The soluble 60-kDa tumour necrosis factor receptor: no difference found between patients with relapsing-remitting multiple sclerosis and controls: increasing levels are associated with the recovery from Guillain-Barré syndrome

We determined serum and cerebrospinal fluid (CSF) levels of the soluble 60-kDa tumour necrosis factor (TNF) receptor (sTNF-R p60) in 50 patients with relapsing-remitting multiple sclerosis (MS) and in 18 patients with Guillain-Barré syndrome (GBS). Neither in serum nor in CSF samples was there a statistically significant difference between mean receptor concentrations of patients with MS (serum: 1064, SD 262 pg/ml; CSF: 555, SD 130 pg/ml), with other noninflammatory neurological diseases (serum: 1008, SD 248 pg/ml; CSF: 530, SD 112 pg/ml) and with healthy control subjects (serum: 918, SD 180 pg/ml). In order to determine disease activity, magnetic resonance imaging (MRI) of the brain was performed in all MS patients. The mean sTNF-R p60 levels of patients who showed gadolinium DTPA enhancement on MRI were not different from those without enhancement (1034, SD 274 pg/ml vs 1099, SD 248 pg/ml in serum samples and 546, SD 109 pg/ml vs 565, SD 152 pg/ml in CSF samples). In GBS, the sTNF-R p60 levels of serum and CSF samples were significantly higher than in MS and all control groups except for the group with viral meningitis (VM) (GBS: 1544, SD 834 pg/ml in serum, 882, SD 147 pg/ml in CSF; VM: 1518, SD 375 pg/ml in serum, 1131, SD 611 pg/ml in CSF; P < 0.001 for serum samples and P < 0.005 for CSF samples). Serial serum sTNF-R p60 measurements in 13 patients with GBS showed an increase in receptor levels parallel with the recovery from the disease (1276, SD 374 pg/ml at the time of disease onset, 1554, SD 482 pg/ml 14–24 days later and 1787, SD 525 pg/ml after 28–32 days). From our results and the conflicting data of previous studies, we could not agree with the suggestion that the assessment of sTNF-R p60 in MS patients is a useful marker for disease activity. In GBS, subsequently increasing sTNF-R p60 levels are associated with recovery from the disease. It remains to be shown whether they might represent a relevant pathogenetic factor during this stage of GBS. Received: 31 October 1997 Received in revised form: 26 January 1998 Accepted: 10 February 1998     

Elevated CSF beta-endorphin immunoreactivity in Rett's syndrome: report of 158 cases and comparison with leukemic children.

Because some symptoms of Rett's syndrome are suggestive of excessive endogenous opioid activity, we measured the levels of beta-endorphin-like immunoreactivity in lumbar CSF from 158 affected female patients and from 13 female controls. The mean (+/- SE) control level of beta-endorphin immunoreactivity in CSF was 35.3 +/- 2.8 pg/ml (range, 23 to 48 pg/ml), whereas those with Rett's syndrome had a mean level of 95.3 +/- 3.6 pg/ml (range, 31 to 293 pg/ml). The levels of beta-endorphin immunoreactivity in initial CSF samples exceeded the control range in 90% of the patients with Rett's syndrome. The mean beta-endorphin immunoreactivity was also elevated in CSF from leukemic children (119.2 +/- 16.9 pg/ml; range, 40 to 159 pg/ml), relative to the control group. These results are consistent with the hypothesis that some symptoms of Rett's syndrome may be associated with excessive endogenous opioid levels in the CNS.     

Vasopressin in the cerebrospinal fluid of febrile children with or without seizures

Immaturity in water and electrolyte balance in the brain has been considered to increase the susceptibility of young animals and children to febrile convulsions (FCs). Arginine-vasopressin (AVP) is involved in the regulation of several centrally mediated events such as modulation of fever and the ease with which water permeates into and out of the brain. To evaluate the possible role of AVP in the control of water balance and susceptibility to convulsions during fever we measured the AVP concentration in the cerebrospinal fluid (CSF) and plasma of febrile children with or without convulsions. The febrile population consisted of 47 children, of whom 29 experienced seizures during fever. Seven children with epileptic symptoms and 18 children without seizures were included as nonfebrile controls. The CSF AVP concentration in febrile children without seizures and in nonfebrile convulsive children was significantly lower (0.60 ± 0.07 pmol / 1, mean ± SEM,P < 0.01 and 0.65 ± 0.19 pmol/l,P < 0.05, respectively) than in nonfebrile children without convulsions (0.83 ± 0.06 pmol/1). However, the levels of CSF AVP were not significantly different in children with FCs (0.71 ± 0.06 pmol/1) compared with other groups. CSF AVP correlated with the CSF osmolality (r = 0.33, P = 0.02). No statistical differences in plasma AVP levels between the groups could be found. The present data provide support for the hypothesis of synchronous regulation of osmolality and AVP concentration in CSF. During fever the concentration of CSF AVP was lower in nonconvulsive children compared with nonfebrile nonconvulsive children. CSF AVP levels were not affected in febrile children by convulsions.     

Cerebrospinal fluid somatostatin levels in febrile seizures and epilepsy in children

We analysed the level of cerebrospinal fluid (CSF) somatostatin in children with febrile seizures and epilepsy. In the febrile seizure group (n = 23), the somatostatin level was 83.9 +/- 11.2 pg/ml, which was significantly higher than that of age-matched controls. CSF samples obtained within 3 h of the last seizure had higher somatostatin levels (106.1 +/- 12.4 pg/ml;n = 14) than did the CSF obtained after 3 h (49.4 +/- 15.6 pg/ml;n = 9). The mean somatostatin level in the epilepsy group was 35.3 +/- 4.3 pg/ml (n = 34), and was distributed as follows: 27.6 +/- 3.6 pg/ml in the idiopathic generalized epilepsy group (n = 16), 44.0 +/- 9.4 pg/ml in the symptomatic generalized epilepsy group (n = 13), and 37.2 +/- 10.1 pg/ml in the partial epilepsy group (n = 5). The levels in each group were significantly higher than those in age-matched controls. Somatostatin is a hypothalamic tetradecapeptide with excitatory effects on neurons in children with febrile seizures and epilepsy. The finding that patients with convulsive disease had elevated levels of CSF somatostatin suggests that somatostatin release is somehow related to seizure activity. It remains to be determined whether this is due to increased release from over-active excitatory neurons or leakage from damaged or anoxic neurons, secondary to seizure activity.     

Cerebrospinal fluid arginine vasopressin in degenerative disorders and other neurological diseases.

Arginine vasopressin (AVP) was determined in plasma and lumbar CSF from 46 patients with Parkinson's disease, dementia, cerebrovascular disease, multiple sclerosis and other, mostly peripheral neurological disorders. The mean plasma concentration of AVP was 1.62 microU/ml, the CSF concentration 1.14 microU/ml and the gradient CSF/plasma 0.72. There was a good correlation between the plasma and the CSF values in most patients. No sex difference could be found. A slight decrease of the CSF values could be found with increasing age. Significantly higher CSF-AVP values were found in patients with cerebrovascular disease, whereas lower CSF values were found in patients with dementia and Parkinson's disease. However there were decreased CSF/plasma gradients in patients with dementia and Parkinson's disease to about 0.30 compared to 0.98 in patients with peripheral neurological disorders. Patients with multiple sclerosis had an increased IgG index indicating an intrathecal IgG production but there was no obvious correlation between this and the AVP concentrations in plasma and CSF, nor with the total CSF protein content, nor with the albumin and IgG concentrations in plasma and CSF.     

Neuron-specific enolase levels in the cerebrospinal fluid of neurologically healthy children

Levels of neuron-specific enolase (NSE) levels in the cerebrospinal fluid (CSF) of children without neurological disease were assessed. CSF samples were obtained from 37 subjects aged between 1 month and 13 years. All subjects had undergone lumbar puncture for diagnostic purposes, and were subsequently shown not to be suffering any form of neurological disease. NSE levels in CSF were determined by an enzyme immunoassay method. NSE level ranged from below the detection limit to 4.8 ng/ml (1.52+/-1.01 ng/ml). The present results may be useful as a basis for defining reference levels of NSE in CSF in post-neonatal children.     

Interleukin-1β is increased in the cerebrospinal fluid of patients with small infarcts

Background and purpose:  Interleukin-1beta (IL-1β) and interleukin-6 (IL-6) are involved in inflammatory responses during large vessel occlusion in animal models. The aim of this study was to investigate the intrathecal levels of cytokines in patients with acute small infarcts.
Methods:  Forty patients with acute minor stroke and 32 non-stroke patients (including 29 age- and gender-matched subjects) who received operations with spinal anesthesia were studied prospectively and underwent measurements of cerebrospinal fluid (CSF) IL-1β and IL-6 levels.
Results:  After an age- and gender-matched analysis of 58 patients (29 pairs), the mean intrathecal levels of IL-1β were 0.80 pg/ml in patients with small infarcts and 0.59 pg/ml in non-stroke patients ( P  <   0.0001). In addition, the mean CSF levels of IL-6 were 21.54 pg/ml and 7.52 pg/ml in the stroke and control groups, respectively ( P  =   0.38). These results were consistent with the data without matching. The CSF levels of IL-1β in the 40 stroke patients were significantly higher than in the 32 non-stroke controls ( P  <   0.0001).
Conclusions:  The proinflammatory cytokine IL-1β, but not IL-6, remained elevated in the CSF of patients in the acute stage of small infarcts.     

Vitamin B12 levels in serum and cerebrospinal fluid of people with Alzheimer's disease

Vitamin B12 levels in the serum and the cerebrospinal fluid (CSF) were compared between patients with Alzheimer's disease (AD) and senile dementia of Alzheimer's type (SDAT) (AD group) and patients with multi-infarct dementia (MID group). The B12 levels in the serum and the CSF were 742 +/- 359 pg/ml and 28 +/- 7 pg/ml (mean +/- SD), respectively, in the AD group, and 962 +/- 254 pg/ml and 50 +/- 26 pg/ml, respectively, in the MID group. CSF B12 levels were significantly lower in the AD group than in the MID group, whereas the serum levels were not different. At the same time, the serum levels of almost all patients were within the normal range, whereas the CSF levels were 25 pg/ml or lower in 10 of 12 AD patients. Therefore, this low level in the CSF is considered to be a characteristic finding in the AD group.     

Intracerebroventricular infusion but not bolus injection of vasopressin increases the cerebrospinal fluid pressure in awake rabbits

The effect of intracerebroventricular infusion or injection of arginine vasopressin (AVP) was examined in awake rabbits with permanent ventricular cannulae. Intracerebroventricular infusion of artificial cerebrospinal fluid (CSF) 43 μl min^–1 containing AVP concentrations exceeding 0.4 ng ml^–1, equivalent to an AVP infusion rate of 17.2 pg min^–1, caused a dose-dependent increase in intracranial pressure (ICP) of 3 to 5 mmHg after 30-50 min of AVP infusion. Intracerebroventricular bolus injection of equivalent doses of AVP did not provoke changes in ICP. At the end of the experiments cisternal CSF concentrations of AVP were higher after infusion of AVP than after injection of the same amount of AVP. The mean arterial blood pressure increased slightly in the group of animals infused with AVP at rates above 17.2 pg min^–1. It is concluded that intracerebroventricular infusion of AVP increases ICP in awake rabbits but the mechanism responsible for the elevation of ICP remains speculative.     

Level of transforming growth factor beta 1 is elevated in cerebrospinal fluid of children with acute bacterial meningitis

We investigated the levels of transforming growth factor beta 1 (TGF-β1) in cerebrospinal fluid (CSF) in children with meningitis, with a view to prognostic relevance. CSF TGF-β1 levels on admission were measured by a sandwich enzyme immunoassay in children with bacterial meningitis (n = 16), aseptic meningitis (n = 12), and control subjects without evidence of central nervous system (CNS) infection (n = 16). Patients were followed up for a mean duration of 13 months, and neurodevelopmental sequelae was determined for those with bacterial meningitis. On admission, CSF TGF-β1 levels were significantly higher in children with bacterial meningitis (mean, standard error, 32.92, 2.36 pg/ml) as opposed to those with aseptic meningitis (25.26, 1.72 pg/ml) (P = 0.0155), or control subjects (20.53, 1.05 pg/ml) (P < 0.0001). The CSF TGF-β1 levels in children with aseptic meningitis were higher than those in the control group, but without significance (P = 0.02). No apparent correlation existed between CSF TGF-β1 levels and CSF protein or cell counts in patients with bacterial meningitis. No significant difference in CSF TGF-β1 levels was found between patients with or without major sequelae following bacterial meningitis. Received: 19 March 1997 Received in revised form: 24 June 1997 Accepted: 20 August 1997     

Interleukin 1beta and interleukin 6 relationship with paediatric head trauma severity and outcome.

BACKGROUND: Based on the known inflammatory role of interleukins (IL), we evaluated IL-1beta and IL-6 expressions and their association with the severity of traumatic brain injury (TBI; Glasgow Coma Scale [GCS]) and the outcome (Glasgow Outcome Score [GOS]) recorded in a paediatric population. DESIGN: The design was a perspective observational clinical study carried out in the paediatric intensive care unit of the University Hospital. METHODS: We measured the IL-1beta and IL-6 levels in 14 children with severe TBI (patients) and in 12 children with obstructive hydrocephalus (control group). Cerebrospinal fluid (CSF) and plasma samples were collected 2 h (T1) and 24 h (T2) after TBI. Interleukins were assayed using the immunoenzymatic method. RESULTS: The IL-1beta mean level was significantly lower than the IL-6 mean level both in the CSF and plasma of TBI children. In the CSF, the IL-1beta level increased from 55.71+/-72.79 pg/ml at T1 to 106.10+/-142.12 pg/ml at T2 and the IL-6 level increased from 405.43+/-280.28 pg/ml at T1 to 631.57+/-385.35 pg/ml at T2; a similar trend was observed in plasma. We found a statistically significant correlation between the increase in CSF and plasma interleukin levels between T1 and T2 and head injury severity (GCS相似文献   

Intracerebroventricular infusion but not bolus injection of vasopressin increases the cerebrospinal fluid pressure in awake rabbits

The effect of intracerebroventricular infusion or injection of arginine vasopressin (AVP) was examined in awake rabbits with permanent ventricular cannulae. Intracerebroventricular infusion of artificial cerebrospinal fluid (CSF) 43 microliters min-1 containing AVP concentrations exceeding 0.4 ng ml-1, equivalent to an AVP infusion rate of 17.2 pg min-1, caused a dose-dependent increase in intracranial pressure (ICP) of 3 to 5 mmHg after 30-50 min of AVP infusion. Intracerebroventricular bolus injection of equivalent doses of AVP did not provoke changes in ICP. At the end of the experiments cisternal CSF concentrations of AVP were higher after infusion of AVP than after injection of the same amount of AVP. The mean arterial blood pressure increased slightly in the group of animals infused with AVP at rates above 17.2 pg min-1. It is concluded that intracerebroventricular infusion of AVP increases ICP in awake rabbits but the mechanism responsible for the elevation of ICP remains speculative.     

Serum and cerebrospinal fluid concentration of inflammatory proteins MIP-1-alpha and MIP-1-beta and of interleukin 8 in the course of borreliosis

Chemokines constitute a group of cytokines with a strong chemotactic action, playing an important role in the pathogenesis of inflammatory responses, including infectious meningitis. The results of in vitro experiments suggest synthesis of chemokines during Borrelia burgdorferi infection. The aim of this study was to investigate serum and cerebrospinal fluid (CSF) concentrations of the following chemokines: interleukin-8 (Il-8) and macrophage inflammatory protein 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta) in patients with neuroborreliosis. The study group consisted of 20 patients admitted to Neuroinfections and Infectious Diseases Department of the Medical University in Bia?ystok. The control group consisted of 12 healthy persons from whom blood samples were obtained, and 10 patients without meningitis, from whom CSF samples were taken for diagnostic purposes. Chemokine concentrations were measured with ELISA kits before treatment (baseline) and after 2 weeks of antibiotic therapy (post-treatment). Mean serum concentrations of chemokine were elevated in neuroborreliosis patients at baseline (Il-8--mean +/- SD = 668.25 +/- 661.51 pg/ml, MIP-1 alpha--124.90 +/- 89.37 pg/ml, MIP-1 beta--233.40 +/- 298.40 pg/ml) as compared to these in the control group (Il-8-23.72 +/- 7.68 pg/ml, MIP-1 alpha--36.81 +/- 4.74 pg/ml, MIP-1 beta--70.41 +/- 16.41 pg/ml). Post-treatment mean concentrations of Il-8 (197.70 +/- 285.56 pg/ml) and MIP-1 beta (102.70 +/- 42.56 pg/ml) remained significantly elevated, while the mean concentration of MIP-1 alpha (53.65 +/- 38.50 pg/ml) was insignificantly higher than that in the control group. The Il-8 mean concentration was the most elevated comparing to the controls and has decreased most significantly during the treatment. CSF concentrations of chemokines were significantly elevated both at baseline (Il-8--754.95 +/- 535.83 pg/ml, MIP-1 alpha--24.35 +/- 4.88 pg/ml, MIP-1 beta--27.6 +/- 8.38 pg/ml) and post-treatment (Il-8--98.20 +/- 74.74 pg/ml, MIP-1 alpha--18.60 +/- 2.87 pg/ml, MIP-1 beta--16.90 +/- 4.38 pg/ml) in comparison with the controls (Il-8--10.43 +/- 2.70 pg/ml, MIP-1 alpha--8.17 +/- 1.54 pg/ml, MIP-1 beta--7.27 +/- 1.58 pg/ml). MIP-1 alpha and MIP-1 beta CSF concentrations were significantly lower than their concentrations in serum. The Il-8 CSF concentration did not differ significantly from its serum concentration. However, in some patients Il-8 CSF concentration was much higher than that in the serum, which suggests its significant synthesis within the cns and its role in the pathogenesis of B. burgdorferi meningitis. Chemokine CSF concentrations were not correlated with cytosis and CSF protein concentration. The results indicate the induction of Il-8, MIP-1 alpha and MIP-1 beta synthesis in the course of neuroborreliosis and a decrease of their concentrations during 2 weeks of treatment, however, without reaching the normal values.     

Levels of transforming growth factor alpha (TGF-a)in human cerebrospinal fluid

In this study, we investigated cerebrospinal fluid of patients with various neurologicalsymptoms for the presence of transforming growth factor alpha (TGF-a). 41 samples ofcerebrospinal fluid were collected by lumbar puncture performed routinely due to the clinicalsuspicion of neurological disease from 22 females (age 15–80 years, median 42 years) and from19 males (age 18–82 years, median 48 years). A highly sensitive and specific radioimmunoassaywas used to determine the concentration of TGF-a in the samples. The detection limit of the assaywas about 200 pg TGF-a. There was no cross-reactivity to human EGF. We showed CSF indeeddoes contain TGFa. As TGF-a was detected in all 41 samples investigated, this growth factorappears to be a constant component of CSF. The mean concentration was 5.5 ng TGF-a (S.D.±2.7 pg/ml, range 1.1 to 13.9 pg/ml). There was no significant correlation between TGF-aconcentration in CSF and age (r=−0.006) and there was no significant differencebetween females (mean 5.8±3.10 pg/ml) and males (mean 5.2±1.96 pg/ml). No diagnosis wasover represented in patients with TGF-a concentrations above or below 1 S. D. off the mean.However, highest concentrations of TGF-a were found in the group of patients with peripheralneurological sensory dysfunctions and polyneuropathy. We conclude that TGF-a is not only aconstant component of human cerebrospinal fluid in adults but could also be significantly involvedin the pathophysiology of various neurological diseases. The earlier hypothesis that TGF-a couldmainly have a role in brain development needs hence to be re-evaluated.     

BDNF serum and CSF concentrations in Alzheimer's disease, normal pressure hydrocephalus and healthy controls

Alzheimer's disease (AD) and normal pressure hydrocephalus (NPH) are common forms of dementia in the elderly. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain. BDNF serum and cerebrospinal fluid (CSF) concentrations were assessed by a sensitive ELISA in 27 AD patients in comparison to 9 NPH patients and 28 age-matched healthy controls (10 CSF samples). We found a significant decrease of BDNF serum concentration in AD (18.6ng/ml) and NPH patients (18.1ng/ml) as compared to healthy controls (21.3ng/ml; p=0.041/p=0.017). BDNF serum concentrations did not correlate with CSF levels, age or MMSE scores both in AD and NPH patients. In unconcentrated CSF samples, BDNF could be detected in AD patients in 8/27 cases (29.6%; mean of 4.6pg/ml), in NPH patients in 1/9 cases (11.1%; mean of 6.4pg/ml) and in the control subjects in 5/10 cases (50%; mean of 1.6pg/ml) with no significant differences as regards mean concentration and frequency of detectable BDNF in CSF. The decrease of BDNF serum levels in AD and NPH may reflect a lack of trophic support and thus contribute to progressive degeneration in both diseases. In contrast to serum, CSF seems to be no useful source to determine BDNF in AD or NPH because of too low concentrations. Further examinations have to follow to elucidate the potential sources and the meaning of reduced BDNF levels in the blood in AD and NPH.     

Decreased β-phenylethylamine in CSF in Parkinson's disease

OBJECTIVE—To determine the concentrations ofβ-phenylethylamine (PEA) in CSF in patients with Parkinson'sdisease, and to evaluate the relation between concentration of PEA inCSF and severity of Parkinson's disease.
METHODS—Using gas chromatography-chemicalionisation mass spectrometry, CSF concentrations of PEA were measuredin 23 patients with Parkinson's disease (mean age, 64.0 (SD 8.2)years), of whom three were at Hoehn and Yahr stage II, 11 were at stageIII, and nine were at stage IV. Comparison was made with eight patientswith neuropathy (mean age, 57.0 (SD 19.2) years) and 12 controlswithout neurological disease (mean age, 57.6 (SD 4.8) years).
RESULTS—Concentrations of PEA in CSF inParkinson's disease were significantly lower (mean 205 (SD 131) pg/ml)than in patients with peripheral neuropathy (433 (SD 254) pg/ml) andcontrols (387 (SD 194) pg/ml). The concentrations of PEA in CSFcorrelated negatively with Hoehn and Yahr stage (P<0.01).
CONCLUSIONS—There are decreased CSF concentrationsof PEA in patients with Parkinson's disease.

     

Decreased Levels of Amyloid-beta 1-42 in Cerebrospinal Fluid of Creutzfeldt-Jakob Disease Patients

Creutzfeldt–Jakob disease (CJD) is a rare neurodegenerative disease caused by the prion protein. In the search for biochemical markers for CJD, cerebrospinal fluid (CSF) of 101 patients was analysed for 14-3-3 protein, hTau-protein and amyloid-beta 1-42 (Abeta_1-42). The 14-3-3 test had a specificity of 91.5% and a sensitivity of 84%. The hTau test resulted in 95% specificity and 74% sensitivity, when a cut-off of 1530 pg/ml was used. Abeta_1-42 detection in CSF of 29 probable or definite CJD patients revealed significantly decreased values (p=0.01) compared to a group of 22 neurological controls. In the CJD patients a mean of 319+/-102 pg/ml was found. In the neurological control group a mean of 553+/-268 pg/ml was observed. In patients with a false positive 14-3-3 test (n=5) a mean of 716+/-441 pg/ml was found. We conclude that determination of Abeta_1-42 levels in CSF can be useful for identifying false positive 14-3-3 results in suspected CJD patients. We also compared the presence of senile plaques and the Abeta_1-42 levels in CSF of CJD patients. No clear correlation between them was found in this series. This signifies that the deceased Abeta_1-42 levels in CSF are not just due to plaque retention but that other mechanisms must also play a role.     

Mediator release in cerebrospinal fluid of human immunodeficiency virus-positive patients with central nervous system involvement.

In this study we evaluated the release of some mediators of inflammatory reactions such as histamine (H), leukotriene B4 (LTB4), leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) in the cerebrospinal fluid (CSF) of 15 patients with acquired immunodeficiency syndrome (AIDS), eight with opportunistic infections of the central nervous system (CNS) and seven without HIV-related neurological pathology, and of 25 HIV-negative control subjects with other neurological diseases. The cerebrospinal LTB4 level was increased in all the AIDS patients (mean 348 pg/ml); the control group revealed normal levels of LTB4 in the CSF (mean 63.2 pg/ml). The PGD2 level in the HIV-positive (mean 264 pg/ml) patients was higher than of the control subjects (mean 50 pg/ml), while low LTC4 levels were found both in the HIV-positive and control groups. We did not find any significant concentration of H in the CSF of either the HIV-positive or the control subjects. These findings may be due to the presence of chronic HIV infection or to the opportunistic infections of the CNS that so often occur in the latest stages of the disease.     

Levels of transforming growth factor alpha (TGF-alpha) in human cerebrospinal fluid.

In this study, we investigated cerebrospinal fluid of patients with various neurological symptoms for the presence of transforming growth factor alpha (TGF-alpha). 41 samples of cerebrospinal fluid were collected by lumbar puncture performed routinely due to the clinical suspicion of neurological disease from 22 females (age 15-80 years, median 42 years) and from 19 males (age 18-82 years, median 48 years). A highly sensitive and specific radioimmunoassay was used to determine the concentration of TGF-alpha in the samples. The detection limit of the assay was about 200 pg TGF-alpha. There was no cross-reactivity to human EGF. We showed CSF indeed does contain TGFalpha. As TGF-alpha was detected in all 41 samples investigated, this growth factor appears to be a constant component of CSF. The mean concentration was 5.5 ng TGF-alpha (S.D. +/- 2.7 pg/ml, range 1.1 to 13.9 pg/ml). There was no significant correlation between TGF-alpha concentration in CSF and age (r = -0.006) and there was no significant difference between females (mean 5.8+/-3.10 pg/ml) and males (mean 5.2+/-1.96 pg/ml). No diagnosis was over represented in patients with TGF-alpha concentrations above or below 1 S.D. off the mean. However, highest concentrations of TGF-alpha were found in the group of patients with peripheral neurological sensory dysfunctions and polyneuropathy. We conclude that TGF-alpha is not only a constant component of human cerebrospinal fluid in adults but could also be significantly involved in the pathophysiology of various neurological diseases. The earlier hypothesis that TGF-alpha could mainly have a role in brain development needs hence to be re-evaluated.     

Changes in centrally released arginine vasopressin by stimulation of the medullary reticular formation]

It has been reported that after 40 minutes of stimulation of the medullary reticular formation (MORF), widespread significant increase by 1.4% to 2.8% in brain water content occurs in white matter of the injured hemisphere. Recent studies indicate that centrally released arginine vasopressin (AVP) influences water permeability of the brain in both normal and pathological conditions. The present study was carried out to clarify the effect of electrical stimulation of MORF on centrally released AVP. The cats were divided into three groups. In group A (16 cats), electrical stimulation of MORF (1msec, 5V, 50Hz) was carried out for 80 minutes in normal cats. In group B (11 cats), stimulation was started 17 hours after cold injury under the same conditions and carried out for 80 minutes. In group C (10 cats), angiotensin II was administered to elevate blood pressure to the same degree as during MORF stimulation 17 hours after cold injury. AVP concentrations in the cerebrospinal fluid (CSF), plasma and brain tissue of the injured and non-injured white matter were measured by radioimmunoassay. Plasma osmolality was also determined by the freezing point depression method. Normal values (mean +/- S. D.) of CSF and plasma AVP were 4.0 +/- 2.2 and 9.9 +/- 3.6 pg/ml respectively. Plasma AVP and osmolality did not show significant changes before and at the end of experiments in all groups. There were no significant changes in CSF AVP by induced hypertension for 80 minutes (Group C). Stimulation of the medullary reticular formation resulted in significant and progressive increase in CSF AVP in normal and injured brain (Group A, B).(ABSTRACT TRUNCATED AT 250 WORDS)