Inhibin immunoreactivity in gonadal and non-gonadal tumors

Inhibin immunoreactivity was estimated in a number of gonadal and non-gonadal tumors. Dog Sertoli cell tumors and human granulosa cell and Leydig cell tumors contained high concentrations of inhibin-like material. Levels, comparable with those in normal testes and ovaries were detected in human testicular non-seminomas and in ovarian cystadenomas, thecomas and adenofibromas. No activity was found in human testicular Sertoli/Leydig cell tumors and seminomas and in ovarian adenocarcinomas, teratomas and a dysgerminoma. Furthermore, human adrenal cortical tissue (tumor and hyperplastic adrenal) contained inhibin immunoreactivity. No activity was found in human tumors of the stomach, gut, liver, kidney, pancreas and mammary gland or in meningiomas. It is concluded that inhibin is not a good marker for specific gonadal tumors. Inhibin might have intratumor actions a growth or differentiation factor.     

Somatostatin cells in rat antral mucosa: qualitative and quantitative ultrastructural analyses in different states of gastric acid secretion.

In the gastrointestinal tract somatostatin is localized in endocrine cells and in neurons. The antral somatostatin (D-) cell shares features of both cell types. The activity of the antral D-cell is regulated by intragastric pH. Therefore different states of gastric acidity were induced experimentally in order to study D-cell morphology at the electron microscopical level. The morphological findings were related to measurements of plasma and tissue concentrations of the peptide. The D-cell is characterized by extensive membrane interdigitations with neighbouring cells. Changes in the activity of antral D-cells are reflected by an increase in cytoplasmic secretory granule density and a shift of secretory granules towards basal cell processes. Direct endocrine cell contacts at the level of the perikarya were rarely observed. The intracellular distribution of secretory granules suggests that cell communication is more likely to take place at the level of the strongly immunoreactive cytoplasmic processes. No evidence for endocrine or exocrine (luminar) secretion was observed morphologically. This is in agreement with the concept of paracrine secretion of the antral D-cell.     

Production of tailor made short chain amylose–lipid complexes using varying reaction conditions

When amylose was synthesized using potato phosphorylase in the presence of amylose complexing lipids, monodisperse populations of amylose–lipid complexes were formed. Enzyme dosage and glucose-1-phosphate (glc-1-P)/primer ratio influenced the reaction rate of the enzymic synthesis, presumably by changing the balance between amylose synthesis and amylose–lipid complexation and precipitation, and impacted the molecular weight of the complexes. Lipid characteristics affected the dissociation properties and amylose chain lengths of the amylose–lipid complexes presumably by determining the minimal amylose chain length necessary for complexation and precipitation. Tailor made short chain amylose–lipid complexes can hence be produced by choosing the appropriate reaction conditions. We propose a synthesis mechanism in which the primer is elongated until an amylose chain is obtained which is of sufficient length to complex a first lipid. Further chain extension then occurs, together with subsequent complexation until the complex becomes insoluble and precipitates.     

Long-wavelength sensitive visual pigments of the guppy (<Emphasis Type="Italic">Poecilia reticulata</Emphasis>): six opsins expressed in a single individual

Background

The diversity of visual systems in fish has long been of interest for evolutionary biologists and neurophysiologists, and has recently begun to attract the attention of molecular evolutionary geneticists. Several recent studies on the copy number and genomic organization of visual pigment proteins, the opsins, have revealed an increased opsin diversity in fish relative to most vertebrates, brought about through recent instances of opsin duplication and divergence. However, for the subfamily of opsin genes that mediate vision at the long-wavelength end of the spectrum, the LWS opsins, it appears that most fishes possess only one or two loci, a value comparable to most other vertebrates. Here, we characterize the LWS opsins from cDNA of an individual guppy, Poecilia reticulata, a fish that is known exhibit variation in its long-wavelength sensitive visual system, mate preferences and colour patterns.

Results

We identified six LWS opsins expressed within a single individual. Phylogenetic analysis revealed that these opsins descend from duplication events both pre-dating and following the divergence of the guppy lineage from that of the bluefin killifish, Lucania goodei, the closest species for which comparable data exists. Numerous amino acid substitutions exist among these different LWS opsins, many at sites known to be important for visual pigment function, including spectral sensitivity and G-protein activation. Likelihood analyses using codon-based models of evolution reveal significant changes in selective constraint along two of the guppy LWS opsin lineages.

Conclusion

The guppy displays an unusually high number of LWS opsins compared to other fish, and to vertebrates in general. Observing both substitutions at functionally important sites and the persistence of lineages across species boundaries suggests that these opsins might have functionally different roles, especially with regard to G-protein activation. The reasons why are currently unknown, but may relate to aspects of the guppy's behavioural ecology, in which both male colour patterns and the female mate preferences for these colour patterns experience strong, highly variable selection pressures.

     

ORG 33201: A new highly selective orally active aromatase inhibitor

Org 33201 has been selected as a very potent aromatase inhibitor. The compound is an enantiomer of a SC₂H₅ substituted imidazoylethylphenalene. Org 33201 inhibited human aromatase activity for 50% at a concentration of 2.2 × 10⁹ mol/l. More than 200-fold higher concentrations were needed for the inhibition of other cytochrome P-450 enzymes. In vivo the compound was active in rats (ED₅₀ = 0.035 mg/kg) and dogs (1 mg/kg gave 70% inhibition) after oral administration. It can be concluded that Org 33201 is a potent and highly selective orally active aromatase inhibitor.     

Subendocardial and subepicardial pressure-flow relations in the rat heart in diastolic and systolic arrest

Ischemic heart disease is more apparent in the subendocardial than in subepicardial layers. We investigated coronary pressure-flow relations in layers of the isolated rat left ventricle, using 15 microm microspheres during diastolic and systolic arrest in the vasodilated coronary circulation. A special cannula allowed for selective determination of left main stem pressure-flow relations. Arterio-venous shunt flow was derived from microspheres in the venous effluent. We quantitatively investigated the pressure-flow relations in diastolic arrest (n=8), systolic arrest at normal contractility (n=8) and low contractility (n=6). In all three groups normal and large ventricular volume was studied. In diastolic arrest, at a perfusion pressure of 90 mmHg, subendocardial flow is larger than subepicardial flow, i.e., the endo/epi ratio is approximately 1.2. In systolic arrest the endo/epi ratio is approximately 0.3, and subendocardial flow and subepicardial flow are approximately 12% and approximately 55% of their values during diastolic arrest. The endo/epi ratio in diastolic arrest decreases with increasing perfusion pressure, while in systole the ratio increases. The slope of the pressure-flow relations, i.e., inverse of resistance, changes by a factor of approximately 5.3 in the subendocardium and by a factor approximately 2.2 in the subepicardium from diastole to systole. Lowering contractility affects subendocardial flow more than subepicardial flow, but both contractility and ventricular volume changes have only a limited effect on both subendocardial and subepicardial flow. The resistance (inverse of slope) of the total left main stem pressure-flow relation changes by a factor of approximately 3.4 from diastolic to systolic arrest. The zero-flow pressure increases from diastole to systole. Thus, coronary perfusion flow in diastolic arrest is larger than systolic arrest, with the largest difference in the subendocardium, as a result of layer dependent increases in vascular resistance and intercept pressure. Shunt flow is larger in diastolic than in systolic arrest, and increases with perfusion pressure. We conclude that changes in contractility and ventricular volume have a smaller effect on pressure-flow relations than diastolic-systolic differences. A synthesis of models accounting for the effect of cardiac contraction on perfusion is suggested.