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Biomedical subjects

G Fried

Publications and source records attributed to G Fried.

At least 19 recordsLinked to original sources
PubMed2005

Preoperative evaluation of laparoscopic living renal donors with computerized tomography and its effect on donor morbidity and graft function.

OBJECTIVE: To assess the efficacy of CT angiography (CTA) in evaluating the renovascular anatomy in 50 patients who underwent laparoscopic donor nephrectomy, and to correlate results with donor morbidity and recipient outcome. METHODS: Forty-eight patients were evaluated by CTA prior to laparoscopy. Donors with aberrant renovasculature and their respective recipients were divided into: 1) accurate preoperative CTA ("predictive group", PG), 2) inaccurate CTA ("non-predictive group", NPG). Warm ischemia times (WIT), estimated blood loss (EBL), operative time (OT), and the open conversion rate were compared. Recipient creatinine values on post-operative day 1 and 3 months were recorded with the rate of delayed graft function (DGF) and ureteral complication. Statistical significance was calculated using the student's T-test. RESULTS: Among patients with aberrant vasculature (48%, 23/48) at laparoscopy, 14 were accurately predicted by CT angiography (11 arterial, 3 venous). NPG consisted of 5 duplicated arteries, 1 early arterial branching, and 3 anomalous veins. CT accuracy was 85%. The sensitivity and specificity of the arterial imaging were 65% and 100% respectively, while those of venous imaging were 50% and 100%. EBL, WIT, OT, number of open conversions, and ureteral complications were statistically insignificant between groups (p= 0.05, 95% C.I.). The mean decreases in creatinine between NPG and PG on post-operative day 1 and at 3 months were 45.4% and 54.8%, and 71.5% and 79.1% respectively, both statistically insignificant. Two of 8 in the NPG experienced DGF as compared to 1/8 in the PG. CONCLUSIONS: Despite the lower sensitivity of this study, the discordance between imaging and laparoscopy did not augment donor morbidity or increase adverse recipient outcomes. This may indicate that regardless of the shortcomings of 2-D CTA for living donors, it represents a safe and effective imaging modality when coupled with meticulous laparoscopic dissection and central intraoperative involvement of the transplant surgeon.

Angiography↗
PubMed2004

Estrogen receptor beta is expressed in human embryonic brain cells and is regulated by 17beta-estradiol.

In order to study estrogen effects on developing human neurons, we have established primary cultures of neurons and glia from 8-13-week human embryo cortex and spinal cord. The neuronal identity of the cultures was verified using the neuronal synaptic vesicle and neuronal endosomal membrane markers synaptotagmin, synapsin and synaptophysin, and the glial contribution to the mixed glial-neuronal cultures was verified using the glial marker glial fibrillary acidic protein (GFAP). We here report expression of estrogen receptor beta (ERbeta) in these cells using RT-PCR and sequencing, RNAse protection assay, immunohistochemistry and immunoblotting. We found that both neuronal and mixed glial-neuronal cultures expressed ERbeta. Treatment with 17beta-estradiol gave an increased expression of ERbeta in both types of cultures. These results suggest that ERbeta is expressed in fetal brain and thus may mediate effects of estrogen in the developing nervous system. Furthermore, the results suggest that expression of ERbeta in fetal brain may be regulated by estrogen.

Calcium-Binding Proteins↗
PubMed2002

Effects of nitric oxide donors and inhibitors of nitric oxide signalling on endothelin- and serotonin-induced contractions in human placental arteries.

In order to explore the role of nitric oxide (NO) in the control of fetoplacental vascular tone in normal pregnancy we have examined the effects of NO donors on uteroplacental arteries pre-contracted with the vasoconstrictor endothelin-1 (ET-1) or serotonin (5-HT). We have furthermore examined the effects of guanylate cyclase inhibitors on the NO-induced relaxation. Segments of placental arteries (n=102) obtained from 39 placentas immediately after delivery were mounted in organ baths and superfused with Krebs-Ringer solution at 37 degrees C. The vessel segments were exposed to drugs for various intervals and the tension was recorded isometrically and registered on a polygraph. Cyclic guanosine monophosphate (cGMP) analysis was performed after extraction of vessel segments using a specific radioimmunoassay. The placental artery segments responded to ET-1 and 5-HT with a dose-dependent vasoconstriction. After pre-contraction with ET-1 (10(-7) M) or 5-HT (10(-6) M), the vessels relaxed in response to the NO donors glyceryltrinitrate (GTN) (10(-6) M) and S-nitroso-N-acetyl-penicillamine (SNAP) (10(-5) M). In the presence of the non-specific guanylate cyclase inhibitor LY 83583 (10(-6) M), the vessels responded with a small contraction. In the presence of the soluble guanylate cyclase (sGC) inhibitor 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) the non-treated vessels responded with a relaxation. 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one gave no obvious relaxation in pre-contracted vessels. Addition of 8-Br-cGMP, the cell-permeant analogue of cGMP, with or without pre-contraction had no effect on the vessels. Cyclic guanosine monophosphate analysis showed that GTN treatment caused an increase in cGMP after 12 min. Our results indicate that NO acts as a vasodilator in placental vessels. The cGMP-dependent mechanisms may be involved in NO-induced relaxation but cGMP-independent mechanisms appear also to be involved.

Adult↗
PubMed2002

Delivery rates following IVF treatment, using two recombinant FSH preparations for ovarian stimulation.

BACKGROUND: A prospective, semi-randomized, open, clinical study was conducted to compare ovarian response, pregnancy outcome and delivery rates using two recombinant FSH preparations (Gonal-F and Puregon) for IVF. METHODS: We analysed stimulation parameters and outcome data in 812 initiated treatment cycles where 292 women used Gonal-F and 200 used Puregon. Embryo transfer was carried out in 676 cycles. In the two preparation groups we also compared 170 women previously treated with FSH for IVF with 266 previously untreated. RESULTS: The pregnancy rate with Gonal-F was 26% and with Puregon 28%. Delivery rates were identical, 22%. Clinical pregnancy and delivery rates per cycle with embryo transfer in earlier untreated women were 29.0 and 24.0%, whereas in previously treated women they were 23.5 and 18.8% respectively. After repeated cycles, delivery frequencies consecutively decreased, independent of the FSH preparation used. CONCLUSION: Gonal-F and Puregon seem to be equally potent in achieving follicular development and equally effective, in terms of delivery rates, for use in an IVF programme. Repeated cycles resulted in equally large consecutive decreases in delivery rates, regardless of preparation choice, but were considered worthwhile for up to three stimulation cycles in selected patients.

Adult↗
PubMed2002

Desmopressin in the treatment of menorrhagia in women with no common coagulation factor deficiency but with prolonged bleeding time.

The objective of this study was to investigate the efficacy and safety of desmopressin (1-desamino-8-D-arginine vasopressin) compared with placebo in the reduction of menstrual blood loss in women with menorrhagia and prolonged bleeding time, but without common coagulation factor deficiencies. We performed a randomized, double-blind, cross-over study using 300 microg desmopressin nasal inhalation or placebo treatment in one of the two first treatment cycles. Desmopressin was given only for the 2 days during which the bleeding had been at a maximum in the previous baseline cycle. A third open cycle involved combined treatment with desmopressin and tranexamic acid during the 2 days for all patients. Menstrual blood loss during the treatment periods was compared with blood loss during placebo-treated periods using objective measurement. A significant reduction of menstrual blood loss was found in the cycles treated with combined desmopressin and tranexamic acid compared with placebo. When analyzing the blood loss during the two treatment days, there was a significant reduction in blood loss for the 2 days with desmopressin alone versus placebo. The treatment was well tolerated and no serious adverse events were recorded. In conclusion, we find that nasal desmopressin is a possible complement for the medical treatment of menorrhagia.

Adult↗
PubMed2001

Neurons and glial cells of the embryonic human brain and spinal cord express multiple and distinct isoforms of laminin.

We have identified by immunocytochemistry, Western blotting, and RT-PCR the isoforms of laminin expressed by glial cells and neurons cultured from human embryonic brain and spinal cord. We show that most of the known laminins are present in human neurons and glial cells. Importantly, Western analysis demonstrates that the isoforms of laminin present in embryonic human brain differ from those expressed in human spinal cord. Neurons of the brain and spinal cord also express their distinct and characteristic isoforms of laminin compared to the glial cells of the same CNS regions. These results suggest that, in addition to the known laminins, several novel isoforms may exist in the human embryonic CNS. The observed differences between the isoforms of laminin in brain and spinal cord neurons and glial cells may result from primary structural changes or from posttranslational modifications, e.g., variations in glycosylation. Thus, identification of these novel laminins and determination of their function(s) should further our understanding of the mechanisms of aging, disease, and trauma in the human CNS.

Animals↗
PubMed2000

Munc-18 associates with syntaxin and serves as a negative regulator of exocytosis in the pancreatic beta -cell.

The Munc-18 protein (mammalian homologue of the unc-18 gene; also called nSec1 or rbSec1) has been identified as an essential component of the synaptic vesicle fusion protein complex. The cellular and subcellular localization and functional role of Munc-18 protein in pancreatic beta-cells was investigated. Subcellular fractionation of insulin-secreting HIT-T15 cells revealed a 67-kDa protein in both cytosol and membrane fractions. Immunohistochemistry showed punctate Munc-18 immunoreactivity in the cytoplasm of rat pancreatic islet cells. Direct double-labeling immunofluorescence histochemistry combined with confocal laser microscopy revealed the presence of Munc-18 immunoreactivity in insulin-, glucagon-, pancreatic polypeptide-, and somatostatin-containing cells. Syntaxin 1 immunoreactivity was detected in extracts of HIT-T15 cells, which were immunoprecipitated using Munc-18 antiserum, suggesting an intimate association of Munc-18 with syntaxin 1. Administration of Munc-18 peptide or Munc-18 antiserum to streptolysin O-permeabilized HIT-T15 cells resulted in significantly increased insulin release, but did not have any significant effect on voltage-gated Ca(2+) channel activity. The findings taken together show that the Munc-18 protein is present in insulin-secreting beta-cells and implicate Munc-18 as a negative regulator of the insulin secretory machinery via a mechanism that does not involve syntaxin-associated Ca(2+) channels.

Animals↗
PubMed2000

Clinical activity of cisplatin and prolonged oral administration of etoposide in previously treated, anthracycline-resistant, metastatic breast cancer patients: a phase II study.

BACKGROUND: This phase II study evaluates the antitumor activity and tolerance of cisplatin and prolonged oral administration of etoposide in metastatic breast cancer previously exposed to anthracyclines. PROCEDURE: Twenty-seven patients with metastatic breast cancer who developed tumor progression following anthracyclines wer e entered in the study. The patients were treated with combination chemotherapy of cisplatin 50 mg/m(2) IV day 1 and oral etoposide 50 mg/m(2) days 1-17. Cycles were repeated every 29 days. RESULTS: Twenty-six patients were evaluated for toxicity and response. Complete remission was observed in 1 of 26 (4%) patients and partial remission in 12 of 26 (46%). Median duration of response was seven months. Pain relief was noted in 9 of 15 (60%) of the symptomatic patients. Myelosuppression was the major toxicity encountered and four (15%) patients required hospitalization for granulocytopenic fever. Nonhematologic toxicity was mild. CONCLUSIONS: The combination of cisplatin with prolonged oral etoposide is active and tolerable in the management of patients with relapsed metastatic breast cancer previously treated with an anthracycline-based regimen.

Administration, Oral↗
PubMed2000

Significantly lower rates of BRCA1/BRCA2 founder mutations in Ashkenazi women with sporadic compared with familial early onset breast cancer.

To delineate the clinical, genetic and family history attributes in Jewish Ashkenazi women with early onset (< 42 years) breast cancer we genotyped such women for the three predominant Jewish Ashkenazi mutations in BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT). The study cohort was composed of 172 women diagnosed with breast cancer at or before the age of 42 years, obtained from the oncology department registry. Mutations were identified in 54 women (31%). Of 79 women with a positive family history for breast and/or ovarian cancer, and 93 with no such family history, 45 (57%) and 9 (10%), respectively, were mutation carriers (chi2 = 46; P < 0.001). Contralateral breast cancer occurred in 15 of 54 mutation carriers (28%) compared with 8 of 118 (7%) non-carriers (chi2= 14; P < 0.001). Early onset breast cancer per se is a weak predictor of finding germ line mutation(s) in BRCA1 and BRCA2, unless associated with a positive family history and/or bilaterality.

Adult↗
PubMed2000

Decreased expression of thioredoxin and glutaredoxin in placentae from pregnancies with pre-eclampsia and intrauterine growth restriction.

Pre-eclampsia is one of the major contributors to perinatal morbidity. This study was performed to test a hypothesis which suggests that pre-eclampsia is associated with inadequate control by the thioredoxin system and other related reducing systems. Placental tissue from normal pregnancies (NC), severe pre-eclampsia with fetuses small for gestational age (SPE), mild pre-eclampsia with fetuses small for gestational age (MPE) and pregnancies with small fetuses for gestational age without any sign of pre-eclampsia (IUGR) was collected immediately after delivery. The mRNA levels for thioredoxin and glutaredoxin were determined using a solution hybridization method and the distribution of the proteins in a normal placenta was analysed by immunohistochemistry. Results showed that the thioredoxin mRNA level in the SPE group was decreased to one third of the level in the NC group. Also the IUGR group showed a significant decrease. The glutaredoxin mRNA level in the SPE group was one half of that seen in the NC group. There was significant correlation between the mRNA levels for thioredoxin and glutaredoxin, both in the normal and growth restricted pregnancies. We conclude that the thioredoxin and glutaredoxin reducing systems are affected in placenta from pregnancies with pre-eclampsia and/or growth restriction of fetuses, and that the decrease correlates to the severity of the condition.

Cell Nucleus↗
PubMed2000

Differential sorting of SNAP-25a and SNAP-25b proteins in neuroblastoma cells.

Exocytosis is mediated by high-affinity interactions between different SNARE proteins. The existence of several variants of each SNARE protein suggests that the specificity of fusion may be directed by unique combination of SNARE family members. We examined if two alternatively spliced variants of synaptosomal-associated protein of 25 kD, SNAP-25a and SNAP-25b, possessed distinct cellular distribution if coexpressed within the same neuroblastoma cell. Double-labelling immunofluorescence histochemistry in combination with confocal laser microscopy of individual cell clones revealed a different subcellular localisation pattern for the two SNAP-25 variants. Sucrose density gradient centrifugation of cell homogenates followed by Western blotting showed that the SNAP-25 protein variants associated with intracellular organelles of different density. Taken together, this study shows that two alternatively spliced variants of SNAP-25, differing in only nine amino acids, possess distinct properties at the level of intracellular trafficking, suggesting that the cellular localisation of SNAP-25 protein is regulated at the level of mRNA splicing.

Animals↗
PubMed2000

Recombinant follicle stimulating hormone in in-vitro fertilization treatment-clinical experience with follitropin alpha and follitropin beta.

The objective of this prospective study was to compare the outcome of ovarian hyperstimulation for in-vitro fertilization (IVF) using two different preparations of recombinant follicle stimulating hormone (FSH). The study was based on 296 consecutive IVF cycles in 1997, 199 performed using follitropin alpha (Gonal-F) and 97 performed using follitropin beta (Puregon). Outcome was compared regarding pregnancy rate, oestradiol and progesterone response, endometrial thickness, follicle number, number of retrieved oocytes, fertilized oocytes, sperm count and sperm motility. There was no significant difference in outcome of stimulation. Clinical pregnancy rate was similar, 29.1% for Gonal-F and 28.1% for Puregon. There was no difference in endometrial response, oestradiol response, number of smaller (12-15 mm) or larger (>15 mm) follicles, number of oocytes retrieved, fertilized, divided and replaced, in sperm counts or in sperm progressive motility. There was a lower follicle number in the Puregon group, but not statistically significant. The serum progesterone concentrations on the day of oocyte retrieval, however, were significantly lower in the Puregon group. In conclusion, it was not possible to find significant differences in the IVF programme with regard to stimulation outcome between Gonal-F and Puregon. The results of this study indicate that Gonal-F and Puregon may be equally suitable for use in ovarian stimulation for IVF.

Adult↗
PubMed2000

TGFbeta receptor types I and II and the substrate proteins Smad 2 and 3 are present in human oocytes.

We have recently found that values of the transforming growth factor (TGF)beta1 in human ovarian follicular fluid obtained during ovarian stimulation for IVF were higher in women who subsequently became pregnant following embryo transfer. We therefore postulated that TGFbeta1 may have a beneficial effect on the preimplantation embryo and improve the chances of a successful implantation. We have used reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry to investigate the presence in human oocytes and preimplantation embryos of the essential components of the TGFbeta signalling pathway, TGFbeta receptors type I and II and the substrate proteins Smad 2 and 3. We found that both receptors, as well as Smad 2 and 3, were present in the unfertilized oocyte, whereas only the type I receptor and Smad 2 and 3 were present at the blastocyst stage. At the 4-cell and 8-cell stages neither of the receptors was present, but Smad 2 and 3 were present at both stages. These findings support our hypothesis that the TGFbeta1 in follicular fluid may interact with the oocyte and preimplantation embryo via TGFbeta receptors, and that TGFbeta signalling may be important for the development of the oocyte and the preimplantation embryo.

Activin Receptors, Type I↗
PubMed2000

Synaptotagmin III isoform is compartmentalized in pancreatic beta-cells and has a functional role in exocytosis.

Synaptotagmin is involved in Ca2+-regulated secretion and has been suggested to serve as a general Ca2+ sensor on the membrane of secretory vesicles in neuronal cells. Insulin exocytosis from the pancreatic beta-cell is an example of a Ca2+-dependent secretory process. Previous studies of pancreatic beta-cells were unable to show presence of synaptotagmin I. We now present biochemical and immunohistochemical data showing that synaptotagmin III is present in pancreatic beta-cells as well as in the insulin-secreting cell line HIT-T15 and in rat insulinoma. By subcellular fractionation, we found synaptotagmin III in high-density fractions together with insulin and secretogranin I, indicating colocalization of synaptotagmin III and insulin in secretory granules. We could also show that blockade of synaptotagmin III by a specific antibody inhibited Ca2+-induced changes in beta-cell membrane capacitance, suggesting that synaptotagmin III is part of the functional protein complex regulating beta-cell exocytosis. The synaptotagmin III antibody did not affect the activity of the voltage-gated L-type Ca2+-channel. These findings are compatible with the view that synaptotagmin III, because of its distinct localization in the pancreatic beta-cell, functionally modulates insulin exocytosis. This indicates that synaptotagmin may have a general role in the regulation of exocytosis not only in neuronal cells but also in endocrine cells.

Animals↗
PubMed2000

Fetal erythropoietin and endothelin-1: relation to hypoxia and intrauterine growth retardation.

BACKGROUND: We have examined whether endothelin-1 (ET-1) and erythropoietin (EPO) in amniotic fluid, and EPO in fetal serum obtained by cordocentesis from fetuses with signs of intrauterine growth retardation (IUGR), were correlated to fetal growth and/or chronic fetal hypoxia. METHODS: Amniotic fluid and fetal serum were obtained by cordocentesis from 28 fetuses suspected to have IUGR and subsequently analyzed for EPO and ET-1 by ELISA. These data were correlated to blood gas results and fetal/maternal parameters at delivery. RESULTS: A novel finding was that ET-1 correlated to PO2 in amniotic fluid. The average level of ET-1 in amniotic fluid was 48.3+/-4.7 pmol/L. The results also showed a correlation between EPO levels in amniotic fluid and EPO in fetal serum. Furthermore, EPO correlated weakly to birth weight at delivery. Children with the lowest birth weights had the highest EPO levels. High EPO values, similarly to ET-1, correlated to low pO2 values. The level of EPO in amniotic fluid was 8.0+/-1.6 mIU/ml and in cord blood 29.5+/-9.6 mIU/ml. CONCLUSIONS: The results indicate that ET-1 levels may be a marker for short-term hypoxia, but not for fetal growth, since ET-1 in amniotic fluid was correlated to PO2 at the time of cordocentesis, but not to birth weight. The results also indicate that EPO levels in amniotic fluid and in fetal cord serum are highly correlated, and thus both can be used as markers for fetal growth and chronic hypoxia before the onset of labor.

Adult↗
PubMed1999

[Breast conservation: safe for early breast cancer].

Between 1981-1993 581 women with primary breast cancer were treated by breast conservation. Their mean age was 56 +/- 12 years and 63% were postmenopausal and 37% pre- or perimenopausal. The median follow-up time was 56 months. 45% had pathological Stage I disease, 49% Stage II, 2.5% Stage III and 3.5% clinical Stage I-II disease. 54% of lesions were excised with good margins, 10% with close margins (< 0.5 cm), 9% with microscopic residual, 3% with macroscopic residual, and in 24% margins were not reported. Adjuvant therapy, consisting of combination chemotherapy and/or hormones, was given to 69%. Radiotherapy, usually 50 Gy tangential photon irradiation to the whole breast, was given to 564 (97%); an electron or photon "boost" to the tumor with a median dose of 17.5 Gy was given to 378 (65%). Most of those with positive nodes received 50 Gy to the lymphatic drainage system. 1 year after radiotherapy cosmetic results were rated as "good" or "excellent" in 80%, "moderate" in 17% and "poor" in 3%. The 5-year actuarial survival was 97% in Stage I and 88% in Stage II. 37 patients (6.5%) developed breast recurrence; 11 of these (2%) had simultaneous distant metastases. 5 (< 1%) developed axillary or supraclavicular lymph node metastases, and 81 (14%) developed distant metastases. Most local recurrences were in those younger than 40, and in those with primary tumors > 1.75 cm. The satisfactory level of local control achieved is attributed to the high doses of radiation (up to 75 Gy) administered to those with high risk lesions.

Breast Neoplasms↗
PubMed1998

Effects of acute stress on the contents of catecholamines and neuropeptides in chromaffin tissues of the newborn rabbit.

The neuropeptides enkephalin (ENK), galanin (GAL) and neuropeptide Y (NPY) are abundantly expressed in the paraaortic body (PAB) and adrenal glands of the newborn rabbit. To examine whether these neuropeptides are affected by acute stress, we exposed neonatal rabbits to asphyxia, insulin-induced hypoglycemia, and reserpine. Asphyxia, caused by rebreathing for 60 min in an airtight box, reduced the content of catecholamines (CAs) in the adrenal glands and increased ENK-like immunoreactivity (-LI) in the PAB. Insulin-induced hypoglycemia reduced the content of CAs as well as ENK-LI in the adrenal glands. Reserpine caused a marked depletion of the CAs both in the PAB and in the adrenal glands. In contrast, reserpine did not cause any change in the contents of the neuropeptides in either organ. These data indicate that tissue levels of the neuropeptides GAL-LI and NPY-LI, coexisting with CA in the PAB and the adrenal glands, are not biochemically affected by asphyxia, hypoglycemia or reserpine, whereas tissue levels of ENK-LI are reduced by hypoglycemia and, to some extent, are increased by asphyxia. Furthermore, even the CAs in the PAB were unaffected by asphyxia and hypoglycemia. Also, while reserpine reduces CA content, peptide levels are unaffected.

Adrenal Glands↗