Differential expression of inflammatory cytokines and chemokines in lipopolysaccharide‐stimulated melanocytes from lightly and darkly pigmented skin

Increasing evidence suggests that human epidermal melanocytes play an important role in the skin immune system; however, a role of their pigmentation in immune and inflammatory responses is poorly examined. In the study, the expression of Toll‐like receptor 4 (TLR4) and inflammatory cytokines and chemokines by cultured normal melanocytes derived from lightly and darkly pigmented skin was investigated after cell stimulation with lipopolysaccharide (LPS). The basal TLR4 mRNA level in heavily pigmented cells was higher as compared to their lightly pigmented counterparts. Melanocyte exposure to LPS upregulated the expression of TLR4 mRNA and enhanced the DNA‐binding activity of NF‐κB p50 and p65. We found substantial differences in the LPS‐stimulated expression of numerous genes encoding inflammatory cytokines and chemokines between the cells with various melanin contents. In lightly pigmented melanocytes, the most significantly upregulated genes were nicotinamide phosphoribosyltransferase (NAMPT/visfatin), the chemokines CCL2 and CCL20, and IL6, while the genes for CXCL12, IL‐16 and the chemokine receptor CCR4 were the most significantly upregulated in heavily pigmented cells. Moreover, the lightly pigmented melanocytes secreted much more NAMPT, CCL2 and IL‐6. The results of our study suggest modulatory effect of melanogenesis on the immune properties of normal epidermal melanocytes.     

Diagnostic Accuracy of Cervical Low-Grade Squamous Intraepithelial Lesions Is Improved With MIB-1 Immunostaining.

There is considerable interobserver variation in the diagnosis of low-grade squamous intraepithelial lesion that involves mature squamous epithelium. Our aim was to evaluate the utility of MIB-1 immunostaining as an adjunct test to increase diagnostic accuracy. Consecutive cervical biopsies originally diagnosed as normal (n = 26) or low-grade squamous intraepithelial lesion (n = 23) were reviewed by three pathologists to obtain a consensus diagnosis. MIB-1 immunostaining was performed, and positive staining was defined as a cluster of at least two stained nuclei in the upper two thirds of the epithelial thickness. Human papillomavirus (HPV) DNA detection was performed using a polymerase chain reaction assay. All cases were subsequently reclassified as low-grade squamous intraepithelial lesion (LSIL) or normal (NL) when two or three of three gold standard criteria were satisfied (LSIL gold standard criteria = consensus diagnosis of LSIL, HPV+, MIB-1+; NL gold standard criteria = consensus diagnosis of NL, HPV-, MIB-1-). Using the gold standard diagnoses, we have identified that 14 normal cases (36%) were originally overdiagnosed as LSIL, and one LSIL case (10%) was originally underdiagnosed as normal. All MIB-1-positive cases were HPV+ and identified as LSIL in the consensus review. All MIB-1-negative cases were NL by gold standard criteria. The sensitivity (1.0) and the specificity (1.0) of MIB-1 staining for identifying LSIL were superior to the sensitivity (0.9) and the specificity (0.8) of HPV testing. In conclusion, MIB-1 is a highly sensitive and specific marker for identifying low-grade squamous intraepithelial lesion and is helpful in verifying the diagnosis of equivocal cases.     

A simple and inexpensive particle agglutination test to distinguish recent from established HIV-1 infection.

OBJECTIVES: We sought to modify the Serodia HIV-1/HIV-2 particle agglutination assay (PA), a simple and cost-effective HIV assay that is used globally for the detection of HIV antibodies, as a sensitive/less sensitive test (S/LS) to identify recently infected individuals and to estimate HIV incidence. METHODS: The Serodia PA test was modified as an S/LS test (PA-LS) by using HIV antigen-coated gelatin particles at a dilution of 1:68 and a specific diluent, and calibrated using 37 HIV clade B seroconversion panels (309 samples) from Trinidad and from a commercial source that were tested at dilution intervals from 1:10 to 1:80,000. The greatest sensitivity for correctly classifying samples from recent and established infections was determined by receiver operator curve (ROC) analysis. RESULTS: At a 1:40,000 sample dilution and a days post-seroconversion cutoff of 190 days, the PA-LS test yielded a 97% sensitivity for classifying recent and established infection samples. Furthermore, at a 1:20,000 dilution, the positive predictive value for correctly identifying recently infected individuals was 99%. The PA-LS test offers a 30-44-fold cost saving over currently available S/LS tests. CONCLUSION: A modified, low cost and simple-to-perform PA test is appropriate for use in resource-limited countries, and has exhibited excellence in distinguishing recent from established HIV infection.     

Neuronal plasticity in memory and learning abilities: Theoretical position and selective review

Neural plasticity of modality-nonspecific and modality-specific memory and learning abilities pertains to fluid intelligence and crystallized intelligence, respectively. The limbic system with the novelty neurons of the hippocampus interacts with the prefrontal cortex optimization of the orienting reflex and voluntary attention. Brain-derived neurotrophic factor produced by novelty neurons of the hippocampus contributes to long-term memory formation and improves learning abilities in a wide range of disciplines. Synergistic combination of stimulation with “analytical-specific visual perceptual patterns” and “optimally high” physiological activation of the bilateral electrodermal system optimizes the limbic system and prefrontal cortex activity as demonstrated by enhanced prefrontal N450 ERPs to a memory workload paradigm. This is accompanied by improvements in auditory retention tasks, word memorization, higher school achievement and marks, and an amelioration of “analytical-specific perceptual skills” as measured by the Mangina-Test. Intracerebral ERPs to a memory workload paradigm contributed to the elucidation of limbic structures and neocortical sites involved in memory workload processes. The progressive degeneration of these same structures causes the gradual decline of memory functions observed in early Alzheimer's disease. Research findings indicate that ERPs elicited by a memory workload paradigm are sensitive markers for diagnosis, treatment and clinical follow-up of early Alzheimer's patients. In addition, ERPs provide objective measurement of cholinergic medication effects on cerebral functions involved in memory processes through neuropsychophysiological parameters.     

Contribution of Calcium Channel Subtypes to the Intracellular Calcium Signal in Sensory Neurons: The Effect of Injury

Background: Although the activation-induced intracellular Ca2+ signal is disrupted by sensory neuron injury, the contribution of specific Ca2+ channel subtypes is unknown.

Methods: Transients in dissociated rat dorsal root ganglion neurons were recorded using fura-2 microfluorometry. Neurons from control rats and from neuropathic animals after spinal nerve ligation were activated either by elevated bath K+ or by field stimulation. Transients were compared before and after application of selective blockers of voltage-activated Ca2+ channel subtypes.

Results: Transient amplitude and area were decreased by blockade of the L-type channel, particularly during sustained K+ stimulation. Significant contributions to the Ca2+ transient are attributable to the N-, P/Q-, and R-type channels, especially in small neurons. Results for T-type blockade varied widely between cells. After injury, transients lost sensitivity to N-type and R-type blockers in axotomized small neurons, whereas adjacent small neurons showed decreased responses to blockers of R-type channels. Axotomized large neurons were less sensitive to blockade of N- and P/Q-type channels. After injury, neurons adjacent to axotomy show decreased sensitivity of K+-induced transients to L-type blockade but increased sensitivity during field stimulation.     

Mechanical Testing of Seven Fixation Methods for Generation of Compression Across a Midtarsal Osteotomy: A Comparison of Internal and External Fixation Devices

The purpose of this study was to assess 7 methods of fixation for a midtarsal osteotomy. Polyurethane foam models (N = 6) and cadaver specimens (N = 4-7) were used to examine the force generated by the different constructs of fixation. A midtarsal osteotomy was performed on each specimen in the test groups. The osteotomies were fixated either with 2 parallel 0.062-in Kirschner wires and 40-mm-long, 4-mm partially threaded, cancellous, cannulated titanium screws, an external ring fixator (frame), a frame with wires tensioned (tension), a frame with wires tensioned and compressed toward the osteotomy (tension and compression), a frame with tension, compression, and parallel Kirschner wires, or a frame with tension, compression, and two 4.0 cannulated parallel screws, respectively. Each model was fixated, and the force generated by the construct across the osteotomy was recorded via the use of pressure-sensitive film. Statistical analysis of the data in the polyurethane foam group determined that the use of frame with tension, compression, and two 4.0 parallel cannulated screws was statistically superior to 1) frame, 2) frame with tension, 3) 2 parallel Kirschner wires, 4) two 4.0 cannulated parallel screws, and 5) frame with tension and compression. A cadaver study determined that the frame with tension, compression, and 2 parallel Kirschner wires was statistically superior to 1) frame and 2) two parallel Kirschner wires. These findings suggest that there is a difference in the force generated by the type of fixation construct across a midtarsal osteotomy.     

Human leukocyte antigen and adult living-donor liver transplantation outcomes: an analysis of the organ procurement and transplantation network database.

Human leukocyte antigen (HLA) compatibility has no clinically significant impact in cadaveric liver transplantation. Less is known regarding living-donor liver transplantation (LDLT). Our prior analysis of the Organ Procurement and Transplantation Network (OPTN) database suggested a higher graft failure rate in patients who underwent LDLT from donors with close HLA match. We further investigated the effect of HLA-A, -B, and -DR matching on 5-yr graft survival in adult LDLT by analyzing OPTN data regarding adult LDLT performed between 1998 and 2005. We evaluated associations between 5-yr graft survival and total, locus-specific, and haplotype match levels. Separate analyses were conducted for recipients with autoimmune (fulminant autoimmune hepatitis, cirrhosis secondary to autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis) or nonautoimmune liver disease. Multivariable Cox proportional hazard models were used to evaluate interactions and adjust for potential confounders. Among 631 patients with available donor/recipient HLA data, the degree of HLA match had no significant effect on 5-yr graft survival, even when analyzed separately in recipients with autoimmune vs. nonautoimmune liver disease. To be able to include all 1,838 adult LDLTs, we considered a first-degree related donor as substitute for a close HLA match. We found no difference in graft survival in related vs. unrelated pairs. In conclusion, our results show no detrimental impact of close HLA matching on graft survival in adult LDLT, including in recipients with underlying autoimmune liver disease.     

Multiple chop wounds in Hong Kong

Knife injuries can be classified into stabbing injuries and multiple laceration or multiple chops, the latter being much more common in Chinese communities. It is the mark of criminal gang attacks with their tendency to use long knives and choppers rather than guns. The intention is often to wound rather than kill. A survey of 89 cases revealed that 90% of the victims are men, with a mean age of 27 years; 75% was admitted to the hospital at night, and in 78% of the cases the assailants were persons unknown, or so we were told by the victims. The reasons for the attacks were also not given. Most of the women victims were assaulted by their spouse. Some 74% of the patients suffered three to six lacerations; 62% of the injuries were on the extensor surfaces of the upper limbs, while the hand and the back of the trunk were also common sites. The type of management differs from that for stabbing injuries. There were no fatalities, and less than half of the patients required blood transfusion. The average hospital stay was 6.2 days. The morbidity of these injuries involves damaged tendons and nerves.