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Biomedical subjects

A Nelson

Publications and source records attributed to A Nelson.

At least 109 records · Page 6Linked to original sources

Characterization of an antigenic determinant preferentially expressed by type I epithelial cells in the murine thymus.

A hamster monoclonal antibody (MAb), designated 8.1.1, was raised against murine thymic stromal cell lines and was found to react with cell surface molecules expressed by a morphologically distinct population of epithelial cells of the murine thymus comprising the subcapsular environment, cells investing vascular structures throughout the thymus, and some of the cellular elements in the medulla. The epithelial nature of the labeled cells was confirmed with immunoelectron microscopy. Reactivity with MAb 8.1.1 was associated with thymic epithelial cells in contact with basal laminae. Ontological studies of thymic tissue demonstrated that the epitope recognized by this MAb was expressed before Day 14 of gestation, although the restricted subcapsular and medullar expression of 8.1.1 was not apparent until sometime after birth. MAb 8.1.1 also reacted with a number of extra-thymic tissues, including lamina propria of gut, glomeruli and tubules in the kidney, mesothelia covering a number of organs, and the dermis and epidermis of skin. Within the epidermis, reactivity of MAb 8.1.1 was largely restricted to basal epithelial cells. Immunochemical analysis of 8.1.1 reactivity with detergent-soluble extracts of thymic stromal cell lines and thymus tissue indicated that detergent-soluble extracts of thymic stromal cell lines and thymus tissue indicated that the epitope recognized by this MAb was associated with a glycoprotein bearing terminal N-acetylglucosamine residues and possessing an Mr of approximately 36-38 KD under reducing or non-reducing conditions.

Animals↗

Sexual behaviors of African-American male college students and the risk of HIV infection.

A survey of the rates of sexually transmitted diseases and protective sexual behaviors among a population of African-American male college students demonstrates that although monogamy, avoidance of casual sexual activity, and the avoidance of the use of drugs and alcohol during sexual activity tends to decrease the risk of exposure to human immunodeficiency virus, consistent condom use is the only sexually related behavior that is significantly protective.

Acquired Immunodeficiency Syndrome↗

Structure-antinociceptive activity of neurotensin and some novel analogues in the periaqueductal gray region of the brainstem.

Neurotensin, an endogenous tridecapeptide, produces a potent, naloxone-insensitive antinociceptive response when it is microinjected into the periaqueductal gray region of the rat brainstem. In the present study, the ED50 for neurotensin in inducing antinociception was 1.5 nmol, two times more potent than morphine. We sought to find whether neurotensin's antinociceptive effects were mediated by the same receptor that mediates its other functions. We found that the structure-activity relationship of neurotensin-induced antinociception was different from that required for the stimulation of intracellular cyclic GMP production in neuroblastoma clone N1E-115 and the binding to N1E-115 cells, human brain tissue, or rat periaqueductal gray. These data suggest there exists a subtype of neurotensin receptors in neural tissue that mediates its antinociceptive actions.

Analgesics↗

Reduced D2 dopamine and muscarinic cholinergic receptor densities in caudate specimens from fluctuating parkinsonian patients.

Binding of spiperone and 3-quinuclidinyl benzilate (QNB), both labeled with hydrogen 3 (3H), were measured in caudate tissue obtained from 8 living parkinsonian patients at the time of cerebral transplantation. This was clinically homogeneous group of patients. All remained predominantly responsive to levodopa, although with marked disability secondary to clinical fluctuations (short-duration responses) and medication-induced dyskinesias; all were receiving substantial doses of levodopa and 6 of the 8 patients were additionally receiving bromocriptine or pergolide. Binding densities of dopamine D2 receptors, as measured by [3H]spiperone binding, were reduced in this group of patients, compared to caudate specimens from autopsy control subjects. This findings may reflect medication-induced receptor downregulation. Parallel changes occurred with muscarinic cholinergic receptors; [3H]QNB binding was significantly reduced, compared to autopsy control values. This reduction of muscarinic receptors might be due to loss of nigrostriatal terminals that are known to contain muscarinic receptors. Alternatively, muscarinic receptors may have been downregulated by increased corticostriatal glutamatergic input to cholinergic cells, inferred to be present based on the prominent levodopa-induced dyskinesias. Finally, receptor deficits could have been a reflection of more widespread degenerative cerebral disease, although levodopa-refractory symptoms were generally not pronounced in these patients.

Adult↗

Neuroleptic binding to muscarinic M2 receptors of normal human heart in vitro and comparison with binding to M1 and dopamine D2 receptors of brain.

We determined by radioligand binding the equilibrium dissociation constants (Kd's) for seventeen neuroleptics at muscarinic M2 receptors of human heart atrium and compared these data with our previous data for binding to muscarinic M1 and dopamine D2 receptors of human brain. At the M2 receptor, the most potent compound was thioridazine; the least, molindone. If selectivity is defined as Kd at one receptor less than or equal to 0.1 Kd at the other receptor, no compound was selective for the M2 subtype. Two compounds, clozapine and triflupromazine, were selective for the M1 subtype. Thus, few neuroleptics have the assumed preferred property of M1 over M2 subtype selectivity. Such a feature could reduce extrapyramidal side effects, while reducing the likelihood of certain cardiac side effects.

Antipsychotic Agents↗

Bronchoalveolar lavage in the prediction of post-thoracotomy chest infection.

A prospective study was carried out on 75 patients undergoing pulmonary surgery to determine the relationship between perioperative lung flora and postoperative infections. Seventy-five patients having pleurectomy or pneumonectomy received cefuroxime prophylaxis; 1.5 g i.v. at induction followed by 6 further doses of 0.75 g i.v. over 48 h. Bronchoalveolar lavage samples were taken perioperatively via bronchoscopy in pleurectomy patients and from excised lung in patients undergoing lung resection. Patients were monitored for development of chest infection during the first 10 days after operation. Bacterial pathogens were cultured from 12 out of 54 lavage samples. The most common pathogen was Haemophilus influenzae and all the organisms were sensitive to cefuroxime. Eight patients (10.7%) developed postoperative chest infection. The likelihood of developing postoperative chest infection was 42% (5 out of 12 patients) in those patients whose lavage culture was positive for bacterial pathogens compared to 4.8% (2 out of 42 patients) for those whose culture was negative (chi 2 test, p less than 0.001). These results suggest that the culturing of bacterial pathogens from lavage samples from resected lung is a significant predictor of postoperative chest infection in patients undergoing pulmonary resection.

Bronchoalveolar Lavage Fluid↗

HIV and other sexually transmitted diseases among female prostitutes in Kinshasa.

In 1988, 1233 prostitutes from different geographic areas of Kinshasa participated in a cross-sectional survey on HIV infection and other sexually transmitted diseases (STDs). Despite relatively good knowledge about AIDS and STDs, the reported preventive behaviour was poor. Only 12% of the women reported regular use of condoms, while greater than 50% of the women reported regular use of antibiotics and 38% reported doing nothing specific to prevent STDs. Thirty-five per cent of the women were HIV-positive compared with 27% in a similar survey in Kinshasa in 1986. The prevalence of other STDs was very high, ranging from 5% for genital ulcer disease (GUD) to 23% for gonococcal infection. HIV-positive women were older than HIV-negative women (26.9 versus 25.4 years; P less than 0.001), had a significantly lower level of reported condom use (9 versus 14%, P = 0.009), and reported more frequent use of antibiotics to prevent STDs (55 versus 42%, P = less than 0.001). The prevalence of syphilis, gonorrhoea, chlamydial infection and trichomoniasis was not higher in HIV-positive women compared with HIV-negative women. However, HIV-positive women had a higher prevalence of GUD (9 versus 3%, P less than 0.001), antibodies against Haemophilus ducreyi (82 versus 57%, P less than 0.001), antibodies against herpes simplex virus type 2 (96 versus 76%, P less than 0.001), condylomata accuminata (5 versus 1%, P = 0.003) and cytologic evidence of human papilloma virus on Papaniclaou cervical smear (11 versus 5%, P = 0.006). This study confirms the high incidence of HIV and other STDs among prostitutes in Africa.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Epithelial heterogeneity in the murine thymus: a cell surface glycoprotein expressed by subcapsular and medullary epithelium.

A monoclonal antibody (MAb), G8.8, was raised against glycoconjugates isolated from a cloned line of murine medullary thymic epithelial cells. Flow cytometric analysis of the reactivity of this MAb with cultured thymic epithelium demonstrated that the ligand was expressed on the cell surface. Immunohistochemical examination of normal murine thymus revealed labeling of cells in the subcapsular and medullary areas. Immunoelectron microscopy revealed surface labeling restricted to cells possessing ultrastructural features of epithelium (desmosomes, tonofilaments, and cytoplasmic cysts). During thymic ontogeny, G8.8+ cells predominated in fetal development at the earliest time point examined (Day 14 of gestation). There was an expansion of the cortical epithelial component so that by Day 18 cortical and medullary compartments could be clearly distinguished. Immunoprecipitation of radioiodinated thymic stroma with MAb G8.8 detected a molecule with an apparent Mr of approximately 38 KD under non-reducing conditions. When reduced, the apparent Mr was slightly increased (42 KD). This MAb also exhibited reactivity with gut and epidermal epithelium and some tubular epithelium in the kidney, but did not react with epithelial parenchymal cells of the liver.

Animals↗

Binding of benzodiazepines and some major metabolites at their sites in normal human frontal cortex in vitro.

Using [3H]flunitrazepam in radioligand binding assays, we determined equilibrium dissociation constants (Kd's) at 37 degrees C for 22 benzodiazepines (15 parent compounds and 7 major metabolites) at benzodiazepine binding sites in human frontal cortex. This list included several compounds never studied before at human receptors. Although dissociation was too rapid to measure reliably at this temperature, the Kd's for flunitrazepam were not significantly different when either rapid filtration or centrifugation was used to separate the bound from free radioligand. The most potent compound was triazolam (Kd = 0.54 nM); the least potent, chlordiazepoxide (Kd = 684 nM). The Kd's were significantly lower (about 3- to 7-fold) for several compounds tested at an equilibrium temperature of 0 degrees C compared to those obtained at 37 degrees C. There was a strong correlation for 15 compounds for the log Kd at rat brain receptors (data obtained from the literature) vs. the log Kd for human brain. In addition, the log Kd's of the various benzodiazepines for their receptor were significantly correlated with the log of their minimum daily dosages used to treat patients. Many of the benzodiazepines have clinically important active metabolites that have higher affinity for benzodiazepine binding sites in human brain than their parent compounds. Such data have important implications in the clinical use of these compounds.

Aged↗

Interaction of hydrophobic organic compounds with mercury adsorbed dioleoylphosphatidylcholine monolayers.

The interaction of hydrophobic organic compounds with biological membranes is an important factor in their biological activity. A fundamental insight into the mechanisms can be obtained by examining the influence of these substances on model membrane systems. The effect of four groups of hydrophobic aromatic compounds on a mercury-adsorbed dioleoylphosphatidylcholine (DOPC) monolayer is described in this paper. The compounds studied were: (1) polynuclear aromatic hydrocarbons (PAH), (2) polychlorinated biphenyls (PCB), (3) neurotoxic pesticides, and (4) phenothiazines. The monolayer properties were measured using phase-sensitive a.c. voltammetry and cyclic voltammetry. The response of the monolayer to these compounds is recorded as a change in the form of the capacity-potential curve especially with respect to two capacity peaks which correspond to two well-defined phase transitions. Planar aromatic molecules cause a negative shift of the capacity peaks, however, as the molecule becomes more globular the response becomes less and the peaks become suppressed. It is shown that planar aromatic molecules exert their effect by penetrating the hydrocarbon region of the monolayer and that there is a molecular size cut-off for higher membered PAH molecules. In addition, the monolayer is not so sensitive to the bulky PCB which have a more disruptive effect on the phase transitions and thus on the mechanisms of self-assembly of the monolayer. A direct correlation is shown between the biological membrane activity of the phenothiazines and their effect on the monolayer at submicromolar levels. A molecular selectivity of phospholipid monolayers to these compounds is indicated which has implications for their effect on biological membranes.

Adsorption↗

Distribution of thymocytes expressing gamma delta receptors in the murine thymus during development.

We have examined the appearance of thymocytes expressing gamma delta TCR within the developing thymus by using immunohistochemical techniques and flow cytometry in conjunction with the mAb 3A10, which recognizes a determinant associated with the constant region of the delta-chain. gamma delta+ Cells were first detected at day 16 of gestation, attained maximal levels at day 17 of gestation, and declined thereafter. By using the Ulex europeus agglutinin to identify medullary epithelial cells in situ, we observed a striking colocalization of gamma delta+ thymocytes and U. europeus agglutinin-positive medullary epithelial cells during late fetal and neonatal periods of development. In the thymuses of adult mice, gamma delta+ thymocytes were scattered throughout cortical and medullary areas of the thymus and most concentrated in the subcapsular areas of the thymus. Ultrastructural immunohistochemistry confirmed the close association between medullary thymic epithelial cells and gamma delta+ thymocytes in the neonatal thymus and also showed that some TCR-gamma delta molecules were patched to areas of contact with medullary epithelial cells. In contrast to the cellular distribution of either CD3 molecules or the TCR-alpha beta, where extensive intracellular labeling of thymocytes has been observed, cytoplasmic accumulation of delta-chain was not detected.

Animals↗

Banning alcohol in a major college stadium: impact on the incidence and patterns of injury and illness.

To evaluate the effect of banning alcohol on the incidence of injuries and illness among spectators, we reviewed 4 years (1983 to 1986) of medical incident reports from a major collegiate football stadium. At no time had alcoholic beverages been sold inside the stadium, but before 1985, fans were allowed to bring alcohol into the stadium. In 1985, this practice was banned. During the study period, 340 medical incidents (M = 12.6/game) were reported. Several alterations of specific injury/illness patterns were noted after initiation of the ban: heat-related illness occurred more frequently before initiation of the ban, whereas extremity injuries and syncope (fainting from coronary insufficiency) occurred with greater frequency afterwards. The injury/illness rates per 10,000 fans were 2.95 in 1983, 2.45 in 1984, 1.92 in 1985, and 3.48 in 1986. There was no significant change in the overall incident rate after the ban. Evaluation of medical incidents revealed an alteration in specific injury/illness patterns but no change in overall incidence after institution of the ban. Future investigations are needed to elucidate more clearly the impact of banning alcohol on injury/illness rates and patterns at mass gatherings.

Adolescent↗

A systematic effort to reduce smoking at the worksite.

Smoking control is a key element of worksite health promotion. This three-stage study in a large state human services agency included a baseline survey, an assessment of the effects of competition on recruitment to a self-help cessation program, and examination of the outcome of the cessation program. In stage 1, scales for measuring smoking-related attitudes and the social environment were developed and used to study norms for smoking. Regression analysis was used to ascertain correlates of smokers' intentions to quit and to join a self-help program and non-smoker assertiveness. In stage 2, an evaluation using a quasi-experimental design indicated that competition was moderately effective in increasing the recruitment of all employees to the Great American Smoke-Out (70 vs. 17%) and of smokers to a self-help cessation program (28 vs. 6%). In stage 3, the self-reported quit rate at the end of the program was 28% and the biochemically-verified six months' cessation rate was 7%. Efforts are needed to strengthen, using ethical means, the norms for not smoking at the worksite and to increase both the recruitment to and the effectiveness of smoking cessation programs.

Adult↗

Ender rods versus external fixation in the treatment of open tibial fractures.

This is a retrospective nonrandomized study of 66 open tibial fracture patients that compares comparable population treated at one trauma center. The fractures were treated with either Ender rods or external fixation. Of these, 29 fractures were eliminated from the study due to incomparable variables. Thus, the study group consisted of a total of 37 tibial fractures: 20 treated by Ender rods and 17 treated by external fixation. Open tibial fractures treated with Ender rods had a significantly lower number of complications than those treated with external fixation. The group treated with Ender rods also had a significantly lower number of surgical procedures per patient in Grades I and II open tibial fractures. There were no statistical differences regarding weeks to union or hospital days. Ender rods are superior to external fixation removed early in the treatment of Gustilo's Grades I, II, and IIIA open fractures with either stable or unstable fracture configuration (Orthopaedic Trauma Association Grades IA-IC, IIA-IID, and IIIA-IIIC). Perhaps future study will allow sufficient numbers to determine whether Ender rods can be used in Grades IIIB and IIIC open tibial fractures, but there are no data at this time to support this conclusion.

Adult↗

Large-scale isolation of covalently closed circular DNA using gel filtration chromatography.

The isolation of covalently closed circular (ccc) DNA free of contamination by RNA and other forms of DNA is fundamental to molecular biology. A variety of methods have been explored but CsCl density-gradient centrifugation remains the method most widely used for preparative scale resolution. The process is expensive, time-consuming, requires the use of large amounts of the carcinogen ethidium bromide, and is subject to considerable variation in yield and purity. To avoid these problems, we have devised a procedure for the preparation of cell lysates which results in consistently good yields of biologically active ccc DNA minimally contaminated with chromosomal DNA fragments and RNA. Lysates are deproteinized, precipitated with CaCl2 to remove rRNA, concentrated by ethanol precipitation, and applied to a Sephacryl S-1000 column which resolves chromosomal fragments, open circular plasmid DNA, and residual RNA from the ccc DNA. We have found that substituting the gel filtration column for CsCl density-gradient centrifugation results in substantially better purification as well as reducing processing time, cost, and degree of difficulty. The time required from harvest of cells to final recovery of DNA is about 16 h. We have used the method to isolate plasmids from 4.4 to 12 kb and, with slight modifications, recombinant M13 replicative form DNAs.

Acrylic Resins↗