Apolipoprotein E epsilon4 allele and schizophrenia.
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Adult↗
Biomedical subjects
S Yokota
Publications and source records attributed to S Yokota.
Apolipoprotein E epsilon2 allele and early onset schizophrenia.
To explore the role of apolipoprotein E (ApoE) in schizophrenia, we investigated ApoE phenotypes in a group of patients with schizophrenia. Serum samples were obtained from 122 schizophrenic patients and 126 controls in Japan and were examined using isoelectric focusing/immunoblotting. This experiment showed a trend toward a decreased frequency of ApoE epsilon4 in schizophrenia and no link between ApoE epsilon4 and familial schizophrenia or early onset schizophrenia. On the other hand, a decreased frequency of ApoE epsilon2 in early onset schizophrenia was detected. These results suggest that ApoE epsilon2 protects against early onset schizophrenia, and that ApoE epsilon4 is not involved in the development of schizophrenia in Japanese.
Adult↗
A second isoform of 3-ketoacyl-CoA thiolase found in Caenorhabditis elegans, which is similar to sterol carrier protein x but lacks the sequence of sterol carrier protein 2.
We cloned a full-length cDNA of the nematode Caenorhabditis elegans that encodes a 44-kDa protein (P-44, 412 residues) similar to sterol carrier protein x (SCPx). Mammalian SCPx is a bipartite protein: its 404-residue N-terminal and 143-residue C-terminal domains are similar to 3-ketoacyl-CoA thiolase and identical to the precursor of sterol carrier protein 2 (SCP2; also termed non-specific lipid-transfer protein), respectively. P-44 has 56% sequence identity to the thiolase domain of SCPx but lacks the SCP2 sequence. Northern blot analysis revealed only a single mRNA species of 1.4 kb, which agrees well with the length of the cDNA (1371 bp), making it improbable that alternative splicing produces an SCPx-like fusion protein. The sequence similarities of P-44 to conventional thiolases are lesser than that to SCPx. Purified recombinant P-44 cleaved long-chain 3-ketoacyl-CoAs (C(8-16)) in a thiolytic manner by the ping-pong bi-bi reaction mechanism. The inhibition of P-44 by acetyl-CoA was competitive with CoA and non-competitive with 3-ketooctanoyl-CoA. This pattern of inhibition is shared with SCPx but not with conventional 3-ketoacyl-CoA thiolase, which is inhibited uncompetitively with respect to 3-ketoacyl-CoA. From these results, we concluded that nematode P-44 and mammalian SCPx constitute a second isoform of thiolase, which we propose to term type-II 3-ketoacyl-CoA thiolase.
Acetyl-CoA C-Acetyltransferase↗
Characterization and distribution of O-glycosylated carbohydrates in the cell adhesion molecule, contact site A, from Dictyostelium discoideum.
This paper presents further investigation of the properties of carbohydrate II in the cell adhesion molecule, contact site A, from Dictyostelium discoideum. A purified contact site A was digested with Achromobacter protease I to produce a 31-kDa fragment to which carbohydrate II was mainly bound and a 21-kDa fragment containing the NH2 terminus of contact site A, which was identified as Ala-Pro-Thr-Ile-Thr-Ala. The NH2 terminus of the 31-kDa fragment was Thr-Glu-Ala-Thr-Thr-Ser. It was estimated from the cDNA sequence data of contact site A that more than 20 Ser/Thr residues exist as target sites for the O-linked oligosaccharides in the 31-kDa fragment, but not for the N-linked oligosaccharides. These results suggest that carbohydrate II exists as clustered O-linked oligosaccharides in the COOH terminus of contact site A. The results of two-dimensional electrophoresis confirm that oligosaccharides of contact site A contain sialic acids. Immunoelectron microscopy was carried out to define the organelle in which O-glycosylation by carbohydrate II occurs and how carbohydrate II antigens are distributed on the cell surface. The results show that O-glycosylation can occur in the Golgi apparatus in D. discoideum as observed in other cells, although this O-glycosylation was inhibited by tunicamycin. Furthermore, gold particles were densely concentrated in cell-cell contact regions but sparsely distributed in noncontact regions.
Animals↗
Binding of 8-mer to 11-mer peptides carrying the anchor residues to slow assembling HLA class I molecules (HLA-B*5101).
The binding of 303 8-mer to 11-mer peptides carrying the anchor residues at P2 and the C-terminus to HLA-B*5101 molecules was examined by a stabilization assay in which peptides were incubated with RMA-S-B*5101 cells at 26 degrees C for 3 h. Analysis of the binding of these peptides to HLA-B*5101 molecules showed that Pro and Ala at P2, and Ile, Val, and Leu at the C-terminus functioned as anchor residues, while Gly at P2 and Met at the C-terminus were weak anchors. Pro was a stronger anchor residue than Ala at P2, while Ile was the strongest anchor at the C-terminus. Among 8-mer to 11-mer peptides, the 9-mer peptides showed the strongest binding to HLA-B*5101 molecules. This is in contrast to our recent findings that 10-mer and 11-mer peptides bind to HLA-B*3501 molecules as effectively as 9-mer peptides. Since both HLA class I molecules have the same B-pocket and the binding peptides carry the same anchor residues, it is assumed that the structure of the F-pocket may restrict the length of binding peptides. The ability of HLA-B*5101 binding peptides to stabilize the HLA-B*5101 molecules was markedly lower than that of HLA-B*3501 binding peptides to stabilize the HLA-B*3501 molecules. It is known that HLA-B*5101 is a slow assembling molecule, while HLA-B*3501 assembles rapidly. The results imply that the slow assembling of HLA-B*5101 molecules results from the low affinity of peptides to HLA-B*5101 molecules.
Cell Line↗
Predominant role of N-terminal residue of nonamer peptides in their binding to HLA-B* 5101 molecules.
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Amino Acid Sequence↗
Spontaneous remission of chronic hepatitis C in children.
UNLABELLED: The clinical course of 48 children with chronic hepatitis C (33 boys, 15 girls; mean age: 12.2 years) was monitored for more than 3 years to clarify its natural course. All patients were positive for the second-generation antibody to hepatitis C virus (anti-HCV) and for serum hepatitis C virus (HCV) RNA. All but one patient had a history of blood transfusion. Serum levels of alanine aminotransferase (ALT) had been abnormal for more than 1.5 years. Spontaneous remission defined as a biochemical remission lasting more than 1 year in association with the disappearance of serum HCV RNA, occurred in 4 (8.3%), however, in 25%, HCV RNA was still detectable in the liver even after its disappearance from serum. In this patient, the level of antibody to HCV core antigen (anti-HCV core) did not decrease significantly and serum HCV RNA eventually reappeared. The serum titre of HCV RNA in the 4 children with spontaneous remission was lower than in the remaining 44 children. Spontaneous remission may occur in children with chronic hepatitis C in whom the serum titre of HCV RNA is low and serum level of anti-HCV core decreases significantly. Assessment of the intrahepatic HCV RNA is necessary to confirm complete remission. CONCLUSION: A low serum titre of HCV RNA and a significant decrease in the serum titre of anti-HCV core were associated with spontaneous remission in children with chronic hepatitis C. Intrahepatic HCV RNA assessment is necessary to confirm complete remission.
Adolescent↗
Interphase detection of BCL6/IgH fusion gene in non-Hodgkin lymphoma by fluorescence in situ hybridization.
We characterized a t(3;14)(q27;q32) translocation in nine patients with B-cell, non-Hodgkin lymphoma (B-NHL) by fluorescence in situ hybridization (FISH). Fluorescence in situ hybridization with immunoglobulin heavy chain (IgH) and BCL6 gene probes detected t(3;14) rapidly and accurately, including complex t(3;14) in three patients; one with t(3;12;8;14)(q27;p13;q24.1;q32) and two with t(3;?;14)(q27;?;q32). Among these nine patients, seven escaped from cytogenetic detection by our G-banding analysis. Double-color FISH with IgH (Y6) and BCL6 (cosB5-1) showed fusion of BCL6 and IgH genes on der(3)t(3;14) in all nine patients, suggesting that der(3) may play a critical role in the development of lymphoma carrying complex as well as standard t(3;14) translocations. BCL6/IgH fusion gene was also demonstrated in interphase nuclei at a frequency of 23% to 91.5% over the cut-off value in control studies (9.0 +/- 2.76%). The breakpoints assessed by FISH with two cosmid clones containing BCL6 probes, cosB5-1 and cosB5-2, were within the cluster region in seven patients including one with complex type, but were not evaluated in two patients with t(3;?;14), because of the loss of partner chromosome. Using double-color FISH with these two BCL6-specific probes, none of an additional 32 patients in whom mitotic spreads were available showed 3q27 translocations. Fluorescence in situ hybridization with IgH and BCL6 gene probes is a rapid and sensitive method to detect t(3;14) in routine cytogenetic studies.
Aged↗
Mutation of CDKN2 is infrequently detected in myelodysplastic syndrome.
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Carrier Proteins↗
Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho).
FLT3 is a member of receptor tyrosine kinases expressed in leukemia cells, as well as in hematopoietic stem cells. Recently, a somatic alteration of the FLT3 gene was found in acute myeloid leukemia, as an internal tandem duplication (FLT3/ITD) which caused elongation of the juxtamembrane (JM) domain of FLT3. Here we characterized the FLT3/ITD and investigated its clinical significance in acute promyelocytic leukemia (APL). Seventy-four newly diagnosed patients with APL, who were treated with the same protocol in a multi-institutional study, were studied for the FLT3/ITD. Genomic and message sequences of the FLT3 gene were amplified by means of polymerase chain reaction (PCR), and elongated PCR products were sequenced. Fifteen patients (20.3%) had FLT3/ITD, all of which were transcribed in frame. Location of the duplicated fragments (six to 30 amino acids) varied from patient to patient. However, they always contained either Y591 or Y599, but the tyrosine kinase domain was not significantly affected. This finding implied that signal transduction of FLT3 is amplified by the duplication. Clinically, the presence of FLT3/ITD was related to high peripheral white blood cell counts as well as peripheral leukemia cell counts (P < 0.0001), high LDH level (P = 0.04), and low fibrinogen concentration (P = 0.04). These data suggest that FLT3/ITD plays a significant role in progression of APL.
Adult↗
Tandem duplications of the FLT3 receptor gene are associated with leukemic transformation of myelodysplasia.
We recently reported an internal tandem duplication of the human flt3 receptor gene (FLT3) as a somatic mutation in 17% of acute myelogenous leukemia (AML). The present study revealed the duplication at the juxtamembrane and the first tyrosine kinase domains of FLT3 in seven of 92 (8%) patients with myelodysplastic syndrome (MDS) and AML with trilineage myelodysplasia (AML/TMDS), the diseases which may represent neoplastic changes of pluripotent stem cells. A tandem duplication of exon 11 of FLT3 was harbored by two of 58 (3%) patients with MDS and five of 34 (15%) with overt leukemia, including MDS-derived leukemia, AML/TMDS and therapy-related leukemia. Although the duplicated regions varied within exon 11 in each case, they occurred in-frame, and altered mRNA expressions were demonstrated by reverse-transcription polymerase chain reaction. Two cases of MDS with a FLT3 duplication transformed to overt leukemia within a few months. Longitudinal analyses in two other patients with leukemia revealed that the duplication was a late genetic event during the disease course; one of whom showed two independent duplications of FLT3 at the terminal therapy-resistant phase. Of seven patients with the FLT3 duplication, six had abnormal karyotypes, and four harbored a point mutation of the N-RAS and/or TP53 genes. Patients with FLT3 mutations have poor prognoses. This study uncovered the fact that the accumulation of genetic events, including FLT3 duplication, correlates with leukemic transformation from antecedent myelodysplasia and with subsequent disease progression.
Aged↗
Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines.
In this study, we examined a large number of patients to clarify the distribution and frequency of a recently described FLT3 tandem duplication among hematopoietic malignancies, including 112 acute myelocytic leukemia (AML), 55 acute lymphoblastic leukemia (ALL), 37 myelodysplastic syndrome (MDS), 20 chronic myelogenous leukemia (CML), 30 non-Hodgkin's lymphoma (NHL), 14 adult T cell leukemia, 15 chronic lymphocytic leukemia (CLL) and 38 multiple myeloma (MM). We also evaluated 71 cell lines derived from 11 AML, 31 ALL, two hairy cell leukemia, three acute unclassified leukemia, 10 CML, 12 NHL including six Burkitt's lymphoma, and two MM. Using genomic PCR of exon 11 coding for the juxtamembrane (JM) domain and first amino acids of the 5'-tyrosine kinase (TK) domain, this length mutation was found only in AML (22/112, 20%) and MDS (1/37). According to the FAB subclassification, they were 5/18 (28%) of M1, 4/29 (14%) of M2, 3/17 (18%) of M3, 6/24 (25%) of M4, 4/20 (20%) of M5 and 1/9 of refractory anemia with excess of blast in transformation. In the various cell lines examined, this abnormality was determined in only one derived from AML and never found in other hematological malignancies. The sequence analysis of the abnormal PCR products revealed that 23 of 24 showed internal tandem duplication with or without insertion of nucleotides. In one AML, insertion and deletion without duplication was determined. All 24 lengthened sequences were in-frame. Duplication takes place in the sequence coding for the JM domain and leaves the TK domain intact. In conclusion, we emphasize that the length mutation of FLT3 at JM/TK-I domains were restricted to AML and MDS. Since all these mutations resulted in in-frame, this abnormality might function for the proliferation of leukemic cells.
Acute Disease↗
Action of human interleukin-4 and stem cell factor on erythroid and mixed colony formation by peripheral blood-derived CD34+ c-kit(high) or CD34+ c-kit(low) cells.
We studied the interaction of interleukin (IL)-4 and other burst-promoting activity (BPA) factors, such as IL-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-9 and stem cell factor (SCF), on erythroid burst-forming unit (BFU-E) and erythrocyte-containing mixed (CFU-Mix) colony formation in serum-free culture. IL-4 alone did not support mixed colony formation in the presence of erythropoietin (Epo). However, IL-4 showed weak but significant BPA when peripheral blood (PB)-derived CD34+c-kit(low) cells were used as the target population. The BPA of IL-4 was much weaker than that of IL-3, which exerted the most potent activity, as previously reported. When CD34+c-kit(high) cells were used as the target, four factors known to have BPA, IL-3, GM-CSF, IL-9 and SCF, could express BPA. In contrast, IL-4, alone failed to support erythroid burst formation. Interestingly, IL-4 showed a remarkable enhancing effect with SCF in promoting the development of erythroid burst and erythrocyte-containing mixed colonies from CD34+c-kit(low) and CD34+c-kit(high) cells. Delayed addition of SCF+Epo or IL-4+Epo to the cultures initiated with either IL-4 or SCF alone clearly demonstrated that SCF was a survival factor for both BFU-E and CFU-Mix progenitors. In contrast, the survival effect of IL-4 was much weaker than that of SCF, and appeared to be more important for progenitors derived from CD34+c-kit(low) cells than for those derived from CD34+c-kit(high) cells. It was recently reported that CD34+c-kit(low) cells represent a more primitive population than CD34+c-kit(high) cells. Taken together, these results suggest that IL-4 helps to recruit primitive progenitor cells in the presence of SCF.
Antigens, CD34↗
Expression of a betaine aldehyde dehydrogenase gene in rice, a glycinebetaine nonaccumulator, and possible localization of its protein in peroxisomes.
Betaine aldehyde dehydrogenase (BADH) catalyzes the last step in the plant biosynthetic pathway that leads to glycinebetaine. Rice plants (Oryza sativa L.), albeit considered a typical non-glycinebetaine accumulating species, have been found to express this enzyme at low levels. This observation evokes an interest in phylogenic evolution of the enzyme in the plant kingdom. It is reported here that rice plants possess the ability to take up exogenously added betaine aldehyde through the roots and convert it to glycinebetaine, resulting in an enhanced salt-tolerance of the plants. A gene encoding a putative BADH from the rice genome was also cloned and sequenced. The gene was found to contain 14 introns, and the overall nucleotide sequence of the coding region is c. 78% identical to that of the barley BADH cDNA. Cloning of a partial BADH cDNA from rice was accomplished by reverse transcription-polymerase chain reaction (RT-PCR). The nucleotide sequence of the cloned fragment was found to be identical to the corresponding exon regions of the rice genomic BADH gene. The deduced amino acid sequences of rice and barley BADH both contain a C-terminal tripeptide SKL, a signal known to target preproteins to microbodies. This localization was confirmed by an immuno-gold labeling study of transgenic tobacco harboring barley cDNA, which showed BADH protein inside peroxisomes. Northern blot analysis revealed that the level of BADH mRNA is salt-inducible.
Aldehyde Oxidoreductases↗
Pretreatment with topical 60% lidocaine tape reduces pain on injection of propofol.
UNLABELLED: We determined whether pretreatment with topical 60% lidocaine tape reduced the incidence of pain on injection of propofol compared with mixing intravenous lidocaine with propofol. In a randomized, double-blind trial, 90 patients were allocated to one of three groups: pretreatment with a bioocclusive dressing and administration of a premixed solution of propofol 180 mg and 2 mL of normal saline (Group A); pretreatment with 60% lidocaine tape and a premixed solution of propofol and normal saline (Group B); or pretreatment with a bioocclusive dressing and a premixed solution of propofol 180 mg and lidocaine 40 mg (Group C). The incidences of pain in Groups A, B, and C were 86.7%, 33.4%, and 20%, respectively. Group B and Group C had a significantly lower incidence of pain than Group A. There was no significant difference in the incidence of pain between Group B and Group C. There was no significant difference in the distribution of site of pain on injection of propofol among the three groups. Pretreatment with topical 60% lidocaine tape reduced the incidence of pain on injection of propofol similar to that of intravenous lidocaine mixed with propofol. IMPLICATIONS: Pretreatment with topical 60% lidocaine tape reduces the pain associated with injection of propofol, a frequently used intravenous anesthetic. This approach should increase patient comfort during induction of anesthesia.
Administration, Cutaneous↗
Mixed connective tissue disease in childhood: a nationwide retrospective study in Japan.
Sixty-six children with mixed connective tissue disease (MCTD) were analyzed by a nationwide prospective study. The diagnostic significance of Raynaud's phenomenon and positive anti-RNP antibody was confirmed, and additional symptoms including swelling of fingers, facial erythema, and polyarthralgia, and laboratory findings such as positive rheumatoid factor, hypergammaglobulinemia, and increased levels of myogenic enzymes, were variably positive. These clinical and laboratory characteristics of MCTD were critically different from those of systemic lupus erythematosus, indicating that MCTD is an independent entity of disease.
Adolescent↗
Human FLT3 ligand acts on myeloid as well as multipotential progenitors derived from purified CD34+ blood progenitors expressing different levels of c-kit protein.
We studied the effect of human flt3/flk2 ligand (FL) on the proliferation and differentiation of purified CD34+ blood progenitors which express different levels of c-kit protein in clonal cell culture in comparison with that of stem cell factor (SCF). FL alone did not support significant colony formation. However, FL significantly enhanced neutrophil colony (CFU-G) formation in the presence of granulocyte-colony stimulating factor (G-CSF) by peripheral blood (PB)-derived CD34+c-kit- cells which contained a large number of CFU-G. In addition, FL could synergistically increase the number of CFU-G supported by a combination of interleukin (IL)-3 and G-CSF, as did SCF. As we reported previously, SCF showed a significant burst-promoting activity (BPA). In contrast, FL did not exhibit any BPA on PB-derived CD34+c-kithigh cells in which erythroid-burst (BFU-E) was highly enriched. However, FL could synergize with IL-3 or GM-CSF in support of erythrocyte-containing mixed (E-Mix) colony by PB-derived CD34+c-kithigh or low cells in the presence of Epo. Replating of E-Mix colonies derived from CD34+c-kithigh cells supported by IL-3+Epo+SCF yielded more secondary colonies than those supported by IL-3+Epo or IL-3+Epo+FL. When PB-derived CD34+c-kitlow cells which represent a more immature population than CD34+c-kithigh cells were used as the target, number of secondary colonies supported by IL-3+Epo, IL-3+Epo+SCF or IL-3+Epo+FL was comparable. However, the number of lineages expressed in the secondary culture was significantly larger in the primary culture containing IL-3+Epo+FL than in that containing IL-3+Epo. These results suggest that FL not only acts on neutrophilic progenitors, but also on more immature multipotential progenitors.
Antigens, CD↗
[Analysis of children with tuberculosis in the past 20 years].
To characterize the clinical features of childhood tuberculosis, we analyzed the symptoms, signs, and laboratory findings of the 89 children with tuberculosis admitted to the Yokohama City University Hospital from 1975 to 1994. Compared with the numbers of patients admitted from 1975 to 1979, those of patients of the past 5 years (from 1990 to 1994) were reduced by half. Of the 89 subjects, 56.2% were below 3 years of age and 24.7% were under 1 year of age. 51.7% had primary complex and 20.2% had serious tuberculosis (tuberculous meningitis 14.6%, miliary tuberculosis 3.4%, and bone and joint tuberculosis 2.2%). Tuberculous children below 3 years of age consisted of primary complex (60.0%) and serious tuberculosis (32.0%). The majority (86.0%) of tuberculous children below 3 years of age had not received BCG vaccination. In 55 (61.8%) of 89 subjects, the sources of tuberculosis were clarified. Of these subjects, 83.6% were infected in the family. The rate of BCG inocluation tended to decrease with decreasing age, especially that of children below 3 years of age was 14.0%. Of the 89 subjects, only 16.9% proved to be smear-positive. Taken together, in order to eliminate tuberculous children below 3 years of age, the following is necessary; (1) BCG inoculation in early infancy, (2) early diagnosis of index cases with adult tuberculosis, and (3) prompt and appropriate family contact examination.
Adolescent↗