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Biomedical subjects

R Glick

Publications and source records attributed to R Glick.

At least 19 recordsLinked to original sources
PubMed2001

Treatment of the T98G glioblastoma cell line with antisense oligonucleotides directed toward mRNA encoding transforming growth factor-alpha and the epidermal growth factor receptor.

Antisense oligonucleotides (oligos) complementary to mRNA encoding transforming growth factor-alpha (TGF-alpha) and its target, the epidermal growth factor receptor (EGFR), are efficacious against human prostate and breast cancers carried in athymic nude mice. Glioblastomas, also regulated by EGFR expression, would appear to be similarly susceptible, and we now employ them against the T98G tumor model. T98G cells were distributed into wells and allowed to adhere prior to addition of oligos (12.5 microM) directed against TGF-alpha and/or EGFR for 6 d of treatment before thymidine radiolabeling. Supplemental media and oligos (25 microM final concentration) were added after d 3. Statistically significant inhibition by oligos directed against TGF-alpha, EGFR, and their combination was 13.8%, 26.3%, and 18.1%, respectively. In a subsequent experiment cells were incubated with increasing amounts of each oligo and their combination for 3 d prior to radiolabeling. Statistically significant inhibition of growth for either oligo at every concentration was found. Cells incubated with 6.25, 12.5, 25, and 50 microM antisense directed against TGF-alpha had a mean inhibition of 29.3%, 33.3%, 21.7%, and 46.6%, respectively. Cells similarly treated with oligos against EGFR had a mean inhibition of 77.9%, 80.3%, 82.0%, and 83.7%, respectively, and cells incubated with 6.25, 12.5, 25 and 50 microM of each oligo had a mean inhibition of 74.7%, 70.6%, 70.8%, and 76.3%, respectively. Lastly, in a paired experiment, cells treated with 0, 0.39, 0.78, 1.56, 3.125, and 6.25 microM of oligos, either specifically directed against EGFR or a random control, for 3 d were evaluated for both thymidine incorporation and EGFR expression. Statistically significant inhibition of 3H-thymidine incorporation was seen in cells with the oligo specifically directed against EGFR at 3.125 microM and 6.25 microM when compared to non-oligo containing controls. This was accompanied by a comparable significantly decreased expression of a low-MW reactive derivative of EGFR at 3.125 microM and 6.25 microM in Western blots, and of a high-MW reactive EGFR at 6.25 microM. The significant effect against high-MW EGFR was observed vs both the non-oligo containing control and the random sequence. Oligo concentrations between 0.78 and 1.5 microM also resulted in decreased expression of the low-MW form, but not significant differences in thymidine radiolabeling. In recovery experiments, cells treated initially with greater oligo concentrations required significantly increased time to recover, particularly in cells treated with EGFR directed oligos. Intracellular uptake and nuclear localization was demonstrated with FITC tagged oligos. In summary, even at relatively low oligo concentrations and short exposure, oligos against TGF-alpha, and particularly EGFR, significantly inhibit in vitro growth of the T98G glioblastoma, possibly mediated by decreased EGFR expression.

Blotting, Western↗
PubMed1996

The fate of training cases.

The authors regard the treatment of analytic patients as a crucial, formative and ultimately integrative experience in a candidate's development that has received remarkably little direct attention as an aspect of analytic education. From 1983 to 1992 a questionnaire was sent to all graduates of the Columbia University Psychoanalytic Center for Training and Research asking for information on training cases, both those terminated before graduation and those still ongoing at the time of graduation. The authors report data on pre-graduation candidate case experience, treatment duration of training cases, the impact of graduation on the course of analysis and on a global assessment of the outcome. 70 per cent of the 71 who graduated between 1983 and 1992 returned the questionnaire. The survey showed that before graduation the average candidate had a cumulative nine-year experience of treating training cases. 35 per cent of cases terminated before graduation and were invariably considered to have an unsuccessful outcome. Thus the 'failed case' was a common event and should be anticipated as part of a candidate's education. There was no evidence of precipitous termination of cases after graduation; in fact the data suggest that graduation has no discernible effect on the timing of termination. The vast majority of candidates at Columbia continue to be supervised after graduation, which suggests that graduation is only a marker in the training of an analyst, rather than the point of completion. With respect to outcome, 23 per cent of the 151 terminated cases were rated successful. Though this finding is consistent with previous reports, the methodological limitations of this study limit the confidence in this result. One of the important issues raised by these results is the impact of training requirements on the candidate's education and the Fate of Training Cases.

Clinical Competence↗
PubMed1993

Expression of 300-kilodalton intermediate filament-associated protein distinguishes human glioma cells from normal astrocytes.

The availability of biochemical markers to distinguish glioma cells from normal astrocytes would have enormous diagnostic value. Such markers also may be of value in studying the basic biology of human astrocytomas. The vimentin-binding, 300-kDa intermediate filament (IF)-associated protein (IFAP-300kDa) has recently been shown to be developmentally expressed in radial glia of the central nervous system of the rat. It is not detected in the normal or reactive astrocytes of the adult rat nor in neonatal rat brain astrocytes in primary culture. In the present study, double-label immunofluorescence microscopy using antibodies to IFAP-300kDa and glial fibrillary acidic protein (GFAP, an astrocyte-specific IF structural protein) identifies this IFAP in GFAP-containing tumor cells from examples of all three major types of human astrocytomas (i.e., well-differentiated, anaplastic, and glioblastoma multiforme). Astrocytoma cells in primary cultures prepared from all three astrocytomas also express this protein. It is not detectable in normal adult brain tissue. Immunoblot analyses using the IFAP-300kDa antibody confirm the presence of a 300-kDa polypeptide in fresh astrocytoma preparations enriched for IF proteins. These results suggest the utility of IFAP-300kDa as a marker for identification of human glioma cells both in vitro and in situ.

Astrocytes↗
PubMed1993

Insulin-like growth factor-I and binding protein-1 can modulate fetal brain cell growth during maternal starvation.

1. Stimulation of brain cell growth by fetal plasma is reduced when levels of IGF-I are low and IGFBP-1 are high. 2. Fetal brain cells respond to IGFs in cell culture, and effects of plasma are reduced by addition of IGFBP-1. 3. Increased levels of IGFBP-1 and reduced availability of IGF-I may contribute to reduced brain growth when maternal nutrition is impaired.

Animals↗
PubMed1992

Insulin-like growth factor I and low-density-lipoprotein cholesterol in women during high- and low-fat feeding.

In vitro studies suggest that insulin-like growth factor I (IGF-I) may modulate hepatic production and peripheral utilization of lipoproteins. We measured blood concentrations of IGF-I; total, high-density-lipoprotein, and low-density-lipoprotein (LDL) cholesterol; and apolipoproteins in 18 women with above average cholesterol after high- and low-fat diet periods. Total cholesterol fell 6% (P less than 0.02) during the low-fat diet because of reduced concentrations of LDL cholesterol (P less than 0.01). Serum concentrations of IGF-I were inversely correlated with total and LDL cholesterol and apolipoprotein B during both high-fat (r = -0.676, P less than 0.005; r = -0.745, P less than 0.001; and r = -0.504, P less than 0.04, respectively) and low-fat (r = -0.656, P less than 0.005; r = -0.757, P less than 0.001; and r = -0.695, P less than 0.001, respectively) diets. IGF-I increased with reduced fat intake in obese subjects only. Thus, IGF-I may contribute to the regulation of LDL cholesterol in mildly hypercholesterolemic women but may not mediate the beneficial response to reduced fat intake.

Adult↗
PubMed1988

Use of Halifax interlaminar clamps for posterior C1-C2 arthrodesis.

Eight patients with atlantoaxial instability secondary to trauma or rheumatoid arthritis were treated with posterior C1-C2 arthrodesis using the Halifax interlaminar clamp and autogenous bone graft or methylmethacrylate. Thus far, with an average follow-up of 6 months, satisfactory stability has been achieved with no instrument failure.

Arthritis, Rheumatoid↗
PubMed1987

Phenylpropanolamine: an over-the-counter drug causing central nervous system vasculitis and intracerebral hemorrhage. Case report and review.

Phenylpropanolamine (PPA) is the major ingredient in more than 70 over-the-counter preparations including diet pills, nasal decongestants, and the legal "look-alike" stimulants. Structurally and functionally similar to amphetamine and ephedrine, PPA has recently been associated with several neurological manifestations including psychosis, stroke, severe headache, seizures, and intracerebral hematoma. We report a case of intracerebral hematoma and subarachnoid hemorrhage in a young woman with angiographic and biopsy-proven vasculitis of the central nervous system (CNS) induced by PPA in her diet pills. From review of the literature, we distinguish drug-induced vasculitis as a separate entity from primary CNS vasculitis, both clinically and pathologically. This report should alert physicians, in general, to this potentially fatal side effect of PPA, a commonly used over-the-counter drug. Also, neurosurgeons in particular should consider the possibility of drug-induced vasculitis when faced with cases of intracerebral or subarachnoid hemorrhage without apparent cause.

Adult↗
PubMed1983

A method for the purification of E. coli plasmid DNA by homogeneous lysis and polyethylene glycol precipitation.

A procedure is described for the isolation and purification of E. coli plasmid DNA by polyethylene glycol precipitation. The method is rapid, simple, inexpensive and amenable to both small and large scale manipulation. This procedure involves lysis of bacterial cells by treatment with pronase in sodium dodecyl sulfate, removal of chromosomal DNA by centrifugation, precipitation of residual nucleic acids with polyethylene glycol and removal of RNA by precipitation with LiCl. Plasmid DNA purified as described is pure enough for restriction endonuclease analysis, for use as a vector for the cloning of cDNA or synthetic DNA, or for use as a template in an E. coli transcription-translation cell-free system.

DNA↗
PubMed1982

Doctor shopping with the child as proxy patient: a variant of child abuse.

Over a three-year period, we have seen in consultation four children whose mothers cited complaints referable to every organ system and which had persisted for many years. The parents had consulted a total of 99 physicians in eight states. Absence from school ranged from 40 to 200 days a year. Physical examinations of all patients and extensive and repeated laboratory studies were normal. On psychiatric examination the mothers exhibited paranoid thinking and a conviction of serious medical illness in their child which approached delusional proportions. They resisted psychiatric consultation and refused psychotherapy. The mother-child relationship was remarkably symbiotic, the two teen-age patients essentially voicing complaints which were indistinguishable from those reported by their mothers. The fathers invariably supported their wives' concerns. Subsequently, parents and children left treatment, continuing to "doctor shop." Long-standing multisystem complaints in a child with normal growth and maturation are incompatible with any known significant organic disease, but suggest a serious emotional problem within the family. Further, parents who take such children from doctor to doctor are frequently disturbed themselves and may use an offspring as a proxy patient. An accurate diagnosis depends on careful history-taking from parents, patient, health professionals, and schools.

Absenteeism↗
PubMed1981

High does epsilon-aminocaproic acid prolongs the bleeding time and increases rebleeding and intraoperative hemorrhage in patients with subarachnoid hemorrhage.

epsilon-Aminocaproic acid (EACA) has been used to prevent rebleeding in patients with intracranial aneurysms because it crosses the blood-brain barrier and is an inhibitor of fibrinolysis. Recommended doses have ranged from 24 to 48 g/day. We now describe an inhibitory effect on platelet function at the higher dose range. In vitro, a dose-dependent inhibition of adenosine diphosphate- and collagen-induced platelet aggregation was observed with concentrations of EACA beginning at 7.6 mM. In vivo, prolongation of the template bleeding time was observed in all eight patients receiving 48 g/day (greater than 20 minutes in four), in all five on 36 g/day (greater than 20 minutes in three), and in none of seven on smaller doses. More importantly, rebleeding and excessive intraoperative bleeding (requiring more than 1 litre of blood replacement) occurred predominantly in patients receiving the larger doses of EACA. Within 48 hours of the discontinuation of EACA, the bleeding times returned to normal values in all but one patient. We conclude that EACA exerts a dose-dependent inhibitory effect on platelet function and that patients receiving doses in excess of 24 g/day may be at risk of serious bleeding. Patients receiving EACA should be monitored with serial bleeding time tests.

Adult↗
PubMed1979

Loss of synapses in the cerebellar cortex of the senescent rat.

Numbers of synapses were compared in the cerebellar cortex of adult (12 months of age) and senescent (25 months of age) male rats of the Fisher-344 strain. The total number of axodendritic synapses was found to be 24% lower in the senescent rats as compared with adults. A differential analysis of synapses involving dendritic shafts and spines showed no significant change in numbers of synapses involving shafts, but a highly sigificant 33% decrease in numbers involving spines in senescent rats. These data suggest that the selective age-related loss of synapses involving dendritic spines (but not shafts) in the cerebellar cortex results from the impairment with advanced age of specific afferent neurons and/or a selective age-related vulnerability of dendritic spines.

Aging↗
PubMed1978

Role of two-dimensional surface characteristics in pictorial depth perception.

The purpose of the present experiment was to test the hypothesis that flat surface information for the plane of projection is the essential difference between ordinary and pictorial perception. Adults were asked to make relative size judgments of pairs of squares and triangles placed and pictured at various distances. The conditions were: real scene controls, life-size slides and prints, and real scenes viewed through clear glass, textured glass, a screen and a 50-mm lens. The error rate was significantly lower with real scenes than with either slides or prints which did not differ. The control data for real scenes were used for comparison to test for the effects of interposed flat surfaces on size judgments of real scenes. Viewing real scenes through either a clear glass pane or a 50-mm lens increased the error rate two and one-half times that of the controls for real scenes. Neither textured glass nor a screen significantly affected error rate. Results were interpreted as supporting the hypothesis that information about a flat surface for the plane of projection is the critical variable determining the special character of picture perception.

Depth Perception↗
PubMed1977

Pictorial perspective: perception of size, linear, and texture perspective in children and adults.

Perception of size, linear, and texture perspective was investigated in third-grade and sixth-grade children and in college adults in three separate studies. A matching task required the observer to choose from a set of four alternative real scenes the correct match for the test stimulus, which was either a picture or a real scene. Correct performance required that the subject utilize perspective information for both size and distance distance relations. Erroneous choices available to the subject indicated errors in size judgement, in distance judgment, or in both simultaneously. View was either restricted at the correct station point or was free, with head motion. There were no significant effects of grade level. For all three groups, mean percent correct was nearly 100% with the real-scene test stimuli, and significantly below the chance level with the picture test stimuli. Errors in size judgment occurred most frequently, indicating that the geometrically correct rate of perspective convergence was too rapid to be seen by the subjects as perceptually acceptable. With size-perspective information alone, the number of size plus distance errors also increased significantly. There was no significant effect of viewing condition.

Adult↗
PubMedDate not supplied

Diagnosis and management of anomalies of the craniovertebral junction.

The term craniovertebral junction refers to an area comprising the inferior portion of the occipital bone surrounding the foramen magnum and the first two cervical vertebrae. A variety of anomalies of bony, meningeal, and neural elements are known to occur in this region, producing a wide spectrum of clinical symptoms. These can range from dizziness, ataxia, and nuchal headaches to obvious quadriparesis and cranial nerve palsies. Often the symptoms are vague with an evolution marked by temporary exacerbations and remissions. The diagnosis can be difficult, and in our experience is best achieved by combining a neurotologic and neurologic evaluation. We discuss here the symptoms and diagnosis in ten patients with lesions at the craniovertebral junction. The surgical management of two cases of basilar invagination is described, and the controversies regarding the technique are discussed.

Adult↗
PubMedDate not supplied

In vivo establishment of T98G human glioblastoma.

Human derived T98G glioblastoma has long been utilized as an in vitro model for epidermal growth factor receptor (EGFR)-mediated growth regulation. Recently, T98G has been employed to develop new types of therapy directed at limiting EGFR expression such as by administration of antisense oligonucleotides directed against EGFR encoding mRNA. A major limitation to extending this model for in vivo application is that T98G implanted s.c. or intracerebrally has been reported not to grow in nude mice. In an effort to extend this model to permit in vivo studies, we evaluated the use of Matrigel and orthotopic (intracranial) implantation techniques. When equal volumes of Matrigel were mixed with T98G cell suspensions, tumors developed at both flank and orthotopic locations. Four groups of nude mice were inoculated into the flanks with either 10(5), 10(6), 4 x 10(6) or 10(7) T98G cells in a 150 microliters total volume with Matrigel. In 1/5, 3/5, 1/5 and 1/3 mice receiving 10(5), 10(6), 4 x 10(6) and 10(7) cells, respectively, tumors developed 11, 15, 15 and 15 weeks, respectively, following inoculation. Out of 4 mice inoculated orthotopically (intracranially into the frontal lobe) with only 4 x 10(4) cells and Matrigel, 2 developed tumors. However, all mice (4/4) inoculated orthotopically with 4 x 10(5) cells in a 10 microliters total volume with Matrigel developed tumors. Two were identified histologically following a scheduled sacrifice at 36 and 60 days and two more at 103 and 118 days after sacrifice following abnormal behavior. The best tumor establishment efficacy combined orthotopic implantation of 4 x 10(5) T98G cells with Matrigel. These techniques permit the use of T98G glioblastoma as an in vivo model for new forms of therapy.

Animals↗
PubMedDate not supplied

Treatment of premenstrual dysphoric symptoms in depressed women.

Although research has established a strong association between premenstrual dysphoric symptoms and depression, there is little data on the effect of antidepressents on premenstrual symptoms. This study compared the efficacy of three treatments--imipramine, phenelzine, and placebo--on the premenstrual symptoms of women with atypical depression who had responded to treatment for their depressive symptoms. The Premenstrual Assessment Form (PAF) was used to rate the type and degree of premenstrual symptomatology. After 12 weeks, at least two-thirds of the women on active medication showed improvement on most measures of premenstrual symptoms to the degree that they had essentially no premenstrual problems after treatment. By comparison, only half of a group of women who had responded to placebo treatment of 6 weeks duration showed such improvement.

Adolescent↗