Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs.

More than 50% of patients with aggressive B lymphomas and the majority of patients with low grade lymphomas are not cured by current therapeutic strategies. The lymphomas express the B cell antigen CD20 on the cell surface and this antigen serves as target for antibody-directed therapies. Clinical studies with encouraging results have been underway with the use of a chimeric anti-CD20 antibody (IDEC-C2B8), consisting of human IgG1-6 constant regions and variable regions from the murine monoclonal anti-CD20 antibody IDEC-2B8.

Signal transduction pathways involved in BCR-ABL transformation.

BCR-ABL is an oncogenic fusion gene found in patients with chronic myelogenous leukaemia (CML) and acute lymphocytic leukaemia whose oncogenic potential has been demonstrated using in vitro and in vivo model systems. Current research efforts are focused on defining the mechanism by which BCR-ABL transforms cells, with a view toward applying insights from these studies to the treatment of CML patients. BCR-ABL contains tyrosine residues, an SH2 domain, an SH3 domain, and proline-rich sequences.

Reduced cortical ecto-ATPase activity in rat brains during prolonged status epilepticus induced by sequential administration of lithium and pilocarpine.

Considerable evidence indicates that ATP, acting intracellularly of as a neurotransmitter, can influence nerve cell physiology in a variety of ways. Defects in the functioning of ATP-metabolizing enzymes could therefore lead to disturbances in neurotransmission and creation of sustained neuronal discharges characteristic of status epilepticus. In this study we investigated synaptosomal ATPase changes in rat brains during lithium/pilocarpine-induced status epilepticus.

Prediction of outcome for patients with cutaneous melanoma.

Most patients with primary melanoma are cured by local surgery, but a significant minority develop fatal metastases. The ability to identify patients with progressive disease is central to efficient management: permitting optimal deployment of adjunctive therapy and sparing the non-progressing majority the morbidity of aggressive therapy. Accurate prediction on an individual patient basis is the ideal, but the best current prognosticators permit only assignment to risk categories.

Immunologic activation during pregnancy: serial measurement of lymphocyte phenotype and serum activation molecules in HIV-infected and uninfected women.

Immunologic alterations occur during pregnancy, but the effect of pregnancy on HIV infection is controversial. We characterized some of the immunologic alterations with potential to influence HIV disease in 99 infected and 46 uninfected women during pregnancy and up to 6 months post-partum. Immunophenotyping to quantitate the major lymphocyte subsets and determine expression of activation and adhesion molecules on T cells was performed using 3-color staining and laser flow cytometry.

Recent structural solutions for antibody neutralization of viruses.

Structural studies of virus-antibody interactions can offer insights into mechanisms of virus neutralization and immune escape. Crystallography and cryoelectron microscopy can reveal the structural relationship between receptor-binding sites and neutralization epitopes, as well as whether molecular rearrangements occur upon antibody binding.

Chest teleradiology in a teaching hospital emergency practice.

Objective: New standards for hospital accreditation and health care reimbursement may require that faculty subspecialists be more available after regular working hours to supervise residents in academic radiology departments. We designed a receiver operating characteristic study to determine whether a thoracic radiologist who evaluated computed radiography (CR) images of the chest at a home-based teleradiology workstation could add significant value to a junior resident's interpretations of films within the hospital for acutely ill patients.

Subjects And Methods: Using a hybrid cassette, we obtained analog chest films and CR images simultaneously for each of 252 acutely ill patients in the emergency department and in an intensive care unit.

Pravastatin increases survival and inhibits natural killer cell enhancement factor in liver transplanted rats.

Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been shown to decrease the number of acute rejection episodes in cardiac and renal transplant patients. This study evaluates the effects of pravastatin on survival of rats following liver transplant and attempts to elucidate the mechanisms of these effects. Both survival and natural killer cell enhancing factor (NKEF) studies utilized Dark Agouti rats for donor livers transplanted into Brown Norway rats as recipients.

The performance of simple instruments in detecting geriatric conditions and selecting community-dwelling older people for geriatric assessment.

Background: comprehensive geriatric assessment (CGA) appears to be less effective when performed in outpatient clinics than in hospital settings. The effectiveness of outpatient CGA might be improved by selectively targeting frailer community-dwelling elderly people. The purpose of this study was to evaluate the clinical performance of rapidly-administered standard screening measures for geriatric syndromes in selecting community-dwelling older people for outpatient CGA.

The EVT tube and bifurcated endograft systems: technical considerations and clinical summary. EVI Investigators.

Endovascular exclusion of abdominal aortic aneurysms (AAAs) is an investigational technique under scrutiny around the world. The tube and bifurcated versions of the Endovascular Grafting System (EGS) developed by Endovascular Technologies are the subjects of FDA-approved multicenter trials in the United States (US). Similar studies are under way in Europe, Australia, and the United Kingdom.

The Neuropsychiatric Inventory: assessing psychopathology in dementia patients.

The Neuropsychiatric Inventory (NPI) was developed to assess psychopathology in dementia patients. It evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavior disturbances, and appetite and eating abnormalities. The severity and frequency of each neuropsychiatric symptom are rated on the basis of scripted questions administered to the patient's caregiver.

The use of autologous transplantation in the treatment of malignant disorders.

Autologous transplantation uses high dose chemotherapy (with or without radiation therapy) followed by hematopoietic stem cell support in an attempt to cure certain malignant conditions. Autotransplantation can be considered as a treatment modality, if the tumor demonstrates a steep dose-response curve, marrow toxicity is the major dose limiting side effect of the active chemotherapeutic agents, and the source of the cells used for hematopoietic reconstitution is free of viable tumor cells. Hematopoietic stem cells can be obtained from peripheral blood after recovery from chemotherapy induced neutropenia or following treatment with hematopoietic growth factors and these peripheral blood stem cells are the predominant product used for autologous transplants at the present time.

Prenatal ontogeny of the epidermal growth factor receptor and its ligand, transforming growth factor alpha, in the rat brain.

Transforming growth factor alpha (TGF alpha) interacts with the epidermal growth factor receptor (EGF-R) to produce its biological effects. TGF alpha induces the proliferation and differentiation of central nervous system (CNS) astrocytes and pluripotent stem cells, as well as the survival and differentiation of postmitotic CNS neurons. Both TGF alpha and EGF-R have been localized to the postnatal CNS.

Identification of a ferritin light chain pseudogene near the glycerol kinase locus in Xp21 by cDNA amplification for identification of genomic expressed sequences.

We used cDNA amplification for identification of genomic expressed sequences (CAIGES) to identify genes in the glycerol kinase region of the human X chromosome. During these investigations we identified the sequence for a ferritin light chain (FTL) pseudogene in this portion of Xp21. A human liver cDNA library was amplified by vector primers, labeled, and hybridized to Southern blots of EcoRI-digested human genomic DNA from cosmids isolated from yeast artificial chromosomes in the glycerol kinase region of Xp21.

Harmonic imaging of porcine intraovarian arteries using sonographic contrast medium: initial findings.

The purpose of this study was to visualize, using harmonic gray-scale imaging, blood flow in porcine intraovarian arteries after intravenous injections of a bubble-based sonographic contrast medium. Five female pigs underwent laparotomy. Surgically isolated ovaries were scanned intraperitoneally by an ultrasound system reconfigured with software changes to accomplish harmonic imaging.

Retinoic acid synthesis in normal and Alzheimer diseased brain and human neural cells.

Retinoids play fundamental roles in CNS development, but their distribution, metabolism, and function within the mature human CNS are unknown. In these studies, extracts of autopsy tissues recovered from histopathologically confirmed control and Alzheimer diseased brains were tested for their ability to synthesize retinoic acid. Retinaldehyde dehydrogenase (RLDH), the enzyme that forms retinoic acid from retinaldehyde, was present in hippocampus, frontal cortex, and parietal cortex.

The effects of temperature upon calcium exchange in intact cultured cardiac myocytes.

Cardiac myocyte Ca transport systems, such as sarcoplasmic reticulum Ca-ATPase and sarcolemmal Na/Ca exchange (Na/Ca), are critically dependent on temperature. The purpose of this work was to study the effect of temperature on cellular Ca compartmentation and its exchange characteristics in intact functional neonatal cultured myocytes. The Na/Ca mediated Ca exchange (CaNa/Ca)--including its sarcoplasmic reticulum (SR) and sarcolemmal (SL) contributions, a slow exchange component related to mitochondrial Ca and the La displaceable Ca pool were studied combining isotopic and gas-dissection techniques for membrane isolation.

PET in oncology: will it replace the other modalities?

Medical imaging technology is rapidly expanding and the role of each modality is being redefined constantly. PET has been around since the early sixties and gained clinical acceptance in oncology only after an extreme number of scientific publications. Although PET has the unique ability to image biochemical processes in vivo, this ability is not fully used as a clinical imaging tool.

Calcifying subpopulation of bovine aortic smooth muscle cells is responsive to 17 beta-estradiol.

Background: Arterial calcification, common in atherosclerosis, is associated with an increased risk of clinical events such as myocardial infarction. We previously identified a subpopulation of bovine aortic medial cells, calcifying vascular cells (CVCs), that have osteoblastic characteristics and form bone mineral in vitro in the form of calcified nodules. To assess whether estrogen modulates arterial calcification as well as bone calcification, we tested CVCs for estrogen receptors and for the effect of 17 beta-estradiol on formation of calcified nodules, calcium content, alkaline phosphatase activity, and osteocalcin concentration in the culture medium.

Progression of metastatic human prostate cancer to androgen independence in immunodeficient SCID mice.

Prostate cancer mortality results from metastasis to bone and hormone-independent tumor growth. Models to study these progressive changes are lacking. Here we describe the propagation of advanced human prostate cancer by direct transfer of surgical samples from patients into immune-deficient male SCID mice.

Characterization of feline immunodeficiency virus integrase and analysis of functional domains.

The wild-type and mutant derivatives of the integrase protein of feline immunodeficiency virus (FIV) were cloned and expressed in Escherichia coli. The purified proteins were examined using various model DNA substrates for their catalytic activities: 3'-end processing, 3'-end joining, and disintegration. The reactions required the presence of either Mn2+ or Mg2+ as a divalent cation.

Evidence for the presence of an unusual nitric oxide- and citrulline-producing enzyme in rat kidney.

We have found an enzymatic activity obtained from rat kidney capable of producing citrulline and NOx. (nitrate and nitrite) which was resistant to inhibition by conventional arginine analogues. This enzyme activity does not require any calcium or calmodulin and was found to be induced during pregnancy.

Esophageal distension induced gastric relaxation is mediated in part by vagal peripheral reflex mechanism in rats.

The effect of short-term lower esophageal distension on intragastric pressure (IGP) and the related neural pathways involved were investigated in urethane-anesthetized rats in which enteric nervous system connections were interrupted by ligations of the pylorus and the gastroesophageal junction while keeping the gastric vagus nerve trunks intact. Under these conditions, lower esophageal distension with a bolus of 0.2 to 0.

Acute activation of circulating polymorphonuclear neutrophils following in vivo administration of cocaine. A potential etiology for pulmonary injury.

Crack cocaine has become a major drug of abuse in the United States and its use is associated with a broad spectrum of pulmonary complications. The present study was conducted to determine whether controlled in vivo administration of cocaine (inhaled or IV) alters the function of circulating inflammatory cells in a manner capable of contributing to acute lung injury. Subjects who regularly smoked crack cocaine were asked to abstain from illicit drug use for at least 8 h, and were then administered one of the following treatments on each of 4 study days: inhaled cocaine base (45 mg), inhaled placebo (4.

The kinetics and regulation of the induction of type II nitric oxide synthase and nitric oxide in human fetal glial cell cultures.

Our understanding of how human glial cells are induced to produce nitric oxide and how the production is regulated may allow us to better design therapeutic strategies for treating inflammatory diseases of the central nervous system in man. Cultures of human fetal astrocytes and microglia produce inducible nitric oxide synthase and nitric oxide in response to Interferon gamma and Interleukin 1 beta. The mRNA for the enzyme was induced by 2 h and returned to baseline by day 2; the protein was expressed by 24 h and was present in cells for the entire 7 days of culture.