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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

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

Concentrations of immunoglobulin classes in subcompartments of the sheep lung.

The concentrations of IgA, IgG and IgM were measured in plasma, lung lymph and lung lavage fluid from adult sheep. Immunoglobulin concentrations in lymph and lavage fluid should fall sequentially during diffusive flux from the vascular compartment as a result of molecular sieving at the capillary endothelium and the alveolar epithelium. This was seen only for the IgG class. High concentrations of IgA and IgM in the interstitial (lymph) and luminal (lavage) compartments of the lung (relative to plasma levels) suggest either local synthesis of these classes or the existence of class specific active transport.

Animals

Systematic recording of behaviors and skills of retarded and psychotic children.

The design, administration, and scording of the first edition of the Children's Handicaps, Behavior & Skills (HBS) structural interview schedule, intended to elicit information concerning metally retarded or psychotic children, are described. A high level of reliability was achieved with experienced interviewers and good informants. In a study of 104 such children, the levels of overall agreement between parent and professional informants on the 62 sections of the schedule were, in general, 70% or above. Agreement was better for rating absence of skills or behavioral abnormalities than for rating their presence. This tendency was particularly marked for the behavioral abnormaliteis. Parents, when compared with professional workers, tended to describe their children as having higher developmental skills, more social contact but also more repetitive and difficult behavior.

Adolescent

Splenic necrosis in mice infected with cytomegalovirus.

Necrosis of the spleen is seen in mice of certain strains after injection of large doses of murine cytomegalovirus. Necrosis begins in perifollicular areas containing infected cells which do not appear to be macrophages, and in severe cases the entire spleen is involved. Necrosis is first visible three days after infection and is not prevented by treatment of mice with corticosteroids, cyclophosphamide, or theta antiserum. There is a striking loss of nucleated cells from the spleen at two to four days after infection, in the absence of splenic necrosis. The pathogenesis of splenic necrosis, which is seen also in certain other viral infections, remains unexplained.

Age Factors

The role of macrophages in mice infected with murine cytomegalovirus.

Quantitative studies were made of the infection of mouse peritoneal macrophages in vitro by cytomegalovirus, using virus assays and immunofluorescence. The efficiency of infection was low. Broth-induced peritoneal macrophages were about four times more resistant to infection than unstimulated macrophages and it was even more difficult to infect activated macrophages taken from mice 6 days after intravenous infection. Peritoneal macrophages (unstimulated) were infected at least 15 times more readily by tissue culture-passed (attenuated) virus than by salivary gland (virulent) virus, but macrophages prevented the spread of tissue culture virus to underlying susceptible mouse embryo fibroblasts, whereas they did so much less effectively with virulent salivary gland virus. The pathogenesis of infection was studied in intact mice by immunofluorescence, and the observations paralleled the in vitro findings. When large doses of salivary gland virus were injected intravenously, infected Kupffer cells (liver macrophages) were occasionally seen and the inoculated virus directly infected large numbers of hepatic cells. In similar experiments with tissue culture-passed virus, there was initial infection of occasional Kupffer cells, which only rarely gave rise to infected hepatic cells. Differences in the extend of Kupffer cell infection by the two strains of virus were not detected in these experiments. Salivary gland virus also usually failed to infect splenic or lymph node macrophages. Occasional infected mononuclear cells were seen in the blood, lung and bone marrow, but were not identified. Infected cells were very rarely seen in the thymus, even in suckling mice.

Animals

Effect of individual, small group, and large group method of presentation on modal performance in college men and women.

The present study investigated individual, small group, and large group methods of presentation in inter- and intra-modal functioning within auditory and visual modes along a temporal dimension. Subjects were 52 men and 70 women, ranging in age from 17 to 36 yr. Auditory and visual stimuli were presented by electronic means in a same-different matching task. Four separate conditions were investigated: auditory-auditory, visual-visual, auditory-visual, and visual-auditory. An analysis of variance, conducted for three methods of presentation, indicated no significant differences. Thus, group testing is feasible in modal research.

Adolescent

Inter- vs intramodal performance of college men and women: a replication.

Intermodal and intramodal functioning in the auditory and visual sensory modes along a temporal dimension were investigated for 52 male and 52 female college students, ranging in age from 17 to 33 yr. Auditory and visual stimuli were presented electronically in a same-different matching task. Four separate conditions were investigated, auditory-auditory, visual-visual, auditory-visual, and visual-auditory. An analysis of variance showed women made significantly more correct responses than men. No significant differences were found between the groups' performance on intramodal and intermodal tasks. Results are consistent with an earlier report by Gould (1977).

Adolescent