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PubMed1984

Immunoelectron microscopic application of monoclonal antibodies for identification of lymphocyte subsets bearing tubuloreticular inclusions or parallel tubular arrays.

Reactions of mouse monoclonal antibodies with T-cell, B-cell, or NK cell antigens were localized for electron microscopy by the formation of avidin-biotin-peroxidase complexes using direct or indirect labeling techniques. The techniques proved advantageous for identification of lymphocyte subsets bearing two different types of cytoplasmic structures: tubuloreticular inclusions (TRI) which have been related to interferon treatment or to diseases involving systemic immune dysfunctions, and parallel tubular arrays (PTA) which may be normal structures. Mononuclear cell samples were isolated from the peripheral blood of patients with systematic lupus erythematosus (SLE), acquired immunodeficiency syndrome (AIDS), or chronic hepatitis B (CHB). Results depended upon the fixation, the type of specific antibody, and the concentrations employed. Brief fixation in 1% glutaraldehyde/1% paraformaldehyde proved useful for stable preservation of both the inclusion fine structure and surface antigen activity, even after prolonged storage in buffer. The T-cell subset antigens (Leu-2a and Leu-3a) were more labile than the pan-T-cell antigen (Leu-1), the B-cell surface antigen (Leu-10), or the NK cell antigen (Leu-7). Localization of the former was improved by a two-step labeling procedure with primary and secondary antibodies. Both TRI and PTA were identified in T cells. Either type of inclusion could be found in the suppressor/cytotoxic or helper/inducer T-cell subsets. TRI also were found in a few anti-Leu-10 reactive cells. A crystalline form of PTA was identified in anti-Leu-1 and anti-Leu-7 reactive cells.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Spirostomum spp. (Ciliophora, Protista), a suitable system for endocytobiosis research.

Among ciliate genera, only Paramecium and Euplotes species have been studied extensively as host organisms of bacterial endocytobionts. In this article, we show that members of the genus Spirostomum may also serve as a suitable system for endocytobiosis research. Two strains of Spirostomum minus (Heterotrichea, Ciliophora) collected in Germany and Italy, respectively, were found to harbor different types of bacterial infections. Bacteria of various sizes and shapes were observed in the cytoplasm or in the nuclei of the ciliates. The bacteria in the cytoplasm were either surrounded by a peribacterial membrane or lay naked. One of the bacterial species was found in the vicinity of the contractile fibrillar system (myonemes) of the ciliates. In rare cases, another type of bacteria was observed associated with mitochondria. The macronuclei of both the Italian and the German strains were crowded with endocytobionts. The endonuclear bacteria in the two S. minus strains differed with respect to their cytoplasmic structures but they were of similar size and both were rod shaped. According to the results of in situ hybridization, the endonuclear bacteria of the Italian strain belong to the subgroup of alphaproteobacteria, whereas the bacteria associated with the fibrillar system appeared to be gram-positive bacteria with high G+C content. While both the German and the Italian strains were found to permanently maintain their endocytobionts, they were at least partly colonized by different bacteria. This is taken as an indication that geographically separated populations of ciliates may be stably infected by different endocytobionts, possibly due to different ecological conditions. For S. minus and S. ambiguum a total of 7 different bacterial endocytobionts have now been recorded. We recommend the members of the genus Spirostomum as a suitable system for endocytobiosis research.

Animals↗
PubMed1996

Complement activation by C-reactive protein on the HEp-2 cell substrate.

The complement (C) activation by C-reactive protein (CRP) in acute-phase sera is routinely tested in our laboratory by means of an indirect immunofluorescence method (C3-IFT) on rat kidney sections. This C3-IFT assay is based on the binding of CRP to the renal tissue followed by the fixation of C4 and C3 components to distinct vessel-associated medullary structures as a result of CRP-mediated C activation in vitro. While the activation cascade leading to the deposition of C4 and C3 could previously be deduced experimentally, we were unable as yet to visualize CRP and the components of the C1 complex on kidney sections when testing patients' sera by indirect immunofluorescence. In an attempt to analyze the mechanisms of unexpectedly negative C3-IFT results (e.g. bacterial endocarditis) we employed monolayers of fixed HEp-2 cells which have previously been shown to be a suitable substrate for CRP binding. By incubating purified native CRP supplemented with normal human serum as a source of C we detected the C components Clq, Clr, Cls, C4 and C3 in the same speckled immunofluorescent pattern on HEp-2 cell nuclei as described characteristically for CRP binding. The serial activation steps from CRP up to C3 could also be followed on HEp-2 cells using C3-IFT-positive acute-phase sera. However, certain C3-IFT-negative acute-phase sera showed an arrest between Cls and C4 of the CRP-mediated C activation cascade. HEp-2 cells can thus be used to monitor the process of autologous C activation initiated by endogeneous CRP in patients' sera. In contrast to native CRP, urea-modified CRP (mCRP) did not bind to HEp-2 cell nuclei, but was detected in association with distinct filamentous cytoplasmic structures. Unlike its native counterpart, binding of mCRP was not followed by a deposition of C components.

Animals↗
PubMed1997

[Action of physical agents on microorganisms].

Among numerous physical agents exerting their deleterious effect on microorganisms only a few have been applied to sterilisation or disinfection used for medical purposes. Temperature is the most important agent, which from one side in a very wide range enables supporting of metabolic processes of psycho-, mezo- and thermophilic microorganisms, but beyond these limits causes their death. High temperature induces at first damage of cytoplasmic membrane and then denaturation of RNA leading to death. On the other hand, a low temperature slowly decreasing below 0 degree C induces crystallisation of water in cells and destruction of cytoplasmic structures. Ultraviolet radiation causes mutations resulting in stopping of DNA replication in all forms of the microorganisms. The same way of the lethal activity is exerted by ionising radiation. Its kinetic energy induces mutations affecting not single bases but also whole operons making gene expression impossible. Gaseous plasma is a new physical agent applied recently to sterilisation. High frequency energy initiates generation of the plasma from hydrogen peroxide vapours in a high vacuum and creates reactive species particles from the vapours that collide and kill microorganisms. On the other hand, application of ultrasound radiation to killing of microorganisms needs for further studies because of a high variability depending upon used frequency and energy. It is not known, for example, if destruction of microorganisms by ultrasounds is related to a phenomenon of cavitation or thermal energy. Nevertheless, even a range of frequency and energy used in commercial microwave ovens kills vegetative cells of coliform rods in about 15 minutes.

Bacteria↗
PubMed2001

Analysis of RNA associated with P granules in germ cells of C. elegans adults.

P granules are cytoplasmic structures of unknown function that are associated with germ nuclei in the C. elegans gonad, and are localized exclusively to germ cells, or germ cell precursors, throughout the life cycle. All the known protein components of P granules contain putative RNA-binding motifs, suggesting that RNA is involved in either the structure or function of the granules. However, no specific mRNAs have been identified within P granules in the gonad. We show here that P granules normally contain a low level of RNA, and describe conditions that increase this level. We present evidence that several, diverse mRNAs, including pos-1, mex-1, par-3, skn-1, nos-2 and gld-1 mRNA, are present at least transiently within P granules. In contrast, actin and tubulin mRNA and rRNA are either not present in P granules, or are present at relatively low levels. We show that pgl-1 and the glh (Vasa-related) gene family, which encode protein components of P granules, do not appear essential for RNA to concentrate in P granules; these proteins may instead function in events that are a prerequisite for RNAs to be transported efficiently from the nuclear surface.

Animals↗
PubMed1995

Microcompartmentation, metabolic channelling and carbohydrate metabolism.

The inter-organelle cytoplasm of eukaryotic cells was once considered to be a homogeneous solution in which many of the enzymes of intermediary metabolism are soluble; however, advances in cell biology have revealed an intricate picture at the microscopic level of cytoplasm structure. Consequently, a great deal of constraint is required when extrapolating to the intact cell from enzyme studies in vitro, a point made frequently in the literature of the last decade or so. The idea of spatial organization is now accepted and covers a wide variety of local microenvironments and possibly localized metabolic channelling. The latter, although accepted as a phenomenon, is controversial in terms of its physiological significance. This review covers evidences showing that both glycolytic and glycogenolytic enzymes are microcompartmentalized. The potential significance of this compartmentation appears to involve metabolic chanelling, a process by which rearrangement of enzymes on a dynamic cytomatrix leads to "channels" in which metabolic substrates are passed from one enzyme to the next. The combined effects of such enzyme proximity and their activation as a result of the altered kinetic properties conferred upon the enzymes by their cytoskeletal associations favours maximal rate of reaction. These and other aspects of microcompartmentation and metabolic channelling are discussed.

Animals↗
PubMed2000

Ethanol induced apoptosis in human HL-60 cells.

In this study flow cytometric and morphologic methods of apoptosis detection in human promyelocytic leukemia cell line HL-60 were compared. HL-60 cells were harvested at 4, 7, 16, 24 a 48 hours after induction of apoptosis by 3 % ethanol. Little changes were observed both by flow cytometry (decrease of forward scatter, increase of unprocessed cells staining with APO2.7 antibody) and viability determination by Trypan-blue staining until after 7 hours. However, after 4 hours morphologic changes were observed in the nuclear and cytoplasmic structures using Diff-Quik stained cytospin preparations and standard light microscopic techniques (50% apoptotic cells). The same results were obtained by flow cytometric measurement of sub-diploid DNA content (sub-G1 cells), and an increase of staining with APO2.7 antibody in cells permeabilised by digitonin prior to staining. After 7 hours almost all cells exhibited apoptotic morphology. After 16 hours the cell size (forward scatter) decreased significantly, and 54% of unprocessed cells were APO2.7 positive. After 24 hours only 6% of cells were alive (high forward scatter) and these cells were APO2.7 negative. The HL-60 cells did not proliferate during the cultivation in 3% ethanol, and after 48 hours all stained by Trypan blue. HL-60 leukemic cells were CD34-/AC133-, CD33+/CD15+, and only 2% of the cells were CD95+. Induction of apoptosis by ethanol did not enhance CD95 antigen expression.

AC133 Antigen↗
PubMed2001

A role for Hsc70 in regulating nucleocytoplasmic transport of a temperature-sensitive p53 (p53Val-135).

Mouse temperature-sensitive p53(Val-135) accumulates in the nucleus and acts as a "wild-type" at 32 degrees C while it is sequestered in the cytoplasm at 37 degrees C. The cytoplasmic p53(Val-135) relocalized into the nucleus upon inhibition of the nuclear export at 37 degrees C, whereas a mutation in a major bipartite nuclear localization signal (NLS) caused constitutive cytoplasmic localization, indicating that it shuttled between the cytoplasm and the nucleus by its own nuclear export signal and NLS rather than tethered to cytoplasmic structures. Although the full-length p53(Val-135) did not bind the import receptor at 37 degrees C, a C-terminally truncated p53(Val-135) lacking residues 326-390 did bind it. Molecular chaperones such as Hsc70 were associated with p53(Val-135) at 37 degrees C but not at 32 degrees C. When the nuclear export was blocked by leptomycin B, only a fraction lacking Hsc70 was specifically accumulated in the nucleus. Immunodepletion of Hsc70 from the reticulocyte lysate caused p53(Val-135) to bind the import receptor. This binding was blocked by supplying the cell extract containing Hsc70 but not by the addition of recombinant Hsc70 alone. We suggest that the association with the Hsc70-containing complex prevents the NLS from the access of the import receptor through the C-terminal region of p53(Val-135) at 37 degrees C, whereas its dissociation at 32 degrees C allows rapid nuclear import.

Amino Acid Sequence↗
PubMed2000

Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system.

HIV-1 infection of the brain results in chronic inflammation, contributing to the neuropathogenesis of HIV-1 associated neurologic disease. HIV-1-infected mononuclear phagocytes (MP) present in inflammatory infiltrates produce neurotoxins that mediate inflammation, dysfunction, and neuronal apoptosis. Neurologic disease is correlated with the relative number of MP in and around inflammatory infiltrates and not viral burden. It is unclear whether these cells also play a neuroprotective role. We show that the chemokine, fractalkine (FKN), is markedly up-regulated in neurons and neuropil in brain tissue from pediatric patients with HIV-1 encephalitis (HIVE) compared with those without HIVE, or that were HIV-1 seronegative. FKN receptors are expressed on both neurons and microglia in patients with HIVE. These receptors are localized to cytoplasmic structures which are characterized by a vesicular appearance in neurons which may be in cell-to-cell contact with MPs. FKN colocalizes with glutamate in these neurons. Similar findings are observed in brain tissue from an adult patient with HIVE. FKN is able to potently induce the migration of primary human monocytes across an endothelial cell/primary human fetal astrocyte trans-well bilayer, and is neuroprotective to cultured neurons when coadministered with either the HIV-1 neurotoxin platelet activating factor (PAF) or the regulatory HIV-1 gene product Tat. Thus focal inflammation in brain tissue with HIVE may up-regulate neuronal FKN levels, which in turn may be a neuroimmune modulator recruiting peripheral macrophages into the brain, and in a paracrine fashion protecting glutamatergic neurons.

Adult↗
PubMed1967

A peculiar configuration of agranular reticulum (canaliculate lamellar body) in the rat pinealocyte.

A cytoplasmic structure exhibiting a peculiar configuration of agranular reticulum has been found in the rat pinealocyte, and has been designated a canaliculate lamellar body. It consists of a number of fenestrated, flat cisternae which are closely spaced. They bear some distant resemblance to the annulate lamellae previously reported in a variety of cell types. Profiles of stacks of lamellae in a plane of section always display two distinct aspects, the surface and the cross-sectional views of flat cisternae. A surface view shows the hexagonal arrangement of pores or fenestrations. The pores in successive lamellae are aligned precisely, one behind the other, so that clear, cylindrical channels are seen running perpendicular to the lamellae as indicated by transverse sections of the lamellar stacks. Large canaliculate lamellar bodies are composed of many extended series of lamellar stacks which pursue a tortuous course and cross one another. Occasionally the canaliculate lamellar body is located deep in a nuclear invagination, which reminds one of the so-called nuclear pellets (Kernkugeln) reported by light microscopy. The functional significance of the body is unknown.

Animals↗
PubMed2003

A panel of monoclonal antibodies to cytoplasmic GW bodies and the mRNA binding protein GW182.

GW182 is a mRNA binding protein characterized by 60 repeats of glycine (G):tryptophan (W) motifs and is localized in cytoplasmic structures referred to as GW bodies (GWBs). Current evidence suggests that this unique protein plays a role in mRNA processing. To enable a more detailed study of GW182 and GWBs in cells and tissues, including their role in mRNA processing, we developed four monoclonal antibodies (MAbs) that bind the human recombinant GW182 protein. These MAbs can be used for Western blot analysis and indirect immunofluorescence (IIF) on cultured cells and tissues. Of special interest, one of the MAbs, 2D6, can be used to identify GW182 and GWBs in formalin-fixed and paraffin-embedded tissues after using an antigen retrieval method (ARM). All the MAbs described in this study immunoprecipitate the GW182 protein. Epitope mapping using overlapping 15-mer peptides representing the full-length GW182 showed that the major antibody-binding domains of these MAbs are distinct. These MAbs are valuable tools for cell biologists and pathologists to study the location and function of the novel GW182 protein in tissue culture cells, as well as cryopreserved or archived tissues.

Amino Acid Sequence↗
PubMed1993

Nanomelic chondrocytes synthesize, but fail to translocate, a truncated aggrecan precursor.

Cartilage extracellular matrix (ECM) is composed primarily of type II collagen and large, link stabilized aggregates of hyaluronic acid and chondroitin sulfate proteoglycan (aggrecan). Maturation and function of these complex macromolecules are dependent upon sequential processing events which occur during their movements through specific subcellular compartments in the constitutive secretory pathway. Failure to complete these events successfully results in assembly of a defective ECM and may produce skeletal abnormalities. Nanomelia is a lethal genetic mutation of chickens characterized by shortened and malformed limbs. Previous biochemical studies have shown that cultured nanomelic chondrocytes synthesize a truncated aggrecan core protein precursor that disappears with time; however, the protein does not appear to be processed by the Golgi or secreted. The present study investigates the intracellular trafficking of the defective aggrecan precursor using immunofluorescence, immunoelectron microscopy and several inhibitors. Results indicate that nanomelic chondrocytes assemble an ECM that contains type II collagen, but lacks aggrecan. Instead, aggrecan precursor was localized intracellularly, within small cytoplasmic structures corresponding to extensions of the endoplasmic reticulum (ER). At no time were precursor molecules observed in the Golgi. In contrast, normal and nanomelic chondrocytes exhibited no difference in the intracellular or extracellular distribution of type II procollagen. Therefore, retention of the aggrecan precursor appears to be selective. Incubation of chondrocytes at 15 degrees C resulted in the retention and accumulation of product in the ER. After a return to 37 degrees C, translocation of the product to the Golgi was observed for normal, but not for nanomelic, chondrocytes, although the precursors disappeared with time. Ammonium chloride, an inhibitor of lysosomal function, had no effect on protein loss, suggesting that the precursor was removed by a non-lysosomal mechanism, possibly by ER-associated degradation. Based on these studies, we suggest that nanomelic chondrocytes are a useful model for examining cellular trafficking and sorting events and the processes by which abnormal products are targeted for retention or degradation. Further investigations should provide insight into the mechanisms underlying chondrodystrophies and other related diseases.

Aggrecans↗
PubMed1965

Wound healing and collagen formation. V. Quantitative electron microscope radioautographic observations of proline-H3 utilization by fibroblasts.

The uptake, intracellular transport, and secretion of protein by guinea pig wound fibroblasts was studied by electron microscope radioautography using L-proline-3,4-H(3) as a tracer. Experiments were performed to determine the curve of concentration of free amino acid in the blood after intraperitoneal administration of the labeled proline. Radioautographs were quantitatively analyzed and the concentration of isotope, in grains per unit area, was determined for the following cellular and extracellular compartments: ergastoplasm, Golgi complex, peripheral cytoplasmic structures, and collagen. The concentration of label, expressed as number of grains per unit area of each subcellular system, reveals the period during which each cellular compartment is maximally labeled, and presents a clearer picture of the passage of the label through each of these compartments. The data demonstrate appearance of the label at maximum concentration in the ergastoplasm 15 minutes after injection, and this compartment remains maximally labeled for 2 hours. In the Golgi complex, concentration is not maximal until 60 minutes after injection of isotope, and appears to decrease before or at about the same rate as that of the ergastoplasm. The present experiment is consistent with previous light microscope radioautographic studies, and no storage phase was found in the fibroblasts. The findings are not simply consistent with a direct precursor-product relationship between the contents of the ergastoplasm and those of the Golgi complex. Morphologic observations of regions in the fibroblast interpretable as possible sites of communication between the ergastoplasm and the extracellular space, together with the kinetic studies, permit the suggestion of an alternate pathway of passage of at least some of the synthesized protein directly from the ergastoplasmic cisternae to the cell exterior.

Animals↗
PubMed1996

alpha-spectrin is required for germline cell division and differentiation in the Drosophila ovary.

During Drosophila oogenesis, developing germline cysts are spanned by a large cytoplasmic structure called a fusome, containing alpha-spectrin and the adducin-like product of the hu-li tai shao (hts) gene. We found that fusomes contain two additional membrane skeletal proteins: beta-spectrin and ankyrin. hts was shown previously to be required for cyst formation and oocyte differentiation; the role of the fusome itself, however, and the organization and function of its other components, remains unclear. Using the FRT/FLP recombinase system to generate clones of alpha-spectrin-deficient cells in the ovary, we have shown that alpha-spectrin is also required for cyst formation and oocyte differentiation, but that its role in each process is distinct from that of Hts protein. Furthermore, alpha-spectrin is required for these processes in germline cells, but not in the follicle cells that surround each cyst. We have also found that the organization of membrane skeletal proteins is more dependent on alpha-spectrin in the fusome than at the plasma membrane in other cells. Our results suggest that the fusome and its associated membrane skeleton play a central role in regulating the divisions and differentiation of cyst cells.

Animals↗
PubMed1997

Three-dimensional structure of the cytoplasmic face of the G protein receptor rhodopsin.

Rhodopsin is a G protein receptor from a many-membered family of membrane receptors. No high-resolution structure exists for any member of this family due to the insolubility of membrane proteins and the difficulty in crystallizing membrane proteins. Two new approaches to the structure of rhodopsin are described that circumvent these limitations: (1) individual solution structures of the four cytoplasmic domains of rhodopsin are fitted with the transmembrane domain; (2) the solution structure of a complex of the four cytoplasmic domains is determined from nuclear magnetic resonance data. The two structures are similar. To test the validity of these structures, specific site-to-site distances measured on intact membrane-bound rhodopsin are compared to the same distances on the structures reported here. Excellent agreement is obtained. Furthermore, the agreement is obtained with distances measured on the activated form of teh receptor and not with distances on the dark-adapted form of rhodopsin. This approach may prove to have general applicability for the determination of the structure for membrane proteins.

Circular Dichroism↗
PubMed1996

Sequential ultrastructural and biochemical changes induced by microcystin-LR in isolated perfused rat livers.

The cyanobacterial hepatotoxin, microcystin-LR (MCLR), is a potent protein phosphatase inhibitor that disrupts actin microfilament, cytokeratin intermediate filament, and microtubule networks in hepatocytes. To determine ultrastructural and biochemical changes that develop concurrently with microcystin-induced cytoskeletal disorganization, isolated rat livers were perfused with MCLR at 0.1 to 5.0 micrograms/ml for 5 to 40 min. Lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase changed over time, but trends for toxin-treated and control livers did not differ. The earliest toxin-induced ultrastructural changes, observed in livers perfused at 0.1 microgram/ml for 15-20 min or at 0.3 microgram/ml for 5-10 min, were loss of hepatocyte microvilli in the space of Disse, widening of sinusoidal fenestrae, disruption of sinusoidal endothelium, dilation of bile canaliculi with loss of microvilli, and widening of hepatocyte intercellular spaces. Lesions progressed with increasing toxin concentrations and exposure times. In livers perfused with MCLR at 0.5 microgram/ml for 10-20 min, hepatocytes had plasma membrane blebs and concentric whorls of rough endoplasmic reticulum, and there was marked disassociation of hepatocytes resulting in disrupted hepatic cords. At toxin concentrations of 2.0 or 5.0 micrograms/ml for 10-20 min, there was mild dilation of mitochondrial cristae, cytoplasmic vacuolization or invagination of plasma membranes, redistribution of organelles, and sometimes nuclear degenerative change. Some hepatocytes exhibited clusters of plasma membrane blebs radiating from round cytoplasmic structures, which may be composed primarily of condensed microfilaments.

Animals↗
PubMed1998

Signaling through human killer cell activating receptors triggers tyrosine phosphorylation of an associated protein complex.

Our understanding of the biology of human natural killer (NK) cells has significantly advanced in recent years upon identification of a family of NK cell-expressed genes that encode killer cell inhibitory receptors (KIR). Individual KIR can selectively bind various HLA class I allotypes and consequently transduce inhibitory signals that block NK cell lysis of ligand-bearing target cells. A distinct subset of related and linked genes express truncated versions of KIR that are otherwise highly homologous in amino acid sequence. Interestingly, these receptors appear to transmit stimulatory signals into NK cells and have been termed killer cell activating receptors (KAR). In this report, we demonstrate that recognition of HLA-Cw3 by the p50 KAR, NKAT8, can potentiate the cytotoxic response of appropriate NK cell clones. Specific cross-linking of this KAR with a monoclonal antibody resulted in intracellular calcium mobilization, protein tyrosine phosphorylation, and phosphorylation of the MAP kinases, ERK1 and ERK2. In addition, we identified a KAR-associated disulfide-linked dimer of a 13-kDa protein that was absent in the Jurkat T cell line and is predicted to participate in these activation signaling events. Upon treatment of NK cells with pervanadate, the disulfide-linked p13 and additional proteins of 25, 30, 37 and 50-95 kDa were identified as KAR-associated tyrosine phosphoproteins. Importantly, p13 was inducibly tyrosine phosphorylated upon cross-linking of NKAT8, which strongly suggests that the associated p13 provides KAR with appropriate cytoplasmic structure to couple with tyrosine kinase-mediated signaling effectors.

Cell Line↗
PubMed1986

Correlation of female sex steroid hormone receptors with histologic and ultrastructural differentiation in adenocarcinoma of the endometrium.

A series of 43 patients with endometrial adenocarcinoma were evaluated in order to investigate the relationships of the estrogen receptor (ER) and the progesterone receptor (PR) with the histologic and nuclear grades and the ultrastructural differentiation of these tumors. Twenty-six neoplasms were positive (greater than or equal to 10 fmole/mg protein) for both receptors, 1 was positive for the ER only, 9 were ER-PR+, and 7 were ER-PR-. Twenty carcinomas were histologic Grade I, 12 Grade II, and 11 Grade III. Distribution of nuclear grade was 11 Grade I, 18 Grade II, and 14 Grade III. Both histologic and nuclear grades were found to be significantly related to the presence or absence of both the ER and the PR. Several cytoplasmic structures (cilia, primary lysosomes, intracytoplasmic lumens) were highly specific but of low sensitivity for predicting the receptor status of these tumors. To a limited extent, ultrastructural markers were associated with histologic differentiation.

Adenocarcinoma↗