The pathway of gustatory fibers of the human ascends ipsilaterally in the pons.
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Adult↗
Biomedical subjects
A Takagi
Publications and source records attributed to A Takagi.
Hepatic disposition characteristics of recombinant human interleukin-11 (rhIL-11) in the perfused rat liver.
The hepatic disposition characteristics of recombinant human interleukin-11 (rhIL-11) were investigated in perfused rat liver to clarify the mechanism of hepatic clearance which is a major contributor to the rapid clearance of rhIL-11 in vivo. We analyzed the disposition characteristics of [(111)In]-labeled rhIL-11 using a single-pass constant infusion mode at different concentrations of rhIL-11. The venous outflow rapidly reached a steady-state condition at every concentration. Liver extraction ratio at steady-state (Ess) was decreased with increase in the concentration, suggesting that there is a saturable interaction between the liver cells and rhIL-11 molecule. Cellular localization experiments demonstrated that rhIL-11 was taken up by both liver parenchymal and nonparenchymal cells depending on their surface area, suggesting that this uptake was mediated by electrostatic interaction due to cationic charges in the cytokine.
Animals↗
Basic studies on N''-ursodeoxycholyldiethylenetriamine-N,N,N'-triacetic acid for the dissolution of calcified gallstones.
A novel calcium-chelating agent, N"-ursodeoxycholyldiethylenetriamine-N,N,N'-triacetic acid (UDCA-DTTA), was synthesized to study its ability to dissolve calcified gallstones. The chelating activity of the compound was demonstrated by dissolving calcium carbonate in vitro at a high dissolution rate. In the presence of the agent, sliced human gallstone with a composition of more than 50% calcium bilirubinate was thoroughly dissolved, indicating that calcium bilirubinate was dissolved from the gallstone. The ability to dissolve calcium was comparable to that of EDTA. However, the laminar structure of the sliced gallstone did not disappear in the presence of EDTA, whereas the structure disappeared in the presence of UDCA-DTTA. All these results indicate that UDCA-DTTA is an interesting compound as a parent substance for developing a prodrug for an oral or intravenous agent to dissolve calcium-containing gallstones.
Administration, Oral↗
Fas and Fas ligand system may mediate antiproliferative activity of gonadotropin-releasing hormone receptor in endometrial cancer cells.
Gonadotropin-releasing hormone (GnRH) receptor-bearing tumors undergo apoptosis in vivo and in vitro with GnRH analogs. We recently showed that GnRH stimulation induces intratumoral expression of the apoptosis-inducing Fas ligand in human reproductive tract tumors. To provide a potential association of Fas/Fas ligand system with the antiproliferative signaling process of GnRH receptor, we evaluated a correlation between the Fas ligand expression and the number of viable cells in two types of GnRH receptor-bearing endometrial carcinomas that differ in Fas content. Surgically removed uterine endometrial carcinomas had been screened for the presence of GnRH receptor and Fas before analyses. Fas ligand protein was characterized by immunoblotting of membrane proteins with the specific antibody. After a lag time of 2 days, incubation with a GnRH analog leuprolide (10 microM) induced significant growth inhibition of the Fas- and GnRH receptor-bearing cells (p<0.01). Time course analysis showed that Fas ligand production, which was already observed at day 2 (p<0.01), precedes the onset of reduction in viable cell number. The stimulatory effect of GnRH on Fas ligand expression and reduction of viable cells revealed dose-dependency. The analog at concentration of 10 microM induced up to 90% reduction in cell number. In contrast, the growth of Fas-negative cells was not affected by the analog, although Fas ligand appeared in response to the GnRH analog (p<0.01). These data demonstrate that the co-presence of Fas could be essential for GnRH to promote antiproliferative action in endometrial cancer cells carrying GnRH receptor. The hormone may act through intratumor Fas and Fas ligand system to induced growth inhibition in GnRH-sensitive tumors.
Adenocarcinoma↗
[Familial combined hyperlipidemia].
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Apolipoprotein B-100↗
Restricted usage of T-cell receptor Valpha-Vbeta genes in infiltrating cells in the aortic tissue of a patient with atherosclerotic aortic aneurysm.
We report a rare case of an atherosclerotic aortic aneurysm with lymphocyte infiltration in which T-cell receptor (TCR) Valpha as well as Vbeta gene usage was restricted. Immunohistochemical studies showed that the infiltrating cells mainly consisted of macrophages, natural killer (NK) cells, cytotoxic T lymphocytes (CTLs) and T-helper (Th) cells, and that there were almost no infiltrating delta T lymphocytes, and human leukocyte antigen (HLA) class I and 65-kD heat-shock protein (HSP-65) was not strongly expressed in the aortic tissue. Although the immunohistochemical data were consistent with an ordinary atherosclerotic aortic aneurysm, in which TCR Valpha-Vbeta gene usage is known to be polyclonal, the restricted TCR gene usage suggests that a certain autoimmune mechanism was involved in the pathogenesis of this case similar to Takayasu's arteritis, in which massive infiltration of delta T lymphocytes and strong expression of HSP-65 in the aortic tissue are characteristic.
Aged↗
[Effect of long-term administration of prednisolone on serum creatine kinase and muscle pathology of mdx mouse].
For palliative therapy of Duchenne muscular dystrophy (DMD), corticosteroids have been tried since 1970. According to recent reports, corticosteroids maintained muscular strength to some extent and prolonged period of ambulation. However, their mechanism of action is mostly unclear. In the present study, mdx mice were injected with 0.6 mg prednisolone 3 times a week for 30 weeks. Serum creatine kinase (CK) values remained 23% of controls. In muscle pathology of the quadriceps muscle, fibers with peripheral nuclei were increased, suggesting reduction of muscle necrosis. In pathological examination of liver, pyknotic cytoplasmic masses and formation of vacuoles were observed. Present study showed that prednisolone might attenuate muscle fiber necrosis at least for 30 weeks. Prednisolone may reduce secondary tissue reactions, which develop more serious muscle damage.
Animals↗
Racial differences in polymorphic allele heterozygosities of the human hepatic triglyceride lipase gene.
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Asian People↗
Gi protein activation of gonadotropin-releasing hormone-mediated protein dephosphorylation in human endometrial carcinoma.
OBJECTIVE: Gonadotropin-releasing hormone receptor is demonstrated in uterine endometrial carcinomas. This study was performed to determine gonadotropin-releasing hormone receptor-mediated membrane events and to identify the guanosine triphosphate binding protein (G protein) subtypes linked to gonadotropin-releasing hormone receptor in the tumors. STUDY DESIGN: Endometrial carcinomas surgically removed had been screened for gonadotropin-releasing hormone receptor expression before plasma membrane isolation. The phosphoprotein level was observed in the phosphorus 32-labeled incorporation from [gamma-32P]adenosine triphosphate into the isolated plasma membranes. The Gi (alpha subunit) protein was detected by immunoblotting and pertussis toxin-catalyzed adenosine diphosphate ribosylation. RESULTS: Incubation of phosphorus 32-labeled membranes with a gonadotropin-releasing hormone analog in the presence of guanosine thiotriphosphate caused a remarkable loss of phosphoprotein from 35 kd protein. This dephosphorylation action was dose dependent of the gonadotropin-releasing hormone analog, and the maximal effect (90% loss) occurred at 100 nmol/L. Pertussis toxin brought about adenosine diphosphate ribosylation of an immunodetected G alpha i. Gonadotropin-releasing hormone analog alone or guanosine thiotriphosphate alone had no effect. Pretreatment of the membrane with the pertussis toxin completely inhibited gonadotropin-releasing hormone-mediated dephosphorylation of the 35 kd protein. CONCLUSION: These data demonstrate the coupling of gonadotropin-releasing hormone receptor to protein dephosphorylation through Gi, raising the possibility that the antimitogenic action of gonadotropin-releasing hormone may occur by release of the action of protein phosphorylation to promote cell growth.
Adenosine Diphosphate Ribose↗
Development of a direct DNA sequencing method for detecting heterozygous mutations of the human lipoprotein lipase gene.
OBJECTIVE: The purpose of this study was to develop an improved method of direct DNA sequencing, which makes it possible to identify heterozygous mutations of the lipoprotein lipase (LPL) gene in order to understand the underlying genetic disorder of type IV hyperlipoproteinemia. METHODS AND RESULTS: The direct sequencing method was improved by devising primers for amplifying the LPL gene and for sequencing DNA amplified by the polymerase chain reaction (PCR)T since the reported base sequences of the introns flanking exons of the LPL gene were limited to 40 bases. Improvement was achieved by attaching nine additional bases to both the PCR amplification primer and sequencing primer, and by optimizing the Tm value of the sequencing primers by adjusting the sequence of the nine extra bases. Use of the sequencing primers having suitable Tm values (48 degrees C-58 degrees C) made it possible to reduce nonspecific bands on the sequence ladder pattern and to identify heterozygous mutation sites in LPL gene exons 5 and 6 as model cases. CONCLUSION: Our improved direct sequencing method is useful for identifying heterozygous mutation sites in human LPL gene exons and splicing consensus regions.
Base Sequence↗
Frequent expression of Fas in gonadotropin-releasing hormone receptor-bearing tumors.
OBJECTIVE: Fas, a cell surface receptor, mediates cell death by means of apoptosis in a variety of cell types. Gonadotropin-releasing hormone (GnRH) receptor-bearing tumors undergo the apoptosis with GnRH analogs. The authors attempted to determine the frequency with which Fas is present in the GnRH receptor-bearing tumors. STUDY DESIGN: Surgically removed gynecological tumors were screened for GnRH receptor expression prior to analyses. Fas was characterized by immunoblotting of membrane proteins with the specific antibodies. Fas messenger ribonucleic acid (mRNA) was determined by reverse transcription-polymerase chain reaction using oligonucleotide primers synthesized according to the published Fas sequence. RESULTS: Immunoreactive Fas and Fas mRNA were detected in a high proportion (94.4%) of the specimens from endometrial carcinomas (8 of 9), ovarian carcinomas (7 of 7), and uterine leiomyosarcomas (2 of 2); all these expressed GnRH receptor. There was neither substantial Fas nor GnRH receptor in 9 cervical carcinomas. Cloned cell lines gave identical results to those obtained in their respective mother tumors. CONCLUSION: These data might suggest the frequent expression of Fas in the GnRH receptor-bearing tumors, but not in the GnRH receptor-negative tumors. Despite a poorly understood processes of apoptosis at present, there may be at least some similarity in signal transduction pathway utilized by GnRH analogs and Fas ligands.
Adenocarcinoma↗
Mutation of D. radiodurans in a gene homologous to ruvB of E. coli.
Following the digestion of chromosomal DNA of Deinococcus radiodurans with a restriction enzyme a partial genomic library was constructed using lambda phage as a vector. A phage clone whose DNA can complement the deficiency in a radiation-sensitive mutant of D. radiodurans was isolated. Following the subcloning using phasmid vector, a hybrid plasmid containing 1.2 kb inserted DNA was obtained. After the determination of nucleotide sequence, the deduced amino acid sequence showed close homology to RuvB protein of Escherichia coli; approximately 81% of the amino acids (310 residues in total) was homologous (152 were identical and 100 amino acids were similar). The putative protein has a conserved ATP binding domain characteristic of DNA helicases. However, we could not find an SOS promoter and ORF for RuvA protein in the sequence upstream of ruvB in contrast to the E. coli homologue. The mutant was transformed with exogenous DNA at the same rate as the wild-type cells, but it was moderately sensitive to UV, gamma-rays and to interstrand cross-linking reagents.
Amino Acid Sequence↗
Renal disposition of recombinant human interleukin-11 in the isolated perfused rat kidney.
PURPOSE: To clarify the mechanism of the renal clearance of recombinant human interleukin- 11 (rhIL- 1), we investigated the renal disposition characteristics of rhIL-11 in the perfused rat kidney. METHODS: The disposition characteristics of (111)In-labeled rhIL-11 were analyzed using a single-pass indicator dilution technique and statistical moment analysis in the perfused rat kidney under filtering and nonfiltering conditions. RESULTS: Steady-state distribution volume (Vd) calculated from the venous outflow patterns of rhIL-11 at the doses of 0.3 to 10 microg/kidney was between 0.35 and 0.40 ml/g kidney. However, Vd at the highest dose decreased to a value almost identical to that of bovine serum albumin, suggesting that there is a reversible and saturable interaction between the capillary wall and rhIL-11 molecule. In filtering kidney, a remarkable accumulation of rhIL-11 was observed while its urinary excretion was highly restricted at all doses. In nonfiltering kidney, rhIL-11 showed a decreased but still significant renal uptake. Taken together, the marked renal uptake of rhIL-11 may be explained by both efficient tubular reabsorption and significant uptake from the capillary side. These processes were not saturable within the tested dose range. These characteristics of rhIL-11 are likely based on non-specific electrostatic interaction with the tissues due to its cationic charge in the cytokine. CONCLUSIONS: The renal disposition processes of rhIL-11 were clarified at organ level in a quantitative manner. These findings agree well with previous observations in an in vivo disposition study in mice.
Animals↗
Effects of a high-fat diet on azoxymethane-induced aberrant crypt foci and fecal biochemistry and microbial activity in rats.
To shed light on the association of dietary fat with the development of colon cancer, we studied the ability of azoxymethane (AOM) to induce aberrant crypt foci (ACF) and biochemical changes in rats fed high- or normal-fat diets. Six-week-old male Fischer 344 rats were placed on a high-fat [7% (wt/wt) soybean oil + 15% (wt/wt) beef tallow] or a normal-fat (7% soybean oil, AIN-93G) diet. Rats fed each of these diets were given two weekly subcutaneous injections of AOM (15 mg/kg body wt) or saline at seven and eight weeks of age. Fecal samples were obtained at 10 weeks of age, and animals were sacrificed for ACF scoring and analysis of cecal contents at 13 weeks of age. We observed greater numbers of ACF in the high- than in the low-fat group. Biochemically, rats fed the high-fat diet showed dramatically elevated fecal and cecal long-chain free fatty acid levels and intestinal alkaline phosphatase activity. These animals also showed increased cholesterol and decreased coprostanol levels. We did not detect significant differences in the fecal and cecal concentrations of total and soluble bile acids or total neutral sterols (cholesterol + coprostanol) between the two groups. Thus a high-fat diet does show certain striking effects on colon biochemistry in rats.
Alkaline Phosphatase↗
Cytotoxicity and motility of Helicobacter pylori.
To clarify the relationship between interleukin-8 (IL-8) production and virulent factors, we examined the motility and cytotoxicity of H. pylori, suggested to be a major cause of chronic gastritis and peptic ulcers. Our results demonstrated that among cytotoxic strains of H. pylori, high-motility strains induced more IL-8 than low-motility strains. There was no correlation between cytotoxicity and motility of H. pylori. Four restriction fragment length polymorphism (RFLP) patterns were observed in the flaA PCR products. There was no correlation between flaA RFLP and motility. In conclusion, our findings suggest that both cytotoxicity and motility are virulent factors in the pathogenesis of gastric mucosal injury.
Animals↗
Detection of SRY in 45,X/47,XYY mosaicism leading to phenotypic female.
SRY on the Y chromosome initiates male sex determination. We tested a phenotypic female with sex chromosome mosaicism, X/XYY, for SRY expression. SRY was determined by polymerase chain reaction (PCR) amplification in genomic DNA from a female patient with a sex chromosome mosaic complement, 45,X/47,XYY, followed by sequencing analyses. The patient yielded the PCR product with predicted size and homology to the consensus sequence of SRY. The demonstration of SRY provides evidence that the female phenotype in the presence of sex chromosome mosaicism, X/XYY, may result from alterations in another part of the sex-determining pathway or downstream from SRY.
Adolescent↗
Analysis of interleukin-8 secretion induced by Helicobacter pylori from the gastric epithelial cell line MKN45: a mechanism independent of the intensity of cytotoxicity.
Interleukin (IL)-8, a potent chemoattractant and activator of neutrophils, has been implicated to have a major role in the pathogenesis of gastric mucosal injury by Helicobacter pylori infection. We examined the relationship between cytotoxicity and IL-8 secretion induced by H. pylori. Furthermore, whether the vacuolating cytotoxin of H. pylori mediates IL-8 secretion from gastric epithelial cell lines was examined. Among the inflammatory cytokines, messages for IL-6, IL-8 and transforming growth factor-beta 1 were produced by gastric cancer (MKN45) cells in response to exposure to the cytotoxic strain of H. pylori. MKN45 incubated with the viable cytotoxic strain of H. pylori secreted IL-8. In contrast, the supernatant of neither the cytotoxic nor the non-cytotoxic strain induced IL-8 secretion. There was no correlation between IL-8 secretion and the intensity of cytotoxicity. In conclusion, these findings suggest that IL-8 secretion from MKN45 induced by H. pylori is mediated by factors other than cytotoxicity.
Bacterial Proteins↗
A comparison of patients with premature thelarche and idiopathic true precocious puberty in the initial stage of illness.
A comparative study of patients with premature thelarche and patients with idiopathic true precocious puberty was conducted. The age at the first visit tended to be lower for those with precocious puberty. In comparison with normative data for children, the frequency of low birthweight and small for date (SFD) status was greater in the 55 patients with premature thelarche, but SFD was also frequent in the 18 patients with precocious puberty. The height, weight and Kaup's index were all within the normal range for these two groups. The ratios for bone age/chronologic age and bone age/height age tended to be high in both groups. In the patients with premature thelarche, the blood luteinizing hormone (LH) level showed a normal response, and the blood follicle stimulating hormone (FSH) level a hyper-response, to stimulation with luteinizing hormone-releasing hormone (LH-RH). In contrast, both the blood LH and FSH levels showed a normal response to LH-RH stimulation in most of the patients with precocious puberty, and a hyper-response was rare among them. Although the blood estradiol (E2) level was higher in patients with precocious puberty than in those with premature thelarche, about 50% and 90% of the patients in the respective groups had normal levels. These results suggest that normal responses of blood LH and excessive responses of blood FSH to LH-RH loading may be useful in some patients for diagnosing premature thelarche at an early stage.
Age Determination by Skeleton↗