Biomedical subjects
Publications and source records attributed to P Schulz.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Lithium (Li+) does not undergo metabolism, is unbound to proteins from plasma, and excreted in major part by the kidney. We studied the disposition of single doses of Li+ given orally to 5 normal subjects, once as a conventional form and once as a slow release form. Renal clearances of Li+ were lower during night time, plasma clearances were 22 to 43 ml/min when not corrected for urinary recovery and 21 to 28 ml/min when corrected. Urinary recovery (measured on 96 hours) was 65.0 to 99.7% and was individually less stable than plasma clearance. Other observations that might have clinical relevance were that the rate of Li+ absorption from the digestive tract varied more from one subject to another than between the two pharmaceutical forms, that the 24 hours renal clearance and the extend of urinary recovery on 96 hours could not be predicted from short term measurements of Li+ (in urine and plasma), and that the known circadian changes in the rate of Li+ elimination were confirmed.
Explore the source record for details and available documents.
The authors found that 12 (57%) of 21 consecutive male patients with borderline personality disorder who presented for psychiatric treatment at two distant geographic sites were homosexual. They then obtained the sexual histories of 80 patients who met standardized criteria for borderline disorder and found that 17 (21%) of these patients were homosexual, four (5%) were bisexual, and nine (11%) had diagnoses of paraphilias. Ten (53%) of the 19 men with borderline disorder were homosexual, compared with seven (11%) of the 61 women. Homosexuality was 10 times more common among the men and six times more common among the women with borderline personality disorder than in the general population or in a depressed control group.
The influence of neuroleptics on central dopaminergic receptors is anatomically quite non-specific. Neuroleptics also have numerous pharmacological actions other than on dopamine. Taken together, these effects only explain some of the adverse reactions or drug interactions of neuroleptics and predict very poorly the treatment efficacy in given patients.
Explore the source record for details and available documents.
A cAMP-resistant mutant (Kin-8) isolated from Y1 mouse adrenocortical tumor cells harbors a specific lesion in the regulatory subunit of the type 1 cAMP-dependent protein kinase. This mutant also is resistant to the effects of corticotropin and cAMP on steroidogenesis, growth and morphology, suggesting an obligatory role for the protein kinase in regulation of adrenocortical functions. In this study, the cAMP-resistant phenotype of the Kin-8 mutant was reverted by transformation with DNA from cAMP-responsive Y1 cells, and the biochemical basis of the transformation was explored. Initially, Y1 mouse adrenocortical tumor cells were evaluated for their competence as recipients in DNA-mediated transformation experiments, by measuring their ability to incorporate and express a bacterial gene (neo) encoding resistance to neomycin. Y1 cells were transfected with the plasmid pSV2-neo (an SV40-neo hybrid vector designed for expression in animal cells) and screened for resistance to the neomycin analog, G418. Neomycin-resistant transformants were recovered from Y1 cells at a frequency of approximately one per 10(3) cells per 10 micrograms of DNA, and had specific neo sequences integrated into their high molecular weight (mw) DNA. The Y1 mutant, Kin-8, then was transformed with pSV2-neo DNA plus high mw DNA prepared from cAMP-responsive Y1 cells. Cells competent for transformation were recovered by selective growth in the neomycin analog G418, and these transformants were screened for recovery of morphological responses to cAMP. Several colonies capable of rounding up in the presence of cAMP were recovered after transformation with DNA from Y1 cells. These transformants also recovered the ability to round up in the presence of corticotropin, and were able to respond to both corticotropin and cAMP with increased steroidogenesis. Transformants generated from either Y1 or Kin-8 cells were unstable. Y1 cells lost resistance to neomycin when grown in the absence of G418 at a frequency of 4% per generation. Similarly, Kin-8 transformants lost their sensitivity to cAMP in subsequent culture passages. In some of the cAMP-responsive transformants, cAMP-dependent protein kinase activity was recovered and approached the activity seen in cAMP-responsive Y1 cells. The recovery of a normal protein kinase by transformation appeared to have been sufficient to reverse the cAMP-resistant phenotype of Kin-8 cells. In other cAMP-responsive transformants, protein kinase activity was not appreciably affected by cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)
Single low doses (0.25 mg) of dexamethasone were given at 11 p.m., 2, 5 and 8 a.m. on separate days to five normal subjects. The concentrations of cortisol in plasma on the next day were significantly decreased compared to results after placebo administration, and cortisol suppression was maximal after dexamethasone had been given at 8 a.m. Our findings suggests that the postulated phase-advance of circadian rhythms is not a major cause of cortisol non-suppression in depressives given dexamethasone.
Rats received 10 mg/kg/day of haloperidol during up to 9.5 weeks. Substance P, Leu- and Met-enkephalins, were studied in brain using immunohistochemical methods. Haloperidol modified the peptides immunoreactivity in most brain areas. The time necessary to observe the effects of haloperidol on the peptides varied individually, depending on the peptide and the brain area. Moreover, inversions of these effects were often observed, generally occurring between in 5th and 7th day of drug administration. Substance P was increased after haloperidol in the hypophysis, a finding hereto not described. This descriptive study identified none of these three peptides as a single and specific target for dopaminergic receptor blockade. Methodological issues in evaluating the effects of neuroleptics on brain peptides are discussed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effects of forskolin on the regulation of steroidogenesis and growth were examined in the Y1 adrenocortical tumor cell line, and the roles of cAMP and cAMP-dependent protein kinase in these actions of forskolin were evaluated. Forskolin, like corticotropin, stimulated steroidogenesis 3-fold and inhibited growth by 90%. In mutants of the Y1 cell line harboring specific defects in cAMP-dependent protein kinase activity, the responses to forskolin were attenuated. The resistance of the protein kinase mutants to the diterpene was closely correlated with their resistance to corticotropin and with impaired responses of their protein kinases to cAMP. These results indicate that cAMP and cAMP-dependent protein kinase are obligatory components of forskolin's actions on Y1 adrenal cells. Forskolin, at concentrations which were approximately 100-times greater than those required to stimulate steroidogenesis, caused cAMP to accumulate. Apparently, only a small fraction of the cAMP generated in response to forskolin was required to stimulate steroidogenesis or inhibit growth.
We have investigated the modulation of prostatic acid phosphatase expression in the human prostatic cancer cell line LNCaP in response to the natural androgens testosterone and dihydrotestosterone, the female sex steroid estradiol and the synthetic androgen R1881 (methyltrienolone). Testosterone and dihydrotestosterone at 1 microgram/ml enhance the acid phosphatase synthesis by a factor of 3.5, while a hundred-fold lower concentration of the synthetic androgen R1881 induces an almost five-fold increase in the expression of this enzyme. The stimulation by all androgens tested and estradiol was dose-dependent. The synthetic glucocorticoid triamcinolone acetonide does not modulate the prostatic acid phosphatase expression in LNCaP cells, neither alone nor in combination with R1881.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.