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Biomedical subjects

F Gilbert

Publications and source records attributed to F Gilbert.

At least 91 records · Page 5Linked to original sources
PubMed1988

Membrane excitability expressed in human neuroblastoma cell hybrids.

The voltage-sensitive Na+ channel is responsible for the action potential of membrane electrical excitability in neuronal tissue. Three methods were used to demonstrate the presence of neurotoxin-responsive Na+ channels in two hybrid cell lines resulting from the fusion of excitable human neuroblastoma cells with mouse fibroblasts. Only one of the two electrically active hybrid cell lines maintained the sensitivity of the neuroblastoma parent to tetrodotoxin (TTX). The other hybrid, although electrically active, was not responsive to TTX or scorpion venom. Comparisons of the patterns of expression of membrane excitability and of chromosome complements in these human neuroblastoma cell hybrids suggest that the phenotype of membrane excitability is composed of genetically distinct elements.

Action Potentials↗
PubMed1988

Activation of the 5-HT1A receptor subtype increases rat plasma ACTH concentration.

Serotonergic (5-HT) neuronal pathways regulate the release of adrenocorticotropin hormone (ACTH) from the pituitary gland probably through the action of hypothalamic corticotropin-releasing hormone (CRH). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, dose dependently (0.016-3 mg/kg s.c.) increased rat plasma ACTH concentration. This response was blocked stereoselectively by (-)-pindolol, known to have 5-HT1 antagonist properties, but not by (+)-pindolol, beta 1-, beta 2- or alpha 1-adrenoceptor, dopamine, muscarinic, 5-HT2 or 5-HT3 receptor antagonists. Similar increases of plasma ACTH were induced by other 5-HT1A receptor ligands (buspirone, ipsapirone and gepirone). These results suggest that activation of the 5-HT1A receptor induces the secretion of ACTH from the rat pituitary gland.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

The 5-HT1A agonist 8-OH-DPAT increases consumption of palatable wet mash and liquid diets in the rat.

The 5-HT1A agonist 8-OH-DPAT, at a dose of 30 micrograms/kg, enhanced the consumption of sweetened wet mash and sweetened milk in non-deprived rats. In partially satiated rats, sensitivity to the hyperphagic effect of 8-OH-DPAT on wet mash intake was substantially increased, so that the minimally effective dose was reduced to 3 micrograms/kg. Similarly, 8-OH-DPAT was more efficacious in increasing milk intake in satiated rats. Thus, 30 and 40 micrograms/kg 8-OH-DPAT produced a 4-fold increase of milk intake in completely satiated rats compared to a 2-fold increase in partially satiated animals at a dose of 30 micrograms/kg. The increased intake of liquid and wet mash diets observed after treatment with low doses of 8-OH-DPAT argues against the involvement of non-specific gnawing in the increased consumption of solid food produced by the drug. Rather, the data suggest that 8-OH-DPAT may specifically stimulate appetite by counteracting a tonic serotonergic inhibition of feeding. The present experiments also showed that 8-OH-DPAT attenuates fenfluramine-induced anorexia which is thought to depend on increased serotonergic neurotransmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Prenatal diagnostic options in cystic fibrosis.

There are currently two diagnostic options in cystic fibrosis. These involve assays for certain microvillar enzyme activities in amniotic fluid and recombinant deoxyribonucleic acid studies of markers linked to the cystic fibrosis gene on chromosome 7. The former are reduced in cystic fibrosis homozygotes; the latter make it possible to determine the particular pattern of chromosome 7 markers predictive of a cystic fibrosis homozygote in a specific family. However, neither test is appropriate for, applicable to, or informative in all families. The problems and potential of each approach are discussed.

Adult↗
PubMed1988

Relationship of increased food intake and plasma ACTH levels to 5-HT1A receptor activation in rats.

Various putative agonists of the 5-HT1A receptor subtype induce feeding in rats, probably by activating raphé somatodendritic 5-HT autoreceptors. These drugs also produce a marked increase in plasma concentrations of corticotropin (ACTH). In the present experiment we attempted to localize the site of action of 5-HT1A agonists on the secretion of ACTH and examined the relationship between 5-HT1A agonist-induced feeding and ACTH secretion. Rats were injected with either the high affinity 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.016-1.0 mg/kg, s.c.) or the novel anxiolytics buspirone, gepirone or ipsapirone (2.0-16.0 mg/kg, s.c.), and either had their food intake measured 2 hr post injection or were sacrificed 30-40 min post injection for measurement of plasma ACTH. Plasma ACTH also was measured in rats pretreated with the serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) for three days (150 mg/kg, i.p. per day) and subsequently injected with 8-OH-DPAT (0.3 mg/kg, s.c.). As previously reported, the 5-HT1A agonists increased both food agonists increased both food intake and plasma ACTH concentrations. After 8-OH-DPAT, ipsapirone and gepirone the amount of food consumed was positively correlated with the concentration of plasma ACTH. No such correlation was evident following buspirone. PCPA pretreatment resulted in near total depletion of brain 5-HT content but had no effect on the ACTH rise induced by 8-OH-DPAT. Therefore, in contrast to the presynaptic site previously proposed for 5-HT1A agonist-induced feeding, the present results suggest a agonist-induced feeding, the present results suggest a postsynaptic location for the 5-HT1A receptor mediating ACTH release.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Unilateral microscopic gonadoblastoma in a prepubertal Turner mosaic with Y chromosome material identified by restriction fragment analysis.

A high incidence of gonadal tumors has been demonstrated in patients with gonadal dysgenesis in the presence of Y chromosome material. A unilateral, microscopic gonadoblastoma was found in the dysgenetic gonad of a ten-year-old, phenotypic female, with Turner stigmata and chromosome mosaicisms of three cell populations 45,X/46,X,+mar,/47,X,+mar,+mar. It is often impossible to determine by cytogenetic analysis if the marker chromosome has derived from the X or Y chromosome. The origin of these marker chromosomes was elucidated by the use of DNA probe (pDP34) for male-specific sequences of the Y chromosome. The presence of Y-specific fragments in the patient's DNA led to surgical exploration and the detection of a gonadoblastoma.

Child↗
PubMed1987

Chorionic villus sampling: improved method for preparation of karyotypes after short-term incubation.

A method for the isolation and trypsin-Giemsa banding of metaphases obtained after short-term incubation (48 h) of cytotrophoblast cells from chorionic villus sample is described. A new slide-making instrument, developed expressly to enhance the spreading of chromosomes from metaphases released from small tissue pieces, is responsible for the increase yield of analysable metaphases in this protocol.

Chorionic Villi↗
PubMed1987

Effects of the novel anxiolytics gepirone, buspirone and ipsapirone on free feeding and on feeding induced by 8-OH-DPAT.

The effects of the novel anxiolytics gepirone, buspirone and ipsapirone on free feeding and on feeding induced by the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), were examined. Gepirone dose-dependently increased feeding 2 and 4 h after injection, the magnitude of the response being larger than previously observed with any other 5-HT1A receptor ligand. Previous studies have suggested that buspirone and ipsapirone can block some of the behavioural effects of 8-OH-DPAT. However, gepirone, buspirone and ipsapirone did not inhibit feeding induced by 8-OH-DPAT. These results indicate that gepirone is a very efficacious appetite stimulant in rats and suggest that gepirone, buspirone and ipsapirone act as 5-HT autoreceptor agonists in the feeding model.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Primitive neuroectodermal tumor cell lines: chromosomal analysis of five cases.

A cytogenetic analysis of primitive neuroectodermal tumor (PNET) cell lines was undertaken. PNET are presumed to be embryologically related to, but clinically and histologically distinct from, other tumors of neuroectodermal origin, including neuroblastoma and retinoblastoma. No single chromosome abnormality was found in all five of the tumors studied. In three of the five cases, however, additional 1q material [either as extra chromosome #1 or i(1q)] was found in all cells, and in two of the five, monosomy 13 was noted in all cells; the possible significance of these findings is discussed.

Cell Line↗
PubMed1987

Retinoblastoma, chromosome abnormalities and oncogene expression.

Recurrent chromosomal abnormalities in retinoblastomas involve numbers 13, 1, and 6, as well as homogeneously staining regions (HSR) and double minutes (DMS). Evidence suggesting that chromosome 13 contains a gene responsible for tumorigenesis has already been presented. We postulate that the genetic changes resulting from abnormalities of chromosomes 1 and 6 and the HSR/DMS provide a selective growth advantage to cells in which they occur. Support for this hypothesis, as it relates to the HSR/DMS and oncogene amplification, is discussed.

Chromosome Aberrations↗
PubMed1987

The role of the NH2-terminal portion of pro-opiomelanocortin as a biomarker for human lung cancer.

In an epidemiological study, we evaluated the human amino-terminal portion (IR-hNT) of pro-opiomelanocortin (POMC) as a biomarker for lung cancer by measuring it by radioimmunoassay in the plasma of 180 patients with various histological types of pulmonary carcinoma. Seventy-seven patients with other cancers or benign lung disorders were our controls. An elevated IR-hNT level was measured in 12 percent of the lung neoplasm cases (22% in small-cell carcinoma) and in only 6 percent of the controls. The mean level in the lung cancer group was also higher than in the controls (p = 0.004), while it was higher in patients with small-cell carcinoma than in those with squamous-cell and adenocarcinoma (p = 0.013 and 0.002, respectively). Otherwise, we demonstrated a correlation between IR-hNT levels and altered liver function only in patients with a lung malignancy (p varying between 0.015 and less than 0.001). Finally, survival analysis failed to show that IR-hNT has a prognostic value when measured at the onset of lung cancer. These results allow us to conclude that IR-hNT, although not very sensitive in screening for carcinoma of the lung, may indicate the presence of liver metastases in this disease.

Adrenocorticotropic Hormone↗
PubMed1987

Analysis of fetal intestinal enzymes in amniotic fluid for the prenatal diagnosis of cystic fibrosis.

Amniotic-fluid intestinal alkaline phosphatase activity, gamma-glutamyltranspeptidase activity, and leucine-aminopeptidase activity were quantitated to assess their reliability for the prenatal diagnosis of cystic fibrosis. The results indicate that for each of these enzymes an arbitrary cutoff point could be chosen that would enable one to correctly predict the outcome for the majority of at-risk pregnancies. However, some false positives and false negatives occurred with each enzyme. To obtain optimal diagnostic discrimination, the three enzyme values obtained for each sample were combined into a single linear discriminant function that proved to be a more accurate indicator of the outcome of the pregnancy. This was especially important for those cases in which the predicted outcome as based on the individual enzyme results was in disagreement. From the cases studied here, it appears that this method can be expected to give a correct prediction in approximately 96.5% of all 25%-at-risk pregnancies. False positives can be expected in approximately 1.4% of the pregnancies and false negatives in approximately 2.2%.

Alkaline Phosphatase↗
PubMed1986

Chromosomal abnormalities in human retinoblastoma. A review.

In part because of an association between the tumor and the constitutional chromosome 13q deletion syndrome and the finding of 13q deletions or monosomy 13 in retinoblastoma cells from individuals with normal constitutional karyotypes, chromosome 13q is postulated to contain a gene responsible for tumorigenesis in retinoblastoma. A review of the cytogenetics of retinoblastoma (incorporating an analysis of five previously unpublished cases and 77 cases from the literature) revealed recurrent abnormalities (in addition to those involving number 13, 21% of cases) that included: additional copies of 1q material (44%), isochromosome (6p) (45%), monosomy 16 (18%), marker 1p+ (13%), and homogeneously staining regions and double minutes (9%). Possible roles for these chromosome abnormalities in tumor development are discussed.

Alleles↗
PubMed1986

Familial neuroblastoma. Case reports, literature review, and etiologic considerations.

The phenomenon of familial neuroblastoma is discussed in the context of case reports describing disseminated neuroblastoma in two of three half-brothers who share a common unaffected mother and who each have a different father. This family's cytogenetics proved to be unremarkable; also, the mother's peripheral blood DNA did not show tumorigenic capacities in transfection-nude mice experiments. An analysis of reported cases permits an updated examination of the clinical features of this entity and defines the limits of genetic counseling of families of all neuroblastoma patients. Multiple primaries are a hallmark of familial neuroblastoma. Most diagnoses are made in the first 18 months of life and at ages that fall within 12 months of the age of diagnosis of the other affected family member. Difficulties in determining the incidence and penetrance of an inherited susceptibility to neuroblastoma derive from undiagnosed tumors that have undergone regression or spontaneous maturation to benign ganglioneuroma, as well as from early deaths or long-term treatment complications that preclude reproduction and multigenerational pedigrees. Nevertheless, the risk of neuroblastoma in siblings or offspring of the large majority of persons with neuroblastoma appears to be less than 6%. Recent observations concerning chromosomal aberrations and oncogenes in embryonal malignancies are presented in an integrated model of tumorigenesis that corresponds to clinical experience.

Abdominal Neoplasms↗
PubMed1986

Interstitial deletion of the short arm of chromosome 3 (3p14).

Deletions of 3p usually involve the terminal portion (3p25). An interstitial deletion of a proximal 3p segment (3p14) was detected at amniocentesis. The clinical and cytogenetic characteristics of this case and of three previously published cases are reviewed. Cardiovascular and gastrointestinal malformations have not been reported before in association with this particular chromosome abnormality.

Adult↗
PubMed1986

Late increase in serum 1,25-dihydroxyvitamin D one month after surgery for adenomatous hyperparathyroidism.

This study was designed to follow the evolution of serum 1,25(OH)2D after surgery for primary hyperparathyroidism. Ten patients were studied before and for up to 85 d after removal of a single parathyroid adenoma. Blood and 24 h urine were obtained at various time points, for the measurement of serum or urinary phosphate and calcium indices. Before surgery, serum calcium (2.91 +/- 0.06 mmol/l; mean +/- SEM), parathyroid hormone (354 +/- 47 pg/ml) and 1,25(OH)2D (61.2 +/- 7.8 pg/ml) were elevated while serum phosphate (1.01 +/- 0.07 mmol/l) tended to be low. Relative hypoparathyroidism was evident for up to 5 d after surgery with the lowest value for serum parathyroid hormone (41 +/- 16 pg/ml) on day 1, serum calcium (2.12 +/- 0.06 mmol/l) on day 3 and highest value for serum phosphate (1.41 +/- 0.13 mmol/l) on day 5. As expected, serum 1,25(OH)2D levels decreased to 35.9 +/- 4.2 pg/ml 24 h after surgery. Stabilization of serum and urinary parameters to normal values was seen between day 5 and day 27; the only exception was serum 1,25(OH)2D, which increased again at day 27 to 57.6 +/- 5.0 pg/ml, a value as high as that before surgery. It was still elevated at day 50 (58.3 +/- 4.3 pg/ml), but returned towards normal values in three out of four patients (44 +/- 3.9 pg/ml) by day 80. No variation in 25(OH)D or 24,25(OH)2D was seen throughout the study. 1,25(OH)2D values could be related to serum parathyroid hormone values before surgery (r = 0.659, P less than 0.05) but not after. The secondary increase in serum 1,25(OH)2D could not be related to variations in serum calcium, phosphate, parathyroid hormone or diet. Further studies will be required to explain this phenomenon.

Adenoma↗