Regulation of cell growth and differentiation by the colony-stimulating factor 1 receptor.
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Animals↗
Biomedical subjects
J Kato
Publications and source records attributed to J Kato.
[Effects of gonadotropin and estrogen on endogenous growth factor synthesis in the porcine theca].
In order to investigate the effects of FSH, LH and estradiol (E2) on the synthesis of endogenous growth factor from the thecal tissue, porcine thecal tissues obtained from follicles (greater than 3mm) were cultured for 24 hours in serum-free media in the presence of various concentrations of FSH, LH and E2. After the incubation, thecal tissues and thecal conditioned media (CM) were collected. The growth-promoting activity of thecal CM and thecal cytosol of each conditioned group was assayed by measuring 3H-DNA synthesis in mouse BALB/c 3T3 cells. E2 increased the growth-promoting activity of thecal CM significantly in comparison with controls, whereas neither FSH nor LH showed any significant effects. However, the growth promoting activity in the cytosols was almost the same in all conditioned groups. These results indicate that E2 stimulates the synthesis and secretion of thecal growth factor without changing the original properties.
Animals↗
A dominant suppressive mutation in a cellular gene restores the nontransformed phenotype to v-fms-transformed mink cells.
A nontransformed revertant subclone (GVR17) was isolated from mutagen-treated populations of mink epithelial cells which had been transformed by the Susan McDonough strain of feline sarcoma virus (SM-FeSV). The revertant cells, although contact-inhibited for growth and unable to form colonies in semisolid medium, contained two copies of integrated SM-FeSV proviral DNA, expressed high levels of the v-fms oncogene product and its associated tyrosine kinase activity, and yielded rescuable viruses able to transform parental mink epithelial and mouse NIH3T3 cells. The transformed phenotype was suppressed in cell hybrids generated by fusing revertant and v-fms-transformed mink cells, indicating that GVR17 cells harbored a dominant cellular mutation that inhibited transformation by the v-fms oncogene. The revertant cells were refractory to retransformation by retroviruses containing v-fms or v-abl oncogenes, but could be transformed by v-ras-, v-raf-, and v-fes-containing retroviruses. Thus, the suppressing activity in GVR17 cells discriminates between transforming signals mediated by different tyrosine kinases and fails to block the transforming activity of two oncoproteins exhibiting either GTP-binding or serine/threonine kinase activity.
Animals↗
Increased plasma brain natriuretic peptide levels in DOCA-salt hypertensive rats: relation to blood pressure and cardiac concentration.
Four experimental groups of rats treated with (1) DOCA-salt, (2) DOCA or (3) salt, and (4) controls were used to study the participation of brain natriuretic peptide (BNP) in the development of hypertension. Plasma and cardiac tissue concentrations of BNP as well as atrial natriuretic peptide (ANP) were measured in each group by using radioimmunoassays specific to rat BNP or ANP. Plasma BNP levels in DOCA-salt hypertensive group were higher than those in control (p less than 0.01), salt (p less than 0.01) and DOCA (p less than 0.01) groups. A positive correlation was observed between plasma BNP levels and blood pressure (r = 0.70, p less than 0.001) and between plasma ANP levels and blood pressure (r = 0.62, p less than 0.001). Plasma BNP/ANP ratio increased parallel with elevation of blood pressure. Plasma BNP levels correlated negatively with atrial BNP concentration (r = -0.33, p less than 0.05), but positively with ventricular BNP (r = 0.76, p less than 0.001). Compared with controls, tissue BNP-45/gamma-BNP ratio in the DOCA-salt rats was lower in atrium, but higher in ventricle. Thus, in DOCA-salt hypertension atrial BNP decreased with exhaustion of stored BNP-45, while ventricular BNP increased as BNP-45 accumulated. These results suggest that BNP is a novel cardiac hormone, synthesized, processed and secreted in response to changes in blood pressure. BNP may play different roles in controlling blood pressure than those assumed by ANP.
Animals↗
New topoisomerase essential for chromosome segregation in E. coli.
The nucleotide sequence of the parC gene essential for chromosome partition in E. coli was determined. The deduced amino acid sequence was homologous to that of the A subunit of gyrase. We found another new gene coding for about 70 kd protein. The gene was sequenced, and the deduced amino acid sequence revealed that the gene product was homologous to the gyrase B subunit. Mutants of this gene were isolated and showed the typical Par phenotype at nonpermissive temperature; thus the gene was named parE. Enhanced relaxation activity of supercoiled plasmid molecules was detected in the combined crude cell lysates prepared from the ParC and ParE overproducers. A topA mutation defective in topoisomerase I could be compensated by increasing both the parC and the parE gene dosage. It is suggested that the parC and parE genes code for the subunits of a new topoisomerase, named topo IV.
Amino Acid Sequence↗
Presence of sex difference of cytochrome P-450 in the rat preoptic area and hypothalamus with reference to coexistence with oxytocin.
Localization of female type cytochrome P-450 (F1) in the preoptic area and hypothalamus of the rat was examined immunocytochemically using antiserum against purified hepatic P-450 (F1). This antiserum recognizes both P-450 (F1) and P-450 (M3). Western immunoblotting using the antiserum demonstrated that female rat brain contains P-450 (F1) but not P-450 (M3), since microsomes from the brain and liver displayed only one immunoreactive band at 50 kD, coinciding with that of P-450 (F1) purified from female rat liver. On the other hand, the male brain has P-450 (M3) but not P-450 (F1), as liver- and brain-derived microsomes produced single band at 49 kD, which represents a mol. wt. identical to that of P-450 (M3) extracted from male rat liver. These results indicate that P-450 (F1)-like immunoreactivity (LI) occurs in the female rat brain, while P-450 (M3)-LI takes place in the male rat brain. Immunocytochemical analysis further demonstrated the detailed cellular localization of these two P-450-LIs in the preoptic area and hypothalamus of female and male rats. Localization of P-450 (F1)-LI in the female rat hypothalamus resembled that of P-450 (M3)-LI in the male rat hypothalamus. Magnocellular neurosecretory neurons in the paraventricular nucleus and supraoptic nucleus were labeled and were found to contain oxytocin but lack vasopressin when serial sections of these areas were analyzed. In addition, groups of immunoreactive cells were seen in the median preoptic nucleus, medial and lateral preoptic area, caudal portion of the bed nucleus of the stria terminalis, lateral hypothalamus at the level of the paraventricular nucleus, periventricular zone from the preoptic area to the paraventricular nucleus, and parvocellular portion of the paraventricular nucleus.
Animals↗
Human colony-stimulating factor 1 (CSF-1) receptor confers CSF-1 responsiveness to interleukin-3-dependent 32DC13 mouse myeloid cells and abrogates differentiation in response to granulocyte CSF.
Interleukin-3 (IL-3)-dependent mouse myeloid 32DC13 cells differentiate to neutrophils in response to granulocyte colony-stimulating factor (G-CSF). Introduction of the human c-fms gene, which encodes the receptor for CSF-1, into 32DC13 cells gave rise to variants that were able to proliferate in medium containing either murine IL-3 or human recombinant CSF-1, but were unable to differentiate to granulocytes in response to G-CSF. Unlike parental 32CD13 cells, CSF-1-responsive derivatives expressed nonspecific esterase when grown in CSF-1, but did not exhibit many other morphologic, immunologic, or functional properties of mononuclear phagocyte differentiation, or express murine CSF-1 receptors. Accelerated turnover of the human CSF-1 receptor was observed in response to CSF-1 and phorbol esters, but not after stimulation with IL-3 or bacterial lipopolysaccharide. Although both CSF-1 and IL-3 induced tyrosine phosphorylation of heterologous substrates in the dually responsive cells, differences in the patterns of substrate phosphorylation were observed in response to the two hematopoietins. We conclude that expression of the human CSF-1 receptor in 32DC13 cells not only induces CSF-1 responsiveness, but alters its phenotype in a way that prohibits granulocyte differentiation.
Animals↗
Simultaneous determination of pantothenic acid and hopantenic acid in biological samples and natural products by gas chromatography-mass fragmentography.
A method for the simultaneous determination of pantothenic acid and hopantenic acid in plasma samples was developed using gas chromatography-mass spectrometry with multiple ion detection. Plasma samples were directly purified without deproteinization on an ion-exchange resin, and the eluate was extracted with ethyl acetate under acidic conditions. The organic layer was evaporated to dryness under a stream of nitrogen, and the residue was dissolved in an internal standard solution. Pantothenic and hopantenic acids were converted into their trimethylsilyl derivatives by treating with bis(trimethylsilyl)trifluoroacetamide. Aliquots of this solution were injected into the gas chromatograph-mass spectrometer, which was equipped with a wide-bore fused-silica column (DB-17) and analysed by the multiple ion detection method. The detection limits for pantothenic acid and hopantenic acid in plasma were 1 ng/ml each at a signal-to-noise ratio of 5. This method was applied to a study of the assay of pantothenic acid and hopantenic acid in biological samples and natural products.
Animals↗
Leucine-enkephalin-, neurokinin A- and cholecystokinin-like immunoreactivities in the guinea pig tongue.
The occurrence of these neuropeptides was examined by immunofluorescence. Leu-Enk-like immunoreactivity was seen in nerve fibres associated with the epithelium, blood vessels and lingual salivary glands as well as in ganglionic cells within the tongue. Neuropeptide A-like immunoreactivity was found in nerve fibres associated with the epithelium, taste buds, blood vessels and lingual salivary glands. Cholecystokinin-like immunoreactivity was found in some nerve fibres around blood vessels as well as in ganglionic cells. The coexistence of these neuropeptides and substance P was also demonstrated in some nerve fibres and ganglionic cells within the tongue. Like substance P, these neuropeptides could be involved in blood flow regulation, salivation and as trophic factors for taste buds.
Animals↗
The distribution of vasoactive intestinal polypeptides and calcitonin gene-related peptide in the periodontal ligament of mouse molar teeth.
The distribution of VIP- and CGRP-containing nerve fibres was examined by indirect immunofluorescence. There were many such fibres in the lower third of the ligament, some around the blood vessel close to the socket wall. In the middle third of the ligament, some CGRP-containing fibers entered from the lateral wall of the socket; this type of fibre was more numerous in the lower third than in middle third. There were some VIP-containing fibres but no CGRP-containing fibres in the ligament surrounding the furcation of the molar roots.
Alveolar Process↗
Chromatographic characterization of immunoreactive endothelin in rat lung.
Using a specific and sensitive radioimmunoassay for endothelin, combined with gel filtration and reverse phase high performance liquid chromatography, the molecular form of immunoreactive endothelin in the rat lung was investigated. On reverse phase high performance chromatography, the major immunoreactive endothelin in the rat lung emerged at a position identical to that of authentic endothelin-1. After oxidation of the immunoreactive endothelin by H2O2, the immunoreactivity migrated to a position identical to that of Met-sulfoxide endothelin-1. These data indicate that the major immunoreactive endothelin in the rat lung is not endothelin-3 (putative rat/human endothelin), but is identical or very similar to endothelin-1 (porcine/human endothelin).
Amino Acid Sequence↗
AlgR3, a protein resembling eukaryotic histone H1, regulates alginate synthesis in Pseudomonas aeruginosa.
A regulatory mutation (alg52) in a Pseudomonas aeruginosa alginate-negative mutant (strain 8882) is complemented efficiently by the gene algR2 and somewhat inefficiently by a second gene termed algR3. algR3 and algR2 are located on a 4.4-kilobase-pair HindIII-BamHI fragment, which has been completely sequenced. algR2 has previously been characterized. Introduction of kanamycin-resistance cassettes and deletion-subcloning experiments involving various open reading frames in the HindIII-BamHI fragment have localized the algR3 gene, which encodes a 340-amino acid polypeptide. This highly basic regulatory protein contains 17% lysine and 36% alanine. The predicted amino acid sequence shows no significant similarity with any bacterial proteins and yet is highly similar to the sea urchin Lytechinus pictus histone H1 subtype of protein. Promoter localization by reverse transcriptase mapping of the algR3 gene shows the presence of Escherichia coli sigma 70 recognition sequences, and coupled transcription/translation experiments in E. coli demonstrate the presence of a 39-kDa polypeptide encoded by the cloned algR3 gene.
Alginates↗
Kinetics of internalization and cytotoxicity of transferrin-neocarzinostatin conjugate in human leukemia cell line, K562.
Human serum transferrin was conjugated with an anticancer-active polypeptide, neocarzinostatin, by using N-succinimidyl 1-3-(2-pyridyldithio)propionate. The conjugate consisted of 1.8 mol of neocarzinostatin per 1 mol of transferrin on average and retained cytotoxic activity against human tumor cells. This conjugate was capable of binding to the transferrin receptor of human myelogenous leukemia K562 cells and was internalized by endocytosis. The LD50 values of the conjugate and neocarzinostatin alone in the presence of excess native bovine transferrin were 0.20 microgram/ml and 1.80 micrograms/ml, respectively, suggesting that the effect of the conjugate was greater than that of neocarzinostatin alone. A pulse-chase experiment using 125I-labeled conjugate revealed that 25% of the internalized conjugate was degraded in lysosomes and the rest was recycled back to the cell surface without degradation. About 75% of this conjugate recycled back to the cell surface in 18.3 min (3.4 min for receptor binding and 14.9 min for recycling to the cell surface through the acidosomes), while the rest was delivered from the cell surface to the lysosome in 19.6 min. This phenomenon was confirmed by chasing the radioactivity in subcellular fractions separated by Percoll density gradient centrifugation. Therefore, it was concluded that this conjugate is internalized specifically by transferrin receptors and is at least partly transferred to and accumulated in lysosomal compartments, resulting in the inhibition of cellular DNA synthesis.
Antibiotics, Antineoplastic↗
Experimental luxation injuries in immature rat teeth.
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Alveolar Process↗
Cloning and nucleotide sequence of a heat-stable enterotoxin gene from Vibrio cholerae non-O1 isolated from a patient with traveler's diarrhea.
We determined the nucleotide sequence of the heat-stable enterotoxin (STa) gene of the Vibrio cholerae non-O1 strain NRT36 isolated from a patient with traveler's diarrhea. The gene is chromosomally encoded and the presumed product is 78 amino acids in length, with a molecular weight of 8,814, though the genes of Escherichia coli STa(s) (STh and STp) are encoded in plasmid DNA and both products are 72 amino acids in length. The first 18 amino acids at the NH2 terminus were hydrophobic, suggesting that this region of the polypeptide acts as a signal sequence for the toxin. The last 17 amino acids at the COOH terminus were identical to those deduced from the toxin (NAG-ST) produced by V. cholerae non-O1 strain A-5 isolated from a frozen shrimp. The deduced amino acid sequence of the NAG-ST precursor had 50 and 46% homology to those of E. coli STh and STp, respectively. The hydropathy plot analysis of each predicted protein revealed similar profiles between them, suggesting that the NAG-ST precursor has structural similarity to those of E. coli STa(s).
Amino Acid Sequence↗
Genetic analysis of an invasion region by use of a Tn3-lac transposon and identification of a second positive regulator gene, invE, for cell invasion of Shigella sonnei: significant homology of invE with ParB of plasmid P1.
We have previously cloned two distinct regions of the Shigella sonnei form I plasmid pSS120, a 37-kilobase-pair DNA region and a virF region, which were found to be essential for cell invasion in Escherichia coli K-12 (J. Kato, K. Ito, A. Nakamura, and H. Watanabe, Infect. Immun. 57:1391-1398, 1989). The 37-kilobase-pair DNA region was randomly inserted by use of transposon Tn3-lac. At least eight genes were found to be located within the region, as determined by analysis of Tn3-lac-generated lac fusions. Expression of six genes, ipaB, ipaC, invE, invG, invJ, and invK, was apparently regulated by the positive regulator virF. IpaB and IpaC proteins could not found in invE mutants even if the virF gene was present. This observation suggested that the invE region encoded a positive regulator different from the virF gene. The functional relationship between the invE and virF genes was then examined. Translational fusions ipaB::Tn3-lac and invJ::Tn3-lac were used as indicators for gene expression, and the following results were obtained. Full expression of the ipaB and invJ genes required the presence of both the invE and virF regions. virF positively regulated the expression of invE at the transcriptional level. An increase in the copy number of invE enhanced the expression of ipaB and invJ in the absence of virF. These findings strongly indicate that the invE gene product, whose expression is regulated by virF, acts positively on the invasion-associated genes. InvE is a 35,407-dalton protein and has significant homologies with ParB of plasmid P1 and SopB of plasmid F, which are DNA-binding proteins involved in plasmid partitioning.
Amino Acid Sequence↗
Impaired glucose tolerance in patients with polycystic ovary syndrome (PCOS).
Fasting insulin concentration and the insulin response to an oral glucose tolerance test were measured in 15 women with polycystic ovary syndrome (PCOS) and 6 weight-matched normal women. The fasting insulin concentrations were not increased in PCOS in comparison to normal women. Insulin response to an oral glucose test was significantly decreased (p less than 0.05) in PCOS at 30 min, although 63% of these women had mild impairment of glucose tolerance. The glucose response did not differ between the obese PCOS patients and those with nonobesity. No correlations were demonstrated between the fasting serum insulin concentrations and insulin response at 30 min, and both androgens and the luteinizing hormone. These findings suggest that (1) hyperinsulinemia is not a feature of PCOS in Japan; (2) only obese PCOS patients have a tendency of abnormalities in insulin secretion; (3) it is evident that PCOS represents an inadequately characterized disorder of insulin action and a novel paradigm in which to investigate the relationship between reproductive functions and carbohydrate metabolism.
Adult↗
Pharmacological studies on (4S)-1-methyl-3-[(2S)-2-[N-((1S)-1-ethoxycarbonyl-3-phenylpropyl)amino] propionyl]-2-oxo-imidazolidine-4-carboxylic acid hydrochloride (TA-6366), a new ACE inhibitor: I. ACE inhibitory and anti-hypertensive activities.
TA-6366 and its active metabolite 6366A inhibited swine renal angiotensin converting enzyme (ACE) activity with IC50s of 9900 and 2.6 nM, respectively. TA-6366 (0.05-0.5 mg/kg, p.o.) inhibited the angiotensin I (AT-I)-induced pressor response in rats. 6366A augmented bradykinin (BK)-induced contraction of guinea pig ileum more potently than captopril. However, when the augmentation on BK-induced hypotension in rats was used as an indicator, TA-6366 was less active than captopril. TA-6366 increased plasma renin activity and plasma AT-I concentration. Oral administration of TA-6366 lowered the blood pressure in two-kidney one-clip renal hypertensive rats at 0.5 to 2 mg/kg and in spontaneously hypertensive rats (SHRs) at 2 to 10 mg/kg. The antihypertensive effect of TA-6366 was approximately 5 times more potent than that of captopril and almost as potent as that of enalapril. In SHRs, the antihypertensive action of TA-6366 was intensified in potency when administered repeatedly. The duration of action was longer than those of captopril and enalapril. However, TA-6366 had no substantial effect on the blood pressure in DOCA/saline hypertensive rats. These results indicate that TA-6366 is a potent and long lasting antihypertensive agent and that its antihypertensive action is attributable to the inhibition of ACE.
Angiotensin-Converting Enzyme Inhibitors↗