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Biomedical subjects

S Schifter

Publications and source records attributed to S Schifter.

At least 37 records · Page 2Linked to original sources
PubMed1995

Plasma and placental calcitonin gene-related peptide in pregnancies complicated by severe preeclampsia.

OBJECTIVE: Our purpose was to determine the concentration of calcitonin gene-related peptide, a potent vasodilator, in maternal plasma, fetal plasma, and placental tissue from pregnancies complicated by severe preeclampsia. STUDY DESIGN: The following groups were studied: severe preeclampsia (group 1, n = 21), normal pregnancies matched for mode of delivery (group 2, n = 21), and nonpregnant women (group 3, n = 17). Maternal venous blood samples were drawn before labor, and fetal venous samples were drawn from the chorionic plate immediately after delivery. Calcitonin gene-related peptide was also quantified in placental tissue samples from 15 patients in group 1 and 15 patients in group 2. Calcitonin gene-related peptide was measured with a sensitive and specific radioimmunoassay. RESULTS: No differences were found between maternal plasma calcitonin gene-related peptide concentrations in groups 1 and 2 (29.8 +/- 4.2 and 30.4 +/- 4.3 pmol/L, respectively). Both had levels similar to those in group 3 (28.5 +/- 5.4 pmol/L). Maternal plasma concentrations in the preeclamptic group were unchanged 3 days post partum (29.1 +/- 3.6 pmol/L). Fetal plasma calcitonin gene-related peptide concentrations were similar in groups 1 and 2 (30.2 +/- 3.9 and 32.2 +/- 8.8 pmol/L, respectively). A significant correlation was found between maternal and fetal calcitonin gene-related peptide concentrations (r = 0.43, p < 0.01). Like plasma levels, calcitonin gene-related peptide levels in the supernatants of placental extracts were not different in preeclamptic and normal pregnancies (108.0 +/- 70.4 and 100.9 +/- 56.1 fmol/gm, respectively). CONCLUSION: On the basis of plasma and placental concentrations, calcitonin gene-related peptide does not seem to play an important role in the pathophysiologic mechanisms of preeclampsia.

Biomarkers↗
PubMed1995

Molecular characterization of calcitonin gene-related peptide (CGRP) in a rat medullary thyroid carcinoma cell line.

The rat medullary thyroid carcinoma cell line, CA-77, is known to express the calcitonin gene and the cell line has been used for characterization of procalcitonin. The present investigations concentrate on a molecular characterization of the calcitonin gene-related peptide (CGRP) expressed by a subclone of this cell line. The investigations demonstrate that this subclone produces significantly more CGRP compared to calcitonin. Gel chromatography of cell extracts demonstrates heterogeneity for both CGRP and calcitonin, but a significant amount of immunoreactivity elutes corresponding to the elution position for synthetic CGRP and calcitonin, respectively. The gel chromatogram for CGRP demonstrates four immunoreactive peaks with Kd of 0.42, 0.53, 0.68, and 0.85. The immunoreactive peak with Kd 0.42 elutes corresponding to synthetic rat CGRP. The four immunoreactive peaks were characterized by high pressure liquid chromatography followed by sequence analysis and mass spectrometry. The immunoreactive peak with Kd 0.42 was identified as rat alpha-CGRP as was the peak with Kd 0.53. The peak with Kd 0.68 was identified as 19-37 rat alpha-CGRP and the peak with Kd 0.85 as 28-37 rat alpha-CGRP. In summary, we find that the CA-77 cell line expresses large quantities of normally processed amidated alpha-CGRP and specific fragments thereof. However, the cell line does not express detectable levels of rat beta-CGRP. The findings indicate that the CA-77 cell line can be useful for studies of calcitonin/CGRP gene expression.

Amino Acid Sequence↗
PubMed1995

Blunted humoral responses to mental stress and physical exercise in cardiac transplant recipients.

Since recent results have suggested that the relative neuroendocrine response to physical activity is exaggerated following cardiac transplantation, we studied the haemodynamic-neuroendocrine responses to mental stress, and to physical exercise, in heart transplant recipients free of antihypertensive medication. Ten patients were studied 1.7 years (mean) after transplantation and compared with 10 age-matched controls. Plasma levels of catecholamines, renin activity, aldosterone, atrial natriuretic factor, calcitonin gene-related peptide (CGRP), and endothelin were measured, together with blood pressure and heart rate, during mental stress and graded, submaximal ergometry. Mental stress increased blood pressure in both groups (P < 0.02), but heart rate in controls only (P < 0.05). Noradrenaline did not change. Adrenaline rose in controls only (P < 0.05). Plasma renin activity increased in both groups (P < 0.02), while aldosterone increased in controls only P < 0.02). Atrial natriuretic factor, and endothelin were higher in patients (P < 0.01). Mental stress, however, did not induce any changes. No significant differences were found in relative changes (delta %), except for plasma renin activity which was greater in controls (P < 0.05). During ergometry, only delta % noradrenaline was greater in patients (P < 0.05). delta % for all other parameters were either of the same order as in controls, or blunted. Thus, apart from noradrenaline, cardiac transplant recipients, not receiving antihypertensive medication, do not show an exaggeration in the relative neuroendocrine response to mental or physical stress.

Adolescent↗
PubMed1995

Role of histamine and calcitonin gene-related peptide in the hyperemic response to hypertonic saline and H+ back-diffusion in the gastric mucosa of cats.

BACKGROUND: The present study was undertaken to measure the output of histamine and calcitonin gene-related peptide (CGRP) from injured and restituting gastric mucosa into venous blood and to study the effect of acid back-diffusion on the release of these mediators and their role in the hyperemic response to injury. METHODS: Stomachs of cats were perfused with saline at pH 1.0 or 7.4. Gastric mucosal blood flow (GMBF) was determined with radioactive microspheres, and blood flow in the portal vein and celiac artery was determined by transit-time flowmetry. H+ back-diffusion/secretion was measured by pH-stat titration and by measuring the arteriovenous base excess difference. Mucosal injury was produced by exposure to 2 M NaCl. Histamine and CGRP in portal venous blood were measured by radioimmunoassay. RESULTS: During mucosal exposure to 2 M NaCl GMBF increased, and histamine (0.23 nmol/min) and CGRP (1.2 pmol/min) were released from the mucosa into blood. The hyperemic response was reduced by pretreatment with H1 and H2 blockers and still further by addition of the blocker CGRP8-37. After mucosal damage and luminal perfusion at pH 7.4, GMBF and output of CGRP and histamine decreased towards base-line levels within 30 min. During luminal perfusion at pH 1.0 associated with acid back-diffusion, GMBF and histamine output remained high, whereas the output of CGRP decreased to base-line level. Pretreatment with H1 and H2 blockers reduced the hyperemic response as measured 30 min after damage. CONCLUSIONS: The hyperemic response caused by 2 M NaCl is most likely mediated by histamine and CGRP and maintained by histamine released by back-diffusion of H+ through the superficially damaged gastric mucosa.

Animals↗
PubMed1994

Effect of sulpiride or paroxetine on cerebrospinal fluid neuropeptide concentrations in patients with chronic tension-type headache.

In lumbar cerebrospinal fluid (CSF) obtained from patients with chronic tension-type headache (CTH), the concentrations of beta-endorphin, met-enkephalin, dynorphin, cholecystokinin (CCK), calcitonin gene-related peptide (CGRP), and somatostatin were measured before and after 8 weeks of treatment with sulpiride or paroxetine. We previously reported higher than normal met-enkephalin concentrations in CTH. The present study reveals normal basal concentrations of CCK, CGRP and somatostatin and slightly decreased dynorphin in the same patients. Treatment with sulpiride or paroxetine did not change the concentration of any of the neuropeptides measured. These data suggest central changes in opioid systems but not in other peptide systems (CCK, CGRP, somatostatin) involved in nociceptive processing at the level of the spinal cord dorsal horn/nucleus caudalis of the trigeminal nerve in CTH. Such central changes might be pathophysiologically important or merely secondary to other more important occurrences. The lack of changes in neuropeptide concentrations during drug treatment makes planning of studies involving CSF analysis easier, but also limits the probability of obtaining information on specific neuropeptide systems through CSF analysis.

Adult↗
PubMed1994

Calcitonin gene-related peptide in medullary thyroid carcinomas: characterization of molecular forms including the amidated C-terminus.

CGRP was extracted from three familial and four sporadic medullary thyroid carcinomas (MTC) and was measured by an assay specific for the amidated C-terminus. The antibody showed equal affinity for alpha- and beta-CGRP. All tumors contained high concentrations of CGRP (range: 63-7889 pmol/g) compared to spinal cord (86 pmol/g), thyroid gland (4 pmol/g), and two small-cell lung carcinomas (4 and 1 pmol/g, respectively). The concentration of calcitonin (CT) was determined with an assay specific for an epitope involving the midportion and C-terminal end of the molecule. In six of the seven tumors investigated, concentrations of CT were found to be higher than for CGRP. Gel chromatography showed heterogeneity with respect to CGRP immunoreactivity. Thus, in all seven extracts, three peaks were seen with Kd values 0.37, 0.63, and 0.80, respectively. This profile of immunoreactive CGRP was similar to that obtained from human medulla spinalis, thereby indicating normal posttranslational processing of pro-CGRP in MTC tumors. Further characterization of the three main peaks identified by gel chromatography was performed on pooled fractions from one of the tumors using HPLC, sequencing, and mass spectrometry. The immunoreactive peak with Kd 0.37 was identified as human beta-CGRP, the peak with Kd 0.63 as 19-37 beta-CGRP, and the peak with Kd 0.80 as 25-37 beta-CGRP. No alpha-CGRP was identified in this tumor. This indicates selective expression of beta-CGRP, at least in the tumor investigated.

Amides↗
PubMed1994

Diurnal variation in blood pressure in patients with biventricular assist devices and retained, nonpumping native hearts.

BACKGROUND: Studies indicate that centrally mediated rhythms in sympathetic tone play a prominent role in diurnal cardiovascular variability. Recent evidence from heart transplant recipients, in whom blood pressure does not decline during sleep despite normal variability in plasma norepinephrine, however, suggests that afferent cardiac nervous traffic is necessary for the generation of diurnal variability. This implies that in the presence of an innervated heart excluded from the systemic circulation, blood pressure would still decrease during sleep. To assess this hypothesis, we studied 24-hour blood pressure, heart rate, and neuroendocrine variability in patients with biventricular assist devices in whom the retained native hearts had ceased to pump. METHODS AND RESULTS: Eight patients were free of medication and were studied every 3 hours. Pump rates and output were kept constant throughout the study. Blood pressure showed a significant decline during sleep, as did norepinephrine and epinephrine (all P < .05). Atrial natriuretic factor showed a significant increase around midnight (P < .01). Significantly elevated levels were found for all hormones studied except for aldosterone and endothelin. CONCLUSIONS: Our results suggest that diurnal variations in cardiac function or in catecholamine levels (indicative of sympathetic activity) as found in cardiac transplant recipients alone are not responsible or sufficient for producing a nocturnal drop in blood pressure. The presence of an innervated heart appears crucial in this respect. This could be of importance for the understanding of circadian cardiovascular pathophysiology.

Adult↗
PubMed1993

A new highly sensitive radioimmunoassay for human calcitonin useful for physiological studies.

A highly sensitive and specific radioimmunoassay (RIA) for human calcitonin-like immunoreactivity (CT-LI) has been developed. The assay is performed directly without extraction and may be used for measurements in plasma or serum as well as buffer solutions. The detection limit of the assay is < 0.4 pmol/l, intra- and interassay variations 5 and 10%, respectively when calculated from a control sample within the range of normal concentrations. The recovery of calcitonin (CT) varied between 87 and 118% in the concentration range 10-130 pmol/l. Measurements of CT-LI in sera from 70 normal individuals, showed significantly lower concentrations in women as compared to men, 7.4 pmol/l +/- 2.1 pmol/l and 9.1 pmol/l +/- 2.2 pmol/l, respectively (mean +/- S.D.), P < 0.005. The chromatographic profile of immunoreactive CT in normal serum was investigated by gel chromatography and high pressure liquid chromatography (HPLC) and showed heterogeneity of circulating CT-LI, but with the majority eluting corresponding to the elution position of synthetic human CT. The study of physiological variations in CT levels has so far been hindered by the limitations in assay sensitivity. It is hoped that the significantly improved sensitivity of the presently described assay may contribute towards the elucidation of the physiological functions of CT.

Adolescent↗
PubMed1993

Plasma levels of parathyroid hormone, vitamin D, calcitonin, and calcium in association with endurance exercise.

Nine male marathon runners were investigated during habitual training (week 0), after 3 weeks of training break (week 3), and after 2 weeks (week 5) and 4 weeks (week 7) of retraining. Maximal oxygen uptake, body fat (BF), and plasma levels of 25(OH)D3, 1,25(OH)2D3, parathyroid hormone (PTH), calcitonin (CT), albumin, and albumin-corrected calcium were determined throughout weeks 0-7. The maximal oxygen uptake decreased after training break and increased during retraining (P = 0.002). BF did not change significantly. Plasma 1,25(OH)2D3 was elevated after training break and decreased after 2 and 4 weeks of retraining [week 0: 44.0 +/- 3.7 (SEM) pg x 1(-1); week 3: 52.4 +/- 6.0 pg x 1(-1); week 5: 42.0 +/- 2.8 pg x 1(-1); week 7: 36.9 +/- 2.3 pg x 1(-1); P = 0.03]. Plasma 25(OH)D3 did not change significantly. Plasma PTH increased throughout the training break and retraining (week 0: 1.36 +/- 0.25 pmol x 1(-1); week 3: 2.02 +/- 0.43 pmol x 1(-1); week 5: 2.23 +/- 0.60 pmol x 1(-1); week 7: 2.63 +/- 0.34 pmol x 1(-1); P = 0.03). Albumin-corrected calcium values were transiently decreased during retraining (week 3: 2.77 +/- 0.08 mM; week 5: 2.47 +/- 0.05 mM; week 7: 2.66 +/- 0.07 mM; P = 0.01). Plasma CT did not change during training break, but was transiently decreased during retraining (week 0: 9.97 +/- 0.39 pmol x 1(-1); week 3: 9.91 +/- 0.37 pmol x 1(-1); week 5: 8.19 +/- 0.50 pmol x 1(-1); week 7: 9.02 +/- 0.45 pmol x 1(-1); P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Acute effects of nasal salmon calcitonin on calcium and bone metabolism.

Effects of a single dose of 200 IU of nasal salmon calcitonin (SCT) on calcium metabolism and biochemical markers of bone turnover were investigated in 12 healthy male volunteers in a randomized, placebo-controlled, cross-over design. The nasal spray was given in the morning, and subsequently blood and urine samples were collected for 26 hours. There was a significant decrease in serum ionized calcium with a nadir 4 hours after administration of nasal SCT accompanied by a significant increase in serum parathyroid hormone (P = 0.01) and serum calcitriol (P = 0.04). Nasal SCT did not reduce urinary hydroxyproline/creatinine. Urinary deoxypyridinoline/creatinine was lowered significantly 2 hours after administration of nasal SCT and throughout the first 24 hours, but remained unchanged for the last 2 hours. On a 24-hour basis, urinary deoxypyridinoline/creatinine decreased from 14.1 (3.5) nmol/mmol to 11.7 (3.2) nmol/mmol after nasal SCT (P = 0.04). Nasal SCT did not change the serum levels of alkaline phosphatase, osteocalcin, and the carboxyterminal propeptide of type 1 procollagen. The results indicate that nasal SCT given as a single dose provokes a modest decrease in bone resorption lasting several hours, but leaves bone formation unaffected.

Administration, Intranasal↗
PubMed1993

Calcitonin gene-related peptide in small cell lung carcinomas.

OBJECTIVE: Calcitonin gene-related peptide (CGRP) is a regulatory peptide encoded by the calcitonin gene. CGRP is expressed in increased amounts by the cells of medullary thyroid carcinomas and has been demonstrated by immunohistochemistry to occur in neuroendocrine cells and nerve fibres of lung tissue. MEASUREMENTS: Serum CGRP levels were measured in patients with small cell lung carcinomas before treatment (n = 74) and immediately before the second course of chemotherapy (n = 30). In-situ hybridization and immunohistochemistry were performed on tumour tissue and CGRP was extracted from two tumours and characterized by gel chromatography and high pressure liquid chromatography. RESULTS: Serum CGRP levels were elevated in small cell lung carcinomas when compared with healthy controls of similar age and sex (median values 55.0 vs 36.6 pmol/l, P < 0.001), and 27% had levels above the upper normal range. Serum CGRP levels decreased following the initial course of chemotherapy (P < 0.05) but remained elevated when compared to the controls (P < 0.001). In-situ hybridization for CGRP mRNA was positive in three of 17 tumours and immunohistochemistry was positive in seven of 31 tumours investigated. CGRP immunoreactivity extracted from two tumours was characterized by gel chromatography and high pressure liquid chromatography. A major part of the immunoreactivity was demonstrated to represent the intact molecule. CONCLUSIONS: We found that patients with small cell lung carcinomas had elevated concentration of serum calcitonin gene-related peptide but only 27% had values above the upper normal range. Serum CGRP is therefore of limited value as a tumour marker. Intact CGRP can be extracted from tumour tissue, but in-situ hybridization and immunohistochemistry showed positive reactions in only a few of the tumours investigated. The elevated serum CGRP levels are therefore likely to be largely of extratumoral origin.

Adult↗
PubMed1993

Comparative pharmacokinetics of single-dose administration of mammalian and bacterially-derived recombinant human granulocyte-macrophage colony-stimulating factor.

Pharmacokinetics of recombinant human non-glycosylated bacterially-synthesized (E. coli) granulocyte-macrophage colony-stimulating factor (GM-CSF) were studied following single intravenous (i.v.) and subcutaneous (s.c.) bolus injection, and compared to equivalent doses of glycosylated mammalian-derived CHO-GM-CSF. Each route of administration gave a different GM-CSF concentration-time profile. The highest peak serum concentrations (Cmax) were observed following i.v. bolus injection. After i.v. administration, a two-phase decline in concentration was noted for both types of GM-CSF with a significantly shorter t1/2 alpha of 7.8 minutes for the E. coli GM-CSF versus 20.0 min for the CHO-GM-CSF, while no significant difference was observed for the terminal phase. Following s.c. administration of equivalent doses, a higher peak serum concentration was observed in the E. coli-treated patients and, again, a faster elimination where pretreatment serum levels were reached after 16-20 h, versus more than 48 h after administration of CHO-GM-CSF. Although the non-glycosylated E. coli GM-CSF thus seems to undergo a faster elimination that the glycosylated CHO-GM-CSF no significant difference could be demonstrated in the in vivo effect of corresponding doses of the two compounds with respect to stimulation of granulopoiesis--with reservation for small patient numbers and a large individual variations in response.

Animals↗
PubMed1993

Treatment of psoriasis vulgaris with topical calcipotriol has no short-term effect on calcium or bone metabolism. A randomized, double-blind, placebo-controlled study.

The purpose of this double-blind, placebo-controlled study was to examine whether the vitamin D analogue calcipotriol, topically applied to psoriatic skin lesions, had any effect on calcium or bone metabolism. Thirty-four outpatients with psoriasis vulgaris were randomized to treatment with either calcipotriol ointment (50 micrograms/g) or vehicle ointment twice daily for 3 weeks. The patients were put on a calcium energy fixed diet and examined once weekly. The mean amount of calcipotriol ointment used was 40.3 g/week (range 8.2-95.4 g/week). The results of biochemical markers on calcium and bone metabolism showed no significant differences between the two groups. No correlation was found between the amount of ointment used and changes in parameters on calcium and bone metabolism during the 3-week treatment. It is concluded that calcipotriol ointment (50 micrograms/g), applied in doses of 8.2-95.4 g/week for 3 weeks to psoriatic skin lesions, has no effect on calcium or bone metabolism.

Administration, Cutaneous↗
PubMed1993

Development and application of a sensitive radioimmunoassay for human granulocyte-macrophage colony-stimulating factor able to measure normal concentrations in blood.

A radioimmunoassay (RIA) for human granulocyte-macrophage colony-stimulating factor (GM-CSf) was developed based on antibodies from rabbits immunized with glycosylated recombinant human (rh) GM-CSF. The antibodies are specific for human GM-CSF and do not crossreact with other human hematopoietic growth factors or mouse GM-CSF. The antibodies also react with nonglycosylated rhGM-CSF, so E. coli-derived rhGM-CSF can be assayed as well. The RIA has a measuring range of about 10 to 200 pg/mL. Normal blood was found to contain 13 to 24 pg/mL (95% limits) with a mean of 18.5 pg/mL (n = 34). Monoclonal antibodies against GM-CSF could remove GM-CSF from normal human serum, thus ensuring that the GM-CSF measured in serum is real and does not represent nonspecific reactivity with our polyclonal rabbit antibodies. While previously published methods have been unable to measure GM-CSF in human serum under normal conditions, our more sensitive RIA does confirm the presence of small amounts of GM-CSF in serum or plasma and can therefore be used to detect fluctuations of GM-CSF in health and in disease.

Animals↗
PubMed1992

Level and diurnal variations of hormones of interest to the cardiovascular system in patients with heart transplants.

The lack of a nocturnal decrease in blood pressure in cyclosporine-treated cardiac transplant recipients may indicate abnormalities in the mechanism(s) responsible for circadian variability in other physiologic parameters such as in circulating hormones. This possibility was addressed through repeated determinations of circulating catecholamines, neuropeptide Y, pancreatic polypeptide, calcitonin gene-related peptide, plasma renin activity, aldosterone, atrial natriuretic factor and cortisol. The results from 10 patients with heart transplants were compared with those of 12 age-matched, healthy control subjects. Both groups were studied during 24-hour supine rest. There was no difference between patients and control subjects in mean levels of catecholamines, neuropeptide Y, pancreatic polypeptide and aldosterone. Patients had higher levels (+/- SD) of plasma renin activity (6.4 +/- 1.3 vs 2.6 +/- 0.4 ng/ml/hour, p less than 0.001), calcitonin gene-related peptide (47.7 +/- 9.9 vs 33.3 +/- 5.7 pmol/liter, p less than 0.01) and atrial natriuretic factor (93.0 +/- 56.7 vs 20.7 +/- 8.9 pg/ml, p less than 0.001) than control subjects, respectively. Cortisol was not detected in patients. Abnormal diurnal profiles in patients were found for calcitonin gene-related peptide, aldosterone and atrial natriuretic factor, and for pancreatic polypeptide, together with decreased levels, in patients with greater than 6 months follow-up. Except for hormones reflecting sympathetic nervous activity, all hormonal systems studied showed abnormalities in level or circadian rhythmicity, or both. The pancreatic polypeptide results suggest that parasympathetic neuropathy could develop in cyclosporine-treated heart transplant recipients.

Adrenal Cortex Hormones↗
PubMed1992

Calcitonin and PDN-21 as tumour markers in MEN-2 family screening for medullary thyroid carcinoma.

Calcitonin is expressed in medullary thyroid carcinomas (MTC). It is processed from a large molecular weight precursor and is flanked at its C-terminal end by a 21 aminoacid peptide (PDN-21) formed in equimolar concentrations to calcitonin by enzymatic cleavage of the prohormone. This investigation compared basal measurements of calcitonin and PDN-21 and the response of the two peptides following pentagastrin stimulation in normal controls and in family members with C-cell hyperplasia or early neoplasia. The results showed that calcitonin and PDN-21 may both be used in family screening for the MEN-2 syndrome, but the unstimulated circulating concentrations of calcitonin were higher and more influenced by C-cell hypersecretion than PDN-21 (P less than 0.01), and the increase in stimulated concentrations of calcitonin were significantly higher than for PDN-21 (P less than 0.01). These findings may be explained by differences with respect to secretion and metabolic clearance rate for the two peptides.

Adolescent↗