Mode of vascularization of control and basic fibroblast growth factor-stimulated prefabricated skin flaps

This study, using 62 rabbits, examines the rate and pattern of vascular outgrowth from a subcutaneously implanted vascular pedicle, how the newly formed vessels connect to preexisting skin vessels, and whether local application of basic fibroblast growth factor can accelerate the angiogenic process. When the femoral artery and vein of rabbits are implanted beneath the skin, angiogenesis from both the pedicle and small blood vessels within the adjacent skin begins within 3 days. Perfusion with India ink reveals connections between the pedicle and dermal vessels as early as 5 days after implantation of the pedicle. Provided the pedicle does not thrombose, skin flaps based on it may survive completely when elevated as early as 2 weeks after implantation. Flap survival depends on the development of a small number of vascular connections between vessels arising from the pedicle and preexisting dermal vessels. If elevation is delayed until 4 weeks after implantation a flap may survive even if its pedicle has thrombosed. Prolonged release of basic fibroblast growth factor adjacent to the pedicle significantly increases the survival of flaps elevated 1 week after implantation but does not alter the survival of flaps elevated at 2 and 4 weeks.     

Macrophage activation results in bone resorption

Monocytes or macrophages from important accessory cells in the regulation of bone metabolism and destruction. Cells of the mononuclear phagocyte lineage form the precursor cells of the osteoclasts. Soluble products produced by activated macrophages regulate progenitor cell proliferation, recruitment, differentiation, and activity of osteoblasts and osteoclasts. After osteoclasts are removed from the resorption site, macrophages process bone surfaces and create a cement line before osteoblasts enter to form new bone. Although osteolysis associated with normal bone remodeling is seen as an osteoclast driven process, it may be that in chronic inflammation macrophage activation and vascular derangements lead to low pH, local bone demineralization (acid attack), and H+ mediated stimulation of the primary afferent nociceptive nerve fibers (bone pain). Osteoclasts are not able to attach to demineralized bone or to osteoid surfaces. However, if macrophages degrade the demineralized organic bone matrix, chemotactic factors and attachment sites for osteoclasts are produced. In such a scenario, the osteoclast-osteoblast mediated activation, resorption, and formation cycle would be secondarily activated. Such events may play a role in the most common orthopaedic problem related to macrophage activation, aseptic loosening of orthopaedic joint implants, which is secondary to a chronic foreign body reaction and to micromovement.     

The small-cell variant of mycosis fungoides. A clinicopathological and quantitative electron microscopic study on 14 patients

Small-cell variants of Sézary syndrome and mycosis fungoides (MF) have been described. However, in these studies the nuclear area of the small-cell variant of MF (SC-MF) as compared to histological classical MF (CL-MF) was not characterized objectively by quantitative electron microscopy. In a 14-year follow-up period, of a total of 76 patch/plaque stage MF patients seen in the Department of Dermatology of the University Hospital Utrecht, 14 (18%) had an infiltrate composed of atypical lymphocytes characterized by a distinctly smaller cell diameter and smaller, hyperchromatic, deeply indented nuclei as compared to the usual cell type of MF. The aim of the investigation was to confirm this observation objectively using quantitative electron microscopy (morphometry) and to define SC-MF as compared to CL-MF. The study was performed on the 14 patients with SC-MF, and 10 patients with clinical and histological CL-MF and 4 patients with chronic eczema. Electron micrographs of sections obtained from each biopsy were analysed by computer to produce the following data: a nuclear contour index (NCI), the mean nuclear area (MNA), the mean nuclear area of the cells above the 75th percentile (P75NA) and the percentage of cells larger than 30 microm2. The values of MNA differed significantly between patients with SC-MF and those with CL-MF (17.6 vs 23.2 microm2; P = 0.02), as did the values of P75NA (20.7 vs 27.9 microm2; P = 0.01). The NCI of the SC-MF and CL-MF patients were similar. These results are consistent with our observations that SC-MF does indeed exist.     

APPLICATION OF d-ELECTRON ALLOY DESIGN THEORY TO DEVELOPMENT OF HOT CORROSION RESISTANT Ni-BASE SINGLE CRYSTAL SUPERALLOYS——Ⅰ Characterization of Phase Stability

为应用d-电子合金设计理论(或新相分计算法(New PHACOMP))设计发展新型抗热腐蚀单晶高温合金,首先对高Cr抗热腐蚀IN738LC系列合金Ni—16Cr—9.5Al—4.0Ti-8.0Co—0.55Nb—0.06Zr—0.05B—0.47C-Ta—W—Mo(at-％)的相稳定性进行了综合评价得出抑制σ相析出的稳定性临界条件为Mdt<0.991或Mdγ<0.93同时证明这两个临界电子参数具有等价性,可以用Mdt代替Mdγ简化合金设计过程.这一结果可适用于其它高Cr系列抗热腐蚀镍基合金的d-电子合金设计     

DNA-Directed alkylating agents. 7. Synthesis, DNA interaction, and antitumor activity of bis(hydroxymethyl)- and bis(carbamate)-substituted pyrrolizines and imidazoles

A series of bis(hydroxymethyl)-substituted imidazoles, thioimidazoles, and pyrrolizines and related bis(carbamates), linked to either 9-anilinoacridine (intercalating) or 4-(4-quinolinylamino)benzamide (minor groove binding) carriers, were synthesized and evaluated for sequence-specific DNA alkylation and cytotoxicity. The imidazole and thioimidazole analogues were prepared by initial synthesis of [(4-aminophenyl)alkyl]imidazole-, thioimidazole-, or pyrrolizine dicarboxylates, coupling of these with the desired carrier, and reduction to give the required bis(hydroxymethyl) alkylating moiety. The pyrrolizines were the most reactive alkylators, followed by the thioimidazoles, while the imidazoles were unreactive. The pyrrolizines and some of the thioimidazoles cross-linked DNA, as measured by agarose gel electrophoresis. Strand cleavage assays showed that none of the compounds reacted at purine N7 or N3 sites in the gpt region of the plasmid gpt2Eco, but the polymerase stop assay showed patterns of G-alkylation in C-rich regions. The corresponding thioimidazole bis(carbamates) were more selective than the bis(hydroxymethyl) pyrrolizines, with high-intensity bands at 5'-NCCN, 5'-NGCN and 5'-NCGN sequences in the PCR stopping assay ( indicates block sites). The data suggest that these targeted compounds, like the known thioimidazole bis(carbamate) carmethizole, alkylate exclusively at guanine residues via the 2-amino group, with little or no alkylation at N3 and N7 guanine or adenine sites. The cytotoxicities of the compounds correlated broadly with their reactivities, with the bis(hydroxymethyl)imidazoles being the least cytotoxic (IC50s >1 microM; P388 leukemia) and with the intercalator-linked analogues being more cytotoxic than the corresponding minor-groove-targeted ones. This was true also for the more reactive thioimidazole bis(carbamates) (IC50s 0.8 and 11 microM, respectively), but both were more active than the analogous "untargeted" carmethizole (IC50 20 microM). The bis(hydroxymethyl)pyrrolizine analogues were the most cytotoxic, with IC50s as low as 0.03 microM.     

Crystal growth in dental enamel: the role of amelogenins and albumin

Amelogenin-mineral interactions were investigated using an in vitro binding approach. Rat incisor enamel matrix proteins (mainly amelogenins) were dissolved in synthetic enamel fluid and allowed to equilibrate with deproteinised developing enamel crystals. The results showed that amlogenin proteins of 21, 23, 24, 26 and 27-kDa (corresponding to nascent and partially degraded amelogenins) were associated with the crystals whilst the lower Mr amelogenins (< 21 KDa) remained free in the synthetic enamel fluid. These data suggest the nascent and partially degraded amelogenins may interact with developing enamel crystals and could influence their growth. Albumin-mineral interactions were investigated by extracting developing rat incisor enamel with synthetic enamel fluid. Insoluble material (including the enamel crystals) was then further extracted with 0.1 M phosphate buffer (pH 7.4) to desorb any mineral bound proteins. Western blotting using anti-albumin antibodies showed that almost all of the albumin from the secretory stage enamel and a significant proportion of the albumin present in early transition stage was extractable in the synthetic enamel fluid. However, synthetic enamel fluid did not extract albumin from late transition or maturation stage tissue, which could only be removed following further extraction with phosphate buffer. Albumin degradation was apparent during the transition and maturation stages, where it is degraded and ultimately removed. This binding pattern may be related to amelogenin degradation and removal during the transition stage, permitting albumin access to the previously obscured crystal surfaces. That the secretory stage matrix appears to "protect" secretory stage crystals from albumin may be an important consideration in the aetiology of enamel hypoplasias (i.e. incomplete crystal growth) and when using dissociative extraction procedures for the identification of mineral bound proteins.