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Biomedical subjects

J G Clark

Publications and source records attributed to J G Clark.

At least 55 records · Page 3Linked to original sources
PubMed1989

Pulmonary venoocclusive disease following bone marrow transplantation.

We report two cases of pulmonary venoocclusive disease (PVOD) in children with acute lymphoblastic leukemia treated by marrow allograft transplantation following conditioning with high-dose 1-3 bis chloroethyl-1 nitrosourea (BCNU), etoposide (VP-16), and cyclophosphamide (Cy). Both patients developed symptomatic pulmonary hypertension documented by right heart catheterization. Open-lung biopsy of one patient demonstrated PVOD evident even on frozen sections stained with hematoxylin and eosin. High-dose methylprednisolone was associated with significant clinical improvement in both patients. Pulmonary symptoms resolved in one patient who subsequently died in leukemic relapse. PVOD resolved in the other patient, only to recur when steroids were discontinued and then again respond to reinstitution of therapy. More aggressive therapy for malignant diseases may increase the incidence of PVOD. Prompt recognition of its subtle clinical and histological manifestations allows early institution of steroid therapy, which may be beneficial.

Bone Marrow Transplantation↗
PubMed1989

Biopsy diagnosis and clinical outcome of persistent focal pulmonary lesions after marrow transplantation.

We reviewed the results of all percutaneous fine needle aspirations (FNA) and open lung biopsies (OLB) after bone marrow transplantation at our center (1984-1987) for the evaluation of focal lung lesions that developed or persisted despite antibiotic administration. We sought to determine the prevalence and types of infections, the yield of diagnostic procedures, and the clinical outcome of these focal lesions. Infection was documented in 78% (18/23) of all lesions and was fungal in each case. FNA detected fungal lung infection with a sensitivity of 67% (10/15) but had a negative predictive value of only 50% (5/10). Complications occurred in 15% of FNA. OLB without prior FNA was performed in 6 cases and demonstrated fungal infections in 5. Overall, seven of the 18 patients with localized invasive fungal lung disease recovered after antifungal therapy. This study demonstrates that focal lung lesions that develop or persist despite antibiotics after BMT are most often fungal. FNA may safely identify these localized infections in selected patients and with appropriate treatment recovery may be achieved.

Biopsy, Needle↗
PubMed1989

Effects of interferon-gamma on expression of cell surface receptors for collagen and deposition of newly synthesized collagen by cultured human lung fibroblasts.

We used cultured human diploid lung fibroblasts as a model system to examine the effects of recombinant IFN-gamma on synthesis of collagen, matrix deposition of newly synthesized collagen, and the expression of cell surface receptors for collagen. Using [3H]proline-labeled cells we found that IFN-gamma resulted in dose-dependent inhibition of fibroblast collagen synthesis. Pulse-chase experiments to analyze compartmentalization of newly synthesized collagen showed that the decrease in collagen synthesis was confined to the soluble pool of procollagen in the medium, while extracellular matrix associated collagen was not changed, indicating that a larger proportion of newly synthesized collagen was deposited into the matrix in IFN-gamma exposed fibroblasts (34.2 vs. 25.3%). This increase in the efficiency of collagen matrix deposition was associated with enhanced expression of a cell surface receptor for collagen as detected by indirect immunofluorescence labeling and analysis by flow cytometry. Fibroblasts (IMR-90) cultured in the presence of IFN-gamma (1,000 U/ml) exhibited a twofold increase in mean linear fluorescence intensity compared with cells cultured under control conditions. The distribution of log fluorescence intensity in both control and IFN-gamma exposed cells was normally distributed about the mean, indicating that discrete subpopulations with respect to receptor expression were not present. Increased fluorescence intensity and log normal distribution of fluorescence intensity also were identified in IFN-gamma-treated lung fibroblasts from a normal adult individual and two strains obtained from patients with pulmonary fibrosis. These results indicate that IFN-gamma modulates fibroblast collagen matrix deposition as well as collagen synthesis. The associated increase in collagen receptors suggests that cytokine-mediated modulation of the cell surface maybe a contributing factor in regulation of fibroblast collagen accumulation in the extracellular matrix or in cellular interaction with collagen-containing matrix. Such an effect could modulate the interaction of fibroblasts with extracellular matrix at sites of inflammation and play an important role in the remodeling of matrix during repair from tissue injury.

Adult↗
PubMed1989

Autonomy for all.

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Hearing Aids↗
PubMed1988

Mechanical ventilation after marrow transplantation. Risk factors and clinical outcome.

The risk factors for and the outcome of mechanical ventilatory support after marrow transplantation were analyzed in 1,089 consecutive marrow recipients. Of 232 patients receiving ventilatory support at this center, 63 (27%) survived an initial episode of ventilatory support. In contrast, 74% of nonventilated patients survived at least 6 months after transplantation. Among patients with malignant disease (n = 992), a multivariate regression model revealed 3 pretransplant factors that were associated with ventilatory support: age greater than or equal to 21 yr (RR = 1.6, 95% confidence intervals [Cl] = 1.3, 2.0), hematologic malignancy in relapse (RR = 2.1, 95% Cl = 1.7, 2.4), and HLA nonidentical donor-recipient pair (nonidentical graft) (RR = 1.7, 95% Cl = 1.4, 2.1). Survival after ventilatory support was not found to be associated with any pretransplant or post-transplant factors examined. We conclude that although the risk factors for mechanical ventilatory support after marrow transplantation can be defined, we are unable to identify characteristics predictive of survival after such support. The implications of these findings in relation to patient selection and future research activities are discussed.

Adult↗
PubMed1988

Open lung biopsy diagnosis of diffuse pulmonary infiltrates after marrow transplantation.

The results were reviewed of 111 open lung biopsies (OLB) performed on 109 marrow transplantation recipients with diffuse pulmonary infiltrates between January 1983 and July 1987. We determined the frequency and types of infections identified, and the relationship to time after transplantation. Infection was found in 70 of the 111 cases (63 percent) and cytomegalovirus (CMV) was present in 90 percent of all cases with infection. Infection was identified in only five of 26 (19 percent) cases within the first 30 days after transplant, and when present, was viral. The prevalence of infection after 30 days (over 75 percent of 85 cases) was significantly higher (chi 2 = 26.2, p = 0.00001). Bacterial or yeast infections were found in only four cases (4 percent) (two cases each), and Pneumocystis carinii in six cases (6 percent). Simultaneous infection with two or more organisms was found in four cases (4 percent). Four of 25 autopsies performed within ten days after OLB revealed fungal infections with Aspergillus not detected at OLB. Thus, the prevalence of infection detected by OLB is low within the first 30 days after marrow transplantation among patients receiving broad spectrum antibiotics. CMV infection is found in most transplantation recipients who undergo OLB with diffuse infiltrates between days 30 and 180.

Anti-Bacterial Agents↗
PubMed1988

Rapid detection of cytomegalovirus pulmonary infection by bronchoalveolar lavage and centrifugation culture.

Cytomegalovirus infection remains a major cause of morbidity and mortality in marrow transplant recipients. Results of a rapid centrifugation viral culture of bronchoalveolar lavage specimens from 33 marrow transplant recipients with pneumonia were compared with those for conventional viral culture of concurrently or subsequently obtained lung tissue. The centrifugation culture results were also compared to results of cytologic and immunochemical examination of these specimens. Centrifugation culture was positive within 16 hours of inoculation in 22 of 23 (96%) specimens from patients with positive conventional culture of lung tissue. Detection of cells positive for cytomegalovirus by immunofluorescent antibody staining or cytologic identification was less sensitive (59% and 29%, respectively). There was no evidence of cytomegalovirus in specimens from patients without evidence of cytomegalovirus pulmonary infection by any technique. The sensitivity (96%) and specificity (100%) of centrifugation culture of specimens from marrow transplant recipients approach that of viral culture of lung tissue.

Adolescent↗
PubMed1987

Modulation of the effects of alveolar macrophages on lung fibroblast collagen production rate.

Alveolar macrophages (AM) may function as effector cells that can either stimulate or inhibit lung fibroblast collagen production. However, conditions that determine the predominant effect of AM on fibroblasts are not well understood. To delineate factors that modulate the effects of AM on lung fibroblasts, we studied the interaction of AM products and fibroblasts in vitro. The AM were obtained by bronchoalveolar lavage of hamsters with bleomycin-induced pulmonary fibrosis. Conditioned medium (CM) from the AM cultures was incubated in varying amounts with lung fibroblast (IMR-90) cultures. After metabolic labeling with [3H]proline, fibroblast collagen production based on procollagen-specific radioactivity was determined (Anal Biochem 1984; 140:478). Macrophage CM in concentrations greater than 5% suppressed collagen production, an event attributed to the macrophage-derived suppressive factor that we have previously characterized (J Clin Invest 1983; 72:2082). Macrophages were also determined to produce PGE2 in culture (500 pg/10(6) cells). Authentic PGE2 at concentrations found in CM was found to suppress fibroblast collagen production, indicating that AM-derived PGE2 contributes to the suppressive activity in CM. To examine possible stimulatory factors in CM, the fibroblasts were preincubated with indomethacin. This approach was based on our previous observation that AM-derived suppressive factor increases endogenous fibroblast PGE2 and that its activity can be blocked by indomethacin. Macrophage CM in a concentration of 20% did not suppress the collagen production of indomethacin-treated fibroblasts. However, CM concentrations of 5 and 10% increased collagen production (173 and 143% of control values, respectively), indicating the presence of stimulatory factor(s) in macrophage-conditioned medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Risk factors for airflow obstruction in recipients of bone marrow transplants.

Obstructive lung disease is a complication of bone marrow transplantation. To identify risk factors we analyzed pulmonary function tests of 281 adult patients 1 year after marrow transplantation. The forced expiratory volume at 1 second divided by the forced vital capacity (FEV1/FVC) was used to measure airflow rates. Factors associated with a lower year-1 FEV1/FVC (%) included increased age (p less than 0.0001), male gender (p = 0.02), cigarette smoking (p = 0.01), lower FEV1/FVC before transplantation (p less than 0.0001), HLA-nonidentical grafts (p = 0.001), chronic graft-versus-host disease (p = 0.0002), and immunosuppressive therapy with methotrexate (p = 0.01). There was no significant association between the year-1 FEV1/FVC and underlying disease, dose of conditioning irradiation, or development of acute graft-versus-host disease. Linear multivariate regression analysis, after controlling for the FEV1/FVC before transplantation, shows both chronic graft-versus-host disease and administration of methotrexate independently associated with decrements in the year-1 FEV1/FVC. The combined occurrence of chronic graft-versus-host disease and methotrexate also was strongly associated with decreases in the year-1 FEV1/FVC, indicating an interaction of these risk factors.

Adult↗
PubMed1985

Alaryngeal speech intelligibility and the older listener.

Past investigations of alaryngeal speech intelligibility have focused on comparative intelligibility as perceived by young normally hearing adults. However, the spouses and social companions of laryngectomees may have significantly different auditory capabilities compared to young listeners. This report presents a comparison of alaryngeal and laryngeal speech identification performance for a group of young normally hearing listeners and a group of older adult listeners representative of the age of the laryngectomee's social companions. The speech signals investigated included normal laryngeal speech, artificial larynx speech, traditional esophageal speech, and tracheoesophageal speech. The results obtained reveal not only differences in speech signals but also a difference in the proficiency of speech perception for the two groups, favoring the younger listeners. The results of the speech identification measures in the presence of auditory competition revealed greatest intelligibility for the artificial larynx speech signal and poorest for the tracheoesophageal speech signal.

Adult↗
PubMed1984

Fibroblast procollagen production rates in vitro based on [3H]hydroxyproline production and procollagen hydroxyproline specific activity.

In vitro procollagen production rates can be determined by culturing cells in the presence of [3H]proline and measuring the subsequent formation of [3H]hydroxyproline. Values of actual procollagen production can be calculated if the total radioactivity and the specific activity of the newly synthesized procollagen is known. A simple microanalytical method for measuring procollagen specific activity in order to determine procollagen production by lung fibroblasts in vitro is reported. Confluent fibroblasts (IMR-90) were cultured in fresh medium containing [3H]proline, and [3H]hydroxyproline production and prolyl hydroxylation were measured. Hydroxyproline specific activity of nondialyzable procollagen in culture medium as well as extracellular and intracellular free proline specific activity were determined by an ultramicromethod in which the radiolabeled amino acids were reacted with [14C]dansyl chloride of known specific activity [Airhart et al. (1979) Anal. Biochem. 96, 45-55]. Procollagen production rates were readily determined by this method using 5 to 20 microCi [3H]proline and approximately 10(6) cells. It was found that 3H-procollagen production rate into culture medium was constant after a lag of 1.6 h, while procollagen production rate (0.23 pmol/microgram DNA . h) was constant from time zero to 9 h. The specific activities of extracellular and intracellular free proline were not constant during the labeling period, nor were they equal to procollagen specific activity. These data indicate that free proline pool specific activities are not a valid measure of procollagen specific activity. The experimental approach described obviates the need to define or characterize the proline precursor pool from which procollagen is synthesized, and may be readily applied to determine fibroblast procollagen production rates in vitro.

Fetus↗
PubMed1984

Anetoderma: biochemical and ultrastructural demonstration of an elastin defect in the skin of three patients.

Three patients with localized cutaneous lesions characteristic of anetoderma were studied. Clinically, the onset of the disease was between the ages of 17 and 25, and numerous flaccid, saclike skin lesions developed over several subsequent years. Histologically, the lesions were characterized by paucity and fragmentation of the elastic fibers. Electron microscopy demonstrated that the elastic fibers, both in papillary and deep reticular dermis in the lesional skin, were fragmented and irregular in appearance. The concentration of elastin, determined by a radioimmunoassay of desmosine, an elastin-specific cross-link compound, was markedly reduced in the lesions, as compared with unaffected skin from the same patients or with normal skin from unrelated control subjects. In contrast, the concentrations of hydroxyproline, an index of collagen, or deoxyribonucleic acid (DNA), a measure of cellularity, were not changed in the lesions. Thus, the results indicate that in the three patients studied, the elastic fibers are defective and reduced in quantity. These observations suggest that the deficiency of elastin in the dermis may lead to development of the cutaneous lesions of anetoderma.

Adult↗
PubMed1984

Ultraviolet radiation-induced connective tissue changes in the skin of hairless mice.

Hairless mice (Skh/ hr1 ) were exposed to ultraviolet A (UVA; peak irradiance at 365 nm), or to ultraviolet B (UVB; peak irradiance at 313 nm) radiation. The animals received 12 treatments on alternate days. Connective tissue changes in the skin were monitored by assaying hydroxyproline and desmosine as an indication of collagen and elastin concentrations, respectively. The activities of prolyl hydroxylase and collagen glucosyl-transferase, enzymes participating in the biosynthesis of collagen, were also assayed. The concentration of elastin was significantly increased in mice treated with UVA or UVB. The concentration of collagen was unaffected by the treatments, but the activity of prolyl hydroxylase, reflecting collagen synthetic capacity, was decreased in UVA-treated mice. The collagen glucosyl-transferase activity was unchanged. Irradiation of purified human prolyl hydroxylase with UVA in vitro decreased the enzyme activity at higher doses, but UVB had no effect. The results indicate that definitive changes in the biochemistry of dermal connective tissues can be induced by exposure of mice to UV irradiation.

Animals↗
PubMed1984

Enteric parasites in workers occupationally exposed to sewage.

To determine if parasitic infections occur more frequently among workers exposed to wastewater than among controls, parasitologic examinations were performed on stool specimens collected over a 12-month period from sewer and highway maintenance workers. Three of 56 sewer maintenance workers (5.4%) had at least one positive specimen compared with 10 of 69 highway workers (14.5%). The highest rate was found among highway workers engaged in street cleaning. Contrary to studies conducted outside the United States, the present study does not indicate that parasitic infections occur more frequently among sewer workers than among controls in the urban midwestern United States. The results of this study indicate that there may be a risk of parasitic infections among street cleaners.

Adult↗
PubMed1983

Bleomycin-induced pulmonary fibrosis in hamsters. An alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphate and suppresses fibroblast proliferation and collagen production.

Bleomycin-induced pulmonary fibrosis in hamsters is associated with collagen accumulation that results from increased lung collagen synthesis rates. However, 1-2 wk after intratracheal instillation of bleomycin, lung collagen synthesis rates decline toward control values. To evaluate the potential role of the bronchoalveolar macrophage in regulating lung collagen production, we studied the effects of macrophages from normal and bleomycin-treated hamsters upon fibroblasts in vitro. We observed: (a) Medium from macrophage cultures decreased fibroblast [3H]thymidine incorporation and nondialyzable [3H]hydroxyproline production in a dose-dependent manner. Fibroblast cell counts were decreased in exposed cultures, and fibroblast viability was unchanged. Procollagen prolyl hydroxylation and prolyl-transfer RNA-specific activity were not altered by macrophage medium; this indicates that [3H]hydroxyproline reflects collagen production rate under the experimental conditions. (b) The suppressive effect of macrophage medium was selective for collagen since collagen production decreased more than noncollagen protein production. (c) Medium from bleomycin-treated hamster macrophages suppressed fibroblast proliferation and collagen production to a greater degree than medium from normal hamster macrophages. (d) Fibroblast suppression by macrophage medium was associated with increased fibroblast endogenous prostaglandin E2 production and intracellular cyclic AMP (cAMP). (e) Incubation of fibroblasts with indomethacin before exposure completely inhibited prostaglandin E2 production and increases in cAMP, and eliminated suppression of fibroblast proliferation and collagen production. The macrophage-derived suppressive factor has an apparent molecular weight of 20,000-30,000 and is heat stable. It does not appear to be species restricted since both hamster and human lung fibroblasts are similarly suppressed. It is at least in part preformed in macrophages obtained by lavage, but its production can also be stimulated in vitro. We concluded that alveolar macrophages release a product that stimulates endogenous fibroblast prostaglandin E2 production and cAMP formation with resultant suppression of fibroblast proliferation and collagen production. Enhanced release of suppressive factor by macrophages during a time when lung collagen production is declining in bleomycin-induced pulmonary fibrosis suggests that macrophages may limit collagen accumulation in pulmonary fibrosis.

Animals↗
PubMed1983

Elastic fibers in human skin: quantitation of elastic fibers by computerized digital image analyses and determination of elastin by radioimmunoassay of desmosine.

The elastic fibers in the skin and other organs can be affected in several disease processes. In this study, we have developed morphometric techniques that allow accurate quantitation of the elastic fibers in punch biopsy specimens of skin. In this procedure, the elastic fibers, visualized by elastin-specific stains, are examined through a camera unit attached to the microscope. The black and white images sensing various gray levels are then converted to binary images after selecting a threshold with an analog threshold selection device. The binary images are digitized and the data analyzed by a computer program designed to express the properties of the image, thus allowing determination of the volume fraction occupied by the elastic fibers. As an independent measure of the elastic fibers, alternate tissue sections were used for assay of desmosine, an elastin-specific cross-link compound, by a radioimmunoassay. The clinical applicability of the computerized morphometric analyses was tested by examining the elastic fibers in the skin of five patients with pseudoxanthoma elasticum or Buschke-Ollendorff syndrome. In the skin of 10 healthy control subjects, the elastic fibers occupied 2.1 +/- 1.1% (mean +/- SD) of the dermis. The volume fractions occupied by the elastic fibers in the lesions of pseudoxanthoma elasticum or Buschke-Ollendorff syndrome were increased as much as 6-fold, whereas the values in the unaffected areas of the skin in the same patients were within normal limits. A significant correlation between the volume fraction of elastic fibers, determined by computerized morphometric analyses, and the concentration of desmosine, quantitated by radioimmunoassay, was noted in the total material. These results demonstrate that computerized morphometric techniques are helpful in characterizing disease processes affecting skin. This methodology should also be applicable to other tissues that contain elastic fibers and that are affected in various heritable and acquired diseases.

Amino Acids↗