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Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 883 records · Page 49Linked to original sources

Correlation of differentiation state and silver staining of nucleolar organizers in the promyelocytic leukemia cell line HL-60.

We have applied nucleolar organizer region (NOR) silver staining to the promyelocytic leukemia cell line HL-60, before and after dimethylsulfoxide (DMSO) mediated differentiation. The results demonstrated a gradual suppression of rDNA transcription during terminal maturation of these bone-marrow-derived cells and support our hypothesis that there are characteristic NOR staining profiles for different bone marrow cell types.

Cell Cycle↗

Expression of canine parvovirus-beta-galactosidase fusion proteins in Escherichia coli.

Cloned DNA fragments encoding portions of canine parvovirus (CPV) structural proteins were inserted into plasmid expression vectors. These plasmids expressed CPV-beta-galactosidase fusion proteins under the transcriptional control of the Escherichia coli lac promoter-operator. The fusion proteins were purified and used to immunize rabbits. Rabbit antibodies raised against these fusion proteins were shown to immunoprecipitate authentic CPV structural proteins from infected cell extracts. This demonstrated that the CPV-beta-galactosidase fusion proteins expressed in bacteria elicit antibodies which can recognize determinants of authentic CPV proteins. However, none of the antibodies neutralizes CPV virus particles.

Animals↗

Conformationally restricted retinoids.

A series of conformationally restricted retinoids was synthesized and screened in two assays used to measure the ability of retinoids to control cell differentiation, namely, the reversal of keratinization in tracheal organ culture from vitamin A deficient hamsters and the inhibition of the induction of mouse epidermal ornithine decarboxylase by a tumor promoter. These compounds had bonds corresponding to selected bonds of the E-tetraene chain of retinoic acid (1) held in a planar cisoid conformation by inclusion in an aromatic ring. The meta-substituted analogue 3 of 4-[(E)-2-methyl-4-(2,6,6-trimethylcyclohexenyl)-1,3-butadienyl+ ++]benzoic acid (2) was far less active than 2 in both assays. In contrast, the vinyl homologue of 2 (4) and the 7,8-dihydro and 7,8-methano analogues (5 and 6) had activity comparable to that of 2. Analogues of 4-[(E)-2-(1,1,4,4-tetramethyl-1,2,3,4-tetrahydro-6-naphthyl)propenyl] benzoic acid (7) were also screened. Replacement of the tetrahydronaphthalene ring of 7 by a benzonorbornenyl group (9) significantly reduced activity, as did removal of the vinylic methyl group from 9 (10). Replacement of the propenyl group of 9 by a cyclopropane ring (12) also reduced activity. Replacement of the tetrahydronaphthalene ring of 7 by 4,4-dimethyl-3,4-dihydro-2H-1-benzopyran and -benzothiopyran rings (13 and 14) also decreased activity. Inclusion of the 7,9 double bond system of 1 in an aromatic ring (15 and 16) reduced activity, whereas inclusion of the 5,7 double bond system in an aromatic ring enhanced activity (7 and 19). Inclusion of the 11,13 and 9,11,13 double bond systems in aromatic rings (2 and 18) also reduced activity below that of 1. Retinoic acid, 7, 13, 14, and 19 inhibited papilloma tumor formation in mice. Toxicity testing indicated that 7 was more toxic than 1, 13, 14, and 19, 19 was more toxic than 1, and 13 and 14 were less toxic than 1.

Animals↗

Stroop interference based on the synaesthetic qualities of auditory pitch.

The equivalence of perceptual experience across the sensory modalities, most vividly observed in synaesthetes, is rarely discussed in contemporary cognitive psychology. It is suggested, however, that the concepts and paradigms of human information processing are ideally suited to test, for example, the fundamental assumption that the synaesthetic qualities of a stimulus are rapidly and automatically encoded. In a preliminary experiment subjects were asked to rate each of four auditory tones on a series of 7-point scales defined by pairs of antonyms. The results confirmed that a pure auditory tone has a range of qualities, determined by its pitch, that are shared by stimuli in other modalities. The main experiment used a paradigm based on the Stoop interference effect. Here the 50 Hz and 5500 Hz tones served as incidental stimuli and the subjects were required to respond as quickly as possible by pressing one of two keys depending on which one of four possible words appeared in the centre of the screen. Subjects were found to respond more slowly when the qualities of the tone were incongruent with the synaesthetic qualities represented by the test word. The results confirm that synaesthetic qualities of pitch are rapidly and automatically encoded and that the products of this encoding automatically interact with the mechanisms responsible for identifying word meaning and/or with the post-identification decision processes.

Concept Formation↗

Thioesterase II, a new marker enzyme for human cells of breast epithelial origin.

Metabolic, enzymologic, and immunohistochemical techniques have been used to show that a human cell line of breast epithelial origin synthesized medium chain fatty acids via the ubiquitous fatty acid synthetase and a mammary-specific chain-terminating enzyme, thioesterase II. Previous studies in our laboratory with rodents indicated that thioesterase II is expressed exclusively in mammary epithelial cells, an observation consistent with the physiologic role of the enzyme in milk fat synthesis. Results of the present study suggest that the enzyme exhibits a similar cell specificity in its expression in humans and that the specificity is maintained in normal and neoplastic tissues. Thus thioesterase II was detected immunohistochemically in normal human breast epithelia derived from both lactating and nonlactating breast tissue, in cultured cells derived from both primary breast epithelial tumors and from a metastatic tumor of breast origin, and in several human breast epithelial cell lines; the enzyme could not be detected in HeLa cells, in a colon carcinoma, or in a mammary myoepithelial cell line. These findings raise the possibility that thioesterase II may be of use as a diagnostic tool to identify human tumors of breast epithelial origin.

Adolescent↗

Suppression of spermatogenesis by testosterone in adult male rats: effect on fertility, pregnancy outcome and progeny.

The relationship between decreasing spermatogenic activity and fertility, pregnancy outcome and the progeny is poorly understood. To study this relationship a model where testosterone is given by a sustained release device is used. Adult male Sprague-Dawley rats received empty or testosterone-filled implants measuring 0.5, 1.0, 2.0, 3.0, 4.0 and 8.0 cm. On Day 90 and again on Day 104 each male was exposed to two females in proestrus. Twenty days later the females were killed. Corpora lutea, implantation sites, resorptions and live normal and abnormal fetuses were counted. Sperm counts in the caput-corpus region of the epididymis in the 3.0-, 4.0- and 8.0-cm testosterone treatment groups were 12.6%, 3.0% and 29.9% of control, while those in the caudal region were 19.8%, 4.0% and 50.8% of control, respectively. The number of females with spermatozoa in the vagina after breeding was significantly diminished only in animals treated with the 4.0-cm testosterone implants (control, 95.8%; 4.0-cm, 50%) while the number of pregnant females per sperm-positive females was markedly reduced in the females mated with both the 3.0-cm and 4.0-cm testosterone implants (control, 82.6%; 3.0-cm, 10.0%; 4.0-cm, 7.7%). There was no effect on the numbers of corpora lutea, on the incidence of pre- or post-implantation loss, malformations, or on the numbers of pups/litter. Individual animals with a decrease in caudal epididymal spermatozoal reserves to less than 5 million, however, are infertile. A decrease in epididymal spermatozoal reserves mediated by testosterone does not cause an increase in teratogenicity in the resultant progeny.

Animals↗

Injectable ibuprofen: preliminary evaluation of its ability to decrease peritendinous adhesions.

Peritendinous adhesions continue to limit the full return of hand function following flexor tendon injury and repair. Pilot studies in rabbits demonstrated the ability of ibuprofen (Motrin) to reduce intra-abdominal adhesions. In this study, ibuprofen injected at the site of flexor tendon repair significantly reduced the restrictive effects of peritendinous adhesions in primates.

Animals↗

Testosterone, erythropoietin and anaemia in patients with disseminated bronchial cancer.

In 21 newly diagnosed male patients with disseminated bronchial cancer, anaemia was associated with a reduced serum concentration of testosterone. Erythropoietin levels were increased in anaemic patients. The results suggest a normal erythropoietin response to anaemia in this condition. The reduced testosterone concentration is associated with normal levels of luteinizing hormone and its significance in the pathogenesis of the anaemia is uncertain.

Adult↗

Early development of an infant with 18q- syndrome.

The early intellectual and psychological development of an infant with 18q- syndrome is described. In this syndrome, which is a rare chromosomal disorder, there is a deletion of a portion of the long arm of chromosome 18. The few previously published accounts have indicated a varying degree of intellectual retardation. This child proved to be moderately delayed only and her development over the first 24 months of age is described in some detail. The family was receiving an intensive home advisory service offered to help maximize the development of pre-school handicapped infants in the area, and it is suggested that in general terms this particular disorder is not remarkably different in respect of psychological prognosis from the more common Down's syndrome, involving trisomy 21, and shows an equally favourable response to such a service. The peculiar appearance of such infants may, however, pose particular problems of parental adjustment.

Abnormalities, Multiple↗

Splenic siderosis and parenteral iron dextran in maintenance haemodialysis patients.

The histological features of 40 spleens surgically removed from maintenance haemodialysis patients are reported. Twenty-four of the 40 (60%) showed massive iron loading and a significant direct correlation was found between iron loading and the amount of intravenous iron dextran administered. Since parenteral iron dextran appears to be a major factor in causing iron overload in haemodialysis patients its use as a method of iron replacement in these patients would appear inappropriate.

Blood Transfusion↗

Low molecular mass bronchial proteinase inhibitor and alpha 1-proteinase inhibitor in sputum and bronchoalveolar lavage.

The concentration of a low molecular mass bronchial mucus inhibitor of proteolytic enzymes (BMPI) was measured in lung secretions from patients with chronic bronchitis and compared to the concentrations of albumin and alpha 1-proteinase inhibitor (alpha 1-PI). The concentration of all three proteins was lower in bronchoalveolar lavage samples than in sputum obtained from the same patient. However the relationship between the proteins (concentrations relative to each other) was similar in both secretions suggesting the differences in concentrations were only dilutional. The molar concentration of BMPI in both secretions was generally greater than that of alpha 1-PI suggesting that most of the anti-elastase screen (congruent to 75%) was due to the former protein. Furthermore inhibitory studies using both purified leukocyte elastase and porcine pancreatic elastase show that the inhibitory capacity of lung alpha 1-PI varied and accounted for about 16% of the total inhibition of leukocyte elastase in sputum. However, the inhibitory function of alpha 1-PI was less in bronchoalveolar lavage fluids compared to sputum (p less than 0.05) and accounted for about 5% of the total inhibitory capacity for leukocyte elastase. It is concluded that alpha 1-PI contributes only a part of the anti-elastase screen of secretions from patients with chronic bronchitis. Furthermore it is inactivated to a varying degree in most secretions and its remaining inhibitory capacity represents only a minor proportion of the total inhibitory capacity.

Aged↗

Optimization of assay conditions in monoclonal-based immunoradiometric assay.

The production of relatively large amounts of pure monoclonal antibodies (MAb) has facilitated the development of MAb-based immunometric assays for a variety of clinically important analytes. 'Two-site' heterogeneous assays are now available which incorporate a labelled MAb and a second, different MAb coupled to a solid support. These assays possess certain advantages over the corresponding immunoassays including speed, precision, working range and specificity. They are largely dependent on two specific molecular interactions (labelled MAb-antigen; antigen--solid support MAb) and thus one might expect them to be particularly sensitive to assay conditions. With reference to two MAb--based two-site immunoradiometric assays (for human growth hormone and prolactin) which are being developed in this laboratory we wish to report the effect of various conditions including pH, ionic strength, buffer species etc. on assay response in order to emphasize the need for careful optimisation of monoclonal antibody based assays.

Animals↗