Biomedical subjects

Christopher Chang

Publications and source records attributed to Christopher Chang.

9 recordsLinked to original sources

PubMed2025

Efficient storage and regression computation for population-scale genome sequencing studies.

MOTIVATION: The growing availability of large-scale population biobanks has the potential to significantly advance our understanding of human health and disease. However, the massive computational and storage demands of whole genome sequencing (WGS) data pose serious challenges, particularly for underfunded institutions or researchers in developing countries. This disparity in resources can limit equitable access to cutting-edge genetic research. RESULTS: We present novel algorithms and regression methods that dramatically reduce both computation time and storage requirements for WGS studies, with particular attention to rare variant representation. By integrating these approaches into PLINK 2.0, we demonstrate substantial gains in efficiency without compromising analytical accuracy. In an exome-wide association analysis of 19.4 million variants for the body mass index phenotype in 125 077 individuals (AllofUs project data), we reduced runtime from 695.35 min (11.5 h) on a single machine to 1.57 min with 30 GB of memory and 50 threads (or 8.67 min with 4 threads). Additionally, the framework supports multi-phenotype analyses, further enhancing its flexibility. AVAILABILITY AND IMPLEMENTATION: Our optimized methods are fully integrated into PLINK 2.0 and can be accessed at: https://www.cog-genomics.org/plink/2.0/.

Humans↗

PubMed2006

Comparison of outcomes after laparoscopic adjustable gastric banding in African-Americans and whites.

BACKGROUND: Race may affect outcomes after bariatric surgery. This study compares outcomes in terms of weight loss and comorbidity resolution between African-Americans and whites after laparoscopic adjustable gastric banding (LAGB). METHODS: Data from 959 patients undergoing LAGB between July 2001 and July 2004 were prospectively collected and entered into an electronic registry. Propensity score matching analysis was used to match whites to African-Americans on the basis of age, gender, and preoperative body mass index (BMI). Preoperative comorbidities (diabetes, hypertension, obstructive sleep apnea, hypercholesterolemia, and hypertriglyceridemia) were also compared. Operative time (OR), length of stay (LOS), comorbidity resolution, and percent excess weight loss (%EWL) at 1, 2, and 3 years were analyzed. All data were updated through May 2006. RESULTS: A total of 65 white LAGB patients were matched to 58 African-American LAGB patients on the basis of age, gender, and preoperative BMI. The preoperative mean age and BMI were 37 +/- 19 years and 47 +/- 7 kg/m2, respectively. A total of 55% of the white group and 64% of the African-American group had one or more comorbidities (P = NS). Median OR time and LOS were similar in both groups: 50 minutes and 23 hours, respectively. The majority of patients in both groups had major improvement or resolution of one or more comorbidities (61% whites vs 77% African-Americans, P = NS). There was, however, a significant difference in %EWL between whites and African-Americans at each time interval (49% vs 39% at 1 year; 55% vs 44% at 2 years; 52% vs 41% at 3 years; P < .05 for all values.). CONCLUSION: Despite the disparity in weight loss with the LAGB in African-Americans and whites, both patient populations experienced a similar improvement/resolution of obesity-related comorbidities.

Adult↗

PubMed2006

Campylobacter jejuni colonization of mice with limited enteric flora.

We have developed experimental murine Campylobacter infection models which demonstrate efficient establishment and reproducible, high-level colonization. Following oral inoculation, wild-type C3H mice with normal enteric flora were colonized inconsistently and inefficiently by C. jejuni strain 81-176. However, C3H mice with a limited gut flora (LF) were efficiently colonized at high levels (10(8) CFU/g of stool or large intestine tissue) followed by clearance after several weeks. Large intestine tissue showed minimal to mild inflammation at days 7 and 28 postinoculation. In striking contrast, C3H SCID mice with the same limited flora remained persistently colonized at a consistently high level until they were euthanized 8 months postinoculation. Lower gastrointestinal tract tissue from LF-SCID mice showed marked to severe inflammation in the colon and cecum at days 7 and 28 and intense inflammation of the stomach at day 28. These findings indicate that although the innate response alone cannot block colonization persistence, it is sufficient to orchestrate marked gut inflammation. Moreover, the adaptive immune response is critical to mediate C. jejuni clearance from the colonized gut. To validate our LF murine model, we verified that motility and chemotaxis are critical for colonization. Insertion-deletion mutations were generated in motB and fliI, which encode products essential for motility and flagellar assembly, and in the presumptive chemotaxis gene cheA (histidine kinase). All mutants failed to establish colonization in LF mice. Our limited flora murine colonization models serve as tractable, reproducible tools to define host responses to C. jejuni infection and to identify and characterize virulence determinants required for colonization.

Animals↗

PubMed2006

Airborne environmental injuries and human health.

The concept that the environment in which we live can have detrimental effects on our health has existed for centuries. Obvious examples of substances that can cause human diseases include infectious agents, poisons, chemicals and other noxious agents, drugs, and physical stimuli such as bright lights and loud sounds. Some less obvious agents can include allergens, nontangible agents such as colorless, odorless gases and aerosolized toxins. In recent decades, humans have developed various new materials and compounds. Additionally, we are now producing known compounds, and even naturally occurring substances, in vastly increased amounts. Many of these substances are generally believed to threaten the health of our environment. However, there is also a considerable amount of hype and exaggeration regarding some of these agents (e.g., mold) that is unsubstantiated. This article extensively reviews the data on a large number of airborne-related illnesses and attempted to place scientific reality in the context of clinical medicine.

Air Pollutants↗

PubMed2005

Methylation of human papillomavirus genomes in cells of anal epithelia of HIV-infected men.

Intra-anal malignancies disproportionately affect individuals who engage in anal intercourse because of infection with human papillomaviruses (HPVs), with an increased risk attributed to infection with HIV because of a declining immunity against HPVs. Long-term persistence of HPVs suggests yet other mechanisms that determine the clinical outcome, however. Because methylation of HPV DNA represses oncogene expression in cervical samples, we investigated whether this mechanism also occurs in HIV-positive men and studied the methylation of CpG dinucleotides overlapping with the HPV-16 enhancer and promoter in 16 anal samples. Similar to cervical infections, the average methylation frequency was 12.3%, with heterogeneities between clones from different and the same samples. In low-grade anal intraepithelial neoplasia (AIN), methylation was high in CpGs overlapping the viral enhancer but rare in promoter positions, whereas methylation was high in promoter regions in high-grade AIN, especially in samples with a high load of viral genomes. The viral replication origin was never methylated. We also detected de novo methylation at methylated (me) CpA, meCpT, and meCpC dinucleotides. Our study expands the observation and mapping of HPV DNA methylation to anal infections and the HIV-positive patient population. As observed at the cervix, DNA methylation may force HPVs into latency with functional replication but repressed transcription. Escape from this repression is a prerequisite for neoplastic progression; however, methylation resumes because of chromosomal integration of HPV genomes but spares some HPV genomes in each cell that maintain the transformed phenotype. DNA methylation, taken together with virus load, may be useful to diagnose the emergence of a population of tumor cells.

Anal Canal↗

PubMed2005

Mold hysteria: origin of the hoax.

The topic of building related illness came into the public's eye as a major health issue in the mid 1970s, when several cases of pneumonia were found to be associated with an infectious agent in Philadelphia. This agent was subsequently found to be a gram-positive bacterium known as Legionella pneumoniae. During the ensuing 30 years, a myriad of symptom constellations, disorders, clinical syndromes and illnesses have been attributed to indoor living or working environments. Over time, there appeared to be no limit to claims of building related illness, and it was "reported" that almost any kind of clinical symptom, real or imaginary, could be blamed on indoor environments. As society became more and more litigious, many of these disorders were erroneously played out in courtrooms rather than medical offices, creating a circus atmosphere surrounding this class of disorders. With the advent of the internet, as well as other advances in telecommunications, these issues eventually became part of a media frenzy, and all truths could be thrown out the window as issues became more and more decided upon by emotions and unfounded beliefs, rather than scientific data and logical thinking.

Compensation and Redress↗

PubMed2004

The Campylobacter jejuni dccRS two-component system is required for optimal in vivo colonization but is dispensable for in vitro growth.

A Campylobacter jejuni two-component signal transduction system (TCSTS), designated dccR-dccS (diminished capacity to colonize; Cj1223c-Cj1222c), has been found to be important for in vivo colonization but dispensable for in vitro growth. A DeltadccR response regulator mutant generated using the virulent strain 81-176 background exhibited significantly reduced colonization of immunocompetent limited flora (I-LF) mice, severe combined immunodeficient limited flora (SCID-LF) mice, and 1-day-old chicks. A DeltadccS sensor kinase mutant was likewise defective for colonization in the I-LF mouse model. DeltadccR-infected SCID-LF mice also exhibited dramatically reduced inflammation relative to wild type-infected SCID-LF mice. Despite this diminished colonization capacity, the DeltadccRS mutants were indistinguishable from wild type for growth under numerous in vitro conditions as well as for various phenotypes. Microarray analysis identified several genes encoding putative periplasmic and membrane proteins as being regulated by this two-component system; binding of purified His-tagged DccR to the promoter region of two of these genes supports a direct protein-DNA interaction. A conserved repeat sequence was identified in the promoter regions of these genes and in three other promoter regions in the genome, including that of an operon encoding a putative type I secretion system. Two of the regulated target genes were found to be essential for optimal colonization. Both the two-component system and the putative regulated genes have uncharacterized homologues in other Campylobacter and Helicobacter spp., suggesting that they may perform an important function in colonization among a variety of related pathogenic species.

Adaptation, Physiological↗

PubMed2004

Indoor air quality and human health: truth vs mass hysteria.

Indoor air quality is an important issue, because anything we breathe can potentially affect our health. To determine if there is a real health risk, well-designed scientifically valid studies must be performed. Although much attention has focused on sick building syndrome, chemical sensitivities, and mycotoxicosis, there actually is very little evidence that these conditions have an adverse effect on human health. In contrast, real health issues have been shown to exist regarding indoor air triggers of allergies and asthma. Outdoor allergens are difficult to avoid because the pollen grains we encounter outdoors, which are the size that can cause allergies, are windborne and can travel for miles. However, indoor allergens can cause severe allergic symptoms and may also have a priming effect on an individual's susceptibility to simultaneous or subsequent exposure of other outdoor allergens. Therefore, it is important to minimize exposure to indoor allergens. Determination of individual susceptibility can be paired with knowledge of the patient's indoor exposure pattern to produce a customized management plan of avoidance, which can be used in conjunction with pharmacological treatment of allergies and asthma, as well as immunotherapy.

Air Pollution, Indoor↗

PubMed2002

Pathogenesis and natural history of osteonecrosis.

BACKGROUND AND OBJECTIVES: Osteonecrosis (avascular necrosis) is a relatively common disorder seen by both rheumatologists and orthopedic surgeons. The vast majority of cases are secondary to trauma. However, for non-traumatic cases, there often remains a diagnostic challenge in defining the cause of bone death. The goal of this article is to review data extensively in the medical literature with respect to the pathogenesis of osteonecrosis, its natural history, and treatment. METHODS: A review of 524 studies on osteonecrosis was performed, of which 213 were selected and cited. RESULTS: Non-traumatic osteonecrosis has been associated with corticosteroid usage, alcoholism, infections, hyperbaric events, storage disorders, marrow infiltrating diseases, coagulation defects, and some autoimmune diseases. However, a large number of idiopathic cases of osteonecrosis have been described without an obvious etiologic factor. Although corticosteroids can produce osteonecrosis, careful history is always warranted to identify other risk factors. The pathogenesis of non-traumatic osteonecrosis appears to involve vascular compromise, bone and cell death, or defective bone repair as the primary event. Our understanding of the pathogenesis of osteonecrosis is now much better defined and skeletal scintigraphy and magnetic resonance imaging have enhanced diagnosis greatly. Early detection is important because the prognosis depends on the stage and location of the lesion, although the treatment of femoral head osteonecrosis remains primarily a surgical one. CONCLUSIONS: Osteonecrosis has been associated with a wide range of conditions. Many theories have been proposed to decipher the mechanism behind the development of osteonecrosis but none have been proven. Because osteonecrosis may affect patients with a variety of risk factors, it is important that caregivers have a heightened index of suspicion. Early detection may affect prognosis because prognosis is dependent on the stage and location of the disease. In particular, the disease should be suspected in patients with a history of steroid usage, especially in conjunction with other illnesses that predispose the patient to osteonecrosis. RELEVANCE: A better understanding of the pathophysiology, diagnosis and treatment of osteonecrosis will help the physician determine which patients are at risk for osteonecrosis, facilitating early diagnosis and better treatment options.

Adolescent↗