Studies on inhibition of TSH stimulation of adenyl cyclase activity in thyroid plasma membrane preparations by propranolol.

Propranolol (1 mM) was found to inhibit TSH stimulation of adenyl cyclase activity in a subcellular fraction from bovine thyroid enriched in plasma membranes. However, stimulation due to PGE1 or NaF was not similarly inhibited. Since (i) and inhibition was observed at concentrations of propranolol between 10-minus 4 and 10- minus 3M, and appeared to be noncompetitive (ii) the optical isomers of propranolol were equipotent, (iii) inhibition was specific for propranolol since it was not observed with the closely related drug practolol (1 mM), and (iv) quinidine (1 mM) and the local anaesthetics lignocaine and aptocaine also proved inhibitory, we concluded that propranolol inhibition of TSH stimulation was due to its "quinidine-like" properties (i.e., relatively specific and characteristic membrane-active properties) and not to its action as a beta-adrenergic antagonist.

Studies on isoproterenol stimulation of adenyl cyclase in membrane preparations from the bovine thyroid.

Catecholamine stimulation of adenyl cyclase activity associated with bovine subcellular fractions enriched in plasma membranes is described. The relative potencies of isoproterenol (IPNA), epinephrine (E), and norepinephrine (NE) were 4.7:1.0:0.02, which is characteristic for a beta-adrenergic receptor system. Stimulation with IPNA (5 times 10- minus 6 M) was inhibited by propranolol. The inhibition was stereospecific for the L-isomer of propranolol and a concentration as low as 2 times 10- minus 8 M was required to effect 50% inhibition. Both these observations, and the competitive kinetics of inhibition which applied to the system, confirmed the classification of a beta-adrenergic receptor system. Phentolamine, an alpha-antagonist, also inhibited IPNA stimulation, although high doses (5 times 10- minus M) were required to cause total inhibition. Inhibition was also observed with quinidine (1 mM) and lignocaine (10- minus 2 M).

Mediation of spinal nerve injury induced tactile allodynia by descending facilitatory pathways in the dorsolateral funiculus in rats.

Evidence exists to indicate that tactile allodynia arising from peripheral nerve injury is integrated predominately at supraspinal, rather than spinal, sites. In the present experiments, the possibility that disruption of descending pathways through the dorsolateral funiculus (DLF) might alter expression of nerve-injury induced tactile allodynia was explored. Male, Sprague-Dawley rats received L(5)/L(6) spinal nerve ligation (SNL). Lesions to the DLF were made ipsilateral or contralateral to SNL. Tactile allodynia was determined by measuring withdrawal thresholds to probing with von Frey filaments. Rats with DLF lesions presented no apparent motor deficits and did not alter sensory threshold in sham-SNL operated rats. DLF lesions made ipsilateral to SNL completely blocked tactile allodynia in SNL rats. Contralateral DLF lesions and sham surgery did not have any effect on SNL-induced allodynia. These results indicate that tactile allodynia after peripheral nerve injury is dependent upon tonic activation of net descending facilitation from supraspinal sites and support the hypothesis of tonic activation of descending facilitation as a basis for chronic pain.

Correction for the presence of cross-reactants in saturation assays: application to thyroxine cross-reactivity in 3,3',5'-(reverse)-triiodothyronine radioimmunoassay.

Cross-reaction of anti-3,3',5'-triiodothyronine (rT3) antisera with thyroxine has proved problematical in the development of radioimmunoassays for rT3. Results of experimental work with two antisera with differing specificities are presented which illustrate certain aspects of cross-reacting assay systems. The mathematical theory of a single binding-site, two ligand assay is discussed and extended by use of a multiple binding-site computer model to a two binding-site, two ligand system. It is suggested that for the practical evaluation of the nature and extent of cross-reaction, a family of response curves for the hormone should be drawn, each curve representing the addition of a fixed mass of the cross-reactant to a set of standard incubation mixtures. Such curves will reveal whether the antiserum is (a) specific, implying that assay results require no correction, (b) behaves as a single binding site system, in which case measurement of the relative potency of the two ligands at the point on the response curve generated by the serum sample will enable an algebraic correction to be made, given that the T4 concentration is known or (c) behaves as a multiple binding-site system where correction necessitates the use of a nomogram.

[Bilateral retinal arteritis with multiple aneurysmal dilatations]. / Artérite rétinienne bilatérale avec dilatations anévrysmales multiples.

Bilateral retinal arteritis with multiple aneurysmal dilatations was described for the first time by Kincaid and Schatz in 1983. We have reported a typical case of this disease which occurred in a 49-year-old woman: retinal abnormalities were followed up during two years by repeated fluorescein angiographies. The etiology of the disease and its connexions with periarteritis nodosa are discussed. While the patient was given steroid therapy per os during 16 months, new segmental inflammation of retinal arteries were observed. Inflammation affecting retinal arteries would result in weakening of the arterial wall and aneurysmal outpouchings.

Hydrolysis of 125-I-labelled thyroglobulin by pancreatin, pronase and pepsin.

1. Pancreatin or Pronase hydrolysis of partially purified heat-denatured (125)I-labelled thyroglobulin does not release all the iodoamino acids from peptide linkage. 2. The addition of thyroidal proteases is essential to obtain maximum hydrolysis of thyroglobulin. 3. Pronase plus a fresh non-radioactive thyroid homogenate gives the best hydrolysis results, but peptide ;mapping' shows that about 10% of the radioactivity remains in the form of peptides. 4. These peptides have approximately the same R(F) as the iodotyrosines on one-dimensional chromatograms developed in butan-1-ol-2n-acetic acid (1:1, v/v). 5. Peptic hydrolysis of thyroglobulin releases virtually all of the iodothyronines but little of the iodotyrosines, in contrast with the action of pancreatin. 6. Hydrolysis of thyroglobulin with pepsin followed by Pronase plus a source of thyroidal proteases is satisfactory, but the results are not superior to those obtained by using Pronase plus a source of thyroidal proteases.

[Rhabdomyosarcoma of the bladder]. / Rabdomiosarkoom van die blaas.

Two cases of rhabdomyosarcoma of the bladder are reported. These tumours mainly occur in male children. They may arise in any part of the bladder and usually cause dysuria, lower urinary tract obstruction and a palpable suprapubic mass. The clinical, radiological and cystoscopic findings are typical. The histology may vary from a myxomatous appearance to a clear rhabdomyosarcomatous lesion. Early radical surgery, combined with radiotherapy and cystostatic agents is the treatment of choice.

The association of actin with a thyroid lysosomal fraction.

A lysosome-enriched fraction was prepared from bovine thyroid tissue using sucrose gradient centrifugation. An inhibitor of DNAase I was found to co-sediment and co-purify with the lysosomal fraction. This inhibitory activity is blocked by heavy meromyosin in the absence of ATP, and a component of 42000 molecular weight can be isolated by affinity chromatography on DNAase I linked to Sepharose. These results are consistent with the presence of an actin-like protein in a lysosome-enriched preparation from bovine thyroid tissue. Also, an increase in the level of membrane-associated actin is observed in response to thyrotropin stimulation of the thyroid tissue

The transport of neonates to an intensive care unit.

OBJECTIVE: To describe the mode of transport, the type of patient transferred and outcome as defined by death or discharge from hospital. DESIGN: A retrospective study was done of all neonates transferred from outside the designated drainage area of the hospital. SETTING: The study was done at the level 3 Neonatal Intensive Care Unit at Tygerberg Hospital for the period January-September 1992. PARTICIPANTS: From a total of 58 infants 52 were enrolled; they originated over a vast area of the western and northern Cape Province. MAIN OUTCOME MEASURES: Reasons for transfer, mode of transport and survival were measured. RESULTS: None of the infants died during transport. In total 11 (21%) of the 52 died. Categorising outcome according to transport method showed 100% survival of babies transported by fixed-wing aircraft, 94% survival if transport was by helicopter, and 70% survival if transported by ambulance. The non-survivors had a higher mean gestational age (P < 0.05) than the survivors and included 8 (73%) with asphyxia-related meconium aspiration syndrome. When the primary referral diagnosis was considered, 8 (27%) of 29 infants with respiratory failure of any cause, and 2 (28%) of those with neurological problems, died. All the infants transported because of a surgical emergency survived. CONCLUSION: These results show a high survival rate in transported infants, with the highest mortality in the asphyxia-related meconium aspiration syndrome and the infants transported by ambulance. The preponderance of infants with meconium aspiration syndrome might reflect the standard of perinatal care provided in the outlying regions of the western and northern Cape.