Psychopathology and treatment of 30,344 twins in Sweden.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
J Nowak
Publications and source records attributed to J Nowak.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Heterogeneity of complement receptor on erythrocytes of patients with some autoimmune disorders.
Explore the source record for details and available documents.
Alleles↗
[Binding of HIV-1 by "soluble" CD4 receptor--new therapeutic possibilities in AIDS].
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
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↗
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↗
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↗
Leg haemodynamics during reconstructive vascular surgery.
Explore the source record for details and available documents.
Aged↗
Evidence for an extra-renal origin of urinary prostaglandin E2 in healthy men.
In order to verify the validity of the assumption that male urinary Prostaglandin (PG) E2 reflects its renal production, PGE2 and PGF2 alpha concentrations were measured by radioimmunoassay in the renal venous plasma (RVP) and urine (U) of 12 male and 4 female healthy volunteers. While women had a similar PGE2/PFG2 alpha ratio in RVP (0.59 +/- 0.18) and U (0.41 + 0.06), men and a significantly (P less than 0.05) higher ratio in U (1.43 +/- 1.72) as compared to RVP (0.54 +/- 0.16). This was largely due to considerably higher and more variable U-PGE1 concentrations (roughly 6 times higher than female values), despite almost identical RVP levels. The possibility of an increased U excretion of a cross-reacting member of the PG-system, as a cause of such apparently high PGE2-like immunoreactivity (LI), was ruled out by TLC characterization of PGE2-LI with three different anti-PGE1 sera. Thus, male U-PGE2 may variably reflect an extra-renal source, such as contamination with trace amounts of seminal fluid. It is concluded that, unless such a contamination can be monitored and corrected for, measurement of male U-PGE1 should be considered of questionable relevance to renal PG-synthesis.
Chromatography, Thin Layer↗
Prostaglandins contribute to the vasodilation induced by nicotinic acid.
The significance of endogenously formed prostaglandins in the vasodilation induced by nicotinic acid (NIC) was investigated. The forearm venous plasma level of radioimmunoassayed PGE (R-PGE) and the forearm blood flow (FBF) were measured in 13 healthy male volunteers at rest and during infusion of NIC. Each subject was subsequently re-studied after pretreatment with the PG synthesis inhibitor, naproxen. In the absence of naproxen, NIC infusion resulted in an almost four-fold rise in the release of R-PGE and a 60% increase in FBF. Pretreatment with naproxen did not affect the basal release of R-PGE or the basal FBF but inhibited both the release of R-PGE and the increase in FBF following NIC. The data support the hypothesis that the vasodilating effect of NIC is largely dependent upon an increased vascular formation of PG.
Adult↗
Human forearm and kidney conversion of arachidonic acid to prostaglandins.
The capacity of the human forearm and kidney to synthetize different prostaglandins (PGs) was studied, together with the quantitative relationship between the various PGs formed in these organs. 14C-labelled arachidonic acid (14C-AA) was infused in healthy male volunteers at a constant rate into the brachial or the renal artery, with simultaneous sampling of regional venous blood. The venous plasma content of 14C-PGs was extracted, separated with thin-layer chromatography (TLC) and quantified using fractionated liquid scintillation spectrometry. Most of the 14C-AA infused was metabolized and radiopeaks parallel to unlabelled standards of PGD2, PGE2, PGF2 alpha, 6-keto-PGF1 alpha and 13,14-dihydro-15-keto-PGE2 (Me) were obtained. The chromatograms of both the forearm and the kidney plasma contained all the peaks described, but the relative distribution of the 14C-PGs differed between the two tissues. In the cubital venous plasma, the main PG (apart from Me) was 6-keto-PGF1 alpha, indicating a considerable synthesis of PGI2 in the forearm. In the renal venous plasma, on the other hand, PGD2 accounted for the largest part of the authentic 14C-PGs found. Besides the tissue differences, large inter-individual variations were observed. The results demonstrate the existence of both a considerable tissue specificity and an appreciable inter-individual variation in the local conversion of AA to PGs in man.
Adult↗
A study on the role of endogenous prostaglandins in the development of exercise-induced and post-occlusive hyperemia in human limbs.
The contribution of endogenous PGs to the development of functional (exercise-induced) and reactive (post-occlusive) hyperemia was investigated in healthy volunteers. Leg blood flow during dynamic leg exercise was estimated by an indicator dilution technique. Forearm blood flow during supine leg exercise and forearm and calf blood flow following 5 min of arterial occlusion were measured plethysmographically. All subjects were examined before and after pretreatment with indomethacin, a PG synthesis inhibitor. During leg exercise, and in the absence of indomethacin, a 10-fold rise in leg blood flow was observed. Forearm blood flow increased moderately. Both these blood flow effects of exercise were unaffected by indomethacin. Following arterial occlusion a marked hyperemia developed in the forearm and the calf. Indomethacin significantly reduced the magnitude of the reactive hyperemia both in the forearm and in the calf, decreasing both the peak value and the duration of the vasodilation. These data reveal differences between the mechanisms behind functional and reactive hyperemia in man, suggesting an appreciable contribution of endogenous PGs to post-occlusive vasodilation only.
Adult↗