Perforating papules in chronic renal failure. Metastatic calcinosis cutis with transepidermal elimination.
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Adult↗
Biomedical subjects
W Huang
Publications and source records attributed to W Huang.
Localization of basic residues required for receptor binding to the single alpha-helix of the receptor binding domain of human alpha2-macroglobulin.
To better understand the structural basis for the binding of proteinase-transformed human alpha2-macroglobulin (alpha2M) to its receptor, we have used three-dimensional multinuclear NMR spectroscopy to determine the secondary structure of the receptor binding domain (RBD) of human alpha2M. Assignment of the backbone NMR resonances of RBD was made using 13C/15-N and 15N-enriched RBD expressed in Escherichia coli. The secondary structure of RBD was determined using 1H and 13C chemical shift indices and inter- and intrachain nuclear Overhauser enhancements. The secondary structure consists of eight strands in beta-conformation and one alpha-helix, which together comprise 44% of the protein. The beta-strands form three regions of antiparallel beta-sheet. The two lysines previously identified as being critical for receptor binding are located in (Lys1374), and immediately adjacent to (Lys1370) the alpha-helix, which also contains an (Arg1378). Secondary structure predictions of other alpha-macroglobulins show the conservation of this alpha-helix and suggest an important role for this helix and for basic residues within it for receptor binding.
Amino Acid Sequence↗
ESR and U-series analyses of teeth from the palaeoanthropological site of Hexian, Anhui Province, China.
ESR and U-series analyses of teeth from the palaeoanthropological site of Hexian which contained Homo erectus remains, illustrate the limited effectiveness of stand-alone ESR and U-series age estimates on faunal materials. The problem lies in the unknown U-uptake history causing very large uncertainties in the age results of both techniques. This study demonstrates the particular strength that lies in the integration of ESR and U-series dating analyses allowing the estimation of the U-uptake history. We obtained a combined ESR/U-series age estimate of 412 +/- 25 ka (average of six analyses on two teeth). This pinpoints the deposition of the faunal remains to the time of the transition between oxygen isotope stages 12 and 11. This is in agreement with the faunal composition which show a mixture of cold adapted northern mammals and more subtropical-tropical southern elements. The age also implies that the advanced Hexian Homo erectus occurred at a similar time as the less advanced Homo erectus specimens at Locality 1 at Zhoukoudian (LI-LIII).
Animals↗
SKF 38393 enhances odor detection performance.
The purpose of this study was to determine the influence of the D1-selective partial agonist SKF 38393 on the odor detection performance of rats using high precision olfactometry and a go/no-go operant task. Previous studies have found that the D2 receptor partial agonist quinpirole decreases such performance, but the influences of D1 receptor activation are unknown. In experiment 1, such detection performance to the odorant ethyl acetate was enhanced by SKF 38393, relative to saline, in male rats at 7.5 and 10.0 mg/kg i.p. dose levels, but not at the lower doses of 1.0, 2.5, and 5.0 mg/kg. In experiment 2, this enhancement was replicated at the 7.5 and 10.0 mg/kg doses and was shown to occur at the 12.5 mg/kg dose as well. In experiment 3, similar enhancement was shown for the odorant eugenol in female rats at the 7.5, 10.0 and 12.5 mg/kg doses, suggesting this effect is neither sex-specific nor confined to the odorant ethyl acetate. In experiment 4, a 0.025 mg/kg dose of the D1 receptor antagonist SCH 23390 depressed the enhancement produced to ethyl acetate by 7.5 mg/kg SKF 38393 to control levels. Overall, these data demonstrate that, in contrast to quinpirole, SKF 38393 improves odor detection performance in the rat and that this phenomenon can be attenuated by the D1 receptor blocker SCH 23390.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
The Bw4/Bw6 difference between HLA-B*0802 and HLA-B*0801 changes the peptides endogenously bound and the stimulation of alloreactive T cells.
HLA-B*0801 is unique among HLA-B allotypes in having dominant amino acid anchors at positions 3 and 5 of the peptide-binding motif. HLA-B*0802 is a variant of HLA-B*0801 in which the Bw6 sequence motif is replaced by a Bw4 sequence motif. This change, involving substitutions at positions 77, 80, 81, 82, and 83 of the B*08 heavy chain, is probably the result of a single evolutionary event of interallelic conversion. Moreover, the difference between B*0802 and B*0801 is sufficient to stimulate a cytotoxic T-cell response. To assess further the functional impact of the Bw4 motif on a B8 background, we compared the peptide-binding specificity of the B*0801 and B*0802 allotypes by sequencing the mixture of peptides endogenously bound to B*0802 and 12 individual peptides purified from that mixture. The HLA-B*0802 allotype, while able to bind some peptides bound by B*0801, has a broader repertoire of endogenously bound peptides than B*0801: the peptides bound by B*0802 are more variable in length and exhibit greater diversity in the carboxyl-terminal amino acid which interacts with the F pocket.
Amino Acid Sequence↗
Backwards bifurcations and catastrophe in simple models of fatal diseases.
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Acquired Immunodeficiency Syndrome↗
Characterization of mutations in patients with autoimmune polyglandular syndrome type 1 (APS1).
Autoimmune polyglandular syndrome type 1 (APS1), also known as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), is an autosomal recessive disorder characterized by the failure of several endocrine glands as well as nonendocrine organs. The autoimmune regulator (AIRE) gene responsible for APS1 on chromosome 21q22.3 has recently been identified. Here, we have characterized mutations in the AIRE gene by direct DNA sequencing in 16 unrelated APS1 families ascertained mainly from the USA. Our analyses identified four different mutations (a 13-bp deletion, a 2-bp insertion, one nonsense mutation, and one potential splice/donor site mutation) that are likely to be pathogenic. Fifty-six percent (9/16) of the patients contained at least one copy of a 13-bp deletion (1094-1106del) in exon 8 (seven homozygotes and two compound heterozygotes). A nonsense mutation (R257X) in exon 6 was also found in 31.3% (5/16) of the USA patients. These data are important for genetic diagnosis and counseling for families with autoimmune endocrine syndromes.
Female↗
Alteration in the brain content of substance P (1-7) during withdrawal in morphine-dependent rats.
Previous studies have shown that substance P (SP) may modulate the abstinence reaction to opioid withdrawal. Its N-terminal fragment SP1-7 may inhibit the intensity of the withdrawal reactions in morphine dependent mice. This study was designed to determine whether the endogenous concentrations of the SP1-7 fragment in the brain are affected during naloxone-precipitated withdrawal in the male rat. The amounts of the peptide was assessed by a specific radioimmunoassay in extracts of discrete brain regions (including the cerebral cortex, hippocampus, hypothalamus, nucleus accumbens, striatum, substantia nigra, ventral tegmental area and the spinal cord) during morphine tolerance and withdrawal. The results indicated that the concentrations of SP1-7 were significantly elevated in the ventral tegmental area both in morphine tolerant rats and during naloxone-precipitated withdrawal. During morphine withdrawal significant increases in the peptide concentration were also observed in the hypothalamus and the spinal cord. It was concluded that the enhanced content of SP1-7 may also indicate the involvement of the SP system during opioid withdrawal in the rat. The enhanced production of SP1-7 may reflect an increased release and/or metabolism of SP, which, in turn, counteracts the withdrawal.
Animals↗
Drug trafficking and drug use among urban African-American adolescents: a causal analysis.
OBJECTIVE: To test the hypothesis that involvement in drug trafficking leads to illicit drug use among urban African-American adolescents. METHODS: Self-reports of substance use, illicit drug use, and drug trafficking were obtained at baseline and every 6 months for 24 months from 383 African-American early adolescents. Transitions between involvement in drug trafficking and illicit drug use over time were examined. Path analysis was conducted to examine the causal relation between drug trafficking and drug use. RESULTS: Among the 35 youth who were initially involved only in drug trafficking, 22 (67%) subsequently used illicit drugs. Of the 53 youth who were initially involved only in illicit drug use, only 19 (42%) continued using drugs at later waves (p < 0.05). Path analysis revealed that baseline drug trafficking had a strong effect on subsequent drug trafficking and drug use, whereas baseline drug use did not have an effect on subsequent drug use or drug trafficking. CONCLUSIONS: Initiation of drug trafficking by adolescents appears to lead to sustained involvement in drug-related activities, including continued drug trafficking and drug use. By contrast, initiation of drug use does not necessarily lead to continued involvement in drug-related behaviors.
Adolescent↗
Superantigen activation and kinetics of cytokines in the Long-Evans rat.
This study was conducted to identify and quantify, over time, selected cytokine responses in Long-Evans rats that were exposed to staphylococcus enterotoxin B (SEB). The kinetics of selected cytokines [interleukin-2 (IL-2), IL-6, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF)] and phenotype and cell cycle analysis of T lymphocytes were determined in Long-Evans rats administered a single intraperitoneal (i.p.) dose of either 50 microg or 500 microg of SEB. Rats injected with 50 microg SEB had significantly elevated levels of IL-2, IL-6 and IFN-gamma in their serum 2 hr post-injection. IL-2 serum levels were significantly elevated at 2 hr and returned to near control values by 12 hr while both IL-6 and IFN-gamma peaked at 6 hr but remained significantly increased at 24 hr post SEB exposure. A 500 microg dose of SEB did not further enhance these cytokine responses. When spleen cells were collected for culture 2 hr after rats were injected i.p. with 50 microg SEB and cocultured with SEB, TNF and IL-6 levels were significantly increased after 2 hr incubation, while IL-2 and IL-6 were significantly elevated at 6 hr. Production of all these cytokines in spleen cell cultures continued to increase over the 24 hr sampled. Peritoneal cells were collected for culture either at 1 hr or 2 hr after injection of either 50 microg or 500 microg of SEB. IL-6 was significantly increased after 1 hr in culture while TNF was significantly increased by 2 hr regardless of whether the cells were harvested 1 or 2 hr after SEB injection. The greatest response for both IL-6 and TNF occurred when cells from animals injected with 50 microg SEB were restimulated in vitro with SEB. The peak levels for IL-6 were at 12 hr post SEB exposure while TNF peaked at 6 hr. The percentage of CD4+ cells was significantly increased at 48 hr and 72 hr post SEB (50 microg) administration while the percentage of CD8+ cells remained similar to control values for the 168-hr test period. A similar pattern was observed in cell cycling where the CD4+ cells proliferated up to 2 days post SEB injection and then were significantly suppressed at day 3. The CD8+ cells were comparable to control values. These studies demonstrate that the cytokine responses in Long-Evans rats exposed to a superantigen are somewhat similar to those that occur in mice and humans, e.g. a rapid short increase in the production of IFN-gamma and TNF that was accompanied by an increase in the production of IL-2. Additional responses noted in this species, however, were a marked increase in IL-6 production, as well as an early increase in the number and cycling of CD4+ cells followed by a down-regulation of these events. These activities occurred in the absence of notable histopathological alteration of lymphoid organs. The results indicate that the Long-Evans rat is an acceptable animal model to investigate the pathogenesis of superantigen-induced disease and that IL-6 may be an active mediator of this process.
Animals↗
Cloning and functional characterization of a sigma receptor from rat brain.
We have cloned a sigma receptor from rat brain and established its functional identity using a heterologous expression system. The cloned cDNA (1,582 bp long) codes for a protein of 223 amino acids that possesses a single putative transmembrane domain. The amino acid sequence of the rat brain sigma receptor is highly homologous to that of the sigma receptor recently cloned from guinea pig liver and a human placental cell line but is not related to any other known mammalian receptors. When expressed in HeLa cells, the rat brain sigma receptor cDNA leads to a two- to threefold increase in haloperidol binding, and this cDNA-induced binding is sensitive to inhibition by several sigma receptor-specific ligands. Kinetic analysis using the heterologous expression system has revealed that the rat brain sigma receptor interacts with haloperidol with an apparent dissociation constant (K(D)) of 3 nM. Functional expression of the cloned rat brain sigma receptor in HeLa cells also leads to an increase in the binding of two other sigma ligands, namely, (+)-pentazocine and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (PPP). Pharmacological characterization of the cloned rat brain sigma receptor reveals that it exhibits severalfold higher affinity for clorgyline than for 1 ,3-di(2-tolyl)guanidine, it interacts with progesterone and testosterone, and its interaction with PPP is markedly enhanced by phenytoin. In addition, transfection of MCF-7 cells, which do not express type 1 sigma receptor mRNA or activity, with the cloned rat brain cDNA leads to the appearance of haloperidol-sensitive binding of (+)-pentazocine, a selective type 1 sigma receptor ligand. These data show that the cloned rat brain cDNA codes for a functional type 1 sigma receptor. Northern blot analysis with poly(A)+ RNA isolated from various rat tissues has indicated that the sigma receptor-specific transcript, 1.6 kb in size, is expressed abundantly in liver and moderately in intestine, kidney, brain, and lung.
Amino Acid Sequence↗
Effects of C-peptide on renal function at the early stage of experimental diabetes.
BACKGROUND: C-peptide has been reported to have biological effects on renal function early in the course of diabetes. This investigation was initiated to elucidate and amplify these findings with respect to protein leakage, hyperfiltration and renal functional reserve in diabetic rats. METHODS: Acute effects of 140 minutes i.v. infusion of human C-peptide (0.5 nmol x min(-1) x kg(-1) body wt) on renal function and urinary protein leakage were studied in anesthetized diabetic male rats two weeks after streptozotocin injection without insulin treatment. Streptozotocin-induced diabetic rats were studied with (N = 6) and without C-peptide (N = 11) treatment. The two groups showed a similarly elevated blood glucose concentration during the study. Age-matched normal rats served as controls (N = 5). Glomerular filtration rate (GFR) was measured by inulin clearance in the basal state and during a 60-minute glycine infusion (0.22 mmol x min(-1) x kg(-1) body wt)-resembling a protein load challenge-to test the renal functional reserve in all three groups. RESULTS: In the basal state, the non-C-peptide-treated diabetic rats displayed increased GFR and increased total protein leakage compared with normal rats. Whereas normal rats responded to glycine infusion with an increase in GFR, no increase occurred in diabetic rats not treated with C-peptide. In diabetic rats given C-peptide, this reduced the initial glomerular hyperfiltration prior to glycine infusion. This indicates a specific effect, since a control peptide with the same amino acid composition as C-peptide, but in a randomized sequence, had no such effect. C-peptide also restored half of the normal renal functional reserve and resulted in 70% lower (P < 0.05) total protein leakage compared with that in rats not given C-peptide. CONCLUSION: Thus, short-term infusion of C-peptide had beneficial effects on protein leakage and hyperfiltration and improved the renal functional reserve in rats with experimental diabetes.
Animals↗
Glycine receptor reduction within segmental gray matter in a rat model in neuropathic pain.
Glycine is an amino acid neurotransmitter found in the spinal cord and is closely associated with interneurons that modulate afferent activity. We have previously shown that low segmental glycine concentrations or blockade of normal glycinergic activity lowers the threshold for pain thresholds. In addition, intrathecal glycine infusion increases the pain threshold in animal models of neuropathic pain. However, the role of the glycine receptor in neuropathic pain is not clear and is the basis for the current study. Using a unilateral sciatic nerve constriction injury model of neuropathic pain, the strychnine sensitive glycine receptor population was studied using immunohistochemical techniques. Glycine receptors are reduced in number in the dorsal horn bilaterally in injured animals. Glycine and related compounds are potentially valuable agents for treating chronic pain conditions in humans. A better understanding of glycine-receptor interactions should prove valuable as these compounds are studied in greater depth.
Animals↗
Sequence variation in ZFX introns in human populations.
DNA variation in human populations was studied by examining the last intron of the ZFX gene (about 1, 151 bp) with a worldwide sample of 29 individuals. Only one polymorphic site was found, which is located in an Alu sequence. This polymorphism is present at an intermediate frequency in all populations studied, and could be a shared polymorphism or due to migration among populations in Asia, Europe, and Africa. The nucleotide diversity is 0.04%, supporting the view that the level of nucleotide variation in nuclear DNA is very low in humans. From the sequence data, the age (T) of the most recent common ancestor of the sampled sequences is estimated: the mode of T is about 306,000 years, and the 95% confidence interval of T is 162,000-952,000 years. This mode estimate is considerably older than the estimates from Y-linked sequences.
Animals↗
The separate effects of E60Q in Lactobacillus casei thymidylate synthase delineate between mechanisms for formation of intermediates in catalysis.
X-Ray crystal structures of Lactobacillus casei thymidylate synthase (TS) mutant complexes of E60D with dUMP, and E60Q with dUMP or FdUMP, as well as ternary complexes with folate analog inhibitor CB3717, are described. The structures we report address the decrease in rate of formation of ternary complexes in the E60 mutants. Structures of ternary complexes of L.casei TS mimic ligand-bound TS just prior to covalent bond formation between ligands and protein. Ternary complex structures of L.casei TS E60Q show the ligands are not optimally aligned for making the necessary covalent bonds. Since CB3717 is an analog of the open, activated form of the cofactor, these structures suggest that the slow rate of ternary complex formation in E60 mutants is at least partly the result of impaired alignment of ligands in the active site after binding and activation of the cofactor. Binary complexes of TS E60Q and TS E60D with substrate (dUMP) show no change in dUMP position or occupancy. These results are consistent with the fact that Kd(dUMP) and Km(dUMP) are almost the same, and the rates of folate-independent debromination of 5-bromo-dUMP are even higher than for wild type TS.
Amino Acid Substitution↗
Beta-adrenergic blockade accelerates conversion of postoperative supraventricular tachyarrhythmias.
BACKGROUND: Postoperative supraventricular tachyarrhythmia is a common complication of surgery. Because chemical cardioversion is often ineffective, ventricular rate control remains a principal goal of therapy. The authors hypothesized that patients with supraventricular tachyarrhythmia after major noncardiac surgery who receive intravenous beta-adrenergic blockade for ventricular rate control would experience conversion to sinus rhythm at a rate that differs from those receiving intravenous calcium channel blockade. METHODS: The rate of conversion to sinus rhythm at 2 and 12 h after treatment was examined in 64 cases of postoperative supraventricular tachyarrhythmia. After adenosine administration, patients who remained in supraventricular tachyarrhythmia were prospectively randomized to receive either intravenous diltiazem or intravenous esmolol for ventricular rate control (unblinded). Loading and infusion rates were adjusted to achieve equivalent degrees of ventricular rate control. RESULTS: Patients were similar with regard to age and Apache III score. Most patients in both groups had atrial fibrillation (esmolol, 79%; diltiazem, 81%), and none experienced stable conversion with adenosine. Patients randomized to receive esmolol experienced a 59% rate of conversion to sinus rhythm within 2 h of treatment, compared with only 33% for patients randomized to receive diltiazem (intention to treat, P = 0.049; odds ratio, 2.9; 95% confidence interval, 1.046 to 7.8). After 12 h of therapy, the number of patients converting to sinus rhythm increased in both groups (esmolol, 85%; diltiazem, 62%), and the rates of conversion no longer differed significantly. Ventricular rates when supraventricular tachyarrhythmia began and after 2 and 12 h of rate control therapy were similar in the two treatment groups. The in-hospital mortality rate and length of stay in the intensive care unit were not significantly influenced by treatment group. CONCLUSIONS: Among adenosine-resistant patients in the intensive care unit with atrial fibrillation after noncardiac surgery, intravenous esmolol produced a more rapid (2-h) conversion to sinus rhythm than did intravenous diltiazem.
Adrenergic beta-Antagonists↗
Correlates of stress level in Chinese mothers of a child with mental retardation.
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Adolescent↗
Cooperative assembly of RNA polymerase II transcription complexes.
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Animals↗