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Biomedical subjects

G Fried

Publications and source records attributed to G Fried.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1998

Cysteine string protein (CSP) is an insulin secretory granule-associated protein regulating beta-cell exocytosis.

Cysteine string proteins (CSPs) are novel synaptic vesicle-associated protein components characterized by an N-terminal J-domain and a central palmitoylated string of cysteine residues. The cellular localization and functional role of CSP was studied in pancreatic endocrine cells. In situ hybridization and RT-PCR analysis demonstrated CSP mRNA expression in insulin-producing cells. CSP1 mRNA was present in pancreatic islets; both CSP1 and CSP2 mRNAs were seen in insulin-secreting cell lines. Punctate CSP-like immunoreactivity (CSP-LI) was demonstrated in most islets of Langerhans cells, acinar cells and nerve fibers of the rat pancreas. Ultrastructural analysis showed CSP-LI in close association with membranes of secretory granules of cells in the endo- and exocrine pancreas. Subcellular fractionation of insulinoma cells showed CSP1 (34/36 kDa) in granular fractions; the membrane and cytosol fractions contained predominantly CSP2 (27 kDa). The fractions also contained proteins of 72 and 70 kDa, presumably CSP dimers. CSP1 overexpression in INS-1 cells or intracellular administration of CSP antibodies into mouse ob/ob beta-cells did not affect voltage-dependent Ca2+-channel activity. Amperometric measurements showed a significant decrease in insulin exocytosis in individual INS-1 cells after CSP1 overexpression. We conclude that CSP is associated with insulin secretory granules and that CSP participates in the molecular regulation of insulin exocytosis by mechanisms not involving changes in the activity of voltage-gated Ca2+-channels.

Animals↗
PubMed1998

Transforming growth factor-beta1, insulin-like growth factors, and insulin-like growth factor binding proteins in ovarian follicular fluid are differentially regulated by the type of ovarian hyperstimulation used for in vitro fertilization.

OBJECTIVE: To determine the effects of hMG and highly purified FSH on follicular production of the ovarian growth factors transforming growth factor-beta1 (TGF-beta1), insulin-like growth factors I and II (IGF-I and IGF-II), and insulin-like growth factor binding proteins-1 and -3 (IGFBP-1 and IGFBP-3). DESIGN: Controlled clinical study. SETTING: University IVF program. PATIENT(S): One hundred twenty women who were <38 years old and had a >3-year duration of infertility in their present relationship participated in the study. INTERVENTION(S): Follicular fluid and matched serum were collected at oocyte pick-up and analyzed for growth factors and E2 with the use of ELISA and RIA. MAIN OUTCOME MEASURE(S): Levels of TGF-beta1, IGF-I. IGF-II, IGFBP-1 and IGFBP-3 in follicular fluid and levels of E2 in serum were measured. RESULT(S): Compared with highly purified FSH, ovarian hyperstimulation with hMG produced lower levels of TGF-beta1 and IGF-I and higher levels of IGFBP-1. Levels of IGF-II and IGFBP-3 were similar with the 2 treatments. CONCLUSION(S): In patients undergoing IVF, the follicular expression of TGF-beta1, IGF-I, and IGFBP-1 was regulated differently by highly purified FSH compared with a preparation containing FSH and LH in a 1:1 ratio (hMG). The results indicate that FSH and LH control ovarian production of these growth factors differentially.

Adult↗
PubMed1998

The NMDA receptor antagonist amantadine reduces surgical neuropathic pain in cancer patients: a double blind, randomized, placebo controlled trial.

Neuropathic pain is often severe, persistent, and responds poorly to analgesic medications. Recent evidence suggests that N-methyl-D-aspartate (NMDA) receptor antagonists may be effective in the treatment of neuropathic pain. The present trial was designed to test the efficacy of acute administration of the NMDA receptor antagonist amantadine in relieving surgical neuropathic pain in patients with cancer. The study sample consisted of 15 cancer patients with the diagnosis of surgical neuropathic pain. Two 500 ml infusions of either 200 mg amantadine or placebo were administered over a 3 h period, in a randomized order, 1 week apart from each other. Spontaneous and evoked pain were measured for 48 h before treatment, during treatment, and for 48 h following treatment. An average pain reduction of 85% was recorded at the end of amantadine infusion vs. 45% following placebo administration. The difference in pain relief between the two treatments was statistically significant (P = 0.009). Mean pain intensity remained significantly lower during the 48 h following amantadine treatment as compared with the 48 h prior to treatment (31% reduction; P = 0.006), whereas no such effect was found with the placebo (6% reduction; P = 0.40). Amantadine, but not the placebo, also reduced 'wind up' like pain (caused by repeated pinpricking) in four patients. We conclude that amantadine infusion is a safe and effective acute treatment for surgical neuropathic pain in cancer patients. Further trials with long-term oral or parenteral amantadine treatment should be conducted.

Adult↗
PubMed1998

Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides.

Alzheimer's disease (AD) is characterized by the accumulation of cerebral plaques composed of 40- and 42-amino acid beta-amyloid (Abeta) peptides, and autosomal dominant forms of AD appear to cause disease by promoting brain Abeta accumulation. Recent studies indicate that postmenopausal estrogen replacement therapy may prevent or delay the onset of AD. Here we present evidence that physiological levels of 17beta-estradiol reduce the generation of Abeta by neuroblastoma cells and by primary cultures of rat, mouse and human embryonic cerebrocortical neurons. These results suggest a mechanism by which estrogen replacement therapy can delay or prevent AD.

Alzheimer Disease↗
PubMed1998

Endothelin-induced contractions in placental arteries is mediated by both ETA- and ETB-receptors.

We have examined the contractile response to the vasoconstrictor endothelin-1 (ET-1) in uteroplacental arteries from normal pregnant women in the presence and absence of specific ET-receptor antagonists and agonists, and the vasodilator nitric oxide. Segments of placental arteries (n = 97) obtained from 37 placentas immediately after delivery were mounted in organ baths superfused with Krebs-Ringer solution at 37 degrees C. The tension was recorded isometrically and registered on a polygraph. We found that the placental artery segments responded to ET with a dose-dependent vasoconstriction. Half-maximal response was obtained at 2.6 x 10(-8) M. At 10(-7) M, the contractile response was 52% of the maximum KCl-response. The ET-1 induced contraction at 10(-7) M was inhibited by 74% after addition of the ETA-antagonist BQ-123 (10(-6) M), and by 58% by the ETB-antagonist BQ-788 (10(-6) M). Both BQ-123 and BQ-788 almost completely abolished the response to ET (10(-7) M). The selective ETB-agonist IRL-1620 also elicited vasoconstriction in the placental artery with a half maximal response at 8 x 10(-7) M. On a molar basis at 10(-7) M, the contraction by IRL-1620 as compared to ET was 30-fold lower. The contractile response of IRL-1620 (10(-6) M) was inhibited by 99% by BQ-788 (10(-6) M). After pre-contraction of the placental arteries with ET-1 (10(-7) M), the vessels relaxed in response to the nitric oxide donor, nitroglycerin (10(-6) M). The present results show that ET-1 contracts placental arteries through both ETA- and ETB-receptor activation. Nitric oxide (10(-6) M) was able to relax more than half of the initial ET-1 contraction, indicating that nitric oxide may be an important vasodilator in the placenta.

Adult↗
PubMed1998

Increase in transforming growth factor beta1 in ovarian follicular fluid following ovarian stimulation and in-vitro fertilization correlates to pregnancy.

We have analysed the content of the growth and differentiation regulating peptide, transforming growth factor beta1 (TGFbeta1), in follicular fluid from patients undergoing in-vitro fertilization (IVF), and correlated concentrations of TGFbeta1 with the outcome of the IVF treatment and the concentrations of 17beta oestradiol in serum at ovum retrieval. A total of 88 women with infertility of >3 years duration and age <38 years participated in the study. During IVF treatment, follicular fluid and matched serum samples were collected at ovum retrieval and analysed for TGFbeta1, oestradiol, progesterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) using radioimmunoassay and enzyme-linked immunosorbent assay. We found that the TGFbeta1 content in the follicular fluid at the time of oocyte retrieval correlated positively with subsequent pregnancy. In 29 women who became pregnant following IVF, follicular fluid TGFbeta1 values were significantly higher (P=0.005) than in 59 women where IVF was unsuccessful. In the pregnant group, TGFbeta1 values correlated positively with oestradiol at ovum retrieval. TGFbeta1 also correlated positively with the number of fertilized oocytes. TGFbeta1 may thus be important for successful human pre-embryo development, contribute to successful embryo implantation and development and may be necessary for the establishment of pregnancy.

Adult↗
PubMed1998

Phorbol esters and synthetic diacylglycerols inhibit gamma-aminobutyric acid uptake in human spermatozoa: an effect mediated by protein kinase C?

Protein kinase C (PKC) and protein kinase A (PKA) are present in human spermatozoa and probably involved in the cascade systems leading to acrosomal exocytosis. We have investigated the possibility that these two protein kinases are involved in the regulation of gamma-aminobutyric acid (GABA) uptake in human spermatozoa. Swim-up preparations of human spermatozoa were exposed to phorbol 12-myristate 13 acetate (PMA) and 1-oleoyl-2-acetyl-sn-glycerol (OAG), which are activators of PKC, and to dibutyryl cyclic AMP (dbcAMP), a PKA activator, and subsequently incubated with radiolabelled GABA. Accumulated intracellular GABA was measured in a scintillation counter. Both PMA and OAG caused inhibition of GABA uptake while dbcAMP was without effect. The inhibitory effect on GABA uptake observed following exposure to the PKC activators could, however, not be counteracted by preincubation of the sperm samples with the PKC inhibitors staurosporine or H-7. The inhibitory effect on GABA uptake following addition of PMA was enhanced by prolonged exposure to the reagent and by increased capacitation prior to addition of the reagent. A small numerical increase in the percentage of acrosome-reacted cells was observed following exposure of the sperm cells to the highest concentrations of PMA, OAG and dbcAMP. No sperm motility parameters were affected by the treatment protocols as measured using computer-assisted semen analysis (CASA).

Diglycerides↗
PubMed1998

Plasma leptin in infants: relations to birth weight and weight loss.

BACKGROUND: The hormone leptin, produced in the adipose tissue, is involved in the regulation of body weight. The release of the hormone is increased in obese adults and decreased after fasting in human adults. This study investigated whether the plasma leptin level was related to the infant's birth weight and whether the level was reduced in connection with the physiological weight loss during the neonatal period. METHODS: We measured the plasma leptin level in cord blood from infants who were large for gestational age (LGA) (n = 15), small for gestational age (SGA) (n = 16), and appropriate for gestational age (AGA) (n = 38). AGA infants (n = 120), who were exclusively breastfed, were also studied during their first 4 postnatal days in a cross-sectional method. One blood sample was collected before breastfeeding from each infant. Plasma leptin concentrations were determined by radioimmunoassay. RESULTS: The median (range) concentration of leptin from cord blood was increased in LGA infants and decreased in SGA infants compared with the level in AGA infants. There was a positive correlation between the log of the plasma leptin level in cord blood and both the infant's birth weight (r = 0.76; n = 69) and the body mass index (r = 0.63; n = 69). The normal 3% to 6% weight reduction that occurs during the first 4 postnatal days was associated with a 26% decrease in the plasma leptin level in healthy breastfed infants. CONCLUSIONS: The plasma leptin level is highly correlated to the size of adipose tissue mass and decreases in connection with the initial physiological weight loss in newborn infants. These data provide evidence that leptin is highly related to the nutritional status already during the fetal and neonatal periods.

Adipose Tissue↗
PubMed1997

Living with mastectomy and breast conservation treatment: who suffers more?

Sixty-five patients who underwent modified radical mastectomy were compared with 55 breast conservation patients, all of whom were in stage I, II or III of breast cancer and were under treatment at an oncology clinic in northern Israel. The main findings indicate no differences between the groups in physical, psychosocial, marital or medical interaction, according to the CARE scale. These findings reflect the results of similar comparative studies conducted during the 1980s and 1990s as documented in the literature. Sexual interaction showed statistical differences favoring the women who had undergone mastectomies.

Adult↗
PubMed1997

Insulin-like growth factor I in fetal serum obtained by cordocentesis is correlated with intrauterine growth retardation.

We examined whether insulin-like growth factor-I (IGF-I) and one of its binding proteins (IGFBP-1) in fetal serum obtained by cordocentesis is correlated with intrauterine growth retardation (IUGR) and weight estimation by ultrasound. Cordocentesis sera from 27 fetuses suspected of having IUGR were analysed for IGF-I and IGFBP-1 by radioimmunoassay. The results showed that IGF-I concentrations were correlated significantly with birth weight (P < 0.001) and placenta weight (P < 0.05). Mean fetal concentrations of IGF-I were 38 +/- 18 microg/l. In patients (n = 11) with a weight deviation at delivery <-33%, IGF-I concentrations were 24.1 +/- 13.2 microg/l. IGFBP-1 was inversely correlated with birth weight (P < 0.006) and concentrations of IGF-I. Mean plasma concentrations of IGFBP-1 were 234.2 +/- 161.4 microg/l. Furthermore, IGF-I concentrations were correlated with the weight deviation estimated by ultrasonography at the time of cordocentesis (P < 0.007), as well as with the weight deviation at delivery (P < 0.0001). The actual weight deviation at delivery was correlated more strongly with fetal IGF-I concentrations than with the estimated weight deviation at cordocentesis. The lowest concentrations of IGF-I were found in patients with a weight deviation <-33%. Very low concentrations of IGF-I are thus associated with IUGR, indicating that IGF-I measured in fetal serum may increase the predictive value of ultrasonographic weight estimation.

Cordocentesis↗
PubMed1997

Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern.

The estrogen receptor (ER) is a ligand-activated transcription factor that mediates the effects of the steroid hormone 17 beta-estradiol, in both males and females. Since the isolation and cloning of ER, the consensus has been that only one such receptor exists. The finding of a second subtype of ER (ER beta) has caused considerable excitement amongst endocrinologists. In this article, we present data regarding the genomic structure and chromosomal localization of the human ER beta gene, demonstrating that two independent ER genes do exist in the human. Furthermore, we present data regarding the tissue distribution of human ER beta, showing that this receptor is expressed in multiple tissues. For instance, ER beta is found in developing spermatids of the testis, a finding of potential relevance for the ongoing debate on the effects of environmental estrogens on sperm counts. In addition, we find ER beta in ovarian granulosa cells, indicating that estrogens also participate in the regulation of follicular growth in the human.

Amino Acid Sequence↗
PubMed1996

Progesterone stimulates GABA uptake in human spermatozoa.

Progesterone can initiate the mammalian sperm acrosome reaction in vitro, and studies on the effect of progesterone and several other steroids have demonstrated an increased calcium influx following binding to the sperm membrane. We have previously presented data indicating the presence of a GABA transport protein in human spermatozoa. In this study, we have examined the uptake of radiolabelled GABA into human spermatozoa in the presence of progesterone, other steroids known to elevate intracellular calcium, and steroids known to be ineffective as stimulators of calcium influx. The results demonstrate a twofold increase in GABA uptake following preincubation with progesterone or steroids known to stimulate calcium influx. Steroids with minor effects on calcium influx were less effective as stimulators of GABA uptake.

Biological Transport↗
PubMed1996

[Experience with conservative therapy in primary breast cancer: experiences Northern Israel Oncology Center, 1981-1990].

Between 1981 and 1990, 346 patients with primary breast cancer were treated using breast conservation. Mean age was 55 +/- 13 years and median follow-up 53 months. 36.5% were in pathological Stage I, 55% in Stage II, and 4% in Stage III, while 4.5% were in clinical Stages I-II. 60% of the lesions were excised with good margins, 12% with close margins (0.5 cm), 2.5% with macroscopic residuals, 7.5% with microscopic residuals and 18% with margins that could not be determined. Level II lymph node dissection was performed in 334 patients (97%). Adjuvant therapy (combination of chemotherapy and/ or hormones) was given to 223 (64%). Radiotherapy, usually 50-55 Gy tangential photon irradiation to the whole breast, was given to 335 (97%); electron or photon "boost" to the tumor bed was given to 234 (70%); most patients received 20 Gy. Most node-positive patients received 50 Gy to the lymphatic drainage system. A year after completion of radiotherapy cosmetic results were rated as good in 195/212 (92%), moderate in 17/212 (8%), but in none as poor. 5-year actuarial survival was 90% for Stage I and 81% for Stage II disease. 24 (7%) developed breast recurrence, 8 of whom (2%) also had distant metastases; 5 (1.5%) developed supraclavicular lymph node metastases and 59 (17%) distant metastases. Predictors of poor survival or local recurrence were: age under 40 years, premenopausal status, multifocality, and blood/lymph vessel infiltration by tumor cells. The satisfactory level of local control achieved is attributed to the high doses of radiation administered in high-risk lesions (up to 70 Gy total tumor dose).

Actuarial Analysis↗
PubMed1996

Changes in enkephalin and neuropeptide Y-like immunoreactivity in rabbit chromaffin tissues during perinatal development.

Enkephalin-like immunoreactivity (ENK-LI), neuropeptide Y (NPY)-LI and dopamine-beta-hydroxylase (DBH)-LI were found within the chromaffin cells of both the paraaortic body and the adrenal medulla of the newborn rabbit using immunohistochemistry. Cells positive to DBH-LI were abundant in both the paraaortic body and the adrenal medulla. ENK-LI positive cells were frequent in the paraaortic body, but more sparse in the adrenal medulla. A few cells staining for NPY-LI could be detected in both organs. Some nerve fibers within these organs also contained substance P-LI and calcitonin-gene related peptide-LI. The tissue contents of ENK-LI and NPY-LI, as measured by radioimmunoassay, increased after birth in the adrenal glands and were significantly higher than the fetal levels from 1 week of age. In the paraaortic body the lowest content of ENK-LI was found around birth, whereas the content of NPY-LI was highest at that time. With advancing postnatal age, the content of ENK-LI increased, whereas the content of NPY-LI decreased. At each age, there was a higher content of ENK-LI as compared to NPY-LI in both organs. This indicates that the synthesis of ENK-LI and NPY-LI in the paraaortic body is differently regulated during perinatal development.

Adrenal Medulla↗