Disseminated Fusarium oxysporum Infection in Hemophagocytic Lymphohistiocytosis

Abstract The portal of entry of disseminated Fusarium spp. infections is still not clearly defined. We report on a disseminated Fusarium oxysporum infection occurring during a long period of severe neutropenia in a child with hemophagocytic lymphohistiocytosis. A nasogastric feeding tube was the possible source of entry of the fungus.     

Ig VH gene mutational patterns indicate different tumor cell status in human myeloma and monoclonal gammopathy of undetermined significance

Plasma cell tumors display a wide spectrum of clinical progression, ranging from aggressive multiple myeloma to a benign form known as monoclonal gammopathy of undetermined significance (MGUS), which requires no treatment. Because both diseases involve mature Ig- secreting plasma cells, the reason for this variation in malignant behavior is unclear. However, assessment of malignant potential is desirable for choice of treatment protocols. Ig variable (VH) gene sequences analysis has previously shown the tumor cell of multiple myeloma to be postfollicular, with mutated homogeneous clonal sequences indicating no continuing exposure to the somatic hypermutation mechanism, and this was confirmed in 7 of 7 patients. Comparison of the VH gene sequences in the monoclonal cells in MGUS yielded a different result, with 3 of 7 patients demonstrating mutated heterogeneous sequences consistent with the tumor cells remaining under the influence of the mutator. In 1 of 3 of these patients, an IgM-positive precursor cell was identified that expressed heterogeneous VH sequences similar to those of the isotype-switched plasma cell. These results indicate that the clonal cells in MGUS differ from those in myeloma and suggest that the difference may reflect malignant potential.     

Development and testing of multi-phase glazes for adhesive bonding to zirconia substrates

Objectives

The aims of the study were to develop and test multi-phase glaze coatings for zirconia restorations, so that the surface could be etched and adhesively bonded.

Methods

Zirconia disc specimens (n = 125, 16 mm × 1 mm) were cut from cylinders of Y-TZP (yttria-stabilized tetragonal zirconia polycrystals) ZS-Blanks (Kavo, Everest) and sintered overnight. Specimens were subjected to the recommended firing cycles, and next sandblasted. The specimens were divided into 5 groups of 25, with Group 1 as the sandblasted control. Groups 2–5 were coated with overglaze materials (P25 and IPS e.max Ceram glazes) containing secondary phases. Group 2 was (wt%): 10% hydroxyapatite (HA)/P25 glaze, Group 3: 20% IPS Empress 2 glass–ceramic/glaze, Group 4: 20% IPS Empress 2 glass/glaze and Group 5: 30% IPS Empress 2 glass/glaze. After sintering and etching, Monobond-S and composite resin cylinders (Variolink II, Ivoclar-Vivadent) were applied and light cured on the test surfaces. Specimens were water stored for 7 days. Groups were tested using the shear bond strength (SBS) test at a crosshead speed of 0.5 mm/min. Overglazed and the fractured specimen surfaces were viewed using secondary electron microscopy. Room and high temperature XRD and DSC were carried out to characterize the materials.

Results

The mean (SD) SBS (MPa) of the test groups were: Group 1: 7.7 (3.2); Group 2: 5.6 (1.7); Group 3: 11.0 (3.0); Group 4: 8.8 (2.6) and Group 5: 9.1 (2.6). Group 3 was significantly different to the control Group 1 (p < 0.05). There was no significant difference in the mean SBS values between Group 1 and Groups 2, 4 and 5 (p > 0.05). Group 2 showed statistically lower SBS than Groups 3–5 (p < 0.05). Lithium disilicate fibres were present in Groups 3–5 and fine scale fibres were grown in the glaze following a porcelain firing cycle (Groups 4 and 5). XRD indicated a lithium disilicate/minor lithium orthophosphate phase (Group 3), and a tetragonal zirconia phase for the sintered Y-TZP ZS-Blanks. DSC and high temperature XRD confirmed the crystallization temperatures and phases for the IPS Empress 2 glass.

Conclusions

The application of a novel glass–ceramic/glaze material containing a major lithium disilicate phase might be a step in improving the bond strength of a zirconia substrate to a resin cement.     

Bone marrow in sickle cell anaemia at time of anaemic crisis

Samples of bone marrow from 33 Ghanaian children with homozygous sickle cell anaemia who presented with profound anaemia (haemoglobin less than 5 g/dl) were studied. The principal finding was depression of erythropoiesis (aplastic crisis) in 14 children and erythroid hyperplasia in 17. A splenic sequestration crisis was clinically diagnosed in the remaining two children. Stainable iron was absent in the marrow of 14 children and reduced in another five. Megaloblastic changes compatible with folate deficiency were present in 8 children. It is suggested that iron and folate deficiencies may complicate sickle cell anaemia in children living in geographical areas where nutritional deficiencies are prevalent.     

In vivo induction of pyrimidine dimers in human skin by UVA radiation: initiation of cell damage and/or intercellular communication?

Pyrimidine dimers participate as important factors in ultraviolet-induced lethality, mutagenicity and tumorgenicity. Substantial efforts have been made in recent years to understand the induction of pyrimidine photodimers and their repair in human skin cells exposed to low physiological fluences of UV-light. Dimers are known to be efficiently induced after UVC and UVB irradiation, but these photoproducts are also highly induced in DNA isolated from human skin irradiated with UVA. By using a sensitive immunohistochemistry dimer detection assay, we confirm that in vivo UVA radiation induces substantial amounts of these DNA changes in the epidermis; in addition, this technique detects them far into the reticular dermis. A considerable number of these photodimers were also seen in non-irradiated control skin up to two centimeters from the irradiation site. All the lesions persist for at least two days post-irradiation. These results sustain the hypothesis that pyrimidine dimer formation and excision could be a modality of epidermal communication.     

Epstein-Barr virus (EBV) DNA levels in palatine tonsils and autologous serum from EBV carriers

A real-time polymerase chain reaction was employed to detect and quantitate Epstein-Barr virus (EBV) DNA in tonsils and autologous sera from EBV-seropositive children. EBV DNA was found in 95% of tonsils from 21 children and in 50% from 18 children with serum IgG titers to the virus capsid antigen (VCA) of > or =1:160 and 1:10 to 1:80, respectively (P = 0.002). Tonsils from children with titers > or =1:160 harbored more EBV DNA copies per mg tissue (mean, 1,237; range, < 2-13,998) than from children with titers 1:10 to 1:80 (mean, 23; range, < 2-226; P < 0.0001). By contrast, EBV DNA was detected only in serum from 25% of 20 children with titers > or = 1:160. Thus, ample differences in tonsillar EBV replication are mirrored inconstantly by detectable EBV in autologous serum suggesting that EBV DNA quantitation in tonsils may serve for refined monitoring of individuals at risk of EBV-associated lymphoproliferation.     

T-lymphocyte killing by T101-ricin A-chain immunotoxin: pH-dependent potentiation with lysosomotropic amines

To maximize T-lymphocyte killing with anti-pan-T-lymphocyte immunotoxin (IT), prepared by linking ricin A-chain to monoclonal antibody (MoAb) T101 (T101-RTA IT), we have established the nature and the extent of parameters that influence the sensitivity of T lymphocytes to the IT. We showed that peripheral blood T lymphocytes, which are much less susceptible than malignant T cells to the T101-RTA IT, could become highly sensitive to the IT when used in conjunction with NH4Cl. However, enhancement of the IT by NH4Cl only occurred when the pH rose above neutrality. This pH-sensitive process of IT activation by NH4Cl, which led to an all-or-nothing effect within an extremely narrow pH window of 0.7 pH unit width, is due to the fact that NH3 is the effective enhancing component of NH4Cl. We also showed that F(ab')2 or Fab containing IT were much more effective than those produced using the whole IgG counterpart. From these data, we defined a procedure for an optimal and specific elimination of T lymphocytes in vitro by treating them with (Fab)T101-RTA at 10(-8) mol/L at pH 7.8 in the presence of NH4Cl for two hours. This peripheral blood cell processing elicited an abrogation of three logs of functional T-cell response. Under the same conditions, there was no reduction in the number of marrow hematopoietic precursor granulocyte-macrophage colony-forming units (CFU-GM).     

Modulation of ATP-sensitive potassium channel activity by flash-photolysis of ‘caged-ATP’ in rat heart cells

We have used caged-ATP to investigate the kinetic behavior of K_ATP channels in ventricular cells from rat heart. In whole cells, loaded with caged-ATP, an increase of intracellular [ATP] following a UV light flash produced a decrease of K_ATP channel current that was too slow ( 300 ms) to be explained by the expected timecourse of ATP release ( 3 ms) and the time-course of channel blockade by ATP ( 20 ms). In isolated membrane patches, caged-ATP itself caused partial blockade of K_ATP channels. Under these conditions, photorelease of ATP caused channel activity to decline further. The results suggest that caged-ATP can bind to the K_ATP channel but, on binding, decreases the open probability to a lesser extent than does ATP. Additionally, the observations indicate that for photolytically-generated ATP to bind to the channel, caged-ATP must first unbind (slowly) from the channel. We conclude that caged-ATP is not fully caged with respect to its allosteric action on the K_ATP channel.