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Biomedical subjects

D J Anderson

Publications and source records attributed to D J Anderson.

At least 325 records · Page 18Linked to original sources

The treatment of migraine with variable frequency photo-stimulation.

Variable Frequency Photo-stimulation (VFP) goggles are a form of portable stroboscope, using red Light Emitting Diodes to alternately illuminate the right and left eyes, with the eyelids closed, at a rate of 0.5 to 50 Hz. VFP goggles were used in the treatment of 7 patients with migraine headache. Of 50 migraine headaches recorded, 49 were rated by the patient as being helped and 36 as being stopped by using the VFP goggles. Treatment reduced the median duration of headache in all patients. The interval between migraine headaches appeared to be increased in the two cases with a follow up of more than 18 months. We conclude in this preliminary study that VFP appears to be effective in the treatment of migraine.

Adult↗

Indeterminate mediastinal invasion in bronchogenic carcinoma: CT evaluation.

The computed tomographic (CT) scans of 80 patients with bronchogenic carcinoma classified as indeterminate for direct mediastinal invasion were retrospectively reviewed after the patients had undergone thoracotomy. Forty-eight (60%) of the masses were resectable, without invasion of the mediastinum, 18 (22%) focally invaded the mediastinum but were technically resectable, and 14 (18%) invaded the mediastinum and were not technically resectable. Although in most circumstances in this relatively small subset of patients CT was not helpful in differentiating masses with and without mediastinal invasion, CT was able to separate a large group of masses that were likely to be technically resectable. Thirty-six (97%) of 37 masses with one or more of these CT findings were considered technically resectable: contact of 3 cm or less with mediastinum, less than 90 degrees of contact with aorta, and mediastinal fat between mass and mediastinal structures. Of these 36 masses, 28 were resectable without mediastinal invasion, and eight were resectable with focal limited mediastinal invasion.

Adult↗

Pneumothorax: appearance on lateral chest radiographs.

The appearance of pneumothorax on lateral radiographs obtained with the patient erect were reviewed in 100 patients (122 total examinations). A pneumothorax could be seen on the lateral projection in 89% of the examinations (109 of 122). The displaced pleural line was most frequently identified anteriorly or posteriorly and was less commonly identified at the lung apex or in a subpulmonic location. In 11 cases, an air-fluid level was the only recognizable finding of a pneumothorax on the lateral projection. Although in 27% of examinations (32 of 122) the pneumothorax was either not seen (11%) (n = 13) or was a subtle finding (16%) (n = 19), in 14% of examinations (17 of 122) the lateral projection provided helpful information to supplement the posteroanterior projection.

Adult↗

Surgical implantation and biocompatibility of central nervous system auditory prostheses.

As part of a program to determine the feasibility of a CNS auditory prosthesis, the tissue reaction to electrodes chronically implanted in the cochlear nucleus (CN) of the guinea pig was examined. Varied open operative approaches and microelectrode designs were utilized. Silicon substrate thin film and platinum-iridium wire electrodes, tethered and untethered, were placed successfully in different divisions of the CN. Implantation through a posterior suboccipital approach was most successful. Histologic examinations demonstrated a glial cell proliferation confined to the area of the electrode track that never exceeded 15 microns in width. No neuronal loss or significant effect on cell morphology was seen, and reactive cells were absent. Electrode migration was apparent in a minority of animal preparations. Although potential problems were identified, our findings lend support to the feasibility of implanting a neuroprosthesis in the CN and have helped to establish methods for future studies of chronic intranuclear stimulation.

Animals↗

Auditory brainstem prosthesis: biocompatibility of stimulation.

As part of a program to develop a central auditory system prosthesis, we have examined the reaction of tissue to different levels of stimulation from electrodes chronically implanted in the cochlear nucleus of the guinea pig. Tolerance and histologic reaction to 20 hours of periodic electrical stimulation of the cochlear nucleus were analyzed. Intraoperative and postoperative electrically evoked middle latency responses were monitored during stimulus trials. The threshold necessary to generate the middle latency responses was frequently below 50 microA. In the animals that received 50 and 100 microA of biphasic charge-balanced stimulation (corresponding to approximately 200 and 400 microC/cm2 phase), adverse tissue reaction was minimal, and glial proliferation along the electrode tract never exceeded 25 microns in width. Stimulation intensities of 150 and 200 microA (approximately 600 and 800 microC/cm2 phase) produced significant tissue response at the site of the electrode terminus, with necrosis, cell loss, and reactive cells present. Therefore neuronal damage was observed to occur at an intensity far greater than that required for eliciting an electrophysiologic response.

Animals↗

Multiple-channel stimulation of the cochlear nucleus.

To further test the feasibility of a central nervous system auditory prosthesis, the characteristics of the electrically evoked middle latency response were studied in a series of acutely anesthetized pigmented guinea pigs, with multi-channel penetrating cochlear nucleus electrodes placed into the cochlear nucleus under direct visualization. These stimulating electrodes consisted of a silicone substrate, with five stimulating pads each, sputtered with iridium. Monopolar and bipolar stimulation were used. Threshold, latency, and input-output functions of the electrically evoked middle latency response were studied. Systematic differences were observed, depending on the site and parameters of stimulation. Principally, higher currents were required to produce waves of equal amplitude when the electrodes were closely spaced. For near electrode pairs, the maximum wave amplitudies obtainable within the limits of tissue safety were much lower than for distant electrode pairs. The slope of the growth function curve was steeper for widely spaced electrodes than for adjacent sites. Monopolar stimulation demonstrated maximum wave amplitudes with the lowest current intensity, implying current spread to the entire cochlear nucleus with this stimulation montage. In some cases, threshold differences were observed, higher thresholds being associated with closely spaced electrodes. These findings are consistent with simple models of the electric fields expected to be generated by these electrode arrays. The results support the hypothesis that activation of subpopulations of auditory brainstem neurons with multi-channel penetrating microelectrodes is possible.

Animals↗

Healthy and institutionalized: health and related conditions among older persons with developmental disabilities.

The life expectancy of mentally retarded citizens has increased significantly in recent decades. At the same time, we have learned that this special population is nearly twice as likely as the general population to develop severe mental illness. These facts, coupled with the psychological and physiological changes that accompany aging in general, are increasingly challenging the mental health professionals of today. We provide an overview of mental retardation in the elderly, as well as the types, treatments, and attendant challenges of associated mental illness.

Aged↗

The effects of RU 486 on immune function and steroid-induced immunosuppression in vitro.

The effect of RU 486 [17 beta-hydroxy-11 beta-(4-dimethylamino-phenol)17 alpha-(prop-1-ynyl)estra- 4,9diene-3-one] on [3H]thymidine incorporation into Concanavalin-A-stimulated human peripheral blood mononuclear cells and its influence on the suppressive effects of cortisol and progesterone were investigated. Cortisol suppressed lymphocyte thymidine incorporation at 10(-5), 10(-6), and 10(-7) M (17.6%, 20%, and 38% of control, respectively; P less than 0.01). Cortisol-induced suppression was reversed when low concentrations of RU 486 (10(-7) and 10(-6) M) were added. RU 486 at 10(-5) M further suppressed lymphocyte thymidine incorporation when added to cultures with cortisol. Progesterone significantly inhibited lymphocyte thymidine incorporation at 10(-5) M (8.2% of control; P less than 0.01). No reversal of progesterone-induced suppression of thymidine incorporation was seen when RU 486 was added to cultures; rather, further suppression of thymidine incorporation was seen. RU 486 alone in culture at concentrations achieved therapeutically (10(-5) M) significantly inhibited thymidine incorporation (7.2% of control; P less than 0.01). These findings suggest that RU 486 may have dose-dependent mixed agonist/antagonist effects on cortisol-induced immunosuppression. The lack of an antagonist effect of RU 486 on progesterone suggests that progesterone's immunosuppressive effects may not be receptor mediated. Finally, our findings would suggest that some immunosuppression may be seen at currently used doses of RU 486.

Adult↗

Bronchial impaction in lobar collapse: CT demonstration and pathologic correlation.

Bronchial (or mucoid) impaction refers to the accumulation of inspissated secretions (mucus and/or inflammatory products) within a bronchus, usually accompanied by bronchial dilatation. This process may be caused by abnormal mucociliary transport and excessive production of mucus. In other cases, a discrete lesion may be present that obstructs the bronchus with inspissated secretions accumulating distal to the obstructing lesion. Lobar collapse may result in either case if a lobar bronchus is occluded by the excessive mucus or a discrete obstructing lesion. The CT manifestations of bronchial impaction in four patients with lobar collapse are described. In two patients, the lobar collapse and distal bronchial impaction were produced by a central obstructing bronchogenic carcinoma, whereas the other two patients had an abnormal mucus accumulation without a discrete bronchial obstruction. On CT, the impacted bronchi, best seen on postcontrast images, appeared as relatively low-attenuation branching structures extending from the hilum peripherally into the more opaque enhancing atelectatic lung. In the three patients who had surgical resection of the involved lobe, pathologic examination confirmed the dilated bronchi, filled with mucus (one patient), fibrinopurulent exudate (one), or mucous plugs with Aspergillus hyphae (one). This unique pattern of impaction within a collapsed lobe should be recognized on CT and prompt a search for a possible central obstructing lesion.

Bronchi↗

[HIV in sperm].

HIV in the semen is located in the mononuclear cell fraction, which contains CD4 lymphocytes and monocytes/macrophages, i.e. the classic HIV host cells. In addition, HIV is also present in cell-free seminal fluid. The results on HIV binding to spermatozoa are still controversial. Genital tract infections are a possible cofactor that might increase the risk of HIV transmission by way of the semen, because they lead to a marked increase in the number of potential HIV host cells in semen.

HIV Infections↗

Muscarinic M2 receptor-mediated cyclic AMP reduction in mechanically dissociated rat cortex.

The coupling of the muscarinic receptor to the inhibition of the adenylate cyclase system was studied in adult rat cortical tissue dissociated by teasing tissue minces through finely meshed Nitex filters. The intracellular ATP stores in the final preparation were metabolically prelabeled with [3H]adenine and the [3H]cAMP formed in the tissue was isolated by ion exchange chromatography. Forskolin (3-30 microM) elevated [3H]cAMP levels 5- to 9-fold over basal in the preparation, with maximum stimulation achieved by 10-15 min. In the dissociated cortex, carbachol inhibited forskolin-elevated [3H]cAMP levels with an EC50 value of 1.4 microM; maximal inhibition was in the range of 20-30%. Atropine completely blocked the response (Ki = 1.8 nM), which showed that carbachol stimulates a muscarinic receptor to inhibit [3H]cAMP levels in this preparation. Pirenzepine, an M1-selective antagonist, blocked the response to carbachol with low potency (Ki = 467 nM), which indicated that an M2 muscarinic receptor subtype mediates [3H]cAMP inhibition in the cortex. The response to 10 microM carbachol was not affected by 10 mM EGTA, 50 microM D-tubocurarine, or 100 nM tetrodotoxin; thus, activation of nicotinic receptors or a neuronal release process was not involved. [3H]cAMP reduction in response to muscarinic stimulation was also observed in dissociated tissue prepared from other brain regions. A robust response was encountered in striatal preparations (maximal inhibition 40%), while hippocampal responses were smaller and less reproducible than in the cortex. The striatal response was shown to be pharmacologically similar to the cortical response.

Animals↗

Non-selectivity of amitriptyline for subtypes of brain muscarinic receptors demonstrated in binding and functional assays.

The characteristics of interaction of amitriptyline, a tricyclic antidepressant, with rat brain muscarinic receptors were assessed using both radioligand binding and functional assays. In competition studies, amitriptyline displaced muscarinic ligand binding from a single high-affinity site in homogenates of various brain regions which have a different distribution of M1 and M2 receptor subtypes. The affinity of amitriptyline for muscarinic receptors was also comparable in all brain regions. Furthermore, amitriptyline identified a single species of muscarinic receptors in intact cells dissociated from the cerebral cortex and in cerebrocortical slices. The non-selectivity of amitriptyline for muscarinic receptor subtypes in these preparations was in contrast to the selectivity exhibited by pirenzepine. This non-selective nature of amitriptyline was also evident in functional assays, since this antidepressant was equipotent at antagonizing M1-mediated increase in phosphoinositide hydrolysis and M2-mediated inhibition of cyclic AMP formation in dissociated cortical cells. Atropine was also equipotent at blocking both responses but was 20- to 30-fold more potent than amitriptyline. These results demonstrate that amitriptyline behaves as a non-selective muscarinic antagonist using both radioligand binding and functional measurements.

Amitriptyline↗

Variables affecting toxicity of human sera in mouse embryo cultures.

It has been reported that sera from women with reproductive disorders can inhibit mouse embryo development. While performing tests on this subject in our laboratory, two unexpected variables were identified that can influence the effect of human serum on mouse embryo cultures. In a standard embryo culture system in which heat-inactivated sera (10% final concentration) were added to two-cell mouse embryos and percentage blastocyst development was scored after 4 days, sera that had been collected into standard clinical Monoject blood collection red-stopper tubes were significantly more embryotoxic than sera collected from the same subjects into 15-ml Falcon centrifuge tubes (P less than 0.005). Furthermore, we observed that sera from laboratory personnel that worked with mice often inhibited mouse embryo development. To study this effect further, sera were collected from five fertile individuals who were routinely exposed to mice and from fertile women with no previous exposure to rodents. Sera from the mouse-exposed group were significantly more inhibitory than sera from the nonexposed control group (P less than 0.005). The effect was observed in the ammonium sulfate-precipitated immunoglobulin fraction of the mouse-exposed group's sera, and high titers of antibodies reactive with mouse spleen cells were detected in sera and immunoglobulin fractions from this group by enzyme-linked immunosorbent assay (ELISA). Embryotoxic activity was neutralized by absorption with mouse lymphocytes, but not with rabbit or human lymphocytes, suggesting that a heterophilic antimouse antibody is the factor responsible for this effect. These data emphasize the importance of including extensive controls in experiments addressing toxic effects of human sera on mouse embryos.

Animals↗

Effects of products of activated leukocytes (lymphokines and monokines) on the growth of malignant trophoblast cells in vitro.

Supernatants from activated leukocyte cultures and individual lymphokines and monokines were added to cultures of JEG-3 human gestational choriocarcinoma cells in vitro, and effects on cell proliferation were measured. Activated leukocyte culture supernatants, recombinant gamma-interferon, tumor necrosis factor, and colony-stimulating factor significantly inhibited JEG-3 proliferation. In contrast, high doses of both interleukin 1 and 2 stimulated JEG-3 proliferation. Low doses of B cell growth factor stimulated JEG-3 proliferation, whereas the highest dose was inhibitory. Further understanding of the effects of lymphokines and monokines on trophoblastic growth may provide important insights into immunologic mechanisms affecting early pregnancy development and tumor-host interactions in gestational trophoblastic neoplasia.

Biological Products↗

The induction of a neural-specific gene, SCG10, by nerve growth factor in PC12 cells is transcriptional, protein synthesis dependent, and glucocorticoid inhibitable.

We describe features of the regulation of a neural-specific gene, SCG10, which is induced by nerve growth factor (NGF) during the neuronal differentiation of the rat pheochromocytoma cell line PC12. Induction of SCG10 mRNA occurs within 12-24 hr of exposure to NGF, is sustained in the continued presence of the neurotrophic factor, and involves a mechanism that is, at least in part, transcriptional. Unlike the rapid, transient transcriptional activations of genes such as c-fos, SCG10 induction requires ongoing protein synthesis, suggesting the participation of a de novo synthesized regulatory protein in mediating the effects of NGF on this gene. Although c-fos itself may play this role, its induction is clearly insufficient to cause an induction of SCG10. NGF, FGF, and, to a lesser extent, phorbol esters induced SCG10, whereas EGF and dibutyryl cAMP did not. In these characteristics, SCG10 induction appears to constitute a reliable molecular index of the transcription-dependent neuronal differentiation induced by NGF. Glucocorticoids, which inhibit NGF-induced neurite outgrowth from normal primary chromaffin cells, partially blocked SCG10 induction in PC12 cells. A reciprocal pattern of regulation by NGF and glucocorticoids was observed for tyrosine hydroxylase mRNA. These data suggest that environmental signals such as NGF may act on specific genes, both positively and negatively, to control the choice of alternative fates by developing neural crest cells.

Animals↗

Cross-reactivity of monoclonal antibodies directed against lymphocyte markers with trophoblast cells of normal placenta, hydatidiform mole, and gestational choriocarcinoma.

The current study was undertaken to characterize the expression of trophoblast-lymphocyte cross-reactive antigens on normal, molar, and malignant trophoblast. A panel of monoclonal antibodies directed against lymphoid cell markers were tested in immunofluorescence assay on cryostat sections of placenta and mole and on monolayers of choriocarcinoma cells. NKH-1, a monoclonal antibody to natural killer cells, reacted with both molar and placental villous trophoblast and with two choriocarcinoma cell lines. NKH-2, a monoclonal antibody reactive with a subset of natural killer cells, did not react with placental villous trophoblast but reacted with molar villous trophoblast in three of five moles tested and with both choriocarcinoma cell lines. B5, a monoclonal antibody which reacts with activated B cells, reacted with both choriocarcinoma cell lines but did not react with normal placental or molar trophoblast. MY7, a monoclonal antibody to myeloid colony-forming cells, reacted with only one of the choriocarcinoma cell lines. Trophoblast-lymphocyte cross-reactive antigens may be important in the immunobiology of gestational trophoblastic disease by modulating interactions between the trophoblast and the maternal immune system.

Antibodies, Monoclonal↗

The NGF-inducible SCG10 mRNA encodes a novel membrane-bound protein present in growth cones and abundant in developing neurons.

We have characterized and sequenced cDNA clones corresponding to the neural-specific SCG10 mRNA. The predicted amino acid sequence is novel and not strongly homologous to that of any known polypeptide. The protein is encoded by two mRNAs that differ in their choice of polyadenylation site. Immunocytochemical localization experiments using an affinity-purified antibody (against an SCG10-TrpE fusion protein) reveal accumulations of punctate staining in the perinuclear cytoplasm, axons, and growth cones of cultured neurons. SCG10 levels are maximal in the embryonic CNS but are dramatically reduced in the adult. Preliminary cell fractionation experiments suggest that the protein is tightly associated with membranes but is not itself an integral membrane protein. The apparent localization and timing of expression of the SCG10 protein are reminiscent of GAP-43, but the sequences of the two polypeptides are unrelated. Cross-hybridizing mRNAs and antigenically related proteins are found in several nonneuronal cell lines that do not express SCG10.

Aging↗