PubMed Health⌕ Search

Biomedical subjects

W Jacobson

Publications and source records attributed to W Jacobson.

At least 37 records · Page 2Linked to original sources
PubMed1985

Direct effects of the adrenergic neurotoxin DSP4 on central opiate receptors: implications for neuroendocrine studies.

We have shown that the noradrenergic neurotoxin DSP4 can acutely abolish naloxone-induced secretion of LH in the rat. A part of this influence is clearly related to an unexpected interaction with hypothalamic opiate ( [3H]-naloxone) binding sites. Injection of DSP4 (50 mg/kg) can severely reduce opiate binding assayed in vitro. In addition, the drug is very potent in blocking opiate receptors in vitro, as determined in slice and homogenate assays. Consideration must now be given to the possibility that many previous studies on acute effects of DSP4 undoubtedly involved the opiatergic system in addition to noradrenergic terminals. Thus, DSP4 is not the drug of choice for experiments designed to probe catecholamine-opiate interactions in the control of LH release.

Amines↗
PubMed1985

The noradrenergic neurotoxins DSP4 and xylamine bind to opiate receptors.

DSP4 and xylamine compete with [3H]-naloxone for opiate binding sites with IC50 values of approximately 1 microM. This effect can be blocked by excess naloxone but not by the noradrenaline uptake inhibitors cocaine or desipramine. Other drugs containing the 2-chloroalkylamine structure--phenoxybenzamine, dibenamine, chloroethyl clonidine, the cholinotoxin AF-64 and 2-dimethylaminoethyl chloride--were similarly tested. Phenoxybenzamine and dibenamine were also able to compete with [3H]-naloxone for binding at the opiate receptor. Experiments in vivo demonstrated that DSP4, like other opiates, can rapidly reduce LH secretion in the rat. This effect is prevented by naloxone but not by desipramine. These data suggest the use of caution in interpreting the results of experiments in which DSP4 and xylamine are used as "specific" noradrenergic uptake inhibitors or as neurotoxins.

Amines↗
PubMed1985

The induction of pulmonary phospholipidosis and the inhibition of lysosomal phospholipases by amiodarone.

Administration of high doses of amiodarone to young adult rats leads to phospholipidosis of the lung, with extensive phospholipid storage by type II pneumonocytes and alveolar macrophages. Biochemical analysis reveals an increase in the total phospholipid content of the lung and in the proportion of phosphatidylcholine. The cause of the phospholipidosis is suggested to be the inhibition of lysosomal phospholipases, responsible for catabolizing phospholipids. It is shown that amiodarone is a potent inhibitor of phospholipases prepared from the soluble fraction of adult rabbit lung lysosomes.

Amiodarone↗
PubMed1984

Brain slices in radioligand binding assays: quantification of opiate, benzodiazepines and beta-adrenergic ([3H] CGP-12177) receptors.

We have characterized and quantified specific binding of [3H]-flunitrazepam (FNZ; (benzodiazepine), [3H]-naloxone (NAL; (opiate) and [3H] CGP-12177(CGP; (beta-adrenergic) to thick slices (230-400 micron) of mouse and rat brain. The binding sites are stereospecific, saturable and of high affinity. In all cases, the binding of the ligands is readily reversible and demonstrates the appropriate drug specificity. In mouse brain [3H]-NAL binding is elevated by chronic treatment with naloxone (via capsules). We have been unsuccessful in quantifying beta adrenoreceptors with the archetypal ligand [3H]-dihydroalprenolol (DHA). However, the use of [3H]-CGP 12177 enabled us to detect high-affinity beta adrenoreceptors in brain slices. [3H]-CGP also permits the demonstration of rapid and reversible agonist-induced down-regulation (internalization) of beta binding sites. We have been successful in quantifying beta adrenergic sites in single pineal glands of rat and hamster.

Animals↗
PubMed1984

Opiate ([3H]-naloxone) binding to hypothalamic and cerebral cortical slices of mouse brain.

We have characterized the binding of [3H]-naloxone to thick (400 microns) slices of hypothalamus and cerebral cortex from mouse brain. Binding is reversible, saturable, stereospecific, thermolabile, readily displaceable by opiates and sensitive to phenoxybenzamine and phentolamine. Values for KD and Bmax are very close to published figures obtained in brain homogenates. Metabolic inhibitors (ouabain and azide) have no effect on specific binding. The assay is rapid, simple and involves minimal tissue preparation.

Animals↗
PubMed1984

Benzodiazepine ([3H])-flunitrazepam) binding sites in cerebellar and cerebral cortical slices of mouse brain.

We have characterized and quantified the specific binding of [3H]-flunitrazepam ( FNZ ) to thick (230 micron) slices of mouse brain. The binding site has the characteristics of a benzodiazepine receptor, i.e., binding of FNZ is reversible, stereospecific, saturable and of high affinity. Clonazepam, but not R05 -4864, readily displaces the label. In contrast to results from homogenate assays, neither GABA nor bicuculline has any effect on [3H]- FNZ binding. However, as previously reported, the slice assay confirms the lower number of benzodiazepine receptors in "emotional" mouse brain. In addition, we have confirmed that the neurotoxin DSP4 can modify [3H]- FNZ binding though in our hands this compound elevates rather than reduces binding. The speed, simplicity and minimal tissue preparation involved suggests that this slice assay could be a valuable addition to neurochemical studies of neurotransmitter receptors.

Animals↗
PubMed1984

The effect of components of rabbit pulmonary surfactant on the activity of phospholipases.

This study investigates the ability of two components of pulmonary surfactant, protein and phosphatidylglycerol, to inhibit the action of phospholipases against phosphatidylcholine. Broncho-alveolar protein, prepared by de-lipidation of rabbit lung lavage material had an inhibitory effect on phospholipases A1 and A2 from rabbit lung lysosomes, comparable to the effect of bovine serum albumin. The degree of inhibition was found to increase with increasing enzyme activity. De-lipidated broncho-alveolar protein was separated into two fractions by gel chromatography. Inhibitory activity was associated only with the second peak, corresponding to rabbit albumin. The effect of phosphatidylglycerol (PG) on the activity of phospholipases A against dipalmitoyl phosphatidylcholine and unsaturated phosphatidylcholine (USPC) was investigated, and compared with the effects of two substrate analogues on the hydrolysis of USPC. There was no indication of true inhibition by PG, but some stimulation of USPC hydrolysis by 10 mol % PG. The relevance of these findings to the fate of surfactant in vivo is discussed.

Animals↗
PubMed1984

Developmental changes in enzyme activities in fetal and neonatal rabbit lung. Cytidylyltransferase, cholinephosphotransferase, phospholipases A1 and A2, beta-galactosidase, and beta-glucuronidase.

Lungs were obtained from rabbit fetuses (on each day from d 24 to d 30 of gestation), neonates and adults, and were fractionated for enzyme assays. The developmental profile of cytidylyltransferase shows a decrease in specific activity from d 25 to d 29 (P less than 0.05) then a sharp rise from d 30 to adult values in d 0 neonates (P less than 0.05). Cholinephosphotransferase specific activity changes little from d 25 to birth, apart from a non-significant peak on d 29. There is a sharp rise from neonatal d 0 to adult values on d 1 (P less than 0.01). The specific activity of microsomal phospholipase A2 declines from d 25 to reach adult values in the neonate (P = 0.05). In contrast, the specific activity of lysosomal phospholipase A2 rises from d 24-28 then falls in the neonate (P less than 0.05). Adult values are higher than those in the fetus and neonate. Three other lysosomal enzyme specific activities rise to d 28 then decline: phospholipase A1, beta-galactosidase, and beta-glucuronidase. The results demonstrate that the level of microsomal phospholipase A2 does not control the extent of remodelling of phosphatidylcholine for surfactant production. Lysosomal phospholipase A2 only increases in parallel with the other lysosomal enzymes, indicating an increase in the number of lysosomes in the lung.

Age Factors↗
PubMed1982

Lectin staining of carbohydrates of haemic cells. III. The cells of Hodgkin's disease and other lymphomas.

When stained for reactive sialyl groups with fluorescein-labelled Aprotinin (FLA), lymphocytes of three diffuse lymphomas were uniformly faintly fluorescent. The nodules of a nodular lymphocytic lymphoma showed dimly fluorescing lymphocytes surrounded by brightly fluorescing, apparently normal cells. The spleens of eight patients with Hodgkin's disease showed involvement in six cases. With FLA, the two uninvolved spleens contained only brightly fluorescing lymphocytes, whereas the foci of Hodgkin's lesions in the six spleens and in eight involved lymph nodes from a further eight patients contained varying proportions of brightly and dimly fluorescing lymphoid cells. Mononuclear Hodgkin's cells and bi- or multinucleated Reed-Sternberg cells fluoresced faintly. Fluorescein-labelled Ricinus communis agglutinin (FL-RCA) for galactose, and Concanavalin A (FL-Con A) for mannose or glucose, showed eosinophils, reticulin and collagen fibres especially in nodular sclerosing Hodgkin's disease, whereas all lymphocytes, Hodgkin and Reed-Sternberg cells stained faintly with either lectin. The reduction of reactive sialyl groups in malignant lymphocytes of lymphomas and Hodgkin's lesions is similar to that in lymphocytic leukaemias. It is suggested that in Hodgkin's disease these lymphocytes together with the Hodgkin and Reed-Sternberg cells represent the malignant component, whereas the brightly fluorescent normal lymphocytes, together with histiocytes, eosinophils (and neutrophils) represent a reactive component in the lesions. Similarly, the reactive lymphocytes in sarcoid lesions and sinus histiocytosis were brightly fluorescing.

Aprotinin↗
PubMed1982

The relationship of myelin basic protein (arginine) methyltransferase to myelination in mouse spinal cord.

The relationship between the activity of myelin basic protein (arginine) methyltransferase and myelination in the mouse spinal cord has been examined. The activity of this methylase increases between 8 and 45 days postnatal age and correlates well with other parameters of myelination. A comparison of myelin basic protein methylase with histone methylase activity during development indicates that each is a distinct, specific enzyme activity. Together, these results are considered to establish myelin based protein methylase as a myelination-related enzyme.

Aging↗
PubMed1981

Bone regeneration in animals and in man. A contribution to understanding the relative value of animal experiments to human pathophysiology.

Under both normal and pathophysiological conditions the relationship between bony histology and the regionally associated vascular pattern was studied. Three independent methods of research were employed (microangiography, fuchsin stained ground sections, polychrome sequential labeling) and, thus, the limitations inherent in each method were minimized. Animals of different ages and different species were found to have relatively different amounts of primary and secondary bone. In all instances primary bone was associated with a network vascular pattern emanating from the periosteal surface and secondary bone was associated with an arborial vascular pattern arising from the endosteal circulation. Adult dogs, unlike sheep, were found to have a significant complement of secondary bone and, therefore, in consideration of human bony regeneration, the dog is a superior experimental model.

Age Factors↗
PubMed1980

Lectin staining of carbohydrates of haemic cells; the cells of normal blood and bone marrow and of the myeloid leukaemias.

Plant proteins and aprotinin (a protein of beef lung), labelled with fluorescein isothiocyanate, were used as histochemical tools for the demonstration of carbohydrates. Sialic acid (or glucuronate) was stained with aprotinin (FLA); galactose was stained with Ricinus communis agglutinin (FL-RCA) and mannose (or glucose) with Concanavalin A (FL-Con-A). Normal human bone marrow and blood were examined as were the cells of patients with acute and chronic myelogenous leukaemia. The plasmalemma, cytoplasm and nuclear membrane of the cells of the normal granulocytic series were stained well with FLA, but the corresponding leukaemic cells fluoresced less intensely. Chromatin was weakly stained in both normal and leukaemic cells. FLA-RCA and FL-Con A stained the plasmalemma, cytoplasm and nuclear membrane weakly, but did not demonstrate chromatin. There was no detectable difference between normal and leukaemic cells. Eosinophil and basophil granules--in contrast to those of the neutrophils--stained well with all three compounds, in both the normal and leukaemic cells. In megakaryocytes and platelets the plasmalemma and cytoplasm were well stained with FLA. The cytoplasm of megakaryocytes and the plasmalemma of platelets stained particularly well with FL-RCA. The cytoplasm of both platelets and megakaryocytes showed up strongly with FL-Con A. In the erythroblastic series all three compounds stained the plasmalemma. The remaining cellular components were weakly stained, except the chromatin; that of the late erythroblasts showed up particularly well with FLA. Lymphocytes, monocytes and reticulin cells of the bone marrow were also stained with all three reagents. Reticulin fibres were stained strongly with FLA and FL-Con-A.

Aprotinin↗
PubMed1980

Computer-based diagnostic reporting for serum electrolytes.

Desk-top computers equipped with 16K memory and programmed in BASIC can be used to produce interpretive reports of selected laboratory data by the assignment of a numerical code. A tetral algorithm is programmed in a three-dimensional matrix, charted by columns designating specific diagnostic considerations for serum electrolyte abnormalities (an adaptation of Dito's coding procedure for protein electrophoresis). The code consists of the numbers 4 (high), 2 (normal), and 1 (low), with no basis for borderline abnormal results. The program is easily updated with additions of diagnostic considerations (column headings) or with additional codes corresponding to such conditions (code listings under column headings). Diagnostic reports can be easily produced by the use of a tractor-feed printer or similarly interfaced printing equipment for use on the patient chart, and file copies are easily generated by a "rerun" loop incorporated into the software.

Acid-Base Equilibrium↗