shukoor65/lab-rag-model huggingface dataset:
Fc epsilon RI-mediated hydrolysis of phosphoinositides in ghosts derived from rat basophilic leukemia cells. Aggregation of the high affinity receptor for IgE (Fc epsilon RI) on mast cells by a polyvalent Ag leads to hydrolysis of phosphoinositides (PI) catalyzed by phospholipase C (PI-PLC). To understand this phenomenon in molecular terms, it is important to obtain active, cell-free preparations. In extensive preliminary studies, we could not demonstrate Fc epsilon RI-mediated activation of PI-PLC in plasma membranes prepared by conventional methods from rat basophilic leukemia cells. We now report a stepwise approach involving preparation of cytoplasts from such cells and then hypotonic lysis of the cytoplasts to obtain active membrane vesicles. These membranes, best described as "ghosts," appear to reseal after losing greater than 90% of their soluble, cytoplasmic components and contain receptors that when aggregated, activate PI-PLC to hydrolyze endogenous phospholipids. Per unit of plasma membrane, the ghosts retain approximately 25% of Fc epsilon RI-mediated stimulation of PI-PLC relative to the cells. This activity requires ATP, magnesium, phosphoenolpyruvate, and, to a limited degree, calcium. Although an adequate amount of phosphatidylinositol biphosphate is present, the predicted spike of (1,4,5)-inositol trisphosphate is not seen, and the predominant inositol phosphate isomer is (1,4)-inositol bisphosphate. This is the first report of Fc epsilon RI-mediated activation of PI-PLC in a cytoplasm-depleted system that demonstrates activation of endogenous enzyme acting on endogenous substrate. In addition, it is the first such report for any receptor of the Ig superfamily.
Virchow-Troisier's lymph node in hepatocellular carcinoma. Virchow-Troisier's lymph node is rarely found in patients with hepatocellular carcinoma. When present, it may or may not accompany spread of the tumor to mediastinal lymph nodes. In a 20-year-old South African black man with hepatocellular carcinoma, a Virchow-Troisier's node was evident clinically and confirmed at necropsy. Mediastinal lymph nodes were not involved by tumor, and the malignant cells probably gained access to the thoracic duct by way of lymphatic spread to the hepatic lymph nodes in the porta hepatitis and the celiac nodes, both of which were seen at necropsy to be extensively invaded by tumor.
How much testing is needed after myocardial infarction? Both physicians and patients should be encouraged by the tremendous progress made in the clinical care of patients with heart disease during the last 20 years. However, the number of invasive and noninvasive tests is vast, so they need to be applied judiciously, using a reasonable set of clinical principles to recognize the needs of the individual patient. In the case of myocardial infarction, one of the most important prognostic factors is left ventricular systolic function, which is commonly measured by the ejection fraction. This measurement can be made with a left ventriculogram, radionuclide ventriculogram, or two-dimensional echocardiogram, the choice depending on individual circumstances.
Epidemiology, pathophysiology, and management of isolated systolic hypertension in the elderly. Isolated systolic hypertension (ISH) is a common disorder in the elderly, carrying with it a high risk of cardiovascular morbidity and mortality. Environmental and age-related factors believed to contribute to ISH include obesity, declining physical activity, stress, and such dietary changes as increased salt intake and decreased intake of calcium and potassium. Increased rigidity of the aorta resulting in reduced compliance is an important hemodynamic feature, but factors that increase peripheral resistance also appear to play a role. Antihypertensive drugs have been shown to effectively and safely lower the systolic blood pressure elevations characteristic of ISH. To date, use of low drug doses and careful titration of dosage have avoided significant orthostatic hypotension and undue lowering of the diastolic pressure. Studies of relatively small groups of patients suggest that antihypertensive drugs can lower the risk of cardiovascular morbidity/mortality associated with ISH but the definitive answer awaits results of the ongoing large-scale Systolic Hypertension in the Elderly Program trial. In the interim, management should begin with conservative measures such as weight loss, salt restriction and, possibly, calcium supplementation. If this fails, drug therapy should be considered in patients with systolic blood pressures above 180 mm Hg and in those with systolic readings between 160 and 180 mm Hg who have concomitant cardiovascular risk factors. To date, no controlled trials of sufficient size have demonstrated that one drug class is more effective than another in treating ISH. Drug therapy should be tailored to the individual patient, starting with a low dose of a single drug and, if necessary, slowly increasing dosage until a systolic blood pressure under 160 mm Hg is attained.
Retinoblastoma. The long-term appearance of radiated intraocular tumors. A retrospective analysis of 50 patients with retinoblastoma was undertaken to determine the appearance of intraocular retinoblastoma that had received external beam radiation a minimum of 10 years previously. Of the 91 tumors found in 59 eyes, 76 (84%) continued to be ophthalmoscopically visible after 10 years. The most common ophthalmoscopic appearance was a Type III regression pattern. The type of radiation regression pattern correlated with the pretreatment volume of the tumor. The largest tumors (mean, 10.0 disc diameter [dd]) became Type I regression patterns, whereas the smallest tumors (mean, 1.0 dd) completely disappeared. This represents the first long-term follow-up of the intraocular status of radiated retinoblastoma.
L-type cardiac calcium channels in doxorubicin cardiomyopathy in rats morphological, biochemical, and functional correlations. Doxorubicin (DXR) is an effective antitumor agent in a wide spectrum of neoplasms. Chronic treatment is associated with cardiomyopathy and characteristic myocardial ultrastructural changes, which include swelling of the t tubules. Accordingly, we investigated excitation-contraction coupling in cardiomyopathic rat heart resulting from chronic DXR treatment. Using the whole-cell patch clamp technique, we studied the L-type calcium channel in single cells enzymatically isolated from normal (CTRL) and DXR rat hearts. Despite similar cell dimensions, the total membrane capacitance was significantly smaller in the DXR cells (138 +/- 9 pF) than in the CTRL cells (169 +/- 11 pF) (mean +/- SEM, n = 9, P less than 0.05). The mean current and the current density-voltage relationships of the CTRL and the DXR cells were significantly different (n = 9, P less than 0.001) with the maximal peak L-type calcium current (ICa) density increased from 6.4 +/- 0.9 in CTRL cells to 10.5 +/- 2.4 microA/cm2 in the DXR cells (P less than 0.05). There was no shift either in the current-voltage relationship or the steady-state inactivation curve in the two cell groups. However, the fast time constant of inactivation was increased at a membrane voltage of -10 to 10 mV. Calcium channel antagonist equilibrium binding assays using [3H]-PN200-110 revealed no difference in the maximal receptor binding capacity (CTRL, 194 +/- 27 and DXR 211 +/- 24 fmol/mg protein; P greater than 0.05, n = 6) and in receptor affinity (CTRL, 0.15 +/- 0.05 and DXR 0.13 +/- 0.03 nM; P less than 0.05). These data suggest that a decrease in effective capacitance might be associated with t-tubular damage. Despite this decrease, ICa was increased in the DXR cells. Such an increase may result from an alteration in the properties of the calcium channels and/or recruitment of "hibernating" channels in the remaining surface and t-tubular membranes.
Hypersomnia in bipolar depression: a comparison with narcolepsy using the multiple sleep latency test. OBJECTIVE: This study characterized objectively the hypersomnia frequently seen in the depressed phase of bipolar affective disorder. On the basis of previous work in sleep and affective disorders, it has been hypothesized that the hypersomnia is related to greater REM sleep. This hypothesis was tested by using a multiple sleep latency test to compare bipolar affective disorder with narcolepsy, a well-defined primary sleep disorder associated with known REM sleep dysfunction. METHOD: Twenty-five bipolar depressed patients were selected on the basis of complaints of hypersomnia. They underwent 2 nights of polysomnography followed by a multiple sleep latency test. Data on their nocturnal sleep and daytime naps were compared with similar data on 23 nondepressed narcoleptic patients referred for sleep evaluation. RESULTS: Despite their complaints of hypersomnia, no abnormalities were noted for the bipolar group in the results from the multiple sleep latency test. Contrary to the working hypothesis, REM sleep was notably absent during daytime naps in the depressed patients, in marked contrast to the findings for the narcoleptic group. CONCLUSIONS: The complaint of sleepiness in the hypersomnic bipolar depressed patient appears to be related to the lack of interest, withdrawal, decreased energy, or psychomotor retardation inherent in the anergic depressed condition, rather than an increase in true sleep propensity or REM sleep propensity.
Overzealous resuscitation of an extremely malnourished patient with nutritional cardiomyopathy. Overzealous resuscitation of the severely malnourished patient may be associated with life-threatening complications. A variety of electrolyte, hemodynamic, septic, and nutritional derangements may result in sudden decompensation and even death. We present a case that dramatically illustrates these complications and focuses on the key role of underlying nutritional cardiomyopathy.
Role of quinsy tonsillectomy in the management of peritonsillar abscess. Peritonsillar abscess (PTA) is the most frequent complication of acute tonsillitis requiring surgical intervention. Debate continues concerning optimal therapy in terms of patient morbidity and cost-effectiveness. A retrospective study was performed on 45 tonsillectomies for PTA in military personnel from December 1986 through December 1988. Twenty-three quinsy (abscess) tonsillectomies and 22 interval tonsillectomies were identified. Parameters studied were age, sex, abscess location, interval prior to operation, blood loss, operative time, operative experience, and combined hospital and convalescent days for the two groups. Significant differences were noted between the quinsy and interval tonsillectomy groups concerning the average number of days hospitalized (3.0 versus 4.5) and their respective convalescent periods (10.3 versus 17.3). We conclude that quinsy tonsillectomy is the best management for PTA in a young work force when the optimal treatment choice is between interval or acute tonsillectomy.
Preventing death after traumatic rupture of the aorta. A chest film may help save a life. Traumatic rupture of the aorta is a life-threatening injury that necessitates immediate diagnosis and surgical repair. Diagnosis depends on recognition of findings on a plain chest film, specifically, mediastinal widening, left hemothorax, and an apical cap sign. Aortography should be done immediately to establish the diagnosis when clinical and/or radiographic findings suggest a rupture.
Pediatric emergency transport and the private practitioner. A mail survey of 182 pediatricians and 92 family practitioners in Pennsylvania was conducted to determine their methods of transport of seriously ill children from their offices to referral centers and their involvement with professional transport services. Although most physicians (93.1%) stated that they had professional services available to them (at their office location), more than half (53.8%) indicated that the patient's family automobile was their most commonly used method of transport of ill children to tertiary care centers. This was true regardless of the disease entity involved, including suspected epiglottitis. Practice setting had little influence on transport method. However, in general, younger children were judged to need ambulance transport more often than older children. Reasons cited for not using professional transport from the office included a perceived better efficiency of the family car (61.8%), the prohibitively high expense of professional transport (9.8%), and failure to consider professional transport (6.5%). Further study of this component of office preparedness is suggested.
Lowe oculocerebrorenal syndrome in a female with a balanced X;20 translocation: mapping of the X chromosome breakpoint. A Hispanic girl with Lowe oculocerebrorenal syndrome (OCRL), an X-linked recessive condition characterized by cataracts, glaucoma, mental retardation, and proteinuria, is reported. A balanced X;20 chromosomal translocation with the X chromosome breakpoint at q26.1 was found with high-resolution trypsin-Giemsa banding. Somatic cell hybridization was used to separate the X chromosome derivative and the chromosome 20 derivative in order to position, with respect to the translocation breakpoint, several DNA loci that are linked to the Lowe syndrome locus (Xq24-q26). DXS10 and DXS53 were found to be distal to the breakpoint, whereas DXS37 and DXS42 were located proximal to it. These studies suggest that the OCRL locus lies in the region between these probes. The translocation chromosome originated from an unaffected male without a visible translocation, indicating that the most likely cause of OCRL in this patient is the de novo translocation that disrupted the OCRL locus.
Long-term clinical follow-up of adult idiopathic pulmonary hemosiderosis and celiac disease. A 22-year-old man with a history of repeated whole blood transfusions since the age of 7, was admitted to the hospital for dyspnea and blood-stained sputum. A complete blood cell count, a test for reticulin antibodies, an x-ray film of the chest, a transbronchial biopsy and a biopsy of the small bowel were performed and the results confirmed the diagnosis of IPH, associated with CD. The patient has been asymptomatic for four years on a gluten-free diet. In cases of IPH, it may be important to investigate the coexistence of CD because treatment of the latter could lead to a better prognosis.
Prednisone inhibits the appearance of inflammatory mediators and the influx of eosinophils and basophils associated with the cutaneous late-phase response to allergen. To better define the effect of systemic glucocorticoids on the cutaneous early and late phase response (LPR), nine atopic subjects were examined in a double-blind cross-over study using skin chambers fixed over denuded skin blisters. A challenge was carried out by placing allergen in the chamber for 60 min in subjects who received either a 3-day pretreatment with 60 mg/day of prednisone or placebo. Skin chamber cell counts and inflammatory mediators (histamine, PGD2, and leukotriene C4 (LTC4)) were measured at hourly intervals for 12 h. Prednisone pretreatment did not alter the immediate skin erythema or release of histamine but ablated the late secondary erythema and rise in histamine. The median histamine values during h 10, 11, and 12 in the placebo and prednisone pretreatment visits were 3.73 and 0.22 ng/ml, respectively (p less than or equal to 0.02). Prednisone did not alter PGD2 production; however, LTC4 production was suppressed during the LPR. The cumulative median LTC4 values during h 7, 8, and 9 were 5.6-fold (p less than or equal to 0.05) more after placebo than after prednisone pretreatment. Prednisone altered cellular traffic more dramatically than it did inflammatory mediators. The influx of eosinophils, which peaked during the 9th and 10th h in placebo-treated patients, was completely blocked by prednisone (p less than or equal to 0.02) for every h from 6 through 12. The influx of basophils, which started during the 9th h and peaked during the 12th h in placebo-treated patients, was suppressed at all time points (p less than or equal to 0.02) in prednisone-treated patients. There was no significant alteration in neutrophil transit into the skin chambers induced by prednisone. We suggest that the selective blockade of eosinophil and basophil influx by prednisone and the associated decrease in inflammatory mediators may contribute to the blockade of the clinical expression of the cutaneous LPR.
Separate sex-influenced and genetic components in spontaneously hypertensive rat hypertension. Previous results from our laboratory indicated two major genetic components of spontaneously hypertensive rat (SHR) hypertension, an autosomal component and a Y chromosome component. Two new substrains, SHR/a and SHR/y, were developed using a series of backcrosses to isolate each of these components. The SHR/a substrain has the autosomal loci and X chromosome from the SHR strain and the Y chromosome from the Wistar-Kyoto (WKY) rat strain. The SHR/y substrain has only the Y chromosome from the SHR and autosomal loci and X chromosome from the WKY strain. Throughout these breeding programs parents were chosen at random without selection for blood pressure. Males of both substrains maintained blood pressures over 180 mm Hg. Comparisons of blood pressure in these new substrains with the original parental strains can be used to determine the relative proportions of each genetic component in hypertension. The Y chromosome component contributes 34 mm Hg, which is the difference between SHR/y male and WKY male blood pressure. The total autosomal component contributes 46 mm Hg, which is the difference between SHR/a male and WKY male blood pressure. The autosomal component is a sex-influenced trait; males in the SHR/a strain have significantly higher pressures than SHR/a females. Of the 46 mm Hg estimated for the autosomal component, 41 mm Hg is the result of these loci interacting with male phenotypic sex. This sex-influenced component is separate and distinct from the Y chromosome component.
Elective total hip arthroplasty in patients older than 80 years of age. Elective total hip arthroplasties (THA) were performed in 91 patients (101 hips) older than 80 years of age at operation. A control group of 87 patients (102 hips) aged 64 to 67 years who had elective THA was chosen statistically to represent the average THA patient. There were 51 minor and eight major perioperative complications in the elderly group and 26 minor and two major complications in the control group. The only in-hospital death was in the control group. The mean hospital stay was two days longer in the elderly group. Five years postoperatively, 83% of the patients in both groups were ambulating without pain. The mean hip score improved from 49 to 84 points in the elderly group and from 52 to 88 points in the control group. These functional results justify elective THA in patients older than 80 years of age.
Fractures of the dens complicating ankylosing spondylitis with atlantooccipital fusion. Patients with ankylosing spondylitis are prone to fractures. Fractures tend to occur in the lower cervical spine disc space. We describe 2 patients with odontoid fractures. Both patients had atlantooccipital fusion which may have increased their susceptibility for dens fractures. One patient had Crohn's disease.
Cytokine influence on killing of fresh chronic lymphocytic leukemia cells by human leukocytes. The feasibility of combining the Lym-1 monoclonal antibody (MoAb) with interferon-gamma (IFN-gamma) in the treatment of chronic lymphocytic leukemia (CLL) was evaluated. We used an in vitro tumor lysis model that incorporated fresh CLL cells from 21 different patients as targets for two distinct normal human leukocyte effector subsets, neutrophils, and peripheral blood mononuclear cells (PBMCs). Lym-1 antigen (Lym-1-Ag) expression varied greatly and did not correlate with the expression of other CLL-associated antigens such as CD5, CD19, or HLA-DR. CLL cells were not lysed by neutrophils alone or with IFN-gamma in the absence of Lym-1. Neutrophil Lym-1-dependent cytotoxicity (ADCC) in the absence of IFN-gamma was weak and inconsistent. IFN-gamma exposure induced MoAb-dependent lysis of 80% of 21 CLL targets and resulted in an eightfold augmentation of neutrophil ADCC against the remainder. Cytotoxicity correlated directly and positively with Lym-1-Ag expression. Confirmation of the need for interaction between neutrophil IgG Fc receptors (Fc gamma Rs) and the Fc portion of the Lym-1 MoAb was obtained by demonstrating that purified Staphylococcus aureus Protein A (SpA) inhibited ADCC. IFN-gamma exposure caused no consistent alternations in Lym-1-Ag expression on CLL cells so that target antigen upregulation was unlikely to account for augmentation of neutrophil ADCC. PBMCs alone, exposed to interkeukin-2 (IL-2) or IFN-gamma, or with Lym-1 in the presence or absence of IL-2 or IFN-gamma were unable to lyse CLL targets. PBMCs were able to kill Raji Burkitt lymphoma cells in conjunction with Lym-1, so their ability to interact with Lym-1-coated targets and their lytic functions appeared intact. These results emphasize the importance of examining fresh tumor cells with different leukocyte effector subsets before designing a clinical trial that combines a therapeutic MoAb with a cytokine.
Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Idiopathic pulmonary fibrosis is an inexorably fatal disorder characterized by connective tissue deposition within the terminal air spaces resulting in loss of lung function and eventual respiratory failure. Previously, we demonstrated that foci of activated fibroblasts expressing high levels of fibronectin, procollagen, and smooth muscle actin and thus resembling those found in healing wounds are responsible for the connective tissue deposition and scarring in idiopathic pulmonary fibrosis. Using in situ hybridization and immunohistochemistry, we now demonstrate the presence of transforming growth factor beta 1 (TGF-beta 1), a potent profibrotic cytokine, in the foci containing these activated fibroblasts. These results suggest that matrix-associated TGF-beta 1 may serve as a stimulus for the persistent expression of connective tissue genes. One potential source of the TGF-beta 1 is the alveolar macrophage, and we demonstrate the expression of abundant TGF-beta 1 mRNA in alveolar macrophages in lung tissue from patients with idiopathic pulmonary fibrosis.
Vasopressin-dependent kidney hypertrophy: role of urinary concentration in protein-induced hypertrophy and in the progression of chronic renal failure. Recent experiments have shown that the kidney adapts to chronic variations in urine concentration. Glomerular filtration rate (GFR), kidney weight relative to body weight, thickness of inner stripe of the outer medulla, volume of epithelium in early thick ascending limb, and internephron heterogeneity are all decreased by chronic water diuresis and increased by chronic stimulation of urine concentration. It was further shown that the intrarenal pattern of hypertrophy observed after high protein (HP) intake, but not that observed after compensatory hypertrophy or normal growth with age, is exactly similar to that observed after chronic stimulation of urine concentration. Since solute-free water reabsorption (TcH2O) is markedly enhanced by HP diet, this suggests that the increases in GFR and renal mass observed after HP intake are, at least in part, an adaptive response of the kidney to increased urinary concentrating activity. The beneficial effects are induced by protein restriction in chronic renal failure (CRF) could thus be due, in part, to the reduction of this concentrating activity. This hypothesis was confirmed by an experiment performed in rats with experimental chronic renal failure (CRF) in which a chronic increase in water intake, reducing urine osmolality and TcH2O, without any change in food composition or consumption, reduced proteinuria, systemic hypertension, kidney hypertrophy, incidence of glomerulosclerosis, and mortality.