“Unblocking” Serum Activity <Emphasis Type="Italic">in vitro</Emphasis> in the Polyoma System may Correlate with Antitumour Effects of Antiserum <Emphasis Type="Italic">in vivo</Emphasis>

In a variety of tumour systems, individuals carrying progressively growing neoplasms have lymphoid cells with a specific cytotoxic effect on cultured tumour cells from the same individual^1–4. Since the sera of tumour-bearing individuals have been shown to prevent tumour cell destruction by immune lymphocytes in vitro^2,5–8 and since this serum blocking activity appears early in primary and transplant tumour development^5,7, it has been suggested that the appearance of this serum blocking activity might be responsible for the progressive growth of tumours in individuals having cytotoxic lymphocytes. Counteraction of this blocking activity would thus be of primary importance in facilitating the function of an already existing or bolstered cell-mediated immunity. The serum blocking activity might be inhibited in various ways, by preventing the formation of blocking antibody or by interfering with its action (“unblocking”), as demonstrated in Moloney sarcoma regressor sera⁹. This type of serum also has a therapeutic effect on Moloney sarcomas in vivo^10,11, which has been tentatively attributed to its unblocking activity^8,9 or, possibly, to a complement-dependent cytotoxicity¹⁰. Tumour growth in the Moloney sarcoma system, however, might be due in part to continuous recruitment of neoplastic cells by virus-induced transformation and so the therapeutic effect could be due to a virus-neutralizing serum activity^9,10.     

On the mechanism of ATP-induced shape changes in the human erythrocyte membranes: the role of ATP

In the preceding paper (Sheetz, M. and S.J. Singer. 1977. J Cell Biol. 73:638-646) it was shown that erythrocyte ghosts undergo pronounced shape changes in the presence of mg-ATP. The biochemical effects of the action of ATP are herein examined. The biochemical effects of the action of ATP are herein examined. Phosphorylation by ATP of spectrin component 2 of the erythrocyte membrane is known to occur. We have shown that it is only membrane protein that is significantly phosphorylated under the conditions where the shape changes are produced. The extent of this phosphorylation rises with increasing ATP concentration, reaching nearly 1 mol phosphoryle group per mole of component 2 at 8mM ATP. Most of this phosphorylation appears to occur at a single site on the protein molecule, according to cyanogen bromide peptide cleavage experiments. The degree of phosphorylation of component 2 is apparently also regulated by a membrane-bound protein phosphatase. This activity can be demonstrated in erythrocyte ghosts prepared from intact cells prelabeled with [(32)P]phosphate. In addition to the phosphorylation of component 2, some phosphorylation of lipids, mainly of phosphatidylinositol, is also known to occur. The ghost shape changes are, however, shown to be correlated with the degree of phosphorylation of component 2. In such experiment, the incorporation of exogenous phosphatases into ghosts reversed the shape changes produced by ATP, or by the membrane-intercalating drug chlorpromazine. The results obtained in this and the preceding paper are consistent with the proposal that the erythrocyte membrane possesses kinase and phosphates activities which produce phosphorylation and dephosphorylation of a specific site on spectrin component 2 molecules; the steady-state level of this phosphorylation regulates the structural state of the spectrin complex on the cytoplasmic surface of the membrane, which in turn exerts an important control on the shape of the cell.     

Selective inhibition of prostaglandin biosynthesis by gold salts and phenylbutazone

Gold salts and phenylbutazone selectively inhibit the synthesis of PGF_2α and PGE₂ respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE₂ and PGF_2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function.     

Patellofemoral cartilage stresses are most sensitive to variations in vastus medialis muscle forces

The purpose of this study was to evaluate the effects of variations in quadriceps muscle forces on patellofemoral stress. We created subject-specific finite element models for 21 individuals with chronic patellofemoral pain and 16 pain-free control subjects. We extracted three-dimensional geometries from high resolution magnetic resonance images and registered the geometries to magnetic resonance images from an upright weight bearing squat with the knees flexed at 60°. We estimated quadriceps muscle forces corresponding to 60° knee flexion during a stair climb task from motion analysis and electromyography-driven musculoskeletal modelling. We applied the quadriceps muscle forces to our finite element models and evaluated patellofemoral cartilage stress. We quantified cartilage stress using an energy-based effective stress, a scalar quantity representing the local stress intensity in the tissue. We used probabilistic methods to evaluate the effects of variations in quadriceps muscle forces from five trials of the stair climb task for each subject. Patellofemoral effective stress was most sensitive to variations in forces in the two branches of the vastus medialis muscle. Femur cartilage effective stress was most sensitive to variations in vastus medialis forces in 29/37 (78%) subjects, and patella cartilage effective stress was most sensitive to variations in vastus medialis forces in 21/37 (57%) subjects. Femur cartilage effective stress was more sensitive to variations in vastus medialis longus forces in subjects classified as maltrackers compared to normal tracking subjects (p?=?0.006). This study provides new evidence of the importance of the vastus medialis muscle in the treatment of patellofemoral pain.     

A web server to locate periodicities in a sequence

Summary : FT is a tool written in C++, which implements the Fourier analysis method to locate periodicities in aminoacid or DNA sequences. It is provided for free public use on a WWW server with a Java interface. Availability : The server address is http://o2.db. uoa.gr/FT Contact : shamodr@atlas.uoa.gr      

A randomized controlled trial comparing patellar retention versus patellar resurfacing in primary total knee arthroplasty: 5-10 year follow-up

ABSTRACT: BACKGROUND: The primary purpose of this randomized controlled trial (RCT) was to compare knee-specific outcomes (stiffness, pain, function) between patellar retention and resurfacing up to 10 years after primary total knee arthroplasty (TKA). Secondarily, we compared re-operation rates. METHODS: 38 subjects with non-inflammatory arthritis were randomized at primary TKA surgery to receive patellar resurfacing (n = 21; Resurfaced group) or to retain their native patella (n = 17; Non-resurfaced group). Evaluations were performed preoperatively, one, five and 10 years postoperatively by an evaluator who was blinded to group allocation. Self-reported kneespecific stiffness, pain and function, the primary outcomes, were measured by the Western Ontario McMaster Osteoarthritis Index (WOMAC). Revision rate was determined at each evaluation and through hospital record review. RESULTS: 30 (88%) and 23 (72%) of available subjects completed the five and 10-year review respectively. Knee-specific scores continued to improve for both groups over the 10-years, despite diminishing overall health with no significant group differences seen. All revisions occurred within five years of surgery (three Non-resurfaced subjects; one Resurfaced subject) (p = 0.31). Two revisions in the Non-resurfaced group were due to persistent anterior knee pain. CONCLUSIONS: We found no differences in knee-specific results between groups at 5-10 years postoperatively. The Non-resurfaced group had two revisions due to anterior knee pain similar to rates reported in other studies. Knee-specific results provide useful postoperative information and should be used in future studies comparing patellar management strategies. ClinicalTrials.gov identifier NCT01500252.     

Gender differences exist in the hip joint moments of healthy older walkers

Gender differences in the incidence of symptomatic hip osteoarthritis (OA), changes in hip cartilage volume and hip joint space and rates hip arthroplasty of older people are reported in the literature. As the rate of progression of OA is in part mechanically modulated it is possible that this gender bias may be related to inherent differences (if they exist) in walking mechanics between older males and females. The purpose of this study was to examine potential mechanisms for gender differences in hip joint mechanics during walking by testing the hypotheses that females would exhibit higher hip flexion, adduction and internal rotation moments but not significantly greater normalized ground reaction forces (GRFs). Forty-two healthy subjects (21 male, 21 female), ages 50–79 yr were recruited for gait analysis. In support of the hypotheses, greater external hip adduction and internal rotation along with hip extension moments were found for females compared to males after normalizing for body size for all self-selected walking speeds. Differences in walking style (kinematics) were the main determinants in the joint kinetic differences as no differences in the normalized GRFs were found. As external joint moments are surrogate measures of the joint contact forces, the results of this study suggest the hip joint stress for the female population is higher compared to male population. This is in favor of a hypothesis that the increased joint contact stress in a female population could contribute to a greater joint degeneration at the hip in females as compared with males.     

Amiloride does not alter NaCl avoidance in Fischer-344 rats

Fischer-344 (F-344) rats differ from other common rat strains in that they fail to show any preference for NaCl at any concentration in two- bottle preference tests. Because 100 microM amiloride partially blocks the NaCl-evoked chorda tympani (CT) response in electrophysiological studies, we tested NaCl preference (0.068-0.273 M) in F-344 rats with and without 100 microM amiloride solution as the solvent. A third group was tested with unadulterated NaCl solutions following CT transection. Amiloride had no significant effect on the NaCl preference-aversion function, whereas CT transection significantly reduced NaCl avoidance. These results suggest that the amiloride-sensitive component of the NaCl response is not necessary for F-344 rats to display avoidance of NaCl, but the entire CT input is.