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Biomedical subjects

J Newman

Publications and source records attributed to J Newman.

At least 109 records · Page 6Linked to original sources

An experimental test of "the mozart effect": does listening to his music improve spatial ability?

This experiment was designed as a test of the 1993 findings of Rauscher, Shaw, and Ky who reported a positive effect of listening to classical music on spatial reasoning. Present results do not demonstrate the "Mozart effect." In our study, 114 students were pretested on items from the Raven's Progressive Matrices--Advanced Form, then instructed to listen to either 8 min. of Mozart's music, relaxation instructions, or silence. Then subjects were posttested on an equivalent set of Raven's items. The subjects were also asked to provide information about their musical background and preferences. All instructions and treatments were audiotaped and played to individual subjects through earphones in the university language laboratory, ensuring standardization of procedures. Subjects in all 3 treatment groups showed a practice effect, but this improvement in Raven's scores was not dependent on the type of treatment received. There were no differences in Raven's scores among groups before or after treatment so our results do not confirm the prior ones. There was no evidence that the brief music had a different effect on subsequent problem solving according to listeners' musical background and training.

Adolescent↗

Characterization of biomedical polymer surface interaction with human factor Xa.

Two surface analytical spectroscopic techniques (namely, angular-dependent X-ray photoelectron spectroscopy and static secondary ion mass spectrometry) were used to characterize the nature and composition of the surface and near-surface layers formed on three biomedical polymers (namely, low-density polyethylene, expanded polytetrafluoroethylene, and a silicone elastomer) when exposed to Factor Xa in a buffer solution under adsorption conditions. It is shown that the results extracted from the spectroscopic measurements are consistent with each other. The clinical significance of the results is discussed in terms of screening biomedical polymers for use in fabricating cardiovascular system components.

Biopolymers↗

Sarcoidosis in systemic sclerosis: report of 7 cases.

OBJECTIVE: To describe the clinical, radiologic, and pathologic features of coexistent systemic sclerosis (SSc) and sarcoidosis, 2 conditions of unknown cause associated with altered cellular immune response. METHODS: We reviewed clinical information, results from laboratory and radiologic studies, and lung or lymph node biopsy samples of 7 patients with concurrent SSc and sarcoidosis evaluated at 2 academic referral centers between 1989 and 1993. RESULTS: Each patient fulfilled American College of Rheumatology criteria for the classification of SSc. SSc and sarcoidosis developed simultaneously in 4 patients, whereas in 3 others sarcoidosis was diagnosed more than 6 years after the onset of SSc. The onset of sarcoidosis was characterized by fever, weight loss, or increasing respiratory symptoms. Each patient had radiographic evidence of intrathoracic lymphadenopathy and/or interstitial lung disease. Examination of lung or lymph node biopsies demonstrated noncaseating granulomas. Treatment with corticosteroids was associated with improved lung function. CONCLUSION: Since sarcoidosis coexists with SSc more frequently than previously suggested, it should be considered in patients with SSc presenting with new pulmonary symptoms. Recognizing sarcoidosis in patients with SSc is important, since these patients may benefit from corticosteroid therapy.

Adrenal Cortex Hormones↗

Structure of an effector-induced inactivated state of ribulose 1,5-bisphosphate carboxylase/oxygenase: the binary complex between enzyme and xylulose 1,5-bisphosphate.

BACKGROUND: Ribulose 1,5-bisphosphate carboxylase/oxygenase (rubisco) catalyzes the addition of CO2 to ribulose 1,5-bisphosphate in all photosynthetic organisms. During catalysis, the bisphosphate is depleted by reactions other than carboxylation and some of the products are potent inhibitors of rubisco. We have used one of these, xylulose 1,5-bisphosphate as an analogue of the natural substrate and co-crystallized it with the enzyme. RESULTS: We have solved the crystal structure of Synechococcus rubisco with bound xylulose 1,5-bisphosphate to 2.3 A and compared it with the previously solved 2'-carboxylarabinitol 1,5-bisphosphate (2CABP) enzyme quaternary complex. Unlike 2CABP, xylulose 1,5-bisphosphate forms a binary complex with no activating CO2 or essential metal present. Five flexible elements that restrict access to the active site in the 2CABP complex also close off the active site in the xylulose 1,5-bisphosphate complex, stabilized by interactions with the hydrated form of the analogue. CONCLUSIONS: Xylulose 1,5-bisphosphate induces closure of critical loops of the protein without essential cofactors resident at the active site. In the case of rubisco in one species, catalysis is completely inhibited.

Models, Molecular↗

The structure and antigenicity of a type C foot-and-mouth disease virus.

BACKGROUND: Picornaviruses are responsible for a wide range of mammalian diseases and, in common with other RNA viruses, show considerable antigenic variation. Foot-and-mouth disease viruses (FMDVs) constitute one genus of the picornavirus family and are classified into seven serotypes, each of which shows considerable intratypic variation. This antigenic variation leads to continuing difficulties in controlling the disease. To date the structure of only one serotype, O, has been reported. RESULTS: The three-dimensional structure of a serotype C (isolate C-S8c1) FMDV, has been determined crystallographically at 3.5 A resolution. The main chain conformation of the virion is very similar to that of type O1 virus. The immunodominant G-H loop of VP1, the presumed site of cell attachment, is disordered in both types of virus indicating a functional role for flexibility of this region. There are significant changes in the structure of other antigenic loops and in some internal regions involved in protomer-protomer contacts, including the entire amino-terminal portion of VP2, described here for the first time for a picornavirus. Antigenic sites have been identified by genetic and peptide mapping methods, and located on the capsid. The data reveal a major new discontinuous antigenic site (site D) which is located near to the three-fold axis and involves residues of VP1, VP2 and VP3 which lie adjacent to each other on the capsid. CONCLUSION: In FMDV type C, amino acid substitutions seen in mutants that are resistant to neutralization by monoclonal antibodies (MAbs) map to predominantly surface-oriented residues with solvent-accessible side-chains not involved in interactions with other amino acids, whereas residues which are accessible but not substituted are found to be more frequently involved in protein-protein interactions. This provides a molecular interpretation for the repeated isolation of the same amino acid substitutions in MAb-resistant variants, an observation frequently made with RNA viruses. This first comparison of two FMDV serotypes shows how subtle changes at antigenic sites are sufficient to cause large changes in antigenic specificity between serotypes.

Amino Acid Sequence↗

The structure of an immunodominant loop on foot and mouth disease virus, serotype O1, determined under reducing conditions.

Residues 136-159 of VPI of foot and mouth disease virus (FMDV) comprise the G-H loop of the protein and form a prominent feature on the surface of virus particles. This sequence contains an immunodominant neutralizing epitope, which can be mimicked with synthetic peptides, and includes an Arg, Gly, Asp motif which has been implicated in the binding of the virus to cellular receptors. Crystallographic analysis of native virus particles failed to resolve the structure of this region due to its disordered state. However, reduction of a disulphide bond between cysteine residues 134 of VP1 and 130 of VP2 caused the G-H loop to collapse onto the surface of the virus particle and allowed its conformation to be determined.

Amino Acid Sequence↗

Organization and transcription of the class I phycoerythrin genes of the marine cyanobacterium Synechococcus sp. WH7803.

The nucleotide sequences of the class I phycoerythrin (PE) alpha- and beta-subunit genes (cpeA and cpeB) from the marine cyanobacterium Synechococcus sp. WH7803 are reported. The cpeB gene is located upstream of cpeA with a separation of 56 nucleotides and the two genes are co-transcribed as a transcript of 1.3 kb, with the transcription startpoint being localized to 110-111 bp upstream of cpeB. The sequence of the promoter region bears no similarity to promoters reported for other cyanobacterial PE genes. Pentanucleotide repeats found upstream of some PE operons, particularly in the case of cyanobacterial strains capable of chromatic adaption, are not found in Synechococcus sp. WH7803; instead the sequence 5'-CGGTT-3' is repeated three times in the promoter region.

Amino Acid Sequence↗

Genetic and environmental factors in scleroderma.

Recent epidemiologic research on scleroderma has been directed toward both genetic and environmental factors. The nature of any genetic contribution is unknown, although the major histocompatibility complex region is important in determining antibody response. Environmentally, an occupational basis in a small proportion of cases seems likely. There is no evidence to support the hypothesis that silicone gel breast implants are an important risk factor in the development of scleroderma.

Environmental Exposure↗

Effects of chemotherapy on ultrastructure of oesophageal squamous cell carcinoma.

Seven oesophageal squamous carcinomas, treated with pre-operative chemotherapy (mitomycin-C, ifosfamide and cisplatin-MIC), with a course finishing 21 days prior to resection, were examined by electronmicroscopy. In one treated case detailed light microscopy failed to reveal any tumour. Five of the remaining six tumours showed cytotoxic damage in that apoptosis and unusual necrotic changes were observed in almost all the neoplastic cells. These features were not seen in untreated cases. In four additional cases, who received one pulse of MIC followed by biopsy or resection within 3-6 days, apoptotic changes were very pronounced and extensive and most neoplastic cells presented unusual degeneration with characteristic derangement of the cytoskeleton, destruction of organelles and accumulation of glycogen. The ultrastructural appearance of 18 untreated resected oesophageal squamous carcinomas was studied for comparison with the treated tumours. The study has demonstrated ultrastructural changes resulting from chemotherapy. Results suggest that the regimen is more effective against squamous carcinomas than against adenocarcinomas of the oesophagus, as judged by comparison with the results of a previous study.

Adult↗

Ectopic human chorionic gonadotrophin (HCG) production: is the detection by serum analysis of HCG of clinical relevance in transitional cell carcinoma of the bladder?

OBJECTIVE: To assess the potential value of ectopic beta-human chorionic gonadotrophin (beta HCG) measurement in the clinical management of transitional cell carcinoma (TCC). PATIENTS AND METHODS: A prospective serological study of 163 consecutive patients undergoing cystoscopy as new or review cases was performed to assess any correlation between beta HCG production and histological grading or stage. RESULTS: Ten per cent of patients with TCC had a raised beta HCG level but there was no correlation with tumour differentiation, staging or prognosis. CONCLUSIONS: beta HCG has no role as a tumour marker for TCC and therefore appears unlikely to play a part in the clinical management or treatment of urothelial tumours.

Biomarkers, Tumor↗

Nipple pain.

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Breast Feeding↗

Intracapillary glomerular metastases in a nephrectomy specimen removed for ipsilateral renal cell carcinoma.

A case of intraglomerular metastases observed in a nephrectomy specimen removed for primary renal cell carcinoma is reported. The intraglomerular metastases arose by dissemination of malignant cells into the systemic circulation via invasion of the renal veins. Intraglomerular metastases are therefore an indicator of malignant dissemination which in turn should be associated with a poor prognosis. It is recommended that in nephrectomies undertaken for primary renal cell carcinoma at least one random block of renal cortex should be examined to confirm or exclude intraglomerular metastases.

Carcinoma, Renal Cell↗

Phase II study of merbarone (NSC 336628) in patients with advanced gastric carcinoma.

Merbarone, 5-(N-phenylcarboxamido)-2-thiobarbituric acid (NSC 336628), is a derivative of barbituric acid and represents a unique class of antineoplastic agents. We treated 16 patients with advanced gastric carcinoma in a phase II study of merbarone. All patients were previously untreated with chemotherapy or biological therapy. The starting dose of merbarone was 1000mg/m2 infused over 24 hr for 5 consecutive days every 21 days. A median of two courses (range, 1-7) was given. None of the patients achieved a complete or partial response; however, 3 patients achieved a transient minor response. Toxicity was mild to moderate in most patients, but 1 patient died of treatment-related neutropenia and sepsis. Our data suggest that merbarone at this dose and schedule is inactive against gastric carcinoma. The evidence of minor response suggests that analog research may be worthwhile to pursue.

Antineoplastic Agents↗

The X-ray structure of Synechococcus ribulose-bisphosphate carboxylase/oxygenase-activated quaternary complex at 2.2-A resolution.

The structure of the hexadecameric ribulose-bisphosphate carboxylase/oxygenase from Synechococcus PCC6301 has been solved to 2.2-A resolution. Crystallization was in the presence of CO2, Mg2+, and 2'-carboxyarabinitol bisphosphate to form a stable enzyme quaternary complex that mimics one of the intermediate states of the carboxylation reaction. The structure was solved by molecular replacement using the coordinates of spinach carboxylase. The deviations in C alpha positions of the L- and S-subunits are only 0.3 and 2.0 A, respectively, and localized at specific regions of the two polypeptides. One region that shows significant divergence of the peptide backbone is loop 6 of the beta barrel in the L-subunit. Two other elements, the C terminus, and a highly conserved loop of the N-terminal domain of a second L-subunit, interact with loop 6 in the quaternary complex. These three regions, plus two other flexible segments, completely enfold the bisphosphate inhibitor. Significant alteration in their spatial relationship must occur to allow substrates or products access to and from the active site. The active site residues, activating cofactors, and inhibitor are well resolved in the electron density map. The disposition of these groups around the essential metal provides some indication of their role at different stages of the catalytic cycle.

Amino Acid Sequence↗

Structure determination and refinement of ribulose 1,5-bisphosphate carboxylase/oxygenase from Synechococcus PCC6301.

The structure of an activated quaternary complex of ribulose 1,5-bisphosphate carboxylase/oxygenase (rubisco) from Synechococcus PCC6301 has been solved by molecular replacement. The protein crystallizes in an orthorhombic P2(1)2(1)2(1) unit cell with a complete L(8)S(8) complex consisting of 4608 residues (37 680 non-hydrogen atoms) in the asymmetric unit. Data were collected both on film and image plate using synchrotron radiation; there were 218 276 unique reflections in the final 2.2 A data set. The eightfold non-crystallographic symmetry could be used both to improve map quality and to reduce the computing requirements of refinement. The coordinates were refined using strict non-crystallographic symmetry constraints. The stereochemistry of the final model is good, and the model has an R value of 20.0% for the reflections between 7 and 2.2 A.

Journal Article↗

A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy.

Twenty-six patients, whose B-cell lymphoma had relapsed after conventional therapies, were treated in a phase I dose escalation study with an immunotoxin consisting of a mouse CD22 monoclonal antibody (RFB4:IgG1K) coupled to chemically deglycosylated ricin A chain (dgA). Two to 12 doses of the immunotoxin were infused intravenously at 48-hour intervals. The peak serum concentration and half-life (T1/2) did not correlate directly with the dose and averaged 3.8 micrograms/mL and 7.8 hours, respectively. The main dose-limiting toxicity was caused by the vascular leak syndrome (VLS) consisting of weight gain, edema, serum albumin decrease, and critically by pulmonary edema. Myalgia occurred frequently and was only dose limiting in one patient who developed rhabdomyolysis. The presence of lymphoma cells in the blood (> or = 10(10)/L) and clinically detectable splenomegaly were associated with reduced toxicity and a shorter T1/2. Nine of 24 evaluable patients (37.5%) made antibody to either mouse Ig or dgA. There were five partial responses (PR) and one complete response (CR) lasting 30 to 78 days. High peak concentrations of immunotoxin in the serum, a long T1/2, and large areas under the curve (AUC) correlated with both clinical response and toxicity. None of three patients with CD5+ lymphomas (including two CLL patients) had more than mild toxicity or responded to the immunotoxin.

Adult↗

Structure of a major immunogenic site on foot-and-mouth disease virus.

Attachment of foot-and-mouth disease virus (FMDV) to its cellular receptor involves a long and highly antigenic loop containing the conserved sequence, Arg-Gly-Asp, a motif known to be a recognition element in many integrin-dependent cell adhesion processes. In our original crystal structure of FMDV the Arg-Gly-Asp-containing loop ('the loop'), located between beta-strands G and H of capsid protein VP1, was disordered and hence essentially invisible. We previously surmised that its disorder is enhanced by a disulphide bond linking the base of the loop (Cys 134) to Cys 130 of VP2 (ref. 8). We report here the crystal structure of the virus in which this disulphide is reduced. Reduced virus retains infectivity and serological experiments suggest that some of the loop's internal structure is conserved. But here its structure has become sufficiently ordered to allow us to describe an unambiguous conformation, which we relate to some key biological properties of the virus.

Aphthovirus↗