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Biomedical subjects

J Gould

Publications and source records attributed to J Gould.

At least 55 records · Page 3Linked to original sources

Nicotinic acetylcholine receptors in human neuroblastoma (SH-SY5Y) cells.

Whole-cell patch-clamp recordings were used to investigate nicotinic acetylcholine receptors (nAChRs) in the human neuroblastoma cell line, SH-SY5Y. Acetylcholine, nicotine and the neuronal nAChR agonist dimethylphenylpiperazinium iodide (DMPP), but not muscarine, all evoked inward currents in the cells (voltage-clamped at -60 mV). DMPP's actions were concentration- and voltage-dependent, and were antagonised by the neuronal nAChR antagonist mecamylamine (1-3 microM). Atropine was ineffective at 0.1 microM, but at 1 microM caused significant reductions in current amplitudes. Pre-incubation of cells with 2 microM alpha-cobratoxin had no effect on the actions of DMPP, and inward currents could also be induced when extracellular NaCl was replaced with CaCl2. DMPP also reversibly depolarized SH-SY5Y cells. These findings clearly identify nAChRs in SH-SY5Y cells, and provide two possible mechanisms by which receptor activation may lead to noradrenaline release, namely by triggering Ca2+ influx through the nAChR itself or by opening voltage-gated Ca2+ channels.

Acetylcholine↗

Sequence of lamprey vitellogenin. Implications for the lipovitellin crystal structure.

The amino acid sequence of lamprey vitellogenin has been predicted from the nucleotide sequence of cloned cDNA. The sites of proteolytic cleavage that produce the lipovitellin complex from the vitellogenin have been located by comparing the N-terminal sequences of two lamprey lipovitellin polypeptides with the predicted sequence. These results also confirm that the vitellogenin sequence derived here corresponds to the lipovitellin complex for which the crystal structure has been solved previously. Predictions of secondary structure indicate that the region most likely to correspond to the large alpha-helical domain of the crystallographic model consists of vitellogenin residues 300 to 600. Similar to the lipovitellins of Xenopus laevis, lamprey lipovitellin appears to lack approximately 200 C-terminal residues that are present in vitellogenin. However, the lamprey lipovitellin differs from those of Xenopus and chicken in two respects. First, most of the serine-rich domain that is present as the phosvitin polypeptide in the lipovitellins of the higher vertebrates appears to be lost in the maturation of lamprey vitellogenin to lipovitellin. Second, the domains that constitute the large lipovitellin-1 polypeptide in Xenopus and chicken are present in two polypeptides in lamprey, owing to an additional proteolytic processing event.

Amino Acid Sequence↗

Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma.

Idarubicin, a new analogue of daunorubicin, was administered i.v. at a dose of 15 mg/m2 to 31 previously treated patients with unfavorable non-Hodgkin's lymphoma. Clinical characteristics included median age, 69 years; performance status, 1; and prior chemotherapeutic regimens, 1. Twenty of the patients were relapsing after prior therapy and 11 were refractory; 29 had received prior anthracycline or anthracenedione. Responses were observed in 43% of patient (3 complete remission and 10 partial remission) with a median duration of 10+ months (2-29+ months). Idarubicin was well tolerated with nonhematological toxicities (nausea/vomiting, mucositis, and anorexia) seen in less than 50% of patients. Median hematological values during the first cycle for this dosage included WBC, 1,300/mm3; platelets, 129,000/mm3; and hemoglobin, 10.9 mg/dl. With dose escalation, hematological toxicity was dose limiting. Symptomatic cardiac toxicity was observed in one patient who had received maximum dose doxorubicin and radiotherapy. Median values for the cardiac ejection fraction during the full course of therapy for the entire group of patients were 0.62 (initial) and 0.60 (final). Idarubicin in i.v. form is an active drug in previously treated patients with unfavorable non-Hodgkin's lymphoma.

Adult↗

Nosocomial Pseudomonas pickettii bacteremias traced to narcotic tampering. A case for selective drug screening of health care personnel.

Three patients in a university hospital developed nosocomial infusion-related Pseudomonas pickettii bacteremia. Investigation identified six additional patients who had received intravenous fluid contaminated by P pickettii but did not become ill. All nine patients had had surgery, and each of these patients but only nine of 19 operated-on control patients had received intravenous fentanyl citrate in the operating room; the mean dose given to the nine case patients was far greater than that given to control patients. Fentanyl in 20 (40%) of 50 predrawn 30-mL syringes was shown to be contaminated by P pickettii. Contamination was caused by theft of fentanyl from predrawn synringes and replacement by distilled water contaminated by P pickettii. Narcotic theft by health care personnel may cause patients to suffer pain needlessly and can also result in dire unanticipated consequences, such as nosocomial bacteremia. Whereas drug testing in the workplace is highly controversial, we believe that testing of health care personnel is indicated when drug abuse or theft is suspected.

Adult↗

Transformation of Zea mays L. Using Agrobacterium tumefaciens and the Shoot Apex.

Agrobacterium tumefaciens is established as a vector for gene transfer in many dicotyledonous plants but is not accepted as a vector in monocotyledonous plants, especially in the important Gramineae. The use of Agrobacterium to transfer genes into monocot species could simplify the transformation and improvement of important crop plants. In this report we describe the use of Agrobacterium to transfer a gene into corn, the regeneration of plants, and detection of the transferred genes in the F(1) progeny. Shoot apices of Zea mays L. variety Funk's G90 were cocultivated with A. tumefaciens EHA 1, which harbored the plasmid pGUS3 containing genes for kanamycin resistance (NPT II) and beta-glucuronidase (GUS). Plants developed from these explants within 4 to 6 weeks. Fluorometric GUS assays of leaves and immature seeds from the plants exhibited low GUS activity. Both NOS and GUS gene fragments were amplified by polymerase chain reaction in the DNA isolated from the F(1) generations of one of the original transformed plants. Southern analysis showed both GUS and NPT probes hybridized to DNA in several of the F(1) progeny, demonstrating the incorporation of GUS and NPT II genes into high molecular weight DNA. These data establish successful gene transfer and sexual inheritance of the genes.

Journal Article↗

Nine-gunshot suicide.

In this article, we describe an unusual case of suicide involving nine gunshot wounds to the anterior chest. This illustrates that individuals may function for a short time with fatal wounds and stresses the importance of a complete investigation.

Female↗

The mucilage secreted by roots and its possible role in cell-cell recognition for the adhesion of fungal pathogens to root surfaces of Zea mays L.

The outer cells of the roots of plants secrete a mucilage which lubricates the root and keeps it moist. The mucilage is secreted from the Golgi apparatus in vesicles which fuse at the plasma membrane. In maize roots a complex of at least three polysaccharides and glycoproteins are formed, some of which have a large proportion of fucose in their composition. The synthesis of these compounds can be readily monitored because fucose can be easily identified, and especially because exogenous fucose is not catabolized but is incorporated intact into the polymers. The synthesis of the polymers seems to be initiated in the endoplasmic reticulum in conjunction with polyprenoid oligosaccharides that contain fucose. Lipid-oligosaccharides of nine sugar residues can be obtained from the membrane preparations of the root cells. These compounds are polyprenyl diphosphate derivatives. A GDP-fucose:polyprenyl phosphate transfucosylase occurs in the endoplasmic reticulum, whereas fucosyl transferase that transfers fucose to a polymer occurs mainly in the Golgi apparatus. The indirect evidence suggests that oligosaccharides of polyprenyl diphosphate compounds are transferred to proteins, elaborated in the Golgi apparatus, and large molecular weight polysaccharides are finally exported as the mucus. Part of the mucus is acidic and in some respects resembles pectin. The presence of fucose in such large quantities in maize root mucilage suggested that this might have some significance for the recognition of these plants by parasitic root fungi. The adsorption of mucilage by pathogenic fungi was investigated with two types of fungi, a highly specialized ectotrophic root-infecting fungus, e.g. Phialophora radicicola and a vascular wilt fungus capable of attacking a great variety of tissues, e.g. Fusarium moniliforme. The adsorption of radioactively labelled and fluorescently labelled polymers by the pathogenic fungi was investigated. The character and proportion of fungal surfaces present in vitro were standardised by the production and semi-synchronous germination of populations of conidia. Changes in appearance of fungal walls, present before and after germination, were examined ultrastructurally. There was polyanionic material on hyphal but less on conidial surfaces of the ectotrophic root-infecting fungi. In contrast this material was present to similar extents on both hyphal and conidial surfaces of F. moniliforme.(ABSTRACT TRUNCATED AT 400 WORDS)

Adhesives↗

Duodenal perforation as a delayed complication of placement of a biliary endoprosthesis.

Duodenal perforation may occur at the time of insertion of a biliary endoprosthesis or following endoscopic manipulation of such a stent. The possibility of perforation as a late sequela of stent migration, after percutaneous placement of an endoprosthesis, however, has not been emphasized. In the authors' experience with a 12-F soft-stent endoprosthesis, duodenal perforation occurred in four of 50 patients following initially satisfactory stent placement. One intraperitoneal perforation necessitated immediate surgical intervention. The three retroperitoneal perforations were treated conservatively.

Adult↗

Plasma cell karyotype in multiple myeloma.

Karyotypic abnormalities were studied in multiple myeloma and were correlated with clinical features. Among 115 evaluable patients, 46% had an abnormal karyotype. Trisomy 3, 5, 9, and 15 and monosomy 13 and 16 were the most common clonal abnormalities. Translocations described previously in other B cell malignancies occurred in nine patients, including four with t(8;14)(q24;q32) translocations. The association of all t(8;14) abnormalities with IgA protein type suggested a pathogenetic relationship between a specific karyotypic abnormality and myeloma protein type. Hypodiploidy occurred mainly in patients with only Bence Jones protein, was associated with resistance to therapy, and justified the early consideration of investigational therapies.

Chromosome Aberrations↗

Identification of sequences in a yeast histone promoter involved in periodic transcription.

Sequences between a pair of divergently transcribed histone genes in Saccharomyces cerevisiae are able to confer periodic transcription during the cell cycle. This conclusion contrasts to our previous hypothesis that an ars (autonomously replicating sequence) 3' to this locus is a transcription timer for yeast histone genes. The promoter sequences required for periodic expression have been localized by deletion analysis, and isolated elements have been analyzed by insertion into a heterologous promoter. Two cell-cycle-specific promoter functions have been identified. One function activates transcription in a cell-cycle-dependent manner. The other periodically represses transcription. Negative regulation may be the predominant form of cell-cycle control, because removal of the repressing function results in constitutive expression of the histone genes.

Base Sequence↗

Cell-cell recognition of host surfaces by pathogens. The adsorption of maize (Zea mays) root mucilage by surfaces of pathogenic fungi.

The adsorption of radioactive mucilage by pathogenic fungi was shown to be dependent upon time, the composition of mucilage, the type of fungal surface (conidia, hyphae, hyphal apices), fungal species, pH and bivalent cations. All fungal adhesins were inactivated by either proteinase or polysaccharase treatments. Adsorption was not inhibited by the numberous mono-, di- and oligo-saccharides that were tested individually, but it was inhibited absolutely by several polysaccharides. This suggested that adsorption of mucilage by pathogens involved conformational and ionic interactions between plant and fungal polymers but not fungal lectins bound to sugar residues of mucilage. Several fractionation schemes showed that pathogens bound only the most acidic of the variety of polymers that comprise mucilage. There was not any absolute distinction between ability to bind radioactive mucilage and type of pathogen or non-pathogen. However, there were notable differences in characteristics of adsorption between two types of pathogen. Differences were revealed by comparison of the adsorption capacities of conidia and germinant conidia and chromatography of radioactive mucilage on germinant conidia. An ectotrophic root-infecting fungus (a highly specialized pathogen) bound a greater proportion of mucilage than did a vascular-wilt fungus (of catholic host and tissue range) with more than one class of site for adsorption. In contrast with the vascular-wilt fungus, sites for adsorption on the specialized pathogen were present solely on surfaces formed by germination.

Adsorption↗

The Lowe and Costello Symbolic Play Test in socially impaired children.

The Symbolic Play Test was given to 31 socially impaired and 29 sociable children retarded in language comprehension, with the same range of age (5 to 12 years) and intelligence (profoundly retarded to normal). Play test age and spontaneous pretend play were at a similar level in the sociable children, but, in the socially impaired, spontaneous pretend play was lower than the play test age would predict. In some of the latter it was absent, and in the others it was narrow and repetitive in form. For subgroups of socially impaired and sociable children with similar play ages, there was no significant difference in language comprehension age. The discrepancy, in socially impaired children, between levels on tests and spontaneous use of skills was discussed.

Age Factors↗

Serum C-reactive protein in normal and infected neonates.

Serum C-reactive protein determinations were performed on well and sick neonates, in order to gain information about normal values and its value in the diagnosis of neonatal septicaemia. The median value in 48 cord sera was 200 micrograms/l (range 15 to greater than 6,000 micrograms/L); there was no correlation between paired maternal and cord serum CRP levels (12 pairs). Thirty-six children were followed from birth for a mean of 20 days. There were 21 episodes of confirmed infection in 16 children, each associated with a sustained rise in C-reactive protein, often commencing before there was clinical evidence of infection. In four patients with raised levels, infection was suspected, but no firm evidence was obtained. In the remaining 16 children there were no values above 10 mg/l, and the 95th centile was about 6 mg/l, with no difference between values obtained in the first three days of life and those found subsequently. Hyaline membrane disease and jaundice were not associated with a rise. Raised serum C-reactive proteins is a good indicator of the presence of infection in the neonatal period.

C-Reactive Protein↗

ran1+ controls the transition from mitotic division to meiosis in fission yeast.

We have investigated the genetic and physiological control of meiosis in fission yeast. Nutritionally depleted h+/h- diploid cells become irreversibly commited to meiosis immediately prior to the initiation of premeiotic S phase. Premeiotic DNA synthesis requires matP+, matM+, mei2+ and mei3+ but not the mitotic cell cycle control gene, cdc2+. ran1+ is an essential gene, loss of which provokes sexual conjugation, premeiotic DNA synthesis, pseudo-meiosis and the sporulation of haploid cells. Our experiments suggest that sexual differentiation is achieved physiologically by the inhibition of ran1+ activity in a two-step process. In the first step, partial inhibition of ran1+ in starved haploid cells, leads to cell cycle arrest in G1 followed by sexual conjugation. In the second step, a pathway requiring the matP+, matM+ and mei3+ genes of the newly-formed zygote, further inhibits ran1+ and thereby commits the cell to meiosis. mei2+ is required for meiotic commitment after full inhibition of ran1+. ran1+ is normally essential for vegetative cell reproduction but is inessential in cells which have abnormally high levels of cAMP-dependent protein kinase. We propose that the ran1+ gene encodes a highly controlled protein kinase which shares key substrates with cAMP-dependent protein kinase.

Alleles↗