Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice

Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1 μg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1 μg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.     

A case of apparent trisomy 21 without the Down''s syndrome phenotype.

We describe a case of apparent trisomy 21 that does not fulfill the criteria for the clinical diagnosis of Down's syndrome (DS). Our patient was subjected to karyotype analysis and found to have full, non-mosaic trisomy 21 in both blood lymphocytes and skin fibroblasts, while examination of the term placenta, which was performed earlier in the course of a different study, had shown mosaicism (73%) for trisomy 21. FISH analysis showed no obvious rearrangement of the DS chromosomal region in any of the chromosomes 21. Molecular analysis using polymorphic markers on chromosome 21 verified the existence of trisomy for the entire long arm of the chromosome and showed that the origin of the extra chromosome was maternal and was probably the result of a mitotic error. In contrast with the above, the clinical evaluation using the Jackson checklist of 25 signs failed to establish the diagnosis of DS. We believe that our patient might present mosaicism in other tissues that are not available for analysis and can be regarded as an extreme example in the continuous spectrum of karyotype phenotype associations in mosaic cases.     

NO enhances presynaptic currents during cerebellar mossy fiber-granule cell LTP

Nitric oxide (NO) is a candidate retrograde messenger in long-term potentiation (LTP). The NO metabolic pathway is expressed in the cerebellar granule cell layer but its physiological role remained unknown. In this paper we have investigated the role of NO in cerebellar mossy fiber-granule cell LTP, which has postsynaptic N-methyl-d-aspartate (NMDA) receptor-dependent induction. Pre- and postsynaptic current changes were simultaneously measured by using extracellular focal recordings, and NO release was monitored with an electrochemical probe in P21 rat cerebellar slices. High-frequency mossy fiber stimulation induced LTP and caused a significant NO release (6.2 +/- 2.8 nM; n = 5) in the granular layer that was dependent on NMDA receptor as well as on nitric oxide synthase (NOS) activation. Preventing NO production by perfusing the NOS inhibitor 100 microM NG-nitro-l-arginine (L-NNA), blocking extracellular NO diffusion by 10 microM MbO2, or inhibiting the NO target guanylyl cyclase (sGC) with 10 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-dione (ODQ) prevented LTP. Moreover, the NO donor 10 microM 2-(N,N-diethylamino)-diazenolate-2-oxide.Na (DEA-NO) induced LTP, which was mutually occlusive with LTP generated by high-frequency stimulation, prevented by ODQ, and insensitive to NMDA channel blockade (50 microM APV + 25 microM 7-Cl-kyn) or interruption of mossy fiber stimulation. Thus NO is critical for LTP induction at the cerebellar mossy fiber-granule cell relay. Interestingly, LTP manipulations were accompanied by consensual changes in the presynaptic current, suggesting that NO acts as a retrograde signal-enhancing presynaptic terminal excitability.     

Serum Lactate Dehydrogenase Enzyme as a Tumor Marker in Potentially Malignant Disorders: A Systematic Review and Meta–Analysis

Background:Oral cancer is often preceded by Potentially Malignant Disorders (PMDs) and important role of biochemical markers for early diagnosis has been well documented; however, there is limited evidence of Serum lactate dehydrogenase (SLDH) as an effective biochemical marker in diagnosis of PMDs. The present meta-analysis was conducted to assess if serum LDH can be a used as standard biomarker for PMDs and consequently aid in diagnosis of oral cancer. Methods:A comprehensive search was conducted in Medline, Scopus, Web of Science, EBSCO host, Cochrane databases and Google Scholar for studies evaluating estimation of SLDH in PMDs. Search strategy included all types of studies evaluating level of SLDH in patients with PMDs. PRISMA guidelines were followed for the meta-analysis. Fixed-effects model was used to assess the mean differences in SLDH levels between healthy controls and PMDs. Results:A total number of nine studies were included in meta-analysis after screening for inclusion and exclusion criteria. Potentially malignant disorder was significantly associated with increased serum LDH level compared to healthy controls (pooled SMD: 1.83 (95% CI, 1.52, 2.15) (P < 0.00001; Subgroup analysis of OSMF (Oral Submucous Fibrosis) studies showed significant association with increased serum LDH level compared to healthy controls (pooled SMD: 2.57 (95% CI, 2.16, 2.98; P < 0.00001). Sensitivity analysis for the five studies reflected a significant reduction in I² values to 24 % (P=0.26). Funnel plots were derived for any evidence of publication bias among the studies. Conclusion:Meta-analysis suggests that SLDH is increased in potentially malignant disorders compared to healthy controls. The results of this metanalysis should encourage use of SLDH as a biomarker in diagnosis of PMDs.Key Words: Potentially malignant disorders (PMDs), oral cancer, lactate dehydrogenase enzyme, precancerous lesion     

Über ein besonderes fibrohämangiombildendes Syndrom der Lymphdrüsen und der Haut,das in Beziehung zur Gruppe der „Sarcomatosis Kaposi” steht

Zusammenfassung Bei einer 33jährigen Frau mit einer seit langer Zeit bestehenden multiplen und in verschiedenen Gebieten lokalisierten Lymphadenitis erscheinen sekundär und lange Zeit nach der Erkrankung der Lymphknoten Hautgebilde, die klinisch dem Sarcoma idiopathicum haemorrhagicum Kaposi zugeteilt werden können. Die histologische Untersuchung beweist die Gleichwertigkeit beider Prozesse in den Lymphknoten und der Haut, bei dem es sich um Bindegewebsgeschwülste mit der Tendenz zu vasculären hämangiomatösen Bildungen handelt und zeigt besonders in Hinblick auf die Haut die engen histologischen Verbindungen mit derKaposischen Erkrankung auf.Der Verfasser glaubt sich nach eingehender Darlegung der histologischen Eigenheiten der Lymphknotenerkrankung zu dem Schluß berechtigt, daß diese in das Bild des Sarcoma idiopathicum haemorrhagicum Kaposi einmünden und daß daher diese Erkrankung ursprünglich auch in den Lymphknoten beginnen kann. Das sekundäre Auftreten in der Haut bestätigt durch seine histologischen und klinischen Eigenheiten die aufgestellte Diagnose.Mit 10 Textabbildungen.     

Facing somatic symptom disorder in the emergency department

Somatic symptom disorder is a condition in which a patient's subjective report of physical symptoms is associated with distress; disruption of day‐to‐day functioning; or disproportionate thoughts, feelings and behaviours regarding the symptoms, whether or not they are associated with an identified medical condition. While somatic symptom disorder affects a considerable proportion of children and adolescents presenting to the emergency department (ED), it has not been well investigated in the ED literature, nor is there much formal training in, or guidelines for, how to care for affected patients in the ED. The aim of this paper is to highlight the historical clues commonly reported by these patients in order to try to help the emergency physicians recognise patients affected by a somatic symptom disorder. Adolescent age, the presence of daily subjective symptoms presenting daily for weeks or months, a long medical history record, an extensive diagnostic workup and, most of all, disproportionate functional impairment related to the symptoms are all features strongly suggestive of this disorder. Emergency physicians should become used to taking advantage of these clues to formulate a positive diagnosis of somatic symptom disorder according to the most recent diagnostic criteria. Emergency physicians have the unique opportunity to contribute to the correct diagnosis and treatment of these patients and to have a positive impact on their prognosis.