Hansen's disease (leprosy). Diagnosis by aspiration biopsy of lymph nodes

A 61-year-old male native of Mexico presented with generalized enlargement of lymph nodes. Fine needle aspiration (FNA) biopsy established lepromatous leprosy as the cause of the lymphadenopathy. The cytologic findings included abundant, frequently multinucleated histiocytes (globus cells), the cytoplasm of which showed multiple vacuoles; cytoplasmic membrane-bound vacuoles were seen free in the background. The vacuoles contained large numbers of acid-fast bacilli. Globus cells, while characteristic, are not specific for Mycobacterium leprae infection and are seen in certain atypical mycobacterioses in immunodeficient patients. This appears to be the first report of lymphadenopathy due to lepromatous leprosy in which the diagnosis was made by FNA biopsy. The immunologic spectrum of leprosy is correlated with clinical and pathologic findings, and the need to remember infectious processes in evaluating lymphadenopathy and the value of reserving air-dried and alcohol-fixed smears for special stains are emphasized.     

Metastatic spindle-cell carcinoma. Cytologic features and differential diagnosis

Fine needle aspiration biopsies of tumors can yield a variety of spindle cells derived from several types of neoplasms. Among these is a rare lesion known as a "spindle-cell carcinoma" or "pseudosarcoma," which may represent a transformation of a preexisting squamous-cell carcinoma that has been subjected to radiotherapy or solar damage. The cytologic, histologic and ultrastructural features of a case of metastatic spindle-cell carcinoma of the rib subjected to fine needle aspiration are presented, and other spindle-cell tumors that should be considered in the differential diagnosis are discussed.     

Risk Factors for Death in 632 Patients with Sickle Cell Disease in the United States and United Kingdom

Background

The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial.

Methods and Results

We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67–75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV<3.0 m/sec (p<0.0001). The hazard ratios for death were 11.1 (95% CI 4.1–30.1; p<0.0001) for TRV≥3.0 m/sec, 4.6 (1.8–11.3; p = 0.001) for NT-proBNP≥160 pg/mL, and 14.9 (5.5–39.9; p<0.0001) for both TRV≥3.0 m/sec and NT-proBNP≥160 pg/mL. Age >47 years, male gender, chronic transfusions, WHO class III–IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death.

Conclusions

A TRV≥3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable.

The study is registered in ClinicalTrials.gov with identifier

{"type":"clinical-trial","attrs":{"text":"NCT00492531","term_id":"NCT00492531"}}NCT00492531     

Protein and cDNA sequences of Bowman-Birk protease inhibitors from the cowpea (Vigna unguiculata Walp.)

The protein and gene sequences of the cowpea Bowman-Birk type trypsin inhibitor which confers enhanced insect resistance to transgenic tobacco plants, and of cowpea trypsin/chymotrypsin inhibitors are presented. There are regions of high conservation and high divergence within the 5 leader, mature protein and 3 non-coding regions of the Bowman-Birk inhibitors and in the genes which encode them in different members of this family within the Leguminosae. The practical implications of this finding for studies on the evolution of plants and the utilization of these genes for enhancing insect resistance is discussed.     

Evaluation of Antibacterial Activity of Lavandulapedunculata subsp. atlantica (Braun‐Blanq.) Romo Essential Oil and Selected Terpenoids against Resistant Bacteria Strains–Structure–Activity Relationships

The genus Lavandula is known for its different uses in traditional medicine. This study is interested in the chemical composition of Lavandulapedunculata subsp.atlantica (Braun‐Blanq. ) Romo as well as evaluating its antibacterial potential against multi‐resistant strains. The analysis of Lavandulaatlantica essential oil (LAEO) allows the identification of 47 components representing 93.6 % of all identified. The main constituent of LAEO was camphor (50.4 %), followed by fenchone (14.1 %) and camphene (5.6 %). The antibacterial assays revealed that LAEO was active against all the studied bacteria. A preliminary study of the relationship between certain terpenoids and antibacterial activity was also carried out in order to note the compound(s) that are responsible for LAEO's antibacterial activity. This study showed that the activity of the essential oil may be due to the presence of certain minor compounds such as carvone, considering the presence of the synergistic effect between the essential oil.     

By Regulating Mitochondrial Ca2+-Uptake UCP2 Modulates Intracellular Ca2+

Introduction

The possible role of UCP2 in modulating mitochondrial Ca²⁺-uptake (mCa²⁺-uptake) via the mitochondrial calcium uniporter (MCU) is highly controversial.

Methods

Thus, we analyzed mCa²⁺-uptake in isolated cardiac mitochondria, MCU single-channel activity in cardiac mitoplasts, dual Ca²⁺-transients from mitochondrial ((Ca²⁺)m) and intracellular compartment ((Ca²⁺)c) in the whole-cell configuration in cardiomyocytes of wild-type (WT) and UCP2^-/- mice.

Results

Isolated mitochondria showed a Ru360 sensitive mCa²⁺-uptake, which was significantly decreased in UCP2^-/- (229.4±30.8 FU vs. 146.3±23.4 FU, P<0.05). Single-channel registrations confirmed a Ru360 sensitive voltage-gated Ca²⁺-channel in mitoplasts, i.e. mCa1, showing a reduced single-channel activity in UCP2^-/- (Po,total: 0.34±0.05% vs. 0.07±0.01%, P<0.05). In UCP2^-/- cardiomyocytes (Ca²⁺)m was decreased (0.050±0.009 FU vs. 0.021±0.005 FU, P<0.05) while (Ca²⁺)c was unchanged (0.032±0.002 FU vs. 0.028±0.004 FU, P>0.05) and transsarcolemmal Ca²⁺-influx was inhibited suggesting a possible compensatory mechanism. Additionally, we observed an inhibitory effect of ATP on mCa²⁺-uptake in WT mitoplasts and (Ca²⁺)m of cardiomyocytes leading to an increase of (Ca²⁺)c while no ATP dependent effect was observed in UCP2^-/-.

Conclusion

Our results indicate regulatory effects of UCP2 on mCa²⁺-uptake. Furthermore, we propose, that previously described inhibitory effects on MCU by ATP may be mediated via UCP2 resulting in changes of excitation contraction coupling.     

Loss of α1β1 Soluble Guanylate Cyclase,the Major Nitric Oxide Receptor,Leads to Moyamoya and Achalasia

Moyamoya is a cerebrovascular condition characterized by a progressive stenosis of the terminal part of the internal carotid arteries (ICAs) and the compensatory development of abnormal “moyamoya” vessels. The pathophysiological mechanisms of this condition, which leads to ischemic and hemorrhagic stroke, remain unknown. It can occur as an isolated cerebral angiopathy (so-called moyamoya disease) or in association with various conditions (moyamoya syndromes). Here, we describe an autosomal-recessive disease leading to severe moyamoya and early-onset achalasia in three unrelated families. This syndrome is associated in all three families with homozygous mutations in GUCY1A3, which encodes the α1 subunit of soluble guanylate cyclase (sGC), the major receptor for nitric oxide (NO). Platelet analysis showed a complete loss of the soluble α1β1 guanylate cyclase and showed an unexpected stimulatory role of sGC within platelets. The NO-sGC-cGMP pathway is a major pathway controlling vascular smooth-muscle relaxation, vascular tone, and vascular remodeling. Our data suggest that alterations of this pathway might lead to an abnormal vascular-remodeling process in sensitive vascular areas such as ICA bifurcations. These data provide treatment options for affected individuals and strongly suggest that investigation of GUCY1A3 and other members of the NO-sGC-cGMP pathway is warranted in both isolated early-onset achalasia and nonsyndromic moyamoya.     

Synthesis,biological evaluation,and molecular docking of new series of antitumor and apoptosis inducers designed as VEGFR-2 inhibitors

Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC₅₀ values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15_a, 15_b, and 15_d showed IC₅₀ from 17.39 to 47.10 µM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15_d which came second with regard to antitumor assay with IC₅₀ = 24.10, 40.90, and 33.40 µM against aforementioned cell lines, respectively. Furthermore, Compound 15_d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15_d showed IC₅₀ of 253 and 381 nM against HER2 and FGFR, respectively.     

Redasoft Plasmid 1.1: software for easy, efficient cloning and map drawing

A computer program is described which creates circular and linear genetic maps with or without sequences, performs restriction analysis, and simulates basic molecular cloning operations. Redasoft Plasmid 1.1 is a user-friendly program for Windows 95/98/NT/2000, designed to generate high quality genetic maps for presentation and publication and to aid the molecular biologist in selecting restriction endonucleases for common molecular cloning experiments. The program incorporates an integrated web browser and can automatically generate complete, labeled maps from sequences on the Internet.