Asymmetric space closure

In a vertically slotted 0.022 X 0.028 inch edgewise system, the use of a two-dimensional ribbon arch--0.022 X 0.016 inch from lateral incisor to lateral incisor and 0.016 X 0.022 inch from the canine to the molars--plus an uprighting spring on the canine maintained incisor position while unilaterally protracting a molar-premolar unit by means of sliding mechanics. Five degrees of labial crown torque was placed in the incisor portion of the wire and the uprighting spring exerted a force of 200 to 250 g. The intra-arch force applied to protract the molar--premolar unit was 300 to 350 g.     

Superficial bladder cancer: intravesical chemotherapy and tumour progression to muscle invasion or metastases

Of 299 patients who presented with superficial bladder cancer (Ta, T1), 60 were treated by intravesical chemotherapy (Epodyl, methotrexate or mitomycin C). The rate of tumour progression to muscle invasion or metastases was identical for each intravesical regime. There was no evidence that mitomycin C promoted tumour progression. Carcinoma in situ in non-tumour-bearing urothelium was the most significant predictive factor for progression to muscle invasion or metastases.     

ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels.

The tarantula venom peptides ProTx-I and ProTx-II inhibit voltage-gated sodium channels by shifting their voltage dependence of activation to a more positive potential, thus acting by a mechanism similar to that of potassium channel gating modifiers such as hanatoxin and VSTX1. ProTx-I and ProTx-II inhibit all sodium channel (Nav1) subtypes tested with similar potency and represent the first potent peptidyl inhibitors of TTX-resistant sodium channels. Like gating modifiers of potassium channels, ProTx-I and ProTx-II conform to the inhibitory cystine knot motif, and ProTx-II was demonstrated to bind to sodium channels in the closed state. Both toxins have been synthesized chemically, and ProTx-II, produced by recombinant means, has been used to map the interaction surface of the peptide with the Nav1.5 channel. In comparison, beta-scorpion toxins activate sodium channels by shifting the voltage dependence of activation to more negative potentials, and together these peptides represent valuable tools for exploring the gating mechanism of sodium channels.     

Angiostatin overexpression in Morris hepatoma results in decreased tumor growth but increased perfusion and vascularization.

Growth of malignant tumors is dependent on sufficient blood supply. Thus, inhibition of tumor angiogenesis is emerging as a promising target in the treatment of malignancies. Human angiostatin (hANG) is one of the most potent inhibitors of endothelial cell proliferation, angiogenesis, and tumor growth in vivo. However, its mechanisms operating in vivo are not well understood. METHODS: To obtain more information about functional changes in the angiogenic process, we established Morris hepatoma (MH3924A) cell lines expressing hANG (hANG-MH3924A). The effects of hANG expression on proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) were measured in coculture experiments in vitro. To evaluate changes in tumor perfusion and blood volume, H2 15O and 68Ga-DOTA-albumin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid) were used for PET studies in vivo. Additionally, immunohistologic quantification of vascularization, apoptosis, and proliferation as well as gene array analyses were performed. RESULTS: Our in vitro experiments demonstrate reduced proliferation and increased apoptosis in HUVECs when being cocultured with hANG-MH3924A. In support, tumor growth of hANG-MH3924A is diminished by 95% in vivo. However, tumor perfusion and blood volume are increased in hANG-MH3924A corresponding to an increased microvessel density. Furthermore, hANG-transfected tumors show changes in expression of genes related to apoptosis, stress, signal transduction, and metabolism. CONCLUSION: hANG expression leads to inhibition of tumor growth, increased apoptosis, and changes in the expression of multiple genes involved in stress reactions, signal transduction, and apoptosis, which indicates a multifactorial reaction of tumors. An enhanced microvessel density is seen as part of these reactions and is associated with increased perfusion as measured by PET.     

Dissociation of GFAP intermediate filaments in EAE: observations in the lumbar spinal cord

Acute experimental allergic encephalomyelitis (EAE) in the Lewis rat is a cell-mediated autoimmune disease of central nervous system myelin. The lesion has been characterized by breakdown of the blood-brain barrier, edema, and periventricular infiltration of macrophages and lymphocytes. At the early stage of the disease, the astrocytes show a marked increase in immunostaining for glial fibrillary acidic protein (GFAP). A corresponding increase in GFAP content, however, cannot be demonstrated. Electron microscopic examination of the early lesion shows a typical reactive astrocytic response expressed by an enlarged watery cytoplasm, particularly at the level of the processes surrounding neurons and blood vessels and in the neuropil itself. The astroglial processes contain numerous glycogen particles (aggregates and single particles). Glial filaments are also conspicuous and are arranged in small bundles or loose thin filaments adjacent to the bundles. The glial filaments that normally appear as tight bundles have expanded and appear less dense. We suggest that the increase in GFAP immunostaining of the astrocytes in the early lesion is due in part to edema, which causes dissociation of the filaments and thereby exposes more antigenic sites to the antibodies.     

Melatonin Receptors on Ovine Pars Tuberalis: Characterization and Autoradiographicai Localization

The functional significance of the pars tuberalis (PT) of the mammalian adenohypophysis has remained an enigma (1, 2). One view of its function is that it acts as an auxiliary gland to support the endocrine role of the pars distalis (PD) (2), as it has been shown to contain immunocytochemically identifiable thyrotrophs and gonadotrophs (1). Many of the cells of the PT are, however, ultrastructurally unique suggesting an independent function for this tissue. Our recent demonstration that the PT of the rat is a major binding site for the ligand iodomelatonin lends further support to this idea (3). We have utilized the highly specific ligand [¹²⁵l]melatonin, and have demonstrated that it binds exclusively, with very high affinity, to the PT but not the PD of the adult sheep adenohypophysis. These findings support the conclusion that the PT has a distinct role in relation to melatonin action and seasonal reproduction.     

A preliminary report of the short-term effect of carbonated beverage consumption on calcium metabolism in normal women

A variety of nutritional factors influence the bioavailability of calcium and increase a woman's risk of osteoporosis. Eight healthy women completed an 8-week metabolic study designed to investigate the effect of nonalcoholic carbonated beverage consumption on calcium metabolism. Compared with women receiving a control diet, women consuming a diet high in nonalcoholic carbonated beverages demonstrated similar mean serum levels of calcium, ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 1,25-dihydroxyvitamin D3, and osteocalcin. Twenty-four-hour urine volume, creatinine clearance, calcium-creatinine ratio, and phosphorus-creatinine ratio were similar during consumption of the diet high in nonalcoholic carbonated beverages and the control diet. Twenty-four-hour cyclic adenosine monophosphate-creatinine ratio was significantly lower in women consuming the diet high in nonalcoholic carbonated beverage compared with women receiving the control diet (342 +/- 27.4 nmol/mmol vs 409 +/- 22.1 nmol/mmol). Consumption of a diet high in nonalcoholic carbonated beverages on a short-term basis does not appear to affect adversely the serum or urinary markers of calcium metabolism.