shukoor65/lab-rag-model huggingface dataset:
DNA sequence analysis and restriction fragment length polymorphism (RFLP) typing of the HLA-DQw2 alleles associated with dermatitis herpetiformis. Dermatitis herpetiformis (DH) is a blistering autoimmune skin disease associated with a 95-100% incidence of the HLA class II antigen HLA-DQw2. Although the precise role of this antigen in the pathogenesis of DH is unclear, one theory proposes that patients with DH possess a molecularly unique subtype of the HLA-DQw2 antigen that causes immune abnormalities eventuating in the clinical manifestations of DH. To test this hypothesis, we performed DNA sequence analysis on the highly polymorphic HLA-DQB1 and HLA-DQA1 loci of eight patients with dermatitis herpetiformis. All DQB1 alleles sequenced were identical to the previously described HLA-DQB*0201 allele from HLA-DQw2 normal subjects. In addition, DQA1 alleles sequenced were identical to those alleles previously associated with HLA-DQw2 (DQA*0201, DQA*0501). These data document that although HLA-DQw2 appears to be a necessary element in the pathogenesis of DH, the development of DH is not dependent on the presence of a unique HLA-DQw2 antigen. HLA-DQ allelic typing by restriction fragment length polymorphism analysis of PCR-amplified HLA-DQA1 and HLA-DQB1 fragments was also performed in ten patients with DH to determine the allelic distribution among both HLA-DR3 (eight patients) and non-DR3 (two patients) DH patients. At the HLA-DQ beta chain locus, all patients possessed the DQB1*0201 allele. At the HLA-DQ alpha chain locus, all HLA-DR3 patients and one non-DR3 patient displayed a pattern consistent with the DQA1*0501 allele, whereas one non-DR3 patient displayed a pattern consistent with the DQA1*0201 allele. These data document that patients with DH do not express a unique HLA-DQw2 heterodimer, that the HLA-DQw2 molecules present in patients with DH have no DNA sequence differences from those found in normal HLA-DQw2 subjects and therefore that susceptibility to DH is not due to a unique HLA-DQw2 molecule.
Gallium-SPECT in the detection of prosthetic valve endocarditis and aortic ring abscess. A 52-yr-old man who had a bioprosthetic aortic valve developed Staphylococcus aureus bacteremia. Despite antibiotic therapy he had persistent pyrexia and developed new conduction system disturbances. Echocardiography did not demonstrate vegetations on the valve or an abscess, but gallium scintigraphy using SPECT clearly identified a focus of intense activity in the region of the aortic valve. The presence of valvular vegetations and a septal abscess was confirmed at autopsy. Gallium scintigraphy, using SPECT, provided a useful noninvasive method for the demonstration of endocarditis and the associated valve ring abscess.
The pathophysiology of chronic relapsing experimental allergic encephalomyelitis in the Lewis rat. Electrophysiological studies were performed in Lewis rats with chronic relapsing experimental allergic encephalomyelitis (EAE) induced by inoculation with guinea-pig spinal cord and adjuvants and treatment with low dose cyclosporin A. During clinical episodes there was conduction failure in the central nervous system (CNS), namely the spinal cord dorsal columns, and in the afferent fibres in the peripheral nervous system (PNS). The following observations indicated that the conduction failure was mainly due to demyelination-induced conduction block: (1) rate-dependent conduction block in the CNS and PNS; (2) temporal dispersion due to slowing of PNS conduction; (3) restoration of PNS conduction by cooling; (4) restoration of CNS conduction by ouabain; (5) previously demonstrated histological evidence of primary demyelination in the dorsal columns, dorsal root ganglia and dorsal roots; and (6) the temporal association of restoration of conduction with remyelination. However, it is likely that CNS and PNS axonal degeneration, which occurs in this disease, also contributed to the conduction failure. In clinical remissions there was restoration of conduction in the CNS and PNS which can be explained by ensheathment/remyelination by oligodendrocytes and Schwann cells, respectively. In most rats during clinical episodes the cerebral somatosensory evoked potential was reduced in amplitude and prolonged in latency, which can be accounted for by demyelination and axonal degeneration in the CNS and PNS components of the afferent pathway. In 2 rats with episodes of EAE, however, this potential was markedly increased in amplitude, which might have been due to demyelination-induced conduction block of descending pathways that normally inhibit synaptic transmission in the afferent pathway. In well-established remission there was residual conduction failure in the CNS and PNS which can be mainly accounted for by axonal degeneration.
Low-dose co-trimoxazole for prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus disease The efficacy and tolerability of low, intermittent doses of co-trimoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole given Monday, Wednesday, Friday) for prophylaxis against Pneumocystis carinii pneumonia (PCP) was assessed retrospectively in 116 patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex at high risk of PCP. 92% were receiving concomitant zidovudine. 71 with previous episode(s) of PCP were followed a mean of 18.5 months (range 3-42). 45 without past PCP but with depletion of CD4 cells to less than 200/microliters were observed for a mean of 24.2 months (range 9-40). PCP did not develop in any patient on co-trimoxazole. 33 (28%) had side-effects, mainly rash, pruritus, and nausea. 15 discontinued co-trimoxazole, but only 11 (9%), who withdrew in the first month, were clearly drug-intolerant. Thus, low-dose, thrice weekly co-trimoxazole completely prevents AIDS-associated PCP, is cost-effective, and well tolerated by more than 85% of patients. Controlled comparisons of this regimen with other prophylactic agents are warranted.
Automated pupil perimetry. Pupil field mapping in patients and normal subjects. The authors developed an automated method of pupil perimetry by linking an infrared video pupillometer to a Humphrey Field Analyzer. Software was developed to automatically analyze the pupil responses to focal light stimuli and display the results graphically. All 76 locations of Humphrey program 30-2 could be tested twice within 5.5 minutes and the relative sensitivity of the field was determined by comparing the amplitude of pupil constriction or latency time at each stimulus location. The mean pupil responses within annular areas at 3 degrees, 9 degrees, 15 degrees, 21 degrees, and 27 degrees were shown to be linearly related to log stimulus intensity over a 15 dB range under low level mesopic conditions (3.15 asb bowl background). In normal subjects, the superior temporal quadrant usually had the greatest mean pupillomotor response and the inferior nasal quadrant had the least. Pupil responses in the temporal field were larger than corresponding locations in the nasal field. Patients with visual field defects who underwent testing by pupil perimetry showed pupillary deficits in the same location within the field, providing evidence that pupil perimetry may be a useful, objective means of assessing visual field function.
Diltiazem-induced psychosis and a possible diltiazem-lithium interaction. Calcium channel blockers are being used increasingly for a variety of cardiovascular problems. Diltiazem hydrochloride, a benzothiazepine derivative, has been reported to have a low incidence of adverse side effects. We report a case of acute psychosis associated with the use of diltiazem in a patient receiving lithium carbonate therapy. Both diltiazem hydrochloride and lithium carbonate have calcium antagonist effects in the central nervous system, and we review their mechanisms of action. A possible synergistic drug interaction between diltiazem and lithium is reported.
Effects of 30-h sleep loss on cardiorespiratory functions at rest and in exercise. The effects of 30-h sleep deprivation on cardiorespiratory function either at rest or in exercise were studied in 15 young healthy male volunteers. All subjects performed 1-min incremental exercise tests on a bicycle ergometer until exhaustion and endurance exercise tests at 3/4 of their maximal work rates. Arterialized venous blood samples were withdrawn at rest and during exercise tests to investigate the influence of sleep loss on blood gases. In addition, resting plasma catecholamine levels were also measured in ten subjects. The results showed that 1) resting heart rate, plasma catecholamine levels, and blood pH were decreased while minute ventilation (VI) and CO2 production (VCO2) were increased after 30 h of sleep loss (P less than 0.05), and 2) the maximal exercise performance was reduced by sleeplessness, as indicated by the decreases in the maximal heart rate, peak VI, peak VCO2, peak O2 consumption, and time to exhaustion (P less than 0.05). However, no significant changes in exercise endurance, arterialized venous pH, and PCO2 were found in exercise after sleep deprivation either. We therefore conclude that 30-h sleep loss alters cardiorespiratory function at rest and the ability to perform maximal exercise but not exercise endurance.
Autoantigen recognition by thyroid-infiltrating T cells in Graves disease. Graves disease is a common form of human autoimmune thyroiditis. It shares many pathological features and HLA associations with other, less easily studied, organ-specific autoimmune conditions such as insulin-dependent diabetes mellitus, and hence it is also a useful model for understanding these other diseases. We have previously shown that thyroid-infiltrating T cells in Graves disease that have been recently activated in vivo specifically recognize autologous thyroid epithelial cells. However, the autoantigens involved were not defined. In this study, we have made use of antigen-independent T-cell cloning techniques to show that at least three different thyroid antigens, three different epitopes on a single antigen, and two HLA class II elements are involved in this recognition process in a single individual. This demonstrates that T cells that are present and activated at the site of a human autoimmune disease may show considerable heterogeneity in their recognition of autoantigen on the target tissue. This contrasts with the limited heterogeneity recently reported in some animal models and has potentially important implications for both our understanding of the autoimmune process in humans and the design of immunotherapies to reverse it.
Solitary expression of CD7 among T-cell antigens in acute myeloid leukemia: identification of a group of patients with similar T-cell receptor beta and delta rearrangements and course of disease suggestive of poor prognosis. In a series of 100 acute myeloid leukemia (AML) patients defined by cytochemistry and immunophenotyping, 20 expressed T-lymphocyte associated antigens on the surface of their blasts. While 15 expressed two or more T-cell antigens, five were found to express only CD7. All patients belonged to the French-American-British type M4, and four were under the age of 40. Despite intensive chemotherapy, four never obtained a complete remission and the fifth died of relapse after an allogenic bone marrow transplantation. While 12 randomly selected T-cell antigen negative AML patients showed only few rearrangements in Ig- or T-cell receptor (TCR) genes, such genetic alterations were demonstrated in four of five patients for the TCR delta gene and in all patients for the TCR beta gene. Interestingly, DNA fragments of similar size were demonstrated in three of five patients for both the beta and delta genes. These data suggest that the solitary presence of CD7 among T-cell antigens in otherwise clearcut AML cases identifies a group of patients with similarities in antigen receptor gene configuration as well as outcome.
Tumor necrosis factor receptors in lymphoid tissues and lymphomas. Source and site of action of tumor necrosis factor alpha. Tumor necrosis factor alpha (TNF alpha), which is produced by germinal center dendritic reticulum cells (DRC) in lymphoid tissue, plays a regulatory role in a local immune response. However no information is available on the nature and location of cells responding to this cytokine. Thus TNF receptor distribution was investigated in situ by immunohistochemistry using monoclonal antibodies directed against the p75 and p55 receptor proteins. Receptor expression was unique and restricted to the lymphoreticular tissue. The p75 receptor was found on activated lymphocytes and interdigitating reticulum cells of the T-cell area, whereas the p55 receptor was confined to the germinal center DRCs, which are the main site of TNF alpha production. The two receptor proteins were expressed on distinct cell populations of the lymphoid system and no coexpression was observed. Preliminary results indicate that TNF receptor (TNFR) expression is regulated; Upregulation of TNFR proteins was found in reactive hyperplasia together with increased TNF alpha expression. In lymphoproliferative disorders, expression of the p75 receptor and TNF alpha was found mainly in high-grade malignant non-Hodgkin lymphomas. In summary, TNF alpha produced by germinal center DRCs might regulate an in vivo immune response through autocrine and paracrine pathways. Thus TNF alpha might signal, through the distinct TNFR proteins, the p55 and p75 receptor, which are expressed on different cell types in lymphoid tissue.
Diagnosis and localization of laceration of the thoracic duct: usefulness of lymphangiography and CT. The usefulness of lymphangiography and CT in the diagnosis and localization of laceration of the thoracic duct was evaluated in 12 patients with chylothorax or chylous ascites after surgery. Bipedal lymphangiography was performed in all 12 patients. The last four patients studied also had CT after lymphangiography. Seven patients had abnormal findings on lymphangiograms; five with leaks from the thoracic duct, one with a lymphocele in a nephrectomy bed, and one with obstructed intestinal lymphatic vessels after thoracotomy. Five patients had no evidence of lymphatic leakage. CT in one patient with evidence of a leak on lymphangiography showed extravasation of contrast medium into the mediastinum and pleural space. CT in three patients with no abnormalities on lymphangiography also showed no abnormalities. Four of the five thoracic duct lacerations and the lymphocele were confirmed surgically. The diagnosis of obstructed intestinal lymphatic vessels was supported clinically. Four of the five patients with normal findings on lymphangiograms had resolution of their pleural effusions and no evidence of recurrence during a follow-up period of 1-27 months. One patient with normal findings on lymphangiography had an alternative diagnosis established at surgery. Laceration of the thoracic duct was accurately diagnosed and localized with lymphangiography, which allowed definitive surgical repair. CT was of little additional value in diagnosing these injuries.
Bilateral diaphragm paralysis after cardiac surgery with topical hypothermia. Bilateral diaphragm paralysis is a rare but important complication of open heart surgery. Two cases were found among 360 prospectively studied patients undergoing open heart surgery during one year. Both patients had insulin dependent diabetes with peripheral neuropathy and this may have contributed to their diaphragm paralysis. The patients were studied postoperatively for one year with measurements of lung function, nocturnal oximetry, diaphragmatic function, and phrenic nerve conduction. Treatment with intermittent positive airway pressure ventilation by nasal mask was effective in both patients. After nine months one patient had recovered completely with normal phrenic nerve conduction and diaphragmatic function; the other continues most of his normal daytime activities, but still requires nasal positive airway pressure ventilation for six hours at night.
Physiological and anatomical evidence for a magnocellular defect in developmental dyslexia. Several behavioral studies have shown that developmental dyslexics do poorly in tests requiring rapid visual processing. In primates fast, low-contrast visual information is carried by the magnocellular subdivision of the visual pathway, and slow, high-contrast information is carried by the parvocellular division. In this study, we found that dyslexic subjects showed diminished visually evoked potentials to rapid, low-contrast stimuli but normal responses to slow or high-contrast stimuli. The abnormalities in the dyslexic subjects' evoked potentials were consistent with a defect in the magnocellular pathway at the level of visual area 1 or earlier. We then compared the lateral geniculate nuclei from five dyslexic brains to five control brains and found abnormalities in the magnocellular, but not the parvocellular, layers. Studies using auditory and somatosensory tests have shown that dyslexics do poorly in these modalities only when the tests require rapid discriminations. We therefore hypothesize that many cortical systems are similarly divided into a fast and a slow subdivision and that dyslexia specifically affects the fast subdivisions.
High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer. DNA methylation abnormalities occur consistently in human neoplasia including widespread hypomethylation and more recently recognized local increases in DNA methylation that hold potential for gene inactivation events. To study this imbalance further, we have cloned and localized to chromosome 19 a portion of the human DNA methyltransferase gene that codes for the enzyme catalyzing DNA methylation. Expression of this gene is low in normal human cells, significantly increased (30- to 50-fold by PCR analysis) in virally transformed cells, and strikingly elevated in human cancer cells (several hundredfold). In comparison to colon mucosa from patients without neoplasia, median levels of DNA methyltransferase transcripts are 15-fold increased in histologically normal mucosa from patients with cancers or the benign polyps that can precede cancers, 60-fold increased in the premalignant polyps, and greater than 200-fold increased in the cancers. Thus, increases in DNA methyltransferase gene expression precede development of colonic neoplasia and continue during progression of colonic neoplasms. These increases may play a role in the genetic instability of cancer and mark early events in cell transformation.
Arachidonic acid and docosahexaenoic acid are increased in human colorectal cancer. Increased arachidonic acid concentrations in experimental rodent colonic cancer have been described recently. In humans, a reduced erythrocyte stearic acid to oleic acid ratio has been reported in patients with colorectal cancer and it has been proposed that similar changes exist in the cancer tissue. The long chain fatty acids in the cancers of 15 patients with colorectal cancer were measured and compared with values in the unaffected mucosa. The values were expressed as mean (SD) mg fatty acid/g tissue and compared by analysis of variance. In the cancer tissue arachidonic acid was increased (0.703 (0.109) mg/g v 0.603 (0.127) mg/g, p less than 0.05) as was docosahexaenoic acid (0.211 (0.066) mg/g v 0.148 (0.039) mg/g, p less than 0.001). In contrast, the stearic acid to oleic acid ratio in the cancer tissue was increased rather than decreased, as previously suggested (0.36 (0.05) v 0.29 (0.7), p less than 0.01). Increased arachidonic acid and docosahexaenoic acid concentrations may be related to reduced lipid peroxidation, which is a feature of rapidly growing cells. Alternatively, the increased arachidonic acid values could be due to enhanced desaturase activity upon linoleic and linolenic acid, leading perhaps to increased formation of prostaglandins and other lipoxygenase products.
bcl-1 rearrangement. Frequency and clinical significance among B-cell chronic lymphocytic leukemias and non-Hodgkin's lymphomas. The authors investigated the structural organization of the bcl-1 locus, a putative oncogene associated with reciprocal chromosomal translocation t(11;14), by Southern blot hybridization analysis and its frequency, distribution, and prognostic significance in a panel of 156 clinically and pathologically well-defined B-cell chronic lymphocytic leukemias (CLLs) and non-Hodgkin's lymphomas (NHLs). The authors detected bcl-1 rearrangements in only 2 of 42 CLLs and 4 of 114 NHLs, specifically 3 of 29 diffuse small lymphocytic and 1 of 10 diffuse small cleaved cell and none of 5 diffuse intermediate lymphocytic, 13 follicular predominantly small cleaved, 17 follicular mixed small cleaved and large cell, 4 diffuse mixed small and large cell, 26 diffuse large cell, and 10 diffuse small noncleaved cell lymphomas. None of seven cases of Rai stage III or IV CLL or seven diffuse large cell lymphomas occurring as Richter's syndrome exhibited bcl-1 rearrangements. In conclusion, the bcl-1 locus rearranges in only about 4% of B-cell CLLs and NHLs, is predominantly rearranged in low-grade B-cell neoplasms, and does not appear to be preferentially associated with those occasional CLLs and low-grade NHLs displaying clinical aggressiveness, advanced clinical stage, or large cell transformation (Richter's syndrome). Therefore the demonstration of bcl-1 rearrangement does not appear to have clinically useful prognostic significance.
Naloxone reverses pattern of obstruction of the distal common bile duct induced by analgesic narcotics in hepatobiliary imaging. It is widely known that narcotics, such as morphine, cause spasm of the sphincter of Oddi, increasing pressure in the common bile duct. This pharmacologic effect has been applied to hepatobiliary scintigraphy in patients with chronic cholecystitis or cholestasis to reducing the time required for a diagnostic study. However, this feature of narcotics could result in delayed or nonvisualization of the small bowel, simulating a distal common bile duct obstruction, in patients requiring parenteral narcotic analgesics who must undergo hepatobiliary scintigraphy. We report on three patients where administration of intravenous naloxone hydrochloride (Narcan), a narcotic antagonist, was helpful in distinguishing narcotic-induced spasm of the sphincter of Oddi from true obstruction of the common bile duct.
Intrarectal sonography. A new technique for the assessment of rectal tumors. Preoperative staging of rectal tumors provides a selective therapeutic approach. Twenty-three patients were evaluated with prospective intrarectal sonography. Endosonography identified all 21 rectal lesions. Two patients with previous rectal carcinoma had no evidence of recurrence. Thirteen of 17 patients (76%) with rectal carcinoma were correctly staged by endosonography. A submucosal leiomyosarcoma and pararectal arachnoid cyst were correctly identified. Preoperative assessment of lymph node status was accurate in five of ten patients (50%). Results of preoperative digital rectal examination predicting rectal wall involvement correlated with pathologic findings in 11 of 15 patients (73%). Intrarectal sonography is an important staging technique for preoperative evaluation of rectal wall invasion and guides appropriate surgical intervention.