Biophysical characterization of macrophage migration enhancement factor (MEF)

Macrophage migration enhancement factor (MEF), a lymphokine produced in the spleen by suppressor-like lymphoid cells, may be an important immunoregulatory molecule of macrophage function. MEF appears to be a potent positive chemokinetic factor and is unusual in that it lacks chemotactic activity. To aid in the development of a purification scheme for MEF we have employed biophysical characterization techniques to define its physical properties. Using the technique of velocity sedimentation in isokinetic sucrose gradients, the S_20w for MEF was determined to be 2.25. The Stoke's radius for MEF was determined by Sephadex G-100 gel filtration to be 28.9 Å. From these measurements the D_20w was calculated to be 7.55 × 10⁻⁷cm²/sec, the mol. wt was calculated to be 28,000, the frictional ratio (|/|₀) was calculated to be 1.45, the axial ratio was calculated to be 1:8, and the dimensions of the molecule were estimated to be 2 × 160 Å. Using the technique of isoelectric focusing in liquid density gradients, the isoelectric point for MEF was estimated to be 8.8. We have also determined by enzyme treatment that MEF is resistant to DNase and RNase and susceptible to proteinase K and L-fucosidase. In addition, MEF partitioned to the aqueous phase during methanol-chloroform extraction procedures. MEF was inactivated at pH 12; at 100°C MEF was stable for 10 min but was inactive after 1 hr. Collectively, these data will facilitate the development of a purification scheme for MEF which will ultimately permit the analysis of the molecule and its function.     

MR-sequences for prostate cancer diagnostics: validation based on the PI-RADS scoring system and targeted MR-guided in-bore biopsy

Purpose

This study evaluated the accuracy of MR sequences [T2-, diffusion-weighted, and dynamic contrast-enhanced (T2WI, DWI, and DCE) imaging] at 3T, based on the European Society of Urogenital Radiology (ESUR) scoring system [Prostate Imaging Reporting and Data System (PI-RADS)] using MR-guided in-bore prostate biopsies as reference standard.

Methods

In 235 consecutive patients [aged 65.7?±?7.9 years; median prostate-specific antigen (PSA) 8 ng/ml] with multiparametric prostate MRI (mp-MRI), 566 lesions were scored according to PI-RADS. Histology of all lesions was obtained by targeted MR-guided in-bore biopsy.

Results

In 200 lesions, biopsy revealed prostate cancer (PCa). The area under the curve (AUC) for cancer detection was 0.70 (T2WI), 0.80 (DWI), and 0.74 (DCE). A combination of T2WI + DWI, T2WI + DCE, and DWI + DCE achieved an AUC of 0.81, 0.78, and 0.79. A summed PI-RADS score of T2WI + DWI + DCE achieved an AUC of 0.81. For higher grade PCa (primary Gleason pattern?≥?4), the AUC was 0.85 for T2WI + DWI, 0.84 for T2WI + DCE, 0.86 for DWI + DCE, and 0.87 for T2WI + DWI + DCE. The AUC for T2WI + DWI + DCE for transitional-zone PCa was 0.73, and for the peripheral zone 0.88. Regarding higher-grade PCa, AUC for transitional-zone PCa was 0.88, and for peripheral zone 0.96.

Conclusion

The combination of T2WI + DWI + DCE achieved the highest test accuracy, especially in patients with higher-grade PCa. The use of ≤2 MR sequences led to lower AUC in higher-grade and peripheral-zone cancers.

Key Points

? T2WI + DWI + DCE achieved the highest accuracy in patients with higher grade PCa ? T2WI + DWI + DCE was more accurate for peripheral- than for transitional-zone PCa ? DCE increased PCa detection accuracy in the peripheral zone ? DWI was the leading sequence in the transitional zone     

Chemistry of the Fe2O3/BiFeO3 Interface in BiFeO3 Thin Film Heterostructures

We investigate the interfacial chemistry of secondary Fe₂O₃ phases formed in a BiFeO₃ (BFO) layer in BFO/ La_0.67Sr_0.33MnO₃ (LSMO)/SrTiO₃ (STO) heterostructures. A combination of high-resolution spherical aberration corrected scanning TEM and spectroscopy results, reveals that specific chemical and crystallographic similarities between Fe₂O₃ and BFO, enable the BFO layer to form a facile host for Fe₂O₃.     

Urotensin I-CRF-Urocortins: A mermaid’s tail

From the individual perspective of the two authors who were long-time colleagues of Karl Lederis at the University of Calgary, the events and personal interactions are described, that are relevant to the discovery of Urotensin I (UI) in the Lederis laboratory, along with the concurrent discovery of Urotensin II (UII) in the Bern laboratory and corticotropin-releasing factor (CRF/CRH) in the Vale laboratory. The fortuitous sabbatical experiences that put Professors Lederis and Bern on the track of the Urotensins, along with the essential isolation paradigm that resulted in the complete sequencing and synthesis of UI and UII are summarized. The chance interaction between Drs. Vale and Lederis who, prior to the publications of the sequences of UI and CRF, realized the sequence commonalities of these peptides with the vasoactive frog peptide, sauvagine, is outlined. Further, the relationship between the pharmacological studies done with UI in the Calgary laboratory and the more recent understanding of the biology and receptor pharmacology for the entire Urotensin I-CRF-Urocortin peptide family is dealt with. The value of a comparative endocrinology approach to understanding hormone action is emphasized, along with a projection to the future, based on new hypotheses that can be generated by unexplained data already in the literature. Based on the previously described pharmacology of the UI-CRF-Urocortin peptides in a number of target tissues, it is suggested that the use of current molecular approaches can be integrated with a ‘classical’ pharmacological approach to generate new insights about the UI-CRF-Urocortin hormone family.     

Drug-related problems in hospitalized patients with HIV infection.

PURPOSE: The type and number of drug-related problems that commonly occur in hospitalized patients with HIV were studied. METHODS: The medical records of HIV-infected patients who were receiving antiretroviral therapy at the time of hospital admission between January 1, 2005, and August 31, 2006, were reviewed. Patients age 18 years or older who had received at least one dose of an antiretroviral for an HIV-related indication during their hospitalization were included in the study. Patients' medical records were evaluated to identify drug-related problems and adverse drug events secondary to antiretroviral therapy. RESULTS: Eighty-three patients were eligible for study inclusion. A total of 176 drug-related problems were identified. The most common drug-related problem identified among medication orders reviewed was inappropriate dosing. Of the 251 orders for antiretroviral agents, 57 drugs were inappropriately dosed. The most common drug-related problems among patients were drug-drug interactions and incomplete antiretroviral regimens. There was no significant difference in the mean length of stay between patients with or without drug-related problems. Admission by physicians who were not infectious diseases specialists was an independent risk factor for having at least one drug-related problem during hospitalization (odds ratio, 3.83; 95% confidence interval, 1.08-13.54). CONCLUSION: A majority of HIV-infected patients at one institution had at least one drug-related problem at hospital admission. The most common problem observed among the medication orders reviewed was inappropriate dosing. The most common drug-related problems observed among patients were drug-drug interactions and incomplete antiretroviral regimens.     

Ergebnisse und Komplikationen nach tiefer Sklerektomie

BACKGROUND: As nonperforating glaucoma surgery, deep sclerectomy seems to offer the advantage of fewer complications than the classic trabeculectomy during the first weeks after surgery. PATIENTS AND METHODS: In this prospective study, 74 eyes of 56 patients received deep sclerectomy. The mean follow-up time was 9.5 +/- 5.8 months. Twelve eyes were treated intraoperatively with additional mitomycin C and 11 eyes had combined cataract procedures. The deep sclerectomies were performed without using material of high viscosity or a collagen implant. RESULTS: The mean preoperative pressure of 24.8 +/- 9 mmHg could be lowered to 16.1 +/- 5.9 mmHg (P < 0.0001). The number of glaucoma medications was reduced from 2.2 +/- 1.1 to 0.6 +/- 1.0 substances. Thirty-eight percent of the eyes needed glaucoma medication again. Complications included chorioidal detachment (n = 9), temporary hyphema (n = 6), and delayed pressure reduction (n = 2). CONCLUSIONS: Deep sclerectomy as nonpenetrating glaucoma surgery lowers the intraocular pressure as well as standard trabeculectomy. Its complication rate is very low during the early postoperative weeks. The number of patients who still need glaucoma medication seems to be higher than after trabeculectomy.     

Nifedipine facilitates neurotransmitter release independently of calcium channels

Nifedipine, a drug used for treatment of hypertension and angina, exerts its effect by calcium channel blockade and nitric oxide production. We report here a previously uncharacterized action of nifedipine on central synaptic transmission that may partially explain its side effects. Nifedipine causes a long-lasting facilitation of tetrodotoxin-insensitive spontaneous glutamate release. This effect is independent of its L-type calcium channel blocking effect, and is not mimicked by other dihydropyridines such as nimodipine, nicardipine, or Bay K 8644. The effect was dose dependent, with EC(50) of 7.8 microM, with the lowest effective dose being 100 nM, a clinically relevant dose. At 10 microM, the increase is 14.7-fold. This effect is largely calcium-independent, because Cd(2+), thapsigargin, or BAPTA-AM [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester] did not inhibit the nifedipine effect. Thus, nifedipine seems to act on the release process downstream of calcium entry or release. Protein kinases A or C do not mediate its effect, because it is not blocked by inhibitors of these kinases. Our finding indicates that nifedipine may be a useful tool as a secretagogue to directly target the release process, but raises caution for its use as an L-type calcium channel blocker.     

Relief of buttock claudication by percutaneous recanalization of an occluded superior gluteal artery

We report a case of a woman presenting with right severe buttock claudication and normal neurological and osteoarticular examination, in whom a guidewire recanalization and percutaneous transluminal angioplasty (PTA) of an occluded right superior gluteal artery (SGA) has provided relief of her symptoms. To our knowledge, this is the first report of percutaneous recanalization of the SGA. PTA can be considered the treatment of choice for buttock claudication caused by SGA stenosis or occlusion.