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Biomedical subjects

H Kaplan

Publications and source records attributed to H Kaplan.

At least 73 records · Page 4Linked to original sources

Assistive devices for the elderly.

This article presents a review of assistive technology as it applies to elderly hearing-impaired people living independently and in group environments. Listening systems for personal communication and large area amplification, telephone, and television use are described. Visual systems that can be used to meet the communication needs of elderly persons and alerting systems are included. Issues that must be considered in the selection of personal and large area listening systems are discussed.

Aged↗

Characterization of the S3 subsite specificity of cathepsin B.

Five synthetic substrates containing different amino acid residues at the P3 position (acetyl-X-Arg-Arg-AMC, where X is Gly, Glu, Arg, Val, and Tyr and where AMC represents 7-amindo-4-methylcoumarin) were used to investigate the S3 subsite specificity of cathepsin B. At pH 6.0, the specificity constant, kcat/Km, for tripeptide substrate hydrolysis was observed to increase in the order Glu < Gly < Arg < Val < Tyr. Molecular modeling studies of substrates containing a P3 Glu, Arg, or Tyr covalently bound as the tetrahedral intermediate to the enzyme suggest that the specificity for a P3 Tyr is because of a favorable aromatic-aromatic interaction with Tyr75 on the enzyme as well as a possible H bond between the P3 Tyr hydroxyl and the side chain carboxyl of Asp69.

Amino Acid Sequence↗

Analysis of clonal CD8+ T cell expansions in normal individuals and patients with rheumatoid arthritis.

In the course of studying the circulating TCR repertoire in humans, we noted several individuals with an increase in the percentage of CD8+ T cells expressing a particular V region. In some cases, these CD8 expansions were dramatic, occupying over 40% of the total CD8 repertoire. Using a panel of mAbs to different TCR V regions, we found that over 30% of healthy adults (> 35 years of age) harbor an expansion that alters the peripheral blood CD8 TCR repertoire. A wide range of V regions were expressed by these expansions. Considering that the mAbs used cover only a portion of the V beta repertoire, the data suggest that over 70% of adults are likely to harbor such expansions. Junctional region sequencing showed that the CD8 subset expansions were clonal, and serial studies as long as 4 years showed that they persisted indefinitely. Expansions were not identified in the CD4 population. Discordant expression of one large V beta 6.7+ clone was found in one identical twin set, suggesting the possibility that an environmental exposure is involved in their generation and/or expansion. In one large family, we found five family members with a large CD8 subset expansion. Remarkably similar usage of J beta regions was noted, and two individuals demonstrated V beta 3-expressing clones with homologous CDR3 regions, differing by only one major substitution. The repertoire data from this family suggest that the T cell clones have arisen in response to a common Ag. Studies of patients with rheumatoid arthritis found a significantly increased frequency of circulating CD8 subset expansions that expressed a different V region repertoire compared with the healthy individuals studied. Overall, our results emphasize a frequent alteration in the human CD8 TCR repertoire, most likely related to an environmental exposure, in both healthy individuals and patients with rheumatoid arthritis. The presence of these expansions will be important to consider in any study of human TCR repertoire, and their implication for health and disease will be important to understand.

Adolescent↗

Tenidap in rheumatoid arthritis. A 24-week double-blind comparison with hydroxychloroquine-plus-piroxicam, and piroxicam alone.

OBJECTIVE: To compare the clinical efficacy, effect on serum C-reactive protein (CRP), serum amyloid A (SAA), and plasma interleukin-6 (IL-6) levels, and safety of tenidap with a combination of hydroxychloroquine-plus-piroxicam, and piroxicam alone, in the treatment of rheumatoid arthritis (RA) patients. METHODS: A double-blind, randomized, multicenter study in which patients with active RA were treated with tenidap 120 mg/day, hydroxychloroquine 400 mg/day and piroxicam 20 mg/day, or piroxicam alone 20 mg/day, for 24 weeks. RESULTS: At weeks 12 and 24, tenidap produced greater improvements than piroxicam based on 5 primary efficacy parameters; this improvement showed statistical significance in 4 of the 5 measures at week 12, and in 3 of the 5 measures at week 24. Clinical improvements in the hydroxychloroquine-plus-piroxicam-treated with tenidap. Compared with piroxicam, tenidap was associated with significantly greater reductions in serum CRP concentrations at 4, 12, and 24 weeks, and significantly greater reductions in SAA concentrations at weeks 12 and 24. The decrease in SAA concentrations was also significantly greater at weeks 4 and 24 in the tenidap-treated group than in the hydroxychloroquine-plus-piroxicam-treated group. Significant reductions in plasma IL-6 levels were observed at weeks 4, 12, and 24 within the tenidap group, and at week 24 within the hydroxychloroquine-plus-piroxicam-treated group. The overall occurrence of side effects, including gastrointestinal side effects, was similar in all 3 treatment groups. A small proportion of tenidap-treated patients (6.4%) manifested mild, nonprogressive, reversible proteinuria of presumed renal proximal tubular origin, and 3-4% of patients had elevated transaminase levels. CONCLUSION: In the treatment of patients with RA, tenidap is as effective as the combination of hydroxychloroquine-plus-piroxicam, and is more effective than piroxicam alone; moreover, tenidap's safety profile is comparable to that observed with piroxicam alone, and with hydroxychloroquine-plus-piroxicam. The clinical response observed in this study, as well as the prompt decreases in acute-phase protein levels of CRP and SAA, and in plasma IL-6 levels, suggest that tenidap represents a new type of antiarthritic medication, with properties similar to, but not identical to, a therapeutic combination of a nonsteroidal antiinflammatory drug with disease-modifying antirheumatic drugs.

Adult↗

A protein complex from Choristoneura fumiferana gut-juice involved in the precipitation of delta-endotoxin from Bacillus thuringiensis subsp. sotto.

A 75 kDa protein from spruce budworm (Choristoneura fumiferana) gut-juice has been isolated and shown to cause a specific precipitation of the delta-endotoxin from Bacillus thuringiensis subsp. sotto. This 75 kDa protein, separated by either column chromatography or SDS-PAGE, caused precipitation of the sotto toxin in both agarose diffusion gels and the PAGE gels. The precipitation event leads to limited proteolysis of the toxin and loss of larval toxicity. SDS-PAGE analysis of the precipitated toxin indicates that proteolysis of the toxin is not a prerequisite for precipitation. The protein responsible for precipitation, exhibits elastase-like activity and appears to be a complex which partially dissociates during boiling in SDS-PAGE sample buffer. Gut-juice from gypsy moth, forest tent caterpillar and white mark tussock moth also precipitated delta-endotoxin, but silkworm gut-juice gave a much weaker response. These results provide further evidence that, in the larval gut, differential processing of delta-endotoxin may play a role in the expression of activity towards various insect larvae.

Amino Acid Sequence↗

Four strikes against physical mapping of DNA.

Physical mapping is a central problem in molecular biology and the human genome project. The problem is to reconstruct the relative position of fragments of DNA along the genome from information on their pairwise overlaps. We show that four simplified models of the problem lead to NP-complete decision problems: Colored unit interval graph completion, the maximum interval (or unit interval) subgraph, the pathwidth of a bipartite graph, and the k-consecutive ones problem for k > or = 2. These models have been chosen to reflect various features typical in biological data, including false-negative and positive errors, small width of the map, and chimericism.

Base Sequence↗

Revised Communication Self-assessment Scale Inventory for Deaf Adults (CSDA).

The 125-item Communication Self-assessment Scale Inventory for Deaf Adults evaluates difficult communication situations, their importance to the client, communication strategies, and attitudes toward hearing loss. Each scale contains subscales, and the scales may be used independently of each other. The original 115-item scale was revised to improve internal consistency of some of the subscales and modify language in some items. Internal consistency reliability, test-retest reliability, and normative data are presented. The scales were presented to a group of prelingually deaf adults and adolescents who differed in the frequency of hearing aid use, primary mode of communication home, school, and work, and educational background. Subjects responded to some of the scales and subscales in a significantly different manner based on these parameters.

Adolescent↗

Cardiovascular magnetic resonance imaging goes beyond anatomy.

Magnetic resonance imaging (MRI) provides noninvasive functional information as well as a three-dimensional anatomic display of the cardiovascular system. MRI of protons, phosphorus, or sodium nuclei is currently being investigated to characterize cardiovascular pathology, and the potential benefits of paramagnetic contrast agents are becoming apparent. Finally, techniques to quantitate blood flow, vascular pressures, chamber volumes, ventricular ejection fractions, and cardiac output are being developed.

Contrast Media↗

Methotrexate in rheumatoid arthritis. A five-year prospective multicenter study.

OBJECTIVE: To evaluate the efficacy and tolerability of oral methotrexate (MTX) in rheumatoid arthritis (RA) in a long-term prospective trial. METHODS: One hundred twenty-three patients with RA who completed a 9-month multicenter randomized trial comparing MTX and auranofin enrolled in this 5-year prospective study of MTX. RESULTS: Significant (P = 0.0001) improvement compared with baseline was noted in all clinical disease variables, functional status, and the Westergren erythrocyte sedimentation rate (ESR). "Marked improvement" occurred in 87 (71%) and 85 (69%) of the patients, respectively, in the joint pain/tenderness index and the joint swelling index at the last evaluable visit. Forty-four patients (36%) withdrew during the study. Eight (7%) withdrew due to lack of efficacy, and 8 (7%) due to adverse experiences, including 1 patient with cirrhosis. At 5 years, 64% of patients were still taking MTX and completed the study. CONCLUSION: This large prospective study of long-term MTX treatment demonstrates sustained clinical response and improvement in the Westergren ESR and functional assessment scores, with an acceptable toxicity profile.

Adult↗

Three-dimensional co-localization of nucleolar argyrophilic components and DNA in cell nuclei by confocal microscopy.

Silver dots deposited specifically on proteins of the nucleolar organizer regions (Ag-NOR proteins) after a one-step silver staining technique were visualized in cells in culture, in cells in smears, and in tissue sections, with a scanning laser confocal microscope working in the reflectance mode. After specific labeling of DNA with the fluorescent dye chromomycin A3, DNA and silver dots could be observed either individually or simultaneously. Therefore, it was possible to study the three-dimensional organization of nucleolar silver-stained structures relative to DNA with a high X, Y, and Z resolution. Our results showed that the argyrophilic components are organized as a twisted necklace structure within interphase nucleoli of cells in culture. We also demonstrated a striking three-dimensional symmetric disposition of NORs within the two sets of chromosomes in telophase cells. Similar results were obtained for cells in smears, although their three-dimensional organization was somewhat disturbed due to air-drying. We also demonstrated that silver dots cannot be visualized in the reflectance mode within sections of paraffin-embedded tissues. However, their simultaneous demonstration in non-confocal transmitted light, together with that of DNA in confocal mode, appeared very useful to study their localization within nuclei and mitotic chromosomes.

Adenocarcinoma↗

Nabumetone in elderly patients with osteoarthritis: economic benefits versus ibuprofen alone or ibuprofen plus misoprostol.

Nonsteroidal anti-inflammatory drugs (NSAIDs) vary in their potential to produce gastropathy. We compared the 3-month direct medical costs, including those associated with treating NSAID-induced adverse events, of nabumetone, ibuprofen, or ibuprofen plus misoprostol in 171 elderly patients with osteoarthritis. Total direct medical costs per patient treated were $US183 for nabumetone, $US252 for ibuprofen, and $US270 for ibuprofen plus misoprostol. Differences resulted from higher costs associated with treatment of drug-related adverse events with ibuprofen, and higher drug acquisition prices with the combination regimen. Sensitivity analyses demonstrated that direct costs with nabumetone approached those for the other 2 regimens if the price of nabumetone increased by 60%, the probability of lesion formation with nabumetone increased 4-fold, the probability of a lesion greater than 0.5cm being symptomatic and needing treatment was 31%, or the price of misoprostol decreased by 50%. Although this study found more lesions because of mandated endoscopies than might be recognised or treated in clinical practice, the results suggest an economic benefit of nabumetone.

Aged↗

Evidence that the CryIA crystal protein from Bacillus thuringiensis is associated with DNA.

Toxin generated by activation of the Bacillus thuringiensis CryIA(c) crystal protein (protoxin) with bovine trypsin was separated into two components by anion-exchange chromatography. One component (T2) was DNA-associated toxin, and the other was the DNA-free toxin (T1). Only one major protoxin component was observed, and it was found to be associated with DNA. The DNA from the T2 toxin varied in size from 100 to 300 base pairs, whereas the crystal and the solubilized protoxin contained 20-kilobase DNA as the major DNA component. DNase treatment converted the T2 toxin to the DNA-free T1 toxin. In contrast, the DNA in the crystal and the solubilized protoxin was resistant to DNase digestion and was not dissociated from the protein by 1.5 M NaCl. The protoxin and DNA appeared to elute as a complex with a molecular mass of > 2 x 10(6) Da on gel-filtration chromatography. No toxin was generated from the protoxin with trypsin after extensive digestion of the protoxin with DNase or dissociation of the DNA by succinylation of the lysine residues. It is proposed that DNA binds to the COOH-terminal half of the crystal protein and is essential for maintaining the conformational integrity required for crystal formation and generation of toxin.

Bacillus thuringiensis↗

Purification and characterization of a trypsin-like digestive enzyme from spruce budworm (Choristoneura fumiferana) responsible for the activation of delta-endotoxin from Bacillus thuringiensis.

A trypsin-like enzyme purified from spruce budworm (Choristoneura fumiferana) gut juice has a molecular mass of 25 kDa and its pH activity profile indicates a pKa of 8. Sequence homology with bovine trypsin of the N-terminus and active site, and the ionization dependence for catalysis, reflect the typical trypsin-like activities measured. The action of this enzyme (designated CFT-1) is compared to the neat gut juice with regard to the proteolytic activation of the delta-endotoxin from Bacillus thuringiensis.

Amino Acid Sequence↗