Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
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The examination of cerebrospinal fluid has provided useful information for diagnosis of CNS infections. The progress of analytical technology has brought the possibility to detect very small amounts of chemical substances. I thought that new information from brain should be obtained by using modern analytical technology for several substances in CSF. Free amino acid pattern, glutamine, homocarnosine, glutamic acid decarboxylase (GAD), neuron specific enolase (NSE) and 2',5'-oligoadenylic acid synthetase (2-5 A) in CSF have been examined for information of brain injury and dysfunctions. The results are as follows. 1) The individual difference and constancy of free amino acid pattern in CSF were found in children without any neurological diseases. 2) The levels of free amino acids in CSF increased in the acute phase of bacterial meningitis. 3) High levels of glutamine in CSF of children with acute bacterial meningitis were normalized during the recovery phase. 4) A marked imbalance of free amino acids in CSF was found in children with Lennox-Gastaut syndrome. 5) A decrease of homocarnosine levels in CSF was related with the degree of unconsciousness in children suffering from neurological diseases. 6) High GAD activities in CSF were observed in the acute phase of aseptic meningitis and after intrathecal injection of methotrexate for the therapy against meningeal leukemia. 7) High NSE activities in CSF were found in the acute phase of bacterial meningitis, intracranial hemorrhage, encephalopathy and encephalitis. 8) High 2-5A activities CSF were measured in the acute phase of mumps meningitis with subsequent decreases during the recovery phase. These results suggest that several substances in CSF are useful as markers of brain injury and dysfunction.
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PMID:[Cerebrospinal fluid as informative source of the brain]. 201 95

We report the development of a unique enzyme-linked immunosorbent assay (ELISA) which makes possible the detection of leukemia-associated P24 antigen, utilizing its ability to bind the Ricinus communis agglutinin (RCA1) and a monoclonal antibody, SJ-9A4 simultaneously. Using the RCA1/SJ-9A4-ELISA, P24 antigen, as few as 50 X 10(3) cells from a common acute lymphoblastic leukemia (C-ALL) cell line could be detected. The presence of D-galactose gave complete and specific inhibition of P24 antigen binding to RCA1. Matched concentrations of D-glucose and D-sucrose had no effect on binding. The release of the P24 antigen into the culture medium by a C-ALL cell line maintained at 37 degrees C could be detected; however, no P24 antigen was present in the culture medium when the cells were maintained at 4 degrees C. Sequential analysis of the culture medium for soluble P24 antigen revealed that release of the P24 antigen associated with cell growth. Molecular sieve chromatography of concentrated culture medium indicated that shed P24 antigen was eluted in the macromolecule fraction. P24 antigen was detected in the cerebrospinal fluid (CSF) of four patients with P24 positive ALL at the time of relapse of the central nervous system (CNS) and was undetectable while in complete remission. The CSF from three patients with P24 negative ALL and three patients with aseptic meningitis had no detectable activity.
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PMID:Shedding of leukemia-associated P24 antigen by lymphoblastoid cell lines. 244 10

To diagnose lymphoproliferative central nervous system (CNS) involvement we have used monoclonal antibodies in an immunocytochemical method for differentiation of cells in cerebrospinal fluid (CSF) and peripheral blood. The cell distribution in 9 patients with B-cell lymphoma and 7 patients with chronic lymphatic leukemia was compared to that in a group of patients with aseptic meningitis. Most patients with neoplastic CNS involvement showed a high proportion of CSF B cells (OKB2+ and/or OKB7+) and a concurrently low proportion of CSF T cells (anti-Leu 1+). Proliferating cells expressing transferrin receptor (OKT9 labeled) were increased in the CSF of 2 patients with neoplastic CNS involvement. In 2 patients with infectious CNS complications, the cell distribution in CSF did not differ from that in patients with aseptic meningitis. Patients with leukemia who had no CNS symptoms, and also 1 patient with meningitis and blood-brain barrier damage, showed a normal cell distribution in CSF despite high B-cell numbers in the peripheral blood. This indicates a selective passage of leukocytes into the CNS and/or local proliferation.
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PMID:Cell surface markers for diagnosis of central nervous system involvement in lymphoproliferative diseases. 353 2

We compared orosomucoid levels in cerebrospinal fluid (CSF) in patients with aseptic meningitis, multiple sclerosis, ischemic and hemorrhagic stroke, CNS-affecting leukemia/lymphoma, and CNS-tumor with the levels in a reference group not having neurologic diseases. Because of possible blood brain barrier damage, we corrected for orosomucoid derived from serum by using the orosomucoid index, i.e. (CSF/serum orosomucoid)/(CSF/serum albumin). Elevated CSF orosomucoid was found in several diseases. In no case, however, was there any evidence of intrathecal synthesis of the protein. We concluded that CSF orosomucoid determination, when used as the only, measure, is of limited clinical value.
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PMID:Comparison of concentration of orosomucoid in serum and cerebrospinal fluid in different neurological diseases. 361 10

The cerebral spinal fluid (CSF)-protein profiles of ten children with previously untreated acute lymphoblastic leukemia (ALL) were investigated by agarose gel electrophoresis. The profiles were determined at diagnosis and during the fifth to eighth week of treatment when preventive therapy for central nervous system (CNS) leukemia (skull irradiation, intrathecal methotrexate (ithMTX) was administered. The profiles were compared with those obtained from a control group of 67 children and those from 42 patients with acute aseptic meningitis. The data from the latter group demonstrated the CSF-protein pattern of partial blood-CSF barrier (B-CSF-B) breakdown. The children with ALL showed no or only minor signs of a B-CSF-B impairment at diagnosis and after four weeks of systemic treatment. However, CSF changes indicative of a lesion of the B-CSF-B increased in all children continuously during CNS prophylaxis. The protein profile at the end of combined chemotherapy and radiotherapy was very similar to that in patients with acute aseptic meningitis. These observations point to neurotoxic side effects on the CNS barrier system with the combination of cranial radiation and ithMTX. A striking finding was restricted heterogeneity of gamma-globulin, observed in the CSF of nine out of the ten children with ALL before or during treatment. The significance of this abnormality is unknown.
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PMID:Changes of CSF-protein pattern in children with acute lymphoblastic leukemia during prophylactic CNS therapy (Berlin protocol). 693 68

Regulation of circulating iron is important in bacterial, yeast, and fungal infections. In the present study, cerebrospinal fluid levels of ferritin, an iron-binding protein, were determined in controls and in patients with central nervous system pyogenic and viral infections. Among 441 controls, cerebrospinal fluid ferritin level was higher than 18 ng/mL in two relapsed patients with central nervous system leukemia, 12 with bacteremia or pneumonia, and one with hemorrhagic herpes simplex encephalitis. Cerebrospinal fluid ferritin levels were more than 18 ng/mL in 13 of 63 patients diagnosed with nonhemorrhagic aseptic meningitis/ventriculitis, when defined solely by negative cerebrospinal fluid culture. Conversely, cerebrospinal fluid ferritin exceeded 18 ng/mL in culture-proven meningitis (46 of 47 cases) and ventriculitis (five of five cases). Cases of indolent cryptococcus and tuberculous meningitis showed modest increases despite traditional cerebrospinal fluid markers, at times, being normal. Cerebrospinal fluid ferritin levels did not correlate with cerebrospinal fluid neutrophil count, cerebrospinal fluid protein concentration, serum ferritin level, or patient age. In 16 of 19 cases monitored sequentially during ongoing antibiotic treatment, levels remained over 18 ng/mL (average, 15.0 days; range, 1 to 54 days). This observation suggests that obtaining cerebrospinal fluid ferritin levels is helpful whenever traditional laboratory benchmarks normalize, as during acute or chronic antibiotic therapy, or create confusion with positive cultures stemming from sample contamination.
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PMID:A persistent biochemical marker for partially treated meningitis/ventriculitis. 778 15

We describe the results of clinical studies investigating the role of monoclonal antibody (MoAb) targeted radiotherapy in the treatment of central nervous system (CNS) leukaemia. Seven children, aged 3-16 years, in second or subsequent meningeal relapse of acute lymphoblastic leukaemia (ALL), have been treated. Each patient received a single injection into the cerebrospinal fluid (CSF) of between 629 and 1,702 MBq of 131-Iodine (131I) conjugated to MoAb HD37 (CD19, n = 2), WCMH 15.14 (CD10, n = 4) or both antibodies (n = 1). One patient underwent a course of repeated targeted therapy following his initial treatment. Acute toxicity was manifest in five patients by a transient aseptic meningitis. Myelosuppression was observed in four children. Pharmacokinetic studies investigated whole body, blood and CSF clearance of radioisotope. Progressively more rapid systemic clearance of 131I was noted in the patient receiving repeated therapy, indicating the development of the human anti-mouse Ig (HAMA) response. Dosimetric studies revealed a radiation dose to the red bone marrow of between 0.6 and 2.2 Gy. The dose to the subarachnoid CSF was between 12.2 and 25.3 Gy, over six times higher than that to the surface tissue of the brain and spinal cord and between 40 and 140 times higher than that to the whole brain. In all but one patient, a transient complete response, in terms of disappearance of lymphoblasts from the CSF, was observed. These studies demonstrate the feasibility of targeted radiotherapy in CNS ALL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The potential of targeted radiotherapy in the treatment of central nervous system leukaemia. 786 76

Although it has been recognized previously that several markers are present in the cerebrospinal fluid (CSF), their clinical usefulness of these markers in the diagnosis of malignant lymphoma infiltrating to the CNS has not yet been established. In order to determine their diagnostic usefulness as markers of meningeal infiltration by lymphoma cells in patients with adult T-cell leukemia (ATL), we measured some soluble factors in the CSF of patients with ATL and non-ATL patients. Soluble CD4 (sCD4) was highly elevated in all patients with ATL and meningeal infiltration. The CSF level of the soluble interleukin-2 receptor (sIL-2R; sCD25) was markedly elevated in 13 (72.2%) of 18 patients with ATL and meningeal infiltration. Levels of sCD4 and sCD25 in the CSF of patients with ATL and meningeal infiltration were significantly higher than in non-ATL patients (p < .01 and p < .001, respectively). These findings indicate that levels of sCD4 and sCD25 in the CSF are probably associated with meningeal infiltration by leukemia cells expressing CD4 and CD25 on surface membranes. CSF levels of sCD4 in 14 (60.9%) of 23 ATL patients and sCD25 in 13 (72.2%) of 18 ATL patients without meningeal infiltration were moderately elevated. These findings suggest that a small number of leukemic cells which were not detected by conventional CSF examination may have infiltrated the meninges in these patients. Sequential measurements of sCD4 and sCD25 in CSF obtained from patients with meningeal infiltration by leukemic cells showed that sCD4 and sCD25 levels reflected the activity of leukemic meningitis and correlated with the number of cells in CSF. However, the levels of sCD4 in CSF did not fall below the limit of detection even when the number of cells in CSF became normal. It is thought that the level of sCD4 in CSF is a more sensitive marker for detecting the infiltration of leukemic cells in CSF than the number of cells present in the CSF considering the clinical course of two patients with acute type ATL. Therefore, ATL patients with meningeal infiltration should receive treatments until sCD4 levels become normal and not just until the number of cells become normal. Our results also suggest that measurement of CSF levels of sCD4 and sCD25 is useful for the differential diagnosis of aseptic meningitis and meningeal infiltration by leukemic cells in patients with smoldering ATL. We conclude that measurement of soluble factors in CSF plays an important role in diagnosis, prophylaxis and treatment of meningitis in patients with ATL.
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PMID:Significance of elevated levels of soluble factors in the cerebrospinal fluid in patients with adult T-cell leukemia. 859 Aug 44

Two polymerase chain reaction (RT-PCR) assays were developed to allow rapid detection of enteroviral RNA in cerebrospinal fluid samples (CSF). Primers homologous to the conserved 5' noncoding region of the enterovirus genome were designed. The RT-PCR product size was approximately 500 bp (479 bp for Poliovirus, 500 bp for Coxsackievirus) and was visualized using ethidium bromide-stained gels. Assay 1 utilized Moloney Murine Leukaemia Virus Reverse Transcriptase (MMLV-RTase) for reverse transcription and Taq polymerase for subsequent PCR. Assay 2 utilized a thermoactive DNA polymerase of Thermus thermophilus (rTth enzyme) for both reverse transcription and DNA amplification. In addition, in Assay 2 reverse transcription and PCR were accomplished within the same reaction tube. Both assays detected between 1 and 0.02 TCID50 of prototype strains of Polio and Coxsackie type B viruses propagated in VERO cell and spiked in a pooled preparation of CSF samples from patients with noninfective neurological disorders. However, Assay 1 was 10-fold more sensitive than Assay 2 when applied to the detection of enteroviral RNA in CSF samples from patients with etiologically well characterized acute aseptic meningitis.
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PMID:Two different PCR assays to detect enteroviral RNA in CSF samples from patients with acute aseptic meningitis. 863 6

The authors studied complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases (LM). One hundred twenty consecutive patients with LM (71 females and 49 males) ranging in age from 10 to 72 years (median 42 years) were treated with involved-field radiotherapy and intraventricular chemotherapy using an Ommaya reservoir and intraventricular catheter system. The diagnosis of LM was determined by a combination of clinical presentation (114 patients); cerebrospinal fluid cytological studies (100); or neuroradiographic studies (42). Systemic tumor histological findings included breast (34 patients); non-Hodgkin's lymphoma (22); melanoma (16); primitive neuroectodermal tumors including medulloblastoma (10); glial neoplasms, leukemia, small cell lung, nonsmall cell lung, and colon (six each); prostate and kidney (three each); and gastric cancers (two). Sixteen patients, all with non-Hodgkin's lymphoma, also had acquired immune deficiency syndrome. Patients received one to four (median two) chemotherapeutic drugs and underwent a total of 1110 cycles of intraventricular chemotherapy (median 10). Intraventricular chemotherapy administration and diagnostic Ommaya reservoir punctures totaled 4400, with a median of 46 per patient. Complications included aseptic/chemical meningitis (52 patients); myelosuppression due to intraventricular chemotherapy (21); catheter-related infections (nine); unidirectional catheter obstruction (six); intraventricular catheter malpositioning (two); Ommaya reservoir exposure (two); leukoencephalopathy (two); and chemotherapy-related myelopathy (one). There were no treatment-related deaths; however, seven patients (6%) required additional surgery for either catheter repositioning (two) or reservoir removal (five). Seven patients with catheter-related infections were treated successfully with intraventricular and systemic antibiotic drugs, thereby preserving the Ommaya system. The authors conclude that Ommaya reservoirs are convenient and pharmacologically rational systems for administering intraventricular chemotherapy. Overall, serious complications requiring surgery are infrequent (6%) and most often secondary to catheter infections, Ommaya reservoir exposure, or initial catheter malpositioning. In the majority of instances, catheter infections may be managed medically, as may the most common complications of intraventricular chemotherapy including aseptic meningitis (43% of patients) and myelosuppression (18%).
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PMID:Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases. 964 98


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