Biomedical subjects
Publications and source records attributed to T Thorsen.
Primary breast carcinomas (23) with axillary-node metastases that also showed tumour cells in the efferent nodal vessels, tended to be of higher histological grade than those (21) without efferent vascular invasion. Nuclear hyperchromatism and mitosis is the factor of importance to grading in this respect. This factor also differentiated between RE+ and RE- carcinomas in this material.
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Ketamine/diazepam solution was used as the only anaesthetic in 105 patients selected for neuroradiological examinations. A rapid intravenous injection, m ml/kg bodyweight, followed by continous drip infusion constituted the method used. No important side effects were seen, except psychotomimetic reactions in two cases. Cardiovascular disturbances were absent and no significant intracranial pressure rise occurred in nine patients examined.
The prognostic value of oestrogen receptor analysis is demonstrated in 150 patients with infiltrating breast carcinoma. Recurrence of tumour was earlier and more frequent in the receptor negative than in the receptor positive cases. There was more early deaths in the receptor negative group. The mean follow-up time was 30 months.
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The stimulant effect of L-dopa (125 to 500 mg) was compared to dextroamphetamine and methylphenidate, 15, and 20 mg, respectively, on growth hormone secretion in 20 hyperactive children. All three stimulants were responsible for peak GH concentration in serum at 60 minutes after drug ingestion; there was no significant difference between the mean GH level at any time of sampling. Seven of the children were retested with L-dopa and dextroamphetamine after six to eight months of treatment with methylphenidate. After treatment, there was a tendency to higher zero time levels of GH, and to delayed and/or paradoxical response to dextroamphetamine. The findings indicate an acute and a probably long-term effect of dextroamphetamine and methylphenidate on the homeostasis of growth hormone. The possible long-term adverse effects of these drugs on the growth of children indicates the need for caution to the widespread use of these agents.
The efficiency of L-dopa alone and L-dopa plus a dopa-decarboxylase inhibitor (carbidopa) in provoking growth hormome (GH) secretion was studied 40 children with short stature. By preventing the extracerebral metabolism, carbidopa increases the availability of L-dopa to the brain. The study was designed as paired series of growth hormone stimulation tests in which the effect of L-dopa alone, in different dosage schedules, was compared with the same dose level of L-dopa plus carbidopa, When L-dopa was given in full dose (125-500 mg), there was no significant difference in the serum GH concentrations at any time of sampling. In the lower dose level, the stimulant effect of L-dopa alone tended to be exceeded by the combination of L-dopa and carbidopa. The serum GH responses to the different schedules indicate that an optimal hypothalamic dopamine concentration for GH release could be achieved with a considerably lower dose of L-dopa than those employed in previously reported studies. When L-dopa is combined with a dopa decarboxylase inhibitor, the children have the advantage of less side effects in the form of nausea and vomiting.
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In an effort to develop a bacterial expression system for horseradish peroxidase (HRP), we inserted the gene encoding HRP into the pET-22b(+) vector (Novagen) as a fusion to the signal peptide PelB. A similar construct for cytochrome c peroxidase (CcP) leads to high CcP activity in the supernatant. Expression of the wild-type HRP gene in the presence of isopropyl-beta-D-thiogalactopyranoside (IPTG) yielded no detectable activity against ABTS (azinobis(ethylbenzthiazoline sulfonate)). However, weak peroxidase activity was detected in the supernatant in the absence of IPTG. The HRP gene was subjected to directed evolution: random mutagenesis and gene recombination followed by screening in a 96-well microplate format. From 12 000 clones screened in the first generation, one was found that showed 14-fold higher HRP activity than wild-type, amounting to approximately 110 microg of HRP/L, which is similar to that reported from laborious in vitro refolding. No further improvement was obtained in subsequent generations of directed evolution. This level of expression has nonetheless enabled us to carry out further directed evolution to render the enzyme more thermostable and more resistant toward inactivation by H2O2. These results show that directed evolution can identify mutations that assist proteins to fold more efficiently in Escherichia coli. This approach will greatly facilitate efforts to "fine-tune" those many enzymes that are promising industrial biocatalysts, but for which suitable bacterial or yeast expression systems are currently lacking.
Several proteins have been quantitated in cytosols prepared from benign and malignant tumors of the breast; orosomucoid, albumin, transferrin, complement 4, C-reactive protein alpha 2-macroglobulin and hemoglobin. With the exception of hemoglobin, concentrations of the proteins measured were significantly intercorrelated. Their relative abundance was close to that reported in blood, except for alpha 2-macroglobulin and hemoglobin which were present in lower amounts. From hemoglobin measurements it can be concluded that blood contamination contributed less than 10% to the cytosol proteins measured. When compared to albumin, none of the proteins investigated occurred in concentrations sufficient to indicate local synthesis of a magnitude that would significantly influence tumor environment. From the present data it can be concluded that extracellular proteins constitute about 50% of total cytosol protein. This indicates an exceptional capillary leakage in breast tumors possibly related to abnormal hormonal influences. There were, however, large individual variations and about 10% of the cytosols could be predicted to contain negligible amounts of cell-derived protein. There was a highly significant difference between benign and malignant tumors in their cytosol content of extracellular protein, benign tumors containing nearly twice as much albumin. It is suggested that measurement of an extracellular protein (albumin) should be included in tumor characterization to correct for cellularity and representativity of tumor samples used for steroid receptor determinations and for measurements of other parameters using "cytosol" protein to express specific activity.