[Future activities of the Committee for Changing Terminology of Mental Disorders].
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Humans↗
Biomedical subjects
S Takagi
Publications and source records attributed to S Takagi.
Telomere shortening and the clinicopathologic characteristics of human colorectal carcinomas.
BACKGROUND: It has been reported that shortening of telomeres and strong activation of telomerase occur frequently in colorectal carcinomas. In the current study, the authors examined the correlations between the telomere length of colorectal carcinomas and their clinicopathologic characteristics as well as the activity of telomerase to clarify whether telomere length might represent the biologic behavior of tumors and the mode of tumor development. METHODS: Telomere length was examined by Southern blot analysis in 61 invasive colorectal carcinomas and corresponding normal mucosas. Telomerase activity was assayed by the telomeric repeat amplification protocol with minor modifications. RESULTS: Shortening of the telomere was detected in 38 (62.3%) and elongation in 3 (4. 9%) of the 61 carcinomas. The telomere shortening occurred more frequently in nonulcerating polypoid carcinomas than in ulcerating carcinomas (P = 0.0373) and also occurred more frequently in ascending colon carcinomas than in sigmoid colon or rectal carcinomas (P = 0.0259 and P = 0.0407, respectively). However, no significant correlation was found between the activity of telomerase and the length of telomere. CONCLUSIONS: The results of this study indicate that telomere length may represent the biologic behavior of individual tumors and possibly the mode of development of colorectal carcinomas.
Aged↗
Molecular cloning of a novel human CC chemokine (Eotaxin-3) that is a functional ligand of CC chemokine receptor 3.
Previously, we mapped the novel CC chemokine myeloid progenitor inhibitory factor 2 (MPIF-2)/eotaxin-2 to chromosome 7q11.23 (Nomiyama, H., Osborne, L. R., Imai, T., Kusuda, J., Miura, R., Tsui, L.-C., and Yoshie, O. (1998) Genomics 49, 339-340). Since chemokine genes tend to be clustered, unknown chemokines may be present in the vicinity of those mapped to new chromosomal loci. Prompted by this hypothesis, we analyzed the genomic region containing the gene for MPIF-2/eotaxin-2 (SCYA24) and have identified a novel CC chemokine termed eotaxin-3. The genes for MPIF-2/eotaxin-2 (SCYA24) and eotaxin-3 (SCYA26) are localized within a region of approximately 40 kilobases. By Northern blot analysis, eotaxin-3 mRNA was constitutively expressed in the heart and ovary. We have generated recombinant eotaxin-3 in a baculovirus expression system. Eotaxin-3 induced transient calcium mobilization specifically in CC chemokine receptor 3 (CCR3)-expressing L1.2 cells with an EC(50) of 3 nM. Eotaxin-3 competed the binding of (125)I-eotaxin to CCR3-expressing L1.2 cells with an IC(50) of 13 nM. Eotaxin-3 was chemotactic for normal peripheral blood eosinophils and basophils at high concentrations. Collectively, eotaxin-3 is yet another functional ligand for CCR3. The potency of eotaxin-3 as a CCR3 ligand seems, however, to be approximately 10-fold less than that of eotaxin. Identification of eotaxin-3 will further promote our understanding of the control of eosinophil trafficking and other CCR3-mediated biological phenomena. The strategy used in this study may also be applicable to identification of other unknown chemokine genes.
Amino Acid Sequence↗
Reaction of calcium phosphate cements with different amounts of tetracalcium phosphate and dicalcium phosphate anhydrous.
Calcium phosphate cements (CPCs) with different amounts of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) (TTCP/DCPA molar ratio from 0.25 to 2.00) were prepared to further understand the setting reaction and the factors that could influence the properties of CPCs. Quantitative X-ray diffraction patterns, Fourier transform IR spectra, and diametral tensile strength of the set mass were measured along with pH measurements of the CPC suspension. Calcium-deficient hydroxyapatite (d-HAP) with a calcium to phosphate molar ratio of approximately 1.5 was formed initially in the CPC setting consisting of an equimolar mixture of TTCP and DCPA. This gradually transformed into stoichiometric HA (s-HA) with increasing incubation time. The s-HA was formed in the initial stage when the CPC contained an excess amount of TTCP. In contrast, maturation to s-HAP was slow when the CPC contained excess amounts of DCPA. The highest mechanical strength of set CPC was associated with an equimolar mixture of TTCP and DCPA, and the mechanical strength decreased as the TTCP/DCPA molar ratio deviated from 1.00. We concluded, therefore, that the setting reaction and the nature of the resulting set mass are dependent on the molar ratios of TTCP and DCPA.
Bone Cements↗
New p73 variants with altered C-terminal structures have varied transcriptional activities.
p73 has been identified as a protein which shares significant homology with the tumor suppressor p53. We found two new types of splicing variant mRNAs for p73 expressed in MCF-7 cells which we named p73gamma and epsilon. Sequence analysis revealed that these mRNAs encode variant p73 proteins bearing distinct carboxy-terminal structures, which are also different from the previously reported variants p73alpha and beta. The mRNAs encoding p73gamma and epsilon as well as alpha and beta were confirmed to be expressed in normal human tissues in varied patterns. All of these splicing variants activated promoter with the p53-binding consensus sequence, but to different degrees. Furthermore, suppressive effects of p73alpha, gamma and epsilon, but not beta, on endogenous p53 activity were observed when transiently expressed in HepG2 and MCF-7 cells. These results suggested that the carboxy-terminal regions of p73 which were altered by alternative splicing affect these transactivation abilities and modulate the functions of p73 molecules.
Alternative Splicing↗
Association of protein-tyrosine phosphatase PTP-BAS with the transcription-factor-inhibitory protein IkappaBalpha through interaction between the PDZ1 domain and ankyrin repeats.
PTP-BAS is a membrane-associated protein tyrosine phosphatase containing a band-4.1 homology region and five PDZ (PSD-95 Dlg ZO-1) [discs-large homology region ('DHR')/Gly-Leu-Gly-Phe ('GLGF')] domains. The second and fourth PDZ domains were reported to associate with Fas/CD95. By using the first PDZ domain as a bait in yeast two-hybrid screening, we have identified IkappaBalpha as a binding protein. IkappaBalpha associated with PDZ1 through the stretch of the N-terminal three ankyrin repeats. The association was also confirmed in HeLa cells by co-immunoprecipitation experiments. Inhibition of PTP-BAS by expression of dominant-negative PTP-BAS mutant resulted in tyrosine-phosphorylation of IkappaBalpha. Tyrosine-phosphorylation of IkappaBalpha is a key event in activation of nuclear factor (NF)-kappaB during reoxygenation. PTP-BAS may thus play a regulatory role in activation of NF-kappaB under high oxidative stress.
Ankyrins↗
Laparoscopic common bile duct exploration: long-term outcome.
HYPOTHESIS: Transcystic laparoscopic common bile duct exploration (LCBDE) with biliary endoscopy results in excellent long-term clinical outcome and patient satisfaction. DESIGN: Prospective cohort study of unselected patients found to have common bile duct stones during laparoscopic cholecystectomy between October 1989 and April 1998. A mailed survey assessed symptoms, outcome, and satisfaction. SETTING: A large community teaching hospital. PATIENTS: Two hundred seventeen patients with common bile duct stones. INTERVENTION: Transcystic LCBDE with choledochoscopy. MAIN OUTCOME MEASURES: Success of LCBDE, morbidity, postoperative symptoms, and satisfaction. RESULTS: One hundred sixteen surveys (54%) were returned. Mean follow-up was 60 months. The LCBDE procedure failed in 6 patients and endoscopic retrograde cholangiopancreatography was performed in 4 patients (3%). One patient had unsuspected retained stones. No patient had late recognition of retained stones or a bile duct stricture. Abdominal pain was present in 90 patients (89%) preoperatively and in 29 patients (26%) postoperatively (P = .001). The LCBDE procedure reduced 3 specific pain profiles: epigastric, from 47% (n = 54) to 7% (n = 8); back, from 31% (n = 36) to 6% (n = 7); and shoulder, from 18% (n = 21) to 2% (n = 2). When pain persisted, it was different in character in 15%. All nonpain symptoms (such as nausea, bloating, indigestion, and gas) were reduced from 78% (n = 91) to 34% (n = 39) (P = .001) except diarrhea. Diarrhea was present in 24 patients (22%) preoperatively and postoperatively, though it was a new postoperative symptom in 11 patients (11%). One hundred two patients (95%) were satisfied or mostly satisfied with LCBDE. CONCLUSIONS: Pain and nonpain symptoms, while reduced significantly after LCBDE, may persist. The LCBDE procedure does not result in common bile duct strictures or a significant rate of retained stones. This relatively new treatment for common bile duct stones is safe and effective.
Cholecystectomy, Laparoscopic↗
Development of poorly differentiated adenocarcinoma and carcinoid due to long-term Helicobacter pylori colonization in Mongolian gerbils.
A Mongolian gerbil model was used to clarify whether long-term colonization by Helicobacter pylori is an important risk factor for the development of gastric cancer. Fifty-nine gerbils (3 controls and 56 gerbils inoculated with H. pylori) were killed at various times (average, 23 months) more than 12 months after H. pylori inoculation. In the H. pylori-inoculated group, poorly differentiated adenocarcinoma was observed in the pylorus of 1 gerbil, and carcinoid was observed in the fundus of the stomach in 18 gerbils. No lesions were found in the stomachs of the 3 control gerbils. The results imply that long-term colonization by H. pylori is an important risk factor for the development of gastric adenocarcinoma and carcinoid.
Adenocarcinoma↗
Crohn's disease is associated with novel polymorphisms in the 5'-flanking region of the tumor necrosis factor gene.
BACKGROUND & AIMS: Tumor necrosis factor (TNF) is considered to play an important role in the pathogenesis of Crohn's disease (CD). Recently, 3 polymorphisms in the 5'-flanking region of the TNF gene at positions -1031, -863, and -857, which are related to high transcriptional promoter activity, have been identified in the Japanese population. In an effort to understand potential genetic association with CD, we evaluated patients diagnosed with CD and ulcerative colitis (UC) in the presence of other novel polymorphisms. METHODS: Blood samples were obtained from 103 patients with CD and 76 patients with UC. Polymorphisms in the TNF gene at their respective positions were analyzed by direct sequencing, and the allele frequencies were compared with those determined previously in a healthy Japanese population. RESULTS: Allele frequencies of -1031C, -863A, and -857T in normal controls were 16.0%, 14.0%, and 17.7%, respectively. Polymorphic allele frequencies at positions -1031, -863, and -857 were 24.3%, 21.8%, and 27.2% in CD and 11.8%, 11.2%, and 11.8% in UC, respectively. The frequencies at all 3 positions were significantly higher in CD patients than in UC patients or healthy controls. Among the subgroups of CD, small bowel disease showed the highest frequencies. CONCLUSIONS: Although the findings need to be confirmed in other populations with larger numbers of patients, TNF gene polymorphisms -1031C, -863A, and -857T are positively associated with CD; they may influence not only the susceptibility to CD but also the disease location.
Adult↗
Effect of powder grinding on hydroxyapatite formation in a polymeric calcium phosphate cement prepared from tetracalcium phosphate and poly(methyl vinyl ether-maleic acid).
The primary aim of this study was to determine if cements based on poly(methyl vinyl ether-maleic acid) (PMVE-Ma) and tetracalcium phosphate resulted in hydroxyapatite formation. In addition, the mechanical strength of this type of polymeric calcium phosphate cement was evaluated. Cements were prepared by mixing, in a powder/liquid mass ratio of 3.0, an aqueous solution of PMVE-Ma (mass fraction = 25%) and tetracalcium phosphate powders ground for various periods of time. The tetracalcium phosphate powders and set cements were characterized by means of X-ray powder diffraction and scanning electron microscopy. Mechanical strengths of the cements were tested 24 h after mixing. Prolonged grinding of tetracalcium phosphate powder decreased particle size and/or crystallite size and increased lattice distortion. This enhanced the reactivity of the tetracalcium phosphate powder and elevated the extent of crosslinking between PMVE-Ma molecules, resulting in improved mechanical strength. Hydroxyapatite formation was detected in the cement prepared with the most finely ground tetracalcium phosphate powder. The conversion of residual tetracalcium phosphate particles to more thermodynamically stable hydroxyapatite crystals will reduce the solubility of the polymeric cement and increase its biocompatibility.
Calcium Phosphates↗
Levels of human defensin-1, an antimicrobial peptide, in saliva of patients with oral inflammation.
OBJECTIVE: The purpose of this study was to investigate the presence of an antimicrobial peptide, human defensin-1, in the saliva of patients with oral inflammation. STUDY DESIGN: Whole saliva samples were collected from patients with oral inflammation and from healthy volunteers. Human defensin-1 in saliva was isolated and purified by reversed-phase high-performance liquid chromatography. The amino acid sequence and molecular weight of defensin-1 were determined. The concentration of defensin-1 in saliva was quantified by high-performance liquid chromatography. Serum C-reactive protein concentration was measured by particle-enhanced turbidimetric immunoassay. RESULTS: The salivary defensin-1 concentration was significantly higher in patients with oral inflammation than in healthy volunteers; furthermore, in patients with oral inflammation, the concentration was significantly higher before treatment than after treatment. In the patients with oral inflammation, there was a strong positive correlation between salivary defensin-1 concentration and serum C-reactive protein concentration. CONCLUSIONS: The findings suggest that defensin-1 in saliva may be a convenient marker of inflammation associated with oral disease.
Adult↗
Schizophrenia: is it time to replace the term?
The attitudes of Japanese psychiatrists toward their patients who suffer from schizophrenia were investigated. We were concerned specifically with whether the psychiatrists inform their patients of the suspected diagnosis. We discuss how the term 'schizophrenia' may influence a psychiatrist's decision to inform his patients of the diagnosis. A self-reported questionnaire was distributed to 150 executive board members of the Japanese Society of Psychiatry and Neurology and analysis of the data obtained from 110 respondents was carried out. The results showed that the concepts that psychiatrists use when they give a diagnosis of schizophrenia vary considerably. Fifty-nine per cent of the respondents informed their patients of a diagnosis of schizophrenia on a case-by-case basis, while 37% informed only the patients' families. A tree analysis showed that the most important predictors for informing the patients of the diagnosis were assumptions about the public image of schizophrenia and a negative impression of the term schizophrenia, translated as 'Seishin Bunretsu Byou' in Japanese. The results revealed that the Japanese term for schizophrenia influences a psychiatrist's decision to inform patients of the diagnosis and that, by changing the term to a less stigmatized one, the disclosure of information about schizophrenia to patients would be promoted.
Attitude of Health Personnel↗
Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine.
Helper T cells are classified into Th1 and Th2 subsets based on their profiles of cytokine production. Th1 cells are involved in cell-mediated immunity, whereas Th2 cells induce humoral responses. Selective recruitment of these two subsets depends on specific adhesion molecules and specific chemoattractants. Here, we demonstrate that the T cell-directed CC chemokine thymus and activation-regulated chemokine (TARC) was abundantly produced by monocytes treated with granulocyte macrophage colony stimulating factor (GM-CSF) or IL-3, especially in the presence of IL-4 and by dendritic cells derived from monocytes cultured with GM-CSF + IL-4. The receptor for TARC and another macrophage/dendritic cell-derived CC chemokine macrophage-derived chemokine (MDC) is CCR4, a G protein-coupled receptor. CCR4 was found to be expressed on approximately 20% of adult peripheral blood effector/memory CD4+ T cells. T cells attracted by TARC and MDC generated cell lines predominantly producing Th2-type cytokines, IL-4 and IL-5. Fractionated CCR4+ cells but not CCR4- cells also selectively gave rise to Th2-type cell lines. When naive CD4+ T cells from adult peripheral blood were polarized in vitro, Th2-type cells selectively expressed CCR4 and vigorously migrated toward TARC and MDC. Taken together, CCR4 is selectively expressed on Th2-type T cells and antigen-presenting cells may recruit Th2 cells expressing CCR4 by producing TARC and MDC in Th2-dominant conditions.
Antigen-Presenting Cells↗
Defensin-1, an antimicrobial peptide present in the saliva of patients with oral diseases.
OBJECTIVES AND DESIGN: A preceding paper has noted a detection of defensin-1 (HNP-1), a peptide with antimicrobial and cytotoxic properties, in the saliva of patients with oral squamous cell carcinoma. The present study deals with the presence of HNP-1 in the saliva of patients with various oral diseases. METHODS: Whole saliva samples were obtained from the patients. HNP-1 in the saliva was isolated and purified by HPLC and the amino acid sequence of the peptide was determined. The molecular weight of HNP-1 was measured by mass spectrometry. The concentration of HNP-1 in saliva was determined by comparing the height of eluted HNP-1 with that of a synthetic HNP-1 standard. RESULTS: The concentrations of HNP-1 in the saliva of patients with oral lichen planus (n = 5), leukoplakia (n = 4), and glossitis associated with iron deficiency (n = 4) were 8.3 +/- 4.3 micrograms ml-1, 13.2 +/- 7.9 micrograms ml-1, and 11.4 +/- 4.9 micrograms ml-1, (mean +/- s.d.), respectively. These concentrations were significantly higher than those in healthy subjects (0.8 microgram ml-1) (P < 0.01). In contrast, salivary HNP-1 concentrations in patients with glossodynia (n = 4) and oral discomfort (n = 4) were similar to those in healthy subjects. CONCLUSIONS: Since HNP-1 is a non-specific defensive peptide present in neutrophils, it may play an important role in the protection against diseases such as oral lichen planus, leukoplakia, and glossitis associated with iron deficiency.
Adult↗
Mobile intracardiac calcinosis: a new risk of thromboembolism in patients with haemodialysed end stage renal disease.
Cardiac calcinosis is a common complication of end stage renal disease. A newly observed risk of thromboembolism is reported in four patients with mobile cardiac calcinosis, treated with long term dialysis. Rapidly growing mobile calcification was confirmed by echocardiography. Each patient had an imbalance in serum calcium x inorganic phosphate (Ca x P product >/= 50); this imbalance could not be treated due to the sudden death of the patient or the need for surgical resection to prevent recurrent cerebral thromboembolism. Histological examination revealed intracardiac calcinosis in three cases, and each case showed haemodialysis hypoparathyroidism (intact PTH < 160 pg/ml). Thromboembolism in such cases is rare, however it indicates a need for cautious echocardiographic monitoring in end stage renal disease in patients with an uncontrolled Ca x P product.
Aged↗
Cold acclimation of guinea pig depressed contraction of cardiac papillary muscle.
Guinea pigs were exposed to 5 degrees C for 3 wk, and the contractions of myocardial papillary muscle were compared with preparations dissected from control animals kept at approximately 25 degrees C. Developed tension of the papillary muscle per cross-sectional area was significantly (t-test, P < 0.05) decreased after cold exposure (19,200 +/- 8,160 vs. 3,020 +/- 2,890 dyne/cm2; 1 Hz). Time to peak tension was significantly faster in cold-exposed guinea pigs (126.4 +/- 11.1 ms; 1 Hz) than in controls (162.7 +/- 8. 7 ms). The magnitude of the developed tension after application of ryanodine (2 mM) to muscles from cold-exposed animals was decreased to 37.5 +/- 8.3% of control at 1 Hz, whereas in muscles from control animals, tension was decreased to 82.4 +/- 7.7%. The ryanodine-sensitive component of contraction was not significantly changed in control guinea pigs at frequencies >0.5 Hz, whereas in muscles from cold-acclimated guinea pigs, there was a "positive staircase." These results suggested that reversal of the Na+/Ca2+ exchanger is predominantly involved in the positive staircase in control guinea pigs, whereas rate-dependent increases in the Ca2+ store in the sarcoplasmic reticulum may be involved in the staircase after cold acclimation.
Acclimatization↗
Successful stenting on tortuous coronary artery with accordion phenomenon: strategy--a case report.
Guidewire manipulation through tortuosities is difficult. Straightening a tortuous coronary artery by using a stiff guidewire has been recognized to induce vessel wall shortening referred to as an "accordion phenomenon." With inappropriate identification as dissection or thrombus formation, the risk of performing unnecessary dilation at the pseudo-narrowing site exists. The authors describe here two cases showing the accordion phenomenon induced by a stiff guidewire during successful stenting at a tortuous right coronary artery. In another case, the authors experienced an "accordion phenomenon" at the proximal edge of the Palmaz-Schatz stent implanted in a tortuous right coronary artery. The stent edge was better positioned at the straight portion than at the contour portion in a tortuous coronary artery.
Aortic Dissection↗
Prognostic significance of magnetic resonance imaging of femoral marrow in patients with myelodysplastic syndromes.
PURPOSE: To investigate whether the abnormalities observed on femoral marrow magnetic resonance images are related to the development of leukemia and survival of patients with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: The findings on magnetic resonance images of the femoral marrow were evaluated over periods of 1 to 92 months (median, 18 months) in 42 consecutive adult patients with newly diagnosed MDS. Magnetic resonance images were obtained by the T1-weighted spin echo method and the short T1 inversion recovery technique. RESULTS: Magnetic resonance images showed that the femoral marrow patterns changed from fatty, faint, or nodular to scattered or uniform as the disease progressed. Development of acute myeloid leukemia was observed in only 13 patients whose marrow exhibited a scattered or uniform pattern. The overall survival of the 29 patients with a scattered or uniform marrow pattern was significantly shorter than that of the 13 patients with a fatty, faint, or nodular marrow pattern (10.7% v 73.3% at 7 years; P < .01). The period of leukemia-free survival was also significantly shorter in the patients with a scattered or uniform marrow pattern versus a fatty, faint, or nodular pattern (37.7% v 100% at 7 years; P < .01). CONCLUSION: Magnetic resonance images of the femoral marrow can provide valuable information for assessing the prognosis and determining the most appropriate management of patients with MDS.
Acute Disease↗