The neural type II regulatory subunit of cAMP-dependent protein kinase is present and regulated by hormones in the rat ovary

In this study purified isoforms of rat ovarian regulatory subunit of type II cAMP-dependent protein kinase (R-II) were compared with R-II purified from rat brain. A special neural form of R-II has been previously described in bovine brain. Analysis by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved three isoforms of rat ovarian R-II (R-II54, Mr = 54,000; R-II52, Mr = 52,000; and R-II51, Mr = 51,000) compared to two R-II isoforms in rat brain (R-II54 and R-II52). Polychromatic silver-stained peptide maps of purified R-II subunits indicated that peptides generated from both rat ovarian R-II52 and R-II51 were similar (if not identical) to the peptides of the neural form, R-II52, purified from rat brain. These peptides differed markedly from those generated from R-II54 of either rat ovary, brain, or heart. Ovarian R-II52/51 photoaffinity labeled with 8-N3-[32P]cAMP and analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis was shown to consist of three (rather than two) isoelectric variants, which were similar to three variants resolved from rat brain R-II and clearly distinct from that of rat heart R-II54. An antibody which recognized both the R-II54 and R-II52/51 isoforms of rat ovarian extracts also recognized both forms of rat brain R-II (R-II54 and R-II52) and similar forms in extracts of rat adrenal and parotid glands. These results strongly suggest that the R-II52 isoform previously designated as a neural specific form of R-II is present in high concentrations in a nonneural tissue, the rat ovary.     

Constituents of marsh grass: Survey of the essential oils in Juncus roemerianus

The essential oil of Juncus roemerianus was isolated by steam distillation with a yield of 0·01 % of the fresh grass. Analysis by combined GLC-MS gave evidence for the presence of 78 compounds. They included 13 benzene derivatives, 11 polycyclic (mostly naphthalene type) compounds, 8 cyclohexyl compounds, 32 acyclic compounds, 9 terpenoids, and 6 furan derivatives. In total, these compounds accounted for 46·6% of the oil. Due to the presence of tetrachlorobenzene and benzyl cyanide, other halogenated compounds and alkaloids can be anticipated.     

Identification and quantitative analysis of the volatile substances emitted by maturing cotton in the field

When atmosphere from cotton plants (Gossypium hirsutum L., var. Deltapine Smoothleaf) was condensed by passing it over the expansion coil of an air conditioner and three 1-hour collections per day (early morning, noon, and late afternoon) were made, the total essential oils were found to consist of 50 to 60% β-bisabolol (I_k 1660) and γ-bisabolene (I_k 1550) and 30 to 40% geraniol (I_k 1250), myrtenal (I_k 1328), nerolidol (I_k 1520), and β-caryophyllene oxide (I_k 1590). As the plant matured, trans-2-hexanol was produced in concentrations of 7 to 27%. Before fruiting, β-bisabolol made up as much as 60% of the total essential oil transpired by the plants, and as the concentration of β-bisabolol increased, that of γ-bisabolene decreased.     

Treatment of metal-contaminated water using bacterial sulfate reduction: results from pilot-scale reactors

Simple anaerobic reactors were installed to treat metal-contaminated water in an underground coal mine and at a smelting residues dump in Pennsylvania. The reactors consisted of barrels and tanks filled with spent mushroom compost, within which bacterial sulfate reduction became established. Concentrations of Al, Cd, Fe, Mn, Ni, and Zn were typically lowered by over 95% as contaminated water flowed through the reactors. Cadmium, Fe, Ni, and some Zn were retained as insoluble metal sulfides following their reaction with bacterially generated H(2)S. Aluminum, Mn, and some Zn hydrolyzed and were retained as insoluble hydroxides or carbonates. Reactor effluents were typically circumneutral in pH and contained net alkalinity. The principal sources of alkalinity in the reactors were bacterial sulfate reduction and limestone dissolution. This article examines the chemistry of the reactor systems and the opportunities for enhancing their metal-retaining and alkalinity-generating potential. (c) 1992 John Wiley & Sons, Inc.     

Antenatal imatinib treatment reduces pulmonary vascular remodeling in a rat model of congenital diaphragmatic hernia

The pathophysiology of congenital diaphragmatic hernia (CDH) is constituted by pulmonary hypoplasia and pulmonary hypertension (PH). We previously reported successful treatment with imatinib of a patient with CDH. This study examines the effect of antenatal imatinib administration on the pulmonary vasculature in a rat model of CDH. Pregnant rats were given nitrofen to induce CDH. Controls were given olive oil. Half of the CDH fetuses and half of the controls were treated with imatinib antenatally E17-E21, rendering four groups: Control, Control+Imatinib, CDH, and CDH+Imatinib. Lung sections were obtained for morphometry and immunohistochemistry, and protein was purified for Western blot. Effects of nitrofen and imatinib on Ki-67, caspase-3, PDGF-B, and PDGF receptors were analyzed. Imatinib significantly reduced medial wall thickness in pulmonary arteries of rats with CDH. It also normalized lumen area and reduced the proportion of fully muscularized arteries. Imatinib also caused medial thinning in the control group. Cell proliferation was increased in CDH, and this proliferation was significantly reduced by imatinib. PDGF-B and PDGFR-β were upregulated in CDH, and imatinib treatment resulted in a downregulation. PDGFR-α remained unchanged in CDH but was significantly downregulated by imatinib. Antenatal imatinib treatment reduces development of medial wall thickness and restores lumen area in pulmonary arteries in nitrofen-induced CDH. The mechanism is reduced cell proliferation. Imatinib is an interesting candidate for antenatal therapy for PH in CDH, but potential side effects need to be investigated and more specific targeting of PDGF signaling is needed.     

Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study

Introduction

The human monoclonal antibody adalimumab is known to induce an anti-globulin response in some adalimumab-treated patients. Antibodies against adalimumab (AAA) are associated with non-response to treatment. Immunoglobulins, such as adalimumab, carry allotypes which represent slight differences in the amino acid sequences of the constant chains of an IgG molecule. Immunoglobulins with particular IgG (Gm) allotypes are racially distributed and could be immunogenic for individuals who do not express these allotypes. Therefore, we investigated whether a mismatch in IgG allotypes between adalimumab and IgG in adalimumab-treated patients is associated with the development of AAA.

Methods

This cohort study consisted of 250 adalimumab-treated rheumatoid arthritis (RA) patients. IgG allotypes were determined for adalimumab and for all patients. Anti-idiotype antibodies against adalimumab were measured with a regular radio immunoassay (RIA), and a newly developed bridging enzyme linked immunosorbent assay (ELISA) was used to measure anti-allotype antibodies against adalimumab. The association between AAA and the G1m3 and the G1m17 allotypes was determined. For differences between groups we used the independent or paired samples t-test, Mann-Whitney test or Chi square/Fisher's exact test as appropriate. To investigate the influence of confounders on the presence or absence of AAA a multiple logistic regression-analysis was used.

Results

Adalimumab carries the G1m17 allotype. No anti-allotype antibodies against adalimumab were detected. Thirty-nine out of 249 patients had anti-idiotype antibodies against adalimumab (16%). IgG allotypes of RA patients were associated with the frequency of AAA: patients homozygous for G1m17 had the highest frequency of AAA (41%), patients homozygous for G1m3 the lowest frequency (10%), and heterozygous patients' AAA frequency was 14% (P = 0.0001).

Conclusions

An allotype mismatch between adalimumab and IgG in adalimumab-treated patients did not lead to a higher frequency of AAA. On the contrary, patients who carried the same IgG allotype as present on the adalimumab IgG molecule, had the highest frequency of anti-adalimumab antibodies compared to patients whose IgG allotype differed from adalimumab. This suggests that the allotype of adalimumab may not be highly immunogenic. Furthermore, patients carrying the G1m17-allotype might be more prone to antibody responses.