Spindle cell carcinoma of the breast: a case report and discussion

Spindle cell carcinoma of the breast is a rare subtype of metaplastic carcinoma with likelihood of aggressive behavior and lack of specific treatment options. Spindle cell carcinomas of the breast are typically "Triple Negative" and have distinct clinical, radiographic and pathological characteristics. We present, in this report, the case of a woman diagnosed with spindle cell carcinoma of the breast, and review the literature on this rare but intriguing disease.     

Enhanced expression of secretable influenza virus neuraminidase in suspension mammalian cells by influenza virus nonstructural protein 1

Influenza neuraminidase (NA) is a major target for anti-influenza drugs. With an increasing number of viruses resistant to the anti-NA drug oseltamivir, functionally active recombinant NA is needed for screening novel anti-NA compounds. In this study, the secretable NA (sNA) head domain of influenza A/Vietnam/DT-036/05 (H5N1) virus was expressed successfully in human embryonic kidney (HEK-293T) cells and shown to be enzymatically active. The inclusion of a plasmid encoding nonstructural protein 1 (NS1) of influenza A/Puerto Rico/8/34 virus with the sNA plasmid in the cotransfection demonstrated an increase in H5N1 sNA expression by 7.4 fold. Subsequently, the sNA/NS1 cotransfection protocol in serum-free 293-F suspension cell culture was optimized to develop a rapid transient gene expression (TGE) system for expression of large amounts of H5N1 sNA. Under optimized conditions, NS1 enhanced H5N1 sNA expression by 4.2 fold. The resulting H5N1 sNA displayed comparable molecular weight, glycosylation, K(m) for MUNANA, and K(i) for oseltamivir carboxylate to those of H5N1 NA on the virus surface. Taken together, the NS1-enhancing sNA expression strategy presented in this study could be used for rapid high-level expression of enzymatically active H5N1 sNA in suspension mammalian cells. This strategy may be applied for expression of sNA of other strains of influenza virus as well as the other recombinant proteins.     

Expression of amyloid-β in mouse cochlear hair cells causes an early-onset auditory defect in high-frequency sound perception

Increasing evidence indicates that defects in the sensory system are highly correlated with age-related neurodegenerative diseases, including Alzheimer''s disease (AD). This raises the possibility that sensory cells possess some commonalities with neurons and may provide a tool for studying AD. The sensory system, especially the auditory system, has the advantage that depression in function over time can easily be measured with electrophysiological methods. To establish a new mouse AD model that takes advantage of this benefit, we produced transgenic mice expressing amyloid-β (Aβ), a causative element for AD, in their auditory hair cells. Electrophysiological assessment indicated that these mice had hearing impairment, specifically in high-frequency sound perception (>32 kHz), at 4 months after birth. Furthermore, loss of hair cells in the basal region of the cochlea, which is known to be associated with age-related hearing loss, appeared to be involved in this hearing defect. Interestingly, overexpression of human microtubule-associated protein tau, another factor in AD development, synergistically enhanced the Aβ-induced hearing defects. These results suggest that our new system reflects some, if not all, aspects of AD progression and, therefore, could complement the traditional AD mouse model to monitor Aβ-induced neuronal dysfunction quantitatively over time.     

Simple,Efficient, and Cost-Effective Multiplex Genotyping with Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry of Hemoglobin Beta Gene Mutations

A number of common mutations in the hemoglobin β (HBB) gene cause β-thalassemia, a monogenic disease with high prevalence in certain ethnic groups. As there are 30 HBB variants that cover more than 99.5% of HBB mutant alleles in the Thai population, an efficient and cost-effective screening method is required. Three panels of multiplex primer extensions, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were developed. The first panel simultaneously detected 21 of the most common HBB mutations, while the second panel screened nine additional mutations, plus seven of the first panel for confirmation; the third panel was used to confirm three HBB mutations, yielding a 9-Da mass difference that could not be clearly distinguished by the previous two panels. The protocol was both standardized using 40 samples of known genotypes and subsequently validated in 162 blind samples with 27 different genotypes (including a normal control), comprising heterozygous, compound heterozygous, and homozygous β-thalassemia. Results were in complete agreement with those from the genotyping results, conducted using three different methods overall. The method developed here permitted the detection of mutations missed using a single genotyping procedure. The procedure should serve as the method of choice for HBB genotyping due to its accuracy, sensitivity, and cost-effectiveness, and can be applied to studies of other gene variants that are potential disease biomarkers.To date, 739 point mutations in the hemoglobin, β (HBB) gene causing β-thalassemia (MIM# 141900) have been reported in HbVar: A Database of Human Hemoglobin Variants and Thalassemias (http://globin.cse.psu.edu/globin/hbvar/menu.html, accessed March 2009), but each ethnic group has a limited number of common mutations and a considerable number of rarer mutations.¹ The c.79G>A (also known as CD26G>A or Hb E) is the most frequent HBB variant in Southeast Asia including Thailand.² “Thai” generally refers to speakers of Thai (Tai) languages. The ethnic groups of Thailand comprise Thais (constituting 85% of the population) and Hill Peoples living primarily in the north, as well as other groups including the Chinese and minorities in the south.³ In the Thai population, approximately 40 HBB mutations have been identified,⁴ of which 30 variants account for more than 99.5% of all mutant HBB alleles

Distributions of metals in the food web of fishponds of Kolleru Lake,India

The distributions of trace metals (Pb, Cd, Cr Mn, Zn and Cu) in water, sediment, plankton and four fish species (Labeo rohita, Catla catla, Pangasius pangasius and Cirrhinus mrigala) from fishponds of Kolleru Lake, India were determined using atomic absorption spectroscopy. The concentrations of lead (0.01–0.03 mg/l) and copper (0.01–0.08 mg/l) in water and cadmium (3.0–9.0 mg/kg), chromium (47–211 mg/kg) and copper (10–64 mg/kg) in sediment were above the EPA threshold effects level (TEL) and are of biological concern. The abundance orders of metals were Mn>Cd>Cu>Pb in water, Mn>Cr>Zn>Cu >Pb>Cd in sediment and Cu>Mn>Cr>Zn>Pb>Cd in plankton. The concentrations of the metals in the muscles of these four fish species apparently decrease in the order Zn>Cu>Cr>Mn=Pb>Cd and were well below WHO permissible limits that were safe for human consumption.     

Ceruloplasmin oxidase activity as a biomarker of lead exposure

The most sensitive method used in monitoring the blood lead-level is atomic absorption spectrophotometry. Its limitation due to its high cost has made delta-aminolaevulinic acid dehydratase (delta-ALAD) inhibition more popular. This work demonstrates that ceruloplasmin (Cp), the blue-colored copper containing alpha-2 globulin (alpha(2) globulin) glycoprotein in serum, can serve as a high-potential biomarker for lead exposure. Sephadex G-200 column chromatography demonstrated that lead-intoxicated patient serum transferrin and ceruloplasmin are bound to lead. The ceruloplasmin's oxidase and delta-ALAD activities are reduced when the blood-lead level increases (thresholds of 10.0 and 12.5 mug/100 mL respectively), with a correlation coefficient of -0.8643 and -0.6785 which accurately estimate a blood lead level of 74.7% and 46.0%, respectively. When the blood-lead level was less than 20 mug/100 mL, correlation coefficients of -0.5785 and -0.6963 suggested that Cp may serve as a good biomarker. Other advantages in using Cp in monitoring the blood-lead level were its stability: the enzyme was more stable at -20 degrees C, for more than 2 wk, and its practical and rapid determination procedure.     

Squamous cell carcinoma of ascending colon. A case study

We report here a case of squamous cell carcinoma of Ascending colon occurring in a 58 year old male. Squamous cell carcinomas are known to occur in the Ano rectum frequently, but are extremely rare in colon especially the right colon.     

The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus

Debio-025 is an oral cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double-blind, placebo-controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log(10) after a 14-day oral treatment with 1200 mg twice daily (P < 0.0001) with an effect against the 3 genotypes (1, 3, and 4) represented in the study. In addition, the absence of viral rebound during treatment indicates that Debio-025 has a high barrier for the selection of resistance. In Debio-025-treated patients, cyclophilin B (CypB) levels in peripheral blood mononuclear cells decreased from 67 +/- 6 (standard error) ng/mg protein (baseline) to 5 +/- 1 ng/mg protein at day 15 (P < 0.01). CONCLUSION: Debio-025 induced a strong drop in CypB levels, coinciding with the decrease in hepatitis C viral load. These are the first preliminary human data supporting the hypothesis that CypB may play an important role in hepatitis C virus replication and that Cyp inhibition is a valid target for the development of anti-hepatitis C drugs.     

Paediatric burn prevention: an epidemiological approach

OBJECTIVE: To study the mechanism of burn in hospitalized paediatric burn patients in order to develop a focused burn prevention campaign. METHODS: Acute paediatric burn patients were identified from the unit admission records. Detailed medical records were reviewed to identify the key demographic and management information including the country of residence, age, gender, extent of injury, specific treatment and hospital stay. Parents were then contacted to provide detailed information about the mechanism of the accident, first aid given, living density and parent's educational level. RESULTS: Two hundred and eighty-four admissions were identified in a 5-year period. Two hundred and twenty-four of these patients came from a defined regional population served by the hospital. The median age of patients was 3 and male to female ratio 1:0.74. The most common age group for burns was 1-2 years. The most common type of burns were scalds. Domestic burns accounted for 84.7% of admissions. Median burn area was 4% of the total body surface area with a range of 0.2-45%. Fifty percent of patients had no first aid treatment prior to presentation at the hospital. More accidents happened in homes with a high living density and the majority of parents had both completed secondary education. The most dangerous location in the house was the living room, followed by the bathroom, kitchen then bedroom. The majority of burns were related to hot drinks, followed by hot food and then bathing. CONCLUSION: Detailed investigation of burn incidents can reveal repeated mechanisms of injury, which direct the focus of preventive strategies.