Gene/Protein Disease Symptom Drug Enzyme Compound
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 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the accompanying article, we established that in the rat distal colon expression of H, B, and Le(b) blood group antigens by goblet cells is phenotypically fetal in nature. Because of the cocarcinogenic property of ethanol, the present study examined the effects of dietary ethanol consumption, fasting, and withdrawal on the expression of these antigens in the adult rat colon. To that effect, male adult Sprague-Dawley rats were pair-fed ethanol-containing or control Lieber-DeCarli liquid diets for 3 weeks. The effects of ethanol withdrawal were studied in rats fed the ethanol-containing diet for 3 weeks followed by the control diet for 1, 3, and 6 days. In rats fed the control diet, no antigen expression in the distal colon was observed, as expected. Ethanol feeding for 3 weeks resulted in a striking reappearance of H, B, and Le(b) antigens in goblet cells of the distal colon. In colonic crypts, a lower-to-upper crypt gradient of increasing numbers of positive goblet cells was present, suggesting that the induction of antigen expression paralleled the differentiation of goblet cells. After an overnight fast, the number of positive cells was significantly decreased. Withdrawal of ethanol for 1 day further decreased the number of positive goblet cells. The decrease was reflected by a downward shift in the number of positive cells per crypt column, which was more striking in the lower and mid-crypt segments than in the upper segment, suggesting that antigen expression was more labile in immature differentiating goblet cells than in mature ones. No antigen staining of goblet cells was detected after 3 and 6 days of ethanol withdrawal. Hence, expression of H, B, and Le(b) antigens by goblet cells of the distal colon can be modulated by ethanol consumption. Expression in the distal colon of A and Le(a) antigens, which did not exhibit a fetal phenotype, was not affected by ethanol feeding. In conclusion, because of the oncofetal phenotype of H, B, and Le(b) antigens, their reappearance in the distal colon may serve as a cytochemical marker for early recognition of epithelial changes of the colon in ethanol-related cocarcinogenesis before more overt manifestations of neoplasia.
Anat Rec 2000 08 01
PMID:Blood group antigen expression in the rat colon II. Modulation by dietary ethanol consumption. 1090 32

Two unrelated coatimundi (Nasua nasua) had bilaterally enlarged adrenal glands at necropsy, and sections of the glands from both animals had histopathological features consistent with neoplasia. They were differentiated from an adrenal cortical tumour on the basis of their light microscopical morphology, immunoperoxidase staining and electron microscopic studies and a final diagnosis of phaeochromocytoma was made. To the authors' knowledge, these are the first reported cases of phaeochromocytoma in coatimundi.
Vet Rec 2001 Jun 30
PMID:Phaeochromocytoma in two coatimundi (Nasua nasua). 1146 8

Eleven thousand Americans each year are affected by paralysis, a devastating injury that possesses associated annual costs of $7 billion (American Paralysis Association, 1997). Currently, there is no effective treatment for damage to the central nervous system (CNS), and acute spinal cord injury has been extraordinarily resistant to treatment. Compared to spinal cord injury, damage to peripheral nerves is considerably more common. In 1995, there were in excess of 50,000 peripheral nerve repair procedures performed. (National Center for Health Statistics based on Classification of Diseases, 9th Revision, Clinical Modification for the following categories: ICD-9 CM Code: 04.3, 04.5, 04.6, 04.7). These data, however, probably underestimate the number of nerve injuries appreciated, as not all surgical or traumatic lesions can be repaired. Further, intraabodominal procedures may add to the number of neurologic injuries by damage to the autonomic system through tumor resection. For example, studies assessing the outcome of impotency following radical prostatectomy demonstrated 212 of 503 previously potent men (42%) suffered impotency when partial or complete resection of one or both cavernosal nerve(s). This impotency rate decreased to 24% when the nerves were left intact (Quinlan et al., J. Urol. 1991;145:380-383; J. Urol. 1991;145:998-1002).
Anat Rec 2001 08 01
PMID:Peripheral nerve injury: a review and approach to tissue engineered constructs. 1150 Aug 17

Six new phenol (anthraquinone or stilbene) glycosides with an acyl group at 6-position of the glucopyranose moiety were isolated from rhubarb (the roots of Rheum palmatum) cultivated in Japan, together with 22 known compounds. Most of these compounds were evaluated for cytotoxic activity against tumor and normal cells and for induction of DNA damage by spore rec-assay. Among them, emodin and aloe-emodin showed higher cytotoxic activities against human oral squamous cell carcinoma (HSC-2) and salivary gland tumor (HSG) cell lines than against normal human gingival fibroblasts (HGF). Chrysophanol 8-O-beta-(6'-acetyl)glucopyranoside, 4-(4'-hydroxyphenyl)-2-butanone 4'-O-beta-D-(2"-O-galloyl-6"-O-cinnamoyl) glucopyranoside, and 6"-O-(4'''-hydroxybenzoyl) resveratroloside exhibited relatively higher cytotoxic activities against all these cells. The other glycosides of anthraquinone or stilbene showed weaker cytotoxic activity against these tumor cell lines, but may be considered as cancer chemopreventive agents. Spore rec-assay with a recombination deficient mutant of Bacillus subtilis M45 demonstrated the DNA damage-inducing activity of emodin and aloe-emodin 15-O-beta-D-glucopyranoside among, rhubarb phenols.
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PMID:Cytotoxic and DNA damage-inducing activities of low molecular weight phenols from rhubarb. 1172 65

Natural killer (NK) cell function is largely modulated by growth factors and cytokines. In particular, interleukin (IL)-2, IL-12, and IL-15 have major effects on the proliferative and cytotoxic activities of NK cells against tumor and virus-infected cells. It is thought that the members of the protein kinase C (PKC) family of serine/threonine kinases play an important role in mediating the pleiotropic effects of cytokines on their target cells. We have investigated the downstream effects generated in purified human NK cells by IL-2, IL-12, and IL-15 on PKCalpha and PKCepsilon--a canonical and a novel isoform of PKC, respectively. By means of Western blotting, PKC activity assays, and immunofluorescence performed on highly purified preparations of primary human NK cells, we demonstrate that: 1) the three cytokines have similar effects on PKCalpha and PKCepsilon activities; 2) whereas PKCepsilon activity is induced by cytokine stimulation, PKCalpha activity is inhibited; and 3) both the induction of PKCepsilon and the inhibition of PKCalpha functional activity are relatively early events in NK cells, while longer cytokine stimulations do not generate significant variations in enzyme activity, suggesting that the activation of both the canonical and novel isoforms of PKC are events required in the early phases of cytokine-induced NK cell stimulation.
Anat Rec 2002 02 01
PMID:NK-active cytokines IL-2, IL-12, and IL-15 selectively modulate specific protein kinase C (PKC) isoforms in primary human NK cells. 1178 41

In this study we used magnetic resonance imaging (MRI) to investigate neuroanatomical structure in the brain of a white whale (Delphinapterus leucas) that died from a large tumor within the brainstem. This specimen was also compared with a normal white whale brain using MRI. MRI scans of the white whale specimen show how the tumor deformed surrounding brain structure. Histopathological analysis indicated a poorly differentiated carcinoma of uncertain origin. These analyses demonstrate the usefulness of supplementing histological analyses of pathology with studies of gross morphology facilitated by MRI.
Anat Rec 2002 Dec 01
PMID:Description of a poorly differentiated carcinoma within the brainstem of a white whale (Delphinapterus leucas) from magnetic resonance images and histological analysis. 1242 Feb 92

Because the Falck-Hillarp formaldehyde fluorescence method, which was superbly applied to identify catecholaminergic and serotonergic neurons, is not applicable to histamine, the first author (T.W.) developed an antibody to L-histidine decarboxylase (HDC) for identification of the histaminergic neuron system in the brain. The anti-HDC antibody was of great use for mapping the location and distribution of this histaminergic neuron system. (S)-alpha-fluoromethylhistidine, a specific and potent irreversible inhibitor of HDC, was also very useful in studies on functions of the neuron system. The activity of HDC is increased by various agents, treatments, and physiological conditions. We found new compounds that increased HDC activity (i.e., tetradecanoylphobol acetate (TPA), other tumor promoters, and staphylococcal enterotoxin A); and using mast cell-deficient mutant (W/W(v)) mice, we obtained evidence that this increase occurred in macrophages. To further characterize the mechanism of increases in HDC activity, the second author (H.O.) cloned human HDC cDNA and a human HDC gene. In studies on the regulation mechanism of the HDC gene, which is expressed only in limited types of cells such as mast cells, enterochromaffin-like cells in the stomach, cells in the tuberomammillary nucleus of the brain, and macrophages, CpG islands in the promoter region of the HDC gene were found to be demethylated in cells expressing the gene, whereas they are methylated in other cells that do not express the HDC gene. In collaboration with many other researchers, we developed HDC knockout mice. The resulting research is producing a lot of interesting findings in our laboratory as well as in others. In summary, HDC has been and will be useful in studies on functions of histamine.
Chem Rec 2002
PMID:L-histidine decarboxylase as a probe in studies on histamine. 1246 48

Rad51 protein plays a pivotal role in homologous recombination (HR), which is involved in double-strand break repair and in genome maintenance. Despite interactions with tumor suppressor proteins, the role of mammalian Rad51 and more generally of HR in tumor prevention is not clearly established. Indeed, both high and low frequencies of HR as well as high and low levels of RAD51 expression have been reported in tumors and in precancerous conditions. To address the question of the impact of HR on tumorigenesis, we used Chinese hamster ovary (CHO) p53-defective cell lines overexpressing the mouse MmRAD51, which stimulates HR (we name these lines: Hyper-rec lines). In parallel, we used CHO cell lines expressing a RAD51 dominant-negative form that specifically inhibits gene conversion without affecting cell viability (Hypo-rec lines). These different lines were injected into nude mice to measure their tumorigenicity. Hypo-rec lines generated a higher frequency of tumors, which also exhibited faster growth, compared to control and Hyper-rec lines. Consistent with tumorigenicity, Hypo-rec cells exhibit spontaneous centrosome duplication defects and aneuploidy. These results are the first direct evidence of involvement of RAD51 in tumor repression.
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PMID:Overexpression of mammalian Rad51 does not stimulate tumorigenesis while a dominant-negative Rad51 affects centrosome fragmentation, ploidy and stimulates tumorigenesis, in p53-defective CHO cells. 1457 20

Loss of MHC class II expression in B-cell lymphoma has been associated with a higher tumorigenicity resulting from lower titers of tumor-infiltrating lymphocytes. This report aims towards the identification of the molecular mechanism leading to defective MHC class II expression in a B-cell lymphoma cell line, Rec-1. We evidenced a coordinated alteration of HLA-D gene transcription, reminiscent of B lymphoblastoid cell lines from patients with MHC class II deficiency. Genetic complementation performed between these cell lines and the lymphoma cells indicated that Rec-1 is altered in the MHC2TA gene. MHC2TA encodes the class II transactivator (CIITA), the master regulator of HLA-D gene expression. However, the coding sequence of the Rec-1 CIITA transcript did not reveal any mutation that could hamper the activity of the encoded protein. In agreement with the genetic complementation analysis, we evidenced a highly residual CIITA protein expression in the Rec-1 cell line resulting from a transcriptional defect affecting MHC2TA expression. Anti-HLA-DR monoclonal antibody treatment has proved efficient in the destruction of B lymphoma cells. Our data indicate that the appearance of variants losing CIITA, and thereby HLA-DR, expression will require a thorough monitoring during such immunotherapy protocols.
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PMID:Defective class II transactivator expression in a B lymphoma cell line. 1497 5

In contrast to normal cells, the glycoprotein profile on epithelial tumor cells is distinctly altered. Due to an incomplete formation of the glycan side-chains resulting from a premature sialylation, additional peptide epitopes become accessible to the immune system in mucin-type glycoproteins on tumor cells. These tumor-associated structure alterations constitute the basis for a selective immunological attack on cancer cells. For the construction of immunostimulating antigens, glycopeptide partial structures from the mucins MUC1 and MUC4 carrying the tumor-associated sialyl-T(N), alpha2,6-sialyl-T and alpha2,3-sialyl-T antigens have been synthesized. Employing different linkers such as the allylic HYCRON or the fluoride-sensitive PTMSEL anchor, the antigenic glycopeptide structures were constructed on the solid phase utilizing pre-assembled glycosyl amino acid building blocks prepared in solution by convergent chemical or chemoenzymatic strategies. The proliferation of cytotoxic T cells has been induced applying a construct composed of a sialyl-T(N) MUC1-glycopeptide conjugated with a tetanus toxin T cell peptide epitope.
Chem Rec 2004
PMID:Synthesis of tumor-associated glycopeptide antigens for the development of tumor-selective vaccines. 1499 20


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