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Biomedical subjects

J Kleinerman

Publications and source records attributed to J Kleinerman.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1977

Peripheral airways as a determinant of ventilatory function in the human lung.

We have investigated the morphological differences responsible for the variability in two tests of pulmonary function, maximal expiratory flow rates (MEF) and the frequency dependence of dynamic compliance (CDYN ratio). Functional measurements were obtained from 53 normal and minimally diseased postmortem human lungs. Morphological measurements performed on these same lungs included airway diameter at three levels in the bronchial tree, the amount of bronchial gland mass, and the alveolar surface to volume ratio. Multiple regression analysis suggests that the diameter of the peripheral conduction airways (membranous bronchioles) is the major morphological determinant for both MEF and the CDYN ratio in lungs at any particular age. Age-dependent changes in both functional tests were associated primarily with differences in the alveolar surface to volume ratio. Minimal emphysema and a lesion associated with cigarette smoking, respiratory bronchiolitis, have no demonstrable effect on either MEF or the CDYN ratio. These studies provide further evidence that the peripheral conducting airways are a major determinant of ventilatory function in the normal human lung.

Adolescent↗
PubMed1977

Diffuse pulmonary ossification.

Diffuse pulmonary ossification (DPO) was a complication of "shock lung" after aortic valve replacement in a 52-year-old man. The relationship of DPO to shock lung is discussed. A possible mechanism for this complication is based on the development of a fibrin-platelet-fibroblastic interaction that may establish an intraalveolar lattice for collagen deposition by the fibroblast. The development of acidosis and mechanical forcer may potentiate fibroblastic transformation into an osteoblast. The mechanical forcer may influence the shape of the bone in the lung.

Aortic Valve↗
PubMed1977

Some effects of nitrogen dioxide on the lung.

Nitrogen dioxide (NO2) when inhaled in different concentrations and for varying times produces pulmonary injuries which are dependent on the anatomic site in the lung and the duration of exposure. Single exposures to high concentrations of NO2 for 5-6 hr produce an intense cellular proliferation which regresses within 48 hr in all lung regions except the terminal respiratory bronchiole region and the alveoli where the proliferation persists for 4-7 days. This same delayed response is also observed in more chronic exposures. Histologically, the lesion in the terminal and respiratory bronchioles may resemble an obliterative bronchiolitis, but the lesion clears if further exposure is terminated. Prolonged exposure to 2 ppm NO2, 20-22 hr per day for 7 days per wk, produces an increase in total pulmonary upstream resistance in animals killed immediately after exposure; this resistence returns to normal values within 3 mo after removal from exposure. The internal surface area (ISA) is decreased after 12 mo exposure to NO2, but this loss of surface progresses during the recovery period in air, suggesting an autonomous progression of the tissue destructive process. Exposure to 3.64 ppm NO2 with and without fly ash for periods of 12-14 mo causes no increase in pulmonary resistance and no alteration in lung surface. Lung phospholipids and protein synthesis appear to be depressed following exposure to NO2. Lecithin is significantly increased. The synthesis of proteases by alveolar macrophages is increased during NO2 exposure. Pigmented alveolar macrophages present in animals exposed to NO2 simulate those found in human lungs of young cigarette smokers in the terminal and respiratory bronchioles. The mechanism of tissue injury by oxidants such as NO2 may involve free radical formation, and peroxidation of lipids or proteins.

Air Pollutants↗
PubMed1976

Identification of functional tumor vessels by resorcin-crystal violet stain infusion.

A resorcin-crystal violet solution of low viscosity injected into the circulatory plexus supplying a tumor is used to identify and characterize functional tumor vessels. Unstained sections of tumor tissue demonstrate heavily stained vascular endothelium with no leakage of stain to extravascular tissue for intact vessels, and little or no background staining. The method is simple to apply for tumor vessel morphology and morphometry.

Capillaries↗