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Biomedical subjects

F Stewart

Publications and source records attributed to F Stewart.

At least 91 records · Page 5Linked to original sources
PubMed1988

Bladder damage in mice after combined treatment with cyclophosphamide and X-rays. The influence of timing and sequence.

The response of the mouse bladder to single doses of cyclophosphamide (CY), X-rays, or their combination was assessed from the development of functional damage (haematuria and increased frequency of urination). For the combined treatments, a single dose of CY (100 mg.kg-1) was given immediately before or at intervals of up to 9 months before irradiation, or at one week to 9 months after irradiation. Damage after X-rays alone was expressed late, with no functional changes earlier than 5 months. CY alone, by contrast, caused a marked increase in urination frequency and haematuria within one week. There was subsequently partial recovery although some residual damage persisted for at least one year. CY given before or after X-rays caused an early, X-ray dose-related expression of damage. These results suggest that the drug precipitated some of the latent radiation injury. There was also a second wave of damage after the combined treatments and the response at 9-12 months was always more severe than after X-rays alone. This increased late damage could be explained in terms of additive drug and radiation toxicities. Since drug given up to 9 months before or after irradiation caused more severe bladder damage than X-rays alone, CY should be avoided in clinical situations where the bladder has been irradiated.

Animals↗
PubMed1987

Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene.

Two glucocorticoid response elements (GREs) located 2.5 kb upstream of the transcription initiation site of the tyrosine aminotransferase gene were identified by gene transfer experiments and shown to bind to purified glucocorticoid receptor. Although the proximal GRE has no inherent capacity by itself to stimulate transcription, when present in conjunction with the distal GRE, this element synergistically enhances glucocorticoid induction of gene expression. Cooperativity of the two GREs is maintained when they are transposed upstream of a heterologous promoter. An oligonucleotide of 22 bp representing the distal GRE is sufficient to confer glucocorticoid inducibility. As evidenced by the mapping of DNAase I hypersensitive sites, local alterations in the structure of chromatin at the GREs take place as a consequence of hormonal treatment.

Base Sequence↗
PubMed1987

Nucleotide (cDNA) sequence encoding the horse gonadotrophin alpha-subunit.

Several cDNA clones corresponding to mRNA for the alpha-subunit of the horse (Equus caballus) pituitary and placental (chorionic) gonadotrophic hormones have been isolated and sequenced. Polyadenylated mRNA was purified from horse pituitary glands (the source of FSH and LH) and horse placental tissues (the source of chorionic gonadotrophin; CG). The mRNA preparations were characterized by in-vitro translation and Northern hybridization techniques using human and ovine gonadotrophin cDNA clones as probes. Complementary DNA libraries were created from the pituitary and placental mRNAs and a human CG alpha-subunit probe was used to isolate several horse alpha-subunit cDNA clones. The alpha-subunit nucleotide sequence from both sources of tissue was identical, thereby indicating that in the horse (as in man) the same gonadotrophin alpha-subunit gene is expressed in the pituitary and placenta. Our results are consistent with transcription of a single alpha-subunit gene for all the glycoprotein hormones in the horse, and we suggest that the reported differences between the horse CG and FSH alpha-subunit amino acid sequences determined by conventional peptide sequencing methods arose due to errors in the FSH alpha-subunit sequence. Comparison of the deduced amino acid sequence of the horse alpha-subunit with that of other alpha-subunit sequences indicated a number of significant differences which may be related to the unusual receptor-binding properties of the equine gonadotrophins.

Animals↗
PubMed1987

Application of recombinant DNA techniques to structure-function studies of equine protein hormones.

Complementary (c)DNA libraries have been made from horse pituitary gland and endometrial cup tissues with the aim of isolating the genes for the horse gonadotrophins (FSH, LH and CG) and growth hormone (GH). Southern (DNA) and Northern (RNA) blotting techniques were used to demonstrate that several heterologous (human and ovine) cDNA probes would be adequate for isolating the horse genes. A human cDNA probe was then used to isolate the horse gonadotrophin alpha-subunit cDNA from the pituitary and endometrial cup libraries. The nucleotide sequences from both tissue sources were identical, thereby confirming that there is a single gene for the alpha-subunit in the horse. As soon as the gonadotrophin beta-subunit sequences become available, they will be expressed along with the alpha-subunit to obtain biologically active hormones. Horse GH cDNA has also been isolated by using a sheep cDNA probe and its DNA sequence has been determined. It was subsequently used to demonstrate that horse endometrial cups, but not the allantochorion taken at the same stage of gestation, contains mRNA for a GH-like protein. This mRNA could be due to a low level of expression of the GH gene or to expression of the gene(s) for a GH-related protein such as prolactin or placental lactogen.

Animals↗
PubMed1986

Renal damage in mice after treatment with cisplatinum alone or in combination with X-irradiation.

Functional kidney damage in mice was measured (using clearance of 51Cr-EDTA) from 1 to 39 weeks after treatment with single doses of cisplatinum (c-DDP), X rays, or their combination. After c-DDP alone renal damage was observed within 1 week. From 1 to 7 weeks there was recovery of function after low drug doses but after doses in excess of 6 mg/kg some damage persisted. After irradiation alone there was no measurable change in function for 20 weeks. Beyond this time there was a dose dependent and progressive deterioration of function. c-DDP given before or after irradiation caused more damage than either agent alone. During the first 20 weeks independent toxicities accounted for most of this effect but at later times modification of radiation damage possibly contributed. The greatest enhancements were observed when c-DDP was given 1/2 hour before to 1 day after irradiation (Dose Modifying Factor, DMF, 1.3). c-DDP given 3 to 4 weeks before X rays caused only a slight enhancement of damage (DMF 1.1).

Animals↗
PubMed1986

The RBE for mouse bladders after irradiation with 1 to 8 fractions of d(4)+ Be neutrons.

Mouse bladders were irradiated with 1,2,4 or 8 fractions of electrons or neutrons. Urination frequency was scored from 9 to 14 months after irradiation and this was used as a measure of the extent of bladder damage. The RBE for neutrons relative to 1.8 MeV electrons increased from 3.2 for large single doses to 5.4 for 8 fractions. Repair of sublethal injury after electron irradiation was considerable, with 63-72% of each fractionated dose repaired. Repair after neutron irradiation was less, with only 35-43% of each fractionated dose recovered. Linear-quadratic analysis of all the fractionated bladder data yielded an alpha/beta ratio for electrons of 6-7 Gy and, surprisingly, the alpha/beta ratio for neutrons was only slightly higher at about 8 Gy.

Animals↗
PubMed1984

Syndrome of multiple pterygia, camptodactyly, facial anomalies, hypoplastic lungs and heart, cystic hygroma, and skeletal anomalies: delineation of a new entity and review of lethal forms of multiple pterygium syndrome.

Three unrelated stillborn infants (cases 1-3) are presented here with a distinct constellation of multiple anomalies: namely, multiple pterygia involving chin-to-sternum, cervical, axillary, antecubital, crural and/or popliteal areas, flexion contractures of multiple joints, small chest, hydrops, characteristic abnormal facial appearance with hypertelorism, markedly flattened nasal bridge with hypoplastic nasal alae, cleft palate, micrognathia, apparently low-set malformed ears, short neck with a cystic hygroma at the back of the neck and head, and pulmonary and cardiac hypoplasia. Radiographic studies, in addition, showed scalp edema, microbrachycephaly, flattened mandibular angle, lack of normal curvature at the cervico-thoracic junction, marked bony fusion of posterior spinous processes of older fetuses (cases 1, 2), thin crowded ribs, markedly hypoplastic scapulae, hypoplastic iliac wings, ischia and pubic bones, undermodeling of tubular bones, and radio-ulnar synostosis. Histologic studies of the skeletal system showed cartilaginous and bony fusion of the spinous processes (cases 1, 2), fusion of epiphyseal cartilages of distal humerus and proximal ulna, a poorly developed joint space, an abnormal growth plate, and weak safranin staining of the resting cartilages (cases 1, 2). To the best of our knowledge, this pattern of anomalies constitutes a previously undescribed syndrome. Prenatal diagnosis of this entity is possible by ultrasonographic studies on the basis of nonimmune fetal hydrops, a cystic hygroma at the back of the head and neck, diminished fetal activity, short and fixed limbs, and/or maternal hydramnios. Three additional cases (cases 4-6) are also presented to show a possible heterogeneity of this syndrome.

Abnormalities, Multiple↗
PubMed1984

Effects of fibrinogen in vivo on dentine permeability in the dog.

Dentine permeability measurements were made each hour for 6 h in tooth cavities prepared in control dogs or dogs which had been pretreated with a purified fraction of snake venom to deplete their plasma of fibrinogen. The control dogs exhibited a progressive fall in dentine permeability (approximately 50 per cent reduction in 6 h); the permeability in the fibrinogen-depleted dogs only fell 15 per cent in 6 h. The results implicate plasma proteins, particularly high molecular-weight proteins such as fibrinogen, as agents which reduce dentine permeability in vivo.

Animals↗
PubMed1984

Mammogenesis and changing prolactin receptor concentrations in the mammary glands of the tammar wallaby (Macropus eugenii).

All 4 mammary glands of the tammar wallaby showed a steady increase in weight and prolactin receptor concentration during the luteal phase of the oestrous cycle to reach a peak at oestrus. Removal of the corpus luteum abolished this mammogenesis , while pregnancy, which in this species is a day or so shorter than the oestrous cycle, had no effect. This provides an explanation for the previous finding that pregnancy is not a necessary pre-requisite for lactation in marsupials and that nonpregnant animals will lactate very successfully, provided the suckling stimulus is applied at the correct stage of the oestrous cycle. During lactation, only the gland supplying the teat to which the pouch young was attached developed and showed any further increase in prolactin receptors; the other 3 glands remained small and inactive. These results indicate the importance of the suckling stimulus and milk withdrawal on the initiation and maintenance of lactation.

Animals↗
PubMed1983

Blood flow changes in transplanted mouse tumours and skin after mild hyperthermia.

The influence of moderate hyperthermia on the vascular perfusion of four different tumour types and of normal mouse skin was investigated. The 86Rb extraction technique was used to measure changes in perfusion relative to total cardiac output, both during and after a one hour heat treatment at 42.5 degrees C. Perfusion of the SA FA tumour increased slightly during the first 30 minutes of heating but had returned to control values by the end of a 1 hour heating period. After heating, the relative perfusion of all four tumour types fell significantly below control values by 24 hours and remained low for 1-2 days (SA FA tumour) before returning to control values. Relative perfusion of normal skin was progressively increased during heating and remained elevated for 24 hours after the end of treatment before returning to control levels.

Animals↗
PubMed1982

Prolactin and luteinizing hormone receptors in marsupial corpora lutea: relationship to control of luteal function.

Prolactin and LH receptor concentrations in tammar wallaby corpora lutea (CL) have been examined and related to the control of luteal function in this and other marsupial species. During embryonic diapause, quiescent CL contained high concentrations of prolactin receptors. This was consistent with an earlier suggestion that prolactin may act directly on the CL to maintain its quiescent state. However, despite an apparent seasonal change in the mechanism by which the CL is maintained in quiescence, the number of luteal prolactin receptors remained constant throughout the year. Reactivation of quiescent CL led to an approximate halving of prolactin receptors on a per cell basis, but pregnancy had no effect. None of the wallaby CL showed any significant degree of LH binding, although wallaby follicles and testicular tissue did show binding. This lack of LH binding was consistent with previous findings that quiescent wallaby CL reactivate in response to hypophysectomy and are refractory to LH when cultured in vitro. Parturition, which occurs approximately 2 days before ovulation in this species, had no effect on numbers of either prolactin or LH receptors despite the occurrence of a peak of plasma prolactin at this time. The red kangaroo, which also exhibits embryonic diapause, showed a similar pattern of luteal receptor numbers with high prolactin and negligible LH binding, whereas the brush-tailed possum, which does not exhibit embryonic diapause, gave a pattern more like that seen in Eutheria with many more LH than prolactin receptors.

Animals↗
PubMed1981

Biological functions and receptor binding activities of equine chorionic gonadotrophins.

The role of equine chorionic gonadotrophin (CG, formerly termed Pregnant Mare serum Gonadotrophin, PMSG) in maintaining equine pregnancy was investigated by examining the effects of this hormone on the maternal ovaries during early gestation and relating these findings to the receptor binding activities of CG in vitro. Measurement of plasma progestagen profiles in mares and donkeys carrying horse, donkey, mule ( female horse X male donkey) and hinny (female donkey X male horse) conceptuses confirmed that CG induced several secondary ovulations and thus maintained maternal progestagen concentrations. However, in mares carrying horse and mule conceptuses and in donkeys carrying donkey conceptuses the growth of the follicles that gave rise to the secondary corpora lutea occurred before CG was secreted and the CG did not express any FSH-like activity. Nevertheless, in donkeys carrying hinny pregnancies the CG secreted by the hinny conceptus stimulated massive follicular growth in addition to luteinization, presumably because of an enhanced sensitivity of donkey ovaries to hinny CG which, as demonstrated in previous studies, is a mixture of horse and donkey CG and hence has considerably more FSH-like activity than normal donkey CG. In-vitro receptor binding experiments showed that both horse and donkey gonadal tissues possessed a low binding affinity for horse CG compared to that exhibited by equivalent gonadal tissues of other species. Furthermore, horse CG bound with low, but significant, affinity to horse and donkey LH receptors and donkey FSH receptors, but exhibited negligible binding to horse FSH receptors. We suggest that in equids the receptor-mediated refractoriness to the gonadotrophic activities of the intraspecific chorionic gonadotrophin protects the ovaries during pregnancy.

Animals↗
PubMed1981

Macropodid marsupial testicular gonadotrophin receptors and their use in assays for marsupial gonadotrophins.

The interactions of several mammalian follicle-stimulating hormones and luteinizing hormones with specific gonadotrophin receptors in macropodid marsupial testicular homogenates were investigated with a view to developing radioreceptor assays for marsupial FSH and LH. Testes from Eastern grey kangaroos and tammar wallabies possessed high affinity (dissociation constant congruent to 10(-10) mol/l) saturable receptor sites which were highly specific for LH or FSH. Luteinizing hormone receptor sites bound only highly purified LH preparations (human, ovine and rat) but did not bind highly purified FSH, TSH or prolactin while FSH receptor sites were equally specific for highly purified FSH preparations. These sites demonstrated a degree of species specificity in that marsupial pituitary extracts were relatively more potent in these assays than in assays using gonadotrophin receptors from rat testes. Serum from hypophysectomized female tammar wallabies had little effect on the slope and position of the LH standard curve but significantly depressed the dose-response curve for FSH. For this reason it was not possible to develop a radioreceptor assay for serum FSH using marsupial testicular FSH receptors. However, gonadotrophin receptors from both rat and marsupial testes have been employed in the successful development of radioreceptor assays for marsupial pituitary LH and FSH and marsupial serum LH.

Animals↗