Influence of angiotensins (I,II & III) on prostaglandin production by minced rat renal medulla

Minced rat renal medulla was incubated for 30 min at 37 °C in the presence of angiotensin, I, II or III (100 ng/ml) to determine the existence of a direct stimulating effect on prostaglandin (PG) production. PGE₂, PGF_2α, 6-keto PGF_1α and Thromboxane B₂ (TXB₂)_were determined by radioimmunoassay.For analysis of data variance, the results were separated according to whether the net output of PGE₂ was above or below 1.5 ng PGE₂ equivalent/mg tissue/30 min. Under low-output conditions, angiotensin I, II or III stimulated PGE₂ production significantly (p<0.02) and tended to augment PGF_2α production, while under high-output conditions no effect on PGE₂ or PGF_2α production was observed.Under either output condition, angiotensin I, II or III had no effect on 6-keto PGF_1α and TXB₂.     

Bombesin inhibits insulin release from isolated pancreatic islets of rats in vitro.

The effect of bombesin on insulin release from isolated pancreatic islets of rats was examined in vitro. Bombesin, at the doses ranging from 10 ng/ml to 1 microgram/ml, significantly inhibited 16.7 mM glucose-induced insulin release, while bombesin had no inhibitory effect on insulin release at 8.3 mM and 3.3 mM glucose. Moreover, bombesin also suppressed insulin release elicited by 10 mM arginine at the doses of 100 ng/ml and 1 microgram/ml. These results indicate that bombesin has a direct inhibitory action on insulin release.     

3H]thymidine autoradiographic and alkaline phosphatase histochemical studies of intestinal metaplasia of the human stomach

The relationship between cell proliferation and enzyme activity in intestinal metaplasia of the human stomach was studied using a combined method of [3H]thymidine autoradiography and alkaline phosphatase histochemistry on the same section. Three types of intestinal metaplasia were observed depending on variations in both enzymatic activity and isotope labelling. One type shows alkaline phosphatase-positive cells along the entire length of the glands with [3H]thymidine-labelled cells localized only at the bottom of the glands, resembling the duodenum. In another type of intestinal metaplasia, alkaline phosphatase-positive cells are present on the surface and/or upper half of the glands with mitotically active cells occupying the lower part of the glands. The third variety of intestinal metaplasia is characterized by the absence of alkaline-phosphatase activity and [3H]thymidine-labelled cells present in an extended zone in the lower half of the glands. Differences in labelling patterns of [3H]thymidine and the activity of marker enzyme in various types of intestinal metaplasia seem to reflect variations in cell differentiation during intestinalization of gastric mucosa.     

Biotransformation of reticuline into coreximine,scoulerine, pallidine,and isoboldine with rat liver enzyme

(±)-Reticuline (1) was biotransformed into the protoberberine alkaloids, coreximine (12) and scoulerine (10), the morphinandienone alkaloid, pallidine (14), and the aporphine alkaloid, isoboldine (16). The transformation was stimulated by O₂ and the cofactor NAD, NADP, or NADPH, NADPH being more effective than the other cofactors. The N-methyl group of (±)-reticuline was not incorporated intact into protoberberines.     

A new method for the determination of optical purity of synthetic peptides

A novel and very accurate method was established for the determination of the optical purity of a peptide by use of the following procedure: (1) hydrolysis of the peptide in deuterium chloride, (2) gas chromatographic separation of each amino acid enantiomer on a chiral phase, and (3) determination of the D /L ratio by mass fragmentography. In this manner, one can estimate the true chiral purity of each amino acid residue with an accuracy of ～0.2%. The recemization effected during hydrolysis could be eliminated in principle, since the artificially formed DL -amino acids are necessarily labeled at the α-position with deuterium and can thus be distinguished mass spectrometrically from the D - and L -isomer originally present in the peptide. The versatility of the method was proven by analysis of model peptides, as well as by a racemization test in fragment condensation.     

Synthesis of phosphorothioate analogues of oligodeoxyribonucleotides and their antiviral activity against human immunodeficiency virus (HIV)

Nuclease-resistant phosphorothioate analogues of oligodeoxynucleotides (oligos) were synthesized by sulfurization of either internucleoside phosphite linkages, in a repetitive manner during chain extension, or internucleoside hydrogen phosphonate linkages, in a single step following chain assembly. These analogues were tested as antiviral agents against human immunodeficiency virus (HIV). In a cytopathic effect inhibition assay using HIV-uninfected susceptible T cells (tetanus toxoid-specific normal T cells) co-cultured with irradiated chronically HIV-infected cells, phosphorothioate oligomers inhibited the cytopathic effect and replication of several isolates of HIV-1 and HIV-2. Thus phosphorothioate analogues of oligos could inhibit cell-to-cell transmission of the virus as well as the infection by cell-free virus particles and also could inhibit a variety of isolates of human retroviruses.     

Immunolocalization of 67 kDa elastin-binding protein in perinatal rat lungs

Summary 67 kDa elastin-binding protein (RL-67EBP) has been isolated from neonatal rat lungs by the use of an elastin-coupled affinity column, followed by elution with either lactose or synthetic elastin hexapeptide (VGVAPG), and immunohistochemistry has been used on perinatal rat lungs to determine the tissue localization of this protein. No immunoreactive structures occur in fetal lungs, or in the lungs of day-1 and-4 neonates. On day-7 after birth, immunoreactive cells appear in the subepithelial connective tissue of the intrapulmonary airways, from day-10 on, these cells become evenly distributed in the alveolar parenchyma. Occasionally, some cells occur in the alveolar air space, being free from the surface of the alveolar septum. Unpermeabilized cells obtained by bronchoalveolar lavage, show cell surface immunoreactivity, indicating that RL-67EBP is expressed on the surface membrane of the cells. From these findings, it is suggested that the immunoreactive cells are blood-borne monocytes, and that RL-67EBP may function as an elastin peptide receptor by which monocytes mobilize through interstitial connective tissue during their migration from blood to alveolar air space, where they eventually differentiate into alveolar macrophages.