Idiotype as a tumor-specific marker in childhood B cell acute lymphoblastic leukemia

Immunoglobulin (Ig) or idiotype (Id) is a tumor-specific target in those B cell malignancies that express this molecule on their surface. We explored the biology of B cell acute lymphoblastic leukemia (B cell ALL) using Id as a tumor marker. In this report we describe the development of anti-Id monoclonal antibodies (MAB) for two children with B cell ALL. These reagents were used retrospectively to study tumor kinetics and to detect residual disease after chemotherapy. In both cases serum Id values were strikingly high at diagnosis (1.2 mg/mL and 10.8 mg/mL), suggesting that the tumor cells were relatively mature B cells capable of significant antibody production. In both patients the serum Id levels fell with the institution of therapy and confirmed that the patients were in remission. Increasing serum Id predicted relapse four months before conventional methods in patient 1, and Id proved to be a more sensitive measure of tumor burden than Southern blot analysis of rearranged Ig genes in bone marrow samples. Surprisingly, low levels of Id were redetected in the second patient just before completing therapy and have persisted for over a year despite the absence of clinical evidence of recurrent disease. Thus, serum Id levels reflect tumor burden during initial therapy but may not necessarily predict tumor progression after a complete clinical remission.     

Early detection of antibodies against rDNA-produced HIV proteins with a flow cytometric assay

There is evidence that some human immunodeficiency virus (HIV)-infected individuals have prolonged periods of seronegativity. A flow cytometric immunoreactive bead (IRB) assay is described for quantitative, simultaneous, and early detection of antibodies to HIV. Polystyrene beads of four diameters, each size coated with a different HIV recombinant DNA-produced protein (p24, p31, gp41, or gp120), bound anti- HIV antibodies detected with fluorescent antiglobulin. The IRB assay was performed on a panel of blood donor samples, many giving consistently false-positive enzyme immunoassay (EIA) and indeterminant Western blot (WB) results. The IRB assay proved as sensitive and more specific than currently licensed EIA and WB tests. Results on serial samples from eight HIV-infected individuals indicated that quantitation of anti-p24 by IRB assay may be useful in monitoring disease progression. Sequential pre- and post-EIA seroconversion sera from 35 HIV-infected homosexual men were tested by the IRB assay using IgM- and IgG-specific fluorescent probes. All 35 cases were IRB assay positive for at least one rDNA-p either before (17 of 35, 49%) or at the time of EIA positivity. Eleven cases (31%) initially had only IgM anti-HIV, primarily to gp41 (17%). In two individuals, the IgM response was detected at least 18 months before EIA seroconversion. The IRB assay is a widely applicable analytic procedure, potentially useful in pretransfusion anti-HIV screening of blood.     

Does the handling time of unrefrigerated human fecal specimens impact the detection of <Emphasis Type="Italic">Clostridium difficile</Emphasis> toxins in a hospital setting?

Background  

The stability of Clostridium difficile toxins is an important factor in determining the accuracy of the enzyme immunoassay (EIA). The Centers for Disease Control has stated that C. difficile toxins may become undetectable in unrefrigerated stool specimens within 2 h after collection.     

Dysglycemias in pregnancy: from diagnosis to treatment. Brazilian consensus statement

There is an urgent need to find consensus on screening, diagnosing and treating all degrees of DYSGLYCEMIA that may occur during pregnancies in Brazil, considering that many cases of DYSGLYCEMIA in pregnant women are currently not diagnosed, leading to maternal and fetal complications. For this reason the Brazilian Diabetes Society (SBD) and the Brazilian Federation of Gynecology and Obstetrics Societies (FEBRASGO), got together to introduce this proposal. We present here a joint consensus regarding the standardization of clinical management for pregnant women with any degree of Dysglycemia, on the basis of current information, to improve medical assistance and to avoid related complications of Dysglycemia in pregnancy to the mother and the fetus. This consensus aims to standardize the diagnosis among general practitioners, endocrinologists and obstetricians allowing the dissemination of information in basic health units, public and private services, that are responsible for screening, diagnosing and treating disglycemic pregnant patients.     

Interaction of benzylidene-anabaseine analogues with agonist and allosteric sites on muscle nicotinic acetylcholine receptors

Background and purpose

Benzylidene-anabaseines (BAs) are partial agonists of the α7 nicotinic acetylcholine receptor (nAChR) but their mechanism(s) of action are unknown. Our study explores several possibilities, including direct interactions of BAs with the nAChR channel.

Experimental approach

Functional and radioligand-binding assays were used to examine the interaction of two BA analogues, 3-(2,4-dimethoxybenzylidene)-anabaseine (DMXBA) and its primary metabolite 3-(4-hydroxy-2-methoxybenzylidene)-anabaseine (4OH-DMXBA) with both agonist and non-competitive antagonist (NCA)-binding sites on muscle-type nAChRs.

Key results

Both BAs non-competitively inhibited ACh activation of human fetal muscle nAChRs and sterically inhibited the specific binding of the NCAs [piperidyl-3,4-3H(N)]-(N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine ([³H]TCP) and [³H]dizocilpine to Torpedo nAChRs in the desensitized state. These compounds modulated [³H]tetracaine, [¹⁴C]amobarbital and [³H]TCP binding to resting nAChRs by allosteric mechanisms. Both BAs enhanced [³H]TCP binding when the nAChR was initially in the resting but activatable state, suggesting that both compounds desensitized the Torpedo nAChR. Although DMXBA failed to activate human fetal muscle nAChRs, 4OH-DMXBA was found to be a partial agonist. [³H]Nicotine competition-binding experiments confirmed that 4OH-DMXBA has higher affinity than DMXBA for the agonist sites, and that DMXBA is also a competitive antagonist.

Conclusions and implications

3-(4-hydroxy-2-methoxybenzylidene)-anabaseine is a partial agonist for human fetal muscle nAChRs, whereas DMXBA only has competitive and NCA activities. The NCA-binding site for BAs overlaps both the phencyclidine-and dizocilpine-binding sites in the desensitized Torpedo nAChR ion channel. The desensitizing property of BAs suggests another possible mode of non-competitive inhibition in addition to direct channel-blocking mechanisms.     

Bacterial contamination of donor blood at the Tamale Teaching Hospital,Ghana

Background

Transfusion of bacterially contaminated blood can result in sepsis and will constitute a substantial health burden to the patient.

Objective

To assess the level of transfusion related sepsis and the bacterial types responsible for the contamination at the Tamale Teaching Hospital in Ghana.

Method

We sampled 80 refrigerated donor blood at the blood bank and cultured them for bacteria. The antimicrobial sensitivities of the isolates were also determined.

Results

14 blood bags representing 17.5% grew isolates of various bacteria. Ten (10) of the 14 isolates were Gram positive cocci representing 71.42% making it the commonest contaminant. 50% of the gram positive cocci were identified to be coagulase negative staphylococci and 21.42% were Staphylococcus aureus. There were 14.28% isolates which were Gram positive rods, and were identified to be Corynebacterium diphtheroids. There were two isolates which were Gram negative rods; one was identified as Escherichia coli and the other one Klebsiella pneumoniae. Sensitivity among the organisms were varied; as all the 14 (100%) of the organisms isolated were sensitive to amikacin, only 14.28% of the coagulase negative staphylococci were sensitive to co-trimoxazole, 28.5% were sensitive to ampicillin, 42.8% were sensitive to cefuroxime and 71.4% were sensitive to ciprofloxacin. Sensitivity to gentamicin was observed to be 85.7% and 28.5% were sensitive to Tetracycline. Only the 10 Gram positive cocci were tested against erythromycin and Cloxacillin; where 70.00% were sensitive to cloxacillin and 90% were sensitive to erythromycin.

Conclusion

All the Staphylococcus aureus isolated were resistant to both ampicillin and cotrimoxazole. Potential dangers and consequences of transfusing multidrug resistance bacteria have been discussed.     

Safety and tolerability of the antimicrobial peptide human lactoferrin 1-11 (hLF1-11)

Background  

The treatment of patients with haematological malignancies by means of haematopoietic stem cell transplantation (HSCT) is often accompanied by life threatening infections. With emerging antimicrobial resistance there is an increased need for new agents, with a beneficial safety profile. Therefore we evaluated the safety of the promising new antimicrobial peptide human lactoferrrin 1-11 (hLF1-11) in healthy volunteers and patients.