Evaluation of two live, cold-passaged, temperature-sensitive respiratory syncytial virus vaccines in chimpanzees and in human adults, infants, and children

Two live-attenuated, cold-passaged (cp), temperature-sensitive (ts) candidate vaccines, designated cpts530/1009 and cpts248/955, were attenuated, genetically stable, and immunogenic in chimpanzees and were highly attenuated for human adults. In respiratory syncytial virus (RSV)-seropositive children, cpts530/1009 was more restricted in replication than cpts248/955. In seronegative children, 10(4) pfu of cpts248/955 was insufficiently attenuated, and a high titer of vaccine virus was shed (mean peak titer, 10(4.4) pfu/mL), whereas 10(4) pfu of cpts530/1009 was relatively attenuated and restricted in replication (mean peak titer, 10(2.0) pfu/mL). At a dose of 10(5) pfu, cpts530/1009 was immunogenic in seronegative children (geometric mean titer of RSV neutralizing antibodies, 1:724). Transmission of either vaccine to seronegative placebo recipients occurred at a frequency of 20%-25%. Of importance, vaccine viruses recovered from chimpanzees and humans were ts. In contrast to previous studies, this study indicates that live attenuated RSV vaccines that are immunogenic and phenotypically stable can be developed. Additional studies are being conducted to identify a live RSV vaccine that is slightly more attenuated and less transmissible than cpts530/1009.     

Effectiveness of bacillus Calmette-Guerin (BCG) vaccination in the prevention of leprosy; a case-finding control study in Nagpur, India

Among numerous available materials for osseous repair and reconstruction, those presenting osteoinductive characteristics and promoting bone regeneration are preferable. Fresh autologous bone is one of the most effective, but it has some disadvantages and risks. Demineralized bone matrix (DBM) is considered to be a valid alternative, because it seems to show osteogenic potential, ascribed to the presence of bone morphogenetic proteins. In addition it can be prepared without difficulty and preserved without losing osteoinductive properties. The aim of the study was to evaluate the osteoinductive ability of xenogenic DBM, by testing DBM powder obtained from rabbit long bones, in cell culture of murine fibroblasts, alone or associated with electromagnetic field (EMF), that are known to exhibit biologic effects on cells: in particular they are used in orthopedics to improve bone formation. At the end of experiment, alkaline phosphatase (ALP) activity, calcium levels and cell proliferation and morphology were evaluated. A statistically significant stimulation of ALP activity and cell proliferation and a morphological change of fibroblasts were found. The results obtained show how DBM and EMF have different effects on cells, and that together they have synergic action toward bone induction.     

Normal cerebrospinal fluid suppresses the in vitro development of cytotoxic T cells: role of the brain microenvironment in CNS immune regulation

A simple and fast method for diffusion blotting of proteins from precast SDS-PAGE gels (0.5 mm) was developed. The efficiency of protein transfer was evaluated using 14C labelled proteins. Diffusion blotting for three minutes, gave a transfer of 10% compared to electroblotting. By doubling the transfer time for each subsequent imprint, four imprints were made from the same lane with similar amounts of protein transferred onto each imprint. With a transfer time of three minutes each, it was possible to obtain at least ten imprints with all the proteins visible in all the imprints. There was no detectable loss in resolution as compared to electroblotting. The method also works well with an immuno-detecting system. The number of imprints which can be obtained, is dependent on the sensitivity of the detection system and the amount of protein applied. The greatest advantage of diffusion blotting compared to electroblotting is that several imprints can be made from each lane, and different antisera can be tested on identical imprints. The gel remains on its plastic support which prevents it from stretching and compression; this ensures identical imprints and facilitates more reliable molecular mass determination. If only a few imprints are made, sufficient protein remains within the gel for general protein staining. These advantages make diffusion blotting the method of choice when quantitative protein transfer is not required.     

Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators

BACKGROUND: Although diabetes is a major risk factor for coronary heart disease (CHD), little information is available on the effects of lipid lowering in diabetic patients. We determined whether lipid-lowering treatment with pravastatin prevents recurrent cardiovascular events in diabetic patients with CHD and average cholesterol levels. METHODS AND RESULTS: The Cholesterol And Recurrent Events (CARE) trial, a 5-year trial that compared the effect of pravastatin and placebo, included 586 patients (14.1%) with clinical diagnoses of diabetes. The participants with diabetes were older, more obese, and more hypertensive. The mean baseline lipid concentrations in the group with diabetes--136 mg/dL LDL cholesterol, 38 mg/dL HDL cholesterol, and 164 mg/dL triglycerides--were similar to those in the nondiabetic group. LDL cholesterol reduction by pravastatin was similar (27% and 28%) in the diabetic and nondiabetic groups, respectively. In the placebo group, the diabetic patients suffered more recurrent coronary events (CHD death, nonfatal myocardial infarction [MI], CABG, and PTCA) than did the nondiabetic patients (37% versus 25%). Pravastatin treatment reduced the absolute risk of coronary events for the diabetic and nondiabetic patients by 8.1% and 5.2% and the relative risk by 25% (P=0.05) and 23% (P<0.001), respectively. Pravastatin reduced the relative risk for revascularization procedures by 32% (P=0.04) in the diabetic patients. In the 3553 patients who were not diagnosed as diabetic, 342 had impaired fasting glucose at entry defined by the American Diabetes Association as 110 to 125 mg/dL. These nondiabetic patients with impaired fasting glucose had a higher rate of recurrent coronary events than those with normal fasting glucose (eg, 13% versus 10% for nonfatal MI). Recurrence rates tended to be lower in the pravastatin compared with placebo group (eg, -50%, P=0.05 for nonfatal MI). CONCLUSIONS: Diabetic patients and nondiabetic patients with impaired fasting glucose are at high risk of recurrent coronary events that can be substantially reduced by pravastatin treatment.     

Development and evaluation of a procedure for fitting multi-channel compression hearing aids

Hearing aids with multi-channel compression are often fitted on the basis of loudness scaling data obtained using narrow bands of noise or tones. Here, we report the development and evaluation of an alternative fitting procedure based on the use of speech signals. The parameters of the hearing aid (the gains in each channel for high and low input levels) are adjusted adaptively under computer control on the basis of the listener's responses. The goal is that speech at 85 dB SPL should be judged as 'loud', speech at 60 dB SPL should be judged as 'quiet', and speech at both levels should be judged as 'neither tinny nor boomy'. The procedure was evaluated using a two-channel compression hearing aid, the remote control of which allowed two programs to be stored. One program was based on our fitting procedure. The other was either based on the manufacturer's recommended full fitting procedure (which included loudness scaling with bands of noise), or was based on the audiogram alone, using the manufacturer's algorithm. After an acclimatization period of at least two weeks, subjects were then asked to fill in a questionnaire about their experiences with the two programs in different listening situations. The results generally indicated a preference for the program based on our adaptive fitting procedure. We also conducted laboratory measurements of speech intelligibility, in quiet and in a background of a single competing talker. These showed no clear difference between programs, although scores overall were very high. We conclude that our adaptive procedure gives very satisfactory results in everyday life. Parameter values giving good comfort also give good intelligibility. The procedure typically takes between five and 10 minutes per ear, which is quicker than most loudness scaling procedures.     

Amino acid alterations in the benA (beta-tubulin) gene of Aspergillus nidulans that confer benomyl resistance

We report the cloning and sequencing of 18 mutant alleles of the benA, beta-tubulin gene of Aspergillus nidulans that confer resistance to the benzimidazole antifungal, antimicrotubule compounds benomyl, carbendazim, nocodazole, and thiabendazole. In 12 cases, amino acid 6 was changed from histidine to tyrosine or leucine. In four cases, amino acid 198 was changed from glutamic acid to aspartic acid, glutamine, or lysine. In two cases, amino acid 200 was altered from phenylalanine to tyrosine. These data, along with previous data indicating that amino acid 165 is involved in the binding of the R2 group of these compounds [Jung and Oakley, 1990: Cell Motil. Cytoskeleton 17:87-94], suggest that regions of beta-tubulin containing amino acids 6, 165, and 198-200 interact to form the binding site of benzimidazole antimicrotubule agents. These results also suggest that the presence of phenylalanine at amino acid 200 contributes to the great sensitivity of many fungi to benzimidazole antimicrotubule agents.     

The perceptual structure of pathologic voice quality

Although perceptual assessment is included in most protocols for evaluating pathologic voices, a standard set of valid scales for measuring voice quality has never been established. Standardization is important for theory and for clinical acceptance, and also because validation of objective measures of voice depends on valid perceptual measures. The present study used large sets (n = 80) of male and female voices, representing a broad range of diagnoses and vocal severities. Eight experts judged the dissimilarity of each pair of voices, and responses were analyzed using nonmetric individual differences multidimensional scaling. Results indicate that differences between listeners in perceptual strategy are so great that the fundamental assumption of a common perceptual space must be questioned. Because standardization depends on the assumption that listeners are similar, it is concluded that efforts to standardize perceptual labels for voice quality are unlikely to succeed. However, analysis by synthesis may provide an alternate means of modeling quality as a function of both voices and listeners, thus avoiding this problem.     

HIV-1: is Nef a PAK animal?

HIV-1 Nef is clearly essential for efficient viral replication in vivo, but it has been difficult to determine why. Recent evidence that Nef specifically activates a PAK-dependent signalling cascade may be the first step in defining the mechanism of action of this enigmatic viral protein.