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Biomedical subjects

L Carter

Publications and source records attributed to L Carter.

At least 55 records · Page 3Linked to original sources

Interleukin 1 beta and corticotropin-releasing factor inhibit pain by releasing opioids from immune cells in inflamed tissue.

Local analgesic effects of exogenous opioid agonists are particularly prominent in painful inflammatory conditions and are mediated by opioid receptors on peripheral sensory nerves. The endogenous ligands of these receptors, opioid peptides, have been demonstrated in resident immune cells within inflamed tissue of animals and humans. Here we examine in vivo and in vitro whether interleukin 1 beta (IL-1) or corticotropin-releasing factor (CRF) is capable of releasing these endogenous opioids and inhibiting pain. When injected into inflamed rat paws (but not intravenously), IL-1 and CRF produce antinociception, which is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively, and by the immunosuppressant cyclosporine A. In vivo administration of antibodies against opioid peptides indicates that the effects of IL-1 and CRF are mediated by beta-endorphin and, in addition, by dynorphin A and [Met]enkephalin, respectively. Correspondingly, IL-1 effects are inhibited by mu-, delta-, and kappa-opioid antagonists, whereas CRF effects are attenuated by all except a kappa-antagonist. Finally, IL-1 and CRF produce acute release of immunoreactive beta-endorphin in cell suspensions freshly prepared from inflamed lymph nodes. This effect is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively. These findings suggest that IL-1 and CRF activate their receptors on immune cells to release opioids that subsequently occupy multiple opioid receptors on sensory nerves and result in antinociception. beta-Endorphin, mu- and delta-opioid receptors play a major role, but IL-1 and CRF appear to differentially release additional opioid peptides.

Analysis of Variance↗

Temporal analysis of the anti-inflammatory effects of decentralization of the rat superior cervical ganglia.

Bilateral decentralization of the superior cervical ganglia (SCG) reduced the pulmonary inflammation that develops 4-8 h after induction of anaphylaxis in Nippostrongylus brasiliensis-sensitized rats. Histamine levels in peritoneal lavage fluid and rat mast cell protease type II in serum were increased to comparable levels in sham-operated and decentralized rats. In vitro stimulation of alveolar macrophages (ALM) with lipopolysaccharide (LPS) provoked tumor necrosis factor-alpha (TNF-alpha) release that was two to three times greater with unchallenged decentralized rats than with sham-operated rats. However, after allergen challenge LPS-stimulated TNF-alpha release from ALM of sham-operated rats increased threefold and lasted at least 24 h, whereas with decentralized rats release of this cytokine actually decreased at 4 and 8 h. The increase in the phagocytosis and respiratory burst of circulating neutrophils seen at 4 and 8 h after allergen challenge in sham-operated rats was reduced significantly by decentralization. These results suggest that the attenuation of anaphylaxis-induced pulmonary inflammation that occurs with decentralization of the SCG is primarily associated with downregulation of neutrophil and macrophage functions.

Anaphylaxis↗

Decentralization of the superior cervical ganglia inhibits mast cell mediated TNF alpha-dependent cytotoxicity. 1. Potential role of salivary glands.

Decentralization or ganglionectomy of the superior cervical ganglia (SCG) reduces pulmonary inflammation, as well as chemotaxis and activation of circulating neutrophils. However, the protective effect of decentralization was abolished when combined with removal of the submandibular glands (sialadenectomy) in the same animals. Thus, it has been postulated that the submandibular glands (SMG) release an anti-inflammatory factor(s) that is controlled by cervical sympathetic nerves. Decentralization of SCG did not modify in vitro histamine release or in vivo levels of rat mast cell protease II, but it reduced mast cell (MC)-mediated tumor necrosis factor alpha (TNF alpha)-dependent cytotoxicity. Combined decentralization/sialadenectomy abrogated the inhibition of MC cytotoxic activity, as we have shown previously for pulmonary inflammation and neutrophil functions. However, sialadenectomy alone inhibited MC-mediated TNF alpha-dependent cytotoxicity, an observation which suggests that SMG produce a factor(s) that can potentiate MC cytotoxic activity. Studies of the effects of SMG-derived factors, such as epidermal growth factor, nerve growth factor, and transforming growth factor beta (TGF beta), showed that only pretreatment of MCs with TGF beta 10(-8) g/ml inhibited MC-mediated TNF alpha-dependent cytotoxicity. Thus, the modulation of MC-mediated TNF alpha-dependent cytotoxicity by cervical sympathetic innervation and SMG is complex and distinct from the modulation of pulmonary inflammation and neutrophil functions identified previously.

Animals↗

Tissue-selective inhibition of prostaglandin synthesis in rat by tepoxalin: anti-inflammatory without gastropathy?

BACKGROUND: Inhibition of prostaglandin synthesis is likely a primary mechanism for both the anti-inflammatory and ulcerogenic effects of nonsteroidal anti-inflammatory drugs (NSAIDs). The present study examined the mechanism underlying the ability of a novel anti-inflammatory drug, tepoxalin, to suppress prostaglandin synthesis without inducing gastric mucosal injury. METHODS: The effects on prostaglandin synthesis by various tissues of tepoxalin, diclofenac, and indomethacin were examined in vivo and in vitro. These compounds were also studied in two inflammation models. The capacity of indomethacin and tepoxalin to induced antral ulceration in the rabbit was compared. RESULTS: In most tissues, tepoxalin was a weaker inhibitor of prostaglandin synthesis than the two NSAIDs. However, at a site of peripheral inflammation, tepoxalin was comparable with the NSAIDs in suppressing prostaglandin synthesis and in exerting anti-inflammatory effects. Indomethacin induced penetrating antral ulcers in rabbits whereas tepoxalin produced no detectable mucosal injury. CONCLUSIONS: The ability of tepoxalin to suppress inflammation without causing gastric mucosal injury appears to be related to its differential suppression of prostaglandin synthesis in various tissues. Compounds that selectively inhibit prostaglandin synthesis at sites of inflammation may represent a class of anti-inflammatory drugs without detrimental effects on the stomach.

Animals↗

Inhibition of neutrophil chemotaxis and activation following decentralization of the superior cervical ganglia.

Recent studies have shown that bilateral decentralization (sympathectomy) of the superior cervical ganglia (SCG) of rats sensitized to the parasite Nippostrongylus brasiliensis attenuated the development of pulmonary inflammation following allergen challenge. Sympathectomy inhibited total leukocyte infiltration into lung lavage fluids, particularly neutrophil infiltration. To define the effects of decentralization of the SCG on neutrophil responses, peripheral blood neutrophils of rats were isolated and tested in in vitro chemotaxis and phagocytosis assays. Neutrophils from rats that were sympathectomized 7 days previously displayed a marked reduction in chemotaxis to N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4 compared to neutrophils from sham-operated or unoperated groups. Although the degree of chemotaxis was greater in blood neutrophils from parasite-infected rats than from uninfected rats, sympathectomy markedly reduced the chemotactic responses of both groups. In addition, neutrophils of sympathectomized rats were unresponsive to lipopolysaccharide-induced metabolic activation as assessed by in vitro phagocytosis and oxidative reduction of nitroblue tetrazolium. Thus, decentralization of the SCG of rats affects the chemotactic responses and functions of neutrophils. Understanding the role of the sympathetic nervous system in modulating the behavior of neutrophils will shed light on the interactions between the nervous and immune systems.

Animals↗

Hemoprotein-dependent production of a neutrophil-activating factor from arachidonic acid.

Hemoproteins have been suggested to contribute to various forms of tissue injury by catalyzing the peroxidation of lipids. In this study, the ability of hemoglobin to catalyze the production of a neutrophil-activating factor from arachidonic acid was examined. Incubation of arachidonic acid, hydrogen peroxide, and hemoglobin at 37 degrees C for 30 min resulted in the production of a lipid-extractable substance that was chemotactic for neutrophils in vitro and could stimulate leukocyte adherence in vivo. These actions could be inhibited by two leukotriene B4 (LTB4) receptor antagonists. The peroxidation product cross-reacted significantly with an antibody directed against LTB4, but not with an antibody directed against LTC4. The production of this factor was hemoprotein dependent. Immunoreactive LTB4 and biological activity were produced only when hemoglobin, or another hemoprotein, cytochrome c, was present in the reaction mixture. The amount of the factor produced could be increased in a concentration-dependent manner by increasing the amounts of arachidonic acid or hydrogen peroxide in the reaction mixture. The production of this factor could be inhibited by 5-aminosalicylic acid, catalase, or deferoxamine. Separation of the lipid-extractable products of the peroxidation of arachidonic acid on high-performance liquid chromatography revealed that the immunoreactive (with anti-LTB4) and chemotactic substance had a retention time distinct from that of LTB4 and the hydroxyeicosatetraenoic acids. A lipid-extractable substance with significant cross-reactivity to anti-LTB4 could also be produced if plasma was substituted for arachidonic acid in the reaction mixture.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminosalicylic Acids↗

Marked antiinflammatory effects of decentralization of the superior cervical ganglia.

Intravenous challenge with parasite antigens in Nippostrongylus brasiliensis-sensitized rats resulted in anaphylactic shock and, in some animals, death. Surviving animals showed significant drop in mean arterial blood pressure, cardiac output, and blood flow to the trachea, bronchioles, and mesentery. After anaphylaxis, changes in the cellular and protein composition in bronchoalveolar lavage fluids (BALF) were assessed. 8 h after antigen challenge, there was significant influx of inflammatory cells and an increase in the levels of histamine and serum-derived immunoglobulins (IgG and IgM) in BALF. Chemotactic activity for neutrophils was also present in BALF. Once we established this anaphylaxis-induced model of pulmonary inflammation, we sought to determine whether or not the superior cervical ganglia (SCG) modulate this inflammation. We performed bilateral superior cervical ganglionectomy or decentralization of the SCG. Our results show that decentralization significantly reduced mortality (by 68%) after anaphylaxis. Furthermore, the increases in levels of serum-derived proteins, histamine, and influx of cells (especially neutrophils) observed in BALF after anaphylaxis were attenuated by both decentralization and ganglionectomy. By contrast, hemodynamic parameters in the respiratory tract and the presence of neutrophil chemotactic activity in BALF were not influenced by decentralization. Thus, the severity of pulmonary inflammation initiated by systemic anaphylaxis is depressed by bilateral ganglionectomy or decentralization of SCG.

Animals↗

The sodium-22 influx in erythrocytes from black males and females.

In order to establish a standard for sodium influx in erythrocytes for the black population, 22Na+ uptake was measured in 29 normotensive black volunteers. Nineteen males and 10 females during the follicular phase of the menstrual cycle were studied utilizing the procedure of Gambhir et al. (1). In the males, cell concentrations ranging from 0.64 to 2.0 X 10(9)/ml showed an influx of 0.42 to 1.34% of the total 22Na+ added, and in the females, using the same erythrocyte concentrations, the 22Na+ influx ranged from 0.37 to 1.1%; these differences were not significant. Intraassay variation of the 22Na+ data was 4.8%. Interassay variations have been explained elsewhere (1). These data provided a range of observed values for 22Na+ uptake in erythrocytes from a subpopulation of normotensive black males and females for comparison with hypertensive patients.

Adult↗

Anti-sperm antibodies in homosexual men: prevalence and correlation with sexual behaviour.

The sera of 60 homosexual males were examined for the presence of antibodies to sperm using an indirect immunobead test (IBT). Six of 60 (10%) had antibodies of IgG isotype; in addition two of the six had antibodies of IgA isotype. The presence of antibodies was associated with the practice of unprotected receptive anal intercourse in the previous six months. Antibodies were not found in homosexual men who were celibate, or who practised only oral intercourse during the same period. There was no correlation between the presence of anti-sperm antibodies and antibodies to human immunodeficiency virus (HIV), or numbers of T lymphocytes. These preliminary results lend support to the hypothesis that antigen presentation in the lower gut may be a source of sensitisation against sperm. The possibility that anti-sperm antibodies may be a marker of receptive anal intercourse merits further investigation.

Adult↗

Antibody responses in the liver and bile of rats injected with horse erythrocytes.

The intravenous injection of 1 ml of a 0.1% (or higher %) suspension of horse red blood cells (HRBC) into rats results in the appearance of high levels of agglutinating activity in bile as well as serum. Lower doses of HRBC induce reduced responses in both fluids, demonstrating that the biliary response is as dose-dependent as the serum response. The presence of IgM anti-HRBC antibody forming cells (AFC) in the liver in numbers equivalent to those detected in the spleen at day 6 of the study suggests them to be the most likely source of the biliary antibody. Also, the injection of HRBC into other parenteral sites (intramuscular [i.m.], intraperitoneal [i.p.] and intrathoracic cavity [i.t.]) results in a biliary response which is considered to originate from the IgM-, IgG- and IgA-anti-HRBC AFC detected in the liver, again in numbers approximating those detected in the spleen. Splenectomy of rats immunized i.p., i.m. and i.t. had only a minimal effect on the liver and biliary responses, indicating that AFC arising in peripheral lymphoid tissues can also relocate in liver. It is concluded that the liver is a major site of antibody synthesis following parenteral immunization leading to substantial levels of antibody being secreted into the gastrointestinal tract.

Animals↗

The 20 questions task with families of schizophrenics: divergent findings.

The study attempted to replicate and extend the results of an earlier study by Wild and Shapiro (16), establishing the utility of Mosher and Hornsby's (8) 20 Questions Task as a means of differentiating families with schizophrenic patients from those of psychiatrically hospitalized but nonschizophrenic individuals. In the current study, Wild and Shapiro's original design was expanded and revised by (a) diagnosing patients using Research Diagnostic Criteria rather than hospital diagnoses and (b) including families with schizophrenic daughters and/or one-parent families, in addition to intact families with schizophrenic sons. Families were comparable on age, intelligence, and socioeconomic variables. The results failed to replicate those reported by Wild and Shapiro, and indicated that the 20 Questions Task was sensitive to differences in family constellation and offspring gender as well as offspring diagnosis. The findings suggest that forms of familial communication deviance detected with the 20 Questions Task may not be unique to families of schizophrenics, thus highlighting the need to expand research on family communication deviance in families with schizophrenic offspring to families with varied family constellations and characteristics.

Attention↗

Role of direct contact, real-time breast ultrasound: one year's experience.

Direct contact US was used for evaluation of 206 patients referred for a palpable mass not visualized on mammography or for evaluation of a smooth, well-marginated mass or masses on mammography; 67 solid lesions, 90 simple cysts, 7 complex cysts, 2 hematomas, and 1 case of mastitis were identified. Thirty-nine additional lesions appeared as normal breast tissue by ultrasound. Surgical biopsy was performed in 40 women. Of the 29 sonographically-visible solid lesions that were biopsied, five were carcinomas. Of the seven lesions not visualized by ultrasound that were biopsied, two were carcinoma (mean diameters 0.9 and 0.4 cm). Of the 4 complex cysts biopsied, 1 intraductal carcinoma (0.4 cm) was found and this was surgically felt to be an incidental cancer adjacent to a hemorrhagic cyst. In the patient population studied, there was no significant difference in biopsy confirmation of carcinoma whether lesions were identified on ultrasound or whether mammographic or palpable lesions appeared as normal breast tissue by ultrasound. Standoff devices were not used. Without the use of standoff devices, in our patient population, the lack of sonographic detection of a palpable or mammographically demonstrated mass should not dissuade or delay surgical biopsy.

Adult↗

Bacillus sporulation gene spo0H codes for sigma 30 (sigma H).

The DNA sequences of the spo0H genes from Bacillus licheniformis and B. subtilis are described, and the predicted open reading frames code for proteins of 26,097 and 25,447 daltons, respectively. The two spo0H gene products are 91% identical to one another and about 25% identical to most of the procaryotic sigma factors. The predicted proteins have a conserved 14-amino-acid sequence at their amino terminal end, typical of sigma factors. Antibodies raised against the spo0H gene product of B. licheniformis specifically react with RNA polymerase sigma factor protein, sigma 30, purified from B. subtilis. We conclude that the spo0H genes of B. licheniformis and B. subtilis code for sigma 30, now known as sigma H.

Amino Acid Sequence↗

Comparison of human erythrocyte insulin binding and adenosinetriphosphatase activity.

Twelve healthy, non-obese male volunteers were selected to measure cellular magnesium (Mg(++)), calcium (Ca(++)), sodium/potassium (Na(+)/K(+)), and adenosinetriphosphatase (ATPase) activities. Measurements were performed using a crude hemolysate as well as a membrane fraction representing cytosolic pump activity. Binding-site data were subjected to Scatchard analysis for determination of receptor number and affinity.There were 432 ± 1.87 insulin-binding sites per cell. ATPase activity was measured in units of moles of inorganic phosphate (Pi) released per gram of hemoglobin (Hgb) every two hours (μmol of Pi/g of Hgb/2 h). Na(+)/K(+)-ATPase activity in the hemolysate and membrane fractions was 18 ± 0.99 μmol of Pi/g of Hgb/2 h and 11.0 ± 0.88 μmol of Pi/g of Hgb/2 h, respectively. Calcium-ATPase activity was 136 ± 1.92 μmol of Pi/g of Hgb/2 h in the hemolysate, and 82 ± 2.07 μmol of Pi/g of Hgb/2 h in the membrane. Magnesium-ATPase activity in these fractions measured 24 ± 1.09 and 16 ± 0.91, respectively.Linear regression analysis of binding capability vs pump activity failed to disclose a significant relationship. Given the narrow range of values in this small study group, a much larger sample size will be required before a relationship can be established.

Adenosine Triphosphatases↗