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Biomedical subjects

J Frick

Publications and source records attributed to J Frick.

At least 19 recordsLinked to original sources

Feasibility and limits of bone marrow mononuclear cell expansion following irradiation.

PURPOSE: To define the ability of bone marrow mononuclear cells (BMMNC) to expand after irradiation and to determine the amount of apoptosis in irradiated expanded cells. MATERIALS AND METHODS: Non-human primate BMMNC were irradiated in vitro at doses ranging from 0 to 4 Gy and were cultured during 1 week in the presence of interleukin 3, interleukin 6, stem cell factor, thrombopoietin and fms-like tyrosine kinase-3 ligand. The expansion yield of BMMNC, colony-forming cells and CD34(+) cells were compared with non-irradiated control cultures. Apoptosis in expanded cells was also defined by annexin V/propidium iodine staining. RESULTS: Irradiation of BMMNC up to 1 Gy did not modify the ability of haematopoietic cells to expand. At higher doses, expansion of haematopoietic cells is reduced as compared with non-irradiated cultures but it remains significant. This reduction in expansion of BMMNC was related to radiation-induced apoptosis. CONCLUSION: The results suggest that it is possible to expand haematopoietic cells after irradiation doses at least up to 2 Gy. This suggests a possible use of cell therapy for the treatment of radiation accident victims.

Animals↗

Effective long-term androgen suppression in men with prostate cancer using a hydrogel implant with the GnRH agonist histrelin.

OBJECTIVES: To evaluate the effectiveness of a hydrogel implant containing the gonadotropin-releasing hormone (GnRH) agonist histrelin in suppressing testosterone production in men with prostate cancer and to determine the effective dose (one, two, or four implants). METHODS: Forty-two men with prostate cancer and indications for androgen ablation were treated with one, two, or four implants. In two of the clinics, comprising 27 subjects, the treatment period was 12 months, with replacement with the same number of implants at 12-month intervals. In a third clinic, which treated 15 subjects, the implants were left in place for up to 30 months. The total experience was 605 treatment months. RESULTS: The histrelin levels were detected in serum proportional to the number of implants placed. The response, however, was similar among all three dose levels, with testosterone and luteinizing hormone essentially completely suppressed. Serum testosterone levels decreased from 21.9 +/- 17.6 nmol/L to 0.93 +/- 1.57 nmol/L within 1 month and were maintained at 0.55 +/- 0.24 nmol/L at 6 months and 0.60 +/- 0.28 nmol/L after 12 months of treatment. Of the 38 assessable patients, 35 (92%) had castrate levels of testosterone within 4 weeks of the initial implant placement. All patients followed for up for 12 months after placement of the initial set of implants maintained suppression of testosterone production while the implant was in place. CONCLUSIONS: The histrelin hydrogel implant provided adequate and reliable delivery of the potent GnRH agonist histrelin during at least 1 year using a single implant in men with prostate cancer. No apparent advantages were found in using more than one implant, and the question of the possible effectiveness of even lower doses remains open. This treatment modality appears to be both safe and effective.

Aged↗

Clinical outcome of microsurgical subinguinal varicocelectomy in infertile men.

The present study assesses the clinical outcome of microsurgical subinguinal varicocelectomy in infertile men, especially with regard to sperm count, motility and fertility. Between June 1990 and October 1998, 272 patients had subinguinal microsurgical varicocelectomy operations for clinical varicoceles, and their long-term results were assessed. In nearly all the patients there was a significant improvement in sperm count and sperm motility after 3 and 6 months. Very few complications arose from this procedure. We concluded that microsurgical subinguinal varicocelectomy is an effective treatment for clinical varicoceles in infertile men. The significant improvement in the quality of spermatozoa, the low complication rates and the remarkably high pregnancy rates make this a valuable alternative to in vitro reproduction techniques.

Adolescent↗

Level of Flt3-ligand in plasma: a possible new bio-indicator for radiation-induced aplasia.

PURPOSE: To follow plasma Flt3-ligand (FL) concentrations in irradiated animals in order to evaluate it as an indicator of bone marrow damage for the management of accidental radiation-induced aplasia. MATERIALS AND METHODS: Non-human primates were irradiated at doses ranging from 2 to 8 Gy, using whole- or partial-body irradiation. Plasma FL concentrations and blood cell counts were determined daily. RESULTS: FL concentrations increased as early as day 2 after irradiation, whatever the irradiation dose. Increase in plasma FL concentration on day 5 post-irradiation was correlated with radiation dose and with the severity of radiation-induced aplasia. During the course of aplasia, FL concentrations in plasma were inversely correlated with neutrophil counts. A peak in FL concentration appeared before the neutrophil nadir, and the subsequent decrease in FL concentration was correlated with the recovery of blood-cell populations. CONCLUSIONS: Monitoring plasma FL concentration can be used as an indicator of radiation-induced marrow aplasia, and this may be of use in accidental irradiation situations.

Animals↗

Release of endotoxin-binding proteins during major elective surgery: role of soluble CD14 in phagocytic activation.

Our previous study demonstrated that soluble CD14 (sCD14) modulates the biologic activity of circulating endotoxin, which appears after surgery. In this study, we examined the behavior of endotoxin-binding proteins, such as sCD14, lipopolysaccharide-binding protein (LBP), and bactericidal/permeability-increasing protein (BPI), in patients' plasma after major abdominal surgery and the phagocytic secretion of sCD14 from peripheral blood mononuclear cells (PBMCs) throughout the observation period. In a prospective study, 15 patients undergoing major abdominal surgery (gastrectomy, n = 3; pancreatectomy, n = 10: colectomy, n = 2) were involved in this study. The endotoxin-binding proteins were perioperatively (preoperatively; postoperative hour 6; days 1, 2, 3, 4, 5, 7, and 10) measured by an enzyme-linked immunosorbent assay (ELISA). To exclude the hemodilution effect of samples, each parameter was corrected by dividing the respective value by the albumin concentration. The phagocytic activity at each time point was tested as an ex vivo sCD14 secretion from PBMCs in the presence and absence of exogenously added endotoxin, Escherichia coli 055B5 (1 ng/ml). Significant endotoxemia (0.35 +/- 0.13 EU/ml; p < 0.05) was observed 6 hours after the beginning of surgery. The sCD14/albumin value rapidly increased at 6 hours after surgery, peaked on day 1, and sequentially declined, whereas the BPI/albumin and LBP/albumin ratios increased more gradually and peaked on day 2. The secretion of sCD14 from 2 x 10(6) PBMCs was significantly enhanced from 6 hours after operation. The increased plasma level of sCD14 may be explained by the parallel-enhanced sCD14 PBMC production. Activated secretion of these endotoxin-binding proteins may play a role in regulating the biologic activity of circulating endotoxin.

Acute-Phase Proteins↗

CD135 (Flk2/Flt3) expression by human thymocytes delineates a possible role of FLT3-ligand in T-cell precursor proliferation and differentiation.

The expression of the Flk2/Flt3 molecule (CD135), the receptor for Flt3 ligand (FL), was investigated in the human thymus. Results showed that there is a high level of expression of CD135 by thymocyte populations, especially by intrathymic T-cell precursor populations. As these results suggested a role for FL in the regulation of thymic T-cell precursor differentiation and/or proliferation, we used an in vitro model of thymic stromal cell cultures in order to delineate the activity of FL on human CD7(high)CD3-CD4-CD8- triple negative intrathymic T-cell precursors. Results showed that FL, either alone or in combination with stem cell factor (SCF) induced the proliferation of CD7(high) precursors, but to a lower extent than interleukin-7 (IL-7) or IL-7 + SCF, used as positive controls. In the presence of FL + SCF, CD7(high) cells developed mainly towards a CD11b+ phenotype whereas IL-7 + SCF preferentially induce a CD3+TcRgammadelta+CD8+ phenotype. Taken together, these data suggest that FL may play a role in inducing the proliferation of CD7(high) human intrathymic T-cell precursors, but also in the induction of a myeloid differentiation pathway within the human thymus.

Cell Differentiation↗

Peptidergic innervation of the human clitoris.

In the present study, the distributions of neuropeptides in the normal human clitoris and in a clitoris from an adrenogenital syndrome (AGS) was demonstrated by immunohistochemistry (IHC). Immunohistochemical screening detected a complex network of nerve fibers containing vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM), neuropeptide tyrosine (neuropeptide Y), C-flanking peptide of neuropeptide Y (CPON), calcitonin gene-related peptide (CGRP) and substance P immunoreactivities. Special attention was given to the VIP-related peptide helospectin, that has been detected in neuronal elements in the clitoris. No visible differences between the localization and distribution of peptidergic nerve fibers of normal and hypertrophic clitoris from AGS have been observed. Co-localization studies showed the co-existence of VIP, PHM and partly helospectin and neuropeptide Y with CPON within nerve fibers in the cavernous tissue and substance P and CGRP co-expression in nerve fibers especially underneath and within the glans clitoris.

Adrenal Hyperplasia, Congenital↗

Differences in the DNA-stainability of spermatozoa from fertile and suspected infertile men.

The aim of this work was to determine whether it is possible to distinguish between fertile (control group, already fathers) and infertile men (suspected infertility), by comparing the fluorescence intensity of the sperm-DNA after incubation with appropriate dyes. First we examined two different DNA-specific dyes (DAPI and YOYO-1) using bull spermatozoa. Based on good results in immunohistochemical applications, YOYO-1 was chosen for further work. The fluorescence-intensity of 200 single, morphologically normal spermatozoa in each semen sample were measured in a cytophotometer, means + SD determined and histograms delineated. Of 20 samples from the control group, 17 had markedly higher fluorescence-intensity than did 7/15 of the suspected infertile men. It is concluded that the DNA of the latter seven samples was less accessible to the dye than was the DNA of the control group. There are cases of infertility known in which there is loss of one or more of the DNA-binding proteins, which in spermatozoa are mainly (85%) protamines. The relationship between the stainability of the sperm-DNA and the packaging with DNA-binding proteins is discussed. Two of the histograms showed abnormalities in the distribution of the fluorescence-intensities, one sample was extremely fragile and most of the sperm lysed during the staining-procedure. Five samples showed normal histograms in comparison with the control group.

Animals↗

Conservative treatment of acute Ormond's disease.

Ormond's disease is a chronic inflammatory process of the retroperitoneum, which sometimes takes a very acute course. We report the case of a man with acute bilateral hydronephrosis. Diagnosis was based on typical criteria seen by magnetic resonance imaging, which made biopsy unnecessary.

Acute Disease↗

[A pill for the man? Current status of fertility control in the man].

Taking all facts into consideration from animal experiments and clinical studies with regard to the development of a male contraceptive you must be aware that the 'pill for men' will hardly be available in this century. Because of the increasing interest of the industry and the effort of the WHO and other similar institutions, like the Population Council of New York, to develop a male pill the stagnation of the past 20 years could be overcome, and it may be possible to have an adequate method in 2005. In all probability this will be a combination of hormones either from a gestagen plus testosterone preparation or a potent LHRH agonist and/or antagonist, also in combination with a long-acting testosterone preparation, with testosterone levels within the normal range. Nowadays it cannot be said which role gossypol will finally play. There are studies going on with gossypol with some promising results.

Contraceptive Agents, Male↗

Predicting lettuce canopy photosynthesis with statistical and neural network models.

An artificial neural network (NN) and a statistical regression model were developed to predict canopy photosynthetic rates (Pn) for 'Waldman's Green' leaf lettuce (Latuca sativa L.). All data used to develop and test the models were collected for crop stands grown hydroponically and under controlled-environment conditions. In the NN and regression models, canopy Pn was predicted as a function of three independent variables: shootzone CO2 concentration (600 to 1500 micromoles mol-1), photosynthetic photon flux (PPF) (600 to 1100 micromoles m-2 s-1), and canopy age (10 to 20 days after planting). The models were used to determine the combinations of CO2 and PPF setpoints required each day to maintain maximum canopy Pn. The statistical model (a third-order polynomial) predicted Pn more accurately than the simple NN (a three-layer, fully connected net). Over an 11-day validation period, average percent difference between predicted and actual Pn was 12.3% and 24.6% for the statistical and NN models, respectively. Both models lost considerable accuracy when used to determine relatively long-range Pn predictions (> or = 6 days into the future).

Carbon Dioxide↗

Effect of active immunization against luteinizing hormone-releasing hormone on the androgen-sensitive Dunning R3327-PAP and androgen-independent Dunning R3327-AT2.1 prostate cancer sublines.

BACKGROUND: The objective of this study was to determine the effect of active immunization against LHRH on the growth characteristics and histology of subcutaneously implanted tumors of the androgen-sensitive Dunning R3327-PAP and androgen-independent R3327-AT2.1 rat prostate adenocarcinoma sublines. RESULTS: We herein demonstrate that 1) active immunization with an LHRH-diphtheria toxoid-conjugate (LHRH-DT) leads to the downregulation of gonadotropins and testosterone and consequently the atrophy of testosterone-dependent organs such as the testes, prostate, and androgen-sensitive Dunning R3327-PAP tumors, 2) growth inhibition of Dunning R3327-PAP tumors is caused by suppression of cell division rather than by an increase in cell death and is associated with an increase of the tumor stroma content, and 3) volume increase of the androgen-independent Dunning R3327-AT2.1 tumor is slightly but significantly reduced, indicating a local stimulatory LHRH loop within this tumor cell line.

Analysis of Variance↗

Follicle-stimulating hormone activates a cAMP-dependent chloride conductance in TM4 Sertoli cells.

The effect of follicle-stimulating hormone (FSH) on the electrical properties of TM4-Sertoli cells was investigated. Addition of 5 IU/ml FSH caused a dose-dependent and reversible depolarization of the resting membrane potential by +15.3 +/- 1.0 mV accompanied by a decrease of the input resistance. The depolarization was completely abolished in chloride-free solutions. The reversal potential of the effect was close to the calculated reversal potential for chloride. We conclude that FSH activates a chloride conductance in cultured TM4 Sertoli cells.

Animals↗

Endocrine profiles after radiotherapy in stage I seminoma: impact of two different radiation treatment modalities.

BACKGROUND AND PURPOSE: In patients with stage I seminoma treated with elective lymph node irradiation, testicular scatter doses are often thought to be responsible for later disturbances in fertility. We studied the influence of radiation field extensions and testicular doses on hormonal function. MATERIALS AND METHODS: FSH (follicle stimulating hormone) and LH (luteinizing hormone) were evaluated before radiotherapy (RT) and by serial analyses after treatment for 4 years. Twenty-three patients were irradiated by hockey stick fields with a mean dose of 31.9 Gy (+/-4.7 SD) and a mean scatter dose of 54 8 cGy (+/-16.6 SD). Twenty-one patients received limited RT to the paraaortic nodes with 28.1 Gy (+/-2.4 SD). The mean testicular dose was only 25 cGy (+/-7.8 SD). All patients had normal pre-treatment hormonal values. RESULTS: Six months after the end of RT, mean FSH values were significantly elevated in the hockey stick group (P = 0.032), returning to normal after 3 years. The increase in LH was also significant, but stayed within normal ranges. Limited RT resulted in a minimal, dose-dependent increase of FSH; no changes in LH were noted. CONCLUSIONS: In patients with a normal hormonal status after semicastration, FSH is a reliable monitor for transient radiation-induced effects. To avoid treatment-related disturbances in spermatogenesis, scatter doses should be reduced to less than 20 cGy.

Adult↗

alpha-Glucosidase activity in the rat epididymis under different physiological conditions.

The estimation of alpha-glucosidase activity in semen is widely used as a marker of epididymal function. In the present studies, glucosidase activity was evaluated in the different segments of the rat epididymis under various physiological conditions. In addition, the effect of two known male antifertility agents, gossypol and alpha-chlorohydrin, on enzyme activity was evaluated. Enzyme activity was absent from the epididymis of rats aged 10 and 20 days but became detectable at 30 days of age when the adult pattern of distribution (highest activity in the caput epididymis) was established. Enzyme activity was reduced significantly in all segments of the epididymis at 7 days after castration and a significant decrease in activity was also observed following the administration of either gossypol or alpha-chlorohydrin. These findings are consistent with a role for alpha-glucosidase in sperm maturation in the epididymis.

Aging↗