Search PubMed⌕ Search

Biomedical subjects

G Raghu

Publications and source records attributed to G Raghu.

At least 73 records · Page 4Linked to original sources
PubMed1991

Reversed helper/suppressor T-lymphocyte ratio in bronchoalveolar lavage fluid from patients with breast cancer and Pneumocystis carinii pneumonia.

Pneumocystis pneumonia (PCP) usually occurs in patients with hematologic malignancies and acquired immunodeficiency syndrome (AIDS). Patients with solid tumors represent a very small fraction of the reported cases of PCP. Over an 18-month period, PCP was diagnosed in three patients who had received radiation and chemotherapy for breast cancer. In all three patients, there was no serologic or clinical evidence of AIDS. Direct staining of bronchoalveolar lavage fluid (BAL) revealed Pneumocystis carinii, and cellular analysis of BAL revealed an increased percentage of lymphocytes with reversed helper/inducer:suppressor/cytotoxic T-cell (CD4:CD8) ratio. Because decreased CD4:CD8 ratio in BAL is commonly accepted as findings consistent with hypersensitivity pneumonitis and AIDS, we conclude that similar findings in patients without AIDS are not specific for hypersensitivity pneumonitis, and P. carinii should be ruled out in the appropriate clinical setting.

Adult↗
PubMed1991

Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial.

Twenty-seven newly diagnosed patients with idiopathic pulmonary fibrosis (IPF) who were previously untreated for IPF were enrolled in a prospective, double-blind, randomized, placebo-controlled study to compare the therapeutic effect of combined prednisone/azathioprine (n = 14) with prednisone plus placebo (n = 13). Prednisone was started at 1.5 mg/kg/day (not to exceed 100 mg/day) for the first 2 wk followed by a biweekly taper to a maintenance dose of 20 mg/day. Azathioprine was administered at a daily dose of 3 mg/kg (not to exceed 200 mg/day). The patients tolerated the use of azathioprine well with few associated side effects. Changes in lung function at 1 yr, as measured by resting alveolar-arterial oxygen difference P[A-a]O2, FVC, and single breath diffusing capacity for carbon monoxide (DLCOSB), were all somewhat better in the azathioprine/prednisone group compared with the prednisone alone group, although none of these comparisons were statistically significant. Six of 14 (43%) patients randomized to prednisone plus azathioprine died during the 9-yr follow-up period, compared with 10 of 13 (77%) patients randomized to prednisone plus placebo. A Cox model survival analysis shows a nonsignificant but potentially large survival advantage for azathioprine/prednisone (hazard ratio 0.48, with 95% confidence interval increasing from 0.17 to 1.38). When adjusted for age, the survival advantage of azathioprine/prednisone becomes marginally significant (hazard ratio 0.26, with 95% confidence interval increasing from 0.08 to 0.88; p = 0.02 by large sample approximation, p = 0.05 by randomization test). We conclude that combined prednisone and azathioprine is a safe and possibly effective regimen for the treatment of IPF.(ABSTRACT TRUNCATED AT 250 WORDS)

Azathioprine↗
PubMed1990

Esophagobronchial fistula and mediastinal tuberculosis.

A 59-year-old man was seen with what preoperatively was thought to be an acquired esophagobronchial fistula secondary to an old burned-out infection with tuberculosis. At operation the gross and microscopic findings were most compatible with a congenital H-shaped esophagobronchial fistula. However, cultures of calcified lymph nodes grew Mycobacterium tuberculosis. The need for culturing calcified tissue to assure proper treatment is emphasized.

Bronchial Fistula↗
PubMed1990

Transplantation studies in mice with congenital hemolytic anemia.

Sphha/sphha anemic mice have an abnormality in the erythroid membrane protein, alpha spectrin, and exhibit multiple related clinical abnormalities, including spherocytosis, shortened red cell survival, chronic hemolysis, hemosiderosis, and extramedullary hematopoiesis. In addition, these mutant mice exhibit a granulocytosis and lymphocytosis, lymph node hyperplasia, elevated serum immunoglobulins, membranoproliferative glomerulonephritis, and decreased lifespan--abnormalities that are less clearly attributable to a spectrin defect. In order to further elucidate the mechanisms of disease in these animals, we undertook a series of bone marrow transplantation experiments. Transplantation of anemic marrow into lethally irradiated congenic +/+ mice resulted in chronic spherocytosis, hemolytic anemia, peripheral leukocytosis, and extramedullary hematopoiesis. Additionally, transplant recipients of anemic marrow which had received a higher radiation dose (12 Gy) had increased numbers of peripheral blood CD4+ and CD8+ lymphocytes, a hypocellcular thymus, and a severe pneumonitis characterized by nodular areas of consolidation and edema. Mice receiving congenic +/+ marrow and irradiated with the same radiation dose exhibited minimal pulmonary abnormalities. Anemic mice transplanted with congenic +/+ marrow usually died, but the survivors exhibited reversal of some clinicopathological changes. These results would suggest that the clinical abnormalities of sphha/sphha mice are in part attributable to abnormalities of hematopoietic stem cells but may also involve defects in other cell types. The pathogenesis of the accompanying lymphoid abnormalities observed in this mutant anemic mouse and any correlation with the erythroid spectrin defect are presently unknown. The pulmonary disease that develops in the transplant recipients of anemic marrow needs to be characterized further but may represent a unique model of lung injury.

Anemia, Hemolytic, Congenital↗
PubMed1990

Identification of a closely linked DNA marker, DXS178, to further refine the X-linked agammaglobulinemia locus.

X-linked agammaglobulinemia (XLA) is an inherited recessive disorder in which the primary defect is not known and the gene product has yet to be identified. Utilizing genetic linkage analysis, we previously localized the XLA gene to the map region of Xq21.3-Xq22 with DNA markers DXS3 and DXS17. In this study, further mapping was performed with two additional DNA probes, DXS94 and DXS178, by means of multipoint analysis of 20 families in which XLA is segregating. Thirteen of these families had been previously analyzed with DXS3 and DXS17. Three crossovers were detected with DXS94 and no recombinations were found between DXS178 and the XLA locus in 9 informative families. Our results show that XLA is closely linked to DXS178 with a two-point lod score of 4.82 and a multipoint lod score of 10.24. Thus, the most likely gene order is DXS3-(XLA,DXS178)-DXS94-DXS17, with the confidence interval for location of XLA lying entirely between DXS3 and DXS94. In 2 of these families, we identified recombinants with DXS17, a locus with which recombination had not previously been detected by others in as many as 40 meiotic events. Furthermore, DXS178 is informative in both of these families and does not show recombination with the disease locus. Therefore, our results indicate that DXS178 is linked tightly to the XLA gene.

Agammaglobulinemia↗
PubMed1989

Collagen synthesis by normal and fibrotic human lung fibroblasts and the effect of transforming growth factor-beta.

Collagen accumulation is a major feature of pulmonary fibrosis and other fibrotic lesions. We have studied the synthesis of collagens in fibroblasts cultured from normal and fibrotic human lung specimens and evaluated how it is affected by transforming growth factor-beta (TGF-beta). Fibroblasts were obtained from normal and fibrotic adult human lungs (n = 11; normal = 6, idiopathic pulmonary fibrosis = 5). They were exposed to TGF-beta and pulse-labeled with [3H]proline and [3H]glycine. Collagen production was measured as bacterial collagenase-susceptible radioactivity, and collagen mRNA levels were determined by a solution hybridization assay using labeled procollagen alpha 1[I] cDNA clone HF677 as probe. Synthesis of collagen types I, III, and V were assessed after separating them by DEAE-cellulose chromatography and SDS-polyacrylamide gel electrophoresis. The results showed that both normal and fibrotic lung fibroblasts synthesized similar amounts of collagen. Type I was the major collagen species synthesized by both normal and fibrotic cell types, and the relative proportion of type I, III, and V collagens was similar in both cell types. TGF-beta caused a two to fourfold increase in stimulation of collagen production and collagen mRNA levels, and no differences were detected in the response of normal and fibrotic lung fibroblasts. All collagen types were stimulated by the TGF-beta. TGF-beta did not increase fibroblast proliferation and the majority of normal and fibrotic lung cells exposed to TGF-beta remained in G1 phase of the cell cycle. We conclude that fibroblasts of normal and fibrotic human synthesize similar amounts of collagens.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1988

Differential proliferation of fibroblasts cultured from normal and fibrotic human lungs.

We studied the behavior of the cell cycle of cultured, early-passage human diploid pulmonary fibroblastlike cells (HDPFC) when grown in the presence of several growth factors. The rates of growth and growth fractions were studied in cultures from different origins. As much as 85 +/- 5% (SE) of HDPFC cultured from specimens with early fibrosis were cycling when the cells were grown in basal media supplemented with 10% serum or growth factors. In contrast, 55% +/- 8% (SE) of HDPFC from normal lung and only 31% +/- 5% (SE) of HDPFC cultured from specimens with dense fibrosis were cycling in those culture conditions. Results obtained by removal of any of the five growth factors from the defined medium indicated that the altered growth patterns were not related to any single growth factor tested. These studies are consistent with the hypothesis that HDPFC cultured from specimens with early fibrosis have a greater proliferative potential than HDPFC from late fibrosis.

Adult↗
PubMed1987

Pulmonary fibrosis following pneumonia due to acute Legionnaires' disease. Clinical, ultrastructural, and immunofluorescent study.

During a recent nosocomial outbreak, 20 critically ill patients with acute Legionnaires' disease were admitted to the intensive care unit of Hopital Bichat, Paris. Pulmonary specimens were obtained at surgery or immediately after death in 12 patients and were examined by light, immunofluorescent, and electron microscopy. Five of these 12 patients showed evidence of pulmonary fibrosis. In all of these five patients, infection with Legionella pneumophila was evidenced by bacteriologic methods, and other diseases known to cause fibrosis were excluded. The condition of four patients deteriorated rapidly with respiratory failure, and they died with pulmonary fibrosis. Only one patient finally recovered but was left with pulmonary sequelae. Two distinctive morphologic patterns were observed, one in which interstitial fibrosis was predominant and one in which intra-alveolar organization and fibrosis were also present. The alveolar epithelial lining and the basement membranes were disrupted in all patients, as evidenced by ultrastructural observations and by immunofluorescent studies showing gaps in the distribution of type 4 collagen and laminin. Types 1 and 3 collagen accumulated in areas corresponding to thickened interstitium and intra-alveolar fibrosis. Thus, some patients who survive the acute pneumonia of Legionnaires' disease may develop pulmonary fibrosis, and this process may lead to functional impairment or death despite prompt and appropriate treatment.

Adult↗
PubMed1986

Lipopolysaccharide-mediated injury to cultured human glomerular endothelial cells.

Lipopolysaccharide induced a dose-dependent detachment of human glomerular cells in vitro. The detachment occurred 24 hr after exposure to endotoxin. Human umbilical vein endothelial cells were not affected by more prolonged exposure or higher concentrations of lipopolysaccharide in the medium. The lipopolysaccharide effect was independent of complement components or leukocytes.

Animals↗
PubMed1986

Reexpansion hypotension. A complication of rapid evacuation of prolonged pneumothorax.

Three cases of hypotension are described that followed rapid evacuation of persistent unilateral pneumothorax. Common features included the presence of a pneumothorax for approximately one week before treatment commenced and profuse unilateral reexpansion edema, a rising hematocrit reading, hypotension, and anuria after evacuation of the pneumothorax in spite of a relatively normal pulmonary capillary wedge pressure. In one case, cardiac output was measured and found to be low (1.54 and 1.65 L/min/sq m), with a pulmonary capillary wedge pressure of 10 to 14 mm Hg. Death due to cardiovascular collapse occurred in one patient; ischemic colitis, acute renal failure, disseminated intravascular coagulation, and ischemic necrosis of both humeral heads occurred in another. The cases presented and the literature reviewed suggest that cardiovascular compromise was the end result of the combined effects of intravascular volume depletion and myocardial depression.

Adult↗
PubMed1986

Cytoskeletal changes as an early event in hydrogen peroxide-induced cell injury: a study in A549 cells.

Hydrogen peroxide (H2O2) and other oxygen metabolites have been implicated in the pathogenesis of cell and tissue injury. The nature of the injury occurring in cells exposed to oxygen metabolites is unknown. A549 cells, derived from human lung carcinoma, were exposed to glucose-glucose oxidase or hydrogen peroxide in vitro. The distribution of actin and cytokeratin filaments, as well as 51chromium (51Cr) release and trypan blue dye exclusion were assessed. Both glucose-glucose oxidase and H2O2 resulted in changes which were time- and dose-dependent. Alterations in the cytoskeleton were detected by immunofluorescence microscopy at two hours, at which time the cells excluded trypan blue dye, while 51Cr release and trypan blue uptake first occurred at 8 h and required a five-fold greater concentration of glucose oxidase. The addition of catalase to glucose-glucose oxidase or H2O2, or inactivation of glucose oxidase by boiling, abrogated the injury. Therefore, one of the early targets of H2O2-induced cell injury may be the cytoskeleton.

Actins↗
PubMed1985

Extracellular matrix in normal and fibrotic human lungs.

Polyclonal affinity-purified antibodies to human collagen types I, III, and IV, and laminin were used to compare the extracellular matrix (ECM) in 10 normal and 32 abnormal lungs by indirect immunofluorescence. In normal lungs, type IV collagen and laminin codistributed in a uniform linear pattern along the epithelial and endothelial basement membranes. Type III collagen was found within the alveolar septa and interstitium in an interrupted ribbonlike pattern and was aggregated at the entrance rings of the alveoli. Type I collagen was distributed irregularly within the alveolar wall and was less prominent than type III collagen. In patients with pulmonary disease not characterized by interstitial fibrosis (n = 15), the distribution of ECM components studied was essentially normal. In pulmonary disease in which interstitial fibrosis was the characteristic feature, such as idiopathic pulmonary fibrosis (IPF) and adult respiratory distress syndrome (ARDS) (n = 17), collagen types I and III accumulated in the expanded interstitium. Type III collagen was initially predominant in the thickened alveolar septa and interstitium, whereas type I collagen appeared to be the principal collagen at later stages in the disease course. The basement membrane was disrupted early in the disease course with invasion of the alveolar spaces by interstitial collagens similar in type to those present in the adjacent interstitium.

Adult↗
PubMed1985

The effects of chronic bronchitis and chronic air-flow obstruction on lung cell populations recovered by bronchoalveolar lavage.

Bronchoalveolar lavage is used to evaluate parenchymal inflammation in patients with diffuse lung disease. Normal values for lavage cell counts and proteins are derived primarily from young subjects who are free from lung disease; however, older patients who undergo bronchoalveolar lavage often have used cigarettes for long periods of time and have developed variable degrees of chronic bronchitis and/or chronic air-flow obstruction. Therefore, we evaluated the effects of cigarette use, chronic bronchitis, and chronic air-flow obstruction on lavage cell populations by performing bronchoalveolar lavage in 48 male patients who were undergoing diagnostic fiberoptic bronchoscopy. Sixteen patients (33%) had elevated percentages of neutrophils (greater than or equal to 10%) in lavage fluid. Fourteen of these (87.5%) had chronic cough and/or phlegm production, but only 9 (64.3%) met criteria for definite chronic bronchitis. Patients with moderate or severe air-flow obstruction, defined spirometrically, had significantly greater percentages of lavage neutrophils and lower percentages of macrophages than did patients with mild or no air-flow obstruction. The first lavage aliquot contained the greatest proportion of neutrophils and the smallest proportion of macrophages. The percentage of neutrophils declined and the percentage of macrophages increased in sequential aliquots. The data indicate that patients with chronic cough and/or phlegm production and chronic air-flow obstruction may have increased proportions of neutrophils in bronchoalveolar lavage fluid in the absence of diffuse parenchymal lung disease or infections. These variables must be taken into account when interpreting lavage cellular analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗
PubMed1984

Polymyositis and interstitial lung disease in a patient with anti-Jo1 prototype.

The most common marker autoantibody among patients with polymyositis is anti-Jo1. The patient (John P.) providing the prototype serum for this specificity had both interstitial lung disease and polymyositis. A preliminary survey by Ouchterlony analysis and counter immunoelectrophoresis of serum from 15 patients with idiopathic interstitial lung disease revealed no anti-Jo1 or other precipitating autoantibodies. This provides no evidence to suggest that anti-Jo1 has specificity for interstitial lung disease per se. However, this autoantibody may serve as a possible marker for some patients with overlap of polymyositis and interstitial lung disease. The several interesting features about this patient's diseases and course are discussed.

Antibody Specificity↗
PubMed1984

Diagnosis of right hemidiaphragmatic rupture by liver scintigraphy.

We report two cases of traumatic rupture of the right hemidiaphragm with liver herniation following blunt abdominal trauma. In both, the diagnosis was not immediately suspected, and liver scintigraphy was later diagnostic. Focal elevation of the central portion of the right lobe of the liver was present in both cases. In one case the herniated liver was surrounded by a band-like photon-deficient collar. Liver scintigraphy can be quickly performed by portable technique and may allow for early diagnosis.

Adolescent↗
PubMed1983

Antibodies to Mi-1 in SLE: relationship to other precipitins and reaction with bovine immunoglobulin.

Precipitating antibodies to Mi-1, a protein antigen purified from calf thymus nuclear extract, have been reported in a small percentage of patients with dermatomyositis (DM) but not in patients with other connective tissue diseases or controls. Mi-1 shares certain characteristics with immunoglobulin, including the ability to react with rabbit anti-bovine immunoglobulin G (BIgG). A more extensive survey for anti-Mi-1 has been performed, involving 51 normal controls, 67 patients with polymyositis (PM) or DM, 47 patients with rheumatoid arthritis (RA), 41 SLE patients without any other precipitating antibodies to saline extractable tissue antigens on routine testing, and 247 patients, many with SLE, known to have other precipitins. Anti-Mi-1 was found in 13 patients from the latter group (5.25%) and two patients with PM or DM (3.0%), and was not found in other groups. It was found in seven of 95 (7.4%) with anti-nRNP, three of 32 (9.4%) with anti-Sm (with or without anti-nRNP) and three of 120 (2.5%) with anti-Ro (SSA). Anti-Mi-1 cross-reacts directly with BIgG but differs from ordinary rheumatoid factor in its frequent reaction with Fab2 fragments and restricted species specificity. Thus, anti-Mi-1 can be found in patients with diseases other than DM, including SLE, most often in patients with antibodies to nRNP.

Arthritis, Rheumatoid↗
PubMedDate not supplied

High resolution CT in respiratory bronchiolitis-associated interstitial lung disease.

High-resolution CT findings have been described for several diffuse lung diseases. Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is an inflammatory lung disorder associated with cigarette smoking. This condition has only recently been described and distinguished from desquamative interstitial pneumonitis, which it closely resembles. We describe high-resolution CT findings in five cases of biopsy-proven RB-ILD. The findings are variable and range from no detectable abnormality to atelectasis, ground-glass opacities, emphysema, and linear and reticular interstitial abnormalities.

Adult↗