Search PubMed⌕ Search

Biomedical subjects

C Petersen

Publications and source records attributed to C Petersen.

At least 73 records · Page 4Linked to original sources
PubMed2000

Power Doppler endometrial evaluation as a method for the prognosis of embryo implantation in an ICSI program.

PURPOSE: The objective of the present study was to evaluate power Doppler of the endometrium as a parameter for the prognosis of embryo implantation in patients who underwent intracytoplasmic sperm injection (ICSI). METHODS: The power Doppler was performed on a transverse section at the level of the uterine fundus on the day of human chorionic gonadotropin in 185 patients who submitted to ovarian stimulation for ICSI. The endometrium was divided into four equal quadrants and classified as grade I, II, III, or IV according to the visualization of the power Doppler in the quadrants. The color Doppler signal was considered to be positive when it reached at least the basal layer of the endometrium. RESULTS: Age, number of days of stimulation, number of follicles > or = 16 mm, number of oocytes in metaphase II retrieved, and fertilization rate did not differ patients with the four different types of endometrial grades. Endometrial thickness and the pulsatility index of uterine artery also were similar for the four grades. The rate of embryo implantation also did not differ significantly (P = 0.53) among groups: grade I = 10%; grade II = 11.6%; grade III = 15.4%; grade IV = 10.5%. The pregnancy rates were grade I = 25%; grade II = 29.7%; grade III = 37.5%; grade IV = 23.8% (P = 0.44). CONCLUSIONS: Our data demonstrate that isolated evaluation of endometrial vascularization with power Doppler is not an important factor for the prediction of pregnancy in an ICSI program.

Adult↗
PubMed2000

The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42.

PAR (partitioning-defective) proteins, which were first identified in the nematode Caenorhabditis elegans, are essential for asymmetric cell division and polarized growth, whereas Cdc42 mediates establishment of cell polarity. Here we describe an unexpected link between these two systems. We have identified a family of mammalian Par6 proteins that are similar to the C. elegans PDZ-domain protein PAR-6. Par6 forms a complex with Cdc42-GTP, with a human homologue of the multi-PDZ protein PAR-3 and with the regulatory domains of atypical protein kinase C (PKC) proteins. This assembly is implicated in the formation of normal tight junctions at epithelial cell-cell contacts. Thus, Par6 is a key adaptor that links Cdc42 and atypical PKCs to Par3.

Adaptor Proteins, Signal Transducing↗
PubMed2000

The challenge of p53 as prognostic and predictive factor in gliomas.

In recent years, increasing interest in genetic abnormalities and biologic factors such as the tumour suppressor gene p53 as possible predictive and prognostic factor in gliomas has emerged. Inactivation of p53 can result in resistance to apoptosis, one of the mechanisms thought to explain the failure to respond to DNA-damaging agents. Thus, inactivation of p53 might be associated with a worse prognosis. Considering the inconsistent results of several recent studies, it has remained controversial whether p53 actually can be related to response to treatment and patients' prognosis. Therefore, a systematic review of the literature was performed, which included 28 publications. Techniques for assessing the inactivation of p53 varied widely. Overall, approximately 50% or more of astrocytoma specimens evaluated by immunohistochemistry stained positively for p53, regardless of histologic grade. Eight studies were restricted to comparably treated patients within a single histologic group. In most instances, non-restrictive inclusion criteria and use of statistical methods, which were not sufficient to correct the possible bias, make it difficult to reach unequivocal conclusions. However, it appears that the prognostic information of p53 is at best marginal, especially when compared to established parameters such as grading, age, etc. Its predictive value, which most likely is rather limited too, can hardly be judged without prospective studies also evaluating other biological factors as well as end-points other than time to radiological progression.

Astrocytoma↗
PubMed2000

Effect of changing the weekly dose intensity of fractionated irradiation on local control of two human squamous cell carcinomas in nude mice.

PURPOSE: To compare the effect of fractionated irradiation with increasing, constant or decreasing weekly dose intensity on local tumour control. MATERIALS AND METHODS: Human squamous cell carcinomas, FaDu and GL, were grown in nude mice. Thirty fractions were applied under ambient conditions with increasing, constant or decreasing weekly dose intensity within a constant overall treatment time of 6 weeks. Dose intensity was changed every 2 weeks. Irradiations were terminated in some groups of animals after 20 fractions in 4 weeks. Endpoint was the tumour control dose 50% (TCD50) at day 120 (FaDu) or day 180 (GL) after end of treatment. RESULTS: In FaDu tumours the TCD50 value of 60 Gy (95% CI 56; 63) for fractionated irradiation with decreasing dose intensity, i.e. high initial doses, was slightly but significantly lower than the TCD50, of 68 (60; 81) after low initial doses (p=0.03). The TCD50 value of 62 Gy (57; 68) after constant doses was intermediate (constant vs increasing p =0.30; constant vs decreasing p=0.15). The higher efficacy of high initial doses in FaDu tumours was explained by local control occurring already during the course of irradiation. In GL tumours the TCD50 values were 52 Gy (43; 62) after high initial dose intensity, 50 Gy (43; 66) after constant doses, and 55 Gy (42; 89) after low initial dose intensity. These values were not statistically different (p-values 0.20-0.75). CONCLUSIONS: The data support the view that initial dose concentration during fractionated irradiation does not enhance radioresistance of FaDu and GL tumours, for instance by an earlier onset of clonogen repopulation.

Animals↗
PubMed2000

Antioxidant effect of oral dipyridamole during cerebral hypoperfusion with human carotid endarterectomy.

We sought to test the hypothesis of an antioxidant effect of dipyridamole in vivo in a model of cerebral hypoperfusion. Twenty-one patients (65+/-10 years, 11 men) undergoing carotid endarterectomy were allocated in two groups (group 1, 10 with dipyridamole, 200 mg p.o., 3-4 h before surgery; group II, 11 with placebo) in a double-blind placebo-controlled randomized design. Blood was sampled from ipsilateral jugular bulb, and plasma vitamin E content was assayed before, after 15 and 30 min of clamp, and 2 and 10 min after declamping. In 12 of them, lipoperoxides were assayed. Vitamin E plasma content decreased significantly in group II (rest, 3.71+/-0.22 mmol/mol of cholesterol, 100%) after clamp (91.5% of rest, p < 0.01) and remained unchanged during declamping (90.9% of rest, p < 0.01), but did not change in group I (rest, 3.5+/-0.44 mmol/mol of cholesterol, 100%) during clamping (99.9% of rest; p = NS) and after declamping (97.6% of rest; p = NS). Lipoperoxide concentration did not change in group I (rest, 302+/-8 a.u.; clamp, 296+/-13 a.u.; p = NS vs. rest; declamp, 304+/-8 a.u.; p = NS vs. rest), and increased significantly in group II (rest, 313+/-5 a.u.; clamp, 352+/-9 a.u.; p < 0.01 vs. rest; declamp, 343+/-6 a.u.; p < 0.05 vs. rest). Cerebral oxidative stress associated with human carotid endarterectomy can be attenuated by pretreatment with oral dipyridamole.

Aged↗
PubMed2000

Progressive familial intrahepatic cholestasis: partial biliary diversion normalizes serum lipids and improves growth in noncirrhotic patients.

OBJECTIVES: Progressive familial intrahepatic cholestasis (PFIC) usually presents with pruritus, jaundice, hepatomegaly, and growth failure. A group of PFIC is recognized by marked elevation of total serum bile acids, decreased serum apolipoprotein A-1, and high-density lipoprotein, but normal gamma-glutamyltranspeptidase and cholesterol. Although medical therapy generally fails, partial external biliary diversion (DIV) has been used with promising results for cholestasis. However, little has been reported of its effect on linear growth, synthetic liver function, and lipid metabolism. METHODS: DIV was performed on six noncirrhotic children with PFIC, all suffering from severe pruritus and cholestasis, refractory to medical treatment. Stature was below -1 (median, -2.3) standard deviation score (SDS) for height in all cases. All patients had markedly enhanced bile acids (307 +/- 72 microl/L), markedly decreased high-density lipoprotein (20 +/- 7 mg/dl), and apolipoprotein A-1 (58 +/- 37 mg/dl), but normal gamma-glutamyltranspeptidase and cholesterol. In addition, cholinesterase activity, monoethylglycinexylidide test, and Fischer's ratio indicated a significantly reduced synthetic liver function in all children but the youngest. RESULTS: After DIV, all patients were consistently relieved of pruritus, and experienced normalization of all liver function tests, including cholinesterase activity, monoethylglycinexylidide test, and Fischer's ratio, as well as the serum lipid profile within 1 yr. In addition, a marked catch-up growth (median, +/- 1.3 SDS) was evident after 1 yr in all cases. CONCLUSIONS: This report shows an excellent result of DIV in noncirrhotic PFIC patients and compares favorably with other reports. All patients experienced complete remission, including normalization of synthetic liver function and lipid metabolism. For the first time we have shown that DIV can also be associated with an accelerated growth in these patients.

Adult↗
PubMed2000

The interleukin-1 system in the testis.

The interleukin-1 (IL-1) family consists of two agonist proteins, IL-1 alpha and IL-1 beta, and one antagonist, IL-1 receptor antagonist (IL-1ra), which blocks the action of the agonists by binding and competing at the IL-1 receptor level. IL-1 beta and to a lesser extent IL-1 alpha were originally described as rapidly inducible proinflammatory cytokines released by activated macrophages. However, IL-1 alpha has been found to be constitutively produced by certain tissues, and noninflammatory functions have been proposed for this protein, although they have not yet been well elucidated. Consistent with this suggestion, we previously showed that the intact rat testis constitutively produces large amounts of IL-1 alpha at both the mRNA and protein levels. The expression of IL-1 alpha was found to be confined to Sertoli cells, with evidence of a developmental as well as a stage-dependent production pattern. In more recent studies, we have found indications that the testis can also initiate production of IL-1 beta upon stimulation with inflammatory inducers such as endotoxin. Further, we have detected constitutive testicular expression of IL-1ra, opening up the possibility that IL-1 action in the testis may be specifically regulated by paracrine mechanisms. Recent data have demonstrated that the testis can produce more than one isoform of IL-1 alpha with indications of both post-transcriptional and post-translational modifications, resulting in at least three distinct bio- and immunoreactive IL-1 alpha proteins. We conclude that all three classical IL-1 ligands and novel IL-1 alpha isoforms are present in the testis and may serve as paracrine mediators under physiological or pathophysiological conditions. The function of this testicular IL-1 agonist-antagonist network is a current focus of investigation.

Animals↗
PubMed2000

Enhancement of intrinsic tumor cell radiosensitivity induced by a selective cyclooxygenase-2 inhibitor.

The antitumor effects of the selective cyclooxygenase (COX)-2 inhibitor SC-236 alone and in combination with radiation were investigated using the human glioma cell line U251 grown in monolayer culture and as tumor xenografts. On the basis of Western and Northern blot analyses, these cells express COX-2 protein and mRNA to levels similar to those in the human colon carcinoma cell line HT29. Treatment of U251 cells in monolayer culture with 50 microM SC-236 resulted in a time-dependent decrease in cell survival as determined by a clonogenic assay. The cell death induced by SC-236 was associated with apoptosis and the detachment of cells from the monolayer. After 2 days of drug treatment, the cells that remained attached were exposed to graded doses of radiation, and the clonogenic assay was performed. Comparison of the survival curves for drug-treated and untreated cultures revealed that SC-236 enhanced radiation-induced cell death. In these combination studies, SC-236 treatment resulted in a dose-enhancement factor of 1.4 at a surviving fraction of 0.1, with the surviving fraction at 2 Gy (SF2) reduced from 0.61 to 0.31. These data indicate that in vitro SC-236 induces U251 apoptotic cell death and enhances the radiosensitivity of the surviving cells. To extend these investigations to an in vivo situation, U251 glioma cells were grown as tumor xenografts in the hind leg of nude mice, and SC-236 was administered in drinking water. SC-236 alone slowed tumor growth rate, and when administered in combination with local irradiation, SC-236 caused a greater than additive increase in tumor growth delay. These in vitro and in vivo results suggest that the selective inhibition of COX-2 combined with radiation has potential as a cancer treatment.

Animals↗
PubMed1999

The role of the synthetic enzyme GAD65 in the control of neuronal gamma-aminobutyric acid release.

We have studied GABAergic synaptic transmission in retinal ganglion cells and hippocampal pyramidal cells to determine, at a cellular level, what is the effect of the targeted disruption of the gene encoding the synthetic enzyme GAD65 on the synaptic release of gamma-aminobutyric acid (GABA). Neither the size nor the frequency of GABA-mediated spontaneous inhibitory postsynaptic currents (IPSCs) were reduced in retina or hippocampus in GAD65-/- mice. However, the release of GABA during sustained synaptic activation was substantially reduced. In the retina both electrical- and K(+)-induced increases in IPSC frequency were depressed without a change in IPSC amplitude. In the hippocampus the transient increase in the probability of inhibitory transmitter release associated with posttetanic potentiation was absent in the GAD65-/- mice. These results indicate that during and immediately after sustained stimulation the increase in the probability of transmitter release is not maintained in GAD65-/- mice. Such a finding suggests a decrease in the size or refilling kinetics of the releasable pool of vesicles, and various mechanisms are discussed that could account for such a defect.

Animals↗
PubMed1999

Inhibition of cellular growth by increased guanine nucleotide pools. Characterization of an Escherichia coli mutant with a guanosine kinase that is insensitive to feedback inhibition by GTP.

In Escherichia coli the enzyme guanosine kinase phosphorylates guanosine to GMP, which is further phosphorylated to GDP and GTP by other enzymes. Here I report that guanosine kinase is subject to efficient feedback inhibition by the end product of the pathway, GTP, and that this regulation is abolished by a previously described mutation, gsk-3, in the structural gene for guanosine kinase (Hove-Jensen, B., and Nygaard, P. (1989) J. Gen. Microbiol. 135, 1263-1273). Consequently, the gsk-3 mutant strain was extremely sensitive to guanosine, which caused the guanine nucleotide pools to increase dramatically, thereby initiating a cascade of metabolic changes that eventually led to growth arrest. By isolation and characterization of guanosine-resistant derivatives of the gsk-3 mutant, some of the crucial steps in this deleterious cascade of events were found to include the following: first, conversion of GMP to adenine nucleotides via GMP reductase, encoded by the guaC gene; second, inhibition of phosphoribosylpyrophosphate synthetase by an adenine nucleotide, presumably ADP, causing starvation for histidine, tryptophan, and pyrimidines, all of which require PRPP for their synthesis; third, accumulation of the regulatory nucleotide guanosine 5',3'-bispyrophosphate (ppGpp), a general transcriptional inhibitor synthesized by the relA gene product in response to amino acid starvation.

Cell Division↗
PubMed1999

Impact of overall treatment time on local control of slow growing human GL squamous cell carcinoma in nude mice treated by fractionated irradiation.

BACKGROUND AND PURPOSE: The impact of overall treatment time of fractionated irradiation on local control of slow growing human GL squamous cell carcinoma (SCC) was determined. MATERIALS AND METHODS: Moderately well differentiated and keratinizing human GL SCC with a volume doubling time of 8 days were transplanted subcutaneously into the right hindleg of NMRI (nu/nu) mice and irradiated with 30 fractions under ambient conditions over 2, 3, 4.5, 6 and 10 weeks. Endpoint of the experiments was local tumor control at day 180 after end of treatment. RESULTS: The tumor control dose 50% (TCD50) increased from 40 to 57 Gy when the treatment time was extended from 2 to 10 weeks. The data can be well described by a linear increase in TCD50 with time. The recovered dose per day (D(r)) was 0.28 Gy (95% confidence interval 0.06; 0.48). The fit to the data was not significantly improved by assuming a biphasic (dog-leg) time course with constant TCD50 values in the initial part of treatment followed by a more rapid increase of TCD50 thereafter. CONCLUSIONS: D(r) in GL SCC was significantly less than the value of 1.0 Gy (0.7; 1.3) previously reported for poorly differentiated, non-keratinizing and fast growing human FaDu SCC (Baumann M, Liertz C, Baisch H, Wiegel T, Lorenzen J, Arps H. Impact of overall treatment time of fractionated irradiation on local control of human FaDu squamous cell carcinoma in nude mice. Radiother. Oncol. 1994:32:137-143), indicating important heterogeneity of the time factor between different tumors of the same histological type.

Algorithms↗
PubMed1999

Review of 1028 bulbar eviscerations and enucleations. Changes in aetiology and frequency over a 20-year period.

PURPOSE: To evaluate possible changes in aetiology and frequency of bulbar eviscerations and enucleations. METHODS: A total of 1028 cases from three two-year periods: 1975-76, 1985-86 and 1995-96 collected by the Eye Pathology Institute were reviewed. RESULTS: A significant decrease (p<0.001) in number of enucleations was observed from 358 in 1975-76 to 214 in 1995-96, corresponding to an almost equivalent increase in number of eviscerations from 5 in 1975-76 to 83 in 1995-96. The total number of eye removals decreased significantly (p<0.01) over the last two periods from 368 in 1985-86 to 296 in 1995-96. This was primarily caused by a decrease in the number of glaucoma-related enucleations from 32.7% in 1975-76 to 15.0% in 1995-96. The reduction in number was not fully balanced by the increase in glaucoma-related eviscerations. CONCLUSION: Over the last 20 years there has been a change in choice of operation from enucleation to evisceration.

Adolescent↗
PubMed1999

Impact of preirradiation of the tumour bed on cell production rate and cell loss of human FaDu squamous cell carcinoma growing in nude mice.

PURPOSE: To explore whether the tumour bed effect (TBE) in FaDu squamous cell carcinoma growing in nude mice is caused by a reduced tumour cell production rate and/or by increased tumour cell loss. MATERIALS AND METHODS: Human FaDu tumours were studied in NMRI nude mice. The volume doubling time (VDT) between 100 and 400 mm3 was determined for tumours in unirradiated subcutaneous (sc) tissues (group 1), tumours in sc tissues preirradiated with 12.5 Gy (group 2), tumours irradiated in situ with 12.5 Gy (group 3), and tumours from group 3 re-transplanted into unirradiated sc tissues (group 4). Labelling index (LI), potential doubling time (Tpot), relative necrotic area and apoptotic index (AI) were evaluated in tumours from groups 1 and 2. RESULTS: The median VDT were 2.6 days (95% CI 2-4) in group 1 and 7.0 days (4-15) in group 2 (p<0.001). The VDT were not significantly different between groups 2 and 3, and group 1 and 4. In groups 1 and 2, the Tpot values (3.1 +/- 0.6 days (SD) versus 2.9 +/- 0.5 days) and the LI were identical (10 +/- 1.5%). The median relative necrotic area was significantly larger in group 2 (37% [23-42]) compared with group (6% [0.3-27]). The apoptotic index was low (0.2%) and did not differ between groups 1 and 2. CONCLUSIONS: The results indicate that the TBE in FaDu squamous cell carcinoma is not caused by a reduced cell production rate in the viable tumour compartment. Rather, the TBE reflects a decreased viable tumour cell compartment due to increased cell loss. Necrosis appears to be the major component of the tumour bed induced cell loss in FaDu tumours, whereas apoptosis has no impact on the TBE in this model.

Animals↗
PubMed1999

Outer dense fibre proteins from human sperm tail: molecular cloning and expression analyses of two cDNA transcripts encoding proteins of approximately 70 kDa.

The outer dense fibres (ODF) are a main cytoskeletal structure of the sperm tail. Despite their importance in the morphology and function of the sperm tail, their constituents are poorly described. Here we investigate the protein composition of human outer dense fibres. Our results suggest that human ODF consist of about 10 major and of at least 15 minor proteins, where all major proteins are ODF1, ODF2 or ODF2-related proteins. From a human testis cDNA library, we isolated two slightly different cDNAs encoding ODF2 proteins of approximately 70 kDa. Human ODF2 cDNAs and their encoded proteins are very similar to those isolated from rat and mouse pointing to a high evolutionary pressure residing on these proteins. Transcription of ODF2 is restricted to testis tissue and more specifically to round spermatids as was demonstrated by a non-radioactive in-situ hybridization. ODF2 proteins were detected in the sperm tail. Their distribution along the length of the sperm tail shows that the ODF normally extend to about half the principal piece of the sperm tail. The former result opens the possibility for a screening regarding the distribution of sperm tail proteins related to motility disorders.

Amino Acid Sequence↗
PubMed1998

A rapid method of Sertoli cell isolation by DSA lectin, allowing mitotic analyses.

We have developed a rapid and convenient method of Sertoli cell preparation for studying the growth kinetics of these cells in in vitro culture. Datura Stramonium agglutinin (DSA)-coated dishes were used to rapidly purify single Sertoli cells from immature rat testis. We have monitored by immunohistochemical markers the degree of contamination of our Sertoli cell preparation by other cell types. The cell preparation is essentially free of germ cells and interstitial cells and contains a minimal percentage of myoid cells. Sertoli cells isolated with this method retain functional activities such as the FSH responsiveness in terms of cAMP production. In addition, we have studied the proliferative activity of Sertoli cells isolated by lectin binding from rats of different ages. Sertoli cells exhibited a characteristic pattern of proliferation which was a function of the donor animal age. The proliferative activity of isolated Sertoli cells decreased with age, being much higher in 3 day-old rats than in older animals. A similar pattern was observed when the mitotic activity of Sertoli cells in response to mitogens present in the testicular extracts from 5 day-old rats was evaluated. The method described here reduces or eliminates many of the drawbacks of the conventional procedures used to isolate Sertoli cells, thus providing a useful tool in studies of growth kinetics and regulation of cell proliferation in vitro.

Aging↗