Tracking of markers and onset of disease among HIV-1 seroconverters

Repeated measurements on persons infected with HIV-1 indicate that infection has a dynamic impact on several markers of immune suppression and activation. The objectives of this report are: (a) to provide a statistical model for the correlation structure of serial measurements of immunological markers, and (b) to identify features of marker profiles associated with the timing of AIDS diagnoses. We analyse data obtained from 328 seroconverters participating in the Multicenter AIDS Cohort Study on whom the date of HIV-1 seroconversion is known within +/- 4.5 months. Immunological markers considered here are CD4 cell counts, serum beta 2-microglobulin and serum neopterin. The statistical model for HIV-related changes in markers consists of (1) a piecewise linear regression model for the trajectories of markers over time and (2) a two-parameter autocorrelation function that generalizes Markovian and simple random effects autocorrelation structures. Application of this model for marker measurements revealed a high degree of tracking, as the estimated autocorrelation function exhibited sub-exponential decay over time. Though current marker levels are most informative on future values, there is substantial information (memory) in previous measurements. A feature suggested by the analysis of groups formed according to the length of the AIDS-free period, is the sequential divergence of the CD4 trajectories where steeper declines occurred with a two-year lag prior to AIDS onset. For AIDS cases diagnosed 3-5 and 5-7 years after seroconversion, the rates of decline compared with those free of AIDS for at least 4 years were steeper by 95 and 46 per cent respectively at two years prior to AIDS.     

Effect of ethanol on the protein secondary structure of the human gastric mucosa, in vitro

The effect of ethanol on the secondary conformational structure of proteins of the human gastric mucosa was investigated by attenuated total reflection/Fourier transform infrared (ATR/FT-IR) spectroscopy. The IR peak intensity and position of each structural component of gastric mucosa was found to change significantly with the ethanol concentration and length of exposure. The peak intensity due to the beta-sheet and/or beta-turn conformational structure in amide I and II bands of gastric mucosa clearly increased after treatment with ethanol. Moreover, the peak at 1635 cm-1 shifted to 1630 cm-1 after treatment with 40% ethanol for 3 h, or 80% ethanol for 1 h, and a distinct shoulder also appeared at 1643 cm-1. This shift occurred more rapidly and was more pronounced after exposure of mucosa to 80% ethanol, compared with the effect of 40% ethanol, but the alpha-helical structure at the amide I and II bands was not influenced by either concentration of ethanol. Ethanol treatment might also transform the secondary structure of amide III in gastric mucosa from an alpha-helix to a mainly random coil with extensive unfolding. The absorption between 1180 and 980 cm-1, which is assigned to glycoprotein structure, was also reduced after treatment with ethanol. This strongly indicates that ethanol influences the conformation of the lipids and proteins of human gastric mucosa, leading to their deformation.     

Influence of the blight of Morinda officinalis How on microscopic structure and constituents of the host

The results showed that microscopic structure in biennial roots, the contents of B and Mn in nutritive organ and beta-sitosterol content in roots, stems of Morinda officinalis were affected markedly. The total sugar content in the roots and aerial stems was decreased by 5.42%-15.29%.     

Preparation and evaluation of sodium diclofenac controlled-release tablets. II. Dibasic calcium phosphate as a retardant in mixtures for direct compression

Malignant melanoma of the skin has become a real problem due to the increasing number of cases. No other tumor is induced by long term UV-radiation of the skin. Excision of the primary tumor is the treatment of choice in this disease. Before excision of the tumor lymphoscintigraphy is the first choice in diagnosis to demonstrate the draining lymph vessels and lymph node groups of an malignant melanoma for later operation. This work current the status quo of lymphoscintigraphy in malignant melanoma of the trunk.     

Kinetics and mechanism of an NADPH-dependent succinic semialdehyde reductase from bovine brain

An NADPH-dependent succinic semialdehyde reductase has been purified from bovine brain by several chromatographic procedures. The preparation appeared homogeneous on SDS/PAGE. The enzyme is a monomeric protein with a molecular mass of 28 kDa. A number of properties of the bovine brain enzyme, such as substrate specificity, specific activity, molecular mass, optimum pH, amino acid composition, and kinetic parameters, have been determined and compared with those reported for preparations from other sources. The results indicate that the enzyme isolated from bovine brain in the present study is different from those reported for preparations from other sources. The inhibition kinetic patterns obtained when the products of the reaction or substrate analogs are used as inhibitor of the reaction catalyzed by the enzyme are consistent with an ordered sequential mechanism involving the formation of an intermediate ternary complex and in which NADPH is the first substrate to bind the enzyme.     

Detection of undegraded oligonucleotides in living sea urchin eggs by fluorescence resonance energy transfer

A method was investigated for monitoring the integrity of oligonucleotides in solution and in cells using fluorescence resonance energy transfer (FRET) between two different fluorochromes attached to a single oligonucleotide. A 10-meric oligodeoxynucleotide labeled with fluorescein at its 5'-end and with rhodamine X at its 3'-end (F-ODN-R) was used. The oligomer had a specific absorption spectrum with peaks at 497 nm and 586 nm, which corresponded to fluorescein and rhodamine X, respectively. When excited at 494 nm, F-ODN-R had a specific fluorescence spectrum with peaks at 523 nm and 610 nm. The digestion of F-ODN-R with an endonuclease caused the increase in light intensity at 523 nm and the decrease at 610 nm. To examine effects in vivo, living sea urchin eggs were injected with a solution of F-ODN-R and excited with blue light at 470-490 nm. Two fluorescent images, a green image at 520-560 nm and a red image at above 580 nm, were obtained when a single egg was viewed under a fluorescence microscope. Eggs injected with the digested F-ODN-R emitted only green fluorescence. These results indicated that the integrity of oligonucleotides can be estimated in living cells by monitoring FRET after double-labeling of the oligonucleotides with fluorescein and rhodamine X.     

Field-focusing hyperthermia and magnetic resonance imaging (MRI) with a grounded probe and a commercial MRI scanner

A method for performing magnetic resonance imaging (MRI) and producing field-focusing hyperthermia sequentially in phantoms and rat tissues with a grounded hyperthermic probe and a commercial MRI scanner was demonstrated. In the treatment mode the MRI scanner was used as a radiofrequency (RF) power source, and an invasive, electrically grounded, tuned probe was used to produce hyperthermia in phantoms via induced eddy current convergence. Temperature increases of 4.5 degrees C/5 minutes in a dielectrically uniform phantom and 5.0 degrees C/6 minutes in the peritoneum of a rat were measured in the vicinity (3-5 mm) of the grounded probe with the transmitter of the MRI scanner working at 2 per cent duty cycle. The advantage of this combined diagnostic and therapeutic approach is that the position of the hyperthermic probe can be monitored before each treatment, with observation of the tumor during and after treatment, if desired. In addition, the total cost is significantly less than that of both an MRI scanner and an RF hyperthermia treatment system.