Expression of protocadherin-γC4 protein in the rat brain

It has been proposed that the combinatorial expression of γ-protocadherins (Pcdh-γs) and other clustered protocadherins (Pcdhs) provides a code of molecular identity and individuality to neurons, which plays a major role in the establishment of specific synaptic connectivity and formation of neuronal circuits. Particular attention has been directed to the Pcdh-γ family, for which experimental evidence derived from Pcdh-γ-deficient mice shows that they are involved in dendrite self-avoidance, synapse development, dendritic arborization, spine maturation, and prevention of apoptosis of some neurons. Moreover, a triple-mutant mouse deficient in the three C-type members of the Pcdh-γ family (Pcdh-γC3, Pcdh-γC4, and Pcdh-γC5) shows a phenotype similar to the mouse deficient in whole Pcdh-γ family, indicating that the latter is largely due to the absence of C-type Pcdh-γs. The role of each individual C-type Pcdh-γ is not known. We have developed a specific antibody to Pcdh-γC4 to reveal the expression of this protein in the rat brain. The results show that although Pcdh-γC4 is expressed at higher levels in the embryo and earlier postnatal weeks, it is also expressed in the adult rat brain. Pcdh-γC4 is expressed in both neurons and astrocytes. In the adult brain, the regional distribution of Pcdh-γC4 immunoreactivity is similar to that of Pcdh-γC4 mRNA, being highest in the olfactory bulb, dentate gyrus, and cerebellum. Pcdh-γC4 forms puncta that are frequently apposed to glutamatergic and GABAergic synapses. They are also frequently associated with neuron-astrocyte contacts. The results provide new insights into the cell recognition function of Pcdh-γC4 in neurons and astrocytes.     

Therapeutic plasma exchange in the management of sepsis and multiple organ dysfunction syndrome: A report of three cases

Sepsis with multi organ dysfunction syndrome (MODS) is the most common cause of death in patients in noncoronary intensive care units. Currently, there are no specific treatments that reduce mortality in patients with sepsis and MODS. We report three patients who received therapeutic plasma exchange (TPE) for sepsis with MODS who completely recovered. The first patient, a 3‐year‐old male presented with Methicillin‐resistant Staphylococcus aureus‐associated respiratory, renal, coagulation, hepatic, and neurologic dysfunction. After 5 TPEs, the patient fully recovered. The second patient was a 36‐year‐old pregnant female who developed MODS at 22 weeks of gestation. She had developed respiratory, hepatic, renal, cardiovascular, neurologic, and coagulation dysfunction following pneumonia and concurrent urinary tract infection resulting in an intrauterine fetal demise. After 8 TPEs, the patient was discharged home with only mild residual hepatic dysfunction. The third patient, a 50‐year‐old female with a history of seizure disorder, was found unresponsive in over 100°F heat and diagnosed with Staphylococcus aureus‐associated MODS. Her respiratory, coagulation, neurologic, renal, and hepatic systems were affected. The patient underwent 6 TPEs after which she had marked improvement. In conclusion, TPE may be an effective adjunct therapy in MODS by possibly removing toxic mediators and replacing deficient factors using donor plasma. J. Clin. Apheresis 29:127–131, 2014. © 2013 Wiley Periodicals, Inc.     

Cytotoxic T lymphocytes produce immune interferon in response to antigen or mitogen

Interferon (IFN) was found to be secreted by cloned lines of murine cytotoxic T lymphocytes in response to mitogenic or antigen specific stimulation. The IFN produced was shown to be of the immune type based on its sensitivity to pH 2.0 and on the ability of an antiserum to immune IFN to neutralize the antiviral activity.     

The CD8 population in CD4-deficient mice is heavily contaminated with MHC class II-restricted T cells

In experiments to study the impact of deficiency in CD4+ T cell help on the magnitude of CD8+ cytotoxic T cell response to pathogens, it was noted that in CD4 gene knockout mice, the CD8 population made significant responses to several nominally major histocompatibility complex (MHC) class II-restricted epitopes in addition to the expected responses to MHC class I-restricted epitopes. A similar response by CD8+ T cells to class II-restricted epitopes was not observed in wild-type mice, or in mice that had been acutely depleted of CD4+ T cells just before the immunization. Coincident with this unexpected response to class II-restricted epitopes, it was also observed that the CD8+ response to the class I-restricted epitopes was consistently lower in CD4-/- mice than in wild-type mice. Further experiments suggested that these two observations are linked and that the CD8 population in CD4-/- mice may contain a majority of T cells that were actually selected by recognition of MHC class II molecules in the thymus. These results have implications for understanding CD4 versus CD8 lineage commitment in the thymus, and for the practical use of CD4-/- mice as models of helper deficiency.     

Amiodarone‐induced bone marrow granulomas

Amiodarone hydrochloride, a class III antiarrhythmic agent used to treat supraventricular and ventricular cardiac dysrhythmias. In this report we describe two patients receiving amiodarone for atrial fibrillation who underwent bone marrow biopsies to investigate paraproteinaemia (case 1) or severe thrombocytopenia (case 2). Multiple bone marrow granulomas were found in both patients, without evidence of any other cause. In both patients the granulomas disappeared after amiodarone withdrawal, suggesting a direct association.