Large arachnoid cysts at the cranial base

Two infants who presented with macrocephaly had very large noncommunicating cysts at the cranial base that were displacing the brain. Only one of the patients was hydrocephalic; he eventually underwent ventriculoperitoneal shunting after craniotomy and attempted internal drainage of the cyst. The other infant had a cystoperitoneal shunt. Both have done well after 4 and 6 years of follow-up, respectively. These large arachnoid cysts are bilateral lesions with the potential for severe surgical complications and a questionable possibility of cure. The authors recommend systematic radiological investigation to decide the appropriate therapy, including an analysis of the patency of the subarachnoid pathways with radionuclide cisternography and cystography. Simple cystoperitoneal shunting may be the appropriate therapy for most of these large lesions. (Neurosurgery, 6: 76--81, 1980).     

Genetic influence on serum igd levels

In order to better understand the factors determining serum levels of IgD, total serum IgD and IgE were studied in 23 nonallergic twin pairs, consisting of 16 monozygotic (Mz and 7 same-sex dizygotic (Dz) pairs. Both immunoglobulins were measured by a paper disc solid phase radioimmunoassay, sensitive to 1 microgram/dl of IgD and 1 I.U./ml of IgE. Also studied were 10 paired sera taken at different times from 10 healthy subjects of similar mean age to the twins and 21 randomly paired sera from unrelated subjects. The intrapair variance of both serum IgD and serum IgE levels were significantly less in Mz than in Dz twins (P less than 0.05). Thus, there appears to be a genetic influence over serum IgD levels, probably to a similar degree to that previously shown to exist for serum IgE levels. Heritability was calculated to be 0.759 for IgD and 0.697 for IgE. Also, the intraclass correlation coefficient (rI) for IgD in monozygotic twin pairs was 0.9370 (P less than 0.001) and for IgE was 0.8602 (P less than 0.001). It appears likely that the number of genetic loci controlling serum IgD levels is similar to, or less than, the number controlling serum IgE levels because the random pair/Dz pair variance ratio was lower for IgD than for IgE.     

Evaluation and treatment of head and neck venous vascular malformations

Congenital venous vascular malformations of the head and neck are low-flow, nonproliferative lesions that should be distinguished from hemangiomas. The characteristic history and clinical findings can establish the diagnosis. Direct percutaneous puncture and contrast injection at the time of treatment delineate the lesion and its drainage pattern. Treatment must be individualized according to lesion extent, patient tolerance and physician experience. Sclerotherapy with ethanol has proved to be a successful treatment modality for these lesions, as demonstrated in this study of 57 patients. Surgery is used for treatment of clinically significant residual disease. A multidisciplinary approach to evaluation and treatment is key to successful management.     

A multimodal analysis of personal negativity

This study examined how unhappiness and self-dissatisfaction are related to behavior, self-perception, social reputation, and the way one is treated by others. Varying in personal negativity (PN)--a composite of unhappiness, dissatisfaction with life, low self-esteem, and nonclinical depression--146 undergraduates (82 women and 64 men) engaged in 3 interactions. Participants' behavior and the behavior of their interaction partners was coded from videotapes. Personality ratings were obtained from participants and from 2 close acquaintances. PN was closely associated with maladaptive social interactions, negative behavioral responses by others, and a negative social reputation and self-image. Although women more clearly expressed PN behaviorally, men and women showed generally similar patterns of correlates. These results suggest that even subclinical levels of unhappiness and self-dissatisfaction may have important consequences.     

Fine specificity of the myelin-reactive T cell repertoire: implications for TCR antagonism in autoimmunity

The use of altered peptide ligands (APL) to modulate T cell responses has been suggested as a means of treating T cell-mediated autoimmune disorders. We have assessed the therapeutic potential of TCR antagonist peptides in autoimmunity using murine experimental autoimmune encephalomyelitis (EAE) as a model. The Tg4 transgenic mouse expresses an MHC class II-restricted TCR specific for the immunodominant encephalitogenic epitope of myelin basic protein, Ac1-9 (acetylated N-terminal nonamer). We have used T cell lines derived from Tg4 mice to define the TCR contact residues within Ac1-9. APL with appropriate substitutions at the primary TCR contact residue were effective antagonists of Tg4 T cells. These antagonist APL, however, were found to induce EAE in susceptible, nontransgenic strains of mice. Underlying this, the Ac1-9-specific T cell repertoire of normal mice, rather than reflecting the Tg4 phenotype, showed considerable diversity in fine specificity and was able to respond to the Tg4 antagonist APL. Defining antagonist APL in vitro using T cell clones, therefore, was not a reliable approach for the identification of APL with EAE-suppressing potential in vivo. Our findings highlight the complexities of the autoreactive T cell repertoire and have major implications for the use of APL in autoimmune diseases.     

The synthesis of sialylated oligosaccharides using a CMP-Neu5Ac synthetase/sialyltransferase fusion

Large-scale enzymatic synthesis of oligosaccharides, which contain terminal N-acetyl-neuraminic acid residues requires large amounts of the sialyltransferase and the corresponding sugar-nucleotide synthetase, which is required for the synthesis of the sugar-nucleotide donor, CMP-Neu5Ac. Using genes cloned from Neisseria meningitidis, we constructed a fusion protein that has both CMP-Neu5Ac synthetase and alpha-2,3-sialyltransferase activities. The fusion protein was produced in high yields (over 1200 U/L, measured using an alpha-2,3-sialyltransferase assay) in Escherichia coli and functionally pure enzyme could be obtained using a simple protocol. In small-scale enzymatic syntheses, the fusion protein could sialylate various oligosaccharide acceptors (branched and linear) with N-acetyl-neuraminic acid as well as N-glycolyl- and N-propionyl-neuraminic acid in high conversion yield. The fusion protein was also used to produce alpha-2,3-sialyllactose at the 100 g scale using a sugar nucleotide cycle reaction, starting from lactose, sialic acid, phosphoenolpyruvate, and catalytic amounts of ATP and CMP.     

Disparity in expression of protein kinase C alpha in human glioma versus glioma-derived primary cell lines: therapeutic implications

Intracellular signal transduction by the protein kinase C (PKC) family of enzymes plays a critical role in carcinogenesis and cellular growth regulation. Recent studies have suggested that the PKC isoform alpha may be a critical target for antiglioma therapy in humans (G. H. Baltuch et al., Can. J. Neurol. Sci., 22: 264-271, 1995). We studied the expression and subcellular distribution of the PKC alpha isoform in human high- and low-grade gliomas and also in glioma-derived cell lines with immunoblot analyses. Cell lines derived from high-grade gliomas expressed higher levels of PKC alpha than did cell lines derived from low-grade gliomas. In glioblastoma-derived cell lines, PKC alpha was mainly expressed in the soluble (cytosolic) fraction, indicating an inactive state of the enzyme. When analyzed in freshly frozen samples from human gliomas, the expression of PKC alpha was at similar levels in high- and low-grade tumors and was also similar to the levels in normal brain tissue controls. The PKC partial antagonist bryostatin 1, currently undergoing Phase II testing in patients with malignant gliomas, was capable of specifically down-regulating PKC alpha in vitro in glioblastoma-derived cell lines. However, this was not associated with significant growth inhibition. We conclude that the observed overexpression of PKC alpha in glioblastoma-derived cell lines may be an artifact of in vitro growth. Furthermore, we conclude that expression of PKC alpha in glioma-derived cell lines is not essential for cellular growth in vitro because down-regulation of PKC alpha following treatment with bryostatin 1 was not associated with growth inhibition.