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Biomedical subjects

P Koivisto

Publications and source records attributed to P Koivisto.

51 records · Page 3Linked to original sources
PubMed1990

Synthesis and stability of 2'-deoxyguanosine 3'-monophosphate adducts of dimethyl sulfate, ethylene oxide and styrene oxide.

Deoxyguanosine 3'-monophosphate (dGMP) was alkylated at the 7-position by dimethyl sulfate, ethylene oxide and styrene oxide in aqueous media and glacial acetic acid, respectively, to yield reasonable quantities of the products, which were purified by HPLC. dGMP adducts are needed as standards for the 32P-postlabelling assay. The stability of the adducts was studied at 37 degrees and neutral pH. The half-lives of disappearance of 7-methyl-dGMP and the beta-isomers of the styrene oxide adducts were about 250 min; 7-hydroxy-ethyl-dGMP and the alpha-isomers of the styrene oxide adducts had respective half-lives of 340 and 440 min. In all cases the main degradation product was the corresponding guanine adduct. The results demonstrate considerable lability of the 7-alkylation products of dGMP which has to be taken into consideration in devising the 32P-postlabelling assay.

Alkylating Agents↗
PubMed1990

32P-postlabelling of 2-hydroxyethylated, ethylated and methylated adducts of 2'-deoxyguanosine 3'-monophosphate.

Ethylene oxide, diethyl sulphate and dimethyl sulphate were used to synthesize the corresponding 7-alkylation products of 2'-deoxyguanosine 3'-monophosphate (dGMP). The purified adducts were used as substrates in the 32P-post-labelling reaction with T4 polynucleotide kinase. The kinetics of phosphorylation were studied with 7-(2-hydroxyethyl)-dGMP: most net product was formed by 15 min and only a small increase was seen until 4 h. When different concentrations of the adducts were tested, a complete phosphorylation was noted for 7-methyl-dGMP to the lowest tested amount of 1 fmol. The efficiencies of phosphorylation for 7-ethyl- and 7-hydroxyethyl-dGMP were 1.5 and 0.5% respectively. The proportions phosphorylated were uniform over the concentration range tested. The results demonstrate dramatic differences in the efficiency of phosphorylation between structural analogues, which is probably related to a decreased affinity of the substrate to the enzyme or to an interference in the transfer of the phosphate group on the active site of the enzyme.

Alkylation↗
PubMed1990

Gallbladder disease, bile composition and bile acid absorption after partial ileal bypass.

The incidence of gallbladder disease (gallstones or cholecystectomy) in 24 ileal bypass patients and in 24 unoperated matched controls, all heterozygous for familial hypercholesterolemia, was studied during a follow-up period of nine years on average. Gallbladder disease developed in 6 patients with ileal bypass and in one control patient (p less than 0.05). The operated patients who developed gallbladder disease were slightly older and had a higher serum cholesterol concentration at the start than those who did not, but otherwise the development of gallbladder disease could not be predicted by serum lipids or serial measurement of bile acid and cholesterol synthesis. At the end of the follow-up, the unoperated subjects had gained in weight. Moreover, the biliary lipid composition and the cholesterol saturation index of the bile were similar in the operated (n = 10) and unoperated (n = 10) patients studied. Indirect measurements suggested that the bile acid secretion was not changed by the operation, although the fractional bile acid absorption was significantly lowered in the operated subjects, especially in three subjects taking cholestyramine. All these three subjects had supersaturated bile. It is concluded that ileal bypass carries an increased risk of gallbladder disease although the cholesterol saturation index of the bile shows no significant difference between the operated and the control patients when studied years after the operation, when the control patients have gained in weight.

Adult↗
PubMed1988

Risk of brain infarction in familial hypercholesterolemia.

We followed 54 subjects with heterozygous familial hypercholesterolemia for an average of 10 (range 3-14) years. Half were treated surgically with partial ileal bypass and the other half (matched for age, sex, coronary heart disease, blood pressure, diabetes mellitus, smoking, obesity, and serum cholesterol concentration) were treated conservatively with diet and hypolipidemic drugs. The mean decrease in serum cholesterol concentration from the average value of 522 mg/dl on entry into the study was 32% in the surgically treated group and 10% in the conservatively treated group. One quarter of the subjects (14 of 54) had symptomatic cerebrovascular disorders and one tenth (six of 54) suffered a brain infarction at a mean age of 43 (range 30-57) years. Two thirds of the brain infarctions occurred during follow-up. The method of treatment of familial hypercholesterolemia did not affect the number of new cerebrovascular events. The incidence of brain infarction was 7.4/1000/yr. The risk of brain infarction in these subjects with familial hypercholesterolemia was at least 20 times higher than in the general population. We conclude that symptomatic subjects with familial hypercholesterolemia have not only a high risk of coronary heart disease but also a high risk of cerebrovascular disorders.

Adult↗
PubMed1987

High density lipoprotein, apoproteins A-I and A-II and postheparin plasma lipolytic enzymes after ileal bypass.

Apoproteins A-I and A-II, and the activities of lipoprotein lipase (LPL) and hepatic lipase (HL), were studied in 16 patients 3-12 years after ileal bypass operation and in 13 controls, all heterozygous for familial hypercholesterolemia, to investigate why the operated subjects had a higher HDL cholesterol level than the unoperated controls. HDL- and HDL2-cholesterol and apoprotein A-I were higher, HDL3-cholesterol was similar and apoprotein A-II tended to be lower in the operated than the control subjects. The activities of LPL and HL were similar in the 2 groups. HL was negatively correlated with HDL2-cholesterol, whereas LPL was not associated with any of the HDL components. The controls had gained in weight during the follow-up, but the HDL components were not correlated with relative body weight. It is concluded that in familial hypercholesterolemia ileal bypass results in higher HDL- and HDL2-cholesterol and apoprotein A-I level than conservative treatment and that postheparin plasma lipolytic enzymes do not explain the higher level of these HDL components in the operated subjects.

Adult↗
PubMed1987

Fecal bile acids related to small-bowel length before and after ileal exclusion.

We studied the relationship among the small-bowel length, the fecal excretion of bile acids and neutral steroids, and cholesterol synthesis in 16 patients with familial hypercholesterolemia before and 1 month after the ileal bypass operation. The mean small-bowel length measured during the operation was 6.3 +/- 0.3 (SEM) m before and 4.3 +/- 0.2 m after the bypass of the distal third of the small bowel. The preoperative fecal bile acid excretion was negatively correlated (r = 0.63, p less than 0.01) with the small-bowel length, whereas this correlation was insignificant for fecal neutral steroid excretion and cholesterol synthesis. Postoperative amounts of fecal bile acids and neutral steroids and cholesterol synthesis were negatively correlated with the length of the small bowel remaining in function (r = -0.52, -0.51, and -0.62, respectively). Our study suggests that fecal bile acid excretion and, hence, bile acid synthesis are related to the small-bowel length even under physiologic conditions.

Adult↗
PubMed1986

Adaptation of cholesterol and bile acid metabolism and vitamin B12 absorption in the long-term follow-up after partial ileal bypass.

Cholesterol and bile acid metabolism and vitamin B12 were studied in 19 patients with heterozygous familial hypercholesterolemia in an 8-yr follow-up (3-12 yr after ileal bypass operation), and in 11 unoperated controls. Absorption of cholesterol and vitamin B12 were decreased by the operation, but improved slowly, and at 8 yr cholesterol absorption was normal. Cholesterol excretion as fecal neutral steroids was not increased by the operation, and at 8 yr the flux of endogenous cholesterol to the gut was similar in the operated and control patients. Cholesterol absorption was positively correlated with mouth to anus transit time in the unoperated patients. Fecal bile acid excretion was increased immediately after the operation and continued to increase even after the second postoperative year. In the operated patients fecal excretion of fat, water, and dry matter were positively correlated with fecal bile acid excretion. Our study suggests that adaptive changes occur slowly after ileal bypass, resulting in gradual normalization of cholesterol absorption, despite continuing bile acid malabsorption, and that the intestinal transit time is related to steroid absorption even under physiologic conditions.

Adult↗
PubMed1986

Electrical resistance of vaginal secretion in the bitch.

Five multiparous and four nulliparous bitches had the electrical resistance of vaginal secretions measured by an ohmmeter. The bitches were examined daily, starting on the first day of vulval bleeding and continuing until the first day when exfoliated vaginal epithelial cells became predominantly noncornified. In contrast to cattle, sheep, and swine, the electrical resistance of the vaginal secretions in the bitch increases during pro-oestrus and continues to be high while the bitch is showing oestrous behaviour and a high percentage of eosinophilic superficial cells in the vaginal smear. Ovulation, as determined by a rise of serum progesterone above 5 ng/ml, occurs within the period of elevated resistance. Optimal conditions for conceptions coincide with the last 3 d of elevated resistance.

Journal Article↗
PubMed1984

Long-term effects of ileal bypass on lipoproteins in patients with familial hypercholesterolemia.

Partial ileal bypass is effective in reducing circulating cholesterol levels. In our study the 10 year effects of the procedure on serum lipids and lipoproteins were studied in 27 patients with heterozygous familial hypercholesterolemia. The ileal bypass patients were compared with conservatively treated case controls matched for age, sex, serum cholesterol level, relative body weight, blood pressure, and smoking habits and also for the existence of diabetes and coronary heart disease. Serum triglycerides were initially slightly higher in the patients undergoing ileal bypass. During the 10 year follow-up eight surgically treated and seven control patients suffered fatal or nonfatal myocardial infarctions. Of these all but one male subject who underwent surgery had had manifest coronary heart disease at entry. Male sex, smoking, triglyceride levels, and angina were significant predictors of new coronary events. The fall in serum cholesterol in patients who underwent ileal bypass and had fatal myocardial infarctions was smaller than in the corresponding subjects without events. The serum lipid levels of the survivors at the end of the 10 year follow-up showed that ileal bypass, as compared with the conservative treatment, had led to a larger decrease in total serum cholesterol (-33% vs -11% in the control patients; p less than .001); lower total serum cholesterol (360 vs 468 mg/dl; p less than .001), low-density lipoprotein (LDL) cholesterol (236 vs 324 mg/dl, p less than .001), and LDL apoprotein B levels (186 vs 231 mg/dl; p less than .001); and higher serum high-density lipoprotein (HDL) (46 vs 38 mg/dl; p less than .05) and HDL2 cholesterol levels (25 vs 16 mg/dl; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗