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Biomedical subjects

S Gilbert

Publications and source records attributed to S Gilbert.

At least 19 recordsLinked to original sources
PubMed1992

Desensitization of the human V2 vasopressin receptor. Homologous effects in the absence of heterologous desensitization.

Three main pathways have been implicated in desensitization of receptors that stimulate adenylylcyclase (AC): cAMP-mediated phosphorylation; cAMP-independent phosphorylation, and receptor internalization. Cell lines derived from the murine Ltk- cell were found useful in exploring the contribution of cAMP-dependent phosphorylation in V2 vasopressin receptor desensitization. The HTB-2 cell expresses the human V2 vasopressin receptor, introduced by transfection of human genomic DNA, and the prostaglandin E1 (PGE1) receptor, endogenous to the Ltk- cell. The A7 cell expresses the hamster beta 2-adrenoceptor, which undergoes the above-mentioned desensitization processes. Treatment of HTB-2 cells with arginine-vasopressin (AVP) had no effect on AC responsiveness to PGE1, but promoted desensitization of the AVP response. This was seen as a 5-6-fold right shift in the dose-response curves for AVP action (cAMP accumulation in intact cells and AC stimulation in homogenates and isolated membranes) and in a decrease in the maximum effect of AVP on these parameters. AVP treatment caused a decrease in cell surface receptors to approximately 75% of control without changes in KD, as determined by Scatchard analysis. When cAMP was increased by treatment with 10 microM PGE1 and isobutylmethylxanthine, desensitization of the PGE1 receptor was observed but not of the AVP receptor. In A7 cells the same treatment caused, as expected, a 3-fold right shift in the dose-response curve for AC stimulation by isoproterenol, indicating that L cells can mediate heterologous desensitization. These data demonstrate that the V2 vasopressin and the PGE1 receptors undergo homologous desensitization in the absence of cAMP-mediated phosphorylation and that this component is not required for vasopressin receptor internalization.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Molecular cloning of the receptor for human antidiuretic hormone.

Antidiuresis, the recovery of water from the lumen of the renal collecting tubule, is regulated by the hypothalamic release of antidiuretic hormone (ADH), which binds to specific receptors on renal collecting tubule cells, stimulates adenylyl cyclase and promotes the cyclic AMP-mediated incorporation of water pores into the luminal surface of these cells. We report here the isolation of the human ADH receptor gene using a genomic expression cloning approach. The gene was used to clone the complementary DNA from a human renal library. The deduced amino-acid sequence of the receptor yields a hydropathy profile characteristic of receptors with seven putative transmembrane regions. This and the comparison with other cloned receptors indicates that the ADH receptor is a member of the superfamily of G-protein-coupled receptors.

Amino Acid Sequence↗
PubMed1991

Quantification of hepatobiliary function as an integral part of imaging with technetium-99m-mebrofenin in health and disease.

A study was undertaken to check the feasibility of measuring the hepatic extraction fraction (HEF) and excretion T-1/2 values as an integral part of hepatobiliary imaging with technetium-99m-mebrofenin in health and disease. In 18 controls subjects, the HEF was 100% and the T-1/2 excretion mean +/- s.e. value was 15.23 +/- 1.4 min. The mean appearance times of the common bile duct (CBD), gallbladder (GB), and small intestine were 15.8 +/- 1.52, 20.2 +/- 2.7, and 23.8 +/- 3.08 min, respectively. Rising serum bilirubin in patients decreased HEF and increased T-1/2 excretion value resulting in delayed appearance of CBD, GB, and small intestine. In control subjects and patients with bilirubin less than 5 mg%, T-1/2 excretion values at 30, 40, and 50 min were similar to those values calculated using the entire 60 min of data, suggesting that the hepatic phase study time could be reduced to 30-40 min and still use the normal reference values established for 60 min. In patients with bilirubin greater than 5 mg%, the data collection duration should be continued for 60 min.

Aniline Compounds↗
PubMed1991

Television and the 3- to 10-year-old child.

A questionnaire on the use of television was administered to the parents of 387 children aged between 3 and 10 years. All families owned at least one television set and 57.6% of families owned two or more sets, with one in the child's bedroom in 10.6% of cases. Television was turned on all day in 16% of cases, mostly in families with low level of parental education (P less than .01). Television was on at mealtime in 54.5% of cases; 45.2% of children were watching television for between 7 to 16 hours per week, and the heavy viewers belonged to families with low levels of maternal education (P less than .05). About one third of children watched television without any interdiction set by their parents. According to age, from 28% to 40% of children watched violence on television. Parents believed that television facilitates learning (65.3%) but were concerned about violence (22.7%) and commercials (7.4%). Finally, 63.3% of parents reported that they would like to obtain more information about television use. According to this survey, many children are watching television without any limits being set by their parents and are witnessing violent scenes at an impressionable and vulnerable age. The pediatrician should include at routine office visits parental guidance on the mediation of television effects through coviewing, content discussion with children, and program selection.

Analysis of Variance↗
PubMed1989

Human IgM monoclonal proteins that bind 3-fucosyllactosamine, asialo-GM1, and GM1.

Analysis of monoclonal human Ig that occur in association with lymphoproliferative diseases has provided valuable information about antibody structure and idiotypes. We analyzed 940 human sera that contained monoclonal IgM proteins for their ability to bind to four carbohydrate epitopes. Ten sera bound asialo-GM1, five of these sera also bound GM1, 10 bound to 3-fucosyllactosamine (3-FL), and one each bound to levan and galactan. Although the antibody activity in each serum was associated with a single L chain isotype, both kappa and lambda isotypes were represented among the proteins that bound to asialo-GM1 and to 3-FL. Some antibodies against asialo-GM1 were highly specific for this compound, whereas others cross-reacted with the structurally related gangliosides GM1 and GD1b. The antibodies to asialo-GM1 also varied considerably in their ability to lyse liposomes that contain asialo GM1. An association of IgM mAb against gangliosides with peripheral neuropathies has been reported recently, but only one of five patients whose antibodies reacted with GM1 ganglioside had a neuropathy. The antibodies that bound 3-FL exhibited narrower specificity, and less than 10% cross reactivity was noted with structurally related carbohydrates. The frequency of monoclonal proteins that bound 3-FL and asialo-GM1, approximately 1:100 sera for each specificity, was surprisingly high in view of the fact that both of these epitopes are expressed in human tissues. We suggest that these antibodies may be poly-specific and/or that the subset of B lymphocytes that synthesizes these anti-carbohydrate antibodies undergoes malignant transformation more frequently than other B lymphocytes.

Antibodies, Monoclonal↗
PubMed1988

Monoclonal antibodies that bind to galactosylgloboside (SSEA-3 antigen).

The 3-fucosyllactosamine (3-FL) antigenic determinant, Gal(beta 1-4)[Fuc(alpha 1-3)]-GlcNAc-R, is very immunogenic in BALB/c mice. A panel of monoclonal antibodies was raised against a novel glycosphingolipid that contains a terminal 3-FL structure (structure 1): (formula: see text) Surprisingly, most of these antibodies reacted with the internal galactosylgloboside structure rather than with the terminal 3-FL epitope. The specificities of two of these antibodies, 5A3 and 8A7, were analyzed by enzyme-linked immunosorbent assay and immunostaining procedures, and compared with MC631 (anti-SSEA-3), the only other monoclonal antibody known to bind to galactosylgloboside. 5A3 and 8A7 bound equally well to structure 1 and to galactosylgloboside. These antibodies also bound to structure 1 from which the terminal galactose, or the galactose and fucose, had been removed, but not to globoside or sialylated galactosylgloboside. In contrast, MC631 did not bind to structure 1 but, as described previously, did bind to globoside and sialylated galactosylgloboside. Galactosylgloboside is a developmentally regulated antigen of mouse embryos, human teratocarcinomas, and mouse embryonic brain. Antibodies 5A3 and 8A7 will complement MC631 in the analysis of the distribution and regulation of galactosylgloboside.

Antibodies, Monoclonal↗
PubMed1987

Diagnosis of sclerosing cholangitis with technetium 99m-labeled iminodiacetic acid planar and single photon emission computed tomographic scintigraphy.

The purpose of this study was to determine whether 99mTc-iminodiacetic acid planar biliary scintigraphy combined with single photon emission computed tomography could detect sclerosing cholangitis and provide additional information regarding the extent and severity of disease. Thirteen patients with sclerosing cholangitis and 13 normal control subjects were studied. Scintigraphic results were also compared with previously reported studies of patients with isolated common bile duct obstruction and with primary biliary cirrhosis. The planar scintigraphy in patients with sclerosing cholangitis showed beading or bandlike constrictions of the biliary tract corresponding to lesions seen on cholangiography, and the image pattern was distinctly different from images obtained from patients with isolated common bile duct obstruction or primary biliary cirrhosis. The single photon emission computed tomography images of the liver in patients with sclerosing cholangitis demonstrated multiple focal areas of 99mTc-iminodiacetic acid retention, representing bile stasis in intrahepatic bile ducts. Compared to controls, the mean hepatic clearance half-time of 99mTc-iminodiacetic acid was markedly delayed in patients with sclerosing cholangitis (6-10 times normal). Individual patients with sclerosing cholangitis had wider variation in isotope clearance half-time from three regions of the liver than patients with isolated common bile duct obstruction, consistent with regional difference in disease severity and variable impairment of bile flow. In 4 patients with sclerosing cholangitis with incomplete filling of the right and left hepatic ducts at cholangiography, planar and single photon emission computed tomographic scintigraphy provided evidence of significant intrahepatic sclerosing cholangitis. In conclusion, combined 99mTc-iminodiacetic acid planar and single photon emission computed tomographic scintigraphy is a sensitive noninvasive test for the diagnosis of sclerosing cholangitis and reliably differentiates sclerosing cholangitis from isolated common bile duct obstruction or primary biliary cirrhosis. Measurement of isotope clearance half-time provides quantitative physiologic data that may be useful in the longitudinal follow-up of patients with sclerosing cholangitis.

Adult↗
PubMed1987

Potential methodologic problems with in vivo immunoneutralization of pancreatic polypeptide.

Dogs with chronic pancreatic fistulae were given 0.5 ml of nonimmune rabbit serum or antibody S5, an antibody raised against the C-terminal pancreatic polypeptide (PP) hexapeptide. A 3-h infusion of secretin (125 ng/kg/h) and CCK8 (50 ng/kg/h) was started 30 min after injecting serum. Exogenous BPP (400 pmol/kg/h) was administered during the middle secretin/CCK hour. In a second protocol, 30 min after injecting nonimmune serum or PP-anti-serum, the animals were fed 15 g/kg cooked ground beef. Pretreatment with S5 enhanced secretin/CCK-induced bicarbonate outputs; protein outputs did not differ. Exogenous BPP inhibited pancreatic secretion, even in S5-treated animals. Meal-induced pancreatic secretion was not altered by S5 pretreatment. Significant increments in PP were measured by radioimmunoassay during administration of secretin/CCK and during BPP infusion. Anti-PP pretreatment abolished the former and significantly decreased, but did not abolish, the latter. The meal evoked significant postprandial increments in PP which were essentially abolished following S5 pretreatment. A physiological role for PP cannot be proved or refuted because antiserum pretreatment failed to block the effects of exogenous hormone. The latter must be established before excluding a peptide's physiological role based on negative in vivo immunoneutralization data.

Animals↗
PubMed1986

Fast axonal transport by neurons from the jellyfish Cyanea capillata.

Neurons of the motor nerve net of Cyanea capillata were examined using video-enhanced DIC optics. A variety of organelles were visible within the axons and many were mobile. To quantify the movement organelles were divided into three classes (large, medium, and small) and the rates, direction, and types of movement displayed by the different particle types examined. The overall behavior and rates of movement of transported particles were comparable with those in axons from other species. The largest particles, mainly mitochondria were the slowest moving but were the only particles to reverse their direction of movement or to undergo interactions with other particles. The fastest movement was by the small particles, but both they and medium sized particles were transported continuously. In addition, the linear elements in these axons underwent considerable lateral movement.

Animals↗
PubMed1986

Measurement of gallbladder volume and dynamics by combined SPECT and planar scintigraphy.

A new method is described for measurement of gallbladder volume based on three-dimensional single photon emission computed tomography (SPECT). The technique was first validated in a body phantom that used a balloon to represent the gallbladder. The balloon was inflated with a known volume and SPECT volume was calculated by summing the voxels in each transaxial slice above a percentage count threshold. The SPECT and true volume showed a high linear correlation between 15 to 90 ml (r = 0.99). The mean fasting gallbladder volume using a technetium-99m-labelled hepatobiliary agent in nine normal subjects was 26 +/- 2 ml (range 18 to 39 ml). By combining the SPECT measurement with a planar technique, it was also possible to evaluate gallbladder emptying parameters. Following a 3 min infusion of 10 ng kg-1 of cholecystokinin octapeptide (CCK), the mean gallbladder ejection rate was 1.2 +/- 0.2 ml min-1 and the residual volume was 12 +/- 2 ml. SPECT offers a new noninvasive method for accurate measurement of gallbladder volume.

Adult↗
PubMed1986

Heterophilic antibody as a source of error in immunoassay.

We describe our experience with a young woman believed to be hypothyroid and menopausal because of erroneously elevated TSH, LH, and FSH estimates. These errors were found to be due to the presence of antibodies to rabbit IgG in the patient's blood. We found that antibody-limited assays for TSH, LH, and FSH using antisera raised in rabbits were affected by this problem unless rabbit IgG was included, whereas antibody-excess assays were not. These problems were most simply detected by observing inappropriate results when measurements were made in dilutions of the patient's serum. The presence of endogenous antibody directed against antibodies used in immunoassays is a significant potential source of error requiring awareness on the part of both the clinician caring for such patients and the clinical laboratory making the measurements.

Adult↗
PubMed1986

Mandibular involvement by oral squamous cell carcinoma.

Detecting mandibular bone involvement by oral carcinoma prior to definitive therapy poses a difficult problem for the head and neck surgeon. A retrospective study of 104 patients who underwent segmental mandibular resection for oral squamous cell carcinoma was undertaken to detect the incidence of mandibular bone involvement. Specimens from 23 patients (22%) demonstrated tumor invasion on decalcified histologic examination. Histologic evidence of bone involvement was correlated with the site of lesion, stage of the disease, the grade of tumor, the clinical impression of bone involvement, and the presence or absence of neck disease. Bone invasion on histologic examination was also compared with preoperative bone scans and radiographs. The data obtained demonstrates significant mandibular involvement with alveolar tumors and lesions clinically adjacent to the mandible. There was also a high incidence of histologic bone involvement in patients who had radiologic or bone scan evidence of tumor erosion. We support segmental mandibulectomy on the basis of providing adequate tumor margins for patients fulfilling these criteria.

Adult↗
PubMed1985

Developing a rating interview guide.

Nursing administrators have spent considerable time and effort developing various interview tools that will meet the needs of the institution, however, of equal importance is the method of evaluating responses obtained during the interview process. This article discusses a master tool designed as a base from which a variety of interview tools can be developed. Weighted scoring reflects the strengths of the applicant consistent with the position requirements and in an equitable manner.

Administrative Personnel↗
PubMed1985

Epidemiology of blindness in Nepal.

This report presents the major findings of the Nepal Blindness Survey, the first nationwide epidemiological survey of blindness, which was conducted in 1979-80. The survey was designed to gather data that could be used to estimate the prevalence and causes of blindness in the country. Ancillary studies were conducted to obtain information on socioeconomic correlates and other risk factors of blinding conditions and patterns of health care utilization.The nationwide blindness prevalence rate is 0.84%. Cataract is the leading cause of blindness, accounting for over 80% of all avoidable blindness. Trachoma is the most prevalent blinding condition, affecting 6.5% of the population. Very few cases of childhood blindness were detected.The implications of the survey findings for programme planning, health manpower development, and health education are discussed.

Adolescent↗
PubMed1985

Estimation of thyroxin, triiodothyronine, thyrotropin, free thyroxin, and triiodothyronine uptake by use of magnetic-particle solid phases.

We evaluated solid-phase radioassays involving small, uniform magnetic particles (MAGIC, Corning Medical), obtaining data on total serum thyroxin (T4), triiodothyronine (T3), thyrotropin (TSH), free thyroxin (FT4), and T3 uptake for a total of 301 serum samples from euthyroid patients; patients receiving replacement thyroxin; patients receiving estrogen, or who were pregnant; hyperthyroid, hypothyroid, and nonthyroidally ill patients; and patients receiving salicylates, phenytoin, or heparin. We found each procedure to be technically simple and precise (between-assay CVs for T4 2.8-8.2%, T3 9-7.4%, TSH 2.9-4.5%, FT4 3.6-11%, T3 uptake 2.2-3.7%). The magnetic separations are rapid (2 to 5 min), reproducible, and complete. Each MAGIC assay produced clinically appropriate results. These assay systems offer the convenience associated with noncentrifugation assays and excellent analytical performance.

Binding Sites↗