Structure of mammalian steroid receptors: evolving concepts and methodological developments.
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Affinity Labels↗
Biomedical subjects
J Stevens
Publications and source records attributed to J Stevens.
Spontaneous renal allograft rupture 4 years after transplantation.
Previously, the longest reported interval between clinical renal transplantation and 'spontaneous' renal allograft rupture was 170 days. We here report a case with an interval of 4 years between renal transplantation and the delayed 'spontaneous' renal allograft rupture (DSR). The aetiology appears to be a vigorous rejection confirmed by operative and pathological findings. The patient who was a cadaver donor recipient presented with pain and tenderness at the transplant site, falling haematocrit, hypotension and azotaemia. The details of this presentation are discussed and the need for immediate transplant nephrectomy is emphasized.
Graft Rejection↗
Cervical myelography with iohexol.
An open, non comparative study of cervical myelography in 68 adult patients using iohexol (Omnipaque) containing 300 mg I/ml is reported. Satisfactory visualisation was achieved in all cases. Minor adverse effects occurred in 13 patients (19%); they were headache (8), neck or back pain (3), vomiting (3), nausea (1), dizziness (1) and nystagmus (1) and were of minor degree in most and moderate in a few, lasting more than 24 hours in only one patient. EEG performed in 39 patients before and 24 h after the myelogram showed no seizure activity or significant change. Iohexol is a very satisfactory drug for all types of myelography.
Adolescent↗
Successful pregnancy with sickle cell disease and renal transplantation.
Renal transplantation has been very effective in the treatment of end-stage renal disease. Over 750 cases of successful pregnancies in these patients have been reported, and only 15 patients with sickle cell disease (homozygous hemoglobin S) have had renal allografts. The present study documents the first case of a successful pregnancy in a patient with sickle cell disease and renal transplantation. The combined complications increase the risks in view of the susceptibility of certain vital organs in pregnancy. Careful multidisciplinary management enhances successful outcome.
Adult↗
The spatiotemporal building blocks of X-, Y- and W-ganglion cell receptive fields of the cat's retina.
The spatiotemporal distribution of excitation and inhibition has been characterized in 283 X-, Y- and W- cat retinal ganglion cells. Cells were classified by their latency from optic chiasm stimulation, responses to moving bars and gratings and responses to flashed gratings. As expected from earlier LGN studies the responses of retinal X-cells and Y-cells had distinct spatiotemporal profiles. The Y-cells had a relatively constant or homogeneous spatial distribution of responses while X-cells had a heterogeneous spatial arrangement. As has been previously reported in LGN, retinal X- and Y-fields had four independent spatiotemporal components or response domains; primary excitation (PE), primary inhibition (PI), secondary excitation (SE) and, finally, secondary inhibition (SI). In contrast, W-receptive fields had a few as a single response domain or as many as eight. An unexpected discovery was that all of these W-receptive fields were constructed from spatiotemporal domains, identical to those found in X-receptive fields. Thus, taking on-center and off-center cells into account we have found a total of 16 different spatiotemporal response components or "building blocks" for X- and Y-cells and the X-building blocks appear to be used in the construction of W-receptive fields.
Animals↗
Spontaneous change of human plasma angiotensin I converting enzyme isoelectric point.
The isoelectric point of angiotensin I converting enzyme (ACE) spontaneously changes from 4.3 to 4.6 during purification from human plasma. The spontaneous change in pI corresponds to that occurring with neuraminidase-treated but not with EDTA-treated samples. There is no detectable difference in the molecular weight of, or lectin binding by, the two forms of ACE with different pI's. These data indicate that ACE in the circulation contains a greater amount of sialic acid than purified ACE. The implication is that purified ACE isoenzymes which differ in sialic acid content may not reflect tissue-specific isoenzymes but rather artifacts of purification.
Chemical Phenomena↗
Verapamil suppresses atherosclerosis in cholesterol-fed rabbits.
The effect of verapamil, a drug that reduces the concentration of intracellular calcium, on atherogenesis was evaluated in rabbits fed a cholesterol-rich diet for 10 weeks. Ten rabbits received oral verapamil, 8 mg/kg daily; eight received the same oral dose and 0.5 mg/kg daily subcutaneously; nine received oral lanthanum, 35 mg/kg daily, and nine were controls. Over the 10 week period, all groups had average serum cholesterol levels greater than 1,500 mg/dl (normal = 90 +/- 63 mg/dl). At the end of the experiment, the aortas were removed, opened and stained for lipid with Sudan IV. The extent of atherosclerosis was determined by planimetry. The group receiving oral and parenteral verapamil had significantly less atherosclerosis (25 +/- 26% of total intimal area; mean +/- standard deviation), as compared with the controls (73 +/- 24%). Reduction of atherosclerosis with oral verapamil (51 +/- 22%) and lanthanum (59 +/- 31) was not statistically significant. Indexes of contractility in isolated right ventricular papillary muscles (developed tension at maximal length [Lmax] and maximal velocity of shortening [Vmax]) were reduced in the group treated with oral and parenteral verapamil, but not in the others. It is concluded that verapamil suppresses the development of atherosclerosis in rabbits fed a cholesterol-rich diet.
Adenosine Triphosphatases↗
Clinical trial of iohexol for lumbar myelography.
Iohexol containing 180 mg I/ml was used in 80 patients for myelography by lumbar injection. By using an adequate volume, between 10 and 20 ml, satisfactory films were obtained in all cases. Minor adverse effects occurred in 12 patients (15%) and were more frequent in women than men; they were headache (5), nausea (3), vomiting (2), back or limb pain (5), and skin rash (1) and were of minor degree in 10 cases, moderate in the other two and lasted more than 24 h in only one case. There was no change in vital signs or neurological examination related to the studies. No patient suffered difficulty with concentration, personality change or seizures. Electroencephalograms performed on 21 patients before and during the 24 h after iohexol showed no seizure or focal activity or any significant change. Repeat lumbar punctures were performed on ten patients during the 24 h following myelography. One of these, a patient with symptoms due to disc prolapse, whose CSF was abnormal prior to the myelogram, showed a slightly increased cellular response. There was no significant change in any other case. Iohexol is a very satisfactory contrast medium for myelography and compares favourably with other non-ionic contrast media.
Adolescent↗
Capillary haemangioblastoma of bone resembling a vertebral haemangioma.
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Adult↗
Absence in glucocorticoid-resistant mouse lymphoma P1798 of a glucocorticoid receptor domain responsible for biological effects.
Glucocorticoid-resistant (CR), in contrast to glucocorticoid-sensitive (CS), mouse lymphoma P1798 was shown to lack antiglucocorticoid receptor immunoactivity. Antibodies raised against the purified rat liver glucocorticoid receptor (GR) cross-reacted with the GR from CS, but not with the GR from CR, P1798 lymphoma. Using highly specific antisera against the GR in an indirect competitive enzyme-linked immunosorbent assay, it was demonstrated that alpha-chymotrypsin digestion of the GR from CS P1798 lymphoma caused a separation of a "resistant-like" nonimmunogenic steroid and DNA-binding domain (Stokes' radius, 3.3 nm) from an immunoactive domain (Stokes' radius, 2.6 nm). In contrast to CS P1798 lymphoma, neither before nor after alpha-chymotrypsin digestion, immunoactivity could be found in the cytosol from CR P1798 lymphoma. This was assayed after chromatography on DNA-cellulose or gel filtration on Agarose A (0.5 m). These results suggest that the domain of the CS GR containing the immunoactive determinant(s), normally removed by limited proteolysis by alpha-chymotrypsin, appears to be missing in CR P1798 lymphoma cytosol. It seems that this domain plays an important role in the mechanism of action of glucocorticoids. This might suggest that a mutation has occurred affecting the genome resulting in defective transcription of the receptor gene(s) in CR P1798 lymphoma.
Animals↗
Renal transplantation in heroin addicts.
On the basis of our experience, therefore, we believe that the reformed heroin addict is a good candidate for cadaveric donor renal transplantation if he can be discouraged from returning to heroin use. The fact that the majority of the patients in our study returned to marijuana smoking after transplantation has raised the issue of its role as a possible immunosuppressant.
Adult↗
Successful management of Pseudomonas endogenous endophthalmitis.
A 38-year-old man acquired a Pseudomonas aeruginosa wound infection after transplant nephrectomy. After an initial response to therapy, Pseudomonas sepsis developed, and he was readmitted to the hospital. Two days after admission, blurred vision developed. Ocular examination revealed a severe vitritis and exudate in the pupillary space on the right side. Endogenous endophthalmitis was suspected, and a diagnostic vitreous aspiration yielded P aeruginosa on culture. The patient was treated with intravitreal, subconjunctival, and topical antibiotics as well as periocular steroids, and was able to achieve useful vision before his death from his systemic illness.
Adult↗
Cysteine conjugate beta-lyase.
Cysteine conjugate beta-lyase from rat liver, an enzyme participating in a shunt from mercapturic acid synthesis, has been purified and found to be active with a number of compounds that bear nonpolar leaving groups on the beta-carbon of an amino acid substrate. Pyridoxal phosphate is considered to be a participant in the reaction. In addition to aromatic thioethers of cysteine, the enzyme is also active with two aliphatic amino acid derivatives, S-1,2-dichlorovinyl-L-cysteine and beta-chloroalanine. Evidence is presented that catalysis results in "suicide" inhibition with a partition ratio of about 600 for each of the substrates.
Animals↗
Mast cells in spotted mutant mice (W Ph mi).
Mast cells derived from haematopoietic tissue are deficient in numbers in spleen, stomach and skin of Harwell mice doubly mutant at the spotting W locus: seven viable combinations of four mutants. Most combinations have variably impaired viability, anaemia and infertility; but homozygous WshWsh are normal in these respects yet still lack mast cells. The effect of the W gene on mast cells acts in recessive fashion. Effects of doubly mutant W genes on mast cells and coat colour, the latter usually regarded as dominant, appear more closely related than other pleiotropic effects. The spotting gene Ph, closely linked to W, has but marginal effects on mast cells, whereas mi, another spotting gene, quite unrelated to W affects mast cells in the spleen in a dominant way. Thus, splenic mast cells may be a special category of a heterogeneous population. Peptic ulceration, recorded in W/Wv mice of Jackson stock, was not seen in Harwell mice. We suggest that this lesion is due to genetic complementation or environmental causes.
Animals↗
The tetraphasic action of lidocaine on CNS electrical activity and behavior in cats.
Effects of intravenously administered lidocaine on CNS electrical activities were studied in cats with surface and depth electrodes implanted chronically in the brain. Lidocaine was administered using a constant rate infusion pump. The changes induced in CNS electrical activities were correlated with the behavioral changes in the unrestrained freely moving state. During infusion of lidocaine at the rate of 1 mg . kg-1 . min-1, a sequence of changes was observed: the initial stage was represented by diffuse EEG slowing and a decrease of reticular neuronal firing, associated with behavioral depression; the second stage by low-voltage fast-wave EEG and increase of reticular neuronal firing, associated with agitation and/or catatonic behavior; the third stage by reappearance of slow-wave EEG and decrease of reticular neuronal firing, associated with a behavioral depression; and the fourth stage by an epileptiform EEG and increase of reticular neuronal firing associated with generalized tonic or tonic/clonic convulsions. Higher rates of infusion, such as 4, 8, and 15 mg . kg-1 . min-1, diminished the manifestation of the signs of both electrographic and behavioral depression, leaving the signs of excitation unaffected or somewhat enhanced. These findings support the widely prevailing view that recording the surface EEG is not valuable diagnostically in detecting the onset of local anesthetic intoxication, in that the preconvulsive CNS state can be represented by either a high-voltage slow-wave or low-voltage fast-wave pattern in the surface EEG.
Animals↗
Integrated shope virus DNA is present and transcribed in the transplantable rabbit tumour Vx-7.
To facilitate a molecular analysis of Shope papilloma virus-induced neoplastic cells, we have established a cell line from Vx-7, a transplantable tumour originally induced by the Shope virus. Single phase molecular hybridization and Southern transfer methods were employed to assess copy number and physical state of the DNA, and the extent of transcription. Both tumour and cell line were found to contain multiple copies of the virus genome and these were all integrated into the host cell DNA. Transcripts corresponding to a complexity of approx. 1% of the virus genome were detected at low abundance. These results are discussed relative to our earlier findings with tumours induced directly by virus, and to requirements for maintenance of the Vx-7 tumour over the 30 years that it has been in existence.
Animals↗
Long-term study of propranolol in the treatment of migraine.
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Adult↗
Basic isoferritin and hypercalcaemia in renal cell carcinoma.
A 63-year-old man with iron loss anaemia and hypercalcaemia was found to have a renal cell carcinoma. Despite the iron-deficient blood and bone marrow picture, the serum ferritin concentration was markedly raised. This was mainly due to a "basic isoferritin". The serum parathormone concentration was normal. The serum ferritin and calcium concentrations returned to normal after the tumour was removed. We propose that the renal cell carcinoma cells in this patient secreted the basic isoferritin as well as humoral factor(s) responsible for hypercalcaemia.
Adenocarcinoma↗