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Biomedical subjects

P Petrou

Publications and source records attributed to P Petrou.

17 recordsLinked to original sources

Electron beam patterning of biomolecules.

The patterning of biomolecules on semiconducting surfaces is of central importance in the fabrication of novel biodevices. In the process of patterning, it is required that the biomolecule preserves its properties and the substrate is not damaged by the chemicals, the temperatures or the patterning beams involved in the procedure. Recently, both DUV and electron beam microlithography have been used in order to deposit protein layers in predefined patterns. Various approaches have been used, some involving photoresists. Contrast between exposed and unexposed regions, resolution of adjacent features and sensitivity to dose variation, are the key issues. The approach followed in this paper consists of a direct patterning of a biotin layer, deposited on an amino-silane primed silicon nitride surface, using an electron beam. After irradiation, the surface is covered by bovine serum albumin (BSA), which acts as a blocking material to protect the exposed areas from streptavidin adsorption. Using 20 keV e-beam energy and doses, in the range 100-1000 microC/cm(2), submicrometer dense lines of 1-microm pitch have been obtained. The results have been tested by fluorescence optical microscopy.

Biotin↗

The murine gene, Traube, is essential for the growth of preimplantation embryos.

Little is known about the genetic control of preimplantation development. We have isolated, characterized, and mutated a previously undescribed mouse gene, Traube (Trb), essential for preimplantation development. Similar protein coding sequences are found in rats, humans, and yeast. The TRB protein contained two amino-terminal acidic domains, a leucine zipper, and three putative nuclear localization signals. The Trb gene was expressed at low levels ubiquitously early in development and became restricted to the liver and the central nervous system from E11.5 onward. Myc-tagged TRB protein was localized to the nucleus, and in a large proportion of the cells to the nucleoli. The Trb mutant embryos halted in development at the compacted morula stage at E2.5. At E3.5 they started to decompact and a day later they disintegrated and died. The observed defect was cell autonomous, as mutant cells failed to participate in the formation of chimeric embryos. The Trb mutant embryos showed a 50% reduction of the total cell number. The mutant embryos exhibited a paucity of ribosomes, polyribosomes, and rough endoplasmic reticulum. This paucity of ribosomes together with the localization of TRB to the nucleoli, the site of ribosome synthesis, suggests that TRB is involved in the synthesis of ribosomes.

Alleles↗

Perturbations of arginine vasopressin secretion during inflammatory stress. Pathophysiologic implications.

Pro-inflammatory cytokines, such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha), released from inflammatory foci, can activate the hypothalamus to produce corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP). These hypothalamic peptides in synergy increase ACTH production by the pituitary gland and hence corticosteroid (CS) secretion by the adrenal cortices. CS dampens inflammation. The pituitary also produces prolactin (PRL), which is pro-inflammatory, and macrophage inhibitory factor (MIF), which by counteracting the anti-inflammatory and immunosuppressive effects of CS, is pro-inflammatory. Lewis rats develop a variety of induced-autoimmune inflammatory conditions, such as streptococcal cell wall arthritis, whereas the histocompatible F344 Fisher rats are resistant to this condition. Lewis rats have a defective hypothalamic-pituitary adrenal (HPA) response to a variety of hypothalamic stimuli, but have augmented systemic secretion of AVP. Patients with rheumatoid arthritis (RA) have deficient CS with exaggerated PRL responses to inflammatory stimuli. Within inflammatory foci, CRH is pro-inflammatory. AVP, which augments autologous mixed lymphocyte reactions, can replace the IL-2 requirement for gamma IFN production by T cells via V1a receptors, and potentiates primary antibody responses, is also pro-inflammatory. Lewis rats have significantly high plasma levels, hypothalamic content, and in vitro release of AVP in comparison to the inflammatory disease-resistant Fischer rats. Immunoneutralization of AVP attenuates inflammatory responses. In Sprague-Dawley rats, AVP potentiates PRL secretion. Preliminary studies in patients with RA have shown that the circulating levels of AVP are significantly increased, which might be a compensatory response to low CS levels or a result of elevated levels of IL-6 in these patients but could nevertheless contribute to rheumatoid inflammation. A similar observation has been made in patients with ankylosing spondylitis.

Animals↗

Taube nuss is a novel gene essential for the survival of pluripotent cells of early mouse embryos.

The cells of the inner cell mass constitute the pluripotent cell population of the early embryo. They have the potential to form all of the tissues of the embryo proper and some extra-embryonic tissues. They can be considered a transient stem cell population for the whole of the embryo, and stem cells maintaining the same capacity can be isolated from these cells. We have isolated, characterised and mutated a novel gene, taube nuss (Tbn), that is essential for the survival of this important cell population. The taube nuss protein sequence (TBN) was highly conserved between human, mouse, Xenopus laevis, Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thaliana, particularly in a domain that is not present in any published proteins, showing that TBN is the founding member of a completely new class of proteins with an important function in development. The Tbn gene was expressed ubiquitously as early as E2. 5 and throughout embryonic development. It was also expressed in adult brain with slightly higher levels in the hippocampus. The Tbn mutant embryos developed normally to the blastocyst stage and contained inner cell masses. They hatched from the zonae pellucidae, implanted and induced decidual reactions, but failed to develop beyond E4.0. At this time the trophoblast cells were viable, but inner cell masses were not detectable. At E3.75, massive TUNEL-positive DNA degradation and chromatin condensation were visible within the inner cell masses, whereas the cell membranes where intact. Caspase 3 was expressed in these cells. In vitro, the inner cell mass of mutant embryos failed to proliferate and died after a short period in culture. These results indicate that the novel protein, taube nuss, is necessary for the survival of the inner cell mass cells and that inner cell mass cells died of apoptosis in the absence of the taube nuss protein. As cell pruning by apoptosis is a recognised developmental process at this stage of development, the taube nuss protein may be one of the factors regulating the extent of programmed cell death at this time point.

Amino Acid Sequence↗

Dermatoglyphics and ankylosing spondylitis.

Dermatoglyphics "the epidermal ridge configurations of the fingers, toes, palms and soles", not only help identify individuals, but have been proved to give important information about some genetic disorders. This study was aimed at finding a possible correlation between the dermatoglyphic differences in patients with ankylosing spondylitis (AS) and the HLA B27 antigen. The dermatoglyphic patterns of AS patients were compared with the data of control subjects. Significant dermatoglyphic abnormalities were found, but there proved to be no connection between the HLA B27 antigens. We therefore conclude that HLA B27 does not contribute to the development of dermatoglyphic abnormalities. It seems, however, that our findings provide some new nosographic information to the natural picture of AS.

Adolescent↗

Excessive and dysregulated secretion of prolactin in rheumatoid arthritis: immunopathogenetic and therapeutic implications.

Prolactin (PL) is essential for the normal function of the immune system. It is required for the induction of a number of autoimmune conditions in experimental animals. The role of prolactin in the immunopathogenesis of autoimmune human disease has not been established. RA is characterized by a variety of immune and inflammatory processes which determine disease activity. It has a pronounced diurnal periodicity with a peak at 03.15 hours. Since PL has a diurnal rhythm of secretion in man with a peak at about 02.00 hours, it may contribute to the nocturnal worsening of RA. We show that patients with RA secrete an excess of prolactin as evidenced by an upregulated diurnal periodicity and an abnormal increase in plasma prolactin concentration following surgery. By contrast, patients with chronic osteomyelitis, who had chronic inflammation of similar severity to patients with RA, had a normal prolactin diurnal rhythm and response to surgery. Hence, the abnormal changes in prolactin physiology seen in RA appear to be a feature of the disease per se rather than related to chronic inflammation. The elevated levels of prolactin may contribute to disease activity by augmenting immune processes and may be an additional genetic factor, independent of HLA-DR4, in the immunopathogenesis of RA. Furthermore, the effective inhibition of prolactin secretion and/or action may have potential as therapy for RA.

Adult↗

Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis.

OBJECTIVE: To determine the integrity of the hypothalamic-pituitary-adrenal (HPA) axis responses to immune/inflammatory stimuli in patients with rheumatoid arthritis (RA). METHODS: Diurnal secretion of cortisol and the cytokine and cortisol responses to surgery were studied in subjects with active RA, in subjects with chronic osteomyelitis (OM), and in subjects with noninflammatory arthritis, who served as controls. RESULTS: Patients with RA had a defective HPA response, as evidenced by a diurnal cortisol rhythm of secretion which was at the lower limit of normal in contrast to those with OM, and a failure to increase cortisol secretion following surgery, despite high levels of interleukin-1 beta (IL-1 beta) and IL-6. The corticotropin-releasing hormone stimulation test in the RA patients showed normal results, thus suggesting a hypothalamic defect, but normal pituitary and adrenal function. CONCLUSION: These findings suggest that RA patients have an abnormality of the HPA axis response to immune/inflammatory stimuli which may reside in the hypothalamus. This hypothalamic abnormality may be an additional, and hitherto unrecognized, factor in the pathogenesis of RA.

Adult↗

[Recurrent juvenile pancreatitis in dermatomyositis].

The authors present the case history of an 11-year-old girl who suffered from the rarely occurring grave juvenile dermatomyositis associated with recurring pancreatitis. Factors which may cause pancreatitis: juvenile dermatomyositis as underlying disease, steroid-, cytostatic- and thiazide diuretic treatment are analysed.

Adrenal Cortex Hormones↗

24-hour blood pressure differences in hypertension and normotension in bed-confined subjects.

This study investigates whether the degree of hypertension may be evaluated by information derived from the 24-h blood pressure (BP) curve unrelated to the pressure height. We performed 24-h BP intra-arterial monitoring in 52 bed-confined subjects (10 normotensives, 10 borderlines, and 32 hypertensives on WHO criteria). Computer analysis of 1152 BP values per subject per 24-h revealed the following: During the night hours, the percentage of the 1152 systolic BP values greater than or equal to 160 (in mmHg) increased (or did not change if 100%) in all subjects with mean 24-h systolic BP (24-h BP) greater than 170 and it decreased (or did not change if 0%) in all subjects with 24-h BP less than 150. The change in the percentage of the 1152 diastolic BP values greater than or equal to 95 during the night hours did not correlate to either the mean 24-h diastolic or systolic BP. The higher the mean 24-h systolic BP, the lower the skewness of the distribution of the 1152 systolic BP values (p less than 0.01). No such correlation existed between the skewness of the distribution of the 1152 diastolic BP values and either the mean 24-h diastolic or systolic BP. It is concluded that both the change in systolic BP during the night hours and the skewness of its distribution during the 24-h monitoring period are correlated to the severity of hypertension.

Adult↗

Intraaortic balloon assistance in intractable cardiogenic shock.

The efficacy of intraaortic counterpulsation (IABP) in severe cardiogenic shock after acute myocardial infarction is questioned because of the lack of a large controlled series. Out of 52 patients treated for severe, prolonged cardiogenic shock 3 improved with 'conventional' treatment. Forty-nine patients did not improve and were in 'intractable' shock for an average of 10.74 +/- 7.14 h (means +/- SD). Of these, 34 were treated with IABP. Ten survived longer than a month. Of the remaining 15 patients of similar age, severity and duration of shock, in whom the balloon could not be made to operate, none survived. It is suggested that intraaortic counterpulsation can save a number of patients with severe protracted cardiogenic shock after all other available treatment modalities have failed.

Adult↗

Left intraventricular "pseudo-augmentation". A new principle of mechanical assistance.

A new technique is described, utilizing an air-driven pump, connected to the left ventricle, without a valve and synchronized with the electrocardiogram. The pump is operated in brief (80 msecs) pulses. When applied at the end-diastolic phase it produces an increase in stroke volume and dp/dt/P and a marked improvement in the function curves of a failing left ventricle, without substantially increasing the mean left atrial pressure. Thus, mechanical assistance to the failing heart can also be based on this new principle, namely the inotropic effect of a brief left intraventricular end-diastolic pseudo-augmentation.

Animals↗