Creatine Kinase Brain Isoenzyme Research Articles

Effect of traditional Chinese medicine acupuncture combined with rehabilitation training on children with cerebral palsy

Objective To evaluate the therapeutic effect of acupuncture combined with rehabilitation training on children with cerebral palsy. Methods A total of 68 children with cerebral palsy who met the inclusion criteria were randomly divided into two groups, 34 in each group. The control group was treated with Bobath therapy combined with Vojta therapy for rehabilitation training, while the observation group was treated with acupuncture on the basis of the control group. Both groups were treated for 12 weeks. Modified Ashworth method was used to assess the muscular tension of lower limbs, the gross motor function scale was used to assess the gross motor function, and the Fugl-Meyer motor function evaluation method was used to evaluate the limb motor function of children. And the serum levels of vascular endothelial growth factor and creatine kinase brain isoenzyme (CK-BB) were detected by ELISA. Results After treatment, the muscle tension score (1.3 ± 0.3 vs. 1.7 ± 0.4, t=4.108) in the observation group was significantly lower than that in the control group, while the GMFM score (55.7 ± 13.7 vs. 37.8±11.4, t=5.881) significantly higher than that in the control group (P<0.01). The serum VEGF (145.67 ± 19.78 ng/L vs. 171.35 ± 22.54 ng/L, t=4.993) in the observation group were significantly lower than those of the control group (P<0.01). The levels of CK-BB (71.46 ± 17.62 U/L vs. 95.76 ± 19.65 U/L, t=5.368) in the observation group were significantly lower than those of the control group (P<0.01). The total effective rate was 94.1% (32/34) in the observation group and 73.5% (25/34) in the control group. There were significant differences between the two groups (χ2=5.314, P=0.021). Conclusions Acupuncture combined with rehabilitation training can improve the muscle tension and gross motor function of children with cerebral palsy, reduce the levels of VEGF and CK-BB in serum of children with cerebral palsy, and improve the clinical effect. Key words: Cerebral palsy; Child; Body acupuncture; Points, scalp stimulation areas; Rehabilitation training; Limb function

Predictive Biomarkers of Recovery in Traumatic Brain Injury

Recent advances in medicine, intensive care and diagnostic imaging modalities have led to a pronounced reduction in deaths and disability resulting from traumatic brain injury. However, there are not sufficient findings to evaluate and quantify the severity of the initial and secondary processes destructive and therefore there are not effective therapeutic measures to effectively predict the outcome. For this reason, in recent decades, researchers and clinicians have focused on specific markers of cellular brain injury to improve the diagnosis and the evaluation of outcome. Many proteins synthesized in the astroglia cells or in the neurons, such as neuron-specific enolase, S100 calcium binding protein B, myelin basic protein, creatine kinase brain isoenzyme, glial fibrillary acidic protein, plasma desoxyribonucleic acid, brain-derived neurotrophic factor, and ubiquitin carboxy-terminal hydrolase-L1, have been proposed as potential markers for cell damage in central nervous system. Usually, the levels of these proteins increase following brain injury and are found in increasing concentrations in the cerebrospinal fluid depending on the injury magnitude, and can also be found in blood stream because of a compromised blood-brain barrier. In this review, we examine the various factors that must be taken into account in the search for a reliable non-invasive biomarkers in traumatic brain injury and their role in the diagnosis and outcome evaluation.

Elevated serum lactate dehydrogenase isoenzymes and aspartate transaminase distinguish Albers-Schönberg disease (Chloride Channel 7 Deficiency Osteopetrosis) among the sclerosing bone disorders

Osteopetrosis (OPT) refers to the consequences of generalized failure of skeletal resorption during growth. Most cases are explained by loss-of-function mutation within the genes that encode either chloride channel 7 (CLCN7) or a vacuolar proton pump subunit (TCIRG1), each compromising acid secretion by osteoclasts. Patients suffer fractures and sometimes cranial nerve entrapment and insufficient medullary space for hematopoiesis. In 1996, we reported that a high serum level of the brain isoenzyme of creatine kinase (BB-CK), the CK of osteoclasts, characterizes OPT dueamong the sclerosing bone disorders (J Clin Endocrinol Metab. 1996;11:1438). Now, we show that elevation in serum of multiple lactate dehydrogenase (LDH) isoenzymes with aspartate transaminase (AST) distinguishes autosomal dominant OPT due to loss-of-function mutation in CLCN7 [Albers-Schönberg disease (A-SD)] among these conditions. Serum total LDH and AST levels as high as 3× and 2×, respectively, the upper limits of normal for age-appropriate controls, were persistent and essentially concordant in A-SD. Serum LDH was elevated in 7 of 9 children and in the 2 adults studied with A-SD. LDH isoenzyme quantitation showed excesses of LDH-2, -3, and -4. Neither total LDH nor AST increases were found in other forms of OPT, including bisphosphonate-induced OPT, or in 41 children and 6 adults representing 20 additional sclerosing bone disorders. Serum TRACP-5b and BB-CK also were markedly elevated in A-SD. Hence, high serum levels of several enzymes characterize A-SD. Elevated serum LDH isoenzymes and AST indicate a disturbance (of uncertain clinical significance) within multiple extraosseous tissues when there is CLCN7 deficiency.

Reduced creatine kinase as a central and peripheral biomarker in Huntington's disease

A major goal of current clinical research in Huntington's disease (HD) has been to identify preclinical and manifest disease biomarkers, as these may improve both diagnosis and the power for therapeutic trials. Although the underlying biochemical alterations and the mechanisms of neuronal degeneration remain unknown, energy metabolism defects in HD have been chronicled for many years. We report that the brain isoenzyme of creatine kinase (CK-BB), an enzyme important in buffering energy stores, was significantly reduced in presymptomatic and manifest disease in brain and blood buffy coat specimens in HD mice and HD patients. Brain CK-BB levels were significantly reduced in R6/2 mice by ∼ 18% to ∼ 68% from 21 to 91 days of age, while blood CK-BB levels were decreased by ∼ 14% to ∼ 44% during the same disease duration. Similar findings in CK-BB levels were observed in the 140 CAG mice from 4 to 12 months of age, but not at the earliest time point, 2 months of age. Consistent with the HD mice, there was a grade-dependent loss of brain CK-BB that worsened with disease severity in HD patients from ∼ 28% to ∼ 63%, as compared to non-diseased control patients. In addition, CK-BB blood buffy coat levels were significantly reduced in both premanifest and symptomatic HD patients by ∼ 23% and ∼ 39%, respectively. The correlation of CK-BB as a disease biomarker in both CNS and peripheral tissues from HD mice and HD patients may provide a powerful means to assess disease progression and to predict the potential magnitude of therapeutic benefit in this disorder.

Clinically effective CK-MB reporting

The clinical utility of measuring the Muscle Brain (MB) isoenzyme of creatine kinase (CK) in the diagnosis of myocardial injury is well established. CK/CK-MB measurement in combination or CK-MB alone is widely used and reporting the results of CK-MB in absolute unit is the common current practice. CK-MB is widely measured by "Immunoinhibition" in India, which gives falsely elevated CK-MB results in the following circumstances: Central nervous system damage, childbirth, macro CK-immunoglobulin complex, in patients with carcinoma of various organs, such as prostate carcinoma and other adenocarcinomas. But, reporting %CK-MB rather than the absolute CK-MB results assists in detection of macroCK (or CK variants), associated proliferative and autoimmune pathologies and their prognosis.

Maximum persisting single lead ST elevation after primary angioplasty: a good predictor of left ventricular dilatation assessed by magnetic resonance imaging

To determine the frequency and predictors of left ventricular dilatation assessed by magnetic resonance imaging among patients with a first acute myocardial infarction treated with successful primary angioplasty and stent. Cine magnetic resonance imaging and late enhancement imaging were prospectively performed in 42 patients 1 month and more than 1 year after successful early reperfusion of a first acute ST elevation myocardial infarction (age 61 +/- 13 years, 76% men, 55% anterior myocardial infarction, and mean symptom-to-balloon time 199 +/- 130 min). Both at the 1-month and at the 15-month magnetic resonance imaging examinations, 57% of patients had left ventricular dilatation (end-systolic volume indexed > 36 ml/m2, values above the upper 95th percentile based on magnetic resonance imaging reference values for left ventricular size in normal participants). The most accurate predictor of left ventricular dilatation was maximum persisting single lead ST elevation 60 min after reperfusion (area under the curve 0.81, P = 0.001). Maximum single lead ST elevation was significantly and independently associated with larger end-systolic volume indexed (beta = 0.35, P = 0.040) after adjusting for muscle and brain isoenzyme of creatine kinase and echocardiographic wall motion score index. More than half of patients with a first acute myocardial infarction have left ventricular dilatation despite successful primary coronary angioplasty. Maximum persisting single lead ST elevation 60 min after mechanical reperfusion represents a simple tool for predicting left ventricular dilatation.

Measurement of tartrate-resistant acid phosphatase and the brain isoenzyme of creatine kinase accurately diagnoses type II autosomal dominant osteopetrosis but does not identify gene carriers.

Autosomal dominant osteopetrosis type II (ADO2) is typically diagnosed from radiographs, which demonstrate the pathognomonic findings of osteosclerosis and endobone formation. Individuals with ADO2 also have elevated serum levels of tartrate-resistant acid phosphatase (TRAP) and the BB isoenzyme of creatine kinase (CK-BB). In the current study, we tested the utility of these enzymes in making or refuting a diagnosis of ADO2. Furthermore, because ADO2 has incomplete penetrance, we examined whether TRAP and CK-BB were helpful in identifying gene carriers. We studied eight families, measured serum levels of TRAP and CK-BB in 52 affected individuals and 12 obligate gene carriers, and compared their values with age-matched controls. Our results demonstrate that affected patients have significantly elevated levels of both TRAP and CK-BB. In contrast, gene carriers have values that are not different from controls. Furthermore, in our study population, TRAP and CK-BB have a high diagnostic sensitivity and specificity, particularly in children. From this large study of ADO2 patients and carriers, we conclude that: 1) TRAP and CK-BB are significantly elevated in patients with ADO2, 2) obligate carriers cannot be adequately identified by measurement of these analytes, and 3) TRAP and CK-BB are highly sensitive and specific diagnostic tests that can efficiently and effectively screen high-risk individuals who have not had previous radiographic assessment.

Measurement of Tartrate-Resistant Acid Phosphatase and the Brain Isoenzyme of Creatine Kinase Accurately Diagnoses Type II Autosomal Dominant Osteopetrosis but Does Not Identify Gene Carriers

Measurement of Tartrate-Resistant Acid Phosphatase and the Brain Isoenzyme of Creatine Kinase Accurately Diagnoses Type II Autosomal Dominant Osteopetrosis but Does Not Identify Gene Carriers

511 Normal range of creatine kinase brain isoenzyme (BB-CK) activity in plasma of fetuses during the second trimester

511 Normal range of creatine kinase brain isoenzyme (BB-CK) activity in plasma of fetuses during the second trimester

Brain‐specific proteins as predictors of outcome in asphyxiated term infants

Perinatal asphyxia is an important cause of neonatalmortality and of neurological disabilities among survi-vors. Infants who sustain perinatal asphyxia severeenough to result in long-term neurological disabilitiesinvariably exhibit anovert neonatal encephalopathy andother organ system involvement in the ”rst few days oflife (1). The main concerns of families and medicalteams taking care of these neonates include not only theimmediate problems of management, but the need foran accurate evaluation of the severity of brain damage,and therefore the prediction of neurological outcome ofthese patients. Recent advances in neuroprotectiveinterventions emphasize even more the importance ofan early identi” cation of those infants at highest risk oflate neurological morbidity.Several methods have been used for early estimationof the damage and prediction of outcome. The mostavailable tools include clinical grading of the encepha-lopathy, electrophysiological assessments such as elec-troencephalogram and evoked responses, neuroimagingand cerebral blood ‘ow studies. However, uncertaintyregarding the eventual neurological outcome remainsduring the ” rst hours after birth; with the exception ofassessment of the electrical activity by means of anamplitude-integrated EEG, the other tools have alimited prognostic value in the earliest hours of life(2, 3).Brain damage induces the release of several sub-stances into the cerebrospinal ‘uid (CSF), e.g. metab-olic products (4, 5), neuro aminoacids (6,7), brain-speci” c proteins (BSPs) (8–11), nerve growth factor(12) and interleukin-6 (13). BSPs seem to be the bestbiochemical markers of brain damage after hypoxic-ischaemic injury. Those such as creatine kinase brainisoenzyme (8), neuron-speci”c enolase (9, 10), myelinbasic protein (10) and glial ” brillary acidic protein (11)in CSF may re‘ect the extent of ongoing brain damageand have shown to be of value in predicting outcome inasphyxiated infants. In this issue of

#685 Serum creatine kinase brain isoenzyme (CK-BB) in the diagnosis of severe osteopetrosis in the newborn, and as a monitoring tool of disease status after hematopoietic transplantation (EII)

#685 Serum creatine kinase brain isoenzyme (CK-BB) in the diagnosis of severe osteopetrosis in the newborn, and as a monitoring tool of disease status after hematopoietic transplantation (EII)

Creatine kinase brain isoenzyme (BB-CK) presence in serum distinguishes osteopetroses among the sclerosing bone disorders.

Creatine kinase (CK) isoenzyme BB-CK is predominantly found in brain and is not normally detected in the blood. A few recent reports, however, have described BB-CK in serum from several patients with osteopetrosis (OP). To evaluate the presence and specificity of BB-CK in serum in the osteopetroses among disorders that increase skeletal mass, we quantitated total CK activity and CK isoenzymes in 15 patients representing the five major clinical forms of OP (2 infantile, 3 intermediate, 7 adult [2 type I, 5 type II], and 3 carbonic anhydrase II [CA II] deficiency cases) and in 22 patients representing 14 other types of sclerosing bone disease. All OP patients (except the two adult type I subjects) had BB-CK readily detected in their serum. Conversely, only 1 of the 22 patients with other sclerosing bone disorders had detectable BB-CK in serum (1 of 3 patients with fibrodysplasia [myositis] ossificans progressiva who had barely measurable activity). In three OP patients (one of two with the infantile form and two of five with adult, type II disease), BB-CK values were sufficiently high that serum total CK activity was elevated. In a newborn with malignant OP, both cord blood plasma and peripheral blood serum had substantial amounts of BB-CK. In three subjects (with adult type II OP), who were restudied 2-6 years later, BB-CK was still elevated in their blood. BB-CK in serum appears to distinguish the osteopetroses among the sclerosing bone disorders. Absence of serum BB-CK in adult type I disease suggests that this condition may not be a genuine form of OP. Assay of BB-CK in fetal blood could be studied as a means for prenatal diagnosis of malignant OP. Why the osteoclast failure that characterizes all true forms of OP is associated with BB-CK in the circulation is a new question for skeletal biologists.

Increased creatine kinase brain isoenzyme concentration in cerebrospinal fluid with meningitis.

CPK-BB (CK-BB) isoenzyme is an intracellular enzyme released in various neurologic conditions, including central nervous system (CNS) infections. Activity of CK-BB in cerebrospinal fluid (CSF) was determined in 80 children by electrophoresis and densitometry. The possible correlation between CNS infection and CK concentrations was assessed. Significantly elevated concentrations of CK activity (P < 0.01) in the CSF were found in children with bacterial meningitis as compared with children with either aseptic meningitis or normal CSF findings. The data suggest the possibility of utilizing CSF CK activity to differentiate between bacterial and viral meningitis in situations where a routine CSF examination is inconclusive.

Clinical significance of creatine kinase isoenzymes for fetal asphyxia in women at labor.

Creatine kinase-brain isoenzyme activity (CK-BB) was measured longitudinally in the serum of 31 pregnant women in the first stage of labor (early and advanced), at delivery, and 1, 6 and 24 h after delivery, in the umbilical cord and in the serum of their neonates on the first day of life. There was no increase in serum CK-BB values of mothers that delivered normally (n = 15) or had an elective cesarean section (n = 5). Pregnant women with signs of fetal distress had an increase in CK-BB levels in the first stage of labor (mean +/- SD 4.5 +/- 4.9 U/l, p < 0.03) and 6 h after delivery (12 +/- 4 U/l, p < 0.0001). Neonates with intrauterine stress also had an increase in their CK-BB to 144 +/- 116 U/l at 6 h of life, in comparison with babies born without signs of stress. It appears that CK-BB during labor and in the first hours of life may be indicative of intrauterine stress.

Characterization of four new cell lines derived from small-cell gastrointestinal carcinoma.

Four human small-cell gastrointestinal carcinoma cell lines were established from tumor tissues of patients with esophageal, gastric or rectal cancer, and were studied morphologically and biochemically in comparison with small-cell lung carcinoma (SCLC) cell lines and common gastric cancer cell lines. Cells from all the small-cell gastrointestinal carcinoma lines were as small as classic SCLC cells and had characteristic neurosecretory granules. Cells from only one line grew as tightly packed spherical aggregates of floating cells, and those of the other 3 grew attached to substrate. Although high levels of creatine kinase brain isoenzyme (CK-BB) were detected in all 4 cell lines, 2 of them showed low levels of aromatic L-amino-acid decarboxylase and 3 had low levels of neuron-specific enolase (NSE). None of the lines showed simultaneous elevation of enzymes. C-myc, N-myc, and L-myc were not amplified in any of the cell lines, but c-myc mRNA was expressed in 2 lines. Our findings indicate that all small-cell gastrointestinal carcinoma cells examined belong to the variant type which is used in the classification of SCLC. Furthermore, the ECC18 line, derived from esophageal cancer, seemed to be of true endocrine cell origin, while the 3 other small-cell gastrointestinal carcinoma lines seemed to arise via neoplastic neometaplasia from adenocarcinoma cells to endocrine cells.

Cellular and Subcellular Compartmentation of Creatine Kinase in Brain

Creatine kinase (CK) catalyzes a reversible transphosphorylation reaction that is believed to play a crucial role in the maintenance and channeling of high energy phosphate in tissues with high energy demands. In rat brain development, cytosolic (nonmitochondrial) CK levels increase rapidly during the peak period of myelination and remain high in the adult. The cellular compartmentation of CK was investigated through the use of primary cultures of neurons, oligodendrocytes and astrocytes. The CK activity in cultured oligodendrocytes, which expressed both enzymatic and immunocytochemical markers of myelin, was the highest of the cell types examined and comparable to levels measured in whole adult brain; these observations suggest a role for CK in myelinogenesis. We found that low density, dividing astrocyte cultures also exhibited high B-CK (brain isoenzyme of CK) immunoreactivity, with the nuclear CK staining being especially intense. We studied these cultured astrocytes in more detail with respect to their intense nuclear CK immunoreactivity. Optical sections of astrocyte nuclei taken with a confocal microscope show that the high B-CK present is actually contained within the nucleus, with a nucleoplasmic distribution that does not co-localize with DNA or RNA. To ascertain whether the high nuclear B-CK in proliferating astrocytes correlated with ongoing cell division, we conducted experiments with confluent, nondividing cultures. These results show that both CK enzyme activity and immunoreactivity are high in the nucleus of proliferating astrocytes, and significantly reduced in the nucleus of quiescent, nondividing astrocytes. The high level of CK protein and activity in the nucleus of proliferating astrocytes suggests a role for CK in cell division/nuclear function.(ABSTRACT TRUNCATED AT 250 WORDS)

Establishment and characterization of a panel of human lung cancer cell lines.

The establishment and characterization of 11 human lung cancer cell lines are described in this article. Nine of these cell lines were established over a 5-year period, from 1983 to 1988, from patients treated at the Kingston Regional Cancer Centre. These include eight definite or probable small cell lung cancer (SCLC) lines and one adenocarcinoma line. In addition, two other SCLC cell lines were characterized. All of the lines have been in continuous culture for more than 2 years. The clinical histories of the patients from whom the cell lines were derived are outlined here. Several features of the cell lines are presented, including the following: (1) a comparison of the histologic features of the cell lines with the original biopsy specimens; (2) the expression of various markers, including cytokeratin, carcinoembryonic antigen, calcitonin, and neuron-specific enolase; (3) activities of the enzymes l-dopa decarboxylase and the brain isoenzyme of creatine kinase; (4) growth characteristics; (5) cloning efficiency in soft agar; (6) tumorigenicity in nude mice; and (7) cytogenetic studies. These cell lines, obtained directly from patients with a spectrum of drug-sensitive and drug-resistant tumors, will be valuable in vitro models of sensitivity and resistance to chemotherapy in lung cancer.

Neonatal CSF Creatine Kinase and CP Risk

Creatine kinase brain isoenzyme (CK-BB) was examined in the cerebrospinal fluid of 150 neonates at the Departments of Pediatrics and Neonatal Medicine and Clinical Chemistry, University Hospital, Ghent, Belgium.

Creatine Kinase Isoenzyme BB Concentrations in the Cerebrospinal Fluid of Newborns: Relationship to Short-term Outcome

Creatine kinase brain isoenzyme (CK-BB) was determined in cerebrospinal fluid of 150 neonates by a newly developed immunoenzymatic assay. Newborns with a documented neurologic disorder (intraventricular hemorrhage, postasphyxial encephalopathy, central nervous system infection, or persistent periventricular intraparenchymal echodensities) showed markedly higher concentrations of immunoreactive CK-BB than did the normal newborns or those with subarachnoid hemorrhage. In neonates with seizures the data suggest that the underlying neurologic disorder accounts for the higher CK-BB values and not the seizures per se. High concentrations of CK-BB in the neonatal period were followed by poor short-term outcome.

Hypoxic risk in twins assessed by serum creatine kinase brain isoenzyme measurement

A marked intrapair discordance in placentas and in many body and organ measurements are risk factors influencing perinatal mortality and morbidity in twins. Asphyxia is the single most important perinatal cause of neurologic morbidity in newborn infants. The higher hypoxic risk for the second twin arises, however, from conclusions based on studies that did not consider the new diagnostic possibility of using blood measurements of the brain-type isoenzyme of creatine kinase (CK-BB) as a marker of perinatal asphyxia. CK-BB levels were measured in cord blood of 60 preterm infants (mean birth weight 1670 ± 390 g, and mean gestational age 33 ± 1.9 weeks) born of twin gestation in the last 3 years. The mean CK-BB values were 48 ± 40 U/1 versus 29 ± 31 U/1 (p > 0.5). Skilful antepartum and perinatal care are the keys for optimal management of both babies, as demonstrated by similar CK-BB values obtained in their cord-blood specimens after birth.