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Biomedical subjects

F Stewart

Publications and source records attributed to F Stewart.

At least 73 records · Page 4Linked to original sources
PubMed1993

Effects of fetal genotype and uterine environment on placental development in equids.

Measurement of the concentrations of equine chorionic gonadotrophin (eCG) in the serum of pregnant mares and Jenny donkeys carrying normal intraspecies and hybrid interspecies pregnancies suggested that the production of this hormone may be influenced by parental gene imprinting. Specifically, a differential expression of maternal and paternal genes may control the size and secretory activity of the structures that secrete eCG, the fetal endometrial cups. However, bisection of an interspecies mule embryo followed by transfer of the resulting demi-embryos and other intact mule embryos to horse and donkey recipients resulted in striking differences in the size, secretory activity and lifespan of the endometrial cups in two types of surrogate mother. This finding has therefore demonstrated the ability of uterine factors to alter profoundly the development and characteristic phenotype of the specialized invasive chorionic girdle portion of the equine trophoblast that gives rise to the endometrial cups.

Animals↗
PubMed1993

Growth hormone secretion in the horse: unusual pattern at birth and pulsatile secretion through to maturity.

A heterologous radioimmunoassay was developed and validated for the measurement of horse GH in plasma. It utilized recombinant-derived bovine GH as the radiolabelled ligand, a guinea-pig anti-porcine GH serum as first antibody and pituitary-derived horse GH as standard. Cross-reactivities were high with all of the pituitary and recombinant-derived GH preparations tested (49-140%) and very low (< 0.3%) with horse FSH, LH and prolactin. A synthetic analogue of GH-releasing factor(1-29) stimulated the expected pattern of GH release in foals. Plasma GH concentrations in foals were low at birth (< 20 ng/ml) but rose sharply to a definite and, in most cases, very large peak (18-195 ng/ml) during the first 30-40 min post partum, followed by a steady decline to basal levels again by 60-100 min post partum. GH secretion was clearly pulsatile in all older foals tested (2 weeks, 1 month and 4 months of age) and in six adults (three mares and three stallions), all bled at 15-min intervals for 7-8 h. Basal levels and pulse amplitudes were higher in foals than in adults and pulse frequency was higher in stallions than in mares (3-5 pulses/8 h vs 1-2 pulses/8 h). Pulsatile secretion was further characterized in one mare by simultaneous sampling of jugular vein and pituitary cavernous sinus blood. Peak GH concentrations in cavernous sinus blood draining the pituitary gland were more than tenfold higher than the corresponding peak concentrations in peripheral circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Should oral contraceptives be available without prescription?

In this paper, it is argued that oral contraceptives should be available without prescription. Prescription status entails heavy costs, including the dollar, time, and psychological costs of visiting a physician to obtain a prescription, the financial and human costs of unintended pregnancies that result from the obstacle to access caused by medicalization of oral contraceptives, and administrative costs to the health care system. After a review and evaluation of the reasons for strict medical control of oral contraceptives in the United States, safety concerns anticipated in response to the proposal discussed here are addressed. Also, concerns that prescription status is necessary for efficacious use are evaluated. It is concluded that neither safety nor efficacy considerations justify prescription status for oral contraceptives. Revised package design and patient labeling could allow women to screen themselves for contraindications, to educate themselves about danger signs, and to use oral contraceptives safely and successfully. Several alternatives to providing oral contraceptives by prescription with current package design and labeling and selling them over the counter are suggested; the proposals discussed would make these safe and effective contraceptives easier to obtain and to use.

Contraceptives, Oral↗
PubMed1992

Structure of tropomyosin at 9 angstroms resolution.

We have used molecular replacement followed by a highly parameterized refinement to determine the structure of tropomyosin crystals to a resolution to 9 A. The shape, coiled-coil structure and interactions of the molecules in the crystals have been determined. These crystals have C2 symmetry with a = 259.7 A, b = 55.3 A, c = 135.6 A and beta = 97.2 degrees. Because of the unusual distribution of intensity in X-ray diffraction patterns from these crystals, it was possible to solve the rotation problem by inspection of qualitative aspects of the diffraction data and to define unequivocally the general alignment of the molecules along the (332) and (3-32) directions of the unit cell. The translation function was then solved by a direct search procedure, while electron microscopy of a related crystal form indicated the probable location of molecular ends in the asymmetric unit, as well as the anti-parallel arrangement. The structural model we have obtained is much clearer than that obtained previously with crystals of extraordinarily high solvent content and shows the two alpha-helices of the coiled coil over most of the length of the molecules and establishes the coiled-coil pitch at 140(+/- 10) A. Moreover, the precise value of the coiled-coil pitch varies along the molecule, probably in response to local variations in the amino acid sequence, which we have determined by sequencing the appropriate cDNA. The crystals are constructed from layers of tropomyosin filaments. There are two molecules in the crystallographic asymmetric unit and the molecules within a layer are bent into an approximately sinusoidal profile. Molecules in consecutive layers in the crystal lie at an angle relative to one another as found in crystalline arrays of actin and myosin rod. There are three classes of interactions between tropomyosin molecules in the spermine-induced crystals and these give some insights into the molecular interactions between coiled-coil molecules that may have implications for assemblies such as muscle thick filaments and intermediate filaments. In interactions within a layer, the geometry of coiled-coil contacts is retained, whereas in contacts between molecules in adjacent layers the coiled-coil geometry varies and these interactions instead appear to be dominated by the repeating pattern of charged zones along the molecule.

Amino Acid Sequence↗
PubMed1992

A pilot study of photodynamic therapy in patients with inoperable non-small cell lung cancer.

26 patients with inoperable non-small cell lung cancer (NSCLC) were treated with photodynamic therapy (PDT) with intravenous Photofrin II 2 mg/kg. 10 out of 11 stage I patients achieved a complete response. The remaining patient, and 11 out of 15 stage III patients had a partial response. No response was seen in 4 patients, 2 of whom had inadequate illumination. Thus, the objective response rate was 85% (22/26). Although lung function did not improve, dyspnoea was ameliorated in 7 (58%) of the partial responders. 4 stage III patients had tumour progression and died of pulmonary haemorrhages 1.5-6 months after PDT. All had received external irradiation, Nd-YAG laser and/or brachytherapy before PDT. 4 patients had grade I-II skin photosensitivity. Although of value in stage I NSCLC, the clinical benefit of PDT in stage III disease was small.

Aged↗
PubMed1992

Naming impairments following recovery from herpes simplex encephalitis: category-specific?

An apparently clear case of category-specific naming impairment selectively affecting animals was detected in a patient who had recovered from herpes simplex encephalitis. However, subsequent investigation demonstrated that these category-specific effects could be eliminated by controlling simultaneously for three factors in picture naming: word frequency, concept familiarity, and visual complexity. The results emphasize the importance of controlling for all factors pertinent to picture naming when attempting to demonstrate category specificity in picture naming. Further testing indicated that deficits were also apparent when naming to definition was required, and some impairment in the ability to answer questions about objects and living things was also noted. Theoretical implications of these data are considered.

Anomia↗
PubMed1991

Cloning the cDNA for horse growth hormone and expression in Escherichia coli.

A 514 bp cDNA transcript coding for 78% of horse (Equus caballus.) GH has been cloned and sequenced. The deduced amino acid sequence corresponded precisely to that previously obtained by protein sequencing and, in addition, provided new sequence information for the signal peptide. The missing 3' fragment of the cDNA was reconstructed using synthetic oligonucleotides and site-specific directed mutagenesis. The complete cDNA sequence was then inserted into an expression vector (PIN-III-lppp-5) which utilizes a bacterial signal peptide to secrete the expressed product into the periplasmic space of Escherichia coli. Western blot analysis of cell lysates and periplasmic fractions prepared from cells harbouring this construct revealed significant quantities of immunoreactive GH and indicated that the bacterial signal peptide was successfully cleaved from the fusion protein on secretion. Recombinant-derived horse GH, recovered by osmotic shock from the periplasm, was active in a heterologous radioimmunoassay and a horse liver radioreceptor assay and resulted in a recovery of 0.5-2 mg GH/l cell culture. An apparent limitation on the secretion rate of horse GH in E. coli, possibly involving a block to translocation across the cytoplasmic membrane, prevented higher levels of expression being obtained.

Amino Acid Sequence↗
PubMed1991

Analysis of horse and donkey gonadotrophin genes using Southern blotting and DNA hybridization techniques.

The number of genes encoding the common alpha-subunit and hormone-specific beta-subunits of the equine gonadotrophins (FSH, LH and CG) were investigated in the horse (Equus caballus), donkey (E. asinus) and 2 horse x donkey hybrids (the mule and hinny). The Southern technique, involving restriction enzyme digestion, blotting and DNA hybridization to 32P-labelled DNA probes was used to estimate the copy number for each gene and to assess the extent to which equids resemble primates, the only other animals that secrete a CG during pregnancy. These methods indicated that, in common with mammals, there was a single copy of the equine gonadotrophin alpha-and FSH beta-subunit genes. Also in common with other mammals, our results are consistent with there being a single LH beta-subunit gene but, unlike primates, no evidence of multiple LH/CG beta-subunit genes was obtained. There was no restriction fragment length polymorphism (RFLP) within species using the 4 enzymes chosen for this study, but the RFLP pattern for the beta-subunit genes differed between species, giving rise to species-specific 'fingerprints'. The mule and hinny Southern blots showed a combination of the horse and donkey fingerprints, consistent with the presence of both genomes in these hybrids and consistent with the expression of both horse and donkey CG by hybrid conceptuses. In man and baboons, multiple genes code for the beta-subunit as a consequence of LH beta-subunit gene duplication.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The behavioral medicine service. An administrative model for biopsychosocial medical care, teaching, and research.

The biopsychosocial model has been promoted for its advantages in many important health problems. However, the lack of administrative practice models specifically designed to develop and promote the model hinder the development of systematic clinical applications. This article describes a successful clinical teaching and research practice, The Behavioral Medicine Service, that was conceptualized and developed based on the biopsychosocial model. Systematic planning enabled the service to take advantage of clinical, research, and teaching opportunities and to reduce the constraints imposed on development from within psychiatry and the institution. Advantages of the organizational model include multidisciplinary treatment teams, a systematic method of biopsychosocial assessment and management planning, and continuity of care between several settings: the medical-surgical wards of a general hospital; a behavioral medicine inpatient unit; and outpatient subspecialty clinics for chronic pain, chronic medical illness, anxiety and stress-related disorders, and drug and alcohol abuse. The Human Behavioral Pharmacology Laboratory forms the research arm of the service. Referrals of a diversity of medical and psychiatric problems create a unique learning opportunity for residents. Billing for multimodal team treatment, training residents, establishing clinical research, and managing a plethora of referrals were developmental challenges addressed by the service.

Behavioral Medicine↗
PubMed1990

Partial cDNA sequence for the donkey chorionic gonadotrophin-beta subunit suggests evolution from an ancestral LH-beta gene.

A 246 bp cDNA clone representing the C-terminal region of the donkey (Equus asinus) chorionic gonadotrophin (CG)-beta subunit was isolated from a placental library. The transcript contained the 3' untranslated region and 42% of the CG-beta subunit coding region (amino acid residues 85-146 of the mature peptide). Comparison of the deduced donkey amino acid sequence with the published horse CG-beta subunit protein sequence (where they overlapped) revealed an overall homology of 61%. However, most of the differences were in the C-terminal extension, which is thought not to be important for gonadotrophic activity, and appeared to be due to two nucleotide insertions in the donkey sequence (compared with a deduced horse nucleotide sequence) leading to a reading-frame shift. Amino acid homology in the disulphide 'core' region was 81%. Some of the differences in this region were in the 'determinant loop' (residues 93-100) and these are interpreted in relation to the observed biological activities of horse and donkey CG. The deduced amino acid sequence of the donkey cDNA indicated that it was larger than the majority of gonadotrophin-beta subunits due to a C-terminal extension. Primate and horse CG (and horse LH) beta subunits have analogous C-terminal extensions. The extension in the donkey subunit is 25 amino acid residues in length, compared with 28 in the horse and 24 in man. Comparisons with other available subunit DNA sequences indicated that, like the human CG-beta gene, the donkey gene probably evolved from an ancestral LH-like beta gene, following nucleotide deletions that allowed readthrough into previously untranslated DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1989

Glucocorticoid- and progesterone-specific effects are determined by differential expression of the respective hormone receptors.

Although glucocorticoids and progestins control vastly different physiological processes, the receptors mediating the effects of these hormones interact with the same DNA sequences. Transfer experiments involving synthetic genes and in vitro binding studies have shown that progesterone and glucocorticoid receptors both recognize the same 15-base pair DNA element (TGTACAGGATGTTCT), raising the question of how the two steroids affect gene expression selectively. We considered the possibility that their selectivity arises from either the differential expression of the receptors in target cells or the differential dependence of receptor function on additional transcription factors. To test these alternatives we introduced a progesterone-receptor expression plasmid into the rat hepatoma cell line Fto2B-3 which contains glucocorticoid receptor but is devoid of progesterone receptor. We report that expression of the progesterone receptor in Fto2B-3 cells renders endogenous glucocorticoid-regulated genes inducible by progestins. Our data show that the responsiveness of a cell to external stimuli can be reprogrammed by the expression of a single transcription factor and that differential expression of hormone receptors is at least one mechanism by which steroid-specific gene activation is achieved.

Animals↗
PubMed1989

Comparison of ascites production for monoclonal antibodies in BALB/c and BALB/c-derived cross-bred mice.

BALB/c male mice were mated with either Swiss-Webster or MF1 females to produce first generation cross-bred offspring. Hybridoma cell lines, from the fusion of P3-NS1-Ag4/1 myeloma cells with spleen cells sensitised to the porcine coronavirus causing transmissible gastroenteritis, were injected intraperitoneally into these mice to produce ascitic fluid containing monoclonal antibodies. Mice of 11 weeks of age weighing between 26 and 34 g were used. The volume of ascites produced by mice injected with four of the five hybrid cell lines tested was greater in the cross-bred offspring than in the BALB/c parent. The fifth cell line gave comparable volumes in the MF1 cross-breed and BALB/c parent but a lesser volume in the Swiss-Webster cross-breed. The antibody titres of the ascites as determined by virus neutralisation, radioimmune and indirect immune fluorescence assays, did not differ significantly between mouse types. The ability to use all offspring from a litter of cross-bred mice, irrespective of sex, and the increased volume of ascitic fluid formed in each mouse, permits fewer animals to be used for the production of ascites in these strains, thereby offering considerable economic and ethical advantages over the use of BALB/c mice.

Animals↗
PubMed1989

The polypeptide of Mr 14,000 of porcine transmissible gastroenteritis virus: gene assignment and intracellular location.

Synthetic oligopeptides, corresponding to an amino acid sequence encoded by a potential Mr 9000 product's open reading frame (ORF-4) at the 3' terminus of the transmissible gastroenteritis virus genome, were used to generate rabbit antiserum. These antibodies produced immune complexes with an Mr 14,000 (14K) polypeptide in infected cells. The 14K product was shown by immune fluorescence to become associated with the cell nucleus, correlating with the onset of nuclear vacuolation, and suggesting a role in pathogenesis for the ORF-4 gene.

Amino Acid Sequence↗