shukoor65/lab-rag-model huggingface dataset:
C4A deficiency and poor prognosis in patients with IgA nephropathy. IgA nephropathy (Berger's disease) is an important cause of end-stage renal failure in persons of Asian and European descent. We performed C4 phenotyping on plasma from 123 patients with IgA nephropathy who resided in several different parts of the United States. All of these patients underwent diagnostic renal biopsy in adulthood. Six patients had a total deficiency for the C4A protein and all six had chronic renal insufficiency (serum creatinine concentration higher than 1.4 mg/dl at last follow-up). In contrast, 47% of the patients without C4A deficiency had chronic renal insufficiency (p = 0.001). The C4 gene defect was due to deletion of both C4A genes in only two individuals, whereas three patients were heterozygous for the C4A gene deletion. We speculate that the functional alteration of the complement system related to C4A deficiency might lead to expression of clinically severe disease in an individual with a genetic susceptibility to IgA nephropathy.
A comparative immunohistochemical study of Kuru and senile plaques with a special reference to glial reactions at various stages of amyloid plaque formation. The authors examined 10 patients with Gerstmann-Straussler syndrome or Creutzfeldt-Jakob disease and 10 with Alzheimer's disease (AD). Immunohistochemistry using anti-prion protein (PrP) and anti-beta/A4 protein (beta/A4) coupled with formic acid pretreatment could detect Congophilic and non-Congophilic deposits. Prion protein deposits were classified into five types and compared with types of beta/A4 deposits. Kuru plaques with multicentric cores and fine granular deposits were a characteristic feature of PrP deposits. Some types of PrP or beta/A4 deposits depend on the anatomic sites. To clarify the relationship of microglia and astrocytes to PrP or beta/A4 deposits, double-immunostaining method was performed. In both kuru and senile plaques, microglia were closely linked to the Congophilic plaques. Astrocytes, however, extended their processes toward the plaques even in the non-Congophilic plaques. These observations strongly suggest that similar glial association with plaque formation may be involved in both kuru and senile plaques, although the amyloid core proteins differ.
Determinant selection in murine experimental autoimmune myasthenia gravis. Effect of the bm12 mutation on T cell recognition of acetylcholine receptor epitopes. C57BL/6 (B6) mice respond to immunization with acetylcholine receptor (AChR) from Torpedo californica as measured by T cell proliferation, antibody production, and the development of muscle weakness resembling human myasthenia gravis. The congenic strain B6.C-H-2bm12 (bm12), which differs from B6 by three amino acid substitutions in the beta-chain of the MHC class II molecule I-A, develops a T cell proliferative response but does not produce antibody or develop muscle weakness. By examining the fine specificity of the B6 and bm12 T cell responses to AChR by using T cell clones and synthetic AChR peptides, we found key differences between the two strains in T cell epitope recognition. B6 T cells responded predominantly to the peptide representing alpha-subunit residues 146-162; this response was cross-reactive at the clonal level to peptide 111-126. Based on the sequence homology between these peptides and the T cell response to a set of truncated peptides, the major B6 T cell epitope was determined to be residues 148-152. The cross-reactivity of peptides 146-162 and 111-126 could also be demonstrated in vivo. Immunization of B6 mice with either peptide primed for T cell responses to both peptides. In contrast, immunization of bm12 mice with peptide 111-126 primed for an anti-peptide response, which did not cross-react with 146-162. Peptide-reactive T cells were not elicited after immunization of bm12 mice with 146-162. These results define a major T cell fine specificity in experimental autoimmune myasthenia gravis-susceptible B6 mice to be directed at alpha-subunit residues 148-152. T cells from disease-resistant bm12 mice fail to recognize this epitope but do recognize other portions of AChR. We postulate that alpha-148-152 is a disease-related epitope in murine experimental autoimmune myasthenia gravis. In this informative strain combination, MHC class II-associated determinant selection, rather than Ag responsiveness per se, may play a major role in determining disease susceptibility.
Transesophageal echocardiography in the detection of potential cardiac source of embolism in stroke patients. To compare the diagnostic yields of transesophageal and transthoracic echocardiography in the detection of potential cardiac sources of embolism, 63 patients (mean +/- SD age 63 +/- 15 [range 18-87] years) with transient ischemic attacks or stroke underwent both procedures. Transthoracic echocardiography revealed a potential cardiac source of embolism in 14% (nine) of the patients, all of whom had clinical evidence of heart disease. Transesophageal echocardiography revealed a potential cardiac source of embolism in 41% (26) of the patients; 27% (seven) of these patients had no clinical cardiovascular abnormalities. Abnormalities detected only by transesophageal echocardiography in the patients with unsuspected cardiac disease included atrial septal aneurysm in two, patent foramen ovale in two, left atrial appendage thrombus in one, and myxomatous mitral valve in two. The 26 patients with an identified cardiac source of embolism were older (67.5 versus 59.4 years, p = 0.04), more frequently in atrial fibrillation (62% [16] versus 8% [3], p less than 0.0001), had a larger left atrium (43 versus 37 mm, p = 0.01) and more commonly had left ventricular hypertrophy (62% [16] versus 32% [12], p less than 0.02) than the 37 patients in whom no cardiac source of embolism was identified. Thus, transesophageal echocardiography is more sensitive than transthoracic echocardiography in the detection of potential cardiac sources of embolism in patients with cerebral ischemic events.
Response of atrial natriuretic factor to acute and chronic increases of atrial pressures in experimental heart failure in dogs. Role of changes in heart rate, atrial dimension, and cardiac tissue concentration. BACKGROUND. This study evaluated the role of changes in heart rate, atrial pressure, volume, and cardiac tissue atrial natriuretic factor (ANF) concentration in the modulation of plasma ANF concentration in a model of pacing-induced heart failure. METHODS AND RESULTS. The effects of acute right ventricular pacing (250 beats/min), acute volume expansion (35 ml/min), and volume expansion after 1 week of right ventricular pacing on plasma ANF concentration were compared in eight dogs (group 1). As shown during right ventricular pacing previously, volume expansion produced significant increases in cardiac filling pressures and left atrial volume. Right ventricular pacing and volume expansion produced similar increments in plasma ANF concentration: from 32 +/- 12 to 168 +/- 153 pg/ml (p less than 0.05) and from 32 +/- 9 to 137 +/- 113 pg/ml (p less than 0.05), respectively. When pacing was initiated after volume expansion, plasma ANF concentration increased further to 462 +/- 295 pg/ml (p less than 0.05) despite little change in filling pressures and left atrial volume. With repeated volume expansion after 1 week of pacing, there were no significant further increases in left atrial volume and plasma ANF concentrations (from 332 +/- 121 to 407 +/- 113 pg/ml) despite significant increases in filling pressures. Atrial and ventricular tissue samples were also obtained from 21 dogs paced to severe heart failure (group 2) and from 14 normal dogs (controls). In all groups, atrial ANF was higher than ventricular ANF concentration. At 1 week (group 1), left atrial appendage ANF concentration (6.2 +/- 2.5 versus 16.1 +/- 10.3 ng/mg) was reduced, whereas left ventricular free wall ANF concentration (0.62 +/- 0.31 versus 0.24 +/- 0.16 pg/mg) was increased compared with that of controls (both p less than 0.001). At severe heart failure (group 2), atrial ANF remained low, whereas ventricular ANF concentration was similar to that of the controls. CONCLUSIONS. These data indicate that in pacing-induced heart failure, changes in heart rate, atrial pressure, and volume all contribute to the increased plasma ANF concentration. However, by 1 week (early heart failure), ANF release is attenuated, perhaps because of the inability of the atria to be stretched further and because of reduced atrial ANF concentration. In addition, the ventricle may be an additional source of ANF.
Lymphocytic adenohypophysitis: a pituitary mass lesion occurring in pregnancy. Proposal for medical treatment. Lymphocytic adenohypophysitis is a nonneoplastic, autoimmune cause of pituitary enlargement and insufficiency. Forty-eight of the 50 reported cases have occurred in women, nearly all in association with pregnancy. Left undiagnosed and untreated, it can progress to pituitary insufficiency and death. Histologic studies show characteristic changes of autoimmune disease with lymphocytic infiltration and destruction of anterior pituitary tissue with fibrotic replacement. Lymphocytic adenohypophysitis is currently diagnosed after other pituitary mass lesions are excluded and has been treated with a combination of neurosurgery and end-organ hormone replacement. However, with improved knowledge of the pathophysiologic characteristics and natural history of the disease and with the ability to make a prospective diagnosis, we believe glucocorticoids may suppress the inflammatory response and protect remaining pituitary tissue. Two previously unreported pregnancy-associated cases are described, including one prospectively diagnosed and treated without neurosurgery during pregnancy. Obstetrician-gynecologists must place lymphocytic adenohypophysitis in the differential diagnosis of pituitary enlargement associated with pregnancy, since treatment is available and the sequelae may be life-threatening.
Hepatocellular carcinoma in Richardson's ground squirrels (Spermophilus richardsonii): evidence for association with hepatitis B-like virus infection. During studies of seasonal obesity, a high frequency of hepatic neoplasms was observed in Richardson's ground squirrels. Of 12 Richardson's ground squirrels examined thoroughly, 7 had mild or moderate degrees of chronic portal hepatitis and 6 (50%) had hepatocellular carcinoma. Serological tests for hepadnavirus surface antigen, anti-core antibody and virion DNA that recognize the ground squirrel hepatitis virus of California ground squirrels (Spermophilus beecheyi) were uniformly negative. Southern blot analyses of EcoRI digests of liver cell DNA demonstrated 3.2 kb fragments that hybridized with a ground squirrel hepatitis virus-specific probe in nontumorous liver tissue from 6 of 10 ground squirrels and in hepatocellular carcinoma specimens from 2 of 5 squirrels indicating infection with a hepadnavirus related to ground squirrel hepatitis virus. Failure, however, to detect serum antibody to ground squirrel hepatitis core antigen suggested probable antigenic differences between the ground squirrel hepatitis virus of California ground squirrels and the putative Richardson's ground squirrel agent. Further studies are required to fully characterize the hepadnavirus of Richardson's ground squirrels and to determine its relationship to hepatocarcinogenesis in this species.
Experimental induction of heterotopic bone. Heterotopic bone can be induced in experimental animals by trauma to the soft tissues, by induction from living cells, or by extracts from bone and teeth. In the first two types, the mechanism of the inductive process is not known, whereas in the latter, a factor isolated from bone matrix induces bone formation. Mesenchymal cells in bone marrow are determined for development into cartilage and bone cells and only an unspecific stimulus, such as trauma or autotransplantation, is sufficient for the development into mature osteogenic tissue. Mesenchymal cells will not differentiate into bone cells unless stimulated by a specific inductive substance, bone morphogenetic protein (BMP). Implanted to a heterotopic site, BMP induces undifferentiated mesenchymal cells into a bone morphogenetic pathway of development, causing heterotopic bone formation. The quantitative inductive response is dependent on the source of the BMP, and the bone formation is also determined by the recruitment of inducible target cells and by the environment at the implantation site. Hence, the environment at the implantation site is of major importance for the amount of bone formed. BMP initiates a cascade of events that is modulated by endocrine and paracrine factors. The heterotopic bone has all the morphologic and biochemical characteristics of orthotopic bone, is subjected to turnover, and even has the intriguing ability to generate the formation of bone marrow. Experimental induction of heterotopic bone has become a most useful method to study osteoneogenesis and has supplied important information on the prerequisites for new bone formation and on the regulation of bone metabolism.
Mechanisms of failure of mitral valve repair: an echocardiographic study. Surgical valve repair for mitral regurgitation has significant advantages over valve replacement, but little is known about the mechanisms of its failure. This echocardiographic study examined abnormalities leading to failed mitral valve repair in two populations: "immediate failure" of the valve repair in the operating room requiring a second run of cardiopulmonary bypass and "late failure" of valve repair necessitating reoperation on another occasion. Intraoperative echocardiography (IOE) after cardiopulmonary bypass was performed in 309 patients undergoing valve repair for mitral regurgitation over a 3-year period. Twenty-six (8%) of these patients had immediate failure of the repair demonstrated by IOE, requiring further repair or replacement during the same thoracotomy. The causes of immediate failure were left ventricular outflow tract obstruction (10 patients), incomplete correction (10 patients), and suture dehiscence (six patients). Echocardiography was performed on 17 patients requiring reoperation for recurrent mitral regurgitation who had undergone previous primary valve repair. These late failures resulted from progressive degenerative leaflet or chordal disease (n = 9) or suture dehiscence of the annular ring or the leaflet resection site (n = 6). In only two patients early in the series did the problem originate from inadequate initial surgery. IOE is an effective marker for unsuccessful mitral valve repair, and affords an understanding of the mechanism of the persistent dysfunction. Immediate failure of mitral repair may be reduced by greater attention to the mechanism of valve dysfunction and by changes in valvuloplasty technique to avoid outflow tract obstruction. Late failure after mitral repair occurs predominantly due to progression of disease, particularly in patients with severe myxomatous or annular abnormalities that are prone to progress.
Sleep apnea and systemic hypertension: a causal association review. OBJECTIVE: To critically examine the causal association between sleep apnea syndrome and hypertension. METHODS: A retrospective systematic critique of five epidemiologic studies published in the English literature during 1978 to 1989 identified on Medline and manual literature searches. The evidence was evaluated using the standard observational criteria for causation: strength of association, consistency, dose-response relationship, temporal sequence, specificity, and biologic plausibility. RESULTS: We found evidence to support a causal association between sleep apnea syndrome and hypertension in consistency and specificity and some evidence to suggest a dose-response relationship. Review of the data dealing with the mechanisms important in the pathogenesis of sleep apnea and hypertension allowed us to advance several theories to provide support for biologic plausibility. CONCLUSION: We concluded that there is a positive association--relative risk estimate between 1.3 and 40--for sleep apnea syndrome and hypertension, but the risk association is unstable. Thus, we believe that there is insufficient data to justify doing polysomnography as part of the routine diagnostic work-up for patients with hypertension.
Accessory receptors regulate coupling of the T-cell receptor complex to tyrosine kinase activation and mobilization of cytoplasmic calcium in T-lineage acute lymphoblastic leukemia. T-lineage acute lymphoblastic leukemia (T-ALL) cells have abundant cytoplasmic CD3/Ti but express low amounts on the cell surface and are deficient in CD3/Ti-mediated signal transduction. Nevertheless, plating T-ALL cells on dishes containing immobilized anti-CD3 monoclonal antibodies with a source of growth factors induced the expression of CD25 (interleukin-2 receptor alpha chain) and stimulated the formation of blast colonies in 12 of 14 cases studied. The proliferative response to CD3 ligation was modulated by the presence of antibodies to the CD2, CD4, or CD8 accessory T-cell receptors. The effect of these accessory receptors on signal transduction mediated by CD3/Ti was next investigated by monitoring cytoplasmic calcium concentration [( Ca2+]i) and by measuring tyrosine phosphorylation after stimulation. Crosslinking CD3, CD2, CD4, or CD8 alone did not induce cytoplasmic calcium mobilization in T-ALLs, but crosslinking the accessory receptors with CD3/Ti induced calcium responses in three of the T-ALLs and enhanced calcium responses in three of the T-ALL cell lines, including HPB-ALL, MOLT-4, and CEM. Crosslinking CD4 but not CD2 with CD3/Ti greatly enhanced tyrosine phosphorylation of multiple substrates in comparison with crosslinking either CD4 or CD3/Ti separately on both normal mature T cells and the CEM T-ALL cell line. Thus, CD4 regulates CD3/Ti signal transduction in T-ALL cells through the tyrosine phosphorylation of substrates whereas CD2 may regulate [Ca2+]i signal transduction through a separate mechanism.
Double-inlet ventricle presenting in infancy. II. Results of palliative operations. The influence of palliation on survival was studied in 191 consecutive infants, presenting at under 1 year of age, with double-inlet ventricle (1973 to 1988, median follow-up 8.5 years). Palliative operations were performed on 154 occasions in 121 patients (63%). Survival after a systemic-pulmonary arterial shunt (n = 57) and banding of the pulmonary trunk (n = 35) was comparable (84% and 77% at 1 year, 62% and 45% at 5 years), but those who underwent repair of aortic arch obstruction fared worse (n = 18, 44% and 22% at 1 and 5 years, p less than 0.001). The remainder did not undergo an operation because of balanced physiology (n = 17, 9% of entire group), complex anatomy (n = 32, 15%), or irreversible low output (n = 19, 12%). Palliative surgery, overall, had a deleterious effect on immediate survival (greater than 1 month relative risk 6.6, p less than 0.001), but, in the survivors, medium-term outcome was improved (greater than 6 months, 0.68, p less than 0.05). This effect was most marked for those undergoing a systemic-pulmonary artery shunt (less than 1 month, 2.52; greater than 6 months, 0.43); by contrast, after banding of the pulmonary trunk, with or without additional repair of the aortic arch repair, medium-term risk was not altered (greater than 6 months, 1.13 and 0.91, respectively). These data will assist the clinician in making decisions concerning the management of infants with double-inlet ventricle and in the judicious use of palliative surgery.
Effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing cardiopulmonary bypass operation. To study the hemostyptic effect of aprotinin (Trasylol) in patients undergoing extracorporeal circulation for coronary artery bypass operations, we randomized 12 of 24 patients to receive aprotinin in high dosage (about 800 mg) during extracorporeal circulation. From the resulting two groups each, one patient was excluded from the study because of postoperative myocardial infarction (control group) and surgical hemorrhage (aprotinin group) leading to a second operation. Although heparin was used for anticoagulation in all 22 patients, all had a marked increase in plasma levels of thrombin-antithrombin III complexes during extracorporeal circulation, indicating an intravasal activation of coagulation. By monitoring the plasma levels of fibrin degradation products in patients without aprotinin therapy, we recorded a concomitant hyperfibrinolysis significantly less pronounced in patients receiving aprotinin (p less than 0.005). The mean total postoperative blood loss was lower in patients receiving aprotinin (620 ml) than in control patients (1000 ml; p less than 0.03). The results confirm previous reports of a hemostyptic effect of aprotinin in cardiac operations. This effect is probably due to a prevention of hyperfibrinolysis.
Gout and hyperuricemia. Accurate diagnosis is essential since gout is overdiagnosed by a factor of three. Asymptomatic hyperuricemia is not associated with adverse consequences and should not ordinarily be treated. The acute attack of gout responds to any nonsteroidal anti-inflammatory drug, and antihyperuricemic therapy with allopurinol, probenecid or sulfinpyrazone is effective in lowering uric acid and preventing further attacks. Except for prophylaxis, colchicine is not recommended for the treatment of gout because of unacceptable levels of toxicity. Diet therapy, once a mainstay of treatment, is usually not indicated since drug therapy alone is far more efficacious.
Reduced cerebral grey matter observed in alcoholics using magnetic resonance imaging. Twenty-eight chronic alcoholics and 36 age- and sex-matched non-alcoholic controls were examined with magnetic resonance imaging and brain morphometric analyses. Results confirmed large increases in subarachnoid cerebrospinal fluid (CSF) volume and mild ventricular enlargement in the alcoholics and revealed associated volume reductions of localized cortical and subcortical cerebral structures. Volume losses in the diencephalon, the caudate nucleus, dorsolateral frontal and parietal cortex, and mesial temporal lobe structures were the most prominent. Significant correlations between increments in cortical and ventricular CSF and decrements in the volume of cortical and subcortical grey matter were noted. Although there was little evidence for relationships between performance on neuropsychological tests and volume of grey matter structures, significant correlations between some cognitive measures and subcortical and cortical fluid volumes were found. The parallels between this pattern of affected structures and recent neuropathological findings are discussed.