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Biomedical subjects

S Spector

Publications and source records attributed to S Spector.

At least 37 records · Page 2Linked to original sources

Morphine and codeine are endogenous components of human cerebrospinal fluid.

We have examined cerebrospinal fluid (CSF) from twelve patients who were not on any medication and found them to contain both morphine and codeine in concentrations of 2 to 339 fmol/ml. These are comparable to the concentration of opioid peptides in spinal fluid. Both morphine and codeine are present mainly in conjugated form from which the free alkaloids can be released by acid hydrolysis.

Adolescent

Histopathology and immunofluorescent immunoglobulins in asthmatics with aspirin idiosyncrasy.

Nearly 700 specimens of polyps and sinus tissues from 12 patients with asthma and aspirin idiosyncrasy were studied with histochemical and immunofluorescent immunoglobulin techniques. Hematoxylin-eosin, Giemsa, and Wright's stains were used for the histochemical analyses. Immunofluorescent antibodies for IgG, IgA, IgM, IgE, IgD, anti-C3, albumin, and fibrin were used. There was a uniform inflammatory reaction in all the tissues. A thick basement membrane and epithelial changes were also present. Immunofluorescent immunoglobulins were consistent in quantity and location in these tissues. IgG, IgA, and IgM were associated with inflammation. IgE was present in all the specimens, but this does not necessarily indicate a reagin-mediated reaction. Anti-C3 excluded the possibility of a hereditary absence of C1 esterase inhibitor.

Adult

The pharmacokinetics of naloxone in the premature newborn.

We examined the pharmacokinetic properties of naloxone in a group of premature infants infused with an intravenous bolus of the drug. Ten infants with a mean birth weight of 1,328 +/- 402 g and a gestational age of 29.4 +/- 2.8 weeks were studied at an age of 4.5 +/- 3.2 days of life. Following administration of 0.4 mg/kg of naloxone, we obtained blood samples at specific time intervals, and stored the serum for later analysis by a radioimmunoassay method. Calculations from the serum concentration versus time relationship resulted in an elimination rate constant of 0.75 +/- 0.39/h, a half-life of 70.5 +/- 35.2 min, a systemic clearance of 39.13 +/- 14.53 ml/min/kg, and an apparent volume of distribution of 3.52 +/- 1.20 liters/kg.

Humans

Steroids and orbital blowout fractures--a new systematic concept in medical management and surgical decision-making.

Thirty-eight patients with computed tomography (CT)-proven orbital fractures and diplopia were studied prospectively to determine the efficacy of steroids in the medical management of orbital fractures. The protocol is based on double-blind assignments to steroid (ST) and non-steroid (NT) treatment groups. Outcome analysis was based on sorting fractures into three CT classes: I-without soft tissue prolapse (n = 15); II-with soft tissue prolapse (n = 14); and III-CT evidence of inferior rectus entrapment (n = 9). Results included resolution of diplopia without surgery in both ST and NT groups in CT classes I and II. Median time course of resolution was compressed to less than 5 days in the ST treatment group, however, versus 13 days in the nontreatment group. All fractures in class III had residual diplopia with five of nine patients having surgical results that were enhanced in the ST treatment group. In addition, enophthalmos was unmasked in the ST treatment group within 1 week of treatment versus 5 months without treatment. A protocol for medical management and surgical decision-making in blowout fracture is presented.

Double-Blind Method

Chemical characterization and regulation of endogenous morphine and codeine in the rat.

Data on the tissue distribution of morphine and codeine in rat are presented. The concentration of these two opiate alkaloids seems to be distributed uniformly in the cortex, midbrain, pons/medulla and cerebellum. The spinal cord and the adrenal gland have high levels of morphine and codeine and the adrenal has more codeine than morphine. The major fraction of the alkaloids reside in a synaptosomal fraction and are present in tissues as the sulfate conjugate. The levels of morphine in the spinal cord and the urinary excretion of morphine are elevated in the arthritic rat model. We used extracted alkaloid samples from arthritic rats spinal cord for analysis by mass spectrometry and found molecular ions identical with morphine and codeine. The results are discussed in the light of possible physiological roles of endogenous morphine and codeine.

Animals

Sustained-release theophylline preparations in asthmatic children. A short-term comparison of two products and the relationship of serum theophylline levels and pulmonary function changes.

In a four-week study, 20 children with chronic asthma were treated in a randomized, double-blind, crossover manner with two sustained-release theophylline preparations (Theo-Dur and Uniphyl) to compare their drug concentrations and clinical efficacy. In addition, the effects of serum theophylline concentration on results of pulmonary function tests (PFTs) were evaluated. Twelve-hour doses (to achieve serum concentrations between 10 and 20 mg/L) of each drug were given for two weeks. Diaries of asthma symptoms and peak flows were kept daily. After 14 days of each treatment, children returned for measurement of theophylline levels and PFTs over a 12-hour period. The two drugs were equally effective in clinically controlling asthma over the two weeks of treatment. Serum theophylline levels obtained over the 12-hour dosing periods were not significantly different. Uniphyl provided less (but not significantly) deviation between peak and trough levels. Analysis of individual patient data did not reveal a predictable relationship between serum theophylline concentrations and results of PFTs.

Adolescent

Presence and formation of codeine and morphine in the rat.

Endogenous codeine and morphine were identified in rat brain by immunological determination following HPLC. To demonstrate occurrence of a biosynthetic pathway to morphine in mammals similar to that used by the poppy plant, (+)-salutaridine, (-)-thebaine, and (-)-codeine were administered to rats intravenously. These compounds, which are intermediates in the synthesis of morphine in Papaver somniferum, caused a marked increase in the codeine and morphine levels in rat tissues. This provides evidence for a biosynthetic pathway to morphine in mammalians.

Animals

Downregulation of [3H]Ro5-4864 binding sites after exposure to peripheral-type benzodiazepines in vitro.

Peripheral-type benzodiazepine (BZD) binding sites undergo a rapid and pronounced downregulation after exposure to these compounds in vitro. Friend erythroleukemia cells were incubated with micromolar concentrations of BZD after which they were washed thoroughly and the binding of the specific peripheral-type BZD radioligand [3H]Ro5-4864 was determined. Exposure to the peripheral-type BZD Ro7-3351 decreased the number of [3H]Ro5-4864 binding sites from 324 to 41 fmol/10(6) cells with no change in affinity. Downregulation appears to require active cellular processes because it is blocked when exposure to BZD is at 4 degrees C rather than at 37 degrees C. Furthermore, whereas [3H]Ro5-4864 binding is decreased substantially in membrane preparations made from downregulated cells, it is not altered when membrane preparations from control cells are exposed to BZD. The time course of downregulation is quite rapid, as it occurs within minutes. In contrast, the return of sites requires days and there is a close relationship between return of sites and growth of new cells. The ability of BZDs to downregulate correlates more closely with affinity for the peripheral-type site than with biological activity. The ability to undergo downregulation is characteristic of receptors and its occurrence suggests that peripheral-type BZD binding sites are functional receptors.

Benzodiazepines

Vitamin D3 derivatives inhibit the differentiation of Friend erythroleukemia cells.

A number of vitamin D3 metabolites inhibit benzodiazepine- and dimethyl sulfoxide-induced differentiation of Friend erythroleukemia cells. The inhibition is dose dependent and occurs at nM concentrations. The order of potency of these compounds is 1,25-dihydroxycholecalciferol greater than 1,25,26-trihydroxycholecalciferol greater than 1,24R,25-trihydroxycholecalciferol greater than 1 alpha-hydroxycholecalciferol greater than 24R,25-dihydroxycholecalciferol greater than 25S,26-dihydroxycholecalciferol. The inhibition is maximal when the vitamin D3 analogs are added together with the inducer, and becomes progressively decreased with delayed addition. These results suggest that the vitamin D3 metabolites may play a regulatory role in erythropoiesis.

Animals

Intussusception.

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Child

Peripheral-type benzodiazepines influence ornithine decarboxylase levels and neurite outgrowth in PC12 cells.

A number of the benzodiazepines (BZDs) inhibit nerve growth factor (NGF)-induced neurite outgrowth in a dose-dependent manner in PC12 cell cultures. The rank order of potency of a series of BZDs for inhibition of neurite outgrowth does not correlate with the order of their affinity constants for the so-called peripheral BZD sites present on PC12 cells. Whereas the inhibition of neurite extension is stereospecific, the binding to the peripheral site is not. The inhibition of neurite outgrowth is not attributable to a blockade of NGF binding to either its fast or slow receptors. Additionally, several other characteristics of NGF stimulation of PC12 cells, such as autoadhesion and the induction of ornithine decarboxylase (OrnDCase), remain unaltered in the presence of BZDs. Many BZDs increase OrnDCase levels in PC12 cells in the absence of NGF. The OrnDCase response to BZDs is blocked by actinomycin D. Furthermore, the structural requirements of BZDs for induction of OrnDCase activity is not identical to that for the inhibition of NGF-induced neurite extension. Thus, unlike attenuation of neurite extension, BZD induction of OrnDCase is not stereospecific. Also, some BZDs block neurite growth but do not induce OrnDCase. We propose that there are at least three sites of action of BZDs on PC12 cells. The first is the well-characterized high-affinity peripheral site. The second distinct locus of action results in a blockade of NGF-induced neurite outgrowth. The structural requirements for the latter effect are essentially indistinguishable from those for BZD induction of hemoglobin synthesis in Friend erythroleukemia cells. The third site of action results in an induction of OrnDCase. Structural requirements for this activity are not identical to those for either the differentiation of Friend cells or the inhibition of neurite outgrowth.

Animals

Scintillation proximity radioimmunoassay utilizing 125I-labeled ligands.

A unique type of radioimmunoassay is described that does not require centrifugation or separation. Microbeads containing a fluorophor are covalently linked to antibody. When an 125I-labeled antigen is added it binds to the beads and, by its proximity, the emitted short-range electrons of the 125I excite the fluorophor in the beads. The light emitted can be measured in a standard scintillation counter. Addition of unlabeled antigen from tissue extracts displaces the labeled ligand and diminishes the fluorescent signal. Application of scintillation proximity immunoassay to tissue enkephalins, serum thyroxin, and urinary morphine is described. Applications of the principle to study the kinetics of interaction between receptors and ligands are discussed.

Chorionic Gonadotropin

Isolation of morphine from toad skin.

A nonpeptide opioid was found in toad skin and purified to homogeneity by using HPLC with electrochemical detection. A nonpeptide opioid also was detected in bovine brain and adrenals as well as rabbit and rat skin, by reversed-phase HPLC following Sephadex G-15 column chromatography. The material in toad skin was identical to morphine by immunological, pharmacological, and physical chemical criteria.

Adrenal Glands

Impaired in vitro interferon, blastogenic, and natural killer cell responses to viral stimulation in acquired immune deficiency syndrome.

The in vitro immune response to herpes simplex virus (HSV), type 1, strain 539, HSV type 2, strain 316D, and cytomegalovirus was studied in 20 patients (14 with acquired immune deficiency syndrome, four with the acquired immune deficiency syndrome-related symptom complex, and two sexually active asymptomatic homosexuals) and 18 heterosexual healthy controls. Peripheral blood mononuclear cells were cultured with 2 X 10(5) plaque-forming units of heat-inactivated viruses, their lymphocyte blastogenic responses were measured after 5 days in culture by [3H]-thymidine incorporation, their interferon production was measured after 24 hr and 5 days, and natural killer (NK) cell activation was measured after 24 hr and 5 days of culture. Blastogenic responses to viruses were significantly low for only HSV, type 1:1.75 X 10(3) cpm in patients' cells compared to 6.36 for controls. Interferon responses to all three viruses were significantly low at both 24 hr and 5 days; e.g., HSV, type 1:139 IU/ml in patients' cells compared to 777 for controls at 24 hr. NK cell responses of patients were lower than those of controls when tested fresh and after 24 hr of incubation: 6.1 versus 11.7% and 9.2 versus 16.8% target cell lysis, respectively. Exposure to viruses boosted NK cell responses of both patients' and controls' cells, but boosting was generally greater among the normal rather than the patients' cells. The abnormalities of response were present in all three patient groups. Addition of interleukin-2 in vitro increased the patient and control blastogenic and NK responses but did not augment the interferon responses. The in vitro responses to both HSV, type 1, and HSV, type 2, correlated significantly with our conventional assays of the percentage and absolute level of T4+-helper lymphocytes in the blood and the blastogenic responses to mitogens, such as phytohemagglutinin, pokeweed mitogen, and concanavalin A. This system should be useful for the study of host defense in acquired immune deficiency syndrome patients and those in high-risk groups, and also for the in vitro evaluation of immunomodulators.

Acquired Immunodeficiency Syndrome