Opposing effects of protein kinase A and C on capacitative calcium entry into HL-60 promyelocytes.

Treatment of HL-60 cells with thapsigargin, a microsomal Ca2+/ATPase inhibitor, led to depletion of intracellular calcium stores followed by capacitative calcium entry. Stimulation of adenylyl cyclase with forskolin enhanced thapsigargin-induced Ca2+ influx. The forskolin effect was confirmed by enhanced fluorescence quenching induced by Mn2+ entry into fura-2 loaded cells. 1,9-Dideoxy-forskolin, an inactive analog of forskolin, did not affect capacitative calcium entry. On the other hand, phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, inhibited thapsigargin-induced Ca2+ entry. Histamine and prostaglandin E2 (PGE2) elevated intracellular adenosine 3′:5′-cyclic monophosphate (cAMP) levels and enhanced the thapsigargin-induced capacitative calcium entry. Incubation with N-[2-(p-bromocynnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), an inhibitor of protein kinase A (PKA), blocked the forskolin effect, and GF109203X, an inhibitor of protein kinase C (PKC), blocked the phorbol 12-myristate 13-acetate effect. The results suggest that protein kinase A regulates capacitative calcium entry positively, but that protein kinase C regulates Ca2+ influx negatively. Furthermore, after differentiation of HL-60 promyelocytes with dimethylsulfoxide to granulocytes, the inhibitory effect of phorbol 12-myristate 13-acetate became more pronounced, whereas the stimulatory effect of prostaglandin E2 did not change. This result suggests that the regulation of capacitative calcium entry by protein kinase C and protein kinase A develops differently during differentiation

A Novel PANK2 Mutation in a Patient with Atypical Pantothenate-Kinase-Associated Neurodegeneration Presenting with Adult-Onset Parkinsonism

BACKGROUND: Pantothenate-kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegenerative disorder that is characterized by progressive extrapyramidal signs, visual loss, and cognitive impairment. PKAN is caused by mutations in the pantothenate kinase gene (PANK2), which is located on chromosome 20p13 and encodes pantothenate kinase, the key regulatory enzyme in coenzyme-A biosynthesis. CASE REPORT: In this report we describe a case of atypical PKAN with a novel PANK2 mutation, presenting with a 10-year history of postural tremor involving both hands. Upon neurological examination, the patient's face was masked and he spoke in a monotonous voice. The patient presented with mild bradykinesia and rigidity that involved all of the extremities. Horizontal saccadic eye movements were slow and fragmented. Brain MRI revealed a typical "eye-of-the-tiger" sign. A mutation analysis revealed three PANK2 mutations: two in exon 3 (Asp 378Gly and Leu385CysfsX13) and one in exon 4 (Arg440Pro). CONCLUSIONS: Parkinsonism is not an unusual presenting symptom in patients with atypical PKAN, and so it is important for physicians to consider PKAN in the differential diagnosis of patients presenting with young-onset parkinsonism.ope

Variability of Response Time as a Predictor of Methylphenidate Treatment Response in Korean Children with Attention Deficit Hyperactivity Disorder

PURPOSE: Methylphenidate (MPH) is an effective medication for the treatment of attention deficit hyperactivity disorder (ADHD). However, about 30% of patients do not respond to or are unable to tolerate MPH. Based on previous findings, we hypothesized that great variability in response time (RT) among Korean children with ADHD on a computerized continuous performance attention test would be related to poor MPH treatment response. MATERIALS AND METHODS: Children (ages 6-18 years) with ADHD were recruited for a prospective 12-week, open-labeled, multicenter study to examine optimal dosage of OROS methylphenidate. Of the 144 subjects selected, 28 dropped out due to adverse events, medication noncompliance, or follow-up loss, and an additional 26 subjects with comorbid disorders were excluded from statistical analyses. We defined 'responders' as subjects who received a score of less than 18 on the attention deficit hyperactivity disorder rating scale (ARS; Korean version, K-ARS) and a score of 1 or 2 on the Clinical Global Impression-Improvement scale (CGI-I). RT variability was assessed with the ADHD diagnostic system (ADS). RESULTS: Fifty-nine (67%) subjects responded to MPH treatment. The non-responders showed greater RT variability at baseline (Mann Whitney U = 577.0, p < 0.01). Baseline RT variability was a significant predictor of MPH response (Nagelkerke R(2) = 0.136, p < 0.01). It predicted 94.9% of responder, 17.2% of non-responder and 69.3% of overall group. CONCLUSION: High RT variability may predict poor response to MPH treatment in children with ADHDope

Antimicrobial resistance surveillance of bacteria in 1999 in Korea with a special reference to resistance of enterococci to vancomycin and gram-negative bacilli to third generation cephalosporin, imipenem, and fluoroquinolone.

The trend of antimicrobial resistance of bacteria isolated from patients in 30 Korean hospitals in 1999 was analyzed with a particular attention to cefotaxime- or fluoroquinolone-resistant gram-negative bacilli, imipenem-resistant Pseudomonas aeruginosa, and vancomycin-resistant enterococci. Adequacy of susceptibility testing, and any change in the frequencies of isolated species were also analyzed. The results showed that only 20% and 30% of hospitals tested the piperacillin-tazobactam and cefoxitin susceptibility of Enterobacteriaceae, respectively, only 24% of hospitals the piperacillin-tazobactam susceptibility of P. aeruginosa, and 17% of hospitals the fusidic acid susceptibility of staphylococci. Among the isolates 26.3% were glucose-nonfermenting gram-negative bacilli, and 34.7% of Enterococcus were Enterococcus faecium. Slight decline of cefotaxime-resistance rate to 20% was noted in Klebsiella pneumoniae, while fluoroquinolone-resistance rate was 68% in Acinetobacter baumannii. The ceftazidime- and imipenem-resistance rates were 17% and 18%, respectively in P. aeruginosa. The vancomycin-resistance rate of E. faecium rose significantly to 15.1%, but the rates varied significantly depending on hospitals suggesting presence of different degree of selective pressure or nosocomial spread. In conclusion, the prevalence of imipenem-resistant P. aeruginosa and the increase of vancomycin-resistant E. faecium were the particularly worrisome phenomena observed in this study

Parkinsonsim due to a Chronic Subdural Hematoma

Subdural hematoma is a rare cause of parkinsonism. We present the case of a 78-year-old man with right-side dominant parkinsonism about 3 months after a minor head injury. MRI reveals a chronic subdural hematoma on the left side with mildly displaced midline structures. The parkinsonian features were almost completely disappeared after neurosurgical evacuation of the hematoma without any anti-parkinson drug

Unilateral Standing Leg Tremor as the Initial Manifestation of Parkinson Disease

Background: The aim of this study was to analyze the different forms of leg tremors exhibited while standing in patients with Parkinson disease (PD), and to determine if the type of leg tremor exhibited is indicative of prognosis or treatment response in PD patients. Methods: We studied the clinical characteristics of five PD patients (all women; mean age, 59 years, range, 53–64 years) with unilateral standing leg tremor as the initial manifestation of PD, including their electrophysiological findings and the results of long-term follow-up. Results: For each patient, parkinsonism either existed at the time of onset of the initial symptoms or developed later. Patient responses to drugs were generally good, but one patient showed a poor response to drugs, even though she had only a low frequency leg tremor. For two patients whom we could observe during the 10-year follow-up period, neither the leg tremor nor parkinsonism was aggravated. Conclusions: There are two forms of unilateral standing leg tremor in PD. One form is high frequency, similar to the primary orthostatic tremor. The other is low frequency and similar to the parkinsonian resting tremor. Based on these observations, it appears that progression might be slow if PD patients have standing leg tremor as the initial manifestation

A DSPP Mutation Causing Dentinogenesis Imperfecta and Characterization of the Mutational Effect

Mutations in the DSPP gene have been identified in nonsyndromic hereditary dentin defects, but the genotype-phenotype correlations are not fully understood. Recently, it has been demonstrated that the mutations of DSPP affecting the IPV leader sequence result in mutant DSPP retention in rough endoplasmic reticulum (ER). In this study, we identified a Korean family with dentinogenesis imperfecta type III. To identify the disease causing mutation in this family, we performed mutational analysis based on candidate gene sequencing. Exons and exon-intron boundaries of DSPP gene were sequenced, and the effects of the identified mutation on the pre-mRNA splicing and protein secretion were investigated. Candidate gene sequencing revealed a mutation (c.50C > T, p.P17L) in exon 2 of the DSPP gene. The splicing assay showed that the mutation did not influence pre-mRNA splicing. However, the mutation interfered with protein secretion and resulted in the mutant protein remaining largely in the ER. These results suggest that the mutation affects ER-to-Golgi apparatus export and results in the reduction of secreted DSPP and ER overload. This may induce cell stress and damage processing and/or transport of dentin matrix proteins or other critical proteins

Lead exposure may affect gingival health in children

Abstract Background Several studies have reported the harmful effects of lead poisoning. However, the relationship between lead exposure and oral health of children has not been well defined. The aim of this study was to investigate the relationship between blood lead level (BLL) and oral health status of children. Methods A total of 351 children (aged 7–15 years) were recruited from the pilot data of the Korean Environmental Health Survey in Children and Adolescents, which was designed to examine environmental exposure and children’s health status in South Korea. Blood samples were taken to determine BLLs and oral examinations were performed to assess oral health parameters, including community periodontal index (CPI), gingival index (GI), and plaque index (PI). Information regarding socioeconomic status, oral hygiene behavior, and dietary habits was collected from parents and guardians. Results The participants were divided equally into four quartiles, with quartile I comprised of children with the lowest BLLs. There were significant differences for PI (p < 0.05) among the quartile groups. Using logistic regression models, we found a significant relationship between BLL and oral health parameters. The crude odds ratios for CPI, GI, and PI in the third quartile were 5.24 (95% CI: 1.48-18.56), 4.35 (95% CI: 1.36-13.9), and 4.17 (95% CI: 1.50-11.54), respectively, while the age and gender-adjusted odds ratios were 7.66 (95% CI: 1.84-31.91), 6.80 (95% CI: 1.80-25.68), and 3.41 (95% CI: 1.12-10.40), respectively. After adjustments for age, gender, parent education level, and frequency of tooth brushing, the adjusted odds ratios were 7.21 (95% CI: 1.72-30.19), 6.13 (95% CI: 1.62-23.19), and 3.37 (95% CI: 1.10-10.34), respectively. Conclusions A high BLL might be associated with oral health problems in children, including plaque deposition and gingival diseases