Florid reactive lymphoid hyperplasia of the lower female genital tract (lymphoma-like lesion): a benign condition that frequently harbors clonal immunoglobulin heavy chain gene rearrangements.

Lymphoma-like lesions (LLL) of the lower female genital tract are florid reactive inflammatory processes that mainly occur in women in their reproductive years. Histologically, they are characterized by a dense lymphoid infiltrate with admixed large cells that is often suspicious for lymphoma. In contrast to lymphoma, however, they are superficial lesions that typically show surface erosion and a mixed lymphoid infiltrate and do not have evidence of a mass, deep invasion, or prominent sclerosis.

Chronic sclerosing sialadenitis (Küttner tumor) is an IgG4-associated disease.

Background: Chronic sclerosing sialadenitis is a fibroinflammatory disease of the salivary glands, characteristically of the submandibular gland. One prior Asian study proposed that chronic sclerosing sialadenitis is a part of the spectrum of IgG4-associated disease. This association has not been confirmed in Western populations.

Characteristics of cutaneous marginal zone lymphomas with marked plasmacytic differentiation and a T cell-rich background.

Primary cutaneous marginal zone lymphoma (MZL) is a common B-cell lymphoma of skin and is characterized by an infiltrate of neoplastic marginal zone B cells typically within the marginal zones of reactive lymphoid follicles and the interfollicular region. However, in our experience, many cases have underemphasized features such as marked plasmacytic differentiation and/or a prominent T-cell component, which may obscure the neoplastic B cells and lead to misdiagnosis. We wanted to draw attention to these features and have studied 15 cases of MZL with marked plasmacytic differentiation, 10 of which had numerous T cells, some with cytologic atypia, and few B cells in the interfollicular region.

Low-molecular-weight heparin use in a case of noncardiogenic multifocal perinatal thromboembolic stroke.

A full-term neonate suffered multifocal cerebral infarctions due to multiple large vessel thrombi. Thrombophilia and cardiovascular assessments were negative, but due to the severity of the lesions and the concern for expansion of the thrombi or future embolic events, treatment with low-molecular-weight heparin (LMWH) was initiated. No complications from treatment were experienced.

Detection of the nt230[del4] MDR1 mutation in dogs by a fluorogenic 5' nuclease TaqMan allelic discrimination method.

For detection of the nt230[del4] MDR1 mutation, a 4-bp deletion in the canine MDR1 (ABCB1) gene, a TaqMan allelic discrimination assay was designed that allows for MDR1 genotyping without post-PCR processing. Directly after completion of the PCR amplification, the MDR1 genotype can be assigned based on selective fluorescence measurement. For primer selection the locus of a potential 265A>G single nucleotide polymorphism was omitted; this locus is covered by the oligonucleotide PCR primers from most of the hitherto established MDR1 genotyping methods.

Study of the transport of thyroid hormone by transporters of the SLC10 family.

Transport of (sulfated) iodothyronines across the plasma membrane is required for their intracellular metabolism. Rat Na(+)/taurocholate cotransporting polypeptide (Ntcp; Slc10a1) has been identified as an important transporter protein. We demonstrate that among the 7 members of the solute carrier family SLC10, only human SLC10A1 mediates sodium-dependent transport of the iodothyronine T4 and iodothyronine sulfates T3S and T4S.

Pathogenetic pathways in ovarian endometrioid adenocarcinoma: a molecular study of 29 cases.

It has been recently suggested that ovarian serous carcinoma follows a dualistic pathway with low-grade carcinomas arising from borderline tumors and high-grade carcinomas originating de novo. Similarly, our group has shown that based on their molecular profile endometrioid borderline tumors could predate low-grade endometrioid ovarian carcinomas (EOC). It is not clearly understood if low-grade EOC is in turn related to high-grade EOC, or if high-grade EOC may also arise de novo.

Race bias tracks conception risk across the menstrual cycle.

Although a considerable body of research explores alterations in women's mating-relevant preferences across the menstrual cycle, investigators have yet to examine the potential for the menstrual cycle to influence intergroup attitudes. We examined the effects of changes in conception risk across the menstrual cycle on intergroup bias and found that increased conception risk was positively associated with several measures of race bias. This association was particularly strong when perceived vulnerability to sexual coercion was high.

The role of p-glycoprotein in limiting brain penetration of the peripherally acting anticholinergic overactive bladder drug trospium chloride.

The aim of the present study was to characterize the role of the drug-efflux transporter P-glycoprotein (P-gp) for the disposition of trospium chloride, a widely used anticholinergic drug for the treatment of overactive bladder. P-gp-deficient mdr1a,b(-/-) knockout mice were given either 1 mg/kg trospium chloride orally or 1 mg/kg intravenously to analyze brain penetration, intestinal secretion, and hepatobiliary excretion of the drug. The concentrations of trospium chloride in the brain were up to 7 times higher in the mdr1a,b(-/-) knockout mice compared with wild-type mice (p < 0.

Selective inhibition of Pfmrk, a Plasmodium falciparum CDK, by antimalarial 1,3-diaryl-2-propenones.

The cyclin dependent protein kinases, Pfmrk and PfPK5, most likely play an essential role in cell cycle control and differentiation in Plasmodium falciparum and are thus an attractive target for antimalarial drug development. Various 1,3-diaryl-2-propenones (chalcone derivatives) which selectivity inhibit Pfmrk in the low micromolar range (over PfPK5) are identified. Molecular modeling shows a pair of amino acid residues within the Pfmrk active site which appear to confer this selectivity.

Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice.

P-glycoprotein, which is encoded by the multi-drug resistance gene (MDR1), highly restricts the entry of ivermectin into the brain by an ATP-driven efflux mechanism at the blood-brain barrier. In dogs with a homozygous MDR1 mutation though, ivermectin accumulates in the brain and provokes severe signs of neurotoxicosis and even death. In contrast to ivermectin, selamectin is safer in the treatment of MDR1 mutant dogs, suggesting that selamectin is transported differently by P-glycoprotein across the blood-brain barrier.

Antidepressant medications, neuroleptics, and prominent eye movements during NREM sleep.

Eye movements during stage 2, 3, and 4 sleep have been associated with the use of several selective serotonin reuptake inhibitor (SSRI) medications. This activity has been postulated to be a serotonin effect. The authors identified all cases of nonrapid eye movement (NREM) eye movements observed over a 36-month period in an accredited hospital-based sleep center and then correlated the findings with the patient's medications.

In silico microarray probe design for diagnosis of multiple pathogens.

Background: With multiple strains of various pathogens being sequenced, it is necessary to develop high-throughput methods that can simultaneously process multiple bacterial or viral genomes to find common fingerprints as well as fingerprints that are unique to each individual genome. We present algorithmic enhancements to an existing single-genome pipeline that allows for efficient design of microarray probes common to groups of target genomes. The enhanced pipeline takes advantage of the similarities in the input genomes to narrow the search to short, nonredundant regions of the target genomes and, thereby, significantly reduces the computation time.

Patient- and physician-rated measures demonstrate the effectiveness of ropinirole in the treatment of restless legs syndrome.

Objectives: To investigate the effect of twice-daily ropinirole in patients with early evening restless legs syndrome (RLS) symptoms, particularly focusing on the relationship of patient- and physician-rated assessment of treatment outcomes.

Methods: In this multicenter, double-blind, randomized, 12-week, flexible-dose study, patients with primary RLS, with symptom onset no earlier than 5 PM and a baseline International Restless Legs Syndrome Study Group Rating Scale (IRLS) total score > or = 20 received ropinirole 0.5 to 6.

Expression of histone 1 (H1) and testis-specific histone 1 (H1t) genes during stallion spermatogenesis.

In eukaryotic cells, the major protein constituents of the chromatin are histones, which can be divided into five classes, identified as H1, H2A, H2B, H3 and H4. During normal spermatogenesis, a testis-specific H1t is expressed in primary spermatocytes and believed to facilitate histone to protamine exchanges during spermiogenesis. In equine testes we detected the H1 protein at 22kDa by western blot analysis while H1t was detected at 29kDa.

Phase I trial of tipifarnib in children with newly diagnosed intrinsic diffuse brainstem glioma.

The purpose of this study is to estimate the maximum-tolerated dose (MTD) and describe toxicities and preliminary clinical effects of tipifarnib, a farnesyltransferase (FTase) inhibitor, administered concurrently with radiation therapy in children with newly diagnosed intrinsic diffuse brainstem glioma (BSG). Children >or=3 and View Article and Find Full Text PDF

Cloning and molecular characterization of the orphan carrier protein Slc10a4: expression in cholinergic neurons of the rat central nervous system.

We report on the cloning and molecular characterization of the rat carrier Slc10a4 and its cellular localization in the CNS by immunohistochemistry. Slc10a4 is the rat counterpart of the human orphan carrier SLC10A4, which was recently reported to be highly expressed in brain and placenta. Both carriers belong to the solute carrier family SLC10, formerly named the "sodium/bile acid cotransporter family.

Quantitative magnetic resonance angiography of the cerebrovasculature in physiologic and pathologic states.

Background: In the past, clinical decisions regarding treatment of neurovascular disorders leading to ischemia have been guided by the percentage of stenosis of the vessel in question. However, such an approach assumes a predictable and stable relationship between the percentage of stenosis and the degree of flow reduction it causes. Historically, this type of relationship has been difficult to document.

In vivo relevance of Mrp2-mediated biliary excretion of the Amanita mushroom toxin demethylphalloin.

To determine which efflux carriers are involved in hepatic phalloidin elimination, hepatobiliary [(3)H]-demethylphalloin (DMP) excretion was studied in normal Wistar rats and in Mrp2 deficient TR(-) Wistar rats as well as in normal wild-type FVB mice, Mdr1a,b(-/-) knockout mice, and Bcrp1(-/-) knockout mice by in situ bile duct/gallbladder cannulation. A subtoxic dose of 0.03 mg DMP/kg b.

Adrenocorticotropin-secreting pancreatoblastoma.

We present a 3-year-old child with Cushing's syndrome due to an ACTH-secreting metastatic pancreatoblastoma. This malignancy is a rare cause of Cushing's syndrome, particularly at pediatric age. We describe her course including the use of ketoconazole to alleviate hypercortisolemia.

Phase I and pharmacokinetic study of the oral farnesyltransferase inhibitor lonafarnib administered twice daily to pediatric patients with advanced central nervous system tumors using a modified continuous reassessment method: a Pediatric Brain Tumor Consortium Study.

Purpose: A dose-escalation phase I and pharmacokinetic study of the farnesyltransferase inhibitor lonafarnib (SCH66336) was conducted in children with recurrent or progressive CNS tumors. Primary objectives were to estimate the maximum-tolerated dose (MTD) and to describe the dose-limiting toxicities (DLTs) and pharmacokinetics of lonafarnib. Farnesylation inhibition of HDJ-2 in peripheral blood was also measured.

The novel putative bile acid transporter SLC10A5 is highly expressed in liver and kidney.

Here we report the identification, cloning, and characterization of SLC10A5, which is a new member of Solute Carrier Family 10 (SLC10), also known as the "sodium/bile acid cotransporter family". Expression of SLC10A5/Slc10a5 was examined by quantitative real-time PCR and revealed its highest expression levels in liver and kidney in humans, rat and mouse. In rat liver and kidney, Slc10a5 expression was localized by in situ hybridization to hepatocytes and proximal tubules, respectively.

Molecular and phylogenetic characterization of a novel putative membrane transporter (SLC10A7), conserved in vertebrates and bacteria.

The 'Solute Carrier Family SLC10' consists of six annotated members in humans, comprising two bile acid carriers (SLC10A1 and SLC10A2), one steroid sulfate transporter (SLC10A6), and three orphan carriers (SLC10A3 to SLC10A5). In this study we report molecular characterization and expression analysis of a novel member of the SLC10 family, SLC10A7, previously known as C4orf13. SLC10A7 proteins consist of 340-343 amino acids in humans, mice, rats, and frogs and show an overall amino acid sequence identity of >85%.