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The avian lung: is there an aerodynamic expiratory valve?

The unidirectional gas-flow pattern through the avian lung is thought to result from 'aerodynamic valves'; support for this hypothesis lies mainly in the failure to find any evidence for anatomical valves. During expiration, air flows from the caudal air sacs through the major exchange area of the lung, the paleopulmonic parabronchi, instead of bypassing the lungs via the intrapulmonary bronchus. We tested whether the effectiveness of this expiratory flow control mechanism depends on aerodynamic factors, especially convective inertial forces that depend on gas density and flow velocity. In pump-ventilated, anaesthetized geese, a bolus of tracer gas was introduced into both the right and left caudal thoracic air sacs during an end-inspiratory pause. During the first expiration, the rise of tracer levels within the caudal trachea was measured. Valve efficacy was positively correlated with the rate of expiratory gas flow, V·ao (range 8­200 ml s-1). At flows assumed to occur during exercise in geese (V·ao>100 ml s-1), the expiratory valve efficacy was approximately 95 %; it was less effective at lower flows. Surprisingly, the density (rho) of the background gas (rho of He/O2=0.43 g l-1, Ar/O2=1.72 g l-1 or SF6/O2=5.50 g l-1) had no effect on expiratory valving. We suggest two possible mechanisms that might explain this unusual combination of flow dependence without density dependence. (1) If airway geometry changes occurred between experiments with different gases, flow in the vicinity of the expiratory valve may have varied independently from flow measured at the airway opening. (2) Alternatively, valving may depend on dynamic compression of the intrapulmonary bronchus, which could depend mainly on viscous resistance and thus on flow velocity but not gas density.

Journal Article↗

Characterization of vanadium bromoperoxidase from Macrocystis and Fucus: reactivity of vanadium bromoperoxidase toward acyl and alkyl peroxides and bromination of amines.

Vanadium bromoperoxidase (V-BrPO) has been isolated and purified from the marine brown algae Fucus distichus and Macrocystis pyrifera. V-BrPO catalyzes the oxidation of bromide by hydrogen peroxide, resulting in the bromination of certain organic acceptors or the formation of dioxygen. V-BrPO from F. distichus and M. pyrifera have subunit molecular weights of 65,000 and 74,000, respectively, and specific activities of 1580 units/mg (pH 6.5) and 1730 units/mg (pH 6) for the bromination of monochlorodimedone, respectively. As isolated, the enzymes contain a substoichiometric vanadium/subunit ratio; the vanadium content and specific activity are increased by addition of vanadate. V-BrPO (F. distichus, M. pyrifera, and Ascophyllum nodosum) also catalyzes the oxidation of bromide using peracetic acid. In the absence of an organic acceptor, a mixture of oxidized bromine species (e.g., hypobromous acid, bromine, and tribromide) is formed. Bromamine derivatives are formed from the corresponding amines, while 5-bromocytosine is formed from cytosine. In all cases, the rate of the V-BrPO-catalyzed reaction is much faster than that of the uncatalyzed oxidation of bromide by peracetic acid, at pH 8.5, 1 mM bromide, and 2 mM peracetic acid. In contrast to hydrogen peroxide, V-BrPO does not catalyze formation of dioxygen from peracetic acid in either the presence or absence of bromide. V-BrPO also uses phenylperacetic acid, m-chloroperoxybenzoic acid, and p-nitroperoxybenzoic acid to catalyze the oxidation of bromide; dioxygen is not formed with these peracids. V-BrPO does not catalyze bromide oxidation or dioxygen formation with the alkyl peroxides ethyl hydroperoxide, tert-butyl hydroperoxide, and cuminyl hydroperoxide.

Amines↗

Stimulation of protein degradation by low pH in L6G8C5 skeletal muscle cells is independent of apoptosis but dependent on differentiation state.

BACKGROUND: In chronic renal failure, metabolic acidosis increases protein degradation (PD) in skeletal muscle, an effect which in vivo requires glucocorticoid (GC). This disorder is poorly understood, but can be studied in vitro using L6G8C5 rat skeletal muscle cells. Two potential confounding factors in studies of PD in culture are apoptosis and dedifferentiation, both of which resemble catabolic states. The aim of this study was to determine the extent to which these factors contribute to the observed effects of acid and GC on PD. METHODS: PD was measured in intact cells by pre-labelling cell protein with [(14)C]phenylalanine. Apoptosis was assessed morphologically by staining DNA with Hoechst 33342, by terminal deoxynucleotide transferase-mediated nick-end labelling and by cell-surface binding of Annexin V. Differentiation was assessed morphologically from myotube fusion and from activity of the marker enzyme creatine phosphokinase (CPK). RESULTS: In undifferentiated myoblasts, pH had no detectable effect on apoptosis provided that serum was present and GC (dexamethasone; 5 nmol/l) decreased apoptosis. In spontaneously fused cultures in 2% serum, inhibition of apoptosis with caspase-3 inhibitor (C3I; Ac-Asp-Met-Gln-Asp-CHO; 50 micro mol/l) only decreased PD by 9% at pH 7.4. In contrast, the proteasome inhibitor MG132 decreased PD by 79%. Acid (pH 7.1) increased PD, with no requirement for GC, and this effect was blocked by MG132, but not by C3I. Differentiation was unaffected by 1-4 days of exposure to acid or GC. However, differentiation to myotubes led to decreased sensitivity of PD to acid. This effect of acid was lost completely in highly fused myotubes, but was partly restored by 500 nmol/l dexamethasone. CONCLUSIONS: Stimulation of PD in these cells by acid and GC is not an artefact of apoptosis or dedifferentiation, but differentiation state does determine whether PD responds spontaneously to acid or (as in vivo) only does so in the presence of GC.

Acidosis↗

Expressed swine VH genes belong to a small VH gene family homologous to human VHIII.

The sequences of 34 swine H chain V-regions expressed with either IgG, IgA, or IgM C regions in adult swine and newborn piglets are described and compared. Sixteen of these V-regions were cloned by using a specific leader primer whereas 18 were cloned by anchored PCR. According to the operational criterion of VH family classification, i.e., > 80% DNA sequence similarity, all sequences belong to a homogeneous VH gene family. A total of 31 additional VH-bearing C mu clones obtained by anchored PCR from colostrum-deprived newborn piglets hybridized equally with a probe for C mu and a pan-VH probe. When the consensus sequence of the expressed swine VH genes were compared with those of VH gene for humans (VHI, II, III), mouse (VHI, II, III), rabbit, and chicken, swine VH genes seem to have common ancestry with the human VHIII family, rabbit VH genes, and the single functional VH gene of the chicken. The leader peptides of all clones obtained by anchored PCR showed < 1% variability, and the deduced amino acid sequences from aa4 to aa25 in all 34 clones are identical. Framework (FR)1 and FR2 are conserved whereas FR3 shows greater variability. A total of 23 of 30 JH sequences were identical, suggesting preferential use of one JH. This frequent, putative JH sequence is not similar to any JH gene in humans. Identical genomic Southern hybridization patterns, each with 13 bands of differing intensity and regardless of stringency, were obtained when either a leader or a pan-specific VH probe was used. Analyses of individual genomic bands by single strand conformational polymorphism and sequence analysis suggest that the number of VHIII-related genes in the swine genome is < 20.

Amino Acid Sequence↗

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗