Isolation and Characterization of Streptococcus mutans Phage as a Possible Treatment Agent for Caries

Streptococcus mutans is a key bacterium in dental caries, one of the most prevalent chronic infectious diseases. Conventional treatment fails to specifically target the pathogenic bacteria, while tending to eradicate commensal bacteria. Thus, caries remains one of the most common and challenging diseases. Phage therapy, which involves the use of bacterial viruses as anti-bacterial agents, has been gaining interest worldwide. Nevertheless, to date, only a few phages have been isolated against S. mutans. In this study, we describe the isolation and characterization of a new S. mutans phage, termed SMHBZ8, from hundreds of human saliva samples that were collected, filtered, and screened. The SMHBZ8 genome was sequenced and analyzed, visualized by TEM, and its antibacterial properties were evaluated in various states. In addition, we tested the lytic efficacy of SMHBZ8 against S. mutans in a human cariogenic dentin model. The isolation and characterization of SMHBZ8 may be the first step towards developing a potential phage therapy for dental caries.     

Effect of complement consumption by cobra venom factor on the the course of primary infection with simian immunodeficiency virus in rhesus monkeys

Cobra venom factor (CVF)-induced consumption of complement proteins was used to investigate the role of complement in vivo in the immunopathogenesis of simian immunodeficiency virus of macaques (SIVmac) infection in rhesus monkeys. Repeated administration of CVF was shown to deplete complement to <5% of baseline hemolytic activity of serum complement for 10 days in a normal monkey. Three groups of SIVmac-infected animals were then evaluated: monkeys treated with CVF resulting in complement depletion from days -1 to 10 postinfection, monkeys treated with CVF resulting in complement depletion from days 10 to 21 postinfection, and control monkeys that received no CVF. CD8+ SIVmac-specific cytotoxic T lymphocyte (CTL) generation and CD4+ T lymphocyte depletion during primary infection were not affected by CVF treatment. Viral load, assessed by measurements of plasma p27gag antigen and viral RNA, was transiently higher during the first 4 weeks following infection in the CVF-treated monkeys and the subsequent clinical course in these treated animals was accelerated. These results suggest that complement proteins may participate in immune defense mechanisms that decrease virus replication following the initial burst of intense viremia during primary SIVmac infection. However, we cannot rule out that the observed increased virus replication was induced by immune activation resulting from the administration of a foreign antigen to these monkeys.     

Acquired homozygosity of the rearranged bcr allele during the acute leukemic phase of a patient with Ph-negative chronic myeloid leukemia

A 45-year-old male patient with Ph-negative chronic myeloid leukemia (CML) had rearranged bcr-3' and bcr-5' gene regions in Southern blot studies when leukemia was diagnosed. During development of terminal blast crisis, successive blood samples showed a progressive decrease in the amount of germline bcr DNA and its complete loss by full blast crisis. There were also increased amounts of rearranged bcr DNA consistent with acquired homozygosity. A similar result was obtained with an IgV lambda probe and indicated homozygosity of a significant part of chromosome 22. The bcr-abl gene complex behaves as a somatic dominant in CML, and we suggest that its acquired homozygosity is a mechanism of bcr-abl amplification similar to duplication of the Ph chromosome commonly found in the blast crisis of CML.     

Use of porcine factor VIII in the treatment of patients with acquired hemophilia

Data have been collected from 47 centers in Europe and North America on the treatment with porcine factor VIII concentrate of 74 acute bleeding episodes in 65 patients with acquired hemophilia. The median initial anti-human factor VIII auto-antibody inhibitor level was 38 Bethesda unit (BU)/mL (range 1.2 to 1,024) whereas that against porcine was 1 BU/mL (range 0 to 15). The mean initial dose of porcine factor VIII infused was 84 IU/kg, which increased the plasma factor VIII:C activity by 0.85 IU/mL. Therapy was continued for a mean of 8.5 days during which time the average number of infusions was 11. Objective clinical responses were rated as good or excellent in 78% of recipients. Side effects were uncommon; only one patient experienced a severe anaphylactic reaction necessitating the discontinuation of porcine FVIII therapy. After therapy, no increase in the median level of anti- human FVIII or anti-porcine antibody was noted in the group as a whole, although 13 patients showed individual increases in either anti-human or anti-porcine antibody levels or both of more than 10 BU/mL. Of the 7 patients who subsequently rebled, 5 were successfully re-treated and 2 did not respond to further porcine factor VIII treatment. Porcine factor VIII is safe and clinically effective treatment for bleeding episodes associated with acquired hemophilia and should be considered as first-line therapy for patients whose acquired anti-factor VIII:C antibody cross-reacts with porcine factor VIII:C at low levels.     

Increased vulnerability to demyelination in streptozotocin diabetic rats

Demyelination is a prominent feature in nerve biopsies of patients with diabetic neuropathy. The mechanism is unknown because diabetic rodents, unlike humans, do not consistently develop segmental demyelination. We examined how diabetes influences toxicant-induced demyelination, remyelination, Schwann cell nerve growth factor receptor (p75) expression, and endoneurial macrophage apolipoprotein E (apo E) synthesis in diabetic rats. Postnatal day 17 (P17) rats were given 110 mg/kg streptozotocin intraperitoneally and then fed a diet containing metallic tellurium (Te) from P20 to P27 to induce demyelination. Transverse electron micrographs and immunostained longitudinal cryosections were prepared from sciatic nerve during demyelination and remyelination. Diabetic rats had a mean serum glucose concentration of 490 mg/dl and consumed equivalent doses of peroral Te. The number of demyelinated fibers in electron micrographs was increased significantly by 17% (P < .0011). Endoneurial density of p75-stained Schwann cells was increased in diabetic rats in proportion to the increased number of injured internodes. Density of apo E- and ED1-positive macrophages also was significantly increased in diabetes. There was no delay in macrophage myelin clearance, and remyelination was not compromised. Increased Schwann cell vulnerability to stress, by increasing the turnover rate of myelinated units, may explain why myelin defects accumulate after long-standing diabetes. © 1996 Wiley-Liss, Inc.     

Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance

Neutrophil extracellular traps (NETs) have been shown to worsen acute pulmonary injury including after lung transplantation. The breakdown of NETs by DNAse‐1 can help restore lung function, but whether there is an impact on allograft tolerance remains less clear. Using intravital 2‐photon microscopy, we analyzed the effects of DNAse‐1 on NETs in mouse orthotopic lung allografts damaged by ischemia‐reperfusion injury. Although DNAse‐1 treatment rapidly degrades intragraft NETs, the consequential release of NET fragments induces prolonged interactions between infiltrating CD4⁺ T cells and donor‐derived antigen presenting cells. DNAse‐1 generated NET fragments also promote human alveolar macrophage inflammatory cytokine production and prime dendritic cells for alloantigen‐specific CD4⁺ T cell proliferation through activating toll‐like receptor (TLR) — Myeloid Differentiation Primary Response 88 (MyD88) signaling pathways. Furthermore, and in contrast to allograft recipients with a deficiency in NET generation due to a neutrophil‐specific ablation of Protein Arginine Deiminase 4 (PAD4), DNAse‐1 administration to wild‐type recipients promotes the recognition of allo‐ and self‐antigens and prevents immunosuppression‐mediated lung allograft acceptance through a MyD88‐dependent pathway. Taken together, these data show that the rapid catalytic release of NET fragments promotes innate immune responses that prevent lung transplant tolerance.     

Ageing appearance in China: biophysical profile of facial skin and its relationship to perceived age

Background Perceived age is important to women and is a primary driver for topical product use and facial cosmetic surgery. Changes in facial features and biophysical skin parameters with chronological age and their associations with perceived age have not been described in Asian populations. Objective To investigate the relationship between biophysical properties of the skin, visual features of skin ageing and perceived facial age in Chinese women. Methods Facial photographs were collected of 250 Chinese women, aged 25–70 years in Shanghai, China. The perceived facial age was determined and related to the chronological age for each participant and to a range of visual assessments of skin appearance and objective biophysical measurements of the skin. The profile of changes in these parameters with age was investigated together with the differences in those parameters for women judged to look younger than their chronological age and those judged to look older than their chronological age. Results Large discrepancies in perceived age (up to 29 years) were found in women of the same chronological age. Each objective skin measure and visual assessment parameter had a stronger correlation with perceived age than with chronological age. The strongest relationships to perceived age were for wrinkles and hyperpigmentation. Skin colour, hydration and trans‐epidermal water loss (TEWL) had weaker associations with perceived age. Women judged to look older than their chronological age had significantly higher scores than those judged to look younger for coarse wrinkles and hyperpigmentation across all age groups. The appearance differences between these groups were evident in composite facial images of the same average chronological age. Conclusions We have identified the skin attributes which differ with perceived age in Chinese women. Perceived age is a better measure of the biological age of facial skin than is chronological age in this population.