The influence of polymer structure on the interactions of cationic polymers with DNA and morphology of the resulting complexes

Four cationic polymers used to deliver DNA into cultured cells: polylysine, intact polyamidoamine dendrimer, fractured polyamidoamine dendrimer and polyethylenimine, are examined for their ability to interact with DNA. Complexes between the polymers and DNA were examined using electron microscopy. Similar toroidal structures with diameters of 55 +/- 12 nm were formed from all of the cationic polymers with DNA. The DNA complexes of the fractured dendrimer and polyethylenimine were observed as single, distinct units; their apparent diameters in solution as measured by dynamic light scattering ranged from 90 to 130 nm. The DNA complexes of polylysine and intact dendrimer generally appeared as clusters in electron micrographs; their diameters in solution were larger than 1000 nm, which suggests that their toroidal complexes aggregate in solution. The cationic polymers bind to DNA in a stoichiometry that is nearly 1:1 in primary amines to DNA phosphates. The apparent binding of all cationic polymers to DNA decreases linearly with increasing ionic strength, up to 0.8 M NaCl. Thus, at the concentrations studied, these polymers interact electrostatically with DNA forming a unit structure with toroidal morphology; the extent of aggregation of the unit structures in solution depends upon the characteristics of the individual polymer.     

CD56+ NK lymphomas: clinicopathological features and prognosis

Dosing regimen is an important determinant of both drug cost and patient compliance. This retrospective analysis evaluated dosing regimens and drug acquisition costs for 101 patients identified from medical records in a large metropolitan hospital as having hypertension and/or benign prostatic hyperplasia and receiving alpha-blocker therapy with either doxazosin or terazosin. Although once-daily administration is generally recommended for both drugs, 25 (38%) of 66 patients receiving terazosin were treated twice daily compared with 6 (17%) of 35 patients treated twice daily with doxazosin. This difference was statistically significant. The average (mean +/- SD) daily treatment cost per patient for all individuals receiving terazosin during the period of the record review was $1.68 +/- 0.60. For patients treated with doxazosin, the average was $0.96 +/- 0.65-a highly statistically significant result. If all 66 patients receiving terazosin had been converted to doxazosin at the beginning of the study, annual savings would have been $17,345.00. These results demonstrate the importance of reviewing actual dosing regimens. The fact that doxazosin could be administered to a significantly higher percentage of patients once daily rather than twice daily substantially decreased its cost relative to terazosin. A once-daily treatment regimen may also enhance patient compliance, thereby improving the chances of therapeutic success.     

Gait analysis of adult patients with complete congenital dislocation of the hip

Comprehensive gait analysis is valuable in understanding the performance of patients with lower limb disorders. The gait pattern of adult patients with untreated congenital dislocation of the hip (CDH) has not yet been reported. We studied the gait pattern in nine women (mean age 31.4 years) with Crows group IV CDH. Six had unilateral and three had bilateral involvement. They were not treated during childhood and had no pain at the time of study. A control group comprised 15 normal female subjects of the same age group. Gait was studied using a motion-analysis system, force plateforms, and computer calculation during level walking. Common abnormal gait patterns seen in patients with both unilateral and bilateral CDH were slower walking velocity, which was due to a shorter stride length, less forward tilting of the pelvis, insufficient flexion, and excessive internal rotation of the hips. The patients with unilateral CDH had a shorter step length, lower pelvis, a lateral shift of the ground reaction force, decreased maximum adduction moments of the hip and knee on the diseased side, and increased maximum adduction moments of the hip and knee on the unaffected side. This asymmetry may have been due to leg length inequality. Thus, correlation of the leg length discrepancy may be important for unilateral CDH patients in improving their gait.     

Generation of ultra-broad-band supercontinuum bydispersion-flattened and decreasing fiber

It has been made clear through model simulations that dispersion-flattened and decreasing fiber (DFDF) is one of the most suitable fibers for broad-band supercontinuum (SC) generation. SC generation In a bandwidth of 280 nm with intensity fluctuation less than 15 dB has been experimentally observed by using the DFDF designed and manufactured with an optimized dispersion profile     

Current progress in the production of recombinant human fibrinogen in the milk of transgenic animals

The mammary gland of transgenic animals has several advantages for production of heterologous proteins including a high cell density that results in high concentrations of secreted protein. While the mammary gland appears to be able to secrete fully assembled recombinant human fibrinogen (rhfib) at 0.1 to 5 g/l levels, some unassembled rhfib chains are also secreted. Presently, the relationship between unassembled rhfib and the coordinated translation of each nascent rhfib polypeptide in the mammary epithelia is unknown. The secretion of fully and partially assembled rhfib is widely variable among mammalian cell lines and where previously no cell line has been shown to secrete beta chain alone. We have observed that mammary epithelia can secrete B beta chain into milk as well as immature forms of other recombinant proteins, suggesting it likely uses a different secretory pathway than does the liver. This difference in secretory behavior is possibly due to the natural design of milk, where the precise regulation of post translational modifications and intracellular pools of nascent polypeptides needed to achieve fibrinogen assembly may be less important to fulfill the nutritional function of most milk proteins.     

The noninfectious respiratory complications of infection with HIV

Infection with HIV was first recognized through a clustering of unusual respiratory infections. The lung has been a major target manifesting many of the infectious complications of the immunodeficiency. Noninfectious pulmonary complications in HIV-infected individuals are also common and have been recognized since the advent of the AIDS epidemic. Malignancies involving the respiratory system, specifically Kaposi's sarcoma and non-Hodgkin's lymphoma, are epidemiologically linked to infection with HIV. Although other cancers have been identified in patients with HIV, these malignancies have a relationship to HIV infection that is unknown. Nonetheless, all cancers in the HIV-infected individual appear to follow a very deadly course. Interstitial pneumonitis and an alveolitis are also seen in individuals infected with HIV. Their relationship to the virus is unknown but may involve the lung's immune response to HIV. Pneumothorax and bullous lung disease are the sequela of pulmonary infections in the HIV-infected host. Pulmonary hypertension has been reported in HIV-infected patients, and like the other noninfectious respiratory complications, the link between the disease process and HIV is unknown. Bronchiectasis is now commonly recognized in AIDS patients who have survived prolonged immunosuppression and infection. Bronchoscopists have accumulated a collection of endobronchial lesions uncommonly seen in non-HIV-related pulmonary consultation. In the following review, we discuss the epidemiology, pathology, pathogenesis, clinical features, diagnostic findings, prognosis, and therapeutic options available for each noninfectious pulmonary complication. As the life expectancy for HIV-infected patients increases, the incidence of noninfectious pulmonary complications will rise.     

Technical refinement in the management of circumferentially avulsed skin of the leg

Between 1989 and 1994, 42 patients with circumferential skin avulsion of lower extremities were treated with full-thickness skin graft from defatted avulsed flap. Among them, 39 patients were run over by rubber tires during car accidents; the remaining 3 patients were victims of industrial accidents by roller machines. The full-thickness skin grafts were prepared from the avulsed skin flap in attachment to avoid junctional hypertrophic scarring. They were then secured with multiple skin staples to their anatomical position to improve skin graft take. Initial take of graft averaged 91 percent (ranged from 75 percent to 100 percent). Twelve patients underwent secondary overgrafting after tangential excision of non-viable skin graft. Follow-up averaging 2.6 years revealed stable wounds in most of the patients. Ten patients experienced occasional breakdown of skin graft in the patella and popliteal fossa, which was treated conservatively. Except for five who had deformed contours of the leg due to muscle transfers, the patients were satisfied with the cosmetic appearance of their legs. Compared with conventional methods, this approach provided better appearance and less contracture.     

Alanine scanning mutagenesis of insulin

Alanine scanning mutagenesis has been used to identify specific side chains of insulin which strongly influence binding to the insulin receptor. A total of 21 new insulin analog constructs were made, and in addition 7 high pressure liquid chromatography-purified analogs were tested, covering alanine substitutions in positions B1, B2, B3, B4, B8, B9, B10, B11, B12, B13, B16, B17, B18, B20, B21, B22, B26, A4, A8, A9, A12, A13, A14, A15, A16, A17, A19, and A21. Binding data on the analogs revealed that the alanine mutations that were most disruptive for binding were at positions TyrA19, GlyB8, LeuB11, and GluB13, resulting in decreases in affinity of 1,000-, 33-, 14-, and 8-fold, respectively, relative to wild-type insulin. In contrast, alanine substitutions at positions GlyB20, ArgB22, and SerA9 resulted in an increase in affinity for the insulin receptor. The most striking finding is that B20Ala insulin retains high affinity binding to the receptor. GlyB20 is conserved in insulins from different species, and in the structure of the B-chain it appears to be essential for the shift from the alpha-helix B8-B19 to the beta-turn B20-B22. Thus, replacing GlyB20 with alanine most likely modifies the structure of the B-chain in this region, but this structural change appears to enhance binding to the insulin receptor.     

Use of endoscopic surgery for forehead recontouring

Forehead recontouring in endoscopic surgery is presented. Eleven cases of protruded forehead deformity caused by benign tumor and one case of concave deformity caused by depressed frontal bone fracture were treated. All lesions were approached through incisions made in the hair-bearing area and operated on endoscopically. This method left no scars on the forehead, and the results were satisfactory. It is considered to be an excellent procedure with regard to cosmetic results.