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Biomedical subjects

J Nowak

Publications and source records attributed to J Nowak.

At least 19 recordsLinked to original sources
PubMed1992

Immunoreactive glucagon and insulin in mammary secretion and blood in women during the periparturient period.

The concentrations of glucagon (G) and insulin (I) in the isolated when fraction of colostrum and plasma were determined by radioimmunoassay in 30 women on the last day of pregnancy, on the parturition day and during 7 consecutive postpartum days. The levels of G and I in colostrum were high on the last day of pregnancy (15.41 +/- 0.75 ng/ml and 256.9 +/- 32.7 microU/ml, resp.) and on the day of parturition (13.41 +/- 0.63 ng/ml and 279.5 +/- 41.9 microU/ml, resp.), while relatively lower values were observed on the next day (10.1 +/- 0.41 ng/ml and 194.7 +/- 19.3 microU/ml, resp.). During the next 4 days after parturition the concentrations of these hormones gradually decreased almost to the same basal level as observed in plasma. High hormone concentrations in mammary secretion during the periparturition period were probably caused by intensified transfer through blood-mammary gland barrier, and could reflect increasing needs for these hormones by developing mammocytes and by the newborns adapting to the extrauterine life. In conclusion, a high amount of G and I in mammary secretion may have physiological importance for the neonate. No statistically significant correlation in the hormone concentration between colostrum and plasma were noted.

Colostrum↗
PubMed1991

Cytotoxic activity toward mouse melanoma following immunization of mice with transfected cells expressing a human melanoma-associated antigen.

B78H1 is a mouse melanoma cell line that is weakly antigenic in syngeneic mice. In an attempt to augment their immunogenicity, B78H1 cells were transfected with genomic DNA from a line of human melanoma cells expressing a 96-kDa melanoma-associated antigen (ICAM-1). A selective co-amplification procedure was employed that generated a population of transfected cells (Ui11) that expressed fivefold higher quantities of the melanoma-associated antigen than the cells from which the DNA was obtained. To test the transfected cells' relative capacity to generate a cellular immune response against B78H1 cells, Ui11 cells and B78H1 cells were administered (in parallel) to syngeneic C57BL/6 mice, susceptible to the growth of the melanoma. Each cell line (lethally irradiated beforehand) was injected intraperitoneally at weekly intervals into the mice. After two or three injections, a standard chromium-release assay was employed to detect the presence of cellular immunity toward B78H1 cells. The population of spleen cells from mice immunized with the transfected melanoma cells exhibited higher levels of cytotoxicity toward B78H1 cells than spleen cells from mice immunized with equivalent numbers of nontransfected cells. This observation is consistent with the notion that the transfected human melanoma-associated antigen acted as a "second antigen" capable of potentiating cellular immune responses against the weakly immunogenic determinants of the mouse melanoma cells. The introduction of genes for foreign antigens into weakly antigenic tumor cells may generate immunogens that can lead to augmented anti-tumor cellular immune responses.

Animals↗
PubMed1991

Psychopathology and treatment of 30,344 twins in Sweden. II. Heritability estimates of psychiatric diagnosis and treatment in 12,884 twin pairs.

We estimated the heritability for inpatient psychiatric treatment, treatment with psychoactive medication, and for psychiatric diagnoses in a randomized sample of 12,884 Swedish twin pairs drawn from the general population for a health survey. We found a genetic contribution to treatment and diagnosis, independent of sex and shared environment. The heritability estimate for inpatient treatment was 0.47, for reported treatment with psychoactive medication 0.49, and for an inpatient diagnosis of neurotic or personality disorder 0.60. No statistically significant heritability was found for the diagnoses of alcohol abuse nor for the heterogeneous group of diagnoses of psychoses. This was probably because of the heterogeneity of cases necessary to form large enough groups for analysis, or ascertainment requiring treatment in a psychiatric unit.

Adolescent↗
PubMed1991

Potent vasoconstrictor effects and clearance of endothelin in the human forearm.

The vascular effects of endothelin-1 in humans were investigated by infusion into the brachial artery of healthy volunteers. Endothelin-1 (5-500 pmol min-1) evoked potent and long lasting increase in forearm vascular resistance (FVR) and reduction in venous compliance, suggesting constriction of both resistance and capacitance vessels. The threshold for effect on forearm vascular resistance was at a calculated plasma concentration of 614 pmol 1-1. Endothelin-1 was on a molar basis 10-20 times more potent than noradrenaline as constrictor of both resistance and capacitance vessels. The increase in forearm vascular resistance induced by endothelin-1 lasted more than 30 min and that by noradrenaline less than 3 minutes. The endothelin-1-like immunoreactivity collected in the venous effluent during the infusion was 10-26% of the calculated arterial plasma concentration, indicating local removal of endothelin. After the infusion of endothelin-1 the urine concentration of prostacyclin metabolite increased significantly, indicating release of prostacyclin, whereas the concentration of thromboxane metabolite did not increase. It is concluded that endothelin-1 is a highly potent constrictor of human resistance and capacitance vessels, that it causes release of prostacyclin and that circulating endothelin-1 is efficiently removed by the forearm in vivo.

Adult↗
PubMed1990

Platelet-vessel wall interactions in individuals who smoke cigarettes.

Our studies have shown that there an increased excretion of urinary metabolites of thromboxane A2 in healthy, young male chronic smokers. This arachidonic acid metabolite from platelets reflects evidence of increased activation in vivo. These data contrast with the ex vivo study of platelets in chronic smokers and point out the fact that selection of cells for ex vivo study may not appropriately reflect the in vivo pathophysiologic situation. The platelet activation related to chronic smoking appears to result from both a direct, non-sympathoadrenally mediated activation which is rapidly inducible and reversible as well as a more persistent activation which long outlasts the smoke exposure. This latter mechanism appears to result from persistent vascular damage as reflected by the enhanced prostacyclin metabolite excretion. The acute, direct effect of smoking on the platelet appears to be a minor component of the altered platelet function. This latter inference may account for the inability in some studies to observe a small incremental, acute change superimposed on the persistently increased platelet reactivity secondary to the enhanced interactions with a damaged vasculature.

Blood Platelets↗
PubMed1990

Psychopathology and treatment of 30,344 twins in Sweden. I. The appropriateness of psychoactive drug treatment.

We studied whether regular treatment with tranquilizing and hypnotic drugs among 30,344 twins in Sweden 15-47 years old was associated with robust indicators of poor health. Longitudinal psychiatric diagnoses and subsequent suicides were analyzed with data from cross-sectional health questionnaires. Women were almost twice as likely to report medication, even those with psychiatric inpatient diagnoses. Within each of mental, somatic, and lifestyle domains, medication was more frequent among those with multiple problems. The partial odds for medication for those with a diagnosis of psychosis were 11.81, affective disorder 10.94, neurotic or personality disorder 11.09, alcoholism 5.00, and drug addiction 13.92. We conclude that reported regular treatment with tranquilizing and hypnotic drugs in young Swedish adults was significantly associated with diagnosed and subjective somatic and mental health problems, and thus largely in agreement with current peer guidelines. The reasons why women were more often treated than men requires further study.

Adolescent↗
PubMed1990

Excretion of thromboxane A2 and prostacyclin metabolites before and after exercise testing in patients with and without signs of ischemic heart disease.

We addressed the hypothesis that platelets are not activated in association with effort-induced myocardial ischemia in stable coronary disease. Seventy-two patients undergoing a diagnostic bicycle exercise test were stratified according to the development of chest pain (yes/no, 33/39) and of exercise-induced ST-segment depression of at least 200 microV in the electrocardiogram (yes/no, 12/60). Noninvasive indexes of platelet activation and of platelet/vessel wall interaction (urinary excretion of the 2,3-dinor-metabolites of thromboxane A2 [Tx-M] and prostacyclin [PGI-M], respectively) were analyzed in samples collected in the basal state and after the test. Basal Tx-M and PGI-M did not differ in patients with (236 +/- 35 and 131 +/- 22 pg/mg creatinine, respectively) and without (185 +/- 16 and 101 +/- 13 pg/mg creatinine, respectively) chest pain, or in those with (178 +/- 45 and 162 +/- 41 pg/mg, respectively) and without (216 +/- 22 and 104 +/- 11 pg/mg, respectively) ST-segment depression during the test. Patients without chest pain or without ST-segment depression moderately increased (p less than 0.05) their urinary Tx-M (by 21% and 13%, respectively) and PGI-M (by 28% and 23%, respectively) after exercise. No significant increases were observed in those developing chest pain or ST depression during exercise. These data indicate that effort-induced myocardial ischemia is not associated with an increase in platelet activation or platelet/vessel wall interaction in patients with stable coronary disease.

Coronary Disease↗
PubMed1989

Radioactive labeling of proteins in cultured postimplantation mouse embryos. I. Influence of the embryo preparation method.

Conditions for optimum incorporation of radioactive amino acids into proteins of cultured postimplantation mouse embryos were investigated under the aspect of using these proteins for two-dimensional electrophoretic separations followed by fluorography. The aim was to obtain highly radioactive proteins under conditions as physiological as possible. Embryos at Days 10, 11, and 12 of gestation were prepared in different ways and incubated for 4 h in Tyrode's solution containing [3H]amino acids (mixture) at a concentration of 27 microCi/ml medium. The preparations were: a) yolk sac opened, placenta and blood circulation intact; b) yolk sac and amnion opened, placenta and blood circulation intact (Day 10 embryos only); c) placenta, yolk sac, and amnion removed (embryo "naked"); d) naked embryos cut randomly into pieces (Day 10 embryos only). After incubation whole embryos or certain parts (tail, liver, rest body) were investigated by determining the radioactivity taken up by the protein. The results are given in dpm per mg protein per embryo. Radioactivity of proteins was about 3 times higher in naked embryos than in embryos left in their yolk sacs. This was true for all three stages investigated. However, the degree of radioactivity in the various parts of naked embryos differed by a factor of 15, whereas radioactivity was evenly distributed in embryos incubated in their yolk sacs. Therefore, embryos prepared according to the first method (see above) fulfilled the conditions required at the best.

Amino Acids↗
PubMed1989

Radioactive labeling of proteins in cultured postimplantation mouse embryos. II. Dose and time dependency.

The conditions for optimum incorporation of radioactive amino acids into proteins of cultured postimplantation mouse embryos were investigated under the aspect of using these proteins for two-dimensional electrophoretic separations and fluorography. The aim was to obtain highly radioactively labeled proteins under conditions as physiological as possible. Mouse embryos of Days 8, 10, and 11 of gestation were cultured in Tyrode's solution. Incubation time and concentration of [3H (or 14C)]amino acids in the culture medium were varied over a broad range. Embryos were prepared with placenta and yolk sac or without any embryonic envelopes. After culturing, the physiologic-morphologic state of the embryos was registered on the basis of several criteria. The radioactivity taken up by the total protein of each embryo was determined and calculated in disintegrations per minute per milligram protein per embryo. To approach our aim, embryos of different developmental stages had to be cultured under different conditions. A good compromise for Day-8, Day-10, and Day-11 embryos was: embryos prepared with yolk sac (opened) and placenta, 150 microCi radioactive amino acids added per milliliter medium, incubation for 4 to 5 h. For maximum labeling of proteins it is advisable to culture Day-10 embryos without embryonic envelopes under particular conditions.

Amino Acids↗
PubMed1989

Interaction of human growth hormone and gonadotrophins on the function of rat ovaries.

Hypophysectomized and normal female rats were used for studying the interaction of human growth hormone and gonadotrophins in stimulating the rat ovary. Groups of rats were injected with increasing doses of gonadotrophins (Pergonal or Metrodin) in addition to human growth hormone (Norditropin) or placebo. In the test for follicle stimulating hormone activity the weight of the ovaries was recorded. In the hypophysectomized rats Norditropin and Pergonal or Metrodin had a synergistic stimulating effect on the ovary, resulting in a greater number and a larger follicle size. Norditropin had a slight stimulatory effect of its own. In the ovarian ascorbic acid depletion test for luteinising hormone activity Norditropin had a significant effect of its own. In combination with Pergonal an additive effect was seen. The effect of Norditropin was observed in hypophysectomized rats only.

Animals↗
PubMed1989

Purification and properties of three endopeptidases from baker's yeast.

Three endopeptidases, proteinases A, B, and Y, were purified from baker's yeast, Saccharomyces cerevisiae. Two molecular forms of proteinase A (PRA), Mr 45,000 and 54,000, (estimated on SDS-PAGE) were obtained. Both forms were inhibited by pepstatin and other acid proteinase inhibitors. The enzyme digested hemoglobin most rapidly at pH 2.7-3.2 and casein at pH 2.4-2.8 and 5.5-6.0. The optimum pH for hydrolysis of protein substrates could be shifted to about 5 with 4-6 M urea. Urea also stimulated the enzyme activity by 30-50%. As other acid proteinases, the enzyme preferentially cleaved peptide bonds of X-Tyr and X-Phe type. A proteinase B (PRB) preparation of approximately Mr 33,000 possessed milk clotting activity and showed an inhibition pattern typical for seryl-sulfhydryl proteases. The purified enzyme could be stabilized with 40% glycerol and stored at -20 degrees C without significant loss of activity for several months. The third endopeptidase, designated PRY, of Mr 72,000 when estimated by Sephadex G-100 gel filtration, had properties resembling PRA and PRB. Similar to PRB, it could be inhibited by up to 90% with phenylmethylsulfonyl fluoride and para-chloromercuribenzoate and preferentially hydrolyzed the Leu15-Tyr16 peptide bond of the oxidized beta-chain of insulin. On the other hand, contrary to PRB, it had neither milk clotting activity nor esterolytic activity toward N-acetyl-L-tyrosine ethyl ester and N-benzoyl-L-tyrosine ethyl ester and was stable during storage at -20 degrees C without glycerol. The enzyme also showed a lower pH optimum for hydrolysis of casein yellow than PRB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Redirection of prostaglandin endoperoxide metabolism at the platelet-vascular interface in man.

Prostacyclin (PGI2) is an inhibitor of platelet function in vitro. We tested the hypothesis that PGI2 is formed in biologically active concentrations at the platelet-vascular interface in man and can be pharmacologically modulated to enhance its inhibitory properties. This became feasible when we developed a microquantitative technique that permits the measurement of eicosanoids in successive 40-microliters aliquots of whole blood emerging from a bleeding time wound. In 13 healthy volunteers the rate of production of thromboxane B2 (TXB2) gradually increased, reaching a maximum of 421 +/- 90 (mean +/- SEM) fg/microliters per s at 300 +/- 20 s. The hydration product of PGI2, 6-keto-PGF1 alpha, rose earlier and to a lesser degree, reaching a peak (68 +/- 34 fg/microliters per s) at 168 +/- 23 s. The generation of prostaglandins PGE2 and D2 resembled that of PGI2. Whereas the threshold concentration of PGI2 for an effect on platelets in vitro is approximately 30 fg/microliters, only less than 3 fg/microliters circulates under physiological conditions. By contrast, peak concentrations of 6-keto-PGF1 alpha obtained locally after vascular damage averaged 305 fg/microliters. Pharmacological regulation of PG endoperoxide metabolism at the platelet-vascular interface was demonstrated by administration of a TX synthase inhibitor. The rate of production of PGI2, PGE2, and PGD2 increased coincident with inhibition of TXA, as reflected by three indices; the concentration of TXB2 in bleeding time blood and serum, and excretion of the urinary metabolite, 2,3-dinor-TXB2. These studies indicate that PGI2 is formed locally in biologically effective concentrations at the site of vessel injury and provide direct evidence in support of transcellular metabolism of PG endoperoxides in man.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

The influence of insulin loading tests per os on insulin and glucose concentrations in blood of piglets within 40 hours from birth.

Experiments were conducted to elucidate the time required was showing in what time for postnatal absorption (within 40 hours from birth) and, occurrence of hypoglycaemic activity of exogenous insulin, when high concentrations of the hormone had been present in sow colostrum before parturition, 5 days after parturition, and, occasionally during lactation. The mean insulin concentration in piglet plasma samples from 11 litters amounted to 116.48 pmol/l +/- 101.11 (n = 115), and the glucose concentration was 4.69 pmol/l +/- 1.65 (n = 115), before insulin loading. Oral insulin loading (1.0 I.U./kg body weight) was applied to 10 litters. The piglet litters were separately tested, at different periods, 1, 2, 3, 5, 10, 15, 20, 25, 30, 40 hours after birth. After insulin loading, the mean hormone concentration in plasma samples increased to 447.11 pmol/l +/- 277.01 (n = 83) (P less than 0.001), and the glucose concentration dropped to 2.55 mmol/l +/- 1.08 (n = 83) (P less than 0.001). Insulin absorption from the alimentary tract to blood stopped completely in piglets of litters 10 and 11 examined in 30 and 40 hours after birth. 22 piglets had separated from litters Nos. 4 to 11 and were given intramuscularly injections of 1.0 I.U. insulin. The average hormone concentration in their plasma samples increased to 645.51 pmol/l +/- 44.2 (n = 22) (P less than 0.001), while their average glucose concentration dropped to 2.82 mmol/l +/- 0.13 (n = 22) (P less than 0.001). 24 piglets with hypoglycaemic symptoms from litters orally loaded with insulin and 1 piglet of the intramuscular group, were reanimated by intraperitoneal administration of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗