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Biomedical subjects

N Cohen

Publications and source records attributed to N Cohen.

At least 19 recordsLinked to original sources
PubMed1992

[Cimetidine hepatitis].

A 41-year-old man with rheumatoid arthritis developed severe acute hepatitis 3 days after starting cimetidine for duodenal ulcer. Other causes were ruled out and he recovered after cimetidine was discontinued. Mild transient elevations of hepatic enzymes have been reported in 3.6% of patients taking cimetidine. However, only 12 cases of severe acute hepatitis associated with cimetidine, mostly secondary to idiosyncrasy, have been reported in the English literature. This rare but serious complication of cimetidine should be kept in mind.

Acute Disease↗
PubMed1992

High brain densities of the immunophilin FKBP colocalized with calcineurin.

The immunophilins cyclophilin and FK506 binding protein (FKBP) are small, predominantly soluble proteins that bind the immunosuppressant drugs cyclosporin A and FK506, respectively, with high affinity, and which seem to mediate their pharmacological actions. The Ca(2+)-dependent protein phosphatase, calcineurin, binds the cyclophilin-cyclosporin A and FKBP-FK506 complexes, indicating that calcineurin might mediate the actions of these drugs. A physiological role for the immunophilins in the nervous system is implied by a close homology between the structure of NINA A, a protein in the neural retina of Drosophila, and cyclophilin, as well as by the high density of FKBP messenger RNA in brain tissue. Here we report that the levels of FKBP and mRNA in rat brain are extraordinarily high and that their regional localization is virtually identical to that of calcineurin, indicating that there may be a physiological link between calcineurin and the immunophilins. We also show that at low concentrations FK506 and cyclosporin A enhance the phosphorylation of endogenous protein substrates in brain tissue and in intact PC12 cells, indicating that these drugs may inhibit phosphatase activity by interacting with the immunophilin-calcineurin complexes.

Adenosine Triphosphate↗
PubMed1992

Mechanistic implications of alterations in HL-60 cell nascent DNA after exposure to 1-beta-D-arabinofuranosylcytosine.

To improve our understanding of the mechanism of 1-beta-D-arabinofuranosylcytosine (ara-C) incorporation into DNA, we investigated the physical properties (size, position of nucleoside incorporation) of small fragments of nascent DNA (nDNA) obtained by pH-step alkaline elution of intact HL-60 cells following their exposure to ara-C. In the pH-step alkaline elution procedure, the smallest fragments of nDNA elute at pH 11. Anion-exchange high-performance liquid chromatography (HPLC) of nDNA obtained by 1 h elution at pH 11.0 of lysed HL-60 cells revealed a preponderance of nDNA fragments ranging from 0.5 to 40 kb in control ([3H]-dThd-labeled) cells. Exposure of cells to ara-C (0.8-1 microM) resulted in a loss of the preponderance of radiolabel in fragments of 0.5-40 kb along with redistribution of the radiolabel (from [3H]-dThd or [3H]-ara-C) into smaller nDNA fragments (predominantly < 100 bases in length) as determined by HPLC. We used the ability of pH-step alkaline elution to provide these small nDNA fragments produced by ara-C to investigate the paradoxical behavior of ara-C as a chain terminator in cell-free DNA synthetic systems while being incorporated into an internucleotide position in intact cells. Following the digestion of purified nDNA with micrococcal nuclease and spleen phosphodiesterase II, the proportion of radiolabel in 3'-dNMP (indicating an internucleotide position) or free nucleoside (indicating a chain terminus position) was determined by reverse-phase HPLC. In digests of prelabeled genomic DNA, as expected, > 90% of the radiolabel from [14C]-dThd or [3H]-ara-C was found to exist in an internucleotide position (as determined by co-chromatography with authentic 3'-dTMP or 3'-ara-CMP). In contrast, digests of nDNA that eluted at pH 11.0 revealed a significantly higher proportion of radiolabel in the chain terminus position (29%-35%) when the nDNA was obtained from cells exposed to 1 microM [3H]-ara-C as compared with cells exposed to [3H]-dThd or [3H]-dCyd alone (< 10%). These data obtained from pH-step alkaline elution of intact cells suggest that by causing the inhibition of chain elongation while failing to inhibit the formation of new nDNA replication intermediates, ara-C exposure leads to the production of very small nDNA fragments. This relative chain-terminating effect of ara-C is most apparent in the small nDNA replication fragments that elute at pH 11.0.(ABSTRACT TRUNCATED AT 400 WORDS)

Carbon Radioisotopes↗
PubMed1992

Conditioned immunopharmacologic effects on cell-mediated immunity.

One of the several lines of evidence documenting a relationship between the brain and the immune system is the research on behaviorally induced alterations in immune reactivity. The present review concentrates on the use of immunopharmacologic agents, stress, and antigenic stimuli as unconditioned stimuli (UCSs) in the classically conditioned suppression and enhancement of cell-mediated immune reactions including host-vs-graft and graft-vs-host reactions and delayed type hypersensitivity.

Adjuvants, Immunologic↗
PubMed1992

Long-term retention of 210Pb in man: a unique case of internal contamination.

Knowledge of the long-term effective half-life of 210Pb in man is essential for estimating the cumulative exposure to inhaled short-lived radon daughters from measured values of the 210Pb skeletal burden. For this purpose, the effective half-life has been obtained from sequential measurements of 210Pb made in vivo during a 10-y period and by bioassay of 210Pb excreted in the urine of an individual with a 43-y-old body burden. The long-term effective half-lives obtained by these two methods were 18.1 +/- 4.8 y and 15.8 +/- 0.8 y, respectively. These values are not very different from the estimate of 12.3 y previously adopted by the ICRP.

Accidents, Occupational↗
PubMed1992

Vestibuloocular reflex of rhesus monkeys after spaceflight.

The vestibuloocular reflex (VOR) of two rhesus monkeys was recorded before and after 14 days of spaceflight. The gain (eye velocity/head velocity) of the horizontal VOR, tested 15 and 18 h after landing, was approximately equal to preflight values. The dominant time constant of the animal tested 15 h after landing was equivalent to that before flight. During nystagmus induced by off-vertical axis rotation (OVAR), the latency, rising time constant, steady-state eye velocity, and phase of modulation in eye velocity and eye position with respect to head position were similar in both monkeys before and after flight. There were changes in the amplitude of modulation of horizontal eye velocity during steady-state OVAR and in the ability to discharge stored activity rapidly by tilting during postrotatory nystagmus (tilt dumping) after flight: OVAR modulations were larger, and tilt dumping was lost in the one animal tested on the day of landing and for several days thereafter. If the gain and time constant of the horizontal VOR change in microgravity, they must revert to normal soon after landing. The changes that were observed suggest that adaptation to microgravity had caused alterations in way that the central nervous system processes otolith input.

Animals↗
PubMed1992

Postnephrectomy mesangial cells secrete a factor(s) that stimulate(s) tubular cell growth in vitro.

Rat kidney mesangial cells were procured from 5 sham-operated and 10 previously uninephrectomized rats. They were grown in cell culture medium supplemented with 20% fetal calf serum. Cell free conditioned medium was collected on the 10th day. Tubular cell cultures were then prepared from 18 normal unoperated 3-week-old rats. Tubular cells from each separate kidney sample were grown in pooled-mesangium conditioned medium from sham-operated or from nephrectomized rats, supplied with 20% pooled serum from either sham-operated or nephrectomized animals. 3H-thymidine incorporation of normal tubular cell cultures grown in nephrectomy mesangium conditioned medium supplemented with sera from nephrectomized animals proved to be significantly greater than that of any of the other three experimental variations. No statistically significant difference was evident when either preconditioned medium of postnephrectomy mesangial cells or postnephrectomy serum were used alone.

Animals↗
PubMed1991

Safety and immunogenicity of hydrogen peroxide-inactivated pertussis toxoid in 18-month-old children.

The immunogenicity and adverse effects of an acellular pertussis vaccine consisting of a purified pertussis toxin inactivated with hydrogen peroxide (PTxd) was evaluated. Children aged 15 to 30 months were injected with 10 (n = 33) or 50 micrograms (n = 34) of PTxd or with diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP) (n = 34). All children had previously received three doses of DTP during infancy. Both dosages of PTxd induced higher IgG antibody (p less than 0.05 for 10 micrograms dose and p less than 0.01 for 50 micrograms dose) and pertussis antitoxin responses (p less than 0.01 for 50 micrograms dose) than DTP. The 50 micrograms dose gave slightly higher (though not significantly) antibody responses than the 10 micrograms dose of PTxd. None of the vaccines induced detectable IgM or IgA antibody responses to pertussis toxin. At 24 h, local reactions occurred in none of the children injected with 10 micrograms PTxd, 12% with 50 micrograms PTxd and 78% with DTP. Fever at 24 h occurred in 13% after 10 micrograms PTxd, in none after 50 micrograms PTxd and in 53% after DTP. Recipients of DTP, but not of PTxd, had significant increases in neutrophils and decreases in lymphocytes and haematocrit at 24 h (all p less than 0.05). None of the groups showed changes in blood glucose at 24 h. PTxd induced pertussis toxin antibody levels similar to those observed in patients convalescing from natural pertussis. This acellular pertussis vaccine deserves further evaluation for safety and immunogenicity in infants and for efficacy in preventing pertussis.

Antibodies, Viral↗
PubMed1991

Regulation of in-place asbestos-containing material.

Approximately two-thirds of New York City's 800,000 buildings contain asbestos. Most of this material is damaged or deteriorating. Legislation pending in the New York City Council (Bill number 453) would require virtually all building owners to inspect for asbestos, to develop management and maintenance plans to prevent disturbance of intact material, and to provide notice of the presence of asbestos to building occupants. This paper reviews the legislation and discusses its features that have been questioned. It concludes that regulation of in-place asbestos is necessary and appropriate.

Animals↗
PubMed1991

An improved method for the detection of soluble interleukin 2 receptors in liver transplant recipients by flow cytometry.

A new flow cytometric method (FCM) for detection of soluble interleukin 2 receptor (sIL-2R) in serum was established. Using this method, results from one to forty samples can be obtained in less than 2 hr as compared with 5 hr in an ELISA. Comparing over 300 sera samples tested by both methods, we found the FCM to be as specific and sensitive as the ELISA, but even more reproducible. Regression analysis of ELISAt on FCMt showed there is a strong relationship between the two assays and they mimic each other over time. We studied the daily serum levels of sIL-2R by FCM in 18 liver allograft recipients: 7 were in the stable group, 6 in the rejection group, and 5 had both rejection and infection. Low or decreasing sIL-2R levels correlated with absence of rejection. In patients with rejection episodes, a typical elevation of sIL-2R was followed by a rapid decrease of sIL-2R after successful response to rejection therapy. Patients with multiple complications displayed elevated sIL-2R levels. In conclusion, because of its rapid turnover time and accuracy, the FCM has the potential to determine the appropriate timing of post-transplant liver biopsies.

Antibodies, Monoclonal↗
PubMed1991

Conditioning of the immune response.

Experimental studies in humans and experimental animals document the acquisition and extinction of classically conditioned alterations of different parameters of humoral- and cell-mediated immune responses. Although the aversive effects of cyclophosphamide in a taste aversion learning paradigm has been the most frequently used model, conditioned immunomodulatory effects are not confined to this conditioning procedure, and they are not limited to cyclophosphamide or, for that matter, the use of immunomodulating drugs as unconditioned stimuli. Conditioned changes in immunologic reactivity have also been found to modulate the progression of spontaneously-developing or experimentally-induced pathophysiological processes in experimental animals. The available data on the immunoregulatory effects of conditioning indicate that the immune system, like other systems operating in the interests of homeostasis, is integrated with other physiological processes and is therefore influenced by and capable of influencing the brain.

Animals↗
PubMed1991

Current status of whole-body counting as a means to detect and quantify previous exposures to radioactive materials. Whole-body Counting Working Group.

This report discusses the principles, techniques, and application of whole-body counting with respect to previous radiation exposure. Whole-body counting facilities are located nationwide and have a wide range of capabilities. A listing of these facilities is provided in Appendix A. However, only a few facilities are truly state-of-the-art and have the sophisticated capabilities required to attempt detection of low-level activity in vivo. Measurements made many years after exposure can be extremely difficult to interpret. The precision and accuracy of resulting dose estimates are functions of such factors as the assumptions made concerning intake, time since intake, radionuclide metabolism, and level of intake. The indiscriminate application of metabolic models to current body contents or minimum detectable amounts of radionuclides with relatively short effective half-lives (such as 137Cs) can lead to absurd results when used as a basis for calculating intakes 25 and 40 y ago. Skull counting for 90Sr-90Y and 239,240Pu can set upper limits on possible uptakes and radiation doses, but in the case of 239,240Pu, the limits are rather high. In both cases, the accuracy of the limits depends on the metabolic models used in the calculations. These models (ICRP 1979) were developed to set safety standards for the intakes of radionuclides by workers and are not intended to be used to back-calculate uptakes and radiation doses from measurements made long after the uptake. There are, therefore, large uncertainties in any conclusions derived from these calculations. The experience gained over the years with whole- and partial-body counting has consistently shown that they are of little use in determining body contents of radionuclides resulting from exposure to weapons debris decades earlier. The development of new detectors such as an array of lithium-drifted silicon devices offers some hope of lowering the minimum detectable amount (MDA) for Pu and Am, but such detectors are still several years from routine application and do not represent current state-of-the-art. Furthermore, it is doubtful that such improvements will be sufficient to meet the need of assessing radiation exposures that occurred decades earlier.

Accidents↗