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91.
Giuseppe Micieli Marco Magri Giorgio Sandrini Cristina Tassorelli Giuseppe Nappi 《Cephalalgia : an international journal of headache》1988,8(3):193-201
In this study the variations in pupil diameter induced by different stimuli (dark-light adaptation, light reflex, electric stimulation of the sural nerve) were investigated in episodic (in the active or remission phases) and in chronic cluster headache (CH) patients. Pupil size monitoring was performed with a monocular, infrared TV pupillometer, and sural nerve stimuli were applied after the pain threshold had been measured as the flexion reflex threshold of the biceps femoris muscle (RIII reflex). The results were compared with those obtained in patients with "peripheral" (third neuron) Horner's syndrome and in healthy sex- and age-matched controls. On the symptomatic side we found an impairment of pupil response to light flashes and nociceptive stimuli; similar findings were sometimes evident on the pain-free side, too. These results substantiate previous observations that in cluster headache a dysfunction of the integrative central nervous system pathways also exists intercritically and mostly bilaterally, involving both autonomic regulation and pain perception mechanisms. 相似文献
92.
Garcea Renato; Danio Lucia; Frassetto Serenella; Cozzolino Patrizia; Ruggiu Maria E.; Vannini Maria G.; Pascale Rosa; Lenzerini Luciano; Simile Maria M.; Puddu Marco; Feo Francesco 《Carcinogenesis》1988,9(6):931-938
The effect of dehydroepiandrosterone (DHEA) on the activityof NADPH-producing enzymes and the development of enzyme-alteredfoci has been investigated in the liver of female Wistar ratssubjected to an initiating treatment (a necrogenic dose of diethylnitrosaimine)followed, 15 days later, by a selection treatment [a 15-dayfeeding of a diet containing 0.03% 2-acetylamlnofluorene (2-AAF),with a partial hepatectomy at the midpoint of this feeding].At the end of the selection treatment all rat groups received,for 15 days, a basal diet containing, when indicated, 0.05%phenobarbital (PB) and/or 0.6% DHEA. The effect of DHEA on theactivity of NADPH producing enzymes was also studied in normalrats fed, for 15 days, a diet containing 0.6% DHEA and in theirpair-fed controls. DHEA caused a 4358% inhibition ofglucose-6-phosphate dehydrogenase (G6PD) and, respectively,338420% and 2124% increases in malic enzyme (ME)and isocitric dehydrogenase activities in all rat groups. Thiswas coupled with a great fall in the production of ribulose-5-phosphate,while no change in NADP+/NADPH ratio occurred. Hepatocytes,isolated from DHEA-treated rats, exhibited a very low activityof hexose monophosphate shunt (HMS), which was not stimulatedby methylene blue, an exogenous oxidizing agent that markedlystimulated HMS activity in control hepatocytes. DHEA causeda great fall in the percentage of liver occupied by -glutamyltranspeptidase(GGT)-positive foci, in the rats subjected to the initiation- selection treatments. PB enhanced the development of thesefoci, an effect which was completely overcome by DHEA. In addition,focal cells no longer expressed a G6PD activity higher thanthat of surrounding liver in DHEA-treated rats, but exhibiteda high histochemical reaction for ME. DHEA also caused a greatfall in labelling index of GGT-positive foci. Starting at theend of 2-AAF feeding, a mixture of ribonucleosides (RNs) ofadenine, cytosine, guanine and uracil and of deoxyribonucleosides(DRNs) of adenine, cytosine, guanine and thymine were injectedi.p. every 8 h for 12 days to the rats subjected to the initiation- selection treatments plus PB. Rats were killed 3 days afterthe end of RN and DRN treatments. These treatments completelyovercome the DHEA effect on the development of GGT-positivefoci and DNA synthesis by the focal cells, without affectingG6PD activity of both whole liver and putative preneoplasticfoci. Experiments with labeled nucleosides revealed that RNsand DRNs produced derivatives that were incorporated into liverDNA. These data indicate that liver of DHEA-treated rats produceenough NADPH for reduction of RNs to DRNs and growth. The antipromotingeffect of DHEA could depend on a relative deficiency of nudeosidesfor DNA synthesis, caused by a great fall in pentose phosphateproduction. 相似文献
93.
Testa Rodolfo Abbiati Gianalfredo Ceserani Roberto Restelli Gianvico Vanasia Alessandro Barone Domenico Gobbi Marco Mennini Tiziana 《Pharmaceutical research》1989,6(7):571-577
A series of 21 neuroleptics with different chemical structures (phenothiazines, thioxanthenes, dibenzodiazepines, butyrophenones, benzamides, etc.) was examined for their in vitro interactions with 12 neurotransmitter binding sites in the rat brain (alpha- and beta-noradrenergic, dopaminergic, muscarinic, serotoninergic, histaminic, and opioid receptors, calcium channels, and serotonin uptake binding sites). The biochemical profile obtained from the binding data was compared with reported pharmacological and clinical profiles for this class of compounds by cluster analysis. Cluster analysis on binding data classified the compounds in three main subgroups: benzamides, compounds with an affinity mainly for DA2 and 5-HT2 receptors and inactive at muscarinic receptors, and compounds with a high affinity for alpha 1-adrenergic receptors and muscarinic receptors. The main subgroups resulting from cluster analysis of previously published pharmacological and clinical data for neuroleptics contain compounds common to the present study, with some correlations. The results extend previous observations that a complete binding profile corresponds to the pharmacological and clinical profile of this class of compounds. 相似文献
94.
Carmine M. Carapella Marco G. Paggi Fabio Cattani Giovanni B. Ciottoli Aristide Floridi Bruno Iandolo Laura Raus Antonio Riccio Antonio Caputo 《Journal of neuro-oncology》1989,7(1):103-108
Summary Up-to-date unsatisfactory results obtained in multimodality treatments of malignant glioma have prompted the research of new therapeutic modalities with unconventional modes of action. Lonidamine (LND) is a drug which reduces aerobic glycolytic activity in both human and experimental tumors. This effect mainly depends on the inhibition of mitochondrially-bound hexokinase (HK) which is present in large amounts in malignant cells. A Phase II study was conducted on patients with recurrent glioma; 12 patients were admitted to the study. Clinical side effects were moderate, necessitating a reduction of the dosage in only 1 case. The objective results were evaluated according to the indications of Levin. 2 responders and 3 cases of stable disease were observed out of 10 evaluable patients. The potential value of this new drug is discussed. 相似文献
95.
Preservation and redirection of HPV16E7-specific T cell receptors for immunotherapy of cervical cancer 总被引:6,自引:0,他引:6
Scholten KB Schreurs MW Ruizendaal JJ Kueter EW Kramer D Veenbergen S Meijer CJ Hooijberg E 《Clinical immunology (Orlando, Fla.)》2005,114(2):119-129
Human papilloma virus (HPV) type 16 infections of the genital tract are associated with the development of cervical cancer (CxCa) in women. HPV16-derived oncoproteins E6 and E7 are expressed constitutively in these lesions and might therefore be attractive candidates for T-cell-mediated adoptive immunotherapy. However, the low precursor frequency of HPV16E7-specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer. To overcome this problem, we have isolated T cell receptor (TCR) genes from four different HPV16E7-specific healthy donor and patient-derived human cytotoxic T lymphocyte (CTL) clones. We examined whether genetic engineering of peripheral blood-derived CD8+ T cells in order to express HPV16E711-20-specific TCRs is feasible for adoptive transfer purposes. Reporter cells (Jurkat/MA) carrying a transgenic TCR were shown to bind relevant but not irrelevant tetramers. Moreover, these TCR-transgenic Jurkat/MA cells showed reactivity towards relevant target cells, indicating proper functional activity of the TCRs isolated from already available T cell clones. We next introduced an HPV16E711-20-specific TCR into blood-derived, CD8+ recipient T cells. Transgenic CTL clones stained positive for tetramers presenting the relevant HPV16E711-20 epitope and biological activity of the TCR in transduced CTL was confirmed by lytic activity and by interferon (IFN)-gamma secretion upon antigen-specific stimulation. Importantly, we show recognition of the endogenously processed and HLA-A2 presented HPV16E711-20 CTL epitope by A9-TCR-transgenic T cells. Collectively, our data indicate that HPV16E7 TCR gene transfer is feasible as an alternative strategy to generate human HPV16E7-specific T cells for the treatment of patients suffering from cervical cancer and other HPV16-induced malignancies. 相似文献
96.
Derothe JM Porcherie A Perriat-Sanguinet M Loubès C Moulia C 《Parasitology research》2004,93(5):356-363
The susceptibility to Aspiculuris tetraptera of European Mus musculus hybrids is thought to reflect the disruption of genomic co-adaptation through recombination of the parental genomes. Here, we compared the susceptibility to this parasite between parents and experimental hybrids (intersubspecific until F4, intrasubspecific F1, F2) to clarify the contributions of heterosis and subspecies incompatibility. F1 showed hybrid vigor. Unlike intrasubspecific F2, intersubspecific F2 were less resistant than F1, but revealed no increased susceptibility relative to the parents. Intersubspecific F3 and F4 showed the same hybrid vigor as F1. Heterosis contributed most to the resistance, but the differences between intra- and intersubspecific F2 suggested genomic incompatibilities between subspecies. However, the susceptibility did not increase through the recombination process, showing that disruption of co-adaptation does not directly affect resistance. Even if previous studies still support the selective role of parasites in the current hybrid zone, an alternative hypothesis on the origin of hybrid susceptibility is warranted. 相似文献
97.
Chiara Leoni Elizabeth Katherine Anna Triumbari Catello Vollono Roberta Onesimo Maria Podagrosi Valentina Giorgio Eliza Kuczynska Stefania Veltri Marco Tartaglia Giuseppe Zampino 《American journal of medical genetics. Part A》2019,179(6):940-947
Pain in individuals with RASopathies is a neglected topic in literature. In this article, we assessed prevalence and profile of pain in a sample of 80 individuals affected by RASopathies. The study sample included individuals with Noonan syndrome (N = 42), Costello syndrome (N = 17), and cardio‐facio‐cutaneous syndrome (N = 21). A set of standardized questionnaires and scales were administered (VAS/numeric scale, r‐FLACC, Wang‐Baker scale, NPSI, BPI, NCCPC‐R) to detect and characterize acute and chronic pain and to study the influence of pain on quality of life (PEDs‐QL, SF‐36) and sleeping patterns (SDSC); revision of past medical history and multisystemic evaluation was provided. Available clinical data were correlated to the presence of pain. High prevalence of acute (44%) and chronic (61%) pain was documented in the examined sample. Due to age and intellectual disability, acute pain was localized in 18/35 individuals and chronic pain in 33/49. Muscle‐skeletal and abdominal pain was more frequently reported. The intensity of acute and chronic pain interfered with daily activities in 1/3 of the sample. Pain negatively impacted on QoL and sleeping patterns. This work documents that pain is highly prevalent in RASopathies. Future studies including subjective and objective measures of pain are required to discriminate a somatosensory abnormality from an abnormal elaboration of painful stimuli at a central level. 相似文献
98.
Busse A Sánchez MA Monterroso V Alvarado MV León P 《American journal of medical genetics. Part A》2004,(2):190-194
Four affected siblings in a Costa Rican family presented an aggressive polyneuropathy with widespread involvement of many visceral organs and onset during the third decade of life with rapid loss of muscle mass in the lower limbs and severe dysautonomy. The medical histories include vitreous opacity, cardiac enlargement, dermal and gastrointestinal infiltration, and autonomic dysfunction including circulatory compromise and gastrointestinal disturbances. Histological studies using Congo red stain and immunohistochemical assays with antibodies against the transthyretin (TTR) protein showed widespread deposition of amyloid in extracellular areas, including dermis and gastrointestinal lamina propia, endo- and perineural spaces, and vascular walls. A mutation search in the transthyretin (ttr) gene was performed seeking the cause of this severe form of familial amyloidotic polyneuropathy (FAP). We applied single-stranded conformational polymorphism (SSCP)-analyses followed by sequencing of the four exons of the ttr gene, revealing a point mutation in exon 3, a G to A transition that causes a Glu54Lys codon change. Western blots of plasma proteins incubated with anti-transthyretin antibodies after gel electrophoresis provided separation of wild-type and mutant TTR protein in affected family members. 相似文献
99.
Vasculogenic mimicry has no prognostic significance in pT3 and pT4 cutaneous melanoma 总被引:4,自引:0,他引:4
Massi D Franchi A Paglierani M Ketabchi S Borgognoni L Reali UM Santucci M 《Human pathology》2004,35(4):496-502
The concept of vasculogenic mimicry has been introduced to define periodic acid-Schiff (PAS)-positive channels and loops lined by tumor cells, instead of endothelium, able to contribute to microcirculation in uveal melanomas. Previous studies have shown that the PAS-positive patterns are associated with a poor prognosis in uveal melanoma. The aim of the current study was to investigate whether vasculogenic mimicry has a prognostic impact in pT3 and pT4 cutaneous melanoma. Fifteen patients with pT3 and pT4 cutaneous melanoma who did not experience progression after 10 years of follow-up and 30 matched controls who underwent progression were selected. Tumor sections were stained with PAS reaction, omitting the nuclear counterstaining. For immunohistochemistry, sections were stained with CD31, CD105 (endoglin), and laminin. Differences in the distribution of the PAS-positive patterns and a series of clinicopathological variables were evaluated by the Pearson chi(2) and Mann-Whitney U tests. We observed PAS-positive linear sheets, arcs, elliptical loops, and networks encircling roundish to oval aggregates of melanoma cells. The overall distribution of the PAS-positive patterns did not match with the blood microvessels' architecture as detected by immunohistochemical analysis. No statistically significant differences in the distribution of PAS-positive patterns were found between cases and controls. The presence of a parallel pattern correlated significantly with thickness (P = 0.04), whereas an inverse correlation was found with vessel area (P = 0.05). In conclusion, our results suggest that there is a mismatch between vasculogenic mimicry and tumor angiogenesis and do not support any prognostic role of vasculogenic mimicry in thick cutaneous melanoma. 相似文献
100.
Tezak Z Prandini P Boscaro M Marin A Devaney J Marino M Fanin M Trevisan CP Park J Tyson W Finkel R Garcia C Angelini C Hoffman EP Pegoraro E 《Human mutation》2003,21(2):103-111
Complete laminin alpha2 (LAMA2) deficiency causes approximately half of congenital muscular dystrophy (CMD) cases. Many loss-of-function mutations have been reported in these severe, neonatal-onset patients, but only single missense mutations have been found in milder CMD with partial laminin alpha2 deficiency. Here, we studied nine patients diagnosed with CMD who showed abnormal white-matter signal at brain MRI and partial deficiency of laminin alpha2 on immunofluorescence of muscle biopsy. We screened the entire 9.5 kb laminin alpha2 mRNA from patient muscle biopsy by direct capillary automated sequencing, single strand conformational polymorphism (SSCP), or denaturing high performance liquid chromatography (DHPLC) of overlapping RT-PCR products followed by direct sequencing of heteroduplexes. We identified laminin alpha2 sequence changes in six of nine CMD patients. Each of the gene changes identified, except one, was novel, including three missense changes and two splice-site mutations. The finding of partial laminin alpha2 deficiency by immunostaining is not specific for laminin alpha2 gene mutation carriers, with only two patients (22%) showing clear causative mutations, and an additional three patients (33%) showing possible mutations. The clinical presentation and disease progression was homogeneous in the laminin alpha2-mutation positive and negative CMD patients. 相似文献