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Chenxi Wang

Publications and source records attributed to Chenxi Wang.

At least 19 recordsLinked to original sources
PubMed2006

Inhibin-B levels in healthy young adult men and prepubertal boys: is obesity the cause for the contemporary decline in sperm count because of fewer Sertoli cells?

Inhibin-B is a heterodimeric glycoprotein produced by Sertoli cells. Although inhibin-B levels are low when seminiferous tubules are damaged, studies in normal monkeys reveal that inhibin-B levels also correlate positively with Sertoli cell number. In this study, we measured inhibin-B levels in healthy young adult men aged 18-24 years and in prepubertal boys aged 5-9 years in relation to body mass index (BMI). Inhibin-B levels declined with increasing obesity in young adult men; values were 26% lower in men who were obese compared to normal-weight men. Sex hormone-binding globulin and total testosterone, but not free testosterone, were also lower with increasing BMI; serum follicle-stimulating hormone and luteinizing hormone levels were unaffected by obesity. In prepubertal boys, by contrast, inhibin-B was unaffected by obesity. We propose that reduced levels of inhibin-B indicate that obese men have fewer Sertoli cells than men of normal weight. Moreover, normal values in obese prepubertal boys suggest that the effect of obesity on inhibin-B is established during puberty. Finally, because each Sertoli cell is thought to support a finite number of germ cells, fewer Sertoli cells in obesity may predispose to a lower sperm count in adulthood. We speculate that the escalating prevalence of obesity and insulin resistance among adolescents might negatively influence male reproductive function for the next generation.

Adolescent↗
PubMed2006

Atomic force microscopic examination of chromosomes treated with trypsin or ethidium bromide.

Trypsin treatment is frequently used during chromosome preparation for removal of cellular contaminants, and ethidium bromide (EB) staining of bands is often used to facilitate high-resolution observations by optical microscopy. However, conventional optical microscopy is unable to visualize potential aberrations of chromosome structures caused by these physicochemical treatments. In this article, we use atomic force microscopy (AFM) in the tapping mode to obtain and analyze high-resolution images of chromosome surface structure damage associated with trypsinization and EB treatment. According to our results, the trypsin-based digestion effects became more severe as incubations increased across a range from 10 to 40 s; a digestion time of 10 to 20 s appeared to be most suitable for observation by AFM. In terms of chromosomal damage induced by EB treatment, addition of EB into the media of cultured human blood cells induced chromosomal breakage in a dose-dependent fashion, and the results indicate centromeric region damnifyed severer than arms. Together, these results indicate that EB staining and the standard chromosomal preparative techniques of trypsinization can induce chromosomal damage that may affect the observed results.

Blood Cells↗
PubMed2005

Atomic force microscope tracking observation of Chinese hamster ovary cell mitosis.

CHO cells possess easily identifiable karyotypes, and CHO cell chromosomes are large and few in number, making these cells ideal for mutational and drug toxicity studies and suitable for investigations of animal chromosome structure. Here, we used atomic force microscopy (AFM) in the tapping mode for detailed visualizations of Chinese hamster ovary (CHO) cell chromosomes during various mitotic phases, including typical prophase, prometaphase, metaphase, anaphase and telophase. Based on our detailed observations, we were able to divide metaphase and anaphase into sub-phases: metaphase I, II and III, and anaphase I and II. Furthermore, we used the AFM error-signal mode to visualize chromosomal ultrastructures and cytokinesis. While these visualizations were all successful, we found that the image quality was affected by cellular debris, contamination. Collectively, our results show that the AFM technique has great potential for the detailed study of chromosomes and chromosomal ultrastructures during all phases of the cell cycle, but that careful standards of sample preparation must be maintained.

Anaphase↗
PubMed2005

The effects of intentional weight loss as a latent variable problem.

Although obesity is associated with increased mortality rate and short-term weight loss improves risk factors for mortality, it has not been convincingly shown that weight loss among obese people results in reduced mortality rate. When considering the human literature, it has been pointed out that weight loss is often a sign of illness and that investigators therefore need to separate intentional from unintentional weight loss. It has generally been assumed that among people who state that they do not intend to lose weight, weight change subsequently observed is unintentional. Among such people, weight loss has been consistently associated with increased mortality rate. Complementarily, it has generally been assumed that among people who state that they do intend to lose weight, weight change subsequently observed is intentional. In these people who are intending to lose weight, some studies show apparent benefits of weight loss, some are neutral, and some show deleterious effects. The overall conclusion that some reviewers have drawn from this literature is that intentional weight loss (IWL) is at best not beneficial and may even be harmful with respect to mortality rate. We believe that this conclusion is drawn by inappropriately conflating weight loss (or more generally weight change) among people intending to lose weight with IWL (or change). Herein, under certain assumptions, we: (1) show that the association between mortality rate and weight loss among people intending to lose weight and between mortality rate and IWL are two different things; (2) show that the association between IWL and mortality rate is an inherently unobservable entity; (3) derive a method for estimating the plausible range of true effect of IWL on mortality rate if one is willing to make a number of restrictive, but perhaps reasonable assumptions; and (4) illustrate the method by application to a data set involving middle-age onset calorie restriction in mice.

Animals↗
PubMed2005

Intentional weight loss reduces mortality rate in a rodent model of dietary obesity.

OBJECTIVE: We used a rodent model of dietary obesity to evaluate effects of caloric restriction-induced weight loss on mortality rate. Research Measures and Procedures: In a randomized parallel-groups design, 312 outbred Sprague-Dawley rats (one-half males) were assigned at age 10 weeks to one of three diets: low fat (LF; 18.7% calories as fat) with caloric intake adjusted to maintain body weight 10% below that for ad libitum (AL)-fed rat food, high fat (HF; 45% calories as fat) fed at the same level, or HF fed AL. At age 46 weeks, the lightest one-third of the AL group was discarded to ensure a more obese group; the remaining animals were randomly assigned to one of three diets: HF-AL, HF with energy restricted to produce body weights of animals restricted on the HF diet throughout life, or LF with energy restricted to produce the body weights of animals restricted on the LF diet throughout life. Life span, body weight, and leptin levels were measured. RESULTS: Animals restricted throughout life lived the longest (p < 0.001). Life span was not different among animals that had been obese and then lost weight and animals that had been nonobese throughout life (p = 0.18). Animals that were obese and lost weight lived substantially longer than animals that remained obese throughout life (p = 0.002). Diet composition had no effect on life span (p = 0.52). DISCUSSION: Weight loss after the onset of obesity during adulthood leads to a substantial increase in longevity in rats.

Aging↗
PubMed2004

Atomic force microscopy imaging and 3-D reconstructions of serial thin sections of a single cell and its interior structures.

The thin sectioning has been widely applied in electron microscopy (EM), and successfully used for an in situ observation of inner ultrastructure of cells. This powerful technique has recently been extended to the research field of atomic force microscopy (AFM). However, there have been no reports describing AFM imaging of serial thin sections and three-dimensional (3-D) reconstruction of cells and their inner structures. In the present study, we used AFM to scan serial thin sections approximately 60 nm thick of a mouse embryonic stem (ES) cell, and to observe the in situ inner ultrastructure including cell membrane, cytoplasm, mitochondria, nucleus membrane, and linear chromatin. The high-magnification AFM imaging of single mitochondria clearly demonstrated the outer membrane, inner boundary membrane and cristal membrane of mitochondria in the cellular compartment. Importantly, AFM imaging on six serial thin sections of a single mouse ES cell showed that mitochondria underwent sequential changes in the number, morphology and distribution. These nanoscale images allowed us to perform 3-D surface reconstruction of interested interior structures in cells. Based on the serial in situ images, 3-D models of morphological characteristics, numbers and distributions of interior structures of the single ES cells were validated and reconstructed. Our results suggest that the combined AFM and serial-thin-section technique is useful for the nanoscale imaging and 3-D reconstruction of single cells and their inner structures. This technique may facilitate studies of proliferating and differentiating stages of stem cells or somatic cells at a nanoscale.

Animals↗
PubMed2004

Insufficient production and tissue delivery of CD4+ memory T cells in rapidly progressive simian immunodeficiency virus infection.

The mechanisms linking human immunodeficiency virus replication to the progressive immunodeficiency of acquired immune deficiency syndrome are controversial, particularly the relative contribution of CD4+ T cell destruction. Here, we used the simian immunodeficiency virus (SIV) model to investigate the relationship between systemic CD4+ T cell dynamics and rapid disease progression. Of 18 rhesus macaques (RMs) infected with CCR5-tropic SIVmac239 (n=14) or CXCR4-tropic SIVmac155T3 (n=4), 4 of the former group manifested end-stage SIV disease by 200 d after infection. In SIVmac155T3 infections, naive CD4+ T cells were dramatically depleted, but this population was spared by SIVmac239, even in rapid progressors. In contrast, all SIVmac239-infected RMs demonstrated substantial systemic depletion of CD4+ memory T cells by day 28 after infection. Surprisingly, the extent of CD4+ memory T cell depletion was not, by itself, a strong predictor of rapid progression. However, in all RMs destined for stable infection, this depletion was countered by a striking increase in production of short-lived CD4+ memory T cells, many of which rapidly migrated to tissue. In all rapid progressors (P <0.0001), production of these cells initiated but failed by day 42 of infection, and tissue delivery of new CD4+ memory T cells ceased. Thus, although profound depletion of tissue CD4+ memory T cells appeared to be a prerequisite for early pathogenesis, it was the inability to respond to this depletion with sustained production of tissue-homing CD4+ memory T cells that best distinguished rapid progressors, suggesting that mechanisms of the CD4+ memory T cell generation play a crucial role in maintaining immune homeostasis in stable SIV infection.

Analysis of Variance↗
PubMed2004

Statistical methods for testing effects on "maximum lifespan".

It has been noted that certain interventions such as caloric restriction may increase maximum lifespan, whereas other interventions may increase mean or median lifespan but not maximum lifespan. Here the term "maximum lifespan" is used to refer to the upper percentiles of the distribution of lifespan. This is of great interest because increasing maximum lifespan may be an indicator that an intervention is slowing the general process of aging and not merely retarding the development of specific diseases. However, formal methods for testing maximum lifespan have not been elucidated. Herein, we show via simulation that conditional t-test (CTT), a method that is sometimes used, is invalid. We then offer a new method based on quantile regression and we show that this method is, at worst, conservative and remains powerful and valid.

Animals↗
PubMed2003

Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism.

Several theoretical studies have suggested that large samples of randomly ascertained siblings can be used to ascertain phenotypically extreme individuals and thereby increase power to detect genetic linkage in complex traits. Here, we report a genetic linkage scan using extremely discordant and concordant sibling pairs, selected from 34,580 sibling pairs in the southwest of England who completed a personality questionnaire. We performed a genomewide scan for quantitative-trait loci (QTLs) that influence variation in the personality trait of neuroticism, or emotional stability, and we established genomewide empirical significance thresholds by simulation. The maximum pointwise P values, expressed as the negative logarithm (base 10), were found on 1q (3.95), 4q (3.84), 7p (3.90), 12q (4.74), and 13q (3.81). These five loci met or exceeded the 5% genomewide significance threshold of 3.8 (negative logarithm of the P value). QTLs on chromosomes 1, 12, and 13 are likely to be female specific. One locus, on chromosome 1, is syntenic with that reported from QTL mapping of rodent emotionality, an animal model of neuroticism, suggesting that some animal and human QTLs influencing emotional stability may be homologous.

Adult↗
PubMed2003

Years of life lost due to obesity.

CONTEXT: Public health officials and organizations have disseminated health messages regarding the dangers of obesity, but these have not produced the desired effect. OBJECTIVE: To estimate the expected number of years of life lost (YLL) due to overweight and obesity across the life span of an adult. DESIGN, SETTING, AND SUBJECTS: Data from the (1) US Life Tables (1999); (2) Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994); and (3) First National Health and Nutrition Epidemiologic Follow-up Study (NHANES I and II; 1971-1992) and NHANES II Mortality Study (1976-1992) were used to derive YLL estimates for adults aged 18 to 85 years. Body mass index (BMI) integer-defined categories were used (ie, <17; 17 to <18; 18 to <19; 20 to <21; 21 to 45; or > or =45). A BMI of 24 was used as the reference category. MAIN OUTCOME MEASURE: The difference between the number of years of life expected if an individual were obese vs not obese, which was designated YLL. RESULTS: Marked race and sex differences were observed in estimated YLL. Among whites, a J- or U-shaped association was found between overweight or obesity and YLL. The optimal BMI (associated with the least YLL or greatest longevity) is approximately 23 to 25 for whites and 23 to 30 for blacks. For any given degree of overweight, younger adults generally had greater YLL than did older adults. The maximum YLL for white men aged 20 to 30 years with a severe level of obesity (BMI >45) is 13 and is 8 for white women. For men, this could represent a 22% reduction in expected remaining life span. Among black men and black women older than 60 years, overweight and moderate obesity were generally not associated with an increased YLL and only severe obesity resulted in YLL. However, blacks at younger ages with severe levels of obesity had a maximum YLL of 20 for men and 5 for women. CONCLUSION: Obesity appears to lessen life expectancy markedly, especially among younger adults.

Adult↗
PubMed2003

Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses.

Certain major histocompatibility complex class I (MHC-I) alleles are associated with delayed disease progression in individuals infected with human immunodeficiency virus (HIV) and in macaques infected with simian immunodeficiency virus (SIV). However, little is known about the influence of these MHC alleles on acute-phase cellular immune responses. Here we follow 51 animals infected with SIV(mac)239 and demonstrate a dramatic association between Mamu-A*01 and -B*17 expression and slowed disease progression. We show that the dominant acute-phase cytotoxic T lymphocyte (CTL) responses in animals expressing these alleles are largely directed against two epitopes restricted by Mamu-A*01 and one epitope restricted by Mamu-B*17. One Mamu-A*01-restricted response (Tat(28-35)SL8) and the Mamu-B*17-restricted response (Nef(165-173)IW9) typically select for viral escape variants in early SIV(mac)239 infection. Interestingly, animals expressing Mamu-A*1 and -B*17 have less variation in the Tat(28-35)SL8 epitope during chronic infection than animals that express only Mamu-A*01. Our results show that MHC-I alleles that are associated with slow progression to AIDS bind epitopes recognized by dominant CTL responses during acute infection and underscore the importance of understanding CTL responses during primary HIV infection.

Alleles↗
PubMed2003

Multispecific vaccine-induced mucosal cytotoxic T lymphocytes reduce acute-phase viral replication but fail in long-term control of simian immunodeficiency virus SIVmac239.

Given the current difficulties generating vaccine-induced neutralizing antibodies to human immunodeficiency virus (HIV), the focus of the vaccine community has shifted toward creating cytotoxic-T-lymphocyte (CTL)-based vaccines. Recent reports of CTL-based vaccine trials in macaques challenged with simian/human immunodeficiency virus SHIV-89.6P have supported the notion that such vaccines can ameliorate the course of disease. However, almost all of these studies included Env as an immunogen and since SHIV-89.6P is sensitive to neutralizing antibodies it is difficult to determine the mechanism(s) of protection. Consequently, SHIV-89.6P challenge of macaques may be a poor model for determining vaccine efficacy in humans. To ascertain the effect of vaccine-induced multispecific mucosal CTL, in the absence of Env-specific antibody, on the control of an immunodeficiency virus challenge, we vaccinated Mamu-A*01(+) macaques with constructs encoding a combination of CTL epitopes and full-length proteins (Tat, Rev, and Nef) by using a DNA prime/recombinant modified vaccinia virus Ankara (rMVA) boost regimen. The vaccination induced virus-specific CTL and CD4(+) helper T lymphocytes with CTL frequencies as high as 20,000/million peripheral blood mononuclear cells. The final rMVA vaccination, delivered intravenously, engendered long-lived mucosal CTL. At 16 weeks after the final rMVA vaccination, the vaccinees and naive, Mamu-A*01(+) controls were challenged intrarectally with SIVmac239. Massive early anamnestic cellular immune responses controlled acute-phase viral replication; however, the three vaccinees were unable to control virus replication in the chronic phase. The present study suggests that multispecific mucosal CTL, in the absence of neutralizing antibodies, can achieve a modicum of control over early viral replication but are unable to control chronic-phase viral replication after a high-dose mucosal challenge with a pathogenic simian immunodeficiency virus.

Acute Disease↗
PubMed2003

Expression of the major histocompatibility complex class I molecule Mamu-A*01 is associated with control of simian immunodeficiency virus SIVmac239 replication.

Several HLA alleles are associated with attenuated human immunodeficiency virus disease progression. We explored the relationship between the expression of particular major histocompatibility complex (MHC) class I alleles and viremia in simian immunodeficiency virus SIV(mac)239-infected macaques. Of the common MHC class I alleles, animals that expressed Mamu-A*01 exhibited the best control of viral replication.

Alleles↗
PubMed2002

Estradiol may limit lipid oxidation via Cpt 1 expression and hormonal mechanisms.

OBJECTIVE: Evidence indicates that estrogen depresses hepatic lipid oxidation. We tested the hypothesis that estradiol (E(2)) treatment depresses transcription of carnitine palmitoyltransferase-1 (Cpt 1) mRNA and increases adiposity. RESEARCH METHODS AND PROCEDURES: Six ovariectomized female rats were given a subcutaneous pellet of E(2) (5 mg/d), and six were given placebo. Rats were pair-fed by group for 18 days. Body composition was assessed chemically: mRNA for liver Cpt 1, adipose tissue uncoupling protein-2 (Ucp 2), and quadriceps Ucp 3 by Northern analysis; serum glucose, triglycerides (TGs), and free fatty acids by standard techniques; and serum insulin and glucagon by radioimmunoassay. RESULTS: E(2)-treated rats lost more weight than placebo-treated rats (37.3 +/- 6.0 vs. 16.2 +/- 2.6 g, p < 0.01), but did not differ in final carcass composition (adjusted for eviscerated body mass). E(2)-treated rats had lower liver Cpt 1 (p < 0.001) and skeletal muscle Ucp 3 (p < 0.05) mRNA and lower concentrations of glucose, glucagon, and free fatty acids (p < 0.05). E(2)-treated rats tended to have higher insulin (p = -0.067) and TG (p = 0.097). TG tended to be correlated with Cpt 1 mRNA (r = -0.56 and p = 0.07). DISCUSSION: These results suggest that, although E(2) is likely to suppress lipid oxidation and promote TG synthesis, these effects are not manifested in a relative increase in carcass adiposity after 18 days of treatment, at least under conditions of negative energy balance. The possible role of E(2)-mediated changes in insulin and glucagon secretion on hepatic substrate metabolism warrants further study.

Animals↗
PubMed2002

Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell responses and reduces initial viral replication but does not prevent disease progression following challenge with pathogenic SIVmac239.

Producing a prophylactic vaccine for human immunodeficiency virus (HIV) has proven to be a challenge. Most biological isolates of HIV are difficult to neutralize, so that conventional subunit-based antibody-inducing vaccines are unlikely to be very effective. In the rhesus macaque model, some protection was afforded by DNA/recombinant viral vector vaccines. However, these studies used as the challenge virus SHIV-89.6P, which is neutralizable, making it difficult to determine whether the observed protection was due to cellular immunity, humoral immunity, or a combination of both. In this study, we used a DNA prime/modified vaccinia virus Ankara boost regimen to immunize rhesus macaques against nearly all simian immunodeficiency virus (SIV) proteins. These animals were challenged intrarectally with pathogenic molecularly cloned SIVmac239, which is resistant to neutralization. The immunization regimen resulted in the induction of virus-specific CD8(+) and CD4(+) responses in all vaccinees. Although anamnestic neutralizing antibody responses against laboratory-adapted SIVmac251 developed after the challenge, no neutralizing antibodies against SIVmac239 were detectable. Vaccinated animals had significantly reduced peak viremia compared with controls (P < 0.01). However, despite the induction of virus-specific cellular immune responses and reduced peak viral loads, most animals still suffered from gradual CD4 depletion and progressed to disease.

AIDS Vaccines↗
PubMed2002

Effects of cytotoxic T lymphocytes (CTL) directed against a single simian immunodeficiency virus (SIV) Gag CTL epitope on the course of SIVmac239 infection.

Vaccine-induced cytotoxic T lymphocytes (CTL) have been implicated in the control of virus replication in simian immunodeficiency virus (SIV)-challenged and simian-human immunodeficiency virus-challenged macaques. Therefore, we wanted to test the impact that vaccine-induced CTL responses against an immunodominant Gag epitope might have in the absence of other immune responses. By themselves, these strong CTL responses failed to control SIVmac239 replication.

Animals↗