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Biomedical subjects

R Johansson

Publications and source records attributed to R Johansson.

At least 127 records · Page 7Linked to original sources

A new triphenylethylene compound, Fc-1157a. I. Hormonal effects.

The basic pharmacological and biochemical properties of a new antiestrogen, Fc-1157a, are described. Fc-1157a is bound specifically and with high affinity to estrogen receptors. The binding is competitive with estradiol. Fc-1157a treatment induces translocation of estrogen receptors from cytoplasm to nucleus. The turnover rate of nuclear estrogen receptors is markedly lower than with estradiol, but is more rapid than after tamoxifen. Fc-1157a is an almost pure antiestrogen in rat uterus, but has intrinsic estrogenic activity in mouse uterus. In animal experiments Fc-1157a has shown antitumor properties, which are described in the companion paper.

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↗

Folic acid as an adjunct in the treatment of children with the autism fragile-X syndrome (AFRAX).

Four boys with the combination of infantile autism and the fragile-X syndrome were given oral folic acid and placebo, according to a double-blind crossover design. One boy's behaviour appeared to improve on folic acid, but another boy did not seem to be affected at all. For the remaining two boys the results were equivocal. Further study of folic acid in the treatment of autistic boys with the fragile-X syndrome is warranted.

Adolescent↗

Tumor localization with 18F-2-fluoro-2-deoxy-D-glucose: comparative autoradiography, glucose 6-phosphatase histochemistry, and histology of renally implanted sarcoma of the rat.

Rous sarcoma cells were implanted into the kidney of rats. After 5 days of growth the renal tumor was used for comparing histology with glucose 6-phosphatase (G6Pase) enzyme histochemistry (EHC) and 18F-fluoro-2-deoxyglucose (FDG) auroradiography (ARG). It was found that the regions of the kidney tumor that had retained normal kidney structures were devoid of FDG, whereas there was histochemical staining of normal cortical areas. Regions of tumor growth, on the other hand, retained FDG and lacked G6Pase. Necrotic areas did not accumulate FDG. There was a dramatic decrease in the areas of G6Pase activity as a result of tumor infiltration in the kidney. The results show that FDG, currently being evaluated as a tumor detecting radiopharmaceutical indeed accumulates into areas of vital malignant growth, and they indicate that FDG positron emission tomographic (PET) images reveal the true anatomic location of malignant tissue.

Animals↗

Screening for endometrial carcinoma by endouterine aspiration cytology with analysis of tumor markers in the aspirates. Development and application of a new screening technique.

A new endometrial aspiration technique for office screening of endometrial carcinoma without an anesthesia was studied. In patients without apparent signs of cervical canal stenosis, all of whom were 50 years of age or older, the aspiration attempt was successful in 96%. The aspirates were used for cytologic study and tumor marker assays. The results indicate that screening for endometrial carcinoma should be based on the determination of biochemical tumor markers in the uterine fluid. Lactate dehydrogenase (LD) is recommended as a primary marker, determined as total LD and as LD isoenzyme activity. Endometrial cytology is recommended as a supplementary screening technique in selected cases.

Aged↗

Estrogen receptors in mammary cancer: correlation with age, menopausal status, and response to therapy.

The concentration of estrogen receptor protein (ER) in 113 primary or metastatic breast cancers was studied. ER was found to be correlated with the age of the patient. The ER values were generally lower in premenopausal patients (5.6 fmol/mg cytosol protein) than in postmenopausal patients (32.8 fmol/mg cytosol protein). The ER values of perimenopausal patients (0-5 years since the last menstrual period) were heterogeneous but generally closer to those of the premenopausal patients. Use of the ER determination for allocation of the patients either to hormonal (tamoxifen or nandrolonedecanoate) or to cytostatic (adriamycin-cyclophosphamide or Cooper's regimen) therapy was shown to result in highly satisfactory clinical response rates (including complete and partial remissions and stabilized disease) of 68% and 67%, respectively. The practical limit of ER concentration for selection is between 3 and 10 fmol/mg cytosol protein in breast cancer.

Adult↗

Imaging of canine cancers with 18F-2-fluoro-2-deoxy-D-glucose (FDG) suggests further applications for cancer imaging in man.

18F-2-fluoro-2-deoxy-D-glucose (FDG) is a novel radiopharmaceutical that has gained much interest as a cancer-seeking agent. In this paper two cases of histologically verified canine cancer, an osteosarcoma and a mammary carcinoma, are presented. After an intravenous bolus injection of FDG, accumulation of radioactivity over the neoplastic lesion was followed with a computer-guided specially collimated gamma camera. Ratios of radioactivity between tumour and control areas at 30 min were 2.8 and 2.2 for the osteosarcoma and the mammary carcinoma, respectively. In the osteosarcoma, which was imaged for 3 h, this ratio remained essentially stable. It is reasonable to assume that FDG will be suitable for cancer imaging in man.

Animals↗

Steroid receptors and response of ovarian cancer to hormones in vitro.

Oestrogen receptor (ER) and progesterone receptor (PR) content and the response in vitro to tamoxifen (T), medroxyprogesterone acetate (MPA) and to a combination of the two hormones were determined in 21 epithelial ovarian carcinomas. The response was assessed by the level of adenosinetriphosphate in the cells. ER and PR were detected in 62% and 57%, respectively, with significant variations between the different histopathological cancer types. ER and PR predicted the response in vitro in 62% of the tumours exposed to the combined hormones, and in 38% and 33% of those exposed to T and MPA, respectively. The value of steroid-receptor determinations in selecting the proper hormonal treatment in ovarian cancer is significantly reduced because of the high proportion of incorrect predictions.

Adult↗

Changes in motoneurone firing rates during sustained maximal voluntary contractions.

Tungsten micro-electrodes have been used to record the electrical activity of single motor units in the human adductor pollicis during maximal voluntary contractions. The potentials were characteristic of those from single muscle fibres. In brief maximal contractions, the firing rates of over 200 motor units were obtained from five normal subjects. Four subjects had a similar range (mean 26.4 +/- 6.5 Hz) while the fifth was slightly higher (35 +/- 7.4 Hz). When maximal voluntary force was sustained for 40-120 s, there was a progressive decline in the range and mean rate of motor-unit discharge. In the first 60 s, mean rates fell from about 27 Hz to 15 Hz. There was some evidence to suggest that those units with the highest initial frequencies changed rate most rapidly. It is suggested that this decline in motor unit discharge rates is not responsible for force loss, but that it may enable effective modulation of voluntary strength by rate coding to continue during fatigue.

Action Potentials↗

Contractile speed and EMG changes during fatigue of sustained maximal voluntary contractions.

Measurements were made from the human adductor pollicis muscle of force, contractile speed, and electromyographic activity (EMG) before, during, and after maximal isometric voluntary contractions sustained for 60 s. The use of brief test periods of maximal nerve stimulation with single shocks or trains of shocks enabled various muscle mechanical properties to be studied throughout each contraction. Electrical activity was measured after rectification and smoothing of the surface potentials and also by counting the total number of potentials per unit time from a population of motor units using fine wire intramuscular electrodes. During a 60-s maximal voluntary contraction, the force fell by 30-50%. Throughout the experiment the voluntary force matched that produced by supramaximal tetanic nerve stimulation. This indicated that, with sufficient practice, full muscle activation could be maintained by voluntary effort. However, the amplitude of the smoothed, rectifed EMG and the rate of spike counts declined. Since no evidence for neuromuscular block was found, the decline in EMG and spike counts was attributed to a progressive reduction of the neural drive from the central nervous system, despite maintained maximum effort. After the prolonged voluntary contractions twitch duration was prolonged, mainly as a result of slowing in relaxation rate. Twitch summation in unfused tetani increased. Both the maximum rate of relaxation and the time course of force decay declined by 50-70%. Similar changes were seen in both voluntary contractions and in test periods of stimulation. The percentage change in muscle contractile speed measured by these parameters approximately equaled the percentage change in the surface EMG measured simultaneously. It is concluded that 1) during a 60-s sustained maximal voluntary contraction there is a progressive slowing of contraction speed such that the excitation rate required to give maximal force generation is reduced, 2) the simultaneous decline in EMG may be due to a continuous reduction in motoneuron discharge rate, and 3) the EMG decline may not necessarily contribute to force loss.

Adult↗

Motor-unit discharge rates in maximal voluntary contractions of three human muscles.

Single motor-unit firing rates have been recorded during maximal voluntary contractions using tungsten microelectrodes. Over 300 units from four subjects were sampled from each of three muscles. These were the biceps brachii, adductor pollicis, and soleus, chosen because of known differences in their fiber-type composition and contractile properties. In all cases the contraction maximality was assured by delivering single supramaximal shocks during the voluntary contractions. All motor units were deemed to have already been fully activated if no additional force resulted. Thus for each muscle, the firing rates elicited by a maximal voluntary effort are sufficient to generate a fully fused tetanus in each motor unit. For the biceps brachii and adductor pollicis muscles, the mean firing rates (+/- SD) were 31.1 +/- 10.1 and 29.9 +/- 8.6 Hz, respectively, while for soleus they were only 10.7 +/- 2.9 HZ. For each muscle the firing rates distribution covered approximately a four-fold range about the mean value. The mean firing rates for each muscle varied roughly in proportion to their respective twitch contraction and half relaxation times. These contractile time measurements for both biceps brachii and adductor pollicis agreed well with the mean values reported for human fast-twitch motor units, while those for soleus fell in the range observed for human slow-twitch units. An argument is presented that suggests that, in response to voluntary effort, the range of discharge rates of each motor-unit pool is limited to those only just sufficient to produce maximum force in each motor unit. This suggestion is based on the relationship between the range of motor-unit firing frequencies observed during maximum voluntary contractions, their range of contraction times, and the stimulation frequencies required for maximum force generation. The implications of this hypothesis for motor control are discussed.

Adult↗

Ultrasound assessment of liver veins in congestive heart failure.

The width of the liver veins was measured using ultrasound in 40 normal subjects and in 29 patients with congestive heart failure with and without pleural effusion. The liver veins were significantly wider in the patients, and the widest veins were found in those with pleural effusion. The presence of pleural effusion indicates that right heart failure, causing dilatation of liver veins, is added to pre-existing left heart failure.

Aged↗

Iopamidol compared with Conray in peripheral angiography.

In patients with arteriosclerotic disease in the legs, peripheral angiography was performed double blind with the non-ionic contrast medium Iopamidol and the ionic medium iothalamate meglumine (Conray 60). Iopamidol caused less subjective adverse effects and less changes in blood pressure.

Aged↗