Responses against complex antigens in various models of CD4 T-cell deficiency

The most common models of CD4 T-cell deficiency are mice exogenously injected with anti-CD4 antibody (Ab), CD4 knockout (CD4^−/−) and major histocompatibility complex (MHC) class II knockout (class II^−/−) mice. We recently described the anti-CD4 Ab transgenic mouse (GK) as an improved CD4 cell-deficient model. This review compares this new GK mouse model with the widely available class II^−/− and CD4^−/− mice, when exposed to complex antigens (foreign grafts and during bacterial or viral infection). We highlight here the cytometric and functional differences (including Ab isotype, viral or bacterial clearance, and graft survival) among these CD4 cell-deficient models. For example, whereas grafts are generally rejected in class II^−/− and CD4^−/− mice as quickly as in wild-type mice, they survive longer in GK mice. Also, CD4^−/− mice produce IgG against both simple model and complex antigens, but class II^−/− and GK mice produce small amounts of IgG2a against complex antigens but not simple model antigens. These differences harbinger the caveats in the use of these various mice.     

Levels of quality management of blood transfusion services in Europe

The European blood legislation has defined several key quality elements to achieve Good Manufacturing Practice (GMP) in the field of blood transfusion. During the recent years, the blood legislation is in the process of implementation throughout its member states. Following the Directive 2002/98/EC, Directive 2005/62/EC has given further requirements for quality-management systems to be fulfilled by blood establishments. In addition, GMP/Good Laboratory Practice (GLP) and ISO standards are used inter alia by blood establishments. In order to support the implementation of the blood legislation, the European Public Health Work Plan (2005/2007) has cofunded two projects, led by the German Red Cross and supported by the European Blood Alliance, delivering a common European Standard Operating Procedure (SOP) methodology (EU-Q-Blood-SOP) and criteria and standards for the inspection of blood establishments (EUBIS). The EU-SOP manual will assist blood establishments in preparing for the inspection of their services related to the implementation of quality relevant elements required by the EU Directive 2002/98/EC and its technical annexes. The standards and criteria for inspection of blood establishments will cross-reference existing quality standards to the directive requirements and define requirements for the structure of quality-management systems based on the directive 2002/98/EC and its technical annexes. Based on these requirements, inspection standards and criteria are developed to assist in the independent assessment of quality systems established by individual blood establishments. These assessments are done in relation to the requirements defined by the European Union legislation on blood, in order to safeguard the quality of blood and to achieve continuous improvement of its quality throughout Europe.     

Phospholipases and fatty acid signalling in exocytosis

Vesicle fusion is a ubiquitous biological process involved in general membrane trafficking and a variety of specialized events, for example release of neurotransmitters and hormones, sperm acrosome exocytosis, plasma membrane repair and neurite outgrowth. Many vesicle fusion events have long been known to be activated by phospholipases and products of their activity, such as polyunsaturated arachidonic acid. Polyunsaturated fatty acids (PUFAs) have been proposed to have a number of multiple effectors, including ion channels and the cytoskeleton, but the precise mechanism of PUFA action is still unclear. It was recently reported that omega-3 and omega-6 PUFAs can act on syntaxin, a plasma membrane protein directly involved in vesicle fusion. In this review, we will discuss the role of this new mode of PUFA action in exocytosis.     

Comparative analysis of the mucosal adjuvanticity of the type II heat-labile enterotoxins LT-IIa and LT-IIb

Cholera toxin (CT) and the heat-labile enterotoxin of Escherichia coli (LT-I) are members of the serogroup I heat-labile enterotoxins (HLT) and can serve as systemic and mucosal adjuvants. However, information is lacking with respect to the structurally related but antigenically distinct serogroup II HLT, LT-IIa and LT-IIb, which have different binding specificities for ganglioside receptors. The purpose of this study was to assess the effectiveness of LT-IIa and LT-IIb as mucosal adjuvants in comparison to the prototypical type I HLT, CT. BALB/c mice were immunized by the intranasal (i.n.) route with the surface protein adhesin AgI/II of Streptococcus mutans alone or supplemented with an adjuvant amount of CT, LT-IIa, or LT-IIb. Antigen-specific antibody responses in saliva, vaginal wash, and plasma were assayed by enzyme-linked immunosorbent assay. Mice given AgI/II with LT-IIa or LT-IIb by the i.n. route had significantly higher mucosal and systemic antibody responses than mice immunized with AgI/II alone. Anti-AgI/II immunoglobulin A (IgA) antibody activity in saliva and vaginal secretions of mice given AgI/II with LT-IIa or LT-IIb was statistically similar in magnitude to that seen in mice given AgI/II and CT. LT-IIb significantly enhanced the number of AgI/II-specific antibody-secreting cells in the draining superficial cervical lymph nodes compared to LT-IIa and CT. LT-IIb and CT induced significantly higher plasma anti-AgI/II IgG titers compared to LT-IIa. When LT-IIb was used as adjuvant, the proportion of plasma IgG2a relative to IgG1 anti-AgI/II antibody was elevated in contrast to the predominance of IgG1 antibodies promoted by AgI/II alone or when CT or LT-IIa was used. In vitro stimulation of AgI/II-specific cells from the superficial lymph nodes and spleen revealed that LT-IIa and LT-IIb induced secretion of interleukin-4 and significantly higher levels of gamma interferon compared to CT. These results demonstrate that the type II HLT LT-IIa and LT-IIb exhibit potent and distinct adjuvant properties for stimulating immune responses to a noncoupled protein immunogen after mucosal immunization.     

Ganglion cysts at the gastrocnemius origin: a series of ten cases

Objective To describe ganglion cysts arising close to the origin of the medial and lateral head of gastrocnemius as identified on magnetic resonance (MR) imaging. Design and patients We present a series of ten cases of ganglion cysts arising close to the gastrocnemius origin from the medial and lateral femoral condyles. These were collected over a 6-year period from our imaging database. All patients attended for routine MR imaging of the knee with a variety of clinical presentations. Data collected included patient demographics, ganglion size, ganglion site, clinical presentation and ancillary MR imaging findings. The ten patients in this series consisted of seven males and three females, five right and five left knees, age range 27–68 years, mean age 40.6 years. Results The mean maximal dimension of the ganglion cysts was 26 mm, range 15–40 mm. The medial gastrocnemius origin was involved in eight patients and the lateral origin in two patients. The MR imaging findings consisted of both uni- and multi-loculated cysts, often containing numerous septations with fluid signal characteristics. The cysts were extra-capsular with no clear communication with the joint. One patient presented with a popliteal soft tissue mass and none of the cases required surgical intervention for cyst removal. Conclusions MR imaging may identify ganglion cysts arising in an intra- or extra-articular site around the knee. This series documents the MR imaging characteristics of ganglion cysts arising close to the gastrocnemius origin and discusses the relevance of this imaging finding.     

Magnetic resonance imaging findings of injuries to the calf muscle complex

Objective The objective was to describe the imaging findings following acute injury to the calf musculature. Design and patients We retrospectively reviewed 59 MR examinations in patients who sustained injuries to the calf muscle from April 2001 to September 2004 (48 men, 11 women), with an average age of 31 and 47 years respectively (range in men 20–53; range in women 33–63). Attention was directed to the frequency of muscle involvement, the location of the injury within the musculotendinous unit and the extent of the injury. Results and conclusions A total of 79 separate sites of strain injury were identified (39 solitary, 20 dual). Of the 39 isolated strains, injury to the gastrocnemius was most common (19 out of 39; 48.7%), preferentially involving the medial head in 18 cases and the lateral head in 1 case. The soleus was also commonly involved (18 out of 39; 46.2%), with 2 cases (5.1%) of distal avulsions of the plantaris. Of the 20 dual injuries, a combination of gastrocnemius injury with soleus injury was the most frequent finding (12 out of 20; 60%). Dual injuries of both heads of the gastrocnemius muscles were demonstrated in 4 cases (20%), with the soleus and tibialis posterior injured in 3 cases (15%). A combination of soleus and flexor hallucis longus injury was seen in 1 case (5%). Conclusion This retrospective study utilizing MRI demonstrates that the medial head of the gastrocnemius is the most commonly injured muscle of the calf, closely followed by the soleus, the latter finding rarely reported in the sonographic literature. Dual injuries of the calf muscle complex occur much more commonly than previously reported and may be of prognostic significance.     

Poor results with technetium-99m (V) DMS and iodine-131 MIBG in the imaging of medullary thyroid carcinoma

The value of [99mTc(V)]DMS and [131I]MIBG in imaging medullary carcinoma of the thyroid was investigated in five patients. Results with [99mTc(V)]DMS were negative in all five patients as well as with [131I]MIBG in four patients; however, there was significant tumor uptake in one patient with [131I]MIBG.