Objectives: The purpose of this study was to investigate the changes in serum valproate (VPA) levels and their relationship to progesterone levels during the menstrual cycles of fertile women. Materials and methods: Female patients compliant with VPA (n=14) were included in this study. Serum VPA and progesterone levels were measured during two periods, in which progesterone levels may be the lowest (early follicular phase) and the highest (mid luteal phase). Results: Serum VPA levels were significantly different between the two periods. Serum progesterone levels increased in 64.3% of the sample during menstruation, revealed a noticeable but not significant mean increased. There was no correlation between serum valproate and progesterone levels (r=0.209, p>0.05) in the menstrual phase. Conclusion: This study shows that serum VPA levels varied greatly during the menstrual cycles. The results of this study also implying that VPA levels may be relationship to sex steroid levels in menstrual cycle. Particularly in cyclic premenstrual exacerbation of affective symptoms, this interaction should be considered in the evaluation of treatment may be beneficial.
Spinal trauma can cause simultaneous injury of intervertebral discs (IVD) and anterior longitudinal ligaments (ALL). Injury of IVD is an important factor causing intervertebral disc degeneration (IDD). However, the relationship between ALL injury and IDD has rarely been discussed. Therefore, the purpose of this study was to investigate the effects of ALL injury on degeneration of injured IVD. Thirty-two rabbits were randomly and evenly divided into four groups including sham group, Group A (simple IVD punctured), Group B (IVD punctured with half transverse injury of ALL), and Group C (IVD punctured with entirely transverse injury of ALL). Then, computed tomography, HE staining, intraoperative exploration, immunohistochemistry, and TUNEL staining were used in detecting the degenerative changes in corresponding IVD. At 2 weeks postoperatively, in response to the extent of ALL injury, the middle height of the punctured intervertebral space was reduced. The IVD structure was disorganized and the number of IVD cells was decreasing. The percentage of IL-1β- and TNF-α-immunopositive cells was increased and the percentage of TUNEL-positive IVD cells was also increased. There was a significant difference between Group C and the other groups in the results of immunohistochemistry and TUNEL staining (P<0.05). At 8 weeks postoperatively, the middle height of intervertebral space was significantly lower in Group C than in other groups (P<0.05). Intraoperative exploration found that there was obvious instability of intervertebral space in Group C. Compared with 2 weeks postoperation, the pathological changes were severe. The percentage of IL-1β- and TNF-α-immunopositive cells was decreased and the percentage of TUNEL-positive cells was increased in the corresponding groups. There was a significant difference between Group C and the other groups in the results of immunohistochemistry and TUNEL staining (P<0.05). These findings indicate that IVD injury companied with completed ALL injury might cause obvious spinal instability, which might correspond to severe IDD.
Dual roles of heparanase in vascular calcification associated with human carotid atherosclerosis
Aims: The aim of this study was to determine the relationship between amplification, protein expression and somatic mutation of c-MET in advanced Non-small cell lung cancer. The influence of c-MET abnormalities on clinical outcomes of patients undergoing Crizotinib therapy for treatment of Non-Small Cell Lung Cancer was also evaluated. Methods: c-MET protein expression, gene copy number (GCN) and somatic mutation for exon 14 were detected by Immunohistochemistry, fluorescent In Situ Hybridization and Denaturing High Performance Liquid Chromatography, respectively, in a large series of 196 NSCLC patients. The correlation of c-MET abnormalities and clinical outcome of targeted therapy was analyzed by McNemar’s test. Results: c-MET expression was observed in 28.6% (56/196) cases, and among those 13.8% (27/196) was shown to be FISH positive. Only 2.67% patients in this study carried the c-MET mutation. All cases that were c-MET FISH positive were also shown to express c-MET by IHC. However, only half of the cases that were positive for c- MET expression were found to be FISH positive. Among 31 patients with moderate c-MET IHC staining, 11 cases (35.5%) were FISH positive, while 16/25 cases with high IHC staining were also FISH positive. Six patients received Crizotinib as a first-line or second/third-line therapy. Among them, three cases showed ALK protein expression, two patients showed expression of the ROS1 fusion gene, and one was positive for c-MET expression by IHC. The response to Crizotinib in the three patients positive for ALK were all PR, while the c-MET positive patient showed SD and both cases with expression of the ROS1 gene showed PD. Conclusions: IHC could be a preliminary screening test to facilitate selection of patients with c-MET amplification for ALK inhibitor therapy.
Purpose To explore the association between single nucleotide polymorphisms (SNPs) of TNF-αand IL-10 genes as well as their plasma levels and pathogenesis of diffuse large B-cell lymphoma (DLBCL).Methods Snapshot SNP genotype technique was used to assess genetic variation in 6 SNPs for TNF-α and IL-10 in 38 DLBCL cases and 77 healthy controls,and enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma concentrations of TNF-α and IL-10 in the above population.Results Plasma IL-10 level in DLBCL cases was higher than that in controls (P ＜ 0.05),but there was no significant difference in plasma TNF-αlevel between the two groups (P ＞ 0.05).Of all the candidate SNPs,the geneotype distribution for TNF-α-863C/A showed significant differences between the case and control groups (P ＜ 0.05),and carriers with CA/AA genotypes had more two-fold risks of DLBCL than those with the CC genotype (95％ CI =1.091-4.765,P =0.028).However several other candidate SNPs showed no significant difference in the geneotype distributions between the cases and controls (P ＞ 0.05).After excluding the effects of disease status on plasma TNF-alpha and IL-10 levels,the polymorphism of each gene had no significant effect on the corresponding plasma concentration (P ＞ 0.05).Conclusion TNF-α-863C/A polymorphism may be associated with the risk of DLBCL,and IL-10 play an important role in occurrence and development of DLBCL.
Identification of novel chondroitin sulfate sulfotransferases and proteoglycan core proteins in the nematode C. elegans
This study showed peculiarities of the reaction of proteolytic processes indices on hypobaric hypoxia, influenced by constant light, in the gingival tissues in immature female rats. It has been established that modeling of the hypobaric intermittent hypoxia equal the altitude 4000 meters (2 hours per day for 14 days) decreases proteolysis intensity in the gingival tissues in immature female rats. The pineal gland hypofunction by means of a constant illumination significantly influences upon the character of changes of the proteolytic processes in the gingival tissues, caused by systemic hypobaric hypoxia at a combined use of the indicated influences.
Fatty liver disease (FLD) is the most prevalent form of liver disease worldwide. Overnutrition can induce nonalcoholic fatty liver disease (NAFLD), a spectrum of conditions ranging from simple steatosis [or nonalcoholic fatty liver (NAFL)] to nonalcoholic steatohepatitis and cirrhosis. Some of the epidemiological and pathological studies have also suggested an association between the presence of fatty liver and sudden death. A 37-year-old man was found dead when he was asleep in the bed at home. According to his family, he was single and a costermonger. He was not an athlete, and there was no history of any physical and mental disorder. He was not addicted and did not use any drugs or alcohol. The positive points, in this case, were: a large heart with mild coronary stenosis and steatohepatitis in autopsy and sudden death. Since steatohepatitis did not have any complication such as fat embolism, it can be concluded that the combination of steatohepatitis and cardiovascular disorder led to sudden unexpected death. Heart more than 450 gr is susceptible to arrhythmia, and fatty liver disease can cause cardiovascular changes.
It has been assumed that immunoglobulin (Ig) can only be produced by B-cells and plasma cells. Recently, we have reported that Ig can be expressed by other types of cells such as epithelial cancer cells. In this study, we assessed Ig expression in acute myeloid leukemia (AML). We found that Ig was expressed at a high frequency and level in AML cell lines and primary myeloblasts, but not in monocytes or neutrophils from healthy controls, by RT-PCR, immunohistochemistry and flow cytometry. We further assessed rearrangements of IgG VHDJH transcripts, and found that AML-IgG had restricted or biased V usage, and its gene rearrangements showed evidence of somatic hypermutation. Anti-human IgG reduced cell viability and induced apoptosis in AML cell lines, whereas anti-human IgK increased cell migration and chemotaxis. Furthermore, using receiver operating characteristic (ROC) curve analysis, we identified two distinct groups of AML patients with different expression of Ig and different clinical outcomes. High-levels of Ig expression are associated with monocytic differentiation, multilineage dysplasia, TET2 and KRAS mutations, and poor overall survival. Our findings suggest that AML-Ig may play a role in leukemogenesis and AML progression, and it may serve as a useful molecular marker for prognostic stratification, monitoring minimal residual disease, and target therapy. Biography C Cameron Yin has received her MD from Beijing Medical University and her PhD from the University of Wisconsin-Madison. She is currently an Associate Professor in the Department of Hematopathology at the University of Texas MD Anderson Cancer Center. In addition to clinical responsibilities on the Leukemia, Lymphoma and Molecular Diagnostic services, she has been actively participating in multiple research projects in the molecular genetic abnormalities in leukemia and lymphoma, which has led to over 100 research papers and over 20 book chapters. Clinical applications of immunoglobulin expression in acute myeloid leukemia C. Cameron Yin, MD, PhD Anderson Cancer Center, TX, USA Journal of Oncology Translational Research Journal of Oncology Translational Research ISSN: 2476-2261 Volume 7 | Issue 1 | 07 Citation: C Cameron Yin, Clinical applications of immunoglobulin expression in acute myeloid leukemia, Pathology Congress 2020, 2nd World Congress on Pathology and Clinical Practice, October 30, 2020, Page No-07 2nd World Congress on Pathology and Clinical Practice October 30, 2020
Basal cell carcinoma (BCC) is a nonmelanocytic skin cancer (i.e., an epithelial tumor) that arises from basal cells. The prognosis for patients with BCC is excellent, but if the disease is allowed to progress, it can cause significant morbidity. Very few cases almost none have been reported to show metastasis. in this case report we describe an extremely rare case of recurrent BCC with metastasis.
P diseases are invariably fatal neurodegenerative diseases of humans and animals. They are most widely known as a result of their transmissible nature with Creutzfeldt Jakob Disease (CJD) being transmitted from patient to patient through blood transfusion, certain surgical procedures or by use of human-derived hormone therapies and from animals to humans during the bovine spongiform encephalopathy (BSE) outbreak in the UK. The agent that causes these diseases is primary composed of a misfolded protein, the prion protein, which through further templated misfolding events can create more disease-associated forms resulting in disease transmissibility. Whilst the role of the prion protein in disease transmission and progression is firmly established, still very little consensus on the pathways that cause cell death during disease has been reached. Oxidative stress is a feature of prion disease with markers of oxidative damage appearing in the brain in parallel with the detection of mis-folded protein. Data generated by our group has shown how cellular redox homeostasis changes as prion infection progresses from acute to chronic to eventual cell death. The results suggest that prion propagation exacerbates an apoptotic pathway whereby mitochondrial dysfunction follows mislocalization of the critical anti-oxidant enzyme superoxide dismutase-2 (SOD2) to cytosolic caspases, accelerating its degradation. Increased activity of another SOD family member, SOD1, initially compensates for reduction in SOD2 but eventually cellular capacity to maintain oxidative homeostasis is overwhelmed, thus resulting in cell death.
T classification of B-cell and T-cell non-Hodgkin lymphoma has changed considerably over the last several decades. The currently used World Health Organization (WHO) classification system has a broader consensus among the clinical and biomedical community. However, there are still several challenges in regards to the understanding of tumor biology, clinical outcome and diagnostic accuracy in certain subtypes of lymphomas such as peripheral T-cell lymphoma (PTCL), where the diagnosis is frequently challenging even among expert hematopathologists and often time’s assessment requires additional molecular testing. Recently genome-wide high throughput techniques have greatly improved our understanding of B and T-cell lymphomas. This novel genetic information has not only aided in diagnosis, but has also revealed a landscape of critical molecular events that determine the biological and clinical behavior of a lymphoma. In this presentation, I will summarize the genetic characteristics of major subtypes of B-cell and T-cell lymphomas including diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt lymphoma (BL), and mantle cell lymphoma (MCL) and common subtypes of PTCL including angioimmunoblastic T-cell lymphoma (AITL), anaplastic T-cell lymphoma (ALCL), adult T-cell leukemia/lymphoma (ATLL) and extra-nodal NK/T cell lymphoma (ENKTL), and how can these improve precision in diagnosis and inform prognosis.
Dracaena sanderiana, of the family Liliaceae, is among the ornamental plants most frequently imported into Egypt. Typical anthracnose symptoms were observed on the stems of imported D. sanderiana samples. The pathogen was isolated, demonstrated to be pathogenic based on Koch's rule and identified as Colletotrichum dracaenophilum. The optimum temperature for its growth ranges from 25 to 30 °C, maintained for 8 days. Kemazed 50% wettable powder (WP) was the most effective fungicide against the pathogen, as no fungal growth was observed over 100 ppm. The biocontrol agents Trichoderma harzianum and Trichoderma viride followed by Bacillus subtilis and Bacillus pumilus caused the highest reduction in fungal growth. To the best of our knowledge, this report describes the first time that this pathogen was observed on D. sanderiana in Egypt.
Recent large-scale genomic studies have classified medulloblastoma into four subtypes: Wnt, Shh, Group 3 and Group 4. Each is characterized by specific mutations and distinct epigenetic states. Previously, we showed that a chromatin regulator SMARCA4/Brg1 is required for Gli-mediated transcription activation in Sonic hedgehog (Shh) signaling. We report here that Brg1 controls a transcriptional program that specifically regulates Shh-type medulloblastoma growth. Using a mouse model of Shh-type medulloblastoma, we deleted Brg1 in precancerous progenitors and primary or transplanted tumors. Brg1 deletion significantly inhibited tumor formation and progression. Genome-wide expression analyses and binding experiments indicate that Brg1 specifically coordinates with key transcription factors including Gli1, Atoh1 and REST to regulate the expression of both oncogenes and tumor suppressors that are required for medulloblastoma identity and proliferation. Shh-type medulloblastoma displays distinct H3K27me3 properties. We demonstrate that Brg1 modulates activities of H3K27me3 modifiers to regulate the expression of medulloblastoma genes. Brg1-regulated pathways are conserved in human Shh-type medulloblastoma, and Brg1 is important for the growth of a human medulloblastoma cell line. Thus, Brg1 coordinates a genetic and epigenetic network that regulates the transcriptional program underlying the Shh-type medulloblastoma development.
Post-hepatectomy liver failure (PHLF) is a leading cause of morbidity and mortality following major liver resection. The development of PHLF is dependent on the volume of the remaining liver tissue and hepatocyte function. Without effective pre-operative assessment, patients with undiagnosed liver disease could be at increased risk of PHLF. We report a case of a 60-year-old male patient with PHLF secondary to undiagnosed alpha-1-antitrypsin deficiency (AATD) following major liver resection. He initially presented with acute large bowel obstruction secondary to a colorectal adenocarcinoma, which had metastasized to the liver. There was no significant past medical history apart from mild chronic obstructive pulmonary disease. After colonic surgery and liver directed neo-adjuvant chemotherapy, he underwent a laparoscopic partially extended right hepatectomy and radio-frequency ablation. Post-operatively he developed PHLF. The cause of PHLF remained unknown, prompting reanalysis of the histology, which showed evidence of AATD. He subsequently developed progressive liver dysfunction, portal hypertension, and eventually an extensive parastomal bleed, which led to his death; this was ultimately due to a combination of AATD and chemotherapy. This case highlights that formal testing for AATD in all patients with a known history of chronic obstructive pulmonary disease, heavy smoking, or strong family history could help prevent the development of PHLF in patients undergoing major liver resection.
Aclinical diagnosis of Osteoarthritis can be made by focusing on the following six clinical symptoms and signs: persistent knee pain, limited knee stiffness (<30 minutes), reduced function, crepitus, restricted movement and bony enlargement. The majority of patients can be managed adequately by following treatment algorithm recommended by the European League against Rheumatism (EULAR) and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESECEO). Basic principles consist of the need for a combined pharmacological and non-pharmacological treatment with a core set of initial measures, including information access/education, weight loss if overweight and an appropriate exercise program. Four multimodal steps were then established. Step 1 consists of background therapy, either non-pharmacological (physical therapy) or pharmacological treatment. The latter consists of chronic Symptomatic Slow-Acting Drugs for OA (SYSADOA) with paracetamol at-need; topical NSAIDs are added in the still symptomatic patient. In patients with varus deformity and medial compartment knee disease, open high tibial osteotomy is recommended. Step 2 consists of the advanced pharmacological management in the persistent symptomatic patient and is centered on the use of oral COX-2 selective or non-selective NSAIDs, chosen based on concomitant risk factors, with intraarticular corticosteroids or hyaluronate for further symptom relief if insufficient. In Step 3, the last pharmacological attempts before uni-compartmental or total knee replacement are represented by short-term weak opioids and other central analgesics. Finally, Step 4 consists of end-stage disease management and surgery, with classical opioids as a difficult-to-manage alternative when surgery is contraindicated.
C laboratories are rapidly implementing next-generation sequencing (NGS) tests for mutation analysis, however there are few guidelines regarding sample quality for successful results. We aimed to establish tissue quality parameters for successful NGS in solid tumors and to improve NGS performance. Using a 50-gene hotspot mutation panel we identified the major cause for unsuccessful NGS analysis being DNA 10 mm2. Independent factors leading to lower NGS success were cellular tumor areas and decalcification procedures. Tumor type and paraffin block age did not affect success. We optimized workflow and showed improved NGS success rates with pronounced improvement among tiny samples and cytology samples. Identifying preanalytical tissue factors allows us to improve NGS performance and to successfully test tumors obtained from minimally invasive procedures.
Background Carpal tunnel syndrome is the most surgically treated entrapment neuropathy.Ultrasound-guided ultraminimally invasive release is performed with 1 mm incision, in an ambulant regimen, with local anaesthesia, without the need for ischemia and simultaneous bilateral release is possible even in patients with diseases considered contraindications for classic techniques. Methods The instrument set included long needles (a 16–gauge, 1.7 mm diameter Abbocath);, a V-shaped straight curette, a blunt dissector, a hook knife (Aesculap 2,3 mm, and an ultrasound device (Alpinion ECube15) with a 10–17MHz linear transducer. Surgical technique The patient is placed supine, with the hand on a table and the palm up. We first try to delineate the midpoint between the nerve and the ulnar vessels, at the entry point and along the release tract through the carpal ligament, trying to define Nakamichi zone´s midpoint. We insert the small and medium V-shaped straight curette guided by the needle. We puncture 3-four times the fascia, under US control in order to facilitate the insertion of the hook-knive. We insert the hook knife following the curve of the blade so as not to enlarge the incision. The release starts 2–3 mm proximal to the superficial palmar arch, at the end of the ligament, and proximally we extend the release proximal to the pisiform. Results We have operated on 31 hands in 20 patients, (11 bilateral cases). There were 13 women and 4 men. The Phalen test, Tinel test, reverse Phalen test, carpal compression test, and grip strength significatively improved. Two patients with residual numbness and thenar atrophy despite clinical improvement. There were no infections nor nerve damage. Conclusions Ultrasound-guided surgery seems to be safe, helpful and successful for carpal tunnel release although some concerns remain. Ultrasound-guided, ultraminimally invasive surgery is an emerging technology that gives the surgeon direct control of the main structures. Since they can be performed on an outpatient basis under local anaesthesia and without a tourniquet, complications and contraindications are minimised. As it causes minimal pain and swelling, recovery is quicker. However, the learning curve is steep, because the surgeon has to perfect the technique with cadavers and become competent in the use of ultrasound. Large randomised controlled trials are necessary comparing this surgical technique with previous ones.
