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Biomedical subjects

T Lin

Publications and source records attributed to T Lin.

At least 199 records · Page 11Linked to original sources

Type I IGF receptors of Leydig cells are upregulated by human chorionic gonadotropin.

The effects of human chorionic gonadotropin (hCG) on type I insulin-like growth factor (IGF) receptors of purified Leydig cells were investigated. Sprague-Dawley rats (50 day-old) were treated with a single injection of hCG 10 units intraperitoneally, type I IGF receptors were then determined daily for 4 days. HCG caused a rapid increase in type I IGF receptors within 24 h, which returned to basal by 72 h. There was no significant change in binding affinity. Our present study indicates that type I IGF receptors of Leydig cells are up regulated by hCG, and this may be one mechanism by which hCG and IGF-I interact to enhance Leydig cell steroidogenesis.

Animals↗

Transforming growth factor-beta inhibits Leydig cell steroidogenesis in primary culture.

The effects of transforming growth factor (TGF) on Leydig cell steroidogenesis in primary culture were investigated. Basal testosterone levels were 3.7 +/- 0.54 ng/ml (mean +/- SE, N = 7). In the presence of hCG (10 ng/ml), testosterone levels increased to 22.77 +/- 3.05 ng/ml. TGF-beta caused a dose dependent inhibition of hCG-stimulated testosterone formation but without effects on basal levels. TGF-beta also inhibited 8-bromo cyclic AMP-induced testosterone formation and hCG-stimulated cyclic AMP formation. In contrast, TGF-alpha had no effect on either basal or hCG-stimulated testosterone formation and did not modify the inhibitory effect of TGF-beta. Present study indicates that TGF-beta can modulate Leydig cell steroidogenesis.

8-Bromo Cyclic Adenosine Monophosphate↗

Immuno-enhancing activity of the amino-terminal domain of human prealbumin: isolation, characterization and synthesis.

A decapeptide isolated from highly purified preparations of human prealbumin was able to restore azathioprine (Az) sensitivity, a property of a sub-class of T-lymphocytes, to the spleen rosette-forming cells (RFC) of adult thymectomized (ATx) mice in vitro. The peptide was sequenced by the Edman method and shown to correspond to the ten amino-terminal residues of prealbumin, Gly-Pro-Thr-Gly-Thr-Gly-Glu-Ser-Lys-Cys. Synthesis of this peptide by solid phase methodology confirmed its activity both in vitro and in vivo. Synthesis of a number of structural analogues indicated that the amino-terminal deca, undeca and dodecapeptides of prealbumin as well as some of their derivatives were also able to restore Az sensitivity to RFC in vitro and in vivo. The Cys10 residue and the Glu7 residues both contributed significantly to potency in vitro. Removal of up to three amino acids from the N-terminus of the decapeptide led to a progressive loss of activity. The data indicates that the ability of human prealbumin to restore the Az sensitivity to the RFC of adult Tx mice is intrinsic to the protein and resides in the amino-terminal domain of the molecule.

Amino Acid Sequence↗

Frequency-dependent ultrasonic differentiation of normal and diffusely diseased liver.

The attenuation coefficient in 38 pathologically graded in vitro liver specimens was measured over a frequency range from 1.25-8 MHz and fitted to the power law model. The attenuation in the normal group (n = 17) exhibited a frequency dependence of the form 0.399f1.139; in the mild disease group (n = 13), it exhibited a dependence of the form 0.395f1.212; and in the moderate/severe disease group (n = 8), it exhibited a dependence of the form 0.391f1.325. Using a Student's t test, it is shown that, due to these differences in the frequency dependence, the statistical significance level at which the null hypothesis regarding the difference between the mean attenuation slopes of any two of these categories is rejected, is a strong function of frequency in the range of 1-4 MHz. The significance level relating to the difference between the normal and moderate/severe disease group is more than one order of magnitude better than the other categories. In all cases, no substantial improvement occurs beyond 4 MHz. It is also shown that attenuation slope values at 3 MHz confirm in vivo literature results obtained via different techniques.

Fatty Liver↗

Suppression of the delayed-type hypersensitivity and cell-mediated immune responses to Listeria monocytogenes induced by Pseudomonas aeruginosa.

Pseudomonas aeruginosa-mediated suppression of the immune response to Listeria monocytogenes was investigated in mice. Because delayed-type hypersensitivity (DTH) footpad swelling to L. monocytogenes was suppressed equally in lipopolysaccharide-responsive and -hyporesponsive mouse strains, the lipopolysaccharide component of P. aeruginosa could not have been the suppressive agent. Mucoid P. aeruginosa cells were no more suppressive than their nonmucoid revertants; therefore, mucoid coating was not an additional immunosuppressive element. Interleukin-1 and macrophage inhibitory factor production to L. monocytogenes and clearance of L. monocytogenes from mouse spleens were all decreased by prior Pseudomonas infection, indicating that cell-mediated immunity, as well as DTH, was decreased to a sublethal Listeria dose. The timing of Pseudomonas exposure relative to Listeria sensitization was varied. P. aeruginosa injected 24 or 6 h before or at the same time as L. monocytogenes depressed DTH to Listeria challenge 7 days later. Animals treated in this way could not respond to reinfection with L. monocytogenes at 13 days. P. aeruginosa administered to L. monocytogenes-sensitized mice at the time of footpad challenge was suppressive, but these mice responded normally upon reinfection. It appears that P. aeruginosa induced two types of suppression to L. monocytogenes: a transient suppression, affecting DTH challenge but not resensitization, and a longer lasting suppression that did not permit mice exposed to P. aeruginosa at the time of Listeria sensitization to respond to subsequent Listeria exposure.

Animals↗

Correlations of sound speed with tissue constituents in normal and diffuse liver disease.

The speed of sound in normal and diffusely-diseased liver specimens was measured. There were four experimental groups, consisting of normal (n = 21), fatty (n = 7), fibrotic (n = 7) and mixed fatty and fibrotic (n = 9). These classifications were based on histological grading. We found that the results corroborate and extend most of the results of Bamber and coworkers. Specifically, no significant correlation was found between speed of sound and fibrosis score; a moderate correlation was found between speed of sound and tissue water content; and a relatively good correlation (r = -0.670, p less than 0.1%) was found between the speed of sound and the histological fat score, which increased to r = -0.819 (p less than 0.1%) when a correction for variations in water content was used.

Fatty Liver↗

Direct stimulatory effects of insulin-like growth factor-I on Leydig cell steroidogenesis in primary culture.

Insulin-like growth factor-I (IGF-I) in concentration as low as 10 ng/ml significantly increased basal testosterone formation and 100 ng/ml of IGF-I increased testosterone production more than two fold in primary cultures of purified mature Leydig cells. IGF-I also markedly potentiated hCG-induced testosterone formation in a dose-dependent manner. Furthermore, IGF-I enhanced 8-bromo cyclic AMP induced steroidogenesis and hCG-stimulated cyclic AMP formation. The binding of 125I-IGF-I to purified Leydig cells was linear with a binding affinity of 0.56 +/- 0.07 X 10(9) M-1 and a capacity of 167 +/- 10.2 fmol/mg protein. Insulin and multiplication-stimulating activity were less potent than IGF-I in competing the binding of 125I-IGF-I to purified Leydig cells. This suggests that Leydig cells contain specific type I IGF receptor and IGF-I could modulate Leydig cell steroidogenesis.

Animals↗

Isolation and characterization of a 37,000-dalton protein associated with the erythrocyte membrane.

We have purified a 37,000-dalton polypeptide (p37) from the red cell membrane that was found in previous studies to undergo a lineage-specific alteration in its membrane association. Our data suggest that p37 associates with the red cell membrane through electrostatic interactions that are resistant to 0.5 M NaCl or 10 mM EDTA. Conditions found to elute p37 from red cell ghosts include H2O at pH 12, 0.1 N NaOH + 1 mM ethanol and 1.0% Triton X-100. p37 was purified substantially from ghosts by Triton X-100 solubilization followed by sequential DEAE-Sephadex and CM-Sephadex chromatography. When p37 was analyzed by two-dimensional gel electrophoresis, a family of isoelectric focusing variants was detected ranging in pI from 7.0 to 7.8. All of the isoelectric focusing variants showed homology to one another when compared serologically with anti-p37 antibodies or by limited peptide mapping using Staphylococcus aureus V8 protease. The isoelectric focusing variants appear to represent distinct, yet related polypeptides rather than degrees of post-translational modifications to a single species, inasmuch as all of the variants are present in anti-p37 immunoprecipitates prepared from in vitro translations programmed with p37 mRNA.

Cell Line↗

Chronic testosterone cypionate therapy in men with secondary impotence.

There have not been studies assessing the effects of chronic testosterone cypionate (TC) therapy on circulating levels of testosterone (T), estradiol (E2), free T, bioavailable T (BAT), luteinizing hormone (LH), and sexual function in impotent men with low T levels. This study was a double-blind crossover using 200 mg of TC or placebo given intramuscularly every 14 days for six injections and the other medication given for six doses. Blood was drawn before each injection. Mean concentrations of T, E2, free T, and BAT were the same on TC or on placebo, but serum LH was significantly suppressed during intramuscular TC. With TC statistically significant improvements in libido and in potency were noted. Five of the men were able to have vaginal sex while taking TC. TC injections every 14 days do not appear to maintain increased T concentrations for 2 full weeks, and other dosage/injection schedules are being evaluated, but there were improvements in libido and potency.

Aged↗

Characterization of insulin and insulin-like growth factor I receptors of purified Leydig cells and their role in steroidogenesis in primary culture: a comparative study.

Characterization of insulin and type I insulin-like growth factor (IGF-I) receptors and the effects of insulin and IGF-I on steroidogenesis were evaluated by using purified adult Leydig cells from Sprague-Dawley rats. Purified Leydig cells were found to contain both high and low affinity binding sites for insulin, with Ka values of 1.08 X 10(9) and 1.1 X 10(7) M-1, respectively. Using affinity cross-linking of [125I]iodoinsulin to plasma membrane insulin receptor, several bands were identified by autoradiography under nonreduced conditions with mol wt of 230,000, 280,000, and 300,000. After reduction with 50 mM dithiothreitol, only one band was identified with a mol wt of 130,000, consistent with the alpha-subunit of insulin receptor. Purified Leydig cells also contain specific type I IGF receptors with estimated binding affinity of 0.6 X 10(9) M-1. Multiple high mol wt bands (greater than 250,000) were identified under nonreduced conditions by affinity cross-linking. Under reduced conditions, one band with an approximate mol wt of 135,000 was identified. Purified Leydig cells (10(5) cells/ml) were cultured in Dulbecco's Modified Eagle's Medium-Ham's F-12 Nutrient Mixture (1:1) containing 0.1% fetal calf serum at 37 C in a humidified atmosphere of 5% CO2-95% air. Insulin and IGF-I stimulated testosterone formation as early as 3 h after administration, and their effects were completely blocked by the addition of a protein synthesis inhibitor, cycloheximide (1 microgram/ml). Insulin and IGF-I also significantly potentiated hCG-and 8-bromo-cAMP-induced testosterone formation. Furthermore, insulin and IGF-I potentiated hCG-stimulated cAMP formation. This suggests that insulin and IGF-I have effects at both the LH receptor sites and the steps beyond adenylate cyclase. The ED50 values of insulin and IGF-I-stimulated testosterone formation were comparable (25 ng/ml). In conclusion, we found that Leydig cells contain specific insulin and type I IGF receptors, and both insulin and IGF-I are capable of modulating Leydig cell steroidogenesis.

Animals↗

[Cooperative phase II study of epirubicin (EPI) in bladder cancer, renal pelvic and ureteral tumors--Urological Cooperative Study Group of EPI].

A phase II study of a new anthracycline anti-cancer antibiotics, epirubicin (EPI), was undertaken in 71 patients with urothelial malignancies; 40 with advanced urothelial malignancies and 31 with superficial bladder cancer. Out of them 32 patients with advanced stage of urothelial cancer were evaluated for the systemic use of EPI, while 30 patients with superficial bladder cancer for intravesical use. Intravenous administration of this new anticancer antibiotic, at a dosage of 60 mg/m2 every three weeks, showed the response rate of 20.0% for advanced bladder cancer and 14.3% for renal pelvic and ureteral tumors. In cases of superficial bladder cancer, at a dosage of 60 mg/30 ml X 3 day every week in principal, the response rate was 66.7%. Eight out of 30 patients showed complete disappearance of the tumor. Twelve patients also showed more than 50% tumor regression. As for adverse effects no serious cardiotoxicity was demonstrated. Anorexia and other gastrointestinal side effects, such as nausea and vomiting, were also seen. Alopecia and myelosuppression were the major adverse effects among patients with systemic EPI administration. With intravesical use of EPI, cystitis syndrome was the major toxicity. However, no systemic side effects were noted in these cases. In conclusion, EPI was assumed to be effective for the treatment of advanced urothelial tumors and superficial bladder cancer.

Aged↗

Mechanism of action of gonadotropin-releasing hormone stimulated Leydig cell steroidogenesis. III. The role of arachidonic acid and calcium/phospholipid dependent protein kinase.

Gonadotropin-releasing hormone agonist (GnRHa) markedly increased testosterone formation from 2.35 +/- 0.13 ng/ml of the controls to 14.92 +/- 0.33 ng/ml (mean +/- SE) in isolated and purified rat Leydig cells. GnRHa-induced testosterone formation was completely blocked by phospholipase A2 inhibitor (chloroquin, 10(-4) M), but was potentiated by the addition of either cyclo-oxygenase inhibitor (indomethacin) or lipoxygenase inhibitor (nordihydroguaiaretic acid, NDGA). Arachidonic acid also directly stimulated Leydig cell steroidogenesis and activated Ca/phospholipid dependent protein kinase. Steroidogenic effects of arachidonic acid were also potentiated by the addition of either indomethacin or NDGA. These results suggest that arachidonic acid may be important in mediating direct stimulatory effects of GnRH on Leydig cell steroidogenesis, and the conversion of arachidonic acid to either prostaglandins or leukotrienes is not required for its steroidogenic effect.

Animals↗

The effects of homogeneous human prealbumin on in vitro and in vivo immune responses in the mouse.

A highly purified preparation of human prealbumin was shown to potentiate the sensitivity of rosette spleen forming cells of adult thymectomized mice to azathioprine in vitro and in vivo and to induce the appearance of the Thy 1, 2 antigen in vitro on spleen cells of adult thymectomized mice. Prealbumin also enhanced IgM antibody synthesis to sheep red blood cells (SRBC) in vitro in 12 week old mice and in vivo in aged (45 - 58 week old) and nude (nu/nu) mice. In vivo administration, to mice that had been pre-treated with hydrocortisone, resulted in a decrease in the specific activity of thymocyte terminal deoxynucleotidyl transferase. The data indicate that the prealbumin molecule possesses immunopotentiating properties in a number of in vitro and in vivo immunocompromised murine models and that the immuno-enhancing properties of the partially purified preparation previously described were in fact due to the prealbumin component and not to other contaminating proteins.

Adjuvants, Immunologic↗

The role of calcium/phospholipid-dependent protein kinase in Leydig cell steroidogenesis.

Purified rat Leydig cell cytosol was found to contain a protein kinase which was dependent on the presence of both calcium and phospholipids (phosphatidylserine and diolein), i.e. calcium/phospholipid-dependent protein kinase. The peak of Ca/phospholipid-dependent protein kinase was separated from type I and type II cAMP-dependent protein kinase by DE-52 chromatography. 4 beta-Phorbol-12-myristate-13-acetate (PMA), a tumor-promoting agent, could substitute for diolein in activation of Ca/phospholipid-dependent protein kinase. PMA caused dose-dependent increments of testosterone formation by Leydig cells, whereas inactive phorbol esters had no significant effects. PMA-induced testosterone formation was dependent on extracellular calcium and could be blocked by the addition of the calcium channel-blocking agent nifedipine. Since PMA can directly activate Ca/phospholipid-dependent protein kinase and increase testosterone formation, these results suggest that Ca/phospholipid-dependent protein kinase may be involved in modulating Leydig cell steroidogenesis in addition to the classical cAMP-dependent protein kinase pathway.

8-Bromo Cyclic Adenosine Monophosphate↗