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Biomedical subjects

B F Trump

Publications and source records attributed to B F Trump.

At least 109 records · Page 6Linked to original sources
PubMed1986

Immunocytochemical evaluation of primary human esophageal carcinomas and their xenografts for keratin, beta-chorionic gonadotropin, placental lactogen, alpha-fetoprotein, carcinoembryonic antigen, and nonspecific cross-reacting antigen.

The unlabeled antibody peroxidase-antiperoxidase technique was used to examine esophageal neoplasms for the tumor markers beta-human chorionic gonadotropin, human placental lactogen (HPL), alpha-fetoprotein, carcinoembryonic antigen (CEA), and nonspecific cross-reacting antigen (NCA) before and after xenotransplantation to athymic nude mice. In addition, keratin was used as an epithelial cell marker. Immunoreactive beta-human chorionic gonadotropin was detected in four of seven primary tumors and in three of seven xenografts. Two of seven primary tumors contained HPL immunoreactive cells while four of seven tumor xenografts had HPL immunoreactivity. alpha-Fetoprotein was detected in two of seven primary tumors and in one of seven xenografts. NCA and CEA were detected in six of seven primary tumors and in all tumor xenografts. Five of seven primary neoplasms and six of seven tumor xenografts were found to contain both NCA and CEA, while one tumor and its xenografts displayed only NCA immunoreactivity. All seven primary carcinomas displayed keratin immunoreactivity, but only six of the seven xenograft tumors showed keratin positive cells. When a tumor marker was detected in a primary tumor, it was usually found in at least some of the xenografts arising from that tumor. However, marker loss did occur with repeated passage of tumors in some cases. On the other hand, markers were expressed in xenografts which were not present in the corresponding primary tumor. In three instances, HPL was detected in xenografts derived from HPL negative primary carcinomas. This was also true for CEA and NCA in one case. These results show that tumor markers are expressed to varying degrees by tumors growing as xenografts in nude mice. In primary tumors, HPL is associated with poorly differentiated squamous cell carcinomas and this marker was found to appear in HPL negative tumors as the tumor cells became less differentiated while growing as xenografts in nude mice.

Animals↗
PubMed1986

Expression of LeY and extended LeY blood group-related antigens in human malignant, premalignant, and nonmalignant colonic tissues.

The LeY determinant, a difucosylated type 2 blood group-related antigen, is a positional isomer of the Leb blood group antigen and a fucosylated derivative of the LeX antigen. The LeX antigen behaves like an oncodevelopmental tumor-associated antigen in human colon cancer, and extended polyfucosyl LeX antigens are more specific for colon cancer tissues than are simple, monofucosyl LeX antigens. The present investigation compared the expression of simple and extended LeY antigens in a variety of malignant and nonmalignant human colonic tissues to gain insight into the normal distribution and cancer-associated expression of these antigens. Monoclonal antibody AH-6, which recognizes the LeY epitope irrespective of its carrier carbohydrate chain, stained the majority of specimens regardless of malignant potential or location within the colon. In contrast, CC-1 and CC-2 monoclonal antibodies, which recognize extended LeY structures, and KH-1, which is specific to trifucosyl LeY, preferentially stained malignant colonic tissues and rarely stained normal colonic mucosae. Mucosa immediately adjacent to cancer usually stained with AH-6 but not with KH-1, CC-1, or CC-2. Extended or trifucosyl LeY antigen expression was limited exclusively to premalignant (adenomatous) polyps and was invariably absent from nonpremalignant (hyperplastic) polyps. Moreover, among adenomatous polyps, extended LeY antigen expression tended to correlate with three parameters of malignant potential: larger polyp size; villous histology, and severe dysplasia. AH-6 failed to distinguish between hyperplastic and adenomatous polyps. In second-trimester fetal colonic mucosa, AH-6 bound to both proximal and distal segments whereas KH-1, CC-1, and CC-2 bound only to proximal segments. We conclude that in human colon, the LeY hapten is an oncodevelopmental cancer-associated antigen and extended LeY antigens are highly specific markers for malignancy and premalignancy.

Antibodies, Monoclonal↗
PubMed1986

Periodic acid-Schiff-lead hematoxylin as a marker for the endocrine phenotype in human lung tumors.

Periodic acid-Schiff-lead hematoxylin is evaluated for light microscopic diagnosis of pulmonary endocrine cell tumors. Twenty-eight aldehyde-fixed primary human lung tumors were examined by electron microscopy. Fifteen were classified as endocrine (one carcinoid, six small-cell carcinomas, and an "atypical" group of eight with diverse histologies), based on possession of characteristic submicronic, dense-cored cytoplasmic granules. Electron probe analysis in the carcinoid tumor established that dense-cored granules were equivalent to lead hematoxylin-stained granules, which were visible in glycol methacrylate sections as seen on light microscopy. Lead hematoxylin-positive granules were also seen in seven of eight "atypical" tumors, three small cell carcinomas, a glucagonoma, and a chemodectoma. Findings were equivocal in two small cell carcinomas, and negative in all other lung tumors. In overall diagnostic acuity, periodic acid-Schiff-lead hematoxylin equals electron microscopy, surpasses argyrophilia, serotonin fluorescence, and immunolocalization of polypeptide hormones. It is approached only by antineuron-specific enolase immunoreactivity.

Benzopyrans↗
PubMed1986

Comparative ultrastructural effects of aflatoxin B1 on mouse, rat, and human hepatocytes in primary culture.

Human, rat, and mouse hepatocytes in primary culture were treated with aflatoxin B1 (AFB1) and examined for ultrastructural alterations. As early as 1 h following in vitro exposure to AFB1, there were ultrastructural changes in the nuclei of rat and human hepatocytes. The most prominent change in the nuclei was a segregation of nucleolar components that resembled the segregation in liver cells of rats exposed to AFB1 in vivo. The nucleolar segregations were developed by incubating rat hepatocytes for 24 h in a medium containing as little as 0.01 micrograms of AFB1 per ml. The minimum concentration to induce the same change in human hepatocytes was 0.1 micrograms/ml. No distinct nucleolar alteration was observed in mouse hepatocytes incubated in a medium containing 10 micrograms of AFB1 per ml. Irregular nuclear chromatin condensation also developed in the cells exposed to a higher concentration of AFB1, whereas little damage was observed in mitochondria and lysosomes. The similarity in morphological changes between our in vitro model and in vivo models previously investigated indicates that the hepatocytes in primary culture maintain the biological properties necessary for carcinogen responses similar to liver cells in vivo. In addition, the morphological changes in cultured rat and mouse hepatocytes induced by AFB1 correlate with in vivo experiments insofar as mice are relatively resistant, whereas rats are sensitive to AFB1 carcinogenesis. Thus, cultured hepatocyte systems may be a valuable tool to study genetic damage which may lead to hepatocellular carcinomas in human and animal livers.

Aflatoxin B1↗
PubMed1986

Rapid detection of xenotransplanted human tissues using in situ hybridization.

A rapid and sensitive method for the identification of human tissues xenotransplanted in nude mice was developed. An in situ hybridization technique made it possible to distinguish between cells of human origin and cells of murine origin in formalin-fixed paraffin sections. High-molecular-weight DNAs extracted from human or mouse tissues were sonicated, nick-translated with 32P-dCTP, and used as hybridization probes. Dot blot hybridization of 32P-labeled probes revealed clear species-specific signals. Formalin-fixed paraffin-embedded tissue samples from repopulated tracheal transplants, containing either human tracheal epithelial cells or human renal tubular cells, were used. Cells of human and murine origin were distinguishable by in situ hybridization with sonicated DNA probes. This method has several advantages; simple preparation of probes, high sensitivity, and applicability to formalin-fixed paraffin-embedded tissue sections. In situ hybridization with sonicated DNA probes should provide a powerful tool for verifying the human origin of xenotransplanted tissues in nude mice.

Animals↗
PubMed1986

Lewisx- and sialylated Lewisx-related antigen expression in human malignant and nonmalignant colonic tissues.

Biochemical studies have revealed that some normal cells express the LeX trisaccharide Gal beta 1----4(Fuc alpha 1----3)GlcNAc either on short-chain fucolipids or as a single immunodeterminant on glycolipid oligosaccharide side chains. Cancer cells, including those from colonic adenocarcinomas, express this antigen on longer type 2 blood group side chains as difucosylated or trifucosylated fucolipids. Moreover, sialylated forms of difucosylated LeX also accumulate in colon cancer but not in normal colonic mucosa. In the present study, six monoclonal antibodies which selectively recognize the various LeX-related antigens were used for immunohistochemical examination of these antigens in serial sections of human colonic tissue. All of these antigens were oncodevelopmental in human colon. Monoclonal antibodies anti-SSEA-1 and AH8-183, directed against short-chain, monofucosylated LeX, were unable to discriminate well between normal and malignant colonic tissue. However, the other four antibodies were much better at distinguishing cancer from normal tissue. FH6 was the most specific in that no normal tissues bound this antibody. However, FH6 failed to stain poorly differentiated cancers and some colloid-type carcinomas. FH4, which was also highly specific, stained almost all cancers, regardless of the degree of differentiation. FH4 primarily stained cancer cell cytoplasm, whereas the sialylated antigen defined by FH6 predominantly stained cell membranes. Differences were noted between the expression of LeX-related antigens in autopsied normal mucosa compared to mucosa of benign colonic diseases. Monoclonal antibodies recognizing long-chain polyfucosylated and sialylated LeX-related antigens appear to be useful tools for detection of colon cancer.

Antibodies, Monoclonal↗
PubMed1986

Comparison of T-antigen expression in normal, premalignant, and malignant human colonic tissue using lectin and antibody immunohistochemistry.

The Thomsen-Friedenreich antigen has been implicated as a cancer-associated antigen in some human organs including the colon. Most previous studies of Thomsen-Friedenreich antigen expression in the colon used peanut agglutinin (PNA) to identify the immunodeterminant in tissues. However, evidence from other organs suggests that anti-T antibodies have specificities which differ from those of peanut lectin. To elucidate the nature of the T-immunodeterminant in colonic mucosa, we compared staining by PNA to that of a polyclonal (PAb) and monoclonal (MAb) anti-T antibody. PNA demonstrated the best sensitivity (91%) in cancer tissues but the lowest specificity (68%) in normal mucosa. Staining with MAb was only 76% sensitive but 100% specific. Sensitivity and specificity of PAb were intermediate between PNA and MAb. MAb stained fewer adenomatous polyps than either PNA or PAb, but staining appeared to correlate with premalignant features of the polyps. PNA-binding sites were more prevalent than either PAb or MAb in hyperplastic polyps. Cell cytoplasm was stained by both antibodies more often than by PNA. The majority of fetal colonic specimens stained with all three reagents suggesting that Thomsen-Friedenreich antigen may be an oncodevelopmental antigen in human colon. Differences in staining patterns in some tissues may be due to different antigenic specificities among PNA, PAb, and MAb.

Adenoma↗
PubMed1986

Calcification in aging canine aortic valve.

Aging changes of aortic valves are thought to underlie the mechanism of calcification, which leads to calcific aortic stenosis in humans. The study of calcification in the aging valvular connective tissue has been hindered by the lack of a suitable animal model. In search of the model, canine aortic valves demonstrated age changes including calcification remarkably similar to those in humans. The mechanism of calcification was studied in the aortic valves of aged Beagles by electron microscopy. Fibroblasts in the canine aortic valves showed the most prominent age changes. The cells accumulated numerous residual bodies and appeared to disintegrate. The resultant membranous cellular degradation products which sequestered in the extracellular space were the nidi of calcification. It appeared that the membrane of cell debris played an important role in calcification. Canine aortic valve is an ideal model for the study of calcification in relation to aging of the valvular connective tissue.

Aging↗
PubMed1985

Carcinoma in situ in nonpolypoid mucosa of the large intestine. Report of a case with significance in strategies for early detection.

A case of carcinoma in situ of the flat, nonpolypoid mucosa of the large intestine in a 32-year-old man is reported. This case is of unusual importance because it was detected by endoscopy and was effectively managed; it sheds further light into the histogenesis of large intestinal carcinomas; and it points to alternate strategies for early detection and prevention of large intestinal carcinomas.

Adult↗
PubMed1985

Transformation of human bronchial epithelial cells transfected by Harvey ras oncogene.

Transfection of normal human bronchial epithelial (NHBE) cells with a plasmid carrying the ras oncogene of Harvey murine sarcoma virus (v-Ha ras) changed the growth requirements, terminal differentiation, and tumorigenicity of the recipient cells. One of the cell lines isolated after transfection (TBE-1) was studied extensively and shown to contain v-Ha ras DNA. Total cellular RNA from TBE-1 cells hybridized to v-Ha ras structural gene fragment probes five to eight times more than RNA from parental NHBE cells. The TBE-1 cells expressed phosphorylated v-Ha ras polypeptide p21, showed a reduced requirement for growth-factor supplements, and became aneuploid as an early cellular response to v-Ha ras expression. As the transfectants acquire an indefinite life-span and anchorage independence they became transplantable tumor cells and showed many phenotypic changes suggesting a pleiotropic mechanism for the role of Ha ras in human carcinogenesis.

Animals↗
PubMed1985

Isolation and culture of hepatocytes from human liver of immediate autopsy.

Human livers were removed at immediate autopsy (IA) from brain death patients within 1 h after cessation of cardiac function. Viable hepatocytes were isolated successfully from these IA livers by perfusion of an intact lobe with collagenase or by digestion of a small tissue wedge with collagenase-dispase. The yields of hepatocytes ranged from 1 to 3 X 10(6) cells/g liver in the five cases studied. Approximately 70 to 90% of the cells excluded trypan blue dye. In the isolated hepatocytes, 632 pmol/mg protein of cytochrome p450 and 536 pmol/mg protein cytochrome b5 were measured. The cells attached to the dishes in 4 h and produced monolayer cultures with a high success rate. The cells maintained in primary cultures for several days and developed ultrastructural features characteristic of human hepatocytes in vivo. The cultured hepatocytes can hydroxylate benzo[a]pyrene, conjugate the metabolites, and have a benzo[a]pyrene hydroxylase activity of 48.7 pmol/mg DNA per h, which is comparable to that of rat hepatocytes. The liver cells repaired DNA damage caused by exposures to aminofluorene and acetylaminofluorene in culture.

Animals↗
PubMed1985

Isolation, culture and characterization of human renal tubular cells.

Tubular cells have been isolated, characterized and cultured from more than 70 adult cadaver kidneys (postmortem time less than or equal to 12 hr.). Confluent monolayers were observed at 7 days after seeding (10(6) cells/ml.) and cells demonstrating normal human karyotypes have been passaged up to 6 times. Primary isolates and monolayer cultures were negative for Factor VIII activity, and strongly positive for gamma-glutamyltransferase activity and keratin. Ultrastructurally primary isolates consisted of cells with numerous mitochondria, microvilli, cytoplasmic filaments and well-developed endocytotic apparati. Monolayer cultures examined at 7, 14, 21 and 72 days demonstrated less prominent microvilli and the additional structures of desmosomes and cell junctions. Membrane-associated and cytosolic enzyme activities were measured up to 28 days in culture. The membrane-associated enzymes gamma-glutamyltransferase and alkaline phosphatase both exhibited approximately 10-fold decreases in activity during the 1st 7 days in culture. There was an approximately 5-fold increase in pyruvate kinase activity during the same time period, while fructose-1,6-bisphosphatase activity exhibited a 5-fold decrease. Glucose-6-phosphatase activity did not change during the 28 day culture period examined. From 7 to 28 days no further changes were noted in any of the enzyme activities measured. Decreased membrane-associated enzyme activity corresponded to the ultrastructural observation of less prominent microvilli. Increases in glycolytic enzyme activity and decreases in gluconeogenic enzyme activity may reflect the presence of glucose in the culture medium. The morphologic and biochemical evidence suggests that primary isolates and cultures are proximal tubule cells which should provide a well-defined in vitro human system for future studies.

Adolescent↗
PubMed1985

What's new in in vitro studies of exocrine pancreatic cell injury?

Exocrine pancreas in vitro models are useful for the study of pancreatic differentiation, secretion mechanisms, cell injury, and lysosomal processing of secretory product. Syrian hamster pancreas in explant organ culture undergoes a series of morphologic changes which parallel in vitro acinar cell injury, differentiation, and phenotypic alteration. Within 48 hours, the cultured acinar cells show morphologic evidence of sublethal cell injury. Autophagy and crinophagy are particularly striking. The autophagic processes can be inhibited by the addition of the protein synthesis inhibitor cycloheximide or by culture at lowered temperatures (20 degrees C). Acinar cells lethally damaged show pyknotic nuclei, high amplitude swelling, and necrosis. Approximately 25% of each explant is viable after 72 hr in culture and the viability remains constant at 25-35% for up to 60 days of culture. The morphological changes of the explants are consistent with many of the features of pancreatitis and carcinoma of the exocrine pancreas. There is an increase in the ductal elements and a decrease in acini over time in culture. This may be due to: (a) an increased replication of ductal epithelial cells concomitant with necrosis of acinar epithelial cells and/or (b) phenotypic alteration of acinar cells to ductal cells. Acinar cell necrosis and phenotypic alterations may in part be due to the activation of lysosomal degradation pathways. Processes which inhibit lysosomal activation proved protective against these alterations, while processes which promote zymogen activation were deleterious.

Animals↗
PubMed1985

Studies on the mechanisms of altered exocrine acinar cell differentiation and ductal metaplasia following nitrosamine exposure using hamster pancreatic explant organ culture.

Syrian golden hamster pancreatic organ explants were treated with either methylnitrosourea (MNU) or N-methyl-N-nitroso-N'-nitroguanidine (MNNG). In control explants treated with only dimethylsulfoxide, there was evidence of autophagy and crinophagy in acinar cells. Carcinogen-exposed explants showed increased numbers of autophagic and crinophagic vacuoles. In long-term cultured explants there was an increase in the number of ducts over zero time control tissues. Eosinophilic cells similar to hepatocyte-like cells were seen in 90% of the carcinogen-treated explant experiments and in 45% of the controls. Nitrosamine exposure did not induce an increase in the overall amount of necrosis measured morphometrically. Nitrosamine exposure in vitro appears to lead to a sequence of events that follow carcinogen metabolism by the acinar cells. The changes that follow include altered cell morphology and toxic cell injury evidenced by autophagic and crinophagic processes, regeneration of ductal appearing cells, the appearance of hepatocyte-like cells and an overall increase in the amount of ductal metaplasia. Within some of these ductal foci, several ductules show atypical features.

Animals↗
PubMed1985

Cis-diamminedichloroplatinum (II)-induced acute renal failure in the rat: enzyme histochemical studies.

Enzyme histochemical techniques were utilized to examine the progression and extent of proximal tubular injury during the development of cis-diamminedichloroplatinum (II) (CDDP)-induced acute renal failure. Acute renal failure was induced in male rats by the intraperitoneal administration of 10 mg CDDP/kg body weight. At 6, 24, 48, 72, and 96 hr following treatment, renal function was assessed and tissue was collected for renal morphologic and enzyme histochemical studies. The enzymes examined were gamma-glutamyl transpeptidase, alkaline phosphatase, sodium-potassium ATPase (nitrophenyl phosphatase), acid phosphatase, glucose-6-phosphatase, succinic dehydrogenase, alpha-glycerophosphate dehydrogenase, and lactic dehydrogenase. By 24 hr, the activity of acid phosphatase was reduced throughout the proximal tubule, with the greatest decrease occurring in the P3 segment of the proximal tubule located in the outer stripe of the outer medulla. Changes in the histochemical staining of the remaining enzymes were not consistently observed until 48 or, in some cases, 72 hr. These alterations involved all portions of the proximal tubule with the most severe changes involving P3. The results of the enzyme histochemical studies along with the morphologic findings indicating that the initiation of CDDP-induced acute renal failure, first apparent at 48 hr in this model, is associated with cell injury throughout the proximal tubule. The majority of the histochemical changes did not become apparent until late in the course of tubular injury. This suggests that most of the changes in enzyme activity represent nonspecific effects of CDDP-induced tubular injury, as opposed to direct enzyme inhibition by the drug.

Acid Phosphatase↗
PubMed1985

Histochemical studies of dense-core granulated tumors of the lung. Neuron-specific enolase as a marker for granulated cells.

It is well known that carcinoid tumors and some small-cell carcinomas of the lung contain dense-core granules (DCGs). Moreover, a small number of tumors presenting with epidermoid, large-cell, or adenocarcinoma histologic characteristics (so-called atypical endocrine tumors), also contain DCGs. Herein, we describe certain histochemical features of DCG tumors and compare them with other major lung tumor types that lack DCGs (non-DCG tumors). All DCG tumors contained neuron-specific enolase and many contained serotonin. These markers were not present in any non-DCG tumor. Other histochemical markers (glycogen, mucosubstances, corticotropin, beta-human chorionic gonadotropin, keratin, somatostatin, and calcitonin) were found in a proportion of DCG and non-DCG tumors, but were, in general, more common in non-DCG tumors and atypical endocrine tumors than in carcinoids and small-cell carcinomas. alpha-Fetoprotein was rarely found in non-DCG tumors, and was never observed in DCG tumors. The atypical endocrine group represents a class of tumors with a remarkably mixed and varied phenotype. Their potential significance is discussed and methods to facilitate their diagnosis are suggested.

Adenocarcinoma↗