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Biomedical subjects

R P Sherwin

Publications and source records attributed to R P Sherwin.

At least 19 recordsLinked to original sources

Air pollution: the pathobiologic issues.

In defining the adverse effects of ambient levels of ozone on the human lung, research has tended to emphasize direct cause and effect responses. However, disease is generally multicausative and the lung has relatively few ways to respond to injury. Moreover, all adult lungs have some disease. Thus, pathogenesis is more appropriately addressed by asking "What role does the agent in question play in the causation, promotion, facilitation, and/or exacerbation of disease that is present?" Our recent studies of the lungs of 107 ostensibly healthy youths between 14 and 25 years of age (violent death cases in Los Angeles County) add suggestive evidence to epidemiologic and experimental data indicating that air pollution is adversely affecting the human lung. We found 80% of the youths with some degree of presumably subclinical Centriacinar Region disease and, in 27%, the Centriacinar Region disease was severe and extensive. Centriacinar Region disease has been linked to infectious organisms, cigarette smoke, ozone, mineral dusts, and other noxious agents. Recently, a mild form of Centriacinar Region disease has been produced in primates exposed to a level of ozone (0.15 ppm) that is frequently exceeded in Los Angeles. Since there is suggestive evidence that air pollution in Los Angeles increases the rate of decline of lung function, we suspect that there has also been an increase in the rate of structural decline, manifest in part by accentuated Centriacinar Region disease. The health significance of Centriacinar Region disease is just beginning to be appreciated. At the very least, reserve depletion reflected in the Centriacinar Region disease implies some reduction in lung performance and some increase in susceptibility to disease in general. At worst, the unexpected severity of the Centriacinar Region disease may be a bellwether for an impending rise in clinically manifested lung disease for the general population. An urgent research need is the monitoring of health through inventories of the functional and structural units of the human lung, with special emphasis on subpopulations of cell societies of the lung. The feasibility of applying image analysis for large volume objective quantitations has been demonstrated and should be implemented. Multicity studies, in cooperation with Offices of the Medical Examiner-Coroner and autopsy services in general, can help meet the critical need for increased sensitivity in the monitoring of the public health in a changing environment.

Air Pollutants

Latex condom deterioration accelerated by environmental factors: I. Ozone.

Commercial non-lubricated latex condoms were unpackaged and exposed in an environmental chamber to ozone levels (0.3 ppm) commonly present in urban smog conditions. Deterioration was observed by scanning electron microscopy after 18 hours exposure. Loss of mechanical strength was quantitated by measurement of the air pressures necessary to burst the condom and volumes at burst. After 24 hours exposure to ozone the latex surface was covered with craters and after 48 hours the pressure required to burst the condom was 44% that of control samples. Data suggest the need for study of the effectiveness of lubrication and packaging in protecting condoms from environmental factors which may accelerate deterioration.

Contraceptive Devices, Male

Acute and chronic pericholangiolitis in association with multifocal hepatic lymphangiomatosis.

Multifocal, lymphangiomatous lesions were found in the right lobe of the liver of a 9-year-old girl who died seven days after head trauma. We believe the lesions represent a cystic and pseudoneoplastic dilatation of liver lymphatics secondary to a posttraumatic complication, acute and chronic inflammation primarily of small bile ducts, and canaliculi (pericholangiolitis). The findings provide new evidence that inflammation and fluid overload, in the absence of a congenital malformation, are cardinal factors in the pathogenesis of some forms of lymphangiomatosis.

Bile Canaliculi

Desquamative interstitial pneumonia in an infant. Mimicry of sudden infant death syndrome.

A 15-week-old infant girl, without a prior history of overt illness, was found dead while sleeping between her two parents. The gross examination at autopsy showed only congested lungs, and the initial diagnosis was sudden infant death (SID). On microscopic examination, a desquamative interstitial pneumonia (DIP) was observed. The widespread, patchy intraalveolar histiocytic desquamation was associated with lymphocytic infiltration of bronchiolar and aveolar walls, which together provided convincing evidence that an interstitial pneumonitis was the cause of death. A viral etiology seems most likely in view of the accompanying chronic inflammation of bronchial submucosal glands.

Cause of Death

The effect of ozone and simulated high altitude on murine lung elastin: quantitation by image analysis.

Four subgroups of a colony of 50 mice were housed in environmental chambers supplied by particle- and pollutant-filtered air. The animals were exposed to 0.35 ppm ozone and/or simulated high altitude (380 mm Hg) for four weeks, with exposure 4 1/2 hours/day and 5 days/week. Lung elastin area and alveolar wall area were quantitated by computer assisted image analysis of paraffin embedded sections stained with aldehyde fuchsin and metanil yellow. Compared to the controls, the combination of ozone and simulated high altitude resulted in a 54.5% increase in lung elastin area (p less than 0.005), and simulated high altitude by itself increased elastin area by 19.6% (p less than 0.05). Simulated high altitude with and without ozone exposure also increased alveolar wall area (24.8%, p less than 0.01; and 9.7%, NS, respectively). Ozone exposure alone had a reverse effect: a 16.1% decrease in elastin area (p less than 0.1), and a 6.5% decrease in alveolar wall area (NS). Since an intact lung scaffolding is required for full restoration of injured alveolar epithelium and since intact lung elastin is critical for proper lung compliance, the results suggest that ozone exposure at high altitude is most likely to have an adverse effect on lung structure and function.

Altitude

Recent trends in mesothelioma incidence in the United States.

Mesothelioma incidence rates based on data from population-based cancer registries in New York State (exclusive of New York City), Los Angeles County, California, and the SEER Program of the National Cancer Institute were analyzed for trends, using original cancer registry diagnoses. Results indicate a significant increase in incidence during 1973-80 for pleural mesothelioma among white males older than 55 at time of diagnosis but not for other age-race-sex-site subgroups. A histopathologic review of New York State and Los Angeles County cases by two independent pathologists, expert in the diagnosis of mesothelioma, lowered the overall estimates but a significant upward trend remained. The observed trend does not appear to be related to changes in diagnostic practice. The results of a five-member panel of expert pathologists will be published in a separate methodology paper.

Adolescent

Effect of 0.3 ppm ozone exposure on type II cells and alveolar walls of newborn mice: an image-analysis quantitation.

Newborn Swiss-Webster mice were exposed to intermittent 0.3 ppm ozone (O3) for 6 wk, and the lungs of 137 exposed and 138 control animals (275 of the 301 in the colony) were suitable for computer-assisted image-analysis quantitation. Data were obtained on numbers and areas of lactate dehydrogenase stained type II cells, and also area, perimeters, and linear intercepts of the alveolar wall. As noted in an earlier study of adult mice, ozone exposure increased all cell and wall measurements. In contrast to the adult animal findings, there was a greater increase in mean type II cell area (p = 0.07) than in numbers of type II cells, with the latter increase falling short of statistical significance. The increase in cell area at the expense of cell number may largely be due to cell pairing or multicell clustering, events that would mask type II cell hyperplasia. Ozone effects on the type II cell population implicate damage to the type I alveolar lining cells. Moreover, the increases in alveolar wall measurements that were found in both the adult and developing mouse lung imply an alteration of the lung scaffolding, and this raises the question of impaired regeneration of the epithelial lining.

Age Factors

Juxtanuclear lymphocytes in histocultures of mammary cancer.

Juxtanuclear lymphocytes in histocultures of mammary cancer. Am J Clin Pathol 71: 64-71, 1979. This is the first report of a special orientation of autochthonous lymphocytes at a juxtanuclear zone of human mammary cancer cells in primary histocultures. The phenomenon, juxtanuclear orientation of lymphocytes, was observed in 99 histocultures from 16 of 45 (35%) successfully explanted cancers. A total of 686 instances of juxtanuclear orientation of lymphocytes was counted, versus 354 instances of random lymphocytic activities; juxtanuclear/random ratios ranged from 0.2 to 5.2. Ratio determinations may be potentially useful for assistance in evaluating prognosis; the preliminary findings are inconclusive but suggest that a ratio of one or more may indicate a more favorable clinical course. The immediate importance of juxtanuclear orientation of lymphocytes is that it offers a new measurement of pathologic lymphocytic activity that should have applications in basic and clinical studies of host responses in general.

Breast Neoplasms

Silicate pneumoconiosis of farm workers.

Abnormal numbers of birefringent particles have been found in the lungs of seven patients (five vineyard workers, one farmer, and one rural resident) in association with a spectrum of early to late interstitial inflammation and fibrosis. Nodular granulomas of the type seen in silicosis were absent. Scanning electron microscopy and energy dispersive x-ray analysis of 177 individual particles (less than 5 micrometer.) in situ in the lungs of four of the patients showed mostly silicates (notably aluminum, silicon, and potassium), with 5 to 10 per cent silicon dioxide. An analysis of particles less than 5 micrometer. from both vineyard and non-vineyard soil showed lung and soil particles to have a similar composition. The presence of large amounts of silicates in the lung tissues, in association with chronic inflammation and fibrosis, implicates the silicates in the causation of the fibrosis. The silicate deposits may, in large part, be a marker, reflecting a mixture of toxic soil additives or pesticides found in commercial clay silicate products or in dusts from the soil itself. The findings do not exclude lung pathology of a similar nature in regions outside of the farm.

Aged

Influence of 0.5 ppm nitrogen dioxide exposure of mice of macrophage congregation in the lungs.

The lungs of 12 mice, half of which were exposed to continuous 0.5 ppm nitrogen dioxide for 3 weeks, were explanted in culture, and the instances of macrophage congregation were quantitated according to numbers of target cells involved, categories of congregation from three to 11 or more, numbers of macrophages participating in each category for the total cultures, and the influence of delaying explantation for 24 and 96 hr. A total of 9042 macrophages and 2140 epithelial and spindle target cells were counted in the outgrowths from 306 explants. The incidence of macrophage congregation (or numbers of target cells) was greater for the cultures from the NO2-exposed animals, both with respect to total incidences between groups (p leads to) and the 0-hr (p less than 0.001) and 24-hr (p less than 0.01) culture subgroups. In addition, the values for T3 to T6 macrophage congregation were individually and consistently greater for the exposed animal group. Postmortem interval stress at 96 hr appeared to result in large colonies, but they were reduced greatly in number. Also the incidence of macrophage congregation fell by 28% as compared to 0-hr and 24-hr subgroups.

Animals

Intranuclear rodlets in an intrathyroid tumor associated with hyperparathyroidism.

A tumor excised from the thyroid gland has been shown by electron microscopy to contain distinctive, intranuclear rodlets. This is the first report of such rodlets in a non-neuronal human tumor. While the parathyroid-like hormonal activity, histopathology, and clinical course are consistent with a parathyroid adenoma, the finding of the rodlets raises the question of origin from a special, neuron-related cell of the parathyroid or thyroid. The unusual cellular granularity and the abundant interstitial fibrillae also suggest an unusual cell of origin. Alternatively, a special metabolic activity may account for the rodlets, or they may have been overlooked in prior studies of adenomas.

Adenoma

Lymphocytocidal lymphocyte trapping by human lymph node cells: a tissue culture-ultrastructural study.

An ultrastructural study was carried out on 25 lymphocyte-trapping cells selected from tissue cultures of human axillary lymph nodes. The trapping cells contained several hundred intravacuolar lymphocytes, most of which showed degenerative changes. The principal findings are: (a) a braod spectrum of lymphocyte degeneration; (b) a consistent pattern of lymphocyte degeneration beginning with perinuclear vacuoles and ending with breakdown of the nuclear envelope; (c) the viable lymphocytes tended to be located in a juxtanuclear region; (d) a lysosomal relationship was suggested for lymphocyte degeneration but not for lymphocyte trapping; and (e) degeneration of the trapping cell, or lymphocytes associated with other cells, was not observed. The sequence of degenerative changes differs from those reported for several classes of lymphocytocidal agents. There were no morphologic properties of the trapping cell which served to identify it more specifically. The findings, together with previous time-lapse film observations, warrant further investigation of the hypothesis that lymphocytocidal lymphocyte trapping may be involved in the control of lymphocyte populations.

Cell Membrane

Diazo replication of the lung: an improved methodology.

The methodology of diazo replication has been improved to provide replicas of 60 mum-thick lung sections with high contrast and sharp delineation of airways and air spaces. The newly introduced techniques are critical temperature control, embedment in isopentane, Bismarck brown staining, and parallel light, halogen lamp illumination.

Histological Techniques

Cyclic nucleotide phosphodiesterases in neoplastic and nonneoplastic human mammary tissues.

Cyclic nucleotide phosphodiesterase activity was studied in 33 malignant neoplastic, 2 benign neoplastic, and 18 nonneoplastic human mammary tissues. Enzyme activity, using both cyclic adenosine 3':5'-monophosphate and cyclic guanosine 3':5'-monosphosphate as substrates, was measured in whole homogenates over a concentration range of 1 to 100 muM. Specific activity was calculated at substrate concentrations of 1 muM (low KM enzyme activity) and 100 muM (high KM activity). Diethylaminoethyl cellulose chromatography was used to separate the different enzyme species. The malignant neoplastic tissues had higher levels of both low-KM cyclic adenosine 3':5'-monophosphate and low-KM cyclic guanosine 3':5'-monophosphate phosphodiesterases. Further, the mean value of the ratio of low-km cyclic adenosine 3':5'-monophosphate to low-KM cyclic guanosine 3':5'-monophosphate activity was higher for the cancer tissues than for the nonneoplastic tissues. Diethylaminoethyl cellulose chromatography indicated the presence of three enzymes in both neoplastic and nonneoplastic mammary tissue. The kinetic as well as regulatory properties of the separated enzymes indicated that they are distinct enzyme activities. The phosphodiesterase properties were similar for neoplastic and nonneoplastic tissues and resembled those described previously in many other mammalian tissues. While both neoplastic and nonneoplastic tissues had detectable levels of the protein activator for phosphodiesterase, the cancer tissues appeared to have a higher level.

3',5'-Cyclic-AMP Phosphodiesterases

Autoradiographic localization of glycoprotein in human breast cancer cells maintained in organ culture after incubation with (3H)fucose or (3H)glucosamine.

Explants of nine infiltrating duct carcinomas of the human female breast, maintained in organ culture, were exposed to the glycoprotein precursors, L-[3H]furcose and [3H]glucosamine, in order to determine the cellular distribution of newly synthesized glycoprotein as revealed by autoradiography with the light and electron microscopes. Explants were incubated with a single isotope for 2 hr, at which time some of the labeled explants were removed for autoradiographic analysis while the rest were transferred to nonradioactive medium for an additional 24 hr. After exposure to label for 24 hr, autoradiography with each isotope was similar and showed strong reactions over most tumor cells. The reactions were due to clumps of silver grains over intracytoplasmic lumina within single tumor cells and silver grains over Golgi saccules, cytoplasmic vesicles, lysosome-like bodies, lateral and basal plasma membranes, and microvilli. Extracellular ductular structures were also heavily labeled. At the later sampling time, Golgi saccules often showed a reduced reaction while the reactions over other organelles and intracellular and extracellular ductular structures remained strong. The observations suggest that in our in vitro system the tumor cells are metabolically active and complete the synthesis of the carbohydrate side chains of glycoproteins within the Golgi apparatus. From there, some of the newly synthesized glycoprotein appears to migrate to plasma membranes and lysosome-like bodies. Furthermore, our data support the notion that many duct carcinomas of the breast exhibit secretory activity by showing that some newly synthesized glycoprotein also appears to become products that are secreted into intracellular and extracellular ductular structures.

Autoradiography