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Biomedical subjects

J Kleinerman

Publications and source records attributed to J Kleinerman.

At least 37 records · Page 2Linked to original sources
PubMed1985

Pseudomembranous necrotizing bronchial aspergillosis. A variant of invasive aspergillosis in a patient with hemophilia and acquired immune deficiency syndrome.

A 15-yr-old male hemophiliac developed the acquired immune deficiency syndrome (AIDS). His terminal illness was characterized by rapidly progressive respiratory failure with intermittent wheezing, nonresponsive to bronchodilator and steroid therapy. Postmortem examination revealed a pseudomembrane covering the mucosa of the lower trachea and bronchi of both lungs. This pseudomembrane was composed predominantly of fungal hyphae speciated as Aspergillus niger. There was widespread transmural necrotizing bronchitis and fungal invasion that extended to involve a narrow zone of peribronchial tissues. The intervening lung parenchyma was free of fungal disease. This unique form of bronchitis is a distinct variant of invasive aspergillosis and merits recognition because of its clinical and prognostic implications.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Fetal lung hypoplasia associated with maternal smoking: a morphometric analysis.

Our recently reported animal (rat) model of maternal cigarette smoke exposure during pregnancy is characterized by fetal growth retardation and lung hypoplasia. We have further defined the fetal lungs using quantitative histologic techniques. Compared to controls, lung volume at term is reduced in the experimental animals (0.28 versus 0.33 ml, p less than 0.005). Saccules (fetal "alveoli") are reduced in number (3 X 10(6) versus 5.5 X 10(6), p less than 0.005) and increased in size (average saccular volume: 35 X 10(-9) versus 21 X 10(-9) ml, p less than 0.025). These changes in size and number are consequences of reduced formation of saccule partitions (septal crests) in the experimental lungs (volume density: 0.013 versus 0.018, p less than 0.025). Internal surface area is decreased in the hypoplastic lungs (161 versus 198 cm2, p less than 0.001). The total length of parenchymal elastic tissue is diminished (224 versus 354 M, p less than 0.05). In short the hypoplastic lungs contain fewer, larger saccules and the surface potentially available for gas exchange is reduced. These results show that maternal smoking in rats adversely modifies fetal lung growth. If these observations are applicable to humans, then reduced lung growth in children of smoking mothers may begin antenatally.

Animals↗
PubMed1984

Diagnosis of lung cancer by fibreoptic bronchoscopy: problems in the histological classification of non-small cell carcinomas.

Specific cell typing in lung cancer has important implications for assessment of prognosis and the planning of treatment. Cell typing is, however, often difficult and the problem has been compounded by the universal use of the flexible fibreoptic bronchoscope, which yields specimens only 2 mm in diameter. We have reviewed the records of 107 patients who had a diagnosis of lung cancer established by fibreoptic bronchoscopy and who subsequently underwent staging biopsy or surgical resection. Examination of tissue obtained by surgical resection yielded a different cell type from that identified in specimens obtained at fibreoptic bronchoscopy in 11 of 32 patients with a bronchial biopsy specimen diagnostic of squamous cell, three of 44 patients with a diagnosis of adenocarcinoma, six of seven thought to have a poorly differentiated carcinoma, and 21 of 24 patients with a diagnosis of large cell carcinoma. In all, 41 of the 107 surgically removed specimens (38%) differed in cell type from their corresponding bronchoscopic specimens. Accurate cell typing by specimens obtained at fibreoptic bronchoscopy may be extremely difficult. If clearcut morphological criteria cannot be satisfied, the diagnosis of "lung cancer, non-small cell type" should be made.

Adenocarcinoma↗
PubMed1984

Quantitative studies of argyrophilic APUD cells in airways. III. The effects of sensitization and anaphylactic shock.

A morphometric study of argyrophilic APUD cells in airways and intestine of guinea pigs during sensitization with ovalbumin and anaphylactic shock is reported. The APUD cell densities are expressed as APUD cell number/mm of airway or gut perimeter length and as APUD cell/100 epithelial cells. The latter ratio is useful to distinguish specific changes in APUD cells from generalized epithelial changes. Control guinea pigs have greater densities of APUD cells in the larynx (0.075 +/- 0.021 APUD/100 nuclei) than in more distal airways: trachea (0.025 +/- 0.007), bronchi (0.013 +/- 0.003), and bronchioles (0.003 +/- 0.002). In the ileal mucosa APUD cells are present in greatest density: 10.0 +/- 3.0 APUD/100 nuclei. Immunization with ovalbumin followed by sham challenge with saline results in 2- to 10-fold increases in APUD cell densities in all airway sectors as compared to control subjects. These differences are statistically significant in the trachea and bronchioles when ratios of APUD cells/mm are compared to control subjects but only in bronchioles when the ratios of APUD cells/100 nuclei are calculated. Immunization with ovalbumin followed by challenge with this antigen results in similar changes in large airways. However, bronchiolar APUD cells exhibit a 30-fold decrease in density when compared to immunized-sham challenged animals within the limits of our ability to quantitate them. Our findings suggest that argyrophilic APUD cells participate in the complex physiologic events that take place in the lung during sensitization and anaphylaxis.

APUD Cells↗
PubMed1984

Problems in the diagnosis of small cell carcinoma of the lungs by fiberoptic bronchoscopy.

Fiberoptic bronchoscopy (FOB) with the aid of endoscopic biopsies and brush cytology is recognized as a valuable approach in the diagnosis of lung cancer. However, histologic classification of lung cancer based on tiny specimens obtained from FOB can be difficult. Correct identification of small cell carcinoma of the lung is especially important because its recognition usually precludes surgery. In a review of 770 patients who underwent FOB biopsies at The Mount Sinai Hospital, New York, in individuals with proven lung cancer 150 instances of small cell carcinoma were encountered. In four of these instances subsequent surgery, such as scalene node biopsy, mediastinoscopy, or thoracotomy, was performed because clinically and radiologically the tumors did not behave as small cell carcinomas. Pathologic examination of larger tissue samples from these neoplasms provided the following final diagnoses: bronchial carcinoid, adenocarcinoma, squamous cell carcinoma, and small cell carcinomas-combined type. Analysis of the FOB biopsies and brush cytology usually permit diagnosis of small cell carcinoma of the lung. However, in instances where the biologic behavior of a tumor casts doubt on the diagnosis of small cell carcinoma, further studies should be performed, including radionuclide scans, and bone marrow and other biopsies before denying the patient a chance of surgical cure.

Aged↗
PubMed1982

Quantitative studies of argyrophilic APUD cells in airways: II. The effects of transplacental diethylnitrosamine.

The effects of transplacental administration of diethylnitrosamine (DEN) on the densities of epithelial and APUD cells in the large and small airways of developing hamsters have been studied quantitatively. The APUD cells are quantitated by relating them to the number of airway epithelial cells; APUD cells are present in similar densities in the large airways (0.12 APUD cells/100 cells) and small airways (0.14) of 2-day-old control hamsters. At 4 days an increase in the densities of APUD cells and an increase in epithelial cells is observed in the small airways, whereas those in the large airways decrease slightly. At later periods there is a progressive decline in the density of APUD cells in the control hamsters. Exposure in utero to DEN results in a generalized increase in APUD cells in 2-day-old hamsters, which is more pronounced in bronchioles (fivefold increase). The effect disappears in older animals. It also results in a transient increase in tracheal epithelial cell density in 7-day-old hamsters. Whether the selective and transient APUD cell hyperplasia induced by transplacental administration of DEN results from proliferation of these cells or from differentiation of other types of epithelial cells into APUD cells requires further study.

APUD Cells↗
PubMed1982

Immunocytochemical studies of APUD cells in airways: effects of nitrosodiethylamine and nitrogen dioxide.

The amine precursor uptake and decarboxylase (APUD) cells and neuroepithelial bodies (NEBs) in airways of adult rats have been studied by immunocytochemical methods for the presence of adrenocorticotropic hormone (ACTH), growth hormone (hGH), calcitonin, and bombesin in control animals and following exposure to nitrosodiethylamine and nitrogen dioxide (NO2). Calcitonin-like immunoreactivity (CLIR) is present in APUD cells of the trachea and bronchioles and in NEBs in the lung. Rats treated with nitrosodiethylamine and NO2 exhibit increased numbers of argyrophilic cells but no increase in cells containing specific intracytoplasmic CLIR. The presence of ACTH, hGH, and bombesin in respiratory tract APUD cells was not observed. These studies indicate that APUD cells in the trachea and bronchioles of adult rats harbor endocrine cells with immunohistochemical characteristics similar to C cells of the thyroid, and that these cell do not appear to be altered in number when rats are treated with agents known to produce an increase in APUD cells.

APUD Cells↗
PubMed1981

Lung injury and repair in the blotchy mouse. Effects of nitrogen dioxide inhalation.

We studied the reparative process after inhalation exposure to 20 ppm of nitrogen dioxide (NO2) in the lungs of hemizygous blotchy male (Blo/g) and heterozygous blotchy female (Bio/+) mice. Age-matched siblings (C3Hf) without the blotchy gene at X-chromosome locus (+/y) and +/+) served as control animals. After exposure to NO2 for 28 days, there was a marked progression in the extent of emphysema in Blo/y mice associated with a significant decrease of internal surface area (p < 0.05) and an increase in the mean linear intercept (p < 0.005). In contrast, +/y, Blo/+, and +/+ mice showed mild airspace enlargement without decrease in internal surface area after similar exposures. Blo/y mice killed 1 month after cessation of NO2 exposure showed a persistent, mild chronic bronchiolitis that was more frequent and of greater severity than that present in control +/y mice. Alveolar macrophages in the Blo/y mice were larger than those in +/y, +/+, and Blo/+ mice both before and after exposure to NO2. Crystalloid inclusions were observed in the enlarged alveolar macrophages of the Blo/g mice only after exposure to NO2, but were not seen in control animals. These observations indicate that the pattern of lung injury and repair after subacute exposure to 20 ppm of NO2 in the Blo/y mouse differs from that present in age-matched siblings in that inherited abnormalities in alveolar macrophage function may exist in addition to the previously described alterations in connective tissue proteins. Both of these alterations may influence the development of emphysema in the blotchy male mouse.

Animals↗
PubMed1981

Quantitative studies of APUD cells in airways of rats. The effects of diethylnitrosamine and NO2.

A method of quantitating the airways amine precursor uptake decarboxylase (APUD) cells is proposed that relates these cells to total airway epithelial cells or airway length. In control rats, these values were 0.13 APUD cells/100 epithelial cells in the trachea, 0.03 in the large airways, and 0.02 in the small airways. In order to evaluate the ability of this method to determine changes in number of APUD cells, rats were exposed to diethylnitrosamine (DEN) and nitrogen dioxide (NO2), which have been reported to increase the number of airways APUD cells. The NO2 exposure was associated with a twofold increase in APUD cells of the trachea only without associated epithelial hyperplasia; DEN produced marked epithelial hyperplasia in the trachea and bronchi with a disproportionate increase in APUD cells in the bronchial epithelium only. The basis of this differential effect requires further study.

APUD Cells↗
PubMed1980

APUD cells and neuroepithelial bodies in hamster lung: methods, quantitation, and response to injury.

A comparative study of the Falck-Hillarp Technique, a modification of Eaton-Fedde procedure and silver staining of aldehyde-fixed tissue was carried out to determine the most efficient procedure to demonstrate neuroendocrine cells of the hamster and rat lung. The modified Eaton-Fedde procedure is the most efficient method of observing these cells, and is also the easiest to perform. With this method, the normal hamster lung contains a total of 2.00 x 10(-1) to 3.00 x 10(-1) neuroendocrine cells/mm in the small and large bronchioles. In the larger airways approximately 3.51 x 10(-1) neuroepithelial bodies (NEB)/mm are observed. Immediately after 24-hour exposure to NO2 the number of APUD cells dropped to approximately 25% of the control levels. These cells were decreased to 50% of the control levels throughout the 28 days of exposure. The number of NEB decreased transiently after 24 hours of NO2 but returned to normal numbers by day 14. We recommend the application of fluorescence techniques coupled with standardised sections and quantitative methods of study for analysis of APUD cells and NEB.

APUD Cells↗
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↗