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Biomedical subjects

J Tao

Publications and source records attributed to J Tao.

At least 55 records · Page 3Linked to original sources

Epstein-Barr virus-associated high-grade B-cell lymphoma of mucosal-associated lymphoid tissue in a 9-year-old Boy.

We report an unusual case of Epstein-Barr virus (EBV)-associated mucosal-associated lymphoid tissue (MALT) lymphoma involving the lungs, kidneys, and axillary lymph nodes in a child with congenital hypoadrenalism and panhypopituitarism. The patient presented with an aggressive clinical course and histologic evolution. Initial biopsies (1994) of the lung and kidney revealed histologic features of low-grade B-cell MALT lymphoma with lymphoepithelial lesions within the renal tubules and bronchial epithelium. Subsequent biopsies (1996, 1997, and 1999) revealed progressively greater cytologic atypia, polymorphism, and necrosis; an increased mitotic rate; and a preponderance of large cells, indicative of progression from a low-grade to a high-grade MALT lymphoma. Immunophenotyping of the lung and lymph node lesions revealed identical surface marker profiles: cells were CD19(+), CD20(+), immunoglobulin (Ig) G(+), kappa(+), lambda(-), CD5(-), CD10(-), CD23(-), and IgM(-), and also negative for T-cell markers. Genotypic analysis demonstrated the presence of immunoglobulin heavy chain rearrangement and monoclonality of EBV in the lung lesion by Southern blot hybridization and polymerase chain re()action (PCR). The clinicopathologic features suggest that these lesions might represent an immunosupression-related continuum of low-grade to high-grade MALT lymphomas. Infection with EBV may have contributed to this tumor's aggressive clinical and histologic evolution.

Biomarkers, Tumor↗

Effects of hyperbaric oxygen on ventricular performance, pulmonary blood volume, and systemic and pulmonary vascular resistance.

The cardiovascular effects of hyperbaric (3 atm abs) air, 100% oxygen, and hyperbaric oxygen (HBO2) at 3 atm abs were investigated in 13 pentobarbital-anesthetized dogs. We measured heart rate, arterial pressure, pulmonary artery pressure, right atrial pressure, left and right ventricular pressure, and cardiac output. From these we determined end diastolic pressure, +/-maximal dp/dt, maximal (dp/p), end systolic elastance, cardiac work, and systemic (SVR) and pulmonary vascular resistance (PVR). Pulmonary blood volume was obtained from the mean transit time of ascorbic acid. The significant results with HBO2 were a decrease in heart rate, cardiac output, and cardiac work. All left ventricular performance indices decreased, without a change in preload or afterload. In contrast, only right ventricular -dp/dt decreased. SVR increased but PVR did not change; 100% O2 produced similar but less pronounced responses. Hyperbaric air had only mild effects. Pulmonary blood volume and lung wet/dry ratio did not change. Our data suggest that HBO2 may act by a differential effect on the autonomic innervation of the right and left ventricles. The resultant ventricular imbalance may be of clinical importance in the mechanism of pulmonary edema in patients in congestive heart failure undergoing hyperbaric therapy.

Animals↗

A 1063G-->A mutation in exon 12 of glycoprotein (GP)IIb associated with a thrombasthenic phenotype: mutation analysis of [324E]GPIIb.

We report the molecular, genetic and functional analysis of a case of thrombasthenic phenotype. The proband showed absence of platelet glycoprotein (GP)IIb and very low content of GPIIIa, and both his parents showed a marked reduction in the levels of platelet GPIIb-IIIa. Single-stranded conformational polymorphism-polymerase chain reaction (SSCP-PCR) analysis and direct sequencing of PCR-amplified GPIIb exon-12 revealed the presence of a G-->A transition at position 1063 with the expected substitution of glutamate 324 with lysine (K). This mutation did not alter the level of GPIIb mRNA. Co-expression of normal or mutant [324K] GPIIb with normal human GPIIIa in Chinese hamster ovary (CHO) cells failed to show surface exposure of [324K]GPIIb-IIIa complexes. Pulse-chase and immunoprecipitation analysis demonstrated that [324K]GPIIb cDNA was translated into proGPIIb, but neither mutant GPIIb heavy chain (GPIIbH) nor [324K]GPIIb-GPIIIa complexes were detected, suggesting that this mutation is the underlying molecular basis for the thrombasthenic phenotype. Mutation analysis demonstrated that 324E of GPIIb could be replaced by other negatively charged or polar amino acids (AAs) without impairing the surface expression of GPIIb-IIIa. However, substitution of 324E of GPIIb for a positively charged AA other than K prevented the expression of GPIIb-IIIa complexes. These observations suggest that a domain encompassing 324E of GPIIb is essential for heterodimerization with GPIIIa and its substitution for a positively charged residue precludes normal subunit association.

Animals↗

Biological effects of C-type natriuretic peptide in human myofibroblastic hepatic stellate cells.

During chronic liver diseases, hepatic stellate cells (HSC) acquire a myofibroblastic phenotype, proliferate, and synthetize fibrosis components. Myofibroblastic HSC (mHSC) also participate to the regulation of intrahepatic blood flow, because of their contractile properties. Here, we examined whether human mHSC express natriuretic peptide receptors (NPR). Only NPR-B mRNA was identified, which was functional as demonstrated in binding studies and by increased cGMP levels in response to C-type natriuretic peptide (CNP). CNP inhibited mHSC proliferation, an effect blocked by the protein kinase G inhibitor 8-(4 chlorophenylthio)-cGMP and by the NPR antagonist HS-142-1 and reproduced by analogs of cGMP. Growth inhibition was associated with a reduction of extracellular signal-regulated kinase and c-Jun N-terminal kinase and with a blockade of AP-1 DNA binding. CNP and cGMP analogs also blunted mHSC contraction elicited by thrombin, by suppressing calcium influx. The relaxing properties of CNP were mediated by a blockade of store-operated calcium channels, as demonstrated using a calcium-free/calcium readdition protocol. These results constitute the first evidence for a hepatic effect of CNP and identify mHSC as a target cell. Activation of NPR-B by CNP in human mHSC leads to inhibition of both growth and contraction. These data suggest that during chronic liver diseases, CNP may counteract both liver fibrogenesis and associated portal hypertension.

Adipocytes↗

Autologous peripheral blood stem cell transplantation for Waldenstrom's macroglobulinemia.

We report a 50-year-old male patient with Waldenstrom's macroglobulinemia poorly responsive to conventional chemotherapy, who went on to receive high-dose melphalan as conditioning before autologous PBSC infusion. Autologous hematopoiesis was reconstituted 5 weeks after transplant. Complete remission was confirmed by blood and marrow examination. The patient remains well at 12 months, with no detectable monoclonal IgM in his serum and absence of plasmacytoid lymphocytes in his marrow. Our results suggest that, at least in this case, high-dose chemotherapy with autologous PBSC support was an effective therapeutic approach for Waldenstrom's macroglobulinemia.

Hematopoietic Stem Cell Transplantation↗

Epstein-Barr virus-associated polymorphic B-cell lymphoproliferative disorders in the lungs of children with AIDS: a report of two cases.

Patients infected with HIV experience a spectrum of lymphoproliferative disorders, including generalized reactive lymphadenopathy to atypical lymphoproliferative lesions and lymphomas. Polymorphic B-cell lymphoproliferative disorders are rare and not well documented. We studied lung lesions from two children infected with HIV: an atypical polymorphic B-cell hyperplasia in a 14-year-old boy and a malignant polymorphic B-cell lymphoma in a 21-month-old girl. Morphologically, both lung lesions revealed similar polymorphic lymphoid infiltrations with numerous mitoses in case 1 and extensive necrosis and architectural distortion in case 2. Immunophenotypic examination showed no predominance of kappa or lambda light chain in case 1 and a predominance of kappa light chain in case 2. Genotypic analysis demonstrated an absence of immunoglobulin and T-cell receptor gene rearrangements in case 1 and the presence of biallelic immunoglobulin heavy chain rearrangement and a single clonal Epstein-Barr virus (EBV) in case 2. The clinical course was indolent in case 1 and aggressive in case 2. The clinicopathologic features were similar to those of posttransplantation lymphoproliferative disorders suggesting that these lung lesions might represent an immunosuppression-related spectrum of benign to malignant diseases. EBV infection may play a role in the pathogenesis of these lesions. This study highlights the importance of the molecular characterization of AIDS-associated lymphoproliferative disorders in children in establishing a definitive diagnosis.

Adolescent↗

[Studies on chemical constituents and pharmacological effects of the stem of Cynomorium songaricum Rupr].

OBJECTIVE: In order to exploit the medicinal resources and provide a scientific evidence for the clinical use and quality of Cynomorium songaricum control, the chemical constituents and pharmacological effects of the stem of the plant were studied preliminarily. METHOD: The chemical constituents were studied by spectral analysis and chemical method. The pharmacological effects were studied by an experiment on the defecation and deficiency of kidney function. RESULT AND CONCLUSION: Seven compounds were isolated from the stem of C. songaricum and identified as beta-sitosterol(I), palmitic acid (II), ursloic acid (III), daucosterol (IV), (-)-catechin (VI), naringenin-4'-O-pyranogluoside (VII) and succinicyacid (XII). Compounds VI and XII were isolated from this species for the first time. The pharmacological results show that the different extracts facilitate catharsis and replenish the deficiency of kidney yang.

Animals↗

Truncation of glycoprotein (GP) IIIa (616-762) prevents complex formation with GPIIb: novel mutation in exon 11 of GPIIIa associated with thrombasthenia.

This work reports the molecular genetic study of a patient who suffered from Glanzmann thrombasthenia (GT). Structural analysis of the glycoprotein (GP) IIb and GPIIIa genes showed the presence of a homozygous G1846-->T transversion in exon 11 of GPIIIa that changes Glu616-->Stop. Cytometric and immunochemical analysis indicated that platelet GPIIb-IIIa was absent in the proband but present at normal levels in the heterozygous relatives. The following observations indicate that this mutation is responsible for the thrombasthenic phenotype of the proband. (1) We failed to detect mutations other than [T1846]GPIIIa in the coding region of both GPIIb and GPIIIa genes. (2) The G1846-->T mutation was observed in either parent and a brother of the proband, but none of 100 unrelated individuals carried this defect. (3) Pulse-chase and immunoprecipitation analysis of GPIIb-IIIa complexes in cells transiently cotransfected with cDNAs encoding normal GPIIb and [T1846]GPIIIa showed neither maturation of GPIIb nor complex formation and surface exposure of GPIIb-triangle upGPIIIa. These observations indicate that the sequence from Glu616 to Thr762 in GPIIIa is essential for heterodimerization with GPIIb. Polymerase chain reaction-based analysis demonstrated the presence of normal levels of full-length GPIIIa-mRNA in the proband and in heterozygous relatives. In addition, a shortened transcript, with a 324-nucleotide deletion, resulting from in-frame skipping of exons 10 and 11, was detectable upon reamplification of the DNA. Thus, unlike other nonsense mutations, [T1846]GPIIIa does not lead to abnormal processing or reduction in the number of transcripts with the termination codon.

Adult↗

Platelet-derived growth factor-BB and thrombin generate positive and negative signals for human hepatic stellate cell proliferation. Role of a prostaglandin/cyclic AMP pathway and cross-talk with endothelin receptors.

Proliferation of myofibroblastic hepatic stellate cells (HSC) in response to growth factors is essential for the development of liver fibrosis. We have reported that prostaglandins (PG) and cyclic AMP (cAMP) inhibit growth of human HSC. This PG/cAMP pathway transduces the endothelin (ET) B-mediated antiproliferative effect of endothelin-1 (ET-1) and up-regulates ETB receptors. Here, we show that platelet-derived growth factor (PDGF)-BB and thrombin, although mitogenic, generate growth inhibitory PGE2 in myofibroblastic human HSC. The two peptides elicit early PGE2 and cAMP synthesis, and also promote delayed induction of cyclooxygenase (COX)-2. Both early and delayed production of PGE2 counteract the mitogenic effect of PDGF-BB and thrombin because: (i) pretreatment with the COX inhibitor ibuprofen markedly enhances the mitogenic effect of both peptides; (ii) blocking early synthesis of PGE2 greatly enhances extracellular signal-regulated kinase (ERK) activation by both growth factors; (iii) enhancement of DNA synthesis by ibuprofen is only lost when the inhibitor is added after COX-2 induction has occurred. Finally, PDGF-BB and thrombin raise ETB receptors through the PG pathway. Thus, ibuprofen blunts growth factor-induced increase in ETB receptors. Up-regulation of the growth inhibitory ETB receptors by both mitogens may enhance the antiproliferative effect of ET-1 and thereby establish a negative feedback of their mitogenic effect. Our results shed light on novel growth inhibitory signals evoked by two mitogenic growth factors expressed during liver injury.

Adipocytes↗

Role of NF-kappaB in the antiproliferative effect of endothelin-1 and tumor necrosis factor-alpha in human hepatic stellate cells. Involvement of cyclooxygenase-2.

During chronic liver diseases, hepatic stellate cells (HSC) acquire an activated myofibroblast-like phenotype and proliferate and synthesize fibrosis components. Endothelin-1 (ET-1), which inhibited the growth of human myofibroblastic HSC, increased the formation of two NF-kappaB DNA binding complexes; this effect was also observed with tumor necrosis factor-alpha (TNF-alpha). The complexes were identified as the p50/p50 and p50/p65 NF-kappaB dimers. Activation of NF-kappaB was associated with the degradation of the inhibitory protein IkappaB-alpha; no IkappaB-beta was detected. Activation of NF-kappaB and degradation of IkappaB-alpha were prevented by the NF-kappaB inhibitors sodium salicylate and MG-132. In addition to cyclooxygenase-1 (COX-1), COX-2 is also constitutively expressed in human HSC, and the use of dexamethasone and of SC-58125, a selective COX-2 inhibitor, revealed that COX-2 accounts for basal COX activity. Moreover, COX-2 mRNA and protein were up-regulated by ET-1 and TNF-alpha, whereas COX-1 was unaffected. Induction of COX-2 and stimulation of COX activity by ET-1 and TNF-alpha were prevented by sodium salicylate and MG-132, suggesting that activation of NF-kappaB by either factor is needed for stimulation of COX-2. Finally, SC-58125 and dexamethasone reduced the growth inhibitory effect of ET-1 and TNF-alpha, indicating that activation of COX-2 is required for inhibition of HSC proliferation. Taken together, our results suggest that NF-kappaB, by inducing COX-2 expression, may play an important role in the negative regulation of human myofibroblastic HSC proliferation.

Adipocytes↗

Application of geographical information systems to co-analysis of disease and economic resources: dengue and malaria in Thailand.

Two vector-borne communicable diseases, malaria and dengue, are among a number of diseases of particular importance in relation to economic development in Southeast Asia and thus need to be assessed in relation to economic parameters in the region. Geographical Information Systems (GIS) provide one means of comparing disease and resource data versus time and place, to facilitate rapid visualization by planners and administrators. Given that Thailand is a global epicenter of multidrug resistant falciparum malaria and of dengue hemorrhagic fever, both of which are mosquito-borne, application of GIS methods to these two diseases gives opportunity for comparison of resource needs and allocation in relation to disease epidemiologic patterns. This study examined per capita gross provincial product (GPPpc) and health care resources in relation to geographic distribution of malaria and dengue in Thailand. The two diseases vary greatly in overall seasonal patterns and in relation to provincial economic status, and present differing demands on resource utilization: planned integration of control of malaria and dengue could utilize such analyses in relation to resource sharing and consideration of allocative efficiency. The concentration of malaria (and to a lesser extent dengue) along international border areas underscores the desirability of multi-country coordination of disease management and control programs. Because socio-economic and disease data are collected by quite different means and in different time frames, there are some limitations to the dynamic interpolation of these two broad data sets, but useful inferences can be drawn from this approach for application to overall planning, at both national and multi-country levels.

Dengue↗

[Preoperative staging of esophageal carcinoma: comparison of endoesophageal ultrasonography, computerized tomography and conventional clinical staging].

OBJECTIVE: To evaluate the value of different methods in preoperative staging of esophageal carcinoma. METHOD: Thirty-six patients undergoing resection of esophageal carcinoma were examined with endoesophageal ultrasonography (EU) before operation. Eight of 36 patients could not be evaluated because of severe esophageal stenosis. Computerized tomography (CT) was performed in 21 patients. Comparison was made between stagings based on EU, CT as well as the conventional clinical staging system, respectively with surgical-pathological staging after resection. RESULT: The accuracy of conventional clinical staging for esophageal cancer was only 36%. The accuracy of CT in T, N and pTNM staging was 38.1%, 57.1% and 47.6% respectively. For EU, the figures were 77.8%, 72.2% and 72.2%, and were improved to be 85.7%, 78.6% and 83.1% when untraversable patients were excluded. CONCLUSION: While conventional clinical staging system lacks accuracy in evaluating esophageal carcinoma, CT makes only moderate improvement. Based on direct morphological examination of lesions, EU is highly accurate in preoperative staging of esophageal carcinoma, especially in evaluating the extent of luminal wall invasion and regional lymph node involvement. Therefore, EU is of critical value in the therapeutic selection for esophageal carcinoma.

Endosonography↗

[FTIR study on structure of pearl and nacre of mollusk shell].

Pearl and nacre of mollusk shell (Hyriopsis cumingii) were studied with high resolution Fourier transformation infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The results of X-ray diffraction indicate that the samples are still aragonite after thermal treatment at 160 degrees C for 5hr, however, the significant variations of peak position and band width of FTIR spectra reveal the interaction between organic matrix and inorganic crystal in biomineralized materials. The variations of spectra were studied by a curve-fitting algorithm and the band related to the interaction is revealed.

Animals↗

Aminoacyl tRNA synthetases as targets for new anti-infectives.

Because resistance has developed to mainline antibiotics, including vancomycin, new antibiotics are now being aggressively sought. For this purpose, aminoacyl tRNA synthetases are being pursued as targets for new drugs. These enzymes are universal and are essential for cell viability. The key to their usefulness lies in being able to find drugs that inhibit a pathogen synthetase but not its human cell counterpart. The possibility for species-specific inhibition was originally demonstrated with a natural product and has now been demonstrated with prototypical drugs that are based on the structure of an intermediate of the aminoacylation reaction. Efficacy of a rationally designed inhibitor has been shown in vivo with a pathogen infection established in an animal model. Although many challenges remain, these early results suggest that synthetases will continue to be of major interest for development of new anti-infectives.

Adenosine Monophosphate↗

Kinase-independent potentiation of B cell antigen receptor-mediated signal transduction by the protein tyrosine kinase Src.

Signal transduction mediated by the B cell Ag receptor involves the activation of multiple protein tyrosine kinases that are members of the Src family (i.e., Fyn, Lyn, Blk, Lck). To determine whether members of the Src family possess common physical and/or enzymatic properties that enable them to potentiate signal transduction via the B cell Ag receptor, we expressed the protein tyrosine kinase Src in the B lymphoma cell line K46-17 mu m lambda. Based on coprecipitation analysis and two-color immunofluorescence, this heterologous Src family kinase was observed to physically associate with the B cell Ag receptor. Additional experiments demonstrated that B cell Ag receptor cross-linking results in increased tyrosine phosphorylation and activation of Src. Several parameters of B cell activation, including tyrosine phosphorylation of intracellular substrates, calcium mobilization, and transcription factor activation, were potentiated in cells that expressed Src when compared with control cells. To determine whether potentiation of Ag receptor-mediated signaling by Src was dependent on its catalytic activity, a kinase-deficient form of Src was expressed in K46-17 mu m lambda cells. Transfectants expressing kinase-deficient Src exhibited an enhanced responsiveness to stimulation through the B cell Ag receptor that was comparable with transfectants expressing wild-type Src. Additionally, kinase-deficient Src was observed to associate with the endogenous kinase Lyn in an activation-dependent manner. These findings indicate that members of the Src family may potentiate Ag receptor-mediated signaling via a kinase-independent mechanism(s) that involves amplification of kinase recruitment to the Ag receptor activation complex.

Adjuvants, Immunologic↗

Elongation factor Ts of Chlamydia trachomatis: structure of the gene and properties of the protein.

A putative structural gene cluster containing four open reading frames (ORFs) located downstream of the omp1 gene of Chlamydia trachomatis mouse pneumonitis (MoPn) was cloned and sequenced. A GenBank survey indicated that the identified cluster is similar to the rpsB-tsf-pyrH(smbA)-frr region of Escherichia coli. The second ORF was 846 bp encoding a 282-amino-acid polypeptide with a calculated M(r) 30,824. Alignment of this deduced protein sequence and E. coli elongation factor Ts (EF-Ts, product of tsf) demonstrated 34% identity and an additional 14% similarity. The putative chlamydial tsf gene was expressed in E. coli as a nonfusion protein and as a 6x His-tagged fusion protein. By SDS-PAGE analysis, the molecular weights of the nonfusion recombinant protein and a protein of chlamydial elementary bodies (EBs), which was recognized by monoclonal antibodies derived from the nonfusion recombinant protein, are 34 kDa. The purified recombinant 6x His-tagged fusion protein increased the rate of GDP exchange with both Chlamydia and E. coli elongation factor Tu (EF-Tu). These data show that the second gene of the identified cluster is tsf. Unlike EF-Ts from any other species, its activity was comparable to that of E. coli EF-Ts in exchange reaction with E. coli EF-Tu.

Amino Acid Sequence↗

Mutation analysis of chromosome 19 calmodulin (CALM3) gene in Alzheimer's disease patients.

The calcium buffering capacity of lymphoblasts from patients suffering of late onset Alzheimer's disease (AD) has been reported to be diminished. Calmodulin is a calcium binding protein codified by three genes, one of them (CALM3) maps to chromosome 19, nearby a gene, apoE, associated with late onset AD. In this study we screened for structural changes in the CALM3 gene from AD patients by PCR-SSCP analysis. We observed several point mutations in the intronic flanking regions of exons 3 and 4 of CALM 3 gene. However, we failed to detect any structural changes in the regions encoding the calcium binding domains of this gene. Similar results were obtained by RT-PCR analysis of CALM3 transcripts from AD patients carrying apoE epsilon4 allele. It is concluded that structural alterations in the CALM3 gene are not associated with the altered Ca2+ homeostasis shown by lymphoblasts from these patients.

Age of Onset↗