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R Adler

Publications and source records attributed to R Adler.

At least 145 records · Page 8Linked to original sources
PubMed1986

Conjugates between monoclonal antibodies to HBsAg and cytosine arabinoside.

Chemotherapeutic agents such as cytosine arabinoside (ARA-C) and adenine arabinoside (ARA-A) have been shown to eliminate or suppress replication of some DNA viruses. These effects were however associated with systemic side-effects to the treated hosts. We are currently exploring a strategy to construct conjugates between these antiviral agents and monoclonal antibodies directed against viral surface proteins. Such conjugates should enable specific delivery of the antiviral agents to their preferred site of action. In the present study, monoclonal antibodies to hepatitis B virus surface antigen (HBsAg) of the IgG2a and IgM isotypes were conjugated to ARA-C via a dextran bridge. The use of dextran enables the binding of a high number of drug molecules to the antibody with minimal loss of activity. Briefly, partially oxidized dextran was coupled to ARA-C and then to monoclonal anti-HBs. Following the conjugation process, the IgG2a anti-HBs-(dex)-ARA-C conjugate retained its capacity to bind to HBsAg fixed to a solid matrix as compared to non-conjugated homologous antibodies. Conjugates between ARA-C and IgM anti-HBs lost a significant degree of their binding activity to purified HBsAg. However, conjugates containing anti-HBs of both isotypes bound specifically to PLC/PRF/5 human hepatoma cells that express HBsAg on their cell surface. Conjugates containing non relevant monoclonal antibodies did not bind to target cells. Pharmacologic activity of the various compounds was assessed by an [3H]thymidine incorporation assay in hepatoma cells in culture. IgM and IgG2a containing conjugates caused suppression of [3H]thymidine incorporation into PLC/PRF/5 cells. This effect was more pronounced for conjugates containing monoclonal IgM anti-HBs.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1986

Generation of enriched populations of cultured photoreceptor cells.

This laboratory has recently described a monolayer culture system that allows the survival and differentiation of chick embryo retinal neurons and photoreceptors in the absence of contamination by connective tissue, endothelial, glial, or pigmented epithelial cells. The authors report here that the photoreceptor cells can be further purified by exploiting the selective toxicity of kainic acid (KA) and beta-bungarotoxin (BBT), which are known to destroy many retinal neurons without affecting photoreceptors. When added to retinal cultures, both KA and BBT caused developmental stage- and concentration-dependent degeneration without affecting the number or qualitative properties of photoreceptors. Some retinal neurons were already sensitive to KA after only 2 days in vitro, and their number increased as the cultures matured. The maximum effect of KA (a loss of 60% of the neurons) was obtained with an 8-24 hr treatment with 2 mM KA after 6 days in vitro. Neuronal sensitivity to BBT showed a developmental pattern similar to KA. However, maximum neuronal losses produced by BBT were higher (70% of the neurons) and occurred at lower concentrations (1-2 nM). Combined treatments with KA and BBT did not show additive effects or potentiation between toxins. KA- or BBT-induced neuronal degeneration was accompanied by a greater than 90% loss of neuronal markers such as choline acetyltransferase activity or high-affinity GABA uptake. Transmission electron microscopy showed the integrity of photoreceptor cells in KA- and BBT-treated cultures. These results show that both KA and BBT are useful tools for the generation of enriched photoreceptor populations in vitro.

Animals↗
PubMed1986

Demographic and personality characteristics of couples undergoing in vitro fertilisation.

Two hundred and fifty-eight (258) couples requesting in vitro fertilisation (IVF) were interviewed by a social worker prior to commencing treatment. At the time of admission to hospital 147 women and 134 men completed a questionnaire which incorporated the Eysenck Personality Inventory and the Spielberger State-Trait Anxiety Inventory. Forty-three women conceived and 26 couples (14.2%) required extra counselling or support after their involvement in the programme. Couples seeking IVF did not differ significantly from the rest of the population with respect to occupation, education, alcohol, cigarette and medication use. The personality characteristics of couples seeking IVF did not differ significantly from a local comparison group. Personality and psychosocial characteristics did not identify those couples who were more likely to become pregnant by IVF. However, couples who required extra counselling were more likely to have required similar help in the past. Women requiring counselling also scored significantly higher on the Eysenck neuroticism scale and the Spielberger State-Trait anxiety scales compared to those women who did not require extra counselling or support. The male partners scored significantly lower on the Eysenck scale of extroversion compared to male partners of couples who did not require support or counselling. We conclude that these inventories may be of value in identifying certain couples who require extra care during attempted conception by IVF.

Adult↗
PubMed1985

Coexistence of high-affinity uptake mechanisms for putative neurotransmitter molecules in chick embryo retinal neurons in purified culture.

We report here that high-affinity uptake mechanisms for two or three putative neurotransmitter molecules coexist in many of the neurons present in glia-free, purified neuronal monolayers from chick embryo retina. Replicate cultures were incubated with the tritiated forms of the amino acids gamma-aminobutyric acid (GABA), taurine (TAU) and aspartate (ASP) either individually or in binary or tertiary combinations. Incubation conditions were those typically used to analyze high-affinity uptake mechanisms. At the end of the incubation period the cultures were either lysed in water for measurement of intracellular radioactivity by liquid scintillation counting, or fixed in glutaraldehyde and prepared for autoradiography. Our results indicate that there is coexistence of uptake mechanisms for putative neurotransmitters in retinal cells. Biochemical measurements showed that, at the concentrations used in these experiments, two or more radioactive amino acids could be taken up simultaneously by the cultured populations without extensive inhibition. Moreover, the percentage of cells that appeared autoradiographically labeled in cultures exposed to two or more radioactive amino acid was less than the sum of the percentages of labeled cells when each amino acid was applied individually. Numerical analysis of the autoradiographs was carried out to determine the percentage of cells that could take up only one, only two, or the three putative amino acid neurotransmitters under investigation. This analysis showed that approximately 20% of the neurons have only the mechanism for TAU, whereas very few if any neurons have high-affinity uptake mechanisms for GABA alone or ASP alone. Our experiments have identified populations of cells that take up GABA and TAU (but not ASP) or ASP and TAU (but not GABA). Interestingly, we have not seen any neurons that can take up ASP and GABA and cannot take up TAU, although as many as 50% of the neurons can take up ASP, GABA, and TAU simultaneously. By showing simultaneous uptake of different putative neurotransmitters within individual neurons, our results emphasize the concept that the presence in a given neuron of a high-affinity uptake mechanism for a particular molecule is not a sufficient criterion to assign a neurotransmitter function to that molecule in that neuron.

Absorption↗
PubMed1985

Adjuvant specific immunotherapy of resectable squamous cell lung carcinoma. Analysis at the eighth year.

From June 1976 to June 1981, 86 patients with resectable (Stage I and II) squamous cell lung carcinoma were entered into a randomized controlled study with three arms: Control Group - no treatment postoperatively. Specific Immunotherapy Group - three monthly doses of 500 micrograms of tumor associated antigen (TAA) emulsified with complete Freund's adjuvant (CFA). Nonspecific Immunotherapy Group - three monthly doses of CFA emulsified in saline. All the patients in the study received skin tests with PPD (5TU) and 100 micrograms of the same TAA used for the immunotherapy at 1, 4, 6, 9, and 12 months postoperatively. Patients in both immunotherapy groups showed a tendency for a better disease-free interval and overall survival compared to those of the control, but these interval and beneficial therapeutic effects were statistically significant only in the Group III patients who had no hilar lymph node metastasis (T1N0 and T2N0). Although Group III was originally designated as a nonspecific immunotherapy group, retrospectively, it should be called a lowdose specific immunotherapy group because these patients actually received a total of 500 micrograms of TAA (as skin tests) and three doses of CFA at separate sites.

Adjuvants, Immunologic↗
PubMed1985

Responses of cultured neural retinal cells to substratum-bound laminin and other extracellular matrix molecules.

The responses of cultured chick embryo retinal neurons to several extracellular matrix molecules are described. Retinal cell suspensions in serum-free medium containing the "N1" supplement (J. E. Bottenstein, S. D. Skaper, S. Varon, and J. Sato, 1980, Exp. Cell Res. 125, 183-190) were seeded on tissue culture plastic surfaces pretreated with polyornithine (PORN) and with one of the factors to be tested. Substantial cell survival could be observed after 72 hr in vitro on PORN pretreated with serum or laminin, whereas most cells appeared to be degenerating on untreated PORN, PORN-fibronectin, and PORN-chondronectin. Cell attachment, although quantitatively similar for all these substrata, was temperature-dependent on serum and laminin but not on fibronectin or untreated PORN. In a short-term bioassay, neurite development was abundant on laminin, scarce on serum and fibronectin, and absent on PORN. No positive correlation between cell spreading and neurite production could be seen: cell spreading was more extensive on PORN and fibronectin than on laminin or serum, while on laminin-treated dishes, spreading was similar for neurite-bearing and non-neurite-bearing cells. Laminin effects on retinal neurons were clearly substratum dependent. When bound to tissue culture plastic, laminin showed a dose-dependent inhibitory effect on cell attachment and did not stimulate neurite development. PORN-bound laminin, on the other hand, did not affect cell attachment but caused marked stimulation of neurite development, suggesting that laminin conformation and/or the spatial distribution of active sites play an important role in the neurite-promoting function of this extracellular matrix molecule. Investigation of the embryonic retina with ELISA and immunocytochemical methods showed that laminin is present in this organ during development. Therefore, in vivo and in vitro observations are consistent with the possibility that laminin might influence neuronal development in the retina.

Animals↗
PubMed1985

In vivo and in vitro models of demyelinating diseases. XII. Persistence and expression of corona JHM virus functions in RN2-2 Schwannoma cells during latency.

The coronavirus JHMV persistently infects rat Schwannoma cells RN2-2 at 32.5 degrees C and enters a host-imposed reversible, latent state at 39.5 degrees C. JHMV can remain up to 20 days in the latent state and about 14 days before the cultures lose the capacity to resume virus production upon return to 32.5 degrees C. Although persistently and latently infected RN2-2 cells display resistance to superinfection by a heterologous agent VSV, these cells do not release detectable soluble mediators (e.g., interferon) of the antiviral state. Nevertheless, RN2-2 cells are competent to synthesize and release interferon when treated with the appropriate inducers. These observations suggest that interferon does not play any role or may not be the major factor in the control of latency in the Schwannoma cell. Hybridization with virus-specific cDNAs shows that all viral mRNAs are present during latency and that viral mRNAs are present in the polysomes of infected cells at 39.5 degrees C. Western immunoblotting with hybridoma antibodies demonstrates that viral specific proteins are produced at the restrictive temperature. These results suggest that despite the absence of production of infectious virus at 39.5 degrees C, there is active transcription and translation into virus-specified products.

Animals↗
PubMed1985

Timing and motivation in pediatric career choices.

A total of 257 third-year residents in pediatrics, internal medicine, and family practice were asked about their career goals for the year following their residency and in five years, and information was obtained from them about their motives for career choices. The authors specifically examined the following: humanitarian interests; intellectual motivation; service motives; and practical, personal, and financial considerations. The characteristics of the residency training program which may have influenced their career choices were also examined. A majority of the 214 pediatric residents said they had not considered going into pediatrics on entry to medical school. Of these residents, 109 planned academic pursuits for the following year, while only 81 of the 109 anticipated an academic career within five years. Intellectual stimulation, geographic location, and an "opportunity to clarify goals" were the three most frequently mentioned factors in choosing positions for the following year.

Career Choice↗
PubMed1985

Diabetes induced by streptozocin results in a decrease in immunoreactive beta-endorphin levels in the pituitary and hypothalamus of female rats.

Immunoreactive beta-endorphin (IR-BE) was measured by radioimmunoassay in the anterior pituitary (AP), neurointermediate lobe of the pituitary (NIL), and hypothalamus of female rats 4 wk after being made diabetic by a single injection of streptozocin (STZ). STZ-induced diabetes resulted in a significant reduction in the content and concentration of IR-BE in the AP and the content of IR-BE in the hypothalamus. Total hypothalamic protein was also significantly diminished. IR-BE levels in the NIL were unchanged. Column chromatography indicated that the reduction in IR-BE in the AP of the diabetic female rats represented a decrease in peptides that co-eluted with beta-endorphin and beta-lipotropin. In the hypothalamus, the reduction in IR-BE was represented solely by a decrease in a peptide co-eluting with beta-endorphin. Beta-lipotropin was not detectable in the hypothalami of control or diabetic female rats. These results suggest that, in the rat, diabetes may produce alterations in the mechanism(s) that regulate endogenous opiate levels in the pituitary and hypothalamus.

Animals↗
PubMed1984

[Conversion: mimicry of somatic symptoms].

Certain symptoms represent the neutralization of intrapsychic conflicts by means of physical symptoms. They mimic symptoms of organic origin and protect the individual from acting out repressed wishes. Since they mimic and protect, the expression "nervous mimicry" seems adequate. The dream, the game of charades and colloquial language present analogies which render the conversion of psychic conflicts into physical symptoms understandable. A clinical vignette is used to elucidate the mechanism of conversion and to illustrate the positive criteria on which the diagnosis of "conversion symptom" must be based.

Adaptation, Biological↗
PubMed1984

Expression of phenylethanolamine N-methyltransferase in sympathetic neurons and extraadrenal chromaffin tissue of chick embryos in vivo and in vitro.

Previous studies suggested the existence of two populations of cells in the mammalian sympathetic nervous system which differ in their ability to express phenylethanolamine N-methyltransferase (PNMT), the enzyme which specifically subserves the biosynthesis of epinephrine: (1) sympathoblasts and their progeny, the noradrenergic sympathetic neurons (PNMT negative); and (2) phaeochromoblasts , the precursors of the adrenergic cells of the adrenal gland and extra-adrenal chromaffin tissue (PNMT-positive). We sought to determine whether similar differences between sympathoblasts and phaeochromoblasts exist in other classes of vertebrate embryos. Using immunohistochemical and biochemical techniques to assay PNMT in sympathetic organs, we have found that chick embryo paravertebral ganglia contain PNMT activity both in vivo and in vitro. In vitro PNMT immunostaining was detected in principal neurons as well as in small process bearing neurons similar to mammalian SIF cells. In vivo, cells containing PNMT were seen not only in the adrenal gland, but also in other sympathetic structures such as the extra-adrenal chromaffin tissue and, unexpectedly, also in some cells of the kidney. Tyrosine hydroxylase, the first enzyme of the catecholamine (CA) biosynthetic pathway, was found in the same cells which could be stained with PNMT antibodies as well as in the sympathetic ganglia. Thus, we conclude that in contrast to the rat, chick sympathoblasts share with phaeochromoblasts the property of expressing all the CA enzymes, including PNMT.

Adrenal Medulla↗
PubMed1984

Expression of cone-like properties by chick embryo neural retina cells in glial-free monolayer cultures.

We report here that cells present in embryonic chick retinal monolayer cultures express differentiated properties characteristic of chick cones developing in vivo. Cell suspensions from 8-d chick embryo retina (a stage when photoreceptor differentiation has not yet started) were cultured for up to 7 d in low density, glial-free monolayers. Under these conditions, monopolar cells represent approximately 40% of the total number of process-bearing neurons. After 6 d in vitro, most of these monopolar cells showed morphological features reminiscent of developing chick cones. These features could be detected with phase-contrast microscopy, lectin cytochemistry, and transmission and scanning electron microscopy. Characteristic cone traits expressed by cultured monopolar cells included the following: (a) a highly polarized organization; (b) a single, short, usually unbranched neurite; (c) the polarized position of the nucleus close to the origin of the neurite; (d) characteristic cone inner segment features such as abundant free ribosomes, a polarized Golgi apparatus, a cluster of mitochondria distal to the nucleus, a big, membrane-bound, pigment-containing vacuole reminiscent of the "lipid droplet" characteristic of chick cones, and at least in some cases, a well-developed paraboloid; (e) the presence of a complex of apical differentiations including abundant microvilli and in some cases also a cilium-like process; and (f) the staining of the apical region of the cell with peanut lectin, which has been shown to be selective for chick embryo cones (Blanks, J.C., and L.V. Johnson, 1983, J. Comp. Neurol., 221:31-41; and Blanks, J.C., and L.V. Johnson, 1984, Invest. Ophthalmol. Visual Sci., 25:546-557). This pattern of differentiation achieved by 8-d chick retina cells after 6 d in vitro is similar to that shown by 14-d-old chick embryo cones in vivo. Outer segments are not present at this stage of development either in vivo or in vitro. This experimental system is now being used to search for cellular and molecular signals controlling survival and differentiation of cone cells.

Animals↗
PubMed1984

[Pain].

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Brain↗