Prognostic factors for surgical resection in patients with multidrug-resistant tuberculosis.

Although surgical lung resection could improve prognosis in some patients with multidrug-resistant tuberculosis (MDR-TB), there are no reports on the optimal candidates for this surgery. The aim of the present study was to elucidate the prognostic factors for surgery in patients with MDR-TB. Patients who underwent lung resection for the treatment of MDR-TB between March 1993 and December 2004 were included in the present study. Treatment failure was defined as greater than or equal to two of the five cultures recorded in the final 12 months of treatment being positive, any one of the final three cultures being positive, or the patient having died during treatment. The variables that affected treatment outcomes were identified through univariate and multivariate logistic regression analysis. In total, 79 patients with MDR-TB were included in the present study. The treatment outcomes of 22 (27.8%) patients were classified as failure. A body mass index <18.5 kg x m(-2), primary resistance, resistance to ofloxacin and the presence of a cavitary lesion beyond the range of the surgical resection were associated with treatment failure. Low body mass index, primary resistance, resistance to ofloxacin and cavitary lesions beyond the range of resection are possible poor prognostic factors for surgical lung resection in multidrug-resistant tuberculosis patients.     

Comparison of airway diameter measurements from an anthropomorphic airway tree phantom using hyperpolarized 3He MRI and high-resolution computed tomography.

An anthropomorphic airway tree phantom was imaged with both hyperpolarized (HP) 3He MRI using a dynamic projection scan and computed tomography (CT). Airway diameter measurements from the HP 3He MR images obtained using a newly developed model-based algorithm were compared against their corresponding CT values quantified with a well-established method. Of the 45 airway segments that could be evaluated with CT, only 14 airway segments (31%) could be evaluated using HP 3He MRI. No airway segments smaller than approximately 4 mm in diameter and distal to the fourth generation were adequate for analysis in MRI. For the 14 airway segments measured, only two airway segments yielded a non-equivalent comparison between the two imaging modalities, while eight more had inconclusive comparison results, leaving only four airway segments (29%) that satisfied the designed equivalence criteria. Some of the potential problems in airway diameter quantification described in the formulation of the model-based algorithm were observed in this study. These results suggest that dynamic projection HP 3He MRI may have limited utility for measuring airway segment diameters, particularly those of the central airways.     

Human anti-JC virus serum reacts with native but not denatured JC virus major capsid protein VP1

The immunoreactivity of human anti-JC virus (JCV) serum against the major capsid protein VP1 of JCV was analyzed by Western blot, dot blot, and hemagglutination inhibition (HAI) assays. JCV-positive human serum reacted with native but not denatured JCV major capsid protein VP1, as demonstrated by dot blot and Western blot. Rabbit antiserum raised against native JCV capsid had immunoreactivities similar to those of human anti-JCV serum. These results indicate that the antigenecity of native and denatured JCV VP1 is different. In addition, both JCV-positive human serum and rabbit antiserum raised against native JCV capsid protein inhibited the hemagglutination activity of JCV capsid particles. In contrast, rabbit antiserum raised against denatured JCV VP1 did not inhibit hemagglutination. These findings reveal that denaturation may alter the antigenic epitopes of JCV VP1. Therefore, keeping the JCV capsid protein native appears to be essential for serological or other immunological analyses of the virus.     

Novel HLA-A*11 allele, A*1120, identified by sequence-based typing

In this report, we describe the identification of a human leucocyte antigen-A*11 (HLA-A*11) nucleotide sequence variant, a new HLA-A*1120 by using sequence-based typing (SBT). The new allele was detected during routine HLA typing by high-resolution SBT. Allele A*1120 showed one nucleotide difference with A*110101 at codon 152 (GCG-->GAG) resulting in an amino acid change from alanine to glutamate. Residue 152 is located on alpha(2)-helix of HLA class I molecule and involved in peptide binding by constructing E pocket of peptide-binding groove, implying that the change of the residue 152 would affect the binding affinity of peptides to A*1120 allele.     

Transcriptome analysis in blastocyst hatching by cDNA microarray

BACKGROUND: Hatching is an important process for early embryo development, differentiation and implantation. However, little is known about its regulatory mechanisms. By integrating the technologies of RNA amplification and cDNA microarrays, it has become possible to study the gene expression profile at this critical stage. METHODS: Pre-hatched and hatched ICR mouse embryos (25 blastocysts in each group were used in the triplicate experiments) were collected for RNA extraction, amplification, and microarray analysis (the mouse cDNA microarray, 6144 genes, including expressed sequence tags). RESULTS: According to cDNA microarray data, we have identified 85 genes that were expressed at a higher level in hatched blastocyst than in pre-hatched blastocysts. In this study, 47 hatching-related candidate genes were verified via re-sequencing. Some of these genes have been selected and confirmed by real-time quantitative RT-PCR. These hatching-specific genes were also expressed at a lower level in the delayed growth embryos (morula or blastocyst without hatching at day 6 post hCG). These genes included: cell adhesion and migration molecules [E-cadherin, neuronal cell adhesion molecule (NCAM), lectin, galactose binding, soluble 7 (Lgals7), vanin 3 and biglycan], epigenetic regulators (Dnmt1, and SIN3 yeast homolog A), stress response regulators (heme oxygenase 1) and immunoresponse regulators [interleukin (IL)-2-inducible T-cell kinase, IL-4R, interferon-gamma receptor 2, and neurotrophin]. The immunostaining of E-cadherin and NCAM showed strong and specific localization in hatched blastocyst. CONCLUSIONS: This work provides important information for studying the mechanisms of blastocyst hatching and implantation. These hatching-specific genes may have potential as new drug targets for controlling fertility.     

Characterization of four newly established human colorectal adenocarcinoma cell lines from Chinese patients.

Four colon adenocarcinoma cell lines, CC-M2, CC-M3, CC-M4, and CC-M2NM, have been established from surgical specimens of 18 unselected patients without the use of "feeder" cells and additional growth factors (e.g., insulin, hydrocortisone, etc.) in the culture medium. The methods of primary cultivation of tissue explants are described. Studies of determination of morphology, growth curve, plating efficiency, chromosomal analysis, CEA and beta-HCG synthesis, and tumorigenicity, were done to characterize the cell lines. Significant variations have been found in one of the four cell lines, both in vitro and in vivo studies. There are distinct phenotypes in the established cell lines which may be useful in studying the cell differentiation and progression of colorectal cancer.     

Failure of stimulated skeletal muscle mainly contributed by passive force: an in vivo rabbit model

OBJECTIVE: To evaluate the role of active and passive muscle forces in the failure mechanism of stimulated muscle. DESIGN: An in vivo rabbit model. BACKGROUND: Eccentric contractions can result in a greater incidence of muscle injury. However, the relative role of the active and passive muscle force in the failure mechanism of the activated muscle is not well elucidated. METHODS: After anaesthesia, New Zealand white rabbits were fixed in a frame on a materials testing machine. The triceps surae muscle-tendon units were passively stretched to rupture with our without continuous nerve stimulation. The force and muscle length were simultaneously recorded. Active muscle force, passive muscle force, and ratio of the active to passive muscle were calculated and depicted against strain. RESULTS: The results showed that the mean maximal passive force of triceps surae muscle was 293.1 N at a strain of 38%. The mean peak active muscle force was 21.5 N at a strain of 21%. The ratio of active to passive muscle force reached its peak first, followed by the active muscle force, and then the passive muscle force. The ratio of active to passive muscle force at the peak total force was only 3.3%. CONCLUSIONS: The stimulated muscle can exert its maximal response at extreme physiological extension. Injury of the stimulated muscle is caused mainly by passive muscle force.     

Enhanced stability and clinical absorption of a form of encapsulated vitamin A for food fortification

Food fortification is an effective strategy to address vitamin A (VitA) deficiency, which is the leading cause of childhood blindness and drastically increases mortality from severe infections. However, VitA food fortification remains challenging due to significant degradation during storage and cooking. We utilized an FDA-approved, thermostable, and pH-responsive basic methacrylate copolymer (BMC) to encapsulate and stabilize VitA in microparticles (MPs). Encapsulation of VitA in VitA-BMC MPs greatly improved stability during simulated cooking conditions and long-term storage. VitA absorption was nine times greater from cooked MPs than from cooked free VitA in rats. In a randomized controlled cross-over study in healthy premenopausal women, VitA was readily released from MPs after consumption and had a similar absorption profile to free VitA. This VitA encapsulation technology will enable global food fortification strategies toward eliminating VitA deficiency.

Vitamin A (VitA) plays an essential role in visual health, immune function, and fetal growth and development (1). VitA deficiency (VAD) arises from diets with insufficient fat-soluble micronutrients (MNs) and is currently estimated as the second most common cause of malnutrition, after iron, globally (2). VAD can lead to xerophthalmia (preventable childhood blindness) and weakened host resistance to infection, which can increase the risk of mortality from infectious diseases, such as measles and COVID-19 (3, 4). The WHO estimated that VAD affected 190 million preschool-age children (33.3% of the preschool-age population) and >19 million pregnant women (15.3% of the pregnant population) globally in the period spanning 1995–2005 (5). The most severely affected regions still reached VAD prevalence levels of 48% in sub-Saharan Africa and 44% in South Asia in children in 2013 (6). To reduce the high burden of VAD, a VitA supplementation program was implemented worldwide in 1990 that distributed high-dose VitA capsules every 4–6 mo to over 80% of the total child population in low-income countries (7). This project effectively reduced all-cause mortality caused by severe VAD by 12% (8). However, progress toward VAD elimination was limited to a rate of improvement of only ~0.3% per year from 1990 to 2007, showing that more impactful strategies are required (9, 10).To raise and maintain serum retinol levels, frequent intake of VitA at physiological doses is proven to be more effective than one or two high doses administered over 6 mo (11). However, VitA food fortification is challenging due to its poor stability, which can lead to poor bioavailability after degradation, and fat solubility, which limits the inclusion of VitA in water-based and dry food matrices (12). To prevent VitA degradation and improve miscibility, VitA has previously been encapsulated within matrices composed of polysaccharides (13), proteins (14), and/or lipids (15); however, these materials provide limited protection during storage and cooking (16 –18) and can take up to 3 h to release in the stomach (19). Poor protection and slow release of VitA prevent effective absorption. Therefore, the ideal microparticle (MP) platform for VitA fortification should meet these criteria: i) protect VitA against degradation during storage and cooking; ii) rapidly release VitA in the gastrointestinal tract with high absorption; and iii) readily mix with various food matrices at a tunable concentration to meet the dynamic needs of the target population.We hypothesized that by encapsulating VitA with a pH-responsive hydrophobic polymer, we could enhance stability during storage and cooking and ensure its rapid release in the gastrointestinal tract for subsequent absorption. A commercially available, FDA-approved basic methacrylate copolymer (BMC), also known as either Eudragit® E PO or GRAS-status Eudraguard®, was identified from our previous work (20). BMC is generally regarded as safe with an acceptable daily intake of 20 mg/kg body weight (21). VitA-encapsulated BMC MPs were prepared by emulsion at the laboratory scale and by a commercial process at the kilogram scale. Our VitA-BMC-S MPs readily mix with flour and bouillon cubes and demonstrate enhanced stability under cooking and long-term storage conditions (over 12 mo) in comparison to a leading commercial encapsulated VitA product. The bioavailability of VitA from VitA-BMC MPs was first demonstrated in a rodent model, resulting in a ninefold increase in the accumulation of VitA in the liver from cooked VitA-BMC MPs, as compared to cooked unencapsulated free VitA. In a human clinical study, the absorption of VitA from bread fortified with VitA-BMC-S MPs was investigated, with or without the codelivery of encapsulated iron sulfate (FeSO₄) and folic acid (FA), MNs that children and pregnant women globally are also often deficient in (22, 23). The results indicate that VitA is readily released and absorbed from VitA-BMC-S MPs, and the codelivery of encapsulated iron and free FA does not influence the absorption of VitA. In total, we demonstrated scalable production of MP-encapsulated VitA with enhanced stability and good bioavailability in humans, which could potentially mitigate the high burden of VAD and be codelivered with other MNs.