Biomedical subjects

A Giangreco

Publications and source records attributed to A Giangreco.

9 recordsLinked to original sources

PubMed2001

Ethanol stimulates apolipoprotein B mRNA editing in the absence of de novo RNA or protein synthesis.

Apolipoprotein B (apoB) mRNA editing involves a site-specific modification of cytidine to form uridine. The reaction is catalyzed in the nucleus by a multi-protein editosome. Rat hepatic editing is regulated during development, metabolically and in response to ethanol. Ethanol stimulated editing in hepatocytes within minutes of exposure. In the present study, we show that ethanol stimulated apoB mRNA synthesis and apoB mRNA editing. Significantly, the proportion of edited apoB mRNA also increased following ethanol treatment of transcription or translation arrested cells. These data suggested that ethanol could regulate editing activity using pre-existing editosomal proteins. In addition, the presence of a suppressor of apoB mRNA editing activity was suggested by the finding that inhibition of mRNA or protein synthesis alone was sufficient to increase the proportion of edited RNA. It is proposed that the level of editing activity observed in hepatocytes may be the end result of positive and negative regulatory proteins.

Animals↗

PubMed2001

Mercapturic acids (N-acetylcysteine S-conjugates) as endogenous substrates for the renal organic anion transporter-1.

Mercapturic acids are N-acetyl-L-cysteine S-conjugates that are formed from a range of endogenous and exogenous chemicals. Although the kidney is a major site for elimination of mercapturic acids, the transport mechanisms involved have not been identified. The present study examined whether mercapturic acids are substrates for the renal basolateral organic anion transporter-1 (Oat1) from rat kidney. This carrier mediates uptake of organic anions from the bloodstream in exchange for intracellular alpha-ketoglutarate. Uptake of [(3)H]p-aminohippuric acid (PAH) in Oat1-expressing Xenopus laevis oocytes was strongly inhibited by S-(2,4-dinitrophenyl)-N-acetyl-L-cysteine (DNP-NAC) and by all other mercapturic acids tested, including the endogenous mercapturic acid N-acetyl-leukotriene E(4). Inhibition by the mercapturic acids was competitive, which is consistent with the hypothesis that these compounds are substrates for Oat1. This conclusion was supported by the direct demonstration of saturable [(35)S]DNP-NAC uptake in Oat1-expressing oocytes. [(35)S]DNP-NAC uptake was inhibited by PAH and other mercapturic acids and was stimulated in oocytes preloaded with glutarate. The apparent K(m) value for DNP-NAC uptake was only 2 microM, indicating that this mercapturic acid is a high affinity substrate for Oat1. Together, these data indicate that clearance of endogenous mercapturic acids is an important function of the renal organic anion transporter.

Acetylcysteine↗

PubMed2001

Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion.

Stem cells with potential to contribute to the re-establishment of the normal bronchiolar epithelium have not been definitively demonstrated. We previously established that neuroepithelial bodies (NEBs) sequester regenerative cells that contribute to bronchiolar regeneration after selective chemical depletion of Clara cells, a major progenitor cell population. Two candidate stem cells were identified on the basis of proliferative potential after chemical ablation: a pollutant-resistant subpopulation of Clara cells that retain their expression of Clara cell secretory protein (CCSP) (variant CCSP-expressing [CE] cells or vCE cells) and calcitonin gene-related peptide (CGRP)-expressing pulmonary neuroendocrine cells (PNECs). In the present study, two populations of label-retaining cells were identified within the NEB: CGRP-expressing cells and a subpopulation of CE cells. To investigate contributions made by CE and CGRP-expressing cells to epithelial renewal, CE cells were ablated through acute administration of ganciclovir to transgenic mice expressing herpes simplex virus thymidine kinase under the regulatory control of the mouse CCSP promoter. CGRP-immunoreactive PNECs proliferated after depletion of CE cells, yet were unable to repopulate CE cell-depleted airways. These results support the notion that vCE cells represent either an airway stem cell or are critical for stem cell maintenance, and suggest that PNECs are not sufficient for epithelial renewal.

Animals↗

PubMed2000

Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration.

Remodeling of the conducting airway epithelium is a common finding in the chronically injured lung and has been associated with increased risk for developing lung cancer. Pulmonary neuroendocrine cells and clusters of these cells termed neuroepithelial bodies (NEBs) play a central role in each of these processes. We previously developed an adult mouse model of airway injury and repair in which epithelial regeneration after naphthalene-induced Clara cell ablation occurred preferentially at airway branch points and gave rise to nascent Clara cells. Continued repair was accompanied by NEB hyperplasia. We now provide the following evidence that the NEB microenvironment serves as a source of airway progenitor cells that contribute to focal regeneration of the airway epithelium: 1) nascent Clara cells and NEBs localize to the same spatial domain; 2) within NEB, both Clara cell secretory protein- and calcitonin gene-related peptide-immunopositive cells are proliferative; 3) the NEB microenvironment of both the steady-state and repairing lung includes cells that are dually immunopositive for Clara cell secretory protein and calcitonin gene-related peptide, which were previously identified only within the embryonic lung; and 4) NEBs harbor variant Clara cells deficient in cytochrome P450 2F2-immunoreactive protein. These data suggest that the NEB microenvironment is a reservoir of pollutant-resistant progenitor cells responsive to depletion of an abundant airway progenitor such as the Clara cell.

Animals↗

PubMed2000

Conditional clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells.

The neuroepithelial body (NEB) is a highly dynamic structure that responds to chronic airway injury through hyperplasia of associated pulmonary neuroendocrine (PNE) cells. Although NEB dysplasia is correlated with preneoplastic conditions and PNE cells are thought to serve as a precursor for development of small cell lung carcinoma, mechanisms regulating expansion of the PNE cell population are not well understood. Based on studies performed in animal models, it has been suggested that NEB-associated progenitor cells that are phenotypically distinct from PNE cells contribute to PNE cell hyperplasia. We have previously used a Clara cell-specific toxicant, naphthalene, to induce airway injury in mice and have demonstrated that naphthalene-resistant Clara cells, characterized by their expression of Clara cell secretory protein (CCSP), and PNE cells contribute to airway repair and associated hyperplasia of NEBs. This study was conducted to define the contribution of NEB-associated CCSP-expressing progenitor cells to PNE cell hyperplasia after Clara cell ablation. Transgenic (CCtk) mice were generated in which herpes simplex virus thymidine kinase was expressed within all CCSP-expressing cells of the conducting airway epithelium through the use of transcriptional regulatory elements from the mouse CCSP promoter. Chronic administration of ganciclovir (GCV) to CCtk transgenic mice resulted in selective ablation of CCSP-expressing cells within conducting airways. Proliferation and hyperplasia of PNE cells occurred in the absence of detectable proliferation among any other residual airway epithelial cell populations. These results demonstrate that PNE cells function as a self-renewing progenitor population and that NEB-associated Clara cells are not necessary for PNE cell hyperplasia.

Animals↗

PubMed1988

Appendicitis and schistosomiasis.

A retrospective clinical and pathological study of 15 cases associated with schistosomiasis drawn from 1920 patients undergoing appendicectomy is discussed. The average age of the patients was 31.6 years with a 12:3 male predominance. Hepatomegaly, past or present jaundice, or splenomegaly were not observed. One patient had a previous history of similar right lower quadrant pain for several days. Eighty per cent of the cases showed an inflammatory reaction on pathological examination. In the remaining 20 per cent no inflammation was seen, but there was severe congestion mainly involving the subserosal blood vessels. Schistosoma haematobium was present in 80 per cent of the cases.

Animals↗

PubMed1985

Frequency of milk expression and milk production by mothers of nonnursing premature neonates.

The relationship between frequency of expression and milk output was studied in 25 healthy mothers of premature infants with gestational ages at birth of 28 to 37 weeks. Mothers expressed milk from days 5 to 11 post partum based on card selection, either four or more times per day or three or less times per day using an electric pump. Based on a second card selection, milk expression was either maintained at the same frequency or changed to the opposite frequency for a second week. On days 11 and 18, all milk expressed was quantitated. Of the 25 mothers studied, nine mothers changed expression frequency from four or more times per day to three or less times per day or vice versa, while nine expressed at the same frequency both weeks. These data indicate that frequent expression was associated with a significantly greater milk production (342 +/- 229 mL) than infrequent expression (221 +/- 141 mL). Thus, a low-cost, noninvasive method of enhancing milk production by mothers of nonnursing, prematurely delivered infants was to encourage frequent milk expression.

Adult↗

PubMed1982

CT scan modification in the treatment of mediastinal Hodgkin's disease.

Seventy-one patients with Hodgkin's disease who were initially treated at Johns Hopkins with radiation or radiation-chemotherapy from 1975--1980 had a five-year cumulative disease-free survival of I-A--100% (12 patients); II-A--85% (33 patients); II-B--83% (seven patients); III-A--75% (ten patients); and III-B--66% (nine patients). Fifty patients with mediastinal masses at the time of treatment demonstrated no marginal misses, two mediastinal recurrences (96% local control), and three lung disseminations. CT scan data yielded stage and treatment modification in 60% (9/15) of recent patients with mediastinal Hodgkin's disease. This demonstrates the need for routine thoracic scans and individual treatment planning in all mediastinal cases. Recommendations for combination treatment in early stage disease are made only for pericardial or extrathoracic chest wall extension based on CT scan findings, our low failure rates, radiation organ tolerances, and available relapse data in the literature, not arbitrary size designations from upright chest radiographs. It can be concluded that patients with mediastinal Hodgkin's disease require CT scan analysis to identify unusual patterns of presentations, sites at risk, and to allow for proper application of radiation portals and/or chemotherapeutic management.

Drug Therapy, Combination↗

PubMed1980

Sputum cytologic diagnosis of Hodgkin's disease involving the lung.

The development of pulmonary lesions during the course of Hodgkin's disease (HD) represents a diagnostic problem. Invasive studies are usually necessary to differentiate pulmonary parenchymal involvement with HD from infectious complications. A retrospective review has revealed five cases in which sputum cytodiagnosis of HD involving the lung was made. All cases were confirmed by either histopathologic examination or response to therapy. The cytology reveals a polymorphic picture with a large number of lymphoid mononuclear cells, macrophages, and unclassified cells. These cells usually have single nuclei that are lobulated and contain prominent nucleoli. Occasionally, classic Reed-Sternberg cells are present. Such evidence makes the specimen diagnostic of HD. This experience suggests that sputum cytodiagnosis may be useful adjunctive diagnostic tool in the evaluation of the conditions of patients with HD and pulmonary lesions and may make more invasive diagnostic procedures unnecessary.

Adult↗