Involvement of regional lymph nodes after penetration of Schistosoma mansoni cercariae in naive and infected mice

The very low density lipoprotein receptor (VLDL-r) is a cell-surface molecule specialized for the internalization of multiple diverse ligands, including apolipoprotein E (apoE)-containing lipoprotein particles, via clathrin-coated pits. Its structure is similar to the low-density lipoprotein receptor (LDL-r), although the two have substantially different systemic distributions and regulatory pathways. The present work examines the distribution of VLDL-r in the central nervous system (CNS) and in relation to senile plaques in Alzheimer disease (AD). VLDL-r is present on resting and activated microglia, particularly those associated with senile plaques (SPs). VLDL-r immunoreactivity is also found in cortical neurons. Two exons of VLDL-r mRNA are differentially spliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycosylation domain near the transmembrane portion of the molecule. The other set of splice forms appears to be brain-specific, and is responsible for the presence or absence of one of the cysteine-rich repeat regions in the binding region of the molecule. Ratios of the receptor variants generated from these splice forms do not differ substantially across different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A beta complexes in the brain. Further characterizations of apoE receptors in Alzheimer brain may help lay the groundwork for understanding the role of apoE in the CNS and in the pathophysiology of AD.     

Plasma membrane phospholipid fatty acid composition of cultured skin fibroblasts from schizophrenic patients: comparison with bipolar patients and normal subjects

Recent studies have found lower red cell plasma membrane contents and composition of the long chain polyunsaturated essential fatty acid derivatives, particularly arachidonic acid and docosahexaenoic acid, in a subgroup of chronic schizophrenic patients. These fatty acids are particularly enriched in the brain. Red blood cell levels of fatty acids are influenced by diet, medications, and other factors. Cell plasma membrane compositions of arachidonic and docosahexaenoic acids were therefore examined in cultured skin fibroblasts from 12 schizophrenic patients, 8 of whom were drug-naive and in a first episode of psychosis, 6 bipolar patients, and 8 normal control subjects. Docosahexaenoic acid as well as total n-3 essential fatty acid contents were significantly lower in cell lines from schizophrenic patients than in cell lines from bipolar patients and normal subjects, with no difference between the latter two groups. Arachidonic acid levels did not differ across the groups. The essential fatty acid profile observed is consistent with deficient delta-4 desaturase activity in schizophrenic patients.     

Bone mineralisation, body fat and anthropometric measurement in mothers delivering preterm

Twenty mothers of preterm babies who had survived to 1 year old, were matched for age and parity of the mother and time of birth of the baby, with 20 mothers delivering fullterm. Bone mineral, body composition and anthropometric measurements were obtained for each mother and analysed using paired t-tests. The only significant difference (P < 0.01) between the groups was a lower fat-free mass in the preterm mothers calculated from skinfold thickness measurements.     

Growth and function of human parathyroid tissue transplanted to athymic mice

The morphology, cell proliferation and function of transplanted normal, hyperplastic and adenomatous human parathyroid tissue was studied after transplantation to athymic mice. The iPTH was evaluated in relation to morphology. Human parathyroid tissue collected during surgery for hyperparathyroidism was implanted subcutaneously into athymic mice (nu/nu-BALB/cA) and was analysed 1, 4, 7 and 12 weeks after transplantation. The transplants were examined by light and electron microscopy and by autoradiography after continuous infusion of 3H-thymidine. The relative amount of viable tissue was evaluated using a computer image analysing programme. Graft function was evaluated by measuring human iPTH in mouse serum. A transplant take ratio of 93% was observed. The proliferation rate in adenoma grafts at 12 weeks after transplantation was five and fifteen times that observed in normal and hyperplastic transplants, respectively. In normal and adenoma groups, a continuous increase in iPTH concentrations was observed, but in the hyperplastic group the iPTH remained on the same level. The secretion of iPTH in relation to the amount of transplanted tissue and the fraction of viable tissue was at the same level at 12 weeks in normal and adenomatous grafted animals. In conclusion, human parathyroid tissue was successfully transplanted and maintained its original structure. The growth potential, but not the iPTH secretion, was significantly higher in adenoma grafts compared to grafts from hyperplastic and normal glands.     

AK-5 tumor-induced expression of interleukin-12: role of IL-12 in NK-mediated AK-5 regression

Spontaneous regression of AK-5, a histiocytic tumor, is mediated by CD3-, CD8+ NK cells through ADCC. The onset of AK-5 regression is associated with the induction of humoral immune response and the augmentation of effector function. The mechanism of tumor cell death involves both necrosis and apoptosis. Interleukin-12, a 75-kDa heterodimeric cytokine, has multiple effects on T and NK cells. We have investigated the role of IL-12 in the NK cell-mediated AK-5 tumor regression process. Subcutaneous transplantation of AK-5 tumor induced the expression of IL-12 (p35 and p40) message by Day 6-8 in the splenocytes of syngenic rats. Similarly, analysis of serum samples from tumor-bearing animals showed the presence of circulating IL-12 around the same time. Interaction of immune cells with antibody-tagged AK-5 cells in vitro also triggered the expression of IL-12 message and protein by 3 hr. The circulating IL-12 in the sera of tumor-rejecting animals, as well as rIL-12, stimulated NK cell proliferation, expression of CD16 and CD25, and the activation of NK cells function. These observations suggest that the ability of the AK-5 tumor to induce the endogenous production of IL-12 may be responsible for keeping the NK cells constantly in an activated state, thus demonstrating an efficient mechanism for the complete regression of the tumor.     

The synthesis of symmetrical and unsymmetrical P1/P1' cyclic ureas as HIV protease inhibitors

Cyclic urea SD146, a potent HIV protease inhibitor bearing a flat resistance profile, possessed poor solubility and bioavailability, which precluded further development of the compound. In an effort to improve upon the pharmacokinetic profile of the compound, several analogs modified at the P1/P1' residues were prepared and evaluated. Several of those compounds displayed significant improvement of physical properties.     

Reflections on the Michigan splint and other intraocclusal devices

It seems obvious in retrospect that the treatment of disorders by interocclusal devices followed two paths: stabilization splints and functional orthopedic appliances. The dividing line between them is not always clear. Both have some function related to the position of the mandible. They may not differ significantly in their control of occlusal stability (e.g., telescoping devices anchored to stabilization splints). The stabilization splint, as well as other conservative measures, will play an increasing role in accepted therapy for TMD. The use of anterior repositioning devices for TMD, including MPD syndrome, will decrease. Research may provide answers that allow them to be used more specifically and predictably. Perhaps there will be but little change in their use where there is an association of TMD and Class II malocclusion. There will be an increase in the use of interocclusal devices for the treatment of snoring and obstructive apnea. Some additional directions seem to have emerged in the late 1980s and early 1990s: In the absence of pain and significant debilitation, treatment for TMD, if any, is to be reversible. Prevention or aggravation of TMD should be practiced to the extent possible during dental procedures. One long-term, well-designed, prospective study indicated that the incidence and severity of TMD could be reduced by appropriate occlusal adjustment. There is a small, but nevertheless important minority of patients with TMD who progress to persistent pain and/or dysfunction. Initial management of the vast majority of patents with TMD should be use of noninvasive reversible therapies. Surgery is indicated in only a relatively small percentage of cases of TMD. Research on interocclusal devices should not terminate simply because they are in part dental devices (i.e., biomechanical forms of treatment). The diagnosis and treatment of TMD has been called a dilemma, especially for those patients with chronic pain for whom no treatment has been effective. However, it would be ill-advised to abandon what treatment is already known to be effective by allowing those few but psychosocially important patients with chronic pain to determine what should be done for the vast majority of patients with TMD: reversible forms of treatment, including physiotherapy, pharmacologicals, and the stabilization occlusal bite plane splint.