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A protein-binding assay for direct determination of adenosine 3',5'-monophosphate in amniotic fluid, cerebrospinal fluid, plasma, and urine.

An adenosine 3',5'-monophosphate (cyclic AMP)-binding protein was isolated from bovine skeletal muscle. This preparation showed maximum binding capacity for cyclic AMP at the physiological pH of amniotic fluid, cerebrospinal fluid, and plasma and had a high association constant of 1.4x10(9) 1/mol. This preparation of binding protein, together with albumin and EDTA in the assay buffer, gave a sensitive and specific competitive protein-binding assay that permitted direct determination of cyclic AMP in the biological fluids mentioned above.

Amniotic Fluid

Biological correlates of elevated soluble TREM2 in cerebrospinal fluid.

Cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cells-2 (sTREM2) is an emerging biomarker of neuroinflammation in Alzheimer's disease (AD). Yet, sTREM2 expression has not been systematically evaluated in relation to concomitant drivers of neuroinflammation. While associations between sTREM2 and tau in CSF are established, we sought to determine additional biological correlates of CSF sTREM2 during the prodromal stages of AD by evaluating CSF Aβ species (Aβx-40), a fluid biomarker of blood-brain barrier integrity (CSF/plasma albumin ratio), and CSF biomarkers of neurodegeneration measured in 155 participants from the Vanderbilt Memory and Aging Project. A novel association between high CSF levels of both sTREM2 and Aβx-40 was observed and replicated in an independent dataset. Aβx-40 levels, as well as the CSF/plasma albumin ratio, explained additional and unique variance in sTREM2 levels above and beyond that of CSF biomarkers of neurodegeneration. The component of sTREM2 levels correlated with Aβx-40 levels best predicted future cognitive performance. We highlight potential contributions of Aβ homeostasis and blood-brain barrier integrity to elevated CSF sTREM2, underscoring novel biomarker associations relevant to disease progression and clinical outcome measures.

Alzheimer Disease

Eosinophilic granulocytes in cerebrospinal fluid: analysis of 94 cerebrospinal fluid specimens and review of the literature.

Eosinophilic granulocytes in the CSF were observed in 94 of approximately 10,000 qualitative cytologic preparations. Those cases of eosinophilia which occurred in the context of a parasitic disease or a puncture-related hemorrhage were excluded. CSF eosinophilia exceeding 1% was found in 57.5% of the cases and 5% in 23.5%. Increased cell counts were observed in 67.7% of the cases; elevated CSF protein values, in 68% to 73%; blood eosinophils, in 10.4%. There was no reason to suspect a relationship between these findings and the number of eosinophils in the CSF.--Fifty-two percent of the cases involved inflammatory diseases of the nervous system; the 18 cases of abacterial inflammation of unknown etiology were particularly striking. In the remaining cases, eosinophils were found in conjunction with cerebral ischemia and hemorrhage, with tumors, and in a relatively high percentage of children (21%). The frequency of occurrence with drained or undrained hydrocephalus was striking. A review of the pathophysiological function of eosinophils indicated that revived or corpuscular antigens were present in all cases of CSF eosinophilia in which an eosinophilic reaction was induced. Nothing can be said at this time, however, concerning the classification of the antigens.

Cell Count

Hysteresis in the relationship between cerebrospinal fluid absorption minus formation and cerebrospinal fluid pressure in the dog.

In this study the difference between cerebrospinal fluid (CSF) absorption and formation (A -- F) was measured as a function of CSF pressure in the living and dead dog. We determined this relationship between A -- F and CSF pressure during both increasing and decreasing CSF pressures. A hysteresis effect was identified in 78% of living animals, but was not seen in the dead animals. This suggests that the mechanism of CSF absorption in the living dog is nonpassive and pressure-sensitive.

Absorption

Intravenous probenecid loading. Effects on plasma and cerebrospinal fluid probenecid levels and on monoamine metabolites in cerebrospinal fluid.

Probenecid blocks the active transport from cerebrospinal fluid to blood of homovanillic acid and 5-hydroxyindoleacetic acid, thus increasing cerebrospinal fluid levels of these products of central monoamine metabolism. The half-life in plasma of probenecid given as a single intravenous infusion (40 mg per kilogram of body weight) to patients with either Huntington's chorea or Parkinson's disease averaged about 6.6 hours. In cerebrospinal fluid, peak values for homovanillic acid and 5-hydroxyindoleactic acid occurred in samples collected 8 hours after the 1-hour probenecid infusion was started. Even after 4 hours, however, levels of both monoamine metabolites were significantly increased. There was a positive correlation between cerebrospinal fluid levels of probenecid and the increase in 5-hydroxyindoleacetic acid but not homovanillic acid. Compared with the oral administration of probenecid, the intravenous infusion technique produced more consistent elevations in plasma and cerebrospinal fluid probenecid levels, greater increases in cerebrospinal fluid homovanillic acid values, and fewer gastrointestinal side effects.

Administration, Oral

Agarose electrophoresis of cerebrospinal fluid in multiple sclerosis. A simplified method for demonstrating cerebrospinal fluid oligoclonal immunoglobulin bands.

The gamma globulins in cerebrospinal fluid from almost all patients with multiple sclerosis migrate in agarose electrophoresis as abnormal discrete populations, so-called oligoclonal bands. Such bands have also appeared in cerebrospinal fluid from patients with other types of inflammatory pathology such as neurosyphilis, acute idiopathic polyneuropathy, and subacute sclerosing panencephalitis. The demonstration of cerebrospinal fluid oligoclonal bands may aid in the evaluation of patients with early or atypical multiple sclerosis. This report describes a simple method for demonstrating cerebrospinal fluid oligoclonal bands using readily available commercial reagents and apparatus. Oligoclonal bands were seen in cerebrospinal fluid from all patients with clinically definite multiple sclerosis, even though some had normal cerebrospinal fluid gamma globulin levels, and in most patients with presumptive multiple sclerosis or other inflammatory conditions of the nervous system. They were not seen in cerebrospinal fluid of control patients with a variety of other neurologic diseases.

Adolescent

[Anatomical structures, physiology and pathophysiology of cerebrospinal fluid metabolism; a review for an understanding of cerebrospinal fluid findings].

The very different macroscopic and microscopic details of the structures involved in production and reabsorption of cerebrospinal fluid in the different parts of the central nervous system are causing confusing laboratory findings in cerebrospinal fluids, the ingredients of which change even under normal condition in these different parts. Moreover the chemical ingredients of cerebrospinal fluid differ especially from the normal situation during some diseases of the central nervous system. Although we can be sure that there is much more diagnostic information in cerebrospinal fluid, we mainly prefer certain standard methods today, as there are cell counts and measuring of the protein concentration, as diagnostic parameters. Their unspecific changes during several pathologic states do not yet allow to point out the exact localization of the disease, nor can they contribute in every case in finding the cause of the disease. Therefore other and more specific diagnostic laboratory methods are to be developed, which will make possible more precise statements about the nature and the localization of central nervous system diseases.

Absorption

[Statistical analysis of cerebrospinal fluid acid-base equilibrium and cerebrospinal fluid lactate concentration in cases of brain tumors, cerebrocranial injuries and meningoencephalitis].

A statistical analysis of CSF lactate concentration and CSF pH and PCO2 was performed. The values were obtained from 211 samples taken from 76 neurosurgical patients. The values of pH and pCO2 were classified in three groups corresponding to the following three ranges of lactate concentration: below 15 mg%, 15-30 mg%, over 30 mg%. The mean values and standard deviations were calculated: suitable tests: F, t (Student), C (Cochran and Cox) were used. It was established, that statistically significant changes of CSF acid-base balance were present at lactate levels over 30 mg%. Next, the patients with lactate concentrations over 30 mg% were analysed. They were divided into three groups according to etiology: inflammatory changes, injuries, tumours. It was shown, that the CSF acid-base balance in patients with brain tumours is less disturbed then in patients with inflammatory changes or brain injury.

Acid-Base Equilibrium

Immunoelectroosmophoresis (IEOP) for detection of bacterial antigens in cerebrospinal fluid.

365 cerebrospinal fluid specimens from 259 patients were tested by the immunoelectroosmophoretic (IEOP) method to detect bacterial antigens. 25 patients had bacterial meningitis. The bacterial agent was identified by IEOP in 16 of 21 cases with aetiological agents detectable with the antisera employed. No false positive reactions occurred. The test gave true negative results in 340 instances. The rapidity, simplicity, sensitivity, reliability and low cost are emphasized.

Adolescent

Uptake of 5(125I) iodo-2-deoxyuridine (IDU) in plasma and cerebrospinal fluid in a case of herpes encephalitis with a comparative study on the uptake in plasma, cerebrospinal fluid and brain tissue in dogs.

A case of herpes encephalitis diagnosed by brain biopsy and treated with 5-iodo-2-deoxyuridine (IDU) is presented. The infection occurred in a previously well 19-year-old female patient. Plasma and cerebrospinal fluid (CSF) uptake of the substance was determined using 125I labelled IDU. Top CSF levels of IUD and metabolites of less than 4 microgram/ml, about 1/10 of the corresponding plasma level, were obtained after 6 hours of continuous infusion. The result is discussed and compared with a similar study made on 5 healthy beagle dogs where in addition the levels obtained in various parts of the brain were determined. In the animal experiment a mean value of 2.5 microgram/ml of IDU and metabolites was obtained in the CSF after 8 hours, less than 1/20 of the plasma level. The levels in brain tissue were only slightly higher than in the CSF. The causes of therapeutic failures with IDU treatment are discussed.

Adult

Haemophilus influenzae meningitis in infant rats: role of bacteremia in pathogenesis of age-dependent inflammatory responses in cerebrospinal fluid.

Abnormalities in cerebrospinal fluid associated with meningitis due to Haemophilus influenzae type b were characterized in infant rats. After intranasal inoculation of bacteria, the development of intense bacteremia (greater than 10(4) colony-forming units/ml) correlated with cultures of cerebrospinal fluid positive for H. influenzae, with pleocytosis, and with hisotologic evidence of meningitis. The degree of pleocytosis was related to the age of the animal, the amount of time since inoculation, and the severity of the meningitis.

Age Factors