scholarly journals Immune Response to Pneumococcal Polysaccharides 4 and 14 in Elderly and Young Adults: Analysis of the Variable Heavy Chain Repertoire

2005 ◽  
Vol 73 (11) ◽  
pp. 7465-7476 ◽  
Author(s):  
Kris Kolibab ◽  
S. Louise Smithson ◽  
Bradley Rabquer ◽  
Sadik Khuder ◽  
M. A. Julie Westerink
Keyword(s):  
Young Adults ◽  
Somatic Mutation ◽  
Heavy Chain ◽  
Vaccine Efficacy ◽  
The Elderly ◽  
Gene Repertoire ◽  
Elderly Adults ◽  
Variable Heavy ◽  
Gene Usage ◽  
Variable Gene

ABSTRACT Streptococcus pneumoniae is a leading cause of morbidity and mortality in both developed and developing countries. The current pneumococcal polysaccharide (PPS) vaccine is highly effective in young adults; however, vaccine efficacy is dramatically decreased in the elderly population. We hypothesized that the decreased vaccine efficacy in the elderly results from altered variable gene family usage. We have characterized the immunoglobulin G gene usage of the antibody response to PPS4 and PPS14 in 20 young and 20 elderly adults. The variable heavy (VH) gene repertoire of human peripheral B cells was amplified by using PCR. A total of 364 heavy chain sequences with specificity for PPS4 and 305 heavy chain sequences for PPS14 were analyzed from young adults. In addition, a total of 325 sequences for PPS4 and 291 sequences for PPS14 were obtained from elderly adults. Complete sequence identity, somatic mutation frequencies, and VH gene usage was determined in response to PPS4 and PPS14. In all volunteers, the immune response to both polysaccharides consisted predominantly of heavy chains belonging to the VH3 gene family. There were significant differences in the variable gene repertoire between young and elderly adults. Somatic mutation occurred more frequently in sequences derived from young compared to elderly derived sequences. With aging, a loss of oligoclonality was noted in response to PPS4 and PPS14 compared to young adults. The observed differences in VH repertoire, somatic mutation, and loss of oligoclonality may contribute to decreased vaccine efficacy in the elderly.

scholarly journals Immune Response to Pneumococcal Polysaccharides 4 and 14 in Elderly and Young Adults: Analysis of the Variable Light Chain Repertoire

2005 ◽  
Vol 73 (11) ◽  
pp. 7477-7484 ◽  
Author(s):  
S. Louise Smithson ◽  
Kris Kolibab ◽  
Anne K. Shriner ◽  
Neeti Srivastava ◽  
Sadik Khuder ◽  
...  
Keyword(s):  
Young Adults ◽  
Gene Family ◽  
Light Chain ◽  
Vaccine Efficacy ◽  
The Elderly ◽  
Chain Gene ◽  
Light Chain Gene ◽  
Age Related ◽  
Gene Usage ◽  
Variable Light

ABSTRACT Streptococcus pneumoniae is a human bacterial pathogen responsible for serious infections including pneumonia. The currently licensed polysaccharide vaccine provides 60 to 80% protection in young adults, but in the elderly the vaccine efficacy is drastically reduced despite normal antibody levels. We hypothesized that the reduced vaccine efficacy in the elderly results from altered variable gene family usage. We have analyzed the light chain gene usage in 20 young (20 to 30 years of age) and 20 elderly (65 to 86 years of age) adults in response to pneumococcal polysaccharide 4 (PPS4) and PPS14. We generated a variable light chain library using B cells specific for PPS4 and PPS14 from each vaccinated individual. We determined complete sequences and somatic mutation frequencies in all isolated variable light chain fragments. Six gene families, κ1, κ2, κ3, κ4, λ1, and λ3, were identified in response to PPS4 and PPS14 in both age groups. Comparison of young and elderly adults demonstrated significant differences in κ4, λ1, and λ3 gene usage in response to PPS4 and PPS14. With aging, there was a significant increase in κ4 gene usage and a significant decrease in λ1 and λ3 gene usage in response to both PPS4 and PPS14. Although both Vκ1 and Vλ3 gene products demonstrated extensive mutations, there was no age-related difference in mutational frequency per gene family. These findings suggest an age-related change in light chain gene usage in response to PPS4 and PPS14.

scholarly journals Aging is associated with increased propensity for central apnea during NREM sleep

2018 ◽  
Vol 124 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Susmita Chowdhuri ◽  
Sukanya Pranathiageswaran ◽  
Hillary Loomis-King ◽  
Anan Salloum ◽  
M. Safwan Badr
Keyword(s):  
Carbon Dioxide ◽  
Older Adults ◽  
Young Adults ◽  
Nrem Sleep ◽  
The Elderly ◽  
Central Apnea ◽  
Elderly Adults ◽  
Rapid Eye Movement Sleep ◽  
Controller Gain ◽  
Central Apneas

The reason for increased sleep-disordered breathing with predominance of central apneas in the elderly is unknown. We hypothesized that the propensity to central apneas is increased in older adults, manifested by a reduced carbon-dioxide (CO2) reserve in older compared with young adults during non-rapid eye movement sleep. Ten elderly and 15 young healthy adults underwent multiple brief trials of nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation (MV) resulted in hypocapnic central apnea or hypopnea. The CO2 reserve was defined as the difference in end-tidal CO2 ([Formula: see text]) between eupnea and the apneic threshold, where the apneic threshold was [Formula: see text] that demarcated the central apnea closest to the eupneic [Formula: see text]. For each MV trial, the hypocapnic ventilatory response (controller gain) was measured as the change in minute ventilation (V̇e) during the MV trial for a corresponding change in [Formula: see text]. The eupneic [Formula: see text] was significantly lower in elderly vs. young adults. Compared with young adults, the elderly had a significantly reduced CO2 reserve (−2.6 ± 0.4 vs. −4.1 ± 0.4 mmHg, P = 0.01) and a higher controller gain (2.3 ± 0.2 vs. 1.4 ± 0.2 l·min−1·mmHg−1, P = 0.007), indicating increased chemoresponsiveness in the elderly. Thus elderly adults are more prone to hypocapnic central apneas owing to increased hypocapnic chemoresponsiveness during NREM sleep. NEW & NOTEWORTHY The study describes an original finding where healthy older adults compared with healthy young adults demonstrated increased breathing instability during non-rapid eye movement sleep, as suggested by a smaller carbon dioxide reserve and a higher controller gain. The findings may explain the increased propensity for central apneas in elderly adults during sleep and potentially guide the development of pathophysiology-defined personalized therapies for sleep apnea in the elderly.

Age and Gender Differences in Body Attitudes: A Comparison of Young and Elderly Adults

1998 ◽  
Vol 47 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Stephen L. Franzoi ◽  
Virginia Koehler
Keyword(s):  
Young Adults ◽  
Young Women ◽  
Structural Changes ◽  
Elderly Women ◽  
The Elderly ◽  
Age Difference ◽  
Elderly Adults ◽  
Positive Attitudes ◽  
Body Attitudes ◽  
And Gender

One hundred and thirty-two young adults (Mean = 19 years) and 142 elderly adults (Mean = 74 years) evaluated thirty-five different aspects of their own bodies. As hypothesized, elderly adults expressed less positive attitudes than young adults toward body items associated with body functioning (physical coordination, agility, sex drive, health). These differences are consistent with research indicating a progressive decline in bodily function efficiency with advancing age (Christofalo, 1988; Lakatta, 1990). Also as expected, the elderly held less positive attitudes toward body aspects associated with facial attractiveness (lips, appearance of eyes, cheek/cheekbones). These differences are in line with the structural changes that occur in the face as people age, moving them further from cultural beauty standards. One area where these age differences were reversed was in women's attitudes toward weight-related body items: elderly women expressed greater satisfaction than young women toward their appetite, thighs, and weight. The cause of this age difference in women may be due to thinness being a more defining standard of attractiveness for young women, or it could be due to the fact that people typically lose weight after the age of fifty, thus making weight gain less of a concern for older women. Results further indicated that, although men have more positive body attitudes than women, this gender difference is not nearly as pronounced among the elderly.

scholarly journals Validating the Capability for Measuring Age-Related Changes in Grip-Force Strength Using a Digital Hand-Held Dynamometer in Healthy Young and Elderly Adults

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Shu-Chun Lee ◽  
Li-Chen Wu ◽  
Shang-Lin Chiang ◽  
Liang-Hsuan Lu ◽  
Chao-Ying Chen ◽  
...  
Keyword(s):  
Young Adults ◽  
Grip Force ◽  
The Elderly ◽  
Elderly Adults ◽  
Hand Grip ◽  
Age Related ◽  
Jamar Dynamometer ◽  
Maximum Grip ◽  
Age Related Changes

Background. Grip-force performance can be affected by aging, and hand-grip weakness is associated with functional limitations of dasily living. However, using an appropriate digital hand-held dynamometer with continuous hand-grip force data collection shows age-related changes in the quality of hand-grip force control may provide more valuable information for clinical diagnoses rather than merely recording instantaneous maximal hand-grip force in frail elderly adults or people with a disability. Therefore, the purpose of this study was to indicate the construct validity of the digital MicroFET3 dynamometer with Jamar values for maximal grip-force assessments in elderly and young adults and confirmed age-related changes in the maximal and the quality of grip-force performance using the MicroFET3 dynamometer in elderly people. Methods. Sixty-five healthy young (23.3±4.5 years) and 50 elderly (69.5±5.8 years) adults were recruited and asked to perform a validity test of the grip-force maximum voluntary contraction (MVC) using both the dominant and nondominant hands with a Jamar dynamometer and a MicroFET3 dynamometer. Results. A strong correlation of maximal grip-force measurements was found between the MicroFET3 dynamometer and Jamar standard dynamometer for both hands in all participants (p<0.05). Although, the results showed that a lower grip force was measured in both hands by the MicroFET3 dynamometer than with the Jamar dynamometer by 49.9%~57% (p<0.05), but confidently conversion formulae were also developed to convert MicroFET3 dynamometer values to equivalent Jamar values for both hands. Both dynamometers indicated age-related declines in the maximum grip-force performance by 36.7%~44.3% (p<0.05). We also found that the maximal hand-grip force values generated in both hand by the elderly adults were slower and more inconsistent than those of the young adults when using the MicroFET3 dynamometer. Conclusions. This study demonstrated that the digital MicroFET3 dynamometer has good validity when used to measure the maximal grip force of both hands, and conversion formulae were also developed to convert MicroFET3 dynamometer force values to Jamar values in both hands. Comparing with the Jamar dynamometer for measuring grip force, the MicroFET3 dynamometer not only indicated age-related declines in the maximum grip-force performance but also showed slower and more inconsistent maximal hand-grip strength generation by the elderly.

Heavy chain variable gene usage by human B-1 lymphocytes and polyreactive autoantibodies

1997 ◽  
Vol 8 (3) ◽  
pp. 146-150 ◽  
Author(s):  
Neelima M. Bhat ◽  
Marcia M. Bieber ◽  
Nelson N. H. Teng
Keyword(s):  
Heavy Chain ◽  
Gene Usage ◽  
Variable Gene

scholarly journals Life-span changes to adults' language: Effects of memory and genre

1989 ◽  
Vol 10 (1) ◽  
pp. 49-66 ◽  
Author(s):  
Susan Kemper ◽  
Donna Kynette ◽  
Shannon Rash ◽  
Kevin O'Brien ◽  
Richard Sprott
Keyword(s):  
Young Adults ◽  
Digit Span ◽  
The Elderly ◽  
Vocabulary Test ◽  
Elderly Adults ◽  
Clause Structure ◽  
Syntactic Structures ◽  
Current Health ◽  
Age Related ◽  
Language Effects

ABSTRACTThree different language samples were collected from a group of young adults, 18 to 28 years of age, and a group of elderly adults, 60 to 92 years of age: an oral questionnaire eliciting information about the adults' background, education, and current health and activities; an oral statement describing the person they most admired; and a written statement recounting the most significant event in their lives. In addition, the WAIS vocabulary and digit-span tests were administered to the adults. Age-related changes in the length, clause structure, and fluency of the adults' oral answers and oral and written statements were investigated. There was an overall decrement in the complexity of adults' oral and written statements attributable to an age-related loss of left-branching clauses which occurred in all three language samples. Correlations between the length, clause, and fluency measures from the language samples and the education, health, and WAIS vocabulary and digit-span tests revealed that better-educated adults scored higher on the WAIS vocabulary test, produced longer utterances, and used more right-branching clauses, and that adults with greater memory capacity, as measured by the WAIS Digits Backward test, produced more complex utterances and used more right- and left-branching clauses. Judges found the statements from the elderly adults to be more interesting and clearer than those from the young adults. This finding suggests that there is a trade-off between producing complex syntactic structures and producing clear and interesting prose.

scholarly journals The unmutated common ancestor of Gp41 conformational epitope targeting variable heavy chain 1-02 utilizing antibodies maintains antibody dependent cell cytotoxicity

2021 ◽  
Author(s):  
Brian Wrotniak ◽  
Meghan E Garrett ◽  
Sarah Baron ◽  
Hakimuddin Sojar ◽  
Alyssa Shon ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Common Ancestor ◽  
Vaccine Development ◽  
Gene Segment ◽  
Conformational Epitope ◽  
Heptad Repeat ◽  
Clade B ◽  
Variable Heavy ◽  
Dependent Cell ◽  
Variable Gene

In studies on monoclonal Abs (mAbs) from long-term non-progressors (LTNPs), our laboratory has previously described highly mutated Abs against a complex conformational epitope with contributions from both gp41 heptad repeat regions. Despite using the VH1-02 gene segment, known to contribute to some of the broadest neutralizing Abs against HIV, members of these Abs, termed group 76C Abs, did not exhibit broad neutralization.<br />Because of the excessive mutations and use of VH1-02, our goal was to characterize the non-neutralizing functions of Abs of group 76C, to assess targeting of the epitope in various clinical presentations, and to assess the development of these Abs by comparison to their predicted common ancestor. Serum competition assays showed group 76C Abs were enriched in LTNPs, in comparison to VRC-01. Specific group 76C clones 6F5 and 6F11, expressed as recombinant Abs, both have robust ADCC activity, despite their sequence disparity. Sequence analysis predicted the common ancestor of this clonal group would utilize the germline non-mutated variable gene. We produced a recombinant ancestor Ab (76Canc) with a heavy chain utilizing the germline variable gene sequence paired to the 6F5 light chain. Competition with group 76C recombinant Ab 6F5 confirms 76Canc binds HIV envelope constructs near the original group C epitope. 76Canc demonstrates comparable ADCC to 6F5 and 6F11 when targeting both clade B and C HIV constructs. The functional capability of Abs utilizing germline VH1-02 has implications for disease control and vaccine development.

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