Biochemical maturation of the non-innervated chick optic lobe.

The development of the chick optic lobe was impaired following removal of the optic cup of the early embryo. Tectal cell number is reduced but cell size may be relatively normal. Ther was evidence of neuronal cell death and several neuron-associated proteins and enzymes (nerve-specific protein and acetylcholinesterase) showed selectively impaired maturation. However, other nerve-specific enzymes (choline acetyltransferase, tyrosine hydroxylase), develop normally on a per cell basis. The noninnervated optic lobe had a normal blood-brain barrier but a depressed ability to accumulate amino acids from plasma. Levels of 3':5'-cyclic GMP were also reduced in the nonafferented lobe.     

Application of powder failure testing equipment in assessing effect on glidants on flowability of cohesive pharmaceutical powders.

Powder failure testing equipment was used successfully to study the effect of glidants on the flowability of two cohesive pharmaceutical powders, lactose and calcium hydrogen phosphate, using the flow factor as the flowability parameter. Fine silica, magnesium stearate, and purified talc were investigated as glidants; for each host powder-glidant mixture, an optimum concentration of glidant was observed beyond which no further increase in flowability occurred. The order of efficiency of glidants for both host powders was fine silica greater than magnesium stearate greater than purified talc. The mode of action of the three glidants is discussed.     

Immunophenotypic and genetic characterization of a CD8 positive mantle cell lymphoma in a patient with concomitant Mycosis fungoides

Mantle cell lymphoma (MCL) is immunophenotypically characterized by cell surface co-expression of CD19, CD20, CD5, IgM and FMC7. However, the concomitant presence of other antigens distinctive of a particular leukocyte subset, e.g. T-lymphocytes, is an exceptional finding in MCL. Here, the first case of a blastic MCL in leukaemic phase with aberrant expression of the T-cell associated antigen CD8 occurring in a patient with concomitant Mycosis fungoides is described. Comprehensive immunophenotypic analysis showed that the MCL cells expressed the typical B-lymphocytic markers, were CD5 and CD8 positive, but did not express other T-cell proteins, such as CD2, CD3, CD4, CD7, TCRalphabeta and TCRgammadelta. The MCL cells expressed both CD8alpha and CD8beta chains indicating cell surface presence of CD8alphabeta heterodimers. Intriguingly, expression of the cytotoxic enzymes perforin and granzyme A was detected by RT-PCR. Cytogenetic and molecular genetic analysis of the lymphoma cells confirmed cyclin D1 overexpression secondary to the t(11;14)(q13;32) chromosomal translocation. Furthermore, trisomy 11, trisomy 14 and extra copies of t(11;14) translocated chromosomes were detected in sub clones of the analyzed MCL cells. Clinically, an aggressive course of disease including cerebral lymphoma involvement was noted in the reported patient. Hence, systematic studies addressing the incidence, biology and clinical behavior of this form of MCL seem to be justified in future.     

An essential role for an inositol polyphosphate multikinase, Ipk2, in mouse embryogenesis and second messenger production

Phospholipase C and several inositol polyphosphate kinase (IPK) activities generate a branched ensemble of inositol polyphosphate second messengers that regulate cellular signaling pathways in the nucleus and cytoplasm. Here, we report that mice deficient for Ipk2 (also known as inositol polyphosphate multikinase), an inositol trisphosphate and tetrakisphosphate 6/5/3-kinase active at several places in the inositol metabolic pathways, die around embryonic day 9.5 with multiple morphological defects, including abnormal folding of the neural tube. Metabolic analysis of Ipk2-deficient cells demonstrates that synthesis of the majority of inositol pentakisphosphate, hexakisphosphate and pyrophosphate species are disrupted, although the presence of 10% residual inositol hexakisphosphate indicates the existence of a minor alternative pathway. Agonist induced inositol tris- and bis-phosphate production and calcium release responses are present in homozygous mutant cells, indicating that the observed mouse phenotypes are a result of failure to produce higher inositol polyphosphates. Our data demonstrate that Ipk2 plays a major role in the synthesis of inositol polyphosphate messengers derived from inositol 1,4,5-trisphosphate and uncovers a role for their production in embryogenesis and normal development.