Biomedical subjects
Publications and source records attributed to U Carlsson.
In three siblings with familial polyposis coli, adenocarcinoma of the upper gastrointestinal tract appeared many years after colectomy. The risk of extracolonic lesions occurring in familial polyposis underlines the need for regular upper gastrointestinal surveillance after colectomy.
In this study it is shown that the higher molecular weight previously reported for tiger shark carbonic anhydrase (carbonate hydro-lyase, EC 4.2.1.1) compared to other carbonic anhydrases is decreased to a normal value around 30 000 after disulfide reduction of the enzyme. This difference in molecular weight is at least partly due to the existence of disulfide-linked glutathione and cysteine residues. Approx. 3 mol glutathione and a similar amount of cysteine are shown to be bound per mol enzyme. The presence of these factors also has effects on the enzyme activity.
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Data from a health survey including the Hemoccult fecal blood test, together with official cause-specific death rates, were used to assess the magnitude of a controlled trial that would be required to prove a 25 percent reduction of the mortality from colorectal cancer associated with screening. All men in three age groups in the city of Malmö, Sweden, were invited, but 46 percent did not participate in, the Hemoccult screening. One carcinoma and 89 adenomas were detected in 56 of the 2422 who did. With the risk function used in our calculation and a compliance rate of 60 percent, a study population among 45- to 69-year-olds of 605,000 is required to prove an expected 25 percent reduction of the mortality with 90 percent power. Considering the size of such a trial, we question whether a controlled trial is feasible. With known risk functions for death from all causes and death from colorectal cancer, the study population was calculated using variable statistical power, participation rate, and risk reduction. Statistical methods and computer programs are given. In addition, alternative study models to assess the benefits associated with screening are discussed.
A method of rapid ion-exchange chromatography of DEAE-cellulose for preparative purposes is described. Basically, the flow-rate is increased by applying an air pressure on the column. By this technique it is possible to purify gram quantities of protein in 2-4 h with acceptable resolution. In preparations of bovine and porcine carbonic anhydrases the elution times were reduced by a factor of about ten compared to those of conventional methods. The enzymes purified in this way showed a high degree of homogeneity. The method should be generally applicable in protein purification, and especially advantageous in purification of unstable proteins where time-consuming separations often give rise to low yields of active material.
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A modification of affinity electrophoresis for preparative purposes is described. This method has been applied to the purification of human erythrocyte carbonic anhydrases B and C. During conventional affinity chromatography some hemoglobin contamination occurs. By introduction of an electrophoretic purification step after the immobilization of carbonic anhydrase to the affinity gel, the hemoglobin impurity is reduced about eight and two times in the preparations of the B and C enzymes, respectively, compared to the enzymes purified by affinity chromatography.
The progress of 139 patients operated upon for cure of colorectal carcinoma, was followed postoperatively with a standardized protocol. A CEA test was performed for comparison with other parameters. Median observation time was four years. When an upper limit for CEA of 7.5 micrograms/1 was allowed, sensitivity was found to be 78 per cent, specificity 91 per cent, and predictive value of an elevated CEA concentration, 83 per cent. In general, CEA measurement traced recurrence six months before clinical diagnosis. In only a few cases was recurrence first heralded by an abnormality in other blood chemistry test results. CEA may thus be used in postoperative screening for recurrence even though most recurrences, when detected, are not curable.
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1. Carbonic anhydrase (carbonate hydro-lyase, EC 4.2.1.1) has been purified from erythrocytes of hagfish (Myxine glutinosa). A single form with low specific CO2 hydration activity was isolated. The purified carbonic anhydrase appeared homogeneous judging from polyacrylamide gel electrophoresis and gel filtration experiments. The protein has a molecular weight of about 29 000, corresponding to about 260 amino acid residues. This molecular weight is in accordance with other vertebrate carbonic anhydrases with the exception of the elasmobranch enzymes, which have Mr 36 000--39 000. 2. The molecular weight obtained for hagfish carbonic anhydrase indicates that a carbonic anhydrase with Mr approx. 29 000 is the ancestral type of the vertebrate enzyme rather than, as in sharks, a heavier carbonic anhydrase molecule. 3. The circular dichroism spectrum may indicate a somewhat different structural arrangement of aromatic amino acid residues in this enzyme than in the mammalian carbonic anhydrases. 4. The enzyme is strongly inhibited by acetazolamide and also to a lesser extent by monovalent anions. 5. Zn2+, which is essential for activity, appears, contrary to other characterized carbonic anhydrases, less strongly bound in the active site of the enzyme.
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1. The single -SH groups in the human carbonic anhydrases B and C have been modified under denaturing conditions. The modified enzymes recover catalytic activity after dilution of the denaturing medium with buffer. By this method a spin label and a fluorescent probe were specifically introduced into the molecules. 2. The modified and reactivated enzymes have similar kinetic properties, inhibitor-binding constants, circular dichroism spectra, and stabilities towards guanidine hydrochloride as the native enzymes. However, the esterase activity of the modified C enzyme is reduced to about 50%. 3. The spectra associated with the probes are insensitive to inhibitor binding in case of the B enzyme, whereas changes of electron paramagnetic resonance spectrum and fluorescence intensity respectively, were observed for the probe-containing C enzymes. The cysteines are located in different parts of the tertiary structures of the homologous B and C enzymes, and these observations suggest that small conformational changes accompanying inhibitor binding are localized to regions of the molecules near the active-site cavity. 4. During denaturation of the spin-labeled B enzyme in 1.7 M guanidine hydrochloride a transient mobilization of the probe occurs, but the mobility is ultimately reduced to a low level. This observation supports previous evidence that denaturation under these conditions, in or near the transition region, mainly yields incorrectly folded molecules rather than stable intermediates between native and fully denatured molecules. 5. During refolding of fully denatured, spin-labeled B and C enzymes the mobility of the probe is drastically reduced within less than 0.1 s after dilution. This would reflect a very short lifetime of the randomly coiled state under these conditions.
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An atypical case of the venereal disease granuloma inguinale, which is very rare in Scandinavia, is reported. The patient presented with recurrent perianal abscess and sinuses, and the diagnosis was not made until histologic examination of an extirpated subcutaneous nodule showed cells containing the pathognomonic Donovan bodies.