North American journal of medicine & science

Print ISSN: 1946-9357
Publications
Significant disparities in cervical cancer incidence and mortality exist among ethnic minority women, and in particular, among Asian American women. These disparities have been attributed primarily to differences in screening rates across ethnic/racial groups. Asian American women have one of the lowest rates of screening compared to other ethnic/racial groups. Yet Asian Americans, who comprise one of the fastest growing populations in the United States, have received the least attention in cancer control research. Studies suggest that various factors, including lack of knowledge, psychosocial and cultural beliefs, and access barriers, are associated with cervical cancer screening behaviors among Asian American women. Indeed, the few interventions that have been developed for Asian American women demonstrate that targeting these factors can yield significant increases in screening rates. It is important to note, however, that the effectiveness of educational interventions is often attenuated if access barriers are not adequately addressed. Hence, interventions that include key essential components, such as the use of community individuals as lay health workers, culturally-tailored and linguistically-appropriate educational materials, and navigation assistance to overcome access barriers, are more likely to be successful in enhancing screening rates. As the benefits of community-based cervical cancer prevention programs become more apparent, it will be essential to identify effective approaches for disseminating such programs more broadly. In conclusion, community-based cervical cancer screening programs have demonstrated promise in addressing existing cervical cancer disparities by increasing awareness and knowledge and promoting recommended screening behaviors. These findings will be instrumental in guiding future community-based programs to reduce cervical cancer health disparities among Asian American women.
 
Breast cancer incidence and the number of breast cancer survivors have been rapidly increasing among Chinese and Korean women in the United States. However, few data are available regarding quality of life in Asian American breast cancer survivors. This qualitative study aims to describe Asian American women's perceptions of quality of life and their breast cancer experiences. In-depth interviews with four Chinese and five Korean American breast cancer survivors and three oncologists were conducted in Chinese, Korean, or English. Interviews were recorded and transcripts were translated into English. Qualitative analyses were performed by two independent coders and then discussed and agreed upon by the research team. The respondents reported that the breast cancer experience had affected various domains of quality of life, but women reported having limited resources with which to cope effectively. Depression, anxiety, and stress were commonly reported, but women rarely discussed these issues with family and friends or sought professional help. As immigrants, women's loneliness and a lack of social support and culturally relevant resources seemed to be major barriers to maintaining good quality of life. Women also expressed interest in learning more about alternative therapies and relaxation skills. These findings can be used to help inform the development of a culturally appropriate intervention for Asian American breast cancer survivors. Future programs may provide information in women's native languages to teach skills to cope with stress and anxiety, increase women's self-efficacy within the context of their cultural background, and enhance social support among women from the same ethnic group.
 
Both plasma amyloid-β peptide 40 (Aβ40) and homocysteine (tHcy) are linked to vascular disease, which is related to depression in the elderly. We sought to study whether the relationship between tHcy and plasma Aβ40 differs in those with and without depression. In a cross-sectional study of 1058 homebound elders, vascular depression was defined as a score ≥ 16 on the Center for Epidemiological Studies Depression scale (CES-D) along with self-reported cardiovascular disease (CVD). Plasma Aβ40 and Aβ42, and serum tHcy and creatinine were measured. Elders with high tHcy had higher concentrations of plasma Aβ40 (median: 147.5 vs. 123.1 pg/ml, P < 0.0001) and Aβ42 (median: 20.2 vs. 16.6 pg/ml, P < 0.0001) than those with low tHcy. In elders with depression, the relationship between logarithm of plasma Aβ40 (LogAβ40), but not LogAβ42, and tHcy was significant (β = +0.010, SE = 0.004, P = 0.007); in contrast, this relationship was not observed in those without depression. Subjects with vascular depression had the highest concentration of tHcy (mean ± SD: 12.8 ± 4.6 vs. 11.7 ± 4.5 vs. 11.9 + 5.5, P = 0.008) compared to those without CVD and those without depression. Depressed subjects without CVD had the lowest concentration of plasma Aβ42 (median: 15.5 vs. 19.1 vs. 18.7, P = 0.01) compared to those with CVD and those without depression. Vascular depression, which is associated with tHcy and Aβ40 in blood, appears to be different from depression that is associated with low plasma Aβ42. This suggests that reducing tHcy and Aβ40 may be an adjunct treatment for vascular depression.
 
Schematic Representation of Human AGT Gene and Protein 
The renin-angiotensin system is an essential regulatory system for blood pressure and fluid homeostasis. Angiotensinogen is the only known precursor of all the peptides generated in this system. While many of the basic understandings of angiotensinogen have come from research efforts to define its role in blood pressure regulation, novel pathophysiological functions of angiotensinogen have been discovered in the last two decades including kidney developmental abnormalities, atherosclerosis, and obesity. Despite the impressive advance in the understanding of angiotensinogen gene structure and protein functions, some fundamental questions remain unanswered. In this short review, we provide contemporary insights into the molecular characteristics of angiotensinogen and its pathophysiological features. In light of the recent progress, we emphasize some newly recognized functional features of angiotensinogen other than its regulation on blood pressure.
 
BACKGROUND: In developing countries, 8 to 71% of patients initiating highly active antiretroviral therapy (HAART) die within the first year of treatment. Apart from baseline CD4 count, viral load, hemoglobin, BMI and stage of the disease, there may be other variables that contribute to AIDS-related mortality. We investigated the potential role of nutrition, lipids and insulin resistance-related phenotypes in predicting early mortality. METHODS: We recruited 210 HAART-naïve HIV/AIDS patients in Lusaka, Zambia. Dietary intake, anthropometric measurements, fasting serum insulin, glucose, and lipid profiles were assessed at baseline. Mortality was assessed after 90 days of follow-up. We used logistic regression models to identify variables associated with mortality. RESULTS: The mean±SD for age, BMI and CD4 count at baseline were 34±7.4 y, 20±3 kg/m(2) and 138±52 cells/μL, respectively. Sixteen patients (7.6%) died during follow-up. Triglyceride concentrations were associated with increased mortality [odds ratio (OR) for 1 mmol/L increase in triglyceride concentration=2.51; 95% CI: 1.34-4.71]. This association remained significant (OR=3.24; 95% CI: 1.51-6.95) after adjusting for age, gender, smoking, alcohol use, total cholesterol, BMI, CD4 count and n3 fatty acid intake. Apart from higher n3 fat intake which was inversely associated with mortality (survivors: 1.81±0.99% total energy/day vs. non-survivors 1.28±0.66% energy/day, P=0.04), there were no other macronutrients associated with mortality. CONCLUSION: Triglyceride concentrations at the time of initiating HAART are independently associated with increased risk for early mortality. If this association is confirmed in larger studies, assessment of triglycerides could become part of routine care of HIV patients initiating HAART in developing countries.
 
The plant Brucea javanica has shown impressive efficacy for treating various diseases including cancer. However, the mechanism by which B. javanica acts is poorly understood. We have established tissue culture assays to study the effects of B. javanica on cervical and several other cancer cells. Our results demonstrated that the aqueous extract from B. javanica is selectively toxic to cancer cells. Induction of apoptosis by B. javanica appears to be a possible mechanism by which it kills cancer cells. Interestingly, a significant increase of p53 protein level was observed in these apoptotic cells. Our studies indicated that both p53-dependent and p53-independent activities contributed to herb-induced cell death. These results imply that further studies with B. javanica may lead to the development of novel anti-cancer drugs.
 
STUDY BACKGROUND: Schizophrenia and autism are both neurodevelopmental disorders that were once considered to be the same disorder expressed in different developmental periods. Although they were separated diagnostically about 40 years ago, they share several clinical and possibly, etiological features. This paper reviews overlaps in four domains of function to consider the issue of whether these similarities are sporadic and likely to represent superficial similarities, or whether the disorders are more likely to share some features in common. METHODS: Representative areas of function were reviewed and compared for aspects of cognition (nonverbal reasoning, memory and language), social function (orienting/joint attention, eye contact and theory of mind), brain function (structural differences) and genetics. To facilitate comparisons with schizophrenia, a focus on high functioning autism/Asperger's disorder was utilized, particularly in the sections on cognition and social function. RESULTS: Significant similarities (and differences) characterized comparisons in each domain. CONCLUSIONS: Disturbed function in similar clinical (in cognition and social function), neurobiological (brain volumes) and genetic (e.g., involvement of the same genes or chromosomal locations) domains in autism and schizophrenia supports the hypothesis that while they are distinct disorders, they are not entirely unique. Additional studies of similarities and differences between them may thus shed light on common etiological mechanisms and hopefully, facilitate the development of novel treatment targets.
 
Autism spectrum disorders (ASD) are neurodevelopmental disorders which are currently diagnosed solely on the basis of abnormal stereotyped behavior as well as observable deficits in communication and social functioning. Although a variety of candidate genes have been identified on the basis of genetic analyses and up to 20% of ASD cases can be collectively associated with a genetic abnormality, no single gene or genetic variant is applicable to more than 1-2 percent of the general ASD population. In this report, we apply class prediction algorithms to gene expression profiles of lymphoblastoid cell lines (LCL) from several phenotypic subgroups of idiopathic autism defined by cluster analyses of behavioral severity scores on the Autism Diagnostic Interview-Revised diagnostic instrument for ASD. We further demonstrate that individuals from these ASD subgroups can be distinguished from nonautistic controls on the basis of limited sets of differentially expressed genes with a predicted classification accuracy of up to 94% and sensitivities and specificities of ~90% or better, based on support vector machine analyses with leave-one-out validation. Validation of a subset of the "classifier" genes by high-throughput quantitative nuclease protection assays with a new set of LCL samples derived from individuals in one of the phenotypic subgroups and from a new set of controls resulted in an overall class prediction accuracy of ~82%, with ~90% sensitivity and 75% specificity. Although additional validation with a larger cohort is needed, and effective clinical translation must include confirmation of the differentially expressed genes in primary cells from cases earlier in development, we suggest that such panels of genes, based on expression analyses of phenotypically more homogeneous subgroups of individuals with ASD, may be useful biomarkers for diagnosis of subtypes of idiopathic autism.
 
A failure to develop language is one of the earliest signs of autism. The ability to identify the neural signature of this deficit in very young children has become increasingly important, given that the presence of speech before five years of age is the strongest predictor for better outcomes in autism. This review consolidates what is known about verbal and preverbal precursors of language development as a framework for examining behavioral and brain anomalies related to speech and language in autism spectrum disorders. Relating the disruptions in the speech network to the social deficits observed will provide promising targets for behavioral and pharmacological interventions in ASD.
 
The TS2-NEO mouse A: The TS2-NEO mouse is outwardly normal in appearance, compared to B: negative control littermates. C: TS2-NEO mice were extremely susceptible to dermatitis, with a tendency to scratch on one side. D: Littermates suffered dermatitis less frequently and had smaller more symmetrical lesions. E: Representative quantitative real-time PCR data showing there is no change in relative expression of exon 8 and 8a in TS2-NEO mice compared to littermates in both heart and brain. F: Topology of the Cav1.2 channel showing the location of the G to R mutation in exon 8 at the intracellular side of S6 in domain I.
Brain Sections A: Asymmetry in perfusion fixed mouse brains. The angles between the midline and the cerebellum were determined and assigned as angles 1, 2 and 3. The ratio of the absolute difference between angles 2 and 3 was found to be significantly different between littermates and TS2-NEO mice. Angle 1 was unchanged. B: Cross section of brain at bregma +0.14 stained with cresyl violet from 2 age matched pairs of TS2-NEO mice and LM controls from postnatal days 137 (i, ii) and 223 (iii, iv).. Scale bar 1 mm, for all panels. Abbreviations: ac, anterior commissure; cc, corpus callosum; Cpu, caudate-putamen. C: The perimeter length of the brain ventricles are not different in TS2-NEO and LM mice, but the area of the ventricles in the TS2-NEO mice (656,000 ± 111,000 μm 2 , n=13) was larger than in littermate controls (370,000 ± 65,000 μm 2 , n = 15, p < 0.05).
Timothy Syndrome (TS) arises from a point mutation in the human voltage-gated L-type Ca(2+) channel (Cav1.2). TS is associated with cardiac arrhythmias and sudden cardiac death, as well as congenital heart disease, impaired cognitive function, and autism spectrum disorders. TS results from a de novo gain-of-function mutation which affects the voltage dependent component of Cav1.2 inactivation. We created a knock-in TS mouse. No homozygous TS mice survived, but heterozygous TS2-NEO mice (with the mutation and the neocassette in situ) had a normal outward appearance and survived to reproductive age. Previously, we have demonstrated that these mice exhibit the triad of Autistic traits. In this paper we document other aspects of these mice including Cav1.2 isoform expression levels, normal physical strength, brain anatomy and a marked propensity towards self-injurious scratching. Gross brain anatomy was not markedly different in TS2-NEO mice compared to control littermates, and no missing structures were noted. The lack of obvious changes in brain structure is consistent with theTS2-NEO mice may provide a significant tool in understanding the role of calcium channel inactivation in both cardiac function and brain development.
 
The purpose of this community-based participatory study was to identify factors associated with colorectal cancer (CRC) screening compliance and non-compliance among Cambodians, Vietnamese, Koreans and Chinese men and women 50 years and older living in the United States. A cross-sectional design was used in the study. The completed sample included 815 Asian Americans which included Cambodians (N=215), Vietnamese (N=195), Koreans (N=94) and Chinese (N=311). A 95-item questionnaire was developed and pilot tested for content validity and reliability. An in-person data collection approach was utilized and participants were given choice in responding in English or their native language. Of the 815 participants, 79.1% (N=645) reported never-screened, 7.9% (N=64), non-compliance, and 13.0% (N=106) compliance. Education was significantly associated with never-screened for CRC for Vietnamese and Chinese; employment status for Cambodians and Koreans; lack of health insurance for Cambodians, Korean and Chinese; English fluency and years lived in the U.S. for Vietnamese, Koreans, and Chinese. Less acculturated Asian Americans were more likely to be never screened, but differentially across ethnic subgroups. Barriers to screening included lack of knowledge, language, transportation, and time. Increased culturally-targeted public awareness and education programs are needed to improve CRC screening and compliance among high risk Asian American ethnic subgroups.
 
Hepatitis C virus (HCV) infection is a major public health problem and a leading cause of chronic liver disease. Chronic HCV infection often follows a progressive course over years and can result in cirrhosis, hepatocellular carcinoma, and need for liver transplantation. In the United States alone, the estimated prevalence of HCV infection is up to 5.1 million persons. The optimal approach to detecting HCV infection is to screen persons for possible history of risks of exposure to virus and to test those selected individuals with risk factors. Both host and viral factors may be important contributors to the natural history of HCV. Currently, effective pharmacologic therapy are available to induce sustained virologic response (SVR) or virologic "cure," which results in improved morbidity and mortality. Patient education before treatment is essential and should include a full discussion of potential side effects. It is important to work collaboratively and closely with patients to ensure early recognition of adverse events and to effectively manage them in order to ensure treatment compliance. This paper provides a thorough overview on screening for the diagnosis, clinical management, and treatment indications and contraindications for chronic hepatitis C.
 
Inorganic nitrate has emerged as a therapeutic agent for cardiovascular disease; however, nitrate can also metabolize to carcinogenic nitrosamines under pathologic conditions. Few large epidemiologic studies have examined circulating levels of nitrate in relation to cardiovascular disease and cancer. Data on the validity of nitrate measurement in blood samples collected in typical epidemiologic settings are needed before nitrate can be evaluated as an exposure in large epidemiologic studies. We measured plasma levels of nitrate in three pilot studies to evaluate its laboratory variability, stability with delayed processing, and reproducibility over time among women from the Nurses' Health Study and healthy female volunteers. Laboratory variability of nitrate levels was fairly low, with a coefficient variation (CV) of 7%. Plasma nitrate levels in samples stored as whole blood on ice for up to 48 hrs before processing were very stable; the overall intra-class correlation (ICC) from 0 to 48 hours was 0.89 (95%CI, 0.70-0.97). The within-person reproducibility over a one-year period was modest, with an ICC of 0.49 (95% CI, 0.33- 0.94). Our results indicate that measurement of nitrate in plasma is reliable and stable in blood samples with delayed processing up to 48 hours. Within-person reproducibility was modest but data from this study can be used for measurement error correction in subsequent analyses. The measurement of nitrate cannot be widely used in epidemiologic research without the documentation of its stability and reproducibility.
 
Cervical cancer is one of the leading causes of cancer death in women worldwide. Human papillomavirus (HPV) infection is necessary but not sufficient for the development of cervical cancer. Genomic instability caused by HPV allows cells to acquire additional mutations required for malignant transformation. Genomic instability in the form of polyploidy has been implicated in a causal role in cervical carcinogenesis. Polyploidy not only occurs as an early event during cervical carcinogenesis but also predisposes cervical cells to aneuploidy, an important hallmark of human cancers. Cell cycle progression is regulated at several checkpoints whose defects contribute to genomic instability.The high-risk HPVs encode two oncogenes, E6 and E7, which are essential for cellular transformation in HPV-positive cells. The ability of high-risk HPV E6 and E7 protein to promote the degradation of p53 and pRb, respectively, has been suggested as a mechanism by which HPV oncogenes induce cellular transformation. E6 and E7 abrogate cell cycle checkpoints and induce genomic instability that leads to malignant conversion.Although the prophylactic HPV vaccine has recently become available, it will not be effective for immunosuppressed individuals or those who are already infected. Therefore, understanding the molecular basis for HPV-associated cancers is still clinically relevant. Studies on genomic instability will shed light on mechanisms by which HPV induces cancer and hold promise for the identification of targets for drug development.
 
Pathologists routinely interpret gross and microscopic specimens to render diagnoses and to engage in a broad spectrum of investigative research. Multiple studies have demonstrated that imaging technologies have progressed to a level at which properly digitized specimens provide sufficient quality comparable to the traditional glass slides examinations. Continued advancements in this area will have a profound impact on the manner in which pathology is conducted from this point on. Several leading institutions have already undertaken ambitious projects directed toward digitally imaging, archiving, and sharing pathology specimens. As a result of these advances, the use of informatics in diagnostic and investigative pathology applications is expanding rapidly. In addition, the advent of novel technologies such as multispectral imaging makes it possible to visualize and analyze imaged specimens using multiple wavelengths simultaneously. As these powerful technologies become increasingly accepted and adopted, the opportunities for gaining new insight into the underlying mechanisms of diseases as well as the potential for discriminating among subtypes of pathologies are growing accordingly.
 
NAD-dependent Class III histone deacetylase SIRT1 is a multiple functional protein and has been demonstrated critically involved in stress response, cellular metabolism and aging through deacetylating variety of substrates including p53, forkhead transcription factors, PGC-1α, NF-κB, Ku70 and histones. Increasing evidences indicate that SIRT1 plays a complex role in tumorigenesis with functions in both tumor promoting and tumor suppressing. This review provides an overview of current knowledge of SIRT1 and its controversies regarding the functions of SIRT1 in tumorigenesis.
 
Werner syndrome is an autosomal recessive disorder associated with premature aging and cancer predisposition. Cells from Werner syndrome patients show increased genomic instability and are hypersensitive to DNA damage agents. Werner syndrome is caused by mutations of the WRN gene. WRN protein is a member of RecQ DNA helicase family. It not only contains a conserved 3'-5' helicase domain as other members of the RecQ family but also contains a unique 3'-5' exonuclease domain. WRN recognizes specific DNA structures as substrates which are intermediates of DNA metabolism. WRN interacts with many other proteins, which function in telomere maintenance, DNA replication, and DNA repair through different pathways.
 
Intrathoracic neurogenic tumors are not uncommon, but presentation as a giant mass in the thoracic cavity is rare. Although several cases of intrathoracic giant malignant peripheral nerve sheath tumor have been reported, only one case of intrathoracic giant benign neurofibroma appears in the literature. In this report, we describe a very rare case of atypical giant neurofibroma in the right thoracic cavity. The patient was a 57 year old African American man, who developed sudden cardiac arrest and passed away in the emergency room. At autopsy, a huge encapsulated firm tumor was found in the right thoracic cavity, attached to the vertebral bodies and superficially adherent to the upper and middle lobes of the right lung. This giant mass weighed 2140 grams and measured 31 x 30 x 5.5 cm. Microscopically, the tumor consisted of interweaving fascicles of spindle cells with scattered atypical nuclei. Immunohistochemical studies showed that tumor cells were focally positive for S100, and negative for SMA, desmin, calretinin, Pan CK, CK5/6, EMA, CD99, CD34 and p53. The overall morphological and immunohistochemical features were diagnostic of an atypical neurofibroma. [N A J Med Sci. 2009;2(4):135-138.]
 
Background: The prognostic significance of the extent and pattern of bone marrow infiltration by Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has been supplanted by newer biologic prognostic markers such as immunoglobulin heavy chain variable region (IgVH) mutation status, CD38 and ZAP70 expression, fluorescence in situ hybridization (FISH) cytogenetics, and serum markers. Expression of CD38 and ZAP-70 correlates with IgVH mutation status, and also provides prognostic value as independent markers. Materials and Methods: Seventy-four cases of CLL/SLL were reviewed and the relationship between expression of CD38, ZAP-70, and bone marrow infiltration was examined. CD38 and ZAP-70 were analyzed by a single laboratory using standardized multiparametric flow cytometry with a threshold of 20% and 30% positive cells for each. Hematoxylin and eosin stained bone marrow biopsy and aspirate clot sections were classified as showing diffuse or non-diffuse (nodular/interstitial) pattern of infiltration; the extent of infiltration was assessed by the proportion of lymphocytes on histologic sections and aspirate smears.
 
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel inflammatory biomarker. Basic research has shown that Lp-PLA2 is involved in the pathogenesis of atherosclerosis. In the past decade, an increasing number of epidemiological studies have investigated the association of Lp-PLA2 with atherosclerosis, but its roles in the different stages of atherosclerosis are not established. By undertaking a systematic review of the epidemiological studies on the relationship between Lp-PLA2 and atherosclerotic cardiovascular disease (CVD)/subclinical atherosclerosis, we tried to evaluate the relationship between Lp-PLA2 and the different stages of atherosclerosis. MEDLINE, Cochrane Library, and National Knowledge Infrastructure (CNKI) were searched up to September 1st, 2011. The references in all the located articles were manually searched. Epidemiological studies on the association of Lp-PLA2 with CVD and subclinical atherosclerosis, with total CVD, coronary heart disease (CHD), stroke, and subclinical atherosclerosis as their observation endpoints or outcome variables, were included in this study. Studies which did not assess the hazard ratio (HR), relative risk (RR), or odds ratio (OR) of Lp-PLA2 or which did not adjust for other known risk factors were excluded. The general information, study design, sample size, outcome variables and their definitions, follow-up duration, Lp-PLA2 measurements, variables adjusted in the multivariate analysis and main results in the literatures were retrieved. Thirty-nine studies were enrolled in this systematic review. Thirty-three studies (49, 260 subjects) investigated the relationship between Lp-PLA2 and CVD, among which 31 showed that increased Lp-PLA2 is associated to high risk for incidence or mortality of CVD: HR/RR per 1 standard deviation (SD) increase = 1.17-1.40; RR for the highest as compared with the lowest quartile was 1.41-3.75 (1.8-2.5 in most studies). Six studies (four cross-sectional studies and two case-control studies, with an overall sample size of 5,537) explored the relationship between Lp-PLA2 and subclinical atherosclerosis; among them, two studies demonstrated that Lp-PLA2 was associated with coronary artery calcification in young adults and men. In conclusion, many epidemiological studies have demonstrated that Lp-PLA2 increases the risk of clinical CVD events. However, whether there is a similar association between Lp-PLA2 and subclinical atherosclerosis remains unclear. Whether Lp-PLA2 exerts its effect during the occurrence of clinical events promoted by unstable plaques or at the early stage of atherosclerosis needs to be clarified in further prospective studies.
 
Acute myeloid leukemia (AML) is a heterogeneous group of diseases with a multitude of molecular genetic aberrations and variable clinical outcome. Clonal chromosomal abnormalities have been identified in over 50% of AML cases, and have been regarded as one of the most important prognostic markers. We present a case of a 28-year-old Caucasian woman with AML without maturation, diploid karyotype, that was resistant to multiple chemotherapies and relapsed after matched unrelated stem cell transplantation. Conventional cytogenetic analysis performed on bone marrow specimens revealed 46,XX,t(2;16)(p21;p11.2),t(11;14)(p13;p11.2). The t(11;14)(p13;p11.2) was confirmed by fluorescence in situ hybridization using a whole chromosome paint probe for chromosome 11. Morphologically, the bone marrow was hypercellular with trilineage hypoplasia and 84% blasts. Flow cytometry analysis showed that the blasts were of myeloid immunophenotype. Molecular studies detected internal tandem duplication of the FLT3 gene and a mutation in exon 12 of the NPM1 gene. The patient then received monotherapy with AC220, achieved a brief remission, and died of relapsed disease 23 months after initial diagnosis. This is the first report of this novel clonal chromosome aberration as evidence of clonal evolution in AML. [N A J Med Sci. 2012;5(1):48-50.]
 
Biomarkers of mitochondrial disease were studies in 133 consecutive autism spectrum disorder patients to determine the prevalence of abnormalities in biomarkers of mitochondrial disease. Biomarkers included traditional biomarkers of mitochondrial disease (lactate, alanine), fatty-acid oxidation defects (acylcarnitine panel) and recently described novel biomarkers of detecting mitochondrial dysfunction in individuals with autism spectrum disorder (alanine-to-lysine ratio, creatine kinase, aspartate transaminase). Biomarkers were collected in the morning fasting state. Abnormal biomarker values were verified by repeat testing. For those with abnormal acyl-carnitine panels, secondary disorders of fatty acid metabolism were ruled out. Abnormalities in lactate, alanine-to-lysine ratio and acyl-carnitine panels occurred in over 30% of children on initial testing. Among the patients with abnormal biomarkers who had repeated testing, abnormalities were confirmed about half of the time except for alanine which was only confirmed 20% of the time. Elevation in alanine-to-lysine ratio was associated with epilepsy and elevation in multiple acyl-carnitines was associated with regression. In order to confirm the significance of certain biomarkers, a wide variety of mitochondrial biomarker values were compared between specific subgroups of children with abnormal biomarkers and matched children without any abnormalities in biomarkers. Lactate, alanine-to-lysine ratio and acyl-carnitine panel groups demonstrated abnormalities in multiple mitochondrial biomarkers, confirming the validity of these biomarkers of mitochondrial dysfunction. This study demonstrates that multiple biomarkers of mitochondrial dysfunction are elevated in a significant portion of children with autism spectrum disorder and lend support to the notion that disorders of energy production may affect a significant subset of children with autism. [N A J Med Sci. 2012;5(3):141-147.]
 
Retinal microvascular abnormalities have been associated with age-related systemic processes, such as atherosclerosis, chronic inflammation, endothelial dysfunction, and other conditions. Current epidemiological studies suggested that retinal microvascular abnormalities may be associated with cognitive decline and thereby may provide a target for early detection and prevention of dementia. However, most of previous studies have been cross-sectional and provided only suggestive evidence. Future prospective studies with assessment of cognitive function on specific domains are required to further evaluate the role of retinal microvascular signs in predicting the development of aging-related cognitive decline and dementia.
 
Molecular genetic testing and molecular pathology are relatively new but rapidly growing fields in China. This article reports on the experience of providing molecular genetic testing at the Center for Clinical Molecular Medicine (CCMM) of Chongqing Medical University in China. This center is the first of such centers in the southwestern region of China and implements a spectrum of genetic tests on constitutional cytogenetics, oncology cytogenetics, molecular cytogenetics, molecular genetics, molecular oncology, metabolic genetics, and newborn screening. The annual test volume had a 78-fold increase in the past five years and reached approximately 380,000 tests in 2012. This tremendous growth reflects both great opportunities and challenges for China’s healthcare system. Some of the challenges such as the lack of a medical genetics professionals and qualified training programs for clinical geneticists, laboratory specialists and genetic counselors are discussed.
 
The sensitivity of intraoperative diagnosis of sentinel lymph node (SLN) metastases in breast cancer is variably low. The purpose of this study was to review the pros and cons of frozen section (FS) and touch preparation (TP) methods, particularly in micrometastases. Intraoperative TP or FS was performed on the SLN of consecutive breast cancer patients from 2007 to 2009. Sensitivity, specificity, and overall accuracy of detecting positive SLNs were calculated for FS and TP groups. There were 396 patients with SLN biopsy. 124 (31.3 %) patients had at least one positive SLN. A total of 1270 lymph nodes were examined intraoperatively, 133 with FS and 1137 with TP. FS was significantly more sensitive than TP, 82.6% and 49.6%, respectively (p<0.0001). There were a total of 57 SLNs with micrometastases. FS was performed on 10 and TP on 47. The sensitivity of FS was 50% and for TP, 19.3% (p<0.0001). Of the 10 positive SLNs using FS, 3 were negative on permanent sections (PS). We conclude that FS is superior to TP as a method of detecting micrometastases in SLNs. However, a significant subset of patients who had positive SLNs on FS became negative on PS. This raises the possibility that some negative SLNs on FS might have been understaged. [N A J Med Sci. 2012;5(1):13-19.]
 
Use of LC-MS/MS methods has improved sample preparation and increased throughput for the measurement of 40 or more organic acids in urine. In order to assess the significance of abnormalities that might be attributed to nutritional inadequacies or other metabolic disturbances, the week-to-week variation of results due to normal physiological responses needs to be established. This study determined the biological variability for 37 organic acids plus hippuric acid, D-arabinitol and 8-hydroxy-2’deoxyguanosine in overnight urine specimens from eight weekly samples submitted by 22 healthy adults. For the 40 analytes, CVb values varied from 12.3 to 74.3. Fourteen of the analytes had CVb values less than 30 and another 19 of them were less than 50. Multiple analytes displayed the property of increasing variability with concentration that may be characteristic of most intermediary metabolites. Linear regression line slopes for CVb vs. concentration were tabulated to assist the use of this information. The 40 analytes display biological variability in the range of disease risk markers such as serum lipoprotein cholesterol concentrations, cancer markers and thyroid hormones. The likelihood of a single measurement being representative of the true mean concentration varies with the analyte and the level found. Data reported here demonstrate reliability of results of urinary organic acid profiling performed under the reported analytical conditions. [N A J Med Sci. 2012;5(3): 148-156.]
 
Chronic Hepatitis C virus (HCV) infection carries a significant clinical burden in the United States, affecting more than 4.6 million Americans. Untreated chronic HCV infection can result in cirrhosis, portal hypertension, and hepatocellular carcinoma. Previous interferon based treatment carried low rates of success and significant adverse effects. The advent of new generation oral antiviral therapy has led to major improvements in efficacy and tolerability but has also resulted in an explosion of data with increased treatment choice complexity. Treatment guidelines are constantly evolving due to emerging regimens and real world treatment data. There also still remain subpopulations for whom current treatments are lacking or unclearly defined. Thus, the race for development of HCV treatment regimens still continues. This review of the current literature will discuss the current recommended treatment strategies and briefly overview next generation agents.
 
We studied the effects of two xanthones compounds isolated from Swertia punicea Hemsl (from Geutianaceae), swertianolin (I) and bellidifolin (II), on Hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) in cultured human hepatocellular carcinoma cell line (HepG 2 ). The HepG 2 cells were first cultured for 24h, various concentrations of these two xanthones were then added to the culture medium. The culture medium containing the two xanthones was exchanged once every 4 days. After 8 days, the cytotoxic activities of these two xanthones were assessed by cytopathic effect. The HepG 2 cells were then treated with the two compounds at a concentration of swertianolin (1.6, 3.1, 6.2, 12.5, 25 m g/ml) and bellidifolin (2.0, 3.9, 7.8, 25.5, 31.2 m g/ml). Four or eight days later, the culture medium was collected and the expression of HBsAg and HBeAg were determined by radioimmunoassay. Our results show that swertianolin can suppress the expression of HBeAg with IC 50 of 8.0 m g/ml, while bellidifolin can inhibit the expression of HBsAg with IC 50 of 13 m g/ml at the eighth days. The Therapeutic Index for swertianolin and bellidifolin are 6.2 and 6.8, respectively. Our findings suggest that swertianolin and bellidifolin have anti-HBV activities in vitro.
 
Many studies have shown the potential benefits of the acupuncture for Parkinson’s disease although lack of the solid scientific data in clinic. To understand the mechanism of acupuncture is not easy, but many clues in this review would be helpful for the study in the future. As we know today that acupuncture may affect multiple factors of the brain activities, which may involve in the pathogenesis and the development of Parkinson’s disease. They include Dopamine, Dopaminergic neurons, Dopaminergic metabolites, Dopamine D2 receptors, Cyclooxygenase-2 (COX-2), inducible Nitric Oxide Synthase (iNOS), brain-derived Neurotrophic factor (BNDF), Superoxide Dismutase (SOD) and Lipids Peroxides (LPO) in the striatum, substantia nigra (SN), and ventral tegmental area (VTA). Different techniques of acupuncture stimulation seem induce the different responses of the neural activities on the animal model. [N A J Med Sci. 2009;2(1):32-34.]
 
Top-cited authors
Grace X Ma
  • Temple University
Maria Mody
  • Massachusetts General Hospital
Frank Chen
  • Villanova University
Sunmin Lee
  • University of California, Irvine
Carolyn Y Fang
  • Fox Chase Cancer Center