Estimation of deformation gradient and strain from cine-PC velocity data

Phase contrast magnetic resonance imaging (MRI) can provide in vivo myocardial velocity field measurements. These data allow densely spaced material points to be tracked throughout the whole heart cycle using, for example, the Fourier tracking algorithm. To process the tracking results for myocardial deformation and strain quantification, we developed a method that is based on fitting the tracking results to an appropriate local deformation model. We further analyzed the accuracy and precision of the method and provided performance predictions for several local models. In order to validate the method and the theoretical performance analysis, we conducted controlled computer simulations and a phantom study. The results agreed well with expectations. Human heart data were also acquired and analyzed, and provided encouraging results. At the signal-to-noise ratio (SNR) level and spatial resolution expected in clinical settings, the study predicts strain quantification accuracy and precision that may allow the technique to become a practical and powerful noninvasive approach for the study of cardiac function, although clinically acceptable data acquisition strategies for three-dimensional (3-D) data are still a challenge.     

Platelet-derived growth factor activates a mammalian Ste20 coupled mitogen-activated protein kinase in airway smooth muscle

Attempts to immunise sheep against natural infestations by Lucilia cuprina larvae have not been effective. Yet it is known that the larvae excrete the immunosuppressant ammonium bicarbonate. The effect of larval ammonium and nonionic ammonia on immunopathobiology was evaluated in 12 infested sheep. The concentration of ammonium in veins draining infested sites was measured in another group of four sheep. Mean jugular unionized ammonia concentration increased 3.5 to 5.6 times above pre-infested control levels. Mean venous ammonium concentrations draining infested sites were 13 times higher than pre-infested jugular or carotid levels. Increases in jugular ammonia concentrations correlated with increased number of larvae, area of infestation, earlier death, neutropenia, eosinopenia, lymphocytopenia, large declines in serum globulins and zinc, and large rises in toxic neutrophils. The high concentrations of toxic unionized ammonia in blood directly permanently damaged neutrophils and lymphocytes and depressed serum globulin production. The results show that the ammonium from the excreta of larvae of L. cuprina may be highly immunosuppressive.     

The membrane protein alkaline phosphatase is delivered to the vacuole by a route that is distinct from the VPS-dependent pathway

Membrane trafficking intermediates involved in the transport of proteins between the TGN and the lysosome-like vacuole in the yeast Saccharomyces cerevisiae can be accumulated in various vps mutants. Loss of function of Vps45p, an Sec1p-like protein required for the fusion of Golgi-derived transport vesicles with the prevacuolar/endosomal compartment (PVC), results in an accumulation of post-Golgi transport vesicles. Similarly, loss of VPS27 function results in an accumulation of the PVC since this gene is required for traffic out of this compartment. The vacuolar ATPase subunit Vph1p transits to the vacuole in the Golgi-derived transport vesicles, as defined by mutations in VPS45, and through the PVC, as defined by mutations in VPS27. In this study we demonstrate that, whereas VPS45 and VPS27 are required for the vacuolar delivery of several membrane proteins, the vacuolar membrane protein alkaline phosphatase (ALP) reaches its final destination without the function of these two genes. Using a series of ALP derivatives, we find that the information to specify the entry of ALP into this alternative pathway to the vacuole is contained within its cytosolic tail, in the 13 residues adjacent to the transmembrane domain, and loss of this sorting determinant results in a protein that follows the VPS-dependent pathway to the vacuole. Using a combination of immunofluorescence localization and pulse/chase immunoprecipitation analysis, we demonstrate that, in addition to ALP, the vacuolar syntaxin Vam3p also follows this VPS45/27-independent pathway to the vacuole. In addition, the function of Vam3p is required for membrane traffic along the VPS-independent pathway.     

Estimation of foetal brain dose from I-131 in the foetal thyroid

The ingestion of I-131 by pregnant women can have consequences for the developing foetus, in particular brain function. As the foetal thyroid accumulates iodine from the twelfth week of gestation onwards, the determination of foetal brain dose resulting from such I-131 accumulation is essential. Normal dosimetric methods fail to treat the case of foetus. Using an approximation method based on the MIRD approach, a foetal dose estimation scheme is developed to allow the determination of foetal brain dose from foetal thyroid irradiation. Dose values are obtained for the foetus based on the maternal intake of I-131. It was found that the choice of biokinetic model for the mother/foetus has a large impact on the determined dose estimate.     

Colour flow duplex imaging of occlusive arterial disease of the lower limb

BACKGROUND: The development of duplex ultrasonography and colour flow imaging has greatly extended the scope of non-invasive assessment of lower limb arterial disease. This review questions whether recent advances might allow colour duplex imaging to displace arteriography as the primary imaging modality for native vessel occlusive disease. METHODS: A literature review was carried out based predominantly on a Medline database search of English language publications from 1985 to 1996. RESULTS: Increasing evidence indicates that colour duplex ultrasonography can accurately image the lower limb native arterial tree, and that colour duplex imaging can replace diagnostic arteriography in a large proportion of patients. CONCLUSION: Arteriography should no longer be considered the gold standard of imaging of peripheral arterial occlusive disease. Future studies should concentrate on the efficacy of colour duplex sonography in guiding clinical decision making.     

Effective use of ribonucleotide reductase inhibitors (Didox and Trimidox) alone or in combination with didanosine (ddI) to suppress disease progression and increase survival in murine acquired immunodeficiency syndrome (MAIDS)

Ribonucleotide reductase inhibitors (RRIs) have been recently shown to inhibit retroviral replication. We examined a new series of RRIs, 3,4-dihydroxybenzohydroxamic acid (Didox) and 3,4,5-trihydroxybenzohydroxamidoxime (Trimidox) for their ability to alter disease progression in murine acquired immunodeficiency syndrome (MAIDS), both alone and in combination with 2',3'-dideoxyinosine (ddI). MAIDS disease was induced by inoculation of female C57BL/6 mice with the LP-BM5 murine leukemia virus (MuLV) and disease progression characterized by extensive peripheral lymphadenopathy and splenomegaly. Efficacy of treatment with these drugs was based upon their ability to influence survival and disease pathophysiology by monitoring the development of splenomegaly. Toxicity was determined by changes in body weight, total peripheral white blood cell count and hematocrit. Didox or trimidox monotherapy was associated with increased survival and decreased disease pathophysiology, with no apparent toxicity. Combined with ddI, their ability to reduce development of viral induced splenomegaly was enhanced compared to trimidox, didox or ddI alone. These results demonstrate RRIs have potent activity in reversing the disease manifestations characteristic of MAIDS. Further studies are warranted to determine human clinical efficacy.     

Double coupling Edman chemistry for high-sensitivity automated protein sequencing

Capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) is a promising new method for the analysis of protein sequencing products. It gives 10 zmol (1 zmol = 10(-21) mol) limits of detection (3 sigma) for fluorescein thiohydantoin (FTH) amino acids. We have developed a separation for the (FTH)-amino acid products generated from 18 of the 20 coded amino acids. The extremely low volume requirement associated with CE-LIF makes it incompatible with commercial sequencers. For this reason, we have also been developing a miniaturized sequencer that can be more easily coupled to our detection system. Both the CE-LIF system and the miniaturized sequencer are described.     

The fetoplacental pressor effects of low-dose acetylsalicylic acid and angiotensin II in the ex vivo cotyledon model

OBJECTIVE: Our purpose was to investigate perfusion pressure changes ex vivo induced by angiotensin II on fetoplacental vasculature pretreated with low-dose acetylsalicylic acid. STUDY DESIGN: Two cotyledons from each of 12 placentas were perfused. The intervillous space of one cotyledon was infused with acetylsalicylic acid (5 x 10(-5) mol/L) similar to the serum concentration of women receiving daily low-dose aspirin therapy (60 to 81 mg). The control cotyledon was infused with an equivalent amount of normal saline solution. Two doses of angiotensin II, 1 x 10(-11.5) and 1 x 10(-10) moles, were injected as boluses into the chorionic arteries of each cotyledon. A 3 x 10(-7) mole dose of angiotensin II was also injected into the intervillous space. Statistical analysis was performed with analysis of variance, and results are expressed as mean pressure change in millimeters of mercury +/- SEM. RESULTS: Perfusion pressure response did not vary between cotyledons pretreated with acetylsalicylic acid and control cotyledons when 3 x 10(-7) moles of angiotensin II was injected into the intervillous space (8.0 +/- 1.9 mm Hg vs 9.8 +/- 1.6 mm Hg, p = 0.59). There were no differences between cotyledons in pressure response to 1 x 10(-11.5) moles of angiotensin II injected into the fetal circuit (5.9 +/- 0.8 mm Hg vs 6.7 +/- 0.9 mm Hg, p = 0.51). However, in the cotyledons pretreated with acetylsalicylic acid there was a decrease in the pressor response to 1 x 10(-10) moles of angiotensin II (14.1 +/- 1.4 mm Hg vs 21.5 +/- 3.3 mm Hg, p = 0.05). CONCLUSIONS: Low-dose aspirin infused into the intervillous space decreases vasoconstriction elicited by angiotensin II in the fetoplacental compartment. This suggests that maternal low-dose aspirin therapy has effects in the fetoplacental circulation in addition to its effects in the maternal circulation.     

Activation of the K-ras oncogene in colorectal neoplasms is associated with decreased apoptosis

BACKGROUND: Recent in vitro data indicate that the oncogenic effects of activated ras genes may be mediated, at least in part, through inhibition of apoptotic cell death. To examine this proposition in vivo, the relationship between mutations of the K-ras gene and the frequency of apoptosis was studied in a series of 69 sporadic colorectal neoplasms (11 adenomas and 58 carcinomas). METHODS: Mutations in codon 12 of K-ras were determined by a single tube, enriched polymerase chain reaction. Apoptotic cells in tumor sections were identified by in situ end-labeling of fragmented DNA, whereas levels of bcl-2 and p53 proteins were determined by immunohistochemistry. RESULTS: Tumors with mutant K-ras had a significantly lower apoptotic index than those with the wild-type allele (P < 0.05). They were also more likely to exhibit positive bcl-2 staining (P < 0.05). Adenomas showed significantly greater bcl-2 positivity than carcinomas (89% and 51%, respectively; P < 0.05). The frequency of apoptosis in these tumors was not related to either bcl-2 positivity or p53 status. CONCLUSIONS: These findings suggest that activation of K-ras in colorectal carcinoma may inhibit apoptosis and thus favor tumor progression. Alternatively, this association may reflect an accumulation of K-ras mutations in cells in which normal apoptotic pathways have been impaired.