Calculations of the ground-state energy for strong- and intermediate-coupling exciton-phonon systems.
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Journal Article↗
Biomedical subjects
W Yi
Publications and source records attributed to W Yi.
cDNA and genomic cloning of human palmitoyl-protein thioesterase (PPT), the enzyme defective in infantile neuronal ceroid lipofuscinosis.
Palmitoyl-protein thioesterase (PPT) is a small glycoprotein that removes palmitate groups from cysteine residues in lipid-modified proteins. We recently reported mutations in PPT in patients with infantile neuronal ceroid lipofuscinosis (INCL), a severe neurodegenerative disorder (J. Vesa et al., 1995, Nature 376: 584-587). INCL is characterized by the accumulation of proteolipid storage material in brain and other tissues, suggesting that the disease is a consequence of abnormal catabolism of acylated proteins. In the current paper, we report the sequence of the human PPT cDNA and the structure of the human PPT gene. The cDNA predicts a protein of 306 amino acids that contains a 25-amino-acid signal peptide, three N-linked glycosylation sites, and consensus motifs characteristic of thioesterases. Northern analysis of a human tissue blot revealed ubiquitous expression of a single 2.5-kb mRNA, with highest expression in lung, brain, and heart. The human PPT gene spans 25 kb and is composed of seven coding exons and a large eighth exon, containing the entire 3'-untranslated region of 1388 bp. An Alu repeat and promoter elements corresponding to putative binding sites for several general transcription factors were identified in the 1060 nucleotides upstream of the transcription start site. The human PPT cDNA sequence and gene structure will provide the means for the identification of further causative mutations in INCL and facilitate genetic screening in selected high-risk populations.
Amino Acid Sequence↗
Growth hormone receptor cytoplasmic domain differentially promotes tyrosine phosphorylation of signal transducers and activators of transcription 5b and 3 by activated JAK2 kinase.
GH-induced activation of JAK2, a GH receptor (GHR)-associated tyrosine kinase, leads to tyrosine phosphorylation and activation of STATs (signal transducers and activators of transcription) 1, 3, and 5. The present study investigates the importance of the GHR cytoplasmic domain in the activation of STAT3 and STAT5b. As the perimembranous Box1 region of the GHR cytoplasmic domain is necessary for activation of wild-type (WT) JAK2 by GH, we examined this question using GHR/JAK2 chimeras that have an activatable JAK2 kinase domain replacing the GHR cytoplasmic domain. STAT5b and STAT3, when each was coexpressed in COS-7 cells with WT GHR and WT JAK2, were both strongly tyrosine phosphorylated in response to GH. Coexpression of STAT3 with GHR/ JAK2 chimeras resulted in a strong GH-independent tyrosine phosphorylation of STAT3 that was 40% as active as that seen with WT GHR plus WT JAK2, whereas STAT5b was more minimally phosphorylated (13% of WT GHR plus WT JAK2) when coexpressed with chimeras devoid of the GHR cytoplasmic domain. Transient coexpression of each STAT together with WT JAK2 and GHR COOH-terminal truncation mutants indicated that a GH-induced STAT3-DNA binding complex, but not a STAT5b-DNA binding complex, was detectable when a GHR devoid of 85% of the cytoplasmic domain COOH-terminus (but eliciting significant JAK2 tyrosine phosphorylation) was expressed. In vitro binding experiments using GST/GHR cytoplasmic domain fusions demonstrated that both STATs could interact at a low basal level with GHR regions distal to residue 317. Phosphorylation of tyrosine residues in those distal regions greatly enhanced the receptor's interaction with STAT5b, but not STAT3. We conclude that GH induces activation of STAT3 and STAT5b by two different pathways: one primarily dependent on activation of JAK2 (STAT3) and another that is additionally reliant on the presence of an intact and tyrosine-phosphorylated GHR cytoplasmic domain (STAT5b).
Animals↗
Regions of the JAK2 tyrosine kinase required for coupling to the growth hormone receptor.
Growth hormone (GH) treatment of cells promotes activation of JAK2, a GH receptor (GHR)-associated tyrosine kinase. We now explore JAK2 regions required for GHR-induced signaling. Wild-type (WT) JAK2 and JAK2 molecules with deletions of the amino terminus (JAK2ATD), carboxyl terminus (JAK2CTD), or kinase-like domain (JAK2PKD) were each transiently coexpressed in COS-7 cells with the rabbit GHR. The following responses were assayed: GH-induced transactivation of a luciferase reporter governed by a c-fos enhancer element; GH-induced shift in the molecular mass of a cotransfected epitope-tagged extracellular signal-regulated kinase molecule; and GH-induced antiphosphotyrosine immunoprecipitability of the transfected JAK2 form. In each assay, WTJAK2 and JAK2PKD allowed GH-induced signaling, whereas JAK2ATD and JAK2CTD did not. Anti-GHR serum coimmunoprecipitated WTJAK2, JAK2PKD, and JAK2CTD, but not JAK2ATD. Finally, a chimera in which the JAK2 kinase domain replaced the GHR cytoplasmic domain signaled GH-induced transactivation. We conclude: 1) kinase-like domain deletion eliminates neither physical nor functional interaction between JAK2 and the GHR; 2) kinase domain deletion eliminates functional but not physical coupling of JAK2 to the GHR; 3) interaction with the GHR appears dependent on the NH2-terminal one-fifth of JAK2; and 4) a GH-responsive signaling unit can include as little as the GHR external and transmembrane domains and the JAK2 kinase domain.
Amino Acid Sequence↗
Detection of congenital cytomegalovirus infection by using chorionic villi of the early pregnancy and polymerase chain reaction.
OBJECTIVE: To detect congenital cytomegalovirus (CMV) infection of chorionic villi in early pregnancy. METHODS: Extraction of DNA of chorionic villi and amplification of the gene of major immediate-early (MIE) antigen of CMV using a polymerase chain reaction (PCR). RESULTS: Sixty-eight specimens of chorionic villi and 16 specimens were positive for CMV infection by PCR. The incidence of congenital CMV infection in the first trimester of pregnancy was 23.5%. CONCLUSIONS: The risk of transmission of CMV from mother to fetus in early pregnancy is very high and potential CMV carriers may transmit CMV to their fetus in early pregnancy.
Chorionic Villi↗
Purification and characterization of a poly-L-lysine-activated serine endoprotease from Lumbricus rubellus.
An endoprotease in earthworm (Lumbricus rubellus) is purified to apparent homogeneity using 125I-lactalbumin as a substrate. The protease has a molecular mass of 27 kDa and is markedly activated by poly-L-lysine or poly-L-arginine. It is a chymotrypsin-like serine protease. Its activity is distributed to coelomic fluid but relatively little to coelomocytes.
Amino Acid Sequence↗
Dental caries in preschool Beijing and Connecticut children as described by a new caries analysis system.
A total of 625 children, 3-4 yr old, 426 from Connecticut Head Start programs and 199 from Beijing area nursery schools, were clinically examined for dental caries. Results were analyzed using the traditional dmfs index as well as a new "Caries Analysis System". This new system differentiated between caries patterns and examined the percentage of affected children (Prevalence), the degree to which these children were affected (Severity) and the proportion of total caries each disease pattern represented (Distribution). The Caries Analysis System revealed differences in caries experience and patterns among the racial/ethnic groups that the dmfs index did not. The Beijing children experienced the greatest Prevalence of all caries patterns; however, the Severity and Distribution of the caries patterns were similar to those of the Connecticut children. Within the group of Connecticut children, White children had the lowest Prevalence but the greatest Severity when compared with the Black and Hispanic children.
Child, Preschool↗
Determinants of endothelium-dependent femoral artery vasodilation in youth.
OBJECTIVE: Decreased endothelium-dependent arterial dilation to reactive hyperemia has been shown in adults to be associated with various manifestations of cardiovascular diseases and cardiovascular risk factors. In a sample of children, we examined the relationships between flow-mediated femoral artery dilation and anthropometric, demographic, cardiovascular, and serum lipid variables that have been associated with cardiovascular diseases. METHOD: Thirty-three asymptomatic, healthy 11 to 14 years olds were randomly selected from participants in a longitudinal cardiovascular health study. There were 17 boys and 16 girls; 21 whites and 12 blacks. Sixteen had documented family history of premature myocardial infarction (ie, < or = 55 years of age) in first-degree relatives and 17 did not. Measurements included fasting lipids, anthropometrics, blood pressure and heart rate at rest and during supine exercise, postural change, and forehead cold stimulation. Femoral artery dilation to reactive hyperemia was measured via high resolution ultrasound. RESULTS: Bivariate analyses indicated flow-mediated dilation was negatively correlated with systolic pressure increases to postural change, forehead cold stimulation and dynamic exercise, greater average skinfold thickness, and body fat via dual x-ray absorptiometry and positively correlated with cardiovascular fitness (all ps < .05). Stepwise multiple regression revealed that cardiovascular fitness and systolic pressure reactivity to exercise significantly predicted flow-mediated dilation accounting for 31% of the variance (p < .01). CONCLUSIONS: Decreased flow-mediated dilation is associated with decreased cardiovascular fitness, increased systolic pressure reactivity to various stressors, and increased indices of body fatness in asymptomatic youth. Further research is warranted to better understand early relationships between this noninvasive measure of endothelial function and cardiovascular risk factors in youth.
Adolescent↗
Endometrial cancer patients have a significant risk of harboring isolated tumor cells in histologically negative lymph nodes.
In this study, we examine the prevalence of finding isolated tumor cells (ITCs) in negative lymph nodes of endometrial cancer patients using immunohistochemistry. Seventy-six endometrial cancer patients with lymph nodes histologically negative for metastatic disease were examined. Nodal tissue sections were stained with anticytokeratin antibodies AE-1 and CAM 5.2. Nodes with single or groups of cells (two to four cells) < or =0.2 mm and showing cytokeratin reactivity were positive for ITCs. Findings were compared to features of the primary tumor and patient outcome. ITCs were present in 31 of 1712 lymph nodes. Fifteen (19.7%) patients had ITC-positive nodes. ITCs involved only pelvic nodes in nine cases, only para-aortic nodes in five cases, and pelvic and para-aortic in one case. Tumor in adnexa was the only pathologic feature associated with nodal ITCs (P= 0.0485). All 15 patients with nodal ITCs were alive at follow-up. One (6.7%) patient suffered recurrent disease but was alive at last encounter. Disease recurred in 5 (8.8%) of 57 patients without nodal ITCs. Two are alive without disease, two alive with disease, and one died from her cancer. In summary, a significant proportion of endometrial cancer patients have ITCs detected by immunohistochemistry in histologically negative regional lymph nodes.
Adult↗