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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 739 records · Page 41Linked to original sources

Experimental studies of blood brain barrier permeability in acute hepatic failure.

Permeability of the blood brain barrier in relation to the development of hepatic encephalopathy was investigated in two animal models of acute hepatic failure, in one of which there was the potential for recovery (D-galactosamine-induced hepatitis). In both this and the hepatic devascularization model, there was an approximate 3-fold increase in the passive permeability of the blood brain barrier to inulin and sucrose. Transport of amino acids was also significantly affected, with approximate 30% increases in the brain uptake of phenylalanine, tyrosine and arginine and a 65% increase in uptake of leucine. These changes are attributed to the action of circulating toxic substances, some of which increase blood brain barrier permeability in normal animals.

Amino Acids↗

Fear-potentiated startle: relationship to the level of state/trait anxiety in healthy subjects.

The startle reflex is potentiated during experimentally induced anxiety (fear-potentiated startle). It is also increased in various anxiety disorders. The present study investigated the relationship between individual differences in fear and anxiety, and startle modulation. The eyeblink component of the acoustic startle reflex was measured in a paradigm involving the anticipation of electric shocks in 22 healthy men who were volunteers. Each subject's fear of shock was assessed with the state portion of the State-Trait Anxiety Inventory (STAI; Spielberger 1983). Fear-potentiated startle, but not baseline startle, differed in the low and high fear subjects. The magnitude of fear-potentiated startle was larger in the high-fear group as compared to the low-fear group. The time-course of startle modulation suggested a longer duration of anticipatory anxiety in the high-fear group. Trait anxiety, which was assessed with the trait portion of the STAI, did not relate to individual differences in either baseline or fear-potentiated startle.

Adolescent↗

Effects of 6-hydroxydopamine and alpha-methyl-para-tyrosine on the acoustic startle response in rats.

The acoustic startle response was measured in rats after depletion of central catecholamines either chronically (through intraventricular injection of 6-hydroxydopamine) or acutely (through intraperitoneal injections of alpha-methyl-para-tyrosine). Chronic depletion resulted in an augmented startle response which could not be attributed to a failure of habituation or enhanced sensitization, while acute depletion depressed startle amplitude. The results were interpreted as evidence that catecholamines normally exert a facilitatory influence on the startle response and that the enhanced response seen in the chronically lesioned animal reflects the potentiation of the role of catecholamine-containing neurons through the development of denervation supersensitivity. This interpretation is consistent with other observations which suggest that catecholamines play a general role in modulating thresholds to aversive events.

Acoustic Stimulation↗

A method of direct chemical brain stimulation in behavioral studies using microiontophoresis.

A method of microiontophoresis for direct chemical brain stimulation in chronic, awake animals for behavioral studies is described. Carbachol-induced drinking was employed to test the method. Fluid-filled micropipettes (tip diameters: 5-15 mu) were stereotaxically implanted in the region of the nucleus of the diagonal band. Up to 3 weeks after recovery, ions could be ejected directly into the brain of awake animals by passing a direct current through the pipette. Iontophoretic ejection of carbachol in doses as low as 0.05 mug elicited drinking. This effect could be blocked by intraperitoneal injection of 0.5 mg/kg scopolamine. Passage of choline ions produced no detectable effect. The microiontophoretic technique allows direct chemical brain stimulation in chronic, awake animals without major changes in tonicity or volume that can occur with crystalline or fluid implants through cannulae. Additionally, the technique allows precise localization, precise control of dosage, and minimal damage at the site of stimulation.

Animals↗

Effects of lysergic acid diethylamide (LSD) on temporal recovery (pre-pulse inhibition) of the acoustic startle response in the rat.

In a series of 6 experiments 40 mug/kg d-lysergic acid diethylamide (LSD) augmented acoustic startle amplitude in rats when long intertone intervals (4, 8, 16, or 32 sec) were used but not when short interstimulus intervals were used (0.02, 0.1, 0.5, 1, or 2 sec). In contrast, 8 mg/kg d-amphetamine augmented startle when either long or short interstimulus intervals were used. The results suggest that LSD augments startle by accelerating the decay of pre-pulse inhibition (temporal recovery process) which may be one mechanism by which LSD can alter sensory processing.

Acoustic Stimulation↗

A new molecular form of PYY: structural characterization of human PYY(3-36) and PYY(1-36).

A radioimmunoassay was developed using an antibody raised in rabbits against synthetic porcine PYY. This radioimmunoassay was used to detect PYY immunoreactivity in human intestinal extracts. Human colonic mucosa was extracted with acid, centrifuged and the supernatant concentrated by low pressure preparative reverse phase chromatography. A subsequent C-18 reverse phase HPLC step separated two peaks of PYY immunoreactivity. Each peak was purified by sequential steps of ion-exchange FPLC and reverse phase HPLC. In the final purification step single absorbance peaks were associated with PYY immunoreactivity. Microsequence, amino acid, and mass spectral analysis of the intact and tryptic fragments of the two peptides were consistent with the structures: YPIKPEAPGEDASPEELNRYYASLRHYLNLVTRQRY-amide [human PYY(1-36)] and--IKPEAPGEDASPEELNRYYASLRHYLNLVTRQRY-amide [human PYY(3-36)]. Human PYY(1-36) differs from porcine PYY only at position 3, with Ile instead of Ala, and position 18, with Asn instead of Ser. PYY(3-36) may differ in its biological activity from the intact peptide. Its high proportions in the colon suggest that it is released into the circulation where it could act as a partial antagonist of PYY(1-36).

Amino Acid Sequence↗

Structural characterization of canine PYY.

PYY was purified from canine colonic mucosa by sequential steps of reverse phase HPLC and ion-exchange FPLC. Microsequence, amino acid and mass spectral analyses of the purified peptide and its tryptic fragments were consistent with the structure: YPAKPEAPGEDASPEELSRYYASLRHYLNLVTRQRY-amide. Canine PYY(1-36) has the identical sequence as porcine and rat PYY but differs from human PYY at position 3, with Ala instead of Ile, and position 18, with Ser instead of Asn. A smaller form, PYY(3-36), was also purified and characterized. It may differ in its biological activity from the intact peptide and could act as a partial antagonist or agonist of PYY(1-36).

Amino Acid Sequence↗

Application of Pavlovian higher-order conditioning to the analysis of the neural substrates of fear conditioning.

In Pavlovian first-order conditioning, a conditioned response is acquired by pairing a neutral stimulus (S1) with a stimulus that has innate motivational value. In higher-order conditioning, a neutral stimulus (S2) is paired with S1 either after (second-order conditioning) or before (sensory preconditioning) first-order conditioning has been acquired. Thus, in higher-order conditioning the motivational value of the reinforcer is acquired rather than innate. This review describes some of the potential uses of higher-order conditioning in investigating the neural substrates of fearful memories. First, because in second-order fear conditioning S2 is not paired directly with a painful stimulus, any effect of a treatment on the acquisition of fear cannot be attributed to the treatment's possible effects on transmission of nociceptive information. Second, higher-order conditioning provides opportunities for analyzing where and how different types of events, or different aspects of the same events, are represented in the brain.

Animals↗

Ogilvie's syndrome in the surgical patient: a new therapeutic modality.

Acute colonic pseudo-obstruction, Ogilvie's syndrome, most often appears as a complication of other clinical conditions. It is characterized by massive colonic dilation in the absence of a mechanical cause. Therapy for this condition has traditionally been colonoscopic decompression via a flexible colonoscope. We performed a retrospective study to assess the efficacy of Cystografin enema for colonic decompression in Ogilvie's syndrome. We present a series of 18 patients who developed Ogilvie's syndrome while hospitalized for trauma (n = 10), burn (n = 1), gastrointestinal surgery (n = 4), and hip replacement (n = 3). The mean pre-enema cecal size was 13 cm (range 10 to 15 cm). The mean postenema cecal size was 8.5 cm (range 6 to 15 cm). Fifteen of the 18 patients underwent Cystografin enema as the primary mode of decompression. Three had undergone prior colonoscopy, which had failed. One of the 18 patients required repeat enema for inadequate decompression after the first enema and one underwent colonoscopy for recurrence. Two patients underwent operative intervention after the enema. There were no complications related to the enema. In all patients we were able to rule out a mechanical cause of large bowel obstruction. We believe the safety, efficacy, and ease of this procedure make Cystografin enema optimal first-line treatment for acute colonic pseudo-obstruction.

Acute Disease↗