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Biomedical subjects

J Gould

Publications and source records attributed to J Gould.

At least 19 recordsLinked 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

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

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

Severe impairments of social interaction and associated abnormalities in children: epidemiology and classification.

The prevalence, in children aged under 15, of severe impairments of social interaction, language abnormalities, and repetitive stereotyped behaviors was investigated in an area of London. A "socially impaired" group (more than half of whom were severely retarded) and a comparison group of "sociable severely mentally retarded" children were identified. Mutism or echolalia, and repetitive stereotyped behaviors were found in almost all the socially impaired children, but to a less marked extent in a minority of the sociable severely retarded. Certain organic conditions were found more often in the socially impaired group. A subgroup with a history of Kanner's early childhood autism could be identified reliably but shared many abnormalities with other socially impaired children. The relationships between mental retardation, typical autism, and other conditions involving social impairment were discussed, and a system of classification based on quality of social interaction was considered.

Adolescent

Effects of maternal drinking on neonate state regulation.

Sleep-awake state distribution during inter-feed intervals over a 24-hour period on the third day of life was investigated by means of a continuous non-intrusive bassinet sleep monitor. 31 infants were studied: 14 born to mothers who drank heavily throughout pregnancy (group A), eight whose mothers modified their heavy drinking (group B) and nine whose mothers never were heavy drinkers (group C). Over the 24-hour period, group A infants slept less than those in group B. In comparison with group C, group A infants had a larger proportion of quiet sleep episodes interrupted by awake or unclassified epochs, and were more restless, with more frequent major body movements. These pilot observations suggest that heavy maternal consumption of alcohol, when continued throughout pregnancy, is associated with a disturbance of sleep-awake state distribution. Successful therapy of heavy drinking during pregnancy may improve the physiological competence of the newborn to regulate sleep-awake states and facilitate interaction between mother and infant.

Adolescent