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Biomedical subjects

S Spector

Publications and source records attributed to S Spector.

At least 73 records · Page 4Linked to original sources
PubMed1989

Studies of HIV infection and the development of Epstein-Barr virus-related B cell lymphomas following transfer of human lymphocytes to mice with severe combined immunodeficiency.

Mice with severe combined immunodeficiency (C.B-17 scid, hereafter SCID) accept xenografts of adult human peripheral blood leukocytes (PBL). The transplanted human PBL expand in number and survive for at least thirteen months and have been shown to reconstitute human immune function at both the T and B cell levels. Human immunoglobulin production is restored, and secondary antibody responses to antigens such as tetanus toxoid can be induced. All SCID mice reconstituted with 50 x 10(6) or more PBL from donors with evidence of exposure to Epstein-Barr virus (EBV) have developed human B cell lymphomas at 8-16 weeks after PBL engraftment, whereas mice reconstituted with PBL from EBV-seronegative donors fail to develop tumors. These tumors involve both lymphatic and non-lymphatic organs, and histologically they resemble large cell or immunoblastic lymphomas. The tumors are associated with high levels of human immunoglobulin secretion and serum electrophoresis reveals oligoclonal immunoglobulin banding patterns. Analysis of tumor DNA shows the presence of EBV genomes and oligoclonal patterns of immunoglobulin JH gene rearrangement. Taken together, these observations suggest an EBV-related proliferation of B lymphocytes leading to the rapid appearance of oligoclonal B cell malignancies following transfer of B lymphocytes from "normal" donors to SCID mice. SCID mice reconstituted with PBL from EBV-seronegative donors have been infected with the LAV-1 strain of human immunodeficiency virus (HIV-1). Virus has been recovered from most infected animals by co-culture of mouse tissue with human T lymphoblasts. Some mice with high virus titers have developed an acute wasting syndrome and depletion of human T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Identification of the convulsant opiate thebaine in mammalian brain.

The convulsant opiate thebaine, an intermediate of morphine biosynthesis, was purified from bovine brain to homogeneity by gel filtration and high-performance liquid chromatography (HPLC) monitored by a radioimmunoassay. The immunoreactive material behaved identically to standard thebaine in two HPLC systems and was confirmed to be thebaine by combined gas chromatography/mass spectrometry. To our knowledge, the presence of thebaine in mammalian tissue has not been demonstrated previously. Codeine and morphine were also found to exist in ovine brain. The presence of thebaine in ovine brain provides strong evidence that morphine and codeine, in various mammalian tissues, are of endogenous origin and actually biosynthesized from a precursor.

Animals↗
PubMed1988

Acquired immunodeficiency syndrome. Magnetic resonance patterns of brain involvement with pathologic correlation.

Magnetic resonance brain scans of 30 patients with either acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were reviewed. Twenty patients had focally abnormal neurological examination results at the time of scanning. Pathological diagnosis was available in nine. Four patterns of abnormality were observed on T2-weighted images. Multiple discrete high-signal foci (pattern A) were found in patients with toxoplasmosis and progressive multifocal leukoencephalopathy. Large, bilateral patchy to confluent high-signal areas within the white matter (pattern B) represented a white matter encephalitis secondary to cytomegalovirus or human immunodeficiency virus. Generalized enlargement of the cortical sulci and ventricles (pattern C) probably reflected atrophic changes from the chronic human immunodeficiency virus infection and prolonged debilitating illness. Solitary high-signal-intensity lesions (pattern D) suggested a nonviral opportunistic infection. Differential diagnosis of brain abnormalities in patients with AIDS can be assisted by recognition of these characteristic patterns.

Acquired Immunodeficiency Syndrome↗
PubMed1988

One-year follow-up of cardiac and coronary artery disease in infants and children with Kawasaki disease.

Of 75 patients meeting clinical criteria for Kawasaki disease, 67 patients were followed with serial ECG and echocardiograms (echo) for at least 1 year. Sixteen patients had coronary artery aneurysms and three had dilated coronary arteries as assessed by initial two-dimensional (2D) echo and/or angiocardiographic studies. ECG findings of first and second-degree heart block and ST-T wave changes (36%) as well as M-mode echo abnormalities (45%) including pericardial effusion, decreased ventricular septal motion, and decreased left ventricular function were all normalized by 6 months, except in two infants who continued to have decreased function and flat ventricular septal motion. In four patients with single proximal coronary aneurysm and two with dilated coronary artery, resolution of lesions occurred by 1 year. Among 11 patients with multiple coronary aneurysms discovered by initial studies, the 2D echo became normal in seven and showed aneurysms in four as corroborated by angiogram. One patient with an isolated distal coronary aneurysm, not seen by initial or serial echo, had a normal follow-up angiogram. Our study suggests that in Kawasaki disease careful, serial, 2D echo is sufficient to monitor the course of coronary artery disease that tends to regress and follow a benign course. However, the long-term effects of this disease on cardiac and coronary arteries remain to be elucidated.

Child↗
PubMed1988

Opioid binding site in EL-4 thymoma cell line.

Using EL-4 thymoma cell-line we found a binding site similar to the k opioid receptor of the nervous system. The Scatchard analysis of the binding of [3H] bremazocine indicated a single site with a KD = 60 +/- 17 nM and Bmax = 2.7 +/- 0.8 pmols/10(6) cells (51 pmols/mg total cell proteins). To characterize this binding site, competition studies were performed using selective compounds for the various opioid receptors. The k agonist U-50,488H was the most potent displacer of [3H] bremazocine with an IC50 value = 0.57 microM. The two stereoisomers levorphanol and dextrorphan showed the same affinity for this site (IC50 = 2.9 microM and 1.9 microM respectively). While morphine, [D-Pen2, D-Pen5] enkephalin and beta-endorphin failed to displace, except at very high concentrations, codeine demonstrated a IC50 = 60 microM, that was similar to naloxone (IC50 = 69 microM).

Analgesics↗
PubMed1988

A multicenter evaluation of the clinical benefits of cromolyn sodium aerosol by metered-dose inhaler in the treatment of asthma.

The efficacy and safety of cromolyn sodium by metered-dose inhaler (MDI) (1 mg per actuation) was evaluated with a double-blind, placebo-controlled, parallel-study design. Subjects with asthma, aged 8 to 58 years, whose asthma was well controlled taking cromolyn sodium capsules by Spinhaler turboinhaler, plus beta 2-agonists, entered the study after being maintained with cromolyn sodium capsules for a minimum of 4 weeks. The investigation began with a 2-week control interval with cromolyn sodium capsules followed by a 4-week single-blind period with placebo capsules. Subjects whose asthma significantly worsened while they were receiving placebo therapy were then randomized to a 10-week double-blind phase in which they received either active cromolyn sodium or placebo by MDI. Efficacy variables included diary data, physician evaluation, and spirometry. Comparisons were made between baseline period scores and each assessment variable over time. Of 155 subjects entered, 93 qualified for the double-blind, randomized phase. Eighty-three subjects completed the study and were analyzed. At baseline there existed no significant differences between the active-treatment and placebo-treatment groups. Significant differences (p less than 0.05) in favor of the cromolyn sodium-treatment group, however, were noted at all time points for daily diary symptoms (cough, breathlessness, and overall asthma severity), physician's assessments at each clinic visit, physician's and patient's overall final assessments, FEV1 at each clinic visit, and FVC and peak expiratory flow rate at the final visit. Concomitant bronchodilator medication use was less in the cromolyn sodium-treatment group. Cromolyn sodium by MDI is highly effective for (1) controlling asthmatic symptoms, (2) improving lung functions, and (3) decreasing the need for concomitant bronchodilators.

Administration, Inhalation↗
PubMed1988

Transformation of thebaine to oripavine, codeine, and morphine by rat liver, kidney, and brain microsomes.

Thebaine, an intermediate of morphine biosynthesis in the poppy plant, Papaver somniferum, was transformed to oripavine, codeine, and morphine by rat liver, kidney, and brain microsomes in the presence of an NADPH-generating system. The formation of morphine, codeine, and oripavine was identified by a specific RIA, HPLC, and GCMS. Thebaine also gave rise to four other compounds, which for the moment are unidentified. NADH dramatically increased the formation of both codeine and morphine when used together with an NADPH-generating system, especially in liver microsomes. NADPH is essential in the formation of oripavine from thebaine and morphine from codeine, while NADH is critical in the conversion of thebaine to codeine and from oripavine to morphine. Carbon monoxide or SKF 525A inhibited the conversion, indicating a role of cytochrome P-450. These results provide evidence for the enzymatic in vitro conversion by mammalian tissues of thebaine to morphine. The pathway is similar to that which exists in plants.

Animals↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗