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Biomedical subjects

B Steiner

Publications and source records attributed to B Steiner.

At least 145 records · Page 8Linked to original sources
PubMed1986

Comparison of the efficacy of subcutaneous and nasal spray buserelin treatment in suppression of testicular steroidogenesis in men with prostate cancer.

The comparative efficacy of subcutaneous injections and intranasal spray in the maintenance of suppression of testicular function in men with advanced prostatic cancer treated with a gonadotropin-releasing hormone (GnRH) agonist, Buserelin, was evaluated in a nonrandomized clinical trial. After a common induction period of 1 week's treatment with 500 micrograms three times daily by subcutaneous injection, patients were allocated into one of two groups for maintenance therapy with either subcutaneous (200 micrograms once daily) or intranasal (400 micrograms nasal spray three times daily) Buserelin therapy. Plasma luteinizing hormone (LH) and sex steroid (testosterone [T], dihydrotestosterone [DHT], and estradiol [E2]) patterns were studied before the start and at days 1, 7, and 14 and months 2, 4, 6, and 12 on maintenance regimens. During the maintenance therapy, age-adjusted T levels were markedly suppressed to near-castrate levels in both treatment groups. Despite this marked suppression, age-adjusted T levels were consistently lower in men treated with the subcutaneous regimen from the 2nd week to the 12th month of treatment in morning pooled specimens as well as in detailed sampling over a 24-hour period after 12 months of continuous treatment. A similar pattern of enhanced suppression by the subcutaneous regimen was also observed for age-adjusted DHT, but not E2, levels during the study. Neither the magnitude nor the time course of T suppression by GnRH analog treatment could be entirely explained by the nature of the decline in plasma LH levels, which fell much less and more gradually over a 12-month period.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1986

Platelet glycoproteins IIb and IIIa: evidence for a family of immunologically and structurally related glycoproteins in mammalian cells.

Human and bovine cultured cell lines and circulating leukocytes were examined for the presence of surface proteins similar to platelet glycoproteins IIb (GPIIb) and IIIa (GPIIIa). Human endothelial cells, smooth muscle cells, and MG-63 fibroblast-like cells were found to have surface proteins that cross-reacted with platelet GPIIb and GPIIIa antibodies, existed as complexes, and had molecular weights similar to those of the corresponding platelet glycoproteins. Bovine endothelial cells and smooth muscle cells also expressed GPIIb- and GPIIIa-like surface proteins. Metabolic labeling studies with [35S]methionine demonstrated that the cultured cells synthesized these glycoproteins. The GPIIIa-like protein in human endothelial and smooth muscle cells had the same isoelectric point as platelet GPIIIa, whereas their GPIIb alpha-like protein was slightly more acidic than platelet GPIIb alpha (pI = 5.2-5.3 versus 5.5). Platelet and endothelial cell GPIIb alpha (but not GPIIIa) showed an increased electrophoretic mobility in Ca2+ -containing versus EDTA-containing gels, implying a Ca2+ -GPIIb alpha interaction. The amino acid sequence of the amino termini of platelet GPIIb alpha and GPIIb beta and of the alpha chains of the leukocyte LFA-1 and Mac-1 glycoprotein complexes had significant sequence homology. These data indicate that glycoproteins that have either immunological cross-reactivity or amino-terminal sequence homology with the platelet GPIIb-IIIa complex are widely distributed in human and non-human adherent cells and circulating leukocytes and suggest that these proteins may be the products of a large gene family whose expression is cell specific.

Amino Acid Sequence↗
PubMed1986

Effect of four serum components on survival of Treponema pallidum and its attachment to rabbit cells in vitro.

Transferrin and, to a lesser extent, insulin were two components of serum that enhanced the survival of Treponema pallidum in microaerophilic, acellular medium. These two components also enhanced the attachment of T pallidum to baby rabbit genital organ (BRGO) cells in both aerobic and microaerophilic tissue culture systems. Growth hormone and epidermal growth factor marginally enhanced the attachment of T pallidum to BRGO cells.

Animals↗
PubMed1985

Evidence that the platelet plasma membrane does not contain a (Ca2+ + Mg2+)-dependent ATPase.

The present study was designed to determine the subcellular distribution of the platelet (Ca2+ + Mg2+)-ATPase. Human platelets were surface labeled by the periodate-boro[3H]hydride method. Plasma membrane vesicles were then isolated to a purity of approx. 90% by a procedure utilizing wheat germ agglutinin affinity chromatography. These membranes were found to be 2.6-fold enriched in surface glycoproteins compared to an unfractionated vesicle fraction and almost 7-fold enriched compared to intact platelets. In contrast, the isolated plasma membranes showed a decreased specific activity of the (Ca2+ + Mg2+)-ATPase compared to the unfractionated vesicle fraction. This decrease in specific activity was found to be similar to that of an endoplasmic reticulum marker, glucose-6-phosphatase, and to that of a platelet inner membrane marker, phospholipase A2. We conclude, therefore, that the (Ca2+ + Mg2+)-ATPase is not located in the platelet plasma membrane but is restricted to membranes of intracellular origin.

Blood Platelets↗
PubMed1985

Structure of human platelet membrane glycoproteins IIb and IIIa as determined by electron microscopy.

The glycoprotein (GP) IIb-IIIa complex was isolated from human platelet membranes and examined for glycoprotein stoichiometry and morphology. To determine the ratio of glycoproteins in the complex, the isolated glycoproteins were solubilized with sodium dodecyl sulfate and separated by high-performance liquid chromatography. Quantitative amino acid analysis of individual glycoproteins showed that the ratio of GP IIb to GP IIIa in the Ca2+-dependent complex was 0.93:1. Morphology was determined by electron microscopy of rotary-shadowed and negatively stained specimens. Individual complexes consisted of two domains: an oblong head of approximately 8 X 10 nm with two rodlike tails extending approximately 14-17 nm from one side of the head. Treatment of the isolated complex with EDTA resulted in the appearance of a mixture of oblong and filamentous structures, which could be separated by a sucrose gradient sedimentation in Triton X-100. As seen by rotary and unidirectional shadowing, GP IIb was a compact structure, approximately 8 X 10 nm in size. Isolated GP IIIa was more heterogeneous but was most often observed in an elongated form, varying in length from 20 to 30 nm and in width from 2 to 3 nm. By comparing these structures to that of the heterodimer complex, it was determined that the oblong domain was GP IIb and the rodlike tails were GP IIIa. Each milligram of isolated GP IIb-IIIa complex bound 0.30 mg of [3H]Triton X-100, indicating that the glycoprotein complex contained limited hydrophobic domains. Upon removal of detergent, GP IIb-IIIa complexes formed aggregates that sedimented in sucrose gradients as a diffuse peak ranging from 14 to 32 s. Examination of these aggregates by electron microscopy showed that they were composed of clusters or "rosettes" of 2 to 20 or more of the GP IIb-IIIa complexes. The orientation of these rosettes was such that the tails were joined in the center, with the head portions directed away from the interacting tails. It thus appears that the primary hydrophobic domains of the GP IIb-IIIa complex exist at the tips of the GP IIIa tails. Because the GP IIb-IIIa complex is an intrinsic membrane glycoprotein, these findings indicate a potential membrane attachment site for the GP IIb-IIIa complexes.

Amino Acids↗
PubMed1985

Does constant infusion of gonadotropin-releasing hormone agonist lead to greater suppression of gonadal function in man than its intermittent administration?

Constant infusion of gonadotropin-releasing hormone agonist (GnRH-A) in the rhesus monkey leads to far greater suppression of spermatogenesis than its intermittent administration. To assess whether administration of GnRH-A by constant subcutaneous infusion will also lead to greater inhibition of gonadal function, we administered either 20 or 200 micrograms of D(Nal2)6GnRH (GnRH-A) to two groups of normal male volunteers, either by a single daily injection or constant subcutaneous infusion through a portable infusion pump, for 28 days. Basal and integrated luteinizing hormone (LH), follicle-stimulating hormone, and testosterone (T) responses were not significantly different between the two methods of GnRH-A administration at either the 20- or 200-microgram dose, even though subjects in the constant infusion group showed more consistent inhibition of basal and 24-hour integrated T concentrations. Significant decline in serum T in both groups occurred in the face of little or no decline in serum LH. It is concluded that the effects of constant infusion of GnRH-A in man are not as striking as those reported in the rhesus monkey and that the antigonadal effects of GnRH-A in man are complex and cannot be explained on the basis of down-regulation of pituitary gonadotropin secretion alone--additional mechanisms may be operative.

Dose-Response Relationship, Drug↗
PubMed1984

24-hour mean pulse. Simple predictor of doxorubicin-induced cardiac damage.

Nineteen adult patients with cancer received six to 10 monthly treatments of doxorubicin and cisplatin. Recumbent pulse was measured for 24 to 30 hours before each treatment. Treatment was stopped for disease progression or when a total doxorubicin dose of 550 mg/m2 was reached. Rising serial 24-hour pulse averages predicted congestive heart failure reliably. No patient had congestive heart failure during therapy, but three patients had congestive heart failure two to four months after receiving 540, 525, and 530 mg/m2 of doxorubicin. In these, two to six months before completion of therapy, the 24-hour rhythm-qualified mean (mesor) of pulse showed a positive slope by linear regression analysis (p less than 0.05) that was apparent at cumulative doxorubicin doses of 300, 420, and 240 mg/m2. All 19 patients received similar total doses of doxorubicin and were followed to death or 12 months after the last doxorubicin dose. In addition, a progressive rise in the 24-hour mean pulse coincided with histologically documented doxorubicin-induced lethal congestive heart failure in Wistar-Kyoto rats of both sexes.

Adult↗
PubMed1984

Hormonal effects of GnRH agonist in the human male: II. Testosterone enhances gonadotrophin suppression induced by GnRH agonist.

Superactive analogues of gonadotrophin releasing hormone and testosterone, when administered together, synergistically inhibit gonadotrophin secretion and spermatogenesis in the rat. In order to determine whether testosterone also enhanced gonadotrophin suppression by GnRH agonist in the human male, two groups of four normal male volunteers first received either 10 or 100 micrograms of a GnRH agonist D(Nal2)6GnRH (GnRH-A) daily for 10 d. After at least a 50 d recovery period, the same subjects received a single injection of 200 mg of testosterone oenanthate (TE) on day 1 in addition to the same dose of GnRH-A daily for 10 d. Serum LH, FSH and testosterone (TS) concentrations were measured daily just prior to the next analogue dose, and on days 1 and 10 at 0, 1, 2, 4, 6, 8, 12, 16 and 24 h after the analogue injection. Daily administration of both 10 and 100 micrograms of GnRH-A alone resulted in an early phase of stimulation followed by progressive decline in LH, FSH and testosterone to levels below baseline by day 10 despite continued administration of GnRH-A. Addition of testosterone to 10 micrograms of GnRH-A resulted in hormonal responses identical to those seen with GnRH-A alone. Combined treatment of testosterone with 100 micrograms of GnRH-A did not blunt the peak LH and FSH responses on day 2, but resulted in significantly lower LH (mean integrated responses: 187 +/- 30 vs. 234 +/- 42 mIU-d/ml) and FSH (mean integrated responses: 20.6 +/- 3.3 vs. 32.8 +/- 4.2 mIU-d/ml) responses from days 3 to 11. By day 11, all subjects receiving combined treatment (GnRH-A 100 micrograms + testosterone oenanthate) had undetectable serum FSH levels. In contrast, serum FSH concentrations on day 11 after treatment with GnRH-A alone were 43.6 +/- 8.9% of control and none of the subjects had values below the limit of detection. Serum testosterone levels in the combined treatment group did not fall below baseline by day 10 in either the 10 (161.4 +/- 48%) or the 100 micrograms GnRH-A groups (104.6 +/- 11.2%), while in the group receiving GnRH-A alone, testosterone levels declined to 45.6 +/- 8.3% and 80 +/- 18.8% with the 10 and 100 micrograms dose respectively. We conclude that addition of a suppressive dose of testosterone to an appropriate dose of GnRN-A significantly enhances gonadotrophin suppression by GnRH-A in the human male.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

Susceptibility of Treponema pallidum to the toxic products of oxygen reduction and the non-treponemal nature of its catalase.

We examined the sensitivity of Treponema pallidum (Nichols strain) to toxic products of oxygen reduction. T pallidum was sensitive to hydrogen peroxide at concentrations similar to those to which obligate anaerobes are sensitive. Accelerated death of T pallidum occurred at hydrogen peroxide concentrations below 50 mumol/l. Agents protective against hydrogen peroxide and the hydroxyl free radical (catalase, peroxidase, and mannitol) significantly enhanced treponemal survival in vitro under all three conditions of aerobiosis tested--that is, air, 3% oxygen, and 3% oxygen in conjunction with a reduced medium. Superoxide dismutase (which provides protection against superoxide radicals) did not enhance treponemal survival in normal media. When superoxide radicals were generated in the medium by means of a xanthine and xanthine oxidase system, however, the enzyme did protect T pallidum. A possible toxic involvement of singlet oxygen was also indicated by enhanced treponemal survival in air in the presence of histidine. Extracts of T pallidum from infected rabbit testes showed catalase activity which, on polyacrylamide gel electrophoresis, had the same relative mobility as purified rabbit catalase. The treponemal catalase activity was neutralised by anti rabbit catalase antiserum (raised in guinea pigs). This confirmed that the catalase was of rabbit origin and not an endogenous enzyme of T pallidum. We discuss the relation of these results to the obligate parasitism of T pallidum.

Animals↗
PubMed1984

Inhibitory effect of syphilitic rabbit serum on DNA synthesis in rabbit cells in vitro.

A previously described toxic factor associated with Treponema pallidum (Nichols) and found in extracts of syphilitic rabbit testes has now also been detected in syphilitic rabbit serum. The toxic factor, which inhibits DNA synthesis in baby rabbit genital organ (BRGO) cells in vitro, is present in rabbit serum up to 30 days after infection with T pallidum.

Animals↗
PubMed1984

The stimulatory and down-regulatory effects of a gonadotropin-releasing hormone agonist in man.

Synthetic long-acting agonistic analogs of GnRH both stimulate and paradoxically inhibit gonadotropin secretion in male animals and humans. To characterize the stimulatory and down-regulatory effects of such a superactive GnRH analog in man, either 10 or 100 micrograms D-( Nal2 ) 6GnRH were administered sc to two groups of seven normal men for 10 days. Serum LH, FSH, and testosterone were determined daily before analog injection and 1, 2, 4, 6, 8, 12, 16, and 24 h after analog injection on days 1 and 10. Both doses of analog led to initial increases in LH, FSH (peak, days 2-3), and testosterone (peak, days 3-4), but by day 10 of analog administration, serum levels of LH, FSH, and testosterone returned to pretreatment levels. The integrated 24-h responses above baseline of serum LH and FSH to both doses of GnRH analog were significantly decreased on day 10 compared to day 1 (P less than 0.05). The integrated 24-h responses of serum testosterone to both doses of agonist were not significantly decreased on day 10 of agonist treatment compared to those on day 1 (P greater than 0.2). Integrated serum testosterone responses above baseline in response to 3000 IU hCG administered 2 weeks before analog treatment and 24 h after the last analog injection were not different (P greater than 0.2). GnRH agonist treatment resulted in proportionate stimulation of LH, FSH, and testosterone consistent with a predominant pituitary effect of the analog at these doses given for 10 days. The stimulatory effects of daily GnRH agonist treatment in men are transient with some down-regulatory effects evident after 10 days of treatment.

Adult↗
PubMed1983

Improvement of the periodate-borohydride surface-labeling method for human blood platelets.

The periodate/sodium boro[3H]hydride ([3H]-NaBH4) method is extensively used for the specific labeling of cell surface glycoproteins. Reduction with tritiated borohydride is also used in other surface-labeling techniques, the neuraminidase/galactose oxidase/[3H]-NaBH4 method (specific for terminal galactose and N-acetyl-galactosamine residues) and the pyridoxal phosphate/[3H]-NaBH4 method (specific for protein). By modification of the reaction conditions during the periodate-oxidation and borohydride-reduction, the ratio of the incorporated to the total added radioactivity could be increased by a factor of 50, while the specific activity of the labeled material was twice as high as in the original method. Alternatively, by another modification, the specific activity of the labeled material could be increased about 10-fold. The influence of the most important parameters was investigated in detail. Sodium dodecyl sulfate gel electrophoresis and fluorography demonstrate that the labeling pattern of the membrane glycoproteins is the same as with the conventional method.

Blood Platelets↗
PubMed1983

Effect of testosterone enanthate on hematopoiesis in normal men.

Testosterone enanthate, a commonly used depot form of androgen, was administered to normal men according to several dose schedules. This resulted in significant increments in serum testosterone levels despite the fact that testosterone concentrations remained within the normal population range in almost all instances. Mild but significant increases in white blood cell, red blood cell, hematocrit, and hemoglobin concentrations were noted. These effects correlated with the dose frequency schedules. Negligible changes in mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were observed. Despite the significant individual increases in blood parameters, all values remained within the normal population range and no clinical manifestations were observed.

Adult↗
PubMed1983

Effect of serum concentration and metabolic inhibitors on the attachment of Treponema pallidum to rabbit cells.

The effect of host-cell metabolism on the attachment of Treponema pallidum to mammalian cells in vitro was studied. The growth of baby rabbit genital organ (BRGO) cells was enhanced by increasing the concentration of serum ("serum shift-up") in the growth medium. Cells starved for 24 h in serum-free medium showed a burst of DNA synthesis when shifted to fresh medium containing 20% serum. In aerobic conditions, they were much more heavily coated with attached T. pallidum than cells shifted to 20% serum after maintenance at serum concentrations of 2.5%, 5% or 10%. This effect was very pronounced during the first few hours of co-incubation. In microaerophilic conditions, the extent of T. pallidum adherence also paralleled the increase in DNA synthesis by BRGO cells. Cycloheximide and methotrexate greatly inhibited DNA and protein synthesis in BRGO cells, but did not affect the motility of T. pallidum. When BRGO cell metabolism was inhibited by these two drugs, attachment of T. pallidum was significantly decreased. These results indicate that T. pallidum attaches best to actively growing BRGO cells in tissue culture. This may explain the apparently preferential parasitism of actively growing tissues by T. pallidum in syphilis in man.

Adhesiveness↗
PubMed1983

Factors affecting the attachment of Treponema pallidum to mammalian cells in vitro.

Attachment of Treponema pallidum (Nichols) to mammalian cells is probably the first step in the pathogenesis of syphilis. It may also be important for the multiplication of T pallidum in vitro. When factors affecting the attachment of T pallidum to mammalian cells in vitro were studied significantly greater numbers of treponemes were found to attach to baby rabbit genital organ (BRGO) cells than to five other mammalian cell lines. When attached to BRGO cells T pallidum survived longer in vitro than unattached treponemes. Eagle's minimal essential medium was superior to three other culture media in increasing attachment and maintaining the survival of treponemes. Dithiothreitol (0.25-1.0 mmol/l) had no effect on the attachment of T pallidum to BRGO cells. Anaerobic conditions were superior to microaerophilic conditions, and the latter were superior to aerobic conditions for the attachment and survival of T pallidum to BRGO cells. Within the range of concentrations tested the number of treponemes attached to the BRGO cells was directly dependent on the concentrations of viable treponemes in the inoculum. Greater numbers of treponemes attached to actively metabolising BRGO cells than to quiescent or slowly growing cells.

Animals↗