Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. We first identified a PAM locus by homozygosity mapping to 4p15, then identified, by a candidate-gene approach, the gene responsible for the disease as SLC34A2 (the type IIb sodium-phosphate cotransporter gene), which is involved in phosphate homeostasis in several organs. We identified six homozygous exonic mutations in the seven unrelated patients with PAM we studied. Three of the mutations were frameshifts, one was a chain termination, one was an amino acid substitution, and one was a deletion spanning the minimal promoter and the first exon. Absence of functional protein product of the gene is compatible with calcium phosphate deposition in alveolar airspaces. We show that impaired activity of the phosphate transporter is presumably responsible for the microliths and that PAM is a recessive monogenic disease with full penetrance. Testicular microlithiasis (TM) is a disease that is more common than PAM. It is often associated with cancer and infertility. Since the gene we identified is also expressed in testis, we searched for mutations in subjects with TM. In 2 of the 15 subjects with TM we studied, we identified two rare variants, one synonymous and the other noncoding, that are possibly associated with the condition.     

Chemical composition effects onto antimicrobial and antioxidant activities of propolis collected from different regions of Turkey

Chrysin, apigenin, flavonoids, flavanones, naringenin, ethyl oleate, 3-4-dimethoxy-cinnamic acid and 9-octadecenoic acid were the predominant components of propolis samples collected from different regions of Turkey. The extracts of P3 from Denizli-Ba?karci, P5 from Denizli and P7 from Tekirda? had effective antibacterial activities on Gram-negatives. Chrysin, which has antibacterial activity, was found to be high concentration. The extracts of P3, P2B from Aydin and P6 from Konya had much more effective antibacterial activities on Gram-positives. The total antioxidant activity increased with the increasing amount of extracts added to linoleic acid emulsion. All doses of propolis ethanol extract displayed antioxidant activity.     

Brain-stem listeriosis: a comparison of SPECT and MRI findings

Listeria monocytogenes, although uncommon as a cause of illness in the general population, can result in serious illness when it affects pregnant women, neonates, the elderly, and immunocompromised individuals. Typically, it is a food-borne organism. This report describes a case of brain-stem listeriosis in a previously healthy 51-year-old woman. The diagnosis was based on clinical findings, the results of cerebrospinal fluid (CSF) analysis, CSF culture, and magnetic resonance imaging (MRI) findings. MRI demonstrated upper brain stem and cerebellar peduncle involvement. In addition, Tc-99m exametazime (HMPAO)-labeled single photon emission computed tomography (SPECT) of the brain revealed bilateral cerebellar hypoperfusion. Antibiotic therapy resulted in partial clinical recovery after 3 weeks. At the end of 6 months, brain-stem findings had nearly resolved. However, although minimal residual findings were observed on MRI at 6 months, bilateral diffuse cerebellar hypoperfusion remained on Tc-99m HMPAO brain SPECT.     

The effect of Trifolium, Raphanus, and Cistus pollen grains on some blood parameters and mesentery mast cells

Three kinds of pollen taxa belonging to 3 families (Fabaceae--Trifolium spp., Brassicaceae--Raphanus spp. and Cistaceae--Cistus spp.) and commonly collected by honeybees were fed to mature male rats separately, in the form of 60 mg/animal/day for a 30-day period. The objective of this study was to investigate any positive effects or possible side effects of the use of pollen on the immune system. This was achieved through blood analysis and cell count on blood, hemoglobin, erythrocyte and immune system cells. The cell concentration of mast cells, degranulization and cell localization were investigated in prepared mesentery tissue samples. Histological investigations of the stomach and duedenum sections of pollen-fed rats were carried out to learn the reason for eosinophil gastroenteritis in the alimentary canal. The eosinophil and lymphocyte levels of rats fed with pollen of Trifolium spp., Raphanus spp., and Cistus spp. were observed to have increased blood cell counts, while neutrophil and monocyte levels decreased; different values were found in basophil leucocytes between the pollen groups. Differing reductions in mesentery mast cell concentration, degranulization and cell localization were found. Within the three separate pollens, the rats having been fed with Cistus spp. pollen were observed to have higher blood lymphocyte, eosinophil, hemoglobin and hematocrit values than those fed with the others, as well as low mesentery mast cell concentration. Hemoglobin values were determined to increase at a proportion of between 10.0-11.3%. No difference was found in other blood parameters. The fat proportion of the male rats fed with the three taxa was between 4.03-8.75%, while that for protein proportion was between 16.11-24.25%. Male rats receiving these taxa did not experience allergic reactions and it is possible to argue that the low protein and fat content of these pollens have a strengthening effect on the immune systems by the increase in lymphocyte content and the amount of hemoglobin leads to an increase of oxygen transport capacity in the tissues.     

Investigation of the in vitro antioxidant behaviour of some 2-phenylindole derivatives: discussion on possible antioxidant mechanisms and comparison with melatonin

Oxidative stress has been implicated in the development of many neurodegenerative diseases and also responsible from aging and some cancer types. Indolic compounds are a broad family of substances present in microorganisms, plants and animals. They are mainly related to tryptophan metabolism, and present particular properties that depend on their respective chemical structures. Due to free radical scavenger and antioxidant properties of indolic derivatives such as indolinic nitroxides and melatonin, a series of 2-phenyl indole derivatives were prepared and their in vitro effects on rat liver lipid peroxidation levels, superoxide formation and DPPH stable radical scavenging activities were determined against melatonin, BHT and alpha-tocopherol. The compounds significantly inhibited (72-98%) lipid peroxidation at 10(-3) M. These values were similar to that observed with BHT (88%). Possible structure-activity relationships of the compounds were discussed.     

Synthesis and antioxidant activity evaluations of melatonin-based analogue indole-hydrazide/hydrazone derivatives

Melatonin (MLT) is a hormone synthesized from the pineal gland. It is a direct scavenger of free radicals, which is related to its capability to defend cells from oxidative stress. Recently MLT-related compounds are under investigation to establish which exhibit the maximum activity with the lowest side effects. In this study 5-chloroindole hydrazide/hydrazone derivatives were synthesized from 5-chloroindole-3-carboxaldehyde and phenyl hydrazine derivatives. All the compounds characterized and in vitro antioxidant activity was investigated against MLT and BHT. Most of the compounds showed strong inhibitory effect on the superoxide radical scavenging assay at 1?mM concentration (79 to 95%). Almost all the tested compounds possessed strong scavenging activity against the DPPH radical scavenging activity with IC(50) values (2 to 60 μM). Lastly, compound 1j revealed stronger inhibitory activity against MLT in the LP inhibitory assay at 0.1mM concentration (51%) while the rest of the compounds showed moderate inhibition.     

Takayasu's arteritis is associated with HLA-B*52, but not with HLA-B*51, in Turkey

Introduction

HLA-B*51 and HLA-B*52 are two close human leukocyte antigen (HLA) allele groups with minor amino acid differences. However, they are associated with two different vasculitides (HLA-B*51 in Behçet's disease and HLA-B*52 in Takayasu's arteritis (TAK)) and with major clinical and immunological differences. In this study, we aimed to screen a large cohort of TAK patients from Turkey for the presence of HLA-B*51 and HLA-B*52 as susceptibility and severity factors.

Methods

TAK patients (n = 330) followed at a total of 15 centers were included in the study. The mean age of the patients was 37.8 years, and 86% were women. DNA samples from the patients and healthy controls (HC; n = 210) were isolated, and the presence of HLA-B*51 or HLA-B*52 was screened for by using PCR with sequence-specific primers.

Results

We found a significant association of HLA-B*52 with TAK (20.9% vs HC = 6.7%, P = 0.000, OR = 3.7, 95% CI = 2.02 to 6.77). The distribution of HLA-B*51 did not differ between TAK patients and HCs (22.7% vs 24.8%, OR = 0.9, 95% CI = 0.60 to 1.34). The presence of HLA-B*52 decreased in late-onset patients (> 40 years of age; 12.0%, P = 0.024, OR = 0.43, 95% CI = 0.20 to 0.91). Patients with angiographic type I disease with limited aortic involvement also had a lower presence of HLA-B*52 compared to those with all other disease subtypes (13.1% vs 26%, P = 0.005, OR = 0.43, 95% CI = 0.23 to 0.78).

Conclusions

In this study, the previously reported association of TAK with HLA-B*52 in other populations was confirmed in patients from Turkey. The functional relevance of HLA-B*52 in TAK pathogenesis needs to be explored further.     

The value of CDX2 and cytokeratins 7 and 20 expression in differentiating colorectal adenocarcinomas from extraintestinal gastrointestinal adenocarcinomas: cytokeratin 7-/20+ phenotype is more specific than CDX2 antibody

Background

Breast carcinomas can be classified into five subtypes based on gene expression profiling or immunohistochemical characteristics. Among these subtypes, basal-like breast carcinomas (BLBCs) are one of the most studied group, due to their poor prognosis. The aim of this study was to investigate the prevalance, morphological and immunohistochemical features of BLBCs, in Turkish population.

Methods

Five hundred invasive breast carcinomas were reviewed for several morphological features and immunostained for oestrogen and progesterone receptors, c-ERB-B2, cytokeratin5/6, cytokeratin14, vimentin and epidermal growth factor receptor (EGFR). Basal-like breast carcinoma was defined as a triple negative tumor with cytokeratin5/6 and/or EGFR positive.

Results

The prevalance of BLBC was 9.6%. All medullary carcinomas and 55.6% of metaplastic carcinomas showed basal-like immunophenotype. Patients with BLBC were younger (p=0.04) and had higher-grade tumors (p<0.0001). Morphologic features associated with BLBC included increased mitosis, nuclear pleomorphism, presence of geographic and/or central necrosis, pushing margin of invasion and stromal lymphocytic response (p<0.0001). Presence of prominent nucleoli and vesicular nuclear chromatin were the cytological features correlated with basal-like phenotype (p<0.0001). On multivariate analyses, BLBCs were associated with high mitotic number (p<0.0001), the presence of vesicular chromatin (p=0.004), high tubular grade (p=0.011), lymphocytic response (p=0.031) and the absence of carcinoma insitu (p=0.039). Vimentin was positive in 53.2% of BLBCs, while cytokeratin14 was less frequently expressed (27.7%).

Conclusions

BLBCs have some distinctive, but not pathognomonical, morphological features. Paying attention to these features and adding cytokeratin14 and vimentin to the immunohistochemical panel can help the definitive diagnosis of BLBCs.

Virtual slide

http://www.diagnosticpathology.diagnomx.eu/vs/5962175467857400     

Note on the occurrence of Pseudo-nitzschia australis and domoic acid in squid from Monterey Bay, CA (USA)

Over the past decade diatom blooms of domoic acid (DA)-producing Pseudo-nitzschia spp. have been responsible for numerous marine mammal and bird mortalities in Monterey Bay, CA. One possible toxin vector is the market squid, Loligo opalescens, a small pelagic mollusk that plays an important role in the near-shore food web of the California Current ecosystem as a favored vertebrate prey species. This study examined the trophic link between toxic Pseudo-nitzschia and L. opalescens using toxin and stomach content analyses of animals collected from Monterey Bay, CA in 2000. Receptor binding assay data (confirmed by tandem mass spectrometry), demonstrated the presence of DA in squid during a toxic Pseudo-nitzschia event, with P. australis frustules observed in stomach samples. Though DA levels were low (<0.5 μg DA g⁻¹ tissue) in L. opalescens during the study period, it is now clear that this potent neurotoxin can occur in squid and is likely delivered through its krill prey species, which are known to retain DA after feeding on toxic Pseudo-nitzschia. Our findings suggest that further study of the relationship between Pseudo-nitzschia blooms and DA contamination of squid is warranted to better evaluate the potential health risk to humans and wildlife associated with this major commercial seafood species and important prey item.