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Biomedical subjects

N Cohen

Publications and source records attributed to N Cohen.

At least 217 records · Page 12Linked to original sources

Increased concanavalin A-induced suppressor cell activity in humans with occupational lead exposure.

E-rosette-forming cells (E-RFC), mitogen-induced blast transformation, OKT4+, OKT8+ cells, and their ratio were found to be normal in 10 subjects chronically exposed to lead with blood levels of 40-51 micrograms%. However, concanavalin A (Con A)-induced suppressor cell activity (SCA) in these subjects was significantly greater than in normal matched controls. The clinical relevance of this observation is not clear, but it may have some bearing on the various immunologic defects described in lead exposure.

Adult↗

3,4-Dihydro-2H-1-benzopyran-2-carboxylic acids and related compounds as leukotriene antagonists.

Evaluation of a series of 3,4-dihydro-2H-1-benzopyran-2-carboxylic acids linked to the 2-hydroxyacetophenone pharmacophore present in the standard peptidoleukotriene antogonist FPL 55712 (1) has led to the discovery of Ro 23-3544 (7), an antagonist possessing greater potency and duration of action vs LTD4 than the standard (aerosol route of administration, guinea pig bronchoconstriction model). Interestingly, this compound also potently inhibited bronchoconstriction induced by LTB4 whereas 1 did not. Attempts to establish structure--activity relationships in this series involved modifications in the 2-hydroxyacetophenone moiety, the linking chain, and the chroman system. All variations produced analogues which were either inactive or possessed reduced potency relative to acid 7. Optical resolution of 7 was achieved by two methods. Absolute configurations of the enantiomers were determined via X-ray crystallographic analyses of an intermediate as well as a salt of the S enantiomer. Although the enantiomers exhibited similar potencies in in vitro assays and in vivo when administered intravenously, significant differences were observed in the guinea pig bronchoconstriction model vs LTC4 and LTD4 when administered by the aerosol route (S antipode 15-fold more potent). The properties of 7 have been compared with several recently reported leukotriene antagonists.

Animals↗

The importance of acid digestion of urine prior to spontaneous deposition of 210Po.

Historically, radiochemical analysis of 210Po in urine has used spontaneous deposition of the nuclide directly from raw urine onto a suitable metal disc. Consequently, the urinary excretion fraction for Po in some current metabolic and dosimetric models is based on studies which inherently assume that metabolized (i.e., filtered out of the blood by the kidneys) 210Po is plated with the same efficiency as tracer 210Po which has been added to urine samples. Urine samples collected after intravenous administration of 210Po citrate to two species of nonhuman primates were divided and simultaneously analyzed via two methods: the historical procedure of plating 210Po from raw urine for one sample and a method which includes the addition of 208Po tracer and sample digestion with concentrated HNO3 prior to 210Po deposition for the other sample. A more significant amount of 210Po was consistently recovered when the urine was wet ashed then when it was not wet ashed. A temporal relationship was found to describe the change in the ratio of the deposition recoveries for the two methods. Possible mechanisms for this phenomenon and its dosimetric implications are discussed.

Animals↗

Cimetidine-related cardiac conduction disturbances and confusion.

A 70-year-old woman free of renal or hepatic dysfunction developed reversible mental confusion, sinus bradycardia, and extreme QT interval prolongation following initiation of intravenous cimetidine 1200 mg daily. The association of mental confusion with cardiac conduction impairment in a single patient in the context of cimetidine toxicity is highly unusual. We review this and other reports on potentially fatal cimetidine-related cardiac conduction disturbances to suggest that in patients at risk, in addition to reducing cimetidine dosage, electrocardiogram (ECG) follow-up is indicated to identify dangerous bradycardia and QT interval prolongation.

Aged↗

Acute resin phenol-formaldehyde intoxication. A life threatening occupational hazard.

1. A 38-year-old previously healthy worker accidentally spilled phenol-formaldehyde resin over a large area of his skin. 2. Several days later he was hospitalized with extensive necrotic skin lesions, fever, hypertension, adult respiratory distress syndrome (ARDS), proteinuria and renal functional impairment. 3. All symptoms improved progressively and eventually disappeared. 4. We propose that toxic materials originating from the necrotic skin lesions and the continued facilitated absorption of the resin and/or its components via the skin lesions were the main factors responsible for this alarming multisystem involvement. 5. Workers handling this material should be instructed to take appropriate precautions and physicians should be alerted to the potential pathophysiological consequences.

Adult↗

Cochlear implantation after transmastoid labyrinthectomy.

Hearing rehabilitation with an intracochlear prosthesis is well documented in patients who have an intact otic capsule prior to implantation. However, the suitability for implantation of patients who have undergone extensive procedures involving the otic capsule such as labyrinthectomy has not been directly addressed. This report documents a case of a patient deafened by a transmastoid labyrinthectomy who subsequently received a cochlear implant. Postimplantation performance of this patient was compared with the performance of three other postlingual implant recipients. The results suggest that labyrinthectomy is not a contraindication to auditory rehabilitation by a cochlear implant. The implications of implantation in a surgically manipulated otic capsule are discussed.

Adult↗

Effect of prolactin on casein and fat synthesis and casein secretion in explants of bovine mammary tissue pretreated in athymic nude mice.

Bovine mammary gland tissue from 4- to 6-mo-old calves was grafted s.c. (dorsum) to 7- to 9-wk-old female athymic "nude" mice. The graft-bearing mice were divided into three groups and were treated with the following hormonal combinations: 1) implantation of a pellet containing estrogen and progesterone followed by injection of estrogen and progesterone, 2) injections of estrogen and progesterone, and 3) injections of estrogen, progesterone, and prolactin. Following in vivo treatment, the grafts were removed and prepared for organ culture. Explants from each treatment were subdivided into two hormonal regimens: 1) insulin and cortisol; 2) insulin, cortisol, and prolactin. An increase in in vitro fat synthesis was observed in explants cultured in the presence of prolactin. This increase was not affected by previous in vivo hormonal treatment. In vitro casein synthesis was not stimulated by the presence of prolactin in the culture medium; however, casein secretion was elevated in explants from grafts from animals that were treated in vivo with estrogen, progesterone, and prolactin. Casein secretion was further increased in explants cultured in the presence of prolactin but rapidly dropped in its absence. Explants that were not implanted in mice responded in long-term organ culture similarly to explants pretreated in vivo.

Animals↗

Age versus schooling effects on intelligence development.

The effect of formal education, as opposed to chronological age, on intelligence development has suffered from inadequate empirical investigation. Most studies of this issue have relied on natural variation in exposure to school among children of the same age, thus confounding differences in schooling with differences in other intelligence-related variables. This difficulty can be overcome by a quasi-experimental paradigm involving comparison between children who differ in both chronological age and schooling. The present study applies this paradigm to the estimation of the independent effects of age and schooling in grades 5 and 6 on raw scores obtained on a variety of general ability tests. The sample included all students in Jerusalem's Hebrew-language, state-controlled elementary schools. The results unambiguously point to schooling as the major factor underlying the increase of intelligence test scores as a function of age and to the larger effect schooling has on verbal than nonverbal tests. These results contribute to our understanding of the causal model underlying intelligence development and call for reconsideration of the conceptual basis underlying the definition of deviation-IQ scores. Some implications of these results concerning the distinction between intelligence and scholastic achievement, the causal model underlying the development of "crystallized" and "fluid" abilities, and the notion of "culture-fair" tests are discussed.

Achievement↗

In vitro fusion of newt macrophages.

Spontaneous formation of multinucleate giant cells is often observed in in vitro cultures of peritoneal adherent macrophages from the newts, Notophthalmus viridescens and Taricha granulosa (urodele amphibians). The frequency of such giant cells in these cultures is increased by the addition of phorbol myristic acetate at the initiation of the cultures. This high frequency of multinucleate cells permitted us to evaluate whether multinucleate giant cells arise by cell fusion and/or by repeated nuclear division without cytokinesis. Cell fusion is readily detectable by scanning electron microscopy. To determine whether nuclear division without cytokinesis also occurs, some cultures were treated with colchicine to arrest mitotic figures; others were pulsed with tritiated thymidine to detect DNA synthesis. Mitotic figures were not seen in acridine orange-stained samples. In monolayers that were processed for autoradiography, only a few nuclei were marked with tritium. These observations suggest that nuclear division does not contribute significantly, if at all, to the formation of multinucleate giant cells from cultured newt peritoneal macrophages.

Animals↗

Reconstruction of a human skull calibration phantom using bone sections from an 241Am exposure case.

New York University Medical Center's Institute of Environmental Medicine (NYUMC/IEM) was called upon by representatives of the United States Transuranic Registry to reconstruct a human skull phantom for the purpose of producing a calibration structure to be used for determining 241Am skeletal content from in vivo measurements. The human skull represented a deposition pattern of 241Am in the bone matrix which had accumulated into the bone via natural metabolic processes after an accidental intake. Soon after death, the skull was sagittally divided and the left lateral side was analyzed radiochemically. Assuming symmetry of deposition, and based on measurements of the right lateral side of the skull performed at NYUMC/IEM as well as results of radiochemical analysis of sections of the left side, the activity content of the right side was estimated to be 307 +/- 4 Bq (8.3 +/- 0.1 nCi). The right side was subsequently paired with a blank left lateral of a control skull and embedded into tissue-equivalent material. The reconstructed skull phantom was then evaluated to determine its applicability as a calibration phantom which could be used to estimate skeletal burdens of 241Am.

Americium↗

Effects of thyroxine-driven precocious metamorphosis on maturation of adult-type allograft rejection responses in early thyroidectomized frogs.

In contrast to the adult pattern of allograft reactivity, larval South African clawed frogs (Xenopus) either become tolerant of adult major histocompatibility complex (MHC) disparate skin grafts or reject them slowly. Larvae fail to reject grafts that are incompatible at minor histocompatibility (H) loci (MHC-identical); rather, they become immunologically tolerant. We report here that early thyroidectomized (thyroidx) larvae, forced to metamorphose precociously on a regimen of thyroxine (T4) treatment, showed larva-like responses in that their ability to reject skin allografts that differed by minor H loci or one MHC haplotype was significantly impaired relative to age-matched intact postmetamorphic controls. During the normal ontogeny of Xenopus, lymphocyte numbers increase in larval life, decrease during metamorphosis, and increase to adult levels at 6-12 months of age. Thyroidectomy and a low-dose regimen of thyroxine treatment limited the number of lymphocytes that developed in larval organs and very dramatically reduced those populations below control levels during metamorphosis. Because these changes were stage-dependent rather than age-dependent, the second wave of lymphopoiesis in thyroidx frogs treated with low T4 may occur out of synchrony with the expression of Class I MHC antigens. Impaired allograft rejection, therefore, may reflect the absence of a population of cells that can effectively recognize minor H alloantigens and/or self and allo Class I antigens.

Animals↗

Effect of levamisole on chemotaxis of granulocytes from uremic patients.

Uremic granulocyte chemotaxis was assessed in the presence of four different concentrations of levamisole. Chemotactic responsiveness of uremic granulocytes was significantly decreased compared to normal, both in the absence of levamisole and with all levamisole concentrations tested. However, with 10(-3) and 10(-4) M levamisole concentrations, uremic granulocyte chemotaxis was similar to that of normal granulocytes without levamisole. Defective chemotactic activity of granulocytes may play a role in the increased susceptibility of uremic patients to infections. Pharmacological correction of this defect may improve the patients' ability to cope with infections.

Adult↗

Behavioural and developmental gains made in a therapeutic preschool and an integrated day care program: a pilot study.

The outcomes after 8 months treatment for mildly delayed, behaviorally disordered preschoolers in a therapeutic preschool were compared with outcomes for similar children integrated into daycare centres on measures of development, language and behaviour. The results provide a measure of the gains achievable in a well resourced and specialized program.

Attention Deficit Disorder with Hyperactivity↗

Should prophylactic anticonvulsants be administered to patients with newly-diagnosed cerebral metastases? A retrospective analysis.

We analyzed a retrospective series of 195 patients with documented intracerebral metastases (ICM) to assess the frequency of late seizure development and the impact of prophylactic anticonvulsants. Eighteen percent of the patients presented with seizures. Of the remaining patients, 40% received prophylactic anticonvulsants (diphenylhydantoin [DPH] in greater than 90%). Ten percent developed late seizures at an interval from the diagnosis of ICM ranging from 1 to 59 weeks. No patient with a posterior fossa lesion developed seizure; conversely, patients with evidence on initial examination of cerebral hemispheric dysfunction had a higher incidence of late seizure development. The incidence of seizure was virtually identical in patients who received DPH compared with those in whom it was withheld, although two thirds of patients who developed seizure while on DPH had a serum anticonvulsant level that was subtherapeutic. Based on the above findings and until prospective data become available, we recommend that anticonvulsants be withheld in newly-diagnosed patients with ICM until the first seizure.

Adult↗

Effect of insulin-like growth factor I on deoxyribonucleic acid synthesis and galactopoiesis in bovine undifferentiated and lactating mammary tissue in vitro.

We have demonstrated that insulin-like growth factor I (IGF-I), at physiological concentrations, is a potent mitogen of bovine undifferentiated mammary epithelial cells cultured in collagen in serum-free medium. Its activity is independent of insulin, although at pharmacological concentrations insulin may substitute for IGF-I. The maximal [3H]thymidine incorporation stimulated by either IGF-I or insulin was only 25-40% of that in medium supplemented with 10% fetal calf serum (FCS) only. Epidermal growth factor (EGF) exhibited low mitogenic activity which was not synergistic with IGF-I in serum-free medium. IGF-I and EGF had low synergistic activity when added separately to 10% FCS-supplemented medium. Strong synergism (100% or more) was observed, however, when both factors were added simultaneously, indicating that their maximum mitogenic effect is dependent on a simultaneous presence of other factors existing in FCS. The galactopoietic effect of IGF-I was tested in organ culture of bovine lactating mammary gland. Neither fatty acid synthesis nor alpha-lactalbumin secretion was stimulated by IGF-I, even at 2000 ng/ml. These results indicate that, at least in our in vitro system, galactopoiesis is not affected by IGF-I.

Animals↗

The ontogeny of interleukin production and responsivity in the frog, Xenopus.

The production of and responsivity to leukocyte-derived lymphokine-rich culture supernatants (SNs) was examined during the ontogeny of the frog, Xenopus. Thymocytes and splenocytes from adult frogs are capable of responding to the T-cell mitogen, phytohemagglutinin-P (PHA). Larval thymocytes are unresponsive to this lectin, whereas larval splenocytes are not. PHA-unresponsive thymocytes can be costimulated with PHA plus either a T-cell growth factor (TCGF)-rich SN or an interleukin-1 (IL-1)-rich SN (from cultures of lipopolysaccharide (LPS)-treated macrophage-enriched peritoneal cells (PCs). Stimulation of larval thymocytes with PHA does not produce a TCGF-rich SN as assayed by proliferation of lymphoblasts. Larval as well as adult splenocytes treated with PHA, however, do produce TCGF. These data are consistent with the hypothesis that the factor limiting mitogen responsiveness of larval thymocytes is the ability of cell populations in the thymus to produce rather than respond to either IL-1 or IL-2.

Animals↗