Lack of effect of dirithromycin on theophylline pharmacokinetics in healthy volunteers.

Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) alone and after a 10 day course of dirithromycin (two 250 mg tablets od). The study phases were separated by a 3 week washout period.

Imaging cells in the developing nervous system with retrovirus expressing modified green fluorescent protein.

To visualize the movements of cells and their processes in developing vertebrates, we constructed replication-incompetent retroviral vectors encoding green fluorescent protein (GFP) that can be detected as a single integrated copy per cell. To optimize GFP expression, the CMV enhancer and avian beta-actin promoter were incorporated within a retrovirus construct to drive transcription of redshifted (F64L, S65T) and codon-modified GFP (EGFP), EGFP tagged with GAP-43 sequences targeting the GFP to the cell membrane, or EGFP with additional mutations that increase its ability to fold properly at 37 degrees C (S147P or V163A, S175G). We have used these viruses to efficiently mark and follow the developmental progression of a large population of cells in rat neocortex and whole avian embryos.

Review and comparison of advanced-generation macrolides clarithromycin and dirithromycin.

We reviewed English-language clinical studies, abstracts, and review articles identified from MEDLINE searches from January 1966-August 1998, and bibliographies of identified articles to compare advanced-generation macrolides dirithromycin and clarithromycin and their use for respiratory tract infections. Both agents have superior adverse effect profiles compared with erythromycin, the original macrolide. Both have broad antibacterial coverage, but clarithromycin usually has a lower MIC90 to susceptible organisms than dirithromycin; for most isolates this difference is not clinically significant.

Isolation of erythropoietin receptor agonist peptides using evolved phage libraries.

Cyclic peptides capable of activating the erythropoietin receptor (EPOR) were isolated from phage display libraries by screening with a novel EPOR-IgG fusion protein reagent. A parental clone ERB1 (EPO Receptor Binder 1) was first isolated from a phage display library displaying 38 random amino acids as an N-terminal fusion with the M13 minor capsid protein, pill. An evolved library was then produced from the parental sequence using an oligonucleotide saturation mutagenesis strategy which yielded EPOR binding sequences with 20 times the relative affinity of ERB1.

Expression and ligand binding assays of soluble cytokine receptor-immunoglobulin fusion proteins.

We have developed a cloning vector for the expression of type I cytokine receptor, NO, extracellular domain (ECD)-mouse IgG1 Fc fusion proteins. The vector has a versatile polylinker that allows in-frame cloning of the receptor ECD with the mouse IgG1 sequence to encode a receptor ECD-IgG1 fusion construct. The receptor-IgG1 fusion proteins are transiently expressed in useful amounts following transfection of the expression vector into COS7 cells and G418 selection.

Intrinsic polarity of mammalian neuroepithelial cells.

Progenitor cells in the mammalian forebrain can undergo either symmetric or asymmetric cell divisions by varying their cleavage orientation. In asymmetric divisions, cells distribute apically and basally localized proteins differentially to their daughters. Here we explore the intrinsic polarity of neuroepithelial cells in the developing telencephalon.

Delayed referral reduces the success of video-assisted thoracoscopic surgery for spontaneous pneumothorax.

Background: Video-assisted thoracoscopic surgery (VATS) is now the generally preferred surgical treatment for spontaneous pneumothorax but is more difficult once pleural adhesions have developed. To test the hypothesis that VATS is under-used because of prolonged pleural intubation, we have audited the effect of preoperative management on subsequent surgical outcome.

Method: Data are expressed as median (range).

Sudden unexpected death resulting from an anomalous hypoplastic left coronary artery.

We present a case of sudden death in a 24-year-old, healthy white female who was physically active and participated in sports, including soccer. Two weeks prior to her death, an insurance physical examination revealed an abnormal electrocardiogram which demonstrated flipped T waves in the anterior leads. There was no other remarkable medical history.

An immunohistochemical study of the distribution of biotin in tissues of pigs and chickens.

An optimised indirect peroxidase-anti-peroxidase immunohistochemical technique was used to detect endogenous biotin in frozen tissue sections from biotin-supplemented and biotin-depleted pigs and chickens. A monoclonal anti-biotin antibody was used as primary antibody in this technique. Immunoreactive biotin was detected in many tissues of both species including liver, kidney, pancreas, adipose tissue, adrenal gland, testis, brain, choroid plexus, cardiac and skeletal muscle, epithelium of the respiratory and digestive systems, skin and lymphoid tissues.

Histopathologic and ultrastructural alterations of white liver disease in sheep experimentally depleted of cobalt.

Many cobalt-deficient sheep develop liver lesions known as ovine "white liver" disease, but the etiology of these changes is controversial. It has been suggested that cofactors are required for development of liver damage in cobalt-deficient sheep. In this study, one group of lambs (n = 5) was fed a diet low in cobalt (4.

Determination of the migratory capacity of embryonic cortical cells lacking the transcription factor Pax-6.

The cerebral cortex forms by the orderly migration and subsequent differentiation of neuronal precursors generated in the proliferative ventricular zone. We studied the role of the transcription factor Pax-6, which is expressed in the ventricular zone, in cortical development. Embryos homozygous for a mutation of Pax-6 (Small eye; Sey) had abnormalities suggesting defective migration of late-born cortical precursors.

Identification of novel human WW domain-containing proteins by cloning of ligand targets.

A recently described protein module consisting of 35-40 semiconserved residues, termed the WW domain, has been identified in a number of diverse proteins including dystrophin and Yes-associated protein (YAP). Two putative ligands of YAP, termed WBP-1 and WBP-2, have been found previously to contain several short peptide regions consisting of PPPPY residues (PY motif) that mediate binding to the WW domain of YAP. Although the function(s) of the WW domain remain to be elucidated, these observations strongly support a role for the WW domain in protein-protein interactions.

Postmitotic neurons migrate tangentially in the cortical ventricular zone.

Patterns of cell movement play a key role in the establishment of the brain's functional architecture during development. The migration of neuronal progenitor cells has been hypothesized to disperse clonally related cells among different areas of the developing cerebral cortex. To test this model, we explored the migratory patterns of cells in the proliferative zone of the intact cortex of the ferret.

Induction of deep layer cortical neurons in vitro.

Transplantation studies suggest that the laminar fates of cerebral cortical neurons are determined by environmental signals encountered just before mitosis. In ferret, E29 progenitor cells normally produce neurons of layers 5 and 6. When transplanted during S-phase into an older ventricular zone, E29 progenitors produce neurons that change their fates and migrate to layer 2/3; however, cells transplanted later in the cell cycle migrate to their normal deep-layer positions even in an older environment (McConnell and Kaznowski, 1991).

Restriction of late cerebral cortical progenitors to an upper-layer fate.

Early in development, neural progenitors in cerebral cortex normally produce neurons of several layers during successive cell divisions. The laminar fate of their daughters depends on environmental cues encountered just before mitosis. At the close of neurogenesis, however, cortical progenitors normally produce neurons destined only for the upper layers.

Cloning of ligand targets: systematic isolation of SH3 domain-containing proteins.

Based on the prevalence of modular protein domains, such as Src homology domain 3 and 2 (SH3 and SH2), among important signaling molecules, we have sought to identify new SH3 domain-containing proteins. However, modest sequence similarity among these domains restricts the use of DNA-based methods for this purpose. To circumvent this limitation, we have developed a functional screen that permits the rapid cloning of modular domains based on their ligand-binding activity.

Construction and screening of M13 phage libraries displaying long random peptides.

We have constructed two phage display libraries expressing N-terminal pIII fusions in M13 composed of 37 and 43 random amino acid domains, respectively. The D38 library expresses 37 random amino acids with a central alanine residue, and the DC43 library contains 43 random amino acids with a central cysteine flanked by two glycine residues, giving the displayed peptide the potential to form disulfide loops of various sizes. We demonstrate that the majority of random sequences in both libraries are compatible in pentavalent display with phage viability.

Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience.

Between 1989 and 1993, 255 tumor biopsies representing 4 tumor histologies (melanoma, breast cancer, colon cancer and renal cell cancer) were received by the Surgery Branch of the National Cancer Institute. Tumor-infiltrating lymphocytes (TIL) were grown from single-cell suspensions of tumor biopsies over the course of 30-45 days. The TIL were grown in medium containing IL-2.

Melanoma tumor-infiltrating lymphocytes derived from four distinct anatomic sites obtained from a single patient: comparison of functional reactivity and melanoma antigen recognition.

Tumor-infiltrating lymphocytes (TILs) were grown from four distinct anatomic sites from a patient with metastatic melanoma. The metastatic sites included a tumor-involved lymph node, a subcutaneous lesion obtained from the chest wall, a portion of bowel, and adrenal gland. TILs grown from each anatomic site over the course of 20 days in the presence of 6,000 IU/ml recombinant interleukin-2 exhibited comparable growth rates.

Strategies for the generation of neuronal diversity in the developing central nervous system.

During development, the neural tube produces a large diversity of neuronal phenotypes from a morphologically homogeneous pool of precursor cells. In recent years, the cellular and molecular mechanisms by which specific types of neurons are generated have been explored, in the hope of discovering features common to development throughout the nervous system. This article focuses on three strategies employed by the CNS to generate distinct classes of neuronal phenotypes during development: dorsal-ventral polarization in the spinal cord, segmentation in the hindbrain, and a lamination in the cerebral cortex.

Cleavage orientation and the asymmetric inheritance of Notch1 immunoreactivity in mammalian neurogenesis.

Neurons in the mammalian central nervous system are generated from progenitor cells near the lumen of the neural tube. Time-lapse microscopy of dividing cells in slices of developing cerebral cortex reveals that cleavage orientation predicts the fates of daughter cells. Vertical cleavages produce behaviorally and morphologically identical daughters that resemble precursor cells; these symmetric divisions may serve to expand or maintain the progenitor pool.