Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein kinase C (PK-C) has been implicated in the action of LHRH because LHRH-induced release of LH is partially mimicked by phorbol esters which activate PK-C, and reduced in magnitude by inhibitors of PK-C. We have used a reverse haemolytic plaque assay for LH to visualize and compare the direct effects on individual rat gonadotrophs of (1) a 2-h exposure to a range of concentrations of LHRH and phorbol 12-myristate 13-acetate (PMA) and (2) a single maximally stimulatory dose (10 nM) of LHRH or PMA, or LHRH in the presence of inhibitors of PK-C (retinal and isoquinolone sulphonamide; H7) over six consecutive 30-min intervals. Quantitative analysis of the size and number of haemolytic plaques indicated that LHRH induced a dose- and time-dependent increase in the amount of LH release by individual gonadotrophs, with no evidence of the priming effect of LHRH. Stimulation by 10nM LHRH induced recruitment of actively secreting gonadotrophs which reached maximum levels by 90 min. There was a delay of 90-120 min before 10 nM PMA caused a significant release of LH, as assessed by both the size and number of plaques. During the first 30 min of exposure, the presence of 10 microM retinal or H7 augmented LHRH-induced secretion of LH, with the absence of any inhibition of the effects of LHRH until 90-120 min, when both the size and number of plaques were reduced compared with those formed in the presence of LHRH alone.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Endocrinol 1989 Jan
PMID:Heterogeneity of responses to LH-releasing hormone and phorbol ester among rat gonadotrophs: a study using a reverse haemolytic plaque assay for LH. 266 9

Smooth muscle cells cultured from the intima of unaffected human aorta accumulate lipids during incubation with the blood serum of patients with coronary heart disease (CHD). Blood sera of most healthy subjects fail to induce the deposition of lipids in cultured cells. Very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins of two subclasses (HDL2 and HDL3) were isolated from the blood of healthy subjects and CHD patients. LDL from the blood of healthy individuals did not raise intracellular lipid levels within 24 hr of cultivation (the maximal concentration used, 1000 micrograms/ml). During the same incubation period, LDL obtained from the blood of CHD patients (200 to 1000 micrograms/ml) caused a 2- to 5-fold rise in cholesteryl esters as well as a 1.5- to 3-fold rise in free cholesterol and triglycerides, whereas intracellular phospholipid levels remained unchanged. There was a direct correlation (r = 0.95) between cholesterol accumulation in the cells incubated with whole sera of CHD patients and cholesterol level in the cells incubated with LDL isolated from these sera. In one of the three cases, the ability to raise the intracellular level of cholesteryl esters was demonstrated by VLDL (500 micrograms/ml) derived from CHD patients' blood. HDL2 and HDL3 did not affect lipid levels in smooth muscle cells cultured from unaffected intima. HDL3 from the blood of CHD patients and healthy subjects (50 to 250 micrograms/ml) reduced cholesteryl ester levels in cells cultured from atherosclerotic plaques 1.5- to 2-fold. HDL2 also decreased the content of cholesteryl esters in plaque cells, though less effectively than HDL3. The data obtained suggest that circulating LDL and, possibly, VLDL in the blood of CHD patients are capable of inducing the accumulation of fat in vascular wall cells.
Exp Mol Pathol 1989 Jun
PMID:Low-density lipoproteins isolated from the blood of patients with coronary heart disease induce the accumulation of lipids in human aortic cells. 272 53

A new protein was found at the site of interaction of cytoskeletal filaments and the plasma membrane in desmosomes of human cardiac muscle intercalated discs. As revealed by the indirect immunofluorescence method, monoclonal antibody XVE2 was able to stain intercalated discs of cardiac muscle and desmosomes of human skin epidermal cells, whereas it did not react with sections from human uterine smooth muscle, vascular tissue and liver. Western immunoblot analysis of extracts of total human heart and uterus demonstrated that a doublet of 65 kDa and 70 kDa polypeptides were the major proteins recognized by the monoclonal antibody XVE2. These 65 kDa and 70 kDa proteins are immunologically distinct from other known intercalated disc proteins such as vinculin, meta-vinculin, filamin, talin, alpha-actinin, desmin and desmoplakins. The distribution of the XVE2 monoclonal antibody antigens raises the possibility that these polypeptides are involved in linking intermediate filaments to the dense plaque of desmosomes of cardiac muscle intercalated discs.
J Mol Cell Cardiol 1989 Feb
PMID:Identification and immunolocalization of a new component of human cardiac muscle intercalated disc. 273 27

9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-adenine (DHC), a specific inhibitor of S-adenosyl-L-homocysteine (AdoHcy) hydrolase, has been used in this study to elucidate the mechanism by which DL-homocysteine (Hcy) potentiates the antiviral effects of AdoHcy hydrolase inhibitors as reported by De Clercq [Biochem. Pharmacol. 36:2567-2575 (1987)]. The potentiating effects of Hcy on the antiviral effects of DHCA were determined using murine L929 cells infected with vaccinia virus. When virus-infected cells were incubated with DHCA alone or in combination with various concentrations of Hcy, the following IC50 values (concentrations of the drug required to reduce by 50% viral plaque formation) were observed: 0.30 microM (0 mM Hcy), 0.15 microM (0.3 mM Hcy), 0.09 microM (1.0 mM Hcy), and 0.04 microM (3.0 mM Hcy). In the drug combination studies, increased cellular toxicity, compared with DHCA alone, was observed only at the highest concentration of Hcy (3.0 mM); thus, at lower concentrations Hcy increased the antiviral effectiveness [ID50 (concentration of the drug required to reduce the increase in cell number by 50%)/IC50] of DHCA. For example the following ID50/IC50 values were observed for DHCA alone or in combination with Hcy: 64 (0 mM Hcy), 113 (0.3 mM Hcy), 151 (1.0 mM Hcy), and 88 (3.0 mM Hcy). In these studies, Hcy was also observed to potentiate the increase in cellular levels of AdoHcy and the ratio of AdoHcy/S-adenosyl-L-methionine (AdoMet) in DHCA-treated cells. In earlier studies, our laboratory has shown that antiviral effects of DHCA are caused by only slight elevations in intracellular levels of AdoHcy [from 50 pmol/mg of protein (controls) to 100-200 pmol/mg of protein (drug-treated)] and slight elevations in the ratios of AdoHcy/AdoMet [from 0.05-0.1 (control) to 0.15-0.20 (drug-treated)]. Thus, in the presence of Hcy, lower concentrations of DHCA are needed to increase the intracellular concentration of AdoHcy and the AdoHcy/AdoMet ratio to levels that suppress replication of vaccinia virus. Murine L929 cells were shown to contain DHCA-sensitive and DHCA-insensitive forms of AdoHcy hydrolase. Based on the results of labeling experiments using [2,8-3H]adenosine and [35S]methionine, the elevated levels of AdoHcy were shown to arise from the reaction of [2,8-3H]adenosine and Hcy, catalyzed by the DHCA-insensitive form of AdoHcy hydrolase.
Mol Pharmacol 1989 Sep
PMID:Elucidation of the mechanism by which homocysteine potentiates the anti-vaccinia virus effects of the S-adenosylhomocysteine hydrolase inhibitor 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-adenine. 277 28

Bacteriophage phi X174 mutants within the 30 base-pair replication origin were constructed using oligodeoxynucleotide-directed mutagenesis. A total of 18 viable base substitution mutants at 13 different positions within the origin region were obtained. The majority of these ori mutants have a plaque morphology and burst size comparable to that of wild-type phi X174. Two phi X174 ori mutants with a reduced growth ability spontaneously acquired additional mutations that enhanced the growth rate. The additional mutation was located at the same site as the original mutation or was located in the N-terminal part of the gene A protein. This latter secondary mutation is responsible for a better binding and/or recognition of the gene A protein to the mutated origin. In a Darwinian experiment wild-type phi X174 outgrows all phi X174 ori mutants, indicating the superiority of the wild-type ori sequence for the reproduction of bacteriophage phi 174. Insertions and deletions were constructed at different positions within the phi X174 replication origin cloned in a plasmid. Small insertions and deletions in the A + T-rich spacer region do not inhibit phi X174 gene A protein cleavage in vitro, but severely impair packaging of single-stranded plasmid DNA in viral coats.
J Mol Biol 1987 Nov 05
PMID:Mutational analysis of the bacteriophage phi X174 replication origin. 282 34

A set of vectors is described which allow the efficient cloning of full-length cDNAs, using a modification of the method of Okayama and Berg [Mol. Cell Biol. 2 (1982) 161-170], and enrichment of specific sequences directly from cDNA libraries by hybridization/selection. The vectors pcDpolyB+ and pcDpolyB- are derived from an expression vector described previously [Okayama and Berg, Mol. Cell Biol. 3 (1983) 280-289] and allow expression of cloned cDNAs in eukaryotic cells from the simian virus 40 early region promoter. The vectors BSB+ and BSB- contain convenient priming sites for sequence analysis and the T3 and T7 RNA polymerase promoters, allowing synthesis of transcripts homologous to either strand of the cDNA. Each of these vectors also contains the intergenic region from the bacteriophage f1 permitting synthesis of single-stranded (ss) copies of the cDNA libraries. Enrichment for cDNAs containing sequences homologous to the hypoxanthine phosphoribosyl transferase gene from an ss copy of a cDNA library by hybridization/selection is demonstrated. Levels of enrichment sufficient for the direct cloning of specific sequences without requiring colony or plaque hybridizations were obtained. Libraries constructed from different cell types can be screened against each other to create sublibraries highly enriched in sequences specific to a single cell type. The availability of cDNA expression libraries enriched for cell-type-specific cDNAs should greatly enhance the efficiency with which cDNAs can be identified on the basis of functional assays.
 ...
PMID:Expression vectors permitting cDNA cloning and enrichment for specific sequences by hybridization/selection. 284 27

Using immunohistochemical and enzyme histochemical methods, we have investigated the presence of mononuclear phagocytic cells around senile plaques in six brains from patients with senile dementia of the Alzheimer type (SDAT). It is generally supposed that reactive microglial cells are involved in amyloid formation "as representatives of the reticuloendothelial system in the brain." We used different monoclonal antibodies directed against cells of the mononuclear phagocyte lineage, antibodies against the macrophage markers alpha 1-antichymotrypsin and lysozyme, and the lectin WGA, in addition to enzyme histochemical staining for nonspecific esterase and acid phosphatase. It was concluded that no macrophages of the mononuclear phagocyte lineage are involved in plaque formation. The role of glial cells in amyloid formation is discussed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Role of microglia in plaque formation in senile dementia of the Alzheimer type. An immunohistochemical study. 287 57

The present study was designed to investigate blood-brain permeability and the possible involvement of plasma proteins and blood-borne cells in amyloid plaque formation in scrapie-affected mice. No abnormal extravasation of intravenously injected horseradish peroxidase (HRP) was found and with immunocytochemical techniques no plasma proteins were detected in neuropil from scrapie-affected mice. In contrast to an earlier report, these findings suggest that the blood-brain barrier is essentially intact in scrapie-affected mice. Using immunohistochemical and enzyme histochemical methods no cells belonging to the monocyte-macrophage lineage were detected in association with amyloid plaques. Thus, by these methods there was no evidence that plasma proteins or blood-borne cells are involved in amyloid plaque formation in scrapie-affected mice. However, astrocytes were consistently found to be associated with amyloid plaques at all stages of their development.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:No evidence for involvement of plasma proteins or blood-borne cells in amyloid plaque formation in scrapie-affected mice. An immunohistoperoxidase study. 289 Feb 38

Male C3H/HeN mice, aged 5 weeks, were inoculated intraperitoneally (i.p.) with different doses (1 x 10(3), 1 x 10(5), 5 x 10(5), 1 x 10(6) pfu) of the herpes simplex virus type-1 (HSV-1) (Miyama + GC strain). The LD50 of this virus was 10(2) pfu (i.p.) per mouse. All the mice in each group died 12 days after inoculation. Adrenal necrosis was found to be dose-dependent, the threshold dose being 5 x 10(5) pfu. In addition, encephalitis and inflammatory cell infiltration in abdominal ganglia appeared in 3-4 days after inoculation. By the plaque method, HSV-1 was detected first in the adrenal glands, then in neurons in the spinal cord and the brain. These findings suggest that in mice inoculated with doses of virus sufficient to infect the adrenal gland, HSV-1 spreads to the central nervous system through peripheral nerves after replication in the adrenal.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Early adrenal infection by herpes simplex virus type-1 (Miyama + GC strain): special reference to inoculation dose and spread from the adrenal to the central nervous system. 289 Dec 15

Hormone secretion from single, rat pancreatic B cells was visualised by a reverse haemolytic plaque assay for C-peptide. Quantitative analysis of the size and number of haemolytic plaques indicated that exposure to 3, 5, 10 and 20 mM glucose resulted in a dose-dependent increase in both the magnitude of C-peptide, and thus, insulin release by individual B cells and the recruitment of activity secreting B cells. Somatostatin and calcitonin gene-related peptide, fragment 28-37 (CGRP28-37) were shown to inhibit glucose-stimulated insulin release as assessed by the size of individual plaques and the number of recruited B cells, and hence to reduce the total area of plaques formed. In the presence of 15 mM glucose, a dose-dependent effect of CGRP28-37 on the secretion of insulin was observed, with the size of plaques formed by individual B cells reduced at concentrations of CGRP28-37 between 10(-5) and 10(-11) M. Thus, both somatostatin and CGRP28-37 can act directly on individual B cells to inhibit their secretory response to increasing levels of glucose. We suggest that these peptides which can be immunolocalised in islet cells may have a role in the regulation of insulin secretion.
Mol Cell Endocrinol 1988 May
PMID:Calcitonin gene-related peptide and somatostatin inhibit insulin release from individual rat B cells. 289 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>