Thorndike's Legacy: Learning, Selection, And The Law Of Effect.
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
A Catania
Publications and source records attributed to A Catania.
Pavlov And Skinner: Two Lives In Science (An Introduction To B. F. Skinner's "Some Responses To The Stimulus 'Pavlov' ").
Explore the source record for details and available documents.
Journal Article↗
Platelet membrane fluidity in non-insulin-dependent diabetes mellitus (NIDDM) subjects, in subjects with vascular atherosclerotic disease (VAD) and in VAD subjects with NIDDM.
Explore the source record for details and available documents.
Aged↗
Mechanisms of antiinflammatory action of the neuroimmunomodulatory peptide alpha-MSH.
The antiinflammatory effects of alpha-melanocyte-stimulating hormone (alpha-MSH) molecules, specifically alpha-MSH(1-13) and its COOH-terminal tripeptide alpha-MSH(11-13), are well established. The peptides have been effective in tests of all major models of inflammation, and more recent tests have been extended to include experimental inflammatory bowel disease, CNS ischemia/reperfusion injury, and bacterial endotoxin-induced inflammation within the brain. The broad effectiveness of alpha-MSH molecules in all major types of inflammation indicates that the peptides exert actions that are very basic to the inflammatory process. Three general mechanisms of antiinflammatory action of alpha-MSH molecules have been identified: inhibition of production of inflammatory mediators by, or inhibition of inflammatory actions of, peripheral host cells; inhibition of peripheral inflammation induced by actions on melanocortin receptors within the brain; inhibition of CNS inflammation by local action of the peptides. It appears that alpha-MSH molecules have multiple actions that modulate the primitive inflammatory response.
Animals↗
The neuropeptide alpha-MSH in HIV infection and other disorders in humans.
We measured plasma concentration of alpha-melanocyte-stimulating hormone (alpha-MSH), a proopiomelanocortin derivative that modulates pyrogenic and proinflammatory effects of cytokines, in infectious and inflammatory disorders in humans to learn if changes in this peptide take place in naturally occurring disease. alpha-MSH was elevated in HIV-infected patients of the CDC groups III and IV. Although the peptide increased in the circulation of normal subjects injected with endotoxin, it was reduced in patients with septic syndrome. alpha-MSH was found in the synovial fluid of arthritis patients, and its concentration was greater in the forms of arthritis marked by greater inflammation. We found that alpha-MSH is increased in the circulation of patients with acute myocardial infarction receiving thrombolytic therapy. Plasma concentrations of alpha-MSH is increased in the circulation of patients with acute myocardial infarction receiving thrombolytic therapy. Plasma concentrations of alpha-MSH were lower in healthy elderly subjects than in young controls. Because an excess of proinflammatory cytokines can have detrimental effects, we investigated the influences of alpha-MSH on the production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in HIV-infected patients and in patients with septic syndrome. Production of these cytokines in whole-blood samples stimulated with endotoxin was significantly reduced by treatment of blood with alpha-MSH. alpha-MSH has been injected into at least 106 human subjects to study its effects on pituitary function, menstrual bleeding, and tanning. The peptide was always well tolerated. alpha-MSH administration could open new perspectives in treatment of inflammatory diseases in humans.
Acquired Immunodeficiency Syndrome↗
Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia.
Inflammatory processes contribute to neurodegenerative disease, stroke, encephalitis, and other central nervous system (CNS) disorders. Activated microglia are a source of cytokines and other inflammatory agents within the CNS and it is therefore important to control glial function in order to preserve neural cells. Melanocortin peptides are pro-opiomelanocortin-derived amino acid sequences that include alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH). These peptides have potent and broad anti-inflammatory effects. We tested effects of alpha-MSH (1-13), alpha-MSH (11-13), and ACTH (1-24) on production of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO) in a cultured murine microglial cell line (N9) stimulated with lipopolysaccharide (LPS) plus interferon gamma (IFN-gamma). Melanocortin peptides inhibited production of these cytokines and NO in a concentration-related fashion, probably by increasing intracellular cAMP. When stimulated with LPS + IFN-gamma, microglia increased release of alpha-MSH. Production of TNF-alpha, IL-6, and NO was greater in activated microglia after innmunoneutralization of endogenous alpha-MSH. The results suggest that alpha-MSH is an autocrine factor in microglia. Because melanocortin peptides inhibit production of pro-inflammatory mediators by activated microglia they might be useful in treatment of inflammatory/degenerative brain disorders.
Adrenocorticotropic Hormone↗
Within-patient variability of hormone and cytokine concentrations in heart failure.
Several studies on disease and treatment effects on neurohormones have been conducted with small numbers of patients, using one blood sample as representative of their states. The aim of this study was to assess the within-patient variability of plasma concentrations of several hormones and cytokines of recent interest, in patients with moderate heart failure and controlled stable background therapy over 3 weeks. Blood for neurohormone and cytokine assays was sampled in duplicate from 18 patients with moderate heart failure. After an initial visit, the patients were kept on stable therapy until the second blood sampling 21 +/- 3 days later. The plasma concentrations of several neurohormones (endothelin, renin, angiotensin II, aldosterone, norepinephrine) and cytokines (interleukin-6 (IL-6), interleukin-13 (IL-13), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF) and soluble receptor type I of tumour necrosis factor-alpha, (sTNF-RI) were measured with immunochemical methods. Some cytokines (IL-13, CNTF and LIF) were not detected. Despite clinically satisfactory ACE inhibition, circulating angiotensin II and aldosterone levels were still elevated in some patients, suggesting aldosterone escape. The between-visit agreement of plasma concentrations measured in duplicate was less than 35% for all circulating factors, except renin which showed a higher variability throughout the 3-week study period.
Aldosterone↗
Polymorphonuclear leukocyte membrane fluidity and cytosolic Ca2+ concentration in diabetes mellitus.
We evaluated polymorphonuclear membrane (PMN) fluidity in 32 subjects with type 1 diabetes mellitus, 38 subjects with type 2 diabetes mellitus and 38 normal control subjects, by marking intact and unstimulated PMN cells with the fluorescent probe 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). We also evaluated PMN cytosolic Ca2+ content by marking intact and unstimulated PMN cells with the fluorescent probe Fura 2-AM. PMN membrane fluidity differentiated normal subjects from type 1 and 2 diabetic subjects. The PMN cytosolic Ca2+ concentration did not discriminate type 1 and 2 diabetic subjects from normal control subjects. No statistical correlation was found between PMN membrane fluidity and PMN cytosolic Ca2+ concentration in any of the groups of subjects, nor were significant correlations found between PMN membrane fluidity and cytosolic Ca2+ concentration in several plasma parameters (serum glucose, cholesterol and triglycerides). In conclusion, in type 1 and 2 diabetic patients we found a decrease in PMN membrane fluidity and this decrease, which was greater in type 2 diabetic patients, may be a marker of PMN dysfunction.
Adult↗
Melanocortin peptides inhibit production of proinflammatory cytokines in blood of HIV-infected patients.
Melanocortins are proopiomelanocortin-derived peptides that include adrenocorticotropic hormone [ACTH (1-39)], alpha-melanocyte-stimulating hormone [alpha-MSH (1-13)], and related amino acid sequences. Melanocortin peptides have potent antiinflammatory/anticytokine activity. Because cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF) can be detrimental in HIV-infected patients, we investigated the effects of melanocortins on production of IL-1 and TNF alpha in the blood of HIV patients. Cytokine production was measured in whole blood samples stimulated with LPS in the presence or absence of alpha-MSH (1-13), alpha-MSH (11-13), ACTH (1-24), or ACTH (1-39). Melanocortins reduced production of both cytokines in a concentration-dependent fashion. In separate experiments on normal peripheral blood mononuclear cells (PBMC), alpha-MSH (1-13) inhibited production of IL-1 beta and TNF alpha induced by HIV envelope glycoprotein gp 120. These results suggest that stimulation of melanocortin receptors in inflammatory cells could be a novel way to reduce production of cytokines that promote HIV replication.
Adrenocorticotropic Hormone↗
Determination of blood flow in the finger using near-infrared spectroscopy.
Wavelengths in the near-infrared range have much better penetrance in organic substances than visible light. We used near-infrared spectroscopy to determine non-invasively blood flow in the fingertip. We used laser Doppler technology to measure skin blood flow as a comparison procedure. We performed several manoeuvres to change blood flow. These included restriction of flow, thermal stimulation and post-occlusion hyperaemia. Near-infrared measurements had coefficients of variation of 10-15% at the various wavelengths, contrasting with variability of 30-40% with laser Doppler measurement. With restriction of blood flow, there was a downward shift in the absorbance curve. With thermal stimulation and with post-occlusion hyperaemia, there was a rise in the curve. The flow-induced shifts in the absorbance curve were particularly pronounced in the range of 850-970 nm. The correlation between absorbance values and laser Doppler-determined blood flow was also highest in this range, averaging about 0.69 (n = 625). Near-infrared spectroscopy can therefore be used to scan the fingertip. The absorbances obtained do reflect changes in blood flow. There is a correlation with skin blood flow, although near-infrared measurements are affected by blood flow in the full breadth of the finger, not just the skin. We can measure this blood flow with significant reproducibility. It may be possible to use near-infrared spectroscopy to measure the concentration of individual blood components.
Fingers↗
Type II diabetics with macrovascular complications: polymorphonuclear leukocyte (PMN) filtration, PMN membrane fluidity and cytosolic Ca2+ content after activation.
We evaluated polymorphonuclear (PMN) filtration parameters, membrane fluidity and cytosolic Ca2+ content in 21 normal subjects and in 18 type II diabetics with macrovascular complications (MVC). Evaluations were carried out at baseline and after in vitro activation prolonged for 5 and 15 min. PMA (4-phorbol 12-myristate 13-acetate) and fMLP (N-formyl-methionyl-leucyl-phenylalanine) were used as stimulating agents. TMA-DPH (1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene) was used as fluorescent probe for the membrane fluidity tests and Fura 2-AM for the cytosolic Ca2+ content. A significant variation was evident in PMN filtration parameters at 5 and 15 min. No variation was present in PMN membrane fluidity and cytosolic Ca2+ content in normals. In type II diabetics with MVC, we found an increase solely in PMN cytosolic Ca2+ content after PMA activation and an early decrease in PMN membrane fluidity and a late increase in PMN cytosolic Ca2+ content after fMLP activation. After PMA activation alone (at 15 min), PMN filtration distinguishes normals from type II diabetics with MVC. The PMN filtration parameters behave similarly in the two groups, but PMN membrane fluidity and cytosolic Ca2+ content behave differently.
Aged↗
Gastric involvement in AIDS associated cryptosporidiosis.
BACKGROUND: Cryptosporidiosis has been shown to be a common cause of diarrhoea in both immunocompetent and immunosuppressed individuals. There are very few data on the distribution of Cryptosporidium parvum along the gastrointestinal tract. AIMS: To evaluate the location of Cryptosporidium parasites in the digestive tract of patients with AIDS. METHODS: Gastrointestinal localisation of C parvum was studied in 71 patients with AIDS who underwent upper and/or lower endoscopy with biopsy for chronic diarrhoeal illness and/or other gastrointestinal disorders of unexplained origin. RESULTS: Twenty four individuals (33.8%) were positive for C parvum, of which 16 (88.9%) had parasites in the gastric epithelium. Most patients with gastric localisation of C parvum did not show specific symptoms indicating the presence of this parasite in the stomach. CONCLUSIONS: Gastric involvement in AIDS related cryptosporidiosis is more frequent than expected, but no clear correlation between gastric location and related clinical and pathological features was observed.
AIDS-Related Opportunistic Infections↗
Relevance of clinical and laboratory findings in the diagnosis of cytomegalovirus encephalitis in patients with AIDS.
A retrospective evaluation was conducted in patients with AIDS and an autopsy diagnosis of cytomegalovirus (CMV) encephalitis to determine the relevance of clinical and laboratory findings in establishing a diagnosis. On autopsy of 100 patients, CMV encephalitis was diagnosed in 13 patients; eight had periventricular CMV encephalitis, four micronodular CMV encephalitis, and one both conditions. Seven patients had had a CMV infection previously (6 cases of retinitis, 1 case of colitis), and at the onset of encephalitis all of them were receiving a maintenance dose of ganciclovir. Examination of the CSF showed specific changes in patients with periventricular encephalitis. CT revealed no characteristic findings, while MRI showed an increased signal intensity on T2 weighted images. CMV DNA amplification by nested PCR was performed in nine patients with CMV encephalitis; PCR was positive in eight patients whose CSF was collected during CMV encephalitis, and negative in one patient whose CSF was collected six months before death. In conclusion, some clinical findings suggest a presumptive diagnosis, especially of periventricular encephalitis, and nested PCR appears to be a reliable and rapid technique for making an antemortem diagnosis.
AIDS-Related Opportunistic Infections↗
Anti-inflammatory actions of the neuroimmunomodulator alpha-MSH.
alpha-melanocyte-stimulating hormone (alpha-MSH) is an endogenous neuroimmunomodulatory peptide that inhibits fever and all major forms of experimental inflammation. In humans, concentrations of alpha-MSH are increased at sites of inflammation, and in plasma in inflammatory disorders and after infection of endotoxin. The effects of this 'anti-cytokine' peptide are mediated through alpha-MSH receptors and regulatory circuits in macrophages and neutrophils, and through descending neural anti-inflammatory pathways that originate from alpha-MSH receptors on neurons within the brain.
Animals↗
alpha-MSH modulates experimental inflammatory bowel disease.
The mechanisms underlying inflammatory bowel disease (IBD) remain obscure but the importance of inflammatory processes is clear and most pharmacological therapies inhibit inflammation. The search for more effective agents with low toxicity continues. To test the possibility that the antiinflammatory/anticytokine peptide alpha-MSH can be used to control IBD, the peptide was administered to a murine colitis model. The peptide treatment had marked salutary effects: it reduced the appearance of fecal blood by over 80%, inhibited weight loss, and prevented disintegration of the general condition of the animals. Mice given alpha-MSH showed markedly lower production of TNF alpha by tissues of the lower colon stimulated with concanavalin A; the inhibitory effect of alpha-MSH on production of inflammatory nitric oxide by lower bowel tissue was even greater. The combined results indicate that alpha-MSH modulates experimental IBD, perhaps by inhibiting production within the gut of the local proinflammatory agents TNF alpha and nitric oxide, or by inhibiting inflammatory processes closely linked to these mediators.
Animals↗
Cytokine antagonists in aged subjects and their relation with cellular immunity.
Host responses to infectious and inflammatory stimuli are altered with aging. Because cytokines and their antagonists are significant factors in these host responses, the present research on aged subjects was designed to investigate plasma concentrations of the cytokines interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) and those of their antagonists IL-1 receptor antagonist (IL-1ra) and soluble TNF receptor (sTNFr). For this research, 122 apparently healthy aged subjects (79.6 +/- 5.8 yr), 39 aged individuals with documented urinary tract infections (UTIs) (81.6 +/- 6.3 yr), and 100 young controls (39.32 +/- 11.2 yr) were included. Plasma IL-1 beta, TNF alpha, IL-1ra, sTNFr (55 kDa), and neopterin were measured using enzyme-linked immunosorbent assay techniques. In subsets of normal aged subjects and UTI patients, we investigated relations between plasma concentrations of cytokine antagonists and IL-2 production by phytohemagglutinin-stimulated peripheral blood mononuclear cells. The results show that plasma concentrations of both IL-1ra and sTNFr were greater in healthy aged subjects than in young controls. Plasma neopterin, a product of activated monocytes/macrophages, was likewise elevated in the aged. IL-1 and TNF were not detectable in the majority of plasma samples. There was a positive correlation between neopterin concentration and both IL-1ra and sTNFr. There was a significant negative correlation between plasma IL-1ra and IL-2 production by phytohemagglutinin-stimulated peripheral blood mononuclear cell in healthy aged subjects. IL-1ra and sTNFr concentrations were significantly greater in patients with UTI than in the healthy aged subjects. In UTI patients IL-2 production in vitro was lower than in healthy subjects, but there was no significant correlation with IL-1ra in plasma. Therefore, plasma concentrations of cytokine antagonists are increased in plasma of apparently healthy aged subjects. Elevated concentrations of neopterin suggest that this increase can be traced to monocyte activation. The negative correlation between plasma IL-1ra and IL-2 production in vitro suggests that enhancement of this cytokine antagonist can contribute to immunodepression of aging. We propose that unapparent infections in aged subjects cause monocyte activation and release of cytokine antagonists. These cytokine antagonists reduce IL-2 production and the capability of T cells to proliferate, thereby inhibiting responses in the elderly.
Adult↗
Post-exercise cutaneous hyperaemia resulting from local exercise of an extremity.
Large changes in skin blood flow occur after exercise. Most studies have concentrated on the systemic effects of vigorous exercise on skin blood flow. We were interested in the post-exercise response in the neighbourhood of focal exercise. We used a painless neuromuscular electronic stimulator to exercise the muscles of the forearm, producing flexion of the fingers. There was no change in blood pressure and only a small increase in heart rate during this exercise. We measured blood flow during a 5-min pre-exercise period and a 5-min post-exercise period at the forearm, at the dorsum of the index finger and on the pad of the index finger. We also measured values on the contralateral non-exercised extremity during exercise as well as during matched time periods in control experiments with no exercise. Exercise did elicit an increased blood flow in the post-exercise period at all three sites compared with the control experiments with no exercise and on the contralateral extremity. For example, the increase in blood flow at the finger dorsum was 2.1 +/- 0.1 ml (min 100 g)-1 after exercise compared with -0.08 +/- 0.09 ml min-1 100 g-1 during the control experiment and 0.1 +/- 0.1 ml (min 100 g)-1 on the contralateral arm (all P < 0.01). The local application of heat at the site of blood flow monitoring produced a substantial increase in the post-exercise response at the two finger locations [27.4 +/- 0.4 ml (min 100 g)-1 at the finger dorsum], but not at the arm. This is the first demonstration that highly focal exercise, unaccompanied by a systemic haemodynamic response, can elicit a post-exercise cutaneous hyperaemia. Local heating produced a large synergistic increase in the post-exercise hyperaemia at sites with arteriovenous microvascular perfusion but not at sites with primarily nutritive perfusion. These findings show that local vasoregulatory changes occur in response to exercise, even in the absence of whole-body haemodynamic and thermal change.
Arm↗
Conservative surgical treatment for a giant thoracoabdominal benign teratoma.
The authors describe an adult patient with a giant, cystic teratoma (33 x 22 x 18 cm) involving the posterior mediastinum and retroperitoneum. A conservative surgical approach consisting of a partial endocystectomy plus injections of tetracycline into the residual cavity, was performed. Two months after surgery, a CT scan showed a 6 x 5 x 3 cm residual cyst. The authors believe that the excision of the inner surface of the cystic lesion and the intracystic administration of tetracycline, may successfully prevent the accumulation of fluid which is the main cause of the progressive enlargement of such benign cystic teratomas.
Humans↗