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Biomedical subjects

P Langer

Publications and source records attributed to P Langer.

At least 19 recordsLinked to original sources

Cloning of human tumor cell lines in porous glass capillary tubes: a further development of the human tumor stem cell assay.

The conventional human tumor stem cell assay for cloning tumor cells for drug sensitivity testing is limited by its inability to test drug combinations. In an attempt to overcome this limitation, we cloned tumor cell lines within porous glass capillary tubes. In contrast to plastic porous tubes, the porous glass membranes were transparent, and colony formation could be judged on an inverted microscope. Human as well as animal cell lines showed sufficient colony growth. Colonies formed within these porous tubes were homogeneously distributed, and their morphology was similar to those formed in the common stem cell assay. Cloning efficiency and colony size depended on the mean pore diameter of the glass membrane, with best colony growth within tubes with a pore diameter ranging from 8.5 nm to 14 nm. A linear relationship between number of cells seeded and number of grown colonies could be demonstrated for the cell lines MDA-231 and Colo 201. Colony growth achieved within porous glass capillary tubes is comparable to that achieved in Petri dishes and in nonporous tubes. We conclude that the porous capillary cloning system meets the basic suppositions for a quantitative cloning assay. Moreover, the porosity of the glass membrane offers the possibility of variable perfusion of medium and drugs. Further investigations will focus on various perfusion modalities and chemosensitivity testing.

Animals

Immediate and dose-response related increase of biliary excretion of reverse triiodothyronine after propylthiouracil administration.

In a group of rats infused with L-thyroxine (0.13 micrograms T4 in 0.6 ml alkaline saline per hour) for 6 h to which an infusion of propylthiouracil (PTU) was added beginning from the 3rd hour (2 mg PTU in 0.6 ml saline per hour) a significant increase of biliary excretion of reverse triiodothyronine (rT3) was found. In another experiment a dose-response related rT3 excretion by bile was observed in groups of rats infused with 0.05, 0.10, 0.20 or 0.40 mg PTU in 1.2 ml alkaline saline per 2 h, all animals receiving a pulse dose of 1 micrograms rT3 at the beginning of PTU infusion. It was concluded that the increase of rT3 excretion results from the inhibition of 5'-deiodinase type I activity in the liver caused by PTU. It thus appears that such phenomenon may be used as in vivo marker of that enzyme activity.

Animals

Acute development of low T3 syndrome and changes in pituitary-adrenocortical function after elective cholecystectomy in women: some differences between young and elderly patients.

From two groups of female patients (young group: 15 patients aged less than 25 years; elderly group: 15 patients aged more than 65 years) who were subjected to cholecystectomy, blood samples were obtained on the day before surgery, on the day of surgery before premedication and after waking up from anaesthesia and also on days 1, 3 and 7 after surgery. In aliquots of sera the levels of TSH, ACTH, thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and cortisol were estimated with the aid of radio-immunoassay (RIA). The differences between the young and elderly subjects were evaluated with the aid of four different statistical tests. Though no changes in the level of T4 were found, the level of T3 was significantly decreased and that of rT3 was significantly increased on Day 1 after surgery. However, the decrease of T3 was expressed more significantly in the young group and, in addition, an increase of rT3 in the same group was found even before premedication. The level of TSH showed a sharp increase at the end of surgery, which was expressed more in the young group. Though no differences between groups were observed in a sharp peak of the ACTH level during surgery, the increase of cortisol level in the elderly group was significantly higher and remained so during the post-operative period.

Adrenocorticotropic Hormone

[The importance of optimal iodine intake, the present status and perspectives in Slovakia].

The concentration of iodine was estimated in 667 urine specimens of boys and girls aged 6-18 years from 5 regions of Slovakia. Only about a half of all values (i.e. 48.43%) was found in the optimum range of 10-20 micrograms/dl, while 40.43% of values wore in the range of iodine deficiency (i.e. less than 10 mu/dl). In addition, there were 10.64% of high values (ie. more than 20 micrograms/dl). These results show that the intake of iodine appears to be 3-4 times higher than before the start of iodine prophylaxis in about 1950, but it still does not reach the optimum level. The increase of iodine intake would be achieved by the replacement of iodide (KI) with iodate (KIO3) which is much more stable. This prevents the looses of iodine from the salt which represent 50 to 75 percent of the original level within 1 to 1 and a half year.

Adolescent

Partial hepatectomy alters serum hormone levels in rats.

The level of thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), thyroxine (T4), 3,5,3'-L-triiodothyronine (T3), corticosterone, testosterone and insulin in serum were measured at 1, 12, 48 and 120 h after partial hepatectomy (PH) or sham operation in rats. After PH the level of ACTH and corticosterone was significantly elevated while that of TSH, T4 and testosterone was decreased and returned to the values found in sham operated animals within 5 days. The level of T3 was unchanged. These results show an increase in the function of pituitary-adrenal axis and a decrease in that of pituitary-thyroid axis shortly following PH with the tendency to return to normal function within five days.

Adrenocorticotropic Hormone

Increase of biliary excretion of reverse triiodothyronine in rats during the infusion of neurotensin possibly resulting from the inhibition of iodothyronine 5'-monodeiodination.

Male rats weighing about 350 g were inserted polyethylene tubes into the bile duct and femoral vein under pentobarbital anaesthesia. After taking the first (control) 2-h bile sample the control group (n = 24) was infused saline for 4 h and the other group (n = 14) was infused neurotensin in a dose of 27 micrograms per animal per 4 h. The concentration of thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) in the bile was estimated by radioimmunoassay. No significant differences between groups were found in the biliary excretion of T4 and T3, while the excretion of rT3 after the infusion of neurotensin was significantly increased which was not the case in controls. Since neurotensin is known to increase glycemia which effect might be or might not be mediated by glucagon, it may be suggested that these results bring an additional support for the previously reported coincidence between a prevailing effect of gluconeogenetic hormones and inhibition of iodothyronine 5'-deiodination in the liver.

Animals

Thyroid volume by ultrasound in boys and girls 6-16 years of age under marginal iodine deficiency as related to the age of puberty.

The results of thyroid volume estimation with the aid of ultrasound in a total of 921 boys and girls 6-16 years of age are reported. The thyroid volume was found to be increasing slowly between the age of 6 and 12 years, but somewhat more remarkable increase occurred at 13 and 14 years of age. However, in both sexes it was nearly doubled at the age of 15-16 years as compared with the values at 13-14 years irrespective of body weight. The thyroid growth rate (as calculated from the least squares analysis of the correlation between thyroid volume and body weight) in girls was significantly higher (P less than 0.001) than in boys. In spite of long-term mandatory iodine prophylaxis the average urinary excretion of iodine as estimated in 69 randomly selected subjects was 78.06 micrograms/g creatinine (geometrical mean). It may be suggested that such intake of iodine, though marginally deficient, may be satisfactory up to the age of about 12-14 years, while it appeared to be inadequate for the adolescents at the age of puberty.

Adolescent

[Acute low triiodothyronine syndrome in the perioperative period].

Serum concentrations of thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) were determined by radioimmunoassay in 11 patients (8 females and 3 males aged 42-65 years) before cholecystectomy and at various time intervals following operation up to 10 days. The surgical procedure was uncomplicated in all the cases studied. The level of rT3 was significantly increased (P less than 0.01) already on the first postoperative day and was then decreasing to its initial value. The levels of T4 and T3 were markedly reduced particularly on postoperative days 2 to 5 (the drop was significant on calculating individual values as percentages of the preoperative level of the given patient). This acutely developing syndrome of low triiodothyronine disappeared spontaneously within 7 to 10 days at a noncomplicated postoperative course.

Acute Disease

Does a short-term draining of bile duct affect the plasma thyroxine level in rats?

In three groups of male rats weighing about 350 g and fed normal pelleted diet the left femoral artery and vein were cannulated under pentobarbiturate anesthesia and in samples of plasma obtained between 0 and 6 h after the injection of heparin the level of thyroxine (T4) was measured with the aid of specific radioimmunoassay. In addition, in Group A (22 animals) and C (17 animals) also the bile duct was cannulated and the total bile was collected into a flask for the same period. In addition, the animals of a Group C were thyroidectomized by electrocoagulation immediately before "O h". The Group B consisted of 18 sham-operated animals in which, in addition to the cannulation of blood vessels, only laparotomy and separation of bile duct without cannulation were made. In all groups a linear decline of plasma T4 level was found corresponding to a half-life of about 11 h. Since there were no significant differences in the slope of regression line between groups, it was concluded that the period of draining bile duct for 6 h was presumably too short to interfere significantly with the absorption of T4 in lower intestine and ileum and that the uniform decline of T4 level in plasma in all groups was presumably due to the effect of pentobarbiturate.

Animals

Short-term effect of acetylsalicylic acid analogue on pituitary-thyroid axis and plasma cortisol level in healthy human volunteers.

The effect of acetylsalicylic acid analogue (aloxiprinum; Superpyrin Spofa) administered perorally in a daily dose of 1 g per 10 kg body weight on serum levels of free thyroxine (FT4), total thyroxine (T4), triiodothyronine (T3), cortisol (F) and thyrotrophin (TSH) was studied in healthy human volunteers. In a first experiment the drug was administered for 3 days to 7 subjects, the total daily dose being divided into 4-5 aliquots, while the same total dose was administered within 4 h to another 8 subjects in a second experiment. In both experiments a highly significant increase of FT4 was found during the period of treatment, while the levels of other hormones i.e. (T3, T4, F and TSH) were decreased, in most cases significantly. After the withdrawal of the drug there was not only a return of all levels to the initial value, but in most cases an "overshoot" above this value was detected.

Adult

Lesions of some central nervous structures result in altered pituitary-thyroid response to acute decrease of blood thyroid hormone level.

Eight groups (3--6 animals each) of rats weighing 350--400 g were subjected to electrolytic lesions of various parts of habenular, thalamic and hypothalamic areas of brain. On the 6th day after the lesion the level of blood thyroid hormone was acutely decreased with the aid of isovolemic exchange transfusion (IET) of thyroid hormone free blood suspension. The level of thyroxine (T4) in plasma was measured before and during 180 min after IET with the aid of specific radioimmunoassay and the changes of its post-transfusion level were evaluated. It was found that in three groups of animals bearing large bilateral lesions either in lateral ventral thalamus or in a central inferior thalamus the response of T4 level during the post-transfusion period is similar to that found in intact control groups from previous experiments. This consists in an increase of T4 level nearly to the initial value within about 120--150 min after IET. In contrast, there was only a slight post-transfusion increase of T4 level in one group with small central lesion in medial superior thalamus and no increase in two groups bilaterally lesioned in habenular area and in another two groups lesioned either in a central part of dorsal hypothalamus or in a central dorsal part of ventral basal hypothalamus. It was concluded that some parts of brain may be involved in managing the appropriate response of pituitary-thyroid axis to acute decrease of thyroid hormone level, no plausible explanation of the mechanism ofthe observed phenomena being offered.

Animals

Changes of LH, TSH, GH, FSH and PRL in pituitaries and sera of rats after thyroidectomy and thyroxine treatment as studied by radioimmunoassay and disc electrophoresis.

Rat pituitary hormones (LH, TSH, GH, FSH and PRL) were located in polyacrylamide gels after the separation of rat pituitary homogenate with the aid of electrophoresis. Furthermore, the incorporation of 3H-glucosamine and 14C-leucine into various protein fractions of incubation media and pituitaries incubated for 6 h in vitro, homogenized and then subjected to disc electrophoresis was measured in six groups of rats: 1. control; 2. two weeks after thyroidectomy (Tx); 3.--6. two weeks after thyroidectomy and injected 20 micrograms L-thyroxine (T4) i.p. per animal at 6, 12, 24 and 48 h before sacrifice, respectively. A decrease of 14C-leucine incorporation into GH and PRL after thyroidectomy was found which was improved by T4 treatment. Moreover, an increase of 3H-glucosamine and 14C-leucine incorporation into TSH zone and origin zone was observed, the former presumably representing the extracted TSH and the latter consisting of unextracted portion of TSH, other hormones and unidentified proteins. Such increase was significantly less after T4 treatment. Finally, changes of radioimmunoassayable LH, TSH, GH, FSH and PRL in pituitaries and sera of analogous groups of rats, but consisting of another animals were measured. The content of TSH in the pituitary slightly increased after Tx, but increased further after T4 treatment. In contrast, the content of all other hormones in the pituitary decreased after Tx, while T4 treatment resulted in a stepwise increase. In plasma, a significant decrease of GH and PRL after Tx was found with no remarkable changes after T4 treatment. The level of LH and FSH was unchanged, while that of TSH increased significantly after Tx and sharply decreased to the original level as early as at 6 h after the injection of T4.

Animals