Apolipoprotein D is down-regulated during malignant transformation of neurofibromas

Apolipoprotein D (apoD) expression was studied in nonneoplastic peripheral nerve, neurofibromas (NFs), and malignant peripheral nerve sheath tumors (MPNSTs) by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. Multiplex quantitative polymerase chain reaction for messenger RNA was performed on a series of formalin-fixed and paraffin-embedded specimens that included 9 MPNSTs, 12 NFs, and 4 normal peripheral nerves. The average apoD expression was 108-fold decreased (DeltaCt = -7.3) in the MPNSTs compared with the NFs (P < .05). ApoD expression levels were 3.0-fold elevated (DeltaCt = 1.7) in the NFs compared with nonneoplastic peripheral nerve (P < .05). In situ hybridization for apoD RNA was performed on a separate series of 10 cases in which each microscopic section included both MPNST and the NF from which it arose. These studies confirmed elevated apoD expression in NFs compared with MPNSTs and demonstrated that this expression was variable among individual cells within the NFs. Differential expression by immunohistochemistry could only be demonstrated in selected areas, most likely because apoD protein is a small molecule that is secreted out of the cell into the extracellular space and plasma. ApoD expression initially increases a small amount with the formation of NFs from nonneoplastic peripheral nerve and subsequently decreases markedly as NFs transform into MPNSTs. This expression pattern may serve as a marker for cell cycle inhibition during peripheral nerve tumorigenesis.     

Genetic components and intellectual functioning during senescence: A 20-year study of aging twins

Psychological test scores of 13 identical and six fraternal pairs of twins aged 77–88 years were analyzed. These individuals are the survivors of a group of senescent twins studied earlier. The identical twins remained more similar than the fraternal ones, and there was a remarkable conservation of cognitive abilities in most individuals. Moreover, preservation of intelligence and longevity may be related.     

Localization of endogenous galactoside-binding lectin during morphogenesis ofXenopus laevis

Summary A monoclonal antibody has been produced againstXenopus laevis galactoside-binding neural-creststage lectin. This antibody inhibits lectin-mediated hemagglutination. Using this antibody in conjunction with immunohistochemical techniques, lectin deposition has been studied in embryos and tadpoles at different stages of morphogenesis, from initial neural crest migration, up to the formation of a swimming tadpole. Lectin levels change during development in different regions of the embryo and tadpole, decreasing in migratory cells, and increasing in sites where cells become more adhesive to one another. The results suggest that galactoside-binding lectins may be an important class of cellular adhesion molecules during these stages of development.     

Antimicrobial use and outcomes in patients with multidrug-resistant and pansusceptible Salmonella Newport infections, 2002-2003

Multidrug-resistant Salmonella Newport with decreased susceptibility to ceftriaxone (MDR-AmpC) is becoming increasingly common in its food animal reservoirs and in humans. Few data exist on rates of antimicrobial use or differences in clinical outcomes in persons infected with MDR-AmpC or other Salmonella strains. We conducted a case-comparison analysis of data from a multistate population-based case-control study to identify antimicrobial treatment choices and differences in clinical outcomes in those infected with MDRAmpC compared to pansusceptible S. Newport. Of isolates from 215 laboratory-confirmed S. Newport cases, 54 (25%) were MDR-AmpC, 146 (68%) were pansusceptible, and 15 (7%) had other resistance patterns; 146 (68%) patients with S. Newport were treated with antimicrobial agents and 66 (33%) were hospitalized. Over two-thirds of cases at low-risk for serious complications received antimicrobial therapy, most commonly with fluoroquinolones, to which this strain was susceptible. There were no significant differences in symptoms, hospitalization, duration of illness, or other outcomes between the persons infected with MDR-AmpC and pansusceptible S. Newport. Although currently prevalent MDR-AmpC S. Newport strains remains susceptible to the antimicrobial most commonly prescribed for it, continued efforts to reduce unnecessary use of antimicrobial agents in food animals and humans are critical to prevent further development of resistance to quinolones and cephalosporins, which is likely to lead to substantial adverse outcomes.     

Comparison of hepatitis C viral loads in patients with or without coinfection with different genotypes

Hepatitis C virus genotyping was assessed for 257 chronic hepatitis C patients with viral loads above 1,000 IU/ml. Twelve patients were coinfected with more than one genotype. Their median viral loads did not differ significantly from those observed for monoinfected patients, which in turn did not vary significantly among different genotypes.     

Surface reactivity of calcium phosphate based ceramics in a cell culture system

Surface reactivity of Calcium Phosphate materials--Hydroxyapatite (HA), Tricalcium Phosphate (beta-TCP), Hydroxyapatite-Tricalcium Phosphate (HA-TCP) were elucidated in a cell culture system. MG-63 osteoblast-like cells were seeded onto the ceramic discs to evaluate changes in the cell morphology and functionality with respect to the different substrates. The dissolution and re-precipitation of calcium phosphate phases on the surface of the discs in the culture medium was found to be prominent on beta-TCP when compared with HA. Low calcium (Ca), magnesium (Mg) and alkaline phosphatase (ALP) levels and high phosphorous (P) levels in the medium of beta-TCP were observed. This indicated that P must have leached out into the medium from beta-TCP and Ca in turn deposited from the medium onto beta-TCP resulting in the apatite phase transformation. The low ALP activity in beta-TCP medium is however an indication of low osteoblastic activity. Under the phase contrast microscope, the osteoblast cells around HA material were found to be confluent and viable, while in the vicinity of beta-TCP only cellular debris was observed. In the case of HA-TCP, only a few viable cells surrounded the material amidst the debris. Scanning electron microscopy revealed numerous cells on the surface of HA showing different cell behaviour like anchorage, attachment, adhesion and spreading in the early time period as the surface was only slightly disturbed with re-crystallisation. But with time the entire surface of HA had changed due to precipitation and re-crystallization which did not support cell behaviour while the cells surrounding the material showed normal growth. On the contrary, cells were scarcely observed on the entirely changed surface of beta-TCP and HA-TCP even from the earlier days of the culture and the morphology of cells surrounding the material too started changing. These results establish that HA promoted the activity of osteoblast cells. HA surface remained unaltered for some time, while the surface of beta-TCP underwent dissolution of surface ions and resulted in the re-crystallization of apatite over the surface. The resulting changes in the surrounding milieu of beta-TCP with high phosphate and low Ca levels probably was responsible for the death of the cells.     

Effect of estradiol and progesterone on daily rhythm in food intake and feeding patterns in Fischer rats

The product of meal number x meal size, over time, is food intake. Because estrogens modulate feeding activity via their action on the hypothalamus, and because there is a diurnal rhythm in the expression of cytoplasmic estrogen receptors and in estrogen binding activity, the present study examined the effects of ovariectomy and later hormone therapy on acute changes in body weight, and on the meal number-to-meal size relationship as reflected by food intake in the dark/light feeding patterns, in adult female rats in the intact state and after ovariectomy. Twelve female Fischer rats were randomized into ovariectomy and sham operation groups. A rat eater meter measured the feeding indexes for 15 days before and 25 days after ovariectomy, and later for 35 days with hormone therapy. We report: (a) mean body weight gain was linear before and up to ovariectomy, while exponential after ovariectomy; (b) increase in daily food consumption is mainly via an increase in food intake during the light phase; (c) light phase meal number remains unchanged, meal size significantly increases, with the resultant increase in overall food intake; (d) during the dark phase, meal size also significantly increases, but is accompanied by a proportional decrease in meal number, resulting in unchanged dark-phase food intake; and (e) estrogen restoration with either estradiol valerate or estradiol-progesterone combination, reversed the above changes. Data show that in the female Fischer 344 rat: (a) changes in daily rhythm in food intake are brought about by differential effects of the hormones on both meal size and meal number in both the total daily levels as well as in the dark-to-light distribution; (b) estadiol appears to have a tonic inhibitory effect on the light phase meal size and a phasic effect on the dark phase meal size and number, but no significant effect on the light-phase meal number; and (c) in the Fischer rats, progesterone augments estradiol's effect on these indicies.     

N-myristoyltransferase: A potential novel diagnostic marker for colon cancer

Background  

Colon cancer is the second leading cause of cancer deaths in the western world. If detected early, colorectal cancer is one of the most treatable forms of cancer. Unfortunately, very few people are screened. N-myristoyltransferase (NMT) catalyzes myristoylation of various proteins including oncoproteins. We have demonstrated earlier the alteration of NMT activity during the progression of colorectal cancer and established NMT as a putative therapeutic target for cancer.     

Changes in the concentration of globulins in naive guinea pigs during feeding by the immature stages of Rhipicephalus evertsi evertsi (Acari: Ixodidae)

The weight of Rhipicephalus evertsi evertsi Neumann nymphs, which as larvae and nymphs completed the entire blood meal on the same individual guinea pig, was significantly lower than the weight of those that as larvae and nymphs fed on two separate naive hosts. Nymphs of the latter category spent 1 wk (from unfed larvae to unfed nymphs) on one animal before their transfer to the second host to complete the blood meal. The albumin concentration of the host blood decreased and was related to the time that the immature ticks spent on the hosts. The albumin/globulin ratio also decreased. The alpha 1 globulin fraction increased soon after the guinea pigs were infested with ticks. No further changes in the levels of the alpha 1 globulin fraction were observed with time. The concentration of serum beta globulins increased only in guinea pigs infested with immature ticks for the entire larval and nymphal feeding period. A second infestation of those guinea pigs with larvae of R. e. evertsi resulted in further increases in the levels of serum beta globulins. The relationships among serum beta globulin levels, the weight of engorged nymphs, and host immunity are discussed.     

Endotoxin-induced gamma interferon production: contributing cell types and key regulatory factors

Gamma interferon (IFN-gamma) is an important mediator of endotoxin (lipopolysaccharide [LPS])-induced immune responses. However, the specific cell types that produce IFN-gamma in response to LPS and the cellular factors that regulate LPS-induced IFN-gamma production have not been fully determined. The present studies were undertaken to characterize the cell populations that produce IFN-gamma after LPS challenge in the spleens of mice and to determine the regulatory factors that modulate LPS-induced production of IFN-gamma. Our studies show that the levels of splenic IFN-gamma mRNA and protein production peak at 6 and 8 h, respectively, after systemic LPS challenge. Approximately 60% of IFN-gamma-producing cells are natural killer (NK) cells (CD3(-)DX5(+)) and 25% are NKT cells (CD3(+)DX5(+)). Most of the remaining IFN-gamma-producing cells are T cells (CD3(+)DX5(-)), macrophages, and dendritic cells. Functionally, interleukin-12 (IL-12) is the major IFN-gamma-stimulating factor after LPS challenge, with costimulation provided by IL-15, IL-18, and B7 proteins. IL-10 is a major inhibitor of LPS-induced IFN-gamma production. Unlike intact heat-killed gram-negative and gram-positive bacteria, the class II major histocompatibility complex did not play a functional role in LPS-induced IFN-gamma production. LPS is a potent stimulus for splenic IL-10, IL-12 p40, and IL-15 mRNA expression, whereas IL-12 p35 and IL-18 mRNAs, as well as B7 proteins, are constitutively expressed in the mouse spleen. Of the factors studied, IL-18 serves as the most potent costimulus with IL-12 for IFN-gamma production, followed by IL-15 and B7 proteins. These data demonstrate that NK cells and NKT cells are the most abundant IFN-gamma-producing cells in the mouse spleen after LPS challenge and that IL-10 and IL-12 are key functional regulators of LPS-induced IFN-gamma production.