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Biomedical subjects

Y Chang

Publications and source records attributed to Y Chang.

At least 109 records · Page 6Linked to original sources

Actions of tachykinins within the heart and their relevance to cardiovascular disease.

Substance P and neurokinin A are tachykinins that are co-localized with calcitonin gene-related peptide (CGRP) in a unique subpopulation of cardiac afferent nerve fibers. These neurons are activated by nociceptive stimuli and exhibit both sensory and motor functions that are mediated by the tachykinins and/or CGRP. Sensory signals (e.g., cardiac pain) are transmitted by peptides released at central processes of these neurons, whereas motor functions are produced by the same peptides released from peripheral nerve processes. This review summarizes our current understanding of intracardiac actions of the tachykinins. The major targets for the tachykinins within the heart are the intrinsic cardiac ganglia and coronary arteries. Intrinsic cardiac ganglia contain cholinergic neurons that innervate the heart and coronary vasculature. Tachykinins can stimulate NK3 receptors on these neurons to increase their excitability and evoke spontaneous firing of action potentials. This action provides a mechanism whereby tachykinins can indirectly influence cardiac function and coronary tone. Tachykinins also have direct effects on coronary arteries to decrease or increase tone. Stimulation of NK1 receptors on the endothelium causes vasodilation mediated by nitric oxide. This effect is normally dominant, but NK2 receptor-mediated vasoconstriction can also occur and is augmented when NK1 receptors are blocked. It is proposed that these ganglion stimulant and vascular actions are manifest by endogenous tachykinins during myocardial ischemia.

Action Potentials↗

The distribution of heat shock proteins in the nervous system of the unstressed mouse embryo suggests a role in neuronal and non-neuronal differentiation.

Heat shock proteins (Hsps) act as molecular chaperones and are generally constitutively expressed in the absence of stress. Hsps are also inducible by a variety of stressors whose effects could be disastrous on the brain. It has been shown previously that Hsps are differentially expressed in glial and neuronal cells, as well as in the different structures of the brain. This differential expression has been related to specific functions distinct from their general chaperone function, such as intracellular transport. We investigated here the constitutive expression of 5 Hsps (the small Hsp, Hsp25, the constitutive Hsc70 and Hsp90beta, the mainly inducible Hsp70 and Hsp90alpha), and of a molecular chaperone, TCP-1alpha during mouse nervous system development. We analyzed, by immunohistochemistry, their distribution in the central nervous system and in the ganglia of the peripheral nervous system from day 9.5 (E9.5) to day 17.5 (E17.5) of gestation. Hsps are expressed in different cell classes (neuronal, glial, and vascular). The different proteins display different but often overlapping patterns of expression in different regions of the developing nervous system, suggesting unique roles at different stages of neural maturation. Their putative function in cell remodeling during migration or differentiation and in protein transport is discussed. Moreover we consider Hsp90 function in cell signaling and the role of Hsp25 in apoptosis protection.

Animals↗

Long-term disability and return to work among patients who have a herniated lumbar disc: the effect of disability compensation.

BACKGROUND: Low-back problems are one of the most frequent reasons for disability compensation claims by workers. However, the effect of Workers' Compensation status on the long-term outcome for workers with sciatica has not been studied in detail, to our knowledge. Therefore, we believe that it is important to describe the long-term outcomes for patients who have herniation of a lumbar disc and sciatica according to the Workers' Compensation status at the time of the preoperative consultation. METHODS: We conducted a prospective, observational study of patients who had sciatica and were seeking care from specialist physicians in community-based practices throughout Maine. Among 440 eligible patients, 199 were receiving Workers' Compensation at the time of entry into the study (baseline) and 241 were not. Three hundred and twenty-six patients (74 percent) completed questionnaires at the time of a four-year follow-up. The outcomes that we assessed included disability compensation and work status as well as relief from symptoms, functional status, and quality of life. RESULTS: Patients who were receiving Workers' Compensation at baseline were more likely to be young, male, and employed as laborers. They reported worse functional status; however, the clinical findings for these patients were similar to those for patients who were not receiving Workers' Compensation. Patients who had been receiving Workers' Compensation at baseline were more likely to be receiving disability benefits at the time of the four-year follow-up compared with those who had not (27 percent of 133 compared with 7 percent of 189; p<0.001); however, they were only slightly less likely to be working at the time of the four-year follow-up (80 percent of 133 compared with 87 percent of 190; p = 0.09). Operative management did not influence these comparisons, but it decreased symptoms and improved functional status. Patients who had been receiving Workers' Compensation at baseline also had significantly less relief from symptoms and improvement in quality of life than patients who had not been receiving Workers' Compensation (all p<0.001). In multivariate models, Workers' Compensation status at baseline was an independent predictor of whether the patient would be receiving disability benefits after four years (odds ratio, 3.5; 95 percent confidence interval, 1.7 to 7.6) but was not an independent predictor of whether the patient would be working on a job for pay at the time of the four-year follow-up (odds ratio, 0.6; 95 percent confidence interval, 0.3 to 1.2). CONCLUSIONS: Even after adjustment for the initial treatment of the sciatica and for other clinical factors, patients who had been receiving Workers' Compensation at baseline were more likely to be receiving disability benefits and were less likely to report relief from symptoms and improvement in quality of life at the time of the four-year follow-up than patients who had not been receiving Workers' Compensation at baseline. Nonetheless, most patients returned to work regardless of their initial disability status, and those who had been receiving Workers' Compensation at baseline were only slightly less likely to be working after four years. Whether or not they had been receiving Workers' Compensation at baseline, patients who had been managed with an operation reported greater relief from symptoms and improvement in functional status at the time of the four-year follow-up compared with patients who had been managed nonoperatively, even though the outcomes with regard to disability and work status in these two groups were comparable.

Adult↗

Tachykinin receptor subtypes in the isolated guinea pig heart and their role in mediating responses to neurokinin A.

Selective tachykinin agonists were used to identify cardiac and coronary responses mediated by specific tachykinin receptor subtypes in isolated, perfused guinea pig hearts. Receptor desensitization with selective agonists and blockade with selective antagonists were used to determine the role of specific subtypes in generating responses to neurokinin A (NKA). Dose-dependent cardiac and coronary effects were evoked by bolus injections of ¿Sar(9), Met(O(2))(11)substance P (¿Sar(9),Met(O(2))(11)SP), GR64349, and ¿MePhe(7)neurokinin B (¿MePhe(7)NKB) (selective agonists for NK(1), NK(2), and NK(3) receptors, respectively). Each agonist caused bradycardia, but GR64349 was most effective (34 +/- 4% decrease in heart rate with 32 nmol, n = 8). Prominent increases in ventricular contractility and perfusion pressure also occurred with 32 nmol of GR64349 (25 +/- 6 and 33 +/- 4%, respectively). ¿Sar(9), Met(O(2))(11)SP was unique in having a high potency for decreasing ventricular contractility and perfusion pressure. Bolus injections of 25 nmol of NKA decreased rate (48 +/- 2%, n = 51), increased contractility (26 +/- 2%), and had biphasic effects on perfusion pressure (24 +/- 1% decrease followed by 9.2 +/- 1.4% increase). Desensitization with GR64349 or treatment with the NK(2) antagonist SR48968 reduced the bradycardic response to NKA by greater than 75% and eliminated the positive inotropic response. The remaining bradycardia occurred through NK(3) receptors. Desensitization with ¿Sar(9),Met(O(2))(11)SP or NK(1) blockade with FK888 eliminated the coronary relaxant action of NKA and enhanced the pressor response. It is concluded that three tachykinin receptor subtypes are present in the guinea pig heart and that each contributes to the overall response evoked by NKA.

Animals↗

Risk factors for cervical stenosis after loop electrocautery excision procedure.

OBJECTIVE: To assess frequency of and identify risk factors for the development of cervical stenosis after loop electrosurgical excision procedure. METHODS: We reviewed outpatient charts of women treated by loop excision for cervical dysplasia between August 1996 and January 1998 in the colposcopy clinic at Massachusetts General Hospital. One hundred sixty-four women were evaluated for cervical stenosis during follow-up. Stenosis was considered present if manual dilation was required to allow endocervical sampling with an endocervical currette 3 mm wide. Multivariable analysis with stepwise logistic regression was used to evaluate age, parity, tobacco use, hormonal status, use of oral contraceptives, pathology, previous loop excision, performance of additional endocervical excision, and dimensions of excision specimens as predictors of cervical stenosis. RESULTS: The average age was 32 years. Cervical stenosis occurred in ten of 164 women (6%, 95% CI 3%, 11%). Among factors analyzed, previous loop excision and volume of excision specimen were the only independent predictors of stenosis. CONCLUSION: Cervical stenosis correlated with history of loop excision and volume of tissue removed, suggesting that women who have second excisions or large excisions should be counseled that their risk of stenosis might be higher.

Adolescent↗

Permeability and single channel conductance of human homomeric rho1 GABAC receptors.

1. Homomeric human rho1 GABAC receptors were expressed in Xenopus oocytes and in human embryonic kidney cells (HEK293) in order to examine their conductance and permeability. 2. Reversal potentials of currents elicited by gamma-aminobutyric acid (GABA) were measured in extracellular solutions of various ionic composition to determine relative permeability of homomeric rho1 receptors. The rank order of anionic permeability was: SCN- > I- > NO3- > Br- > Cl- > formate (For-) > HCO3- > acetate (Ac-) approximately proprionate (Prop-) approximately isethionate (Ise-) approximately F- approximately PO4-. 3. In the oocyte expression system, relative permeabilities to SCN-, I-, NO3-, Br- and HCO3- were higher for rho1 GABAC receptors than alpha1beta2gamma2L GABAA receptors. 4. Expression of rho1 GABAC receptors in Xenopus oocytes and in HEK293 cells gave similar relative permeabilities for selected anions, suggesting that the expression system does not significantly alter permeation properties. 5. The pore diameter of the homomeric rho1 GABAC receptor expressed in oocytes was estimated to be 0.61 nm, which is somewhat larger than the 0.56 nm pore diameter estimated for alpha1beta2gamma2L GABAA receptors. 6. Homomeric rho1 GABA receptors expressed in oocytes had a single channel chord conductance of 0.65 +/- 0.04 pS (mean +/- s.e.m.) when the internal chloride concentration ([Cl-]i) was 20 mM. With a [Cl-]i of 100 mM, the single channel chord conductance was 1.59 +/- 0.24 pS. 7. The mean open time directly measured from 43 GABA-induced channel openings in six patches was 3. 2 +/- 0.8 s. The mean open time in the presence of 100 microM picrotoxin was 0.07 +/- 0.01 s (77 openings from 3 patches). 8. The differences observed in ionic permeabilities, pore size, single channel conductance and mean open time suggest that the rho1 homomeric receptor may not be the native retinal GABAC receptor reported previously.

Animals↗

Involvement of interleukin-10 (IL-10) and viral IL-6 in the spontaneous growth of Kaposi's sarcoma herpesvirus-associated infected primary effusion lymphoma cells.

Primary effusion lymphoma (PEL) is a distinct type of lymphoma associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. To determine the factors responsible for the unrestrained proliferation of PEL, we have studied the growth factor requirements of the PEL-derived BCBL-1 and BC-1 cell lines. Both cell lines were found to be autocrine growth factor dependent and to release human interleukin-6 (IL-6), viral IL-6 (vIL-6), and human IL-10 in the culture supernatant. To establish whether these cytokines contribute to autocrine growth, neutralizing antibodies against human IL-6, vIL-6, human IL-10, and soluble IL-10 receptor were used. These experiments showed that human IL-10 and, to a lesser degree, vIL-6 serve as autocrine growth factors for BCBL-1 and BC-1 cells. Thus, human IL-10 and vIL-6 are growth factors released and used by PEL cells for autonomous proliferation and may be critical to the development and progression of PEL.

Antibodies, Monoclonal↗

Vaccination against lyme disease with recombinant Borrelia burgdorferi outer-surface protein A (rOspA) in horses.

Eight 1-year-old ponies were vaccinated with recombinant OspA (ospA gene derived from B. burgdorferi B31) with adjuvant (aluminium hydroxide). Four ponies were used as non-vaccinated controls with adjuvant. One hundred and twelve days after the first vaccination, the vaccinated and non-vaccinated ponies were challenged by exposure to B. burgdorferi-infected adults tick (Ixodes scapularis) collected from Westchester County, New York (tick infection rate >/=60%). Protection from infection was evaluated by culture for B. burgdorferi from three monthly skin biopsies taken near the site of tick bites. B. burgdorferi was not isolated from any of the vaccinated ponies. In contrast, three of four control ponies challenged by tick exposure were skin culture positive. At the time of tick exposure, vaccinated ponies had antibody to B. burgdorferi demonstrable by KELA (kinetic-ELISA), western blot and a serum growth inhibition assay. Antibodies in the challenge control ponies were only detectable by two to three months after tick exposure and remained at intermediate levels until termination of the study. By western blot analysis, antibodies to OspA first appeared in the sera of vaccinated ponies three weeks after the first vaccination. The absence of additional bands, known to develop when the animal is infected, suggests that infection was blocked after tick exposure of vaccinated ponies. Results from this study show that vaccination with recombinant OspA protected ponies against infection after experimental challenge with B. burgdorferi-infected ticks.

Animals↗

Differential effect of an Ig mu transgene on development of pre-B cells in fetal and adult SCID mice.

Progression of pro-B lymphocytes to the pre-B stage depends on the expression of a pre-B cell receptor (pre-BCR), consisting of an Ig mu H chain, Ig surrogate light chain, and associated signal transducing chains. Mice that are unable to express a pre-BCR show an arrest of B cell development at the pro-B stage. Such is the case for severe combined immune deficient (SCID) mice in which mu chains are not made because of a defect in V(D)J recombination. When mu chains are made, as in SCID mice bearing a functional mu transgene, then B cell differentiation can proceed to the pre-B stage. However, as reported here, a mu transgene (M54) that promotes development of SCID pre-B cells in adult bone marrow fails to do so in fetal liver. We suggest that a pre-BCR containing the M54 mu chain cannot signal progression of pro-B cells to the pre-B stage in the fetal liver microenvironment.

Age Factors↗

Feasibility of bioremediation of trichloroethylene contaminated sites by nitrifying bacteria through cometabolism with ammonia.

The autotrophic ammonia-oxidizing bacteria (Nitrosomonas sp.) are able to dechlorinate trichloroethylene (TCE) through cometabolism using ammonia (NH(3)) as a growth substrate. Cometabolic kinetics models suggest that TCE is a potent competitive inhibitor of NH(3) oxidation because it competes with NH(3) for oxidation by the enzyme of ammonia monooxygenase (AMO). In this study, an enriched culture of nitrifying bacteria was used to investigate the efficiencies of cometabolism of TCE by AMO. In addition, the relationships among specific growth substrate (NH(3)) utilization rate (qNH(3)), specific nongrowth substrate (TCE) cometabolic rate (qTCE), NH(3) and TCE concentrations, and NH(3)/TCE and TCE/NH(3) ratios were also analyzed. We found that the relationships between qNH(3) and NH(3) for the systems with and without TCE followed the Alvarez-Cohen competitive inhibition model and Monod model, respectively. Our results demonstrate that TCE could be cometabolized in a nitrification system when sufficient oxygen and NH(3)200 microg/l) were also found to show inhibitory effects towards NH(3) oxidation in enriched nitrifying culture. We also found that the NH(3)/TCE ratio rather than TCE concentrations alone exhibited strong correlation with qNH(3), much the same as the Ely activity recovery model presented. Our results suggest that the relationship between qTCE and TCE concentrations followed the Oldenhuis enzyme inactivation model for systems without NH(3).

Ammonia↗

Identification of a virulence-associated protein homolog gene and ISRa1 in a plasmid of Riemerella anatipestifer.

Riemerella anatipestifer is the causative agent of polyserositis of ducks and geese. We have previously reported that a 3.9-kb plasmid, pCFC1, carries protein genes (vapD1 and vapD2) that are similar to virulence-associated genes of other bacteria. In the present study, we report the complete sequence of a second plasmid of 5.6 kb, pCFC2. pCFC2 has a 28% G-C content and three large open reading frames (ORFs). One of the ORFs (designated asVapD1) encodes a polypeptide that shares 53.9, 53.9, 48.3, 48.3 and 46.1% identity with virulence-associated proteins of Dichelobacter nodosus, Actinobacillus actinomycetemcomitans, Neisseria gonorrhoeae, Helicobacter pylori and Haemophilus influenzae, respectively. The second ORF encodes a putative DNA replication protein (RepA3) with 309 amino acids and a molecular mass of approximately 36 kDa. A novel insertion sequence (IS) element, designated ISRa1, was found on the plasmid pCFC2. ISRa1 was flanked by 15-bp imperfect inverted repeats (only one mismatched nucleotide). ISRa1 contained an ORF encoding a putative transposase of 292 amino acids. Southern blot analysis indicated that in R. anatipestifer strains examined, ISRa1 was present with 2-20 copies (at least). ISRa1 displayed a sequence approximately 35% homologous to the putative IS982 and RSBst-alpha from Lactococcus lactis ssp. cremoris SK11 and Bacillus stearothermophilus CU21. Three hybridization patterns of genomic DNA of eight R. anatipestifer strains with an ISRa1 probe indicated that ISRa1 might be a useful tool for epidemiological studies.

Amino Acid Sequence↗

Three unrelated viral transforming proteins (vIRF, EBNA2, and E1A) induce the MYC oncogene through the interferon-responsive PRF element by using different transcription coadaptors.

Kaposi sarcoma-associated herpesvirus vIRF is a viral transcription factor that inhibits interferon signaling and transforms NIH 3T3 cells, but does not bind interferon-stimulated response element (ISRE) DNA sequences. Here we show that induction of the MYC protooncogene is required for cell transformation by vIRF, and that vIRF increases MYC transcription up to 15-fold through specific promoter interactions at an ISRE sequence called the plasmacytoma repressor factor (PRF) element. These effects are resistant to cycloheximide but are inhibited by a dominant-negative ISRE-binding protein, indicating that vIRF acts together with a cellular cofactor at the PRF element to directly transactivate MYC. The coadaptor CREB-binding protein (CBP) binds vIRF and synergizes transactivation of MYC, but, unexpectedly, closely related histone acetyltransferases p300 and P/CAF potently suppress vIRF transactivation. On the basis of the prediction that other interferon-inhibiting viral transforming proteins behave similarly, we found that Epstein-Barr virus-induced nuclear antigen 2 (EBNA2) also binds p300/CBP, and that both EBNA2 and adenovirus E1A transactivate MYC through the PRF element. For E1A, P/CAF coactivates MYC, whereas both p300 and CBP suppress E1A transactivation. For EBNA2, both P/CAF and CBP coactivate the MYC promoter, whereas p300 suppresses EBNA2 transactivation. These findings demonstrate that viral transforming proteins can activate as well as inhibit transcription through coadaptor interactions. At some promoters CBP and p300 have previously unrecognized, competitive antagonism to each other. While all three viral proteins target the same promoter element, each has a different coadaptor use profile. These findings are consistent with cellular MYC repression playing a role in innate immunity as well as in control of cell proliferation.

3T3 Cells↗

Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6.

Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is a herpesvirus linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma, and a proportion of Castleman's disease. KSHV encodes viral interleukin-6 (vIL-6), which is structurally homologous to human and murine IL-6. The biological activities of vIL-6 are largely unknown. To gain insight into the biology of vIL-6, we expressed vIL-6 in murine fibroblasts NIH3T3 cells and inoculated stable vIL-6-producing clones into athymic mice. vIL-6 was detected selectively in the blood of mice injected with vIL-6-expressing clones. Compared with controls, vIL-6-positive mice displayed increased hematopoiesis in the myeloid, erythroid, and megakaryocytic lineages; plasmacytosis in spleen and lymph nodes; hepatosplenomegaly; and polyclonal hypergammaglobulinemia. vIL-6-expressing NIH3T3 cells gave rise to tumors more rapidly than did control cells, and vIL-6-positive tumors were more vascularized than controls. Vascular endothelial growth factor (VEGF) was detected at higher levels in the culture supernatant of vIL-6-expressing cells compared with controls, and immunohistochemical staining detected VEGF in spleen, lymph nodes, and tumor tissues from mice bearing vIL-6-producing tumors but not control tumors. Thus, vIL-6 is a multifunctional cytokine that promotes hematopoiesis, plasmacytosis, and angiogenesis. Through these functions, vIL-6 may play an important role in the pathogenesis of certain KSHV-associated disorders.

3T3 Cells↗

Extended duration of DH-JH rearrangement in immunoglobulin heavy chain transgenic mice: implications for regulation of allelic exclusion.

Here we show that suppression of VH-DJH rearrangement in mice bearing a mu heavy (H) chain transgene (mu-tg mice) is associated with an extended period of DH-JH rearrangement, the first step of Immunoglobulin H chain gene rearrangement. Whereas DH-JH rearrangement is normally initiated and completed at the pro-B cell stage, in mu-tg mice it continues beyond this stage and occurs most frequently at the small (late) pre-B stage. Despite ongoing DH-JH rearrangement in late pre-B cells of mu-tg mice, VH-DJH rearrangement is not detectable in these cells. We infer that the lack of VH-DJH rearrangement primarily reflects tg-induced acceleration of B cell differentiation past the stage at which rearrangement of VH elements is permissible. In support of this inference, we find that the normal representation of early B lineage subsets is markedly altered in mu-tg mice. We suggest that the effect of a productive VH-DJH rearrangement at an endogenous H chain allele may be similar to that of a mu-tg; i.e., cells that make a productive VH-DJH rearrangement on the first attempt rapidly progress to a developmental stage that precludes VH-DJH rearrangement at the other allele (allelic exclusion).

Alleles↗

Kaposi's sarcoma-associated herpesvirus: a sexually transmissible infection?

We examined sexual behavior as a risk factor for Kaposi's sarcoma-associated herpesvirus (KSHV) infection and examined the relation between KSHV seropositivity and development of KS in cross-sectional and cohort studies of 130 homosexual men diagnosed with AIDS in Sydney, Australia during the period from 1991 to 1993. KSHV serology was measured using antibody tests to latency-associated nuclear antigen (LANA) and lytically expressed open reading frame (ORF) 65.2. In the cross-sectional analysis, 52% (68) of study subjects were KSHV-seropositive by either assay. KSHV-seropositive men were significantly more likely to be seropositive to both herpes simplex type 2 (odds ratio [OR] 3.0; 95% confidence interval [CI], 1.2-7.5 for LANA and OR 2.8; 95% CI, 1.3-6.0 for ORF 65) and hepatitis A virus (OR 2.2; 95% CI, 1.1-4.5 for ORF 65). KSHV-seropositive men reported nonsignificantly more casual sexual partners and were nonsignificantly more likely to report insertive oroanal contact with casual partners. These data suggest that KSHV might be sexually transmitted among homosexual men. Men were observed until October 1996 for development of KS. Those seropositive to either KSHV assay at baseline were more likely than the seronegative to develop KS during follow-up (rate ratio [RR] 4.4; 95% CI, 1.9-10.2). Of those seropositive for KSHV, 53% developed KS.

AIDS-Related Opportunistic Infections↗

Profile of cytokine expression in nasopharyngeal carcinomas: a distinct expression of interleukin 1 in tumor and CD4+ T cells.

Nasopharyngeal carcinoma (NPC) is an epithelial cancer that is causally associated with Epstein-Barr virus (EBV) infection. NPC tumor biopsies are characterized histopathologically by an abundant infiltration of nonmalignant lymphocytes. We analyzed the expression of various cytokines in NPC tissues to investigate the interaction of the infiltrating lymphocytes and tumor cells. Analysis using reverse transcriptase-PCR revealed the expression of a panel of cytokines in the NPC biopsies: interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IFN-gamma, tumor necrosis factor-alpha, transforming growth factor-beta, and IL-1 receptor types I and II. Elevated expression of IL-1alpha and IL-1beta was observed in primary tumors and NPC metastases compared to control tissues. Interestingly, this increased expression correlated with the EBV-encoded viral IL-10 transcript. To determine which cells were responsible for producing IL-1, we determined the cellular constituents of NPC biopsies by immunoflow cytometric analysis. On the basis of data from these analyses, the three major specific cell populations, epithelial cells, CD4+ T cells, and CD8+ T cells, were selected from five NPC tumors using specific, antibody-coated paramagnetic beads. Reverse transcriptase-PCR of RNA from these fractionated cells showed that transcripts of IL-1alpha and IL-1beta were present not only in the malignant epithelial cells but also in CD4+ T cells infiltrating the tumor, a finding confirmed by immunohistochemical staining. We hypothesize that the unusual synthesis of IL-1alpha and IL-1beta by EBV-positive epithelial cells as well as by CD4+ T cells might contribute to lymphocyte infiltration and/or tumor growth during NPC development.

Biopsy↗

Formation of coding joints in V(D)J recombination-inducible severe combined immune deficient pre-B cell lines.

Characterization of the severe combined immune deficient (scid) defect in the recombination process has provided many insights into the underlying mechanisms of variable (diversity) joining recombination. By using recombination-inducible scid pre-B cell lines transformed with the temperature-sensitive Abelson-murine leukemia virus, we show that large quantities of recombination intermediates can be generated, and their resolution can be followed during further cell culture. In this study, we demonstrate that the ability of these scid pre-B cell lines to resolve coding ends depends on the cell culture temperature. At the nonpermissive temperature of 39 degreesC, scid pre-B cell lines fail to form coding joints and contain mostly unresolved hairpin-coding ends. Once the cell culture is returned to the permissive temperature of 33 degreesC, these same cells make a significant amount of coding joints concomitant with the disappearance of hairpin-coding ends. Thus, the scid cells are capable of resolving coding ends under certain culture conditions. However, the majority of the recovered coding joints contains extensive deletions, indicating that the temperature-dependent resolution of coding ends is still scid-like. Our results suggest that the inability of scid cells to promptly nick hairpin-coding ends may lead to aberrant joining in these cells.

Animals↗