Single vortex creep in Tl2Ba2CaCu2O8 epitaxial thin films.
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Biomedical subjects
Publications and source records attributed to L Fang.
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One hundred thirty-eight pediatric patients have received treatment for malignant solid tumors with ifosfamide with mesna, and 71 have received a combination with ifosfamide/carboplatin/etoposide (ICE). Responses were obtained in many types of pediatric tumors, yet comparison of responses was not possible because of inadequate numbers of tumors of differing histiotypes. Comparison of results between patients with all tumors treated with ifosfamide or ICE indicated that there was a higher response rate for patients treated with ICE, with an estimated odds ratio of 2.74 (95% C.I. 1.45-5.179). Excluding patients without prior chemotherapy and radiotherapy, the odds ratio for 2.801 (95% C.I. 1.45-5.4) suggests a similar result. There remain no guarantees that the more costly treatment with ICE, which requires cytokine support, will offer therapeutic benefits against resistant solid tumors.
The synthesis of prostaglandins in the uterus at term are modulated by two isoforms of the enzyme cyclooxygenase (COX): constitutive COX-1 and inducible COX-2. This study aims to characterize the expression of the protein for COX-1 and -2 in the rat uterus and cervix during the estrous cycle, pregnancy, and labor, and in cultured myometrial cells. Western immunoblotting of proteins was performed and quantitation of protein was obtained densitometrically. Results indicate: 1) the rat uteri, cervix, and isolated myometrial cells express both COX-1 and COX-2 proteins, 2) during pregnancy, both COX-1 and -2 increase, with a dramatic increase at parturition (250%-280%), 3) a 2-fold increase of cervical COX-2 is seen at spontaneous labor, 4) during proestrus and estrus, uterine expression of COX-2 is elevated, 5) both COX-1 and -2 were expressed by rat myometrial cells and treatment with IL-1 beta (10 ng/mL) produced a significant increase in COX-2, and 6) immunocytochemical studies show that both COX-1 and -2 were primarily localized to the epithelial cells of the endometrium and smooth muscle cells in the circular layers of the myometrium in the uterus and to the epithelial cells and smooth muscle cells in the cervix. Thus, we propose that increased expression of COX-2 may be involved at term in increased uterine contractility and cervical ripening.
BACKGROUND: CspA, the major cold-shock protein of Escherichia coli, is transiently induced upon temperature downshift and considered to play an important role in low-temperature adaptation. RESULTS: Overproduction of truncated cspA mRNAs retaining translational ability was found to completely block cell growth at low temperatures. This effect was termed 'low-temperature antibiotic effect of truncated cspA expression (LACE)'. In contrast to the significant reduction of polysomes in normal cells upon cold shock, cells under LACE maintained a high polysome profile, producing only truncated cspA products. Growth inhibition of cells under LACE was suppressed when CspA was overproduced together with the truncated cspA mRNA. CONCLUSION: LACE is caused by the overproduction of a truncated cspA mRNA in the absence of CspA production, which in turn traps all the cellular ribosomes in a non-adaptive form incapable of forming initiation complexes with other cellular mRNAs. LACE may provide a novel approach to the development of a new antibiotic.
During cellular adaptation to low temperature, Escherichia coli transiently synthesizes the major cold-shock protein CspA. It was found that adaptation to cold shock is blocked when the 143-base sequence of the 5' untranslated region (5' UTR) of the cspA mRNA is overproduced. The overproduction of this UTR at 15 degrees C caused the synthesis of not only CspA but also other cold-shock proteins such as CspB and CsdA to be no longer transient but rather prolonged. In addition, inhibition of both the synthesis of cellular proteins other than cold-shock proteins and cell growth was observed. Interestingly, when CspA was also overproduced together with the 5' UTR, normal cold-shock adaptive response was resumed without a prolonged lag period of cell growth. This indicates that the 5' UTR of the cspA mRNA and its gene product CspA play a critical role in the regulation of the expression of cold-shock genes and cold-shock adaptation. An 11-base common sequence (cold box) was found in the 5' UTRs of cspA, cspB, and csdA mRNAs. Indeed, the 25-base sequence within the 5' UTR of the cspA mRNA containing the cold-box sequence was able to prolong CspA production at 15 degrees C. We propose that a putative repressor binds to the cold-box sequence of the cold-shock mRNAs during the adaptive process and this binding in turn blocks the transcription of the cold-shock genes or destabilizes their mRNAs. CspA appears to promote either directly or indirectly the repressor function.
UNLABELLED: Blood catecholamine (CA), glucose and insulin were determined in 30 severe burn patients, of whom 22 were males, and 8 females. Mean burn area was 58.6 percent TBSA. These patients were in hypovolemic shock. RESULTS: CA release was persistent in severe burn patients showing two peaks in shock period and infection period (P < 0.01). The quantity of epinephrine (E) was normal, while norepinephrine (NE) was presistently high (P < 0.01), and it was over two fold of the normal value. The value seemed to reflect the severity of the injury. When CA did not show a rise in the shock period, or lowered abruptly in the sepsis period, the patients were in high risk. Increasing CA produced increase in gluconeogenesis with insufficiency in SI secretion.
By using Boyden Chamber and PACS methods, we analysed the chemotactic activity of five mouse thymic stromal cell (MTSC) lines' culture supernatant for neutrophil, monocyte/macrophage and lymphocyte, and the phenotype of the attracted lymphocyes, MTEC 1, MTEC 2, MTEC 3, MTEC 5 are mouse thymus epithelial cell lines. MTDC 4 is a mouse thymus dendritic cell line. The results indicate that all of the five MTSC supernatants have chemotactic activity for the target cells mentioned above but in different degree. Chemokines produced by the MTSC cells can be classified into three categories: (1) Chemokines produced by MTEC 1 and MTEC 2 are more potent for the attraction of neutrophils and lymphocytes. (2) MTDC 4 derived chemokines are highly potent for the attraction of monocytes/macrophages. (3) Chemokines produced by MTEC 3 and MTEC 5 are equally attractive to neutrophils, lymphocytes and monocytes/macrophages. Most of the MTSC-SN are more potent for the migration of B lymphocyte than for T lymphocyte. The MTSC-SN exhibits higher chemotactic activity to CD4-CD8+ T cell subset than to CD4+CD8-T cell subset. The characterization of chemokines in MTSC-SN will benefit the finding of new chemokines and the analysis of the mechanism of thymus homing.
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The gamma complex of DNA polymerase III holoenzyme, the replicase of Escherichia coli, couples ATP hydrolysis to the loading of beta sliding clamps onto primed DNA. The beta sliding clamp tethers the holoenzyme replicase to DNA for rapid and processive synthesis. In this report, the gamma complex has been constituted from its five different subunits. Size measurements and subunit stoichiometry studies show a composition of gamma 2 delta 1 delta' 1 1 chi 1 psi 1. Strong intersubunit contacts have been identified by gel filtration, and weaker contacts were identified by surface plasmon resonance measurements. An analogous tau complex has also been constituted and characterized; it is nearly as active as the gamma complex in clamp loading activity, but as shown in the fourth report of this series, it is at a disadvantage in binding the delta, delta', chi, and psi subunits when core is present (Xiao, H., Naktinis, V., and O'Donnell, M. (1995) J. Biol. Chem. 270, 13378-13383). The single copy subunits within the gamma complex provide the basis for the structural asymmetry inherent within DNA polymerase III holoenzyme.
The Escherichia coli replicase, DNA polymerase III holoenzyme, derives its processivity from the beta subunit sliding clamp that encircles DNA and tethers the replicase to the template. The beta dimer is assembled around DNA by the gamma complex clamp loader in an ATP-dependent reaction. In this report, the essential contact between the clamp loader and beta is identified as mediated through the delta subunit of the gamma complex. The delta subunit appears to contact the face of the beta dimer ring that contains the two C termini. Surprisingly, ATP is required for the gamma complex to bind beta, but not for delta to bind beta. This indicates that delta is buried in the gamma complex and suggests a role for ATP in exposing delta for interaction with beta. A protease protection assay has been developed to specifically probe the delta subunit within the gamma complex. The results of the assay are consistent with an ATP-induced conformational change in the gamma complex that alters the state of the delta subunit within it. The implication of these key features to the clamp loading mechanism of the gamma complex is discussed.
The cloning and expression of DNA for the three major opioid receptor types (mu, delta, and kappa) present new research opportunities for the characterization of opioid drugs and their interactions with these receptors. Genomic and cDNA clones for opioid receptors exist for several animal species including mouse, rat, guinea pig, and human. These include clones for all three human opioid receptor types. The receptor proteins consist of about 400 amino acids and have the characteristic seven transmembrane domain structure of G-protein-coupled receptors. There is about 60% amino acid identity between opioid receptor types and about 90% identity between a receptor type cloned from different animal species. All opioid receptor types mediate the inhibition of adenylyl cyclase in response to agonist binding. Radioligand binding and functional studies using the cloned receptors tend to support current conclusions on opioid drug receptor selectivity and activity. Investigations of opioid receptor chimeras and single amino acid mutants are providing information on the ligand recognition sites of these receptors and essential support for the development of computational opioid receptor models. A molecular model of the human delta opioid receptor is included in this review.
PURPOSE: To evaluate the usefulness of thallium-201 scintigrams in depiction of supradiaphragmatic lymphadenopathy associated with newly diagnosed Hodgkin disease in pediatric patients. MATERIALS AND METHODS: Thallium-201 and gallium-67 scans of the chest and neck were obtained in 33 consecutive patients. Mediastinal, cervical, supraclavicular, and axillary lymph node activity was evaluated by independent raters, and results were compared in a blinded fashion with those on chest computed tomographic (CT) scans. RESULTS: Gallium and thallium scans demonstrated similar accuracy in depiction of CT-defined mediastinal masses. The kappa statistic indicated moderate to strong agreement with CT results. Similarly, there was no statistically significant difference between the accuracy of thallium and gallium scans in depiction of extramediastinal lymphadenopathy. CONCLUSION: Thallium scintigraphy is effective for depiction of lymphadenopathy in pediatric patients with untreated Hodgkin disease. Serial thallium studies may provide an alternative to gallium scans in monitoring response to treatment.
PURPOSE: We assessed the cumulative risk of malignancies following treatment for Hodgkin's disease in childhood and adolescence and investigated related patient and treatment characteristics. PATIENTS AND METHODS: Medical records of 499 Hodgkin's disease patients treated between 1962 and 1993 were reviewed. There were 385 adolescents (> or = 10 years of age at diagnosis) and 114 preadolescents (< 10 years). Most patients (n = 346) were treated with radiation plus multiagent chemotherapy, while 30 received only chemotherapy and 123 only radiation therapy. Radiation doses ranged from 20 to 42 Gy. RESULTS: At a median follow-up duration of 9 years (range, 0.1 to 27.4), 25 patients have had second malignancies: 19 solid tumors, four acute nonlymphoblastic leukemias (ANLLs), 1 non-Hodgkin's lymphoma (NHL), and one chronic myeloid leukemia (CML). Three patients have had a third malignancy. The estimated cumulative risk of second malignancies increased from 1.5% at 5 years to 7.7% at 15 years. All but two of the patients with second malignancies were > or = 10 years of age at initial diagnosis, which reflects the higher risk among patients treated for Hodgkin's disease as adolescents (P = .01). Second malignancies were more common among female patients (P = .0002), even when those breast cancer were excluded (P = .007), and in those treated for recurrent Hodgkin's disease (P = .02). Patients with ANLL/NHL were older at diagnosis of Hodgkin's disease than those with solid tumors, (median age, 18.3 v 13.8 years; P = .04). There was no difference between groups treated with radiation therapy alone, chemotherapy alone, or radiation plus multiagent chemotherapy. CONCLUSION: Adolescents treated for Hodgkin's disease are at greater at risk of second malignancies than younger patients. Overall, adolescent females treated for recurrent Hodgkin's disease appear to be at greatest risk, while preadolescents appear to be protected from this late complication.
In order to investigate the role of hepatitis B virus (HBV) infection in the pathogenesis of HBV associated glomerulonephritis, 50 cases of glomerulonephritis with positive HBV infection marker antigenemia and/or HBAg detected by immunohistochemistry in renal tissue were collected. The distribution and localization of HBV DNA were observed by using in situ hybridization. In addition, Southern blot analysis was performed in 23 of the 50 cases to reveal the state of renal HBV DNA. Thirty Six cases (72%) were found to be HBV DNA positive by in situ hybridization, which was localized in the nucleus of tubular cells. In 26 cases HBV DNA was simultaneously detected in the nucleus of glomerular mesangial and epithelial cells as well as in the mesangial matrix. Seventeen of the 23 cases proved to be HBV DNA positive by Southern blot analysis. In which 3 cases were identified as having non-replicating free HBV DNA, while 14 cases (82%) were of the integrated form. Since there was abundant evidence of the renal tissue being infected with HBV, it was considered that the HBAg deposited on glomeruli not only originated from circulation but also from the HBV infected glomerular cells. In addition to the humoral immune injury mediated by HBAg-HBAb immune complex, the cellular mechanism mediated by target antigen (HBcAg) may be also involved in the pathogenesis of HBV associated glomerulonephritis.
HBV antigens (HBcAg, HBsAg and HBeAg) in 246 cases of renal biopsy specimens with various types of glomerulonephritis were examined by immunohistochemical techniques. Southern blot hybridization was used to detect HBV DNA in 18 cases. The results showed that HBV antigens were frequently found in the tubular cells in addition to the appearance of HBV antigens on the glomeruli of certain glomerulonephritis. The positive rte of HBcAg in the tubular cells was 21.54%, which is higher than that of glomeruli (10.98%). Renal HBV DNA was positive in 15 cases and among them HBcAg expression in renal tissue in 14 cases and HBV antigenemia in 12 cases. The results suggest that HBV may also be implicated in the pathogenesis of certain cases of glomerulonephritis and the appearance of HBV antigen antibody immunocomplex in renal tissue, aside from originating in the circulation, there is the possibility of it originating from renal cells in situ.
The delta opioid receptor is an important target for analgesic drug development. This report describes the identification of delta opioid receptor clones from human cDNA libraries and the preparation of a human delta receptor cDNA in the pcDNA3 expression vector for transfection studies. The cDNA encodes a 372 amino acid protein that has 93% amino acid identity to mouse and rat delta receptors. COS-7 cells transfected with this clone express over 1.0 pmol receptor/mg protein when measured by saturation binding with [3H]naltrindole. The delta receptor selective ligands NTB, BNTX, [4'-Cl-Phe4]DPDPE and [D-Ala2,Glu4]deltorphin all have Ki values under 10 nM while the affinities of the mu and kappa opioid receptor ligands CTAP and U-69593, respectively, are over 4.0 microM. Agonists show binding to multiple affinity states of the receptor consistent with the presence of G-protein coupled and uncoupled forms of the expressed receptor. The 8-fold higher affinity of NTB relative to BNTX suggests that the human delta receptor is of the delta 2 subtype.
A new biocomposite, based on the incorporation of the enzyme tyrosinase into a graphite-epoxy resin matrix, was used for the effective biosensing of phenolic compounds. The enzyme retains its bioactivity on confinement in the epoxy resin environment. This renewable (polishable) and rigid bioprobe offers convenient quantification for various phenolic substrates. The fast response (steady-state time = 25 s) accrues from the close proximity of the enzyme and graphite sites. The influence of various experimental variables was explored for optimum biosensing performance. Flow-injection monitoring of phenolic compounds at a rate of 50 samples h-1 yielded a detection limit of 1 x 10(-6) mol l-1 and a relative standard deviation of 1.4% (n = 40).
Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catecholamine and catechol drugs such as levodopa and methyldopa. Human COMT activity is inherited as an autosomal co-dominant trait; approximately 25% of white individuals have low activity consistent with homozygosity for a low activity allele, about 50% have intermediate activity (i.e., heterozygous genotype) and 25% have high activity. COMT activity has not been characterized in African-Americans or other black populations. To investigate potential ethnic and gender differences in COMT, we measured erythrocyte COMT activity in 195 unrelated black and 202 unrelated white healthy individuals living in the Southeast United States. Overall, the black population had significantly higher COMT activity than the white population (median 15.7 vs. 11.4 U/ml of packed red blood cell volume; P < .001). Maximum likelihood estimation of COMT activity distribution identified significant ethnic differences, with high activity in 23% of whites and 55% of blacks, intermediate activity in 50% of whites and 38% of blacks and low activity in 27% of whites and 7% of blacks. No greater differences in COMT activity were observed in either ethnic group. We conclude that red blood cell COMT activity is significantly higher in black subjects than white subjects. Hardy-Weinberg estimates indicate that this ethnic difference is due to a higher frequency of high activity COMT alleles in blacks vs. whites (0.74 vs. 0.48).