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Biomedical subjects

A Piccin

Publications and source records attributed to A Piccin.

12 recordsLinked to original sources
PubMed2007

Erythroleukaemia, diabetes insipidus and hypophyseal damage: Two case reports.

We report on two cases of patients who developed diabetes insipidus (DI) before acute erythroleukaemia (EL). A brain MRI showed an empty sella turcica in one case and hypothalamo-hypophyseal peduncle damage in the second case. Reduced levels of TGF-beta1 and Vitamin D3, with associated EVI-1 over-expression and karyotypic abnormalities were documented. These two cases show specific chromosomal/molecular alterations in EL with DI. The hypothesis of pituitary involvement in erythroleukemogenesis is discussed.

Adult↗
PubMed2005

Phenylpropanoid glycosides in Italian Orobanche spp., sect. Orobanche.

We studied the occurrence of phenylpropanoid glycosides (PhG) in five species of the genus Orobanche L., collected in the Latium region of Italy. The presence of orobanchoside and verbascoside in all four species confirms that these PhGs are taxonomic markers of the genus. The results suggest that O. gracilis form. citrina could be a diverse entity.

Classification↗
PubMed2002

Oxidative stress and TGFbeta in kidney-transplanted patients with cyclosporin-induced hypertension. Effect of carvedilol and nifedipine.

Cyclosporin is a powerful stimulator of oxidative stress signaling, leading to TGFbeta production, NO degradation, endothelial dysfunction, hypertension and post-transplant nephropathy. Carvedilol, alpha1-beta-blocker with strong antioxidant activity, may interfere with this chain of events. Therefore, we measured monocyte ecNOS, TGFbeta and heme oxygenase-1 (HO-1) mRNA level and plasma nitrite/nitrate, 3-nitrotyrosine, an estimate of peroxynitrite, and total plasma antioxidant power in kidney-transplanted patients with post-transplant hypertension, before and after treatment with carvedilol, 25 - 50 mg o.d. orally for 4 months (n = 15). The dihydropyridine calcium channel blocker nifedipine (n = 10) was used as comparator antihypertensive drug. Blood pressure fell to a similar extent with both drugs. Carvedilol increased plasma antioxidant power and HO-1 mRNA and reduced 3-nitrotyrosine and TGFbeta mRNA levels, while the same was not observed with nifedipine. Monocyte ec NOS mRNA levels and plasma nitrite/nitrate were higher in the patients than in a normotensive healthy control group and were unaffected by either treatment. In conclusion, carvedilol reduces the oxidative stress and corrects the altered cellular signaling mediated by oxidative stress in CsA-induced post-transplant hypertension. Therefore, it may prevent long-term complications, such as endothelial dysfunction, fibrogenesis and post-transplant nephropathy by decreasing NO degradation and production of TGFbeta, a key fibrogenic cytokine, and by activating HO-1 production.

Adrenergic beta-Antagonists↗
PubMed2001

Analysis of Gq protein alpha subunit mRNA expression in human monocytes: relevance of the purification step.

BACKGROUND: Galphaq is a member of the Gq family of G proteins, which by stimulating the phospholipase Cbeta (PLCbeta)-IP(3)-Ca(++) mediated intracellular signaling systems controls some of the most fundamental cardiovascular cellular processes. The study of Galphaq is complicated by the presence of a pseudogene in human DNA, with signficant homology to the mRNA encoding the alpha subunit of Gq protein. The presence of this pseudogene will cause problems when the analysis of the Galphaq gene expression is based solely on RT-PCR. In this study, we report a simple method for avoiding unwanted amplification of the Galphaq pseudogene and the use of human monocytes as a readily available source for examining Galphaq. METHODS: RT-PCR was carried out on RNA extracted from peripheral blood monocytes of 10 normal subjects using specific primers for Galphaq. RESULTS: When several subjects' Galphaq was examined, the authentic Galphaq mRNA amplification product levels, as a ratio to unpurified pseudogene containing amplification products, declined by up to approximately 70%. CONCLUSION: Given the importance of Gq protein in cardiovascular signal transduction, it is fundamental to provide a reliable assessment of G alpha q gene expression. In addition to accurately assessing Galphaq levels, the use of circulating human monocytes as a useful source of Galphaq for investigating mechanisms involved in the regulation of vascular tone is shown.

Base Sequence↗
PubMed2001

Light-dependent interaction between Drosophila CRY and the clock protein PER mediated by the carboxy terminus of CRY.

BACKGROUND: The biological clock synchronizes the organism with the environment, responding to changes in light and temperature. Drosophila CRYPTOCHROME (CRY), a putative circadian photoreceptor, has previously been reported to interact with the clock protein TIMELESS (TIM) in a light-dependent manner. Although TIM dimerizes with PERIOD (PER), no association between CRY and PER has previously been revealed, and aspects of the light dependence of the TIM/CRY interaction are still unclear. RESULTS: Behavioral analysis of double mutants of per and cry suggested a genetic interaction between the two loci. To investigate whether this was reflected in a physical interaction, we employed a yeast-two-hybrid system that revealed a dimerization between PER and CRY. This was further supported by a coimmunoprecipitation assay in tissue culture cells. We also show that the light-dependent nuclear interactions of PER and TIM with CRY require the C terminus of CRY and may involve a trans-acting repressor. CONCLUSIONS: This study shows that, as in mammals, Drosophila CRY interacts with PER, and, as in plants, the C terminus of CRY is involved in mediating light responses. A model for the light dependence of CRY is discussed.

Animals↗
PubMed2001

Efficient and heritable functional knock-out of an adult phenotype in Drosophila using a GAL4-driven hairpin RNA incorporating a heterologous spacer.

We have developed a modified RNA interference (RNAi) method for generating gene knock-outs in Drosophila melanogaster. We used the sequence of the yellow (y) locus to construct an inverted repeat that will form a double-stranded hairpin structure (y-IR) that is under the control of the upstream activating sequence (UAS) of the yeast transcriptional activator GAL4. Hairpins are extremely difficult to manipulate in Escherichia coli, so our method makes use of a heterologous 330 bp spacer encoding sequences from green fluorescent protein to facilitate the cloning steps. When the UAS-y-IR hairpin is expressed under the control of different promoter-GAL4 fusions, a high frequency of y pigment phenocopies is obtained in adults. Consequently this method for producing gene knock-outs has several advantages over previous methods in that it is applicable to any gene within the fly genome, greatly facilitates cloning of the hairpin, can be used if required with GAL4 drivers to avoid lethality or to induce RNAi in a specific developmental stage and/or tissue, is useful for generating knock-outs of adult phenotypes as reported here and, finally, the system can be manipulated to investigate the trans-acting factors that are involved in the RNAi mechanism.

Animals↗
PubMed2001

Photic entrainment of the circadian clock: from Drosophila to mammals.

Entrainment is as fundamental to an organism's circadian timing as are the molecular mechanisms involved in the functioning of the intracellular clock oscillator. In nature, one of the principle, although not the only, circadian entraining stimulus (Zeitgeber) is provided by the daily light--dark cycles. In animals, the visual processing apparatus alone is inadequate to accomplish the task of transducing circadian photic signals to the clockwork machinery. In fact, it is ever more appreciated by circadian biologists that organisms as divergent as plants and mammals have evolved a wonderfully complex array of partly redundant specializations which can guarantee the precise alignment of biological and environmental time. Research in circadian biology is cruising at such a rate that attempts to review the state of the art can only hope, at best, to provide a snapshot of the speeding cruiser from its wake. This paper will hopefully provide a reasonably sharp portrayal of what is at hand.

Animals↗
PubMed2000

The clock gene period of the housefly, Musca domestica, rescues behavioral rhythmicity in Drosophila melanogaster. Evidence for intermolecular coevolution?

In Drosophila, the clock gene period (per), is an integral component of the circadian clock and acts via a negative autoregulatory feedback loop. Comparative analyses of per genes in insects and mammals have revealed that they may function in similar ways. However in the giant silkmoth, Antheraea pernyi, per expression and that of the partner gene, tim, is not consistent with the negative feedback role. As an initial step in developing an alternative dipteran model to Drosophila, we have identified the per orthologue in the housefly, Musca domestica. The Musca per sequence highlights a pattern of conservation and divergence similar to other insect per genes. The PAS dimerization domain shows an unexpected phylogenetic relationship in comparison with the corresponding region of other Drosophila species, and this appears to correlate with a functional assay of the Musca per transgene in Drosophila melanogaster per-mutant hosts. A simple hypothesis based on the coevolution of the PERIOD and TIMELESS proteins with respect to the PER PAS domain can explain the behavioral data gathered from transformants.

Amino Acid Sequence↗
PubMed1997

Circadian rhythms: from behaviour to molecules.

In higher eukaryotes, circadian behaviour patterns have been dissected at the molecular level in Drosophila and, more recently, in the mouse. Considerable progress has been made in identifying some of the molecular components of the clock in the fly, where two genes, period (per) and timeless (tim), are essential for behavioural rhythmicity. The PER and TIM proteins show circadian cycles in abundance, and are part of a negative feedback loop with their own mRNAs. Within the pacemaker neurons, the PER and TIM products are believed to form a complex which allows them to translocate to the nucleus, but how they repress their own transcription is unclear. TIM is rapidly degraded by light, a feature which permits a compelling molecular description of both behavioural light entrainment and phase responses to light pulses. The regulation of per and tim is altered in different Drosophila tissues, however, and comparative analyses of the two genes outside the Diptera reveals further unusual patterns of tissue-specific regulation. Evolution appears to have modified the way in which the two genes are utilised to generate circadian phenotypes. More recently, the cloning of mouse clock genes, including putative per homologues, opens up exciting possibilities for mammalian molecular chronobiology.

Animals↗
PubMed1994

Big flies, small repeats: the "Thr-Gly" region of the period gene in Diptera.

The region of the clock gene period (per) that encodes a repetitive tract of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran species both within and outside the Drosophilidae. All the non-Drosophilidae sequences in this region are short and present a remarkably stable picture compared to the Drosophilidae, in which the region is much larger and extremely variable, both in size and composition. The accelerated evolution in the repetitive region of the Drosophilidae appears to be mainly due to an expansion of two ancestral repeats, one encoding a Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and asparagine or threonine. In some drosophilids the expansion involves a duplication of the pentapeptide sequence, but in Drosophila pseudoobscura both the dipeptide and the pentapeptide repeats are present in larger numbers. In the nondrosophilids, however, the pentapeptide sequence is represented by one copy and the dipeptide by two copies. These observations fulfill some of the predictions of recent theoretical models that have simulated the evolution of repetitive sequences.

Amino Acid Sequence↗
PubMedDate not supplied

Outcome of bone marrow transplantation in acquired and inherited aplastic anaemia in the Republic of Ireland.

BACKGROUND: Severe Aplastic Anaemia (SAA) and Fanconi Anaemia (FA) are rare haematological disorders characterised by pancytopenia and bone marrow hypoplasia. AIMS: We performed a retrospective study of all patients who underwent BMT for SAA and FA at St James's Hospital, Dublin, and at OLHSC, Crumlin, between 1985 and 2002. METHODS: The medical records of 63 patients, 50 with acquired SAA and 13 with FA, were reviewed. RESULTS: The median age at the time of transplant was 14 years (range 3-43 years). The actuarial survival (OS) (n = 63) was 76% at 17 years. The transplant related mortality (TRM) was 22% (n = 14). The most common cause of death was infection (46%). The survival was significantly better in patients receiving their transplant after 1995 (p = 0.002). Outcome was superior in those receiving less than 20 red cell transfusions prior to transplant: OS 91% (< 20 Units) versus 62% (> or = 20 Units). CONCLUSIONS: These national results are comparable to those of published international series and support the use of BMT in the treatment of SAA and FA. The known adverse effect of prior transfusion was confirmed.

Adolescent↗