Biomedical subjects

M Sjöberg

Publications and source records attributed to M Sjöberg.

24 records · Page 2Linked to original sources

PubMed1992

Thyroid hormone receptors in chick retinal development: differential expression of mRNAs for alpha and N-terminal variant beta receptors.

Thyroid-hormone-dependent development of the neuroretina has principally been described in amphibia. Here, we show by in situ hybridisation that mRNAs coding for three distinct thyroid hormone receptors (TRs), TR alpha and two TR beta variants, are differentially expressed during chick retinal development. We isolated a cDNA for a novel N-terminal variant of chick TR beta (cTR beta 2) that is predominantly expressed in retinal development. Interestingly, in its N-terminal A/B domain cTR beta 2 is 70% homologous to the rat pituitary-specific TR beta 2. Expression of cTR beta 2 mRNA was high at embryonic day 6 (E6) in the retinal outer nuclear layer (ONL) and decreased to low levels at hatching. mRNA for the previously described chick beta receptor, cTR beta 0, was expressed at low levels in both the ONL and the inner nuclear layer (INL) after E10. In contrast, cTR alpha expression occurred in the ONL, INL and ganglion cell layer at intermediate and later stages. Finally, cTR beta 2 confers a stronger trans-activation of reporter gene transcription than cTR beta 0. The distinctive kinetics and localisation of TR alpha and beta gene expression suggest cell- and stage-specific functions for TRs, both individually and in combinations, in chick neuroretinal development.

Amino Acid Sequence↗

PubMed1991

Intracellular modifications of rat alpha 1 inhibitor3. Formation of disulphides, internal thiolester and sulphation.

alpha 1 Inhibitor3 (alpha 1I3) is a monomeric protease inhibitor of about 190 kDa which is secreted by rodent hepatocytes. We have studied intracellular modifications of this protein in [35]methionine-labelled rat hepatocytes by pulse/chase experiments followed by immunoprecipitation and gel electrophoresis under reducing and nonreducing conditions. Directly after the pulse, most of the unreduced alpha 1I3 migrated faster than the reduced form, indicating that disulphide bridges are formed during or shortly after synthesis yielding a compact structure. With increasing chase time however, an increasing portion of the unreduced alpha 1I3 migrated with a mobility lower than that of the reduced protein, half-maximal conversion occurring after about 10 min. This finding suggests that alpha 1I3 undergoes a conformational change in the endoplasmic reticulum, possibly becoming more elongated. During 10-30 min of chase, the protein acquired the capacity to undergo autolytic cleavage upon heating, a property due to the existence of an internal thiolester bond [Howard, J. B., Vermeulen, M. & Swenson, R. P. (1980) J. Biol. Chem. 255, 3820-3823; Esnard, F., Gutman, N., El Moujahed, A. & Gauthier, F. (1985) FEBS Lett. 182, 125-129]. Analysis by subcellular fractionation indicated that this bond is formed in the endoplasmic reticulum. Finally, we show that secreted alpha 1I3 is sulphated, presumably at Tyr618.

Acute-Phase Proteins↗

PubMed1991

Long-term, open catheterization of the spinal subarachnoid space for continuous infusion of narcotic and bupivacaine in patients with "refractory" cancer pain. A technique of catheterization and its problems and complications.

The technique of long-term, open catheterization of the spinal subarachnoid space for infusion of analgesics in patients with refractory cancer pain is sparsely reported in the literature. We report on a technique using 18G Portex nylon catheters and 16G-17G Tuohy needles, and its problems and complications. One hundred fifty-seven catheters were inserted in 142 patients, in most of them (79%) under deep sedation and local anesthesia. Attempts were made to place the catheter tip as close to the painful segments as possible. The catheters were tunneled subcutaneously (87% of them paravertebrally, over the shoulder, and further parasternally to the third chondrocostal cartilage). The Luer connections of the catheters were fixed to the patients' skin with monofilament steel sutures of dimension 0 and connected to a bacterial filter. At the end of the procedure, 10 ml isotonic saline was injected intrathecally to prevent postspinal puncture headache. Absorbent and impermeable dressings were applied over the tunnel exit, catheter Luer connection and bacterial filter. Antibiotics were given on the day of insertion and 2 days thereafter. During the insertion procedure, the following problems and complications were encountered; two or more attempts before successful spinal-dural puncture (32%), accidental puncture of an extradural vessel (10%), difficult dural puncture (18%), absence of free dripping of cerebrospinal fluid (CSF) in spite of successful dural puncture (4%), blood-stained CSF (9%), radicular pain and paresthesiae (4%), difficult advancement of the catheter (6%), difficult tunneling (11%), and bleeding in the tunnel (0.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Long-term intrathecal morphine and bupivacaine in "refractory" cancer pain. I. Results from the first series of 52 patients.

Neither epidural (EDA) or intrathecal (IT) morphine nor EDA opiate + bupivacaine provides acceptable relief of some types of cancer pain, e.g. pain originating from mucocutaneous ulcers, deafferentation pain, continuous and intermittent visceral and ischaemic pain, and that occurring with body movement as a result of a fracture. To improve pain relief in such conditions, we gave combinations of morphine and bupivacaine through open IT-catheters to 52 patients with "refractory", severe (VAS 7-10 out of 10), complex cancer pain (Edmonton Stage-3), for periods of 1-305 (median = 23) days. The efficacy of the treatment was estimated from: 1) daily dosage (intraspinal and total opiates, and intraspinal bupivacaine), and 2) scores of non-opiate analgesic and sedative consumption, gait and daily activities, and amount and pattern of sleep. Forty-four patients obtained continuous and acceptable pain relief (VAS 0-2), 26 of them with daily doses of IT-bupivacaine of less than or equal to 30 mg/day (less than or equal to 1.5 mg/h). Higher IT-bupivacaine doses (greater than 60-305 mg/day), not always giving acceptable pain relief, were necessary in 13 patients with deafferentation pain from the spinal cord or brachial or lumbosacral plexuses or pain from the coeliac plexus, or from large, ulcerated mucocutaneous tumours. By combining IT-bupivacaine with IT-morphine, it was possible to use relatively low IT-morphine doses (10-25 mg/day during the first 2 months of treatment) in more than half of the patients. The IT-treatment significantly decreased the total (all routes) opiate consumption and significantly improved sleep, gait and daily activities. For the whole period of observation (6 months), the IT-treatment was assessed as adequate in 3.8%, good in 23.1%, very good in 59.6% and excellent in 13.5% of the cases. Adverse effects of the IT-bupivacaine (paraesthesiae, paresis, gait impairment, urinary retention, anal sphincter disturbances and orthostatic hypotension) did not occur with doses of 2.5-3.0 mg/h (approx. 60-70 mg/day).

Adult↗

PubMed1990

Contrasting developmental and tissue-specific expression of alpha and beta thyroid hormone receptor genes.

Thyroid hormones and their receptors (TRs) have critical functions in development. Here we show that a chicken TR beta cDNA clone encodes a receptor with a novel, short N-terminal domain. In vitro-expressed TR beta protein bound thyroid hormone with similar affinity as the chicken TR alpha. Comparison of expression of TR alpha and TR beta mRNAs throughout chicken development until 3 weeks post-hatching revealed ubiquitous expression of TR alpha mRNAs (in 14 different tissues) with some variations in levels, from early embryonic stages. In contast, expression of TR beta mRNA was restricted, occurring notably in brain, eye, lung, yolk sac and kidney, and was subject to striking developmental control, especially in brain where levels increased 30-fold upon hatching. Levels also sharply increased in late embryonic lung, but were relatively high earlier in embryonic eye and yolk sac. RNase protection analyses detected no obvious mRNAs for alpha and beta TRs with variant C-termini as demonstrated previously for the rat TR alpha gene. The data suggest a general role for TR alpha and specific developmental functions for TR beta, and that thyroid-dependent development involves temporal and tissue-specific expression of the TR beta gene.

Amino Acid Sequence↗

PubMed1990

Epidural versus intrathecal morphine-bupivacaine: assessment of consecutive treatments in advanced cancer pain.

Twenty-five patients with multifocal and multitype (somatic, visceral, and neurogenic) advanced cancer pain who experienced severe pain despite extradural (ED) morphine and bupivacaine were converted to intrathecal (IT) morphine and bupivacaine. The consecutive ED and IT periods (2-174 days, median = 50 days, and 1-305 days, median = 37 days, respectively) were assessed in clinical terms (daily analgesic dosages giving acceptable pain relief and quality of life expressed as sleeping hours and walking/daily activities). With the IT treatment, the total (all routes) opiate consumption and the daily doses of spinal morphine and spinal bupivacaine decreased significantly at the beginning of the treatment compared to the ED period, and continued to be significantly reduced for up to 1 wk for spinal opiate and bupivacaine and 6 mo for total opiate. The spinal opiate and bupivacaine doses were still lower in 50% of the patients at the end of the IT treatment compared to the end of the ED period. When final ED versus initial (2nd day) IT doses were assessed, the daily median dose ratios were 7.5 for total opiate and 4 for both spinal opiate and bupivacaine. Subsequently, lower daily volumes and higher concentrations were needed for IT administration of the drugs. During the first month of the IT treatment, sleeping and walking scores improved compared to ED treatment. Thus, the IT treatment gave more satisfactory pain relief, and--because of lower daily doses and volume--proved to be more suitable for treatment at home (continuous infusion from external pumps) than the ED treatment.

Adult↗