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Biomedical subjects

J Kleinerman

Publications and source records attributed to J Kleinerman.

At least 19 recordsLinked to original sources
PubMed1991

Desquamative interstitial pneumonia associated with chrysotile asbestos fibres.

The drywall construction trade has in the past been associated with exposure to airborne asbestos fibres. This paper reports a drywall construction worker with 32 years of dust exposure who developed dyspnoea and diminished diffusing capacity, and showed diffuse irregular opacities on chest radiography. He did not respond to treatment with corticosteroids. Open lung biopsy examination showed desquamative interstitial pneumonia. Only a single ferruginous body was seen on frozen section, but tissue examination by electron microscopy showed an extraordinary pulmonary burden of mineral dust with especially high concentrations of chrysotile asbestos fibres. This report emphasises the need to consider asbestos fibre as an agent in the aetiology of desquamative interstitial pneumonia. The coexistent slight interstitial fibrosis present in this case is also considered to have resulted from exposure to mineral dust, particularly ultramicroscopic asbestos fibres.

Asbestos↗
PubMed1991

Neoplasms associated with pulmonary eosinophilic granuloma.

We found a high prevalence of pulmonary and extrapulmonary neoplasms in patients with pulmonary eosinophilic granuloma (PEG) who were studied at our institution. Among 21 patients with PEG, 10 (48%) had associated benign (one patient) or malignant (nine patients) tumors. Patients with tumors were older at the time of diagnosis of PEG (48.9 vs 34.5 years). Tumors included three lung carcinomas, one pulmonary carcinoid tumor, two lymphomas, five extrapulmonary carcinomas, and one mediastinal ganglioneuroma. Two malignant neoplasms developed in each of two patients. Six tumors preceded, three followed, and three occurred concomitantly with the diagnosis of PEG. Slides from eight PEG-associated tumors and 18 control neoplasms from patients without PEG were also stained immunohistochemically for S100 protein. Four PEG-associated (50%) and 11 control (61%) tumors contained S100 protein-positive interstitial cells. Our study suggests, but does not prove, that there may be more than a random association between PEG and neoplasms. Cigarette smoking, moreover, is an important risk factor for both PEG and lung carcinomas. Our immunohistochemical findings indicate that S100 protein-positive cells in tumors usually bear little or no relationship to PEG. In patients with an underlying malignant neoplasm, PEG simulates pulmonary metastases clinically and, occasionally, histopathologically.

Adult↗
PubMed1990

Respiratory tract pathology in patients with severe burns.

The histologic spectrum, pathogenesis, and clinical correlates of tracheobronchial and pulmonary lesions were studied by autopsy in six children and 27 adult burn victims. The burns covered a mean total body surface area of 57.7 +/- 23%. The mean survival time was 17.6 +/- 14.3 days. Patients over 60 years tended to survive longer than younger adults, but older patients had less extensive burns (P less than .01). Moderate or severe renal failure was an important clinical complication in 19 patients (58%). Diffuse alveolar damage (DAD) was observed in 16 patients, acute bronchopneumonia in seven patients, and necrotizing pneumonia in seven patients. Both DAD and pneumonia coexisted in 11 patients. Children most consistently developed pneumonia, 6 out of 6 versus 4 out of 17 younger adults (P less than .05). Factors which may have contributed to the pathogenesis of DAD included septicemia (12 patients), hypotension (nine patients), necrotizing pneumonia (six patients), and oxygen toxicity (four patients), in addition to the common presence of inhalational injury. The onset of DAD appeared late in eight patients with long survival periods, suggesting causal factors other than inhalational injury. However, survival rate did not differ in patients with or without DAD, and there was no correlation between DAD and the extent of burns. Airway lesions reflected the length of survival and showed the following sequence of changes: (1) mucosal necrosis and denudation, (2) acute inflammation and ulceration, and (3) squamous metaplasia. Endotracheal intubation injury and superinfection were confounding factors beyond the first few days of survival.

Acute Kidney Injury↗
PubMed1990

Metabolism of 5-hydroxytryptophan in the isolated perfused rat lung.

The metabolism of 5-hydroxytryptophan (5-HTP) and tryptophan (TRP) in a single pass across the pulmonary circulation was studied in the isolated ventilated perfused rat lung and by high pressure liquid chromatography. The metabolism of 5-HTP was dependent on the rate of lung perfusion and the duration of infusion of 5-HTP, and was a saturable process with an apparent Km of 1.8 mM and Vmax of 0.14 mumol/g/3 min. The indoles found in the lung were 5-HTP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA); only 5-HIAA was detected in the lung effluent. The efflux of 5-HTP from the lung had two exponential components with half-lives of 0.15 and 3.65 min. After an infusion of 3H-5-HTP, the radiolabel that accumulated in lung was located mainly in the soluble fraction. An infusion of TRP resulted in the synthesis of 5-HTP, 5-HT and 5-HIAA in the lung, and 5-HTP was detected in the lung effluent. The results suggest that 5-HT can be synthesized in the intact lung from circulating TRP and 5-HTP. Since the rate of lung metabolism is low and no 5-HT is released into the lung effluent, the contribution of the lung to circulating levels of 5-HT is likely to be insignificant. Synthesis of 5-HT in intact lung suggests an intrapulmonary role for 5-HT.

5-Hydroxytryptophan↗
PubMed1988

High cathepsin B activity in alveolar macrophages occurs with elastase-induced emphysema but not with bleomycin-induced pulmonary fibrosis in hamsters.

Cathepsin B activity was quantitated in alveolar macrophages obtained from hamsters 10, 21, and 105 days after the intratracheal instillation of porcine pancreatic elastase, bleomycin, or normal saline. Alveolar macrophages lavaged from animals receiving elastase contained significantly higher enzyme levels at 21 and 105 days (16,200 and 17,000 U/mg protein/hr, respectively) as compared with saline-treated animals (12,300 units). In contrast, cells from animals receiving bleomycin showed a decrease in activity at 21 and 105 days (9700 and 9900 units, respectively). At 10 days enzyme levels did not differ significantly. The results suggest that cathepsin B levels in alveolar macrophages reflect differences in lung destruction and connective tissue repair in vivo. In addition, the finding of high cathepsin B activity in animals with emphysema suggests the possibility that cysteine proteases contribute to progressive lung destruction initiated by the intratracheal instillation of elastase.

Animals↗
PubMed1979

Reduction of metastatic rate by immunotherapy: a comparison of the immunogenic properties of metastasizing tumor cells versus tumor cells in the primary mass.

The vasculature of a poorly immunogenic, highly metastatic transplantable fibrosarcoma (T-241) maintained in the femoral muscle of C57BL/6J mice was perfused. This permitted collection of tumor cells which had invaded into the tumor vascular channels (ie, metastasizing tumor cells). Also collected as a separate population were tumor cells from the primary tumor mass. Immunization was carried out with these cell populations in conjunction with BCG and the effect on the growth of primary tumor and metastatic rate was evaluated following rechallenge with unfractionated tumor cells. The rate of tumor growth at the primary site was not affected by any of the immunization schedules. However, immunization with venous effluent cells (metastasizing tumor cells) and BCG was two times more effective in reducing the number of pulmonary metastases than immunization using tumor cells isolated from the primary tumor mass. Passively transferred spleen cells from donors immunized with the cell populations listed above had exactly the same effect, that is, no effect on the growth of the primary tumor, but a dramatic reduction in the metastatic rate when effluent tumor cells were used to immunize cell donors. The data point to an antigenic heterogeneity with this particular transplantable tumor.

Animals↗
PubMed1979

Age-related changes in elastic fibers and elastin of lung.

The effect of age on the lung elastic tissue of inbred BALB/c mice were studied. Static compliance of excised lungs increased with age. Morphometrically determined total elastic fiber length increased with lung expansion in age- and sex-matched mice (r = 0.83, P smaller than 0.001), indicating an axial extension of elastic fibers. However, total elastic fiber length of aging lungs fixed at a distending pressure of 15 cm H2O showed no significant change despite an age-related increase in lung volume (male, r = 0.96, P smaller than 0.001; female, r = 0.95 P smaller than 0.001). The correlative finding of decreased elastin content (r = -0.87, P smaller than 0.001) indicates that there is a loss of elastic fibers in the aging lung. It is suggested that the absence of pseudoelastin fibers, as demonstrated by histochemical techniques, accounts for the observed differences in elastin content of aging human and mouse lungs.

Aging↗
PubMed1978

Pi-Z phenotypes in a pulmonary clinic. Their prevalence and physiologic state.

A series of 1,458 consecutive patients referred to the Cleveland Veterans Administration Pulmonary Clinic for pulmonary function studies was evaluated for alpha 1-antitrypsin deficiency by determination of serum trypsin inhibitory capacity (STIC). Protease inhibitor (Pi) phenotyping was performed on all sera with STIC values less than 1.6 mg/ml. The following non-MM phenotypes were found: 1FZ, 32MZ, 2ZZ, 3SZ, 5SS, 33MS, 21M. The prevalence of Pi Z heterozygosity is 2.74%. This figure is not significantly greater than that observed in a healthy population. A group ( n = 12) with heterozygous Z phenotype (MZ + SZ) was compared with a control (MM) group (n = 13) matched for age, race and smoking history from this same population. Our findings indicate similar deviations from predicted normal values in both control (MM) and Z-heterozygotic groups for physiologic tests of airway resistance, lung volumes, diffusing capacity, and static and dynamic compliance. There was no significant difference between MM controls and MZ heterozygotes in the physiologic variables measured.

Adult↗
PubMed1978

Physiologic and morphologic observations of the effects of intravenous elastase on the lung.

Intravenous administration of porcine pancreatic elastase to hamsters produced significant loss of elastic recoil at low volumes. Histology and mean linear intercept of the lungs fixed at a pressure of 20 cm H2O and studied for 3 weeks after administration of elastase were normal. Larger doses of elastase caused immediate fatal, hemorrhagic pulmonary edema. These results confirmed previous morphologic observations of the effects of intravenously administered elastase, but demonstrated that the loss of elastic recoil at low lung volumes is not invariably associated with histologic changes or morphologically with loss of elastin fibers. These observations suggest that submicroscopic lesions may be present and may antedate the earliest morphologic evidence of emphysema and aging in the lung.

Animals↗
PubMed1978

Structure and function of small airways in health and disease.

During the last two decades, great strides have been made in our understanding of the functional aspects of airflow in the periphery of the lung. It seems that the small airways are the important site of obstruction in a variety of chronic respiratory disorders associated with airflow obstruction. This review deals with the anatomic and functional aspects of small airways in normal and diseased lungs. In particular, the basis of obstruction or narrowing that is not dependent on intrinsic airway lesion is reviewed. The variety of pathologic changes in small airways observed in these diseases are outlined along with physiologic tests that are currently used to detect dysfunction at a stage long before they produce symptoms or alter standard tests of lung function.

Aging↗
PubMed1978

Delayed hypersensitivy and experimental interstitial pneumonitis.

The effects of prior sensitization with killed H37Ra tubercle bacilli on the pulmonary reaction to intravenous (IV) challenge with complete Freund's adjuvant (CFA) have been studied and were compared to reactions in nonsensitized CFA-challenged controls. Rabbits that died within 24 hours of challenge demonstrated acute arteritis prior to granuloma formation. Sensitized rabbits had a greater number of exudative cells in the pulmonary lavage fluid and a larger volume of parenchymal infiltrate than did comparable, nonsensitized controls at two and eight weeks. The exudate and infiltrate were diminished in both sensitized and nonsensitized rabbits at eight weeks. An obliterative, granulomatous arteritis was observed in both sensitized and nonsensitized groups receiving IV CFA and was not affected by the state of sensitivation. Granulomatous and collagenous parenchymal lesions regress in both sensitized and nonsensitized groups between two and eight weeks.

Animals↗
PubMed1977

Micrometastases formation: a probabilistic model.

A mathematical model of the process of metastases is formulated in which the hematogenous metastatic process from a solid tumor is considered to consist of a series of stages. A mathematical expression is obtained for the probability that no metastases will have been established by a characteristic time interval after tumor initiation. The murine T241 fibrosarcoma that rapidly and reproduceably produces pulmonary metastases was studied. Estimates of parameters required for the expression of probability of metastases formation were derived experimentally. The probability remains close to one for a characteristic time at which point it drops to zero. This indicates that at least in this experimental system there is a predictable critical time period beyond which micrometastases are virtually certain to have been formed.

Animals↗
PubMed1977

Degradation of basement membrane by murine tumor cells.

Tumor cells from the murine T241 fibrosarcoma, which rapidly and reproducibility produces pulmonary metastases, were tested in vitro for their ability to degrade isolated pulmonary basement membrane. Degradation of basement membrane substrate was quantified by the culture of the substrate with tumor cells and measurement of the solubilized hydroxyproline and hexose glycoprotein at neutral pH. It was found that tumor cells collected in the tumor venous drainage were associated with a significantly greater solubilization of basement membrane than were tumor cells obtained from the primary tumor mass. Tumor cells were also assayed for their ability to solubilize type I collagen purified from human dura. Venous effluent tumor cells solubilized collagen to a significantly greater level than primary tumor cells, spleen cells, or liver cells. These findings raised the possibility that metastasizing tumor cells may be a distinct tumor subpopulation with regard to invasive potential.

Animals↗
PubMed1977

Morphometric study of elastic fibers in normal and emphysematous human lungs.

The length of elastic fibers and the distribution of fiber diameters was determined by morphometry in the parenchyma of human lungs. Studies were done on 33 lungs from male subjects 1 to 85 years of age, including 9 lungs with mild emphysema. These studies suggest that the total length of elastic fibers is present early in life, possible by 10 years of age, and thereafter remains constant. Average fiber diameter increases between infancy and adulthood but probably does not change further beyond the third decade of life. No significant differences could be detected in either total fiber length or fiber diameter in the lungs with mild emphysema compared to normal lungs of the same age.

Adolescent↗