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H Sipilä

Publications and source records attributed to H Sipilä.

18 recordsLinked to original sources

PET studies on the memory processing of word pairs in bilingual Finnish-English subjects.

This study examined the fundamental question whether verbal memory processing in two unrelated languages is mediated by a common neural system or by distinct cortical areas. Ten right-handed, male Finnish--English adult late bilinguals who had acquired the second language after the age of 10 were scanned whilst either encoding/retrieving word pairs in their mother tongue (Finnish) or in a foreign language (English). Within each language, subjects had to encode and retrieve four sets of 12 visually presented paired word associates which were not semantically related. Two sets consisted of highly imageable words (e.g. monkey-table; koira-lasi) and the other two sets of abstract word pairs (e.g. freedom-moral; uhka-suure). Presentation of pseudowords served as a reference condition. An emission scan was recorded after each intravenous administration of O-15 water. Encoding was associated with prefrontal and hippocampal activation. During memory retrieval, precuneus showed a consistent activation in both languages and for both highly imageable and abstract words. Although the brain mechanisms of the two languages share common components, differential activations were found in Broca's area and in the cerebellum as well as in the angular/supramarginal gyri according to the language used.

Adult↗

Myocardial fatty acid oxidation in patients with impaired glucose tolerance.

AIMS/HYPOTHESIS: Fatty acids are an important source of energy in the myocardium. Abnormal myocardial fatty acid metabolism could contribute to the deterioration of cardiac function frequently observed in patients with Type II (non-insulin-dependent) diabetes mellitus. In our previous study, myocardial total uptake of non-esterified fatty acid (NEFA) was measured in patients with impaired glucose tolerance and found to be normal. This study aimed to investigate the subsequent metabolic steps and beta-oxidation of NEFA. METHODS: A total of 6 men with impaired fasting glucose (age 50 +/- 2 years, BMI 29 +/- 1 kg/m2, means +/- SEM) and 6 healthy men (50 +/- 1 years, 25 +/- 1 kg/ m2) were studied in the fasting state. Myocardial blood flow was measured with [15O]H2O and positron emission tomography and myocardial NEFA metabolism with [11C]palmitic acid. RESULTS: Myocardial blood flow was normal and not different between the impaired glucose tolerance and the control group (78 +/- 6 vs 73 +/- 13 ml/100 g/ min, NS). The [11C]palmitic acid uptake indices were similar between the groups (10.4 +/- 0.5 vs 11.2 +/- 0.8 ml/100 g/min, respectively, NS). The clearance of [11C]-palmitate from the myocardium, an index of NEFA beta-oxidation, was similar between the groups (half-times of activity 17.6 +/- 1.6 vs 19.5 +/- 2.3 min, respectively, NS) CONCLUSION/INTERPRETATION: The results indicate that myocardial NEFA uptake and beta-oxidation are not altered in patients with IGT. Thus, it is not likely that altered NEFA metabolism contributes to the deterioration of the cardiac function in patients with IGT or Type II diabetes.

Blood Glucose↗

Use of [11C]acetate and [15O]O2 PET for the assessment of myocardial oxygen utilization in patients with chronic myocardial infarction.

Carbon-11 acetate positron emission tomography (PET) has been widely used to assess regional oxidative metabolism of the heart. However, the accuracy of [11C]acetate PET in assessing oxidative metabolism in infarcted myocardium remains controversial. Thirteen patients with stable coronary artery disease and old myocardial infarction were studied. The 15O-based PET studies yielded regional blood flow (rMBF, ml/min/g) and oxygen consumption (rMMRO2, ml/min/g), which was compared with the myocardial clearance rate constant (kmono) of [11C]acetate in segments with rMBF > or = 75% (group A), 50%-74% (group B) or < 50% (group C) of the normal reference segment. Mean MBF was 0.96 +/- 0.08 ml/g/min in group A, 0.67 +/- 0.06 ml/g/min in group B and 0.42 +/- 0.07 ml/g/min in group C segments. The segmental rMMRO2 correlated linearly with kmono (r = 0.89, P < 0.001, y = 0.61x + 0.026). The kmono/rMMRO2 ratio was comparable in the group A and B segments (0.99 +/- 0.19 vs 1.07 +/- 0.21, P = NS). However, the ratio was significantly higher in the group C segments (1.28 +/- 0.35, P = 0.037). It is concluded that kmono of [11C]acetate correlates linearly with rMMRO2 determined by [15O]O2 inhalation. However, kmono appears to yield higher rMMRO2 estimates than the [15O]O2 method in low-flow areas.

Acetates↗

Enhanced oxygen extraction and reduced flow heterogeneity in exercising muscle in endurance-trained men.

The aim of this study was to investigate the effects of endurance training on skeletal muscle hemodynamics and oxygen consumption. Seven healthy endurance-trained and seven untrained subjects were studied. Oxygen uptake, blood flow, and blood volume were measured in the quadriceps femoris muscle group by use of positron emission tomography and [15O]O2, [15O]H2O, and [15O]CO during rest and one-legged submaximal intermittent isometric exercise. The oxygen extraction fraction was higher (0.49 +/- 0.14 vs. 0.29 +/- 0.12; P = 0.017) and blood transit time longer (0.6 +/- 0.1 vs. 0.4 +/- 0.1 min; P = 0.04) in the exercising muscle of the trained compared with the untrained subjects. The flow heterogeneity by means of relative dispersion was lower for the exercising muscle in the trained (50 +/- 9%) compared with the untrained subjects (65 +/- 13%, P = 0.025). In conclusion, oxygen extraction is higher, blood transit time longer, and perfusion more homogeneous in endurance-trained subjects compared with untrained subjects at the same workload. These changes may be associated with improved exercise efficiency in the endurance-trained subjects.

Adult↗

The translating brain: cerebral activation patterns during simultaneous interpreting.

Brain activation was measured in professional interpreters during simultaneous interpreting (SI) vs. repetition (shadowing) of auditorily presented text by positron emission tomography (PET). SI into the native language (Finnish) elicited left frontal activation increases. SI into the non-native language (English) elicited much more extensive left-sided fronto-temporal activation increases. Our results indicate that SI activates predominantly left-hemispheric structures (particularly the left dorsolateral frontal cortex) previously related to lexical search, semantic processing and verbal working memory. Brain activation patterns were clearly modulated by direction of translation, with more extensive activation during translation into the non-native language which is often considered to a be more demanding task.

Adult↗

Enhanced stimulation of glucose uptake by insulin increases exercise-stimulated glucose uptake in skeletal muscle in humans: studies using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography.

In vitro studies have shown that insulin and exercise stimulate glucose uptake in part via distinct mechanisms. We determined whether a high rate of insulin-stimulated glucose uptake (good insulin sensitivity) is associated with an enhanced ability of exercise to increase glucose uptake in vivo in humans. In our study, 22 normal subjects performed one-legged isometric exercise for 105 min (45-150 min) under intravenously maintained euglycemic-hyperinsulinemic conditions (0-150 min). Rates of oxygen consumption, blood flow, and glucose uptake were quantitated simultaneously in skeletal muscle of both legs using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography. The one-legged exercise, performed at an intensity of 11% of maximal isometric force, was designed to induce similar increases in oxygen consumption in both groups. In the entire group, exercise increased oxygen consumption from 2.3 +/- 0.3 ml x kg(-1) muscle x min(-1) (insulin) to 34.2 +/- 3. ml x kg(-1) muscle x min(-1) (insulin and exercise) (P < 0.001) and muscle glucose uptake from 60 +/- 6 pmol x kg(-1) muscle x min(-1) (insulin) to 220 +/- 22 micromol x kg(-1) muscle x min(-1) (insulin and exercise) (P < 0.001). The exercise-induced increase in glucose uptake was due to marked increases in blood flow (36 +/- 5 ml x kg(-1) muscle x min(-1) [insulin] vs. 262 +/- 20 ml x kg(-1) muscle x min(-1) [insulin and exercise], P < 0.001) rather than glucose extraction, which decreased from 2.0 +/- 0.2 mmol/l (insulin) to 1.0 +/- 0.1 mmol/1 (insulin and exercise) (P < 0.001). The subjects were classified according to their mean rate of whole-body insulin-stimulated glucose uptake into those with high (49 +/- 3 micromol x kg(-1) x min(-1)) and normal (27 +/- 2 micromol x kg(-1) x min(-1)) rates of insulin-stimulated glucose uptake. Both insulin-stimulated (2.4 +/- 1.1 vs. 2.3 +/- 1.2 ml x kg(-1) muscle x min(-1), normal vs. high insulin sensitivity) and exercise- and insulin-stimulated (33 +/- 6 vs. 34 +/- 4 ml x kg(-1) muscle x min(-1)) rates of oxygen consumption were comparable between the groups. Exercise increased glucose uptake more in the group with high insulin sensitivity (195 +/- 25 pmol x kg(-1) muscle x min(-1)) than in the group with normal insulin sensitivity (125 +/- 19 micromol x kg(-1) muscle x min(-1)) (P < 0.05). Muscle blood flow was closely correlated with the rate of oxygen consumption (r = 0.91, P < 0.0001), and insulin-stimulated (30 +/- 5 vs. 35 +/- 6 ml x kg(-1) muscle x min(-1)) and exercise-induced increments (222 +/- 31 vs. 228 +/- 23 ml x kg(-1) muscle x min(-1)) in muscle blood flow were similar between the groups. Glucose extraction remained higher in the group with high insulin sensitivity (1.2 +/- 0.2 mmol/l) than in the group with normal insulin sensitivity (0.7 +/- 0.1 mmol/l, P < 0.05). We conclude that whereas acute exercise per se increases glucose uptake via increasing glucose delivery, good insulin sensitivity modulates exercise-induced increases in glucose uptake by enhancing cellular glucose extraction.

Adult↗

Left hemisphere activation during processing of morphologically complex word forms in adults.

Functional neuroanatomy of the processing of morphologically complex words was studied by measuring regional brain activity by positron emission tomography (PET) during encoding of auditorily presented inflected versus monomorphemic Finnish nouns. Significant increases of activation occurred particularly in the left inferior posterior frontal lobe, corresponding to Broca's area. This suggests that besides their role in the production of grammatical morphology documented earlier, Broca's area and adjacent regions are important for the input processing of morphologically complex words.

Adult↗

Quantitative blood flow measurement of skeletal muscle using oxygen-15-water and PET.

UNLABELLED: The aim of the present study was to evaluate quantitation of muscle blood flow using [15O]H2O and PET. METHODS: The autoradiographic (ARG) and the steady-state methods using PET were used to measure femoral muscle blood flow. A simulation study was performed to examine the errors due to contamination of radioactivity in the blood content in muscle tissue, statistical noise and delay and the dispersion of the input curve in the ARG method. Five separate paired muscle blood flow examinations were carried out for comparison of the ARG and the steady-state techniques, including measurement of muscle blood volume in each subject. To obtain the normal range for resting muscle blood flow, additional measurements with the ARG method were performed in 16 normal subjects. RESULTS: When the integration time in ARG was increased to 200-300 sec, the errors due to arterial blood volume, statistical noise, delay and dispersion of the input curve were significantly reduced. Muscle blood flow values in the ARG (200 sec) and the steady-state studies were in good agreement, and each provided an estimated accuracy of 5%. Resting muscle blood flow averaged 3.12 +/- 1.55 ml/min.100 g muscle (range 1.43-6.72 ml/min.100 g muscle, n = 18). CONCLUSION: The ARG and the steady-state methods provided consistent blood flow values for skeletal muscle when a long tissue integration time (> or = 200 sec) was applied in the ARG study. Based on the lower effective radiation dose and the shorter total scan duration, the ARG method is favored over the steady-state method in the measurement of muscle blood flow.

Adult↗

Evidence for dissociation of insulin stimulation of blood flow and glucose uptake in human skeletal muscle: studies using [15O]H2O, [18F]fluoro-2-deoxy-D-glucose, and positron emission tomography.

We determined the effect of insulin on muscle blood flow and glucose uptake in humans using [15O]H2O, [18F]fluoro-2-deoxy-D-glucose ([18F]FDG), and positron emission tomography (PET). Femoral muscle blood flow was measured in 14 healthy volunteers (age 34 +/- 8 years, BMI 24.6 +/- 3.4 kg/m2 [means +/- SD]) before and at 75 min during a 140-min high-dose insulin infusion (serum insulin 2,820 +/- 540 pmol/l) under normoglycemic conditions. A dynamic scan of the femoral region was performed using PET for 6 min after injection of [15O]H2O to determine the 15O concentration in tissue. Regional femoral muscle blood flow was calculated using an autoradiographic method from the dynamic data obtained with PET and [15O]H2O. Femoral muscle glucose uptake was measured during hyperinsulinemia immediately after the flow measurement using PET-derived [18F]FDG kinetics and a three-compartment model. Whole-body glucose uptake was quantitated using the euglycemic insulin clamp technique. In the basal state, 84 +/- 8% of blood flow was confined to skeletal muscle. Insulin increased leg blood flow from 29 +/- 14 to 54 +/- 29 ml x kg-1 leg x min-1 (P < 0.001) and muscle flow from 31 +/- 18 to 58 +/- 35 ml x kg-1 muscle x min-1 (P < 0.005). Under insulin-stimulated conditions, 81 +/- 8% of blood flow was in muscle tissue (NS versus basal). Skeletal muscle explained 70 +/- 25% of the increase in leg blood flow. No correlation was observed between blood flow and glucose uptake when analyzed individually in identical regions of interest within femoral muscles. These data demonstrate that skeletal muscle accounts for most of the insulin-induced increase in blood flow. Insulin-stimulated rates of blood flow and glucose uptake do not colocalize in the same regions of muscle tissue, suggesting that insulin's hemodynamic and metabolic effects are differentially regulated.

Adult↗

Insulin increases blood volume in human skeletal muscle: studies using [15O]CO and positron emission tomography.

High insulin concentrations increase blood flow in the leg, but it is unknown whether this effect is associated with a change in muscle blood volume. In the present study, we used positron emission tomography combined with inhalation of [15O]carbon monoxide to quantitate the effect of insulin on skeletal muscle blood volume in humans. The reproducibility of the method was determined from two consecutive measurements performed in the basal state in five normal subjects. The coefficient of variation of the repeated measurements was 3.0 +/- 1.8%. In 14 normal subjects [age 35 +/- 3 yr, body mass index 24.9 +/- 1.3 (SE) kg/m2], skeletal muscle blood volume was determined in the femoral region in the basal state and during euglycemic hyperinsulinemia (serum insulin 3,200 +/- 190 pmol/l). The mean muscle blood volume was 3.3 +/- 0.1 ml/0.1 kg muscle in the basal state. Insulin increased muscle blood volume by 9 +/- 2% to 3.6 +/- 0.2 ml/0.1 kg muscle (P < 0.01). The rate of whole body glucose uptake was 53 +/- 6 mumol.kg-1.min-1 and correlated with muscle blood volume during insulin stimulation (r = 0.65, P < 0.02). We conclude that high insulin concentrations exert a true vasodilatory effect in human skeletal muscle.

Adult↗

Uptake of 2-fluoro-2-deoxy-D-[U-14C]-glucose during chemotherapy in murine Lewis lung tumor.

Mice bearing intramuscular Lewis lung tumor were treated with BCNU and doxorubicin (ADM) to study chemotherapy-induced changes in the uptake of 2-fluoro-2-deoxy-[U-14C]glucose (FDG). A decreased FDG uptake, tumor regression and a diminished proportion of aneuploid versus diploid cells as evaluated by DNA flow cytometry were seen after treatment with BCNU but not with ADM; HPLC indicated that most of the 14C activity in tumors was from FDG6-phosphate. The results suggest that changes in FDG uptake reflect the effectiveness of antitumor therapy. FDG may be valuable in follow-up studies of cancer treatment.

Adenosine Triphosphate↗

Determination of 2-fluoro-2-deoxy-D-glucose uptake and ATP level for evaluating drug effects in neoplastic cells.

The glucose analogue 2-fluoro-2-deoxy-D-glucose (FDG) was used to study chemosensitivity of two human ovarian cancer cell lines and of murine L1210 cells. Cell viability was determined by measuring intracellular adenosine triphosphate (ATP) with a bioluminescence method, which has been shown to correlate closely with trypan blue, stem cell, and [3H]TdR assays. All three cell lines were sensitive to cytostatic drugs, which exerted a parallel decrease in the intracellular FDG and ATP levels. The two measures correlated positively (r = 0.66, P less than 0.001), indicating that FDG uptake is closely linked with ATP production. Relatively low hexokinase (HK)-to-glucose 6-phosphatase (HK/G6-Pase) ratios were measured, which suggests that the metabolic trapping of FDG 6-phosphate within the cytosol is incomplete. Apparently, these cell lines may not depend exclusively on glycolysis for their energy requirement. We conclude that cell killing caused by cytostatic drugs is associated with a decreased ATP content and FDG uptake. This indicates that not only ATP but also FDG may be used to study drug effects in vitro.

Adenosine Triphosphate↗

Metabolism of toremifene in the rat.

Toremifene was labelled to a specific activity of about 20 microCi/mmol with tritium at positions 3 and 5 in the para-substituted phenyl ring. At these positions tritium is not eliminated within the metabolic pathways. A mixture of unlabelled and labelled toremifene (5 or 10 mg/kg, 5 microCi/mg) was given i.v. or p.o. to Sprague-Dawley rats. The elimination of radioactivity was followed up by collecting urine and feces daily for 13 days. The elimination of toremifene which was similar after p.o. and i.v. administration took place mainly in the feces. About 70% of the total radioactivity was eliminated within 13 days, of this amount more than 90% in the feces. All applied radioactivity could be detected in three separate fractions according to the oxidative state of the side chain when counted by Berthold TLC Linear Analyzer. Each fraction was further separated into single metabolites by TLC or HPLC. Altogether 9 metabolites were identified and almost all methanol-extractable components were identified. The main metabolic pathways in the rat were 4-hydroxylation and N-demethylation. The side chain was further oxidized to alcohols and carboxylic acids. Small amounts of unchanged toremifene were found in the feces both after p.o. and i.v. administration indicating biliary secretion.

Administration, Oral↗

Biodistribution and scintigraphy of 11C-toremifene in rats bearing DMBA-induced mammary carcinoma.

A new antioestrogenic antitumour compound toremifene was labeled with 11C or 3H. The tissue distribution and tumour uptake of the compounds in DMBA induced breast tumour bearing rats was investigated. 11C-toremifene was localized by gamma camera scintigraphy and tissue counting. 3H-Toremifene was determined by liquid scintillation counting after oxidizing the tissue samples. Toremifene was distributed to several tissues due to the lipophilicity and was not taken up specifically by the tumours to any great extent. However, the radioactivity of the tumours increased as a function of time although it declined e.g. in the liver. The accumulation to the tumour was a slow process and cannot be followed up reliably by such short half-life radionuclides as 11C. The tumour uptake properties of toremifene resemble those of tamoxifen and several other oestrogen receptor binding compounds. These substances have limited use in diagnosing and imaging oestrogen receptor rich breast tumours in man.

9,10-Dimethyl-1,2-benzanthracene↗

Binding of toremifene to human serum proteins.

The in vitro protein binding of toremifene in human serum was measured by ultracentrifugation using 3H-toremifene together with unlabeled toremifene, 50, 500, and 5000 ng/ml. Of the total radioactivity 99.7 per cent was bound to the proteins independent of the concentration of the unlabeled drug. Binding of toremifene to different protein fractions was studied by adding 3H-toremifene and 500 ng/ml of cold toremifene to normal serum. The serum samples were exposed to agarose gel electrophoresis to fractionate different proteins. The radioactivity was localized using a position-sensitive proportional counter. After that the proteins were visualized by staining. Of the total protein bound radioactivity 92 per cent was bound to albumin, about 6 per cent to beta 1 globulin fraction and about 2 per cent to a fraction between albumin and alpha 1 globulins, part of this probably to alpha 1 acid glycoprotein.

Blood Proteins↗

Metabolism of 2-[18F]fluoro-2-deoxyglucose in tumor-bearing rats: chromatographic and enzymatic studies.

The activities of hexokinase and glucose-6-phosphatase, as well as the in vivo metabolic products of 2-[18F]fluoro-2-deoxyglucose ([18F]FDG) (45 min after an i.v. injection), were determined from several tissues of Rous sarcoma implanted rats. The HK/G-6-Pase ratio was found to be high in brain and tumor, and low in liver with intermediate values for kidney and muscle. In accordance with the measured enzyme activities about 90% of the 18F was found as [18F]FDG-6-P in brain, heart and tumor, whereas most of its was as [18F]FDG in liver and kidney. In addition three minor metabolites, tentatively identified as nucleotide-derivatives of [18F]FDG, were formed. Our results suggest that at least Rous sarcoma tumor effectively converts [18F]FDG to [18F]FDG-6-P and thus PET studies with [18F]FDG can be applied to tumor diagnosis and to quantitative measurement of glucose utilization in tumor tissue according to the model of Sokoloff.

Animals↗

Scintigraphy with [18F]2-fluoro-2-deoxy-D-glucose of cancer patients.

Computerized dynamic gamma camera scintigraphy was performed with [18F]2-fluoro-2-deoxy-D-glucose [( 18F]FDG) on 10 patients with different cancers; tumor perfusion was evaluated in four patients with 99mTc-DPD. All tumors were visible in the [18F]FDG scans with tumor-to-tissue image contrast ratios of 1.2-11.7. Tumor perfusion exceeded that of the surrounding normal tissue in three of the four patients studied. Tumor-to-normal tissue [18F]FDG ratios were plotted as a function of the time. Two types of curves emerged: curves showing a linear increase in the ratio and curves showing a constant value for the ratio. These studies show that [18F]FDG can be used for clinical tumor imaging with a gamma camera, and that there appears to be biological differences in tumor uptake of [18F]FDG.

Adult↗

Effects of heparin and a semi-synthetic heparin analogue on platelet aggregation, lipoprotein lipase and other laboratory tests in surgical patients.

Platelet aggregation, lipoprotein lipase activity, coagulation parameters and routine blood chemistry were measured in a randomised study of 21 surgical patients before, immediately after and 3 months after operation. Sodium heparin 5000 IU was given subcutaneously to 11 patients every 12 hours for 7 days, the first injection 2 hours preoperatively; 10 patients received a semi-synthetic heparin analogue (SSHA 75 mg) in the same manner. The groups were sex and age matched. No conclusive changes were found in platelet aggregation. The increase in lipoprotein lipase activity in SSHA patients 2 hours after injection was significantly greater than in heparin patients. Neither of the two drugs induced significant changes in coagulation parameters or routine blood chemistry. The results indicate a difference in the effect on lipoprotein lipase release between heparin and SSHA at the used dosage schedules.

Aged↗