Squamous cell carcinoma with metastasis in a rhesus monkey (Macaca mulatta)

A squamous cell carcinoma of the prepuce and penis with metastases to the inguinal lymph nodes and lung occurred in a rhesus monkey (Macaca mulatta). The primary tumor consisted of eroded nodular masses at the mucocutaneous junction of the prepuce and in the epithelium of the prepuce and penis.     

Leaving group effects on ligand substitution reactions of pentacyanoferrate(II) complexes: rate constant and activation volume correlations

The kinetics of the reaction of cyanide ions with pentacyanoferrate(II) complexes have been studied spectrophotometrically at pressures of 1 bar and up to 1 kbar, at 298.2 K. An excess of cyanide ions was employed and first-order kinetics were observed both in aqueous solution and in aqueous-mono-ol mixtures. For several pyridine derivative leaving groups, neutral or mono-positively charged, the rate constant variation in aqueous medium is only over one half-order of magnitude, although thiourea and quinoxaline are much more labile, dissociating with rate constants about ten and three hundred times greater than this range, respectively. Very modest changes in rate constant are observed upon addition of 40% methanol, and in a few examples studied, kinetic differences become significant only in cosolvent-rich mixtures. Volumes of activation, Δ V^*, are all positive, for reaction in water, confirming the expected bond extension of the leaving group in a D mechanism. Solvation changes and ligand differences do not wholly explain the variation in Δ V^* values, or the changes in this parameter found when cosolvents are added. Reasonably good correlations are found for the logarithms of rate constants both with the pK_a of the ligand and with Δ V^*. Other potential correlations of the leaving group property and kinetic parameter are discussed.     

The role of heat-shock and chaperone proteins in protein folding: possible molecular mechanisms.

Recently some heat-shock proteins have been linked to functions of 'chaperoning' protein folding in vivo. Here current experimental evidence is reviewed and possible requirements for such an activity are discussed. It is proposed that one mode of chaperone action is to actively unfold misfolded or badly aggregated proteins to a conformation from which they could refold spontaneously; that improperly folded proteins are recognized by excessive stretches of solvent-exposed backbone, rather than by exposed hydrophobic patches; and that the molecular mechanism for unfolding is either repeated binding and dissociation ('plucking') or translocation of the protein backbone through a binding cleft ('threading'), allowing the threaded chain to refold spontaneously. The observed hydrolysis of ATP would provide the energy for active unfolding. These hypotheses can be applied to both monomeric folding and oligomeric assembly and are sufficiently detailed to be open to directed experimental verification.     

Apomyoglobin as a molecular recognition surface: expression, reconstitution and crystallization of recombinant porcine myoglobin in Escherichia coli

Recombinant porcine myoglobin has been produced in Escherichia coli using the lambda cII fusion expression system of Nagai and Th?gersen [Nature, 309, 810-812 (1984)]. After processing and reconstitution with haem, the protein is gel-electrophoretically and spectrophotometrically indistinguishable from native pig myoglobin. Large crystals of both native and recombinant porcine myoglobin were grown from 50 mM sodium phosphate, pH 7.1, 80% ammonium sulphate. The crystals belong to space group C2 (a = 156.9 A, b = 42.0 A, c = 92.2 A, beta = 127.9 degrees) and diffract to a nominal 2.5 A resolution. We plan to explore apomyoglobin as a binding surface in studies combining site-directed mutagenesis and X-ray analysis. These experiments will be extended by studying the binding of haem analogues to the mutant apoproteins.     

The lack of an effect of furosemide on uterine prostaglandin metabolism

We determined the effect of 2 mg/kg intravenous furosemide on the production and metabolism of prostaglandin E₂ in the utero-placental unit of pregnant dogs. Uterine venous prostaglandins E₂ and 15-keto-13,14-dihydro E₂ were measured by gas chromatography-mass spectrometry. Even though the dose of furosemide was adequate to effect a good diuresis, neither the production nor the metabolism of prostaglandin E₂ by the uterus was altered by that dose of the drug. Using radioactive microspheres to measure hemodynamic parameters, we observed no change in uterine vascular resistance while renal vascular resistance decreased. Although the renal concentration of furosemide may be higher than the uteroplacental concentration, there is so far no evidence that usual doses of furosemide enhance the production or inhibit the metabolism of prostaglandin E₂.     

Intravenous recombinant secretory leukoprotease inhibitor augments antineutrophil elastase defense.

Secretory leukoprotease inhibitor (SLPI), a 12-kDa serine antiprotease, normally protects the upper airway epithelial surface from attack by neutrophil elastase (NE). In the context that a variety of inflammatory lung diseases are characterized by large neutrophil burdens with resultant high levels of NE in the lung, recombinant SLPI (rSLPI), a molecule identical to natural SLPI, may be an effective means to augment the anti-NE protective screen of the lung. To determine whether intravenous rSLPI will augment respiratory tract and epithelial surface levels of SLPI and anti-NE capacity, rSLPI was administered intravenously to sheep and SLPI levels were quantified in plasma, lung lymph (as a measure of lung interstitial levels), lung epithelial lining fluid (ELF), and urine. rSLPI (1 g) was administered over 10 min, and after 30 min plasma levels of SLPI were 8 microM and decreased with a half-life of 1.8 h. Lymph SLPI levels paralleled the plasma levels: 4 h after infusion the lymph-to-plasma ratio was 0.8. ELF SLPI levels paralleled the lymph levels: 4 h after infusion the ELF-to-lymph ratio was 0.3. Western analysis demonstrated intact SLPI in lymph and ELF, and functional analysis showed increases in lymph and ELF anti-NE capacity that paralleled the levels of SLPI. As might be expected from a protein with a molecular mass of 12 kDa, urine excretion was high, with 20% of the SLPI excreted over 5 h. However, if the rate of infusion was slowed, SLPI excretion decreased significantly, with a 3-h infusion associated with 9% excretion and a 12-h infusion associated with less than 0.2% excretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Parameter redundancy in mark‐recovery models

We provide a definitive guide to parameter redundancy in mark‐recovery models, indicating, for a wide range of models, in which all the parameters are estimable, and in which models they are not. For these parameter‐redundant models, we identify the parameter combinations that can be estimated. Simple, general results are obtained, which hold irrespective of the duration of the studies. We also examine the effect real data have on whether or not models are parameter redundant, and show that results can be robust even with very sparse data. Covariates, as well as time‐ or age‐varying trends, can be added to models to overcome redundancy problems. We show how to determine, without further calculation, whether or not parameter‐redundant models are still parameter redundant after the addition of covariates or trends.