Document O1422d5oabqzBOmR9OOzr18z1

United State* Environmental Protection Agency TS 799 Wethington DC 20460 Official Bueineaa Penalty for Private Uee *300 4 First-Class Mail Postage and Fees Paid EPA Permit No. Q-36 i ,, APOOOf1932 MANUFACTURING CHEMISTS ASSOCIATION 182b CONNECTICUT AVENUE, N.W, WASHINGTON. D. C. 20009 March 21, 1975 TO: Technical Task Group on Vinyl Chloride Research SUBJECT: Items related to vinyl Chloride Attached for your information are the following: 1. A copy of the paper presented by Dr, Gordon of Industrial BIO-TEST Laboratories at the March 5 meeting of the International Academy of Pathology in New Orleans entitled "Comparison of the Morphologic Features of Hepatic Angiosarcoma in Man and Rodents Following Prolonged Exposure to Vinyl Chloride," 2, A news release on the availability of a new book entitled "The Determination ot Vinyl Chloride - A Plant Manual," published by the Chemical Industries Association Limited, Alembic House, 93 Albert Embankment, London SEl 7TU Sincerely, MF/etv Attachments Milton Freifeld, Project Manager AP00011933 t MAR 141975 TOXICOLOOY environmental eciences CHEMISTRY SLANT SCIENCES MEDICAL SCIENCES SwktiltUal B l o - T E s T Jk6Mame&, Jkc, 1810 FRONTAGE ROAD NORTHBROOK; ILLINOIS 0062 March. 1 1 J975 * AHEA COOE 11* TELEPHONE *7**3090 Mr. Milton Freifield Manufacturing Chemists Association * 1825 Connecticut Avenue, N. W. Washington, D. C. 20009 Dear Mr. Freifield: Enclosed is a copy of the full text of the paper which I presented on March 5, 1975, at the International Academy of Pathology meeting in New Orleans. As I indicated, this particular scientific session was arranged in cooperation with the Society of Pharmacological and Environ mental Pathologists (SPEP) and the proffered papers were submitted and presented by members of this organization. Most of the papers dealt with chemically-induced carcinogens, their morphologic features and f iNa nip I am also enclosing a copy of the abstract of my paper as it appeared in the program (Abstracts of Papers) and also appeared in Laboratory Investigation, Vol. 32, No. 3, 1975. The paper was well received. Dr. Squire, Head of the Tumor Pathology Branch at the National Cancer Institute in Bethesda, Maryland, informed me that Dr. Maltoni plans to visit their facility in early April to present his pathologic findings to date. I have been invited and plan to attend unless MCA has some objections. Sincerely, DEG:gz cc: Dr. J. C* Calandra Dr. M. L. Keplinger Donovan E. Gordon, D. V. M. , Ph. D. Section Head, Pathology r AP00011934 DncLubual BIO-TEST ^aluvutt&uel, Sue. MANUSCRIPT FOR PRESENTATION AT THE INTERNATIONAL ACADEMY OF PATHOLOGY MEETING ON MARCH 5, 1975, IN NEW ORLEANS, ENTITLED "COMPARISON OF THE MORPHOLOGIC FEATURES OF HEPATIC ANGIOSARCOMA TN.MAN AND RODENTS FOLLOWING PROLONGED EXPOSURE TO VINYL CHLORIDE. " D. E. Gordon, L. B. Thomas, J. C. Calandra, ft. Popper and G. Kent - Industrial BIO-TEST Laboratories, Inc. , Northbrook, Illinois; National Cancer Institute, Bethesda, Maryland; Northwestern University Medical School, Chicago, Illinois; Mount Sinai School of Medicine, New York, New York; and Northwestern Memorial Hospital, Chicago, Illinois. Ladies and Gentlemen: Vinyl chloride monomer (VCM) is a gas at ambient temperature and atmospheric pressure. It is made by several processes that involve the chlorination of ethyLene or acetyLene. VCM is used primarily in the manu facture of polyvinyl chloride (PVC), a resin which serves as the parent compound for a number of plastics. In May of 1970, Dr. Viola, from Italy, presented a paper at the 10th In ternational Cancer Congress in Houston, Texas, on the carcinogenic effects of vinyl chloride (VC) in rats. He reported tumors in the skin (para-aural carcinomas), lung (epidermoid and adenocarcinomas) and bone (osteochondromas) of Wistar rats that had been exposed to 30, 000 ppm of VC vapor for 4 hours a A day, 5 days a week, for 10 months. This was probably the earliest report of a carcinogenic effect of VC in experimental animals. His study was originaLly designed in an attempt to deveLop an animal model for acroosteolytis, a bone disease that was reported in the early 1960's among VCM and PVC workers. AP00011935 SnduUiial BIO-TEST JaJt&uriyu&A., Umc. 2. In view of Or. Viola's findings* inhalation studies in rats were subsequently initiated in Bologna* Italy, by Dr. Cesare Maltoni in which vapor concentrations of 50 to 10,000 ppm were investigated. Early in 1973, it was disclosed that angiosarcomas of the liver and tumors in other organa (Zymbal's gland tumor of the ear canal and Nephroblastomas of the kidney) had been seen in these animals. At that time* liver tumors had not been reported in rats at exposures of 50 ppm of VC. In view of these findings by Drs. Viola and Maltoni, a vapor in halation study with VCM in mice, rats and hamsters was started in September of 1973 at Industrial BIO-TEST Laboratories, at the voluntary request of the Manufacturing Chemists Association (MCA) which represents a group of 3 l companies in the United States involved in the production of VCM or PVC. The study was designed, by this group, as a life-span study in each of these species to complement Dr. Maltoni's study. The exposures selected were 50, 200 and 2, 500 ppm of VC vapor with exposures 7 hours a day, 5 days a week. Two hundred of each species and each exposure level were used, for a total of 600 animals per exposure level. Preliminary tumor data from animals on this study were reported at the end of the first 8 months when liver angiosarcomas appeared In mice that had died at the 50 ppm and higher levels. This preliminary data was presented on April 15, 1974, to representatives of the Environmental Protection Agency (EPA), Occupational Safety and Health Administration (OSHA) and the National Institute of Occupational Safety and Health (NIOSH). AP00011936 $%ndmifUal BIO-TEST J.akyiai&Ue4, Stic, 3 Meanwhile, the first 3 fatal cases of liver angiosarcomas among vinyl chloride workers in the United States had been reported in January of 1974. With the identification of this rare tumor in humans and experimental animals, there rapidly resulted a- national interest in this problem. Dr. Louis Thomas, at the National Cancer Institute in Bethesda, Maryland, and Dr. Hans Popper, who was at that time a Fogarty Scholar at the National Institute of Health, were asked to review all the angiosarcoma cases among workers in the vinyl chloride industry. In September of 1974, I met with Drs. Thomas and Popper to review slides from both the human and mouse angiosarcoma cases. At that time, Dr.. Thomas had tumor material from 14 or 15 industrial workers. Slides of human angiosarcoma cases of unknown etiology from Dr. Godfrey Kent at Northwestern Memorial Hospital in Chicago were subsequently reviewed. Slide # 1. Gaseous Vinyl Chloride-Induced Hepatic Angiosarcomas in - 15 workers in Polymerization Plants - Rodent Experiments Does Similar Morphologic Evaluation in Man and Mice Enforce Causal Relation and Permit Differentiation From Angiosarcomas of Unknown Etiology? Within 8 Months of Exposure - Hepatic Angiosarcomas Seen in - 2/200 Mice at 50 ppm - 11/200 Mice at 200 ppm - 28/200 Mice at Z, 500 ppm The purpose, then of this presentation is to present some of the comparative. AP000I1937 $ndt**At>Ual B l O - T E S T JaA&ioioMei, Due. 4 early developmental and morphologic features of the human and rodent angiosarcomas that have been studied thus far* In this slide, preliminary tumor data at 8 months from our mouse study revealed an exposure-related relationship in the Incidence of grossly visible liver tumors that were later verified histologicaUy as angiosarcomas. The first hepatic angiosarcoma appeared at 6 months in 1 animal at the Z, 500 ppm level that had died. The gross appearance of these tumors in man and animals was similar. The livers were frequently enlarged and contained solitary to multiple dark red circumscribed or nodular foci. The tumor foci in mice varied in Bize from 1 mm to 3 cm in diameter and the cut surface contained blood-filled cystic spaces associated with necrotic foci. The tumors usually extended up to and involved the capsular surface of the liver. In most of the animals with liver tumors, there was blood present in the peritoneal cavity that resulted from hemorrhages at the capsular surface of these tumors. Internal hemor rhage was one of the major causes of death in these animals. Slide #2. This is a section of human Liver in which there was an angiosarcoma in another portion. The earliest lesion that Drs. Thomas and Popper have been able to detect, and have reported, is this irregular focal sinu soidal dilatation without necrosis of hepatocytes. AP00011938 BIO-TEST P*tc. 5 Slide //3. This is just a higher magnification of the previous field to show a few enlarged sinusoid.al lining ceils. Slide #4. In the human cases, there is a characteristic, progressive portal tract and capsular fibrosis present throughout the liver that can be seen in this Aniline Blue-stained section in which collagen and reticulin fibers stain blue. This feature has not been observed in liver sections from our VC-exposed animals. However, the liver of rodents (rats, mice, hamsters) normally contain less connective tissue within the portal tracts and lobules when compared to the liver of man. SLide 5. This is the earliest lesion in the mouse which again is focal sinusoidal dilatation. Slide #6. At higher magnification, some of the lining cells appear to be slightly increased in size. There is also focal hypertrophy of hepatocytes in these areas. Slide #7. There is also a focal hypertrophy'of hepatocytes in areas without sinusoidal dilatation and some of these hepatocytes are blnucleatcd. AP0001I939 Siuhtitoal B I O - T E S T <,ih>%alt>Mei, $*\c. Slide #8. The next stage in progression of both the- mouse and human lesions is the formation of small to large blood-filled cavities or areas of peliosis. This section is from a mouse. The larger lesions are usually located just beneath the capsule and, microscopically, they are frequently early or advanced lesions of angiosarcoma. Slide #9. At higher magnification of such a peliotic focus, the neoplastic process can be seen extending up to the capsule. Rupture of the capsule at these sites may result in fatal internal hemorrhage. In addition to fresh blood, these peliotic foci contain large fibrin thrombi which are not present in this field. Slide #10. A slightly higher magnification of the angiosarcoma reveals papillary projections of liver cords extending into the peliotic space which are en veloped by neoplastic lining cells. In some areas of these tumors, there is slight widening of the Space of Disse. However, this feature is not as prominent nor as frequent as seen in man. There is also hypertrophy of the entrapped hepatocytes which later undergo necrosis. Slide #1 1. In other areas of the tumor, there are solid sheets of neoplastic cells that have repLaced the liver cords. Slide #12. This is the counterpart of the above liver angiosarcoma in man where we again see a papillary projection of liver cells extending into a bloodfilled space that is covered by neoplastic lining cells. There is a prominent separation of (he Space of Disse which contains a non-neoplastic prolifera tion of different types of cells including macrophages, lipocytes and fibro blasts. APOOOf1940 StuUtikial B I 0 - T E S T Jakyialotiat, 7 Slide #13. i This is another area of the same tumor to show the presence of intracannicular bile thrombi in l^epatocytes due to stasis of bile flow. Slide #14. This Aniline Blue-stained section shows an increase in perisinusoidal connective tissue. Eventually, with destruction of the entrapped hepatocytes, there i9 extensive fibrosis in the area of the angiosarcoma. Now, I would like to briefly show you a series of slides of the developmental lesion and angiosarcoma in rats. Slide #15. Again, this is the. initial lesion, an irregular focal sinusoidal dilata tion without necrosis of hcpatocytes. This lesion seems to occur more frequently in the subcapsular region of the liver lobes. Slide #16. At higher magnification, there is hypertrophy of a few endothelial cells and some nuclei contain mitotic figures. Slide #17. We now see hyperplasia and hypertrophy of the lining celLs which have enveloped most of the liver cords. Some of these cells are clearly neoplastic. AP00011941 HttdHibUal B I O - T E S T $*ic. f8 Slide #16. The hepatocytes in the immediate vicinity of the tumor have now been replaced by these sarcomatous lining cells. Slide #19. A few large pleomorphic tumor cells can be seen in the lumen of one vessel as well as in and along the margin of the tumor. Slide #20. In this trichrome-stained section, there is an absence of collagenous connective tissue in the stroma of the tumor. Slide #21. ' Ta,.i uuo gcLUU. .iif vu. . mv.i. Cello c<ai'i be Seen wlliiiii a jXu la.1 Li acl vessel adjacent to a bile duct. Last Slide. Common Features of Human and Mouse Angiosarcomas Support Etiology and Epidemiology: 1. Multiple, Focal, Sinusoidal Dilatation 2. Blood-filled Sinusoidal Cysts (Peliosis) 3. Proliferated Hepatocytes Enveloped by Sarcoma Cells 4. Progression to Papillary Pattern 5. Vasoformative and Anaplastic Nodules are Rare Dissimilarities: in Mice and Rats 1. Less Fibrosis (in Tumor and Parenchyma) 2* Often Uniform Sarcoma Cells vs. Multipotential Colls in . Widened Tissue Space of Disse in Man AP00011942 $fuiuii/UaL BIO-TEST Jalxnatiniel, Dhc. 9 In summary, there are a number of common features between the human, mouse and rat lesions from exposure to vinyl chloride. These common or similar features are: multiple, focal areas of sinusoidal dilatation. We do not believe that these are angiosarcomas at this stage. We have no way of knowing at just what step, histologically, the angiosarcomas start and then progressively develop into a clinically important tumor. The second point of similarity is that of the pcliotic lesions (blood-filled sinusoidal cysts). Then, there is, at the early stage of angiosarcoma, focal to multifocal hyper trophy and proliferations of hepatocytes, enveloped by sarcoma cells. This progresses to a papilLary pattern and, finally, there may be solid anaplastic areas within the angiosarcoma. There are a couple of points of difference: in the mice and rats, we see very little or no increase in connective tissue in the neoplastic and unaffected portions of the liver when compared with man. Finally, there seems to be a somewhat more uniform population of tumor cells in the animal tumors than in the human. In man, there is a possibility of not only the endothelial lining cells but some of the other cells in the tissue space of Disse being involved in the neoplastic process. Thank you. AP00011943 H ANNUAL MKKTINrt AHRTItACTS I.AMlRATOttY iKVfSTWATION opposed or exaggerated estrogenic stiimilnlion, Most organs. Nonsuppurative meningoencephalitis was pres of these cellular characteristic-s wilh the exception of ent throughout the brain, especially in the pons, cere inlracytoplflsrmc micro/jlamrnLs. are cnmfwiralivcly re* bellar peduncles, and thalamus. SHF appears to be nu duced in severe adenomatous hyperplasia (carcinoma excellent primate model for virus-induced disseminated in situ) and well differentiated ndenocarcinoma, and are intravascular coagulation and other human diseases. absent in neoplasms of lesser differentiation. The grad ual failure to express estrogcn-dcpcndcnt cellular alter ations in these lesions seems to be related to neoplastic dedifferentiation, and to lie independent, of the estradiol receptor content. The subeellular effect of progesterone or synthetic progestin* on hyperplastic and well differ entiated neoplastic endometria is that of epithelial re gression and includes secretory conversion, lysosomal hydrolytic activity, a decrease in the length of micro villi, and lack of cilingenesis. These observations sup port the concept that, progestogens act upon endo metrial hyperplasia and neoplasia by a direct, nonimmunologic, cellular effect, by promoting secretion and inhibiting development of estrogen-influenced cellular specialization. Ultrastructural Changes in Endometrium of Wo men Bearing Copper Intrauterine Devices Amador Gonzalez-Angvi.o and Ramon AznakRamos. Dcpartamento de Invest igacion Cientificn, Centro Medico Nacirmal, Inslituto Mexicano del Seguro Social. Mexico. D. F.. Mexico. Clinical studies have confirmed that the addition of metallic copper to inert polyethylene intrauterine de vices increases significantly their antiferrilitv action. The continuous release of copper by the device has been populated as one of the mechanisms whereby con traception is attained. The aim of the present study was 1o investigate epithelial and stromal changes possibly related to copper deposition. Endometrial biopsies were obtained from 12 young women bearing TCu-200 intra The Pathogenesis of Simian Hemorrhagic Fever: Hematologic and Histopathologic Studies W. E. Gidoens, Jr., and D. Jessup, H. E. Branson, L. A. Mayer, D. R, Benjamin, and W. T. London. Departments of Pathology and laboratory Medicine, the Regional Primate Research ('enter,.University of Washington, Seattle. Washington. 98195, and the .National Institute of Neurological Diseases and Stroke, National Institutes of Health. Bethosda, Maryland 20014. Simian iicimn ifcvci (ioH) <>ii acute viral dis ease of monkeys of the genus Macaco. It has caused several epizootics in primate colonics around the world, resulting in the loss of thousands of monkeys. To under stand more about the pathogenesis of (his disease, we gave five rhesus monkeys intravenous injections of a 10 4 dilution of serum containing the Corbel strain of SHF virus. Blood was taken before inoculation end at uterine contraceptive devices for more than 6 months. Six biopsies were taken at day 10 and six at day *20 of the menstrual cycle. The main changes were located in the cell organelles at day 10 of the cycle. The mitochondria disclosed vacuolation of the matrix and myelin figure for mal inn in 70 to 80 per cent of t he epithel ial cells of four patients. There were also increased numbers of Jysosome# and hyperplasia of Golgi structures. Stromal capillaries showed myelin figures in endothelial cells at day 10. Only in one case nf secretory endometrium were similar alterations present. Preliminary Ftudies by energy-dispersive x-ray analysis (Kevex) failed to reveal copper in various cell organelles. The above observa tions seem to indicate that there is a definite altera tion of mitochondria of epithelial cells which may result in impairment of respiratory- mechanisms and energy production, rendering the endometrial environment in hospitable for the fertilized egg. selected intervals post inoculation (PI) for hematologic, ^Comparison of the Morphologic Features of Hepatic ultrastructural, and coagulation studies. Monkeys were Angiosarcoma in Man and Rodents following subjected to euthanasia at 8. 5. and 7 days PI: one Prolonged Exposure to Vinyl Chloride monkey died spontaneously at 7 days PI. 1). E. Gordon, L. B. Thomas. J. C. Calandra. H. Disseminated intravascular coagulation was a prom Popper, and G. Kent. Industrial Bio-Test labora inent feature of the disenso and was characterized hemn- tories, Inc.. Northbrook. Illinois. National Cancer tologically by markedly decreased plasma fibrinogen Institute, laboratory of Pathology. Bethesria. Mary levels and increased degradation products of fibrinogen land, Northwestern University Medical School. Chi and fibrin. Platelet counts were reduced to about one- cago, Illinois. Mount Sinai School of Medicine. New hair of the preinoeulatidn values. Clink-ally, there was York, New York, anti Northwestern Memorial Hos hyperlhemin. anorexia, weakness, epistaxis, and dys pital. Chicago, Illinois. entery. At pecropsy the blood often failed to clot, and A- cmisnl relationship has been established between (here was hemorrhagic enterocolitis, lymphadenopalhy, flic development of hepai le nngm.snreomns among work splenomegaly, and widespread potechinc and ecchy- ers engaged in the polymerization of vinyl chloride. The mnses. On histopathologic examination, there was ne histologic features of similar hepatic tumors (hat de crosis of lymphocytes in the center# of the Malpighian veloped in rodents (mice and rats) within ! year after corpuscles of the spleen and in the germinal centers of exposure* of 2500. 2tMi. and nti p.p.m. of vinyl chloride the lymph nodes and peribronchial lymphoid follicles, for 7 boors a day, 5 days n week, were compared wilh in the IVxer's patches and the lamina propria of small M cases of those that have occurred in man. T<> dale, and large intestine, mid in the thymus. A consistent the incidence of hepatic angiosarcoma in rodents has lesion teas engorgement of splenic- sinusoids wilh fibrin, been related to the level of exposure in vinyl chloride. and fibrin thrombi wore present in many small arterioles Despite dissimilarities between rodent mul human le and venules in the intestinal mucosa, lung, and other sions, such ns minima! fibrosis in mice, the basic evnlu- wwai ......................................... ..... .nil ipg.,. ,i r -------- -------- ----- ------- - - r AP00011944 Vrf.S2.Nn. 3. mV, ANNUAL MRKTINf? A1WTUACTS S'- {i()M WHS Ihc same. The earliest lesion Wits focnl dilation placenta with nifro-bltic (efraznlium solution, an oxidn> of sinusoids in which the lining cells were increased in i ion-reduction indicator which yields purple formaznn number, piled up. and exhibited hyperehrnmntic nnd pigment at sties of <lohydrogena.se .activity. Areas of bizarre nuclei. Subsequently, sarcomatous lining cells dehydrogenase deficiency had a white to yellow-white enveloped plalcsof hepatocylcs which were hypertrophic appearance and were readily differentiated from adja nnd hyperplastic. They become cords surrounded l)y cent purple-stained tissue in which formazan pigment proliferated lining cells of different typos* in papillary was deposited. Succinic acid dehydrogenase activity arrangement associated with blood.filled cavities' re* was present in the'placentas from uncomplicated preg suiting from sinusoidal ectasia. Eventually, nodules of nancies, whereas placentas from complicated preg anaplastic sarcomatous cells with vascular spaces de nancies showed slight to marked decrease in formazan veloped with hemorrhage and necrosis. This charac pigment* In these placentas, addition of substrate did teristic evolution common to animal nnd man indicates not enhance the intensity of formazan pigmentation. a specific and identifiable effect of vinyl chloride or its Placentas of infants wilh low Apgar scores and placentas metabolites upon hepatic mesenchymal nnd epithelial associated with neonatal morbidity and mortality con cells. It enforces the causal relation of vinyl chloride ex sistently demonstrated reduced enzyme activity. The posure to angiosarcoma formation, bid also assists in the clinical diagnosis of uteroplacental insufficiency was exclusion of vinyl chloride as the cause of some angiosar also associated with absence or marked decrease of suc comas of different appearance. cinic arid dehydrogenase activity. (Supported by Pro fessional Staff Association. The !/os Angeles County- Ultrastructural Changes in Pulmonary Bleomycin Universitv of Southern California Medical Center. Proj Toxicity ect 2-155-0-C.t F. Gyoukry, I. Daskau and P. Gyokkky. Veterans Ad ministration Hospital'and Baylor College of Medi Acquisition of Columnar (Barrett Type) Epithelium cine, Houston. Texas 770111. in the Distal Esophagus after Partial Esophagi* Uilrastructural studies of the nuclei of type I and type gastrectomy II pulmonary epithelial cells and of alveolar septal cells Stanley H. Hamilton and John J. Yarijley. De from patients with diffuse pulmonary fibrosis following part mont of Pathology. The Johns Hopkins University bleomycin treatment revealed that the drug had a dif School ol Medicine and Hospital. Baltimore. Mary ferential effect on the fine morphology of these cells. land 212(b). The most striking alterations were observed in the The origin of the columnar cells in the columnar epi type 1 alveolar cells; their number was markedly de thelium-lined distal esophagus (Barrett esophagus) is creased, with formation of nucleolar fibrillar centers and unknown, ft has been proposed, however, that the co- a large increase in nuclear Iwxlies. These nuclear bodies Itimii.n epithelium may !:c: {!> '-o.ngenjtnl rnsultimr from ranged in size from 0.:l to 0.7 gm. in diameter and were incomplete replacement of embryonic columnar epithe of three main varieties; membranous, beaded, and gran lium; or (21 acquired, being a response to chronic gas ular. Some nuclei contained up to 12 nuclear bodies. tric reflux. There was an abundance of nuclear bodies in all of the We have studied at aulopsy a 74-year-old male who type 1 cells, which contained nucleoli with well defined had undergone partial esophagognstreciomy for squa fibrillar renters. The nuclei of type [I alveolar cells mous carcinoma of the distal esophagus 6 years earlier, (granular pneumonncylesl contained compact nucleoli 'I^e body of the stomach, with fundic mucosa at the with ill defined fibrillar centers and few', if any, nuclear margin, had been annslomosed to the remaining normal bodies. When present, the nuclear bodies were of the esophagus. Postoperativelv there was persistent gastric membranous variety. The nuclei of the alveolar colls reflux. Following death from cardiopulmonary disease, were similar in appearance to those of type 1 cells hut a mild stricture and a O.fi- to 1-cm. circumferential zone did not contain nnricar bodies of the granular variety. of tan mucosa was found in the distal esophagus just We postulate that the above described ultraslnictura! above the suture line. There was no tumor in the area changes, in particular the appearance of fibrillar centers of resection. The circumferential zone resembled mu and nucleolus-derived nuclear lmdles. were induced by cosa of a Barrett esophagus, being composed of co bleomycin. *- lumnar. goblet, nnd endocrine cells. The columnar cells, of the surface and glands showed periodic acid-Schiif A Macroscopic Method for Evaluating Succinic Acid <I'ASl-positive and Aleian Blue (AB)-negativc mucin. Dehydrogenase in Ihc PLaccntn Scattered goblet cells stained with both BAS and AB. T. D. Ham. It. A. Woopmno, N. E. Warner, S. B. Numerous argyrophil cells and scattered argentaffin Fukukawa, and H. W. Pukkku. Department of Pal hoi- cells were demonstrated. ogv. University of Southern California School of Med Findings in this case strongly indicated that the co icine, Ijr Angeles, ('nliforntn. lumnar epithelium in the distal esophagus was acquired, A histochemicnl assay for succinic acid dehydrogenase perhaps stimulated b.v gastric reflux, it has been sug described fur evaluating respiratory enzyme in myocar gested that Harrell epithelium may arise from enrdine dium (Nachlns, M. M.. and Sclmitkn. T. K. Am. J. mucosa. This case also indicated, therefore, that the Pathnl. -t`2; liHfct) was adapted and modified for the presence of cardiac mucosa is not necessary for forma study of lt)(i placentas from normal and complicated tion of columnar epithelium-lined esophagus, although pregnancies. 'Hie method entails incubation of the its origin remained unclear. Metaplasia of squamous i APOOOf1945