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Biomedical subjects

R Newman

Publications and source records attributed to R Newman.

At least 73 records · Page 4Linked to original sources
PubMed1992

Three dimensional structure of the transmembrane region of the proto-oncogenic and oncogenic forms of the neu protein.

The neu proto-oncogene may be converted into a dominantly transforming oncogene by a single point mutation. Substitution of a valine residue at position 664 in the transmembrane region with glutamic acid activates the tyrosine kinase of the molecule and is associated with increased receptor dimerization. Previously we have proposed a model in which the glutamic acid side chain stabilizes receptor dimerization by hydrogen bonding. Other models have been proposed in which the mutation leads to a conformational change in the transmembrane region mimicking that assumed to occur following binding of a natural ligand. Synthetic peptides representing part of the transmembrane region were prepared. Some residues were replaced with serine in order to improve peptide solubility to allow purification and analysis. Both the peptides containing valine and glutamic acid dissolved in water and in an artificial lipid monolayer. The structures of the peptides were determined by NMR spectroscopy to be alpha-helical. No significant difference in conformation was observed between the two peptides. This result does not support the model proposing a conformational change. The receptor structures determined experimentally do allow alternative models involving receptor transmembrane region packing.

Amino Acid Sequence↗
PubMed1992

High growth reassortant influenza vaccine viruses: new approaches to their control.

When a new strain of an influenza virus is required to be incorporated into influenza vaccine, attempts are made to recombine such strains with laboratory adapted viruses, which will grow to high titre in order to improve the yield of the vaccine strain. It is important that such high growth reassortant vaccine strains are not contaminated with genes coding for the antigenic determinants of the high growth laboratory strain. We describe the characterization of two recent high growth reassortants and the application of the polymerase chain reaction to ensure their genetic identity and purity.

Antigens, Viral↗
PubMed1992

"Primatization" of recombinant antibodies for immunotherapy of human diseases: a macaque/human chimeric antibody against human CD4.

Immunoglobulin variable region genes from non-human primates, cynomolgus macaques, were shown to have 85%-98% homology with human immunoglobulin sequences and yet macaques are phylogenetically distant enough to respond against conserved human antigens. Immunoglobulin genes were isolated from monkeys immunized with human CD4 antigen and a human/monkey chimeric anti-CD4 antibody with 91-92% homology to human immunoglobulin framework regions was cloned and expressed. The antibody has an apparent affinity of 3.2 x 10(-11) M and exhibits potent immunosuppressive properties in vitro.

Animals↗
PubMed1992

A method for determining the periodicity of a troponin component in isolated insect flight muscle thin filaments by gold/Fab labelling.

Insect flight muscle has a large component (Tn-H) in the tropomyosin-troponin complex that is not present in vertebrate striated muscle thin filaments. Tn-H is shown by gold/Fab labelling to be present at regular intervals in insect flight muscle thin filaments. The Fab fragment of a monoclonal antibody to Tn-H was conjugated directly with colloidal gold and this probe used to label isolated thin filaments from the flight muscle of Lethocerus indicus (water bug). The distribution of gold particles seen in electron microscope images of negatively stained thin filaments was analysed to show that the probe bound to sites having a periodicity of approximately 40 nm, which is the expected value for the tropomyosin-troponin repeat. Conjugates of Fab with colloidal gold particles of 3 nm diameter labelled almost all sites. Conjugates with gold particles of 5 nm and 10 nm diameter labelled less efficiently (70% and 30%, respectively) but analysis of the distribution of inter-particle intervals among a number of filaments again gave the same fundamental spacing of 40 nm. The error in the measurements (standard deviation approximately +/- 4.2 for 5 nm gold/Fab) is less than earlier estimates for the size of the gold/Fab complex. Measurements on gold/Fab in negative stain suggest that the bound Fab contributes a shell about 2 nm in thickness around the gold particle. The radius of the probe (about 4.5 nm for 5 nm gold/Fab) would then be consistent with the value of error found. The size of the probe suggests that the gold particle binds to the side of the Fab molecule, rather close to the antibody combining site. The potential resolution of the technique may thus be better than originally expected.

Animals↗
PubMed1992

Synthetic peptides from a conserved region of gp120 induce broadly reactive anti-HIV responses.

In our efforts to identify products that might be used for active immunotherapy in human immunodeficiency virus (HIV) infection, we have studied synthetic peptides derived from the CD4 attachment site of gp120. Two peptides have emerged with particularly interesting properties. The first (B138) is linear and spans the envelope residues 421-438; the second (1005/45) encompasses amino acids 418-445 and is cyclized by way of a disulphide bond joining its terminal cysteines. Both species have been shown to inhibit syncytial formation in a conventional bioassay, B138 being the most efficient. Both peptides elicit high titres of anti-peptide antibodies in immunized mice, rabbits and goats, with titres exceeding 1:10(5) in many cases. A substantial portion of this response is directed against gp120 as determined by enzyme-linked immunosorbent assay (ELISA). Analysis by flow cytometry has demonstrated that the antisera are broadly reactive with multiple diverse strains of HIV. The anti-gp120 activity of the anti-peptide antiserum was further confirmed by radioimmuno-precipitation (RIP) assays. Furthermore, RIP analysis and inhibition experiments in a GD4-gp120 binding assay have revealed that anti-peptide sera contain antibodies directed against the CD4 attachment site on gp120 and interfere with this receptor-ligand interaction.

Animals↗
PubMed1991

Evidence for non-V3-specific neutralizing antibodies that interfere with gp120/CD4 binding in human immunodeficiency virus 1-infected humans.

Total anti-gp120 antibodies (total anti-gp120 Abs) were purified from a pool of four human immunodeficiency virus-positive (HIV+) sera by affinity chromatography on a gp120SF2-Sepharose column and exhibited both type- and group-specific neutralizing activities. To dissect the epitope specificity of the group-specific neutralizing antibodies, CD4 attachment site-specific antibodies (CD4-site Abs) were isolated from total anti-gp120 Abs by using a CD4-blocked gp120SF2-Sepharose column. The CD4-site Abs exhibited group-specific neutralizing activities. Another approach to dissecting type- and group-specific neutralizing activities of total anti-gp120 Abs was to separate the third variable region (V3)-specific antibodies (V3-region Abs) from non-V3-region-specific antibodies (non-V3 Abs). The results indicated that V3-region Abs exhibited type-specific neutralizing activities, whereas non-V3 Abs exhibited group-specific neutralizing activities. By comparing the neutralizing activities of V3-region Abs to those of non-V3 Abs, we concluded that V3-region Abs are more effective than non-V3 Abs in neutralizing a specific HIV isolate. Collectively, this study indicates that group-specific neutralizing anti-gp120 antibodies are specific for the CD4 attachment site.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The role of the psychologist expert witness: provider of perspective and input.

The definition and role of the expert witness is reviewed. Two conceptual systems for viewing the world, the scientific method and the adversarial system, are compared. The reconciliation and integration of these two discrepant systems are discussed in terms of input versus outcome. The rules of evidence, as well as problems of communication between the systems, are reviewed with the aim of providing expert witnesses with a better understanding of effective testimony. Finally, collaboration between the two systems is called for in order to provide guidelines for both neuropsychologists and attorneys.

Brain Damage, Chronic↗
PubMed1991

Direct isolation in eggs of influenza A (H1N1) and B viruses with haemagglutinins of different antigenic and amino acid composition.

Influenza A (H1N1) and influenza B viruses from clinical samples were isolated in the amniotic cavity of embryonated hens' eggs by classical techniques and propagated in the allantoic cavity. Virus progeny from different eggs which had been inoculated with virus material from the same clinical sample possessed antigenically distinguishable haemagglutinins (HAs). Virus progeny of some eggs possessed HAs which were serologically identical to those of virus isolated in parallel in mammalian (MDCK) cells. These egg-grown viruses possessing HAs with the antigenic phenotype of mammalian cell-grown viruses appeared to be antigenically related to epidemic influenza virus because post-infection human sera reacted to high titre with the virus HA. Specific nucleotide changes were detected in the HAs of the viruses isolated directly in eggs at positions 163 and 189 for influenza A (H1N1) viruses or positions 141 and 196 to 198 for influenza B viruses. Egg-isolated viruses which possessed the antigenic phenotype of mammalian cell-grown viruses retained glycosylation sites at positions 163 and 196. The viruses isolated directly in embryonated hens' eggs which possessed the HA antigenic phenotype and glycosylation sites of MDCK cell-grown virus can, unlike the latter viruses themselves, be used as candidate influenza vaccine viruses.

Amino Acid Sequence↗
PubMed1990

Diffuse bony metastases at presentation in a child with glioblastoma multiforme. A case report.

At initial diagnosis, an 11-year-old girl with glioblastoma multiforme (GBM) presented with diffuse osteoblastic metastases. Primary brain tumors rarely metastasize outside of the central nervous system (CNS) without prior neurosurgery. Extracranial spread at diagnosis has been previously documented in just two adults. Extracranial metastasis of a childhood glioma without prior neurosurgery at any time during the course of the disease is exceedingly rare. Spread to bone by gliomas is also infrequent, and when they occur, bony metastases are usually isolated to one or two sites in any given patient. The widespread osseous metastases in our patient have been reported in three prior cases of high-grade gliomas. This child's GBM likely reflects a highly aggressive variant with the potential to spread outside the CNS and with a predilection for bone. Oncologists should be aware that GBM may present in this fashion during childhood.

Bone Neoplasms↗
PubMed1990

A host-cell-selected variant of influenza B virus with a single nucleotide substitution in HA affecting a potential glycosylation site was attenuated in virulence for volunteers.

An influenza B virus was passaged in man (virus A) and then in human embryo trachea (C) and into embryonated eggs (D) or directly into eggs (B). Virus A, B, and C had the same (cell-like) haemagglutinin phenotype on reaction with selected monoclonal antibodies while D had an "egg-like" phenotype. The viruses were administered at a dose of 1,000 TCD50 (for MDCK cells) by intranasal inoculation to groups of 27 or 28 volunteers. Viruses A, B, and C all produced disease in six to eight volunteers, whereas D produced no illness and only four volunteers were infected. The viruses shed by the volunteers were indistinguishable from those with which they were inoculated. The haemagglutinin genes of the viruses were sequenced and changes were detected indicating amino acid substitutions at position 196-198 in the attenuated egg-grown virus D whereby a potential glycosylation site present in the other viruses was lost.

Amino Acid Sequence↗
PubMed1990

Nursing turnover in a psychiatric hospital.

Demands for quality nursing care in both psychiatric and general hospitals are increasing as the nation experiences a shortage of registered nurses (RNs). The average national turnover rate in the healthcare industry is almost 23%, and nurses account for 50% of that percentage (1). Because a stable, competent nursing staff is essential to meet the mandates of physicians and patients for quality inpatient care, the failure of a hospital to provide high-quality nursing in today's competitive healthcare climate may cause physicians and patients to go elsewhere. The nursing shortage and high nursing turnover rates have had a negative effect on both general and psychiatric hospitals. The focus of the study described in this article was on a specific psychiatric hospital, and the objective was to determine how hospital management might respond to the current nursing personnel challenges. An action research model was used to determine what employment factors were viewed by nursing personnel as most valuable and how satisfied the nurses were with these factors in their workplace. The results are reviewed.

Attitude of Health Personnel↗
PubMed1989

Hemodynamic study of short- and long-term isradipine treatment in patients with chronic ischemic congestive heart failure.

The acute hemodynamic effects of isradipine on cardiac performance, at rest and during exercise, were examined in nine male patients aged 37 to 69 years with congestive heart failure due to ischemic heart disease. The effects of 10 mg oral isradipine were maximal after two to three hours with significant decreases in blood pressure as well as in systemic and pulmonary vascular resistances, and an increase in cardiac output. There were no significant changes in heart rate or pulmonary capillary wedge pressure. For the same 50-watt bicycle workload pre- and post-drug, the addition of isradipine was associated with lower systemic and pulmonary vascular resistances (systemic vascular resistance, 805 +/- 70 versus 975 +/- 70; p less than 0.01; pulmonary vascular resistance, 144 +/- 27 versus 207 +/- 35 dynes.sec.cm-5; p less than 0.01), and lower pulmonary artery pressures (54 +/- 6/23 +/- 3 versus 66 +/- 7/27 +/- 3 mm Hg; p less than 0.01) during exercise. In a double-blind 12-week trial, body weight decreased during isradipine treatment (71.6 to 68.9 kg; p less than 0.01), but there were no significant changes in exercise duration, radionuclide ejection fraction, or cardiothoracic ratio, and no serious side effects were encountered. These results suggest that isradipine is worthy of further evaluation in long-term treatment of chronic ischemic congestive heart failure.

Adult↗
PubMed1989

Crystallization of p68 on lipid monolayers and as three-dimensional single crystals.

Two-dimensional crystals of p68, a Ca2+ -binding protein that has homology with members of the lipocortin/calpactin family, were obtained by interaction with a phospholipid monolayer. By measuring surface pressure at constant surface area, p68 was found to interact in a Ca2+ -dependent manner specifically with phosphatidylethanolamine, less so with phosphatidylserine and not at all with phosphatidylcholine. With dimyristoyl-phosphatidylethanolamine, two-dimensional crystalline arrays were formed. Image analysis of electron micrographs of these crystals, which diffracted to about 50 A, revealed p3 symmetry with a unit cell of about 178 A by 178 A; the protein densities showed a two-domain structure giving a cylindrical molecule of about 100 A by 35 A diameter packed as trimers. Three-dimensional microcrystals obtained without lipid or Ca2+ were suitable for electron microscopy and gave a tetragonal unit cell of about 256 A by 68 A. The implications of these observations on the structure and lipid specificity of p68 binding are discussed.

Annexin A6↗
PubMed1989

Physical activity, smoking, alcohol consumption, body mass index, and plasma lipid profiles of military reserve officers.

We assessed the physical activity level, smoking habits, alcohol consumption, ponderosity, and plasma lipid profiles of 688 middle-aged male reserve officers. When adjusting for Body Mass Index (BMI), individuals who reported physical activity of three or more times per week had significantly higher levels of high density lipoprotein cholesterol (HDL-C), lower total cholesterol (TC) to HDL-C, and low density lipoprotein cholesterol (LDL-C) to HDL-C ratios than inactive individuals of similar age and body weight. Triglyceride, TC, and LDL-C concentrations were similar in both active and inactive subjects.

Adult↗
PubMed1988

Laryngeal carcinoma in black patients.

The majority of reports on laryngeal carcinoma are from institutions serving a mostly white population. This report is about laryngeal carcinoma in black patients at Harlem Hospital Center. In a retrospective analysis, 113 patients (male-female, 3.5:1) with carcinoma of the larynx were examined. Sixty-seven patients (59%) were between 50 and 60 years of age. There were two patients (2%) with carcinoma in situ, 15 (13%) in Stage I, 40 (35%) in Stage II, 39 (35%) in Stage III, and 15 (13%) in Stage IV. Of the 113 patients, 70 (62%) were treated surgically, Group I; 24 (21%) received radiotherapy only, Group 2; and 19 (17%) refused treatment or died before therapy initiation. For patients in Group 1, the 1-year survival rate was 68% (43 of 63), the 3-year survival rate was 38% (20 of 53), and the 5-year survival rate was 15% (7 of 47). For Group 2, the survival rate was 48% (11 of 23), 30% (7 of 23), and 14% (3 of 22), respectively. In this patient population, laryngeal carcinoma occurred at a younger age than other reported groups, had a higher incidence in females, and had a lower 1-, 3-, and 5-year survival rate.

Adult↗