On the origin of strain hardening in glassy polymers

The influence of network density on the strain hardening behaviour of amorphous polymers is studied. The network density of polystyrene is altered by blending with poly(2,6-dimethyl-1,4-phenylene-oxide) and by cross-linking during polymerisation. The network density is derived from the rubber-plateau modulus determined by dynamic mechanical thermal analysis. Subsequently uniaxial compression tests are performed to obtain the intrinsic deformation behaviour and, in particular, the strain hardening modulus. At room temperature, the strain hardening modulus proves to be proportional to the network density, irrespective of the nature of the network, i.e. physical entanglements or chemical cross-links. With increasing temperature, the strain hardening modulus is observed to decrease. This decrease appears to be related to the influence of thermal mobility of the chains, determined by the distance to the glass-transition temperature (T−T_g).     

Prediction of brittle-to-ductile transitions in polystyrene

In this study it is attempted to predict brittle-to-ductile transitions (BDTs) in polystyrene blends, induced either by an increase in temperature or by a decrease in inter-particle distance. A representative, two-dimensional volume element (RVE) of a polystyrene matrix with 20% circular voids, is deformed in tension. During deformation a hydrostatic-stress based craze-nucleation criterion [1] is evaluated. The simulations demonstrate that crazes initiate at low temperatures while a transition from crazing to shear yielding (BDT) is found around 75 °C. The numerical results correlate well with tensile tests on similar heterogeneous polystyrene. The presence of an absolute length, as experimentally found, is more difficult to explain. Near a free surface a T_g-depression is measured for polystyrene and also the resistance to indentation in polystyrene is lower than expected from bulk properties. Both observations are rationalised by an enhanced segmental mobility of chains near a free surface. As a consequence of these findings, an absolute length-scale could be incorporated in the numerical simulations. For simplicity, the length-scale is modelled by taking a temperature gradient over a thin layer near the internal free surfaces of the RVE. Deformation of the RVE with different absolute length-scales shows that indeed also the experimentally found brittle-to-ductile transition can be predicted if the ligament thickness between the inclusions (‘voids’) in polystyrene is below a critical value of ca. 15 nm.     

An extended pharmacokinetic/pharmacodynamic model describing quantitatively the influence of plasma protein binding, tissue binding, and receptor binding on the potency and time course of action of drugs

An extended pharmacokinetic/pharmacodynamic (PK/PD) model is presented, in which the effect of binding of the drug to plasma proteins and to tissue binding sites in a peripheral compartment, and nonspecific and receptor binding in the effect compartment are taken into account. It represents an extension of the classical Sheiner model, and the model proposed by Donati and Meistelman. The present model is characterized by the following parameters: Kue (exit rate constant of unbound drug from the effect compartment), Pue (ratio of the unbound clearances to and from the effect compartment), fue (fraction of drug in effect compartment that is not bound to nonspecific binding sites), Kd (equilibrium dissociation constant of drug-receptor binding), and Rtot (concentration of receptor binding sites in effect compartment). The rate of association and dissociation of the drug-receptor complex can be incorporated in the model. The influence of the pharmacokinetic parameters (V1, V2, fu, fu2, CLu10, CLu20, CLu12, CLu21) and the PK/PD model parameters (kue, Pue, fue, Kd, Rtot) on various dynamic parameters is analyzed. These include potency (single dose needed to produce 90% effect, ED90), constant infusion dosing rate needed to maintain a constant effect of 90%, time to maximum effect (onset time), and duration to 90% recovery. The neuromuscular blocking agent vecuronium is used as an example. It is shown that both potency and time course of action are strongly dependent on the ratio V1/fu, CLu10, kue, Pue (at equipotent doses the time course is not affected by Pue), fue, Kd, and Rtot (only if Rtot is high), whereas they are less affected by the ratio V2/fu2, CLu20, CLu12, and CLu21. In general, the model parameters affect the ED90 and the time course of action in the same direction, e.g., an increase of V1 results in an increase of ED90 and an increase of onset time and duration. However, the unbound clearance CLu10, the intercompartmental unbound clearance CLu12 and the receptor affinity Kd have an opposite effect on ED90 and the time course parameters, e.g., an increase of CLu10 results in an increase of ED90 and a decrease of onset time and duration. This effect may be responsible for the inverse relationship between onset time and potency of neuromuscular blocking drugs observed in animal experiments and clinical studies. We demonstrate that PK/PD analysis using the traditional effect compartment model (Sheiner model) results in an apparent value of keo, which is a function of kue, fue, Kd, Rtot, as well as the unbound drug concentration in the effect compartment Cue. On the other hand, the model proposed by Donati and Meistelman gives correct values of keo (equal to the product fue.kue), but the receptor affinity Kd and the receptor density Rtot obtained by this method are apparent values, which depend on fu, fue, and Pue.     

Non-Hodgkin lymphoma of the central skull base: MR manifestations

OBJECTIVE: The aim of this study was to demonstrate the MR characteristics of non-Hodgkin lymphoma of the skull base to help in the differential diagnosis of this neoplasm from other conditions. MATERIALS AND METHODS: MR of five patients, 7-64 years old, with pathologically proved lymphomas of the skull base were reviewed. Three cases had primary skull base lesions involving the sphenoid bone and the cavernous sinus. One case with a nasal cavity lesion involving the skull base and one with a relapsing skull base lesion of previously treated tonsillar lymphoma were included. RESULTS: The lesions had signal intensities that were similar to that of gray matter of brain on both T1- and T2-weighted imaging. Bilateral cavernous sinuses were involved with encasement of internal carotid arteries in every case. Postcontrast MR showed homogeneous enhancement of the tumor with dural infiltration along the planum sphenoidale, clivus, or tentorium. The clivus was destroyed or replaced by tumors in adult cases but in two children the clivus was preserved with intact sphenooccipital synchondrosis. In one case the tumor extended to the extracranial portion through the jugular foramen. CONCLUSION: The MR findings of a permeative lesion of the skull base, invasion of the cavernous sinus without arterial narrowing, infiltration along the dural surface, and an iso- or hypointensity with brain on T2-weighted imaging should suggest lymphoma.     

Live animal performance, carcass traits, and meat palatability of calf- and yearling-fed cloned steers

Two groups of Brangus steers produced by nuclear transplantation cloning were used in parallel studies investigating the impact of calf- and yearling-feeding. The first group (n = 8) were fed as calves (CF; n = 4) or yearlings (YF; n = 4) to a constant age end point of 16 mo. The second group (n = 10) were fed as calves (CF; n = 5) or yearlings (YF; n = 5) to a constant live weight end point (530 kg). When slaughtered at the same age, CF and YF steers did not differ (P > .05) in feedlot ADG, but the CF steers were heavier and had higher dressing percentages, numeric yield grades, and quality grades (P < .05). Top loin steaks from the groups of steers did not differ (P > .05) in palatability traits. When fed to a constant live weight, the YF steers gained more rapidly (P < .05) and had lower (P < .05) numeric yield grades than did CF steers. Again CF steers had higher (P < .05) dressing percentages. There was no difference (P > .05) between the treatments in carcass quality grade or meat palatability characteristics. Thus, when finished to a constant weight end point, YF steers gained more rapidly, with no adverse effects on carcass quality grade or palatability traits; however, CF steers consistently produced higher dressing percentages, largely due to greater external fatness.     

Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin

Glycoprotein 330 (gp330) is a member of a family of endocytic receptors related to the low density lipoprotein receptor. gp330 has previously been shown to bind a number of ligands in common with its family member, the low density lipoprotein receptor-related protein (LRP). To identify ligands specific for gp330 and relevant to its localization on epithelia such as in the mammary gland, gp330-Sepharose affinity chromatography was performed. As a result, a 70-kDa protein was selected from human milk and identified by protein sequencing to be apolipoprotein J/clusterin (apoJ). Solid-phase binding assays confirmed that gp330 bound to apoJ with high affinity (Kd = 14.2 nM). Similarly, gp330 bound to apoJ transferred to nitrocellulose after SDS-polyacrylamide gel electrophoresis. LRP, however, showed no binding to apoJ in either type of assay. The binding of gp330 to apoJ could be competitively inhibited with excess apoJ as well as with the gp330 ligands apolipoprotein E, lipoprotein lipase, and the receptor-associated protein, a 39-kDa protein that acts to antagonize binding of all known ligands for gp330 and LRP. Several cultured cell lines that express gp330 and ones that do not express the receptor were examined for their ability to bind and internalize 125I-apoJ. Only cells that expressed gp330 endocytosed and degraded radiolabeled apoJ. Furthermore, F9 cells treated with retinoic acid and dibutyryl cyclic AMP to increase expression levels of gp330 displayed an increased capacity to internalize and degrade apoJ. Cellular internalization and degradation of radiolabeled apoJ could be inhibited with unlabeled apoJ, receptor-associated protein, and gp330 antibodies. The results indicate that gp330 but not LRP can bind to apoJ in vitro and that gp330 expressed by cells can mediate apoJ endocytosis leading to lysosomal degradation.     

Diagnosis of systemic causes of uveitis; a matter of ophthalmologist and internist

OBJECTIVE: To assess how often the aetiology is established in patients with uveitis, what systemic disease are found and what is the contribution of the internist to the diagnostic process. DESIGN: Retrospective study. SETTING: University Hospital Leiden, the Netherlands. METHOD: From January 1987 to April 1992, 342 patients presented with uveitis. All patients underwent a standard ophthalmological examination. Referral to an internist and individualised laboratory screening followed in patients with recurrent, chronic, bilateral or panuveitis. Recorded were: ophthalmological data, results of laboratory screening, results of analysis by the internist, final diagnosis and presence of systemic disease. RESULTS: 149 (44%) patients were examined by the internist, 18 (5.2%) were seen by another specialist. In 169 (49%) patients a specific diagnosis was made. 74 (22%) had a systemic disease, 74 a primary ocular disease. In 28 (8%) a systemic disease was presumed (5% were HLA-B27 positive, 3% had abnormal laboratory results); 5 (1%) patients had endophthalmitis as a complication of a septic process. CONCLUSION: In approximately 1/3 of the patients with uveitis a systemic disease was found. Examination by the internist tailored to the individual patient is essential in the evaluation of uveitis patients.     

Ligature carrier specifically designed for transvaginal sacrospinous colpopexy

The purpose of this paper is to clarify whether copper accumulation in hepatocellular carcinoma (HCC) is a cause of high intensity signal pattern on T1-weighted images (T1-WI) by comparing the histologically proven copper accumulation with MR images. Forty-five surgically resected HCCs were analyzed. Distribution patterns of divalent copper by a modified Timm's method on their maximum cut surfaces were compared with signal patterns on corresponding T1-WI. The degree of copper accumulation in tumor compared with surrounding liver tissue was higher in 6 lesions, equal in 17 lesions, and lower in 22 lesions. High intensity pattern on T1-WI were observed in 3 of 6 lesions (50%), 10 of 17 lesions (59%), and 10 of 22 lesions (45%). Distribution patterns of copper were not correlated with intensity patterns on T1-WI. We conclude that the paramagnetic effect of divalent copper accumulation in HCC is insufficient to influence the MRI.     

Cryptococcosis in tree shrews (Tupaia tana and Tupaia minor) and elephant shrews (Macroscelides proboscides)

OBJECTIVE: To determine the relation between metabolic and anthropometric parameters and circulating leptin concentrations in women with polycystic ovary syndrome (PCOS). DESIGN AND PATIENTS: Correlation of fasting serum leptin concentrations with anthropometric measures and multiple metabolic parameters including insulin and glucose responses to a 2-hour 75-g oral glucose tolerance test (OGTT) in 85 women with PCOS (17-36 years, body mass index (BMI) 29.9 +/- 0.9 kg/m2, mean +/- SD) and 18 control women (25-47 years, BMI 25 +/- 1.7 kg/m2). Diagnostic criteria for PCOS: characteristic ovarian morphology on ultrasound plus at least two of (1) elevated serum testosterone; (2) elevated serum androstenedione; and (3) reduced serum SHBG concentrations. MEASUREMENTS: Concentrations of androgens, lipids, PRL, gonadotrophins, and leptin were measured in the baseline fasting blood sample from an OGTT. Insulin and glucose were measured throughout OGTT. Serum leptin concentrations were measured by radioimmunoassay. RESULTS: Log leptin levels in the PCOS group correlated significantly with BMI (r = 0.85, P < 0.0001) and with 8 other parameters including waist/hip ratio (r = 0.51, P = 0.0005). By stepwise regression analysis, only BMI (P < 0.0001) and plasma high density lipoprotein concentration (P = 0.02) were independently correlated with log leptin levels, both positively. There was no effect of fat distribution, as measured by waist/ hip ratio, on leptin concentrations. Comparison of control subjects to a BMI-matched subgroup of 55 PCOS subjects revealed significantly higher circulating concentrations of LH, testosterone, DHEAS, progesterone and androstenedione, and higher glucose and insulin responses to OGTT in the PCOS group. Leptin levels were not different between the PCOS subgroup and control group (14.8 +/- 1.3 vs 12.1 +/- 2.3 micrograms/l, mean +/- SE, P = 0.26) and the relation of BMI to leptin levels determined by linear regression analysis also did not differ between the two groups. CONCLUSIONS: Our results indicate that circulating leptin concentrations in women with PCOS, a condition characterized by hyperandrogenaemia, increased LH concentrations and insulin resistance, are strongly related to BMI and not independently affected by circulating levels of insulin, gonadotrophins or sex hormones.