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Biomedical subjects

J Kelley

Publications and source records attributed to J Kelley.

At least 109 records · Page 6Linked to original sources
PubMed1983

The colposcopy clinic in a residency training program. Five years' experience with colposcopically directed biopsies followed by conization or hysterectomy.

Five hundred fifty-four patients with abnormal cytologic smears were screened in a special clinic by gynecology residents under faculty supervision using colposcopy and biopsies. Two hundred fifty patients who were evaluated by colposcopy subsequently had conization or hysterectomy. Colposcopically directed biopsies were accurate (comparable to the surgical specimen) in 92%. Three patients had invasive cancer high in the endocervical canal that was found by conization after endocervical curettage and colposcopy had indicated less-severe disease. Persistent or recurrent dysplasia was found in approximately 5% after conization and in none after hysterectomy. Because 23% of patients were lost to follow-up after treatment and an additional 19% had inadequate follow-up, management of CIN III with local destruction (cryocautery, electrocautery, laser) does not seem advisable.

Adolescent↗
PubMed1982

Pulmonary toxicity following gastrointestinal ingestion of kerosene.

The continuous controversy concerning the treatment for acute hydrocarbon ingestions led to a study of the pulmonary effects of kerosene absorption from the gastrointestinal tract in dogs. Gastrostomies and cervical esophageal transections with a proximal esophageal fistula were performed on 11 dogs under general anesthesia. Following a return of normal bowel function each animal was given 20 cc/kg of a commercial-grade kerosene by gastrostomy tube. The dogs were randomly divided into two groups for necropsy at 24 and at 72 hours, and each dog had chest radiographs prior to instillation of the kerosene and at 6, 24, 48, and 72 hours, depending on their group. The dogs were given an overdose of barbiturate for euthanasia. Tissue was randomly selected from the lungs and examined using standard microscopic and histologic techniques. No clinical complications were observed in any of the animals following the kerosene instillation. No radiologic or histologic evidence of pulmonary changes due to kerosene was found. The lack of pulmonary pathologic changes following kerosene ingestion in dogs protected from aspiration suggests that the treatment for kerosene poisoning should be confined to supportive measures. Induction of emesis is contraindicated in the management of hydrocarbon ingestion.

Animals↗
PubMed1982

Increased contractility of isolated lung parenchyma in an animal model of pulmonary fibrosis induced by bleomycin.

The contractile capability of lung parenchymal strips isolated from normal rats was compared with that of strips isolated from rats with pulmonary fibrosis induced by intratracheal instillation of bleomycin sulfate. Subsequently, the population of contractile cells, both muscle and nonmuscle, was analyzed in each strip by histochemical, immunocytochemical, and ultrastructural means. The force (g force/g tissue wet weight) generated by fibrotic strips was approximately double that of the control strips in response to acetylcholine, epinephrine, and potassium depolarizing solution. The content of smooth muscle in fibrotic and control strips was not significantly different. Immunofluorescent examination indicated increased contractile proteins (actin and myosin) in the thickened alveolar walls of the fibrotic strips in areas devoid of histologically demonstrable smooth muscle. Ultrastructural examination of the fibrotic interstitium revealed an increased population of filament-laden cells that appeared related to the contractile interstitial cell, or myofibroblast. The results indicate that parenchymal strips isolated from fibrotic rat lung can generate increased force in vitro. These responses may be related to increased nonmuscle contractile cells in the fibrotic interstitium.

Animals↗
PubMed1981

Pulmonary macrophages alter the collagen phenotype of lung fibroblasts.

Cultured lung fibroblasts produced and secreted interstitial collagen types I and III. The relative proportion of type III collagen increased as a linear function of cell density, with confluent cultures producing 8.6% type III collagen. When human lung fibroblasts were cultured in the presence of newly harvested lung macrophages, the proportion of type III collagen secreted rose to 15.5%. This high level of type III collagen synthesis was greater than could be induced by withdrawal of serum, a perturbation known to alter the proportion of types I and III collagen synthesized by fibroblasts. This effect on fibroblast phenotype was independent of cell density, as both low and high density cultures of fibroblasts responded similarly when cultured with macrophages. There was no evidence that fibroblasts synthesize new or different collagen types (such as type I trimer) in response to macrophages. Optimal conditions for eliciting an effect on fibroblast connective tissue metabolism required interaction of the two cell types for 5-8 days. These in vitro changes are analogous to the sequence of interactions and changes in connective tissue metabolism seen during recovery from tissue injury.

Cell Communication↗
PubMed1981

Renal acidification in the hypothyroid rat. Evaluation by urinary CO2 tension.

We have previously demonstrated an abnormal renal response to chronic acid loading in the hypothyroid rat. The present study was designed to characterize further this defect by examining the renal response to bicarbonate loading. Hypothyroidism was induced by the intraperitoneal injection of Na131I and animals were studied 10 or more weeks thereafter under anesthesia and compared with their age-matched littermates. Insulin clearance of hypothyroid animals was lower and fractional urine flow and sodium excretion rates were higher than in the control rats. At the time of maximal urinary bicarbonate levels, the urine PCO2 exceeded blood values (U - B PCO2) by 41 plus or minus 2 (mean plus or minus SE) mmHg (1 mmHg equals 133.22 Pa) in the controls and 25 plus or minus mmHg in the hypothyroid rats (p less than 0.001). Although maximal urinary bicarbonate concentrations achieved during bicarbonate loading were lower in the hypothyroid animals. U - B PCO2 was consistently less in controls when compared at similar urine bicarbonate concentrations. Thus, the difference in U - B PCO2 was not explained by lower urinary bicarbonate concentrations in the hypothyroid animals. Maximal U - B PCO2 during neutral phosphate loading was significantly less in the hypothyroid rats (38 plus or minus 2 mmHg) than in the controls (68 plus or minus 5 mmHg), p less than 0.001, arguing against a gradient defect of distal hydrogen ion handling. These data indicate that hypothyroid rats exhibit an impairment of distal hydrogen ion secretion.

Animals↗
PubMed1981

Lung cell population density determines the ratio of type III to type I collagens.

Cultured human lung fibroblasts produced 26 to 68% more type III collagen at confluency than at low cell density. This phenomenon occurred in cell lines from normal embryonic and adult lung tissue as well as in cultures established from fibrotic lung tissue. Modulation of the proportions of individual collagen types may be important in the genesis of pulmonary fibrosis.

Adult↗
PubMed1981

Collagen lysyl oxidase activity in the lung increases during bleomycin-induced lung fibrosis.

Intratracheal administration of bleomycin caused pulmonary fibrosis in rats. Bleomycin sulfate (640 micro grams/165 g b.wt. in 0.5 ml of sterile saline) was instilled Intratracheally into male Fisher 344 rats (169 +/- 5 g), whereas control animals received 0.5 ml of sterile saline by the same route. One, 3, 7, 14, 28 and 322 days after instillation, the animals were killed, the lungs were homogenized in 6 M urea, 0.01 M NaCl, 0.001 M potassium phosphate (pH 8.3) and the homogenates were subjected to ultracentrifugation. The 106,000 x g supernate was assayed for lysyl oxidase activity. Total lung hydroxyproline and desmosine content was determined at each time point. Lysyl oxidase specific activity in the lung was elevated significantly 3 days after bleomycin treatment, peaked 14 days after bleomycin treatment at 230% above the control value and was returned toward normal 28 days after treatment. The increase of lysyl oxidase activity preceded the maximal increase of total lung hydroxyproline and desmosine which occurred 28 days after bleomycin instillation.

Amino Acid Oxidoreductases↗
PubMed1980

Utilization of D-phenylglycyl-glycine in Escherichia coli.

Escherichia coli K 12 is able to utilize the dipeptide D-phenylglycyl-glycine as a source of glycine. Growth experiments with a glycine auxotrophic mutant show that utilization of there dipeptide is competitively inhibited by D-alanine at a Ki of 4 x 10(-4) M. In contrast, L-alanyl-L-alanine which is transported via the system specific for dipeptides does not interfere with the utilization of D-phenylglycyl-glycine. This indicates that the dipeptide is hydrolyzed prior to uptake, and D-alanine therefore competes with the uptake of glycine via the transport system common for both amino acids. This was confirmed by examining the growth response of various transport mutants. A mutant deficient in the transport of oligo- and dipeptides grows as well as the wild type on D-phenylglycyl-glycine, whereas the growth of mutants deficient in the transport of glycine is severely impaired or prevented with this dipeptide. It is therefore demonstrated that D-phenylglycyl-glycine is hydrolyzed prior to uptake. This is a mechanism of peptide utilization in E. coli K 12 which is distinct from that described so far for other dipeptides.

Alanine↗
PubMed1980

Bleomycin-induced pulmonary fibrosis in the rat. Prevention with an inhibitor of collagen synthesis.

Pharmacologic treatment of pulmonary fibrosis has been limited to the use of corticosteroids occasionally combined with other immunosuppressive agents. We tested the ability of a proline analogue that is a potent inhibitor of collagen biosynthesis to prevent the manifestations of bleomycin-induced pulmonary fibrosis in an animal model. Bleomycin sulfate was administered by intratracheal instillation to produce pulmonary fibrosis in male Fischer 344 rats. After 28 days lungs from bleomycin-treated animals had histologic, biochemical, and functional alterations consistent with pulmonary fibrosis. Vital capacity and compliance were reduced to 62% and 41% of their respective control values. Lung prolyl hydroxylase activity doubled during the first week after bleomycin, at a time when total lung collagen content remained unchanged. Thereafter total lung collagen content slowly rose to 72% above control values at 28 days. We administered the proline analogue DHP at a dose that completely inhibited the elevated levels of lung prolyl hydroxylase activity. Pulmonary collagen content of animals treated with DHP was only minimally elevated, and functional abnormalities were reduced. Pulmonary compliance increased significantly from 0.25 to 0.44 ml/cm of H2O, and vital capacity increased from 3.94 to 5.65 ml. These studies suggest that proline analogues offer potential for modifying the manifestations of pulmonary fibrosis that occur as a consequence of acute lung injury. Elevation of lung prolyl hydroxylase activity is an early even that serves as a useful index of the acute lung injury produced by bleomycin.

Animals↗
PubMed1980

Assessment of bleomycin lung toxicity using angiotensin-converting enzyme in pulmonary lavage.

Activity of the dipeptidyl hydrolase angiotensin-converting enzyme has been observed to be altered by treatment with bleomycin. We used an animal model of bleomycin lung toxicity to study the effects on angiotensin-converting enzyme activity in various lung fractions. Serum activity of angiotensin-converting enzyme increased only 23% after a single intratracheal instillation of bleomycin. Lung tissue angiotensin-converting enzyme activity fell to 40% of control level (p < 0.05) and returned toward and eventually exceeded control values during the ensuing 6 weeks. However, angiotensin-converting enzyme activity in alveolar lavage fluid from bleomycin-treated rats was elevated 30-fold above the barely detectable levels found in control animals. Angiotensin-converting enzyme activity in lavage fluid was soluble and was not associated with the alveolar cell pellet. Maximum elevation of lavage angiotensin-converting enzyme activity occurred 3 days following bleomycin instillation. Significant transudation of serum into alveolar lavage fluid occurred in bleomycin-treated rats. Nevertheless, this phenomenon would not explain the high levels of angiotensin-converting enzyme activity found in lavage fluid. Elevated lavage angiotensin-converting enzyme levels were detected after doses of bleomycin too low to cause significant sequelae of pulmonary fibrosis. Lavage angiotensin-converting enzyme is a sensitive monitor of tissue response to bleomycin.

Animals↗
PubMed1979

Isolation and characterization of fibroblasts obtained by pulmonary lavage of human subjects.

Cells that possess the morphology and collagen synthetic capacity of fibroblasts were recovered by bronchofiberscopic subsegmental pulmonary lavage from patients with pulmonary fibrosis, from patients with miscellaneous nonfibrotic lung diseases and from healthy volunteers. Lavage cells were placed in tissue culture, observed for 2 to 6 weeks, and compared with human lavage pulmonary alveolar macrophages (PAM), WI-38 and IMR-90 human fetal lung fibroblasts, and adult lung tissue fibroblasts (CLAC-76). Lavage fibroblsts (LF) were identified as proliferating clones in monolayers of nonproliferating PAM and could be subcultured repeatedly. Fibroglasts were propagated from 28 of the 92 lavage specimens cultured. Time-lapse cinematography showed similar distributions of interdivision times for LF, CLAC-76 and WI-38, but the LF and CLAC-76 lines had slower mean migration rates than the fetal line. Light, scanning, and transmission electron microscopy of LF showed attenuated spindle-shaped cells with interdigitating filopodia, flat surfaces with few microvilli, and containing numerous cytoplasmic polyribosomes and rough endoplasmic reticulum. Extracellular fibrils with the appearance of collagen were seen. Collagen synthesis by LF was measured as 3.9% to 4.9% of the cell-associated protein sensitive to bacterial collagenase. This protein was rich in hydroxyproline, and had an electrophoretic migration pattern identical to known collagen. LF did not contain lysozyme although this enzyme was abundant in fresh and 1-week cultured PAM. Thus LF were similar to human fetal and adult lung tissue fibroblasts in their morphology, tissue culture characteristics, constitutive enzymes and collagen synthetic properties but were distinctly different from PAM.

Cell Line↗
PubMed1979

Impaired renal bicarbonate reabsorption in the hypothyroid rat.

We previously demonstrated a decrease of sodium reabsorption in the proximal superficial nephron of the hypothyroid rat. The present clearance studies were designed to examine the renal handling of bicarbonate in hypothyroid rats. Hypothyroidism was induced by the intraperitoneal injection of Na131I and the animals were studied 10 or more wk thereafter under anesthesia and compared to their age-matched litter-mates. As is characteristic of hypothyroid animals, insulin clearance was lower and fractional urine flow and sodium excretion rates were higher than in the control rats. At the peak of the bicarbonate diuresis and at similar blood pH, PCO2, and bicarbonate levels, fractional renal bicarbonate excretion was significantly higher in the hypothyroid animals: 22 +/- 2 vs. 15 +/- 1%, P less than 0.02. This perturbation of bicarbonate reabsorption of the hypothyroid rats was independent of the influence of extracellular fluid volume expansion and appears closely related to the impaired sodium reabsorptive capacity characteristic of experimental hypothyroidism.

Animals↗
PubMed1978

Diagnosis of pneumonia due to Pneumocystis by subsegmental pulmonary lavage via the fiberoptic bronchoscope.

To assess the accuracy of pulmonary lavage in diagnosing pneumonia due to Pneumocystis, we used animals as a model and then prospectively studied 33 immunosuppressed adults with diffuse pulmonary infiltrates. In rats treated with cortisone, Pneumocystis organisms could be found in the effluent from lavage as early as in sections of pulmonary tissue, and the effluent from lavage remained diagnostic throughout the ten weeks of observation. Subsegmental lavage in adult patients was performed through the wedged fiberoptic bronchoscope. Pneumocystis organisms were demonstrated in seven patients by lavage, and no false-negative results were recorded. Pneumocystis organisms were readily identified among the sheets of alveolar macrophages seen in smears of the effluent from lavage that were stained with methenamine silver. Subsegmental lavage via the fiberoptic bronchoscope is an accurate and safe technique for establishing the diagnosis of pneumonia due to Pneumocystis in patients whose respiratory embarrassment or thrombocytopenia makes biopsy of the lung hazardous.

Animals↗