Russell P. Sherwin

Diffuse Interstitial Lung Disease in Systemic Lupus Erythematosus

Abstract The clinical and physiological features of 18 patients with systemic lupus erythematosus and diffuse interstitial lung infiltrations, along with the histopathologic studies in 4 of these s...

A Novel Snake Venom Disintegrin That Inhibits Human Ovarian Cancer Dissemination and Angiogenesis in an Orthotopic Nude Mouse Model

OVCAR-5 is a human epithelial carcinoma cell line of the ovary, established from the ascitic fluid of a patient with progressive ovarian adenocarcinoma without prior cytotoxic treatment. The unique growth pattern of ovarian carcinoma makes it an ideal model for examining the anticancer activity of contortrostatin (CN), a homodimeric disintegrin from southern copperhead venom. FACS analysis revealed that OVCAR-5 is integrin αvβ3 negative, but αvβ5 positive. CN effectively blocks the adhesion of OVCAR-5 cells to several extracellular matrix proteins and inhibits tumor cell invasion through an artificial basement membrane. In a xenograft nude mouse model with intraperitoneal introduction of OVCAR-5 cells, intraperitoneal injection of CN was used for therapy. Tumor dissemination in CN-treated versus control groups was studied by gross examination, and antiangiogenic potential was examined by factor VIII immunohistochemistry and image analysis. CN not only significantly inhibited ovarian cancer dissemination in the nude mouse model, but it also dramatically prevented the recruitment of blood vessels to tumors at secondary sites.

Hyperplasia of Type 2 Pneumocytes and Nitrogen Dioxide (10 ppm) Exposure

An ultrastructural quantitative study of the lungs of 12 guinea pigs exposed continuously to 10 ppm nitrogen dioxide for six weeks, and eight control lungs, revealed greatly increased ratios of type 2 pneumocytes to other cells for the exposed group. The findings, derived from 304 electron photomicrographs at a magnification of 1,700× and a total of 9,307 cells counted, implicate an adverse effect by 10 ppm NO2 on cellular ecology and function, in particular a thickening of the blood-gas barrier through replacement of ultrathin type 1 cells by cuboidal or columnar type 2 pneumocytes. Of 676 type 2 pneumocytes of the exposed group studied for the frequency of “fine and closely packed lamellae,” 66 (9.8%) contained 170 such bodies (2.6/cell) versus 10 of 247 (4%) control type 2 cells containing 17 bodies (1.7/cell). The lungs of the exposed animals also exhibited more frequent intra-cellular and extracellular lipid bodies.

Protein content of lung lavage fluid of guinea pigs exposed to 0.4 ppm nitrogen dioxide.

Lung lavage and disc-gel electrophoresis of the lavage fluid were carried out in a study of 18 guinea pigs, half of which were exposed continuously over a one-week period to 0.4 ppm nitrogen dioxide. Of the nine animal pairs, eight were characterized by higher protein levels for the exposed animals (P < .001). The values for eight of nine control animals were .1097 (arbitrary units) or less, whereas those for eight of nine exposed animals had levels .1164 or higher, with a maximum of .1698. The methodologies represent a relatively simple means of detecting a physiologically important alteration and have the potential of greater sensitivity to and specificity of protein content through new advances in electrophoretic techniques.

Silicone Fluid for the Metering and Monitoring of Nitrogen Dioxide

A method for the continuous delivery of nitrogen dioxide gas to environmental exposure chambers has foeem developed utilizing silicone fluid (DC 200 fluid) as a carrier for the gas and a drop-rate measurement for the metering and monitoring of rate of delivery. An approximately linear relationship was found between drop rate and NO2 concentration as determined with fritted-bubbler samples and meter recordings, With a 4-liter reservoir, little change in drop rate was noted over a 48-hour period, and simple adjustments In height of the reservoir permitted accurate maintenance of the gas concentration in the chamber. The method is particularly advantageous for the continuous delivery of NO2 gas at levels Sess than 5 ppm and has the important attributes of reliability, simplicity of operation, ease of monitoring, and relative safety.

Behavior of cancers of the human lung in short-term tissue cultures.

Forty six human lung cancers have been studied in vitro by phase microscopy, cinemicrography and cytologic staining of monolayers. In addition the in vitro findings have been correlated with histologic examinations of whole lung sections and cancer tissue explants sacrificed at specific intervals. The in vitro study was restricted to short‐term cultures to provide an optimal reflection of in vivo cancer properties. The use of a multidiscipline methodology assured the identification of the in vitro cancer cell and the validity of the findings. Eight distinctive types of in vitro cancer behavior have been found, cellular interactions described and new cytostructural insights gained. Also, in vitro parameters of potential clinical value are suggested, particularly in view of the high yield of lung cancer cells obtainable in short‐term cultures.

Alveolar wall cells of the guinea pig. Increase in response to 2 ppm nitrogen dioxide.

The ratios of lactate dehydrogenase-positive alveolar wall cells (primarily type 2 pneumocytes) to alveoli were determined for the lungs of control and exposed (continuous 2 ppm nitrogendioxide) guinea pigs. The study was divided Into three exposure periods of one, two, and three weeks with four pairs of control and exposed animals evaluated for each period. The findings tentatively indicate disturbances in the microecological aspects of cells of the lung secondary to, but not specific for, NO2 exposure, and further suggest with the support of other studies that type 1 cells are being replaced by type 2 cells. Confirmation of the findings and an exploration of the question of reversibility are part of the ongoing study.

Hypertrophy of Alveolar Wall Cells Secondary to an Air Pollutant

When guinea pigs were exposed to 2 ppm nitrogen dioxide continously for 7, 14, and 21 days, a significant increase was found in the average area per alveolar wall cell (P < .025). The duration of the experiment was also significant (P < .05). The method as used, based on an image analyzer quantitation of 9,824 lactate dehydrogenase- positive alveolar wall cells, can contribute to the basic understanding of the type 2 pneumocyte and potentially to the establishment of air quality standards.

Protein Leakage in the Lungs of Mice Exposed to 0.5 ppm Nitrogen Dioxide

Forty-four mice were continuously exposed to 0.47 ppm nitrogen dioxide for ten, 12, and 14 days. The protein content of homogenized lung tissue was assayed fluorometrically after the animals had received intravenous injections of fluorescamine, a new reagent for protein assay. The mean protein value of all exposed animals was higher than that of the control animals (P less than .025). No correlation was noted between serum fluorophor levels and those in the lung homogenate.

The significance of autochthonous lymphocyte interactions with human breast cancer cells in primary tissue cultures

Short‐term primary tissue cultures of 16 human breast cancers were employed to study cancer cell interactions with autochthonous lymphocytes. Attention was given to 4 lymphocyte interactions, 1 random and 3 special forms, i.e., clustering, congregation, and emperipolesis. Stained tissue culture preparations were used to count the total number of cancer cells and the frequencies of the different lymphocyte interactions with the cancer cells. Comparisons were made of interactions of 2 groups of autochthonous lymphocytes—those already present in the explant of cancer tissue and those of homolateral axillary lymph node origin which were added to the nutrient media. Where lymphocytes were not added, only 29% of the cases had one or more preparations positive for interactions, whereas the corresponding figure for the group with added lymphocytes was 65%. In addition, the frequency of the interactions within each of the positive preparations was increased fourfold. Furthermore, in those preparations where an increased frequency was noted, the yield of viable cancer cells was significantly less than that found in the corresponding cultures without added lymphocytes. Conversely, an increase in cancer yield occurred in those cultures where the addition of lymphocytes failed to increase the frequency of interactions. These and other findings dealing with distinctive lymphocyte responses of an individual to his own cancer provide insight into host defense mechanisms not otherwise available.