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Abstract  Metal foams may be used in direct methanol fuel cells to feed reactants to the catalyst layer and to collect current from the resulting electrochemical reaction. Although the mass transfer from the metal foam to the underlying gas diffusion layer (GDL) is diffusion-dominated, it is found that at a fixed methanol concentration, the limiting current density increases with increasing methanol flow rates. This unexpected result is attributed to the more efficient removal of product CO2 from the GDL. A methodology is developed to estimate the effective diffusion coefficient of methanol in the anode diffusion layer from limiting current density measurements, and to extract the fraction of GDL volume occupied by CO2. [ABSTRACT FROM AUTHOR]

Prognostic factors for survival following allogeneic BMT for AML include age, disease status and cytogenetic risk classification. Lactate dehydrogenase (LDH) levels have not been studied as a potential risk factor. We reviewed our experience with BMT for AML and included LDH at the time of admission in an analysis of prognostic factors for survival. We found that LDH >330 U/l (1.5 times the upper limit of normal at our institution), older age, active disease, peripheral stem cell graft and male-to-male transplant were significant adverse predictors of survival. After accounting for LDH, other factors such as disease status and cytogenetics were not significantly associated with the outcome of BMT. All but one patient with an LDH >330 U/l had active disease. However, when patients in CR were excluded, LDH >330 U/l remained a significant adverse predictor of overall survival (hazard ratio 2.70, 95% confidence interval 1.41–5.16, P=0.003). We conclude that LDH is an important adverse risk factor for survival and should be included in future studies of risk performed on larger patient cohorts.Bone Marrow Transplantation (2007) 40, 753–758; doi:10.1038/sj.bmt.1705811; published online 13 August 2007 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented under the title "Splenic diffuse large B-cell lymphoma in a patient with type 1 Gaucher disease: diagnostic and therapeutic challenges."

Acute myelogenous leukemia (AML) is a difficult disease to treat. Novel treatment strategies, including molecular targeted therapy, are being explored. The c-kit receptor represents a potential therapeutic target for AML. The receptor is expressed on more than 10% of blasts in 64% of patients with de novo AML and 95% of those with relapsed AML. It mediates proliferation and anti-apoptotic effects in AML. This review discusses the biology of c-kit in normal and malignant hematopoiesis and the recent clinical trials targeting c-kit in AML. [ABSTRACT FROM AUTHOR]

Abstract Purpose: A phase I study was performed to determine the maximum tolerated dose (MTD), safety profile and pharmacology of aprinocarsen (ISIS 3521), an antisense oligonucleotide to protein kinase C-α, in patients with refractory solid tumors. Experimental design: Fourteen patients were treated in sequential cohorts of aprinocarsen by 24-hour continuous infusion (CIV), weekly, at doses of 6, 12, 18 and 24 mg/kg. Results: One grade 4 toxicity was observed, transient grade 4 neutropenia at 18 mg/kg. Grade 3 toxicities included neutropenia at 12 mg/kg, fever and hemorrhage at 18 mg/kg, and neutropenia, nausea, and chills at 24 mg/kg. Grade 2 toxicities included thrombocytopenia myalgias, chills, headache, fatigue, fever and nausea/vomiting. Mean prothrombin times and activated partial thromboplastin times (aPTT) increased by 10% and 29% from baseline (p = 0.006 and 0.005). Mean complement split products (Bb and C3a) increased 1.6-fold and 3.6-fold (from p = 0.014 and 0.004, respectively). These changes correlated with dose and were transient with recovery to baseline by day 7. Steady state plasma concentrations (Css) of aprinocarsen were achieved within four hours. Css better described changes in aPTT than dose. Clinical evidence of complement activation was not observed. Conclusions: In contrast to 21-day protracted infusion schedules, delivery of aprinocarsen over a 24-hour infusion schedule showed concentration-dependent effects on coagulation and complement, which are consistent with nonclinical toxicology studies performed in the phosphorothioate DNA antisense drug class. These coagulation and complement changes resulted in a maximum tolerated dose 24 mg/kg. [ABSTRACT FROM AUTHOR]

We explore the metallurgical and materials implications for hypervelocity impact crater formation in some representative materials exposed in space in low-Earth orbit. Radial cracks associated with small size (<0.2 mm) craters in anodized aluminum alloy illustrate the importance of impacting particle flux and size distributions. Novel sectioning and etching of selected craters in stainless steel bolt heads has illustrated the potential for detailed characterization of cracking, phase changes, and extreme deformation proximate to the crater wall while thin sections through the crater and selectively ion-milled to electron transparency have illustrated shock pressure effects on microstructures below the crater for the first time. The use of optical, acoustic, and electron microscopy is illustrated in the characterization of hypervelocity impact crater-related microstructures and these observations point to the essential role to be played by imaging techniques in understanding the environmental effects of space in low-Earth orbit on the behavior of materials and space structures. [ABSTRACT FROM AUTHOR]

Objective: Combining 18F-FDG PET with whole-body MR for paediatric cancer staging is practically feasible if imaging protocols can be streamlined. We compared 18F-FDG PET/STIR with accelerated 18F-FDG PET/FSPGR for whole-body tumour imaging in children and young adults.Methods: Thirty-three children and young adults (17.5 ± 5.5 years, range 10-30) with malignant lymphoma or sarcoma underwent a 18F-FDG PET staging examination, followed by ferumoxytol-enhanced STIR and FSPGR whole-body MR. 18F-FDG PET scans were fused with MR data and the number and location of tumours on each integrated examination were determined. Histopathology and follow-up imaging served as standard of reference. The agreement of each MR sequence with the reference and whole-body imaging times were compared using Cohen's kappa coefficient and Student's t-test, respectively.Results: Comparing 18F-FDG PET/FSPGR to 18F-FDG PET/STIR, sensitivities were 99.3 % for both, specificities were statistically equivalent, 99.8 versus 99.9 %, and the agreement with the reference based on Cohen's kappa coefficient was also statistically equivalent, 0.989 versus 0.992. However, the total scan-time for accelerated FSPGR of 19.8 ± 5.3 minutes was significantly shorter compared to 29.0 ± 7.6 minutes for STIR (p = 0.001).Conclusion: F-FDG PET/FSPGR demonstrated equivalent sensitivities and specificities for cancer staging compared to 18F-FDG PET/STIR, but could be acquired with shorter acquisition time.Key Points: • Breath-hold FSPGR sequences shorten the data acquisition time for whole-body MR and PET/MR. • Ferumoxytol provides long-lasting vascular contrast for whole-body MR and PET/MR. • 18 F-FDG PET/FSPGR data provided equal sensitivity and specificity for cancer staging compared to 18 F-FDG PET/STIR. [ABSTRACT FROM AUTHOR]

The incidence of acute leukemia in children with Down syndrome (DS) is high as compared to general population. Recent findings have demonstrated that DS children with acute myeloid leukemia (AML) have the highest event free survival rates with high dose cytosine arabinoside (Ara-C). We present 3 year-old DS female child with AML-M5, whose chromosomal analysis revealed constitutional t(21;21) alongwith del(5)(q31q33) and a unique translocation t(16;20)(q13;q12). After chemotherapy, child achieved complete clinical remission. Karyotype analysis of remission marrow showed disappearance of abnormal clone of der(20) t(16;20)(q13;q12), del(5q) indicating cytogenetic remission too. This case alongwith supportive literature indicate that pediatric DS-AML is a distinct biologic sub-group differs from that of non-DS-AML with respect to chemosensitivity. [ABSTRACT FROM AUTHOR]

Plasmablastic lymphoma (PBL), an aggressive non-Hodgkin's lymphoma that carries a poor prognosis, previously has been identified almost exclusively in patients infected with the human immunodeficiency virus (HIV). We present a case of a 42-year-old HIV-negative patient presenting with an isolated nasal cavity mass, the typical presentation for PBL. The patient was given systemic chemotherapy, central nervous system prophylaxis, and consolidative locoregional radiotherapy and achieved a complete clinical response. This case suggests PBL should be considered in HIV-negative patients with characteristic findings. [ABSTRACT FROM AUTHOR]

Summary:Reduced-intensity conditioning that harnesses the potential of a graft-versus-tumor (GVT) effect has been proposed as an alternative to conventional myeloablative allogeneic stem cell transplantation. The primary aim is engraftment and this can be achieved with minimal immunosuppression. In this report, we describe the use of such regimens for CML in 17 patients who received human leukocyte antigen (HLA)-matched sibling allografts. Conditioning was with fludarabine, antithymocyte globulin (ATG) and busulfan for the first 11 patients, whereas fludarabine, busulfan and TBI were used for the remaining six patients. Engraftment was prompt in most of the cases. Complications and need for supportive therapy in the immediate post-transplant period were reduced drastically. Only two patients (both in the TBI group) died within the first 100 days. Acute graft-versus-host disease (GVHD) grade II-IV was seen in seven patients. Complications occurred later on. Chronic GVHD was observed in 11/17 patients. Lung infection and GVHD were the major killers. In surviving patients, after a median follow-up of 30 months (range 37-21 months), 6/17 (35.3%) are alive. Five are disease free and one patient is still in relapse even after a second donor lymphocyte infusion. Total treatment time and cost were more than with conventional transplants. We conclude that reduced-intensity transplantation still requires further refinement.Bone Marrow Transplantation (2003) 32, 125-129. doi:10.1038/sj.bmt.1704107 [ABSTRACT FROM AUTHOR]

Macrophage migration inhibitory factor (MIF) is a glycosylated multi-functional protein that acts as an enzyme as well as a cytokine. MIF mediates its actions through a cell surface class II major histocompatibility chaperone, CD74 and co-receptors such as CD44, CXCR2, CXCR4 or CXCR7. MIF has been implicated in the pathogenesis of several acute and chronic inflammatory diseases. Although MIF is a molecule of biomedical importance, a public resource of MIF signaling pathway is currently lacking. In view of this, we carried out detailed data mining and documentation of the signaling events pertaining to MIF from published literature and developed an integrated reaction map of MIF signaling. This resulted in the cataloguing of 68 molecules belonging to MIF signaling pathway, which includes 24 protein-protein interactions, 44 post-translational modifications, 11 protein translocation events and 8 activation/inhibition events. In addition, 65 gene regulation events at the mRNA levels induced by MIF signaling have also been catalogued. This signaling pathway has been integrated into NetPath (http://www.netpath.org), a freely available human signaling pathway resource developed previously by our group. The MIF pathway data is freely available online in various community standard data exchange formats. We expect that data on signaling events and a detailed signaling map of MIF will provide the scientific community with an improved platform to facilitate further molecular as well as biomedical investigations on MIF. [ABSTRACT FROM AUTHOR]

The herpes simplex virus (HSV) recombinant virus R7020 is an attenuated virus designed as a candidate for immunization against both HSV-1 and HSV-2 infections. It was extensively tested in an experimental animal system and in a healthy human adult population without significant untoward effects. We report on the use of R7020 with ionizing radiation as an oncolytic agent for hepatomas. Two hepatoma cell lines were studied, Hep3B and Huh7. R7020 replicated to higher titers in Hep3B cells than in Huh7 cells. Tissue culture studies correlated with hepatoma xenograft responses to R7020. R7020 was more effective in mediating Hep3B tumor xenograft regression compared with Huh7. Ionizing radiation combined with R7020 also showed differential results in antitumor efficacy between the two cell lines in tumor xenografts. Ionizing radiation enhanced the replication of R7020 in Hep3B xenografts. Moreover, the combination of ionizing radiation and virus caused a greater regression of xenograft volume than either R7020 or radiation alone. Ionizing radiation had no effect on the replication of R7020 virus in Huh7 xenografts. These results indicate that a regimen involving infection with an appropriate herpesvirus such as R7020 in combination with ionizing radiation can be highly effective in eradicating certain tumor xenografts. [ABSTRACT FROM AUTHOR]

Neointimal hyperplasia resulting from vascular smooth muscle cell (SMC) proliferation and luminal migration is the major cause of autologous vein graft failure following vascular coronary or peripheral bypass surgery. Strategies to attenuate SMC proliferation by the delivery of oligonucleotides or genes controlling cell division rely on the use of high concentrations of vectors, and require pre-emptive disruption of the endothelial cell layer. We report a genetically engineered herpes simplex virus (HSV-1) mutant that, in an in vivo rabbit model system, infects all vascular layers without prior injury to the endothelium; expresses a reporter gene driven by a viral promoter with high efficiency for at least 4 weeks; exhibits no systemic toxicity; can be eliminated at will by administration of the antiviral drug acyclovir; and significantly reduces SMC proliferation and restenosis in vein grafts in immunocompetent hosts. [ABSTRACT FROM AUTHOR]

We present the case of a young primigravida who developed severe life threatening hemolytic anemia in the last trimester of three successive pregnancies with spontaneous recovery after each delivery and remained normal during the entire nongravid state. Corticosteroid and high-dose intravenous immunoglobulin therapy, although reported as useful, was ineffective in our case. She was managed only with the support with top-up blood transfusions. Extensive investigations were carried out to determine the cause of hemolysis, but these proved unfruitful. Fewer than two scores of such cases have been described in the literature. The paucity of such cases merits its presentation. It is suggested that this anemia should be referred to as "pregnancy-induced hemolytic anemia." [ABSTRACT FROM AUTHOR]

Presents a letter to the editor commenting on neutrophil antigen exposure.

This article reports a case of cystic nephroma to bring awareness about the benign nature of this condition. The patient presented with a painless abdominal mass. Computed tomography showed a homogeneous, multicystic tumor of the superolateral portion of the left kidney with thin septa without solid parts. Histology confirmed the diagnosis of cystic nephroma. [ABSTRACT FROM AUTHOR]

Objective: Acute Leukemia is rare in infants. It is characterized by non-specific symptomatology requiring a high index of suspicion on the part of a pediatrician for referral and diagnosis. It has peculiar biological features, unresponsiveness to treatment and poor prognosis.Methods: Eighteen infants with acute leukemia were seen during 1994 to 2001 and were analyzed on the basis of clinical and laboratory data. There were 13 cases of Acute Lymphoblastic Leukemia (ALL), 4 cases of Acute Myeloid Leukemia (AML) and one case remained unclassifiable, as the surface markers could not be done. Morphologically 9/13 cases of ALL were of FAB L1 type and remaining of L2 subtype, and 2/4 cases of AML were of FAB M1 type and remaining of M2 subtype.Result: Clinical data was available completely only in 11 cases. Hyperleucocytosis was present in 4 cases, organomegaly in 8 cases and lympadenopathy in 5 cases. One patient presented with a chloroma in the retrorbital region although there was no parenchymal involvement of the brain. Immunophenotyping could be done in 13 cases, where 7 cases were diagnosed as CALLA positive-ALL (HLADR+, CD19+, CD10+), 2 cases as Early Pre-B ALL (HLADR+, CD19+, CD10 negative), one as T ALL (cCD3+, CD2+, CD7+) and 3 cases as AML (CD13+, CD33+, HLADR+). None of our patients received treatment. [ABSTRACT FROM AUTHOR]

Chronic HBV infection is the leading cause of liver cirrhosis and hepatic cancer, but the individual responses toward HBV infection are highly variable, ranging from asymptomatic to chronic active hepatitis B inflammation. In this study, we hypothesized that the different individual responses to HBV infection was associated with differences in HBV-specific CD8 T cell-mediated inflammation and cytotoxicity. Blood samples were collected from subjects with asymptomatic HBV-infection, subjects undergoing active chronic HBV flares (active CHB), and subjects with HBV-infected hepatocellular carcinoma (HBV-HCC). By tetramer staining, we found that all three groups had similar frequencies of HBVspecific CD8 T cells. However, after HBV peptide stimulation, the HBV-specific CD8 T cells in asymptomatic subjects had significantly stronger interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and CD107a expression than those in active CHB and HBV-HCC patients. Examination of surface marker expression revealed that the PD-1Tim-3 double-negative cell population was the main contributor to HBV-specific inflammation. In active CHB patients and HBV-HCC patients, however, the frequencies of activated PD-1Tim-3 cells were significantly reduced. Moreover, the serum HBV DNA titer was not correlated with the frequencies of HBV-specific CD8 T cells but was inversely correlated with the frequencies of IFN-g-expressing and CD107a-express cells in response to HBV stimulation. Together, our data demonstrated that the status of HBVspecific CD8 T cell exhaustion was associated with different clinical outcomes of chronic HBV infection. [ABSTRACT FROM AUTHOR]

The two major subtypes of diffuse large B cell lymphoma (DLBCL)-activated B cell-like (ABC) and germinal center B cell-like (GCB)-arise by distinct mechanisms, with ABC selectively acquiring mutations that target the B cell receptor (BCR), fostering chronic active BCR signaling. The ABC subtype has a ∼40% cure rate with currently available therapies, which is worse than the rate for GCB DLBCL, and highlights the need for ABC subtype-specific treatment strategies. We hypothesized that ABC, but not GCB, DLBCL tumors would respond to ibrutinib, an inhibitor of BCR signaling. In a phase 1/2 clinical trial that involved 80 subjects with relapsed or refractory DLBCL, ibrutinib produced complete or partial responses in 37% (14/38) of those with ABC DLBCL, but in only 5% (1/20) of subjects with GCB DLBCL (P = 0.0106). ABC tumors with BCR mutations responded to ibrutinib frequently (5/9; 55.5%), especially those with concomitant myeloid differentiation primary response 88 (MYD88) mutations (4/5; 80%), a result that is consistent with in vitro cooperation between the BCR and MYD88 pathways. However, the highest number of responses occurred in ABC tumors that lacked BCR mutations (9/29; 31%), suggesting that oncogenic BCR signaling in ABC does not require BCR mutations and might be initiated by non-genetic mechanisms. These results support the selective development of ibrutinib for the treatment of ABC DLBCL. [ABSTRACT FROM AUTHOR]

A comprehensive formulation for a class of diffusion problems with non-linear conductivities is derived by unifying and combining the freezing index and Kirchhoff transformation concepts. The transformed equations have appropriate continuity characteristics across the unknown moving boundary. The applicability of the fixed grid algorithm for the total solution domain is, accordingly, demonstrated. Associated finite element formulations and solution procedures for the transformed equations are detailed. In addition, selected numerical results for single and two phase Stefan type problems as well as fluid flow in a prescribed cavity are presented for solution verification and illustration. [ABSTRACT FROM AUTHOR]

The study was conducted in filarial endemic area for various clinical presentations and diagnosis of occult filariasis. A total of 157 cases of various clinical presentations namely tropical pulmonary eosinophilia, monoarthritis, polyarthritis, glomerulonephropathy, tenosynovitis, inguinal lymphadenopathy, generalised lymphadenopathy, retroperitonial lymphadenopathy, endomyocardial fibrosis and acute conjunctivitis were screened for filarial antigen and antibody by enzyme linked immunosorbent assay (ELISA). Out of 157 cases, 107 cases were positive for antigen or antibody, suggesting the role of filarial infection in these clinical presentations. All the 107 cases were treated with diethylcarbamazine citrate (DEC) and some of the patients who were followed showed relief in signs and symptoms. Hence assay of filarial antigen and/or antibody may be useful for diagnosing occult filarial syndromes for better management and further appropriate treatment. [ABSTRACT FROM AUTHOR]

Isolated granulocytes from normal individuals and patients suffering from chronic myeloid leukemia (CML) displayed different fluorescent patterns on treatment with fluorescein isothiocyanate concanavalin A (Fl-Con A). The ligand was internalized by 86% of the normal granulocytes, while 80% of the leukemic granulocytes exhibited Fl-Con A localized on the cell periphery. In further experiments, pretreatment of the normal granulocytes with cytochalasin B, iodoacetamide, 2-deoxyglucose and sodium fluoride (but not with sodium azide or dinitrophenol) was found to drastically inhibit internalization of the ligand. However, pretreatment of granulocytes from CML patients with cytochalasin B and 2-deoxyglucose, caused only a little alteration in the pattern of Fl-Con A labelling relative to untreated cells. These results indicate that CML granulocytes are defective in their ability to endocytose Fl-Con A. We suggest that this differential interaction between Fl-Con A and normal and leukemic granulocytes is a convenient system to study the initial steps in receptor mediated endocytosis of Concanavalin A. [ABSTRACT FROM AUTHOR]

In this work granulocytes from normal human donors and patients suffering from chronic myeloid leukemia (CML) were externally labeled withIodine, using the Iodogen method.Iodine labeled Concanavalin A binding proteins (CBP) and detergent-resistant proteins (DRP) were isolated from the cell lysates and characterized by one- and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D- and 2D-SDS-PAGE). Autoradiographs of the 2D-gels of DRP show seven proteins with Mr 118,000 (spot 1 a), Mr 112,000 (spot 1 b), Mr 78,000-85,000 (spot 2), Mr 85,000 (spot 4), Mr 52,000 (spot 3, 3 a and 3 b). Of this set, spot 1 b, 2 and 4 are also present in the autoradiographs of 2D-gels of CBP and, hence, may be considered to be transmembrane components. Spot 4 is expressed more intensely in the normal granulocytes while spots 3 a and 3 b are mainly expressed on the leukemic granulocytes. [ABSTRACT FROM AUTHOR]

Thin films of SnO were prepared by the radio frequency (13.56 MHz) sputtering technique in a wide range of oxygen/argon concentrations within the sputtering system. The films were analyzed by means of transmission and scanning electron microscopy, x-ray diffractometry and Auger electron spectroscopy. The results showed the films to be polycrystalline with an average grain size of 400 Å. Room temperature resistances of as-sputtered films showed a strong dependence on the oxygen concentration in the sputtering environment. Electrical conductivity studies of these films in oxygen and in hydrogen revealed the fundamental charge transfer mechanisms in the observed gas sensitivity of the material to be due to an interaction of the hydrogen with chemisorbed oxygen ions on the semiconductor surface. Finally, a means of providing selectivity between HS and H responses was studied. [ABSTRACT FROM AUTHOR]

Explosive densification following combustion synthesis of titanium and graphite powder mixtures has been used to fabricate bulk compacts (100-mm diameter × 20-mm thick) of TiC ceramics. A model rocket ignitor was used to initiate the combustion reaction in ≈65 pct dense green pressed reactants of titanium and carbon powder mixtures. Upon completion of reaction, the reacted mass was allowed to cool. After the desired time delay ( t ) and while the reacted mass was still above the ductile-brittle transition temperature, an explosive charge was detonated in contact with a steel driver plate to transmit the pressure into the reacted mass and consolidate it to solid density. Temperature-time cooling profiles for the reacted material were developed using calculations based on a heat flow model. The explosive loading conditions, namely, the densification pressure controlled by the ratio of explosive charge mass (C) to driver plate mass ( M) ratio ( C/M) and the t between the combustion reaction completion and explosive detonation, were observed to critically affect the density and the microstructure of the final compacted reaction product. [ABSTRACT FROM AUTHOR]

Deformation accelerates the development of grain boundary chromium depletion (GBCD), or sensitization, in type 316 austenitic stainless steels (SS). Quantitative assessment of the degree of sensitization (DOS) using the electrochemical potentiokinetic reactivation (EPR) test indicates that the acceleration in GBCD is a function of the amount of strain in the material and temperature of isothermal sensitization treatment. A systematic increase in strain from 0 to 20 pct yields a continuous increase in EPRDOS values below 700°C, while at higher temperatures, a threshold strain of 6 to 10 pct is required to cause accelerated GBCD development. Straining SS above 20 pct also produces higher amounts of chromium depletion, though the (intergranular) sensitization susceptibility of the material could not be quantitatively evaluated due to the presence of grain matrix or transgranular corrosion. Classical C-curve precipitation-sensitization behavior was also noted for strained and unstrained materials, though strain moved the C-curves to the left. Microstructural evaluation of sensitization revealed a systematic increase in grain boundary and twin boundary corrosion on EPR attack surfaces with strain, which corroborated the deformation-induced acceleration of EPRDOS. A time-temperature-strain dependence of transgranular corrosion was also identified on EPR-etched samples strained above 20 pct. These were also reflected in transmission electron microscope (TEM) observations of higher grain boundary carbide precipitation on strained vs unstrained specimens and site-specific carbide precipitation on deformation sites in the material. Kinetic and thermodynamic modeling of deformation effects on carbide precipitation and depletion development in type 316 SS indicated that strain induces a reduction in the activation barrier to diffusion ( Q) and thermodynamic barrier to nucleation (Δ G ) during the precipitation-depletion process. The lowering of Q with strain caused chromium diffusivity and depletion development to be accelerated in strained vs unstrained materials and appears to be due to increased dislocation pipe diffusion with strain. Reduction of Δ G with strain was related to an increase in the free energy change of the grain boundary (Δ G) and accelerated carbide precipitate nucleation in deformed SS. The effect of strain on the kinetics and thermodynamics of the precipitation-depletion process decreases with increasing temperature. [ABSTRACT FROM AUTHOR]

Lectin-receptors on leukocyte and endothelial surfaces are becoming more important in the light of increasing evidence which implicates lectin-carbohydrate interactions in diverse physiological phenomena. This study reports the identification of a major 118 kDa granulocyte surface protein, (Protein 1a) which binds the lectin wheat germ agglutinin (WGA), and is distinctly different from reported WGA binding granulocyte membrane proteins. Protein 1a has been isolated from the Triton-soluble and Triton-insoluble lysates of normal individuals and patients with Chronic Myeloid Leukemia (CML) using a combination of differential solubilization, lectin affinity, ion exchange chromatography and HPLC. The protein from the detergent lysates of both normal and CML granulocytes has similar pI values, lectin affinities, and hydrophobicity. However, its solubility in Triton is different in the two cell types. In 71% of CML cases examined, Protein 1a exhibits decreased Triton solubility suggesting its increased association with the cytoskeleton (CSK). Stimulation of normal granulocytes with WGA leads to the translocation of the soluble form of Protein 1a to the Triton-insoluble fraction. This cytoskeletal recruitment of Protein 1a is sustained only under conditions of excess WGA and occupied receptor. The CSK disruptive agent dihydrocytochalasin B (HCB) releases the insoluble form of the receptor into the Triton-soluble fraction. Investigation of a CSK-involving process such as ligand internalization revealed that CML granulocytes exhibit slower kinetics of internalization of fluorescent WGA molecules. Since Protein 1a is a major WGA receptor on the granulocyte surface, its decreased Triton solubility in CML granulocytes suggests that this may be one of the factors contributing to the defective receptor-mediated endocytosis of WGA by CML cells, arising as a consequence of altered membrane-CSK interaction - a nodal point in the signal transduction cascade. [ABSTRACT FROM AUTHOR]

In this paper, we have correlated the ability of peripheral blood lymphocytes (PBL) from Hodgkin's Disease patients to proliferate in response to a mitogen, phytohaemagglutinin (PHA), with production of lymphokines interleukin-2 (IL-2) and interferon γ (IFNγ), accumulating in the activated lymphocyte culture supernatants. We have also studied the frequency distribution of PHA-responsive and IL-2-producing T cells from PBL using limiting-dilution analysis. We observed that the levels of IL-2 and IFNγ in the supernatants of activated lymphocytes from patients with Hodgkin's disease were significantly reduced compared to those of healthy donors. Substage-B patients showed marked reduction in the ability to produce IFNγ. Levels of IL-2 and IFNγ in the culture supernatants of PBL from Hodgkin's disease patients correlated positively with proliferative responses, when analysed by linear regressison ( r = 0.79 and r = 0.60 respectively). However, production of the two lymphokines by activated lymphocytes from the same patients did not correlate ( r = +0.04). Further, the frequencies of PHA-responsive cells and IL-2-producing cells in the PBL of patients with Hodgkin's disease (ranges 1/111-1/554 and 1/3009-1/6709 respectively) were also less than those of the healthy donors (ranges 1/80-1/181 and 1/761-1/1828 respectively). Proliferation, IL-2 production in bulk cultures and frequencies of PHA-responsive and IL-2-producing cells correlated well in individual healthy donors. Whereas, one patient (BC 11 214) with a frequency of PHA-responsive cells within normal limits had a very low frequency of IL-2-producing cells. Taken together, the results indicate abnormalities in cytokine production and frequency distribution of cells required for amplification of immune response in patients with Hodgkin's disease. [ABSTRACT FROM AUTHOR]

The natural killer (NK) and lymphokine-activated killer (LAK) cell activities of peripheral blood lymphocytes from chronic myeloid leukemia (CML) patients in remission and from healthy donors have been studied. Regression analysis to compare both cytotoxic responses in individual donors and the frequency of LAK cell precursors was also carried out. About 42% of CML patients in remission showed low NK activity (less than the mean percentage NK activity of healthy donors - 2 SD) and were categorised as low NK responders. The stage of remission or the drugs used to bring about remission did not influence the NK status. The LAK activity of low NK as well as normal NK responder CML patients was significantly low against the NK-sensitive K562 cell line and the NK-resistant VIP (melanoma) and T-24 (bladder carcinoma) tumor targets, as assessed by linear regression analysis. Allogeneic leukemic cells were more resistant to killing, especially by patients' LAK cells. The frequency analysis of LAK cell precursors revealed a significant reduction in the LAK cell progenitor frequency in CML patients in remission. [ABSTRACT FROM AUTHOR]

The depressed natural killer (NK) activity, antibody-dependent cellular cytotoxicity (ADCC) and NK cytotoxic factor cytotoxicity in untreated non-Hodgkin's lymphoma patients were found to be elevated after chemotherapy. In vitro treatment of the effector NK cells with interferon α could augment the NK activity in normal subjects and treated patients to a comparable degree. Chemotherapy mainly affected the post-binding events in the NK cytotoxic process by causing an increase in the active killing potential of the NK cells. This study provides a better understanding of changes in the NK cytotoxic mechanism in non-Hodgkin's lymphoma patients and the role of interferon in this process. [ABSTRACT FROM AUTHOR]

Cytotoxic cells (CTCs) generated from peripheral blood lymphocytes of 5 chronic myeloid leukemia (CML) patients in remission on stimulation with autologous leukemic cells and allogeneic lymphocytes (3-cell assay), were propagated in vitro in interleukin-2 (IL-2)-containing medium and periodic stimulation with autologous leukemic cells, for a period of 4 to 6 months. During this period, the cells were assessed for phenotype and for cytotoxic responses in a 4-h Cr release microcytotoxicity assay. The CTCs continued to show specific lysis of autologous leukemic cells and bone marrow (BM) cells. However, the nonspecific lysis of natural killer (NK) targets and the proportion of cells showing NK phenotype (HNK-1 antigen) increased progressively on cultivation in IL-2-containing medium. Therefore cells showing CD8 phenotype and specific cytotoxic function were segregated by cloning CTCs under the condition of limiting dilution in the presence of allogeneic feeder cells and IL-2-containing medium. Three cytotoxic T cell (CTL) clones expressing CD3+, CD8+, and HLA DR+ phenotypes were obtained from CTCs of 2 CML patients. These clonoid populations, maintained in IL-2-containing medium and periodic antigenic stimulation with autologous leukemic cells, showed specific lysis of autologous leukemic cells and BM cells even at lower (10:1) effector:target ratios. They did not kill K562 (erythroblastoid leukemic NK target cell line) cells and autologous phytohemagglutinin-induced blasts. These clones apparently functioned in an MHC-restricted manner as they did not lyse allogeneic CML cells which would also express a similar set of maturation antigens if sensitization was, as it appeared, against these antigens. Finally, interaction of autologous BM cells with CTL clones reduced the colony forming potential of BM cells only to the extent of 18%-30%. The results therefore indicate that such CTL clones can possibly be used in adoptive immunotherapy as they showed minimal BM toxicity. [ABSTRACT FROM AUTHOR]

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2-Nitromethylenethiazolidine has been synthesised and found to be a weak enamine. It reacts with acyl isothiocyanates but not with phenyl isothiocyanate. Oxidative cyclization of the acyl isothiocyanate adducts leads to isothiazolo [3,2-b] thiazole derivatives. The 2-benzoylimino compound 8 undergoes base catalysed fragmentation to give the nitronitrile 9. [ABSTRACT FROM AUTHOR]

Fluid flow at the interface of a porous medium and an open channel is the governing phenomenon in a number of processes of industrial importance. Traditionally, this has been modeled by applying the Brinkman’s modification of Darcy’s law to obtain the velocity profile in terms of an additional parameter known as the “apparent viscosity” or the “slip coefficient”. To test this ad hoc approach, a detailed experimental investigation of the flow was conducted using Laser Doppler Anemometry (LDA) in the close vicinity of the permeable boundary of a porous medium. The porous medium used in the experiments consisted of a network of continuous glass strands woven together in a random fashion. A Hele–Shaw cell was partially filled with a fibrous preform such that an open channel flow is coupled with the Darcy flow inside the preform through the permeable interface of the preform. The open channel portion of the Hele–Shaw cell also acts as an ideal porous medium of known in-plane permeability which is much higher than the permeability of the fibrous porous medium. A viscous fluid is injected at a constant flow rate through the above arrangement and a saturated and steady flow is established through the cell. Using LDA, steady state velocity profiles are accurately measured by traversing across the cell in the direction perpendicular to the flow. A series of experiments were conducted in which fluid viscosity, flow rate, solid volume fraction of the porous medium and depth of the Hele–Shaw cell were varied. For each and every case in which the conditions for Hele–Shaw approximation were valid, the depth of the boundary layer zone or the screening length inside the fibrous preform was found to be of the order of the channel depth. This is much larger as compared to the Brinkman’s prediction of the screening length which is of the order of √ K, where K is the permeability of the fibrous porous medium. Based on this finding, we modified the boundary condition in the Brinkman’s solution and found that the velocity profile results compared well with the experimental data for the planar geometry and the fibrous preforms for volume fractions of 7%, 14% and 21% for Hele–Shaw cell depths of 1.6 and 3.175 mm. For a cell depth of 4.8 cm, in which the Hele–Shaw approximation was not valid, the boundary layer thickness or the screening length was found to be less than the mold or channel depth but was still much larger than the Brinkman’s prediction. [ABSTRACT FROM AUTHOR]

Hele-Shaw cell is a laboratory device consisting of two parallel plates of glass separated by a thin gap. In this cell, in the flow of two immiscible fluids, when a fluid of higher viscosity is displaced by a fluid of lower viscosity, the less viscous fluid is observed to form 'fingers' into the more viscous one due to the unstable interface. The Saffman-Taylor or viscous finger instability has been examined and modeled for over forty years for the rectilinear Hele-Shaw cell and about half as long for the radial Hele-Shaw cell. In this paper, we study, in detail, the early development of viscous instabilities in a radial Hele-Shaw cell. This source flow configuration has been chosen so that the instability can be monitored precisely. The objective of this study is to examine the onset of fingering, i.e. initial number of fingers that form, and the evolution of interface instability. Our experiments suggest that there may be some order in this formation process and one can model this aspect by considering the unsteady velocity components and predicting temporal changes in wavenumber responsible for the initial number of fingers and may be later accounting for the fingertip oscillations and splitting. We injected a water-based fluid into an oil in a radial Hele-Shaw cell at constant flow rate and recorded the movement of the less viscous droplet as it evolved. The relative curvature changes on the expanding droplet boundary was plotted with the angular positions about the interface and subtracting out the average radius, resulting in a plot of the change in amplitude with respect to time for the interface configuration. Three unstable configured tests at kinematic viscosity contrast ( v) of 0.34, 0.68, and 0.94 were run at approximately the same flow rate (2π cm/s). The droplet exhibited oscillatory movement for these unstable configuration. The amplitude and the rate of oscillations were measured from digitized data. The smaller the viscosity difference, the smaller was the amplitude growth rate and resulted in a longer time to form visible finger initiation. [ABSTRACT FROM AUTHOR]

Three cases of acute lymphoblastic leukemia who had multiple vertebral involvement as initial manifestation are presented with review of literature because of its clinical rarity. Importance of early diagnosis and treatment is stressed. In pediatric age group, if there is radiological involvement of vertebrae, then ALL should be considered in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Very few cases of human microsporidial infection have been reported. The advent of AIDS has changed this. There is increasing recognition that microsporidia are important opportunistic pathogens. However, the number of cases reported in the non-HIV population is small. We report here a case of microsporidial infection in a female patient with chronic myeloid leukemia undergoing allogeneic bone marrow transplantation. There was also an associated fungal infection. The diagnosis could be reached only after postmortem and was confirmed by electron micrography. We suggest that transplant patients are another group of patients who are susceptible to this group of opportunistic pathogens. [ABSTRACT FROM AUTHOR]

Programmed −1 ribosomal frameshift (−1 PRF) signals redirect translating ribosomes to slip back one base on messenger RNAs. Although well characterized in viruses, how these elements may regulate cellular gene expression is not understood. Here we describe a −1 PRF signal in the human mRNA encoding CCR5, the HIV-1 co-receptor. CCR5 mRNA-mediated −1 PRF is directed by an mRNA pseudoknot, and is stimulated by at least two microRNAs. Mapping the mRNA-miRNA interaction suggests that formation of a triplex RNA structure stimulates −1 PRF. A −1 PRF event on the CCR5 mRNA directs translating ribosomes to a premature termination codon, destabilizing it through the nonsense-mediated mRNA decay pathway. At least one additional mRNA decay pathway is also involved. Functional −1 PRF signals that seem to be regulated by miRNAs are also demonstrated in mRNAs encoding six other cytokine receptors, suggesting a novel mode through which immune responses may be fine-tuned in mammalian cells. [ABSTRACT FROM AUTHOR]

The availability of human genome sequencehas transformed biomedical researchover thepast decade.However, anequivalentmapfor the human proteome with direct measurements of proteins and peptides does not exist yet. Herewepresent a draft map of the human proteome using high-resolution Fourier-transform mass spectrometry. In-depth proteomic profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary haematopoietic cells, resulted in identification of proteins encoded by 17,294 genes accounting for approximately 84% of the total annotated protein-coding genes in humans. A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream open reading frames. This large human proteome catalogue (available as an interactive web-based resource at http://www.humanproteomemap.org) will complement available human genome and transcriptomedata to accelerate biomedical research in health and disease. [ABSTRACT FROM AUTHOR]