Order and strain in main-chain smectic liquid-crystalline polymers and elastomers.

The layer correlations in main-chain smectic liquid-crystal polymer and elastomer systems have been studied using high-resolution X-ray scattering. In contrast to side-chain smectic polymers, in main-chain systems the polymer chains are oriented parallel to the layer normal. As a result they couple directly to the lamellar structure and any polymer defect is translated into layer distortions. For the homopolymers the resulting X-ray lineshapes are well described by Lorentzians. This is interpreted as an average of algebraically decaying order in domains with dimensions of hundreds of nm and a wide dispersion of sizes. The elastomers show much broader peaks than the correponding polymers. This is attributed to strong non-uniform strain within the finite-size domains due to defects of the layer structure.

Pretransitional behavior above the nematic-isotropic phase transition of an auxetic trimer liquid crystal.

Static light scattering and electric field-induced Kerr measurements were performed above the nematic-isotropic phase transition of a terminal-lateral-lateral-terminal negative Poisson ratio trimer. For both measurements the inverse susceptibility was observed to be nearly linear with temperature, a result inconsistent with our previously reported Kerr data [Phys. Rev. E 58, 2041 (1998)].

Neuroendocrine influences on experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE), a model for human multiple sclerosis, is an inflammatory disease of the CNS mediated by autoreactive T lymphocytes directed against the neuroantigen, myelin basic protein (MBP). EAE is inducible in the Lewis rat, which exhibits an acute monophasic disease, and in selected mouse strains, which show a remitting-relapsing or chronic course of paralysis. We examined the effects of neuroendocrine modulation by restraint stress on these models of EAE. In Lewis rats, daily cycles of restraint resulted in significant suppression of both clinical and histopathologic changes of EAE. Suppression of EAE was more pronounced in the female than in the male rat, which follows from the higher endogenous corticosterone levels in the female. Mechanistic studies suggested that stress affected the processing of MBP or the T-cell idiotype. In the relapsing murine model of EAE, B10.PL mice were restrained beginning either before MBP challenge or after the establishment of relapsing disease. We observed a striking inhibition of EAE clinical signs in mice stressed before challenge relative to nonstressed controls. Interestingly, approximately 10 days after termination of the stress period, clinical signs returned and were as severe or more severe than in control nonstressed animals. Stress administered after relapsing EAE was established had no protective effect. In vitro parameters revealed that only stress initiated before disease induction significantly reduced the frequency of MBP-specific lymphocytes in the spleen and lymph nodes. Both Th1 and Th2 cytokine responses were suppressed in stressed mice. T-cell receptor transgenic mice exposed to restraint showed a marked decreased in the number and functional activity of transgene-positive lymphocytes. In summary, elevated levels of endogenous neuroendocrine hormones exert a profoundly suppressive effect on both acute and chronic models of autoimmune CNS injury.

Brachial plexitis: a rare and often misdiagnosed postoperative complication.

Surgeons should be aware of the brachial plexitis syndrome in order to properly make an early diagnosis and educate the patient and his family on the etiology of this syndrome. It is characterized by the acute onset of shoulder pain, weakness, and paralysis in patients following a variety of surgical procedures.

Experimental autoimmune insulitis. Induction by T lymphocytes specific for a peptide of proinsulin.

Type I diabetes, an autoimmune disease that occurs in humans and animals, is characterized by the destruction of insulin-secreting islet beta-cells of the pancreas. Antibodies directed toward multiple islet protein can be detected before diagnosis of type I diabetes; however, the identity of the inciting autoantigen(s) that targets beta-cells for destruction has not been defined. Autorecognition of many self-proteins by CD4+ T lymphocytes is restricted by the products of class II immune response genes of the major histocompatibility complex (MHC), and in human type I diabetes such a MHC association has been described. The present study uses a rat MHC class II (RT1.Bl) peptide binding motif to predict potentially autoreactive CD4+ T cell epitopes in two key islet beta-cell constituents: the enzyme glutamic acid decarboxylase (GAD) and the insulin precursor hormone proinsulin (PI). Seventeen-amino-acid-long peptide fragments of GAD and PI containing the binding motif were synthesized and used to generate peptide-specific, MHC class II-restricted, CD4+ T cell lines. Once established, the T cell lines specific for rat islet GAD and PI were adoptively transferred to naive, MHC-compatible rats. At 10 days after transfer, insulitis had developed in rats receiving PI-specific T cells, whereas no insulitis was observed in pancreata of rats receiving GAD-specific T cells. Of particular interest is the finding that the pathogenic T cell epitope identified in PI spans the endogenous cleavage site between the B-chain and C-peptide of insulin. Moreover, the PI-specific T cells were able to react specifically with material produced in vitro by a rat insulinoma cell line. These results demonstrate that pathogenic T cell epitopes can be located in portions of molecules that are subsequently degraded during normal enzymatic processing. As PI is found highest concentrations in the beta-cells of pancreatic islets, it is possible that this molecule and not its individual degradation products (ie, insulin and C-peptide) might serve as an autoantigen in the pathogenesis of type I diabetes.

The T-cell repertoire contains cells reactive with hormones of the hypothalamic-pituitary-adrenal axis: recognition of synthetic peptide fragments of corticotropin-releasing hormone (CRH) and pro-opiomelanocortin (POMC) in the Lewis rat.

This report characterizes T-cell lines developed against peptide fragments of the neuroendocrine hormones, corticotropin-releasing hormone (CRH) and pro-opiomelanocortin (POMC). A MHC Class II binding motif containing a serine (S) and glutamic acid (E) residue separated by five intervening amino acids was used as a template for synthesizing peptides that may serve as T-cell epitopes. T-cell lines were generated specifically against a 17-amino-acid peptide of POMC or CRH peptide. These T-cell lines were predominantly CD4+ T cells and proliferated in an antigen-specific fashion. Furthermore, proliferation of T-cell lines specific for peptide-hormones could be inhibited by anti-MHC Class II antibody. In vitro the whole CRH protein could be processed and recognized as antigenic by CRH peptide-specific T cells. In addition, POMC-specific T cells can recognize POMC peptide presented on the membrane of MHC Class II+ POMC T cells. These results indicate that the normal T-cell repertoire of the rat contains elements which can recognize and specifically proliferate to self-proteins of the hypothalamic-hypophyseal axis. Moreover, it seems that T lymphocytes themselves may present antigens which they synthesize. The relationship of these observations to autoimmune reactions affecting the hypothalamus and/or pituitary gland, or T-cell regulation, is the subject of ongoing investigation.

Closure of multiple pressure sores with split total thigh flap.

Pressure sores remain a pervasive and recurrent problem in the chronically bedridden and immobilized insensate patient populations, such as those with spinal cord injury. Various musculocutaneous flaps based on muscles of the buttock and thigh are routinely used to close primary, uncomplicated ulcers. The gluteus maximus, tensor fascia lata, and posterior thigh muscles, for example, can be used to close the majority of primary defects. In the case of extensive and recurrent ulceration, however, particularly when the hip joint or proximal femur is infected or marked heterotopic ossification is present, these conventional flaps are inadequate. The total thigh flap offers a solution to some of these problems by providing a large volume of tissue as a unit to cover the defects, particularly in cases in which other reconstructive options have been exhausted. We describe a modification in the total thigh flap procedure by splitting the flap according to its vascularity to achieve closure of multiple pressure ulcers in a one-stage procedure.

Identification of myocarditogenic peptides derived from cardiac myosin capable of inducing experimental allergic myocarditis in the Lewis rat. The utility of a class II binding motif in selecting self-reactive peptides.

Cardiac myosin (CM) has been implicated as an autoantigen in the induction of experimental allergic myocarditis (EAM). At the present time no myocarditogenic peptides of CM have been identified. To identify CM peptides with myocarditogenic properties we have made use of a putative binding motif for the MHC class II molecule RT1.BI in the rat. The amino acid sequence of CM alpha-chain was scanned and found to contain nine peptides that contain this binding motif, three peptides found only in the cardiac form of myosin were chosen for further study. This manuscript describes the identification of two CM peptides capable of inducing EAM in the Lewis rat. In doing so this study demonstrates the utility of an MHC class II binding motif to (correctly) predict pathogenic, autoimmunity inducing, peptides. Peptides, CM 1, and CM 2 are the first peptides described that are capable of inducing EAM in rats. The utilization of CM 2 peptide has permitted the establishment of a long term, Ag specific cell line capable of adoptively transferring EAM. Moreover, the establishment of CM 2 specific T lymphocyte lines has permitted the description of a detailed proliferative response of a myocarditogenic cell line to a specific cardiac Ag. The identification of CM 1 and 2 formally proves that CM, and not a co-purified contaminant, is an Ag in EAM. Finally, this report documents that experimentally induced giant cell myocarditis is not a separate disease entity arising from a distinct cardiac Ag or CM epitope from regular myocarditis.

Suppression of experimental autoimmune encephalomyelitis by restraint stress: sex differences.

We have recently reported that female Lewis rats exhibit significantly higher basal circadian levels of corticosterone (Cort) than male Lewis rats. The studies reported here were designed to explore whether male and female Lewis rats demonstrate a differential suppression of experimental autoimmune encephalomyelitis (EAE) following exposure to an identical regimen of repetitive restraint stress. Rats were restrained for 1 or 9 h/day beginning 5 days before myelin basic protein (MBP) challenge and extending through the recovery period (18 days post challenge). Both clinical signs and histopathological changes of EAE were more significantly suppressed in 9-h-stressed females relative to male Lewis rats. Investigation of the mechanism underlying the stress-induced suppression of EAE revealed that restraint stress did not alter the clinical course of EAE in rats challenged with MBP 68-88 encephalitogenic peptide, suggesting that restraint stress may affect processing and/or presentation of the MBP molecule. Stressed rats exhibited decreased interleukin-2 and interferon gamma production, and the frequency of MBP-reactive lymphocytes was reduced in comparison to non-stressed rats. Finally, repetitive restraint stress had no effect on blood-spinal cord permeability during EAE. The results presented here underscore the importance of such experimental variables as sex, strain, time of day, and the kinetics of immune response development.

Sex and strain differences in the circadian rhythm fluctuation of endocrine and immune function in the rat: implications for rodent models of autoimmune disease.

This study compares 24-h basal patterns of corticosterone and immunoreactivity for Lewis and Fischer (F344) strain rats. Significant differences in the circadian rhythm of plasma corticosterone were found across sex and strain. Male Lewis rats exhibited significantly lower 24-h corticosterone levels relative to female Lewis and male F344 rats. In addition, male Lewis rats were found to have higher mononuclear cell counts than female Lewis or male F344 rats, particularly in the peripheral blood and spleen compartments. Levels of CD4-bearing lymphocytes in blood, lymph node, and spleen were found to be higher in Lewis rats compared to the F344 strain over a 24-h period. In general, percentages of CD8- and major histocompatibility complex (MHC) class II-bearing lymphocytes were shown to vary over 24 h in all compartments across strains. Given that the Lewis rat has low basal levels of circulating corticosterone, and comparatively higher numbers of CD4-bearing lymphocytes, these factors may play a causative role in the known susceptibility of this strain to many experimental models of autoimmune disease.

Magnitude of initial effect influences development of tolerance to morphine in rats responding under a fixed-ratio schedule of food presentation.

This experiment examined whether development of tolerance to the rate-decreasing effects of morphine can be modulated by the magnitude of the initial effect of morphine. Lever pressing by rats was maintained under a fixed-ratio 30 schedule of food delivery in daily 30 min sessions. Subjects were assigned to two groups, which did not differ in initial sensitivity to morphine, and given daily injections of morphine under dosing schedules chosen to have different initial effects. Group 1 received daily pre-session injections of 10 mg/kg morphine, which initially suppressed lever pressing completely, and post-session injections of saline. Group 2 received morphine in two injections, one pre-session and one post-session. The initial daily doses 10 mg/kg pre- and 9 mg/kg post-session) decreased rates by 30% or less. The proportion of the 10 mg/kg dose administered pre-session was increased gradually over 10 weeks. Group 2 developed greater tolerance than did group 1, as assessed by changes in the dose of morphine required to suppress response rates by > 50%. After 3 months of repeated treatment, the ED(50) of morphine increased 2.5-fold in group 2, but only 1.4-fold in group 1. When the daily dose of morphine was raised to 20 mg/kg (10 mg/kg pre- and 10 mg/kg 14 h post-session) for all subjects, the ED(50) of morphine increased 6.7-fold in group 2, but only 2.6-fold in group 1. During repeated treatment, the groups did not differ in the dose of maloxene required to suppress response rates or elicit weight loss. Following termination of morphine treatment, the ED(50) of morphine returned to original values in group 2, but was 1.8-fold lower than initial values in group 1. Thus, a pronounced [??103] decreasing effect of morphine retarded development of tolerance, perhaps by a conditioning process.

Plasma corticosterone fluctuations in an infant-learning paradigm.

Plasma corticosterone fluctuations of infant rats were examined in a learning task. A blood sample for analysis of plasma corticosterone was collected from groups of 10- and 15-day-old pups following either no disturbance, standard maternal deprivation only, or deprivation and training in an established approach-mother, avoid-shock conflict task. In the latter condition, pups remained in the goalbox either alone or with an anesthetized dam for either 15 or 60 min before blood sample collection. Plasma corticosterone levels were elevated following deprivation plus training in pups of both ages and following deprivation only in the 15-day-old pups. Further, the presence of the dam in the goalbox reduced plasma corticosterone elevations, particularly among 15-day-old pups and at 60 min. These findings suggest that the mother's capacity to moderate the pup's plasma corticosterone response may contribute to her reinforcement value in infant-learning paradigms.

Fracture of the dorsoulnar tubercle of the trapezium.

The dorsoulnar tubercle of the trapezium may fracture, and this fracture may be missed without precise physical examination and correct radiographic studies. If there is persistent localized pain and tenderness in this region and the results of routine wrist radiographic examination are normal, a bone scan should be performed. If there is localized uptake in the area of the trapezium, additional radiographic studies may be necessary to confirm or exclude this fracture. Four patients with this previously unreported fracture and a method for its detection are presented.

Effect of endogenously produced leukotrienes and thromboxane on renal vascular resistance in rabbit hydronephrosis.

Ureteral obstruction in rabbits is characterized by mononuclear cell invasion of the renal cortex and proliferative fibrosis that is associated with exaggerated prostaglandin synthesis in response to vasoactive and inflammatory cell agonists. In this investigation, we studied the effects of the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP) and bradykinin (BK) on eicosanoid synthesis and renal vascular resistance in the ex vivo perfused hydronephrotic kidney (HNK). Administration of fMLP resulted in the dose-dependent synthesis of leukotrienes, thromboxane A2 (TXA2), prostaglandin E2 (PGE2), and prostacyclin (PGI2). Peptidoleukotriene synthesis was monitored by specific radioimmunoassay and by guinea pig ileum bioassay and it was then validated by inhibition of the ileal contractile activity with the peptidoleukotriene receptor antagonist FPL-55712. The leukotrienes produced were identified as LTB4, LTC4, LTD4, and LTE4 by comigration with authentic standards on reverse phase high-performance liquid chromatography (RP-HPLC) and by ultraviolet spectroscopy. BK administration stimulated the synthesis of TXA2, PGE2, and PGI2 but not the synthesis of leukotrienes, in contrast to the results with fMLP, suggesting the involvement of different cell types. Administration of fMLP to the HNK also resulted in a renal vasoconstriction that was partially inhibited by FPL-55712 and that was completely inhibited by the thromboxane synthase inhibitor OKY-1581. Consistent with this result, exogenous administration of LTC4 resulted in the synthesis of TXA2 and in a renal vasoconstriction that was inhibited by either FPL-55712 or OKY-1581.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro cytotoxicity of chrysotile asbestos to human pulmonary alveolar macrophages is decreased by organosilane coating and surfactant.

Human pulmonary alveolar macrophages were used to quantitate the cytotoxic effect of surface-altered chrysotile asbestos. Little difference was observed in mortality between chrysotile asbestos that was surface-treated to a 42% extent by a hydrophobic organosilane or untreated chrysotile. Little or no effect on mortality was observed when human pulmonary alveolar macrophages were cultured with untreated chrysotile or acid-leached asbestos in the presence of 10 mM dipalmitoyl lecithin. However, when human pulmonary alveolar macrophages were cultured with a hydrophobically-treated (to a 42% or 95% extent) chrysotile asbestos in the presence of 10 mM dipalmitoyl lecithin, a statistically significant decrease in mortality was observed compared to untreated chrysotile. No mutagenic activity was observed when V79 cells were cultured with acid-leached, or 42% hydrophobically-treated chrysotile asbestos, even when human pulmonary alveolar macrophages were included as an activation source. The 95% hydrophobically-treated and acid-leached chrysotile also exhibited decreased binding of benzo[a]pyrene compared to untreated chrysotile asbestos.

The influence of chemical carcinogens on natural killer cell function in rats. A comparison of 2-acetylaminofluorene with 4-acetylaminofluorene.

The influence of the carcinogen 2-acetylaminofluorene (2AAF) administration on splenic natural killer (NK) cell function in two strains of rats has been examined and compared with that of the non-carcinogenic analogue 4-acetylaminofluorene (4AAF). In both strains it was observed that daily exposure to 25 mg kg-1 2AAF induced a significant depression of both native and interferon (IFN)-activated NK cell function which was first apparent between 7 and 13 days following initiation of treatment. In contrast 4AAF failed to influence NK cell activity. These data indicate that 2AAF in common with some other carcinogens has the capacity to influence natural cytotoxic function and lend support to the hypothesis that carcinogenic potential may in some cases be associated with immunosuppressive properties.

Effect of retinoic acid, butylated hydroxytoluene, propylgallate and selenium on 2-acetylaminofluorene induced hepatotoxicity.

Rats of the Sprague-Dawley strain were administered 2-acetylaminofluorene (2-AAF) in different diet regimens to ascertain the effect of retinoic acid(RA), butylated hydroxytoluene (BHT), propylgallate (PG), and selenium on induced hepatotoxicity. In the first study, groups of young male albino rats of the Sprague-Dawley strain were fed a diet containing 0.05% 2-AAF. Carcinogen was added to the diet for 3 weeks, omitted 1 week, added 2 weeks, omitted 2 weeks, added 3 weeks, and omitted for the final 4 weeks. Animals were terminated at the end of 15 weeks. Supplementation of the diet by 0.5% BHT, PG or 4 ppm selenium as sodium selenite in the drinking water either throughout the entire feeding period or only during the administration of the carcinogen-free diet greatly inhibited the hepatotoxicity of 2-AAF. In contrast, addition of 0.02% RA to the diet in the above feeding regimens enhanced the hepatotoxicity of 2-AAF. In the second study, male and female Sprague-Dawley rats were administered a diet containing 0.03% 2-AAF for 16 weeks or a diet containing 0.03% 2-AAF supplemented with 0.02% RA for the first 4 weeks and the last 6 weeks of the 16-week feeding period. Addition of the 0.02% RA to the diet enhanced the hepatotoxicity of 2-AAF, especially in the female rats.

Selenium and glutathione peroxidase levels in patients with epidermoid carcinoma of the oral cavity and oropharynx.

Selenium ingestion may inhibit carcinogenesis. Epidemiologic studies have shown that age-adjusted death rates for cancer at most head and neck sites are lower in states where the soil and forage crops contain higher levels of selenium. The mode of action is incompletely understood, but may be mediated through an increase in the activity of the selenium dependent, antioxidant enzyme glutathione peroxidase (GSH-Px). The authors studied blood selenium levels and blood and tissue GSH-Px activities in 50 patients with untreated cancer of the oral cavity and oropharynx. Mean erythrocyte selenium and glutathione peroxidase were significantly depressed when compared to age-matched controls. Mean plasma selenium, on the other hand, was significantly elevated in the cancer patient group. Data from subsets within the cancer patient group were also discussed. GSH-Px activity did not differ in tumor and adjacent normal tissue. The concept of chemoprevention of carcinogenesis with inhibitory chemical compounds is particularly apropos to head and neck cancer control. Further work is indicated to determine if ingestion of supplemental selenium corrects the abnormalities identified here, and what affect, if any, this would have on the development and behavior of squamous cell cancers in the upper aerodigestive tract.

Presence of cellular retinol and retinoic acid-binding proteins in epidermoid carcinoma of the oral cavity and oropharynx.

Epidermoid carcinomas of the oral cavity and oropharynx from six patients were examined for the presence and amount of cellular retinol (CRBP) and cellular retinoic acid-binding (CRABP) proteins. In all cases adjacent, grossly normal tissue was similarly examined. For each example CRBP levels were significantly higher in tumor tissue compared to adjacent tissue. In four cases CRABP was significantly higher. This is of interest because retinol, retinoic acid and their analogs have been shown to inhibit the development of various epithelial tumors, and this inhibition is possibly mediated by these binding proteins.

Anti-oxidative effects of vitamin B2-butyrate on the cardiac mitochondrial disorders induced by adriamycin.

The combined use of CoQ10 with adriamycin has been recommended for reduction of the cardiotoxicity that occurs during cancer chemotherapy. Vitamin B2-butyrate was also investigated in order to determine anti-oxidative effects on adriamycin cardiotoxicity. This vitamin analysis prevented enhanced lipid peroxidation and rectified the respiratory disorders of heart mitochondria induced by adriamycin, however, the deficiency of the CoQ10-pool was not rectified. The combined approach of using CoQ10 for rectifying the deficiency of this component and of using B2-butyrate for reducing lipid peroxidation was indicated for adriamycin cancer chemotherapy.