BBA Clinical

Purpose: Clear cell Renal Cell Carcinomas (ccRCC), the largest group of renal tumours, are resistant to classical therapies. The determination of the functional state of actionable biomarkers for the assessment of these adenocarcinomas is essential. The dysregulation of the oncoprotein, PKB/Akt has been linked with poor prognoses in human cancers. Material & methods: We analysed the status of the PKB/Akt pathway in a representative tumour tissue microarray obtained from the primary tumours and their metastases in 60 ccRCC with long term follow up...

With the substrate DNP-α-GalNAc (2,4-dinitrophenyl- N -acetyl-α-d-galactosaminide) three α- N -acetylgalactosaminidase-like activities could be distinguished in serum, in addition to the classical lysosomal enzyme (Naga, EC 3.2.1.49, pH optimum at 4). Two activities had optima in the pH 5 to 6 region and one peaked around pH 8. Like the Naga activity at pH 4, the activity at pH 8 was detectable under standard assay conditions. However, the two activities in the pH 5 to 6 range were not readily apparent in such assays...

This paper presents a new assay to determine the activity of the lysosomal enzyme α- N -acetylgalactosaminidase (Naga, EC 3.2.1.49) in human serum. It is based on the use of a new chromogenic substrate, DNP-α-GalNAc (2,4-dinitrophenyl- N -acetyl-α-D-galactosaminide) and is performed at pH 4.3 and 37 °C. This allows continuous monitoring of the absorbance of the released DNP. The assay can be performed with a standard spectrophotometer. Compared to established methods using an endpoint assay with MU-α-GalNAc (4-methylumbelliferyl-GalNAc), the present method gives a ca...

OBJECTIVES: 1. Evaluate the effect of washing and cooking iron-fortified rice on iron retention and bioavailability. 2. Evaluate the effect of iron-fortified rice on women with iron deficiency anemia. METHODS: 1. Iron-fortified rice (18 mg/100 g as FeSO4) was cooked in Baton Rouge, Louisiana (C), rinsed and cooked (RC), fried and cooked (FC), cooked with extra water (CW), or soaked and cooked with extra water (SCW), and iron retention was determined. 2. Rice samples were cooked in Kampala, Uganda in a lab (C-Uganda) and households using traditional cooking method (TC-Uganda) and iron retention were determined...

Uptake of low-density lipoprotein (LDL) particles by macrophages represents a key step in the development of atherosclerotic plaques, leading to the foam cell formation. Chemical modification of LDL is however necessary to induce this process. Proatherogenic LDL modifications include aggregation, enzymatic digestion and oxidation. LDL oxidation by one-electron (free radicals) and two-electron oxidants dramatically increases LDL affinity to macrophage scavenger receptors, leading to rapid LDL uptake and fatty streak formation...

We report three signatures produced from SHARPIN gene copy number increase (GCN-Increase) and their effects on patients with breast cancer (BC). In the Metabric dataset (n = 2059, cBioPortal), SHARPIN GCN-Increase occurs preferentially or mutual exclusively with mutations in TP53 , PIK3CA , and CDH1 . These genomic alterations constitute a signature (SigMut) that significantly correlates with reductions in overall survival (OS) in BC patients (n = 1980; p = 1.081e - 6). Additionally, SHARPIN GCN-Increase is associated with 4220 differentially expressed genes (DEGs)...

Threatened miscarriage is the most common gynecological emergency, occurring in about 20% of pregnant women. Approximately one in four of these patients go on to have spontaneous miscarriage and the etiology of miscarriage still remains elusive. In a bid to identify possible biomarkers and novel treatment targets, many studies have been undertaken to elucidate the pathways that lead to a miscarriage. Luteal phase deficiency has been shown to contribute to miscarriages, and the measurement of serum progesterone as a prognostic marker and the prescription of progesterone supplementation has been proposed as possible diagnostic and treatment methods...

AIM: The aim of the present study was to investigate and compare between Low Level Laser Therapy (LLLT) and Ultrasound (US) in treatment of Carpal Tunnel Syndrome (CTS) using the advantage of application of treatment directly over the transverse carpal ligament, as well as over the course of the median nerve in the forearm simultaneously. DESIGN: Fifty patients (25-55 years) with diabetic neuropathy, diagnosed as unilateral carpal tunnel syndrome participated in the study...

Preeclampsia is a pregnancy complication which causes significant maternal and fetal morbidity and mortality worldwide. Although intensive research has been performed in the last 40 years, the pathology of preeclampsia is still poorly understood. The present work is a comparative study of the myometrium of women with normal pregnancy, and those with late- and early-onset preeclampsia (n = 10 for each group). We observed significant changes in the levels of antioxidant enzymes, markers of mitochondrial biogenesis and autophagy proteins in preeclamptic myometrium...

BACKGROUND: Multiple myeloma (MM) is a complex heterogeneous disease. Various risk stratification models have been recommended including cytogenetic and FISH analysis to identify high-risk patients who may benefit from novel treatments, but such facilities are not widely available. The International Scoring System (ISS) using beta-2-microglobulin and albumin remains a widely used prognostic scoring system in many clinical practices; however it is not useful in predicting response to treatment in MM...

BACKGROUND: Cognitive dysfunction has been increasingly recognized in chronic kidney disease (CKD) patients. Senile plaques are important pathophysiological characteristic of cognitive dysfunction. The major component of plaques is the amyloid β (Aβ) peptide released from proteolytic cleavage of amyloid precursor protein (APP). Plasma Aβ has been a focus of the growing literature on blood based biomarkers for cognitive dysfunction. Oxidative stress is prevalent in CKD and it plays an important role in cognitive dysfunction...

AIM: To study physical and chemical structures and properties including calorific value of human adipose tissue in different anatomical location in autopsy-assigned clinical trial. METHODS: A pilot physical and chemical descriptive randomized autopsy-assigned trial. Adipose tissue 252 sampled from 36 individuals at autopsy who between 36 and 63 years old died from road accidents. Interventions: Chemical functional groups and calorific value were studied using infrared and atomic adsorptive spectrometries, elemental chemical analysis and differential scanning calorimetry...

A method of rapidly differentiating lung tumor from healthy tissue is extraordinarily needed for both the diagnosis and the intraoperative margin assessment. We assessed the ability of fluorescence lifetime imaging microscopy (FLIM) for differentiating human lung cancer and normal tissues with the autofluorescence, and also elucidated the mechanism in tissue studies and cell studies. A 15-patient testing group was used to compare FLIM results with traditional histopathology diagnosis. Based on the endogenous fluorescence lifetimes of the testing group, a criterion line was proposed to distinguish normal and cancerous tissues...

Adipose tissue (AT) is involved in dysmetabolism pathogenesis. Regional fat distribution and functioning may contribute to obesity-related metabolic disorders and adverse health outcomes. Specific fat depots are suggested to possess unique biological properties, but specific metabolic profiles of subcutaneous (SAT) and visceral adipose tissue (VAT) remain unknown. We aimed to characterize VAT and SAT glucose metabolism, and their correlation with body mass index (BMI). AT samples from patients (n = 12; F:M, 9:3) with a mean age of 46 years (26-83 years) and an average BMI of 29...

Most studies have considered the negative influence of obesity on fertility in both genders. In the present study, we assessed mitochondrial activity expressed as the mitochondrial potential index (MPI) in cumulus cells from obese women and women with a normal body mass index (BMI) during assisted reproductive therapy. The results revealed a significant reduction of MPI with increased body mass. The lower MPI levels in cumulus cells from obese women may reflect mitochondrial dysfunction caused by oxidative stress, which can affect the cumulus-oocyte complex and have an impact on oocyte development...

DNA polymerase gamma (POLG) is the replicative polymerase responsible for maintaining mitochondrial DNA (mtDNA). Disorders related to its functionality are a major cause of mitochondrial disease. The clinical spectrum of POLG syndromes includes Alpers-Huttenlocher syndrome (AHS), childhood myocerebrohepatopathy spectrum (MCHS), myoclonic epilepsy myopathy sensory ataxia (MEMSA), the ataxia neuropathy spectrum (ANS) and progressive external ophthalmoplegia (PEO). We have collected all publicly available POLG-related patient data and analyzed it using our pathogenic clustering model to provide a new research and clinical tool in the form of an online server...

Classical thinking in endocrine physiology squeezes our diagnostic handling into a simple negative feedback mechanism with a controller and a controlled variable. In the case of the thyroid this is reduced to TSH and fT3 and fT4, respectively. The setting of this tight notion has no free space for any additions. In this paper we want to challenge this model of limited application by proposing a construct based on a systems approach departing from two basic considerations. In first place since the majority of cases of thyroid disease develop and appear during life it has to be considered as an acquired condition...

BACKGROUND: Somatic copy number alterations (SCNAs) occurring in tumors can provide information about tumor classification, patient's outcome or treatment targets. Liquid biopsies, incl. plasma samples containing circulating cell-free tumor DNA (ccfDNA) can be used to assess SCNAs for clinical purposes, however specify and reliability of methods have to be tested. METHODS: SNP microarrays (Affymetrix) were used to generate whole-genome copy number profiles from plasma ccfDNA (OncoScan) and paired tumor biopsies (CytoScan) from ten patients with metastatic cancers...

Laboratory medicine approaches the evaluation of thyroid function mostly through the single determination of the blood level of thyroid stimulating hormone (TSH). Some authors have suggested an upper reference value for TSH of 2.5 mIU/L. This suggestion has not been confirmed by recent clinical studies. These studies have delivered a clinically valid reference range going from 0.3 to 3.5 mIU/L. These values are valid for both for the general population as well as in the setting of fertility and pregnancy...

BACKGROUND: Early studies established that certain lipids were lower in acute myeloid leukemia (AML) cells than normal leukocytes. Because lipids are now known to play an important role in cell signaling and regulation of homeostasis, and are often perturbed in malignancies, we undertook a comprehensive lipidomic survey of plasma from AML patients at time of diagnosis and also healthy blood donors. METHODS: Plasma lipid profiles were measured using three mass spectrometry platforms in 20 AML patients and 20 healthy blood donors...