Carbohydrate-Electrolyte (E-Lyte<Superscript>®</Superscript>) Solution Enhances Bowel Preparation With Oral Fleet<Superscript>®</Superscript> Phospho-soda<Superscript>®</Superscript>

PURPOSE: Bowel preparation with oral sodium phosphate can cause symptomatic dehydration and electrolyte disturbances. This randomized, controlled trial was designed to evaluate whether carbohydrate-electrolyte (E-Lyte^®) solution enhanced bowel preparation and improved patient acceptance with oral sodium phosphate.METHODS: A total of 187 consecutive adults undergoing colonoscopy by two endoscopists were randomized to receive two packets of oral sodium phosphate (Fleet^® Phospho-soda^®) with or without additional supplement of a carbohydrate-electrolyte (E-Lyte^®) solution. All patients and endoscopists completed a standardized questionnaire. Urine-specific gravity and serum biochemistry were randomly performed in 150 and 50 patients, respectively.RESULTS: Ninety patients were randomized to have oral sodium phosphate with E-Lyte^® supplements (Group 1) and 94 patients to sodium phosphate without E-Lyte^® supplements (Group 2). The groups were similar in age and gender, indication for colonoscopy, and previous colonic surgery. Patients taking E-Lyte^® supplement had significantly less dizziness (none, 80 vs. 56 percent; P < 0.001) and a trend toward less nausea (none, 70 vs. 56 percent; P = 0.05). All patients in Group 1 completed the bowel preparation as opposed to 3 percent of Group 2 being unable to complete the preparation. Hypokalemia was significantly more frequent (P = 0.008) in Group 2 patients without E-Lyte^® supplements. More patients in Group 2 needed intravenous rehydration (11 vs. 4 percent). Differences in serum creatinine and urine-specific gravity suggested possibly a lesser degree of hypovolemia in patients taking E-Lyte^® supplements. The quality of bowel cleansing in patients taking E-Lyte^® supplements was considered better by both the endoscopists and patients.CONCLUSIONS: Carbohydrate-electrolyte (E-Lyte^®) solution protects against hypokalemia, improves patient tolerability, and may enhance use of oral sodium phosphate as a bowel-preparation agent.Presented at the meeting of The American Society of Colon and Rectal Surgeons, New Orleans, Louisiana, June 21 to 26, 2003.Fleet^® Phospho-soda^® and E-Lyte^® were supplied by CB Fleet Co., Inc., Lynchburg, VA.     

Marginal expression of CXCR4 on c-kit<Superscript>+</Superscript>Sca-1<Superscript>+</Superscript>Lineage<Superscript>?</Superscript> hematopoietic stem/progenitor cells

Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 are the key regulatory molecules of hematopoietic stem cell (HSC) migration and engraftment to the bone marrow (BM) microenvironment. However, the significance of the ligand–receptor complex on HSC in steady-state BM is not clear. There is currently a lack of information as to how CXCR4 is expressed on HSCs. We herein demonstrate that c-kit⁺Sca-1⁺Lineage⁻ (KSL) cells freshly isolated from BM expressed very low to undetectable levels of CXCR4. Two hours of incubation at 37°C quickly up-modulated the receptor expression on KSL cells. Protein synthesis was not required for this early stage up-regulation, thus suggesting the emergence of intracellularly pooled receptors to the cell surface. However, protein synthesis was involved at the later stage of up-regulation. The up-regulated CXCR4 was functional, as evidenced by the fact that the incubated KSL cells more efficiently migrated to the SDF-1 gradient in vitro. Therefore, although KSL cells are able to express functional CXCR4, the receptors are only marginally expressed in the steady-state BM microenvironment. These observations therefore indicate the limited role of the SDF-1-CXCR4 axis on HSC functionality in a static BM environment.     

Comparison of serological markers between ACPA<Superscript>+</Superscript> and ACPA<Superscript>−</Superscript> of RA patients

Anti-citrullinated protein/peptide antibodies (ACPA) have recently emerged as sensitive and specific serological markers of rheumatoid arthritis (RA), providing superior alternative of the rheumatoid factor (RF) test in the laboratory diagnostics of RA. We compare the change of serum RF, CRP, IgG, IgM, IgA, total complement, C3 and C4. The sera sample was collected from 123 patients with RA. ACPA were detected with ELISA, and RF, CRP and total complement (Ct), C3 and C4 were examined by automatic biochemical analyzer. Serum RF and total complement concentrations were significantly higher in ACPA+ than in ACPA−, but there were no correlation between ACPA and RF and Ct. Between ACPA+ and ACPA−, there were no significant difference of CRP, IgG, IgM, IgA, total complement, C3 and C4. While there were significant correlation between the concentration of C3 and IgM and ACPA in ACPA+. Conclusion: This is the first study to show that ACPA concentration in ACPA+ patients with RA is positively related to serum IgM and C3 levels.     

Intracellular [Na<Superscript>+</Superscript>] modulates synergy between Na<Superscript>+</Superscript>/Ca<Superscript>2+</Superscript> exchanger and L-type Ca<Superscript>2+</Superscript> current in cardiac excitation–contraction coupling during action potentials

Excitation–contraction coupling (ECC) in cardiac myocytes involves triggering of Ca²⁺ release from the sarcoplasmic reticulum (SR) by L-type Ca channels, whose activity is strongly influenced by action potential (AP) profile. The contribution of Ca²⁺ entry via the Na⁺/Ca²⁺ exchanger (NCX) to trigger SR Ca²⁺ release during ECC in response to an AP remains uncertain. To isolate the contribution of NCX to SR Ca²⁺ release, independent of effects on SR Ca²⁺ load, Ca²⁺ release was determined by recording Ca²⁺ spikes using confocal microscopy on patch-clamped rat ventricular myocytes with [Ca²⁺]_i fixed at 150 nmol/L. In response to AP clamps, normalized Ca²⁺ spike amplitudes (ΔF/F ₀) increased sigmoidally and doubled as [Na⁺]_i was elevated from 0 to 20 mmol/L with an EC₅₀ of ~10 mmol/L. This [Na⁺]_i-dependence was independent of I _Na as well as SR Ca²⁺ load, which was unchanged under our experimental conditions. However, NCX inhibition using either KB-R7943 or XIP reduced ΔF/F ₀ amplitude in myocytes with 20 mmol/L [Na⁺]_i, but not with 5 mmol/L [Na⁺]_i. SR Ca²⁺ release was complete before the membrane repolarized to −15 mV, indicating Ca²⁺ entry into the dyad (not reduced extrusion) underlies [Na⁺]_i-dependent enhancement of ECC. Because I _Ca,L inhibition with 50 mmol/L Cd²⁺ abolished Ca²⁺ spikes, our results demonstrate that during cardiac APs, NCX enhances SR Ca²⁺ release by synergistically increasing the efficiency of I _Ca,L-mediated ECC.     

Optical Feedback Training of Inhalation with Autohaler<Superscript>®</Superscript> and Turbuhaler<Superscript>®</Superscript> in COPD Patients

The success of inhalation therapy depends on patients inhalation technique and correct handling of the inhalation device. In this study the effort to train correct handling and optimal inhalation technique of patients using Autohaler^® and Turbuhaler^® was assessed. The Bad-Reichenhall-Aerosol-Therapy-Trial (BREATH) was a prospective, randomized, cross-over trial in 200 patients who were not familiar with either of the test systems. The correct handling of Autohaler^® and Turbuhaler^® was assessed by means of a checklist (observation score). An optimal inhalation maneuver was used evaluated with the computer-based Inhalation Manager (optical feedback, computer score). The Autohaler^® reached 6.58±3.64 (mean ± SD) out of nine points in the observation score and 66.85 ± 29.84% in the computer score before training. After training the scores increased significantly to 8.33 ± 2.08 points and 86 ± 23.40% respectively. The use of the Turbuhaler^® also significantly improved from 4.28 ± 4.24 points and 56.67 ± 42.97% to 7.78 ± 2.74 points and 85.80 ± 27.63%, respectively. The significant improvement of patients inhalation technique after training emphasizes the importance of training in inhalation therapy. In addition, it could be demonstrated that the optical feedback given by the Inhalation Manager was a useful tool for improving the inhalation technique of patients using Autohaler^® and Turbuhaler^®.     

HERG K<Superscript>+</Superscript> channel expression in CD34<Superscript>+</Superscript>/CD38<Superscript>−</Superscript>/CD123<Superscript>high</Superscript> cells and primary leukemia cells and analysis of its regulation in leukemia cells

The human ether-a-go-go-related (herg) gene encoding K⁺ channels (HERG) belongs to an evolutionarily conserved multigene family of voltage activated K⁺ channels. The functional properties of HERG K⁺ channels are complex and their contribution to the repolarization of the cardiac action potential are well understood. Recent studies revealed that HERG K⁺ channels are preferentially expressed in different histogenesis of tumor cells. Leukemia is a cancer that originates in the bone marrow hematopoietic stem cells (HSCs). Leukemia stem cells (LSCs) are critical in the perpetuation of the disease. A better understanding of LSCs and molecular biology will allow the design of more effective therapies. We report in this study that herg was expressed in CD34⁺/CD38⁻/CD123^high LSCs but not expressed in normal bone marrow CD34⁺/CD38⁻ HSCs. In addtion, herg is also expressed in leukemia cell lines K562 and HL-60 and almost all the primary leukemia cells whereas not in the normal bone marrow cells. In addition, the expression of herg mRNA was not associated with the clinical and cytogenetic feature of leukemia. Moreover, HERG K⁺ channels can regulate leukemia cells proliferation and cell cycle. These data provide evidence for the oncogenic potential of HERG K⁺ channels and it may be a novel, potential pharmacological target for leukemia therapy in the future.     

Evolution of recombinant factor VIII safety: KOGENATE<Superscript>?</Superscript> and Kogenate<Superscript>?</Superscript> FS/Bayer

The use of factor VIII (FVIII) concentrates in the treatment of hemophilia A has raised important safety issues, historically of pathogen transmission and increasingly of inhibitor development to FVIII treatment. While manufacturing processes of current recombinant FVIII products have been shaped entirely around preventing pathogen transmission, the same modifications that afford a greater margin of safety could affect immunogenicity of the product, consequences of which could only be seen through long-term clinical experience. This review summarizes pathogen safety and inhibitor reports from clinical trials, post-marketing surveillance studies, and study reports on KOGENATE^® and its successor, Kogenate^® FS/Bayer. Although KOGENATE and Kogenate FS/Bayer are nearly identical products, subtle manufacturing improvements to address the need for greater margins of safety from a pathogen transmission perspective have also led to a potentially improved immunogenicity profile (15% in previously untreated/minimally treated patients with severe hemophilia A for Kogenate FS/Bayer). Notably, there has been no occurrence of pathogen contamination, and minimal de novo inhibitor formation in previously treated patients throughout the use of both products. Overall, KOGENATE and Kogenate FS/Bayer have a long history of safety in a variety of clinical settings, including treatment of bleeding, surgical management, and prophylaxis therapy.     

Acute but not chronic graft-versus-host disease is associated with a reduction of circulating CD4<Superscript>+</Superscript>CD25<Superscript>high</Superscript>CD127<Superscript>low/−</Superscript> regulatory T cells

Defects in central and peripheral tolerance are thought to contribute to life-threatening graft-versus-host disease (GvHD), a severe complication following allogeneic stem cell transplantation (SCT). Recent investigations have demonstrated regulatory T cells (Tregs) to suppress allogeneic immune reactions. Therefore, SCT patients with no or critically low numbers of Tregs may have an increased risk of GvHD. To address this hypothesis, we analyzed the recovery of CD4⁺CD25^highCD127^low/− Tregs in the peripheral blood of patients who have never developed GvHD (n = 6), patients who developed acute/chronic GvHD (n = 18), and patients who developed chronic GvHD without an earlier acute manifestation (n = 5) every 30 days for the first 6 months after peripheral blood SCT (PBSCT). The number of Tregs continuously improved in acute/chronic GvHD patients, but always remained lower than Tregs quantified in patients who never developed a GvHD. In contrast, chronic GvHD patients who did not develop acute GvHD earlier displayed significantly increased Treg cell numbers at the timepoint of chronic inflammation. These results indicate that numerically deficient Tregs following PBSCT are associated with the development of acute but not chronic GvHD.     

Disequilibrium in the CD8<Superscript>+</Superscript>CD28<Superscript>+</Superscript>/CD8<Superscript>+</Superscript>CD28<Superscript>−</Superscript> T Lymphocyte Balance Is Related to Prognosis in Rats with Trinitrobenzenesulfonic Acid-Induced Colitis

Purpose

The CD8⁺CD28⁺/CD8⁺CD28^? T lymphocyte balance is vital for human ulcerative colitis (UC) but has not been defined in experimental colitis. This investigation will try to identify the changes that occur in the CD8⁺CD28⁺/CD8⁺CD28^? T lymphocyte balance during the progression of trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats.

Methods

The frequencies of blood CD8⁺CD28⁺ and CD8⁺CD28^? T lymphocytes were detected in the rats belonging to the normal, model, and treated groups on five days using flow cytometry. The treated rats were administered with mesalazine and were euthanized after a 14-day treatment, as were the normal and model rats. The sensitivity and specificity of the CD8⁺CD28⁺/CD8⁺CD28^? T lymphocyte balance in diagnosing early colitis were analyzed by receiver operating characteristics (ROC) curves. The frequencies of CD8⁺CD28⁺ and CD8⁺CD28^? T lymphocytes in the colon tissue were tested via immunofluorescence. ELISA was used to measure the levels of the cytokines. Immunohistochemistry and Western blotting were used to detect the colonic expression of JAK3, STAT6, NFATc2, and GATA3.

Results

We found that the ratio of CD8⁺CD28⁺/CD8⁺CD28^? T lymphocytes decreased, as did the level of interleukin-7, but not IL-12p40, IL-13, or IL-15, in the blood; however, the ratio increased along with JAK3, STAT6, NFATc2, and GATA3 in the colon of the rats with colitis. The changes were effectively reversed through the administration of mesalazine for 13 days. Surprisingly, the balance in the blood could sensitively distinguish rats with early colitis from normal rats.

Conclusion

These data show that increase in CD8⁺CD28⁺ T cells in blood and decrease in CD8⁺CD28^? T cells in colon are associated with experimental colitis.

     

Taurodeoxycholate Modulates Apical Cl<Superscript>−</Superscript>/OH<Superscript>−</Superscript> Exchange Activity in Caco2 Cells

Bile acid malabsorption has been shown to be associated with diarrhea in cases such as ileal resection Crohn’s disease of the ileum, and radiation enteritis. The mechanisms of bile acid-induced diarrhea are not fully understood. Although the induction of colonic chloride secretion in response to bile acids has been extensively investigated, to date the direct effect of bile acids on intestinal chloride absorption has not been well defined. Therefore, the current studies were undertaken to investigate the effect of bile acids on the apical Cl⁻/OH⁻ exchange process utilizing Caco2 monolayers as an in vitro cellular model. Cl⁻/OH⁻ exchange activity was measured as DIDS-sensitive pH gradient-driven ³⁶Cl uptake. The results are summarized as follows: (i) short-term exposure (20 min) of Caco2 cells to taurodeoxycholate (TDC; 200 μM) and glycochenodeoxycholate (GCDC; 200 μM) acids significantly inhibited apical Cl⁻/OH⁻ exchange (by ∼60–70%); (ii) the Ca²⁺ chelator BAPTA-AM blocked the inhibition by TDC; (iii) the reduction in Cl⁻/OH⁻ exchange by TDC was reversed by the PKC inhibitor, chelerythrine chloride; (iv) functional and inhibitor studies indicated that TDC induced inhibition of Cl⁻/OH⁻ exchange was mediated via the activation of the PKCβI isoform; (v) the effect of TDC on apical Cl⁻/OH⁻ exchange was completely blocked by the PI3 kinase inhibitor LY294002 (5 μM); and (vi) the PKA inhibitor, RpcAMP, had no effect on TDC induced inhibition of Cl⁻/OH⁻ exchange. In conclusion, our studies provide direct evidence for inhibition of human intestinal apical Cl⁻/OH⁻ exchange activity by bile acids via Ca²⁺-, PI3 kinase-, and PKCβI-dependent pathways in Caco2 cells.     

Diminution of Circulating CD4<Superscript>+</Superscript>CD25<Superscript>high</Superscript> T Cells in Na?ve Crohn’s Disease

Crohn’s disease is considered to be caused either by an excess of T-cell effector functions and/or by a defective regulatory T-cell compartment. The aim of this study was to assess in Crohn’s disease the frequency of circulating CD4⁺CD25^high T cells that possess regulatory T-cell functions and CD4⁺CD25^low T cells that contain activated T cells. Flow cytometry of peripheral blood was used to assess CD4⁺CD25^high and CD4⁺CD25^low T-cell frequencies in a cohort of 66 patients with Crohn’s disease in comparison to 19 patients with ulcerative colitis and 31 healthy individuals enrolled as controls. The CD4⁺CD25^high T-cell frequency was significantly lowered in naïve Crohn’s disease (P = 0.013) and in ulcerative colitis (P = 0.001). CD4⁺CD25^low T-cell frequency was increased in Crohn’s disease (P = 0.0001) and in ulcerative colitis (P = 0.0002). Both CD4⁺CD25^high and CD4⁺CD25^low T-cell frequencies are altered in naïve Crohn’s disease resulting in an imbalance between both populations and a relative contraction of the CD4⁺CD25^high T-cell population.     

Adsorptive Depletion of α4 Integrin<Superscript>hi</Superscript>- and CX<Subscript>3</Subscript>CR1<Superscript>hi</Superscript>-Expressing Proinflammatory Monocytes in Patients with Ulcerative Colitis

Background  

Two main functionally distinct monocytes phenotypes are known: the CD14^hiCD16⁻ “classical” and the CD14⁺CD16⁺ “proinflammatory” phenotypes. The latter phenotype is elevated in patients with ulcerative colitis (UC) and is suspected to have a major role in the immunopathogenesis of UC.     

Triplication (/ααα<Superscript>Anti3.7</Superscript>) or deletion (-α<Superscript>3.7</Superscript>/) association in Argentinian β-thalassemic carriers

Prevalence of alpha gene triplication or deletion in -thalassemia carriers was studied in 109 unrelated individuals in Rosario, Argentina. In different populations -^3.7 allele presents a higher prevalence than ^anti3.7; thus, -thalassemia associated with -thalassemia is more frequently observed. Nevertheless, this event was detected in only one case (0.9%), while the association with alpha triplication was present in two subjects (1.8%).     

Val/Leu<Superscript>247</Superscript> and Trp/Ser<Superscript>316</Superscript> polymorphisms in β<Subscript>2</Subscript> glycoprotein I and their association with thrombosis in unselected Chilean patients

It is known that polymorphisms of β ₂-glycoprotein I (β ₂GPI) in exon 7 affect interaction between the phospholipid binding site and the antibodies, and that other polymorphisms in exon 8 increase the generation of antibodies. In this study, we analyzed genetic polymorphisms of β ₂GPI in unselected Chilean patients to determine the prevalence of β ₂GPI polymorphisms in the phospholipid domain in patients with venous and arterial thrombosis and the clinical correlation with thromboembolic complications. This study comprised 149 patients with venous and arterial thrombosis (62 with venous thrombosis and 87 with arterial thrombosis) and 160 healthy controls with no previous history of thrombosis. Polymorphisms of exons 7 and 8 of β ₂GPI, which encode for its fifth domain, were determined by PCR-RFLP. The presence of aPL or anti-β ₂GPI in the patients was detected by ELISA. Anti-β ₂GPI were present in 8/149 patients (5.4%); of these, five had aCL antibodies of low titer. The allele containing Val/Leu²⁴⁷ and Trp/Ser³¹⁶ was significantly more frequent in patients with thrombosis than in the control group (OR=3.1, CI 1.6–6.0, p=0.0003; OR=2.9, CI 1.1–8.6, p=0.027, respectively). These polymorphisms did not correlate with aPL or anti-β ₂GPI but significant differences were observed with venous thrombosis (p=<0.0001) and arterial thrombosis (p=0.026). In conclusion, the β ₂GPI polymorphisms Val/Leu²⁴⁷ and Trp/Ser³¹⁶ are not related to the presence of anti-β ₂GPI antibodies in unselected Chilean patients with venous and arterial thrombosis, but they are significantly associated with venous and arterial thrombosis.     

Low Ambient [Cl<Superscript>−</Superscript>] Increases Ca<Superscript>2+</Superscript> Mobilization and Stimulates Nitric Oxide and Prostaglandin E<Subscript>2</Subscript> Production in Human Bronchial Epithelial Cells

Changes in ionic composition of airway surface fluid may modulate airway epithelial functions. We tested the hypothesis that fluctuations of ambient ionic composition could affect airway epithelial Ca²⁺ dynamics and Ca²⁺-dependent cellular functions, including NO release and PGE₂ production in vitro. The responses of intracellular Ca²⁺ concentration ([Ca²⁺]_i) to changes in extracellular Cl⁻ and Na⁺ concentrations ([Cl⁻]_e, [Na⁺]_e) in the human bronchial epithelial cell line, 16HBE cells, were measured by the fura-2 method. The NO release to the medium after lowering [Cl⁻]_e was measured by an amperometric NO sensor. PGE₂ production was measured by radioimmunoassay. Changing to isotonic low [Cl⁻]_e solution by substitution with gluconate caused a sustained increase in [Ca²⁺]_i in a concentration-dependent manner, with the maximal [Ca²⁺]_i increase from the baseline level being 243 ± 110 nM with Cl-free solution. The effect was not altered by thapsigargin but abolished by EGTA and by Cl channel blockers, including diphenylamine-2-carboxylate, disodium 4,4′-diisothiocyanatostilbene-2,2′-disulfonate, and disodium cromoglycate. In contrast, the effect of reduction of [Na⁺]_e by substitution with N-methyl-D-glucamine⁺ on [Ca²⁺]_i was less than that of reduction of [Cl⁻]_e. The reduction of [Cl⁻]_e caused a concentration-dependent rise in NO contents in the medium and PGE₂ production. This release of NO was inhibited by EGTA but not by dexamethasone pretreatment. These results suggest that the decrease in ambient [Cl⁻] induces Ca²⁺ mobilization probably through Ca²⁺ influx, followed by the release of NO and PGE₂, thereby modulating various cellular functions.     

Ca<Superscript>2+</Superscript>-Sensitisers—A Promising Option to Treat Heart Failure?

Summary Because the number of transplants is still fewer than the number of patients waiting for a donor organ, new concepts of therapy are needed that allow patients to bridge the time gap until heart transplantation or even to improve symptoms while on treatment. Ca²⁺-sensitisers are agents that directly influence myofilaments and/or the cross-bridge-cycle. Depending on the molecular mechanisms underlying their action, Ca²⁺-sensitisers have been divided into three classes. While, a number of Ca²⁺-sensitising drugs have been described, currently only the Ca²⁺-sensitisers pimobendan and levosimendan are in clinical use. This review provides a survey on the molecular mechanisms and the therapeutic effectiveness of Ca²⁺-sensitisers for the treatment of human heart failure.     

Improved experimental radioimmunotherapy of colon xenografts by combining<Superscript>131</Superscript>I-CC49 and Interferon-γ

PURPOSE: This study was designed to determine whether the ability of interferon-γ to upregulate the expression of a human tumor antigen improved the therapeutic efficacy of a radionuclide-conjugated monoclonal antibody. METHODS: Tumor xenografts of the moderately differentiated human colon tumor cell line HT-29 were grown in athymic mice. Constitutive levels of the human tumor antigen, tumor-associated glycoprotein-72, were measured before and after treatment with interferon-γ. Antitumor effects of an¹³¹I-labeled antitumor-associated glycoprotein-72 monoclonal antibody, CC49, were determined by measuring changes in tumor volumes in the respective groups of athymic mice. RESULTS: Interferon-γ induced a time-dependent and dose-dependent increase in tumor-associated glycoprotein-72 expression in the HT-29 tumors. Immunohistochemical staining revealed a more homogeneous tumor-associated glycoprotein-72-positive tumor cell population in tumors isolated from mice treated for eight days with interferon-γ, which accounted for the enhanced tumor localization of¹³¹I-CC49 in mice. That experimental model was used to examine the antitumor effects of combining interferon-γ with¹³¹I-CC49. Administration of 300 μCi of¹³¹I-CC49 to mice bearing HT-29 tumors induced a transient suppression of tumor growth. Conversely, a long-term, sustained HT-29 tumor growth suppression was achieved in mice given 300μCi of¹³¹I-CC49 and interferon-γ. In fact, the cytokine/radioimmunoconjugate combination eradicated any evidence of tumor in approximately 30 percent of the mice. CONCLUSION: The ability of interferon-γ to enhance tumor-associated glycoprotein-72 expression substantially augmented the antitumor effects of the radioimmunoconjugate. Those observations provide additional argument for use of a radioimmunoconjugate in combination with a cytokine to improve tumor diagnosis and therapy.     

Adoptive cell therapy using antigen-specific CD4<Superscript>−</Superscript>CD8<Superscript>−</Superscript> T regulatory cells to prevent autoimmune diabetes and promote islet allograft survival in NOD mice

Aims/hypothesis  

A new differentiation pathway for CD4⁻CD8⁻ (DN) T cells has recently been identified that exhibits the potent function of peripheral converted DN T cells in suppressing immune responses and provides the potential to treat autoimmune diseases. The aim of this study was to determine if the DN T cells converted from CD4⁺ T cells of NOD mice retain the antigen-specific regulatory capacity and prevent autoimmune diabetes in vivo. We also sought to determine if the combination of DN T cells with rapamycin promotes islet allograft survival in autoimmune diabetic NOD recipients.     

Diagnosis of Raynaud’s phenomenon by <Superscript>99m</Superscript>Tc-pertechnetate hand perfusion scintigraphy: a pilot study

We assess the usefulness of ^99mTc-pertechnetate hand perfusion scintigraphy in patients with Raynaud’s phenomenon (RP). The study population consisted of 18 patients with primary RP, 25 patients with secondary RP within systemic sclerosis (SSc), and ten healthy individuals. Gamma camera dynamic first-pass study during the first 60 s and a static scintigraphy after 5 min were recorded following a bolus injection of ^99mTc-pertechnetate via a cubital vein. Regions of interest were drawn on the summed images around the fingers and the palmar region. The fingers-to-palm ratios were then calculated. The mean fingers-to-palm ratio for dynamic study (blood flow) was 0.58 ± 0.19 for the healthy group, 0.45 ± 0.18 for the primary RP, and 0.43 ± 0.21 for the SSc patients. The mean fingers-to-palm ratio for static study (blood pool) was 0.44 ± 0.06 for the healthy group, 0.42 ± 0.06 for the primary RP, and 0.36 ± 0.07 for the SSc patients. Analysis of variance showed these differences to be significant (p = 0.039 from blood flow and p = 0.004 from blood pool). The receiver operating characteristic curve showed sensitivity of 80% and a specificity of 60% when using cutoff values of 0.40 for blood flow and sensitivity of 79% and a specificity of 70% when using cutoff values of 0.37 for blood pool. Our method is able to differentiate between patients with normal and those with abnormal microcirculation of the hands. Dynamic study separates the healthy subjects from patients with RP, while static study separates primary from secondary RP.