Search PubMed⌕ Search

Biomedical subjects

J Wong

Publications and source records attributed to J Wong.

At least 163 records · Page 9Linked to original sources

Radiologic placement of central venous catheters: rates of success and immediate complications in 3412 cases.

OBJECTIVE: To determine the success and immediate complication rates associated with 3412 central venous catheter placements performed in an interventional radiology suite. METHODS: Success and immediate complication rates were prospectively recorded for 3412 consecutive patients who had central venous catheters radiologically placed at a tertiary care centre between July 1993 and October 2000. The indication for placement and the insertion site were also recorded. RESULTS: The most common indication for both short- and long-term venous access was hemodialysis, and the right internal jugular vein was the most common site for catheter insertion. Placement was successful for 98.8% of tunnelled lines and 99.3% of temporary catheters. The rate for immediate complications (including pneumothorax, air emboli, bleeding and arterial puncture) for tunnelled catheter placements was 3.8% and for temporary catheter placements was 1.6%; no major complications were documented. CONCLUSION: Our results lend further evidence to the claim that the success and immediate complication rates of radiologically placed central venous catheters compare favourably with blind placement and surgical placement of central venous catheters.

Adolescent↗

Laparoscopic pancreas-preserving total gastrectomy for proximal gastric cancer. A case and technical report.

Although total gastrectomy with distal pancreatectomy has been the standard surgical treatment for advanced gastric cancer, this procedure is frequently complicated by leakage of pancreatic juice and postoperative diabetes mellitus. We present the case of a 74-year-old woman with proximal gastric cancer who underwent a laparoscopic modification of an open pancreas-preserving procedure first described by Maruyama et al. in 1995. With this novel technique, there is no pancreatic leakage, and at 12-month follow-up our patient remains free of diabetes. Herein we give the details of our new method and offer some caveats for its performance.

Aged↗

Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice.

The in vivo disposition behavior and pharmacokinetic characteristics of galactosylated (Gal), mannosylated (Man) and fucosylated (Fuc) liposomes were compared in this study. For the preparation of the glycosylated liposomes, cholesten-5-yloxy-N-(4-((1-imino-2-beta-D-thiogalactosyle thyl)amino)a lkyl)formamide (Gal-C4-Chol) (Kawakami et al., Biochem. Biophys. Res. Commun. 252 (1998) 78-83) and its mannosylated and fucosylated derivatives (Man-C4-Chol and Fuc-C4-Chol, respectively) were synthesized. The glycosylated liposomes are composed of distearoylphosphatidylcholine (DSPC), cholesterol (Chol), and Gal-C4-Chol (or Man-C4-Chol or Fuc-C4-Chol) with the molar ratio of 60:35:5. After intravenous injection in mice, these three types of [(3)H]cholesteryl hexadecyl ether-labeled glycosylated liposomes were rapidly eliminated from the circulating blood and preferentially recovered in the liver. In contrast, DSPC/Chol (60:40) liposomes without glycosylation were retained for a long time in the circulating blood. The uptake ratios by parenchymal cells (PC) and nonparenchymal cells (NPC) (PC/NPC ratios) for 0.5% Gal, Man and Fuc liposomes were found to be 15.1, 0.6 and 0.2, respectively. The effect of predosing glycosylated proteins and liposomes on the hepatic uptake of 0.5% (3)H-labeled Gal, Man, and Fuc liposomes was investigated and the results support the conclusion that Gal, Man, and Fuc liposomes are taken up by the liver via asialoglycoprotein receptors in PC, mannose receptors in NPC, and fucose receptors in NPC, respectively. Interestingly, Gal liposomes were taken up by NPC rather than by PC at a high dose (5%). Together with the finding that 5% Gal liposomes inhibit the hepatic uptake of (3)H-labeled Fuc liposomes, this suggests that Gal-liposomes administered at a high dose will also be taken up by fucose receptors in NPC, that are considered to act as galactose particle receptors.

Animals↗

Functional complementation of BLNK by SLP-76 and LAT linker proteins.

Recent studies have demonstrated a requirement for the SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa) and LAT (linker for activation of T cells) adaptor/linker proteins in T cell antigen receptor activation and T cell development as well as the BLNK (B cell linker) linker protein in B cell antigen receptor (BCR) signal transduction and B cell development. Whereas the SLP-76 and LAT adaptor proteins are expressed in T, natural killer, and myeloid cells and platelets, BLNK is preferentially expressed in B cells and monocytes. Although BLNK is structurally homologous to SLP-76, BLNK interacts with a variety of downstream signaling proteins that interact directly with both SLP-76 and LAT. Here, we demonstrate that neither SLP-76 nor LAT alone is sufficient to restore the signaling deficits observed in BLNK-deficient B cells. Conversely, the coexpression of SLP-76 and LAT together restored BCR-inducible calcium responses as well as activation of all three families of mitogen-activated protein kinases. Together, these data suggest functional complementation of SLP-76 and LAT in T cell antigen receptor function with BLNK in BCR function.

Adaptor Proteins, Signal Transducing↗

Antiretroviral resistance during successful therapy of HIV type 1 infection.

HIV type 1 (HIV-1) drug resistance mutations were selected during antiretroviral therapy successfully suppressing plasma HIV-1 RNA to <50 copies/ml. New resistant mutant subpopulations were identified by clonal sequencing analyses of viruses cultured from blood cells. Drug susceptibility tests showed that biological clones of virus with the mutations acquired during successful therapy had increased resistance. Each of the five subjects with new resistant mutants had evidence of some residual virus replication during highly active antiretroviral therapy (HAART), based on transient episodes of plasma HIV-1 RNA > 50 copies/ml and virus env gene sequence changes. Each had received a suboptimal regimen before starting HAART. Antiretroviral-resistant HIV-1 can be selected from residual virus replication during HAART in the absence of sustained rebound of plasma HIV-1 RNA.

Anti-HIV Agents↗

Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3.

We present evidence that both corepressors SMRT and N-CoR exist in large protein complexes with estimated sizes of 1.5-2 MDa in HeLa nuclear extracts. Using a combination of conventional and immunoaffinity chromatography, we have successfully isolated a SMRT complex and identified histone deacetylase 3 (HDAC3) and transducin (beta)-like I (TBL1), a WD-40 repeat-containing protein, as the subunits of the purified SMRT complex. We show that the HDAC3-containing SMRT and N-CoR complexes can bind to unliganded thyroid hormone receptors (TRs) in vitro. We demonstrate further that in Xenopus oocytes, both SMRT and N-CoR also associate with HDAC3 in large protein complexes and that injection of antibodies against HDAC3 or SMRT/N-CoR led to a partial relief of repression by unliganded TR/RXR. These findings thus establish both SMRT and N-CoR complexes as bona fide HDAC-containing complexes and shed new light on the molecular pathways by which N-CoR and SMRT function in transcriptional repression.

Animals↗

Is radiation alone adequate treatment to the axilla for patients with limited axillary surgery? Implications for treatment after a positive sentinel node biopsy.

PURPOSE: To estimate the possible efficacy of axillary radiation therapy (AXRT) following a positive sentinel node biopsy (SNB), we evaluated the risk of regional nodal failure (RNF) for patients with clinical Stage I or II, clinically node-negative invasive breast cancer treated with either no dissection or a limited dissection (LD) defined as removal of 5 nodes or less followed by AXRT. MATERIALS AND METHODS: From 1978 to 1987, 292 patients underwent AXRT in the absence of axillary dissection; 126 underwent AXRT following LD. The median dose to the axilla was 46 Gy. The median dose to the supraclavicular fossa was 45 Gy. Among patients found to have positive nodes on LD, adjuvant chemotherapy and tamoxifen were administered to 81% and 7% of subjects, respectively. All patients had potential 8-year follow-up. RESULTS: Six of the 418 patients (1. 4%) developed RNF as a first site of failure within 8 years. Among these 6 patients (1.4%) with RNF as the first site of failure, 4 had simultaneous distant and regional recurrences; and 2 had isolated axillary failures. Three of the 292 patients (1%) with no axillary dissection, none of 84 patients with pathologically negative nodes and 3 of 42 patients (7%) with pathologically involved nodes had RNF as a first site of failure. Radiation pneumonitis developed in 5 patients (1.2%), brachial plexopathy in 5 (1.2%) and arm edema in 4 (1.2%). In all cases, radiation pneumonitis and brachial plexopathy were transient. CONCLUSION: These results imply that AXRT may be an effective and safe alternative to completion dissection for treatment of the axilla following a positive SNB. Further studies comparing these two options in specific patient subgroups are needed.

Aged↗

Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma.

BACKGROUND: Recent studies have shown that the prognosis of recurrent hepatocellular carcinoma (HCC) after resection was dependent on the time of recurrence. The current study investigated whether early and late intrahepatic recurrences were associated with different risk factors and prognostic factors. METHODS: After curative resection of HCC, 246 patients were followed prospectively for recurrence. Intrahepatic recurrences were classified into early (</= 1 year) and late (> 1 year) recurrences. Risk factors for recurrence and prognostic factors for survival after recurrence in each group were analyzed. RESULTS: Early and late intrahepatic recurrences developed in 80 patients and 46 patients, respectively. By multivariate analysis, preoperative tumor rupture (P = 0.022) and venous invasion (P < 0.001) were independent risk factors for early recurrence, whereas cirrhosis (P = 0.018) was the only significant risk factor for late recurrence. By comparing histologic features of resected recurrent and primary tumors, 8 of 9 resected early recurrent tumors (89%) were classified as intrahepatic metastases, whereas all 6 resected late recurrent tumors (100%) were multicentric occurrences. Despite similar treatments, the prognosis for patients with early recurrence was worse than that of patients with late recurrence (median survival of 15.8 months vs. 29.6 months; P = 0.005). Independent prognostic factors for early recurrence were serum albumin level and initial tumor pTNM classification, whereas only serum bilirubin level was found to be an independent prognostic factor for late recurrence. CONCLUSIONS: Early and late intrahepatic recurrences after resection of HCC were associated with different risk factors and prognostic factors. Early recurrences appear to arise mainly from intrahepatic metastases, whereas late recurrences are more likely to be multicentric in origin. The current study suggests that different strategies may be needed for the prevention and management of early and late recurrences. Further studies based on genetic analysis of clonal origins of tumors are required to clarify fully the mechanism of early and late recurrences after resection of HCC.

Adult↗

Placental transforming growth factor-beta is a downstream mediator of the growth arrest and apoptotic response of tumor cells to DNA damage and p53 overexpression.

The p53 tumor suppressor gene and members of the transforming growth factor-beta (TGF-beta) superfamily play central roles in signaling cell cycle arrest and apoptosis (programmed cell death) in normal development and differentiation, as well as in carcinogenesis. Here we describe a distantly related member of the TGF-beta superfamily, designated placental TGF-beta (PTGF-beta), that is up-regulated in response to both p53-dependent and -independent apoptotic signaling events arising from DNA damage in human breast cancer cells. PTGF-beta is normally expressed in placenta and at lower levels in kidney, lung, pancreas, and muscle but could not be detected in any tumor cell line studied. The PTGF-beta promoter is activated by p53 and contains two p53 binding site motifs. Functional studies demonstrated that one of these p53 binding sites is essential for p53-mediated PTGF-beta promoter induction and specifically binds recombinant p53 in gel mobility shift assays. PTGF-beta overexpression from a recombinant adenoviral vector (AdPTGF-beta) led to an 80% reduction in MDA-MB-468 breast cancer cell viability and a 50-60% reduction in other human breast cancer cell lines studied, including MCF-7 cells, which are resistant to growth inhibition by recombinant wild-type p53. Like p53, PTGF-beta overexpression was seen to induce both G(1) cell cycle arrest and apoptosis in breast tumor cells. These results provide the first evidence for a direct functional link between p53 and the TGF-beta superfamily and implicate PTGF-beta as an important intercellular mediator of p53 function and the cytostatic effects of radiation and chemotherapeutic cancer agents.

Adenoviridae↗

Setup error in radiotherapy: on-line correction using electronic kilovoltage and megavoltage radiographs.

PURPOSE: We hypothesize that the difference in image quality between the traditional kilovoltage (kV) prescription radiographs and megavoltage (MV) treatment radiographs is a major factor hindering our ability to accurately measure, thus correct, setup error in radiation therapy. The objective of this work is to study the accuracy of on-line correction of setup errors achievable using either kV- or MV-localization (i.e., open-field) radiographs. METHODS AND MATERIALS: Using a gantry mounted kV and MV dual-beam imaging system, the accuracy of on-line measurement and correction of setup error using electronic kV- and MV-localization images was examined based on anthropomorphic phantom and patient imaging studies. For the phantom study, the user's ability to accurately detect known translational shifts was analyzed. The clinical study included 14 patients with disease in the head and neck, thoracic, and pelvic regions. For each patient, 4 orthogonal kV radiographs acquired during treatment simulation from the right lateral, anterior-to-posterior, left lateral, and posterior-to-anterior directions were employed as reference prescription images. Two-dimensional (2D) anatomic templates were defined on each of the 4 reference images. On each treatment day, after positioning the patient for treatment, 4 orthogonal electronic localization images were acquired with both kV and 6-MV photon beams. On alternate weeks, setup errors were determined from either the kV- or MV-localization images but not both. Setup error was determined by aligning each 2D template with the anatomic information on the corresponding localization image, ignoring rotational and nonrigid variations. For each set of 4 orthogonal images, the results from template alignments were averaged. Based on the results from the phantom study and a parallel study of the inter- and intraobserver template alignment variability, a threshold for minimum correction was set at 2 mm in any direction. Setup correction was applied by translating the treatment couch in the lateral, superior-to-inferior and vertical directions only. During treatment, kV open-field images were acquired for off-line treatment verification and analysis. Each patient study spanned 2-6 weeks. The 14 patient studies were completed with 8248 electronic images acquired and analyzed. RESULTS: Results from the phantom studies showed that the users were able to detect the applied translational shift to better than 2 mm, and mostly to within 1 mm. The intraobserver variability of template alignment was on the order of 1 mm using a sample of either MV or kV patient images. The difference between using MV or kV images was significant for only a few cases. However in most cases, interobserver alignment variability was larger when using MV images than kV. For on-line setup correction, the study procedure added 10 min. to conventional treatment time. Setup variation measured with either kV- or MV-localization images was similar. The initial magnitude of setup error was appreciable, with a mean displacement of about 6.6 +/- 2.4 mm for the 14 patients. On-line correction using either kV- or MV-localization images improved setup accuracy. Over all study patients, setup errors occurred with standard deviations greater than 2 mm in any direction with a frequency of 48% before correction, and were reduced to 16% after correction. On average, kV image-based correction reduced radial setup variation to 2.6 +/- 1.6 mm compared to the 3.3 +/- 1.8 mm attained using MV images. The difference detected between the kV and MV data was not statistically significant when averaged over all patients. However, for on-line corrections in the neck and thoracic regions, using kV-localization images reduced setup error significantly more than using MV images. CONCLUSIONS: In our anatomic template alignment study, interobserver variability was smaller using kV images than MV images. Intraobserver variability was smaller for alignments on kV images

Calibration↗

Evidence of linkage of familial hypoalphalipoproteinemia to a novel locus on chromosome 11q23.

Coronary heart disease (CHD) accounts for half of the 1 million deaths annually ascribed to cardiovascular disease and for almost all of the 1.5 million acute myocardial infarctions. Within families affected by early and apparently heritable CHD, dyslipidemias have a much higher prevalence than in the general population; 20%-30% of early familial CHD has been ascribed to primary hypoalphalipoproteinemia (low HDL-C). This study assesses the evidence for linkage of low HDL-C to chromosomal region 11q23 in 105 large Utah pedigrees ascertained with closely related clusters of early CHD and expanded on the basis of dyslipidemia. Linkage analysis was performed by use of 22 STRP markers in a 55-cM region of chromosome 11. Two-point analysis based on a general, dominant-phenotype model yielded LODs of 2.9 for full pedigrees and 3.5 for 167 four-generation split pedigrees. To define a localization region, model optimization was performed using the heterogeneity, multipoint LOD score (mpHLOD). This linkage defines a region on 11q23.3 that is approximately 10 cM distal to-and apparently distinct from-the ApoAI/CIII/AIV gene cluster and thus represents a putative novel localization for the low HDL-C phenotype.

Cholesterol, HDL↗

Molecular determinants of apoptosis induced by the cytotoxic ribonuclease onconase: evidence for cytotoxic mechanisms different from inhibition of protein synthesis.

Cytotoxic endoribonucleases (RNases) possess a potential for use in cancer therapy. However, the molecular determinants of RNase-induced cell death are not well understood. In this work, we identify such determinants of the cytotoxicity induced by onconase, an amphibian cytotoxic RNase. Onconase displayed a remarkable specificity for tRNA in vivo, leaving rRNA and mRNA apparently undamaged. Onconase-treated cells displayed apoptosis-associated cell blebbing, nuclear pyknosis and fragmentation (karyorrhexis), DNA fragmentation, and activation of caspase-3-like activity. The cytotoxic action of onconase correlated with inhibition of protein synthesis; however, we present evidence for the existence of a mechanism of onconase-induced apoptosis that is independent of inhibition of protein synthesis. The caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe) fluoromethyl ketone (zVADfmk), at concentrations that completely prevent apoptosis and caspase activation induced by ligation of the death receptor Fas, had only a partial protective effect on onconase-induced cell death. The proapoptotic activity of the p53 tumor suppressor protein and the Fas ligand/Fas/Fas-associating protein with death domain (FADD)/caspase-8 proapoptotic cascade were not required for onconase-induced apoptosis. Procaspases-9, -3, and -7 were processed in onconase-treated cells, suggesting the involvement of the mitochondrial apoptotic machinery in onconase-induced apoptosis. However, the onconase-induced activation of the caspase-9/caspase-3 cascade correlated with atypically little release of cytochrome c from mitochondria. In turn, the low levels of cytochrome c released from mitochondria correlated with a lack of detectable translocation of proapoptotic Bax from the cytosol onto mitochondria in response to onconase. This suggests the possibility of involvement of a different, potentially Bax- and cytochrome c-independent mechanism of caspase-9 activation in onconase-treated cells. As one possible mechanism, we demonstrate that procaspase-9 is released from mitochondria in onconase-treated cells. A detailed understanding of the molecular determinants of the cytotoxic action of onconase could provide means of positive or negative therapeutic modulation of the activity of this potent anticancer agent.

Antineoplastic Agents↗

A pyruvate-proton symport and an H+-ATPase regulate the intracellular pH of Trypanosoma brucei at different stages of its life cycle.

Regulation of intracellular pH (pH(i)) and H(+) efflux were investigated in Trypanosoma brucei bloodstream and procyclic trypomastigotes using the fluorescent dyes 2', 7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) acetoxymethyl ester and free BCECF respectively. pH(i) in bloodstream and procyclic trypomastigotes was 7.47+/-0.06 and 7. 53+/-0.07 respectively. Differences in the mechanisms for the regulation of pH(i) were noted between bloodstream and procyclic forms. Procyclic trypomastigotes maintained their pH(i) at neutral over a wide range of external pH values from 6 to 8, and in the absence of K(+) or Na(+). The H(+)-ATPase inhibitors N, N'-dicyclohexylcarbodi-imide (DCCD), diethylstilboestrol and N-ethylmaleimide substantially decreased the steady-state pH(i) and inhibited its recovery from acidification. The rate of H(+) efflux in these forms was determined to be 62+/-6.5 nmol/min per mg of protein, and was substantially decreased by H(+)-ATPase inhibitors. The data support the presence of an H(+)-ATPase as the major regulator of pH(i) in procyclic trypomastigotes. In contrast, bloodstream trypomastigotes were unable to maintain a neutral pH under acidic conditions, and their steady-state pH(i) and recovery from acidification were unaffected by H(+)-ATPase inhibitors, except for DCCD (100 microM). Their steady-state pH(i) was markedly decreased in glucose-free buffer or by >/=10 mM pyruvate, whereas procyclic trypomastigotes were unaffected by similar treatments. The rate of H(+) efflux in bloodstream trypomastigotes was 534+/-38 nmol/min per mg of protein, and was decreased in the absence of glucose and by the addition of pyruvate or DCCD. Pyruvate efflux in these forms was calculated to be 499+/-34 nmol/min per mg of protein, and was significantly inhibited by DCCD, 4, 4'-di-isothiocyanatodihydrostilbene-2,2'-disulphonic acid and alpha-cyanohydroxycinnamic acid. The pyruvate analogues beta-hydroxypyruvate, 3-bromopyruvate, 3-oxoglutarate, oxaloacetate, 3-oxoisovalerate and 3-oxoisohexanoate significantly decreased pH(i), as well as proton and pyruvate efflux, whereas lactate had only a small effect, and no effect was observed with citrate or fumarate. The inhibition by pyruvate analogues of pyruvate efflux, proton efflux and acidification of pH(i) supports the hypothesis that pyruvate efflux is accompanied by proton efflux and that this is the major pH(i) control mechanism in bloodstream forms. Inhibition by H(+)-ATPase inhibitors of residual H(+) efflux in the absence of glucose or in the presence of high extracellular pyruvate indicates a minor role for H(+)-ATPase(s) in control of pH(i) in bloodstream forms.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Transcription of the human c-Src promoter is dependent on Sp1, a novel pyrimidine binding factor SPy, and can be inhibited by triplex-forming oligonucleotides.

The tyrosine kinase pp60(c-src) has been implicated in the regulation of numerous normal physiological processes as well the development of several human cancers. However, the mechanisms regulating its expression have not been addressed. In the present study, we report the presence of two Sp1/Sp3 binding sites and three polypurine:polypyrimidine (Pu:Py) tracts in the c-Src promoter that are essential for controlling expression. We demonstrate that Sp1, but not Sp3, is capable of activating the c-Src promoter and that Sp3 is also capable of inhibiting Sp1-mediated transactivation. The presence of multiple Pu:Py tracts conferred S1 sensitivity on plasmids in vitro, suggesting they are capable of adopting non B-DNA conformations. These tracts specifically bind a nuclear factor we named SPy (Src pyrimidine binding factor), which demonstrates both novel double- and single-stranded binding specificities. Mutations eliminating SPy binding compromised Src transcriptional activity, especially in concert with additional mutations affecting Sp1 binding, suggesting the two factors may cooperate in regulating c-Src expression. Finally, we demonstrate that triplex-forming oligonucleotides designed to target both Sp1 and SPy binding sites can down-regulate c-Src expression in vitro, suggesting a potential therapeutic approach to controlling c-Src expression in diseases where aberrant expression or activity has been documented.

Adenocarcinoma↗

Transarterial chemoembolization for inoperable hepatocellular carcinoma and postresection intrahepatic recurrence.

BACKGROUND AND OBJECTIVES: The role of transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC) has remained controversial, and its efficacy for postresection intrahepatic recurrence has not been fully assessed. A study was performed to evaluate the treatment results and prognostic factors of TACE treatment in these patients. METHODS: Clinicopathologic data and treatment results of 384 patients with inoperable HCC and 100 patients with postresection recurrent HCC treated with TACE were collected prospectively and analyzed. RESULTS: TACE was associated with an overall treatment morbidity rate of 23% (112/484) and mortality rate of 4.3% (21/484). A particularly high mortality rate of 20% (9/45) was observed among patients with tumors > 10 cm and pretreatment serum albumin level </= 35 g/L. The overall 1-year, 3-year, and 5-year survival rates from the time of first TACE treatment were 49%, 23%, and 17% respectively. Tumor size </= 10 cm and serum albumin level > 35 g/L were independent favorable prognostic factors. TACE in patients with postresection recurrent HCC was associated with less morbidity, mortality, and a better survival outcome compared with patients with primary inoperable HCC, but this was largely related to smaller tumor size and better liver function in the former group at the time of TACE treatment. CONCLUSIONS: TACE in patients with inoperable HCC was associated with significant morbidity and mortality, and the survival benefit was limited. Better patient selection in terms of tumor size and liver function may improve treatment results. Patients who have a tumor > 10 cm and poor liver function (serum albumin </= 35 g/L) may not be suitable candidates for TACE treatment.

Adult↗

Massage for low back pain.

BACKGROUND: Low back pain is one of the most common and costly musculoskeletal problems in modern societies. Proponents of massage therapy claim it can minimize pain and disability, and speed return to normal function. OBJECTIVES: To assess the effects of massage therapy for non-specific low back pain. SEARCH STRATEGY: We searched Medline, Embase, Cochrane Controlled Trials Register, Healthstar, CINAHL and Dissertation abstracts from 1966 to 1999 with no language restrictions. References in the included studies and in reviews of the literature were also screened. Contact with content experts and massage associations were also made. SELECTION CRITERIA: This review included randomized, quasi-randomized or controlled clinical trials that investigated the use of any type of massage (using the hands or a mechanical device) as a treatment for nonspecific low back pain. DATA COLLECTION AND ANALYSIS: One reviewer applied the selection criteria and extracted the data. Two reviewers (one blinded to authors, institutions and journals) independently assessed the quality of each trial. A qualitative analysis (best-evidence synthesis) was performed due to clinical heterogeneity among the included trials and insufficient data reported. MAIN RESULTS: Four randomized controlled trials met the inclusion criteria. Two trials were of high and two of low methodological quality. None evaluated massage as the main intervention. Rather, it was the control intervention in studies evaluating manipulation, electrical stimulation, and a lumbar corset. There is limited evidence showing that massage is less effective than manipulation immediately after the first session and moderate evidence showing it is less effective than TENS during the course of sessions in relieving pain and improving activity. At the completion of treatment and at 3 weeks after discharge there is no difference among massage and manipulation, electrical stimulation or corsets, but this evidence is limited. REVIEWER'S CONCLUSIONS: Based on the studies reviewed, there is insufficient evidence to recommend massage as a stand-alone treatment for non-specific low back pain. There is a need for high quality controlled trials to further evaluate the effects of massage for this condition.

Adult↗

B cell immunopoiesis: visualizing the impact of CD40 engagement on the course of T cell-independent immune responses in an Ig transgenic system.

This study tracks the fate of antigen-reactive B cells through follicular and extrafollicular responses and addresses the function of CD40 in these processes. The unique feature of this system is the use of transgenic B cells in which the heavy chain locus has been altered by site-directed insertion of a rearranged V(H) DJ(H) exon such that they are able to clonally expand, isotype-switch and follow a normal course of differentiation upon immunization. These Ig transgenic B cells when adoptively transferred into non-transgenic (Tg) mice in measured amounts expanded and differentiated distinctively in response to T cell-independent (TI) or T cell-dependent (TD) antigens. The capacity of these Tg B cells to faithfully recapitulate the humoral immune response to TI and TD antigens provides the means to track clonal B cell behavior in vivo. Challenge with TI antigen in the presence of agonistic anti-CD40 mAb resulted in well-defined alterations of the TI response. In vivo triggering of Tg B cells with TI antigen and CD40 caused an increase in the levels IgG produced and a broadening of the Ig isotype profile, characteristics which partially mimic TD responses. Although some TD characteristics were induced by TI antigen and CD40 triggering, the Tg B cells failed to acquire a germinal center phenotype and failed to generate a memory response. Therefore, TD-like immunity can be only partially reconstituted with CD40 agonists and TI antigens, suggesting that there are additional signals required for germinal center formation and development of memory.

Adoptive Transfer↗

Differential requirement for the stress-activated protein kinase/c-Jun NH(2)-terminal kinase in RNAdamage-induced apoptosis in primary and in immortalized fibroblasts.

Onconase, an anticancer ribonuclease, damages cellular tRNA and causes caspase-dependent apoptosis in targeted cells (M. S. Iordanov, O. P. Ryabinina, J. Wong, T. H. Dinh, D. L. Newton, S. M. Rybak, and B. E. Magun. Cancer Res. 60, 1983-1994, 2000). The proapoptotic action of onconase depends on its RNase activity, but the molecular mechanisms leading to RNA damage-induced caspase activation are completely unknown. In this study, we have investigated whether onconase activates two signal-transduction pathways commonly stimulated by conventional chemo- and radiotherapy, namely the stress-activated protein kinase (SAPK) cascade and the pathway leading to the activation of nuclear factor-kappa B (NF-kappaB). We found that, in all cell types tested, onconase is a potent activator of SAPK1 (JNK1 and JNK2) and SAPK2 (p38 MAP kinase), but that it is incapable of activating NF-kappaB. Inhibition of p38 MAP kinase activity with a pharmacological inhibitor, SB203580, demonstrated that p38 MAP kinase is not required for onconase cytotoxicity. Using explanted fibroblasts from mice that contain targeted disruption of both jnk1 and jnk2 alleles, we found that JNKs are important mediators of onconase-induced cytotoxicity. Surprisingly, following the immortalization of these same cells with human papilloma virus (HPV16) gene products E6 and E7, additional proapoptotic pathways (exclusive of JNK) were provoked by onconase. Our results demonstrate that onconase may activate proapoptotic pathways in tumor cells that are not able to be accessed in normal cells. These results present the possibility that the cytotoxic activity of onconase in normal cells may be reduced by blocking the activity of JNKs.

Apoptosis↗