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Biomedical subjects

G Fried

Publications and source records attributed to G Fried.

At least 73 records · Page 4Linked to original sources
PubMed1992

Subcellular distribution of serotonin in the lamprey spinal cord.

The subcellular distribution of serotonin (5-hydroxytryptamine; 5-HT) in the lamprey (Ichtyomyzon unicuspis, Lampetra fluviatilis) spinal cord was investigated by using ultracentrifugation on continuous density gradients combined with an electron microscopic analysis of the gradients and of immunostained tissue. Endogenous 5-HT was analyzed by high-performance liquid chromatography with electrochemical detection. After differential centrifugation, the highest levels of 5-HT were found in the particulate fractions. After ultracentrifugation of lysed synaptosomal fractions on continuous sucrose gradients and the subsequent sedimentation of the individual fractions, 5-HT showed a biphasic distribution in the gradient. The two peaks corresponded to 0.30-0.40 M and 0.85-1.05 M sucrose. Electron microscopy of intact tissue showed that some of the boutons were strongly immunoreactive to 5-HT with dense precipitates over large granular vesicles. The area around these large vesicles, however, also showed reaction product. Large granular vesicles could be clearly distinguished in the immunostained axonal varicosities. In tissue not processed for 5-HT immunoreactivity it was seen that the varicosities contained not only large dense-cored vesicles, but also small agranular vesicles. An electron microscopical analysis of the subcellular fractions revealed that the fraction corresponding to the "light" 5-HT peak contained numerous vesicular structures, which in most cases were electron lucent. In the "heavy" fractions, nerve ending particles containing vesicles of various sizes were observed. The results suggest that 5-HT in the lamprey spinal cord may be distributed in more than one subcellular compartment which, apart from the cytosol, possibly corresponds to small and large synaptic vesicles.

Animals↗
PubMed1992

Ontogeny of aromatic L-amino acid decarboxylase-containing tubule cells in rat kidney.

Dopamine plays an important role in regulation of renal sodium transport. Proximal tubule cells produce dopamine after decarboxylation of L-DOPA via the enzyme aromatic L-amino acid decarboxylase (AADC). The presence and cellular localization of AADC-like immunoreactivity (-LI) and AADC mRNA were examined during pre- and postnatal development in rat kidney by indirect immunofluorescence and in situ hybridization histochemistry. Few scattered condensations of AADC-immunoreactive (-IR) tubule cells forming a lumen were detected on gestational day 18. From gestational day 21, many AADC-IR tubule cells were observed in the inner cortex, whereas the outer cortex lacked AADC-LI. Within 24 hours of birth, AADC-IR cells in the inner cortex could be identified as proximal tubule cells. During day 3 and 5 there was an increase in number of AADC-IR proximal tubule cells in the inner cortex, leaving less amount of AADC-negative cells in the outer cortex. Starting from day 8, AADC-IR cells could be seen in the outer cortex. An apparent decrease in AADC-immunofluorescence intensity was observed at 40 days, and at 80 days virtually no AADC-LI could be demonstrated. Intrarenal levels of dopamine showed a tendency to increase between 3 and 20 days, and showed significant decreases between 20 to 40 days and between 40 to 80 days. AADC mRNA was not detected in the kidney at 18 hours after birth, but could be observed in the inner cortex at 6 days. At 12, 19 and 40 days AADC mRNA was seen in the entire cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Endothelin and neuropeptide Y are vasoconstrictors in human uterine blood vessels.

The control of uterine blood flow is regulated by a number of factors including vasoactive present in the endothelium and the perivascular nerves. We examined the effects of two vasoactive peptides, endothelin and neuropeptide Y, on segments of human uterine arteries and veins in vitro. We found endothelin, a potent vasoconstrictor in the uterine artery and vein, giving a slow and long-lasting contraction starting at 10(-9) mol/L. At this concentration, the established vasoconstrictor noradrenaline had almost no effect. Neuropeptide Y had no effect of its own in the human uterine artery, but increased basal tone in uterine veins, and at higher concentrations triggered spontaneous contractions. Neuropeptide Y (10(-7) mol/L) often, but not always, enhanced the contraction induced by noradrenaline (10(-6) mol/L). Neuropeptide Y (10(-7) mol/L) also enhanced the contraction induced by transmural nerve stimulation (20 Hz, 0.4 msec). We conclude that endothelin and neuropeptide Y may modulate the control of human uterine circulation.

Adult↗
PubMed1991

The effect of 19-hydroxy prostaglandins on the human myometrium in vitro.

Human semen contains high amounts of different prostaglandins of which the quantitatively dominating compounds are 19-hydroxy PGE and 19-hydroxy PGF. The effect of PGE and PGF on the contractility of the human uterus is well known whereas the corresponding 19-hydroxy derivatives have not previously been examined in detail. In the present investigation 19-hydroxy PGE1 was shown to dose-dependently decrease the frequency and the amplitude of the contractions in human myometrial tissue in vitro. The effect of seminal 19-hydroxy prostaglandins may thus be of importance for sperm transport through the female genital tract.

Alprostadil↗
PubMed1991

The effect of selective serotonergic neurotoxin treatment on tachykinin levels in the rat ventral spinal cord.

The levels of 5-hydroxytryptamine and tachykinin neuropeptides substance P, neurokinin A, neurokinin B and neuropeptide K were measured in the spinal cord of rats treated by intraventricular injection of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine. The spinal cord levels of 5-hydroxytryptamine as measured by high performance liquid chromatography with electrochemical detection decreased by more than 90% in the ventral and dorsal cord compared to controls. The levels of substance P as measured by radioimmunoassay were significantly reduced (66%, P less than 0.01) in the ventral lumbar cord only. In this region, neurokinin A, neurokinin B and neuropeptide K levels were determined by combined high performance liquid chromatography and radioimmunoassay. The neurotoxin treatment also caused a significant reduction of neurokinin A (72% reduction, P less than 0.01) and a non-significant reduction of neuropeptide K, but virtually no change in the neurokinin B level. Immunohistochemical studies of the ventral lumbar cord of sham-operated animals showed immunoreactivity for 5-hydroxytryptamine as well as for substance P and neurokinin A in nerve fibres around motor neurons. In neurotoxin-treated rats this region was devoid of immunohistochemically detectable substance P- and neurokinin A-positive fibres and showed very sparse or no 5-hydroxytryptamine immunoreactivity. We conclude that among the tachykinins both neurokinin A and substance P, but probably not neurokinin B, co-exist with 5-hydroxytryptamine in nerve terminals in the rat ventral spinal cord.

5,7-Dihydroxytryptamine↗
PubMed1991

Galanin and neuropeptide Y in chromaffin granules from the guinea-pig.

We have examined the subcellular distribution of galanin-like immunoreactivity, neuropeptide Y-like immunoreactivity and the catecholamines noradrenaline and adrenaline in the adrenal medulla from guinea-pigs. By differential centrifugation of the adrenal medulla homogenate the neuropeptides as well as the catecholamines sedimented in a 10,000 g pellet. This pellet was resuspended and further examined in discontinuous and continuous density gradients. In the discontinuous gradient the catecholamines peaked in the heavy bottom fraction, assumed to contain chromaffin granules. Galanin-like immunoreactivity and neuropeptide Y-like immunoreactivity were also enriched in this fraction. However, both neuropeptides showed high levels of sedimentable material also in a fraction of intermediate density. In the continuous density gradient, the sum of sedimentable and soluble catecholamines showed peak values in two fractions corresponding to 1.07 and 1.47 M sucrose, respectively. The NA peak in the denser fraction was more pronounced than the corresponding A peak. Galanin-like immunoreactivity showed only one peak, in the fraction corresponding to 1.07 M sucrose. The data suggest that galanin-like immunoreactivity and neuropeptide Y-like immunoreactivity are partly stored with catecholamines in chromaffin granules. However, galanin-like immunoreactivity and neuropeptide Y-like immunoreactivity was also found in fractions lighter than those containing the bulk of the catecholamines.

Adrenal Medulla↗
PubMed1990

Effects of neuropeptide Y and noradrenaline on uterine artery blood pressure and blood flow velocity in the pregnant guinea-pig.

Neuropeptide Y (NPY) coexists with noradrenaline (NA) in many peripheral sympathetic nerves. Since it has been found that patients with preeclampsia have elevated myometrial levels of both NPY and NA, we have examined the effects of NPY and NA on blood pressure and blood flow velocity in the uterine artery of the term pregnant guinea-pig (n = 7). We found that NPY (10-1000 pmol) significantly increased local blood pressure, with increases ranging from 15.4% (P less than 0.05) to 46.4% (P less than 0.001) as compared to control. NA (10-1000 pmol) had similar effects, increasing local blood pressure (5%-57.5% (P less than 0.01]. NPY had no significant effect on uterine blood flow velocity as measured by pulsed Doppler ultrasound, whereas NA (10-1000 pmol) decreased local uterine blood flow velocity (5.9%-30.2% (P less than 0.05]. The effect of NPY on blood pressure was phentolamine-resistant, indicating that it is not alpha-adrenoceptor-mediated. The results indicate that NPY and NA have significant pressor effects in the local uterine circulation during pregnancy in the guinea-pig.

Animals↗
PubMed1990

Peptide-containing nerves in the human pregnant uterine cervix: an immunohistochemical study exploring the effect of RU 486 (mifepristone).

The presence of several neuropeptides (neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL), enkephalin (ENK), somatostatin (SOM) was established in the early pregnant human cervix using indirect immunofluorescence immunohistochemistry. Several peptides (VIP, NPY, CGRP, GAL) were present both in free nerves among smooth muscle cells and around blood vessels. Others (SP, SOM) were only seen as single varicosities among smooth muscle cells. Randomized treatment of patients with RU 486 (mifepristone) prior to surgical sampling revealed no clearcut differences in peptide immunoreactivities. After RU 486 treatment, however, there was a tendency towards a decrease of NPY- and VIP-immunoreactivity, and an increase of CGRP-immunoreactivity.

Calcitonin↗
PubMed1989

Substance P enhances the release of endogenous serotonin from rat ventral spinal cord.

The effect of the tachykinin neuropeptides, substance P (SP), neurokinin A (NKA) and the neurokinin B (NKB) receptor agonist, senktide, on the potassium-evoked release of endogenous serotonin (5-hydroxytryptamine, 5-HT) was investigated in superfused tissue slices of rat ventral spinal cord, where 5-HT is known to coexist with SP. Endogenous 5-HT was assayed by HPLC with electrochemical detection. The evoked release of 5-HT was significantly enhanced by 10(-4) M SP (190% increase) and 10(-5) M SP (74% increase) but not by 10(-6) M SP, NKA (10(-5) and 10(-4) M) and senktide (10(-5) and 10(-4) M) had no significant effect on the 5-HT release. The results suggest that, in the rat ventral spinal cord, where most of the 5-HT and SP is stored in the same nerve endings. SP but not NKA nor NKB potentiates the evoked release of 5-HT in a dose-dependent manner.

Animals↗
PubMed1989

Evidence for differential storage of calcitonin gene-related peptide, substance P and serotonin in synaptosomal vesicles of rat spinal cord.

Homogenates of rat ventral and dorsal spinal cords were subjected to differential and gradient centrifugation on linear sucrose gradients following lysis of a synaptosomal fraction. The distribution of calcitonin gene-related peptide (CGRP) and substance P (SP) in dorsal spinal cord as well as the distribution of serotonin (5-HT) and SP in ventral spinal cord was determined, using radioimmunoassay (RIA) for CGRP and SP and high-performance liquid chromatography for 5-HT. In dorsal spinal cord. CGRP and SP had an almost identical distribution, with one peak in an intermediate density fraction which according to electron microscopy contained i.a. large dense-cored vesicles, and a second peak in a heavy fraction enriched in synaptosome-like structures. In ventral spinal cord, 5-HT and SP had different distribution patterns; 5-HT peaked in a light fraction containing many small synaptic vesicles, whereas SP peaked in an intermediate density fraction similar to the one in dorsal spinal cord. Both 5-HT and SP had second peaks in high density fractions containing synaptosome-like structures. The study demonstrates that the peptides CGRP and SP, partly coexisting in dorsal spinal cord, both seem to be stored in large vesicles inside synaptosomes, whereas the amine 5-HT and the peptide SP, coexisting in ventral spinal cord, appear to have a differential storage with 5-HT mainly in small vesicles and SP in large vesicles, both inside synaptosomes.

Animals↗
PubMed1989

Sacrococcygeal extradural ependymoma.

A case of lumbosacral extradural myxopapillary ependymoma is reported. The clinical, embryologic, and therapeutic features of this rare lesion are presented. The unusual entity is discussed in the light of previous experience with extradural ependymoma in the lumbosacral region.

Adult↗
PubMed1989

Galanin-, neuropeptide Y- and enkephalin-like immunoreactivities in catecholamine-storing paraganglia of the fetal guinea pig and newborn pig.

The occurrence and distribution of several neuropeptides and transmitter enzymes have been investigated by means of indirect immunofluorescence histochemistry in preaortal and carotid body-like paraganglia of the fetal guinea pig and the newborn pig. Preaortal paraganglia from the celiac and inferior mesenteric ganglion regions in fetal guinea pigs showed cell bodies immunoreactive (IR) for tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), neuropeptide Y (NPY), galanin (GAL) and metenkephalin (ENK). Almost all cells were IR for TH and DBH, whereas NPY-like immunoreactivity (-LI), GAL-LI and ENK-LI occurred less frequently. Direct double-labeling revealed the coexistence of NPY/GAL, NPY/ENK and GAL/ENK in paraganglion cells from the celiac and inferior mesenteric region. Nerve fibers and terminals were IR for ENK; fibers IR for calcitonin-gene-related peptide (CGRP) were present in the inferior mesenteric ganglion region. Preaortal paraganglia cells from the newborn pig showed TH-LI, DBH-LI, GAL-LI and ENK-LI, the distribution pattern being similar to that seen in the guinea pig; however, NPY-LI was absent. Carotid-body-like paraganglia from the newborn pig showed cell bodies IR to TH, GAL and ENK. Few cells were seen with DBH-LI. A rich supply of nerve fibers with CGRP-LI was present; some fibers exhibited ENK-LI and CCK-LI. In the adjacent superior cervical ganglion, ganglion cell bodies showed immunoreactivity to TH, DBH and NPY. A small number of cells were positive for GAL, CGRP and vasoactive intestinal polypeptide (VIP). Physiological activation of the paraganglia, leading to release or increase in catecholamines, may also change the content of the neuropeptides present in the paraganglia.

Animals↗
PubMed1989

Co-release of neuropeptide Y and noradrenaline from pig spleen in vivo: importance of subcellular storage, nerve impulse frequency and pattern, feedback regulation and resupply by axonal transport.

The importance of subcellular storage, nerve impulse rate and pattern, and feedback regulation, as well as resupply by axonal transport for the release of noradrenaline and neuropeptide Y-like immunoreactivity, was studied in the blood perfused pig spleen in vivo. Vasoconstrictor responses were recorded as perfusion pressure changes. Subcellular fractionation experiments using sucrose density gradients showed a bimodal distribution of noradrenaline (peak concentrations at 0.8 and 1.1 M sucrose) while only one main peak of neuropeptide Y was present (at 1.1 M sucrose). Overflow suggesting release of noradrenaline and neuropeptide Y-like immunoreactivity could be detected after 10 s stimulation at 10 Hz. The ratio for the output of noradrenaline and neuropeptide Y upon continuous nerve stimulation in control animals decreased with frequency. After inhibition of noradrenaline reuptake by desipramine the vasoconstrictor response and noradrenaline output were enhanced while the corresponding overflow of neuropeptide Y was reduced by 50% at 0.5 Hz. Stimulation with the irregular or regular bursting patterns at high frequencies caused larger perfusion pressure increase and relative enhancement of neuropeptide Y output compared to noradrenaline than a continuous stimulation both before and after desipramine treatment. A similar fractional release per nerve impulse was calculated both for [3H]noradrenaline (5.6 +/- 1.0 x 10(-5) and neuropeptide Y (7.3 +/- 0.3 x 10(-5). After reserpine treatment combined with preganglionic denervation the vasoconstrictor responses were more long-lasting, neuropeptide Y release was enhanced while noradrenaline content and release were reduced by 99%. The difference in neuropeptide Y overflow between continuous and bursting types of stimulation was smaller after reserpine treatment. After prolonged intermittent stimulation with regular bursts (20 Hz) for 1 h the splenic content of neuropeptide Y was reduced by 58%, while no change was observed for noradrenaline. The maximal perfusion pressure increase upon prolonged nerve stimulation after reserpine was similar in control and reserpine-treated animals, but after reserpine the vasoconstrictor response and neuropeptide Y release were subjected to fatigue. Ligation experiments of the splenic nerves revealed the splenic neuropeptide Y content was resupplied by axonal transport with a calculated total tissue turnover time of 11 days. In contrast, axonal transport contributed only to a marginal extent for the resupply of noradrenaline.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

[Treatment of stage I malignant melanoma].

In 259 patients with malignant melanoma of the skin referred here during 1973-1984, the median follow-up was 46 months. Of 182 with stage I disease, 97 (53.2%) were women and 85 men. Of these, 90.1% were Jews of European extraction and 8.2% were Jews of Asian-African extraction, while only 1.8% were non-Jews. 171 (94%) of the patients were treated by wide excision, with or without skin graft, as primary treatment, while 11 had limited local excision. In 16.4% the primary tumor was located on the upper limbs, in 34.6% the lower limbs, in 27.5% the trunk and in 19.2% the head and neck. 5-year survival was 70%. The 5-year actuarial survival was significantly influenced by: age (those under 50 had better survival, 79.5% vs 58.4%, p less than 0.05); by site of the primary lesion (88.5% for those of the upper limbs vs 59.4% for those of the lower limbs), p less than 0.01]; by depth of invasion as seen microscopically (81.2% for Clark I-II vs 52.8% for Clark IV-V, p less than 0.02); and by site of recurrence (43.4% if local vs 0 for distant, p less than 0.02).

Actuarial Analysis↗
PubMed1989

Somatic complications and contraceptive techniques following legal abortion.

The purpose of this study was to establish the frequency of complications following legal abortion at our hospital, and also to examine the use of contraceptives among these patients. All women who requested abortion in the first or second trimester up to week 15 during an 8-month period (n = 1000) were included in the study. The patients were characterized with regard to age, parity, previous abortion, contraceptive technique before and after the abortion, presence of endocervical/urethral Chlamydia trachomatis and frequency and type of somatic complications following the abortion. The overall frequency of complications (infection, bleeding, recurettage) was 5.4%, and 2.7% were readmitted to the hospital. No certain relation between complication rate and gestational length, age or parity was seen, possibly related to selective prostaglandin pretreatment of the cervix and doxycycline treatment of patients with positive cultures for Chlamydia trachomatis. In contrast to previous Scandinavian studies, we found a smaller proportion of young patients, a low percentage of Chlamydial infections, and an unchanged high rate of failure to use contraceptives.

Abortion, Legal↗