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Biomedical subjects

R Friedman

Publications and source records attributed to R Friedman.

At least 181 records · Page 10Linked to original sources
PubMed1983

Additional evidence that L-5-hydroxytryptophan discrimination models a unique serotonin receptor.

The purpose of the present studies was to investigate further the role of central serotonin (5-HT) in mediating the L-5-hydroxytryptophan (L-5-HTP) discriminative cue. Rats were trained to discriminate the stimulus properties of 35 mg/kg L-5-HTP combined with RO 4-4602, a peripheral decarboxylase inhibitor. Considering that several 5-HT antagonists were unable to block the L-5-HTP discriminative cue in our earlier studies, we extended these studies to include the two other presumed 5-HT antagonists mianserin and BC-105 (pizotyline). Only BC-105 completely blocked the training dose of L-5-HTP. Furthermore, the blockade of the L-5-HTP cue was both graded and surmountable by increasing the dose of L-5-HTP, suggesting a competitive antagonism. In neurochemical studies, the regional brain levels of 5-HT, norepinephrine and dopamine were determined after the injection of the training dose of L-5-HTP. Marked changes in the levels of 5-HT were found, while the levels of the catecholamines were changed only slightly or not at all. Furthermore, dose-response studies of L-5-HTP demonstrated an orderly dose-related increase in the levels of 5-HT in brain and in the percent responding on the L-5-HTP lever, while no such relationship was found for brain catecholamines. These results agree with previous pharmacological studies and suggest that the L-5-HTP discrimination is mediated by a central 5-HT receptor that has pharmacological properties distinct from those receptors identified in previous behavioral models of 5-HT receptor stimulation.

5-Hydroxytryptophan↗
PubMed1983

Experience with the one-stage perineal repair of rectal prolapse.

Our experience with 27 patients undergoing 33 Altemeier procedures for repair of rectal prolapse is presented. The overall recurrence rate during a 1- to 17-year follow-up period is 35 per cent (per patients) or 50 per cent (per operations). There was no mortality and only minimal morbidity, although we were dealing with an elderly group of patients (average age 61 years) with many associated diseases (2.8 diseases per patient). Of 13 patients with successful anatomic repair, ten described it as a success, one developed an anal stricture, and two patients claimed only partial success, despite a perfect anatomic repair, due to lack of improved continence. Our results with the Altemeier procedure for the repair of rectal prolapse are unsatisfactory. However, as the procedure is well tolerated by elderly and sick patients, it should be reserved for those.

Adult↗
PubMed1983

Fracture of the anterior arch of the atlas: the result of direct oropharyngeal trauma.

Isolated anterior arch atlantal fracture is a rare entity. Two cases of fracture of the atlas following direct oropharyngeal trauma are presented. The importance of careful upper cervical spine evaluation under these circumstances is emphasised, especially if a potential disaster following anaesthetic intubation or surgical head manipulation is to be avoided. Computed tomographic scanning is useful not only to demonstrate the site of fracture but also for visualisation of the spinal canal, especially to exclude intracanalicular bony fragments. The risk of further trauma is minimised due to the ease of patient positioning.

Adult↗
PubMed1983

Local and in-transit metastases following definitive excision for primary cutaneous malignant melanoma.

A total of 672 consecutive patients with clinical stage I and stage II primary cutaneous malignant melanoma were treated by excision of 3.0 to 5.0 cm of surrounding skin down to and including the underlying fascia when the lesion exceeded 0.5 mm thickness (Breslow measurement). More conservative margins were taken in locations where such excisions would result in significant cosmetic or functional morbidity and for thinner lesions (less than 0.5 mm). Seven of 658 patients with clinical stage I disease (1.1%) and three of 14 patients with clinical stage II disease (21.4%) developed histologically verified local metastases within 5 cm of the primary excision scar or skin graft. Fifteen patients with stage I disease developed in-transit metastases (2.3%) at a site more than 5.0 cm proximal to the surgical scar or skin graft but not beyond the regional nodal group. Two patients with stage II disease who had developed local metastases also developed in-transit metastases (14.3%). No patient with a lesion less than 1.0 mm thick has had a local recurrence. Nine of the ten patients (90%) who developed local metastases and 12 of the 17 patients (70.6%) who developed in-transit metastases have also developed systemic metastases to date. Local and in-transit metastases following such definitive excision is a significant indicator of disseminated systemic metastatic melanoma.

Humans↗
PubMed1983

Cholinergic receptor site binding, choline acetyltransferase, and acetylcholinesterase activity in the forebrain and brainstem of the Dahl rat model of essential hypertension.

Muscarinic and nicotinic receptor site binding and the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the forebrain and brainstem of Dahl salt-sensitive (DS) and salt-resistant (DR) rats was investigated. The DS line had a greater density of muscarinic sites in the cortex, hypothalamus, and medulla. Hypertensive DS rats had a greater density of sites than normotensive DS rats. ChAT activity was also higher in the cortex and hypothalamus of the DS line than the DR line. No significant differences were found in the activity of AChE or the concentration of nicotinic sites. These results suggest that the central muscarinic cholinergic system may participate in the pathogenesis of hypertension in the DS rat. The data indicate that central cholinergic activity is possibly greater in the DS than the DR rat and that this may help to explain the enhanced pressor response in the DS line after pharmacological activation of the central cholinergic system.

Acetylcholinesterase↗
PubMed1982

The roles of degranulation and superoxide anion generation in neutrophil aggregation.

Human neutrophils when exposed to appropriate stimuli aggregate, generate O(2) and secrete lysosomal constituents. To determine whether a causal relationship may exist between these responses neutrophils were exposed to either N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, or the two calcium ionophores, A23187 and prostaglandin Bx. Each agent elicited all of the above responses. The concentrations required to elicit the aggregation of 30 . 10(6) neutrophils/ml were comparable to that required for O(2) generation or lysozyme release. In a series of experiments designed to dissociate these responses, cells were suspended in a concentration too dilute (3 . 10(6) neutrophils/ml) to permit aggregation to occur. O(2) generation and lysozyme release was measurable and varied in a dose-dependent fashion to the concentration of stimulus. In a second series of experiments, neutrophils were treated with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid to inhibit degranulation without affecting O(2) generation. Aggregation was inhibited in a parallel fashion with lysozyme release. When detectable O(2) was removed from the medium by superoxide dismutase and catalase, aggregation and lysozyme release unaffected showing that aggregation can not be due to the presence of O(2) or its products in the extracellular medium. Neither aggregation of resting cells nor augmentation of fMet-Leu-Phe-induced aggregation was observed when cells were exposed to either supernatants of degranulated neutrophils or constituents of specific granules (lysozyme, lactoferrin). Kinetic analysis showed that in the absence of cytochalasin B degranulation preceded aggregation, while in its presence aggregation preceded degranulation.

Cell Aggregation↗
PubMed1982

Alpha chain crosslinks of human fibrin: purification and radioimmunoassay development for two A alpha chain regions involved in crosslinking.

Rapid and efficient purification methods that include hydrophobic chromatography on Phenyl Sepharose CL-4B have been developed for the peptides that span residues 241-476 (CNBr VIII), and 518-584 (CNBr X) in the A alpha chain of human fibrinogen. Amino acid analysis, NH2-terminal sequence determination, and SDS-PAGE indicated that greater than 95% purity of each peptide was achieved. Sensitive and specific radioimmunoassays capable was achieved. Sensitive and specific radioimmunoassays capable of detecting antigen in the range of 0.1-10.0 pmol/ml have also been developed for CNBr VIII and CNBr X. These assays have been characterized and successfully applied in studies designed to localize the two COOH-terminal A alpha chain regions in column effluents of CNBr-digested fibrinogen and crosslinked fibrin. When these immunoassays were used to study purified preparations of a high molecular weight, crosslink-containing CNBr derivative of a alpha polymer, the data provided immunologic confirmation for the involvement of CNBr VIII and CNBr X in alpha chain crosslinking.

Amino Acid Sequence↗
PubMed1982

The perception and discrimination of arterial pulsations: implications for the behavioral treatment of hypertension.

The perception and discrimination of target visceral responses may be important for the development and control of physiological functions such as blood pressure. Despite this, biofeedback blood pressure studies have almost exclusively used auditory or visual feedback. The present experiment employed psychophysical scaling procedures to investigate subject's ability to perceive and discriminate pulsatile sensations associated with change in the intensity of arterial pulsations. The perceived intensity of these pulsations vary as a function of the relationship between arterial pressure and applied cuff pressure. The results indicated that maximum intensity pulsations were perceived when occluding cuff pressure equalled mean arterial pressure and that the perceived intensity of pulsations decreased monotonically as cuff pressure was varied relative to this point in either the systolic or diastolic direction. Furthermore, the function relating cuff pressure oscillation amplitude to applied cuff pressure was the same as that obtained for perceived pulsation amplitude. The finding that subjects could accurately discriminate different intensities of pulsating sensations suggests the possibility of their being employed as an effective discriminative stimulus in a blood pressure biofeedback procedure.

Behavior Therapy↗
PubMed1982

Arginine and ornithine decarboxylases, the polyamine biosynthetic enzymes of mung bean seedlings.

General properties and relative activities of l-arginine decarboxylase (ADC) (EC 4.1.1.19) and l-ornithine decarboxylase (ODC) (EC 4.1.1.17), two important enzymes in putrescine and polyamine biosynthesis, were investigated in mung bean (Vigna radiata L.) tissues. Both activities increase linearly with increasing concentrations of crude enzyme, but the increase in ADC activity is considerably greater. The decarboxylation reaction is linear for up to 30 to 60 minutes, and both enzymes have a pH optimum of 7.2. alpha-Difluoromethyl-ornithine inhibits ODC activity of excised roots, while increasing ADC activity.High specific activity of both enzymes is detected in terminal buds and leaves, while root and hypocotyl activity is low. Different ADC-to-ODC activity ratios are found in various tissues of mung bean plants. Substantial increase in the activity of both enzymes is detected in incubated sections as compared with intact plants. A comparison of several plant species indicates a wide range of ADC-to-ODC activity ratio.It is suggested that both ADC and ODC are active in plant tissues and that their relative contribution to putrescine biosynthesis is dependent upon the type of tissue and growth process.

Journal Article↗
PubMed1982

Polyamines and root formation in mung bean hypocotyl cuttings : I. Effects of exogenous compounds and changes in endogenous polyamine content.

The effect of several polyamines (putrescine, spermidine, and spermine), their precursors (l-arginine and l-ornithine), and some analogs and metabolic inhibitors (l-canavanine, l-canaline, and methylglyoxal-bis [guanylhydrazone]) on root formation have been studied in mung bean (Vigna radiata [L.] Wilczek) hypocotyl cuttings.Exogenously applied polyamines did not promote adventitious root formation. Rooting was inhibited by l-canavanine and l-canaline, and this inhibition was reversed by the corresponding amino acids l-arginine and l-ornithine. Methylglyoxal-bis (guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase and polyamine biosynthesis, was also found to inhibit root formation. All compounds at concentrations of >10(-4) molarity completely inhibited natural root formation, whereas at <10(-5) molarity only the indole-butyric acid-induced root formation was inhibited.Indole-butyric acid-induced root formation was accompanied by a considerable increase in polyamine levels, more than 2-fold of the control. Whereas senescing (unrooted) cuttings evinced a rapid decline in polyamine content during 48 hours, indole-butyric acid treatment resulted in elevated levels of putrescine and increased putrescine to spermidine ratio. The changes in polyamines were dependent on indole-butyric acid concentration and were organ specific.

Journal Article↗
PubMed1982

Muscle phosphoglycerate mutase deficiency.

A 52-year-old man complained since adolescence of cramps and pigmenturia after 15 to 30 minutes of intense exercise. There was no family history of neuromuscular diseases, and strength was normal. The rise of venous lactate after forearm ischemic exercise was abnormally low. Histochemical and ultrastructural studies of a muscle biopsy showed mild increase of glycogen, which was confirmed by biochemical analysis. Studies of anaerobic glycolysis in vitro showed decrease lactate formation with glycogen and with all hexosephosphate glycolytic intermediates, suggesting a defect below the phosphofructokinase reaction. Muscle phosphoglycerate mutase (PGAM) activity was 5.7% of the lowest control, while all other enzymes of glycolysis had normal activities. Electrophoretic, heat lability, and mercury inhibition studies showed that the small residual activity of PGAM in the patient's muscle was represented by the brain (BB) isoenzyme, suggesting a genetic defect of the M subunit that predominates in normal muscle. The prevalence of the BB isoenzyme in other tissues, including muscle culture, may explain why symptoms were confined to muscle.

Adult↗
PubMed1982

Stimulus-secretion coupling in the human neutrophil: the role of phosphatidic acid and oxidized fatty acids in the translocation of calcium.

Neutrophils, stimulated via their surface receptors by ligands such as f-Met-Leu-Phe or immune complexes, release membrane calcium from intracellular stores and accumulate calcium from the extracellular medium. Both mechanisms provide for a rise in the intracellular concentration of free calcium which appears to be required for later responses of the cell: release of lysosomal enzymes and the generation of superoxide anion as neutrophils undergo an aggregation response. Exogenous ionophores, such as A23187 and PGBx, which move calcium bidirectionally across lipid bilayers, bypass the ligand-receptor step, thereby providing the necessary rise in intracellular calcium. In the course of the remodeling of membrane lipids--within 5 sec after their exposure to a stimulus--neutrophils generate phosphatidic acid, at least in part at the expense of phosphatidyl inositol. Because phosphatidic acid is the only phospholipid whose action in model membranes mimics the action of exogenous ionophores (as it is formed early enough and in sufficient quantities to account for uptake of extracellular calcium), we propose phosphatidic acid as a promising candidate for the role of endogenous ionophore. This ionophoretic action may serve to amplify signals launched by primary changes at the plasma membrane from whence calcium is mobilized during stimulus-secretion coupling. The release of oxidation products of arachidonic acid, be it via the cyclo-oxygenase or lipoxygenase pathway, is a concomitant of neutrophil activation. Indeed, the pathways by which oxidative products of arachidonate are formed may also be influenced by stimulus-specific changes in membrane phospholipids, not the least interesting of which is the generation of phosphatidic acid.

Arachidonate Lipoxygenases↗
PubMed1981

Human muscle phosphoglycerate mutase deficiency: newly discovered metabolic myopathy.

Muscle phosphoglycerate mutase activity was decreased (5.7 percent of the lowest control value) in a 52-year-old man with intolerance for strenuous exercise and recurrent pigmenturia since adolescence. All of the other enzymes of glycolysis had normal activities, and glycogen concentration was normal. Electrophoretic, heat lability, and mercury inhibition studies showed that the small residual activity in the patient's muscle was represented by the brain (BB) isoenzyme of phosphoglycerate mutase, suggesting a genetic defect of the M subunit which predominates in normal muscle. The prevalence of the BB isoenzyme in other tissues, including muscle culture, may explain why symptoms were confined to muscle.

Brain↗