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Biomedical subjects

D Yue

Publications and source records attributed to D Yue.

At least 19 recordsLinked to original sources
PubMed2004

Strong family history predicts a younger age of onset for subjects diagnosed with type 2 diabetes.

AIMS: Age of onset of type 2 diabetes is becoming earlier and with it there is an increase in the development of chronic complications. This study examined the relationship between the strength of family history of diabetes on (i) age of diabetes onset and (ii) prevalence of diabetic complications. RESEARCH DESIGN AND METHODS: Data on family history of diabetes and age of diabetes onset were prospectively collected on 5193 subjects. Family members were deemed to include grandparents, parents, siblings, aunts/uncles and children. To adjust for family size and to assess effects of pathway to diagnosis, we also contacted a subset of 180 patients selected on the basis of the strength of family histories of diabetes. A full assessment for diabetic complications including retinopathy, neuropathy and renal and macrovascular status was performed for the total cohort. RESULTS: The more cases of diabetes found in a family, the younger the age of onset of type 2 diabetes. This phenomenon does not appear to be due to patients with strong family history of diabetes being more concerned about the possibility of having diabetes. The effect of strong family history is also evident in many ethnic groups when examined individually, although they differ from each other in their characteristic age of onset of diabetes. Once adjusted for duration of diabetes, strength of family history does not appear to affect metabolic profiles or prevalence of chronic complications. CONCLUSIONS: There is a strong relationship between the number of affected family members with diabetes and age of developing diabetes. The genetic and environmental factors underlying this phenomenon remain to be elucidated. However, it may be one of the reasons explaining why type 2 diabetes is affecting younger people worldwide.

Adult↗
PubMed2001

Clustering of cardiovascular risk factors with diabetes in Chinese patients: the effects of sex and hyperinsulinaemia.

OBJECTIVE: This study was designed to investigate factors which affect the clustering of cardiovascular risk factors with diabetes in Chinese patients. RESEARCH DESIGN AND METHODS: Six hundred and fifty-four patients with diabetes were assessed comprehensively for diabetes complications and cardiovascular risk factors in a metropolitan hospital in Beijing, China. Insulin resistance and secretion were also evaluated by measurement of glucose and insulin levels before and after a meal tolerance test. Results were analysed according to patient groups stratified by the number of cardiovascular risk factors coexisting with diabetes. RESULTS: Cardiovascular risk factors were common in Chinese diabetic patients. The clustering of three or more of these factors with diabetes occurred more often than by chance alone and was associated with postprandial hyperinsulinaemia. Patients with a high number of risk factors were more prone to macrovascular events but did not have higher albuminuria. Using the commonly adopted lower threshold for diagnosing obesity and central obesity in women, there were more women with multiple risk factors. However, this disappeared if the same criteria were used for men and women. Even in the presence of diabetes, cardiovascular risk factors were inadequately controlled in most patients. CONCLUSIONS: The concurrence of diabetes and other cardiovascular risk factors which constitute the metabolic syndrome is a common phenomenon in urban Chinese diabetic patients. It is associated with hyperinsulinaemia and possibly the female sex. This study emphasises the importance of public health measures to control cardiovascular risk factors in patients with diabetes.

Aged↗
PubMed1999

Synthetase recognition determinants of E. coli valine transfer RNA.

We have studied the interactions between Escherichia coli tRNAVal and valyl-tRNA synthetase (ValRS) by enzymatic footprinting with nuclease S1 and ribonuclease V1, and by analysis of the aminoacylation kinetics of mutant tRNAVal transcripts. Valyl-tRNA synthetase specifically protects the anticodon loop, the 3' side of the stacked T-stem/acceptor-stem helix, and the 5' side of the anticodon stem of tRNAVal against cleavage by double- and single-strand-specific nucleases. Increased nuclease susceptibility at the ends of the anticodon- and T-stems in the tRNAVal.ValRS complex is indicative of enzyme-induced conformational changes in the tRNA. The most important synthetase recognition determinants are the middle and 3' anticodon nucleotides (A35 and C36, respectively); G20, in the variable pocket, and G45, in the tRNA central core, are minor recognition elements. The discriminator base, position 73, and the anticodon stem also are recognized by ValRS. Replacing wild-type A73 with G73 reduces the aminoacylation efficiency more than 40-fold. However, the C73 and U73 mutants remain good substrates for ValRS, suggesting that guanosine at position 73 acts as a negative determinant. The amino acid acceptor arm of tRNAVal contains no other synthetase recognition nucleotides, but regular A-type RNA helix geometry in the acceptor stem is essential [Liu, M., et al. (1997) Nucleic Acids Res. 25, 4883-4890]. In the anticodon stem, converting the U29:A41 base pair to C29:G41 reduces the aminoacylation efficiency 50-fold. This is apparently due to the rigidity of the anticodon stem caused by the presence of five consecutive C:G base pairs, since the A29:U41 mutant is readily aminoacylated. Identity switch experiments provide additional evidence for a role of the anticodon stem in synthetase recognition. The valine recognition determinants, A35, C36, A73, G20, G45, and a regular A-RNA acceptor helix are insufficient to transform E. coli tRNAPhe into an effective valine acceptor. Replacing the anticodon stem of tRNAPhe with that of tRNAVal, however, converts the tRNA into a good substrate for ValRS. These experiments confirm G45 as a minor ValRS recognition element.

Anticodon↗
PubMed1999

Diabetic retinopathy and nephropathy in Fiji: comparison with data from an Australian diabetes centre.

BACKGROUND: As part of a project to improve diabetes care in Fiji, we assessed the magnitude of problems posed by diabetic retinopathy in that country and compared the findings with those from an Australian diabetes centre. The relationship between diabetic retinopathy and nephropathy was also examined in a subset of patients. METHODS: A medical team from Australia screened a total of 446 type 2 diabetic patients (ethnicity: Fijian/Indian 16/84%) for diabetic retinopathy in five towns from the Division of Viti Levu, Fiji. The findings were compared with data obtained from 1659 type 2 diabetic patients who had attended an Australian diabetes centre (ethnicity Indian/ Anglo-Celtic 12/88%). In both cohorts, retinopathy was assessed by direct fundoscopy and a spot urine sample was collected for determination of albuminuria (defined as a concentration > 50 mg/L). RESULTS: The prevalence of diabetic retinopathy increased linearly with duration of diabetes. It was higher in Fiji, even when cases from the same ethnicity (i.e. Indians) and duration were compared (P < 0.05). Extrapolation of the data points suggests a delay in the diagnosis of diabetes in Fiji. Of those patients with retinopathy in Fiji, more than half had moderate to severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy, significantly higher than patients in the Australian cohort (chi2 = 29.2; P < 0.0001). Retinopathy was not a predictor of albuminuria in Fijian Indians (chi2 = 0.4; P = 0.5). In contrast, Australian Indians with retinopathy had significantly more albuminuria (chi2 = 10.2; P = 0.001). CONCLUSIONS: Severe diabetic retinopathy is common in both ethnic groups in Fiji. A delay in the diagnosis of diabetes as well as poor glycaemic control are possible factors. The availability of laser therapy is important to prevent loss of vision, but it is also essential that appropriate training of health professionals is integrated with a programme of diabetic complication screening to support this form of therapy.

Adult↗
PubMed1998

The CCA-adding enzyme has a single active site.

The CCA-adding enzyme (tRNA nucleotidyltransferase) synthesizes and repairs the 3'-terminal CCA sequence of tRNA. The eubacterial, eukaryotic, and archaeal CCA-adding enzymes all share a single active-site signature motif, which identifies these enzymes as belonging to the nucleotidyltransferase superfamily. Here we show that mutations at Asp-53 or Asp-55 of the Sulfolobus shibatae signature sequence abolish addition of both C and A, demonstrating that a single active site is responsible for addition of both nucleotides. Mutations at Asp-106 (and to a lesser extent, at Glu-173 and Asp-215) selectively impaired addition of A, but not C. We have previously demonstrated that the tRNA acceptor stem remains fixed on the surface of the CCA-adding enzyme during C and A addition (Shi, P.-Y., Maizels, N., and Weiner, A. M. (1998) EMBO J. 17, 3197-3206). Taken together with this new evidence that there is a single active site for catalysis, our data suggest that specificity of nucleotide addition is determined by a process of collaborative templating: as the single active site catalyzes addition of each nucleotide, the growing 3'-end of the tRNA would progressively refold to create a binding pocket for addition of the next nucleotide.

Adenosine Triphosphate↗
PubMed1998

Identification of candidate target genes for EVI-1, a zinc finger oncoprotein, using a novel selection strategy.

We have sought to identify and isolate target genes for the zinc finger protein, EVI-1, which has been implicated in the genesis of myelogenous leukemia both in mouse and human. We have approached this with a two-step selection: we first selected for genomic fragments of mouse DNA that bind to the protein with high affinity; second, we employed cDNA hybrid selection to identify gene sequences contained within these fragments. We show that we have constructed a sublibrary of genomic fragments that contains a significant fraction of the EVI-1-binding sites in the mouse genome. Our data has allowed us to estimate that there are approximately 4300 binding sites per haploid genome in the mouse. We further demonstrate that by using cDNA hybrid selection, it is relatively straightforward to isolate cDNAs that correspond to genes embedded in the EVI-1-binding sublibrary. Several of these are novel, but are represented in databases of anonymous human or mouse cDNAs (expressed sequence tags). One selected gene is Itpr2, encoding the inositol trisphosphate type two receptor, which is transcriptionally regulated during myelopoiesis. Finally, using a chimeric EVI-1-VP16-fusion protein under the control of a tetracycline-regulated system, we have shown that this chimeric activator can directly regulate Itpr2.

3T3 Cells↗
PubMed1996

Changes of extracellular matrix in a baboon (Papio hamadryas) model of insulin dependent diabetes: studies using electron microscopy and X-ray diffraction techniques.

Extracellular matrix plays an important role in many physiological functions and its abnormalities are thought to play a key role in the pathogenesis of diabetic complications. In this paper we used the techniques of electron microscopy, immunostaining and X-ray diffraction to document some of the early events in the changes of extracellular matrix in a model of insulin dependent diabetes in baboons. Our results show that thickening of basement membrane and enlargement of mesangium are demonstrable in the glomeruli of prepubertal diabetic baboons within 2 years from the onset of diabetes. Concomitant with this was the accumulation of type IV collagen and laminin in the mesangium. By contrast, even the very sensitive technique of X-ray diffraction failed to demonstrate changes in the equatorial direction of collagen molecules of the skin and tendon. We conclude that changes of glomerular extracellular matrix are demonstrable early in insulin dependent diabetes even in prepubertal baboons. These can be used as endpoints in evaluating the efficacy of pharmacological agents such as aminoguanidine in preventing diabetic complications.

Animals↗
PubMed1996

CCA-adding enzymes and poly(A) polymerases are all members of the same nucleotidyltransferase superfamily: characterization of the CCA-adding enzyme from the archaeal hyperthermophile Sulfolobus shibatae.

We describe the purification, cloning, and characterization of the CCA-adding enzyme [ATP(CTP):tRNA nucleotidyl transferase] from the thermophilic archaebacterium, Sulfolobus shibatae. Characterization of an archaeal CCA-adding enzyme provides formal proof that the CCA-adding activity is present in all three contemporary kingdoms. Antibodies raised against recombinant, expressed Sulfolobus CCA-adding enzyme reacted specifically with the 48-kDa protein and fully depleted all CCA-adding activity from S. shibatae crude extract. Thus, the cloned cca gene encodes the only CCA-adding activity in S. shibatae. Remarkably, the archaeal CCA-adding enzyme exhibits no strong homology to either the eubacterial or eukaryotic CCA-adding enzymes. Nonetheless, it does possess the active site signature G[SG][LIVMFY]xR[GQ]x5,6D[LIVM][CLIVMFY]3-5 of the nucleotidyltransferase superfamily identified by Holm and Sander (1995, Trends Biochem Sci 20:345-347) and sequence comparisons show that all known CCA-adding enzymes and poly(A) polymerases are contained within this superfamily. Moreover, we propose that the superfamily can now be divided into two (and possibly three) subfamilies: class I, which contains the archaeal CCA-adding enzyme, eukaryotic poly(A) polymerases, and DNA polymerase beta; class II, which contains eubacterial and eukaryotic CCA-adding enzymes, and eubacterial poly(A) polymerases; and possibly a third class containing eubacterial polynucleotide phosphorylases. One implication of these data is that there may have been intraconversion of CCA-adding and poly(A) polymerase activities early in evolution.

Amino Acid Sequence↗
PubMed1995

A baboon (Papio hamadryas) model of insulin-dependent diabetes.

Over a period of four years, streptozocin has been used to induce diabetes in 10 baboons, all of whom are insulin dependent. We describe our experience with their husbandry, induction of diabetes, insulin therapy, metabolic control and growth rate. Streptozocin dosage of 60 mg/kg readily induces hyperglycemia with minimal hepatic or renal toxicity. Using a once daily injection of mixed short and intermediate acting insulins at a dosage of 2-4 U/kg, it is possible to maintain a degree of metabolic control similar to that attained in patients.

Aging↗
PubMed1995

[Experimental steroid osteonecrosis in rabbits and pathologic findings].

Osteonecrosis of femoral head was experimentally induced in adult rabbits by employing a combined protocol of hypersensitive vasculitis and administration of high dose corticosteroids. By using India ink introartery infusion microangiography and pathologic examination, we found that the damage of terminal arterioles and interruption of blood supply of terminal arteriole was causative pathogenesis. In the early phase, the haemopoietic necrosis and enlargement of fat cell in the bone marrow occurred. The perfused arterioles decreased, especially in the subchondrol bone. In the later phase, the osteocytes showed necrotic fibrosis in bone marrow. The perfused arterioles increased gradually and repairtive changes began.

Animals↗
PubMed1994

Nucleoside modifications stabilize Mg2+ binding in Escherichia coli tRNA(Val): an imino proton NMR investigation.

The structures of in vitro transcribed Escherichia coli tRNA(Val), which lacks base modifications, and the native tRNA, which contains them, are very similar in the presence of excess Mg2+ (Kintanar, Yue, and Horowitz, unpublished results). To further probe the effects of base modifications on the structure of tRNA, the Mg2+ ion dependence of the downfield region of the 1H NMR spectrum of in vitro transcribed E. coli tRNA(Val) in aqueous phosphate buffer was investigated. The spectra indicate a remarkable conformational change in unmodified E. coli tRNA(Val) coincident with binding or release of Mg2+. Assignment of the imino proton resonances in the low Mg2+ form of the tRNA transcript allows a detailed description of the conformational change. There is near total disruption of the D stem and tertiary interactions in the absence of bound Mg2+. A new strong interaction between the U67-A6 base pair and the G50-U64 wobble pair is observed, indicating a substantial structural rearrangement at the junction of the acceptor and T stems. The binding constants of the strong Mg2+ binding sites in the D loop and near the D stem in unmodified tRNA(Val) are at least 2 orders of magnitude less than in tRNAVal containing base modifications. The metal ion binding site in the anticodon loop is somewhat stronger than metal ion binding sites in the D loop and stem in unmodified tRNA(Val), but it is still weaker than all strong Mg2+ binding sites in native tRNA(Val). Thus, one role of the base modifications found in tRNA is to stabilize or strengthen the Mg2+ binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Effect of nucleoside modifications on the structure and thermal stability of Escherichia coli valine tRNA.

Transfer RNA transcribed in vitro lacks the base modifications found in native tRNA. To understand the effect of base modifications on the structure of tRNA, the downfield region of the 1H NMR spectrum of in vitro transcribed E coli tRNAVal in aqueous phosphate buffer in the presence of excess Mg2+ was investigated. The resonances of all imino protons involved in hydrogen bonds in the helical stem regions and in tertiary interactions were assigned using two-dimensional nuclear Overhauser enhancement spectroscopy (NOESY) and one-dimensional difference nuclear Overhauser effect (NOE) methods. In addition, some aromatic C2 and C8 proton resonances as well as one amino proton resonance were assigned. The chemical shifts of the assigned resonances of unmodified E coli tRNAVal were compared with those of the native tRNA molecule under similar solution conditions. The similarity of the NMR data for unmodified and modified tRNA indicates that the in vitro transcribed tRNA has nearly the same solution structure as the native molecule in the presence of excess Mg2+. The only significant differences were the chemical shifts of resonances corresponding to protons in (or interacting with) bases, indicating the possibility of local structural perturbations. The thermal stability of E coli modified and unmodified tRNAVal in the presence of Mg2+ was also investigated by analyzing the temperature dependence of the imino proton spectra. Several tertiary interactions involving modified nucleosides in native E coli tRNAVal are less stable in the absence of base modifications.

Base Composition↗