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Biomedical subjects

I Lee

Publications and source records attributed to I Lee.

At least 217 records · Page 12Linked to original sources
PubMed1987

Establishment and characterization of a neuroendocrine skin carcinoma cell line.

A neuroendocrine skin carcinoma cell line MKL-1 has been established from a nodal metastasis in a 26-year-old patient. The line grows as irregularly outlined, loosely packed floating aggregates lacking central necrosis. MKL-1 is hyperdiploid and has a mean doubling time of 120 hours. Xenografts of 2 X 10(7) MKL-1 cells produce tumors in nude mice at 4 to 6 weeks after subcutaneous inoculation. The xenografts were morphologically indistinguishable from the original skin primary and the nodal metastasis. Electron microscopy revealed sparse membrane-bound neurosecretory granules, and conspicuous, paranuclear aggregates of intermediate filaments. Immunohistochemical study showed diffuse and consistent staining with neuron-specific enolase, while bombesin, adrenocorticotrophic hormone, Leu-enkephalin, substance P, and vasoactive intestinal polypeptide displayed heterogeneous and variable expression. Uniform staining of all cells appearing as cytoplasmic fibrils and paranuclear aggregates was noted with antibodies to cytokeratin. Appreciable amounts of cytokeratin polypeptides 8, 18, and 19 and IT protein were seen on two-dimensional gel electrophoresis of cytoskeletal preparations from MKL-1 cells and from tumor-rich frozen sections. Immunostaining also showed coexpression of neurofilaments arranged in paranuclear aggregates; gel electrophoresis and immunoblotting demonstrated the presence in MKL-1 cells of prominent amounts of the small neurofilament polypeptide. Focal expression of desmoplakin was noted in the xenografts. The cells reacted with monoclonal antibodies anti-Leu-7 and anti-Leu-M1 but did not react with antibodies to human lymphocyte antigens (HLA)-A, HLA-B, and HLA-C. Cytogenetic analysis revealed the presence of 3 chromosomally abnormal cell lines with the majority of metaphase cells demonstrating a gain of an isochromosome of the short arm of chromosome 5. Thus, MKL-1 cell line shares several characteristics with small cell neuroendocrine bronchopulmonary carcinoma cell lines but shows distinct cytogenetic abnormalities.

Adult↗
PubMed1986

Dose-response range of encainide for benign and potentially lethal ventricular arrhythmias.

A multicenter, 2-week, double-blind, placebo-controlled, parallel group study was performed to determine the dose-response relation of encainide administered 3 times daily and to determine its onset of action. To be included in the study, patients with benign or potentially lethal ventricular arrhythmias were required to have an average of at least 30 ventricular premature complexes (VPCs) per hour on 48-hour Holter monitoring after a 48-hour washout period without antiarrhythmic drug treatment. Patients were randomly assigned to receive either placebo or 10, 25 or 50 mg of encainide 3 times daily (tid) for 2 weeks. Of the 125 patients who entered the study, 122 were available for efficacy analysis. Efficacy was determined using 24-hour Holter monitoring on days 1, 7 and 14. There was no difference in frequency of VPCs or of ventricular tachycardia events in the placebo and 10-mg-tid encainide arms. At doses of 25 and 50 mg of tid, encainide was effective in suppressing VPCs and in reducing the number of episodes of ventricular tachycardia. A positive dose-response relation was identified. The onset of effect of encainide was apparent at 3 hours and lasted for 24 hours with tid dosing. No difference in on-therapy conditions were found among the 4 study arms. No patients were discontinued from the study because of electrocardiographic changes. There was no statistically significant change in vital signs or physical examination data. In 1 patient an elevated serum glucose level developed. No symptomatic proarrhythmic events occurred and none required discontinuation of study medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Histologic variation in the skin lesions of the glucagonoma syndrome.

Three cases of glucagonoma syndrome were seen in 1 year. Study of the skin biopsies from the first two cases led to a correct diagnosis from skin biopsy of the third case, although it was not suggested clinically. In each case serum glucagon levels were high and a pancreatic tumor was found, with complete remission of symptoms in cases 1 and 3 after resection; case 2 refused surgery and has died. A total of nine skin biopsies from the three patients showed a variety of findings: epidermal necrosis; subcorneal pustules, either isolated or associated with necrosis of the epidermis; confluent parakeratosis, epidermal hyperplasia, and marked papillary dermal angioplasia; and suppurative folliculitis. The clinical lesions in this syndrome vary from bright red macules to annular superficial erosions and flaccid pustules. Similarly, several histopathologic features of the disease can occur, which may represent the progression of the disease. No single histologic feature was specific for the disease, but a combination of the features is probably diagnostic. Therefore, multiple skin biopsies are recommended when this diagnosis is suspected.

Adenoma, Islet Cell↗
PubMed1986

The intermediate filament complement of the spectrum of nerve sheath neoplasms.

The intermediate filament complement of the spectrum of nerve sheath neoplasms including 12 typical benign schwannomas, 1 ancient schwannoma, 2 cellular schwannomas, 6 neurofibromas and 4 malignant schwannomas was investigated by immunofluorescence microscopy, two dimensional electrophoresis, and immunoblot analysis. Studies were performed on freshly frozen tumor tissue samples; a broad spectrum of antibodies against all classes of intermediate filaments was utilized. Samples were also studied by electron microscopy, and immunohistochemically for S-100 protein and desmoplakins. By immunofluorescence microscopy, all nerve sheath neoplasms revealed intense positivity for vimentin throughout the cytoplasm while 2 benign schwannomas displayed co-expression of vimentin and glial filament proteins. Two-dimensional gel electrophoresis and immunoblot analysis confirmed the presence of vimentin and showed that it was the predominant protein in all tumors. Electrophoretic analysis of the 2 benign schwannomas that immunostained for glial filament proteins confirmed the presence of this protein which was shown to comigrate with a known human control sample. Neither immunofluorescence microscopy nor biochemical analyses revealed cytokeratin polypeptides, neurofilament proteins, desmin, or desmoplakin in any of the tumors. We conclude that while vimentin is the predominant intermediate filament expressed by the entire spectrum of nerve sheath neoplasms, at least occasional benign schwannomas are capable of co-expressing glial filament proteins. It remains to be determined whether the subgroup of nerve sheath neoplasms that co-expresses vimentin and glial filament proteins is otherwise distinguishable from their more frequent counterparts that express vimentin exclusively.

Adolescent↗
PubMed1986

The clonogenic response of bovine aortic endothelial cells in culture to radiation.

The effect of ionizing radiation on the survival of bovine aortic endothelial (BAE) cells was determined by the in vitro colony formation method. The BAE cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% calf serum, antibiotics, and growth factors obtained from the culture of mouse S-180 cells. The cultured BAE cells were positive to the staining of antibodies against human factor VIII and formed clones in plastic culture flasks with a plating efficiency of about 11%. The survival curve of the BAE cells following an exposure to a single dose of X rays was characterized by D0 = 101 rad, Dq = 65 rad, and an extrapolation number (n) of 1.9. These parameters were not modified by the absence of growth factors at the time of irradiation. The response of BAE cells to radiation was dose-rate dependent. The split-dose studies demonstrated that the BAE cells were able to repair sublethal radiation damage within 1 h after irradiation.

Animals↗
PubMed1986

Malignant mesotheliomas. Improved differential diagnosis from lung adenocarcinomas using monoclonal antibodies 44-3A6 and 624A12.

Forty-three malignant pleural mesotheliomas and 10 known metastatic pulmonary adenocarcinomas to the pleura were studied by immunohistochemistry using monoclonal antibodies 44-3A6 and 624A12. Monoclonal antibodies 44-3A6 and 624A12 were raised against human pulmonary carcinoma cell lines; they recognize a membrane-associated protein of 40,000 mol wt and a specific sugar sequence of lacto-N-fucopentose III, respectively. Samples were also studied with a broad-spectrum antikeratin antibody and a polyclonal antibody to carcinoembryonic antigen (CEA). These investigations were performed on formalin-fixed and paraffin-embedded tissues. The mesotheliomas comprised only grossly evident, pleurectomized, or pneumonectomized cases; they included 22 epithelial, 15 biphasic, and 6 spindle cell types. Electron-microscopic study was also done on 9 cases. None of the mesotheliomas was immunoreactive to 624A12, while 9/10 metastatic pulmonary adenocarcinomas were convincingly immunoreactive. Monoclonal antibody 44-3A6 immunostained all of the metastatic adenocarcinomas strongly, whereas only 10/43 mesotheliomas were focally and weakly immunoreactive. The latter included 5 epithelial and 4 biophasic mesotheliomas and 1 spindle cell mesotheliomas; the immunoreaction was confined to scattered single cells, and the staining pattern was readily discernible from that of adenocarcinomas. Forty of 43 mesotheliomas were strongly immunoreactive with the broad-spectrum anti-keratin antibody, whereas 8/10 metastatic pulmonary adenocarcinomas showed focal and rather weak staining. Seven of 10 metastatic adenocarcinomas were immunoreactive to anti-CEA antibody, while only 15/43 mesotheliomas displayed weak immunoreactivity. It is concluded that monoclonal antibodies 44-3A6 and 624A12 are excellent phenotypic markers of metastatic pulmonary adenocarcinomas to the pleura and thus are useful for the differential diagnosis of pleural mesotheliomas. Given conventionally fixed and processed tissues, it appears that the combined use of these monoclonal antibodies may be more effective for that differential diagnosis than anti-CEA and anti-keratin antibodies.

Adenocarcinoma↗
PubMed1985

Bombesin in human neuroendocrine (NE) neoplasms.

Bombesin is a 14 amino acid peptide isolated from amphibian skin which was found to have stimulatory effects upon gastric and pancreatic secretions, release of gastrointestinal hormones, gallbladder contraction and bronchoconstriction. It is present in amphibian gastric endocrine cells, avian proventriculus endocrine cells and avian brain. In mammals it is present mainly in nerve cells and fibers. The only mammalian endocrine cell shown to date to have bombesin is the P-cell in fetal lung. Bombesin is also found in mammalian brain, with its highest concentration in the hypothalamus. We examined several groups of human neuroendocrine neoplasms for the presence of bombesin by immunohistochemistry. Our findings indicate that bombesin is present 68% of bronchial carcinoids, 65% of pulmonary neuroendocrine carcinomas, 62% of neuroendocrine carcinomas of the skin, 5-10% of pheochromocytomas and extraadrenal paragangliomas and 35% of gastrointestinal carcinoids and neuroendocrine carcinomas. Parallel studies in a wide variety of non neuroendocrine neoplasms failed to reveal the presence of bombesin. We conclude that bombesin is a highly specific marker of neuroendocrine differentiation and thus a valuable tumor marker. Furthermore, its specificity compares favorably with another neuroendocrine marker, neuron specific enolase, an enzyme thought to be present only in neural tissues and neuroendocrine cells but recently found in non neural human tissues and non neuroendocrine neoplasms.

Bombesin↗
PubMed1985

Increased radiosensitivity of tumors by perfluorochemicals and carbogen.

The efficacy of an emulsion of perfluorochemicals (Fluosol-DA) to sensitize RIF-1 tumors of C3H mice to radiation was studied. An i.v. injection of 12 ml/kg of Fluosol-DA (20%) to tumor-bearing animals and keeping the animals in an atmosphere of a mixture of O2 (95%) and CO2 (5%) (carbogen) for 1 hr before and during irradiation of s.c. tumors in the thigh significantly enhanced the tumoricidal effect of radiation as measured with growth delay of the treated tumors. A lesser but significant enhancement of radiation damage in the tumors was also observed when the animals were kept in carbogen for 1 hr without injection of Fluosol-DA. It was concluded that Fluosol-DA increased the delivery of oxygen to hypoxic areas in the tumors and enhanced the response of hypoxic cells to radiation.

Animals↗
PubMed1985

Neuroendocrine skin carcinoma coexpressing cytokeratin and neurofilament proteins.

Neuroendocrine (Merkel cell) carcinomas of the skin have been recognized as such for several years. Given the reported wide variability in the morphology and clinical evolution of these tumors, the notion that may they comprise several variants rather than a single type has been advocated. Electron microscopy has played a key role in the early recognition of these tumors while immunohistochemical studies for various neuroendocrine markers have facilitated their subsequent diagnosis and improved our understanding as to their complexity by the demonstration of immunoreactivity for NSE (neuron specific enolase) and a number of neuropeptides. There has also been considerable interest in the study of the cytoskeletal intermediate filament complement of neuroendocrine neoplasms in general and of those of the skin in particular. Early reports indicated that neuroendocrine skin carcinomas had neurofilaments while subsequent investigations determined that they had cytokeratin. However, more recent studies have indicated that at least some neuroendocrine skin carcinomas could in fact coexpress both aforementioned classes of intermediate filament proteins. This brief report is presented to confirm the latter investigations.

Carcinoma↗
PubMed1985

Paragangliomas of the head and neck: ultrastructural and immunohistochemical analysis.

Eighteen head and neck paragangliomas were studied by light microscopy and light microscopic immunohistochemistry by the peroxidase technique for the presence of NSE (neuron-specific enolase), serotonin, and a battery of neuropeptides. Seven of these tumors were also studied by electron microscopy. All 18 cases demonstrated immunostaining for NSE; 10 of the 11 carotid body tumors had immunostaining for multiple hormones. Considering all 18 cases, the most frequently demonstrated hormonal substances were in order: serotonin, leu-enkephalin, gastrin, substance P, vasoactive intestinal polypeptide (VIP), somatostatin, bombesin, calcitonin, and alpha MSH. In several tumors, adjacent-step sections stained for different hormonal substances strongly suggested reactivity for more than one hormone in given tumor cells. By electron microscopy, all 7 cases studied displayed considerable heterogeneity of the neurosecretory granules with respect to size, shape, and electron density. This demonstrated that branchiomeric paragangliomas are capable of producing a spectrum of neuropeptides in addition to their known amine content. The presence of immunoreactive serotonin in most of these neoplasms was confirmed. In addition to these findings, neurofibrils within the substance of carotid body paragangliomas demonstrated immunoreactivity for somatostatin and a gastrinlike neuropeptide. The significance of the neuropeptides in these neoplasms and their possible presence and role in normal and hyperplastic paraganglia remain to be defined.

Carotid Body Tumor↗
PubMed1985

Monoclonal antibody 44-3A6 as a probe for a novel antigen found on human lung carcinomas with glandular differentiation.

This paper describes an immunoglobulin G1 mouse monoclonal antibody (MCA) 44-3A6 directed against a human adenocarcinoma of the lung, cell line A549. This hybrid is a fusion product of the mouse myeloma SP 2/0.Ag14 and spleen cells from a BALB/c mouse which had been hyperimmunized with A549. Live cell radioimmunoassays, immunofluorescences, and fluorescent activated cell sorter analysis indicate that MCA 44-3A6 reacts with a cell surface antigen. Western blot analysis identifies a major antigen band with the apparent molecular weight of 40,000. Enzyme treatment of A549 target plates shows that the antigen is sensitive to proteases. This MCA does not react with carcinoembryonic antigen. Patients having a variety of different lung carcinomas do not appear to have detectable antigen in their serum, nor does the antigen appear to be shed into culture supernatants by human lung carcinoma cell lines. The antigen is preserved in formalin-fixed, paraffin-embedded tissue sections and shows a cell surface and/or cytoplasmic staining pattern. Immunohistochemical staining of various bronchopulmonary carcinomas demonstrated binding to be restricted to tumors with features of "glandular" differentiation. This MCA may have clinical and diagnostic utility due to its selective binding for a subset of carcinomas of the lung.

Animals↗
PubMed1985

Immunohistochemical analysis of human pulmonary carcinomas using monoclonal antibody 44-3A6.

A monoclonal antibody, 44-3A6, was raised against the human pulmonary adenocarcinoma cell line A549. This antibody recognizes a protein antigen at the cell surface, which is preserved after formalin fixation and paraffin embedding. Immunohistochemical staining of lung tissue with this antibody revealed diffuse immunoreactivity of type II pneumocytes. Bronchial epithelial cells were also focally immunoreactive. Immunostaining of various bronchopulmonary carcinomas demonstrated characteristic patterns of reactivity. All of the 42 adenocarcinomas and 18 carcinoids were strongly immunoreactive either diffusely or focally. The immunoreaction occurred at the cell membrane and/or in the cytoplasm. None of the 39 squamous cell carcinomas, 12 bronchioloalveolar carcinomas, and 30 small cell neuroendocrine carcinomas was immunostained. Ten intermediate cell neuroendocrine carcinomas and 8 well-differentiated neuroendocrine carcinomas were relatively weakly immunoreactive, while 7 and 2 of them were negative. Six adenosquamous carcinomas were focally positive in glandular and "basaloid" areas, whereas squamous areas were negative. Twenty-one large cell carcinomas were focally immunoreactive, while 6 were negative. It appears that MCA 44-3A6 is an effective marker for certain features of "glandular" differentiation, which may be present even in tumors lacking obvious glands, and that it may be useful for the differential diagnosis of various bronchopulmonary carcinomas.

Adenocarcinoma↗
PubMed1985

Coexpression of neuroendocrine markers and epithelial cytoskeletal proteins in bronchopulmonary neuroendocrine neoplasms.

Neuroendocrine (NE) neoplasms of the human bronchopulmonary tract were examined by electron microscopy, immunocytochemistry, and gel electrophoresis of cytoskeletal proteins from microdissected tissue samples. All samples (carcinoids, well-differentiated NE carcinoma, NE carcinomas of intermediate type, NE carcinomas of the small cell type) contained significant numbers of cells that immunostained for one or more of the following neuroendocrine markers tested: bombesin, calcitonin, ACTH, leu-enkephalin, gastrin, serotonin, somatostatin, alpha-melanocyte-stimulating hormone, vasoactive intestinal peptide, glucagon, insulin, substance P, and neuron-specific enolase. Electron microscopy revealed typical NE cell features, including variable abundant and frequently heterogeneous neurosecretory granules. Tumor cells contained filaments specifically stained with different conventional and monoclonal antibodies to cytokeratins and displayed punctate plasma membrane staining with antibodies to desmoplakins, in agreement with the electron microscopic demonstration of tonofilament bundles and desmosomes. Immunocytochemistry for NE markers and cytoskeletal proteins on consecutive sections revealed both cytokeratins and neuroendocrine substances in single cells. Using gel electrophoresis of cytoskeletal proteins of tissue regions extracted with high salt buffer and detergent, we could detect, in the tumors tested, appreciable amounts of cytokeratin polypeptides 8, 18, and 19, i.e., major cytokeratins also found in certain other lung carcinomas such as adenocarcinomas. Tumor cells were not significantly stained with antibodies to other intermediate filament proteins such as vimentin, desmin, glial filament protein, and neurofilament protein. The results show that NE substances can be synthesized in cells containing a typical epithelial cytoskeleton, i.e., cytokeratin filaments and desmosomes. These findings support the notion of an epithelial character of these tumors and appear in contrast with recent reports that neurofilaments are the only type of intermediate filaments present in carcinoids and other pulmonary NE tumors. These observations may have important implications for the histogenesis of NE carcinomas and for diagnostic pathology.

Adrenocorticotropic Hormone↗