brother. Both patients were HLA DR2 positive. At 16 years old, her creatinine clearance was 16 ml/min/1.73 m2. Her brother's creatinine clearance was 25 ml/min/1.73 m2 at 13 years old. We conclude that renal function should be evaluated in patients with Wolfram syndrome and the cause of renal failure in these patients may be rapid and severe diabetic nephropathy.
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PMID:Renal failure in two patients with Wolfram syndrome. 946 37

We studied 733 cadaveric renal transplant patients (747 transplants) under cyclosporin immunosuppression, to: (i) establish the risk profile for acute renal failure (ARF) after renal transplantation in a unit using many sub-optimal donors; (ii) assess the long-term prognostic relevance of ARF; and (iii) explore the synergistic prognostic significance of delayed graft function and acute rejection during the early post-transplant period. Transplanting from a non-heart-beating or elderly donor, protracted cold ischaemia, haemodialysis immediately before transplant surgery, poor HLA matching, and grafting to a hypersensitized recipient without residual renal function, all independently predicted delayed graft function. This delay had no detrimental effect on patient or graft survival, but prolonged ARF was associated with increased mortality from infection. Late markers of graft dysfunction (poor graft function, proteinuria, hypertension) were highly prevalent among grafts affected by ARF, specially in prolonged ARF. Delayed graft function and early acute rejection showed a definite, albeit not strong, additive impact on late graft survival, and also on the prevalence of late markers of graft dysfunction.
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PMID:The prognostic significance of acute renal failure after renal transplantation in patients treated with cyclosporin. 951 10

Eleven leukemia patients who had undergone bone marrow transplants from HLA-A, B, DR genotypically mismatched unrelated donors received FK506 and short-term methotrexate as prophylaxis for graft-versus-host disease (GVHD). Grade III-IV acute GVHD developed in 2 of the patients, and chronic GVHD developed in 4 of the other patients. Adverse drug reaction included reversible nephrotoxicity, hyperglycemia (all patients) and hypertension (9 patients). Hyperglycemia and hypertension of grade 3 or higher occurred mostly in the patients who were on supplemental steroids. However, severe nephrotoxicity was not observed. Complications included cystitis (4 patients), cytomegalovirus colitis (3 patients), Interstitial Pneumonitis (IP) (3 patients), tuberculosis (1 patient), and thrombotic microangiopathy (1 patient). None of patients relapsed. Although close monitoring of FK506 blood concentration and patient clinical signs are required, we concluded that FK506 is effective for GVHD prophylaxis after bone marrow transplantation from HLA-A, B, DR genotypically mismatched unrelated donors, and that adverse reactions due to FK506 are controllable. To determine the long-term effectiveness of this drug, it will be necessary to conduct prospective randomized studies that compare it wiht cycloporin A as a preventive treatment against GVHD in patients who receive bone marrow transplants from HLA genotypically mismatched unrelated donors.
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PMID:[FK506 for the prophylaxis of graft-versus-host-disease after bone marrow transplantation from HLA-genotypically mismatched unrelated donor]. 978 75

Patients with IDDM often develop severe forms of retinopathy, supposed to be associated to risk factors such as hypertension, poor glycemic control and nephropathy. A controversial intervention of a genetic marker was evoked so as some diabetic patients have retinopathy in the absence of known risk factors. HLA-DR and DQ markers were compared in two groups of patients with IDDM respectively constituted of patients with and without severe retinopathy. HLA typing was carried out by polymerase chain reaction (PCR) and restriction fragments of length polymorphism (RFLP). DR9 (p < 10(-4); O.R. = 8.36) and DQA1*0301 (p < 0.05; O.R = 2.92) alleles were positively associated to diabetic retinopathy, at the opposite of DR3 (p < 10(-3); O.R: 0.01) and DQA1* (p < 10(-9); O.R = 0.15). Furthermore, among the genotypes previously considered as risk markers of IDDM in senegalese people, only DR4: DQA1*0301:DQB1*0302/DR9: DQA1*0301: DQB1*0201 was often observed in retinopathy.
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PMID:[HLA-markers and diabetic retinopathy in the Senegalese population]. 982 51

Childhood membranous nephropathy (MNP) with anti-tubular basement membrane (anti-TBM) nephritis is a rare disorder that may have extrarenal manifestations. This article describes a new case to be added to the 10 previously reported. A renal biopsy specimen from a 1-year-old white boy with nephrotic syndrome, microhematuria, and hypertension showed MNP (granular global IgG, IgA and C3, and segmental IgM and C1q) associated with hypercellularity and granular deposits of IgM and C1q in the mesangium, arteriolar IgA, and linear TBM IgG, IgA, and C3. A biopsy at age 4 years showed MNP (IgG and C3) and linear IgG and C3 along the TBM. Six months later, temporary glucosuria suggested a mild tubular dysfunction. Biopsy at age 8 years showed sclerosing MNP (IgG and C3), linear TBM IgG and C3, and chronic active tubulointerstitial nephritis (TIN). Indirect immunofluorescence showed circulating anti-TBM antibodies, and the enzyme-linked immunosorbent assay (ELISA) approach verified strong reactivity with the 58-kd TIN antigen. Despite trials with steroids, chlorambucil, azathioprine, and cyclosporine, end-stage renal disease developed by the age of 9 years. At age 10 years, the patient received a cadaveric kidney transplant. With the patient now aged 12 years, the graft is still functioning well, without any clinical evidence of disease recurrence. Neurological, ocular, and abdominal symptoms, including nonbacterial diarrhea, were observed during the follow-up period. The pathophysiology of these extrarenal symptoms remains unclear. Serotyping and genotyping of HLA antigens (A2, A10, B12, B41, DR5 [1101, 1103-4, 1106 or 1108-1113], DR6 [1303, 1312, or 1413], DRB3 [*0101 and 0201-2 or 0301], DQA1 [*0501 homozygous], and DQB1 [*0301 homozygous]) did not indicate any HLA association similar to those described previously in childhood MNP with anti-TBM nephritis (HLA-B7 in four patients, HLA-DR8 in two patients). The presented case is the fifth in the literature that displays reactivity with the 58-kd TIN antigen, and for which data on HLA antigens are reported.
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PMID:Childhood membranous nephropathy, circulating antibodies to the 58-kD TIN antigen, and anti-tubular basement membrane nephritis: an 11-year follow-up. 985 26


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