Treatment advances in acid secretory disorders: the promise of rapid symptom relief with disease resolution.

Gastric acid-related disorders are common clinical problems associated with a wide range of symptoms. Important advances have occurred over the last 20 yr that have improved our understanding of these disorders as well as our approach to treatment. Today, control of gastric acid secretion represents the cornerstone of effective management of both peptic ulcer disease and gastroesophageal reflux disease (GERD).

Inhibitory effects of deferoxamine on UVB-induced AP-1 transactivation.

Production of reactive oxygen species (ROS) by iron can contribute directly to DNA and protein damage and may contribute to cell signaling and proliferation. We have examined the effects of the iron(III) chelator deferroxamine (DFO) and iron (FeCl(3)) on UVB (290-320 nm)-induced activator protein 1 (AP-1) signaling. The ability of DFO to inhibit UVB-induced AP-1 transactivation was tested in a human keratinocyte cell line stably transfected with a luciferase reporter driven by a single AP-1 element.

Increased ROS levels contribute to elevated transcription factor and MAP kinase activities in malignantly progressed mouse keratinocyte cell lines.

There is evidence that reactive oxygen species (ROS) are important mediators of tumor promotion and progression. The molecular mechanisms involved in ROS-mediated signaling, however, are unclear at present. Using ionizing radiation and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as model physical and chemical carcinogens, we have malignantly progressed 308 cells, a papilloma-producing mouse keratinocyte cell line, and investigated the molecular alterations in the progressed phenotypes.

Synergistic antiallodynic effects of spinal morphine with ketorolac and selective COX1- and COX2-inhibitors in nerve-injured rats.

The possible role of spinal prostanoids in the tactile allodynia and thermal hyperalgesia associated with an experimental model of neuropathic pain was investigated. Neuropathic pain was induced by tight ligation of the L5 and L6 spinal nerves. Tactile allodynia was assessed 7 days after the surgery by measuring hindpaw withdrawal threshold to probing with von Frey filaments.

Characterization of mother-infant HIV type 1 gag p17 sequences associated with perinatal transmission.

The gag p17 matrix sequences of human immunodeficiency virus type 1 (HIV-1) from seven infected mother-infant pairs were analyzed after perinatal transmission. The p17 matrix open reading frame was maintained in 143 of the 166 clones analyzed (86.2% frequency of intact p17 open reading frames).

Inhibition of p38 MAP kinase increases okadaic acid mediated AP-1 expression and DNA binding but has no effect on TRE dependent transcription.

By performing in vitro kinase assays we found in papilloma producing 308 mouse keratinocytes that okadaic acid elevated activities of extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinases (MAPKs). This okadaic acid mediated activation of MAP kinases correlated with increased AP-1 binding to a consensus TPA responsive element (TRE) and elevated TRE dependent transcription. To determine the role of p38 MAP kinases in these processes we employed the specific p38 MAP kinase inhibitor SB 203580.

Toddler-age nodulocystic acne.

Toddler-age nodulocystic acne is a rare disorder for which the etiology remains unknown. We report 2 cases and discuss the safety and efficacy of oral isotretinoin therapy. Oral isotretinoin is safe and effective in treating this condition but requires close monitoring.

Gene by environment interactions in the development of asthma.

Present knowledge suggests that asthma is a heterogeneous condition. Different genetic backgrounds may or may not express themselves as asthma-like symptoms, depending on both the nature and the timing of exposures in the individual. Although particular attention has been paid to environmental factors that may increase the risk of asthma, it is equally important to understand 'protective' exposures that may have decreased during the last decades and may thus explain the reported increases in asthma prevalence.

The natural history of asthma.

Our understanding of the natural history of asthma is improving through the establishment of a more precise definition of asthma linked with information from large-scale longitudinal studies. Risk factors for the development of childhood asthma including sex, atopic status, genetic and familial factors, respiratory infections, and outdoor and indoor pollution are now more clearly understood. New information on the relation of viral wheezing episodes in infancy to later childhood asthma is evolving.

Anticoagulation for prevention of stroke.

One of the important recent advances in stroke prevention is the demonstration that warfarin can substantially reduce the risk for stroke in patients with atrial fibrillation (AF). On average, patients with AF have a stroke risk of 4.5% per year.

Contact areas and pressures between native patellas and prosthetic femoral components.

Contact areas and pressures between native patellas and a prosthetic condylar design femoral component were measured at flexion angles of 30 degrees, 60 degrees, and 90 degrees. These were compared to measurements obtained with a domed all-polyethylene patellar component. Mean native patellar contact areas were found to be fourfold greater than seen with the prosthetic patellar component.

Clearance of [125I]-tumor necrosis factor-alpha from the brain into the blood after intracerebroventricular injection in rats.

To test the hypothesis that brain to blood clearance is a mechanism by which brain inflammation and damage can increase circulating acute phase cytokines, rate of transfer of [125I]-tumor necrosis factor-alpha ([125I]-TNF) from brain to blood was determined. Acid precipitable [125I]-TNF appeared in peripheral blood within 5 min of intracerebroventricular (i.c.

Maintenance of an intact human immunodeficiency virus type 1 vpr gene following mother-to-infant transmission.

The vpr sequences from six human immunodeficiency virus type 1 (HIV-1)-infected mother-infant pairs following perinatal transmission were analyzed. We found that 153 of the 166 clones analyzed from uncultured peripheral blood mononuclear cell DNA samples showed a 92.17% frequency of intact vpr open reading frames.

Identification of adenylyl cyclase isoenzymes in CHO and B82 cells.

The identification of adenylyl cyclase isoenzymes in mammalian host cells is important for the interpretation of data obtained from cell lines heterologously expressing G-protein coupled receptors. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to amplify adenylyl cyclase cDNAs from Chinese hamster ovary (CHO) and mouse fibroblast (B82) cells. The isolated fragments were identified by restriction analyses and by sequencing.

Novel nuclear localization signal between the two DNA-binding zinc fingers in the human vitamin D receptor.

The human vitamin D receptor (hVDR) possesses a unique array of five basic amino acids positioned between the two DNA-binding zinc fingers that is similar to well-characterized nuclear localization sequences in other proteins. When residues within this region are mutated to nonbasic amino acids, or when this domain is deleted, the receptor is still well expressed, but it no longer associates with the vitamin D-responsive element in DNA, in vitro, and hVDR-mediated transcriptional activation is abolished in transfected cells. Concomitantly, the mutated hVDRs exhibit a significant shift in hVDR cellular distribution favoring cytoplasmic over nuclear retention as assessed by subcellular fractionation and immunoblotting.

Endomyocardial biopsy in the heterotopic heart transplant patient.

We present a technique for rapid and easy endomyocardial biopsy of the heterotopic transplanted heart. With a recent resurgence in heterotopic heart transplantation, we believe that ours is a sound technique in obtaining both routine surveillance biopsies as well as evaluating "right-sided pressures" in the "piggy-back" heart.

Inhibitory effects of perillyl alcohol on UVB-induced murine skin cancer and AP-1 transactivation.

The monoterpene perillyl alcohol (POH) has proven efficacious against the formation and progression of a variety of cancers. In this study, we tested the ability of POH to inhibit photocarcinogenesis in a nonmelanoma model of mouse skin carcinogenesis and its ability to inhibit UVB-induced activator protein 1 (AP-1) transactivation in mouse skin and human keratinocytes. POH (10 mM) was applied topically to the ears and shaved dorsal surface of groups of 35 BALB/c mice throughout the experiment, during and after UVB treatment.

Human milk as a potential enteral source of erythropoietin.

In addition to its content of traditional nutrients, milk is a rich source of hormones and peptides, which survive digestion in the neonatal gastrointestinal tract secondary to lower proteolytic activity and increased protein permeability. Previous studies have shown accelerated erythropoiesis or elevated serum erythropoietin (Epo) levels in neonatal (suckling) animals after maternal phlebotomy or maternal hypoxia exposure. We sought to determine whether significant quantities of Epo are present in human milk and whether Epo remains intact under physiologic digestion conditions.

Contractile properties of human nasal dilator motor units.

The technique of intramuscular microstimulation was used to activate facial nerve fibers while acquiring simultaneous twitch force measurements to measure the contractile properties and force-frequency responses of human nasal dilator (ND) motor units. Twitch force amplitude (TF), contraction time (CT), half-relaxation time (HRT), and the maximal rate of rise of force normalized to the peak force (maximum contraction rate, MCR) were recorded from 98 ND motor units in 37 subjects. The average CT, HRT, MCR, and TF were 47.

Conservation of an intact vif gene of human immunodeficiency virus type 1 during maternal-fetal transmission.

The human immunodeficiency virus type 1 (HIV-1) vif gene is conserved among most lentiviruses, suggesting that vif is important for natural infection. To determine whether an intact vif gene is positively selected during mother-to-infant transmission, we analyzed vif sequences from five infected mother-infant pairs following perinatal transmission. The coding potential of the vif open reading frame directly derived from uncultured peripheral blood mononuclear cell DNA was maintained in most of the 78,912 bp sequenced.

Exotic snakebite: envenomation by an African puff adder (Bitis arietans).

We report an envenomation by the African puff adder (Bitis arietans), an exotic snake in the United States. The patient developed swelling and ecchymoses in the affected extremity, and cutaneous necrosis of the envenomated fingertip. There was no significant coagulopathy.

High carboxyhemoglobin concentrations occur in swine during desflurane anesthesia in the presence of partially dried carbon dioxide absorbents.

Background: Increased carboxyhemoglobin concentrations in patients receiving inhalation anesthetics (desflurane, enflurane, and isoflurane) have been reported. Recent in vitro studies suggest that dry carbon dioxide absorbents may allow the production of carbon monoxide.

Methods: The authors used high fresh oxygen flow (5 or 10 l/min) through a conventional circle breathing system of an anesthesia machine for 24 or 48 h to produce absorbent drying.

The use of stereotactic radiosurgical boost in the treatment of medulloblastomas.

Purpose: Starting in 1992, we began using a stereotactic radiosurgical (SRS) boost for the treatment of medulloblastomas. Four patients ranging in age from 7 to 42 years old have since been treated and are the subject of this retrospective study.

Methods And Materials: All patients were initially treated with a maximally debulking surgery and external beam radiotherapy, which were then followed by a stereotactic radiosurgical boost using a modified 6 MeV linear accelerator.

Okadaic acid stimulated TRE binding activity in a papilloma producing mouse keratinocyte cell line involves increased AP-1 expression.

The effects of the non-phorbol ester type tumor promoter okadaic acid, a serine-threonine phosphatase inhibitor, on activator protein 1 (AP-1) DNA binding activity were studied in papilloma producing 308 mouse keratinocytes. Okadaic acid increased AP-1 binding to a consensus TPA responsive element (TRE) within 2 h; maximum stimulation was observed at 6 h followed by a gradual decrease to basal levels within 24 h. Jun B, Jun D and Fos B proteins were identified as the major components of the AP-1 complex binding to the TRE element at 6 h.