Biomedical subjects

H Ren

Publications and source records attributed to H Ren.

187 records · Page 11Linked to original sources

PubMedDate not supplied

Immunogene therapy of recurrent glioblastoma multiforme with a liposomally encapsulated replication-incompetent Semliki forest virus vector carrying the human interleukin-12 gene--a phase I/II clinical protocol.

Glioblastoma multiforme (GBM) is an incurable brain tumor resistant to standard treatment modalities such as surgery, radiation, and chemotherapy. Since recurrent GBM tends to develop predominantly within the infiltrative rim surrounding the primary tumor focus, novel therapy strategies need in addition to focal tumor destruction to target this somewhat diffuse area. This is a phase I/II clinical study in adult patients with recurrent GBM which is aimed at evaluating biological safety, maximum tolerated dose, and antitumor efficacy of a genetically modified replication-disabled Semliki forest virus vector (SFV) carrying the human interleukin 12 (IL-12) gene and encapsulated in cationic liposomes (LSFV-IL12). The vector will be administered in doses of 1 x 10(7)-1 x 10(9) infectious particles by continuous intratumoral infusion, thus exploiting the advantages of convection-enhanced drug delivery in the brain. The present protocol is also designed to investigate systemic and local immune response and to identify factors predicting tumor response to LSFV-IL12 therapy, such as volume of extracellular space of the tumor, volume of contrast enhancing lesion, and immune status of the patients. SFV, an insect alphavirus, infects mitotic and non-mitotic cells and triggers apoptosis in tumor cells within 48-72 h. Preclinical work with the LSFV-IL12 vector in breast and prostate cancer animal models demonstrated its biosafety and some antitumor efficacy. An ongoing phase I clinical study in patients with melanoma and renal cell carcinoma seems also to confirm the biosafety of intravenously administered vectors. This protocol will be the first study of SFV-IL12 therapy of human recurrent GBM.

Adult↗

PubMedDate not supplied

Computed tomography of rounded atelectasis.

High resolution CT of a fixed-inflated air-dried lung was obtained from a patient with rounded atelectasis. The dense periphery of the mass was shown to correspond to an invagination of the pleura, and the central lucency to slightly aerated atelectatic lung parenchyma.

Aged↗

PubMedDate not supplied

Computed tomography of inflation-fixed lungs: the beaded septum sign of pulmonary metastases.

Radiographic identification of pulmonary metastases has proved to be a challenging problem. We applied high resolution CT (HRCT) to 180 post-mortem lung specimens prepared by a method that allows for direct one-to-one pathologic-radiologic correlation. Of the 180 lungs, 32 had pulmonary metastases. The location, number, size, and interstitial changes were evaluated in 32 cases with pulmonary metastases. The pulmonary metastases were peripheral lesions in 94% of these 32 patients, and multiple tumors were found in 91% of these cases. The metastases were less than 1 cm in diameter in 78%. Twenty-two of the 32 cases (69%) had obvious interstitial changes. In 19 of these 22 cases the interstitial change was characterized by the appearance of a "beaded septum" on HRCT. This beaded septal change corresponded directly to tumor growth in pulmonary capillaries and lymphatics and the septal interstitium. This sign was not noted in any of the specimens with pulmonary edema or fibrosis or in normal lungs. We believe that detection of the beaded septum sign on HRCT is highly suggestive of pulmonary metastases.

Adult↗

PubMedDate not supplied

CT-pathology correlation of amiodarone lung.

Eleven isolated lungs from patients who had received amiodarone therapy and 22 other lungs from age-race-sex-matched controls autopsied at The Johns Hopkins Hospital were inflation fixed, air dried, and examined by high resolution CT (HRCT). The HRCT findings were directly correlated with gross and histologic changes in these lungs. Intralobular septal thickening and visceral pleural thickening on postmortem HRCT were significantly more severe in the lungs from patients who had received amiodarone than in the controls (p less than 0.05). These HRCT findings were directly associated with the presence of mural foam cells and intraalveolar foam cells. These results suggest that amiodarone therapy may lead to the accumulation of mural and intraalveolar foam cells, and the accumulation of these foam cells may account for the changes seen on HRCT.

Adult↗

PubMedDate not supplied

Inflation-fixed lungs: pathologic-radiologic (CT) correlation of lung transplantation.

Pulmonary infections and lung rejection are the two major complications of lung transplantation. Although the therapies for these two processes differ greatly, they often cannot be differentiated using standard radiography. We applied high resolution CT (HRCT) to seven lung specimens that were obtained from patients who had received a heart-lung transplant. The lungs were fixed by a method that allows for direct one-to-one pathologic-radiologic correlation. We found: (a) that in contrast to the extensive changes present microscopically, acute lung allograft rejection was characterized by only minor changes on HRCT; (b) that bronchiolitis obliterans, the hallmark of chronic lung allograft rejection, was not reliably identifiable on HRCT; (c) that bronchiectasis with associated peribronchial inflammation and fibrosis, a common finding in lung allograft rejection, was identifiable on HRCT, but that the HRCT appearance of this lesion was not specific for rejection; and (d) that pulmonary infections were often identifiable as a mixed airway-interstitial process on HRCT.

Adult↗

PubMedDate not supplied

CT of inflation-fixed lungs: wedge-shaped density and vascular sign in the diagnosis of infarction.

To evaluate the role of high resolution CT (HRCT) in the diagnosis of pulmonary infarcts, we selected 83 postmortem lung specimens with subpleural densities from a collection of 180 lungs that had been prepared by a method which allows for a direct radiologic-pathologic correlation. Twelve of the lungs had pulmonary infarcts and 71 lungs had other disorders that had produced a subpleural shadow on HRCT. Lungs were evaluated for the presence of wedge-shaped pleural-based densities and for the presence of an associated vascular sign. There was no significant difference in the incidence of wedge-shaped densities on HRCT between lungs with pulmonary infarcts and lungs with pulmonary hemorrhage, pneumonia, tumor, or edema (p greater than 0.05). A vascular sign associated with a subpleural density was, however, more common (p less than 0.01) in lungs with pulmonary infarcts. We suggest that the vascular sign associated with a wedge-shaped density may be of importance in diagnosing pulmonary infarcts by HRCT.

Humans↗

PubMedDate not supplied

Adenosine receptors: protein and gene structure.

Adenosine produces a wide variety of effects throughout the body via activation of cell surface adenosine receptors. Adenosine receptors belong to the family of seven transmembrane domain G protein-coupled receptors and four subtypes have been cloned from a variety of species: the A1AR, A2aAR, A2bAR and A3AR. With a knowledge of both the protein sequence of adenosine receptors and the structure of the A1AR gene, the function and regulation of these receptors can be further explored. Site-directed mutagenesis of the A1AR has resulted in the identification of amino acid residues in transmembrane domains 6 and 7 that are critical in both agonist and antagonist binding. The construction and analysis of A1/A3 chimeric receptors has also revealed regions of adenosine receptors important in ligand binding. These include the distal region of the second extracellular loop of adenosine receptors, which has a role in the binding of both agonist and antagonist ligands. A segment of the exofacial portion of the transmembrane domain 5 of adenosine receptors appears to be involved in the selective recognition of agonist ligands containing a substitution at the 5'-position of the ribose moiety. Isolation of the genomic sequence of the human A1AR, in combination with analysis of the transcript distribution in several tissues, indicates that alternative splicing of the human A1AR occurs in the 5'-untranslated region of the gene. Two distinct transcripts, containing either exons 3, 5 and 6 or exons 4, 5 and 6, exist with exons 3 and 4 apparently mutually exclusive. The exon 4, 5 and 6 transcript has been detected in all tissues that express the A1AR, while the exon 3, 5 and 6 mRNA is found in tissues that display a relatively high A1AR expression. Findings suggest that the presence of two ATG codons in exon 4, upstream of the translation start site, is involved in the repression of the A1AR expression in those tissues containing the exon 4, 5 and 6 transcript.

Animals↗