L-deprenyl as an adjunct to low-dose bromocriptine in early Parkinson''s disease: a short-term, double-blind, and prospective follow-up study

The potential role of allergen-specific IgG antibodies as 'blocking' antibodies in allergen-induced human basophil histamine release was investigated. This was studied in a model with the major grass pollen allergen Lol p I and polyclonal rabbit antisera directed against this allergen and against a synthetic peptide of its C terminus. When allergen and antibodies were allowed to preincubate, Lol p I induced histamine release was inhibited up to 85% by the antiserum against Lol p I. By omitting preincubation, and thereby more closely mimicking an in vivo situation, up to 55% inhibition was realized. This indicates that allergen-specific IgG can act as 'blocking' antibody without preincubation. Immunization of rabbits with a synthetic C-terminal peptide of Lol p I resulted in antibodies reactive with natural Lol p I. Despite their 100-fold lower avidity for Lol p I (as compared with antinatural Lol p I), these antibodies had the capacity to inhibit Lol p I induced histamine release for > 90% (up to 50% without preincubation). This indicates that it is possible to block histamine release induced by a major allergen with low-avidity IgG antibodies directed against a minor proportion of the allergen (25 amino acids). IgE antibodies from the donors studied were unreactive with this synthetic peptide, indicating that for blocking activity identical epitope specificity of IgE and IgG is not essential. This opens interesting perspectives for application of synthetic peptides in immunotherapy, distinct from their effects on T cell reactivity.     

Direct administration and utilization of [1-13C]glucose by fetal brain and liver tissues under normal and ischemic conditions: 1H, 31P, and 13C NMR studies

The acute and delayed effects of anoxia on synaptic transmission and long-term potentiation (LTP) were examined in the CA1 region of rat hippocampal slices. Oxygen deprivation for 20 minutes completely but reversibly depressed excitatory postsynaptic potentials mediated by both N-methyl-D-aspartate receptors (NMDAR) and non-NMDAR. Although LTP was reliably produced by a single tetanus delivered 30 minutes after reoxygenation, LTP could not be induced when a tetanus was delivered 70 to 100 minutes after reoxygenation. A tetanus delivered 100 minutes after reoxygenation produced lasting synaptic enhancement when 100 mumol/L D,L-amino-phosphonovaleric acid (APV), a competitive NMDAR antagonist, was administered during the period of oxygen deprivation. The delayed effects of oxygen deprivation were not blocked when APV was administered after oxygen deprivation. Similarly, the delayed effects on LTP induction were overcome by inhibitors of nitric oxide synthase when the nitric oxide synthase inhibitors were administered during anoxia, but not when administered after oxygen deprivation. These results suggest that untimely activation of NMDAR and nitric oxide release during anoxia produce delayed inhibition of LTP induction and may be involved in the memory defects that occur subsequent to cerebral hypoxia.     

Macrophage-colony forming cells (M-CFC), with different sensitivities to colony stimulating factors, from peritoneal exudates and tissues of chronically inflamed mice

OBJECTIVE AND DESIGN: To determine whether nonadherent macrophage precursors are present within the inflamed peritoneal cavity in mice, we analysed the mononuclear cell populations from different peritoneal tissues. OBJECTS: A group of 90 female mice BDF1 (C57BL/ 6 x DBA/2) was used for the study. Mononuclear cells were harvested from the peripheral blood, bone marrow, peritoneal exudate, omentum, mesentery, parietal peritoneum and diaphragm. TREATMENT: Mice were injected intraperitoneally with 0.2 ml of Freund's incomplete adjuvant. Animals were sacrificed at 6, 13, 16, 21 and 30 days. Three to six animals were examined for each time period. METHODS: Progenitor cell assay was performed in 1 ml of semi-solid agarose (0.3% Seakem GTG) DMEM which was supplied either with recombinant colony stimulating factors or with mesothelial cell-conditioned medium. RESULTS: Nonadherent macrophage-colony forming cells were present in all peritoneal compartments (35-140 precursor cells/5 x 10(4) mononuclear cells). Granulocyte/ macrophage-colony forming cells were found in the inflamed omentum. Combined simultaneous treatment with GM-CSF and M-CSF blocked the proliferation of the exudate and mesentery-derived macrophage precursors, but not other peritoneal tissue-derived macrophage precursors. Sequential stimulation with GM-CSF and M-CSF did not inhibit macrophage colony formation. CONCLUSIONS: GM-CSF can possibly influence the proliferative response induced by M-CSF. Nonadherent macrophage precursors recovered from different tissue compartments seem to differ in their sensitivity to growth regulation.     

Distribution of a reeler gene-related antigen in the developing cerebellum: an immunohistochemical study with an allogeneic antibody CR-50 on normal and reeler mice

We have immunohistochemically investigated the expression of a reeler gene-related antigen in the mouse cerebellum by using a monoclonal antibody, CR-50. This antibody probes a distinct allelic antigen present in normal but not in reeler mutant mice, and this antigen is localized in the brain regions in which morphological abnormalities occur in reeler mice (Ogawa et al., Neuron 14: 899-912, 1995). The developing normal cerebellum showed transient immunoreactivity to CR-50 in a limited set of neurons and in the extracellular space near the pial surface. An early population of CR-50-labeled cells emerged on embryonic day (E) 13 along the dorsal cerebellar surface, comprising the nuclear transitory zone (NTZ). Bromodeoxyuridine labeling revealed the time of origin of these cells to be at E11-12. From E14 to E18, some CR-50-labeled cells were stacked in the inner border of the external granular layer (EGL), whereas others were scattered in deep areas, such as the cerebellar nuclei and the surrounding intermediate zone or white matter. In the first postnatal week, these subcortical structures became immunonegative. However, CR-50 antigen was continuously produced until the second postnatal week by another population of cells occupying i) the premigratory zone (PMZ), the inner half of the EGL, and ii) the internal granular layer (IGL). These later CR-50-positive cells were smaller than the earlier type and showed the morphology typical of granule neurons. Both types of CR-50-labeled cells were positive for a DNA-binding protein, zic. By treating living cerebellar slices with CR-50, the extracellular antigen was localized as a puncutate staining pattern in the NTZ, PMZ, and molecular layer (ML), but not in the subcortical regions and IGL. Purkinje cells were negative for CR-50 and aligned as a monolayer adjacent to the PMZ, though their dendritic trees were closely associated with the extracellular CR-50-antigen in the PMZ and ML. Staining of dissociated cells suggested that the extracellular antigen is initially present throughout the surfaces of the CR-50/anti-zic double positive neurons, and is then rearranged to concentrate on their processes contacting with Purkinje cells. The spatiotemporal expressions of the CR-50 antigen in the cerebellum are consistent with the possibility that this antigen is involved in cell-cell interactions related to the histogenetic assembly of Purkinje cells.     

Colorimetric determination of creatine phosphokinase isoenzymes: detection in tissues and serum, and usefulness as an aid to diagnosis of myocardial infarction

1. A colorimetric procedure for creatine phosphokinase (E.C.2.7.3.2.) isoenzymes suitable for routine laboratory use its described. The method utilizes a commercial product for visualization of CK isoenzymes in both serum and tissues. 2. The technic has been applied as an aid to the diagnosis of acute myocardial infarction. An intermediate migrating isoenzyme band (CK-MB) was detected in sera of 19 patients with clinical evidence of myocardial infarction and two patients with myocardial ischemia. The CK(MB) was absent in three patients presenting with symptoms suspect of, but not clinically confirmed as having myocardial infarction.     

Technetium-99m-MAG3 renal studies in spinal cord injury patients: normal range, reproducibility, and change as a function of duration and level of injury

The normal range, reproducibility, and change as a function of duration and level of injury for Tc-99m-MAG3 renal studies were quantitated in spinal cord injury (SCI) patients. METHODS: Five SCI patients without evidence of renal disease in each of four groups: less than 2 months, 2-12 months, 1-2 years, and greater than 2 years from time of injury, were each studied twice. There were at least two patients with paraplegia and two with tetraplegia in each group. Renal clearance (camera based method), percent function in each kidney, time of peak renal parenchymal activity, and half time of parenchymal activity following the peak were evaluated. The peak and half times were determined with regions of interest (ROIs) over the entire kidney and over just the cortex. All results were compared to normal ranges previously established in normal subjects of the same age range using the same methodology. RESULTS: Renal clearance in the less than 2 month SCI patients was not significantly different from normal subjects in either paraplegic or in tetraplegic individuals. However, clearance in tetraplegics was increased by 28.5% at 2-12 month, increased by 50.6% at 1-2 years, and decreased by 25.9% at greater than 2 years compared to normal subjects (all P < 0.02). Clearance in those with paraplegia showed a similar, but less marked, trend (P = NS). The time of peak parenchymal activity when measured with cortical ROIs did not vary among patient groups or level of injury, but was increased compared to normal subjects (P < 0.05). The percent function in each kidney and half time following the peak were symmetrical, did not differ among patient groups or with level of injury, and did not differ from normal subjects. The parenchymal peak time was significantly shorter with cortical rather than renal ROIs in all patient groups (P < 0.05). In serial studies in the same patient the percent standard deviation in total renal clearance was less than between single studies in different patients, but the decrease was significant for only the right kidney (P < 0.03), and the decrease was not as great as in normal subjects. In addition, the percent standard deviation for percent function in each kidney was significantly less than the percent standard deviations in single studies (P < 0.02). There were no significant differences between intra- and interpatient studies for any other parameter. CONCLUSION: We conclude that: (1) renal clearance measured with Tc-99m-MAG3 in tetraplegic patients increases significantly during the first 2 years following injury and decreases significantly thereafter; there is a similar, but much less marked, trend in paraplegics, (2) parenchymal peak times with cortical ROIs occur later for SCI patients than for normal subjects, and (3) there is more intrapatient variation in total renal clearance and percent renal clearance on a side in SCI patients than in normal subjects suggesting that it may be harder to study SCI patients reproducibly. These findings should be taken into account when performing and interpreting Tc-99m-MAG3 renal studies in SCI patients.     

Bruxing patterns in children compared to intercuspal clenching and chewing as assessed with dental models, electromyography, and incisor jaw tracing: preliminary study

The purpose of the present study was to compare bruxing patterns in children with chewing and maximum intercuspal clenching as defined in a clinical and laboratory environment. Six non-bruxing controls and six children who actively bruxed according to parent reports were evaluated. Both control and experimental subjects were assessed by an initial questionnaire, intraoral examination, extraoral examination, dental study models, incisor mandibular tracking, and bilateral surface electromyographic recordings (e.g., EMG). Bruxing was defined as grinding, clenching, or both in combination. The clinical examination consisted of an intraoral examination of the dentition, number of occlusal contacts, and wear facets. Dental study models were used to substantiate the intraoral findings for occlusal contact and wear facets. The mandibular incisors position was tracked during opening, closing, laterotrusion, protrusion, and chewing and compared to the bruxing movements in the experimental subjects. Bilateral surface EMG signals from the temporalis and masseter muscles were recorded in three maximum intercuspal clenches, ten chewing cycles on sugarless gum, and during simulated bruxing. The dental contacts were equal in number bilaterally in both control and bruxing subjects. Both groups demonstrated wear facets, but the bruxing subjects had more facets. The wear facets indicated lateral excursions but not clenching. Only the incisor jaw tracking and bilateral EMG differentiated the bruxing patterns. In those subjects (n = 4) who clenched during bruxing, the EMG pattern was not similar to that of intercuspal clenching and demonstrated its own unique muscle recruitment for the temporalis and masseter muscles. In the subjects who exhibited lateral excursions for bruxing (n = 2), the pattern of muscle recruitment of the two-closing muscles in terms of amplitude was similar for both the bruxing and chewing gum. Our findings support a concept that bruxing may depend upon factors that modify coactivation of muscle recruitment and do not depend upon occlusal contacts.     

The fetus as an allograft: a longitudinal study of normal human pregnancies studied with mixed lymphocyte cultures between mother-father and mother-child

In a longitudinal analysis of immunological changes in normal human pregnancy, twenty-two pregnant women were studied, with blood samples taken before pregnancy, during its course, at delivery, and 3-5 months after delivery. The blood samples were frozen successively, using a cryobiological freezing system, and were stored until the whole longitudinal series was obtained. The collected material for a longitudinal series was then thawed and tested in one seance. Lymphocyte transformation tests were performed with stimulation with the mitogens phytohaemagglutinin (PHA), pokeweed mitogen (PWM), concanavalin A (Con A) and the specific antigens tuberculin purified protein derivative (PPD), Candida albicans (CA), Staphylococcus aureus (SA) and streptokinase/streptodornase (SK/SD). No changes were found in PHA or in PWM responses, whereas there were significant changes in the Con A response, with lowest values in the middle of pregnancy. PPD, CA, SA and SK/SD responses all reached lowest values towards the end of pregnancy, with increases subsequently, after delivery. These findings seem to show that T suppressor function is increased and B-lymphocyte function decreases during the course of pregnancy.     

Interleukin-6, hepatocyte growth factor, and their receptors in biliary epithelial cells during a type I ductular reaction in mice: interactions between the periductal inflammatory and stromal cells and the biliary epithelium

The interleukin-6 (IL-6)/gp-80 and hepatocyte growth factor (HGF)/met ligand/receptor systems have been shown to stimulate biliary epithelial cell (BEC) DNA synthesis in vitro. The mRNA and protein production of these two in vitro mitogens were mapped in vivo during the first week after bile duct ligation (BDL) when peak BEC DNA synthesis is seen. Changes around the biliary tree were compared with those seen in the peripheral liver using a combination of Northern blotting and a unique biliary tree isolation technique, in which the bile ducts and the surrounding portal stroma and inflammatory cells are separated from the hepatocytes by perfusion digestion. Further localization was performed with in situ hybridization and immunohistochemistry. In the normal liver, there is low-level expression of HGF mRNA by periportal stellate cells, and HGF protein localizes to these cells and to neutrophils; extracellular HGF protein is present in the bile. There is no detectable IL-6 mRNA by Northern analysis or IL-6 protein expression in the normal liver, but both met and IL-6 receptor (IL-6R) mRNA are detectable; met mRNA is expressed strongly in the biliary tree, and met protein is expressed weakly on hepatocytes and strongly on BEC. IL-6R mRNA is weakly expressed in the biliary tree, and IL-6R protein is detectable on hepatocytes, with a periportal-to-perivenular gradient, but not on BEC. During the first 3 days after BDL, HGF mRNA expression is increased in both the biliary tree and in the peripheral liver, and production is localized to stellate cells, periductal neutrophils, and stromal cells, which typically accompany the proliferating ductules. IL-6 mRNA and protein were detected only near the biliary tree after BDL, and not in the peripheral liver, and the production was localized to periductal hematolymphoid cells, which had the morphological appearance of macrophages and/or dendritic cells. There is also a distinct up-regulation of met and gp-80 mRNA and protein in the biliary tree, which is stronger than that seen in the peripheral liver. Met protein expression is increased, and IL-6R(gp-80) protein is induced on the proliferating BEC, consistent with the participation of both the HGF/met and IL-6/gp-80 systems in the early phases of type I ductular reactions. These observations show that periductal hematolymphoid and stromal cells are the source of BEC growth factors, and receptors for these factors are up-regulated on BEC during active ductular proliferation. Complex interactions between the inflammatory, stromal, and BEC results in a dysmorphogenic repair response that eventually leads to cirrhosis.     

Rhabdomyosarcoma mimicking acute leukemia in an adult: report of a case with histologic, flow cytometric, cytogenetic, immunohistochemical, and ultrastructural studies

OBJECTIVES: To measure ground reaction force variables during lameness resulting from impaired tibial nerve function and to determine whether these variables changed significantly as recovery progressed. ANIMALS: 11 healthy Greyhounds of either sex, weighing between 22 and 39 kg. PROCEDURE: On 3 consecutive days before surgery, ground reaction forces were measured by force platform gait analysis at the trot. In dogs under general anesthesia, the left tibial nerve was crushed proximal to innervation of the gastrocnemius muscle. Gait analyses were repeated on days 8 to 10, 28 to 30, 43 to 45, 58 to 60, and 90 to 92 after surgery. Ground reaction force variables and stance time were compared among the 3-day clusters. RESULTS: 10 days after surgery, all dogs had weight-bearing lameness attributed to paralysis of muscles in the caudal compartment of the crus. Nerve regeneration resulted in functional recovery within 3 months. Decreases in vertical force were significant 10 days after surgery; thereafter, changes reflected gradual return of load bearing, with the most marked improvement between 10 and 45 days. At 90 days, vertical force variables were within 3% of presurgical values. Stance time for the left hind limb was significantly longer at 10, 30, and 45 days after surgery and was seen in all dogs, but returned to within 1 % of preoperative stance time at 90 days. The effect of tibial nerve dysfunction on braking or propulsive force was not significant. CONCLUSIONS AND CLINICAL RELEVANCE: The significant changes in vertical ground reaction forces in hind limbs of dogs during lameness that resulted from impaired tibial nerve function are detectable, as is response during recovery, by use of force platform analysis.     

The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus

OBJECTIVE: To describe the rationale and design, and to discuss the preliminary screening data, of the Study to Prevent NIDDM (STOP-NIDDM Trial), an international study on the efficacy of the alpha-glucosidase inhibitor acarbose in preventing or delaying the development of type 2 diabetes in a population with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 1,418 subjects diagnosed with IGT according to the World Health Organization's criteria and having a fasting plasma glucose concentration > or =5.6 mmol/L were randomized in a double-blind fashion to receive either acarbose (100 mg t.i.d.) or placebo for a predictive median follow-up period of 3.9 years. The primary outcome is the development of type 2 diabetes diagnosed using a 75-g oral glucose tolerance test according to the new criteria. The secondary outcomes are changes in blood pressure, lipid profile, insulin sensitivity, cardiovascular events, and morphometric profile. RESULTS: Screening was performed in a high-risk population. As of 1 March 1997, 4,424 subjects had been screened, and data were available for 3,919 (88.5%) subjects. Of these subjects, 1,200 (30.6%) had glucose intolerance. Of the subjects with glucose intolerance, 521 (13.3%) had previously undetected type 2 diabetes, and 679 (17.3%) had IGT. Of the IGT population, 412 (60.7%) subjects were eligible for the study This population had the following characteristics: the mean age was 54.8 years, 52% of the subjects were female, 53% had more than one risk factor for type 2 diabetes, >90% had a family history of diabetes, 78.2% had a BMI > or =27 kg/m2, 47.5% had high blood pressure, 51.2% had dyslipidemia, and 22.8% of the women had a history of gestational diabetes. CONCLUSIONS: Screening of a high-risk population yields one eligible subject per every 10 volunteers screened. This study should definitely answer the question of whether acarbose can prevent or delay the progression of IGT to type 2 diabetes mellitus.     

Autoimmunity, immunodeficiency and mucosal infections: chronic intestinal inflammation as a sensitive indicator of immunoregulatory defects in response to normal luminal microflora

Despite the fact that target antigens and the genetic basis of several autoimmune diseases are now better understood, the initial events leading to a loss of tolerance towards self-components remain unknown. One of the most attractive explanations for autoimmune phenomena involves various infections as possible natural events capable of initiating the process in genetically predisposed individuals. The most accepted explanation of how infection causes autoimmunity is based on the concept of "molecular mimicry" (similarity between the epitopes of an autoantigen and the epitopes in the environmental antigen). Infectious stimuli may also participate in the development of autoimmunity by inducing an increased expression of stress proteins (hsp), chaperones and transplantation antigens, which leads to abnormal processing and presentation of self antigens. Superantigens are considered to be one of the most effective bacterial components to induce inflammatory reactions and to take part in the development and course of autoimmune mechanisms. It has long been known that defects in the host defense mechanism render the individual susceptible to infections caused by certain microorganisms. Impaired exclusion of microbial antigens can lead to chronic immunological activation which can affect the tolerance to self components. Defects in certain components of the immune system are associated with a higher risk of a development of autoimmune disease. The use of animal models for the studies of human diseases with immunological pathogenesis has provided new insights into the influence of immunoregulatory factors and the lymphocyte subsets involved in the development of disease. One of the most striking conclusion arising from work with genetically engineered immunodeficient mouse models is the existence of a high level of redundancy of the components of the immune system. However, when genes encoding molecules involved in T cell immunoregulatory functions are deleted, spontaneous chronic inflammation of the gut mucosa (similar to human inflammatory bowel disease) develops. Surprisingly, when such immunocompromised animals were placed into germfree environment, intestinal inflammation did not develop. Impairment of the mucosal immune response to the normal bacterial flora has been proposed to play a crucial role in the pathogenesis of chronic intestinal inflammation. The use of immunodeficient models colonized with defined microflora for the analysis of immune reactivity will shed light on the mode of action of different immunologically important molecules responsible for the delicate balance between luminal commensals, nonspecific and specific components of the mucosal immune system.     

Use of monoclonal antibody 1H1, anticortactin, to distinguish normal and neoplastic smooth muscle cells: comparison with anti-alpha-smooth muscle actin and antimuscle-specific actin

In preliminary experiments, we found that 1H1, a monoclonal antibody directed against the v-src substrate cortactin, reacts with smooth muscle, myoepithelium, myofibroblasts, and macrophages in formaldehyde-fixed human tissues. To evaluate the use of this antibody as a diagnostic reagent, we tested the immunohistochemical distribution of cortactin in 61 mesenchymal neoplasms, 11 neuroectodermal neoplasms, and eight embryonal epithelial neoplasms. The results were compared with those obtained using antibodies against alpha-smooth muscle actin and muscle-specific actin on a similar set of tissues. With the exception of positive staining in rhabdomyosarcoma, in this series only tumors with smooth muscle differentiation appeared to contain cortactin (16 of 19 leiomyosarcomas, one infantile fibrosarcoma, one malignant fibrous histiocytoma). Immunoelectron microscopy localized cortactin to the actin-associated dense bodies of the microfilament network. We conclude that cortactin may be a useful adjunct to alpha-smooth muscle actin and muscle-specific actin as a marker for the study and diagnosis of smooth muscle neoplasms and related lesions.     

Shyness and low social support as interactive diatheses, with loneliness as mediator: Testing an interpersonal-personality view of vulnerability to depressive symptoms.

Interpersonal approaches to depression are surveyed; it is suggested that interpersonal inhibition, as opposed to interpersonal excess, has been underemphasized as an antecedent of depression. It is proposed that shyness is a vulnerability factor for depressive symptoms in the absence but not in the presence of social support and that loneliness mediates the relation between shyness and depressive symptom increases. Undergraduates (N?=?172) reported on their levels of shyness, social support, loneliness, positive and negative affect, and depressive symptoms, and returned 5 weeks later to complete a similar set of assessments. Results supported hypotheses. Participants who were shy and unsupported were likely to experience increases in depressive symptoms and decreases in positive affect, whereas other students were not. This effect was partially mediated by increases in loneliness and was specific to depressive symptoms and low positive affect; it did not apply to negative affect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypothermia as an indicator of the acute effects of lipopolysaccharides: comparison with serum levels of IL1 beta, IL6 and TNF alpha

1. Hypothermia was investigated as a parameter indicating the severity of the acute effects of lipopolysaccharides (LPS) in BALB/c mice, and was compared with the induction of serum levels of IL1 beta, TNF alpha and IL6. 2. Hypothermia induced by low doses of LPS (10-50 micrograms/mouse IP LPS E. coli 0111:B4) peaked at 2 hr after LPS and then either plateaued (50 micrograms) or declined. LPS, 100 and 300 mu, induced greater degrees of hypothermia that plateaued or continued to increase with time for 8 hr. Higher doses of LPS induced similar levels of hypothermia until 4 hr but then continued to increase markedly until 8 hr. 3. TNF alpha levels peaked early (1-2 hr) and declined rapidly, IL6 levels peaked at 3 hr and then declined slowly, and IL1 beta levels peaked at 4 hr, declined at lower doses of LPS, plateaued at higher doses and continued to slowly increase at highest doses. 4. The peak levels of the cytokines (IL1 beta up to 4 hr) and hypothermia (4 hr) increased in relation to the dose of LPS and maximum responses were apparently achieved in all cases at 300-1000 micrograms LPS. 5. A similar parallel between hypothermia and induction of cytokines was observed in C57BL6 and OF1 mice, which were good and poor responders to LPS, respectively, and with the more potent Shigella dysenteria LPS in BALB/c mice. 6. In conclusion, hypothermia is a useful parameter for indicating the strength of the acute effects of LPS. Further studies are necessary to determine whether or not the cytokines studied here play a causative role in hypothermia.     

Induction of superoxide by 12-O-tetradecanoylphorbol-13-acetate and thapsigargin, a non-phorbol-ester-type tumor promoter, in peritoneal macrophages elicited from SENCAR and B6C3F1 mice: a permissive role for the arachidonic acid cascade in signal transduction

Local production of reactive oxygen intermediates, e.g., superoxide anion, by tumor promoter-stimulated inflammatory macrophages (MPs) may contribute significantly to tumor development in classical models of two-stage chemical-induced carcinogenesis in murine skin. In the studies reported herein, peritoneal MPs elicited from phorbol-ester-sensitive SENCAR mice demonstrated a time- and dose-dependent release of superoxide anion (4-6 nmol/10(6) cells) when stimulated by 200 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) in vitro; MP superoxide response was significantly inhibited (50-70%) by preincubation with 40 microM 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7), a protein-kinase inhibitor. Alternatively, TPA-stimulated MPs derived from relatively resistant B6C3F1 mice generated negligible superoxide under the same conditions. A similar strain-dependent induction of superoxide was observed when MPs were stimulated with thapsigargin (TG), a tumor promoter previously shown to act independently of protein kinase C (PKC). TG-stimulated SENCAR MPs released a significant amount of superoxide (2-3 nmol/10(6) cells) that was not inhibited by H-7; MPs from B6C3F1 mice demonstrated negligible stimulation by TG. Preincubation of SENCAR MPs with 100 microM dibromoacetophenone, an inhibitor of phospholipase A2, completely suppressed the superoxide induced by TPA and TG stimulation. Like TPA, 50 microM 1-oleoyl-2-acetylglycerol, a diacylglycerol analogue and PKC activator, also induced a significant amount of superoxide from SENCAR MPs only. In parallel with the superoxide findings, TPA and TG stimulated significantly greater [3H]arachidonic acid release from prelabeled SENCAR MPs (a 32% and 48% increase, respectively, over unstimulated controls) relative to MPs from B6C3F1 mice. Two-dimensional gel-electrophoretic analysis indicated that TPA-induced phosphorylation of a 47-kDa protein (a presumed substrate for PKC previously linked to NADPH oxidase activation in guinea pig and human polymorphonuclear leukocytes) occurred in MPs from both SENCAR and B6C3F1 mice. Therefore, arachidonic acid production may be a common biochemical pathway by which phorbol-ester--and non-phorbol-ester--type tumor promoters activate MPs in SENCAR mice; such a response may be "permissive" for additive (or synergistic) interactions with PKC-driven signal pathways.     

Acquired C 1-inhibitor deficiency with angioedema due to pleomorphic immunocytoma in a patient with three malignant tumors: long-term follow-up data and presentation of an additional case

Two cases of lymphoma-associated acquired C 1-inhibitor deficiency are described. In both patients, C 1-inhibitor deficiency and related symptoms preceded the diagnosis of the underlying neoplasm by several months. C 1-inhibitor deficiency was most likely due to consumption following immunocomplex formation. In both patients, a close relationship between low levels of C 1-inhibitor and tumor relapse was observed during follow-up. These findings indicate that measurement of C 1-inhibitor and complement factor C4 can be used as markers of disease activity in affected patients.     

Sensitivity to indirect contacts with other persons: AIDS aversion as a composite of aversion to strangers, infection, moral taint, and misfortune.

College students and their parents rated their willingness to wear sweaters previously worn by a target person described as having AIDS, another infectious illness (tuberculosis), a misfortune (maimed in automobile accident), moral taint (convicted murderer), or simply as a healthy but unknown man. Parallel ratings were obtained with respect to beds slept in or automobiles previously owned by the same set of target persons. Results indicated that there are strong individual differences in sensitivity to 4 sources of aversion to indirect interpersonal contagion: infection, misfortune, immorality, and unfamiliarity. Individual sensitivity to any one of these sources predicts sensitivity to the others (rs in the .30s). Aversion to indirect contact with a person with AIDS (by sweater, bed, or car) includes all 4 sources of aversion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)