Integrin CD11b negatively regulates Mincle-induced signaling via the Lyn–SIRPα–SHP1 complex

During mycobacteria infection, anti-inflammatory responses allow the host to avoid tissue damage caused by overactivation of the immune system; however, little is known about the negative modulators that specifically control mycobacteria-induced immune responses. Here we demonstrate that integrin CD11b is a critical negative regulator of mycobacteria cord factor-induced macrophage-inducible C-type lectin (Mincle) signaling. CD11b deficiency resulted in hyperinflammation following mycobacterial infection. Activation of Mincle by mycobacterial components turns on not only the Syk signaling pathway but also CD11b signaling and induces formation of a Mincle–CD11b signaling complex. The activated CD11b recruits Lyn, SIRPα and SHP1, which dephosphorylate Syk to inhibit Mincle-mediated inflammation. Furthermore, the Lyn activator MLR1023 effectively suppressed Mincle signaling, indicating the possibility of Lyn-mediated control of inflammatory responses. These results describe a new role for CD11b in fine-tuning the immune response against mycobacterium infection.

Oligoadenylate synthase-like (OASL) proteins: dual functions and associations with diseases

The study of antiviral pathways to reveal methods for the effective response and clearance of virus is closely related to understanding interferon (IFN) signaling and its downstream target genes, IFN-stimulated genes. One of the key antiviral factors induced by IFNs, 2'-5' oligoadenylate synthase (OAS), is a well-known molecule that regulates the early phase of viral infection by degrading viral RNA in combination with RNase L, resulting in the inhibition of viral replication. In this review, we describe OAS family proteins from a different point of view from that of previous reviews. We discuss not only RNase L-dependent (canonical) and -independent (noncanonical) pathways but also the possibility of the OAS family members as biomarkers for various diseases and clues to non-immunological functions based on recent studies. In particular, we focus on OASL, a member of the OAS family that is relatively less well understood than the other members. We will explain its anti- and pro-viral dual roles as well as the diseases related to single-nucleotide polymorphisms in the corresponding gene.

Different Outcomes of Intractable Temporal Lobe Epilepsy with Regard to the Timing of Surgical Intervention

PURPOSE: We like to examine the clinicopathologic findings of intractable temporal lobe epileptic patients who underwent epilepsy surgery, and different outcomes with regard to the timing of surgical intervention. METHODS: One hundred fourty six patients underwent anterior temporal lobectomy for medically intractable epilepsy between the year of 1993 and 2000. Except 5 patients who had malignancy, 132 patients were included in this study and were followed up for longer than 12 months after surgery. Two groups, under 15 years old(pediatric group) and over(adult group) according to the timing of surgery, were compared with clinical variables(seizure patterns, EEGs and brain MRI findings), pathologic findings and seizure outcomes. Seizure outcomes were divided as favorable in Class I and II or unfavorable in Class III and IV by using Engel's classification. RESULTS: Among 132 patients, 103 patients(78.0%) were classified as favorable and 29 patients(22.0%) unfavorable. Adult group had more favorable outcomes than pediatric group(82.1% vs 55.0%, P=0.007). Pathologic findings were as follows:48 patients(36.4%) had only hippocampal sclerosis, 50(37.9%) hippocampal sclerosis with other pathologic findings, 20(15.2%) cortical dysplasia, 6(4.5%) cortical dysplasia and gliosis, 7(5.3%) only gliosis and 1(0.7%) hippocampal atrophy. Among 98 patients who had hippocampal sclerosis, 81(82.7%) had favorable outcomes. Among 26 patients who had cortical dysplasia, 16(61.5%) had favorable outcomes. In case of hippocampal sclerosis only, pediatric group had more favorable outcomes(85.7% vs 82.9%, P=0.86). But in case of hippocampal sclerosis with other pathologic findings, adult group had more favorable outcomes(50.0% vs 86.4%). In case of cortical dysplasia only, adult group had more favorable outcomes(40.0 % vs 74.3%). CONCLUSION: The seizure outcomes after surgery, pediatric group showed less favorable outcomes than adult group. In case of hippocampal sclerosis only, the outcome of early surgery was good too.

Effects of Dexamethasone Treatment on Blood Pressure in Preterm Infants with Chronic Lung Disease (CLD)

PURPOSE: This study was designed to see the BP changes according to the time course and the duration of dexamethasone (DXM) therapy in premature infants with chronic lung disease (CLD). METHODS: We studied 27 chronic lung disease patients treated with DXM in NICU, Chonnam University Hospital from January 1994 to May 1998. Systolic, diastolic, and mean arterial pressure were recorded at three times (8 AM, 4 PM, midnight) daily. Data were analyzed by time peroid : Pre DXM means 14 days before DXM therapy, DXM during the therapy and Post DXM 14 days after the completion of therapy. Of 27 patients, 16 received short-course (7 days), and 11 long-course therapy (42 days). RESULTS: Mean gestational age of the patients was 29.3 (+/-1.5) weeks and the mean birth weight was 1,169 (+/-262) gm. Systolic, diastolic and mean BP were significantly increased during the DXM therapy compared to pre DXM (76+/-7 mmHg vs 67+/-9 mmHg, P<0.001, 44+/-6 mmHg vs 38+/-6 mmHg, P<0.001, 55+/-6 mmHg vs 49+/-7 mmHg, P<0.001, respectively). Even 14 days after the completion of therapy, systolic, diastolic and mean BP were not decreased to the level of pre DXM therapy. The maximal increase of BP was noted on the second day of treatment. When the BP changes were compared according to the duration of therapy, post DXM BP was decreased to the level of pre DXM in short course, but not in long course group with the higher post DXM systolic BP than that of short course group (78+/-11 mmHg vs 69+/-7 mmHg, P<0.05). CONCLUSION: BP significantly increased during DXM therapy, particularily on the second day of treatment. Also our result suggests that we have to watch the BP carefully more than two weeks after the completion of therapy.

Two Cases of Left Ventricular Tumors Complicating Subaortic Stenosis in Newborn Infants

The most cornmon obstruction of left ventricular outflow in childhood is produced either by a fibrous ring below the aortic valve, or by localized or diffuse muscular hypertrophy of the inter-ventricular septum. Cardiac tumors causing subaortic stenosis in the newborn infant are extremely rare. This report describes two cases of subaortic stenosis caused by a tumor of the left ventricle in newborn infants, both diagnosed by 2-dimensional echocardiography. In one patient, the obstructive portion of the tumor was successfully resected from its attachment to the ventricular septum by aortotomy on day 5. Histologic examination confirmed the diagnosis of rhabdomyoma. This patient developed cutaneous, neurologic and radiologic abnormalities of tuberous sclerosis during the follow-up of 42 months.

Different Phase of Telomere Shortening with Age in Peripheral Blood Mononuclear Cells / 대한소아혈액종양학회지

PURPOSE: Telomeres, special protein and tandem repeat DNA structure that cap the ends of linear eukaryotic chromosomes, are essential for chromosome structure and stability. Human telomeric DNA is known to shorten by 30~200 bp with each somatic cell division. However, the phase of telomere changes has not been studied extensively. METHODS: Telomere length was analyzed in the peripheral blood mononuclear cells (PBMCs) of 39 normal controls aged from newborn to 72 years by Southern blot hybridization using PharMingen's TeloQunatTM Telomere Length Assay Kit (Becton Dickinson Co.). RESULTS: The mean telomere length of the population was 9.68 kb (range, 5.65~14.40 kb). The length (kb) decreased with age (A) by the following regression: T=10.86 0.04 A (T=telomere length in kb; A=age in years) (r= 0.38; P=0.016). The mean telomere lengths according to age groups were: 10.26 kb for less than 15 years; 9.92 kb for 16 to 40 years; 8.03 kb for over 40 years. The telomere length of over 40 years was significantly shorter than that of less than 15 years (P=0.013), and than that of 16 to 40 years (P=0.011). The phase of telomere changes was evaluated by age subgroups. The shortening was fastest in individuals of age <5, while the length showed a plateau or slight increment in age group between 5 to 35. The length decreased steadily with age by the regression of 12.43+/-0.07 A (r= 0.500; P=0.034) in age group over 35. CONCLUSION: Telomere length of PBMCs decreases with age, and the different phase of telomere length shortening may suggest that the shortening of telomere is not a constant process over lifespan, but a dynamic process that is differently regulated in age groups.