Influence of pulsatility on the development of intracardiac jets: an in vitro laser Doppler study.

So far, it has been hypothesized that numerical data obtained in steady flow conditions apply to pulsatile flows. In order to study the modifications of the velocity fields due to pulsatility, jets were produced by 8 orifices (with a diameter "D" of 4.4 to 11.3 mm) included in a chamber of 50 mm. The velocity was measured using laser Doppler anemometry with a pulsatile flow ("pf") and compared to the values obtained in steady ("sf"): at maximum velocity, the longitudinal velocity profile is qualitatively similar to this observed in steady flow: it is made of a plateau followed by an hyperbolic velocity decay in the turbulent area. The length of the core ("Lpf") is strongly related to "D" (Lpf = 3.72 D + 5.49, r = .99) and the velocity decay depends on the ratio between the distance "x" from the orifice and "D" (V/Vo = 2.83D/x + 3.46, r = .85, where V is the velocity at "x" and Vo the initial velocity). During the acceleration and the deceleration, the laminar core is disturbed by turbulences. The comparison of "pf" data with "sf" data demonstrated similar diameters at the origin of the jets (Dpf = 0.96 Dsf + .12, r = .99), but significant (p less than .0001) differences both for "L" and "V/Vo": Lpf = .91Lsf + 6.58, r = .97, V/Vopf = .63 V/Vosf + .34, r = .76. Thus, pulsatility modifies velocity fields and the results obtained in steady flow conditions do not apply to pulsatile jets.     

BALB/c myeloma retroviruses have mink cell focus-inducing activity.

We have determined the in vitro host range of the cloned MO-21 and FL-1 murine myeloma retroviruses grown in SC-1 cells that were originally isolated from cloned MOPC-21 and FLOPC-1 BALB/c plasmacytoma cell lines. These viruses are able to replicate in murine (BALB/3T3, NIH/3T3) as well as numerous heterologous cell lines. These myeloma retroviruses also exhibit mink cell focus-inducing activity. MO-21 and FL-1 shared interference patterns with each other, but their replication was not interfered with by ecotropic, xenotropic, or amphotropic viruses. The lack of cross-interference with ecotropic or xenotropic viruses distinguishes these isolates from other mink cell focus-inducing viruses.     

Responsiveness of microcirculation and local cold vasodilation to capsaicin in the intact and chronically denervated canine tongue

Lingual blood flow and its distribution were determined at rest and in response to local cooling of the tongue (32 degrees C) in 6 anaesthetized, paralyzed and artificially ventilated dogs before and after two intraarterial (i.a.) injections of capsaicin (2.5 mg) at an interval of about 40 min. In 3 dogs, the same protocol was performed after degeneration of the chorda-lingual and glossopharyngeal nerves due to prior transection. In general the first i.a. injection of capsaicin resulted in a marked and the second injection in a smaller decrease of lingual blood flow. Local cooling of the tongue induced significant increases in lingual blood flow before as well as after capsaicin treatment, regardless of whether sensory innervation was intact or degenerated. In both the untreated and capsaicin treated dogs the increase in lingual blood flow during local cooling of the tongue was solely due to an increase in blood flow through the arteriovenous anastomoses, while blood flow through the capillaries of the mucosa and muscles even decreased. The findings suggest that capsaicin-induced vasoconstriction of the tongue vessels is due to a direct effect on vascular receptors. It is further suggested that cold vasodilatation of the canine tongue is not mediated by axon collaterals releasing substance P. Direct thermal effects on the intramural ganglia and the postganglionic vasomotor efferents innervating the AVAs, or on AVAs basal tone itself are suggested as the underlying mechanism.     

Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination

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TNF-α is associated with loss of lean body mass only in already cachectic COPD patients

Background

Systemic inflammation may contribute to cachexia in patients with chronic obstructive pulmonary disease (COPD). In this longitudinal study we assessed the association between circulating C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels and subsequent loss of fat free mass and fat mass in more than 400 COPD patients over three years.

Methods

The patients, aged 40–76, GOLD stage II-IV, were enrolled in 2006/07, and followed annually. Fat free mass and fat mass indexes (FFMI & FMI) were calculated using bioelectrical impedance, and CRP, TNF-α, IL-1ß, and IL-6 were measured using enzyme immunoassays. Associations with mean change in FFMI and FMI of the four inflammatory plasma markers, sex, age, smoking, FEV₁, inhaled steroids, arterial hypoxemia, and Charlson comorbidity score were analyzed with linear mixed models.

Results

At baseline, only CRP was significantly (but weakly) associated with FFMI (r = 0.18, p < 0.01) and FMI (r = 0.27, p < 0.01). Univariately, higher age, lower FEV₁, and use of beta2-agonists were the only significant predictors of decline in FFMI, whereas smoking, hypoxemia, Charlson score, and use of inhaled steroids predicted increased loss in FMI. Multivariately, high levels of TNF-α (but not CRP, IL-1ß or IL-6) significantly predicted loss of FFMI, however only in patients with established cachexia at entry.

Conclusion

This study does not support the hypothesis that systemic inflammation is the cause of accelerated loss of fat free mass in COPD patients, but suggests a role for TNF-α in already cachectic COPD patients.     

Differential response of cycling and noncycling cells to inducers of DNA synthesis and mitosis

The objective of this study was to determine whether cells in G(0) phase are functionally distinct from those in G(1) with regard to their ability to respond to the inducers of DNA synthesis and to retard the cell cycle traverse of the G(2) component after fusion. Synchronized populations of HeLa cells in G(1) and human diploid fibroblasts in G(1) and G(0) phases were separately fused using UV-inactivated Sendai virus with HeLa cells prelabeled with [(3)H]ThdR and synchronized in S or G(2) phases. The kinetics of initiation of DNA synthesis in the nuclei of G(0) and G(1) cells residing in G(0)/S and G(1)/S dikaryons, respectively, were studied as a function of time after fusion. In the G(0)/G(2) and G(1)/G(2) fusions, the rate of entry into mitosis of the heterophasic binucleate cells was monitored in the presence of Colcemid. The effects of protein synthesis inhibition in the G(1) cells, and the UV irradiation of G(0) cells before fusion, on the rate of entry of the G(2) component into mitosis were also studied. The results of this study indicate that DNA synthesis can be induced in G(0)nuclei after fusion between G(0)- and S-phase cells, but G(0) nuclei are much slower than G(1) nuclei in responding to the inducers of DNA synthesis because the chromatin of G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells differ from G(1) cells with regard to their effects on the cell cycle progression of the G(2) nucleus into mitosis. This difference between G(0) and G(1) cells appears to depend on certain factors, probably nonhistone proteins, present in G(1) cells but absent in G(0) cells. These factors can be induced in G(0) cells by UV irradiation and inhibited in G(1) cells by cycloheximide treatment.