Biomedical subjects

G Fried

Publications and source records attributed to G Fried.

At least 55 records · Page 3Linked to original sources

PubMed1996

Controlled ovarian stimulation using highly purified FSH results in a lower serum oestradiol profile in the follicular phase as compared with HMG.

We have examined the efficacy of highly purified follicle stimulating hormone (FSH-HP) for controlled ovarian stimulation in our in-vitro fertilization (IVF) programme, and compared the results obtained with this preparation with those using human menopausal gonadotrophin (HMG) in 15 patients who had received treatment with both FSH-HP and HMG in consecutive cycles (n = 39). No differences were found in the duration of stimulation, which was 13.9 days (HMG) as compared with 14.3 days (FSH-HP). However, in the FSH-HP-treated cycles we found a striking difference in the rise of serum oestradiol, which was significantly lower than in HMG-treated cycles (2953 +/- 938 pmol/l as compared with 6349 +/- 3683 pmol/l on the day before ovum retrieval). Number and size of follicles were similar in the two groups, as were oocyte characteristics. Increase in endometrial thickness at two days prior to ovum retrieval was slightly higher after HMG. The results indicate that in combination with a long gonadotrophin-releasing hormone agonist (GnRHa) protocol, pure FSH is sufficient for adequate follicle recruitment and growth. However, since FSH-HP resulted in markedly reduced concentrations of serum oestradiol as compared to HMG cycles, IVF programmes using repeated oestradiol measurements to decide the day of ovum retrieval must take this into consideration in order not to prolong the stimulation unnecessarily.

Adult↗

PubMed1996

High tubal damage grade is associated with low pregnancy rate in women undergoing in-vitro fertilization treatment.

In order to analyse the relationship between grade of tubal damage and pregnancy rate following in-vitro fertilization (IVF) treatment, 50 consecutive couples with isolated tubal infertility who underwent IVF without previous reconstructive surgery were studied. The couples had tried to conceive for 2.5-5.6 years (mean 3.9 years) and had gone through a complete investigation for infertility. All women fulfilled the standard criteria for normal ovulatory cycles. All males had normal spermiograms. Tubal function was in each case evaluated by hysterosalpingography and laparoscopy. Grade of tubal damage was classified on a scale of I-IV. Patients with milder tubal damage (groups I-II) showed considerably higher take-home baby rate per started cycle (48%) than patients with severe tubal damage (group IV; 6%) (P < 0.001) even though patients in group IV underwent more treatment cycles than patients in groups I-II (2.7 versus 1.8; P < 0.01). In the first treatment cycle nine out of 12 patients in groups I-II became pregnant as compared with only one out of 16 in group IV (P < 0.01). As indicators of lower ovarian response, the women in group IV needed a higher number of gonadotrophin ampoules per cycle (P < 0.001) and exhibited lower pre-ovum retrieval oestradiol concentrations (P < 0.001). Oocyte retrievals per started cycle (I-II: 100%; III: 98%; IV: 84%) did not differ significantly between the groups, neither did pre-embryo replacements (I-II: 95%; III: 80%; IV: 73%) nor pre-embryos per replacement (I-II: 3.0; III: 2.9; IV: 2.8). The present results concerning the role of tubal damage grade for the outcome of IVF treatment should be considered in patient counselling. Further studies are needed to elucidate the mechanisms by which the extent of tubal damage may impair ovarian function and reduce IVF outcome.

Adult↗

PubMed1996

Carrier-mediated gamma-aminobutyric acid uptake in human spermatozoa indicating the presence of a high-affinity gamma-aminobutyric acid transport protein.

Human spermatozoa are capable of a carrier-mediated gamma-aminobutyric acid (GABA) uptake. The uptake is dependent on the concentration of Cl- and Na+ in the external medium, and the kinetics of the carrier resembles high-affinity GABA transport proteins. The time-dependent uptake of GABA displays large interindividual differences and is not correlated to motility parameters or morphology in the individual sample. Incubation of human spermatozoa with radiolabeled GABA was performed. Swim-up preparations of human spermatozoa were incubated with [3H]GABA, and subsequent GABA uptake was measured at various times by scintillation counting. GABA was accumulated intracellularly, and the uptake could be inhibited by preincubation of the samples in 200 microM nipecotic acid. Addition of aminooxyacetic acid in the medium did not alter the results, indicating that the internalized GABA remained unmetabolized intracellularly throughout the observation period. Kinetic analysis of GABA uptake was performed, and the Km for GABA transport was 14 microM. GABA uptake was reduced by equimolar substitution of NaCl in the capacitating medium by KCl, choline chloride, LiCl, N-methyl-D-glucamine (HCl) or D-glucuronic acid (sodium salt). Maximal reduction of [3H]GABA uptake was observed when the Na+ fraction of the medium was replaced with KCl. The results indicate the presence of a high-affinity GABA transport protein in the plasma membrane of human spermatozoa. GABA uptake was subsequently measured in 30 individual semen samples from men of barren couples. Large interindividual differences in GABA uptake was observed, but GABA uptake was not correlated to motility parameters or to morphology in the individual samples analyzed.

Carrier Proteins↗

PubMed1996

Cerebrospinal fluid of newborn infants contains a deglycosylated form of the intermediate filament nestin.

Nestin is an intermediate filament protein found in CNS progenitor cells. Nestin reappears in CNS tumor cells and reactive astrocytes after CNS injury. In this study we investigated whether nestin could be detected in the cerebrospinal fluid (CSF) of newborn infants and whether expression levels change with gestational age (GA) and/or brain injury. Using Western blot analysis, we examined the expression of nestin in the CSF of newborn infants (GA 25-42 wk) with asphyxia (n = 14), periventricular leukomalacia and peri(intra)ventricular hemorrhage (n = 7), and in a control group (n = 11). Protein extract from the periventricular brain tissue of a 1-wk-old infant was also analyzed. Nestin was detected in all the CSF samples and in the protein extract from the periventricular brain tissue. Although the CSF levels of nestin expression did not change with increasing GA, the asphyxia group had significantly lower levels of nestin in the CSF. An unexpected finding was that brain-derived nestin had an apparent molecular mass of approximately 240 kD, whereas all analyzed CSF samples contained two nestin-immunoreactive proteins at 200 and 220 kD. Experimental deglycosylation of the 240-kD form reduced the molecular mass to 220 kD, indicating that nestin undergoes a specific deglycosylation upon release into the CSF.

Apgar Score↗

PubMed1995

Primary Hodgkin's disease of the bone.

A primary extranodal presentation occurs in less than 0.25% of patients with Hodgkin's disease (HD) and we describe the primary clinicopathologic findings in a rare case of a 21-year-old female with primary bony involvement of Hodgkin's disease. The patient presented with microcytic, hypochromic anemia and shoulder pain. The diagnosis of HD (lymphocyte depleted type) was made by biopsy taken from a lytic lesion in the lateral third of the clavicle. Staging work-up revealed an additional lesion in the ilium, but there was no evidence of lymph node involvement. MOPP/ABV (nitrogen mustard, Oncovin, procarbazine, prednisone/adriamycin, bleomycin, and vinblastine) chemotherapy resulted in complete response lasting, to date, 36 months. To the best of our knowledge, this is only the second reported case of disseminated primary Hodgkin's disease of the bone and all have had a favourable response to combination chemotherapy. A review of the literature is also presented.

Adult↗

PubMed1995

Increase in synaptic vesicle proteins in synapsin-transfected NG108-15 cells: a subcellular fractionation study.

We have examined the subcellular distribution of synapsins and synaptophysin in density gradients from synapsin- and vector-transfected NG108-15 cells, since we recently found that transfection of synapsin IIb cDNA into neuroblastoma x glioma hybrid cells (NG108-15) resulted in cell lines that had a more neuronal phenotype than controls. The increase in synapsins and synaptophysin in the transfected cells was maximal in the region of the gradient containing small synaptic vesicles. The transferrin receptor, a marker for early endosomes, did not increase in the synapsin-containing fractions in the transfected cells. Secretogranin I, a soluble protein stored in and secreted from large dense cored vesicles, showed a very pronounced increase in the dense regions of gradients from transfected cells. These subcellular fractionation data suggest a possible role for the synapsins in the regulation of synaptic vesicle function.

Animals↗

PubMed1995

5-Fluorouracil and low-dose leucovorin in metastatic colorectal cancer: a pilot study.

A total of 56 consecutive patients with metastatic colorectal cancer received treatment with 5-fluorouracil (5-FU) given at 425 mg/m2 by rapid intravenous infusion, immediately preceded by leucovorin (LV) given at 20 mg/m2, with cycles being repeated every 4 weeks. Of 48 evaluable patients undergoing this treatment, a tumor response was observed in 16 (33%); a complete response, in 2 (4%); and a partial response, in 14 (29%). The median survival was 8.5 months for all patients and 16.5 months for responders. An improvement in symptoms was seen in 9 (26%) of 34 symptomatic patients. In all 15 (27%) of 44 evaluable patients showed an improvement in performance status. The most significant toxicity attributable to the treatment was mucositis of grade 3 or 4, seen in 27% of the patients. Altogether, 2 patients (3.5%) were hospitalized for treatment-related toxicity. We conclude that the combination of 5-FU and low-dose LV is active in advanced colorectal cancer and is associated with acceptable toxicity.

Adenocarcinoma↗

PubMed1995

Laminin and neuropeptide Y are increased by synapsin transfection in cultured NG108-15 neuroblastoma/glioma hybrid cells.

We have investigated the presence and expression of laminin and neuropeptide Y (NPY) in several NG108-15 cell lines transfected with synapsin Ib, IIa, or IIb. The content of laminin, a basal membrane glycoprotein that promotes adhesion and induces neurite out-growth and neuronal differentiation, was increased in all transfected cell lines examined. In cells that were chemically differentiated with prostaglandin E1 plus 3-isobutyl-1-methylxanthine, laminin levels were increased even further. The content of NPY, suggested to be a neurotransmitter/neuromodulator in peripheral sympathetic neurons as well as in central neurons, was also increased in all transfected cell lines examined. Immunohistochemical analysis combined with confocal laser microscopy showed that NPY staining was granular and very often enriched in neuritic varicosities. The distribution and the staining pattern of NPY were consistent with storage of NPY in large dense-cored vesicles. The results indicate that, in differentiated neurons, the synapsins increase the levels of a neuropeptide transmitter stored in large dense-cored vesicles and of an extracellular matrix protein associated with neuronal maturation.

Glioma↗

PubMed1995

Evidence for gamma-aminobutyric acid specific binding sites on human spermatozoa.

The possible presence of gamma-aminobutyric acid (GABA) specific binding sites on human spermatozoa was investigated. Swim-up preparations of human spermatozoa were incubated with radiolabelled GABA in the presence of unlabelled GABA, alternatively displacers of GABAA/B receptors and GABA transport proteins. The results indicate that GABA specific binding sites are present on the surface of human spermatozoa, and that these binding sites possibly indicate the presence of GABA transport proteins. Furthermore, GABA at different concentrations was added to swim-up preparations of human spermatozoa. Possible effects of GABA on sperm motility, hyperactivation and acrosome reaction were explored. No significant differences were observed between treated groups and controls concerning motility parameters and hyperactivation. Incubation with GABA did not cause any increase in spontaneous acrosome reaction. However, spermatozoa treated with the calcium ionophore A-23187 showed a small but significantly increased ability to undergo the acrosome reaction following preincubation in 10(-4) M GABA (P < 0.05).

Acrosome↗

PubMed1995

Synaptic vesicles and release of transmitters: new insights at the molecular level.

Neurotransmitter release from transmitter storage vesicles is a regulated signalling event that has properties in common with other secretory systems. Biochemical characterization of mammalian synaptic vesicle proteins has recently converged with studies of protein traffic in non-neuronal cells and the genetic dissection of the yeast secretory pathway to give us a considerable amount of new data. Many new synaptic vesicle proteins have been characterized together with plasma membrane proteins with which they interact, and it appears that many of the participating components may be part of a general machinery for secretion. The new results significantly improve our understanding of the molecular mechanisms governing transmitter release. This review discusses the recent progress in terms of synaptic vesicle components and the proposed mechanisms for exocytosis.

Animals↗

PubMed1995

Endothelin-induced contractions in human placental blood vessels are enhanced in intrauterine growth retardation, and modulated by agents that regulate levels of intracellular calcium.

Endothelin-1 (ET-1) is a strongly vasoactive polypeptide that may be involved in the regulation of the uteroplacental blood flow. In the present study we have examined the contractile response to ET-1 in human placental arteries in the presence of several agents that interfere with storage of intracellular calcium, e.g. caffeine, ryanodine and thapsigargin. We have also compared the contractile response to ET-1 in normal pregnancies with that of patients with foetal intrauterine growth retardation (IUGR), a condition with reduced uteroplacental blood flow. We found that the response to ET-1 in the placental arteries from women with normal pregnancies was reduced by 20% in the absence of extracellular calcium. Caffeine relaxed the basal tone of the vessels and reduced the contractile response to ET-1 by 51%. Nifedipine in addition to caffeine resulted in a reduction of 70%. Ryanodine also reduced the tone. Thapsigargin had no effect on the placental arteries at lower concentrations, but gave a progressive and slow contraction at 10(-6) M. The ET-1 induced contraction in placental arteries from IUGR patients was 67% more potent than in placental arteries from women with normal pregnancies, 129% as compared with 77% of the maximal K(+)-induced contraction. We conclude that the ET-1-induced contractile response in the human placental artery is dependent on influx of extracellular calcium as well as mobilization of calcium from intracellular stores. An increased sensitivity to ET-1 in placental arteries may contribute to the reduced uteroplacental blood flow in intrauterine growth retardation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1994

Multiple neuropeptide immunoreactivities in a renin-producing human paraganglioma.

BACKGROUND: A case of a renin-producing paraganglioma of adrenal origin with metastases to the retroperitoneal area, paravaginal area, and the ovary is reported with immunohistochemical findings indicating expression of multiple neuropeptide immunoreactivities. The patient was 23 years old at the time of diagnosis, and died from metastatic spread of the tumor 7 years later. METHODS: Tumor tissue was examined by light microscopy, indirect immunohistochemistry, and electron microscopy. RESULTS: The tumor tissue investigated contained several cells exhibiting opioid peptide-like immunoreactivities (i.e., enkephalin and dynorphin-like immunoreactivity [LI]). A lower number of cells displayed neuropeptide Y-, galanin-, somatostatin-, neurotensin-, substance P-, peptide histidine-isoleucine-, cholecystokinin-, renin-, and calbindin-LI. CONCLUSION: To the authors' knowledge, galanin, dynorphin, peptide histidine-isoleucine, cholecystokinin, and calbindin have not been reported previously to occur in paraganglioma, and renin has been reported to occur very rarely. A review of recent literature suggest that enkephalin-, neuropeptide Y-, and somatostatin-like immunoreactivities may be useful as diagnostic markers for paragangliomas.

Adrenal Gland Neoplasms↗

PubMed1994

Effects of endothelin, calcium channel blockade and EDRF inhibition on the contractility of human uteroplacental arteries.

In order to examine the possibility that endothelin might be important in the regulation of placental blood flow, human uteroplacental vessels were superfused in vitro to study the contractile effect of endothelin as compared with a known strong contractor of placental blood vessels, serotonin (5-HT). The contractile responses were compared in the presence and absence of calcium channel blocking agents, as well as in the presence of L-NMA, an inhibitor of EDRF/nitric oxide. Endothelin (ET, 10(-10)-10(-6) M) and 5-HT (10(-8)-10(-4) M) induced contractions in the vessels. Maximal contractions in the presence of endothelin were elicited at 10(-7) M, whereas 5-HT elicited maximal contractions at 10(-5) M. At 10(-7) M, ET was more potent than 5-HT. The calcium-channel blocking agents nifedipine, diltiazem and NiCl2 relaxed the vessels by 5-15% from baseline. The contractile response to ET in the presence of nifedipine or diltiazem was reduced by 55 and 67%, respectively. The response of 5-HT in the presence of nifedipine was reduced by 58%. The contractile response to 5-HT as well as ET in the presence of both nifedipine and NiCl2 was not significantly lower than in the presence of nifedipine only. The EDRF-inhibiting agent L-NMA caused a small contractile response at concentrations of 10(-6)-10(-5) M. ET as well as 5-HT added after pretreatment with L-NMA produced a larger contractile response than ET or 5-HT alone. The results show that ET has a strong contractile effect on placental blood vessels at concentrations likely to occur during labor and delivery. The mechanism whereby ET as well as 5-HT contracts placental vessel smooth muscle appears to partly involve nifedipine- and diltiazem-sensitive calcium channels, but almost half of the response depends on mobilization of calcium through other means.

Adult↗

PubMed1993

Perinatal development of galanin-like immunoreactivity in chromaffin tissues of the rabbit.

We have analyzed the perinatal development of galanin-like immunoreactivity (GAL-LI) and catecholamines (CA) in the paraaortal paraganglia (PGGL) and adrenal glands. In the PGGL, the tissue content of GAL-LI was highest on the day of birth and decreased postnatally. The fetal levels were lower than at birth. In contrast, the content of CA in the PGGL increased with age. In the adrenal glands, the contents of both GAL-LI and CA also increased with age. During the first postnatal week the contents of both GAL-LI and CA in the PGGL were markedly higher than in the adrenal glands. Chromatographic analysis of GAL-LI in extracts of fetal and postnatal rabbit PGGL, respectively, indicated that most of the GAL-LI from both age groups co-eluted with synthetic porcine GAL. An additional, apparently more polar, component was also detected at both ages, which may represent a differently processed form of the peptide. The high content of GAL-LI in the PGGL at birth may reflect an enhanced synthesis associated with birth.

Adrenal Glands↗

PubMed1993

Classical disseminated Kaposi's sarcoma in HIV-negative patients; an unusually indolent subtype.

Kaposi's sarcoma is a rare neoplasm of characteristic chronicity. The classical form which occurs most often in elderly men of Eastern European origin, comprises both an indolent, cutaneous type marked by spontaneous regression with prolonged survival, and a rarer, disseminated variant is more fulminant. Seven elderly Jewish patients with classical, disseminated, visceral Kaposi's sarcoma were studied; they were neither homosexual nor drug-abusers. All immunologic parameters were normal and serum tests for HIV antibodies, CMV, and EBV were negative. Five of these patients were treated and four responded well, including two complete remissions. The prolonged survival of these patients (82% at 5 years) suggests the existence of an indolent subtype or forme fruste of the usually aggressive form of classical Kaposi's sarcoma.

Adult↗

PubMed1993

Differential release of endogenous 5-hydroxytryptamine, substance P, and neurokinin A from rat ventral spinal cord in response to electrical stimulation.

The release of endogenous 5-hydroxytryptamine (5-HT), substance P (SP), and neurokinin A (NKA) from superfused tissue slices of rat ventral lumbar spinal cord, where SP and NKA coexist with 5-HT in terminals of descending bulbospinal neurons, was investigated. Electrical field stimulation was performed using square-wave pulses of 2-ms duration and 30 mA stimulus intensity. The following four different patterns of stimulation were used: 2 Hz continuous, 20 Hz continuous, 20 Hz intermittent, and 50 Hz intermittent. 5-HT was measured in the slice superfusates by HPLC with electrochemical detection. SP and NKA were measured by radioimmunoassay. The release of 5-HT was significantly enhanced using all stimulation paradigms and the evoked release of 5-HT per pulse was independent of the stimulation frequency. The release was found to be calcium dependent and there was no increase in the efflux of 5-hydroxyindoleacetic acid in response to stimulation. At 2 Hz (continuous), no significant increase in the release of SP was observed. Stimulation at higher frequencies yielded a significant increase in the release of SP per pulse. At 20 Hz, the release was increased by 73% (continuous) and 74% (intermittent), and at 50 Hz (intermittent) by 175% of basal efflux. The evoked release of NKA was also frequency dependent. At 2 Hz (continuous), no significant increase in the release of NKA was observed. At 20 Hz (intermittent), the evoked release per pulse was increased by 33% and at 50 Hz (intermittent) by 53% compared with the basal efflux of NKA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Endothelin contracts human uterine myometrium by a partly dihydropyridine-sensitive mechanism.

The effect of endothelin (ET), a recently discovered 21-amino-acid polypeptide with powerful vasoconstrictor properties, was examined on human uterine myometrial strips in vitro. ET dose-dependently (10(-11)-10(-7) M) increased the contractile force (monitored as contraction amplitude) of the myometrium with significant effects at 10(-8) and 10(-7) M. ET (10(-8) M and up) also increased the basal tone of the myometrium. The calcium channel blocking agents nifedipine (10(-7) M) and diltiazem (10(-6) M) both inhibited the spontaneous tonic contractions of the myometrium. When ET was given in the presence of nifedipine, the tonic contractions were further inhibited, whereas the ET-induced increase in basal tone remained. The same result was obtained with diltiazem (10(-6) M). The results indicate that the contractility of human myometrium may be modulated by ET, and that the effects of ET on the human myometrium are only partly mediated by dihydropyridine-sensitive calcium channels.

Dihydropyridines↗

PubMed1992

Randomised controlled trial of laparoscopic versus mini cholecystectomy. The McGill Gallstone Treatment Group.

Laparoscopic cholecystectomy (LC) has gained wide acceptance for treatment of cholelithiasis in preference to open cholecystectomy, though it has not been formally compared with mini cholecystectomy (MC). We have compared these two techniques in a randomised trial. 70 patients with ultrasound-proven cholelithiasis were randomly allocated LC (38) or MC (32); 37 and 25, respectively, underwent the assigned procedure. The mean hospital stay (including 1 preoperative day) was significantly shorter in the LC than the MC group (median 3 [interquartile range 2-3] vs 4 [3-5], p = 0.001) as was duration of convalescence (mean 11.9 [SD 9.1] vs 20.2 [16.5] days, p = 0.04). The rate of return to normal activities was 1.77 times greater in the LC group than in the MC group (95% confidence interval 1.01-3.11, p = 0.03). In regression analysis, the type of cholecystectomy done was the only variable significantly associated with the duration of convalescence. Although there was significant postoperative improvement in all of three quality of life scores in both groups, LC patients improved more quickly than did MC patients. This randomised trial shows the superior effectiveness of LC over MC in treating cholelithiasis.

Adolescent↗