S-100 Protein Concentration Research Articles

Normal serum concentrations of S-100 protein and changes in cerebrospinal fluid concentrations of S-100 protein during and after thoracoabdominal aortic aneurysm surgery: Is S-100 protein a biochemical marker of clinical value in detecting spinal cord ischemia?

Purpose: This study was performed to determine the concentration of S-100 protein in serum and in the cerebrospinal fluid (CSF) during and 24 hours after thoracoabdominal aortic aneurysm repair. Methods: This prospective study was performed at St. Antonius Hospital in Nieuwegein, The Netherlands. Eight patients who underwent elective thoracoabdominal aortic surgery participated in the study. Arterial blood and CSF samples for analysis of S-100 protein were drawn after induction of anesthesia, during the cross-clamp period of the critical segment, after 5 minutes of reperfusion, during the closure of the skin, and 24 hours after closure of the skin. Results: No increase in S-100 protein concentration could be detected in serum (<0.2 μg/L). The S-100 protein concentration in CSF increased during the procedure in all patients (4.2 ± 3.1 μg/L). However, in one patient, who became paraplegic, the S-100 protein concentration in CSF increased even further after 24 hours (10 μg/L). Conclusions: The preliminary results suggest that S-100 protein in CSF may be a marker of clinical value in evaluating the effects of measures to detect and reduce spinal cord ischemia. (J Vasc Surg 1998;27:344-6.)

S-100 protein plasma levels after aneurysmal subarachnoid haemorrhage.

We investigated the level of S-100 protein in blood as an indicator of brain damage in 71 patients suffering from subarachnoid haemorrhage (SAH) due to ruptured aneurysms. Concentrations of S-100 protein were determined by micro-titre based immunofluorometic assay detecting predominantly S-100b on blood samples obtained 24 hours, 3 days and 7 days after onset of symptoms in patients with SAH and from 120 healthy control subjects. Neurological status was assessed using the Hunt and Hess (HH) scale on admission and by the Glasgow Outcome Scale (GOS) 6 months later. Mean concentrations of S-100 protein in blood were significantly (p < 0.0001) higher in patients 24 hours (0.263 +/- 0.387 microgram/l), 3 days (0.192 +/- 0.288 microgram/l) and 7 days (0.256 +/- 0.442 microgram/l) after onset of SAH symptoms compared to controls (0.050 +/- 0.081 microgram/l). More severe neurological symptoms (higher HH scale scores) on admission correlated with higher S-100 levels on admission (R = 0.70) and Day 3 (R = 0.66) (p < 0.0001). Worse outcome (lower GOS score) 6 months after SAH was also associated with higher plasma concentration of S-100 in the first week after SAH. In summary, this study showed that in patients with SAH due to ruptured aneurysm, S-100 protein levels correlate with early neurological deficit and are as sensitive as HH scores in predicting neurological outcome (GOS scores). Measurement of S-100 protein in blood is a reliable non-invasive method and may be clinically useful to screen for and monitor progression of central nervous system diseases of various origins.

S-100 protein and neuron-specific enolase concentrations in blood as indicators of infarction volume and prognosis in acute ischemic stroke.

Better techniques are needed to monitor infarction volume and predict neurological outcome after ischemic brain infarction. We evaluated the usefulness of serial measurements of S-100 protein versus neuron-specific enolase (NSE) in blood samples from patients with acute stroke. Using nonisotopic sandwich immunoassays, we measured plasma concentrations of S-100 protein and NSE on admission and on days 3, 4, 7, and 14 after infarction in 44 patients (age range, 22 to 86 years; mean age, 65.1 years; 12 female, 32 male). Infarct volume was measured by volumetric CT on day 4 after ictus, and clinical outcome was assessed at discharge from hospital with the Activities of Daily Living Scale and 6 months after infarction with the Glasgow Outcome Scale. Peak blood levels of S-100 protein were found on day 2.5 +/- 1.3, and peak levels of NSE were found on day 1.9 +/- 0.8 after infarction. Peak plasma levels of S-100 protein correlated well with infarct volume (r = .75, P < .001) and with clinical outcome assessed with the Glasgow Outcome Scale (r = .51, P < .001). Serum levels of NSE correlated with infarct volume (r = .37, P < .05) but not with clinical outcome (r = .18, P > .05). The results of our study indicate that measuring blood concentrations of S-100 protein periodically in the first 10 days after cerebral infarction helps to predict infarct volume and the long-term neurological outcome more accurately than periodic measurements of blood concentrations of NSE.

S-100 protein concentration in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

We evaluated S-100 levels in paired cerebrospinal fluid (CSF) and serum samples in a group of 135 patients referred to the German Creutzfeldt-Jakob disease (CJD) surveillance unit from June 1993 to May 1995. The patients were seen in a prospective case control study. The diagnosis of probable CJD during life was made in any patient presenting with rapidly progressive dementia of less than 2 years' duration, typical periodic sharp wave complexes (PSWCs) in the EEG and at least two of the following findings: myoclonus, visual/or cerebellar symptoms, pyramidal and/or extrapyramidal signs and/or akinetic mutism. Patients presenting with the above clinical signs and symptoms but without PSWCs were classified as possible, while those with a dementia of a duration exceeding 2 years and without PSWCs were classified as other. S-100 was determined in paired CSF and serum samples by a commercially available enzyme-linked immunosorbent assay. In a group of 76 patients with definite and probable CJD, S-100 concentration (median 25 ng/ml, range 2-117) in CSF was significantly higher (P < 0.0001) than in 32 patients diagnosed as other (median 4 ng/ml, range 1-19). Serum levels of S-100 were below 0.5 ng/ml in all groups. At a cut-off of 8 ng/ml an optimum sensitivity of 84.2% with a specificity of 90.6% for the diagnosis of CJD by the determination of S-100 in CSF is obtained. S-100 levels exceeding 8 ng/ml in CSF support the diagnosis of CJD in any patient presenting with rapidly progressive dementia.

Serum S-100 protein, relationship to clinical outcome in acute stroke.

The clinical significance of serum S-100 protein, a protein released by damaged brain tissue, was assessed in patients with acute ischaemic or haemorrhagic stroke and matched controls. Serum S-100 protein concentration was significantly elevated in patients with ischaemic stroke [median (SQR): 0.27 (0.90) microgram/L, n = 68] and haemorrhagic stroke [0.43 (0.23 microgram/L, n = 13] compared to controls [0.11 (0.03) microgram/L, n = 51, P < 0.0001]. Although patients with haemorrhagic stroke had higher serum S-100 concentrations compared to patients with ischaemic stroke, this was not quite statistically significant. Serum S-100 concentrations were related to infarct size, large (total anterior circulation) infarcts concentrations having the highest [0.40 (0.22) microgram/L], and small vessel ('lacunar') infarcts concentrations having the lowest [0.20 (0.60) microgram/L, P < 0.0005] concentrations. S-100 protein concentration was also significantly related to clinical outcome at three months measured using three disability and handicap scales (n = 81): modified Barthel index (rs = -0.285, P = 0.01), modified Rankin score (rs = 0.313, P = 0.004) and Lindley score (rs = 0.262, P = 0.018) with high values associated with poor clinical outcome. Similarly high values of serum S-100 protein were observed in patients who died or were discharged to an institution [median (SQR): 0.63 (0.29) microgram/L and 0.37 (0.13) microgram/L, respectively compared to those who were discharged home [0.26 (0.11) microgram/L, P = 0.13]. The present study suggests measurement of serum S-100 protein could be a useful prognostic marker of clinical outcome in acute stroke. Whether S-100 concentrations can be altered by therapeutic intervention in acute stroke remains to be elucidated.

P-2-153 - Age- and sex-related changes of S-100 protein concentrations in cerebrospinal fluid and serum in patients with no previous history of neurological disorder

In order to reveal the enrichment/depletion behaviour of Hg during coal combustion, a separation procedure was applied on three fly ash (FA) samples from two Bulgarian thermoelectric power plants, Maritza 3 TPP and Varna TPP, as follows: (1) FAs from the 1-st and 3-rd rows of the electrostatic precipitators (ESP) of Maritza 3 TPP; and (2) FA from the 5-th row of ESP of Varna TPP. Five fractions were obtained from each bulk FA sample as a result of the sequential separation scheme applied, namely: water leachate of FA; water washed FA (FAW); char concentrate (FAC); magnetic fraction (FAM); and FA residue (FAR). Mercury content of bulk samples and separated fractions, Brunauer–Emmett–Teller (BET) specific surface area, Barrett–Joyner–Halenda (BJH) mesopore volumes, micropore surface area, monolayer capacity, and micropore volumes for porous texture characterization of the FAs and their respective char fractions were also measured.The data obtained reveal that char, which contains mainly unburned organic matter, has an important role in the partial capture and retention of Hg in FAs. Fly ash char fraction (FAC) generated from lower rank lignites (Maritza 3 TPP) has greater enrichment in Hg compared to FAC originated from higher rank bituminous coals (Varna TPP). There is a strong positive correlation between Hg concentration and the BET/Langmuir specific surface area, BJH mesopore volume, micropore surface area and monolayer capacity of the char fraction derived from FA of the 3rd ESP row at Maritza 3 TPP, which suggests that Hg adsorbs on both the mesopores and micropores of the char particles and by volume filling of the pores for the lignite-derived fly ash char sample. In contrast, Hg concentration shows strong positive correlation with the micropore surface area and moderate positive correlation with micropore volume and monolayer capacity of the char fraction obtained from the FAs of the 5th ESP row in Varna TPP. Thus, the adsorption on the micropores of the char particles and subordinate volume filling of the char micropores can be expected as preferable mercury adsorption mechanisms for the bituminous-derived fly ash chars.

44 A new sensitive SANGTEC 100 assay to measure serum concentration of S-100 protein has prognostic value for melanoma patients

44 A new sensitive SANGTEC 100 assay to measure serum concentration of S-100 protein has prognostic value for melanoma patients

Biochemical markers of cerebral damage

Biochemical markers of cerebral damage

Age- and Sex-Related Changes of S-100 Protein Concentrations in Cerebrospinal Fluid and Serum in Patients with No Previous History of Neurological Disorder

S-100 is a calcium-binding protein synthesized in astroglial cells in all parts of the central nervous system (CNS). It is present in the body in different subchains, of which the beta form (96%) predominates in the brain (1). S-100 protein is normally not detectable in serum (1), but previous studies have demonstrated that increased S-100 concentrations in cerebrospinal fluid (CSF) are an index of the active phase of cell injury in patients with acute multiple sclerosis exacerbations, intracranial tumors, acute encephalomyelitis, and spinal cord compression (2). High CSF concentrations of the S-100 protein have also been demonstrated in patients with glioblastoma, cervical compression, polyneuropathy, hydrocephalus, subarachnoid hemorrhage, encephalitis, meningitis, and cerebral infarction (3)(4)(5)(6)(7)(8). A previous study demonstrated age-related reference values for S-100 protein in CSF in children and adults with distinct neurological disorders (9). We sampled serum and CSF from 75 men and 35 women undergoing various surgical procedures in spinal anesthesia.The patients had no actual or previous history of neurological disease. The study was performed to establish reference intervals of S-100 protein in CSF and serum. From August 1995 to June 1996, serum and CSF samples were obtained from 110 patients undergoing surgery in spinal anesthesia. Before inclusion in the study, the patients answered a questionnaire concerning known neurological symptoms or diseases, and their hospital records were investigated. The inclusion criteria were as follows: no history of previous neurological symptoms or disease, no previous investigation in a neurological department, no present symptoms indicating any neurological disease, no evidence of malignant disease, …

Study of the Localization and the Concentration of S-100 Protein in Thyroid Tissues in Various Thyroid Disorders

Study of the Localization and the Concentration of S-100 Protein in Thyroid Tissues in Various Thyroid Disorders

Cardiovascular hemodynamic changes and serum endothelin-1 level in DeBakey type III acute aortic dissection patients with hypertension

Objective: This study was performed to correlate the changes in concentration of S-100 protein in the cerebrospinal fluid (CSF) during and after thoracoabdominal aortic aneurysm (TAAA) surgery with the results of somatosensory and motor evoked potential monitoring. Methods: The study was designed as a prospective study at St Antonius Hospital in Nieuwegein, The Netherlands. The participants were 19 patients who were undergoing elective TAAA surgery. CSF samples for analysis of S-100 protein were drawn after the induction of anesthesia, during the cross-clamp period of the critical aortic segment, after 5 minutes of reperfusion of this segment, during the closure of the skin, and 24 hours after the closure of the skin. In all the patients, continuous intraoperative recording of myogenic motor potentials evoked by transcranial electrical stimulation (tcMEP) and somatosensory potentials evoked by stimulation of the posterior tibial nerve took place to monitor the integrity of the spinal cord. The operative technique consisted of staged or sequential clamping to maximize the beneficial effect of the distal perfusion by the left heart bypass, continuous CSF drainage to keep the CSF pressure below 10 mm Hg, and moderate hypothermia (32°C rectal temperature). We correlated the measured concentrations of S-100 protein in CSF with the results of evoked potential monitoring during surgery and the number of intercostals reimplanted and oversewn. Results: In all the patients, the concentration of S-100 protein was increased in CSF. The highest concentration of S-100 protein was found in the CSF sample taken 5 minutes after reperfusion of the critical aortic segment. There was a good (negative) correlation between the changes in S-100 protein in CSF and the changes in motor evoked potential monitoring during the cross-clamp period. The best (negative) correlation was detected between the S-100 protein elevation in the CSF sample drawn 5 minutes after reperfusion and the tcMEP amplitude reduction during clamping (r = –0.73; P = .007). No relation was found between the S-100 protein dynamics in CSF and somatosensory evoked potential monitoring. A positive (r = 0.58; P = .05) correlation was found between the change in tcMEP amplitude during clamping and the number of reattached intercostals. A moderate to good (r = –0.5 to –0.7; P < .05) correlation between the number of reattached intercostals and the changes in S-100 protein concentration in CSF during TAAA surgery was found. Our data show that transient elevations in S-100 protein after cross clamping are larger in those patients with marked decrease in tcMEP from baseline during the cross-clamp period. Conclusion: A correlation is shown between an increasing concentration of S-100 protein in CSF and a reduction in tcMEP amplitude during cross clamping of the aorta. The S-100 protein in CSF seems to be a marker of potential clinical value in the evaluation of the effects of procedures to detect and reduce spinal cord ischemia. (J Vasc Surg 1999;30:293-300.)

S-100 protein concentration is increased in patients with malignant melanoma

S-100 protein concentration is increased in patients with malignant melanoma

A sensitive ELISA for glial fibrillary acidic protein: application in CSF of children

In the present study we describe a sensitive ELISA for determination of glial fibrillary acidic protein (GFAP). To validate the method combined determinations of GFAP and S-100 protein were performed in cerebrospinal fluid (CSF) of normal children and children with autism. The GFAP ELISA is of sandwich type and uses the biotin-avidin system. Sensitivity was 16 pg/ml. Between-day precision was 0.079 (coeff. of varience). S-100 protein concentrations were measured using a commercially available ELISA kit. Normal CSF from children and young adults were analysed. The CSF levels of GFAP in normal children were low (16–163 pg/ml). Both GFAP and S-100 protein concentrations correlated with age ( P < 0.01 and P < 0.05, respectively), but the GFAP increment was more pronounced, probably reflecting the age-dependent expansion of the fibrillary astrocytes in the central nervous system (CNS). GFAP levels in children with infantile autism were higher than those in normal children of the same age range. S-100 protein concentrations were similar in both groups. High levels of GFAP in combination with normal S-100 protein concentrations in CSF indicates reactive astrogliosis in the CNS. In conclusion, the sensitive ELISA described makes it possible to measure low levels of GFAP present in the CSF of children. Combined assays of GFAP and S-100 protein can be used to discriminate between acute and chronic brain disorders in children.

Age-Related Changes of Neuron-Specific Enolase, S-100 Protein, and Myelin Basic Protein Concentrations in Cerebrospinal Fluid

Studies on cerebrospinal fluid (CSF) concentrations of neuron-specific enolase (NSE), S-100 protein, and myelin basic protein (MBP) in patients with neurological lesions indicate a quantitative relation between the degree of cell damage in the central nervous system (CNS) and the concentration of these CNS-specific proteins in CSF. Thus NSE, S-100, and MBP could be of use as markers for destructive processes in the CNS. We collected 937 specimens of CSF from children and adults (from newborns to age 91 years) who were undergoing a diagnostic lumbar puncture for several clinical indications. Of these, 79 samples from subjects ranging in age from 0.7 to 66 years could be used retrospectively to construct a reference interval according to our criteria. In these 79 samples no sex dependency existed. The relative increase of NSE, S-100, and MBP with age was similar (1% per year), suggesting a common underlying mechanism. These results emphasize the necessity of using age-matched reference values when the CNS-specific proteins are to be evaluated in neurological diseases. We also present three case histories to discuss the possible clinical relevance of the measurement of NSE, S-100, and MBP in children and adults.

Determination of S-100 and glial fibrillary acidic protein concentrations in cerebrospinal fluid after brain infarction.

We initiated the present study to evaluate the clinical value of consecutive concentration determinations of S-100 and glial fibrillary acidic proteins in cerebrospinal fluid from patients with brain infarction. We took sequential samples of cerebrospinal fluid from 28 patients within 48 hours, at 7 days, and at 18-21 days after the ictus. We measured astroglial protein concentrations using an enzyme-linked immunosorbent assay and also determined size of the infarction (computed tomography), clinical state of the patient (simplified activities of daily living test), blood-brain barrier dysfunction (cerebrospinal fluid/serum albumin ratio), and a myelin marker (myelin basic protein). We found a transient increase of both proteins in the cerebrospinal fluid during the first week after the ischemic stroke (p less than 0.05). This increment was significantly correlated with the size of the infarction and the clinical state of the patients. Transient release of astroglial proteins into the cerebrospinal fluid possibly reflects initial focal ischemic damage and, in the later phase, ongoing destruction of astroglial cells in the penumbra zone. We suggest that determinations of cerebrospinal fluid astroglial protein concentrations can be used to estimate ischemic brain damage, which should be of particular value in clinical trials of pharmacological agents, such as calcium antagonists, on stroke patients.

Increases of Neuron-specific Enolase, S-100 Protein, Creatine Kinase and Creatine Kinase BB isoenzyme in CSF following intraventricular catheter implantation

In 15 patients without acute brain injury the concentrations of Neuron-specific Enolase (NSE), S-100 Protein (S-100), Creatine Kinase (CK), and Creatine Kinase BB isoenzyme (CK-BB) in ventricular cerebrospinal fluid (CSF) were measured immediately after lateral ventricle cannulation for diagnostic or treatment purposes. From patients who were treated with a shunt another CSF sample was obtained one week after shunt implantation by puncture of the antechamber of the valve. The CSF concentrations of NSE, S-100, CK and CK-BB after cannulation were found to be of the same order as found in patients with severe head injury, stroke or subarachnoid haemorrhage. One week after shunt implantation the concentrations of S-100, CK and CK-BB had returned to normal levels in almost all patients, while the NSE concentrations remained elevated. These findings indicate that the sampling procedure may result in contamination of CSF with NSE, S-100, CK and CK-BB and they should be taken into account in the prognostic evaluation of enzyme concentrations after brain injury.

S-100 protein in cerebrospinal fluid after aneurysmal subarachnoid haemorrhage: relation to functional outcome, late CT and SPECT changes, and signs of higher cortical dysfunction.

The concentration of S-100 protein measured in ventricular cerebrospinal fluid (CSF) from 32 patients with subarachnoid haemorrhage (SAH) during the acute phase was related to features on admission such as the Hunt and Hess neurological scale and the amount of blood at the first computed tomography (CT). The S-100 values were also related to functional outcome assessed by the Glasgow outcome scale (GOS) at 12 months. Twenty-two patients were re-examined more than 2 years after the SAH, and the initial S-100 values were related to signs of structural brain damage at CT and single photon emission computed tomography (SPECT) and to the results of neuropsychological evaluation (NPE). NPE included standardized tests for memory functions, intellectual functions, visuo-spatial abilities, sensory-motor functions, and concept formation. Life-adjustment was assessed by two separate questionnaires. Tests for agnostic dysfunction and the Western aphasia battery test (WABT) were also performed. Patients who were functionally disabled or ultimately died had significantly higher initial CSF concentrations of S-100 protein than patients showing good recovery. Patients with low-attenuated regions and/or increased ventricular size at CT and/or regionally decreased tracer uptake on SPECT had higher S-100 levels during days 2-8 than had patients showing no such changes. Logistic and multiple regression analysis of all characteristics assessed during the acute phase after SAH showed that the CSF S-100 concentration during days 2-8 was the factor best correlated to GOS and findings on CT and/or SPECT. All patients showed varying degrees of cognitive impairment at follow-up. The results of NPE and the WABT were related to outcome assessed by GOS and to increased ventricular size on CT. Women had a stronger feeling of maladjustment, but the scores for life adjustment were otherwise not related to other outcome criteria. It is concluded that the ventricular CSF S-100 concentration during the acute phase after SAH is related not only to the functional outcome as assessed by GOS but also to signs of brain damage seen on late CT and SPECT.

The S-100 protein in cerebrospinal fluid: A simple ELISA method

A simple ELISA method is described for determinations of S-100 protein concentrations in CSF. The assay has a useful range of 200–3200 pmol/l. The precision of the ELISA was estimated using a pool of CSF. The coefficient of variation was 0.18 within assay, 0.17 between assay and 0.17 between day. The S-100 protein is stable in the CSF as no measurable differences in S-100 concentrations were observed in samples stored at room temperature for 2 days. No correlation between age and S-100 concentration was found when determinations were performed in CSF from neurologically healthy males. Furthermore, no changes of S-100 was observed in a lumbocisternal CSF gradient from patients with normal pressure hydrocephalus. Thus, the described ELISA represents an easy to handle and reliable method, well suited for routine determinations of S-100 protein concentration in the CSF.

S-100 protein in cerebrospinal fluid of patients with subarachnoid haemorrhage: a potential marker of brain damage.

Concentrations of S-100 protein in cerebrospinal fluid (CSF) were measured by a recently developed radioimmunoassay (RIA) in 45 patients with subarachnoid haemorrhage (SAH), 44 with verified ruptured aneurysm. In each of 43 patients 2-15 serial CSF samples were analysed, and in the remainder 1 sample was examined. The concentrations of S-100 protein proved to be related to the brain damage caused by the SAH, indexed as outcome (Glasgow Outcome Scale). The S-100 concentrations were related to the severity of the haemorrhage and to the development of delayed ischaemic deterioration. Delayed ischaemic deterioration (vasospasm) was usually accompanied by an increase in CSF S-100 concentration after 4 days. Patients in whom no S-100 value exceeded 20 ng S-100 per ml during the course of the disease had a favourable outcome, whereas patients in whom one or several CSF samples contained more than 100 ng/ml became severely disabled or vegetative or died. The present study suggests that CSF S-100 analysis may be used as an objective and early measure of the degree of brain damage sustained by the SAH patient.

Detection limits of different approaches in behavioral teratology, and correlation of effects with neurochemical parameters

Five laboratories collaborated in the evaluation of detection limits of different testing concepts in behavioral teratology. In one laboratory, rat dams were treated by gavage with five doses of methylmercury (0.0, 0.025, 0.05, 0.5, and 5.0 mg/kg/day). The treatment period was restricted to days 6 to 9 of gestation. The usual reproduction parameters were assessed in the dams. The offspring (88–99 per group) were subjected to a routine developmental and behavioral testing battery. After completion of these tests, random samples of the animals were further investigated in four other laboratories using the following techniques: auditory startle habituation, visual discrimination and figure-8 activity monitor; wheel-shaped activity monitor and spatial alternation operant conditioning; two-compartment locomotor activity, passive avoidance and male ultrasonic vocalization during sexual behavior; assays of the weight of different brain areas, their glial fibrillary acidic (GFA) protein and S-100 protein concentration. The following dose-dependent effects were noted in ascending dose sensitivity order: delayed vaginal opening; increased and more variable passiveness in spatial alternation; impaired swimming behavior, increased GFA protein concentration in the cerebellar vermis; increased auditory startle amplitude, decreased intertrial interval pokes in the visual discrimination test, increased percentage of visits in passive area of figure-8 activity monitor, increased path iteration frequencies and decreased local activity in the wheel-shaped activity monitor, decreased locomotor activity in the two-compartment monitor, increased cerebellar vermis weight, and decreased S-100 protein in the hippocampus. Therefore, this study showed comparable sensitivities for the behavioral testing battery, for some automated multiparametric test systems and for the neurochemical assays.