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Biomedical subjects

J Roman

Publications and source records attributed to J Roman.

At least 55 records · Page 3Linked to original sources
PubMed1997

Growth and growth hormone secretion in children with cancer treated with chemotherapy.

OBJECTIVE: To evaluate the effect of chemotherapy on growth and growth hormone (GH) secretion. METHODS: We analyzed growth and GH secretion in 60 children in complete remission after treatment by chemotherapy and surgery for malignant solid tumors. None of them received cranial radiotherapy. Growth hormone reserve was assessed by at least two stimulation tests (clonidine, L-dopa, growth hormone-releasing hormone). In 12 children the reserve of GH pretreatment was also evaluated. RESULTS: Growth hormone deficiency (GHD) was observed in 27 of 60 patients (45%). At diagnosis, mean standing height was +0.23 +/- 0.11 standard deviation score (SDS) in the GHD group and +0.16 +/- 0.10 SDS in the non-GHD group. After chemotherapy, mean standing height in the GHD group was -0.28 +/- 0.15 SDS and -0.14 +/- 0.11 in the non-GHD group (p < 0.05), and the growth rate was +0.13 +/- 0.07 SDS in the GHD group and +0.22 +/- 0.18 SDS in the non-GHD group. For a mean follow-up of 30 months, the mean standing height was -0.46 +/- 0.29 SDS in the GHD group and -0.24 +/- 0.16 SDS for the non-GHD group (p < 0.05), and the growth rate was -0.27 +/- 0.19 SDS in the GHD group and -0.16 +/- 0.12 SDS in the non-GHD group (p < 0.05). The GH response to clonidine was significantly less than that found with the other stimuli. There was correlation between the dose intensity of some drugs and the subsequent GH response to stimulation tests. The GHD group was found to have received significantly higher doses of actinomycin D than the non-GHD group (p < 0.05). Growth impairment and GHD were not found to be correlated with duration of treatment and follow-up, tumor type, sex, or age. CONCLUSIONS: Chemotherapy as the sole form of treatment in children with cancer interferes with growth. The observed impairment of growth depends, at least in part, on a GHD related to chemotherapy. The growth rate in conjunction with the GH response to clonidine provides a sensitive measure of GHD associated with chemotherapy.

Adolescent↗
PubMed1996

Extracellular matrix and lung inflammation.

Lung injury triggers an acute inflammatory response characterized by increased expression and deposition of extracellular matrix (ECM) components such as fibronectin and collagen. Although the function of newly deposited matrices in injured lungs is unknown, their ability to affect the migration, proliferation, differentiation, and activation state of cells in vitro suggests an important role in the initiation and maintenance of the inflammatory response in vivo. Interactions between immune and nonimmune cells with the lung ECM are mediated via cell surface receptors of the integrin family which link the ECM with intracellular molecules involved in signal transduction. Activation of integrin-mediated intracellular signals may promote inflammation by facilitating leukocyte recruitment and cytokine expression.

Animals↗
PubMed1996

Immune response and in vivo production of cytokines in patients with liver hydatidosis.

Cytokines play an important role in the human immunological response, but the exact role of cytokines in the human immune response against parasites, especially against Echinococcus granulosus, remains unclear. IL-1, IL-2, IL-4 and tumour necrosis factor (TNF) levels in peripheral blood of 21 patients with liver hydatidosis were evaluated before surgical treatment, and the levels of IgA, IgM, IgG, IgE, specific IgE against E. granulosus, C3, C4 and DF complement fractions and CD20, CD3, CD4, CD8 and CD16 cell percentages were also determined, as was the relationship between these variables and cytokine levels. Data from hydatid patients were compared with data obtained from 21 healthy volunteers. Hydatid patients showed increases of IgG, IgE, IgEs and IL-2 (P < 0.01), and decreases of IL-1 and TNF levels (P < 0.001), but these variables (respectively) increased in patients showing cysts in the central area of the liver or with a wide opening of cysts in the biliary tract. The increase of IL-1, IL-2 and IL-4 showed a close relationship with the number, characteristics and above all the location of cysts within the liver itself. IgG and IL-4 levels and also IgG and IgE levels showed a significant correlation (P < 0.05).

Adolescent↗
PubMed1996

Systemic inflammatory response syndrome caused by chronic salicylate intoxication.

Systemic inflammatory response syndrome (SIRS) is characterized by body temperature abnormalities, tachypnea or hyperventilation, tachycardia, and leukocytosis or leukopenia. Although it is typically associated with a serious infection and referred to as sepsis, SIRS can stem from noninfectious causes, as well. We report the cases of four patients with toxic serum levels of salicylate (33.5 to 67.6 mg/dL) and SIRS, and we discuss mechanisms responsible for SIRS. Our patients showed temperature disturbances (35.5 degrees C to 39.8 degrees C), noncardiogenic pulmonary edema, and mixed acid base disturbances. Other abnormalities included coagulopathy (disseminated intravascular coagulation), encephalopathy, and hypotension. All four patients recovered from SIRS, probably due to early recognition and treatment; only one patient did not survive the hospitalization. Chronic salicylate toxicity should be considered as a cause of SIRS in the absence of a source of infection, since survival appears to be dependent on prompt diagnosis and management.

Acid-Base Imbalance↗
PubMed1996

Fibronectin modulates expression of interleukin-1 beta and its receptor antagonist in human mononuclear cells.

Identification of factors that regulate production of proinflammatory cytokines may provide insight into mechanisms governing lung inflammation. One potential regulatory factor highly expressed in inflamed tissues is fibronectin (FN). To determine the potential effects of FN on interleukin (IL)-1 beta production, we exposed human peripheral blood mononuclear cells to soluble FN. This treatment resulted in the accumulation of IL-1 beta mRNA and enhancement of IL-1 beta protein synthesis and secretion. This effect was dose dependent and appeared to be mediated by the integrin alpha 5 beta 1. Treatment with FN also increased production of IL-1 receptor antagonist (IL-1ra), a naturally occurring inhibitor of IL-1 function. However, the stimulatory effect of FN on IL-1ra production was abolished by costimulation with type I collagen. We conclude that the increased deposition of FN in injured tissues may enhance the expression of IL-1 beta mRNA and augment the production and release of IL-1 beta protein by mononuclear cells. Differential expression of IL-1 beta and IL-1ra resulting in a high IL-1 beta-to-IL-1ra ratio in response to mixed matrices containing FN and type I collagen may be an important regulatory point in inflammation.

Cells, Cultured↗
PubMed1996

Inhibition of apoptotic cell death in B-CLL by interferon gamma correlates with clinical stage.

Apoptosis was evaluated in B cells from 41 patients with B-CLL and 20 healthy aged-matched controls. B cells were cultured with and without gamma-IFN and other cytokines; apoptosis was quantified at regular intervals throughout a 5-day culture period. According to Rai's criteria, 17 patients were classified as good risk, 16 as intermediate and eight as high risk. In vitro, purified B cells from B-CLL patients were evaluated for apoptosis. Maximal apoptosis (44.12%) was observed at day 5 in cells from patients with poor prognosis. The addition of gamma-IFN to the culture media prevented apoptosis in a dose-dependent manner. Maximal inhibition of apoptosis was achieved with 100 IU/ml of gamma-IFN. The degree of inhibition of apoptosis by gamma-IFN was greater in cells from the high-risk group patients than in those from the intermediate and good prognosis group (P < 0.0001). The expression of gamma-IFN receptors in B-CLL cells was evaluated using a MnAb against the extracellular domain of gamma-IFN receptor. After 4 days in culture with gamma-IFN, only cells from the intermediate- and high-risk groups showed an increase in the density of gamma-IFN receptors (P < 0.001). gamma-IFN was not detected in the sera of our study patients. However gamma-IFN was detectable in the media from both normal B cells and B-CLL cells in culture; there was no difference in the amount of gamma-IFN released by cells from the three groups of patients studied. Our results show that in vivo gamma-IFN inhibits apoptosis of B cells from B-CLL patients. The inhibitory effect of gamma-IFN on apoptosis correlates directly with the severity of the disease and this is likely explained by a marked upregulation of gamma-IFN receptors in cells from patients in the high-risk group.

Aged↗
PubMed1995

Fibrin enhances the expression of IL-1 beta by human peripheral blood mononuclear cells. Implications in pulmonary inflammation.

Tissue injury is accompanied by increased vascular permeability and influx of plasma proteins including fibrinogen. Fibrinogen is converted into a fibrin matrix by procoagulants activated at the site of tissue injury and inflammation. This fibrin matrix is thought to participate early in the inflammatory response by providing a temporary protein "scaffold" for inflammatory cell adhesion and migration, and subsequent remodeling of the tissue with permanent extracellular matrix proteins such as collagen. Collagen and fibronectin have been shown to regulate the expression of inflammatory cytokines, but whether fibrin can regulate cytokine expression is not known. We hypothesized that fibrin induces the expression of the proinflammatory cytokine IL-1 beta and sought to explore mechanisms responsible for this induction. In this report, we demonstrate that fibrin stimulates human PBMCs to express IL-1 beta message and protein. We show that induction of IL-1 beta by fibrin is mediated partly by the integrin receptor CD11b/CD18 and modulated by cytoskeletal rearrangement. Fibrin also suppresses production of IL-1 receptor antagonist (IL-1ra) a non-bioactive competitor of IL-1 for IL-1Rs. We propose that injured tissues where the conditions favor coagulation and fibrin accumulation, the interaction between mononuclear cells and the newly formed fibrin matrices may elicit the production of the proinflammatory cytokine IL-1 beta. This proposal is supported by immunohistochemical studies which show the co-distribution of fibrin and IL-1 beta in granulomas in lung sections from patients with the systemic granulomatous disease, sarcoidosis.

CD18 Antigens↗
PubMed1995

Distribution of extracellular matrices, matrix receptors, and transforming growth factor-beta 1 in human and experimental lung granulomatous inflammation.

Aberrant deposition of extracellular matrices (ECMs) may affect lung inflammation by influencing cell adhesion, migration, and activation. Little is known about the expression of ECMs in lungs with granulomatous inflammation. Therefore the authors investigated the distribution of ECMs, matrix receptors of the integrin family, and transforming growth factor-beta 1 (TGF-beta 1) in lungs from patients with pulmonary sarcoidosis and animals with experimental granulomatosis. Immunohistochemistry revealed increased deposition of type I collagen and fibronectin in human lung granulomas when compared with healthy human lungs. Procollagen type I and cellular fibronectin also were increased, suggesting local synthesis of ECM in sarcoid granulomas. These findings were accompanied by increased staining for fibronectin (alpha 5 beta 1) and collagen (alpha 2 beta 1) integrin receptors. The matrix-inducing cytokine TGF-beta 1 was co-distributed with the aforementioned molecules in the granulomas, whereas no significant staining for TGF-beta 1 was found in healthy lungs. Similar to sarcoid lungs, analysis of lung sections obtained from a murine model of granuloma formation revealed increased expression of fibronectin, collagen, integrin receptors, and TGF-beta 1 within granulomas. Based on these observations, there is increased expression of ECM and matrix receptors in both human and experimental lung granulomas. Such alterations may influence the recruitment and activation of inflammatory cells and fibroblasts, promoting granuloma formation and remodeling of tissue by fibrosis. Activation of mononuclear cells resulting in production of TGF-beta 1 is likely to contribute to the changes described.

Animals↗
PubMed1995

Case report: congenital absence of the left pulmonary artery accompanied by ipsilateral emphysema and adenocarcinoma.

Unilateral absence of the left pulmonary artery is a rare congenital anomaly that may remain unrecognized until adulthood, in which case it may lead to inappropriate diagnosis and management. The authors describe a case in which a patient came to their institution with dyspnea and a chest roentgenogram showing a prominent right pulmonary artery, right aortic arch, and a left lung mass accompanied by ipsilateral volume loss. Although the initial evaluation suggested a differential diagnosis that included thromboembolic pulmonary disease and vascular compression by tumor, further workup revealed unilateral absence of the left pulmonary artery accompanied by left lung hypoplasia, and interestingly, ipsilateral emphysema and adenocarcinoma. The embryologic factors responsible for this abnormality and how it may potentially affect the development of emphysema and adenocarcinoma are discussed.

Adenocarcinoma↗
PubMed1995

Reverse splicing of the Tetrahymena IVS: evidence for multiple reaction sites in the 23S rRNA.

Group I introns in rRNA genes are clustered in highly conserved regions that include tRNA and mRNA binding sites. This pattern is consistent with insertion of group I introns by direct interaction with exposed regions of rRNA. Integration of the Tetrahymena group I intron (or intervening sequence, IVS) into large subunit rRNA via reverse splicing was investigated using E. coli 23S rRNA as a model substrate. The results show that sequences homologous to the splice junction in Tetrahymena are the preferred site of integration, but that many other sequences in the 23S rRNA provide secondary targets. Like the original splice junction, many new reaction sites are in regions of stable secondary structure. Reaction at the natural splice junction is observed in 50S subunits and to a lesser extent in 70S ribosomes. These results support the feasibility of intron transposition to new sites in rRNA genes via reverse splicing.

Animals↗
PubMed1994

Ligand binding to monocyte alpha 5 beta 1 integrin activates the alpha 2 beta 1 receptor via the alpha 5 subunit cytoplasmic domain and protein kinase C.

Regulation of the functional status of integrin receptors plays a critical role in inflammation and tissue remodeling, as it affects cell adherence and cytokine secretion. We have previously shown that in monocytes the binding of collagen to the alpha 2 beta 1 integrin induces the release of IL-1, an event that is potentiated by binding of fibronectin (Fn) to the alpha 5 beta 1 integrin. In this study, we have investigated the mechanisms leading to this phenomenon. Fn binding to alpha 5 beta 1 induced intracellular signals which increased the alpha 2 beta 1-dependent adhesiveness of monocytes to collagen without modifications of alpha 2 beta 1 expression. By using Abs against the intracellular region of the alpha 5 subunit of the alpha 5 beta 1 receptor, and specific inhibitors of protein kinase C (PKC), we found that the potentiation effect of Fn on monocyte IL-1 production and their adherence to collagen was dependent on an intact alpha 5 subunit cytoplasmic domain, and required PKC activation. Although the alpha 2 beta 1 could be activated by several intracellular second messengers, including protein kinase A and intracellular calcium, the potentiating effect of Fn was mediated only by PKC. These data provide an example of a novel regulatory mechanism: potentiation of beta 1 integrin-mediated events as a result of ligand binding to another integrin of the same class. They also show that the intracellular region of alpha 5 beta 1 plays a critical role in transducing signals generated by ligand binding to alpha 5 beta 1.

Calcium↗
PubMed1994

Autoimmune haemolytic anaemia presenting 9 years prior to Castleman's disease.

Castleman's disease (CD) is a rare disease of unknown aetiology and pathogenesis. We present an unusual case of abdominal CD in whom the first manifestation was an autoimmune haemolytic anaemia presenting 9 years before the diagnosis. The Coombs test became negative 2 months after surgical resection of the mass, suggesting that the mass was the source of the autoantibody. CD may be present in autoimmune haemolytic anaemia in patients with no evidence of any other disease.

Adult↗
PubMed1994

Lymphoid blast crisis at the onset of chronic myelogenous leukaemia: molecular evidence.

A patient with a typical haematological pattern of acute lymphoblastic leukaemia with BCR and IgH rearrangements was brought into complete remission by treatment. A few weeks later she developed the typical peripheral and bone marrow pattern of chronic myelogenous leukaemia (CML) with persistence of the BCR rearrangement and disappearance of the IgH rearrangement, suggesting that this case is an example of CML presenting in blast crisis without a detectable chronic phase.

Adult↗
PubMed1994

Extravascular coagulation and fibrinolysis in murine lung inflammation induced by the mycobacterial cord factor trehalose-6,6'-dimycolate.

Diffuse pulmonary inflammation in interstitial lung diseases is associated with increased coagulation in the extravascular spaces of the lung. We hypothesized that conditions favoring coagulation over fibrinolysis in the lung are related to inflammation. Pulmonary coagulation and fibrinolysis were studied in two strains of mice susceptible or resistant to the development of lung inflammation in response to the mycobacterial cell wall glycolipid trehalose-6,6'-dimycolate (TDM). Susceptible animals treated with TDM intravenously develop well-organized collections of mononuclear cells in the lung parenchyma referred to as granulomas in this report. More granulomas were found in the susceptible ICR mice than in the resistant A/J mice after intravenous administration of TDM (7 +/- 1 granulomas/mm2 versus 1 +/- 0.3 granulomas/mm2, p = 0.005). Granuloma formation was associated with increased lung procoagulant activity (PCA) measured in bronchoalveolar lavage (BAL) cell lysates from susceptible mice. In contrast, TDM-resistant A/J mice challenged with TDM did not have a significant BAL cell PCA response, but expressed several-fold greater levels of lung BAL fluid plasminogen activator activity (PAA) than ICR mice. To examine the role of coagulation in the TDM pulmonary inflammatory response, susceptible C57Bl/10SnJ mice were anticoagulated by oral administration of warfarin prior to challenge of TDM; these mice developed fewer pulmonary granulomas than TDM-treated mice without warfarin treatment (2.6 +/- 0.5 granulomas/mm2 versus 6.5 +/- 0.8 granulomas/mm2, p < 0.001) but had similar BAL cell PCA and lung inflammatory changes as measured by lung weights and BAL cellularity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Regulation of lung branching morphogenesis by bombesin-like peptides and neutral endopeptidase.

The expression of bombesin-like peptides (BLPs) by pulmonary neuroendocrine cells is transiently upregulated during lung development. A functional role for BLPs is supported by their ability to stimulate lung growth and maturation both in vitro and in vivo during the late stages of lung development. In addition, the cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP), which inactivates BLPs and other regulatory peptides, is also expressed by developing lungs and modulates the stimulatory effects of BLPs on lung growth and maturation. We hypothesized that, in addition to expressing BLPs and CD10/NEP, embryonic lungs must express BLP receptors, and that BLPs may also regulate processes that occur during early lung development such as branching morphogenesis. Using reverse transcriptase-polymerase chain reaction and oligonucleotide primers designed for amplifying a BLP receptor originally isolated from Swiss 3T3 mouse fibroblasts, we found that embryonic mouse lungs express a similar BLP receptor mRNA during the pseudoglandular stage of lung development when branching morphogenesis take place. Subsequently, we evaluated the effects of ligands for this BLP receptor using embryonic mouse lungs in an in vitro model of lung branching morphogenesis. We found that, in comparison with control lungs, treatment with bombesin (1 to 100 nM) resulted in a modest increase in clefts or branching points. In contrast, embryonic mouse lungs treated with the BLP analog [Leu13-psi(CH2NH)Leu14]bombesin (1 microM), which also binds to this BLP receptor but has predominantly antagonistic effects, demonstrated fewer branching points.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗