1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): I. Direct inhibition of O6-alkylguanine-DNA alkyltransferase (AGT) by electrophilic species generated by decomposition.

Purpose: To investigate the interaction of the electrophilic species generated by the decomposition of the antineoplastic prodrug 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M) on the ability of O(6)-alkylguanine-DNA alkyltransferase (AGT) to repair alkylated O(6)-chloroethylguanine and/or N(1),O(6)-ethanoguanine DNA lesions.

Materials And Methods: The contributions of inhibitory electrophilic species generated from VNP40101M towards AGT was assessed using analogues that selectively generated either the chloroethylating or the carbamoylating components of VNP40101M. The activity of AGT was determined from the inhibition of crosslink formation from O(6)-chloroethylguanine and/or N(1),O(6)-ethanoguanine lesions.

Correlation of lamotrigine concentrations between serum and saliva.

Study Objective: To compare the relationship between serum and salivary concentrations of lamotrigine in pediatric and adult epilepsy populations.

Design: Paired-sample pharmacokinetic study.

Setting: University neurology clinic.

1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): II. Role of O6-alkylguanine-DNA alkyltransferase in cytotoxicity.

Purpose: VNP40101M (1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine) is a sulfonylhydrazine prodrug that possesses broad spectrum antitumor efficacy in murine models. VNP40101M activation generates chloroethylating species that alkylate DNA at the O(6)-position of guanine, and a carbamoylating agent, methyl isocyanate, which inhibits O(6)-alkylguanine-DNA alkyltransferase (AGT) in model systems. We determined whether expression of AGT in Chinese hamster ovary (CHO) cells decreased sensitivity to VNP40101M and explored the mechanism of VNP40101M cytotoxicity by employing analogs of VNP40101M that generate reactive intermediates with either carbamoylating or chloroethylating activity.

Macrophage migration inhibitory factor delays apoptosis in neutrophils by inhibiting the mitochondria-dependent death pathway.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine known to activate macrophages and T cells. In this study, we demonstrate that recombinant MIF delays apoptosis of neutrophils in vitro. MIF action is dose and time dependent as well as specific since it was abolished with a neutralizing anti-MIF antibody.

Neurosarcoid presents differently in children than in adults.

Background: Neurosarcoid is seldom recognized in children. In the absence of any large pediatric series, it has been assumed that the presenting signs and symptoms are identical in adults and children.

Objective: To test the hypothesis that childhood neurosarcoid differs in presenting signs and symptoms from neurosarcoid in adults.

Novel membrane protein shrew-1 targets to cadherin-mediated junctions in polarized epithelial cells.

While searching for potential candidate molecules relevant for the pathogenesis of endometriosis, we discovered a 2910-base pair cDNA encoding a novel putative 411-amino acid integral membrane protein that we called shrew-1. The putative open-reading frame was confirmed with antibodies against shrew-1 peptides that labeled a protein of approximately 48 kDa in extracts of shrew-1 mRNA-positive tissue and also detected ectopically expressed shrew-1. Expression of epitope-tagged shrew-1 in epithelial cells and analysis by surface biotinylation and immunoblots demonstrated that shrew-1 is indeed a transmembrane protein.

Topiramate concentration in saliva: an alternative to serum monitoring.

This study examines the relationship between serum and saliva topiramate concentrations, and attempts to determine if saliva may be a useful alternative to serum for therapeutic monitoring. Saliva and blood specimens were collected from 31 epilepsy patients (mean age 10.5 +/- 6.

[Endometriosis--a stem cell disease?].

Endometriosis is an estrogen-dependent and chronic disease with an unknown etiology and pathogenesis. It is however likely and well accepted that retrograde menstruation of endometrial cells into the pelvic cavity is the origin of this disease in many cases. Here we discuss a model in which retrogradely menstruated endometrial cells have different inherent developmental properties because they represent in fact a mixture of different developmental cell stages.

Herpes simplex encephalitis and radiotherapy.

The pathogenesis underlying the reactivation of latent herpes simplex virus remains undefined. This article presents the case of a 15-year-old male who developed herpes simplex encephalitis, as proven by a positive cerebrospinal fluid polymerase chain reaction and supported by magnetic resonance imaging findings during radiotherapy for pontine glioma. The temporal relation of radiotherapy to the occurrence of herpes simplex encephalitis suggests that cranial irradiation may play a role in the reactivation of latent herpes simplex virus.

Selective anterior fusion of thoracolumbar/lumbar curves in adolescents: when can the associated thoracic curve be left unfused?

Study Design: A retrospective multicenter study was conducted to investigate patients with a major thoracolumbar/lumbar adolescent idiopathic scoliosis and an associated minor thoracic curve treated with an anterior instrumentation and fusion of the lower curve.

Objective: To establish criteria for determining when such curves can be successfully treated by an anterior only procedure of the lower curve with acceptable spinal balance and residual thoracic curve.

Summary Of Background Data: Anterior spinal instrumentation techniques have been proved effective for the management of isolated thoracolumbar/lumbar scoliosis with small compensatory thoracic curves.

Hypoxia, hormones, and red blood cell function in chick embryos.

The red blood cell function of avian embryos is regulated by cAMP. Adenosine A(2A) and beta-adrenergic receptor activation during hypoxic conditions cause changes in the hemoglobin oxygen affinity and CO(2) transport. Furthermore, experimental evidence suggests a general involvement of cAMP in terminal differentiation of avian erythroblasts.

Correlation of levetiracetam concentrations between serum and saliva.

Purpose: More than 100 drugs have been evaluated for salivary therapeutic drug monitoring since the 1970s. The most studied drugs are the anticonvulsants phenytoin, phenobarbital, and carbamazepine, demonstrating strong correlations between serum and saliva concentrations. No published data exist for levetiracetam (LEV) to the authors' knowledge.

CNS angiitis in graft vs host disease.

Graft-vs-host disease (GVHD) is a potentially treatable cause of progressive neurologic decline after bone marrow transplantation (BMT). The authors present histologic confirmation of CNS granulomatous angiitis in a child with chronic GVHD after BMT. Since cranial MRI showed only nonspecific findings, CNS vasculitis associated with GVHD after BMT may be underdiagnosed.

Isolation and characterization of T4 bacteriophage gp17 terminase, a large subunit multimer with enhanced ATPase activity.

Phage T4 terminase is a two-subunit enzyme that binds to the prohead portal protein and cuts and packages a headful of concatameric DNA. To characterize the T4 terminase large subunit, gp17 (70 kDa), gene 17 was cloned and expressed as a chitin-binding fusion protein. Following cleavage and release of gp17 from chitin, two additional column steps completed purification.

NTP pattern of avian embryonic red cells: role of RNA degradation and AMP deaminase/5'-nucleotidase activity.

During terminal erythroid differentiation, degradation of RNA is a potential source for nucleotide triphosphates (NTPs) that act as allosteric effectors of hemoglobin. In this investigation, we assessed the developmental profile of RNA and purine/pyrimidine trinucleotides in circulating embryonic chick red blood cells (RBC). Extensive changes of the NTP pattern are observed which differ significantly from what is observed for adult RBC.

Behavioral treatment of migraine in children and adolescents.

Behavioral interventions, particularly biofeedback and relaxation therapy, have demonstrated their effectiveness in the treatment of both adults and older children with migraine in controlled trials. The physiological basis for their effectiveness is unclear, but data from one trial suggest that levels of plasma beta-endorphin can be altered by relaxation and biofeedback therapies. The data supporting the effectiveness of behavioral therapies are less clear-cut in children than in adults, but that is also true for the data supporting medical treatment.

Management of common bile duct stones in a single operation combining laparoscopic cholecystectomy and peroperative endoscopic sphincterotomy.

The diagnosis and treatment strategy to apply to common bile duct stones (CBDS) is always a controversial subject. The aim of this study was to evaluate the treatment of CBDS in a "one-stage" operation by laparoscopic cholecystectomy (LC) and peroperative endoscopic sphincterotomy (ES). Between January 1994 and April 2000, 60 patients, 24 men and 36 women (sex ratio, 1.

A bipartite bacteriophage T4 SOC and HOC randomized peptide display library: detection and analysis of phage T4 terminase (gp17) and late sigma factor (gp55) interaction.

HOC and SOC are dispensable T4 capsid proteins that can be used for phage display of multiple copies of peptides and proteins. A bipartite phage T4 peptide library was created by displaying on tetra-alanine linker peptides five randomized amino acids from the carboxyl-terminus of SOC and five randomized amino acids from the amino terminus of HOC. The bipartite library was biopanned against the phage T4 terminase large subunit gp17 to identify T4 gene products that may interact with the terminase.

Valproate-associated stomatitis.

The purpose of this article is to report a case of severe stomatitis in a patient with pediatric epilepsy taking divalproex sodium. The case was reviewed with detailed oral examinations. This 5-year-old child developed severe stomatitis 18 months after institution of divalproex sodium.

Novel selection marker for mammalian cell transfection.

The availability of selectable markers suitable for use in mammalian cells has permitted the analysis of the influence of the stable overexpression of single or multiple genes on specific cell properties. This powerful technique has led directly to many fundamental advances in molecular biology and increased our overall understanding of cell growth and regulatory events. Although a variety of selectable markers are currently available, some cell lines continue to be naturally resistant to certain markers, making direct selection difficult or not feasible.

Failure of Helicobacter pylori eradication: is poor compliance the main cause?

Objective: The aim of the study was to evaluate whether poor compliance can be considered as the main cause of the low Helicobacter pylori (H. pylori) eradication rate observed in an ambulatory population.

Methods: Seventy-eight patients with non-ulcer dyspepsia or gastroduodenal ulcer in whom H.

[Carpal tunnel syndrome with an unusual cause: a malignant nerve sheath tumor of the median nerve].

We report on the follow-up of a patient who developed symptoms suggestive of carpal tunnel syndrome. Symptoms were however atypical with involvement of the nondominant hand and with selective, fascicular, electroneurographic changes. During the surgical decompression of the median nerve at the wrist a tumor was found, corresponding to an isolated malignant peripheral nerve sheath tumor (MPNST) of mild type.

In search of pathogenic mechanisms in endometriosis: the challenge for molecular cell biology.

Endometriosis, defined histologically as the presence of endometrium-like glands and stroma outside the uterus, is a chronic, invasive and metastasising disease. It shares features with malignant tumours (invasion and metastasis) but is not neoplastic. Despite the fact that endometriosis is one of the most frequent gynaecological diseases, it is under researched, puzzling and highly debated.

cAMP and in vivo hypoxia induce tob, ifr1, and fos expression in erythroid cells of the chick embryo.

During avian embryonic development, terminal erythroid differentiation occurs in the circulation. Some of the key events, such as the induction of erythroid 2,3-bisphosphoglycerate (2,3-BPG), carbonic anhydrase (CAII), and pyrimidine 5'-nucleotidase (P5N) synthesis are oxygen dependent (Baumann R, Haller EA, Schöning U, and Weber M, Dev Biol 116: 548-551, 1986; Dragon S and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 280: R870-R878, 2001; Dragon S, Carey C, Martin K, and Baumann R, J Exp Biol 202: 2787-2795, 1999; Dragon S, Glombitza S, Götz R, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996; Dragon S, Hille R, Götz R, and Baumann R, Blood 91: 3052-3058, 1998; Million D, Zillner P, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 261: R1188-R1196, 1991) in an indirect way: hypoxia stimulates the release of norepinephrine (NE)/adenosine into the circulation (Dragon et al., J Exp Biol 202: 2787-2795, 1999; Dragon et al.

Catheter-related infection in patients on home parenteral nutrition: results of a prospective survey.

Background & Aims: Central venous catheter (CVC) infection is the most frequent complication during home parenteral nutrition (HPN). We prospectively assessed incidence and catheter-related sepsis (CRS)-associated factors in the 42 adult patients enrolled in our HPN centre since its opening.

Methods: Age, frequency of infusions, CVC type, autonomy or nurse/family aid, underlying disease, involved infectious organism(s), hospital stay, efficacy of antibiotic-lock and other infectious complications, were studied.