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Biomedical subjects

T He

Publications and source records attributed to T He.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

Analysis of diagnostic metabolites by capillary electrophoresis-mass spectrometry.

We describe here a procedure by capillary electrophoresis-mass spectrometry (CE-MS) for the direct analysis of urine samples on diagnostic metabolites, which are present in patient urine with metabolic disorders. The method was demonstrated using urine samples spiked with diagnostic metabolites, including glutathione for gamma-glutamyl transpeptidase deficiency, pyroglutamate for generalized glutathione deficiency, adenylosuccinate for adenylosuccinase deficiency, omithine for gyrate atrophy, histidine for histidinemia, and homogentisic acid for alcaptonuria, at concentrations similar to those found in patients' urine. A coaxial sheath liquid flow was used for coupling CE and MS in electrospray ionization mode. Identification of the metabolites is based on their molecular weights and fragmentation patterns. The CE-MS method is highly specific and sensitive comparing to the previously reported method using migration time and UV absorption for identification. It should find broad application in clinical and pharmaceutical research and development.

Electrophoresis, Capillary↗

Traditional and MLC based dose compensator design for patients with hip prostheses undergoing pelvic radiation therapy.

Perturbations in the dose distribution caused by a hip prosthesis when treating pelvic malignancies can result in unacceptable dose inhomogeneities within the target volume. Our results, obtained by in vivo exit dose measurements with diodes, showed a 55% reduction in the dose at the exit dmax of a lateral 15 MV photon beam after passing through a bilateral cobalt-chrome alloy hip prosthesis. Such an inhomogeneous dose distribution may decrease the curability. Solutions such as treatment techniques to avoid the prosthesis are often not the best choice as the dose to the rectum may be unacceptably high. In this work an alternative method of dose compensator is presented. Two types of dose compensators were designed based on a 3-D treatment planning system and CT images of a pelvic phantom containing a hip prosthesis: one was fabricated from a polyethylene-lead slab in the representation of step fringes and placed on a tray in the path of the beam while the other was produced by the use of several fields shaped with a multileaf collimator. The calculation procedures developed by the authors for generating the compensators are described. Results of film measurements performed in a phantom with and without the compensators in place are discussed.

Alloys↗

Decreased expression of manganese superoxide dismutase in transformed cells is associated with increased cytosine methylation of the SOD2 gene.

Tumor cells express lower levels of manganese superoxide dismutase (MnSOD) than their normal counterparts. Enforced expression of MnSOD reverses the malignant phenotype of many transformed cells, suggesting that SOD2 is a tumor suppressor. The SOD2 gene contains a large CpG island spanning > 3.5 kb that starts near the 5' edge of the promoter and extends into intron 2. We hypothesized that the difference in SOD2 expression between tumor cells and their normal cell counterparts might be secondary to differences in their cytosine methylation patterns in this CpG island. To test this hypothesis, we analyzed the methylation status of the SOD2 gene in two cell line models that show differential MnSOD expression between normal and SV40-transformed cells: WI38 and MRC5 and their SV40-transformed variants, WI38-VA and MRC5-VA. We subdivided the SOD2 gene CpG island into 10 individual regions for analysis by bisulfite genomic sequencing. A region located in intron 2 displayed a significant increase in cytosine methylation in both transformed cell lines that expressed low levels of MnSOD mRNA compared with their normal cell counterparts. Recent studies by others have shown that SOD2 intron 2 is a potent transcriptional enhancer. The association between increased cytosine methylation of the SOD2 intron 2 region and decreased MnSOD expression in transformed cells compared with their normal counterparts suggests that an epigenetic mechanism contributes to the differential SOD2 gene expression between these normal and SV40-transformed cells.

Alu Elements↗

Rapid clearance of simian immunodeficiency virus particles from plasma of rhesus macaques.

Perturbation of the equilibrium between human immunodeficiency virus type 1 (HIV-1) and the infected host by administering antiretroviral agents has revealed the rapid turnover of both viral particles and productively infected cells. In this study, we used the infusion of simian immunodeficiency virus (SIV) particles into rhesus macaques to obtain a more accurate estimate of viral clearance in vivo. Consistently, exogenously infused virions were cleared from plasma with an extremely short half-life, on the order of minutes (a mean of 3.3 min). This new estimate is approximately 100-fold lower than the upper bound of 6 h previously reported for HIV-1 in infected humans. In select animals, multiple tissues were collected at the completion of each experiment to track the potential sites of virion clearance. Detectable levels of SIV RNA were found in lymph nodes, spleen, lungs, and liver, but not in other tissues examined. However, only approximately 1 to 10% or less of the infused virions were accounted for by the thorough tissue sampling, indicating that the vast majority of the infused particles must have been degraded over a short period of time. Should the rapid clearance of virions described here be applicable to infected patients, then HIV-1 production and thus the number of productively infected CD4(+) T lymphocytes or the viral burst size must be proportionally higher than previous minimal estimates.

Animals↗

A novel insertion sequence increases the expression of leukotoxicity in Actinobacillus actinomycetemcomitans clinical isolates.

BACKGROUND: The expression of leukotoxin varies among Actinobacillus actinomycetemcomitans strains and is dependent in part on the structure of the ltx promoter region. Highly leukotoxic strains, characterized by a 530 base pair (bp) deletion within the ltx promoter, have been associated with juvenile periodontitis in the United States and Europe. In the present study, we analyzed the ltx promoter structure to elucidate whether A. actinomycetemcomitans from Japanese periodontitis patients exhibits the highly toxic phenotype. METHODS: Forty-five A. actinomycetemcomitans strains, including 43 clinical isolates, the highly leukotoxic strain JP2, and a minimally leukotoxic strain 652 were used in the study. The ltx promoter structure was analyzed by polymerase chain reaction (PCR), with oligonucleotide primers focusing the ltx promoter region, and nucleotide sequencing. Leukotoxic activity was determined by trypan blue exclusion. Western blotting assay was performed to detect the level of leukotoxin polypeptide. RESULTS: A 495 bp PCR product was amplified from JP2, a 1025 bp product from 652 and 41 of the clinical isolates, and a 1926 bp product from the remaining two clinical isolates (AaIS1, AaIS2). Sequencing of the 1926 bp PCR fragment showed that it was similar to that of strain 652 but contained an 886 bp region that was identified as an insertion sequence (IS). Both AaIs strains expressed high levels of leukotoxicity, similar to strain JP2. In addition, a mutant (AaIS-) that had lost the IS element expressed a significantly lower level of leukotoxicity compared with AaIS strains. Furthermore, the levels of leukotoxin polypeptide expressed by these strains were consistent with their whole cell leukotoxicity. CONCLUSIONS: A. actinomycetemcomitans clinical strains which were isolated from Japanese periodontitis patients do not possess the 530 bp ltx promoter deletion. The results of this study suggest that a high level of leukotoxin expression correlates with the insertion of the transposable DNA element.

Adolescent↗

Effect of initial periodontal therapy on the frequency of detecting Bacteroides forsythus, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans.

BACKGROUND: Porphyromonas gingivalis, Bacteroides forsythus, and Actinobacillus actinomycetemcomitans have been described as periodontopathic bacteria, and their presence in subgingival pockets can lead to development of periodontal disease. Until now, clinical parameters have been used to evaluate the effect of conventional periodontal treatment without microbiological parameters. The present study examined the microbiological effects of initial periodontal therapy using DNA probes and the polymerase chain reaction (PCR). METHODS: Twenty-six patients with periodontitis, 10 males and 16 females, were given instructions regarding oral hygiene, then thoroughly treated by conventional scaling and root planing. Bacterial samples were collected on paper points from 4 sites per patient at baseline and after initial therapy (total: 104 sites). Clinical parameters including probing depth, attachment level, and bleeding on probing were also recorded for each site at baseline and after therapy. A DNA probe kit was used to monitor the frequency of B. forsythus, P. gingivalis, and A. actinomycetemcomitans, the last of which was identified by PCR. RESULTS: At baseline, B. forsythus was the bacterium most frequently detected. DNA probe analysis also showed that more than half of the sites were colonized by both B. forsythus and P. gingivalis. Initial therapy resulted in significant clinical improvement such as significant reduction in the frequency of B. forsythus and P. gingivalis detected using the DNA probe. A. actinomycetemcomitans was difficult to detect using the DNA probe, but PCR indicated that levels of A. actinomycetemcomitans did not significantly decrease. CONCLUSIONS: These results indicate that initial conventional therapy can eliminate B. forsythus and P. gingivalis, but not A. actinomycetemcomitans. When levels of these bacteria decreased to below-detectable levels, clinical improvement was significant. These results indicate that monitoring levels of these three periodontopathic bacteria may render periodontal therapy more effective and accurate.

Adolescent↗

Effects of spinach powder fat-soluble extract on proliferation of human gastric adenocarcinoma cells.

Four kinds of assays were used to study the effect of a fat-soluble extract of spinach powder (SPFE) on the proliferation of human gastric adenocarcinoma cell line (SGC-7901) in vitro. These studies included: (i) cell growth assay, (ii) colony forming assay, (iii) MTT colorimetric assay, and (iv) 3H-TdR incorporation assay. The concentrations of SPFE expressed as the level of beta-carotene in the medium were 2 x 10(-8), 2 x 10(-7) and 2 x 10(-6) mol/L beta-carotene in assay (i)-(iii), but 4 x 10(-8), 4 x 10(-7) and 4 x 10(-6) mol/L beta-carotene in assay (iv) respectively. The results indicated that SPFE inhibited the proliferation and colony forming ability of SGC-7901 cells. And in MTT assay, SPFE inhibited the viability of SGC-7901 cells, but no inhibitory effect of SPFE was observed on the viability of lymphocytes in peripheral blood of healthy people. Finally, in the 3H-TdR incorporation test, both SPFE and beta-carotene showed significant inhibitory effects on DNA synthesis in SGC-7901 cells, but SPFE was more effective than beta-carotene.

Adenocarcinoma↗

[Measurement and clinical use of recoil pressure of the respiratory system].

Using the principle that the difference of MIP (maximal inspiratory mouth pressure) between RV (residual volume) and FRC (functional residual capacity) equals Prs (recoil pressure of the respiratory system) at RV, we performed the measurement of Prs at RV in 20 normal subjects, 90 patients with COPD (chronic obstructive pulmonary disease) and 15 patients with ILF (interstitial lung fibrosis). We also performed the correlation analysis of Prs at RV and RV/TLC (total lung capacity) %. The results indicated the Prs values at RV (-2.8 +/- 0.5 kPa) in normal subjects measured in this manner was in accord with the values reported by other authors abroad. The Prs in patients with emphysema decreased and it was highly and negatively correlated with RV/TLC% (r = -0.872), but the Prs in patients with ILF was increased. The results suggest that this method for measurement of Prs is simple, reliable, and clinically useful.

Aged↗

[Direct intramuscular injection of pSV-VEGF(165) augments capillaries formation in a rabbit model of hindlimb ischemia].

OBJECTIVE: To investigate an easier and safer clinical method of gene therapy for treating arterial ischemic diseases in the lower extremity. METHODS: Recombinant plasmid pSV-VEGF(165) constructed in vitro was directly injected into the ischemic hindlimb muscles in rabbit models. 30 days after gene transfer, the capillary density and the capillary to muscle fiber ratio were determined histochemically in the resected samples. RESULTS: The capillary density and the capillary to muscle fiber ratio were significantly higher for pSV-VEGF(165) transfected group than for control group, particularly increased in the shank of the hindlimbs. CONCLUSIONS: Direct intramuscular injection of pSV-VEGF(165) was an easier and efficient gene therapy method, and it significantly augmented the capillary formation in ischemic limbs.

Animals↗

[Application of enzyme-linked immunosorbent assay for cholecystokinin].

An enzyme-linked immunosorbent assay for octapeptide cholecystokinin (CCK) has been developed. Using this method we distinguished two kinds of CCK-related peptides and is also useful for identified the compounds with CCK-like structure in tissue extracts, as well as different antipeptide antisera. The results showed that this method could be applied to preliminary structure analysis of CCK.

Animals↗

Four-year follow-up of Palmaz-Schatz stent revascularization as treatment for atherosclerotic renal artery stenosis.

BACKGROUND: Stent revascularization is perceived as superior to balloon angioplasty and surgical revascularization, but the paucity of stent publications precludes even historical comparison with surgical data. METHODS AND RESULTS: Palmaz-Schatz stent revascularization of renal artery stenosis was successfully performed on 163 consecutive patients for poorly controlled hypertension or preservation of renal function. Of these, 145 were eligible for > or =6-month clinical follow-up of the effect of the procedure on renal function, blood pressure control, number of antihypertensive medications, and survival. At 4 years, systolic and diastolic blood pressures significantly decreased (from 166+/-26 to 148+/-22 mm Hg and from 86+/-14 to 80+/-11 mm Hg, respectively; P<0.05), and blood pressure control was more facile in approximately half of the patients. Creatinine decreased or remained stable in approximately two thirds of the patients. The cumulative probability of survival was 74+/-4% at 3 years, with few deaths related to end-stage renal disease. Survival was good in patients with normal (92+/-4%) baseline renal function, fair (74+/-7%) in those with mildly impaired renal function, and poor (52+/-7%) in patients with elevated baseline creatinine levels (> or =2.0 mg/dL). The combination of impaired renal function and bilateral disease adversely affected survival. CONCLUSIONS: Renal artery stent revascularization in the presence of normal or mildly impaired renal function had a beneficial effect on blood pressure control and a nondeleterious effect on renal function. Survival was adversely affected by renal dysfunction despite adequate revascularization. Early diagnosis and adequate revascularization before the onset of renal dysfunction could beneficially affect blood pressure control, preserve or prevent deterioration of renal function, and improve patient survival.

Actuarial Analysis↗