δ-Thalassemic phenotype due to two “novel” δ-globin gene mutations: CD11[GTC → GGC (A8)-HbA2-pylos] and CD 85 [TTT → TCT (F1)-HbA2-etolia]

δ-Thalassemia reduces the expected HbA₂ percentage, altering the normal as well as the β-thalassemia trait phenotype. An attempt to elucidate the molecular basis of δ-thalassemia in the Greek population, revealed two cases with unknown molecular defects that presented low levels of HbA₂ (about 1.5%). DNA sequence analysis of δ-globin gene identified two “novel” mutations in the coding regions of the gene; the cd11 (GTC→GGC) resulting in the substitution of valine for glycine (:HbA₂-Pylos) and the cd85 (TTT→TCT) resulting in the substitution of phenylalanine for serine (:HbA₂-Etolia). Because these mutations are localized at the helical positions A8 and F1 of the HbA₂ respectively, they potentially cause molecular instability of the tetramer, thus leading to reduced HbA₂ percentage. Hum Mutat 9:344–347, 1997. © 1997 Wiley-Liss, Inc.     

Postnatal screening of renal developmental anomalies. Classical diagnostic methods, risk factors and routine screening

During a 6 years' period (2 years of control, 2 years of risk group and 2 years of routine screening) the authors examined the effect of different diagnostical methods on the frequency of detected renal developmental anomalies. The incidence of documented renal malformations was 1.1% during the use of classical diagnostical methods, 8.3% during the application of intrauterine routine and postnatal risk group screening, and 10.3% after the introduction of postnatal routine screening in 2 years' periods. The advantage of both postnatal risk group and postnatal routine screening was that the greatest part of renal anomalies could have been diagnosed before the appearance of the symptoms of urinary infection. On the basis of effectivity of postnatal routine screening and decrease of uncertainty of postnatal risk group screening authors suggested the introduction of the postnatal routine screening as general practice under our own circumstances.     

Plasma RANTES increase during the first month of life independently of the feeding mode

The chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) plays a significant role in the innate immunity, which is particularly important in the neonatal period. In this study, we aimed to investigate the ability of the neonate to increase plasma levels of RANTES in the first month of life, and the possible impact of breast feeding on this ability. The study population consisted of 125 healthy term neonates that were exclusively breast-fed (n = 62) or formula-fed (n = 63) for at least 1 month after birth. Plasma RANTES concentrations (ELISA) as well as circulating leukocytes and platelets were measured on days 1 and 30 of life. Median RANTES concentrations of the total group showed a significant increase between day 1 [1000 (448–2100) pg/mL] and day 30 [3688 (1488–5400) pg/mL, p < 0.0001], as did median total lymphocyte, T-cell, B-cell, NK-cell and eosinophil counts (all p values <0.0001). Monocyte and platelet counts did not change significantly over the neonatal period. Further analysis according to the mode of feeding showed that RANTES levels as well as leukocyte populations and platelet counts did not differ significantly between breast-fed and formula-fed neonates on either day 1 or 30. Healthy term neonates are capable of increasing plasma RANTES levels during the 1st month after birth independently of the mode of feeding.     

The role of hyperbaric oxygen in the treatment of diabetic foot ulcers

Diabetic foot ulcers are still extremely difficult to heal. Therefore, therapeutic options to improve healing rates are continuously being explored. Hyperbaric oxygen (HBO) has been used in addition to standard treatment of the diabetic foot for more than 20 years. Evidence suggests that HBO reduces amputation rates and increases the likelihood of healing in infected diabetic foot ulcers, in association with improved tissue oxygenation, resulting in better quality of life. Nonetheless, HBO represents an expensive modality, which is only available in few centers. Moreover, adverse events necessitate a closer investigation of its safety. Finally, it is not entirely clear which patients stand to benefit from HBO and how these should be selected. In conclusion, HBO appears promising, but more experience is needed before its broad implementation in the routine care of the diabetic foot.     

Diagnostic and therapeutic changes in renal developmental anomalies detected in childhood

The authors diagnosed 40 renal malformations during 2 years investigated and 2 years control period. On the basis of analysing their patients they came to the conclusion that after the introduction of intrauterine routine ultrasound examinations and screening of childhood risk group the number of recognised renal malformations increased significantly (32 in the investigated and only 8 in the control period). Furthermore the age of patients at the time of diagnosing shifted to the early postnatal period, and the number of patients diagnosed on the basis of the positive urinary investigations decreased significantly. But the intrauterine routine ultrasound investigation at presently applied examination system can consider only one-third of fetal renal malformations. And also an important fact that the increased number of considered patients came from the increasing of patients who have needed operation and did not increase the number of infants who have needed only conservative therapy. According to the small surgical complications they concluded that the risk of the early surgical intervention does not seem to be higher than in case of postponed ones. On the basis of clinical observation with childhood risk group arising the necessarity of the non invasive postnatal routine screening.     

Accurate identification of paraprotein antigen targets by epitope reconstruction

We describe the first successful clinical application of a new discovery technology, epitope-mediated antigen prediction (E-MAP), to the investigation of multiple myeloma. Until now, there has been no reliable, systematic method to identify the cognate antigens of paraproteins. E-MAP is a variation of previous efforts to reconstruct the epitopes of paraproteins, with the significant difference that it provides enough epitope sequence data so as to enable successful protein database searches. We first reconstruct the paraprotein's epitope by analyzing the peptides that strongly bind. Then, we compile the data and interrogate the nonredundant protein database, searching for a close match. As a clinical proof-of-concept, we apply this technology to uncovering the protein targets of para-proteins in multiple myeloma (MM). E-MAP analysis of 2 MM paraproteins identified human cytomegalovirus (HCMV) as a target in both. E-MAP sequence analysis determined that one para-protein binds to the AD-2S1 epitope of HCMV glycoprotein B. The other binds to the amino terminus of the HCMV UL-48 gene product. We confirmed these predictions using immunoassays and immunoblot analyses. E-MAP represents a new investigative tool for analyzing the role of chronic antigenic stimulation in B-lymphoproliferative disorders.     

Pathogenicity of a human thyroglobulin peptide (2340-2359) in mice with high or low genetic susceptibility to thyroiditis

We have previously identified a 20-mer peptide of human thyroglobulin (hTg), p2340 (aa2340-2359), which induced experimental autoimmune thyroiditis (EAT) in AKR/J (H-2(k)) and HLA-DR3 transgenic mice. In this study, we investigated the thyroiditogenic potential of p2340 in 'high responder' CBA/J (H-2(k)) and SJL/J (H-2(s)) or 'low responder' C57BL/6 (H-2(b)) and BALB/c (H-2(d)) mice. Mice were immunized subcutaneously with 100 nmol of p2340 in complete Freund's adjuvant (CFA) and both the proliferative capacity of their lymph node cells in the presence of p2340 or intact Tg and the production of peptide-specific antibodies were investigated. The p2340 peptide was found to contain B-cell and non-dominant T-cell epitope(s) in all strains tested. Moreover, it elicited EAT in CBA/J (2/6, infiltration index (I.I.) 1) and SJL/J (5/5, I.I. 1-3) mice after direct challenge and in BALB/c (4/7, I.I. 1) and C57BL/6 (1/5, I.I. 1) after adoptive transfer of p2340-primed lymph node cells. P2340 is the first Tg peptide found to be pathogenic in low as well as high responder mouse strains and thus will allow us to investigate mechanisms of EAT induction in a genetically resistant host.     

Urine neutrophil gelatinase-associated lipocalin to predict acute kidney injury in preterm neonates. A pilot study

Background

The efficacy of urine neutrophil gelatinase-associated lipocalin (uNGAL) as an early acute kidney injury (AKI) biomarker in preterm neonates was evaluated.

Methods

Thirty-five preterm neonates were prospectively evaluated for serum creatinine (sCre)-documented AKI during the first 14 days of life. Urine samples were collected daily throughout the study period. Of the neonates evaluated, we analyzed 11 who developed AKI (cases) and an equal number of neonates without AKI (controls) matched for gestational and postnatal age (case–control study). uNGAL was measured on the day of AKI occurrence (day 0) and on the 2 days preceding the event (day ?1 and day ?2, respectively) using an enzyme-linked immunosorbent assay.

Results

Cases had significantly higher sCre levels than controls on day 0 (1.21?±?0.48 vs. 0.83?±?0.16 mg/dL, p?=?0.031) but not on days ?1 and ?2. Similarly, uNGAL levels (ng/mL) were significantly higher in cases than in controls only on day 0 (19.1?±?3.5 vs. 13.3?±?7.3, p?=?0.017) and not on days ?1 (18.8?±?3.4 vs. 16.3?±?5.9, p?=?0.118) and ?2 (19.3?±?1.8 vs. 19.4?±?0.8, p?=?0.979). The receiver operating characteristic curve analysis showed no significant ability of uNGAL to predict AKI on days ?2 and ?1.

Conclusions

In this pilot study in preterm neonates, although uNGAL detected sCre-based AKI upon its documentation, it failed to predict its development 1–2 days earlier.