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Biomedical subjects

S Ferri

Publications and source records attributed to S Ferri.

At least 55 records · Page 3Linked to original sources

Cerebrospinal alterations of immunoreactive dynorphin A after unilateral dorsal rhizotomy in the rat.

Possible alterations of immunoreactive dynorphin A (ir-dyn A) were investigated at different levels of the spinal cord and in discrete brain regions of male rats 10, 30 and 60 days after unilateral dorsal rhizotomy, i.e., during the development of deafferentation pain and autotomy behavior that follows afferent nerve interruption. Dorsal rhizotomy caused an increase of spinal ir-dyn A at 10 days in the cervical segment; subsequent assays showed a progressive increase in other spinal regions too. At the last observation, 60 days after rhizotomy, neuropeptide levels were still significantly higher than in sham-lesioned animals in the cervical, thoracic and lumbosacral spinal cord. The spinal ir-dyn A changes were both ipsi- and contralateral to the lesion. No alterations were found in the brainstem and midbrain and a not significant decrease was observed in the hypothalamus. In the striatum and cortex, however, there was a bilateral significant increase 30 days after surgery and a constant and significant elevation was detected in the hippocampus at all three intervals. These data cast additional light on the neurochemical changes caused by the interruption of afferent nerves, followed by development of the deafferentation pain syndrome in laboratory animals and human beings. They also support the concept of central neuroplasticity in pathological pain and indicate that the opioid neuropeptide dynorphin is involved.

Analysis of Variance↗

Frontal lobe dysfunction in schizophrenia and obsessive-compulsive disorder: a neuropsychological study.

Converging evidence suggests there is a specific role of dorso-lateral-prefrontal cortex (DLPC) in schizophrenic disorders and of orbito-frontal cortex (OFC) in obsessive-compulsive disorder (OCD). Here, 25 schizophrenic and 25 OCD patients were evaluated with Wisconsin Card Sorting Test and Object Alternation Test; neuropsychological tools sensitive to DLPC and OFC damage, respectively; and compared with 25 subjects of a control group. Moreover, they all underwent Weigl's Sorting Test and the Word Fluency Test to assess global frontal functioning. The results indicated a DLPC deficit in schizophrenia and an OFC involvement in OCD. These data suggest that functional disorders of the central nervous system can be explored with neuropsychological instruments.

Adult↗

Dactylitis with pitting oedema of the hand in longstanding ankylosing spondylitis.

The case of a patient with seronegative spondyloarthropathy showing oligoarthritis of the hand together with large pitting oedema is reported. Unlike the patients with late onset peripheral spondyloarthropathy described by Dubost and Sauvezie who show minimal involvement of the axial skeleton, the patient has been suffering from AS for about twenty years.

Edema↗

Late onset undifferentiated seronegative spondyloarthropathy.

OBJECTIVE: To define the clinical spectrum of late onset undifferentiated seronegative spondyloarthropathy (uSpA) based on a large number of patients. METHODS: All consecutive patients older than 45 years at the onset of SpA and not meeting criteria for any of the definite categories of the SpA complex seen in the 1988-1993 period were entered in a special register and were followed prospectively. RESULTS: Twenty-three patients (mean age at onset 56.9, range 46-72; mean age at the last visit 61.7, range 48-79) were studied. Of these, 12 had 3 or more clinical and/or radiological manifestations of SpA, while 7 showed only 2, and 4 only one. Of the 10 patients with peripheral arthritis, only 3 had the large pitting edema of the lower limbs described by Dubost and Sauvezie. Of the 4 patients with only one manifestation, 2 had peripheral enthesitis and 2 acute anterior uveitis. CONCLUSION: The clinical spectrum of late onset uSpA is as wide as in children and young and middle aged adults.

Age of Onset↗

Binding profile of benextramine at neuropeptide Y receptor subtypes in rat brain areas.

Binding studies in rat whole brain, frontoparietal cortex and brainstem membrane preparations revealed that benextramine displaced [3H]neuropeptide Y specific binding from a low and a high affinity site with IC50 values in the microM (36 +/- 2, 4.4 +/- 1.4 and 300 +/- 120 microM, respectively) and the pM (29.3 +/- 12.1, 0.35 +/- 0.11 and 0.42 +/- 0.03 pM, respectively) range, whereas in rat hippocampus benextramine displaced [3H]neuropeptide Y specific binding from one site only with an IC50 value of 22.8 +/- 5.7 microM. With the exception of frontoparietal cortex binding assay, benextramine was not able to completely inhibit [3H]neuropeptide Y specific binding revealing the presence of a benextramine nonsensitive third binding site. Benextramine pretreatment followed by membrane washing demonstrated that benextramine inhibited irreversibly both high and low affinity sites.

Adrenergic alpha-Antagonists↗

Structure of a myristoyl-ACP-specific thioesterase from Vibrio harveyi.

The crystal structure of a myristoyl acyl carrier protein specific thioesterase (C14ACP-TE) from a bioluminescent bacterium, Vibrio harveyi, was solved by multiple isomorphous replacement methods and refined to an R factor of 22% at 2.1-A resolution. This is the first elucidation of a three-dimensional structure of a thioesterase. The overall tertiary architecture of the enzyme resembles closely the consensus fold of the rapidly expanding superfamily of alpha/beta hydrolases, although there is no detectable homology with any of its members at the amino acid sequence level. Particularly striking similarity exists between the C14ACP-TE structure and that of haloalkane dehalogenase from Xanthobacter autotrophicus. Contrary to the conclusions of earlier studies [Ferri, S. R., & Meighen, E. A. (1991) J. Biol. Chem. 266, 12852-12857] which implicated Ser77 in catalysis, the crystal structure of C14ACP-TE reveals a lipase-like catalytic triad made up of Ser114, His241, and Asp211. Surprisingly, the gamma-turn with Ser114 in a strained secondary conformation (phi = 53 degrees, psi = -127 degrees), characteristic of the so-called nucleophilic elbow, does not conform to the frequently invoked lipase/esterase consensus sequence (Gly-X-Ser-X-Gly), as the positions of both glycines are occupied by larger amino acids. Site-directed mutagenesis and radioactive labeling support the catalytic function of Ser114. Crystallographic analysis of the Ser77-->Gly mutant at 2.5-A resolution revealed no structural changes; in both cases the loop containing the residue in position 77 is disordered.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Inhibition of proopiomelanocortin expression by an oligodeoxynucleotide complementary to beta-endorphin mRNA.

Gene expression in mammalian cells can be suppressed by oligonucleotides complementary to the target mRNA. This strategy was explored as a means of arresting translation of the prohormone precursor proopiomelanocortin (POMC), used as a model system of peptide messengers that are synthesized and released from endocrine and neuronal cells. The synthesis of the POMC-derived peptides adrenocorticotropin (ACTH) and beta-endorphin (beta-END) was markedly reduced by an oligodeoxynucleotide (ODN) complementary to a region of beta-END mRNA in AtT-20 cells, which retain many of the differentiated phenotypes of corticotrophs; this treatment did not affect the steady-state levels of POMC mRNA. Antisense ODN was stable in cell culture medium for 24 h, and cellular uptake was low (approximately 2.5% of the added ODN); however, the intracellular levels of the ODN were sufficient to form a ribonuclease-resistant duplex with complementary cellular mRNA. Addition of ODN to the cell culture did not affect the cellular levels of chromogranin A-(264-314)/pancreastatin or cell viability and proliferation, as evidenced by bromodeoxyuridine incorporation and ornithine decarboxylase activity. Microinfusion of the antisense ODN in the rat hypothalamic arcuate nucleus, where the majority of POMC-positive brain perikarya are located, significantly reduced ACTH- and beta-END-immunopositive neurons, and antisense ODN-treated rats showed substantially less of the grooming behavior usually observed in a novel environment.

Animals↗

Effect of omega-conotoxin and verapamil on antinociceptive, behavioural and thermoregulatory responses to opioids in the rat.

This study with the rat evaluated the contribution of omega-conotoxin GVIA-(omega-CgTx) and verapamil-sensitive Ca2+ channels in behavioural, antinociceptive and thermoregulatory responses to intracerebroventricular (i.c.v.) injection of [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) and dynorphin A-(1-17), which are selective agonists for putative mu, delta and kappa-opioid receptors, respectively. The rats treated with omega-CgTx (8-32 pmol i.c.v.) showed transient, dose-dependent shaking behaviour, hyperalgesia and hypothermia which gradually disappeared within 4 h. The behaviour of the rats was normal by 24 h. Histological examination of brain sections showed morphological alterations of neurons in the hippocampus, medial-basal hypothalamus and pyriform cortex. antinociception, catalepsy and thermoregulatory responses elicited by DAMGO (0.4 and 2.0 nmol) were significantly prolonged and potentiated by verapamil (20 pmol i.c.v. 15 min before) or omega-CgTx (8 pmol 24 h before). Antinociception and hypothermia induced by DPDPE were antagonized by verapamil and omega-CgTx, whereas only omega-CgTx prevented the behavioural arousal observed after DPDPE. Similarly, hypothermia induced by dynorphin A-(1-17) (5.0 nmol) and by the kappa-opioid receptor agonist U50,488H (215 nmol) was antagonized by the two Ca2+ channel blockers but only omega-CgTx prevented the barrel rolling and bizarre postures caused by the opioid peptide.

Analgesia↗

An assessment of the Wisconsin Card Sorting Test as an indicator of liability to schizophrenia.

In order to test the hypothesis that a poor performance in the Wisconsin test (WCST) may be an indicator of liability to schizophrenia, we compared the WCST performances of patients with DSM III-R schizophrenia, normal controls, and patients with schizotypal personality disorder (SZT PD). While schizophrenic patients performed significantly worse than subjects in the other two groups, schizotypal and normal subjects showed no significant differences in the WCST execution. Moreover, patients with SZT PD with or without positive family history for the schizophrenic spectrum had similar WCST performances. Our observations are in keeping with other studies employing the WCST in paradigms of heightened liability to schizophrenia, and suggest that a poor performance in the test is more probably a feature of the disease process, than a trait marker of vulnerability to the illness demonstrable in high-risk subjects.

Adult↗

[Not Available].

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History, 20th Century↗

Pathology from hydroxyapatite deposits in periarticular tissues. First conclusions on etiopathogenesis.

Biopsies of periarticular tissues from patients with episodes of chronic periarthritis were examinated by histological, ultrastructural and chemico-crystallographic methods. In all samples the mineralogical observations at the optical microscope, showed aggregates of microcrystalline incrustations, whose ultrastructural morphology has been characterized by SEM. The histological observations showed necrosis of collagen fibres and microcrystallization process in cavities and in metaplastic fibrocartilage. The HA deposits in the periarticular tissues, in the next stage of the process, are surrounded and demolished by macrophages and multinucleated giant cells. At the same time granulation tissue carries out the repair process, that begins with the formation of thin parallel collagen fibers interposed with many fibroblasts and numerous small vessels.

Biopsy↗

Non-peptide ligands for opioid receptors. Design of kappa-specific agonists.

A series of phenyl carboxyl esters 5a-d derived from N-(cyclopropylmethyl)normetazocine was synthesized and evaluated for its selectivity at mu, kappa, and delta opioid receptors. Compound 5a, although 43 times less potent than the reference compound U50488, was specific for kappa receptors, having no detectable affinity for either mu or delta receptors. Greater binding affinity was seen with the diastereoisomer having the 1'R,2'S stereochemistry in the cyclopropyl ring of the nitrogen substituent, which was only 12 times less active than U50488. Antinociceptive activity in the mouse tail flick was only slightly lower than that of U50488 (ED50 = 7.66 vs 4.52 mg/kg). Naloxone fully prevented antinociception induced by (1'R,2'S)-5a at the doses of 2.0 mg/kg. Compound (1'R,2'S)-5a is one of the most kappa-selective non-peptide compounds reported to date. The implications of these results in terms of requirements for kappa ligands are discussed.

Animals↗

Ca2+ channel blocking activity of lacidipine and amlodipine in A7r5 vascular smooth muscle cells.

Inhibition of the K(+)-stimulated increase in cytosolic free Ca2+ by a series of 1,4-dihydropyridines was evaluated in A7r5 vascular smooth muscle cells loaded with the fluorescent Ca2+ indicator fura-2 acetoxymethyl ester. The IC50 of the drugs, added to suspended cells 3 min before 150 mM KCl, gave the following order of potency: lacidipine (2.76 nM) > nitrendipine (3.81 nM) > amlodipine (4.56 nM) > nifedipine (10.08 nM). A7r5 cells were also exposed to the 1,4-dihydropyridines, at their IC50, for 25 min, and then repeated washout cycles were performed before adding KCl. The Ca2+ channel blocking activity of nifedipine and nitrendipine gradually diminished, disappearing after four washout cycles 25, 55, 115 and 175 min after drug treatment. Amlodipine and lacidipine displayed slow onset and offset of antagonism, their activity becoming stronger with time, in spite of the repeated washes. [3H]Lacidipine was avidly and promptly entrapped in A7r5 cells and was not removed by washout. However, its potency as a Ca2+ channel blocker was not directly related to the amount of drug locked in the cell since it increased with time, indicating that lacidipine binds to the lipid bilayer of the cell membrane and then gradually diffuses towards a specific binding site. This model can, therefore, predict the Ca2+ blocking properties of 1,4-dihydropyridines with slow onset and offset of antagonism and could be employed to evaluate compounds selective for vascular smooth muscle.

Amlodipine↗