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Biomedical subjects

T He

Publications and source records attributed to T He.

At least 19 recordsLinked to original sources
PubMed2001

Tibioperoneal (outflow lesion) angioplasty can be used as primary treatment in 235 patients with critical limb ischemia: five-year follow-up.

BACKGROUND: In a prospective, nonrandomized, consecutive series of tibioperoneal vessel angioplasty (TPVA), critical limb ischemia (CLI) patients' data were analyzed with regard to immediate and follow-up success. METHODS AND RESULTS: TPVA was successful in 270 of 284 critically ischemic limbs (95%), with 167 limbs (59%) requiring dilatation of 333 ipsilateral inflow obstructions to access and successfully dilate 486 of 529 (92%) tibioperoneal lesions. A clinical success (relief of rest pain or improvement of lower-extremity blood flow) was attained in 270 limbs at risk (95%). Clinical 5-year follow-up of 215 of 221 successful CLI patients (97%) with 266 successfully revascularized limbs revealed that bypass surgery occurred in 8% and significant amputations in 9% of limbs; 91% of the limbs were salvaged. The cohort's probability of survival was 56%: 58% for Fontaine class III and 33% for class IV patients. Class III compared with class IV patients had significantly (P<0.05) fewer surgical bypasses (3% versus 16%) and amputations: above-knee, 1% versus 4%; below-knee, 3% versus 12%; and transmetatarsal, <1% versus 21%. CONCLUSIONS: TPVA, often in combination with inflow lesions, is an effective primary treatment for critical limb ischemia. The poor cumulative survival reflects the existence of severe comorbidities, which could potentially be affected by aggressive and effective cardiovascular diagnostic and therapeutic strategies.

Adult↗
PubMed2001

Giant anharmonicity and nonlinear electron-phonon coupling in MgB2: a combined first-principles calculation and neutron scattering study.

First-principles calculations of the electronic band structure and lattice dynamics for the new superconductor MgB (2) are carried out and found to be in excellent agreement with our inelastic neutron scattering measurements. The numerical results reveal that the E(2g) in-plane boron phonons near the zone center are very anharmonic and strongly coupled to the planar B sigma bands near the Fermi level. This giant anharmonicity and nonlinear electron-phonon coupling is key to quantitatively explaining the observed high T(c) and boron isotope effect in MgB (2).

Journal Article↗
PubMed2001

High critical current density and enhanced irreversibility field in superconducting MgB2 thin films.

The discovery of superconductivity at 39 K in magnesium diboride offers the possibility of a new class of low-cost, high-performance superconducting materials for magnets and electronic applications. This compound has twice the transition temperature of Nb3Sn and four times that of Nb-Ti alloy, and the vital prerequisite of strongly linked current flow has already been demonstrated. One possible drawback, however, is that the magnetic field at which superconductivity is destroyed is modest. Furthermore, the field which limits the range of practical applications-the irreversibility field H*(T)-is approximately 7 T at liquid helium temperature (4.2 K), significantly lower than about 10 T for Nb-Ti (ref. 6) and approximately 20 T for Nb3Sn (ref. 7). Here we show that MgB2 thin films that are alloyed with oxygen can exhibit a much steeper temperature dependence of H*(T) than is observed in bulk materials, yielding an H* value at 4.2 K greater than 14 T. In addition, very high critical current densities at 4.2 K are achieved: 1 MA cm-2 at 1 T and 105 A cm-2 at 10 T. These results demonstrate that MgB2 has potential for high-field superconducting applications.

Journal Article↗
PubMed2001

Superconductivity in the non-oxide perovskite MgCNi3.

The interplay of magnetic interactions, the dimensionality of the crystal structure and electronic correlations in producing superconductivity is one of the dominant themes in the study of the electronic properties of complex materials. Although magnetic interactions and two-dimensional structures were long thought to be detrimental to the formation of a superconducting state, they are actually common features of both the high transition-temperature (Tc) copper oxides and low-Tc material Sr2RuO4, where they appear to be essential contributors to the exotic electronic states of these materials. Here we report that the perovskite-structured compound MgCNi3 is superconducting with a critical temperature of 8 K. This material is the three-dimensional analogue of the LnNi2B2C family of superconductors, which have critical temperatures up to 16 K (ref. 2). The itinerant electrons in both families of materials arise from the partial filling of the nickel d-states, which generally leads to ferromagnetism as is the case in metallic Ni. The high relative proportion of Ni in MgCNi3 suggests that magnetic interactions are important, and the lower Tc of this three-dimensional compound-when compared to the LnNi2B2C family-contrasts with conventional ideas regarding the origins of superconductivity.

Journal Article↗
PubMed2001

Ultraviolet irradiation blocks cellular responses to transforming growth factor-beta by down-regulating its type-II receptor and inducing Smad7.

Transforming growth factor-beta (TGF-beta) is a multi-functional cytokine that regulates cell growth and differentiation. Cellular responses to TGF-beta are mediated through its cell surface receptor complex, which activates transcription factors Smad2 and Smad3. Here we report that UV irradiation of mink lung epithelial cells causes near complete inhibition of TGF-beta-induced Smad2/3-mediated gene expression. UV irradiation inhibited TGF-beta-induced phosphorylation of Smad2 and subsequent nuclear translocation and DNA binding of Smad2/3. Specific cell surface binding of TGF-beta was substantially reduced after UV irradiation. This loss of TGF-beta binding resulted from UV-induced down-regulation of TGF-beta type II receptor (T beta RII) mRNA and protein. UV irradiation significantly inhibited T beta RII promoter reporter constructs, indicating that UV reduction of T beta RII expression involved transcriptional repression. In contrast to its effects on T beta RII, UV irradiation rapidly induced Smad7 mRNA and protein. Smad7 is known to antagonize activation of Smad2/3 and thereby block TGF-beta-dependent gene expression. UV irradiation stimulated Smad7 promoter reporter constructs, indicating that increased Smad7 expression resulted, at least in part, from increased transcription. Overexpression of Smad7 protein to the level induced by UV irradiation inhibited TGF-beta-induced gene expression 30%. Maintaining T beta RII levels by overexpression of T beta RII prevented UV inhibition of TGF-beta responsiveness. Taken together, these data indicate that UV irradiation blocks cellular responsiveness to TGF-beta through two mechanisms that impair TGF-beta receptor function. The primary mechanism is down-regulation of T beta RII, and the secondary mechanism is induction of Smad7.

Animals↗
PubMed2001

Loss of superconductivity with the addition of Al to MgB2 and a structural transition in Mg1-x AlxB2.

The basic magnetic and electronic properties of most binary compounds have been well known for decades. The recent discovery of superconductivity at 39 K in the simple binary ceramic compound magnesium diboride, MgB2, was therefore surprising. Indeed, this material has been known and structurally characterized since the mid 1950s (ref. 2), and is readily available from chemical suppliers (it is commonly used as a starting material for chemical metathesis reactions). Here we show that the addition of electrons to MgB2, through partial substitution of Al for Mg, results in the loss of superconductivity. Associated with the Al substitution is a subtle but distinct structural transition, reflected in the partial collapse of the spacing between boron layers near an Al content of 10 per cent. This indicates that superconducting MgB2 is poised very near a structural instability at slightly higher electron concentrations.

Journal Article↗
PubMed2001

Strongly linked current flow in polycrystalline forms of the superconductor MgB2.

The discovery of superconductivity at 39 K in magnesium diboride, MgB2, raises many issues, a critical one being whether this material resembles a high-temperature copper oxide superconductor or a low-temperature metallic superconductor in terms of its behaviour in strong magnetic fields. Although the copper oxides exhibit very high transition temperatures, their in-field performance is compromized by their large anisotropy, the result of which is to restrict high bulk current densities to a region much less than the full magnetic-field-temperature (H-T) space over which superconductivity is found. Moreover, the weak coupling across grain boundaries makes transport current densities in untextured polycrystalline samples low and strongly sensitive to magnetic field. Here we report that, despite the multiphase, untextured, microscale, subdivided nature of our MgB2 samples, supercurrents flow throughout the material without exhibiting strong sensitivity to weak magnetic fields. Our combined magnetization, magneto-optical, microscopy and X-ray investigations show that the supercurrent density is mostly determined by flux pinning, rather than by the grain boundary connectivity. Our results therefore suggest that this new superconductor class is not compromized by weak-link problems, a conclusion of significance for practical applications if higher temperature analogues of this compound can be discovered.

Journal Article↗
PubMed2001

Pressure dependence of the superconducting transition temperature of magnesium diboride.

We studied the pressure and temperature dependence of the electrical resistivity of the superconducting compound magnesium diboride (MgB(2)). The superconducting transition temperature decreases monotonically with pressure, being parabolic or linear, depending on samples. The rate of decrease under pressure is higher than in conventional superconductors. We discuss our results in terms of the semimetallic character of the electronic band structure of MgB(2).

Journal Article↗
PubMed2001

TNF-alpha down-regulates CXCR4 expression in primary murine astrocytes.

CXC chemokine receptor 4 (CXCR4) is a co-receptor for human immunodeficiency virus (HIV) infection and is believed to be involved in the pathogenesis of AIDS-associated neurologic disorders and brain tumors. The physiological roles of CXCR4 in developmental patterning of the nervous and hematopoietic system; gastrointestinal angiogenesis; and cardiac organogenesis were established by studies in gene-targeted mice. Studies on CXCR4 expression and regulation in neuroepithelial cells are fundamental for understanding its physiopathologic roles in the central nervous system (CNS). We show here that CXCR4 expression by primary mouse astrocytes is suppressed by exposure to tumor necrosis factor-alpha (TNF-alpha). TNF-alpha caused a pronounced down-regulation of CXCR4 mRNA in a dose- and time-dependent manner. TNF-alpha-mediated decrease of CXCR4 mRNA accumulation resulted in decreased CXCR4 protein expression. As a result, the ability of stromal cell-derived factor-1alpha (SDF-1alpha) to induce activation of MAP kinases, Erk1/2 was impaired. The half life of CXCR4 mRNA in the presence and absence of TNF-alpha stimulation was comparable, suggesting that TNF-alpha down-regulated CXCR4 mRNA at the transcriptional level. These results suggest that TNF-alpha could modulate HIV and brain tumor pathogenesis and immune-mediated inflammation in the central nervous system (CNS) by regulation of CXCR4 expression.

AIDS Dementia Complex↗
PubMed2001

TNF-alpha mediates SDF-1 alpha-induced NF-kappa B activation and cytotoxic effects in primary astrocytes.

Stromal-derived cell factor-1 alpha (SDF-1 alpha; CXCL12) and its receptor, CXCR4, are constitutively expressed on neuroepithelial cells and are believed to be involved in both development and pathological processes, such as AIDS-associated neurologic disorders. Here, we demonstrate that SDF-1 alpha activates NF-kappa B, stimulates production of chemokines and cytokines, and induces cell death in primary astrocytes, effects that depend on ongoing secretion of TNF-alpha. SDF-1 alpha upregulated TNF-alpha mRNA and protein secretion, as well as TNF receptor 2 expression. TNF-alpha treatment mimicked SDF-1 alpha induction of NF-kappa B, IL-1 alpha/beta, and RANTES, as well as cell death; neutralizing antibodies against TNF-alpha opposed these responses. We also found that SDF-1 alpha activated Erk1 and Erk2 (Erk1/2) MAPK in a biphasic fashion. Early Erk1/2 activation was stimulated directly by SDF-1 alpha and late activation was mediated by TNF-alpha. PD98059 suppression of early Erk1/2 activation correlated with reduction of SDF-1 alpha-induced TNF-alpha expression. Late Erk1/2 activation was involved in TNF-alpha-stimulated NF-kappa B activation and cytokine induction. SDF-1 alpha was induced in reactive CXCR4-positive astrocytes near axotomized spinal cord motor neurons, consistent with autocrine SDF-1/CXCR4 signaling in these cells. We propose that these novel effects of SDF-1 alpha are relevant to the pathogenic and developmental roles of SDF-1 alpha in the CNS.

Animals↗
PubMed2001

Safety of three toothbrushes.

PURPOSE: To assess the oral soft tissue safety and tolerability of two electric toothbrushes, the Crest Spin Brush and Colgate ActiBrush, and one manual toothbrush, the Oral B 40. MATERIALS AND METHODS: A total of 104 subjects were enrolled in this single center, randomized, examiner-blind parallel study over a 4-wk test period. Subjects were randomized to treatment and were instructed to brush in their normal manner, twice per day for 60 s. A detailed oral soft tissue examination and interview were conducted by a trained clinician at baseline, 3 days and 4 wks to assess clinical signs and symptoms associated with use of the toothbrushes. RESULTS: Over the 4-wk period, a total of 19 subjects (18% of the study population) were observed for signs/symptoms. The adverse events were distributed across test groups with 12 subjects in the Oral B 40 group, 4 subjects in the Crest Spin Brush group, and 3 subjects in the Colgate ActiBrush group experiencing at least one adverse event. All adverse events were mild in severity indicating the general safety of all three toothbrushes. The most frequently encountered event was localized gingivitis. The Oral B 40 test group was observed with more adverse events when compared to the Crest Spin Brush and Colgate ActiBrush at 4 wks but not at 3 days. The proportion of subjects experiencing an adverse event in the Crest Spin Brush test group was similar to that of Colgate ActiBrush group. All three toothbrushes were generally well tolerated by subjects enrolled in the study with the Crest Spin Brush and Colgate ActiBrush being the best tolerated. CLINICAL SIGNIFICANCE: The results of this study indicated that abnormal oral soft tissue findings were distributed among the treatment groups, indicating that daily use of an electric toothbrush is at least as safe as a manual toothbrush.

Adult↗
PubMed2000

Dosimetric improvements following 3D planning of tangential breast irradiation.

PURPOSE: To evaluate the dosimetric difference between a simple radiation therapy plan utilizing a single contour and a more complex three-dimensional (3D) plan utilizing multiple contours, lung inhomogeneity correction, and dose-based compensators. METHODS AND MATERIALS: This is a study of the radiation therapy (RT) plans of 85 patients with early breast cancer. All patients were considered for breast-conserving management and treated by conventional tangential fields technique. Two plans were generated for each patient. The first RT plan was based on a single contour taken at the central axis and utilized two wedges. The second RT plan was generated by using the 3D planning system to design dose-based compensators after lung inhomogeneity correction had been made. The endpoints of the study were the comparison between the volumes receiving greater than 105% and greater than 110% of the reference dose, as well as the magnitude of the treated volume maximum dose. Dosimetric improvement was defined to be of significant value if the volume receiving > 105% of one plan was reduced by at least 50% with the absolute difference between the volumes being 5% or greater. The dosimetric improvements in 49 3D plans (58%) were considered of significant value. Patients' field separation and breast size did not predict the magnitude of improvement in dosimetry. CONCLUSION: Dose-based compensator plans significantly reduced the volumes receiving > 105%, >110%, and volume maximum dose.

Breast Neoplasms↗
PubMed2000

Characterization and evolutionary relevance of the sperm nuclear basic proteins from stickleback fish.

We have characterized the sperm nuclear basic proteins (SNBPs) of the sticklebacks in the suborder Gasterosteoidei. The complete amino acid sequence of the protamines from Aulorhynchus flavidus, Pungitius pungitius, Gasterosteus aculeatus, (anadromous) and G. wheatlandi, as well as the sequences of the protamines of several species pairs of freshwater G. aculeatus, have been determined. Analysis of the primary structure of these proteins has shown that: a) despite the relatively low amino acid complexity and small molecular mass of these basic proteins, they are very good molecular markers at the generic level. The bootstrap parsimony analysis using their sequences provides a phylogenetic relationship for the old anadromous species of Gasterosteoidei which is identical to that obtained from morphological and behavioral analysis; b) the comparison of the sequences also suggests that protamines from the suborder Gasterosteoidei have most likely evolved from a common gene in the early Acanthopterygii by an extension of the carboxy terminal portion of the molecule; c) protamines are not good markers for recent postglacial freshwater isolates of G. aculeatus. However, in the unique case of Enos Lake (British Columbia), we have been able to detect an additional minor protamine component in the benthic forms of G. aculeatus that is not present in the limnetic forms. Thus, this new protamine must have appeared during the past 12,000 years concomitantly with the speciation of benthics and limnetics in this lake.

Amino Acid Sequence↗
PubMed2000

Prevalence of Bacteroides forsythus, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans in subgingival microflora of Japanese patients with adult and rapidly progressive periodontitis.

BACKGROUND, AIMS: This study investigated the prevalence of Bacteroides forsythus, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans among various periodontitis patients and healthy individuals in Japan, and correlated it with clinical parameters. METHOD: Subgingival plaque samples were collected from 21 patients with adult periodontitis (AP), 8 with rapidly progressive periodontitis (RPP) and 15 healthy individuals. RESULTS: The frequency detected in culture was as follows: B. forsythus was found in 47.6% of AP sites and in 37.5% of RPP sites. P. gingivalis was identified in 64.3% of AP and 59.4% of RPP sites. A. actinomycetemcomitans was detected in 4.8% of AP and 3.1% of RPP sites. The 3 species were detected in only 2 of the healthy individuals. The proportion of B. forsythus in the total microflora in culture was 0.07% in the healthy group, 4.1% in AP and 2.4% in RPP. The proportions of P. gingivalis were 0% in the healthy group, 18.8% in AP and 16.2% in RPP. The proportion of A. actinomycetemcomitans was very low in all 3 groups. A DNA probe detected B. forsythus in 78.6% of AP and 65.6% of RPP sites, as well as P.gingivalis in 58.3% of AP and 59.4% of RPP sites. A. actinomycetemcomitans was detected in only 1.2% of AP sites. The 3 species were undetectable in the healthy group. CONCLUSIONS: The prevalence and the proportion of B. forsythus and P. gingivalis were significantly correlated with clinical parameters, suggesting that B. forsythus and P. gingivalis are closely related to AP and RPP in the Japanese population.

Aggregatibacter actinomycetemcomitans↗
PubMed2000

Evidence for recent selection of the CCR5-delta 32 deletion from differences in its frequency between Ashkenazi and Sephardi Jews.

Recent studies have shown higher frequencies of the CCR5-delta 32 allele and the CCR5-delta 32/delta 32 genotype, which confers protection against HIV infection, in northern Europe as compared to Mediterranean countries. Here, we analyse the prevalence of CCR5-delta 32 in 922 HIV seronegative blood donors in Israel to verify its frequency in Jews of Ashkenazi and Sephardi origin. A significant difference (P < 0.001) was found between the CCR5-delta 32 allele frequency in Ashkenazi (13.8%) vs (4.9%) Jews. In contrast, no significant difference was observed in the frequency of the CCR2-641 mutation between Ashkenazi (9.2%) and Sephardi (13.4%) Jews. Using the Island model we calculate that a minimal genetic migration rate of 3% per generation would have been necessary if the higher CCR5-delta 32 prevalence in Ashkenazi is to be fully explained by mixing with the indigenous north-European populations. This putative migration rate is 20-fold higher than that currently estimated from other genes, and would correspond to a non-realistic minimal current admixture of 80%. Thus, our results suggest that a positive selection process for CCR5-delta 32 should have occurred in northern Europe at most a 1000 years ago, after the Ashkenazi Jews separated from their Sephardi kin and moved to north Europe.

Alleles↗
PubMed2000

Genetic characterization of rebounding HIV-1 after cessation of highly active antiretroviral therapy.

Despite prolonged treatment with highly active antiretroviral therapy (HAART), infectious HIV-1 continues to replicate and to reside latently in resting memory CD4(+) T lymphocytes, creating a major obstacle to HIV-1 eradication. It is therefore not surprising to observe a prompt viral rebound after discontinuation of HAART. The nature of the rebounding virus, however, remains undefined. We now report on the genetic characterization of rebounding viruses in eight patients in whom plasma viremia was undetectable throughout about 3 years of HAART. Taking advantage of the extensive length polymorphism in HIV-1 env, we found that in five patients who did not show HIV-1 replication during treatment, the rebound virus was identical to those isolated from the latent reservoir. In three other patients, two of whom had been free of plasma viremia but had showed some residual viral replication, the rebound virus was genetically different from the latent reservoir virus, corresponding instead to minor viral variants detected during the course of treatment in lymphoid tissues. We conclude that in cases with apparent complete HIV-1 suppression by HAART, viral rebound after cessation of therapy could have originated from the activation of virus from the latent reservoir. In patients with incomplete suppression by chemotherapy, however, the viral rebound is likely triggered by ongoing, low-level replication of HIV-1, perhaps occurring in lymphoid tissues.

Adult↗
PubMed2000

Intracellular sequestration of anti-tumor drugs by metallothionein.

Acquired drug resistance is one of the most important problems in cancer chemotherapy. One of the mechanisms proposed to contribute to this phenomenon is the sequestration of alkylating agents by metallothionein (MT) in vivo. In this study cadmium-induced human bladder tumor T24 cells were exposed to the therapeutic agents chlorambucil and melphalan. MT-2a, was shown by capillary electrophoresis to comprise 56% of the MT isoforms in induced cells, and drug adducts of MT-2a were isolated and characterized by HPLC and electrospray ionization mass spectrometry. One to four equivalents of drug were found to be covalently adducted. Major binding sites on metallothionein were located in the C-terminal domain by peptide mapping, consistent with previous studies in vitro.

Alkylation↗