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Biomedical subjects

J Kelley

Publications and source records attributed to J Kelley.

At least 91 records · Page 5Linked to original sources
PubMed1985

Bleomycin selectively elevates mRNA levels for procollagen and fibronectin following acute lung injury.

We employed the technique of dot blot hydridization of radiolabeled cDNA probes to examine the role of specific mRNA content in the control of extracellular matrix turnover in the remodeling rat lung. Following bleomycin instillation, total RNA content gradually doubled during the first 5 days following the initial lung injury, then rose much more rapidly during the ensuing 9 days. Individual mRNAs for procollagens I and III and for fibronectin were selectively enriched 2- to 4-fold above total RNA during the first week after bleomycin instillation. No comparable increases were observed in specific RNAs from liver, indicating that the response observed in the lung was not generalized to other organs. Moreover, the increases in mRNA species for procollagen types I or III in the lung could not be related to the influx of inflammatory cells which migrate into the lungs during acute injury, as cells obtained by alveolar lavage contained no mRNAs for procollagens.

Animals↗
PubMed1985

Secretion of macrophage-derived growth factor during acute lung injury induced by bleomycin.

Monocytes are capable of producing a growth factor which causes fibroblasts to replicate in vitro. This macrophage-derived growth factor (MDGF) may be particularly important in controlling the proliferation of mesenchymal cells in the pulmonary interstitium following acute lung injury. To evaluate the role of macrophages in modulating the proliferative capacity of fibroblasts, we added serum-free culture medium from lavage-derived rat lung macrophages to confluent monolayers of quiescent adult rat lung fibroblasts and monitored their return to the cell cycle both by 3H-thymidine incorporation and by increases in cell number. Growth factor activity secreted in 24 h by untreated macrophages was compared to that from normal macrophages stimulated in vitro by bacterial lipopolysaccharide (LPS) and from macrophages retrieved from lungs injured by intratracheal administration of bleomycin. Unstimulated macrophages from control animals secreted minimal amounts of MDGF; addition of LPS to normal macrophages increased MDGF secretion 3- to 4-fold. Adherent cells obtained by lung lavage of bleomycin-treated animals spontaneously secreted near maximal levels of nondialyzable MDGF with little further stimulation by LPS. The MDGF secreted by LPS-stimulated control cells and by macrophages retrieved from injured lungs share identical elution profiles from DEAE-Sephacel anionic exchange columns, and heat stability profiles. The substance acts as a competence factor when tested on rat lung fibroblasts. These shared physical and biologic properties suggest that the growth factor secreted by cells lavaged from injured lungs is identical to MDGF secreted in response to LPS. Because MDGF release could not be induced by direct exposure of freshly isolated macrophages to bleomycin, we suggest that augmented release of MDGF is an indirect feature of acute lung injury in this model.

Animals↗
PubMed1985

Factor structure of the drinking behavior interview in a private inpatient treatment program.

The 32-item Drinking Behavior Interview (DBI) was administered to 103 patients newly admitted to a private, inpatient, alcohol problems treatment unit. When intercorrelations among the 32 variables were subjected to factor analysis, DBI profiles of alcoholics in this population differed primarily along four major dimensions: close interpersonal relationships, physical symptoms, societal functioning and alcohol consumption. Whereas the DBI has previously been used to define a single composite alcoholism index, these results suggest the importance of considering differences in components of the DBI profile pattern.

Alcohol Drinking↗
PubMed1985

Lymphokine regulation of macrophage-derived growth factor secretion following pulmonary injury.

Rat alveolar macrophages secrete enhanced levels of a growth factor for fibroblasts following acute lung injury. The authors have previously identified this anionic, heat-labile substance as macrophage-derived growth factor (MDGF) and have now focused on how its release by alveolar macrophages is controlled following lung damage. In response to pulmonary injury induced with a single intratracheal instillation of bleomycin sulfate, the lymphocyte count rose from undetectable to 23% of the cells retrieved in lavage fluid. Spontaneous MDGF secretion by macrophages cultured from the same lungs generally paralleled the changes in lymphocyte counts over time. To test whether lymphokine(s) secreted by alveolar lymphocytes regulated MDGF secretion by macrophages in this model, the authors exposed normal macrophages harvested from control rat lungs to lymphokine preparations in vitro. Lymphokines provided a powerful stimulus to normal macrophages, inducing MDGF secretion at dilutions as low as 10(-6). Fractionating T-lymphocyte subsets by adherence to monoclonal antibodies indicated that the W3/25+ cells elaborated the macrophage-stimulating lymphokine, but that OX8+ cells did not. Furthermore, recombinant murine gamma interferon was capable of substituting for native lymphokine in activating MDGF secretion by normal macrophages. It is concluded that immune stimulation of fibroblast proliferation requires cooperative interaction of both lymphocytes and macrophages in this model of acute lung injury.

Animals↗
PubMed1984

Protein synthesis in rat lung. Measurements in vivo based on leucyl-tRNA and rapidly turning-over procollagen I.

The relationships of the specific radioactivities of leucine in serum, leucine acylated to tRNA and leucine in procollagen I, procollagen III and total protein in lungs of unanaesthetized young male rats in vivo were assessed as a function of time during constant intravenous infusion of radiolabelled leucine. The specific radioactivity of free leucine in plasma reached a steady-state plateau value within 30 min of initiation of [3H]leucine infusion. Leucine acylated to tRNA isolated from lungs had the same specific radioactivity as free serum leucine. Leucine in procollagen I rapidly achieved a specific radioactivity equal to that of serum leucine and leucyl-tRNA, indicating that serum leucine and leucyl-tRNA isolated from total lung were in rapid equilibrium with the precursor leucine pool for procollagen I synthesis. On the basis of leucyl-tRNA or free serum leucine as the precursor, half-times of fractional conversion of procollagen I and III were calculated as 9 and 38 min respectively. The incorporation of leucine into mixed lung proteins calculated from the tracer studies was 6.8 mumol/day for the first 30 min of the infusion, after which the calculated rate increased to 15.0 mumol/day. This apparent increase correlated with the appearance of rapidly labelled plasma proteins trapped in the lungs. On the basis of short infusions lasting 30 min or less, followed by vascular perfusion of the lung, the average fractional synthesis rate of mixed pulmonary proteins in young male rats was 20%/day.

Animals↗
PubMed1984

Microquantitation of insoluble tissue collagen (types I and III) by radiodilution assay.

The individual collagen types of the extracellular matrix of small tissue samples have been difficult to quantitate accurately both due to their marked insolubility and their relatively low immunogenicity. Thus no microassay with the sensitivity of a radioimmunoassay is currently available for quantitation of insoluble collagen types I and III in extremely small tissue samples. A radiochemical assay has been developed which allows direct processing of small tissue samples containing as little as 1-3 micrograms of a given collagen alpha chain. Unprocessed lyophilized tissues were digested with cyanogen bromide (CNBr) in the presence of a tritiated probe containing a soluble mixture of 3H-alpha 1(I) and 3H-alpha 1(III) collagen previously extracted and purified from tissue minces incubated with [3H]leucine. The resulting mix of radiolabeled peptides was separated on sodium dodecyl sulfate-polyacrylamide gradient gels. Reduction of the specific radioactivity of free leucine in acid hydrolysates of each individual CNBr peptide can be used to quantitate the amount of collagen types I or III in the original sample. Similar radiodilution analysis using a 3H-alpha 2(I) probe indicated a normal 2:1 ratio of alpha chains of type I collagen in the tissues tested. This method is also applicable to cell culture, easily measuring the collagen associated with fibroblast cell layers or medium in individual microtiter wells. When applied to various tissues of known collagen-type composition, it provides reproducible results which compare well with values published in the literature.

Animals↗
PubMed1984

Diagnosis of allergic conjunctivitis.

Itching was cited as a major symptom of their ocular disease by 49 (80%) of the 61 patients with allergic conjunctivitis. Conjunctival scrapings from 51 patients (84%) demonstrated intact eosinophils or eosinophil granules. Eosinophil granules were a useful and recognizable cytologic feature of allergic conjunctivitis even in the absence of intact eosinophils. We believe that a history of itching and the presence of eosinophils or eosinophil granules in conjunctival scrapings are helpful in diagnosing allergic conjunctivitis.

Conjunctiva↗
PubMed1984

Effects of aldosterone, methylprednisolone and triiodothyronine on the response to water loading in the conscious hypothyroid rat with diabetes insipidus.

The role of the antidiuretic hormone-independent mechanisms underlying the impairment of water excretion in hypothyroidism remains controversial. We examined the excretion of an oral water load (50 ml/kg b.w.) over a 3-hour period before and after the administration of aldosterone, methylprednisolone, both aldosterone and methylprednisolone, and triiodothyronine in 12 hypothyroid and 7 age-matched control Wistar rats of the homozygous Brattleboro strain (DI). Conscious animals were studied to circumvent the adverse influence of anesthetics and to facilitate the re-examination of the same animals. At baseline, the hypothyroid DI rats exhibited a marked impairment in their response to water administration. In comparison to control DI rats they had a lower urine volume, CH2O, CH2O/V and creatinine clearance, and higher urine osmolality (p less than 0.005-less than 0.001). Because of the possibility of decreased delivery of filtrate due to dehydration in the DI animals, a separate group of DI rats received saline in place of the water load. Despite improvement in urine flow with saline, CH2O generation remained decreased in the hypothyroid DI rats. Methylprednisolone increased both urine volume (p less than 0.001) and CH2O (p less than 0.001) in the hypothyroid group, but CH2O formation remained below the values obtained in the control animals. While aldosterone and methylprednisolone alone and in combination improved utilization of distally-delivered filtrate for the formation of CH2O (p less than 0.02-0.005), neither hormone, either alone or in combination, fully corrected the dilution defect. In contrast, the administration of triiodothyronine fully normalized all the observed abnormalities in the hypothyroid rats, suggesting that thyroid hormone deficiency is directly responsible for the abnormal water-excretion in experimental hypothyroidism.

Aldosterone↗
PubMed1984

Effect of duration of diabetes on the protection observed in the diabetic rat against gentamicin-induced acute renal failure.

We have previously shown that the rat with experimental diabetes (DM) of 4-6 months' duration exhibits complete functional and morphologic protection against gentamicin-induced acute renal failure. To assess the role of the duration of the diabetic state per se on the resistance to gentamicin, female Sprague-Dawley rats with diabetes of short (5 days, n = 7), intermediate (5 weeks, n = 5) and long duration (5 months, n = 7) were studied. Diabetes was induced by streptozotocin, 50-65 mg/kg b.w. i.v. Controls were identically treated sex- and age matched nondiabetic rats. The animals were kept in individual metabolic cages for 2 weeks and all received gentamicin 40 mg/kg/day for 9 days. Sham animals (DM and control) received Ringer's solution in place of gentamicin. Prior to gentamicin, plasma glucose levels and creatinine clearances (Ccr) were higher in the DM long duration group (619 +/- 25 (SE) mg/dl; 2.6 +/- 0.2 ml/min, respectively) than in the DM short (514 +/- 24; 2.0 +/- 0.1) and DM intermediate duration (442 +/- 30; 2.1 +/- 0.1) groups, while urine volume and glycosuria were similar. Following gentamicin the three control groups developed acute renal failure (maximal decrease in Ccr of 60 +/- 7, 72 +/- 9 and 71 +/- 7%, respectively; p less than 0.01 to less than 0.001), lysozymuria and acute tubular necrosis. There were no significant differences in the degree of renal impairment observed among the three control groups. In marked contrast, in the three DM groups these changes were absent and the renal cortical gentamicin content was lower than that of the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗