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Biomedical subjects

G R Hillman

Publications and source records attributed to G R Hillman.

At least 19 recordsLinked to original sources
PubMed1991

Simulated scaphoid proximal pole fracture.

Five fresh cadaver upper extremities were studied with use of a static positioning frame, pressure-sensitive film, a microcomputer-based videodigitizing system, and a Sun station image analysis system to assess the load bearing characteristics of the scaphoid in the proximal carpal joint. Specimens were studied in their normal condition, after a proximal pole osteotomy of the scaphoid, and after resection of the proximal pole of the scaphoid. The amount of contact area born through the scaphoid fossa was essentially the same whether the scaphoid was intact, or after a simulated scaphoid fracture of its proximal pole, or after resection of the proximal pole. The scaphoid contact area and pressure, although overall relatively constant, was redistributed after osteotomy, resulting in increased contact area under the distal fragment and no change or a slight decrease in the contact area under the proximal fragment of the scaphoid. After resection of the proximal fragment, all scaphoid contact area and pressure was born by the distal scaphoid fragment. The contact area and pressure characteristics of the lunate remained unchanged in all conditions compared with the normal condition. There were no significant changes in the locations of the centroids of the scaphoid segments and the lunate in any of the conditions tested.

Adult↗
PubMed1990

Magnetic resonance imaging and neuropsychological findings in human immunodeficiency virus infection.

Neurobehavioral functioning and magnetic resonance imaging (MRI) were investigated in 25 patients with various Centers for Disease Control (CDC) stages of human immunodeficiency virus (HIV) infection and in a control group of seven normal subjects. Unequivocal slowing of information processing speed and cerebral atrophy were related to the stage of HIV infection, with patients in CDC group IV exhibiting the most abnormal findings. Slowing of response speed was directly related to the severity of cerebral atrophy.

Adult↗
PubMed1987

Differential effects of p-chlorophenylalanine on indoleamines in brainstem nuclei and spinal cord of rats. II. Identification of immunohistochemically stained structures using computer-assisted image enhancement techniques.

Following intraperitoneal injection of p-chlorophenylalanine (PCPA, 400 and 600 mg/kg) on 3 consecutive days, the brainstem and lumbar cord of rats were removed, frozen-sectioned and immunohistochemically stained (PAP method) for serotonin (5-HT). Using computer-assisted image analysis, the density of 5-HT staining in control, 400 and 600 mg/kg PCPA groups was determined. The mean number of pixels (representing 5-HT staining) was determined in 6 areas in the brainstem containing 5-HT cell bodies (nuclei raphe pallidus, raphe obscurus, rostral and caudal raphe magnus, raphe dorsalis and paragigantocellularis lateralis) and in the dorsal and ventral spinal cord. The results suggest a differential depletion of 5-HT within brainstem nuclei following PCPA treatment in that the most marked dose-related reductions were observed in nucleus raphe obscurus and caudal nucleus raphe magnus. Furthermore, a computer program designed to isolate terminal structures in the spinal cord identified a differential depletion of 5-HT terminals in the dorsal horn versus the ventral horn. The present study describes 3 analytical approaches combining immunohistochemistry with the computer-assisted image analysis technique and allows comparison between groups of animals which received the same or different drug treatments.

Animals↗
PubMed1986

Two-dimensional and three-dimensional movement of human polymorphonuclear leukocytes: two fundamentally different mechanisms of locomotion [corrected].

Patients with an inherited deficiency of the adherence glycoproteins LFA-1, Mac-1, and p150,95 are unable to mobilize polymorphonuclear leukocytes (PMNLs) to peripheral sites of inflammation. LFA-1/Mac-1/p150,95-deficient PMNL exhibited profoundly impaired movement stimulated by chemotactic factors when the cells were required to move over two-dimensional surfaces. Less impairment of movement was demonstrated in three-dimensional movement through cellulose filters. A possible explanation for this difference in cell translational mobility is that movement in cellulose filters is less adherence dependent than movement over a two-dimensional plastic surface. Movement of PMNL in collagen gels is known to be relatively independent of adherence. No deficiency of translational mobility of PMNL from LFA-1/Mac-1/p150,95-deficient patients was observed in collagen gels. Antibodies against the common beta subunit effectively blocked two-dimensional movement but had little effect on three-dimensional movement through cellulose filters or collagen gel matrices. HL-60 cells were employed as a model to investigate the effects of adherence on cell movement. Treatment of HL-60 cells with phorbol myristate acetate resulted in the appearance of Mac-1 and p150,95 on the cell surface. Concurrently, the cells exhibited increased adherence to glass and plastic. In spite of increased adherence, HL-60 cells showed no translational movement, indicating factors other than the ability to adhere were important in cell motility. These experiments implied that PMNLs undergo two fundamentally different kinds of motion, one adherence dependent (two-dimensional movement) and the other largely adherence independent (three-dimensional movement). These findings are consistent with the view that egress of PMNLs from the vascular space is adherence dependent. Movement through extravascular tissues may be adherence independent.

Antigens, Surface↗
PubMed1978

Scanning microfluorimetric studies of anticholinergic drugs in Schistosoma mansoni.

A microfluorimetric technique has been used to analyze fluorescence in specimens of Schistosoma mansoni labeled with a dansylated analog of acetylcholine. Anticholinergic drugs inhibit the fluorescent labeling of living specimens. The effectiveness of anticholinergic agents can be expressed as a fractional decrease in observed fluorescence of specimens, and several drugs have been compared in this context. Atropine, eserine, carbachol and mecamylamine block fluorescence only at high concentrations (10(-4)--10(-3) M) while trifluoperazine and hycanthone block strongly at lower concentrations (10(-5) M). The findings reported here suggest that the relative activity of anticholinergic drugs is different in schistosomes and vertebrates.

Animals↗
PubMed1977

Comparative effects of hycanthone in Schistosoma mansoni and Schistosoma japonicum.

After in vitro hycanthone treatment followed by a 20-hour incubation in drug-free medium, Schistosoma mansoni were still resistant to labeling by a fluorescent analog of acetylcholine. S. japonicum, in contrast with the hycanthone sensitive species, showed prompt reversal of the blocking effects of hycanthone on fluorescent labeling. This finding suggests that differences in the reversibility of hycanthone may correlate with the usefulness of the drug in the therapy of schistosome infections by different species of parasites. Scanning electron microscopy has been used to demonstrate that hycanthone treatment causes degeneration of the integument of S. mansoni, but not S. japonicum, over a period of few days after in vivo exposure to hycanthone. The mechanism by which hycanthone causes this effect is not known.

Acetylcholine↗
PubMed1976

Influence of hycanthone on morphology and serotonin uptake of Schistosome mansoni.

The intrinsic content of serotonin (5HT) and the uptake of 5HT by Schistosoma mansoni taken from mice which were given a single intramuscular therapeutic dose of hycanthone were studied. Drug-exposed worms were found to have intrinsic values of 5HT which were similar or slightly less than controls. Uptake measurements were made on single and on paired worms recovered from mesenteric, portal, or hepatic sites and incubated in 75% horse serum or in Fischer's medium. All groups of treated worms were found to take up, on average, similar or lower amounts of 5HT compared to controls. These findings are in contrast to a recent report of very considerable increases in content or in 5HT acquisition in vitro by hycanthone-exposed parasites. This communication suggests that the mode of action of hycanthone cannot be explained as being due to increased 5HT uptake. Morphological changes in hycanthone-treated worms include loss of body weight and size, loss of hemoglobin pigment from the gut, deterioration of the tegument, and derangement of the vitellaria. The loss of gut contents occurs early after exposure to hycanthone and may indicate that interference with gut physiology and the nutritional state of the worms is one consequence of the drug, although the mechanism of these changes has not yet been elucidated.

Animals↗
PubMed1975

Anticholinergic properties of the antischistosomal drug hycanthone.

The effect of the antischistosomal drug hycanthone on the motor activity of Schistosoma mansoni was studied in vitro. Hycanthone stimulates motor activity at concentrations of 10(-6) to 10(-5) M, and partially blocks the paralytic effects of carbachol and physostigmine. Lucanthone, a closely related although less active congener of hycanthone, does not produce these same effects in vitro. Some blocking of acetylcholine can also be produced by atropine, although this drug is less active in this regard than is hycanthone. These findings suggest that the therapeutic efficacy of hycanthone may be related to interference with acetylcholine receptors in schistosomes. Hycanthone is an inhibitor of acetylcholinesterase (ACHE) from S. mansoni, but is less effective against ACHE of mammalian origin. In contrast, physostigmine inhibits the mammalian enzyme more effectively than it does the helminth enzyme. These observations suggest that schistosome ACHE differs from the mammalian enzyme with respect to the configuration of the active center, and that hycanthone may have a selective affinity for schistosomal cholinergic systems.

Animals↗