Binding properties and expression of the Fc gamma receptors on guinea pig peritoneal macrophages treated with inhibitors of glycosylation.

The effect of inhibition of glycosylation in guinea pig peritoneal macrophages on interaction of their surface Fc gamma receptors with guinea pig and rabbit IgG was studied. The inhibitors used were tunicamycin and monensin. The cells treated with tunicamycin incorporated markedly less [3H]mannose, bound less peanut (PNA) and wheat germ (WGA) lectins and showed diminished ability of binding IgG in comparison with control cells. Treatment of the cells with monensin resulted in an increased incorporation of [3H]mannose, increased binding of PNA but a decreased binding of WGA. Monensin affected binding of guinea pig IgG2 and rabbit IgG to macrophages and had no effect on guinea pig IgG1 binding. Analysis of binding parameters showed that although the number of IgG-binding sites on treated cells was significantly lower, especially in the case of tunicamycin, the apparent association constants were 2-4 times higher than in control cells. The effect of tunicamycin and monensin on parameters of binding of guinea pig IgG2 or rabbit immunoglobulins was much more pronounced than in the case of binding guinea pig IgG1. The results showed that glycosylation modulates expression and IgG binding ability of the Fc gamma receptors on the surface of guinea pig peritoneal macrophages.     

Dynamic beat-to-beat modeling of the QT-RR interval relationship: analysis of QT prolongation during alterations of autonomic state versus human ether a-go-go-related gene inhibition

Methods to correct the QT interval for heart rate are often in disagreement and may be further confounded by changes in autonomic state. This can be problematic when trying to distinguish the changes in QT interval by either drug-induced delayed repolarization or from autonomic-mediated physiological responses. Assessment of the canine dynamic QT-RR interval relationship was visualized by novel programming of the dynamic beat-to-beat confluence of data or "clouds". To represent the nonuniformity of the clouds, a bootstrap sampling method that computes the mathematical center of the uncorrected beat-to-beat QT value (QTbtb) with upper 95% confidence bounds was adopted and compared with corrected QT (QTc) using standard correction factors. Nitroprusside-induced reflex tachycardia reduced QTbtb by 43 ms, whereas an increase of 55 and 16 ms was obtained using the Bazett (QTcB) and Fridericia (QTcF) formulae, respectively. Phenylephrine-induced reflex bradycardia increased QTbtb by 3 ms but decreased QTcB by 20 ms and QTcF by 12 ms. Delayed repolarization with E-4031 (1-[2-(6-methyl-2-pyridyl)ethyl]-4-methylsulfonylaminobenzoyl)-piperidine), an inhibitor of rectifier potassium current, increased QTbtb by 26 ms but QT prolongation calculations using QTcF and QTcB were between 12 and 52% less, respectively, when small decreases in heart rate (5-8 beats per minute) were apparent. Dynamic assessment of beat-to-beat data, using the bootstrap method, allows quantification of QT interval changes under varying conditions of heart rate, autonomic tone, and direct repolarization that may not be distinguishable with use of standard correction factors.     

Immunoglobulins of colostrum--VI. Comparative studies of cytophilic properties of bovine serum and colostral IgG

In our previous studies, using physical-chemical and serological methods, substantial differences between bovine serum and colostral IgG, especially IgG2, have been shown. The structural differences were localized in the Fc region of immunoglobulins studied. The present comparative studies were undertaken to determine whether structural differences in the Fc region of bovine serum and colostral IgG are reflected in the interaction of these immunoglobulins with the guinea-pig peritoneal macrophage Fc gamma receptor. It was found that binding of bovine serum and colostral IgG1 was a saturable process and only quantitative differences in the mode of binding to the Fc receptor were observed. There is, however, a big difference in cytophilic activity of bovine IgG2--no saturable and reversible binding is observed in the case of bovine serum IgG2.     

Immunohistochemical analysis of bcl-2 and p53 expression in breast carcinomas: their correlation with Ki-67 growth fraction

We examined 59 breast cancers for p53 and bcl-2 protein expression by immunohistochemistry. The results were correlated with Ki-67 immunostaining. p53-negativity was noted in 40 cases and the remaining 19 tumours were p53-positive. Thirty-six tumours showed strong expression of bcl-2 and in 23 no staining for this protein was observed. We found statistically significant reverse correlation between expression of p53 and bcl-2 in majority of carcinomas: 31 cases were bcl-2 positive and p53-negative, and 14 tumours were bcl-2-negative and p53-positive. Six carcinomas showed no nuclear staining for Ki-67 and in the remaining 53 the percent of cancer cells positive for Ki-67 ranged from 1 to 60 (mean: 14.6). In these 53 cases we found that bcl-2-positive tumours were characterized by lower proliferation than bcl-2-negative tumours, the mean value of Ki-67 immunostaining being 10.7% and 23.0%, respectively. p53-negative tumours showed lower proliferation than p53-positive tumours: mean Ki-67 index was 10.2% and 23.9%, respectively.We conclude that immunohistochemically detected p53 and bcl-2 proteins show a significant inverse relationship in majority of breast carcinomas and their expression correlates with tumour proliferation (Ki-67 immunostaining).     

Modified tibial nails for treating distal tibia fractures.

OBJECTIVE: To determine the biomechanical consequences of cutting one centimeter off the tip of a tibial nail when treating distal tibia fractures with intramedullary nails. DESIGN: Randomized laboratory investigation using matched pairs of cadaveric tibias with osteotomies made to resemble distal tibia fractures extending to four and five centimeters from the tibiotalar joints. INTERVENTION: The smaller (four-centimeter) distal tibias were stabilized using ten-millimeter diameter tibial nails that had been modified by removing the distal one centimeter of the nail. The five-centimeter distal tibias were stabilized with standard ten-millimeter diameter tibial nails. Each tibia was tested in elastic compression, rotation, and compression-bending on a servohydraulic materials testing machine. MAIN OUTCOME MEASUREMENTS: Stiffness was calculated for each type of loading to compare stability of the modified nail construct to that of the standard nail construct. RESULTS: Four-centimeter distal tibia fragments stabilized with modified nails have comparable stiffness in compression and in torsion to five-centimeter distal tibia fragments stabilized with standard tibial nails. The stiffness in compression-bending was surprisingly low in both groups and differed by only 3.7 percent. CONCLUSIONS: Removal of one centimeter from the tip of a tibial nail allows placement of two distal interlocking screws in tibial fractures located four centimeters from the tibiotalar joint. The fixation strength achieved is comparable to that of standard intramedullary nailing of tibial fractures located five centimeters from the tibiotalar joint using two distal interlocking screws. Fixation strength with these distal fractures, however, is not strong enough to resist moderate compression-bending loads. Thus, patients with distal tibia fractures treated with intramedullary nailing must follow weight-bearing restrictions until significant fracture healing occurs to prevent coronal plane malalignment of the fracture.